original.json

{"questions": [{"body": "What is the association of estrogen replacement therapy and intracranial meningioma risk?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/25335165", "http://www.ncbi.nlm.nih.gov/pubmed/23101448", "http://www.ncbi.nlm.nih.gov/pubmed/22287638", "http://www.ncbi.nlm.nih.gov/pubmed/21067422", "http://www.ncbi.nlm.nih.gov/pubmed/20738039", "http://www.ncbi.nlm.nih.gov/pubmed/20091865", "http://www.ncbi.nlm.nih.gov/pubmed/20730482", "http://www.ncbi.nlm.nih.gov/pubmed/17580362", "http://www.ncbi.nlm.nih.gov/pubmed/16759391", "http://www.ncbi.nlm.nih.gov/pubmed/16570277", "http://www.ncbi.nlm.nih.gov/pubmed/15006250"], "ideal_answer": "Although not definitive, available data suggest an association between the use of hormone replacement therapy and increased meningioma risk.BACKGROUND: Previous studies on association of exogenous female sex hormones and risk for meningioma have yielded conflicting results.There was no significant difference between glioma and meningioma risk in users of estrogen-only HT.Among women who had been using estradiol-only therapy for at least 3 years, the incidence of meningioma was 1.40-fold higher (95% confidence interval: 1.18, 1.64; P<0.001) than in the background population.Estradiol-only therapy was accompanied with a slightly increased risk of meningioma.A retrospective study including more than 350,000 women, about 1400 of whom had developed meningioma, showed that the risk of meningioma was about twice as high in users of postmenopausal hormone replacement therapy as in non-users.Likewise, risk of meningioma was only weakly associated with past use of HRT (OR = 0.7, 95% CI 0.4 - 1.3), and not at all with current use of HRT (OR = 1.0, 95% CI 0.5 - 2.2).", "type": "summary", "id": "56bf3a79ef6e39474100000f", "snippets": [{"offsetInBeginSection": 1178, "offsetInEndSection": 1814, "text": "The meta-analyses yielded significantly increased risks for all CNS tumors, glioma and meningioma in users of estrogen-only [1.35 (1.22-1.49), 1.23 (1.06-1.42) and 1.31 (1.20-1.43), respectively] but not estrogen-progestin HT [1.09 (0.99-1.19), 0.92 (0.78-1.08) and 1.05 (0.95-1.16), respectively]; these differences were statistically significant (p<0.005 for each tumor type). There was no significant difference between glioma and meningioma risk in users of estrogen-only HT. The totality of the available evidence suggests an increased risk of all CNS tumors (and of glioma and meningioma separately) in users of estrogen-only HT. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25335165", "endSection": "abstract"}, {"offsetInBeginSection": 1009, "offsetInEndSection": 1310, "text": "Among premenopausal women, current use of oral contraceptives was associated with an increased risk of meningiomas (OR 1.8, 95% CI 1.1-2.9), while current use of hormone replacement therapy among postmenopausal women was not associated with a significant elevation in risk (OR 1.1, 95% CI 0.74-1.67). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23101448", "endSection": "abstract"}, {"offsetInBeginSection": 1610, "offsetInEndSection": 1838, "text": "The relationship between current use of exogenous hormones and meningioma remains unclear, limited by the small numbers of patients currently on oral hormone medications and a lack of hormone receptor data for meningioma tumors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23101448", "endSection": "abstract"}, {"offsetInBeginSection": 682, "offsetInEndSection": 1052, "text": "Ever use of estradiol-only therapy was associated with an increased risk of meningioma (standardized incidence ratio = 1.29, 95% confidence interval: 1.15, 1.44). Among women who had been using estradiol-only therapy for at least 3 years, the incidence of meningioma was 1.40-fold higher (95% confidence interval: 1.18, 1.64; P<0.001) than in the background population. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22287638", "endSection": "abstract"}, {"offsetInBeginSection": 1291, "offsetInEndSection": 1375, "text": "Estradiol-only therapy was accompanied with a slightly increased risk of meningioma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22287638", "endSection": "abstract"}, {"offsetInBeginSection": 245, "offsetInEndSection": 447, "text": "Results from several prospective, large-scale studies indicate that postmenopausal hormone therapy may increase the risk for diagnosing meningioma by 30-80%, but there is no effect in regard to glioma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21067422", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 232, "text": "A retrospective study including more than 350,000 women, about 1400 of whom had developed meningioma, showed that the risk of meningioma was about twice as high in users of postmenopausal hormone replacement therapy as in non-users. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20738039", "endSection": "abstract"}, {"offsetInBeginSection": 486, "offsetInEndSection": 870, "text": "Compared with never users of HRT, the relative risks (RRs) for all incident CNS tumours, gliomas, meningiomas and acoustic neuromas in current users of HRT were 1.20 (95% CI: 1.05-1.36), 1.09 (95% CI: 0.89-1.32), 1.34 (95% CI: 1.03-1.75) and 1.58 (95% CI: 1.02-2.45), respectively, and there was no significant difference in the relative risks by tumour type (heterogeneity p = 0.2). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20091865", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "BACKGROUND: Previous studies on association of exogenous female sex hormones and risk for meningioma have yielded conflicting results. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20730482", "endSection": "abstract"}, {"offsetInBeginSection": 999, "offsetInEndSection": 1131, "text": "RESULTS: Postmenopausal hormonal treatment, use of contraceptives, or fertility treatment did not influence the risk of meningioma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20730482", "endSection": "abstract"}, {"offsetInBeginSection": 1418, "offsetInEndSection": 1549, "text": "CONCLUSIONS: Overall, we found little indication that reproductive factors or use of exogenous sex hormones affect meningioma risk. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20730482", "endSection": "abstract"}, {"offsetInBeginSection": 813, "offsetInEndSection": 954, "text": "Although not definitive, available data suggest an association between the use of hormone replacement therapy and increased meningioma risk. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17580362", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 208, "text": "BACKGROUND: The role of exogenous hormone exposures in the development of meningioma is unclear, but these exposures have been proposed as one hypothesis to explain the over-abundance of such tumors in women. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16759391", "endSection": "abstract"}, {"offsetInBeginSection": 613, "offsetInEndSection": 812, "text": "RESULTS: Although risk of meningioma appeared modestly elevated in past OC users (OR = 1.5, 95% CI 0.8 - 2.7), and in current users (OR = 2.5, 95% CI 0.5 - 12.6), the confidence intervals were wide. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16759391", "endSection": "abstract"}, {"offsetInBeginSection": 897, "offsetInEndSection": 1073, "text": "Likewise, risk of meningioma was only weakly associated with past use of HRT (OR = 0.7, 95% CI 0.4 - 1.3), and not at all with current use of HRT (OR = 1.0, 95% CI 0.5 - 2.2). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16759391", "endSection": "abstract"}, {"offsetInBeginSection": 1318, "offsetInEndSection": 1716, "text": " Overall, in post menopausal women, HRT use appeared to confer a non-significant protective effect, and was not associated with low or high PR expressing meningiomas.CONCLUSION: This study found little evidence of associations between meningioma and exogenous hormone exposures in women but did suggest that some hormonal exposures may influence tumor biology in those women who develop meningioma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16759391", "endSection": "abstract"}, {"offsetInBeginSection": 1276, "offsetInEndSection": 1608, "text": "The increased odds ratios with African Americans was retained in post-menopausal women, while the protective odds ratios for pregnancy, smoking and oral contraceptives (OCs) became stronger in pre-menopausal women. The pattern by duration and timing of use does not suggest an etiologic role for OCs or hormone replacement therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16570277", "endSection": "abstract"}, {"offsetInBeginSection": 1044, "offsetInEndSection": 1221, "text": "The use of hormone replacement therapy in symptomatic postmenopausal women either with previously treated disease or with dormant tumors is discussed, but remains controversial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15006250", "endSection": "abstract"}]}, {"body": "Which type of genes are modulated by SATB1?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/21841785", "http://www.ncbi.nlm.nih.gov/pubmed/16034473", "http://www.ncbi.nlm.nih.gov/pubmed/15371550"], "ideal_answer": "Repression of the genome organizer SATB1 in regulatory T cells is required for suppressive function and inhibition of effector differentiationFoxp3, acting as a transcriptional repressor, directly suppressed the SATB1 locus and indirectly suppressed it through the induction of microRNAs that bound the SATB1 3' untranslated region.Consistent with previous reports in a non-superantigen in vivo anergy model, mRNA for CD18 and the transcription factor Satb1 (special AT-rich-binding protein 1) was increased in SEB-energized T cells.Release of SATB1 from the control of Foxp3 in T(reg) cells caused loss of suppressive function, establishment of transcriptional T(eff) cell programs and induction of T(eff) cell cytokines.SATB1, a genome organizer that regulates chromatin structure and gene expression, was crucial for the phenotype and function of T(reg) cellsSATB1, a genome organizer that regulates chromatin structure and gene expression, was crucial for the phenotype and function of T(reg) cells", "type": "factoid", "id": "56fcf1b8cf1c325851000005", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "Repression of the genome organizer SATB1 in regulatory T cells is required for suppressive function and inhibition of effector differentiation ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21841785", "endSection": "title"}, {"offsetInBeginSection": 284, "offsetInEndSection": 424, "text": "SATB1, a genome organizer that regulates chromatin structure and gene expression, was crucial for the phenotype and function of T(reg) cells ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21841785", "endSection": "abstract"}, {"offsetInBeginSection": 426, "offsetInEndSection": 616, "text": "Foxp3, acting as a transcriptional repressor, directly suppressed the SATB1 locus and indirectly suppressed it through the induction of microRNAs that bound the SATB1 3' untranslated region. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21841785", "endSection": "abstract"}, {"offsetInBeginSection": 617, "offsetInEndSection": 806, "text": "Release of SATB1 from the control of Foxp3 in T(reg) cells caused loss of suppressive function, establishment of transcriptional T(eff) cell programs and induction of T(eff) cell cytokines. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21841785", "endSection": "abstract"}, {"offsetInBeginSection": 1096, "offsetInEndSection": 1298, "text": "Consistent with previous reports in a non-superantigen in vivo anergy model, mRNA for CD18 and the transcription factor Satb1 (special AT-rich-binding protein 1) was increased in SEB-energized T cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16034473", "endSection": "abstract"}]}, {"body": "What is ChiRP-seq (Chromatin Isolation by RNA Purification sequencing)?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/21963238"], "ideal_answer": "Here we introduce Chromatin Isolation by RNA Purification (ChIRP), where tiling oligonucleotides retrieve specific lncRNAs with bound protein and DNA sequences, which are enumerated by deep sequencing.ChIRP-seq is generally applicable to illuminate the intersection of RNA and chromatin with newfound precision genome wide.Drosophila roX2 RNA occupies male X-linked gene bodies with increasing tendency toward the 3' end, peaking at CES sites.HOTAIR occupancy occurs independently of EZH2, suggesting the order of RNA guidance of Polycomb occupancy.Human telomerase RNA TERC occupies telomeres and Wnt pathway genes.ChIRP-seq of three lncRNAs reveal that RNA occupancy sites in the genome are focal, sequence-specific, and numerous.HOTAIR lncRNA preferentially occupies a GA-rich DNA motif to nucleate broad domains of Polycomb occupancy and histone H3 lysine 27 trimethylation.HOTAIR lncRNA preferentially occupies a GA-rich DNA motif to nucleate broad domains of Polycomb occupancy and histone H3 lysine 27 trimethylation.HOTAIR lncRNA preferentially occupies a GA-rich DNA motif to nucleate broad domains of Polycomb occupancy and histone H3 lysine 27 trimethylation.", "type": "summary", "id": "56af7b820a360a5e45000014", "snippets": [{"offsetInBeginSection": 143, "offsetInEndSection": 1027, "text": "Here we introduce Chromatin Isolation by RNA Purification (ChIRP), where tiling oligonucleotides retrieve specific lncRNAs with bound protein and DNA sequences, which are enumerated by deep sequencing. ChIRP-seq of three lncRNAs reveal that RNA occupancy sites in the genome are focal, sequence-specific, and numerous. Drosophila roX2 RNA occupies male X-linked gene bodies with increasing tendency toward the 3' end, peaking at CES sites. Human telomerase RNA TERC occupies telomeres and Wnt pathway genes. HOTAIR lncRNA preferentially occupies a GA-rich DNA motif to nucleate broad domains of Polycomb occupancy and histone H3 lysine 27 trimethylation. HOTAIR occupancy occurs independently of EZH2, suggesting the order of RNA guidance of Polycomb occupancy. ChIRP-seq is generally applicable to illuminate the intersection of RNA and chromatin with newfound precision genome wide. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21963238", "endSection": "abstract"}]}, {"body": "Is Kanzaki disease associated with deficiency in alpha-N-acetylgalactosaminidase?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/15619430"], "ideal_answer": "Kanzaki disease (OMIM#104170) is attributable to a deficiency in alpha-N-acetylgalactosaminidase (alpha-NAGA; E.C.3.2.1.49), which hydrolyzes GalNAcalpha1-O-Ser/Thr.The residual mutant enzyme in R329W could not associate with GalNAcalpha1-O-Thr and GalNAcalpha1-O-Ser. Our findings suggest that the association of alpha-NAGA with its substrates is strongly affected by the amino acid substitution at R329 and that the association with GalNAcalpha1-O-Thr is more highly susceptible to structural changes.Therefore, the urinary ratio of GalNAcalpha1-O-Ser:GalNAcalpha1-O-Thr was lower and the clinical phenotype was milder in the R329Q mutation.However, the residual mutant enzyme in R329Q catalyzed GalNAcalpha1-O-Ser to some extent.However, the residual mutant enzyme in R329Q catalyzed GalNAcalpha1-O-Ser to some extent.However, the residual mutant enzyme in R329Q catalyzed GalNAcalpha1-O-Ser to some extent.However, the residual mutant enzyme in R329Q catalyzed GalNAcalpha1-O-Ser to some extent.However, the residual mutant enzyme in R329Q catalyzed GalNAcalpha1-O-Ser to some extent.However, the residual mutant enzyme in R329Q catalyzed GalNAcalpha1-O-Ser to some extent.", "type": "yesno", "id": "56f7c44109dd18d46b000013", "snippets": [{"offsetInBeginSection": 12, "offsetInEndSection": 178, "text": "Kanzaki disease (OMIM#104170) is attributable to a deficiency in alpha-N-acetylgalactosaminidase (alpha-NAGA; E.C.3.2.1.49), which hydrolyzes GalNAcalpha1-O-Ser/Thr. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15619430", "endSection": "abstract"}, {"offsetInBeginSection": 1304, "offsetInEndSection": 1875, "text": " Our findings suggest that the association of alpha-NAGA with its substrates is strongly affected by the amino acid substitution at R329 and that the association with GalNAcalpha1-O-Thr is more highly susceptible to structural changes. The residual mutant enzyme in R329W could not associate with GalNAcalpha1-O-Thr and GalNAcalpha1-O-Ser. However, the residual mutant enzyme in R329Q catalyzed GalNAcalpha1-O-Ser to some extent. Therefore, the urinary ratio of GalNAcalpha1-O-Ser:GalNAcalpha1-O-Thr was lower and the clinical phenotype was milder in the R329Q mutation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15619430", "endSection": "abstract"}]}, {"body": "Which transcription factor is considered as a master regulator of lysosomal genes?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/23401004", "http://www.ncbi.nlm.nih.gov/pubmed/23609508", "http://www.ncbi.nlm.nih.gov/pubmed/23393155", "http://www.ncbi.nlm.nih.gov/pubmed/23604321", "http://www.ncbi.nlm.nih.gov/pubmed/22343943", "http://www.ncbi.nlm.nih.gov/pubmed/21804531"], "ideal_answer": "Here, we investigate the role of the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and function, in modulating lysosomal proteostasis in LSDsA lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB.our findings identify TFEB as a specific regulator of lysosomal proteostasisThese data uncover a regulatory network linking an oncogenic transcription factor that is a master regulator of lysosomal biogenesis, TFEB, to mTORC1 and endocytosis.Depletion or inactivation of Rags prevented recruitment of TFEB to lysosomes, whereas expression of active Rags induced association of TFEB with lysosomal membranesthe transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, is induced by starvation through an autoregulatory feedback loop and exerts a global transcriptional control on lipid catabolismIn this paper, we identify a novel role for Rags in controlling activation of transcription factor EB (TFEB), a master regulator of autophagic and lysosomal gene expressionInteraction of TFEB with active Rag heterodimers promoted recruitment of TFEB to lysosomes, leading to mTORC1-dependent phosphorylation and inhibition of TFEB", "type": "factoid", "id": "56cdf40d5795f9a73e00003d", "snippets": [{"offsetInBeginSection": 252, "offsetInEndSection": 424, "text": "In this paper, we identify a novel role for Rags in controlling activation of transcription factor EB (TFEB), a master regulator of autophagic and lysosomal gene expression ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23401004", "endSection": "abstract"}, {"offsetInBeginSection": 426, "offsetInEndSection": 584, "text": "Interaction of TFEB with active Rag heterodimers promoted recruitment of TFEB to lysosomes, leading to mTORC1-dependent phosphorylation and inhibition of TFEB ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23401004", "endSection": "abstract"}, {"offsetInBeginSection": 704, "offsetInEndSection": 868, "text": "Depletion or inactivation of Rags prevented recruitment of TFEB to lysosomes, whereas expression of active Rags induced association of TFEB with lysosomal membranes ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23401004", "endSection": "abstract"}, {"offsetInBeginSection": 560, "offsetInEndSection": 874, "text": "The identification of a master regulator, transcription factor EB (TFEB), that regulates lysosomal biogenesis and autophagy has revealed how the lysosome adapts to environmental cues, such as starvation, and targeting TFEB may provide a novel therapeutic strategy for modulating lysosomal function in human disease ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23609508", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 37, "text": "TFEB regulates lysosomal proteostasis ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23393155", "endSection": "title"}, {"offsetInBeginSection": 763, "offsetInEndSection": 933, "text": "Here, we investigate the role of the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and function, in modulating lysosomal proteostasis in LSDs ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23393155", "endSection": "abstract"}, {"offsetInBeginSection": 1648, "offsetInEndSection": 1724, "text": "our findings identify TFEB as a specific regulator of lysosomal proteostasis ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23393155", "endSection": "abstract"}, {"offsetInBeginSection": 261, "offsetInEndSection": 483, "text": "the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, is induced by starvation through an autoregulatory feedback loop and exerts a global transcriptional control on lipid catabolism ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23604321", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22343943", "endSection": "title"}, {"offsetInBeginSection": 244, "offsetInEndSection": 414, "text": "the Transcription Factor EB (TFEB), a master regulator of lysosomal biogenesis, colocalizes with master growth regulator mTOR complex 1 (mTORC1) on the lysosomal membrane ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22343943", "endSection": "abstract"}, {"offsetInBeginSection": 1063, "offsetInEndSection": 1201, "text": "the lysosome senses its content and regulates its own biogenesis by a lysosome-to-nucleus signalling mechanism that involves TFEB and mTOR ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22343943", "endSection": "abstract"}, {"offsetInBeginSection": 1023, "offsetInEndSection": 1189, "text": "These data uncover a regulatory network linking an oncogenic transcription factor that is a master regulator of lysosomal biogenesis, TFEB, to mTORC1 and endocytosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21804531", "endSection": "abstract"}]}, {"body": "What kind of bonds are connecting keratin molecules?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/25947341", "http://www.ncbi.nlm.nih.gov/pubmed/24367993", "http://www.ncbi.nlm.nih.gov/pubmed/24276370", "http://www.ncbi.nlm.nih.gov/pubmed/24971553", "http://www.ncbi.nlm.nih.gov/pubmed/23466495", "http://www.ncbi.nlm.nih.gov/pubmed/22683767", "http://www.ncbi.nlm.nih.gov/pubmed/22705788", "http://www.ncbi.nlm.nih.gov/pubmed/19925868", "http://www.ncbi.nlm.nih.gov/pubmed/19412554"], "ideal_answer": " The method involves the generation of thiols by controlled reduction of cystine disulfide bonds in keratinossible chemical bonds formed between alpha-keratins and KAbetaPs may derive from electrostatic interactions in addition to cross-linking through disulphide bonds.e solubility test in the dithiothreitol/urea extraction buffer, the amino acid composition analysis and studies on keratin secondary structures suggest that the improved stability in water of thermally treated mats can be ascribed to the formation of amide bonds between acid and basic groups of some amino acid side chains.The interface of the K5-K14 coiled-coil heterodimer has asymmetric salt bridges, hydrogen bonds and hydrophobic contacts, and its surface exhibits a notable charge polarization.A trans-dimer homotypic disulfide bond involving Cys367 in K14's stutter region occurs in the crystal and in skin keratinocytes, where it is concentrated in a keratin filament cage enveloping the nucleus.A good solvent attacks the disulfide bonds between cystine molecules and hydrates the hair shaft.. Feathers and hair consist of cornified epidermal keratinocytes in which proteins are crosslinked via disulfide bonds between cysteine residues of structural proteins to establish mechanical resilience.", "type": "list", "id": "56f96333cf1c325851000004", "snippets": [{"offsetInBeginSection": 11, "offsetInEndSection": 213, "text": " Feathers and hair consist of cornified epidermal keratinocytes in which proteins are crosslinked via disulfide bonds between cysteine residues of structural proteins to establish mechanical resilience. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25947341", "endSection": "abstract"}, {"offsetInBeginSection": 130, "offsetInEndSection": 237, "text": " The method involves the generation of thiols by controlled reduction of cystine disulfide bonds in keratin ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24367993", "endSection": "abstract"}, {"offsetInBeginSection": 1150, "offsetInEndSection": 1313, "text": "ossible chemical bonds formed between alpha-keratins and KAbetaPs may derive from electrostatic interactions in addition to cross-linking through disulphide bonds. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24276370", "endSection": "abstract"}, {"offsetInBeginSection": 144, "offsetInEndSection": 254, "text": "The method involves the generation of thiols by controlled reduction of cystine disulfide bonds in the keratin ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24971553", "endSection": "abstract"}, {"offsetInBeginSection": 565, "offsetInEndSection": 889, "text": "e solubility test in the dithiothreitol/urea extraction buffer, the amino acid composition analysis and studies on keratin secondary structures suggest that the improved stability in water of thermally treated mats can be ascribed to the formation of amide bonds between acid and basic groups of some amino acid side chains. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23466495", "endSection": "abstract"}, {"offsetInBeginSection": 764, "offsetInEndSection": 1045, "text": "s the energy involved in the formation of disulfide bonds is much greater than that of hydrogen bonds or van der Waals interactions the structural transition is likely to be dominated by the requirement that the bonded cysteine residues occur at closely equivalent axial positions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22683767", "endSection": "abstract"}, {"offsetInBeginSection": 381, "offsetInEndSection": 764, "text": "The interface of the K5-K14 coiled-coil heterodimer has asymmetric salt bridges, hydrogen bonds and hydrophobic contacts, and its surface exhibits a notable charge polarization. A trans-dimer homotypic disulfide bond involving Cys367 in K14's stutter region occurs in the crystal and in skin keratinocytes, where it is concentrated in a keratin filament cage enveloping the nucleus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22705788", "endSection": "abstract"}, {"offsetInBeginSection": 1406, "offsetInEndSection": 1753, "text": " the alpha helices which are stabilized by hydrogen bonds and the alpha-helical coiled coils which are stabilized by hydrophobic interactions, is more sensitive to radiation than the supramolecular architecture of the keratin filament and the filament packing within the keratin associated proteins matrix, which is stabilized by disulphide bonds. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19925868", "endSection": "abstract"}, {"offsetInBeginSection": 669, "offsetInEndSection": 768, "text": ". A good solvent attacks the disulfide bonds between cystine molecules and hydrates the hair shaft. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19412554", "endSection": "abstract"}]}, {"body": "What is 2d 4d ratio in athletes.", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/25520769", "http://www.ncbi.nlm.nih.gov/pubmed/24949031", "http://www.ncbi.nlm.nih.gov/pubmed/23444944", "http://www.ncbi.nlm.nih.gov/pubmed/22185395", "http://www.ncbi.nlm.nih.gov/pubmed/22132823", "http://www.ncbi.nlm.nih.gov/pubmed/20733526", "http://www.ncbi.nlm.nih.gov/pubmed/21993037", "http://www.ncbi.nlm.nih.gov/pubmed/20981610", "http://www.ncbi.nlm.nih.gov/pubmed/19954495", "http://www.ncbi.nlm.nih.gov/pubmed/19843265", "http://www.ncbi.nlm.nih.gov/pubmed/16254897"], "ideal_answer": "There was also a lower digit ratio in both females and males.2D:4D had been linked to several traits like athletes' abilities, reproductive success, risk of cancer and cardiovascular disease (CVD).Varsity athletes have lower 2D:4D ratios than other university students.The 2D:4D ratio has been negatively correlated with many factors, including aggression, physical fitness, and athleticism.BACKGROUND: Ratio of second and fourth digit (2D:4D) is known to be germane in analyzing utero concentrations of testosterone and estrogen in human and other vertebrates.Research suggests that prenatal levels of testosterone are related to finger length development and traits beneficial to athletic skill, such as power, endurance, visual-spatial skills, or sensation seeking and dominance behavior.Research particularly focusing on male athletes and popular sports (running and soccer) suggests associations of lower (masculinized) second-to-fourth digit ratio (2D:4D), a putative marker of prenatal androgen action, with better sports performance.We conclude that low right 2D:4D and low right-left 2D:4D difference are predictors of high rugby performance.", "type": "summary", "id": "56bf4035ef6e394741000010", "snippets": [{"offsetInBeginSection": 756, "offsetInEndSection": 1015, "text": "RESULTS: A highly significant difference was found in 2D:4D ratios of both the hands with Kabaddi players having a lower ratio compared to their controls. There was no statistically significant difference in 2D:4D (\u0394 r-l) between Kabaddi players and controls. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25520769", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 308, "text": "BACKGROUND: Ratio of second and fourth digit (2D:4D) is known to be germane in analyzing utero concentrations of testosterone and estrogen in human and other vertebrates. 2D:4D had been linked to several traits like athletes' abilities, reproductive success, risk of cancer and cardiovascular disease (CVD). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24949031", "endSection": "abstract"}, {"offsetInBeginSection": 796, "offsetInEndSection": 857, "text": "There was also a lower digit ratio in both females and males. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23444944", "endSection": "abstract"}, {"offsetInBeginSection": 261, "offsetInEndSection": 489, "text": "Research from other fields is presented to suggest that healthy individuals with low 2D:4D ratio have enhanced sporting prowess, particularly with regard to activities requiring endurance and dependent upon slow-twitch muscles. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22185395", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Varsity athletes have lower 2D:4D ratios than other university students. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22132823", "endSection": "title"}, {"offsetInBeginSection": 283, "offsetInEndSection": 405, "text": "The 2D:4D ratio has been negatively correlated with many factors, including aggression, physical fitness, and athleticism. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22132823", "endSection": "abstract"}, {"offsetInBeginSection": 592, "offsetInEndSection": 1100, "text": "Our results confirmed that both male (mean \u00b1 s(x) : 0.97 \u00b1 0.004) and female (0.98 \u00b1 0.005) varsity athletes had significantly lower ratios than their non-varsity peers (males: 0.99 \u00b1 0.004; females: 1.00 \u00b1 0.006), and that male athletes had significantly lower 2D:4D ratios than female athletes. Overall, males had significantly lower 2D:4D ratios than females (0.98 \u00b1 0.003 vs. 0.99 \u00b1 0.004). A smaller 2D:4D ratio appears to be consistent with participation in varsity sports among both males and females. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22132823", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 462, "text": "Research suggests that prenatal levels of testosterone are related to finger length development and traits beneficial to athletic skill, such as power, endurance, visual-spatial skills, or sensation seeking and dominance behavior. In men, the second digit to fourth digit ratio (2D:4D) has been shown to correlate with success in competitive levels of football (soccer), which suggests that the 2D:4D ratio is a possible marker for level of attainment in sport. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20733526", "endSection": "abstract"}, {"offsetInBeginSection": 1023, "offsetInEndSection": 1456, "text": "Significant differences were found among the different groups (p = 0.000), with significantly lower ratios between football and crew (p = 0.000), football and nonathletes (p = 0.030), and gymnastics and crew (p = 0.001). This research provides a stronger level of evidence that the 2D:4D ratio may help indicate potential athleticism or competition-level achievement, but the external validity may be limited to only specific sports. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20733526", "endSection": "abstract"}, {"offsetInBeginSection": 166, "offsetInEndSection": 271, "text": "Low 2D:4D has been linked to various measures of performance in a range of sports (e.g., soccer, rugby). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21993037", "endSection": "abstract"}, {"offsetInBeginSection": 950, "offsetInEndSection": 1295, "text": "We found that right 2D:4D (but not left 2D:4D or right-left 2D:4D) was significantly negatively correlated with coaches' ratings (r(s) = 0.58) and the competition result (r(s) = 0.30). It appears that in line with other sports that low right 2D:4D (high prenatal testosterone and low prenatal estrogen) correlates to high surfing ability in men. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21993037", "endSection": "abstract"}, {"offsetInBeginSection": 639, "offsetInEndSection": 1085, "text": "Compared with controls, players were larger and had lower 2D:4D for the right and left hand. With regard to number of caps, players with low 2D:4D in their right hand and low right 2D:4D compared with their left (right\u00a0-\u00a0left 2D:4D difference) had high numbers of caps. First-choice players did not differ significantly from second-choice players in their 2D:4D but they did have a lower right\u00a0-\u00a0left 2D:4D difference than second-choice players. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20981610", "endSection": "abstract"}, {"offsetInBeginSection": 1194, "offsetInEndSection": 1306, "text": "We conclude that low right 2D:4D and low right\u00a0-\u00a0left 2D:4D difference are predictors of high rugby performance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20981610", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 264, "text": "Second-to-fourth digit ratio (2D:4D), a widely studied putative marker for masculinization through prenatal androgen exposure, is lower (more masculinized) in athletes than in general population controls, and athletes with lower 2D:4D have higher sporting success. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19954495", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 130, "text": "Digit ratio (2D:4D) predicts sporting success among female fencers independent from physical, experience, and personality factors. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19843265", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "Research particularly focusing on male athletes and popular sports (running and soccer) suggests associations of lower (masculinized) second-to-fourth digit ratio (2D:4D), a putative marker of prenatal androgen action, with better sports performance. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19843265", "endSection": "abstract"}, {"offsetInBeginSection": 710, "offsetInEndSection": 807, "text": "Among female, but not male, fencers, lower 2D:4D was related to better national fencing rankings. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19843265", "endSection": "abstract"}, {"offsetInBeginSection": 1136, "offsetInEndSection": 1269, "text": "Athletes active in the most aggressive form (the sabre) had lower 2D:4D than those active in the other forms (\u00e9p\u00e9e and foil fencing). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19843265", "endSection": "abstract"}, {"offsetInBeginSection": 1031, "offsetInEndSection": 1273, "text": "Our results showed that elite female athletes have significantly lower left hand 2D:4D ratios compared to the control group (P<0.05). Therefore, we can speculate that low 2D:4D ratio may be a positive correlate of sports potential in females. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16254897", "endSection": "abstract"}]}, {"body": "From which sequence does the Alu repeat originate from?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/16343813", "http://www.ncbi.nlm.nih.gov/pubmed/12167372", "http://www.ncbi.nlm.nih.gov/pubmed/9694666", "http://www.ncbi.nlm.nih.gov/pubmed/9395063", "http://www.ncbi.nlm.nih.gov/pubmed/8576966"], "ideal_answer": "Finally, we propose that the origin of Alu subfamilies in human populations may be related to evolution of chromosome Y.Our analysis indicates that about 60 Myr ago, before the prosimian divergence, free left and right monomers formed an Alu heterodimer connected by a 19-nucleotide-long A-rich linker.the presence of Alu-like structural motifs supports the hypothesis of the monophyletic origin of Alu and B1 repeats, i.e., from a common 7SL RNA-derived retroposing monomeric elementThe origin of Alu-derived minisatellites appears to have been mediated by short flanking repeats, as first proposed by Haber and LouisThe origin of Alu-derived minisatellites appears to have been mediated by short flanking repeats, as first proposed by Haber and LouisThe origin of Alu-derived minisatellites appears to have been mediated by short flanking repeats, as first proposed by Haber and LouisThe origin of Alu-derived minisatellites appears to have been mediated by short flanking repeats, as first proposed by Haber and LouisThe origin of Alu-derived minisatellites appears to have been mediated by short flanking repeats, as first proposed by Haber and Louis", "type": "factoid", "id": "56ffd08bcf1c325851000009", "snippets": [{"offsetInBeginSection": 164, "offsetInEndSection": 298, "text": "The origin of Alu-derived minisatellites appears to have been mediated by short flanking repeats, as first proposed by Haber and Louis ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16343813", "endSection": "abstract"}, {"offsetInBeginSection": 1207, "offsetInEndSection": 1327, "text": "Finally, we propose that the origin of Alu subfamilies in human populations may be related to evolution of chromosome Y. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12167372", "endSection": "abstract"}, {"offsetInBeginSection": 354, "offsetInEndSection": 536, "text": "Our analysis indicates that about 60 Myr ago, before the prosimian divergence, free left and right monomers formed an Alu heterodimer connected by a 19-nucleotide-long A-rich linker. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9694666", "endSection": "abstract"}, {"offsetInBeginSection": 662, "offsetInEndSection": 844, "text": "the presence of Alu-like structural motifs supports the hypothesis of the monophyletic origin of Alu and B1 repeats, i.e., from a common 7SL RNA-derived retroposing monomeric element ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8576966", "endSection": "abstract"}]}, {"body": "Which peptide plays a pivotal role in human cystatin C fibrillization?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/25479090"], "ideal_answer": "The pentapeptide LQVVR plays a pivotal role in human cystatin C fibrillization.This peptide was synthesized and self-assembled into amyloid-like fibrils in vitro, as electron microscopy, X-ray fiber diffraction, Attenuated Total Reflectance Fourier-Transform Spectroscopy and Congo red staining studies reveal.Thus, the (47)LQVVR(51) peptide seems to have an important role in HCC fibrillization.Human cystatin C (HCC) is a low molecular weight member of the cystatin family (type2).Normally it is an inhibitor of cysteine proteases, but in pathological conditions it forms amyloid fibrils in brain arteries of young adults.HCC consists of 120 amino acids.An 'aggregation-prone' pentapeptide ((47)LQVVR(51)) was located within the HCC sequence using AmylPred, an 'aggregation-prone' peptide prediction algorithm developed in our lab.An 'aggregation-prone' pentapeptide ((47)LQVVR(51)) was located within the HCC sequence using AmylPred, an 'aggregation-prone' peptide prediction algorithm developed in our lab.", "type": "factoid", "id": "56b1f4300a360a5e4500001b", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 759, "text": "Human cystatin C (HCC) is a low molecular weight member of the cystatin family (type2). HCC consists of 120 amino acids. Normally it is an inhibitor of cysteine proteases, but in pathological conditions it forms amyloid fibrils in brain arteries of young adults. An 'aggregation-prone' pentapeptide ((47)LQVVR(51)) was located within the HCC sequence using AmylPred, an 'aggregation-prone' peptide prediction algorithm developed in our lab. This peptide was synthesized and self-assembled into amyloid-like fibrils in vitro, as electron microscopy, X-ray fiber diffraction, Attenuated Total Reflectance Fourier-Transform Spectroscopy and Congo red staining studies reveal. Thus, the (47)LQVVR(51) peptide seems to have an important role in HCC fibrillization. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25479090", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "The pentapeptide LQVVR plays a pivotal role in human cystatin C fibrillization. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25479090", "endSection": "title"}]}, {"body": "Which kinase is regulating stress granule biogenesis?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/25840010"], "ideal_answer": "5'-AMP-activated protein kinase alpha regulates stress granule biogenesisThis interaction is stimulated by stress and notably occurs in SGsFirst, pharmacological kinase inhibition interfered with SG formation.our data define the master metabolic regulator AMPK as a novel SG constituent that also controls their biogenesisMultiple lines of evidence link AMPK activity to SG biogenesis.Finally, we identified the SG-nucleating protein G3BP1 as an AMPK-2 binding partner.Second, AMPK- knockdown combined with in-depth quantitative SG analysis revealed isoform-specific changes of SG characteristics.Third, overexpression of mutant -subunits further substantiated that AMPK regulates SG parameters.Third, overexpression of mutant -subunits further substantiated that AMPK regulates SG parameters.Third, overexpression of mutant -subunits further substantiated that AMPK regulates SG parameters.", "type": "summary", "id": "56cdf4675795f9a73e00003f", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "5'-AMP-activated protein kinase alpha regulates stress granule biogenesis ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25840010", "endSection": "title"}, {"offsetInBeginSection": 645, "offsetInEndSection": 1162, "text": "Multiple lines of evidence link AMPK activity to SG biogenesis. First, pharmacological kinase inhibition interfered with SG formation. Second, AMPK-\u03b1 knockdown combined with in-depth quantitative SG analysis revealed isoform-specific changes of SG characteristics. Third, overexpression of mutant \u03b1-subunits further substantiated that AMPK regulates SG parameters. Finally, we identified the SG-nucleating protein G3BP1 as an AMPK-\u03b12 binding partner. This interaction is stimulated by stress and notably occurs in SGs ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25840010", "endSection": "abstract"}, {"offsetInBeginSection": 1178, "offsetInEndSection": 1291, "text": "our data define the master metabolic regulator AMPK as a novel SG constituent that also controls their biogenesis ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25840010", "endSection": "abstract"}]}, {"body": "Is the Wnt protein modified by notum?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/25731175", "http://www.ncbi.nlm.nih.gov/pubmed/24992682", "http://www.ncbi.nlm.nih.gov/pubmed/24523458", "http://www.ncbi.nlm.nih.gov/pubmed/22159580", "http://www.ncbi.nlm.nih.gov/pubmed/22669824", "http://www.ncbi.nlm.nih.gov/pubmed/18429952", "http://www.ncbi.nlm.nih.gov/pubmed/15647319", "http://www.ncbi.nlm.nih.gov/pubmed/18505598", "http://www.ncbi.nlm.nih.gov/pubmed/10049571"], "ideal_answer": "the Wnt inhibitor notumKinetic and mass spectrometric analyses of human proteins show that Notum is a carboxylesterase that removes an essential palmitoleate moiety from Wnt proteins and thus constitutes the first known extracellular protein deacylase.Notum deacylates Wnt proteins to suppress signalling activity.the WNT-inhibitor notum.the WNT-inhibitor notum.the WNT-inhibitor notum.the WNT-inhibitor notum.the WNT-inhibitor notum.the WNT-inhibitor notum.the WNT-inhibitor notum.", "type": "yesno", "id": "57089865cf1c32585100000c", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 62, "text": "Notum deacylates Wnt proteins to suppress signalling activity. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25731175", "endSection": "title"}, {"offsetInBeginSection": 860, "offsetInEndSection": 1089, "text": "Kinetic and mass spectrometric analyses of human proteins show that Notum is a carboxylesterase that removes an essential palmitoleate moiety from Wnt proteins and thus constitutes the first known extracellular protein deacylase. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25731175", "endSection": "abstract"}, {"offsetInBeginSection": 794, "offsetInEndSection": 817, "text": "the Wnt inhibitor notum ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24992682", "endSection": "abstract"}, {"offsetInBeginSection": 929, "offsetInEndSection": 953, "text": "the WNT-inhibitor notum. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24523458", "endSection": "abstract"}]}, {"body": "Is vemurafenib effective for hairy-cell leukemia?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/26352686", "http://www.ncbi.nlm.nih.gov/pubmed/25480661", "http://www.ncbi.nlm.nih.gov/pubmed/25774734", "http://www.ncbi.nlm.nih.gov/pubmed/25815361", "http://www.ncbi.nlm.nih.gov/pubmed/25148599"], "ideal_answer": "CONCLUSIONS: A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia.The therapeutic approach of vemurafenib in treatment-refractory hairy cell leukemia is promising and offers an additional treatment option.We present here the successful retreatment of this patient with a second line of vemurafenib.Our data suggest for the first time that vemurafenib at the dose of 240 mg once a day could be sufficient to maintain a complete hematological remission after an initial induction treatment with low-dose vemurafenib (2  240 mg) daily without inducing major toxicity.Our results strongly support and inform the clinical use of BRAF and MEK inhibitors in HCL.The discovery of the BRAF mutation has created a therapeutic target exploited by oral inhibitors like vemurafenib and dabrafenib.Recent identification of the recurrent V600E BRAF mutation in a majority of HCL patients has led some teams to evaluate the clinical potential of vemurafenib, a BRAF V600 specific inhibitor in a limited number of refractory HCL patients.Recently, we published the case of an HCL patient successfully treated with a low dose of vemurafenib.", "type": "yesno", "id": "56c02bc3ef6e394741000018", "snippets": [{"offsetInBeginSection": 1961, "offsetInEndSection": 2090, "text": "CONCLUSIONS: A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26352686", "endSection": "abstract"}, {"offsetInBeginSection": 1509, "offsetInEndSection": 1600, "text": "Our results strongly support and inform the clinical use of BRAF and MEK inhibitors in HCL. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25480661", "endSection": "abstract"}, {"offsetInBeginSection": 2204, "offsetInEndSection": 2344, "text": "The therapeutic approach of vemurafenib in treatment-refractory hairy cell leukemia is promising and offers an additional treatment option. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25774734", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Successful re-treatment of a relapsed V600E mutated HCL patient with low-dose vemurafenib. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25815361", "endSection": "title"}, {"offsetInBeginSection": 113, "offsetInEndSection": 453, "text": "Recent identification of the recurrent V600E BRAF mutation in a majority of HCL patients has led some teams to evaluate the clinical potential of vemurafenib, a BRAF V600 specific inhibitor in a limited number of refractory HCL patients. Recently, we published the case of an HCL patient successfully treated with a low dose of vemurafenib. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25815361", "endSection": "abstract"}, {"offsetInBeginSection": 520, "offsetInEndSection": 881, "text": "We present here the successful retreatment of this patient with a second line of vemurafenib. Our data suggest for the first time that vemurafenib at the dose of 240 mg once a day could be sufficient to maintain a complete hematological remission after an initial induction treatment with low-dose vemurafenib (2 \u00d7 240 mg) daily without inducing major toxicity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25815361", "endSection": "abstract"}, {"offsetInBeginSection": 462, "offsetInEndSection": 591, "text": "The discovery of the BRAF mutation has created a therapeutic target exploited by oral inhibitors like vemurafenib and dabrafenib. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25148599", "endSection": "abstract"}]}, {"body": "Which is the main difference between Alu and B1 repeats?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/20019790", "http://www.ncbi.nlm.nih.gov/pubmed/17407136", "http://www.ncbi.nlm.nih.gov/pubmed/9748291", "http://www.ncbi.nlm.nih.gov/pubmed/8036148", "http://www.ncbi.nlm.nih.gov/pubmed/7681065", "http://www.ncbi.nlm.nih.gov/pubmed/1549107", "http://www.ncbi.nlm.nih.gov/pubmed/1945845", "http://www.ncbi.nlm.nih.gov/pubmed/17852045", "http://www.ncbi.nlm.nih.gov/pubmed/2412135"], "ideal_answer": "Most human Alu and murine B1 repeats are unique.Alu and b1 repeats have been selectively retained in the upstream and intronic regions of genes of specific functional classesHere we show that some members of the mouse B1 Alu sequence family encode a small cytoplasmic RNAAlu and B1 repeats are mobile elements that originated in an initial duplication of the 7SL RNA gene prior to the primate-rodent split about 80 million years ago and currently account for a substantial fraction of the human and mouse genome, respectively The core sequences of these elements contain pol III promoters but must rely on fortuitous downstream oligo(dT) tracts for terminator function.The data demonstrate that a limited set of B1 sequences are expressed as processed RNA polymerase III-transcripts of a high degree of structural conservation.Finally, the unexpected finding that Alu and B1 elements show similar biases in their distribution across functional classes, despite having spread independently in their respective genomes, further supports our claim that the extant instances of Alu and B1 elements are the result of positive selection.", "type": "factoid", "id": "56ffd805cf1c32585100000a", "snippets": [{"offsetInBeginSection": 567, "offsetInEndSection": 718, "text": "The mouse B1 sequence is congruent to 130 nucleotides long and shows homology with the monomeric units of the dimeric 300-nucleotide primate sequence. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2412135", "endSection": "abstract"}, {"offsetInBeginSection": 468, "offsetInEndSection": 565, "text": "Here we show that some members of the mouse B1 Alu sequence family encode a small cytoplasmic RNA ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2412135", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 231, "text": "Alus and B1s are short interspersed repeat elements (SINEs) derived from the 7SL RNA gene. Alus and B1s exist in the cytoplasm as non-coding RNA indicating that they are actively transcribed, but their function, if any, is unknown. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17852045", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 116, "text": "B1 (Alu-equivalent) is a murine short interspersed element whose amplification probably involved an RNA intermediate ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1945845", "endSection": "abstract"}, {"offsetInBeginSection": 1062, "offsetInEndSection": 1221, "text": "The data demonstrate that a limited set of B1 sequences are expressed as processed RNA polymerase III-transcripts of a high degree of structural conservation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1945845", "endSection": "abstract"}, {"offsetInBeginSection": 101, "offsetInEndSection": 145, "text": "B1 is a murine homolog of the human SINE Alu ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1549107", "endSection": "abstract"}, {"offsetInBeginSection": 221, "offsetInEndSection": 415, "text": "These RNAs have conserved a secondary structure motif also present in signal recognition particle (SRP) RNA despite substantial sequence divergence, whereas random B1 and Alu sequences have not. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7681065", "endSection": "abstract"}, {"offsetInBeginSection": 69, "offsetInEndSection": 178, "text": "The modern B1 elements are similar to the left Alu monomer, but with a 9 bp deletion and a 29 bp duplication. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8036148", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 109, "text": "A master sequence related to a free left Alu monomer (FLAM) at the origin of the B1 family in rodent genomes. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8036148", "endSection": "title"}, {"offsetInBeginSection": 307, "offsetInEndSection": 572, "text": " The core sequences of these elements contain pol III promoters but must rely on fortuitous downstream oligo(dT) tracts for terminator function. We show that a B1-Alu gene differs markedly from a classical pol III gene (tRNAiMet) in terminator sequence requirements ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9748291", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 48, "text": "Most human Alu and murine B1 repeats are unique. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17407136", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 126, "text": "Alu and b1 repeats have been selectively retained in the upstream and intronic regions of genes of specific functional classes ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20019790", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 254, "text": "Alu and B1 repeats are mobile elements that originated in an initial duplication of the 7SL RNA gene prior to the primate-rodent split about 80 million years ago and currently account for a substantial fraction of the human and mouse genome, respectively ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20019790", "endSection": "abstract"}, {"offsetInBeginSection": 615, "offsetInEndSection": 778, "text": "we present evidence that Alu and B1 elements have been selectively retained in the upstream and intronic regions of genes belonging to specific functional classes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20019790", "endSection": "abstract"}, {"offsetInBeginSection": 1084, "offsetInEndSection": 1388, "text": "Finally, the unexpected finding that Alu and B1 elements show similar biases in their distribution across functional classes, despite having spread independently in their respective genomes, further supports our claim that the extant instances of Alu and B1 elements are the result of positive selection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20019790", "endSection": "abstract"}]}, {"body": "What is enCHIP?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/23942116", "http://www.ncbi.nlm.nih.gov/pubmed/24201379"], "ideal_answer": "We showed that enChIP using the CRISPR system efficiently isolates specific genomic regions.Identification of telomere-associated molecules by engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP).In this form of enChIP, specific genomic regions are immunoprecipitated with antibody against a tag(s), which is fused to a catalytically inactive form of Cas9 (dCas9), which is co-expressed with a guide RNA (gRNA) and recognizes endogenous DNA sequence in the genomic regions of interest.Telomeres recognized by the tagged TAL protein were immunoprecipitated with an antibody against the tag and subjected to identification of telomere-binding molecules.enChIP-mass spectrometry (enChIP-MS) targeting telomeres identified known and novel telomere-binding proteins.enChIP using the CRISPR system would be a convenient and useful tool for dissecting chromatin structure of genomic regions of interest.Here, we report isolation of telomeres by engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) using a transcription activator-like (TAL) protein recognizing telomere repeats.Here, we established a novel method, engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP), for purification of specific genomic regions retaining molecular interactions.", "type": "summary", "id": "56b2863945561f0573000001", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 131, "text": "Identification of telomere-associated molecules by engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP). ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24201379", "endSection": "title"}, {"offsetInBeginSection": 148, "offsetInEndSection": 628, "text": "Here, we report isolation of telomeres by engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) using a transcription activator-like (TAL) protein recognizing telomere repeats. Telomeres recognized by the tagged TAL protein were immunoprecipitated with an antibody against the tag and subjected to identification of telomere-binding molecules. enChIP-mass spectrometry (enChIP-MS) targeting telomeres identified known and novel telomere-binding proteins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24201379", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Efficient isolation of specific genomic regions and identification of associated proteins by engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) using CRISPR. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23942116", "endSection": "title"}, {"offsetInBeginSection": 116, "offsetInEndSection": 926, "text": "Here, we established a novel method, engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP), for purification of specific genomic regions retaining molecular interactions. We showed that enChIP using the CRISPR system efficiently isolates specific genomic regions. In this form of enChIP, specific genomic regions are immunoprecipitated with antibody against a tag(s), which is fused to a catalytically inactive form of Cas9 (dCas9), which is co-expressed with a guide RNA (gRNA) and recognizes endogenous DNA sequence in the genomic regions of interest. enChIP-mass spectrometry (enChIP-MS) targeting endogenous loci identified associated proteins. enChIP using the CRISPR system would be a convenient and useful tool for dissecting chromatin structure of genomic regions of interest. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23942116", "endSection": "abstract"}]}, {"body": "Which domain of TIA-1 is necessary for stress granule assembly?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/24981173", "http://www.ncbi.nlm.nih.gov/pubmed/18775331", "http://www.ncbi.nlm.nih.gov/pubmed/15371533"], "ideal_answer": "Stress granule assembly is mediated by prion-like aggregation of TIA-1Tia1/Pub1 is a stress granule component carrying a Q/N-rich prion domainThe RSK2 N-terminal kinase domain controls the direct interaction with the prion-related domain of TIA-1Truncation mutants lacking the PRD domain do not induce spontaneous SGs and are not recruited to arsenite-induced SGs, whereas the PRD forms aggregates that are recruited to SGs in low-level-expressing cells but prevent SG assembly in high-level-expressing cellsCodependent functions of RSK2 and the apoptosis-promoting factor TIA-1 in stress granule assembly and cell survivalTIA-1 is an RNA binding protein that promotes the assembly of stress granules (SGs), discrete cytoplasmic inclusions into which stalled translation initiation complexes are dynamically recruited in cells subjected to environmental stress.The RNA recognition motifs of TIA-1 are linked to a glutamine-rich prion-related domain (PRD).We report an unanticipated link between stress granules and the serine/threonine kinase RSK2.Substitution of the PRD with the aggregation domain of a yeast prion, SUP35-NM, reconstitutes SG assembly, confirming that a prion domain can mediate the assembly of SGs", "type": "factoid", "id": "56cdf4875795f9a73e000040", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Tia1/Pub1 is a stress granule component carrying a Q/N-rich prion domain ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24981173", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "Codependent functions of RSK2 and the apoptosis-promoting factor TIA-1 in stress granule assembly and cell survival ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18775331", "endSection": "title"}, {"offsetInBeginSection": 121, "offsetInEndSection": 490, "text": "We report an unanticipated link between stress granules and the serine/threonine kinase RSK2. In stressed breast cells, endogenous RSK2 colocalizes in granules with TIA-1 and poly(A)-binding protein 1, and the sequestration of RSK2 and TIA-1 exhibits codependency. The RSK2 N-terminal kinase domain controls the direct interaction with the prion-related domain of TIA-1 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18775331", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Stress granule assembly is mediated by prion-like aggregation of TIA-1 ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15371533", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 596, "text": "TIA-1 is an RNA binding protein that promotes the assembly of stress granules (SGs), discrete cytoplasmic inclusions into which stalled translation initiation complexes are dynamically recruited in cells subjected to environmental stress. The RNA recognition motifs of TIA-1 are linked to a glutamine-rich prion-related domain (PRD). Truncation mutants lacking the PRD domain do not induce spontaneous SGs and are not recruited to arsenite-induced SGs, whereas the PRD forms aggregates that are recruited to SGs in low-level-expressing cells but prevent SG assembly in high-level-expressing cells ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15371533", "endSection": "abstract"}, {"offsetInBeginSection": 598, "offsetInEndSection": 1078, "text": "The PRD of TIA-1 exhibits many characteristics of prions: concentration-dependent aggregation that is inhibited by the molecular chaperone heat shock protein (HSP)70; resistance to protease digestion; sequestration of HSP27, HSP40, and HSP70; and induction of HSP70, a feedback regulator of PRD disaggregation. Substitution of the PRD with the aggregation domain of a yeast prion, SUP35-NM, reconstitutes SG assembly, confirming that a prion domain can mediate the assembly of SGs ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15371533", "endSection": "abstract"}, {"offsetInBeginSection": 1281, "offsetInEndSection": 1421, "text": "Our results reveal that prion-like aggregation of TIA-1 regulates SG formation downstream of eIF2alpha phosphorylation in response to stress ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15371533", "endSection": "abstract"}]}, {"body": "What is the RESID database?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/15174122", "http://www.ncbi.nlm.nih.gov/pubmed/12520062", "http://www.ncbi.nlm.nih.gov/pubmed/11125090", "http://www.ncbi.nlm.nih.gov/pubmed/10592227", "http://www.ncbi.nlm.nih.gov/pubmed/9847179"], "ideal_answer": "The RESID Database of protein structure modifications.The RESID Database of Protein Modifications is a comprehensive collection of annotations and structures for protein modifications and cross-links including pre-, co-, and post-translational modificationsThe RESID Database contains supplemental information on post-translational modifications for the standardized annotations appearing in the PIR-International Protein Sequence Database.The RESID Database of Protein Modifications as a resource and annotation tool.The RESID Database is a comprehensive collection of annotations and structures for protein post-translational modifications including N-terminal, C-terminal and peptide chain cross-link modifications.The RESID Database is a comprehensive collection of annotations and structures for protein pre-, co- and post-translational modifications including amino-terminal, carboxyl-terminal and peptide chain cross-link modifications.The RESID Database is a comprehensive collection of annotations and structures for protein pre-, co- and post-translational modifications including amino-terminal, carboxyl-terminal and peptide chain cross-link modifications.The RESID Database is a comprehensive collection of annotations and structures for protein pre-, co- and post-translational modifications including amino-terminal, carboxyl-terminal and peptide chain cross-link modifications.", "type": "factoid", "id": "5708992ccf1c32585100000d", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 78, "text": "The RESID Database of Protein Modifications as a resource and annotation tool. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15174122", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "The RESID Database of Protein Modifications is a comprehensive collection of annotations and structures for protein modifications and cross-links including pre-, co-, and post-translational modifications ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15174122", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "The RESID Database is a comprehensive collection of annotations and structures for protein pre-, co- and post-translational modifications including amino-terminal, carboxyl-terminal and peptide chain cross-link modifications. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12520062", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "The RESID Database is a comprehensive collection of annotations and structures for protein post-translational modifications including N-terminal, C-terminal and peptide chain cross-link modifications. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11125090", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 184, "text": "The RESID Database contains supplemental information on post-translational modifications for the standardized annotations appearing in the PIR-International Protein Sequence Database. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10592227", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 54, "text": "The RESID Database of protein structure modifications. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9847179", "endSection": "title"}]}, {"body": "What causes erucism?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/23849585", "http://www.ncbi.nlm.nih.gov/pubmed/22890734", "http://www.ncbi.nlm.nih.gov/pubmed/12500482", "http://www.ncbi.nlm.nih.gov/pubmed/12362487", "http://www.ncbi.nlm.nih.gov/pubmed/11436711", "http://www.ncbi.nlm.nih.gov/pubmed/2510913", "http://www.ncbi.nlm.nih.gov/pubmed/2907699", "http://www.ncbi.nlm.nih.gov/pubmed/19580579", "http://www.ncbi.nlm.nih.gov/pubmed/15361962"], "ideal_answer": "Erucism is defined as urtication by Lepidoptera larvae.Urticating moths (genus Hylesia and Anaphae) protect their eggs and young caterpillars with urticating hairs, thus it is very ambiguous to label erucism as the contact dermatitis produced by caterpillar production or Lepidopterism as the contact dermatitis caused by moth urticating hairs.In the South of Brazil during the last years caterpillars of this butterfly caused a great number of cases of erucism including some deaths.Erucism is a skin reaction to envenomation from certain poisonous caterpillar bristles.The hair on the dorsum of the last instar larvae of the moth may cause urticarial reactions (erucism) as well as eye problems and temporary blindness.We present a case of erucism (caterpillar dermatitis) in a British serviceman deployed in Croatia on Operation Resolute.Although many tropical insects carry infectious diseases, cutaneous injury can occur by other mechanisms, for example erucism (envenomation by caterpillars) or lepidopterism (dermatitis from moths).", "type": "summary", "id": "56c036afef6e394741000019", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 87, "text": "Erucism is a skin reaction to envenomation from certain poisonous caterpillar bristles. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23849585", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 198, "text": "Although many tropical insects carry infectious diseases, cutaneous injury can occur by other mechanisms, for example erucism (envenomation by caterpillars) or lepidopterism (dermatitis from moths). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22890734", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "We present a case of erucism (caterpillar dermatitis) in a British serviceman deployed in Croatia on Operation Resolute. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12500482", "endSection": "abstract"}, {"offsetInBeginSection": 145, "offsetInEndSection": 295, "text": "The hair on the dorsum of the last instar larvae of the moth may cause urticarial reactions (erucism) as well as eye problems and temporary blindness. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12362487", "endSection": "abstract"}, {"offsetInBeginSection": 778, "offsetInEndSection": 919, "text": "In the South of Brazil during the last years caterpillars of this butterfly caused a great number of cases of erucism including some deaths. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11436711", "endSection": "abstract"}, {"offsetInBeginSection": 229, "offsetInEndSection": 518, "text": "Urticating moths (genus Hylesia and Anaphae) protect their eggs and young caterpillars with urticating hairs, thus it is very ambiguous to label erucism as the contact dermatitis produced by caterpillar production or Lepidopterism as the contact dermatitis caused by moth urticating hairs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2510913", "endSection": "abstract"}, {"offsetInBeginSection": 107, "offsetInEndSection": 163, "text": "Erucism is defined as urtication by Lepidoptera larvae. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/2907699", "endSection": "abstract"}, {"offsetInBeginSection": 278, "offsetInEndSection": 719, "text": "Specific syndromes caused by Lepidoptera include erucism (cutaneous reactions from contact with caterpillars, moths, or cocoons), lepidopterism (systemic involvement), ophthalmia nodosa (ocular involvement), dendrolimiasis and pararamose (each with joint symptoms relating to a specific species of caterpillar), lonomism (a severe hemorrhagic disease related to Lonomia species), and seasonal ataxia (related to ingestion of Anaphe venata). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19580579", "endSection": "abstract"}]}, {"body": "Which is the most common editing modification in eukaryotic mRNA?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/23543219", "http://www.ncbi.nlm.nih.gov/pubmed/21469143", "http://www.ncbi.nlm.nih.gov/pubmed/20198873", "http://www.ncbi.nlm.nih.gov/pubmed/20185571"], "ideal_answer": "One of the most common forms of pre-mRNA editing is A-to-I editing, in which adenosine is deaminated to inosine, which is read as guanosine during translation.-to-I RNA editing is a post-transcriptional mechanism frequently used to expand and diversify transcriptome and proteome repertoire in eukaryotic cellsA-to-I editing events in normal and cancerous human keratinocytesThis study describes for the first time A-to-I editing in the coding sequence of a tumor suppressor gene in humans, and suggests that IGFBP7 editing serves as a fine-tuning mechanism to maintain the equilibrium between proliferation and senescence in normal skin.A-to-I RNA editing can alter codons, substitute amino acids and affect protein sequence, structure, and function.denosine deaminases editing adenines in transport RNAs (ADATs) convert adenine into inosine in tRNAs of all eukaryotes; as a result, the diversity of tRNA forms in the cell increases.Deamination of adenine by adenosine deaminases that act on RNA (ADARs) leads to the conversion of adenine into inosine (A-I editing) recognized by the splicing and translation systems as guanine.", "type": "factoid", "id": "56ffdc1ccf1c32585100000b", "snippets": [{"offsetInBeginSection": 205, "offsetInEndSection": 364, "text": "One of the most common forms of pre-mRNA editing is A-to-I editing, in which adenosine is deaminated to inosine, which is read as guanosine during translation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20185571", "endSection": "abstract"}, {"offsetInBeginSection": 209, "offsetInEndSection": 404, "text": "Deamination of adenine by adenosine deaminases that act on RNA (ADARs) leads to the conversion of adenine into inosine (A-I editing) recognized by the splicing and translation systems as guanine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20198873", "endSection": "abstract"}, {"offsetInBeginSection": 882, "offsetInEndSection": 1065, "text": "denosine deaminases editing adenines in transport RNAs (ADATs) convert adenine into inosine in tRNAs of all eukaryotes; as a result, the diversity of tRNA forms in the cell increases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20198873", "endSection": "abstract"}, {"offsetInBeginSection": 66, "offsetInEndSection": 131, "text": "A-to-I editing events in normal and cancerous human keratinocytes ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23543219", "endSection": "title"}, {"offsetInBeginSection": 430, "offsetInEndSection": 543, "text": "A-to-I RNA editing can alter codons, substitute amino acids and affect protein sequence, structure, and function. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23543219", "endSection": "abstract"}, {"offsetInBeginSection": 277, "offsetInEndSection": 428, "text": "-to-I RNA editing is a post-transcriptional mechanism frequently used to expand and diversify transcriptome and proteome repertoire in eukaryotic cells ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23543219", "endSection": "abstract"}, {"offsetInBeginSection": 1340, "offsetInEndSection": 1603, "text": "This study describes for the first time A-to-I editing in the coding sequence of a tumor suppressor gene in humans, and suggests that IGFBP7 editing serves as a fine-tuning mechanism to maintain the equilibrium between proliferation and senescence in normal skin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23543219", "endSection": "abstract"}]}, {"body": "Are there any statistical methods for normalizing and identifying differential regions in histone modification ChIP-seq data?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/22870189"], "ideal_answer": "ChIPnorm: a statistical method for normalizing and identifying differential regions in histone modification ChIP-seq libraries.We correlate the histone marks with gene expression data and confirm that histone modifications H3K27me3 and H3K4me3 act as respectively a repressor and an activator of genes.We show that the ChIPnorm method removes most of the noise and bias in the data and outperforms other normalization methods.We find that most of the promoter regions in protein-coding genes have differential histone-modification sites.In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types.Compared to what was previously reported in the literature, we find that a substantially higher fraction of bivalent marks in ES cells for H3K27me3 and H3K4me3 move into a K27-only state.Compared to what was previously reported in the literature, we find that a substantially higher fraction of bivalent marks in ES cells for H3K27me3 and H3K4me3 move into a K27-only state.", "type": "yesno", "id": "56b29bf545561f0573000003", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "ChIPnorm: a statistical method for normalizing and identifying differential regions in histone modification ChIP-seq libraries. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22870189", "endSection": "title"}, {"offsetInBeginSection": 444, "offsetInEndSection": 1264, "text": "In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types. We show that the ChIPnorm method removes most of the noise and bias in the data and outperforms other normalization methods. We correlate the histone marks with gene expression data and confirm that histone modifications H3K27me3 and H3K4me3 act as respectively a repressor and an activator of genes. Compared to what was previously reported in the literature, we find that a substantially higher fraction of bivalent marks in ES cells for H3K27me3 and H3K4me3 move into a K27-only state. We find that most of the promoter regions in protein-coding genes have differential histone-modification sites. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22870189", "endSection": "abstract"}]}, {"body": "Where does TORC1 sequester during heat stress?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/22727621"], "ideal_answer": "Transient sequestration of TORC1 into stress granules during heat stress.TORC1 reactivation is directed through SG disassembly, suggesting that SGs act as a key determinant for TORC1 reactivation during recovery from heat stressEctopic formation of SGs achieved by Pbp1 overexpression in unstressed cells sequesters TORC1 in this compartment, thereby blunting TORC1 signalingHere we report that TORC1 signaling upon heat stress is regulated by stress granules (SGs), which are cytoplasmic foci formed under certain stresses.Upon heat stress, a physiological SG-inducing condition, TORC1 is also recruited to SGs, which delays reactivation of TORC1 signaling during recovery from heat stressUpon heat stress, a physiological SG-inducing condition, TORC1 is also recruited to SGs, which delays reactivation of TORC1 signaling during recovery from heat stressUpon heat stress, a physiological SG-inducing condition, TORC1 is also recruited to SGs, which delays reactivation of TORC1 signaling during recovery from heat stressUpon heat stress, a physiological SG-inducing condition, TORC1 is also recruited to SGs, which delays reactivation of TORC1 signaling during recovery from heat stress", "type": "summary", "id": "56cdf4fe5795f9a73e000044", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 73, "text": "Transient sequestration of TORC1 into stress granules during heat stress. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22727621", "endSection": "title"}, {"offsetInBeginSection": 240, "offsetInEndSection": 537, "text": "Here we report that TORC1 signaling upon heat stress is regulated by stress granules (SGs), which are cytoplasmic foci formed under certain stresses. Ectopic formation of SGs achieved by Pbp1 overexpression in unstressed cells sequesters TORC1 in this compartment, thereby blunting TORC1 signaling ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22727621", "endSection": "abstract"}, {"offsetInBeginSection": 539, "offsetInEndSection": 705, "text": "Upon heat stress, a physiological SG-inducing condition, TORC1 is also recruited to SGs, which delays reactivation of TORC1 signaling during recovery from heat stress ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22727621", "endSection": "abstract"}, {"offsetInBeginSection": 717, "offsetInEndSection": 872, "text": "TORC1 reactivation is directed through SG disassembly, suggesting that SGs act as a key determinant for TORC1 reactivation during recovery from heat stress ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22727621", "endSection": "abstract"}]}, {"body": "Which signaling pathway is activating the dishevelled proteins?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/19561403", "http://www.ncbi.nlm.nih.gov/pubmed/15936275", "http://www.ncbi.nlm.nih.gov/pubmed/25358879"], "ideal_answer": "Wnt signaling is known to be important for diverse embryonic and post-natal cellular events and be regulated by the proteins Dishevelled and Axin.Intriguingly, within the same tissues where Xenopus Dishevelled (Xdsh) controls cell fate via canonical Wnt signaling,Although Dishevelled is activated by Wnt and involved in signal transduction, it is not clear how Dishevelled-mediated signaling is turned off.The Dishevelled protein mediates several diverse biological processes.Dishevelled (DVL) proteins, three of which have been identified in humans, are highly conserved components of canonical and noncanonical Wnt signaling pathways.Dishevelled (DVL) proteins, three of which have been identified in humans, are highly conserved components of canonical and noncanonical Wnt signaling pathways.Dishevelled (DVL) proteins, three of which have been identified in humans, are highly conserved components of canonical and noncanonical Wnt signaling pathways.Dishevelled (DVL) proteins, three of which have been identified in humans, are highly conserved components of canonical and noncanonical Wnt signaling pathways.", "type": "factoid", "id": "5708a845cf1c32585100000f", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 291, "text": "Wnt signaling is known to be important for diverse embryonic and post-natal cellular events and be regulated by the proteins Dishevelled and Axin. Although Dishevelled is activated by Wnt and involved in signal transduction, it is not clear how Dishevelled-mediated signaling is turned off. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19561403", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "The Dishevelled protein mediates several diverse biological processes. Intriguingly, within the same tissues where Xenopus Dishevelled (Xdsh) controls cell fate via canonical Wnt signaling, ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15936275", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Dishevelled (DVL) proteins, three of which have been identified in humans, are highly conserved components of canonical and noncanonical Wnt signaling pathways. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25358879", "endSection": "abstract"}]}, {"body": "Is nicotinamide effective for skin cancer prevention?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/26488693", "http://www.ncbi.nlm.nih.gov/pubmed/24798949", "http://www.ncbi.nlm.nih.gov/pubmed/23349012", "http://www.ncbi.nlm.nih.gov/pubmed/19804594"], "ideal_answer": "CONCLUSIONS: Oral nicotinamide was safe and effective in reducing the rates of new nonmelanoma skin cancers and actinic keratoses in high-risk patients.Nicotinamide is a safe, widely available vitamin that reduces the immune suppressive effects of UV, enhances DNA repair in keratinocytes and has shown promise in the chemoprevention of non-melanoma skin cancer.Similar differences were found between the nicotinamide group and the placebo group with respect to new basal-cell carcinomas (20% [95% CI, -6 to 39]lower rate with nicotinamide, P=0.12) and new squamous-cell carcinomas (30% [95% CI, 0 to 51] lower rate, P=0.05).Nicotinamide (vitamin B3) prevents UV-induced immunosuppression and carcinogenesis in mice, and solar-simulated (ss) UV-induced immunosuppression in humans. In summary, nicotinamide, by enhancing DNA repair in melanocytes, is a potential agent for the chemoprevention of cutaneous melanoma.Recent double-blinded randomized controlled Phase 2 studies in heavily sun-damaged individuals have shown that oral nicotinamide significantly reduces premalignant actinic keratoses, and may reduce new non-melanoma skin cancers.", "type": "yesno", "id": "56c03d1fef6e39474100001a", "snippets": [{"offsetInBeginSection": 174, "offsetInEndSection": 341, "text": "Nicotinamide (vitamin B3) has been shown to have protective effects against damage caused by UV radiation and to reduce the rate of new premalignant actinic keratoses. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26488693", "endSection": "abstract"}, {"offsetInBeginSection": 1151, "offsetInEndSection": 1820, "text": "ESULTS: At 12 months, the rate of new nonmelanoma skin cancers was lower by 23% (95% confidence interval [CI], 4 to 38) in the nicotinamide group than in the placebo group (P=0.02). Similar differences were found between the nicotinamide group and the placebo group with respect to new basal-cell carcinomas (20% [95% CI, -6 to 39]lower rate with nicotinamide, P=0.12) and new squamous-cell carcinomas (30% [95% CI, 0 to 51] lower rate, P=0.05). The number of actinic keratoses was 11% lower in the nicotinamide group than in the placebo group at 3 months (P=0.01), 14% lower at 6 months (P<0.001), 20% lower at 9 months (P<0.001), and 13% lower at 12 months (P=0.001). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26488693", "endSection": "abstract"}, {"offsetInBeginSection": 2040, "offsetInEndSection": 2192, "text": "CONCLUSIONS: Oral nicotinamide was safe and effective in reducing the rates of new nonmelanoma skin cancers and actinic keratoses in high-risk patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26488693", "endSection": "abstract"}, {"offsetInBeginSection": 70, "offsetInEndSection": 281, "text": "Nicotinamide is a safe, widely available vitamin that reduces the immune suppressive effects of UV, enhances DNA repair in keratinocytes and has shown promise in the chemoprevention of non-melanoma skin cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24798949", "endSection": "abstract"}, {"offsetInBeginSection": 871, "offsetInEndSection": 1005, "text": " In summary, nicotinamide, by enhancing DNA repair in melanocytes, is a potential agent for the chemoprevention of cutaneous melanoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24798949", "endSection": "abstract"}, {"offsetInBeginSection": 156, "offsetInEndSection": 385, "text": "Recent double-blinded randomized controlled Phase 2 studies in heavily sun-damaged individuals have shown that oral nicotinamide significantly reduces premalignant actinic keratoses, and may reduce new non-melanoma skin cancers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23349012", "endSection": "abstract"}, {"offsetInBeginSection": 201, "offsetInEndSection": 357, "text": "Nicotinamide (vitamin B3) prevents UV-induced immunosuppression and carcinogenesis in mice, and solar-simulated (ss) UV-induced immunosuppression in humans. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19804594", "endSection": "abstract"}]}, {"body": "What is the effect that EZH2 has on chromatin?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/25680271", "http://www.ncbi.nlm.nih.gov/pubmed/23688634", "http://www.ncbi.nlm.nih.gov/pubmed/21892963", "http://www.ncbi.nlm.nih.gov/pubmed/19954516", "http://www.ncbi.nlm.nih.gov/pubmed/19026781"], "ideal_answer": "Ezh1 and Ezh2 maintain repressive chromatin through different mechanismsThe chromatin-modifying enzyme Ezh2 is critical for the maintenance of regulatory T cell identity after activationTreg-specific ablation of Ezh2 resulted in spontaneous autoimmunity with reduced Foxp3(+) cells in non-lymphoid tissues and impaired resolution of experimental autoimmune encephalomyelitisthe PRC2-Ezh2 complex, which is bound to the myogenin (MyoG) promoter and muscle creatine kinase (mCK) enhancer in proliferating myoblasts, and the PRC2-Ezh1 complex, which replaces PRC2-Ezh2 on MyoG promoter in post-mitotic myotubesIn this study, we found the inverse correlation between FOXP3 and Ezh2, an enzyme for histone H3K27 trimethylation (H3K27me3) and a central epigenetic regulator in cancerDuring progenitor cell differentiation and ageing, PcG silencer EZH2 attenuates, causing loss of PRC binding and transcriptional activation of INK4b and INK4aWe report that the mammalian homologs Ezh1 and Ezh2 form similar PRC2 complexes but exhibit contrasting repressive roles.Ez that catalyzes di- and trimethylation of histone H3 lysine 27 (H3K37me2/3), marks repressive to transcription.", "type": "summary", "id": "570906fecf1c325851000010", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19026781", "endSection": "title"}, {"offsetInBeginSection": 164, "offsetInEndSection": 399, "text": "Ez that catalyzes di- and trimethylation of histone H3 lysine 27 (H3K37me2/3), marks repressive to transcription. We report that the mammalian homologs Ezh1 and Ezh2 form similar PRC2 complexes but exhibit contrasting repressive roles. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19026781", "endSection": "abstract"}, {"offsetInBeginSection": 1027, "offsetInEndSection": 1185, "text": "During progenitor cell differentiation and ageing, PcG silencer EZH2 attenuates, causing loss of PRC binding and transcriptional activation of INK4b and INK4a ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19954516", "endSection": "abstract"}, {"offsetInBeginSection": 547, "offsetInEndSection": 780, "text": "the PRC2-Ezh2 complex, which is bound to the myogenin (MyoG) promoter and muscle creatine kinase (mCK) enhancer in proliferating myoblasts, and the PRC2-Ezh1 complex, which replaces PRC2-Ezh2 on MyoG promoter in post-mitotic myotubes ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21892963", "endSection": "abstract"}, {"offsetInBeginSection": 394, "offsetInEndSection": 564, "text": "In this study, we found the inverse correlation between FOXP3 and Ezh2, an enzyme for histone H3K27 trimethylation (H3K27me3) and a central epigenetic regulator in cancer ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23688634", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "The chromatin-modifying enzyme Ezh2 is critical for the maintenance of regulatory T cell identity after activation ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25680271", "endSection": "title"}, {"offsetInBeginSection": 291, "offsetInEndSection": 427, "text": "CD28 co-stimulation, an extracellular cue intrinsically required for Treg cell maintenance, induced the chromatin-modifying enzyme, Ezh2 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25680271", "endSection": "abstract"}, {"offsetInBeginSection": 429, "offsetInEndSection": 617, "text": "Treg-specific ablation of Ezh2 resulted in spontaneous autoimmunity with reduced Foxp3(+) cells in non-lymphoid tissues and impaired resolution of experimental autoimmune encephalomyelitis ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25680271", "endSection": "abstract"}, {"offsetInBeginSection": 1007, "offsetInEndSection": 1120, "text": "These studies reveal a critical role for Ezh2 in the maintenance of Treg cell identity during cellular activation ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25680271", "endSection": "abstract"}]}, {"body": "What is Genomicus?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/20185404", "http://www.ncbi.nlm.nih.gov/pubmed/23193262", "http://www.ncbi.nlm.nih.gov/pubmed/25378326"], "ideal_answer": "These new developments have been implemented for Genomicus portal dedicated to vertebrates.The Genomicus server also provides access to ancestral gene orders, to facilitate evolutionary and comparative genomics studies, as well as computationally predicted regulatory interactions, thanks to the representation of conserved non-coding elements with their putative gene targets.Genomicus (http://www.dyogen.ens.fr/genomicus/) is a database and an online tool that allows easy comparative genomic visualization in>150 eukaryote genomes.Here, we describe the graphical modules of Genomicus and show how it is capable of revealing differential gene loss and gain, segmental or genome duplications and study the evolution of a locus through homology relationships.Genomicus: five genome browsers for comparative genomics in eukaryota.Here we present Genomicus, a new synteny browser that can represent and compare unlimited numbers of genomes in a broad phylogenetic view.In addition, Genomicus includes reconstructed ancestral gene organization, thus greatly facilitating the interpretation of the data.AVAILABILITY: Genomicus is freely available for online use at http://www.dyogen.ens.fr/genomicus while data can be downloaded at ftp://ftp.biologie.ens.fr/pub/dyogen/genomicus.", "type": "summary", "id": "56b3efc38525abca1e000006", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 90, "text": "Genomicus: a database and a browser to study gene synteny in modern and ancestral genomes. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20185404", "endSection": "title"}, {"offsetInBeginSection": 470, "offsetInEndSection": 917, "text": "Here we present Genomicus, a new synteny browser that can represent and compare unlimited numbers of genomes in a broad phylogenetic view. In addition, Genomicus includes reconstructed ancestral gene organization, thus greatly facilitating the interpretation of the data.AVAILABILITY: Genomicus is freely available for online use at http://www.dyogen.ens.fr/genomicus while data can be downloaded at ftp://ftp.biologie.ens.fr/pub/dyogen/genomicus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20185404", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 936, "text": "Genomicus (http://www.dyogen.ens.fr/genomicus/) is a database and an online tool that allows easy comparative genomic visualization in>150 eukaryote genomes. It provides a way to explore spatial information related to gene organization within and between genomes and temporal relationships related to gene and genome evolution. For the specific vertebrate phylum, it also provides access to ancestral gene order reconstructions and conserved non-coding elements information. We extended the Genomicus database originally dedicated to vertebrate to four new clades, including plants, non-vertebrate metazoa, protists and fungi. This visualization tool allows evolutionary phylogenomics analysis and exploration. Here, we describe the graphical modules of Genomicus and show how it is capable of revealing differential gene loss and gain, segmental or genome duplications and study the evolution of a locus through homology relationships. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23193262", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 119, "text": "Genomicus update 2015: KaryoView and MatrixView provide a genome-wide perspective to multispecies comparative genomics. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25378326", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1198, "text": "The Genomicus web server (http://www.genomicus.biologie.ens.fr/genomicus) is a visualization tool allowing comparative genomics in four different phyla (Vertebrate, Fungi, Metazoan and Plants). It provides access to genomic information from extant species, as well as ancestral gene content and gene order for vertebrates and flowering plants. Here we present the new features available for vertebrate genome with a focus on new graphical tools. The interface to enter the database has been improved, two pairwise genome comparison tools are now available (KaryoView and MatrixView) and the multiple genome comparison tools (PhyloView and AlignView) propose three new kinds of representation and a more intuitive menu. These new developments have been implemented for Genomicus portal dedicated to vertebrates. This allows the analysis of 68 extant animal genomes, as well as 58 ancestral reconstructed genomes. The Genomicus server also provides access to ancestral gene orders, to facilitate evolutionary and comparative genomics studies, as well as computationally predicted regulatory interactions, thanks to the representation of conserved non-coding elements with their putative gene targets. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25378326", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 70, "text": "Genomicus: five genome browsers for comparative genomics in eukaryota. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23193262", "endSection": "title"}]}, {"body": "Which protein is required for Argonaute 2 recruitment to stress granules and P-bodies?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/21439943", "http://www.ncbi.nlm.nih.gov/pubmed/19458189"], "ideal_answer": "Hsp90 regulates the function of argonaute 2 and its recruitment to stress granules and P-bodiesIn the present study, we show that heat-shock protein (Hsp) 90 activity is required for efficient targeting of hAgo2 to PBs and SGsTreatment with RA reduced the level of the Hsp90 client protein Argonaute 2 and the number of P-bodies.Although stress granules still assembled in RA-treated cells upon heat shock, they were smaller and more dispersed in the cytoplasm than those in untreated cellsProcessing bodies (PBs) and stress granules (SGs) are the two main types of ribonucleoprotein complexes with which Argonautes are associated.we examined whether another Hsp90 inhibitor radicicol (RA) affected P-bodies and stress granules.Targeting of Argonautes to these structures seems to be regulated by different factors.Targeting of Argonautes to these structures seems to be regulated by different factors.Targeting of Argonautes to these structures seems to be regulated by different factors.Targeting of Argonautes to these structures seems to be regulated by different factors.", "type": "factoid", "id": "56cdf5195795f9a73e000045", "snippets": [{"offsetInBeginSection": 392, "offsetInEndSection": 755, "text": "we examined whether another Hsp90 inhibitor radicicol (RA) affected P-bodies and stress granules. Treatment with RA reduced the level of the Hsp90 client protein Argonaute 2 and the number of P-bodies. Although stress granules still assembled in RA-treated cells upon heat shock, they were smaller and more dispersed in the cytoplasm than those in untreated cells ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21439943", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "Hsp90 regulates the function of argonaute 2 and its recruitment to stress granules and P-bodies ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19458189", "endSection": "title"}, {"offsetInBeginSection": 154, "offsetInEndSection": 515, "text": "Processing bodies (PBs) and stress granules (SGs) are the two main types of ribonucleoprotein complexes with which Argonautes are associated. Targeting of Argonautes to these structures seems to be regulated by different factors. In the present study, we show that heat-shock protein (Hsp) 90 activity is required for efficient targeting of hAgo2 to PBs and SGs ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19458189", "endSection": "abstract"}]}, {"body": "Are Sidekick proteins members of the immunoglobulin superfamily?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/18216854", "http://www.ncbi.nlm.nih.gov/pubmed/15703275"], "ideal_answer": "Sidekick-1, a cell adhesion molecule of the immunoglobulin superfamily, is up-regulated in glomerular podocytes in the collapsing glomerulopathy of HIV-associated nephropathy (HIVAN).Here we show that four closely related immunoglobulin superfamily (IgSF) adhesion molecules--Dscam (Down's syndrome cell adhesion molecule), DscamL (refs 6-9), Sidekick-1 and Sidekick-2Here we show that four closely related immunoglobulin superfamily (IgSF) adhesion molecules--Dscam (Down's syndrome cell adhesion molecule), DscamL (refs 6-9), Sidekick-1 and Sidekick-2Here we show that four closely related immunoglobulin superfamily (IgSF) adhesion molecules--Dscam (Down's syndrome cell adhesion molecule), DscamL (refs 6-9), Sidekick-1 and Sidekick-2Here we show that four closely related immunoglobulin superfamily (IgSF) adhesion molecules--Dscam (Down's syndrome cell adhesion molecule), DscamL (refs 6-9), Sidekick-1 and Sidekick-2Here we show that four closely related immunoglobulin superfamily (IgSF) adhesion molecules--Dscam (Down's syndrome cell adhesion molecule), DscamL (refs 6-9), Sidekick-1 and Sidekick-2", "type": "yesno", "id": "5709e947cf1c32585100001d", "snippets": [{"offsetInBeginSection": 523, "offsetInEndSection": 708, "text": "Here we show that four closely related immunoglobulin superfamily (IgSF) adhesion molecules--Dscam (Down's syndrome cell adhesion molecule), DscamL (refs 6-9), Sidekick-1 and Sidekick-2 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18216854", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 183, "text": "Sidekick-1, a cell adhesion molecule of the immunoglobulin superfamily, is up-regulated in glomerular podocytes in the collapsing glomerulopathy of HIV-associated nephropathy (HIVAN). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15703275", "endSection": "abstract"}]}, {"body": "Which molecule is targeted by Daratumumab?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/25865943", "http://www.ncbi.nlm.nih.gov/pubmed/26137203", "http://www.ncbi.nlm.nih.gov/pubmed/25764134", "http://www.ncbi.nlm.nih.gov/pubmed/25988285"], "ideal_answer": "This review focuses on the CD38 antigen and its targeting with daratumumab and provides an update on the results of recent clinical studies involving daratumumab.Interference of daratumumab and three other anti-CD38 MoAbs was studied using fresh-frozen plasma spiked with different MoAb concentrations.BACKGROUND: Daratumumab (DARA), a promising novel therapy for multiple myeloma, is an IgG1 monoclonal antibody that recognizes CD38 on myeloma cells.CONCLUSION: DARA causes panreactivity in vitro by binding to CD38 on reagent RBCs.Daratumumab, an investigated anti-cancer drug targeting CD38, has been of great interest in the treatment of CD38-expressing malignancies, especially multiple myeloma.Here, we describe that treatment of multiple myeloma patients with daratumumab, a novel anti-CD38 MoAb, resulted in false-positive indirect antiglobulin tests (IATs) for all patients for 2 to 6 months after infusion.Daratumumab is a novel, high-affinity, therapeutic human monoclonal antibody against unique CD38 epitope with broad-spectrum killing activity.Daratumumab is a novel, high-affinity, therapeutic human monoclonal antibody against unique CD38 epitope with broad-spectrum killing activity.", "type": "factoid", "id": "56c04412ef6e39474100001b", "snippets": [{"offsetInBeginSection": 189, "offsetInEndSection": 357, "text": "Daratumumab, an investigated anti-cancer drug targeting CD38, has been of great interest in the treatment of CD38-expressing malignancies, especially multiple myeloma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25865943", "endSection": "abstract"}, {"offsetInBeginSection": 347, "offsetInEndSection": 489, "text": "Daratumumab is a novel, high-affinity, therapeutic human monoclonal antibody against unique CD38 epitope with broad-spectrum killing activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26137203", "endSection": "abstract"}, {"offsetInBeginSection": 775, "offsetInEndSection": 937, "text": "This review focuses on the CD38 antigen and its targeting with daratumumab and provides an update on the results of recent clinical studies involving daratumumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26137203", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "BACKGROUND: Daratumumab (DARA), a promising novel therapy for multiple myeloma, is an IgG1\u03ba monoclonal antibody that recognizes CD38 on myeloma cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25764134", "endSection": "abstract"}, {"offsetInBeginSection": 1379, "offsetInEndSection": 1462, "text": "CONCLUSION: DARA causes panreactivity in vitro by binding to CD38 on reagent RBCs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25764134", "endSection": "abstract"}, {"offsetInBeginSection": 279, "offsetInEndSection": 496, "text": "Here, we describe that treatment of multiple myeloma patients with daratumumab, a novel anti-CD38 MoAb, resulted in false-positive indirect antiglobulin tests (IATs) for all patients for 2 to 6 months after infusion. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25988285", "endSection": "abstract"}, {"offsetInBeginSection": 702, "offsetInEndSection": 842, "text": "Interference of daratumumab and three other anti-CD38 MoAbs was studied using fresh-frozen plasma spiked with different MoAb concentrations. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25988285", "endSection": "abstract"}]}, {"body": "Which syndromes are associated with mutations in the EZH2 gene?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/24953053", "http://www.ncbi.nlm.nih.gov/pubmed/25177364", "http://www.ncbi.nlm.nih.gov/pubmed/24760151", "http://www.ncbi.nlm.nih.gov/pubmed/23592277", "http://www.ncbi.nlm.nih.gov/pubmed/24214728", "http://www.ncbi.nlm.nih.gov/pubmed/22177091", "http://www.ncbi.nlm.nih.gov/pubmed/22190405", "http://www.ncbi.nlm.nih.gov/pubmed/21856302", "http://www.ncbi.nlm.nih.gov/pubmed/10780782"], "ideal_answer": "Weaver syndrome and EZH2 mutations Conditionally deleting Ezh2 in mature T cells dramatically reduced the production of BM-destructive Th1 cells in vivo, decreased BM-infiltrating Th1 cells, and rescued mice from BM failure.Mutations at tyrosine 641 (Y641F, Y641N, Y641S and Y641H) in the SET domain of EZH2 have been identified in patients with certain subtypes of non-Hodgkin lymphoma (NHL)The EZH2 gene was previously reported to be located on chromosome 21q22 and was proposed as a candidate gene for some characteristics of the Down syndrome phenotypeConstitutional NSD1 and EZH2 mutations cause Sotos and Weaver syndromes respectively, overgrowth syndromes with considerable phenotypic overlap.Acquired aplastic anemia (AA) is a potentially fatal bone marrow (BM) failure syndromeWe describe the use of an oligo-SNP array for genomic profiling of aCNA and cnLOH, together with sequence analysis of recurrently mutated genes, in a patient with myelodysplastic syndrome (MDS) presenting with normal karyotype and FISH resultThe identification of an EZH2 mutation can therefore provide an objective means of confirming a subtle presentation of Weaver syndrome and/or distinguishing Weaver and Sotos syndromes.", "type": "list", "id": "57090784cf1c325851000011", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "Loss-of-function mutations of EZH2, a catalytic component of polycomb repressive complex 2 (PRC2), are observed in ~\\n10% of patients with myelodysplastic syndrome (MDS), but are rare in acute myeloid leukaemia (AML) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24953053", "endSection": "abstract"}, {"offsetInBeginSection": 249, "offsetInEndSection": 491, "text": "We describe the use of an oligo-SNP array for genomic profiling of aCNA and cnLOH, together with sequence analysis of recurrently mutated genes, in a patient with myelodysplastic syndrome (MDS) presenting with normal karyotype and FISH result ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25177364", "endSection": "abstract"}, {"offsetInBeginSection": 780, "offsetInEndSection": 970, "text": " Conditionally deleting Ezh2 in mature T cells dramatically reduced the production of BM-destructive Th1 cells in vivo, decreased BM-infiltrating Th1 cells, and rescued mice from BM failure. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24760151", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 86, "text": "Acquired aplastic anemia (AA) is a potentially fatal bone marrow (BM) failure syndrome ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24760151", "endSection": "abstract"}, {"offsetInBeginSection": 823, "offsetInEndSection": 967, "text": "Constitutional NSD1 and EZH2 mutations cause Sotos and Weaver syndromes respectively, overgrowth syndromes with considerable phenotypic overlap. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23592277", "endSection": "abstract"}, {"offsetInBeginSection": 1123, "offsetInEndSection": 1422, "text": "EZH2 mutations that cause Weaver syndrome are primarily missense variants and the rare truncating mutations reported to date are in the last exon, suggesting that simple haploinsufficiency is unlikely to be generating the overgrowth phenotype although the exact mechanism has not yet been determined ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23592277", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 34, "text": "Weaver syndrome and EZH2 mutations ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24214728", "endSection": "title"}, {"offsetInBeginSection": 143, "offsetInEndSection": 237, "text": "In 2011, mutations in the histone methyltransferase, EZH2, were shown to cause Weaver syndrome ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24214728", "endSection": "abstract"}, {"offsetInBeginSection": 1225, "offsetInEndSection": 1410, "text": "The identification of an EZH2 mutation can therefore provide an objective means of confirming a subtle presentation of Weaver syndrome and/or distinguishing Weaver and Sotos syndromes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24214728", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 39, "text": "Mutations in EZH2 cause Weaver syndrome ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22177091", "endSection": "title"}, {"offsetInBeginSection": 436, "offsetInEndSection": 496, "text": "These data show that mutations in EZH2 cause Weaver syndrome ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22177091", "endSection": "abstract"}, {"offsetInBeginSection": 649, "offsetInEndSection": 808, "text": "The EZH2 mutation spectrum in Weaver syndrome shows considerable overlap with the inactivating somatic EZH2 mutations recently reported in myeloid malignancies ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22190405", "endSection": "abstract"}, {"offsetInBeginSection": 829, "offsetInEndSection": 963, "text": "EZH2 mutations as the cause of Weaver syndrome and provide further links between histone modifications and regulation of human growth. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22190405", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 168, "text": "Mutations at tyrosine 641 (Y641F, Y641N, Y641S and Y641H) in the SET domain of EZH2 have been identified in patients with certain subtypes of non-Hodgkin lymphoma (NHL) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21856302", "endSection": "abstract"}, {"offsetInBeginSection": 452, "offsetInEndSection": 616, "text": "The EZH2 gene was previously reported to be located on chromosome 21q22 and was proposed as a candidate gene for some characteristics of the Down syndrome phenotype ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10780782", "endSection": "abstract"}]}, {"body": "List available genetic multicolor cell labeling techiniques in Drosophila", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/21297619", "http://www.ncbi.nlm.nih.gov/pubmed/21297621"], "ideal_answer": "Flybow: genetic multicolor cell labeling for neural circuit analysis in Drosophila melanogaster.We used Drosophila Brainbow to study the innervation patterns of multiple antennal lobe projection neuron lineages in the same preparation and to observe the relative trajectories of individual aminergic neurons.Nerve bundles, and even individual neurites hundreds of micrometers long, can be followed with definitive color labeling.Sequences encoding different membrane-tethered fluorescent proteins were arranged in pairs within cassettes flanked by recombination sites.Using the visual system, the embryonic nervous system and the wing imaginal disc, we show that Flybow in conjunction with specific Gal4 drivers can be used to visualize cell morphology with high resolution.We traced motor neurons in the subesophageal ganglion and correlated them to neuromuscular junctions to identify their specific proboscis muscle targets.This provides spatial and temporal control over the stochastic expression of one of two or four reporters within one sample.Flybow combines the Gal4-upstream activating sequence binary system to regulate transgene expression and an inducible modified Flp-FRT system to drive inversions and excisions of cassettes.Two copies of this construct yield six bright, separable colors.", "type": "list", "id": "56b739d976d8bf8d13000005", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Flybow: genetic multicolor cell labeling for neural circuit analysis in Drosophila melanogaster. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21297619", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1080, "text": "To facilitate studies of neural network architecture and formation, we generated three Drosophila melanogaster variants of the mouse Brainbow-2 system, called Flybow. Sequences encoding different membrane-tethered fluorescent proteins were arranged in pairs within cassettes flanked by recombination sites. Flybow combines the Gal4-upstream activating sequence binary system to regulate transgene expression and an inducible modified Flp-FRT system to drive inversions and excisions of cassettes. This provides spatial and temporal control over the stochastic expression of one of two or four reporters within one sample. Using the visual system, the embryonic nervous system and the wing imaginal disc, we show that Flybow in conjunction with specific Gal4 drivers can be used to visualize cell morphology with high resolution. Finally, we demonstrate that this labeling approach is compatible with available Flp-FRT-based techniques, such as mosaic analysis with a repressible cell marker; this could further support the genetic analysis of neural circuit assembly and function. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21297619", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Drosophila Brainbow: a recombinase-based fluorescence labeling technique to subdivide neural expression patterns. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21297621", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1083, "text": "We developed a multicolor neuron labeling technique in Drosophila melanogaster that combines the power to specifically target different neural populations with the label diversity provided by stochastic color choice. This adaptation of vertebrate Brainbow uses recombination to select one of three epitope-tagged proteins detectable by immunofluorescence. Two copies of this construct yield six bright, separable colors. We used Drosophila Brainbow to study the innervation patterns of multiple antennal lobe projection neuron lineages in the same preparation and to observe the relative trajectories of individual aminergic neurons. Nerve bundles, and even individual neurites hundreds of micrometers long, can be followed with definitive color labeling. We traced motor neurons in the subesophageal ganglion and correlated them to neuromuscular junctions to identify their specific proboscis muscle targets. The ability to independently visualize multiple lineage or neuron projections in the same preparation greatly advances the goal of mapping how neurons connect into circuits. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21297621", "endSection": "abstract"}]}, {"body": "Which is the enzyme that degrades decapped mRNAs?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/24510189", "http://www.ncbi.nlm.nih.gov/pubmed/22383165"], "ideal_answer": "XRN1 is a 5'  3' processive exoribonuclease that degrades mRNAs after they have been decappedThe removal of the 5'-cap structure by the decapping enzyme DCP2 and its coactivator DCP1 shuts down translation and exposes the mRNA to 5'-to-3' exonucleolytic degradation by XRN1DCP2 activation by DCP1 occurs preferentially on the EDC4 scaffold, which may serve to couple DCP2 activation by DCP1 with 5'-to-3' mRNA degradation by XRN1 in human cellsDCP2 activation by DCP1 occurs preferentially on the EDC4 scaffold, which may serve to couple DCP2 activation by DCP1 with 5'-to-3' mRNA degradation by XRN1 in human cellsDCP2 activation by DCP1 occurs preferentially on the EDC4 scaffold, which may serve to couple DCP2 activation by DCP1 with 5'-to-3' mRNA degradation by XRN1 in human cellsDCP2 activation by DCP1 occurs preferentially on the EDC4 scaffold, which may serve to couple DCP2 activation by DCP1 with 5'-to-3' mRNA degradation by XRN1 in human cellsDCP2 activation by DCP1 occurs preferentially on the EDC4 scaffold, which may serve to couple DCP2 activation by DCP1 with 5'-to-3' mRNA degradation by XRN1 in human cells", "type": "factoid", "id": "56cdf5315795f9a73e000046", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "The removal of the 5'-cap structure by the decapping enzyme DCP2 and its coactivator DCP1 shuts down translation and exposes the mRNA to 5'-to-3' exonucleolytic degradation by XRN1 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24510189", "endSection": "abstract"}, {"offsetInBeginSection": 1056, "offsetInEndSection": 1227, "text": "DCP2 activation by DCP1 occurs preferentially on the EDC4 scaffold, which may serve to couple DCP2 activation by DCP1 with 5'-to-3' mRNA degradation by XRN1 in human cells ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24510189", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "XRN1 is a 5' \u2192 3' processive exoribonuclease that degrades mRNAs after they have been decapped ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22383165", "endSection": "abstract"}]}, {"body": "Which syndrome is associated with mutant DVL1?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/25817014", "http://www.ncbi.nlm.nih.gov/pubmed/25817016"], "ideal_answer": "Mutations in DVL1 cause an osteosclerotic form of Robinow syndrome.argeted Sanger sequencing in additional subjects with DRS uncovered DVL1 exon 14 mutations in five individuals, including a pair of monozygotic twins.Here, we identified de novo frameshift mutations in DVL1, a mediator of both canonical and non-canonical Wnt signaling, as the cause of RS-OS, an RS subtype involving osteosclerosis, in three unrelated individuals.DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome.DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome.DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome.DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome.DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome.DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome.DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome.", "type": "factoid", "id": "5709ee36cf1c32585100001e", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Mutations in DVL1 cause an osteosclerotic form of Robinow syndrome. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25817014", "endSection": "title"}, {"offsetInBeginSection": 311, "offsetInEndSection": 525, "text": "Here, we identified de novo frameshift mutations in DVL1, a mediator of both canonical and non-canonical Wnt signaling, as the cause of RS-OS, an RS subtype involving osteosclerosis, in three unrelated individuals. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25817014", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25817016", "endSection": "title"}, {"offsetInBeginSection": 634, "offsetInEndSection": 784, "text": "argeted Sanger sequencing in additional subjects with DRS uncovered DVL1 exon 14 mutations in five individuals, including a pair of monozygotic twins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25817016", "endSection": "abstract"}]}, {"body": "Is nintedanib effective for Idiopathic Pulmonary Fibrosis?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/26380465", "http://www.ncbi.nlm.nih.gov/pubmed/26346347", "http://www.ncbi.nlm.nih.gov/pubmed/26039104", "http://www.ncbi.nlm.nih.gov/pubmed/26261848", "http://www.ncbi.nlm.nih.gov/pubmed/25767391", "http://www.ncbi.nlm.nih.gov/pubmed/25628503", "http://www.ncbi.nlm.nih.gov/pubmed/25635490", "http://www.ncbi.nlm.nih.gov/pubmed/25430078"], "ideal_answer": "Nintedanib: evidence for its therapeutic potential in idiopathic pulmonary fibrosisMost recently, pirfenidone and nintedanib, two compounds with pleiotropic anti-fibrotic properties, have been proven effective in reducing functional decline and disease progression in IPF.Nintedanib (Ofev()) is an orally available, small, multiple receptor tyrosine kinase inhibitor developed by Boehringer Ingelheim for the treatment of idiopathic pulmonary fibrosis (IPF) and cancer.This article summarizes the milestones in the development of nintedanib leading to this first approval for IPF.The Phase III INPULSIS trials demonstrated a significant decrease in the annual rate of decline in forced vital capacity in IPF patients treated with 150 mg nintedanib twice daily.Meningococcal group B vaccine (Trumenba) to prevent more types of invasive meningococcal disease; antihemophilic factor (recombinant), porcine sequence (Obizur) to treat bleeding from acquired hemophilia A; and pirfenidone (Esbriet) and nintedanib (Ofev) for idiopathic pulmonary fibrosis.Consequently, nintedanib was given accelerated approval by the FDA in October 2014 for the treatment of IPF.", "type": "yesno", "id": "56c048e2ef6e39474100001d", "snippets": [{"offsetInBeginSection": 532, "offsetInEndSection": 689, "text": "In this review, we present the positive results of recently published clinical trials regarding therapy for IPF, with emphasis on pirfenidone and nintedanib. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26380465", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 83, "text": "Nintedanib: evidence for its therapeutic potential in idiopathic pulmonary fibrosis ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26346347", "endSection": "title"}, {"offsetInBeginSection": 629, "offsetInEndSection": 1217, "text": " In the Phase II TOMORROW trial, treatment with 150 mg of nintedanib twice daily showed a trend to slow the decline in lung function and significantly decrease acute exacerbations in patients with IPF, while showing an acceptable safety profile. The Phase III INPULSIS trials demonstrated a significant decrease in the annual rate of decline in forced vital capacity in IPF patients treated with 150 mg nintedanib twice daily. In the INPULSIS-2 trial, the time to the first acute exacerbation significantly increased in IPF patients who were treated with 150 mg of nintedanib twice daily. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26346347", "endSection": "abstract"}, {"offsetInBeginSection": 1249, "offsetInEndSection": 1372, "text": " Effects on collagen secretion were compared with those of the drugs nintedanib and pirfenidone, recently approved for IPF. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26039104", "endSection": "abstract"}, {"offsetInBeginSection": 124, "offsetInEndSection": 558, "text": "Nintedanib, an orally available, small-molecule tyrosine kinase inhibitor with selectivity for vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) receptors has recently been shown, in two pivotal phase III studies, to effectively slow IPF disease progression. Consequently, nintedanib was given accelerated approval by the FDA in October 2014 for the treatment of IPF. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26261848", "endSection": "abstract"}, {"offsetInBeginSection": 1027, "offsetInEndSection": 1217, "text": "Most recently, pirfenidone and nintedanib, two compounds with pleiotropic anti-fibrotic properties, have been proven effective in reducing functional decline and disease progression in IPF. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25767391", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 289, "text": "Meningococcal group B vaccine (Trumenba) to prevent more types of invasive meningococcal disease; antihemophilic factor (recombinant), porcine sequence (Obizur) to treat bleeding from acquired hemophilia A; and pirfenidone (Esbriet) and nintedanib (Ofev) for idiopathic pulmonary fibrosis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25628503", "endSection": "abstract"}, {"offsetInBeginSection": 412, "offsetInEndSection": 628, "text": " More importantly, the period ends with the publication of two groundbreaking studies that confirmed that two drugs, pirfenidone and nintedanib, slowed disease progression, leading to a historic approval by the FDA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25635490", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 630, "text": "Nintedanib (Ofev(\u00ae)) is an orally available, small, multiple receptor tyrosine kinase inhibitor developed by Boehringer Ingelheim for the treatment of idiopathic pulmonary fibrosis (IPF) and cancer. Nintedanib received its first global approval in the US in October 2014 for the treatment of IPF. Nintedanib has received a positive opinion from the European Medicines Agency's Committee for Medicinal Products for Human Use for the treatment of IPF, and for the second-line treatment in combination with docetaxel of locally advanced, metastatic or locally recurrent non-small cell lung cancer of adenocarcinoma tumour histology. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25430078", "endSection": "abstract"}, {"offsetInBeginSection": 926, "offsetInEndSection": 1037, "text": "This article summarizes the milestones in the development of nintedanib leading to this first approval for IPF. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25430078", "endSection": "abstract"}]}, {"body": "Is EZH2 associated with prostate cancer?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/25017995", "http://www.ncbi.nlm.nih.gov/pubmed/25115397", "http://www.ncbi.nlm.nih.gov/pubmed/23636686", "http://www.ncbi.nlm.nih.gov/pubmed/23286483", "http://www.ncbi.nlm.nih.gov/pubmed/23739676", "http://www.ncbi.nlm.nih.gov/pubmed/22505648", "http://www.ncbi.nlm.nih.gov/pubmed/22272343"], "ideal_answer": "a comprehensive overview of EZH2 in the context of prostate cancerEZH2, an epigenetic driver of prostate cancer.The role of EZH2 in the regulation of the activity of matrix metalloproteinases in prostate cancer cellsAutoregulatory feedback loop of EZH2/miR-200c/E2F3 as a driving force for prostate cancer developmentPolycomb protein EZH2 regulates tumor invasion via the transcriptional repression of the metastasis suppressor RKIP in breast and prostate cancerChIP data on prostate cancer tissue specimens and cell lines suggested EZH2 occupancy and H3K27Me3 marks on the ID4 promoterThe histone methyltransferase EZH2 has been in the limelight of the field of cancer epigenetics for a decade now since it was first discovered to exhibit an elevated expression in metastatic prostate cancerOverexpression of EZH2 confers an invasive phenotype on benign prostate epithelial cellsThe histone methyltransferase enhancer of zeste homolog 2 (EZH2) has recently attracted considerable attention because of its dysregulation in prostate cancer (PCa) and its important function in PCa development.", "type": "yesno", "id": "570908e3cf1c325851000012", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "The role of EZH2 in the regulation of the activity of matrix metalloproteinases in prostate cancer cells ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22272343", "endSection": "title"}, {"offsetInBeginSection": 326, "offsetInEndSection": 440, "text": "EZH2 plays an active role in this process by repressing the expression of TIMP2 and TIMP3 in prostate cancer cells ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22272343", "endSection": "abstract"}, {"offsetInBeginSection": 442, "offsetInEndSection": 618, "text": "The TIMP genes are derepressed by knockdown of EZH2 expression in human prostate cancer cells but repressed by overexpression of EZH2 in benign human prostate epithelial cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22272343", "endSection": "abstract"}, {"offsetInBeginSection": 714, "offsetInEndSection": 802, "text": "Overexpression of EZH2 confers an invasive phenotype on benign prostate epithelial cells ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22272343", "endSection": "abstract"}, {"offsetInBeginSection": 872, "offsetInEndSection": 1004, "text": "EZH2 knockdown markedly reduces the proteolytic activity of MMP-9, thereby decreasing the invasive activity of prostate cancer cells ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22272343", "endSection": "abstract"}, {"offsetInBeginSection": 1034, "offsetInEndSection": 1257, "text": "he transcriptional repression of the TIMP genes by EZH2 may be a major mechanism to shift the MMPs/TIMPs balance in favor of MMP activity and thus to promote ECM degradation and subsequent invasion of prostate cancer cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22272343", "endSection": "abstract"}, {"offsetInBeginSection": 346, "offsetInEndSection": 577, "text": "Expression levels of the novel tumor and metastasis suppressor Raf-1 kinase inhibitor protein (RKIP) have been shown to correlate negatively with those of EZH2 in breast and prostate cell lines as well as in clinical cancer tissues ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22505648", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 145, "text": "Polycomb protein EZH2 regulates tumor invasion via the transcriptional repression of the metastasis suppressor RKIP in breast and prostate cancer ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22505648", "endSection": "title"}, {"offsetInBeginSection": 104, "offsetInEndSection": 344, "text": "Enhancer of zeste homolog 2 (EZH2), which encodes the histone methyltransferase component of the polycomb repressive complex 2 (PRC2), is overexpressed widely in breast and prostate cancers and epigenetically silences tumor suppressor genes ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22505648", "endSection": "abstract"}, {"offsetInBeginSection": 137, "offsetInEndSection": 242, "text": "However, the roles and underlying mechanisms of EZH2 in prostate cancer stem cells (PCSCs) remain unknown ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23739676", "endSection": "abstract"}, {"offsetInBeginSection": 12, "offsetInEndSection": 257, "text": "c-Myc, EZH2 and p27 were defined to modulate the behavior of prostate cancer with pro-tumoral or anti-tumoral effects and had ability in predicting prostate cancer progression, but the research of their co-expression value of prognosis is rarely ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23286483", "endSection": "abstract"}, {"offsetInBeginSection": 1875, "offsetInEndSection": 2089, "text": "Composite index of c-Myc, EZH2, and p27 can be valued as powerful prognosis parameter for intermediate-risk prostate cancer patients after the surgery, and postoperative adjuvant therapy can be adopted accordingly. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23286483", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 46, "text": "EZH2, an epigenetic driver of prostate cancer. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23636686", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 206, "text": "The histone methyltransferase EZH2 has been in the limelight of the field of cancer epigenetics for a decade now since it was first discovered to exhibit an elevated expression in metastatic prostate cancer ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23636686", "endSection": "abstract"}, {"offsetInBeginSection": 583, "offsetInEndSection": 649, "text": "a comprehensive overview of EZH2 in the context of prostate cancer ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23636686", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 85, "text": "EZH2 dependent H3K27me3 is involved in epigenetic silencing of ID4 in prostate cancer ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25115397", "endSection": "title"}, {"offsetInBeginSection": 942, "offsetInEndSection": 1066, "text": "ChIP data on prostate cancer tissue specimens and cell lines suggested EZH2 occupancy and H3K27Me3 marks on the ID4 promoter ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25115397", "endSection": "abstract"}, {"offsetInBeginSection": 1068, "offsetInEndSection": 1334, "text": "Collectively, our data indicate a PRC2 dependent mechanism in ID4 promoter silencing in prostate cancer through recruitment of EZH2 and a corresponding increase in H3K27Me3. Increased EZH2 but decreased ID4 expression in prostate cancer strongly supports this model. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25115397", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 212, "text": "The histone methyltransferase enhancer of zeste homolog 2 (EZH2) has recently attracted considerable attention because of its dysregulation in prostate cancer (PCa) and its important function in PCa development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25017995", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 101, "text": "Autoregulatory feedback loop of EZH2/miR-200c/E2F3 as a driving force for prostate cancer development ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25017995", "endSection": "title"}]}, {"body": "What is STARR-seq?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/23328393"], "ideal_answer": "STARR-seq can be used to identify and quantify enhancer activity in other eukaryotes, including humans.This map reveals the highly complex regulation of transcription, with several independent enhancers for both developmental regulators and ubiquitously expressed genes.When applied to the Drosophila genome, STARR-seq identifies thousands of cell type-specific enhancers across a broad continuum of strengths, links differential gene expression to differences in enhancer activity, and creates a genome-wide quantitative enhancer map.We developed a method termed STARR-seq to directly and quantitatively assess enhancer activity for millions of candidates from arbitrary sources of DNA, which enables screens across entire genomes.We developed a method termed STARR-seq to directly and quantitatively assess enhancer activity for millions of candidates from arbitrary sources of DNA, which enables screens across entire genomes.We developed a method termed STARR-seq to directly and quantitatively assess enhancer activity for millions of candidates from arbitrary sources of DNA, which enables screens across entire genomes.We developed a method termed STARR-seq to directly and quantitatively assess enhancer activity for millions of candidates from arbitrary sources of DNA, which enables screens across entire genomes.", "type": "summary", "id": "56b8ccc5156496395c000003", "snippets": [{"offsetInBeginSection": 157, "offsetInEndSection": 892, "text": "We developed a method termed STARR-seq to directly and quantitatively assess enhancer activity for millions of candidates from arbitrary sources of DNA, which enables screens across entire genomes. When applied to the Drosophila genome, STARR-seq identifies thousands of cell type-specific enhancers across a broad continuum of strengths, links differential gene expression to differences in enhancer activity, and creates a genome-wide quantitative enhancer map. This map reveals the highly complex regulation of transcription, with several independent enhancers for both developmental regulators and ubiquitously expressed genes. STARR-seq can be used to identify and quantify enhancer activity in other eukaryotes, including humans. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23328393", "endSection": "abstract"}]}, {"body": "List the human genes encoding for the dishevelled proteins?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/23836490", "http://www.ncbi.nlm.nih.gov/pubmed/24040443", "http://www.ncbi.nlm.nih.gov/pubmed/19618470", "http://www.ncbi.nlm.nih.gov/pubmed/8817329", "http://www.ncbi.nlm.nih.gov/pubmed/8149913", "http://www.ncbi.nlm.nih.gov/pubmed/7958461", "http://www.ncbi.nlm.nih.gov/pubmed/12883684", "http://www.ncbi.nlm.nih.gov/pubmed/8856345", "http://www.ncbi.nlm.nih.gov/pubmed/16457155"], "ideal_answer": "We have isolated and characterized cDNA clones from two different human dsh-homologous genes, designated as DVL-1 and DVL-3.Dishevelled (Dvl) proteins are key transducers of Wnt signaling encoded by members of a multi-gene family in vertebrates.Wnt signaling activates the gene encoding DVL-1;We report here that the mouse Dishevelled-1 (Dvl-1) and Dishevelled-2 genes encode proteins that are differentially localized in Wnt-overexpressing PC12 cell lines (PC12/Wnt).We report here the divergent, tissue-specific expression patterns for all three Dvl genes in Xenopus embryos, which contrast dramatically with their expression patterns in mice.We have isolated a mouse homolog of the Drosophila dsh segment polarity gene.velopmental processes, including segmentation and neuroblast specification. In this study, we explore the cause of HSCR by studying the expression of DVL-1 and DVL-3 genes and their proteins in the aganglionic segment and the ganglionic segment of colon in HSCR patients.The Dvl-1 gene on chromosome 1p36 belongs to a family of highly conserved secreted proteins which regulates embryonic induction, generation of cell polarity and specification of cell fate through activation of Wnt signaling pathways.", "type": "list", "id": "5709e4b2cf1c32585100001c", "snippets": [{"offsetInBeginSection": 294, "offsetInEndSection": 516, "text": "Dishevelled (Dvl/Dsh) is a multi-module protein and a key regulator of both the canonical Wnt and the PCP pathway. In mouse, all Dvl1(-/-) ; Dvl2(-/-) double mutants display craniorachischisis, a severe form of open NTDs. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23836490", "endSection": "abstract"}, {"offsetInBeginSection": 315, "offsetInEndSection": 511, "text": " In this study, we explore the cause of HSCR by studying the expression of DVL-1 and DVL-3 genes and their proteins in the aganglionic segment and the ganglionic segment of colon in HSCR patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24040443", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 299, "text": "Dishevelled (Dvl) proteins are key transducers of Wnt signaling encoded by members of a multi-gene family in vertebrates. We report here the divergent, tissue-specific expression patterns for all three Dvl genes in Xenopus embryos, which contrast dramatically with their expression patterns in mice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19618470", "endSection": "abstract"}, {"offsetInBeginSection": 145, "offsetInEndSection": 346, "text": "velopmental processes, including segmentation and neuroblast specification. We have isolated and characterized cDNA clones from two different human dsh-homologous genes, designated as DVL-1 and DVL-3. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8817329", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 394, "text": "In the Drosophila embryo dishevelled (dsh) function is required by target cells in order to respond to wingless (wg, the homolog of Wnt-1), demonstrating a role for dsh in Wnt signal transduction. We have isolated a mouse homolog of the Drosophila dsh segment polarity gene. The 695-amino-acid protein encoded by the mouse dishevelled gene (Dvl-1) shares 50% identity (65% similarity) with dsh. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7958461", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 282, "text": "The Dvl-1 gene on chromosome 1p36 belongs to a family of highly conserved secreted proteins which regulates embryonic induction, generation of cell polarity and specification of cell fate through activation of Wnt signaling pathways. Wnt signaling activates the gene encoding DVL-1; ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12883684", "endSection": "abstract"}, {"offsetInBeginSection": 453, "offsetInEndSection": 629, "text": "We report here that the mouse Dishevelled-1 (Dvl-1) and Dishevelled-2 genes encode proteins that are differentially localized in Wnt-overexpressing PC12 cell lines (PC12/Wnt). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8856345", "endSection": "abstract"}, {"offsetInBeginSection": 152, "offsetInEndSection": 255, "text": "Recently, the DVL1 gene was identified as a middle molecule of the Wnt/beta-catenin signaling pathway. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16457155", "endSection": "abstract"}]}, {"body": "Name monoclonal antibody against SLAMF7.", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/26035255", "http://www.ncbi.nlm.nih.gov/pubmed/25287778", "http://www.ncbi.nlm.nih.gov/pubmed/25312647"], "ideal_answer": "This led to development of an anti-SLAMF7 antibody, elotuzumab, showing efficacy against MM.BACKGROUND: Elotuzumab, an immunostimulatory monoclonal antibody targeting signaling lymphocytic activation molecule F7 (SLAMF7), showed activity in combination with lenalidomide and dexamethasone in a phase 1b-2 study in patients with relapsed or refractory multiple myeloma.One of the most promising MoAb is elotuzumab, the only humanized IgG1 MoAb specifically targeting CS1 (SLAMF7), a cell surface glycoprotein that is highly expressed in plasma cells.Elotuzumab is a humanized monoclonal antibody specific for signaling lymphocytic activation molecule-F7 (SLAMF7, also known as CS1, CD319, or CRACC) that enhances natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) of SLAMF7-expressing myeloma cells.Elotuzumab is a humanized monoclonal antibody specific for signaling lymphocytic activation molecule-F7 (SLAMF7, also known as CS1, CD319, or CRACC) that enhances natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) of SLAMF7-expressing myeloma cells.", "type": "factoid", "id": "56c077e9ef6e394741000021", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "BACKGROUND: Elotuzumab, an immunostimulatory monoclonal antibody targeting signaling lymphocytic activation molecule F7 (SLAMF7), showed activity in combination with lenalidomide and dexamethasone in a phase 1b-2 study in patients with relapsed or refractory multiple myeloma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26035255", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 280, "text": "Elotuzumab is a humanized monoclonal antibody specific for signaling lymphocytic activation molecule-F7 (SLAMF7, also known as CS1, CD319, or CRACC) that enhances natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) of SLAMF7-expressing myeloma cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25287778", "endSection": "abstract"}, {"offsetInBeginSection": 183, "offsetInEndSection": 275, "text": "This led to development of an anti-SLAMF7 antibody, elotuzumab, showing efficacy against MM. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25312647", "endSection": "abstract"}, {"offsetInBeginSection": 165, "offsetInEndSection": 347, "text": "One of the most promising MoAb is elotuzumab, the only humanized IgG1 MoAb specifically targeting CS1 (SLAMF7), a cell surface glycoprotein that is highly expressed in plasma cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24941981", "endSection": "abstract"}]}, {"body": "How many genes are imprinted in the human genome?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/24501229", "http://www.ncbi.nlm.nih.gov/pubmed/23083219", "http://www.ncbi.nlm.nih.gov/pubmed/22894909", "http://www.ncbi.nlm.nih.gov/pubmed/17653590", "http://www.ncbi.nlm.nih.gov/pubmed/11932239"], "ideal_answer": "To date, however, fewer than 100 imprinted genes have been identified in the human genome.These unique methylated CpG islands mapped to 23 chromosomal regions, and 12 were differentially methylated regions in uniparental tissues of germline origin, i.e., hydatidiform moles (paternal origin) and complete ovarian teratomas (maternal origin), even though many apparently were methylated in somatic tissues.By applying dsPIG to the mRNA-Seq data, we predicted 94 imprinted genes in 20 cerebellum samples and 57 imprinted genes in 9 diverse tissue samples with expected low false discovery rates. In this study we analyzed the imprinting of 22 genes in human, mouse, and cattle and found that in only 11 was imprinting conserved across the three species.Among approximately 70 known imprinted genes are some causing disorders affecting growth, metabolism and cancer predisposition.Interestingly, we found that, among biallelically expressed genes, at least 18 genes expressed significantly more transcripts from one allele than the other among different individuals and tissues.", "type": "factoid", "id": "57090c33cf1c325851000013", "snippets": [{"offsetInBeginSection": 203, "offsetInEndSection": 331, "text": "Among approximately 70 known imprinted genes are some causing disorders affecting growth, metabolism and cancer predisposition. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24501229", "endSection": "abstract"}, {"offsetInBeginSection": 795, "offsetInEndSection": 984, "text": "By applying dsPIG to the mRNA-Seq data, we predicted 94 imprinted genes in 20 cerebellum samples and 57 imprinted genes in 9 diverse tissue samples with expected low false discovery rates. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23083219", "endSection": "abstract"}, {"offsetInBeginSection": 1237, "offsetInEndSection": 1434, "text": "Interestingly, we found that, among biallelically expressed genes, at least 18 genes expressed significantly more transcripts from one allele than the other among different individuals and tissues. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23083219", "endSection": "abstract"}, {"offsetInBeginSection": 196, "offsetInEndSection": 286, "text": "To date, however, fewer than 100 imprinted genes have been identified in the human genome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23083219", "endSection": "abstract"}, {"offsetInBeginSection": 128, "offsetInEndSection": 379, "text": "Approximately 150 imprinted genes are known to date, in humans and mice but, though computational searches have tried to extract intrinsic characteristics of these genes to identify new ones, the existing list is probably far from being comprehensive. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22894909", "endSection": "abstract"}, {"offsetInBeginSection": 623, "offsetInEndSection": 781, "text": " In this study we analyzed the imprinting of 22 genes in human, mouse, and cattle and found that in only 11 was imprinting conserved across the three species. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17653590", "endSection": "abstract"}, {"offsetInBeginSection": 726, "offsetInEndSection": 1260, "text": "However, 62 unique clones in the library were characterized, all of which were methylated and GC-rich, with a GC content>50%. Of these, 43 clones also showed a CpG(obs)/CpG(exp)>0.6, of which 30 were studied in detail. These unique methylated CpG islands mapped to 23 chromosomal regions, and 12 were differentially methylated regions in uniparental tissues of germline origin, i.e., hydatidiform moles (paternal origin) and complete ovarian teratomas (maternal origin), even though many apparently were methylated in somatic tissues. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11932239", "endSection": "abstract"}]}, {"body": "Is there any association between Jarid2 and miR-155 in Th17 cells?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/24950205", "http://www.ncbi.nlm.nih.gov/pubmed/24856900"], "ideal_answer": "Jarid2 links MicroRNA and chromatin in Th17 cells.miR-155 activates cytokine gene expression in Th17 cells by regulating the DNA-binding protein Jarid2 to relieve polycomb-mediated repression.Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2.(2014) bring microRNAs and chromatin together by showing how activation-induced miR-155 targets the chromatin protein Jarid2 to regulate proinflammatory cytokine production in T helper 17 cells.miR-155-deficient Th17 and T regulatory (Treg) cells expressed increased amounts of Jarid2, a DNA-binding protein that recruits the Polycomb Repressive Complex 2 (PRC2) to chromatin.Mir155 was bound by Th17 cell transcription factors and was highly expressed during Th17 cell differentiation.Defects in Th17 cell cytokine expression and Treg cell homeostasis in the absence of Mir155 could be partially suppressed by Jarid2 deletion.In this issue of Immunity, Escobar etal.PRC2 binding to chromatin and H3K27 histone methylation was increased in miR-155-deficient cells, coinciding with failure to express Il22, Il10, Il9, and Atf3.", "type": "yesno", "id": "56b8f28a156496395c000006", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 50, "text": "Jarid2 links MicroRNA and chromatin in Th17 cells. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24950205", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "In this issue of Immunity, Escobar et\u00a0al. (2014) bring microRNAs and chromatin together by showing how activation-induced miR-155 targets the chromatin protein Jarid2 to regulate proinflammatory cytokine production in T helper 17 cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24950205", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "miR-155 activates cytokine gene expression in Th17 cells by regulating the DNA-binding protein Jarid2 to relieve polycomb-mediated repression. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24856900", "endSection": "title"}, {"offsetInBeginSection": 340, "offsetInEndSection": 1032, "text": "Mir155 was bound by Th17 cell transcription factors and was highly expressed during Th17 cell differentiation. miR-155-deficient Th17 and T regulatory (Treg) cells expressed increased amounts of Jarid2, a DNA-binding protein that recruits the Polycomb Repressive Complex 2 (PRC2) to chromatin. PRC2 binding to chromatin and H3K27 histone methylation was increased in miR-155-deficient cells, coinciding with failure to express Il22, Il10, Il9, and Atf3. Defects in Th17 cell cytokine expression and Treg cell homeostasis in the absence of Mir155 could be partially suppressed by Jarid2 deletion. Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24856900", "endSection": "abstract"}]}, {"body": "What is the Pfam database?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/23603847", "http://www.ncbi.nlm.nih.gov/pubmed/24297255", "http://www.ncbi.nlm.nih.gov/pubmed/20944204", "http://www.ncbi.nlm.nih.gov/pubmed/20537955", "http://www.ncbi.nlm.nih.gov/pubmed/19614588", "http://www.ncbi.nlm.nih.gov/pubmed/18957444"], "ideal_answer": "Over 10,000 such protein families have now been collected in the Pfam database.Protein domains are the common currency of protein structure and function.The Pfam database is an important tool in genome annotation, since it provides a collection of curated protein families.The Pfam database is an important tool in genome annotation, since it provides a collection of curated protein families.The Pfam database is an important tool in genome annotation, since it provides a collection of curated protein families.The Pfam database is an important tool in genome annotation, since it provides a collection of curated protein families.The Pfam database is an important tool in genome annotation, since it provides a collection of curated protein families.The Pfam database is an important tool in genome annotation, since it provides a collection of curated protein families.The Pfam database is an important tool in genome annotation, since it provides a collection of curated protein families.The Pfam database is an important tool in genome annotation, since it provides a collection of curated protein families.", "type": "factoid", "id": "5709f027cf1c32585100001f", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "The Pfam database is an important tool in genome annotation, since it provides a collection of curated protein families. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20537955", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Protein domains are the common currency of protein structure and function. Over 10,000 such protein families have now been collected in the Pfam database. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19614588", "endSection": "abstract"}]}, {"body": "Idarucizumab is an antidote of which drug?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/26069913", "http://www.ncbi.nlm.nih.gov/pubmed/26088576", "http://www.ncbi.nlm.nih.gov/pubmed/25899749", "http://www.ncbi.nlm.nih.gov/pubmed/26088268", "http://www.ncbi.nlm.nih.gov/pubmed/26095746"], "ideal_answer": "Idarucizumab for Dabigatran Reversal.Idarucizumab, an antibody fragment, was developed to reverse the anticoagulant effects of dabigatran.METHODS: We undertook this prospective cohort study to determine the safety of 5 g of intravenous idarucizumab and its capacity to reverse the anticoagulant effects of dabigatran in patients who had serious bleeding (group A) or required an urgent procedure (group B).With Idarucizumab and Andexanet Alfa, specific antidotes have been developed against both, direct thrombin inhibitors as well as direct Factor Xa inhibitors.INTERPRETATION: These phase 1 results show that idarucizumab was associated with immediate, complete, and sustained reversal of dabigatran-induced anticoagulation in healthy men, and was well tolerated with no unexpected or clinically relevant safety concerns, supporting further testing.Three novel molecules (idarucizumab, andexanet, and PER977) may provide the most effective and safest way of reversal.Dabigatran etexilate (DE) dose-dependently prolonged diluted thrombin time and tail-vein bleeding time, which were reversed by idarucizumab.Thus, idarucizumab prevents excess intracerebral hematoma formation in mice anticoagulated with dabigatran and reduces mortality.", "type": "factoid", "id": "56c079b1ef6e394741000022", "snippets": [{"offsetInBeginSection": 197, "offsetInEndSection": 355, "text": "With Idarucizumab and Andexanet Alfa, specific antidotes have been developed against both, direct thrombin inhibitors as well as direct Factor Xa inhibitors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26069913", "endSection": "abstract"}, {"offsetInBeginSection": 847, "offsetInEndSection": 966, "text": "Three novel molecules (idarucizumab, andexanet, and PER977) may provide the most effective and safest way of reversal. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26088576", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Idarucizumab Improves Outcome in Murine Brain Hemorrhage Related to Dabigatran. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25899749", "endSection": "title"}, {"offsetInBeginSection": 145, "offsetInEndSection": 401, "text": "We examined the efficacy of idarucizumab, an antibody fragment binding to dabigatran, in a mouse model of OAC-ICH. Dabigatran etexilate (DE) dose-dependently prolonged diluted thrombin time and tail-vein bleeding time, which were reversed by idarucizumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25899749", "endSection": "abstract"}, {"offsetInBeginSection": 650, "offsetInEndSection": 779, "text": "Thus, idarucizumab prevents excess intracerebral hematoma formation in mice anticoagulated with dabigatran and reduces mortality. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25899749", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 371, "text": "BACKGROUND: Idarucizumab is a monoclonal antibody fragment that binds dabigatran with high affinity in a 1:1 molar ratio. We investigated the safety, tolerability, and efficacy of increasing doses of idarucizumab for the reversal of anticoagulant effects of dabigatran in a two-part phase 1 study (rising-dose assessment and dose-finding, proof-of-concept investigation). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26088268", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 199, "text": "Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy male volunteers: a randomised, placebo-controlled, double-blind phase 1 trial. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26088268", "endSection": "title"}, {"offsetInBeginSection": 3048, "offsetInEndSection": 3337, "text": "INTERPRETATION: These phase 1 results show that idarucizumab was associated with immediate, complete, and sustained reversal of dabigatran-induced anticoagulation in healthy men, and was well tolerated with no unexpected or clinically relevant safety concerns, supporting further testing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26088268", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 37, "text": "Idarucizumab for Dabigatran Reversal. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26095746", "endSection": "title"}, {"offsetInBeginSection": 99, "offsetInEndSection": 468, "text": "Idarucizumab, an antibody fragment, was developed to reverse the anticoagulant effects of dabigatran.METHODS: We undertook this prospective cohort study to determine the safety of 5 g of intravenous idarucizumab and its capacity to reverse the anticoagulant effects of dabigatran in patients who had serious bleeding (group A) or required an urgent procedure (group B). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26095746", "endSection": "abstract"}, {"offsetInBeginSection": 1835, "offsetInEndSection": 1936, "text": ".CONCLUSIONS: Idarucizumab completely reversed the anticoagulant effect of dabigatran within minutes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26095746", "endSection": "abstract"}]}, {"body": "Does a linker histone exist in the yeast genome?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/24023978", "http://www.ncbi.nlm.nih.gov/pubmed/22200500", "http://www.ncbi.nlm.nih.gov/pubmed/22586276", "http://www.ncbi.nlm.nih.gov/pubmed/19017647", "http://www.ncbi.nlm.nih.gov/pubmed/18687885", "http://www.ncbi.nlm.nih.gov/pubmed/16342967", "http://www.ncbi.nlm.nih.gov/pubmed/15050829", "http://www.ncbi.nlm.nih.gov/pubmed/15046982", "http://www.ncbi.nlm.nih.gov/pubmed/11574687", "http://www.ncbi.nlm.nih.gov/pubmed/9516420"], "ideal_answer": "Hho1p is a bona fide linker histoneHho1 chromatin immunoprecipitation followed by sequencing (ChIP-seq) revealed increased genome-wide binding in mature spores and provides novel in vivo evidence of the linker histone binding to nucleosomal linker DNASaccharomyces cerevisiae linker histone-Hho1p maintains chromatin loop organization during ageing.Here, we show in yeast, that the presence of yeast linker histone Hho1p represses expression of a pol II transcribed gene (MET15) embedded in the rDNA.Yeast linker histone Hho1p is required for efficient RNA polymerase I processivity and transcriptional silencing at the ribosomal DNATwo homologous domains of similar structure but different stability in the yeast linker histone, Hho1pCharacteristically, linker histone depleted chromatin generally exhibited longer chromatin loops than the wild-type.In Saccharomyces cerevisiae, HHO1 encodes a putative linker histone with very significant homology to histone H1One of the peculiarities of S. cerevisiae cells is the unusual and less abundant linker histone, Hho1p.Saccharomyces cerevisiae linker histone Hho1p functionally interacts with core histone H4 and negatively regulates the establishment of transcriptionally silent chromatin", "type": "yesno", "id": "5709152ecf1c325851000014", "snippets": [{"offsetInBeginSection": 999, "offsetInEndSection": 1034, "text": "Hho1p is a bona fide linker histone ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/9516420", "endSection": "abstract"}, {"offsetInBeginSection": 136, "offsetInEndSection": 248, "text": "In Saccharomyces cerevisiae, HHO1 encodes a putative linker histone with very significant homology to histone H1 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11574687", "endSection": "abstract"}, {"offsetInBeginSection": 995, "offsetInEndSection": 1089, "text": "HHO1p may play a similar role to linker histones, but at restricted locations in the chromatin ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11574687", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 207, "text": "The putative linker histone in Saccharomyces cerevisiae, Hho1p, has two regions of sequence (GI and GII) that are homologous to the single globular domains of linker histones H1 and H5 in higher eukaryotes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15046982", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "The Saccharomyces cerevisiae homologue of the linker histone H1, Hho1p, has two domains that are similar in sequence to the globular domain of H1 (and variants such as H5) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15050829", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Two homologous domains of similar structure but different stability in the yeast linker histone, Hho1p ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15050829", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Saccharomyces cerevisiae encodes a single linker histone, Hho1p, with two globular domains. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16342967", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 140, "text": "The Saccharomyces cerevisiae linker histone Hho1p, with two globular domains, can simultaneously bind to two four-way junction DNA molecules ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16342967", "endSection": "title"}, {"offsetInBeginSection": 121, "offsetInEndSection": 272, "text": "Here, we show in yeast, that the presence of yeast linker histone Hho1p represses expression of a pol II transcribed gene (MET15) embedded in the rDNA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18687885", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "Yeast linker histone Hho1p is required for efficient RNA polymerase I processivity and transcriptional silencing at the ribosomal DNA ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18687885", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "Saccharomyces cerevisiae linker histone Hho1p is not essential for cell viability, and very little is known about its function in vivo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19017647", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "Saccharomyces cerevisiae linker histone Hho1p functionally interacts with core histone H4 and negatively regulates the establishment of transcriptionally silent chromatin ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19017647", "endSection": "title"}, {"offsetInBeginSection": 813, "offsetInEndSection": 1133, "text": " Unlike canonical linker histones in higher eukaryotes that have a single conserved globular domain, Hho1p possesses two globular domains. We show that the carboxyl-terminal globular domain of Hho1p is dispensable for its function, suggesting that the mode of Hho1p action is similar to that of canonical linker histones ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19017647", "endSection": "abstract"}, {"offsetInBeginSection": 266, "offsetInEndSection": 440, "text": "To identify new proteins involved in spore nuclear organization, we purified chromatin from mature spores and discovered a significant enrichment of the linker histone (Hho1) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22586276", "endSection": "abstract"}, {"offsetInBeginSection": 621, "offsetInEndSection": 837, "text": "Hho1 chromatin immunoprecipitation followed by sequencing (ChIP-seq) revealed increased genome-wide binding in mature spores and provides novel in vivo evidence of the linker histone binding to nucleosomal linker DNA ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22586276", "endSection": "abstract"}, {"offsetInBeginSection": 224, "offsetInEndSection": 327, "text": "One of the peculiarities of S. cerevisiae cells is the unusual and less abundant linker histone, Hho1p. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22200500", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 113, "text": "Hho1p, the linker histone of Saccharomyces cerevisiae, is important for the proper chromatin organization in vivo ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22200500", "endSection": "title"}, {"offsetInBeginSection": 700, "offsetInEndSection": 817, "text": "Characteristically, linker histone depleted chromatin generally exhibited longer chromatin loops than the wild-type. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22200500", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Saccharomyces cerevisiae linker histone-Hho1p maintains chromatin loop organization during ageing. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24023978", "endSection": "title"}]}, {"body": "What is the role of Caenorhabditis elegans Heterochromatin protein 1 (HPL-2) in development?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/22185090", "http://www.ncbi.nlm.nih.gov/pubmed/21437264", "http://www.ncbi.nlm.nih.gov/pubmed/21116703", "http://www.ncbi.nlm.nih.gov/pubmed/16905130", "http://www.ncbi.nlm.nih.gov/pubmed/11850401"], "ideal_answer": "Caenorhabditis elegans Heterochromatin protein 1 (HPL-2) links developmental plasticity, longevity and lipid metabolism.Furthermore, we find that hpl-1 has an unexpected role in vulval development by acting redundantly with hpl-2, but not other genes previously implicated in vulval development.Interestingly, lin-61 genetically interacts with two other synMuvB genes, hpl-2, an HP1 homologous H3K9me2/3 binding factor, and met-2, a SETDB1 homologous H3K9 methyl transferase (H3K9MT), in determining C. elegans vulva development and fertility.We have specifically characterized the intranuclear positioning of in vivo fluorescence of the Caenorhabditis elegans HP1 homologue HPL-2 as a marker for heterochromatin domains in developing embryos.Comparison of our expression data with HPL-2 ChIP-on-chip profiles reveals that a significant number of genes up- and down-regulated in the absence of HPL-2 are bound by HPL-2.Localization studies show that like HPL-2, HPL-1 is a ubiquitously expressed nuclear protein.We show that while the absence of hpl-1 alone results in no obvious phenotype, hpl-1;hpl-2 double mutants show synthetic, temperature sensitive phenotypes including larval lethality and severe defects in the development of the somatic gonad.", "type": "summary", "id": "56b9cabbac7ad10019000002", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "Caenorhabditis elegans Heterochromatin protein 1 (HPL-2) links developmental plasticity, longevity and lipid metabolism. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22185090", "endSection": "title"}, {"offsetInBeginSection": 378, "offsetInEndSection": 834, "text": " We show that HPL-2 regulates the expression of germline genes, extracellular matrix components and genes involved in lipid metabolism. Comparison of our expression data with HPL-2 ChIP-on-chip profiles reveals that a significant number of genes up- and down-regulated in the absence of HPL-2 are bound by HPL-2. Germline genes are specifically up-regulated in hpl-2 mutants, consistent with the function of HPL-2 as a repressor of ectopic germ cell fate. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22185090", "endSection": "abstract"}, {"offsetInBeginSection": 903, "offsetInEndSection": 1060, "text": "HPL-2 regulates the dauer developmental decision, a striking example of phenotypic plasticity in which environmental conditions determine developmental fate. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22185090", "endSection": "abstract"}, {"offsetInBeginSection": 1340, "offsetInEndSection": 1546, "text": "Our results suggest that the worm HP1 homologue HPL-2 may coordinately regulate dauer diapause, longevity and lipid metabolism, three processes dependent on developmental input and environmental conditions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22185090", "endSection": "abstract"}, {"offsetInBeginSection": 1431, "offsetInEndSection": 1679, "text": "Interestingly, lin-61 genetically interacts with two other synMuvB genes, hpl-2, an HP1 homologous H3K9me2/3 binding factor, and met-2, a SETDB1 homologous H3K9 methyl transferase (H3K9MT), in determining C. elegans vulva development and fertility. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21437264", "endSection": "abstract"}, {"offsetInBeginSection": 451, "offsetInEndSection": 652, "text": "We have specifically characterized the intranuclear positioning of in vivo fluorescence of the Caenorhabditis elegans HP1 homologue HPL-2 as a marker for heterochromatin domains in developing embryos. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21116703", "endSection": "abstract"}, {"offsetInBeginSection": 421, "offsetInEndSection": 1277, "text": "While HPL-2 functions in vulval and germline development, no function has so far been attributed to HPL-1. Here we report the characterization of an hpl-1 null allele. We show that while the absence of hpl-1 alone results in no obvious phenotype, hpl-1;hpl-2 double mutants show synthetic, temperature sensitive phenotypes including larval lethality and severe defects in the development of the somatic gonad. Furthermore, we find that hpl-1 has an unexpected role in vulval development by acting redundantly with hpl-2, but not other genes previously implicated in vulval development. Localization studies show that like HPL-2, HPL-1 is a ubiquitously expressed nuclear protein. However, HPL-1 and HPL-2 localization does not completely overlap. Our results show that HPL-1 and HPL-2 play both unique and redundant functions in post-embryonic development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16905130", "endSection": "abstract"}, {"offsetInBeginSection": 644, "offsetInEndSection": 815, "text": "We show that one of the homologues, HPL-2, is required for the formation of a functional germline and for the development of the vulva by acting in an Rb-related pathway. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11850401", "endSection": "abstract"}]}, {"body": "How can DUF families be deciphered?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/19787035", "http://www.ncbi.nlm.nih.gov/pubmed/22629278", "http://www.ncbi.nlm.nih.gov/pubmed/23516388", "http://www.ncbi.nlm.nih.gov/pubmed/25044324", "http://www.ncbi.nlm.nih.gov/pubmed/25010333", "http://www.ncbi.nlm.nih.gov/pubmed/24237627", "http://www.ncbi.nlm.nih.gov/pubmed/24901469", "http://www.ncbi.nlm.nih.gov/pubmed/23572527", "http://www.ncbi.nlm.nih.gov/pubmed/23104832"], "ideal_answer": " These families include proteins with domain of unknown function (DUF) DUF23, DUF246, and DUF266.Targeted attempts at DUF characterization in the laboratory or in silico may draw from these insights and opportunities to discover new associations and corroborate existing ones will arise as more large-scale metagenomic datasets emerge.In a coordinated effort, the four large-scale centers of the NIH Protein Structure Initiative have determined the first three-dimensional structures for more than 250 of these DUF families.Notably, SrfN has been shown to have a role in intracellular infection by Salmonella TyphimuriumThese genes, as most others, can be grouped into families based on sequence similarity.Representatives of this family have been demonstrated to play roles in several cellular processes including stress response, biofilm formation, and pathogenesis.The evidence for these proteins being GTs and their possible roles in cell wall biosynthesis is discussed.The genome projects have unearthed an enormous diversity of genes of unknown function that are still awaiting biological and biochemical characterization.", "type": "summary", "id": "5709f646cf1c325851000021", "snippets": [{"offsetInBeginSection": 549, "offsetInEndSection": 753, "text": " These families include proteins with domain of unknown function (DUF) DUF23, DUF246, and DUF266. The evidence for these proteins being GTs and their possible roles in cell wall biosynthesis is discussed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22629278", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 354, "text": "The genome projects have unearthed an enormous diversity of genes of unknown function that are still awaiting biological and biochemical characterization. These genes, as most others, can be grouped into families based on sequence similarity. The PFAM database currently contains over 2,200 such families, referred to as domains of unknown function (DUF) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19787035", "endSection": "abstract"}, {"offsetInBeginSection": 356, "offsetInEndSection": 545, "text": "In a coordinated effort, the four large-scale centers of the NIH Protein Structure Initiative have determined the first three-dimensional structures for more than 250 of these DUF families. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19787035", "endSection": "abstract"}, {"offsetInBeginSection": 1768, "offsetInEndSection": 2165, "text": "Critically examining domain covariation across metagenomic datasets can grant new perspectives on the roles and associations of DUFs in an ecological setting. Targeted attempts at DUF characterization in the laboratory or in silico may draw from these insights and opportunities to discover new associations and corroborate existing ones will arise as more large-scale metagenomic datasets emerge. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23516388", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 276, "text": "Crystal structures of three members (BACOVA_00364 from Bacteroides ovatus, BACUNI_03039 from Bacteroides uniformis and BACEGG_00036 from Bacteroides eggerthii) of the Pfam domain of unknown function (DUF4488) were determined to 1.95, 1.66, and 1.81 \u00c5 resolutions, respectively ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25044324", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 847, "text": "Bacterial species in the Enterobacteriaceae typically contain multiple paralogues of a small domain of unknown function (DUF1471) from a family of conserved proteins also known as YhcN or BhsA/McbA. Proteins containing DUF1471 may have a single or three copies of this domain. Representatives of this family have been demonstrated to play roles in several cellular processes including stress response, biofilm formation, and pathogenesis. We have conducted NMR and X-ray crystallographic studies of four DUF1471 domains from Salmonella representing three different paralogous DUF1471 subfamilies: SrfN, YahO, and SssB/YdgH (two of its three DUF1471 domains: the N-terminal domain I (residues 21-91), and the C-terminal domain III (residues 244-314)). Notably, SrfN has been shown to have a role in intracellular infection by Salmonella Typhimurium ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25010333", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 502, "text": "Domain of unknown function (DUF) proteins represent a number of gene families that encode functionally uncharacterized proteins in eukaryotes. For example, DUF1618 family members in plants possess a 56-199-amino acid conserved domain and this family has not been described previously. Here, we report the characterization of 121 DUF1618 genes identified in the rice genome. Based on phylogenetic analysis, the rice DUF1618 family was divided into two major groups, each group consisting of two clades. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24237627", "endSection": "abstract"}, {"offsetInBeginSection": 237, "offsetInEndSection": 352, "text": "In this study we identified that a plant specific domain of unknown function, DUF581 is a zf-FCS type zinc finger. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24901469", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 261, "text": "DUF2233, a domain of unknown function (DUF), is present in many bacterial and several viral proteins and was also identified in the mammalian transmembrane glycoprotein N-acetylglucosamine-1-phosphodiester \u03b1-N-acetylglucosaminidase (\"uncovering enzyme\" (UCE)). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23572527", "endSection": "abstract"}]}, {"body": "Was tamoxifen tested for treatment of glioma patients?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/21353747", "http://www.ncbi.nlm.nih.gov/pubmed/20238235", "http://www.ncbi.nlm.nih.gov/pubmed/16710748", "http://www.ncbi.nlm.nih.gov/pubmed/15022287", "http://www.ncbi.nlm.nih.gov/pubmed/12712458", "http://www.ncbi.nlm.nih.gov/pubmed/19810975", "http://www.ncbi.nlm.nih.gov/pubmed/10797257", "http://www.ncbi.nlm.nih.gov/pubmed/10715294"], "ideal_answer": "The addition of high-dose tamoxifen to standard radiotherapy does not improve the survival of patients with diffuse intrinsic pontine glioma.CONCLUSION: This treatment combination produced no significant change in the overall poor prognosis of these patients.Tamoxifen might have a role in the initial treatment of high-grade gliomas and should be studied in future Phase II trials building on the newly established platform of concurrent chemoradiotherapy.In a parallel phase-II-study investigating post-operative treatment with tamoxifen (TAM), carboplatin and radiation therapy for glioblastomas, 16 of 49 patients (33%) showed multifocal recurrence, which developed after a mean of 46 weeks, raising the question of an association with therapy.CONCLUSIONS: Pegylated liposomal doxorubicin administered alone or in combination with tamoxifen is safe and moderately effective in patients with recurrent high-grade glioma.Brainstem Glioma Cooperative Group.Protein kinase C (PKC) inhibitors such as high-dose tamoxifen and hypericin also have been used in the treatment of malignant gliomas.Most tumors responded initially to treatment but recurred as the study progressed.A minority of patients seemed to benefit from the extended use of TX.", "type": "yesno", "id": "56c0968def6e394741000026", "snippets": [{"offsetInBeginSection": 1694, "offsetInEndSection": 1892, "text": "Tamoxifen might have a role in the initial treatment of high-grade gliomas and should be studied in future Phase II trials building on the newly established platform of concurrent chemoradiotherapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21353747", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "The addition of high-dose tamoxifen to standard radiotherapy does not improve the survival of patients with diffuse intrinsic pontine glioma. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20238235", "endSection": "title"}, {"offsetInBeginSection": 769, "offsetInEndSection": 956, "text": "In this study, in which tamoxifen was used in conjunction with radiotherapy, progression free survival was shown to be less good when compared with historical data HR = 3.1 (CI: 1.7-5.7). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20238235", "endSection": "abstract"}, {"offsetInBeginSection": 1013, "offsetInEndSection": 1196, "text": "The addition of high-dose tamoxifen, although well tolerated, confers no clinical benefit to patients treated with diffuse intrinsic pontine glioma treated with standard radiotherapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20238235", "endSection": "abstract"}, {"offsetInBeginSection": 1495, "offsetInEndSection": 1696, "text": "CONCLUSIONS: Carboplatin and high dose tamoxifen has similar response rates to other regimens for recurrent malignant gliomas and are probably equivalent to those found using tamoxifen as monotherapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16710748", "endSection": "abstract"}, {"offsetInBeginSection": 1618, "offsetInEndSection": 1793, "text": "CONCLUSIONS: Pegylated liposomal doxorubicin administered alone or in combination with tamoxifen is safe and moderately effective in patients with recurrent high-grade glioma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15022287", "endSection": "abstract"}, {"offsetInBeginSection": 153, "offsetInEndSection": 288, "text": "Protein kinase C (PKC) inhibitors such as high-dose tamoxifen and hypericin also have been used in the treatment of malignant gliomas. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12712458", "endSection": "abstract"}, {"offsetInBeginSection": 852, "offsetInEndSection": 1028, "text": "Considering these facts, polyethylene-glycol-liposomal doxorubicin with and without tamoxifen was evaluated within two sequential Phase II trials performed at our institution. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19810975", "endSection": "abstract"}, {"offsetInBeginSection": 78, "offsetInEndSection": 369, "text": "In a parallel phase-II-study investigating post-operative treatment with tamoxifen (TAM), carboplatin and radiation therapy for glioblastomas, 16 of 49 patients (33%) showed multifocal recurrence, which developed after a mean of 46 weeks, raising the question of an association with therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10797257", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 180, "text": "Radiation therapy and high-dose tamoxifen in the treatment of patients with diffuse brainstem gliomas: results of a Brazilian cooperative study. Brainstem Glioma Cooperative Group. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10715294", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "PURPOSE: The efficacy of radiation therapy (RT) combined with tamoxifen (TX) was tested in patients diagnosed with diffuse brainstem gliomas in a multicenter trial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10715294", "endSection": "abstract"}, {"offsetInBeginSection": 1183, "offsetInEndSection": 1455, "text": "CONCLUSION: This treatment combination produced no significant change in the overall poor prognosis of these patients. Most tumors responded initially to treatment but recurred as the study progressed. A minority of patients seemed to benefit from the extended use of TX. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10715294", "endSection": "abstract"}]}, {"body": "Do A-type lamins bind euchromatin or heterochromatin?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/22713752", "http://www.ncbi.nlm.nih.gov/pubmed/20130288", "http://www.ncbi.nlm.nih.gov/pubmed/19141474", "http://www.ncbi.nlm.nih.gov/pubmed/11953316", "http://www.ncbi.nlm.nih.gov/pubmed/24153156"], "ideal_answer": "Histone acetylation controls, almost exclusively, euchromatin protein dynamics; lamin A expression regulates heterochromatin protein dynamics, and G9a regulates both euchromatin and heterochromatin protein dynamics.Comparative genomic hybridization (CGH) analyses of microdissected blebs, fluorescence in situ hybridization (FISH), and immunofluorescence localization of modified histones demonstrate that gene-rich euchromatin associates with the LA/C blebsLmna(9/9) MEFs exhibit telomere shortening and heterochromatin alterations but do not activate cathepsin L-mediated degradation of 53BP1 and maintain expression of BRCA1 and RAD51Our results demonstrated that these proteins were always present and that their distributions were related to oocyte maturity, determined by chromatin configuration and oocyte diameterCaspase-6 gene disruption reveals a requirement for lamin A cleavage in apoptotic chromatin condensationThe A- and B-type nuclear lamin networks: microdomains involved in chromatin organization and transcription.These data reveal that the domain encoded by exon 9 is important to maintain telomere homeostasis and heterochromatin structure but does not play a role in DNA repair, thus pointing to other exons in the lamin A tail as responsible for the genomic instability phenotype in Lmna(8-11/8-11) mice", "type": "factoid", "id": "570917bccf1c325851000015", "snippets": [{"offsetInBeginSection": 1243, "offsetInEndSection": 1538, "text": "These data reveal that the domain encoded by exon 9 is important to maintain telomere homeostasis and heterochromatin structure but does not play a role in DNA repair, thus pointing to other exons in the lamin A tail as responsible for the genomic instability phenotype in Lmna(\u03948-11/\u03948-11) mice ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24153156", "endSection": "abstract"}, {"offsetInBeginSection": 850, "offsetInEndSection": 1031, "text": "Lmna(\u03949/\u03949) MEFs exhibit telomere shortening and heterochromatin alterations but do not activate cathepsin L-mediated degradation of 53BP1 and maintain expression of BRCA1 and RAD51 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24153156", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Lamin A \u0394exon9 mutation leads to telomere and chromatin defects but not genomic instability ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24153156", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Caspase-6 gene disruption reveals a requirement for lamin A cleavage in apoptotic chromatin condensation ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11953316", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 108, "text": "The A- and B-type nuclear lamin networks: microdomains involved in chromatin organization and transcription. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19141474", "endSection": "title"}, {"offsetInBeginSection": 667, "offsetInEndSection": 910, "text": "Comparative genomic hybridization (CGH) analyses of microdissected blebs, fluorescence in situ hybridization (FISH), and immunofluorescence localization of modified histones demonstrate that gene-rich euchromatin associates with the LA/C blebs ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19141474", "endSection": "abstract"}, {"offsetInBeginSection": 8, "offsetInEndSection": 103, "text": "Lamin A/C, caspase-6, and chromatin configuration during meiosis resumption in the mouse oocyte ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20130288", "endSection": "title"}, {"offsetInBeginSection": 678, "offsetInEndSection": 862, "text": "Our results demonstrated that these proteins were always present and that their distributions were related to oocyte maturity, determined by chromatin configuration and oocyte diameter ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20130288", "endSection": "abstract"}, {"offsetInBeginSection": 513, "offsetInEndSection": 728, "text": "Histone acetylation controls, almost exclusively, euchromatin protein dynamics; lamin A expression regulates heterochromatin protein dynamics, and G9a regulates both euchromatin and heterochromatin protein dynamics. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22713752", "endSection": "abstract"}]}, {"body": "Do orphan and gene related CpG islands follow power-law-like distributions?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/25242375"], "ideal_answer": "Orphan and gene related CpG Islands follow power-law-like distributions in several genomes: evidence of function-related and taxonomy-related modes of distribution. Our results on power-law-like linearity found in orphan CGI populations suggest that the observed distributional pattern is independent of the analogous pattern that protein coding segments were reported to follow.The power-law-like patterns in the genomic distributions of CGIs described herein are found to be compatible with several other features of the composition, abundance or functional role of CGIs reported in the current literature across several genomes, on the basis of the proposed evolutionary model.Here, an investigation of their distributional characteristics in a variety of genomes is undertaken for both whole CGI populations as well as for CGI subsets that lie away from known genes (gene-unrelated or \"orphan\" CGIs).In both cases power-law-like linearity in double logarithmic scale is found.In both cases power-law-like linearity in double logarithmic scale is found.In both cases power-law-like linearity in double logarithmic scale is found.In both cases power-law-like linearity in double logarithmic scale is found.", "type": "yesno", "id": "56bb154aac7ad10019000003", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 164, "text": "Orphan and gene related CpG Islands follow power-law-like distributions in several genomes: evidence of function-related and taxonomy-related modes of distribution. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25242375", "endSection": "title"}, {"offsetInBeginSection": 477, "offsetInEndSection": 778, "text": "Here, an investigation of their distributional characteristics in a variety of genomes is undertaken for both whole CGI populations as well as for CGI subsets that lie away from known genes (gene-unrelated or \"orphan\" CGIs). In both cases power-law-like linearity in double logarithmic scale is found. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25242375", "endSection": "abstract"}, {"offsetInBeginSection": 1186, "offsetInEndSection": 1703, "text": " Our results on power-law-like linearity found in orphan CGI populations suggest that the observed distributional pattern is independent of the analogous pattern that protein coding segments were reported to follow. The power-law-like patterns in the genomic distributions of CGIs described herein are found to be compatible with several other features of the composition, abundance or functional role of CGIs reported in the current literature across several genomes, on the basis of the proposed evolutionary model. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25242375", "endSection": "abstract"}]}, {"body": "List variants of the MC1R gene.", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/26103569", "http://www.ncbi.nlm.nih.gov/pubmed/25219681", "http://www.ncbi.nlm.nih.gov/pubmed/24917043", "http://www.ncbi.nlm.nih.gov/pubmed/24170137"], "ideal_answer": "The melanocortin 1 receptor (MC1R) gene encodes for a seven-pass transmembrane receptor primarily expressed on melanocytes and melanoma cells. We aim to examine the influence of the MC1R variants (RHC: D84E, R151C, R160W; NRHC: V60L, R163Q and the synonymous polymorphism T314T) on the MM risk in a population from the Canary Islands.for V60L to 2.74 (1.53-4.89) for D84E.All of the investigated variants showed positive associations with NMSC, with consistent significant results obtained for V60L, D84E, V92M, R151C, R160W, R163Q and D294H: SOR (95%CI) ranged from 1.42 (1.19-1.70) for V60L to 2.66 (1.06-6.65) for D84E variant.All of the investigated variants showed positive associations with NMSC, with consistent significant results obtained for V60L, D84E, V92M, R151C, R160W, R163Q and D294H: SOR (95%CI) ranged from 1.42 (1.19-1.70) for V60L to 2.66 (1.06-6.65) for D84E variant.", "type": "list", "id": "570a5343cf1c325851000022", "snippets": [{"offsetInBeginSection": 873, "offsetInEndSection": 1131, "text": "All of the investigated variants showed positive associations with NMSC, with consistent significant results obtained for V60L, D84E, V92M, R151C, R160W, R163Q and D294H: SOR (95%CI) ranged from 1.42 (1.19-1.70) for V60L to 2.66 (1.06-6.65) for D84E variant. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26103569", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 142, "text": "The melanocortin 1 receptor (MC1R) gene encodes for a seven-pass transmembrane receptor primarily expressed on melanocytes and melanoma cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25219681", "endSection": "abstract"}, {"offsetInBeginSection": 716, "offsetInEndSection": 755, "text": "for V60L to 2.74 (1.53-4.89) for D84E. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24917043", "endSection": "abstract"}, {"offsetInBeginSection": 112, "offsetInEndSection": 305, "text": " We aim to examine the influence of the MC1R variants (RHC: D84E, R151C, R160W; NRHC: V60L, R163Q and the synonymous polymorphism T314T) on the MM risk in a population from the Canary Islands. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24170137", "endSection": "abstract"}]}, {"body": "What is the role of photodynamic therapy for meningioma treatment?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/24486853", "http://www.ncbi.nlm.nih.gov/pubmed/23465372", "http://www.ncbi.nlm.nih.gov/pubmed/16788926", "http://www.ncbi.nlm.nih.gov/pubmed/10327048", "http://www.ncbi.nlm.nih.gov/pubmed/8672259", "http://www.ncbi.nlm.nih.gov/pubmed/8384325", "http://www.ncbi.nlm.nih.gov/pubmed/1388826", "http://www.ncbi.nlm.nih.gov/pubmed/1984490", "http://www.ncbi.nlm.nih.gov/pubmed/2176016", "http://www.ncbi.nlm.nih.gov/pubmed/2855780", "http://www.ncbi.nlm.nih.gov/pubmed/21073472"], "ideal_answer": "Photodynamic therapy is being investigated as an adjuvant treatment for intracranial neoplasms.Susceptibility to 5-aminolevulinic acid based photodynamic therapy in WHO I meningioma cells corresponds to ferrochelatase activity.CONCLUSIONS: Efficacy of 5-ALA PDT could be increased by adjunction of ciprofloxacin in conventional clinical dosing and by prolongation of ALA incubation time.These data indicate unique features of AlPc which suggests its application as a potent, non-toxic photosensitizer in the photodynamic therapy of human meningiomas.Photodynamic therapy is a promising treatment for human brain tumors because of the selective retention of certain compounds by tumor cells.It was found that PDT using haematoporphyrin derivative as a photosensitizing drug showed dose-dependent activity against a variety of histological subtypes of meningioma.CONCLUSION: ALA-PDT was more effective in killing U-105MG glioma cells than CH-157MN meningioma cells.We conclude that differences in intracellular PpIX concentrations between HBL-52 and BEN-MEN-1 benign meningioma cells were mainly due to differences in FECH activity and that these differences correspond to their susceptibility to 5-ALA-induced PDT.", "type": "summary", "id": "56c097deef6e394741000027", "snippets": [{"offsetInBeginSection": 1221, "offsetInEndSection": 1382, "text": "CONCLUSIONS: Efficacy of 5-ALA PDT could be increased by adjunction of ciprofloxacin in conventional clinical dosing and by prolongation of ALA incubation time. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24486853", "endSection": "abstract"}, {"offsetInBeginSection": 1023, "offsetInEndSection": 1187, "text": "CONCLUSION: Gefitinib can inhibit ABCG2-mediated PpIX efflux from malignant brain tumor cells to increase the intracellular PpIX and thereby enhance the PDT effect. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23465372", "endSection": "abstract"}, {"offsetInBeginSection": 1528, "offsetInEndSection": 1630, "text": "CONCLUSION: ALA-PDT was more effective in killing U-105MG glioma cells than CH-157MN meningioma cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10327048", "endSection": "abstract"}, {"offsetInBeginSection": 1726, "offsetInEndSection": 1889, "text": "These data indicate unique features of AlPc which suggests its application as a potent, non-toxic photosensitizer in the photodynamic therapy of human meningiomas. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8672259", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "Photodynamic therapy is being investigated as an adjuvant treatment for intracranial neoplasms. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8384325", "endSection": "abstract"}, {"offsetInBeginSection": 563, "offsetInEndSection": 735, "text": "It was found that PDT using haematoporphyrin derivative as a photosensitizing drug showed dose-dependent activity against a variety of histological subtypes of meningioma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1388826", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 141, "text": "Photodynamic therapy is a promising treatment for human brain tumors because of the selective retention of certain compounds by tumor cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/1984490", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 132, "text": "Susceptibility to 5-aminolevulinic acid based photodynamic therapy in WHO I meningioma cells corresponds to ferrochelatase activity. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21073472", "endSection": "title"}, {"offsetInBeginSection": 1175, "offsetInEndSection": 1425, "text": "We conclude that differences in intracellular PpIX concentrations between HBL-52 and BEN-MEN-1 benign meningioma cells were mainly due to differences in FECH activity and that these differences correspond to their susceptibility to 5-ALA-induced PDT. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21073472", "endSection": "abstract"}]}, {"body": "Is NOD1 activated in inflammation?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/24041848", "http://www.ncbi.nlm.nih.gov/pubmed/22870324", "http://www.ncbi.nlm.nih.gov/pubmed/23162548", "http://www.ncbi.nlm.nih.gov/pubmed/23259058", "http://www.ncbi.nlm.nih.gov/pubmed/21330608", "http://www.ncbi.nlm.nih.gov/pubmed/20921147", "http://www.ncbi.nlm.nih.gov/pubmed/19074813", "http://www.ncbi.nlm.nih.gov/pubmed/19074871", "http://www.ncbi.nlm.nih.gov/pubmed/17690884"], "ideal_answer": "NOD1 and NOD2 Signaling in Infection and InflammationNod1 ligands induce site-specific vascular inflammationNOD1 may have a role in mediating infection-associated inflammation.NOD1 expression in the eye and functional contribution to IL-1beta-dependent ocular inflammation in micePolymorphisms in NOD1 are associated with autoinflammatory diseases characterized by uveitis such as Crohn's disease and sarcoidosisDepletion of the gut microbiota suppressed tumor development in Nod1-deficient mice, thus highlighting a link between the commensal bacteria within the intestine and the host innate immune Nod1 signaling pathway in the regulation inflammation-mediated colon cancer development.Phenotyping of Nod1/2 double deficient mice and characterization of Nod1/2 in systemic inflammation and associated renal diseaseThis data supports the potential utility of NOD1 and RIP2 as therapeutic targets in human disease where vascular inflammation is a clinical feature, such as in sepsis and septic shock.In the absence of Nod1 signaling, there is a greater disruption of the intestinal epithelial cell barrier due to chemically induced injury as manifested by increased surface epithelial apoptosis early on during chemically induced colitis and increased intestinal permeability.Nod1 is also critically implicated in shaping adaptive immune responses towards bacterial-derived constituents.", "type": "yesno", "id": "57091eefcf1c325851000016", "snippets": [{"offsetInBeginSection": 14, "offsetInEndSection": 73, "text": "Nod1 and Nod2 control bacterial infections and inflammation ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17690884", "endSection": "title"}, {"offsetInBeginSection": 246, "offsetInEndSection": 370, "text": "The Nod proteins Nod1 and Nod2 are two NLR family members that trigger immune defense in response to bacterial peptidoglycan ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17690884", "endSection": "abstract"}, {"offsetInBeginSection": 372, "offsetInEndSection": 568, "text": "Nod proteins fight off bacterial infections by stimulating proinflammatory signaling and cytokine networks and by inducing antimicrobial effectors, such as nitric oxide and antimicrobial peptides. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17690884", "endSection": "abstract"}, {"offsetInBeginSection": 569, "offsetInEndSection": 680, "text": "Nod1 is also critically implicated in shaping adaptive immune responses towards bacterial-derived constituents. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17690884", "endSection": "abstract"}, {"offsetInBeginSection": 909, "offsetInEndSection": 1035, "text": "Together, Nod1 and Nod2 represent central players in the control of immune responses to bacterial infections and inflammation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17690884", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "The innate immune receptor Nod1 protects the intestine from inflammation-induced tumorigenesis. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074871", "endSection": "title"}, {"offsetInBeginSection": 677, "offsetInEndSection": 1093, "text": "we show that Nod1 deficiency results in the increased development of both colitis-associated and Apc tumor suppressor-related colon tumors. In the absence of Nod1 signaling, there is a greater disruption of the intestinal epithelial cell barrier due to chemically induced injury as manifested by increased surface epithelial apoptosis early on during chemically induced colitis and increased intestinal permeability. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074871", "endSection": "abstract"}, {"offsetInBeginSection": 1094, "offsetInEndSection": 1282, "text": "The increased intestinal permeability is associated with enhanced inflammatory cytokine production and epithelial cell proliferation in Nod1-deficient mice as compared with wild-type mice. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074871", "endSection": "abstract"}, {"offsetInBeginSection": 1283, "offsetInEndSection": 1560, "text": "Depletion of the gut microbiota suppressed tumor development in Nod1-deficient mice, thus highlighting a link between the commensal bacteria within the intestine and the host innate immune Nod1 signaling pathway in the regulation inflammation-mediated colon cancer development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074871", "endSection": "abstract"}, {"offsetInBeginSection": 969, "offsetInEndSection": 1079, "text": " NOD1 protein is expressed in the eye and promotes ocular inflammation in a dose- and time-dependent fashion. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074813", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "NOD1 expression in the eye and functional contribution to IL-1beta-dependent ocular inflammation in mice ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074813", "endSection": "title"}, {"offsetInBeginSection": 151, "offsetInEndSection": 283, "text": "Polymorphisms in NOD1 are associated with autoinflammatory diseases characterized by uveitis such as Crohn's disease and sarcoidosis ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074813", "endSection": "abstract"}, {"offsetInBeginSection": 285, "offsetInEndSection": 457, "text": "NOD1 is homologous to NOD2, which is responsible for an autosomal dominant form of uveitis. Nonetheless, the role of NOD1 in intraocular inflammation has not been explored. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19074813", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 72, "text": "Nod1 and Nod2 regulation of inflammation in the Salmonella colitis model ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20921147", "endSection": "title"}, {"offsetInBeginSection": 291, "offsetInEndSection": 458, "text": "mice deficient for both Nod1 and Nod2 had attenuated inflammatory pathology, reduced levels of inflammatory cytokines, and increased colonization of the mucosal tissue ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20921147", "endSection": "abstract"}, {"offsetInBeginSection": 1249, "offsetInEndSection": 1400, "text": "The present study has demonstrated an unexpected role of Nod1 in the development of site-specific vascular inflammation, especially coronary arteritis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21330608", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 55, "text": "Nod1 ligands induce site-specific vascular inflammation ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21330608", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "Phenotyping of Nod1/2 double deficient mice and characterization of Nod1/2 in systemic inflammation and associated renal disease ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23259058", "endSection": "title"}, {"offsetInBeginSection": 147, "offsetInEndSection": 270, "text": "The present study analyzed Nod1 and Nod2 double deficient (Nod1/2 DKO) mice under physiological and inflammatory conditions ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23259058", "endSection": "abstract"}, {"offsetInBeginSection": 389, "offsetInEndSection": 510, "text": "Several inflammatory disorders, such as Crohn's disease and asthma, are linked to genetic changes in either Nod1 or Nod2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23259058", "endSection": "abstract"}, {"offsetInBeginSection": 1696, "offsetInEndSection": 1835, "text": "Systematic analysis of Nod1/2 DKO mice revealed a possible role of Nod1/2 in the development of renal disease during systemic inflammation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23259058", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 53, "text": "NOD1 and NOD2 Signaling in Infection and Inflammation ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23162548", "endSection": "title"}, {"offsetInBeginSection": 303, "offsetInEndSection": 396, "text": "NOD1 engagement generates an inflammatory response via activation of NF\u03baB and MAPK pathways. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22870324", "endSection": "abstract"}, {"offsetInBeginSection": 1090, "offsetInEndSection": 1246, "text": "In addition we profile novel inhibitors of RIP2 and NOD1 itself, which specifically inhibit NOD1 ligand induced inflammatory signalling in the vasculature. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22870324", "endSection": "abstract"}, {"offsetInBeginSection": 1428, "offsetInEndSection": 1612, "text": "This data supports the potential utility of NOD1 and RIP2 as therapeutic targets in human disease where vascular inflammation is a clinical feature, such as in sepsis and septic shock. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22870324", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "NOD1 expression elicited by iE-DAP in first trimester human trophoblast cells and its potential role in infection-associated inflammation ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24041848", "endSection": "title"}, {"offsetInBeginSection": 267, "offsetInEndSection": 462, "text": "This study aimed to investigate the expression and function of NOD1 in first trimester trophoblast cells, and evaluate the potential role of trophoblast cells in infection-associated inflammation ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24041848", "endSection": "abstract"}, {"offsetInBeginSection": 1503, "offsetInEndSection": 1686, "text": "NOD1 may have a role in mediating infection-associated inflammation. Once iE-DAP is recognized by NOD1, the inflammatory response may be induced via NOD1-RICK-NF-\u03baB-mediated pathways. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24041848", "endSection": "abstract"}]}, {"body": "Could the Menzerath-Altmann law be proved mathematically trivial in genomes?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/25503672"], "ideal_answer": "The view of Menzerath-Altmann law as inevitable is seriously flawed.Here we review the statistical foundations of that test and consider three non-parametric tests based upon different correlation metrics and one parametric test to evaluate if Z  1/X in genomes.Rather than a fact, Z  1/X is a baseline that real genomes do not meet.The most powerful test is a new non-parametric one based upon the correlation ratio, which is able to reject Z  1/X in nine out of 11 taxonomic groups and detect a borderline group.The most powerful test is a new non-parametric one based upon the correlation ratio, which is able to reject Z  1/X in nine out of 11 taxonomic groups and detect a borderline group.The most powerful test is a new non-parametric one based upon the correlation ratio, which is able to reject Z  1/X in nine out of 11 taxonomic groups and detect a borderline group.The most powerful test is a new non-parametric one based upon the correlation ratio, which is able to reject Z  1/X in nine out of 11 taxonomic groups and detect a borderline group.", "type": "yesno", "id": "56bb1b4eac7ad10019000004", "snippets": [{"offsetInBeginSection": 581, "offsetInEndSection": 1101, "text": "Here we review the statistical foundations of that test and consider three non-parametric tests based upon different correlation metrics and one parametric test to evaluate if Z \u223c 1/X in genomes. The most powerful test is a new non-parametric one based upon the correlation ratio, which is able to reject Z \u223c 1/X in nine out of 11 taxonomic groups and detect a borderline group. Rather than a fact, Z \u223c 1/X is a baseline that real genomes do not meet. The view of Menzerath-Altmann law as inevitable is seriously flawed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25503672", "endSection": "abstract"}]}, {"body": "Is Fibroblast Growth Factor 23 a phosphaturic hormone?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/26131357", "http://www.ncbi.nlm.nih.gov/pubmed/25636143", "http://www.ncbi.nlm.nih.gov/pubmed/25404658", "http://www.ncbi.nlm.nih.gov/pubmed/25380933", "http://www.ncbi.nlm.nih.gov/pubmed/24466013", "http://www.ncbi.nlm.nih.gov/pubmed/24434184", "http://www.ncbi.nlm.nih.gov/pubmed/24991914", "http://www.ncbi.nlm.nih.gov/pubmed/24980542", "http://www.ncbi.nlm.nih.gov/pubmed/25007710"], "ideal_answer": "serum levels of a phosphaturic hormone, fibroblast growth factor 23 (Fgf23),This phosphaturic hormone produced in bones is a risk factor for cardiovascular diseases and thus mortality. circulating phosphaturic hormone fibroblast growth factor-23 levels Fibroblast growth factor (FGF) 23 is one of the most recently discovered FGFs. Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that has recently been identified as a CKD-related factor affecting CRS. the phosphaturic hormone fibroblast growth factor 23 (FGF23) and soluble Klotho with all-cause mortality.In particular, diseases caused by changes in the expression and proteolytic control of the phosphaturic hormone fibroblast growth factor-23 (FGF23) have come to the forefront in terms of directing new models explaining mineral metabolismfibroblast growth factor 23 (FGF23), a phosphaturic hormone and regulator of 1,25(OH)2 vitamin D3 (1,25VitD3).PTH can induce skeletal synthesis of another potent phosphaturic hormone, fibroblast growth factor 23 (FGF23),fibroblast growth factor-23 (FGF23), a bone-derived phosphaturic hormone.", "type": "yesno", "id": "570a5c27cf1c325851000023", "snippets": [{"offsetInBeginSection": 498, "offsetInEndSection": 609, "text": "PTH can induce skeletal synthesis of another potent phosphaturic hormone, fibroblast growth factor 23 (FGF23), ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26131357", "endSection": "abstract"}, {"offsetInBeginSection": 978, "offsetInEndSection": 1114, "text": " Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that has recently been identified as a CKD-related factor affecting CRS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25636143", "endSection": "abstract"}, {"offsetInBeginSection": 1080, "offsetInEndSection": 1148, "text": " circulating phosphaturic hormone fibroblast growth factor-23 levels ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25404658", "endSection": "abstract"}, {"offsetInBeginSection": 11, "offsetInEndSection": 199, "text": " Fibroblast growth factor (FGF) 23 is one of the most recently discovered FGFs. This phosphaturic hormone produced in bones is a risk factor for cardiovascular diseases and thus mortality. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25380933", "endSection": "abstract"}, {"offsetInBeginSection": 68, "offsetInEndSection": 179, "text": "fibroblast growth factor 23 (FGF23), a phosphaturic hormone and regulator of 1,25(OH)2 vitamin D3 (1,25VitD3). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24466013", "endSection": "abstract"}, {"offsetInBeginSection": 295, "offsetInEndSection": 368, "text": "fibroblast growth factor-23 (FGF23), a bone-derived phosphaturic hormone. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24434184", "endSection": "abstract"}, {"offsetInBeginSection": 158, "offsetInEndSection": 264, "text": " the phosphaturic hormone fibroblast growth factor 23 (FGF23) and soluble Klotho with all-cause mortality. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24991914", "endSection": "abstract"}, {"offsetInBeginSection": 476, "offsetInEndSection": 713, "text": "In particular, diseases caused by changes in the expression and proteolytic control of the phosphaturic hormone fibroblast growth factor-23 (FGF23) have come to the forefront in terms of directing new models explaining mineral metabolism ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24980542", "endSection": "abstract"}, {"offsetInBeginSection": 787, "offsetInEndSection": 864, "text": "serum levels of a phosphaturic hormone, fibroblast growth factor 23 (Fgf23), ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25007710", "endSection": "abstract"}]}, {"body": "What molecule is targeted by suvorexant?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/26478806", "http://www.ncbi.nlm.nih.gov/pubmed/25667197", "http://www.ncbi.nlm.nih.gov/pubmed/25533960"], "ideal_answer": "Crystal structure of the human OX2 orexin receptor bound to the insomnia drug suvorexant.Suvorexant is the first DORA to be approved and has demonstrated efficacy at decreasing both time to sleep onset and increasing total sleep time compared with placebo. The human OX2 receptor (OX2R) belongs to the  branch of the rhodopsin family of GPCRs, and can bind to diverse compounds including the native agonist peptides orexin-A and orexin-B and the potent therapeutic inhibitor suvorexant.Suvorexant: a dual orexin receptor antagonist for the treatment of sleep onset and sleep maintenance insomnia.CONCLUSION: Suvorexant is the first dual orexin receptor antagonist approved for the treatment of insomnia.CONCLUSION: Suvorexant is the first dual orexin receptor antagonist approved for the treatment of insomnia.CONCLUSION: Suvorexant is the first dual orexin receptor antagonist approved for the treatment of insomnia.CONCLUSION: Suvorexant is the first dual orexin receptor antagonist approved for the treatment of insomnia.CONCLUSION: Suvorexant is the first dual orexin receptor antagonist approved for the treatment of insomnia.", "type": "factoid", "id": "56c1f003ef6e394741000039", "snippets": [{"offsetInBeginSection": 605, "offsetInEndSection": 773, "text": "Suvorexant is the first DORA to be approved and has demonstrated efficacy at decreasing both time to sleep onset and increasing total sleep time compared with placebo. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26478806", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "Suvorexant: a dual orexin receptor antagonist for the treatment of sleep onset and sleep maintenance insomnia. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25667197", "endSection": "title"}, {"offsetInBeginSection": 1221, "offsetInEndSection": 1329, "text": "CONCLUSION: Suvorexant is the first dual orexin receptor antagonist approved for the treatment of insomnia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25667197", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 89, "text": "Crystal structure of the human OX2 orexin receptor bound to the insomnia drug suvorexant. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25533960", "endSection": "title"}, {"offsetInBeginSection": 362, "offsetInEndSection": 594, "text": " The human OX2 receptor (OX2R) belongs to the \u03b2 branch of the rhodopsin family of GPCRs, and can bind to diverse compounds including the native agonist peptides orexin-A and orexin-B and the potent therapeutic inhibitor suvorexant. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25533960", "endSection": "abstract"}]}, {"body": "In which genomic regions are Alu enriched?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/23420552", "http://www.ncbi.nlm.nih.gov/pubmed/12777511", "http://www.ncbi.nlm.nih.gov/pubmed/6165649", "http://www.ncbi.nlm.nih.gov/pubmed/2716062", "http://www.ncbi.nlm.nih.gov/pubmed/11884141", "http://www.ncbi.nlm.nih.gov/pubmed/12832639"], "ideal_answer": "This bias in Alu distribution is independent of the effect of Alu density of the flanking genomic region and is also not affected by the GC content of the gene and its upstream and downstream regions.This study suggests that the majority of Alu insertions in primate genomes are the products of unique evolutionary events.In contrast, they are significantly fewer in genes coding for information pathway components as well as structural proteins.There are regions such as the four homeobox gene clusters, which are nearly devoid of these repeats that contrast with repeat dense regions in other transcriptionally active regions of the genome.The relative proportions of Alu subfamilies (Alu J, Alu S, and Alu Y) are not significantly different in genes with high Alu density belonging to the functional categories of transport, metabolism, and signaling.Sequence analysis demonstrated these \"young\" Alu insertions represented gene conversion events of pre-existing ancient Alu elements or independent parallel insertions of older Alu elements in the same genomic region.", "type": "list", "id": "570921e4cf1c325851000017", "snippets": [{"offsetInBeginSection": 121, "offsetInEndSection": 317, "text": "There are regions such as the four homeobox gene clusters, which are nearly devoid of these repeats that contrast with repeat dense regions in other transcriptionally active regions of the genome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12832639", "endSection": "abstract"}, {"offsetInBeginSection": 427, "offsetInEndSection": 664, "text": "These elements are more clustered in genes which are involved in metabolism, transport, and signaling processes. In contrast, they are significantly fewer in genes coding for information pathway components as well as structural proteins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12832639", "endSection": "abstract"}, {"offsetInBeginSection": 665, "offsetInEndSection": 865, "text": "This bias in Alu distribution is independent of the effect of Alu density of the flanking genomic region and is also not affected by the GC content of the gene and its upstream and downstream regions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12832639", "endSection": "abstract"}, {"offsetInBeginSection": 866, "offsetInEndSection": 1078, "text": "The relative proportions of Alu subfamilies (Alu J, Alu S, and Alu Y) are not significantly different in genes with high Alu density belonging to the functional categories of transport, metabolism, and signaling. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12832639", "endSection": "abstract"}, {"offsetInBeginSection": 1199, "offsetInEndSection": 1332, "text": "We suggest that Alu elements might be involved in regulatory mechanisms and are therefore differentially selected in primate genomes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12832639", "endSection": "abstract"}, {"offsetInBeginSection": 449, "offsetInEndSection": 666, "text": "Sequence analysis demonstrated these \"young\" Alu insertions represented gene conversion events of pre-existing ancient Alu elements or independent parallel insertions of older Alu elements in the same genomic region. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11884141", "endSection": "abstract"}, {"offsetInBeginSection": 1049, "offsetInEndSection": 1171, "text": "This study suggests that the majority of Alu insertions in primate genomes are the products of unique evolutionary events. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11884141", "endSection": "abstract"}, {"offsetInBeginSection": 577, "offsetInEndSection": 745, "text": "Our screening of the Alu insertion loci also resulted in the recovery of several \"young\" Alu elements that resided at orthologous positions in nonhuman primate genomes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12777511", "endSection": "abstract"}]}, {"body": "Describe the usefulness of the SPIKE database in human signaling pathways", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/21097778"], "ideal_answer": "SPIKE (Signaling Pathways Integrated Knowledge Engine; http://www.cs.tau.ac.il/&~spike/) is a database for achieving this goal, containing highly curated interactions for particular human pathways, along with literature-referenced information on the nature of each interaction.The database is accompanied by a stand-alone software tool for analysis and dynamic visualization of pathways.To make database population and pathway comprehension straightforward, a simple yet informative data model is used, and pathways are laid out as maps that reflect the curators understanding and make the utilization of the pathways easy.The database currently focuses primarily on pathways describing DNA damage response, cell cycle, programmed cell death and hearing related pathways.The complete database and the individual maps are freely exportable in several formats.The rapid accumulation of knowledge on biological signaling pathways and their regulatory mechanisms has highlighted the need for specific repositories that can store, organize and allow retrieval of pathway information in a way that will be useful for the research community.Pathways are regularly updated, and additional pathways are gradually added.", "type": "summary", "id": "56bdc452a36a056b3d000001", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 1217, "text": "The rapid accumulation of knowledge on biological signaling pathways and their regulatory mechanisms has highlighted the need for specific repositories that can store, organize and allow retrieval of pathway information in a way that will be useful for the research community. SPIKE (Signaling Pathways Integrated Knowledge Engine; http://www.cs.tau.ac.il/&~spike/) is a database for achieving this goal, containing highly curated interactions for particular human pathways, along with literature-referenced information on the nature of each interaction. To make database population and pathway comprehension straightforward, a simple yet informative data model is used, and pathways are laid out as maps that reflect the curator\u2019s understanding and make the utilization of the pathways easy. The database currently focuses primarily on pathways describing DNA damage response, cell cycle, programmed cell death and hearing related pathways. Pathways are regularly updated, and additional pathways are gradually added. The complete database and the individual maps are freely exportable in several formats. The database is accompanied by a stand-alone software tool for analysis and dynamic visualization of pathways. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21097778", "endSection": "abstract"}]}, {"body": "List sclerostin interaction partners.", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/22206666", "http://www.ncbi.nlm.nih.gov/pubmed/20951118", "http://www.ncbi.nlm.nih.gov/pubmed/17002572", "http://www.ncbi.nlm.nih.gov/pubmed/15199066"], "ideal_answer": "We identified an interaction between sclerostin and the carboxyl-terminal portion of the receptor tyrosine-protein kinase erbB-3.Bone density ligand, Sclerostin, directly interacts with LRP5 but not LRP5G171V to modulate Wnt activity.We show that recombinant sclerostin and noggin bound to each other with high affinity (K(D) = 2.92 nm). Several previously unidentified full-length sclerostin-interacting proteins such as alkaline phosphatase, carbonic anhydrase, gremlin-1, fetuin A, midkine, annexin A1 and A2, and collagen 1, which have established roles in bone formation or resorption processes, were bound to the sclerostin-MBP amylose resin but not to the MBP amylose resin.Several peptides derived from proteins such as Phex, asporin and follistatin that regulate bone metabolism also bound sclerostin.Sclerostin, SOST, the gene affected in this disease, has been postulated to exert its activity by functioning as a BMP antagonist.Other full-length sclerostin-interacting proteins such as casein kinase II and secreted frizzled related protein 4 that modulate Wnt signaling were identified.", "type": "list", "id": "570a6d03cf1c325851000025", "snippets": [{"offsetInBeginSection": 641, "offsetInEndSection": 1277, "text": " Several previously unidentified full-length sclerostin-interacting proteins such as alkaline phosphatase, carbonic anhydrase, gremlin-1, fetuin A, midkine, annexin A1 and A2, and collagen \u03b11, which have established roles in bone formation or resorption processes, were bound to the sclerostin-MBP amylose resin but not to the MBP amylose resin. Other full-length sclerostin-interacting proteins such as casein kinase II and secreted frizzled related protein 4 that modulate Wnt signaling were identified. Several peptides derived from proteins such as Phex, asporin and follistatin that regulate bone metabolism also bound sclerostin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22206666", "endSection": "abstract"}, {"offsetInBeginSection": 321, "offsetInEndSection": 450, "text": "We identified an interaction between sclerostin and the carboxyl-terminal portion of the receptor tyrosine-protein kinase erbB-3. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20951118", "endSection": "abstract"}, {"offsetInBeginSection": 419, "offsetInEndSection": 690, "text": "Sclerostin, SOST, the gene affected in this disease, has been postulated to exert its activity by functioning as a BMP antagonist. However, recent evidence indicates that SOST is highly related to Wise, which can also modulate the Wnt pathway by binding to LRP5 and LRP6. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17002572", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Bone density ligand, Sclerostin, directly interacts with LRP5 but not LRP5G171V to modulate Wnt activity. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17002572", "endSection": "title"}, {"offsetInBeginSection": 197, "offsetInEndSection": 300, "text": "We show that recombinant sclerostin and noggin bound to each other with high affinity (K(D) = 2.92 nm). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15199066", "endSection": "abstract"}]}, {"body": "What is Tarlov Cyst?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/25216402", "http://www.ncbi.nlm.nih.gov/pubmed/25191117", "http://www.ncbi.nlm.nih.gov/pubmed/23400656", "http://www.ncbi.nlm.nih.gov/pubmed/21830055"], "ideal_answer": "A case of symptomatic cervical perineural (Tarlov) cyst: clinical manifestation and management.Tarlov cyst syndrome is a rare, often asymptomatic disorder, characterised by isolated or multiple nerve-root cysts, usually occurring in the sacral spine, near the dorsal root ganglion, between the perineurium and endoneurium.She underwent ultrasound, CT, and eventually MRI evaluations that led to the diagnosis of a giant (6.7  6.4  6.6 cm) Tarlov cyst originating from the right S-2 nerve root sleeve/sacral foramen with intrapelvic extension.TCs are typically benign, asymptomatic lesions that can simply be monitored.Perineural (Tarlov) cysts are most often found in the sacral region and are rare in the cervical spine.We report here a case of multiloculated disseminated perineural or Tarlov cysts (TCs).Tarlov or perineural cysts are nerve root cysts found most commonly at the sacral spine level arising between covering layers of the perineurium and the endoneurium near the dorsal root ganglion and are usually asymptomatic.", "type": "summary", "id": "56c1d848ef6e39474100002f", "snippets": [{"offsetInBeginSection": 753, "offsetInEndSection": 975, "text": "She underwent ultrasound, CT, and eventually MRI evaluations that led to the diagnosis of a giant (6.7 \u00d7 6.4 \u00d7 6.6 cm) Tarlov cyst originating from the right S-2 nerve root sleeve/sacral foramen with intrapelvic extension. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25216402", "endSection": "abstract"}, {"offsetInBeginSection": 174, "offsetInEndSection": 261, "text": "We report here a case of multiloculated disseminated perineural or Tarlov cysts (TCs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25191117", "endSection": "abstract"}, {"offsetInBeginSection": 865, "offsetInEndSection": 941, "text": "TCs are typically benign, asymptomatic lesions that can simply be monitored. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25191117", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 228, "text": "Tarlov cyst syndrome is a rare, often asymptomatic disorder, characterised by isolated or multiple nerve-root cysts, usually occurring in the sacral spine, near the dorsal root ganglion, between the perineurium and endoneurium. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23400656", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Perineural (Tarlov) cysts are most often found in the sacral region and are rare in the cervical spine. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21830055", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "A case of symptomatic cervical perineural (Tarlov) cyst: clinical manifestation and management. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21830055", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "Tarlov or perineural cysts are nerve root cysts found most commonly at the sacral spine level arising between covering layers of the perineurium and the endoneurium near the dorsal root ganglion and are usually asymptomatic. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22787551", "endSection": "abstract"}]}, {"body": "What is the molecular function of the Chd1 protein?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/21623345", "http://www.ncbi.nlm.nih.gov/pubmed/16468993", "http://www.ncbi.nlm.nih.gov/pubmed/16606615", "http://www.ncbi.nlm.nih.gov/pubmed/16263726", "http://www.ncbi.nlm.nih.gov/pubmed/15647753"], "ideal_answer": "Here we identify the chromatin remodelling protein Chd1 (chromo-ATPase/helicase-DNA binding domain 1) as a component of SAGA and SLIKhuman CHD1 binds to methylated H3K4 in a manner that requires both of its tandem chromodomains.the lack of Chd1 combined with the absence of Isw1 and Isw2 impairs nucleosome spacing along the ADH2 gene, and genome-wide in S. cerevisiaeThe ATP-dependent chromatin-remodelling enzyme Chd1 is a 168-kDa protein consisting of a double chromodomain, Snf2-related ATPase domain, and a C-terminal DNA-binding domain.Our findings indicate that yeast and human CHD1 have diverged in their ability to discriminate covalently modified histones and link histone modification-recognition and non-covalent chromatin remodeling activities within a single human protein.Through inclusion of Chd1 sequences in homology searches SLIDE domains were identified in CHD6-9 proteins.However, a key difference is that the Isw1a, Isw2, and Chd1 enzymes are unable to move nucleosomes to positions closer than 15 bp from a DNA end, whereas Isw1b can.", "type": "factoid", "id": "57092332cf1c325851000018", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 95, "text": "The DNA-binding domain of the Chd1 chromatin-remodelling enzyme contains SANT and SLIDE domains ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21623345", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 174, "text": "The ATP-dependent chromatin-remodelling enzyme Chd1 is a 168-kDa protein consisting of a double chromodomain, Snf2-related ATPase domain, and a C-terminal DNA-binding domain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21623345", "endSection": "abstract"}, {"offsetInBeginSection": 449, "offsetInEndSection": 728, "text": "The presence of these domains in ISWI and Chd1 chromatin-remodelling enzymes may provide a means of efficiently harnessing the action of the Snf2-related ATPase domain for the purpose of nucleosome spacing and provide an explanation for partial redundancy between these proteins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21623345", "endSection": "abstract"}, {"offsetInBeginSection": 694, "offsetInEndSection": 827, "text": "Here we identify the chromatin remodelling protein Chd1 (chromo-ATPase/helicase-DNA binding domain 1) as a component of SAGA and SLIK ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15647753", "endSection": "abstract"}, {"offsetInBeginSection": 856, "offsetInEndSection": 1012, "text": "one of the two chromodomains of Chd1 specifically interacts with the methylated lysine 4 mark on histone H3 that is associated with transcriptional activity ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15647753", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 121, "text": "Human but not yeast CHD1 binds directly and selectively to histone H3 methylated at lysine 4 via its tandem chromodomains ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16263726", "endSection": "title"}, {"offsetInBeginSection": 196, "offsetInEndSection": 375, "text": "In the current study, we identify human CHD1, an ATP-dependent chromatin remodeling protein, as a factor that directly and selectively recognizes histone H3 methylated on lysine 4 ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16263726", "endSection": "abstract"}, {"offsetInBeginSection": 597, "offsetInEndSection": 692, "text": "human CHD1 binds to methylated H3K4 in a manner that requires both of its tandem chromodomains. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16263726", "endSection": "abstract"}, {"offsetInBeginSection": 789, "offsetInEndSection": 1034, "text": "Our findings indicate that yeast and human CHD1 have diverged in their ability to discriminate covalently modified histones and link histone modification-recognition and non-covalent chromatin remodeling activities within a single human protein. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16263726", "endSection": "abstract"}, {"offsetInBeginSection": 235, "offsetInEndSection": 397, "text": "We find that the yeast Isw1a, Isw2, and Chd1 enzymes preferentially move nucleosomes toward more central locations on short DNA fragments whereas Isw1b does not. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16606615", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 91, "text": "Analysis of nucleosome repositioning by yeast ISWI and Chd1 chromatin remodeling complexes. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16606615", "endSection": "title"}, {"offsetInBeginSection": 555, "offsetInEndSection": 719, "text": "However, a key difference is that the Isw1a, Isw2, and Chd1 enzymes are unable to move nucleosomes to positions closer than 15 bp from a DNA end, whereas Isw1b can. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16606615", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 103, "text": "The ISWI and CHD1 chromatin remodelling activities influence ADH2 expression and chromatin organization ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16468993", "endSection": "title"}, {"offsetInBeginSection": 794, "offsetInEndSection": 1002, "text": "Here we show that the absence of the Isw1 and Chd1 ATP-dependent chromatin remodelling activities delays the maximal expression of ADH2 without impairing the chromatin remodelling that occurs upon activation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16468993", "endSection": "abstract"}, {"offsetInBeginSection": 1494, "offsetInEndSection": 1701, "text": "Thus, the ISWI and Chd1 remodelling factors are not only involved in transcription-related chromatin remodelling, but also are required to maintain a specific chromatin configuration across the yeast genome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16468993", "endSection": "abstract"}, {"offsetInBeginSection": 1352, "offsetInEndSection": 1492, "text": "the lack of Chd1 combined with the absence of Isw1 and Isw2 impairs nucleosome spacing along the ADH2 gene, and genome-wide in S. cerevisiae ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16468993", "endSection": "abstract"}, {"offsetInBeginSection": 884, "offsetInEndSection": 991, "text": "Through inclusion of Chd1 sequences in homology searches SLIDE domains were identified in CHD6-9 proteins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21623345", "endSection": "abstract"}]}, {"body": "Which eye condition is managed by the athens protocol?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/24763473", "http://www.ncbi.nlm.nih.gov/pubmed/22347790"], "ideal_answer": "Keratoconus management: long-term stability of topography-guided normalization combined with high-fluence CXL stabilization (the Athens Protocol).This protocol was used for the management of cornea blindness due to severe corneal scarring.The Athens Protocol to arrest keratectasia progression and improve corneal regularity demonstrates safe and effective results as a keratoconus management option.Progressive potential for long-term flattening validates using caution in the surface normalization to avoid overcorrection. To evaluate the safety and efficacy of combined transepithelial topography-guided photorefractive keratectomy (PRK) therapeutic remodeling, combined with same-day, collagen cross-linking (CXL).The management of cornea blindness from severe corneal scarring, with the Athens Protocol (transepithelial topography-guided PRK therapeutic remodeling, combined with same-day, collagen cross-linking).The management of cornea blindness from severe corneal scarring, with the Athens Protocol (transepithelial topography-guided PRK therapeutic remodeling, combined with same-day, collagen cross-linking).The management of cornea blindness from severe corneal scarring, with the Athens Protocol (transepithelial topography-guided PRK therapeutic remodeling, combined with same-day, collagen cross-linking).", "type": "factoid", "id": "56bdc79bef6e394741000001", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 146, "text": "Keratoconus management: long-term stability of topography-guided normalization combined with high-fluence CXL stabilization (the Athens Protocol). ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24763473", "endSection": "title"}, {"offsetInBeginSection": 1624, "offsetInEndSection": 1910, "text": "The Athens Protocol to arrest keratectasia progression and improve corneal regularity demonstrates safe and effective results as a keratoconus management option. Progressive potential for long-term flattening validates using caution in the surface normalization to avoid overcorrection. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24763473", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 201, "text": "The management of cornea blindness from severe corneal scarring, with the Athens Protocol (transepithelial topography-guided PRK therapeutic remodeling, combined with same-day, collagen cross-linking). ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22347790", "endSection": "title"}, {"offsetInBeginSection": 8, "offsetInEndSection": 296, "text": " To evaluate the safety and efficacy of combined transepithelial topography-guided photorefractive keratectomy (PRK) therapeutic remodeling, combined with same-day, collagen cross-linking (CXL). This protocol was used for the management of cornea blindness due to severe corneal scarring. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22347790", "endSection": "abstract"}]}, {"body": "What is membrane scission?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/25784211", "http://www.ncbi.nlm.nih.gov/pubmed/25783003", "http://www.ncbi.nlm.nih.gov/pubmed/25353823", "http://www.ncbi.nlm.nih.gov/pubmed/25429432", "http://www.ncbi.nlm.nih.gov/pubmed/24440309", "http://www.ncbi.nlm.nih.gov/pubmed/25202029", "http://www.ncbi.nlm.nih.gov/pubmed/24102355", "http://www.ncbi.nlm.nih.gov/pubmed/25664996", "http://www.ncbi.nlm.nih.gov/pubmed/24016602", "http://www.ncbi.nlm.nih.gov/pubmed/24753582", "http://www.ncbi.nlm.nih.gov/pubmed/24878737", "http://www.ncbi.nlm.nih.gov/pubmed/23252497", "http://www.ncbi.nlm.nih.gov/pubmed/23297414", "http://www.ncbi.nlm.nih.gov/pubmed/24099087"], "ideal_answer": "membrane scission protein dynamin-2. Finally, a membrane scission event must occur to release the free virion Its role in endocytosis may be mediated by its reported interaction with dynamin 2, a 100 kDa GTPase that polymerizes around the necks of budding vesicles and catalyzes membrane scissionESCRT-III is the final complex in the pathway that assembles on endosomes and executes membrane scission of intraluminal vesicles. Furthermore, GTP-dependent membrane scission by dynamin was dramatically elevated by BAR domain proteins.Because the neck's radius is, in general, finite, membrane scission and the consequent pinching off of the vesicle can only occur if it is narrowed to permit the necessary membrane topological reformation. Force produced by actin similarly contributes in membrane scission in endocytosis or Golgi remodeling.Dynamin recruitment and membrane scission at the neck of a clathrin-coated pit.few can mediate membrane scission to complete the budding process.Dynamin-2 is a pleiotropic GTPase whose best-known function is related to membrane scission during vesicle budding from the plasma or Golgi membranes.", "type": "summary", "id": "570a7594cf1c325851000026", "snippets": [{"offsetInBeginSection": 161, "offsetInEndSection": 341, "text": "To promote membrane scission, dynamin proteins polymerize, wrap around, and constrict the membrane; however, the mechanism underlying their role in membrane fusion remains unclear. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25784211", "endSection": "abstract"}, {"offsetInBeginSection": 276, "offsetInEndSection": 463, "text": " Its role in endocytosis may be mediated by its reported interaction with dynamin 2, a 100 kDa GTPase that polymerizes around the necks of budding vesicles and catalyzes membrane scission ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25783003", "endSection": "abstract"}, {"offsetInBeginSection": 135, "offsetInEndSection": 340, "text": "Because the neck's radius is, in general, finite, membrane scission and the consequent pinching off of the vesicle can only occur if it is narrowed to permit the necessary membrane topological reformation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25353823", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 79, "text": "Dynamin recruitment and membrane scission at the neck of a clathrin-coated pit. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25232009", "endSection": "title"}, {"offsetInBeginSection": 147, "offsetInEndSection": 277, "text": "ESCRT-III is the final complex in the pathway that assembles on endosomes and executes membrane scission of intraluminal vesicles. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24440309", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 127, "text": "The scission of biological membranes is facilitated by a variety of protein complexes that bind and manipulate lipid bilayers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25202029", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 151, "text": "Dynamin-2 is a pleiotropic GTPase whose best-known function is related to membrane scission during vesicle budding from the plasma or Golgi membranes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24102355", "endSection": "abstract"}, {"offsetInBeginSection": 207, "offsetInEndSection": 310, "text": " Force produced by actin similarly contributes in membrane scission in endocytosis or Golgi remodeling. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25664996", "endSection": "abstract"}, {"offsetInBeginSection": 12, "offsetInEndSection": 154, "text": "Dynamin 2 (Dyn2) is a ~100kDa GTPase that assembles around the necks of nascent endocytic and Golgi vesicles and catalyzes membrane scission. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24016602", "endSection": "abstract"}, {"offsetInBeginSection": 797, "offsetInEndSection": 833, "text": "membrane scission protein dynamin-2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24753582", "endSection": "abstract"}, {"offsetInBeginSection": 584, "offsetInEndSection": 657, "text": " Finally, a membrane scission event must occur to release the free virion ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23252497", "endSection": "abstract"}, {"offsetInBeginSection": 781, "offsetInEndSection": 888, "text": " Furthermore, GTP-dependent membrane scission by dynamin was dramatically elevated by BAR domain proteins. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23297414", "endSection": "abstract"}, {"offsetInBeginSection": 209, "offsetInEndSection": 275, "text": "few can mediate membrane scission to complete the budding process. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24099087", "endSection": "abstract"}]}, {"body": "What is evaluated with the Hydrocephalus Outcome Questionnaire?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/21778677", "http://www.ncbi.nlm.nih.gov/pubmed/21961548", "http://www.ncbi.nlm.nih.gov/pubmed/21193992", "http://www.ncbi.nlm.nih.gov/pubmed/19714338", "http://www.ncbi.nlm.nih.gov/pubmed/20593981", "http://www.ncbi.nlm.nih.gov/pubmed/18754895", "http://www.ncbi.nlm.nih.gov/pubmed/17644917", "http://www.ncbi.nlm.nih.gov/pubmed/18459898", "http://www.ncbi.nlm.nih.gov/pubmed/16426953", "http://www.ncbi.nlm.nih.gov/pubmed/16238072", "http://www.ncbi.nlm.nih.gov/pubmed/15835099", "http://www.ncbi.nlm.nih.gov/pubmed/15835100"], "ideal_answer": "An instrument to measure the health status in children with hydrocephalus: the Hydrocephalus Outcome Questionnaire.Patients completed lifestyle questionnaires, the hydrocephalus outcome questionnaire (HOQ) and underwent cognitive testing.The HOQ is a simple and very useful measurement for determining outcome in pediatric hydrocephalus.These include general outcome measures such as the Pediatric Evaluation of Disability Inventory and the Functional Independence Measure for Children, which measure physical function and independence in chronically ill and disabled children as well as disease-specific measures for hydrocephalus (Hydrocephalus Outcome Questionnaire), cerebral palsy (gross motor function and performance measures), head injury (Pediatric Cerebral Performance Category and Children's Coma Scale), and oncology (Pediatric Cancer Quality-of-Life Inventory).Measures of QOL were the Hydrocephalus Outcome Questionnaire and the Health Utilities Index Mark 3.In older children with hydrocephalus, the cHOQ appears to be a scientifically reliable means of assessing long-term outcome.We sought to describe the natural history of this disorder, specifically its clinical presentation, disease course and long-term health status impact using the validated, disease-specific Hydrocephalus Outcome Questionnaire (HOQ)", "type": "summary", "id": "56c1d84aef6e394741000030", "snippets": [{"offsetInBeginSection": 166, "offsetInEndSection": 395, "text": "We sought to describe the natural history of this disorder, specifically its clinical presentation, disease course and long-term health status impact using the validated, disease-specific Hydrocephalus Outcome Questionnaire (HOQ) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21778677", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 242, "text": "OBJECT: The Hydrocephalus Outcome Questionnaire (HOQ) is an established means of measuring quality of life, but the cognitive component of this questionnaire has never been formally compared with gold-standard neuropsychological test scores. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21961548", "endSection": "abstract"}, {"offsetInBeginSection": 467, "offsetInEndSection": 591, "text": "Patients completed lifestyle questionnaires, the hydrocephalus outcome questionnaire (HOQ) and underwent cognitive testing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21193992", "endSection": "abstract"}, {"offsetInBeginSection": 507, "offsetInEndSection": 607, "text": "Measures of QOL were the Hydrocephalus Outcome Questionnaire and the Health Utilities Index Mark 3. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19714338", "endSection": "abstract"}, {"offsetInBeginSection": 339, "offsetInEndSection": 604, "text": "METHODS: The families of children between 5 and 18 years of age with previously treated hydrocephalus at 3 Canadian pediatric neurosurgery centers completed measures of QOL: the Hydrocephalus Outcome Questionnaire (HOQ) and the Health Utilities Index Mark 3 (HUI3). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20593981", "endSection": "abstract"}, {"offsetInBeginSection": 1160, "offsetInEndSection": 1285, "text": "In older children with hydrocephalus, the cHOQ appears to be a scientifically reliable means of assessing long-term outcome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18754895", "endSection": "abstract"}, {"offsetInBeginSection": 1325, "offsetInEndSection": 1424, "text": "The HOQ is a simple and very useful measurement for determining outcome in pediatric hydrocephalus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17644917", "endSection": "abstract"}, {"offsetInBeginSection": 109, "offsetInEndSection": 322, "text": "The authors' aim was to quantify the QOL for children with hydrocephalus and identify predictors of long-term outcome, using a reliable and validated outcome measure: the Hydrocephalus Outcome Questionnaire (HOQ). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18459898", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "OBJECTIVE: To compare three separate methods for establishing interpretability for a health status measure, the Hydrocephalus Outcome Questionnaire (HOQ). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16426953", "endSection": "abstract"}, {"offsetInBeginSection": 750, "offsetInEndSection": 1287, "text": "These include general outcome measures such as the Pediatric Evaluation of Disability Inventory and the Functional Independence Measure for Children, which measure physical function and independence in chronically ill and disabled children as well as disease-specific measures for hydrocephalus (Hydrocephalus Outcome Questionnaire), cerebral palsy (gross motor function and performance measures), head injury (Pediatric Cerebral Performance Category and Children's Coma Scale), and oncology (Pediatric Cancer Quality-of-Life Inventory). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16238072", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "An instrument to measure the health status in children with hydrocephalus: the Hydrocephalus Outcome Questionnaire. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15835099", "endSection": "title"}, {"offsetInBeginSection": 198, "offsetInEndSection": 410, "text": " The authors developed a quantitative health status measure, the Hydrocephalus Outcome Questionnaire (HOQ), designed specifically for children with hydrocephalus, which can be completed by the children's parents. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15835099", "endSection": "abstract"}, {"offsetInBeginSection": 1745, "offsetInEndSection": 1959, "text": "CONCLUSIONS: The HOQ for children with hydrocephalus demonstrated excellent reliability and validity properties. This tool will be valuable for a wide range of clinical research projects in pediatric hydrocephalus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15835099", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 189, "text": "OBJECT: In the preceding article, the authors described the Hydrocephalus Outcome Questionnaire (HOQ), a simple, reliable, and valid measure of health status in children with hydrocephalus. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15835100", "endSection": "abstract"}]}, {"body": "How does long-range epigenetic silencing (LRES) occur?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/21098650", "http://www.ncbi.nlm.nih.gov/pubmed/21737484", "http://www.ncbi.nlm.nih.gov/pubmed/17099711", "http://www.ncbi.nlm.nih.gov/pubmed/20736368", "http://www.ncbi.nlm.nih.gov/pubmed/20173741", "http://www.ncbi.nlm.nih.gov/pubmed/20442245", "http://www.ncbi.nlm.nih.gov/pubmed/19956686", "http://www.ncbi.nlm.nih.gov/pubmed/17613553", "http://www.ncbi.nlm.nih.gov/pubmed/22249255", "http://www.ncbi.nlm.nih.gov/pubmed/24035705"], "ideal_answer": "The long-range epigenetic silencing (LRES) can be a frequent occurrence throughout the human genome.Loss of tumour suppressor gene function can occur as a result of epigenetic silencing of large chromosomal regions, referred to as long-range epigenetic silencing (LRES), and genome-wide analyses have revealed that LRES is present in many cancer typesThis demonstrates that long-range epigenetic silencing (LRES) occurs in developmental tumors as well as in adult tumors.Ikaros hypermethylation occurred in the context of a novel long-range epigenetic silencing (LRES) region.By creating an integrated prostate cancer epigenome map using tiling arrays, we show that contiguous regions of gene suppression commonly occur through long-range epigenetic silencing (LRES).Discrete boundaries of the PCDH domain are delimited by abrupt changes in histone modifications; unmethylated genes flanking the LRES are associated with permissive marks which are absent from methylated genes within the domain.Malignant regression of cancer cells by in vitro differentiation resulted in partial reversion of LRES and gain of CTCF binding.", "type": "summary", "id": "57092635cf1c325851000019", "snippets": [{"offsetInBeginSection": 121, "offsetInEndSection": 296, "text": "Long Range Epigenetic Silencing (LRES) is a mechanism of gene inactivation that affects multiple contiguous CpG islands and has been described in different human cancer types. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24035705", "endSection": "abstract"}, {"offsetInBeginSection": 648, "offsetInEndSection": 900, "text": "We demonstrate that LRES also occurs in murine cancer in vivo and mimics the molecular features of the human phenomenon, namely, downregulation of gene expression, acquisition of inactive histone marks, and DNA hypermethylation of specific CpG islands. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24035705", "endSection": "abstract"}, {"offsetInBeginSection": 1517, "offsetInEndSection": 1646, "text": "Malignant regression of cancer cells by in vitro differentiation resulted in partial reversion of LRES and gain of CTCF binding. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24035705", "endSection": "abstract"}, {"offsetInBeginSection": 1663, "offsetInEndSection": 1899, "text": "genes in LRES regions are plastically regulated in cell differentiation and hyperproliferation, but are constrained to a coordinated repression by abolishing boundaries and the autonomous regulation of chromatin domains in cancer cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24035705", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 251, "text": "Loss of tumour suppressor gene function can occur as a result of epigenetic silencing of large chromosomal regions, referred to as long-range epigenetic silencing (LRES), and genome-wide analyses have revealed that LRES is present in many cancer types ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22249255", "endSection": "abstract"}, {"offsetInBeginSection": 647, "offsetInEndSection": 897, "text": " Epigenetic gene silencing has always been envisaged as a local event silencing discrete genes, but recent data now indicates that large regions of chromosomes can be co-coordinately suppressed; a process termed long range epigenetic silencing (LRES) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17613553", "endSection": "abstract"}, {"offsetInBeginSection": 899, "offsetInEndSection": 1290, "text": "LRES can span megabases of DNA and involves broad heterochromatin formation accompanied by hypermethylation of clusters of contiguous CpG islands within the region. It is not clear if LRES is initiated by one critical gene target that spreads and conscripts innocent bystanders, analogous to large genetic deletions or if coordinate silencing of multiple genes is important in carcinogenesis ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17613553", "endSection": "abstract"}, {"offsetInBeginSection": 605, "offsetInEndSection": 725, "text": "This demonstrates that long-range epigenetic silencing (LRES) occurs in developmental tumors as well as in adult tumors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19956686", "endSection": "abstract"}, {"offsetInBeginSection": 1069, "offsetInEndSection": 1297, "text": "Discrete boundaries of the PCDH domain are delimited by abrupt changes in histone modifications; unmethylated genes flanking the LRES are associated with permissive marks which are absent from methylated genes within the domain. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19956686", "endSection": "abstract"}, {"offsetInBeginSection": 234, "offsetInEndSection": 335, "text": "The long-range epigenetic silencing (LRES) can be a frequent occurrence throughout the human genome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20442245", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "Consolidation of the cancer genome into domains of repressive chromatin by long-range epigenetic silencing (LRES) reduces transcriptional plasticity. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20173741", "endSection": "title"}, {"offsetInBeginSection": 145, "offsetInEndSection": 336, "text": "By creating an integrated prostate cancer epigenome map using tiling arrays, we show that contiguous regions of gene suppression commonly occur through long-range epigenetic silencing (LRES). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20173741", "endSection": "abstract"}, {"offsetInBeginSection": 337, "offsetInEndSection": 511, "text": "We identified 47 LRES regions in prostate cancer, typically spanning about 2 Mb and harbouring approximately 12 genes, with a prevalence of tumour suppressor and miRNA genes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20173741", "endSection": "abstract"}, {"offsetInBeginSection": 958, "offsetInEndSection": 1187, "text": "We propose that consolidation or effective reduction of the cancer genome commonly occurs in domains through a combination of LRES and LOH or genomic deletion, resulting in reduced transcriptional plasticity within these regions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20173741", "endSection": "abstract"}, {"offsetInBeginSection": 249, "offsetInEndSection": 405, "text": "It was recently reported that epigenetic suppression of gene expression can also extend to a whole region; this is known as long-range epigenetic silencing. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17099711", "endSection": "abstract"}, {"offsetInBeginSection": 706, "offsetInEndSection": 811, "text": "Ikaros hypermethylation occurred in the context of a novel long-range epigenetic silencing (LRES) region. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21737484", "endSection": "abstract"}, {"offsetInBeginSection": 1027, "offsetInEndSection": 1249, "text": "Our results not only provide the first evidence that LRES can have functional specific effects in cancer but also identify several deregulated Ikaros targets that may contribute to progression in colorectal adenocarcinoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21737484", "endSection": "abstract"}, {"offsetInBeginSection": 12, "offsetInEndSection": 260, "text": "Previously, we showed that gene suppression commonly occurs across chromosome 2q14.2 in colorectal cancer, through a process of long-range epigenetic silencing (LRES), involving a combination of DNA methylation and repressive histone modifications. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21098650", "endSection": "abstract"}, {"offsetInBeginSection": 261, "offsetInEndSection": 466, "text": "We now investigate whether LRES also occurs in prostate cancer across this 4-Mb region and whether differential DNA methylation of 2q14.2 genes could provide a regional panel of prostate cancer biomarkers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21098650", "endSection": "abstract"}, {"offsetInBeginSection": 1178, "offsetInEndSection": 1295, "text": "Consistent with LRES in colorectal cancer, we found regional epigenetic remodeling across 2q14.2 in prostate cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21098650", "endSection": "abstract"}]}, {"body": "Which R/bioconductor package utilizes the Hilbert curve in order to visualize genomic data?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/19297348"], "ideal_answer": "This article argues that the so-called Hilbert curve visualization can complement genome browsers and help to get further insights into the structure of one's data.In many genomic studies, one works with genome-position-dependent data, e.g.This is demonstrated with examples from different use cases.An open-source application, called HilbertVis, is presented that allows the user to produce and interactively explore such plots.AVAILABILITY: http://www.ebi.ac.uk/huber-srv/hilbert/.Using conventional tools, it can be difficult to get a good feel for the data, especially the distribution of features.ChIP-chip or ChIP-Seq scores.ChIP-chip or ChIP-Seq scores.ChIP-chip or ChIP-Seq scores.ChIP-chip or ChIP-Seq scores.ChIP-chip or ChIP-Seq scores.", "type": "factoid", "id": "56bdcc4cef6e394741000002", "snippets": [{"offsetInBeginSection": 12, "offsetInEndSection": 648, "text": "In many genomic studies, one works with genome-position-dependent data, e.g. ChIP-chip or ChIP-Seq scores. Using conventional tools, it can be difficult to get a good feel for the data, especially the distribution of features. This article argues that the so-called Hilbert curve visualization can complement genome browsers and help to get further insights into the structure of one's data. This is demonstrated with examples from different use cases. An open-source application, called HilbertVis, is presented that allows the user to produce and interactively explore such plots.AVAILABILITY: http://www.ebi.ac.uk/huber-srv/hilbert/. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19297348", "endSection": "abstract"}]}, {"body": "What are the functions of the ESCRT machinery?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/26040713", "http://www.ncbi.nlm.nih.gov/pubmed/26339479", "http://www.ncbi.nlm.nih.gov/pubmed/25690770", "http://www.ncbi.nlm.nih.gov/pubmed/25637630", "http://www.ncbi.nlm.nih.gov/pubmed/25624505", "http://www.ncbi.nlm.nih.gov/pubmed/25099357", "http://www.ncbi.nlm.nih.gov/pubmed/24482116", "http://www.ncbi.nlm.nih.gov/pubmed/24148098", "http://www.ncbi.nlm.nih.gov/pubmed/24641493", "http://www.ncbi.nlm.nih.gov/pubmed/24109596"], "ideal_answer": "Since their discovery, however, ESCRTs have been recognized as playing important roles at the plasma membrane, which appears to be the original site of function for the ESCRT machinery.Evidence has accumulated revealing that efficient autophagic degradation requires functional endosomal sorting complex required for transport (ESCRT) machinery.The endosomal sorting complexes required for transport (ESCRT) are needed for three distinct cellular functions in higher eukaryotes: (i) Multivesicular body formation for the degradation of transmembrane proteins in lysosomes, (ii) midbody abscission during cytokinesis and (iii) retroviral budding.Recently it was shown that both recycling endosome and endosomal sorting complex required for transport (ESCRT) components are required for cytokinesis, in which they are believed to act in a sequential manner to bring about secondary ingression and abscission, respectivelyThe endosomal sorting complexes required for transport (ESCRTs) collectively comprise a machinery that was first known for its function in the degradation of transmembrane proteins in the endocytic pathway of eukaryotic cells.", "type": "summary", "id": "570a8dcfcf1c325851000027", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 412, "text": "The endosomal sorting complexes required for transport (ESCRTs) collectively comprise a machinery that was first known for its function in the degradation of transmembrane proteins in the endocytic pathway of eukaryotic cells. Since their discovery, however, ESCRTs have been recognized as playing important roles at the plasma membrane, which appears to be the original site of function for the ESCRT machinery. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26339479", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 169, "text": "Endosomal sorting complexes required for transport (ESCRTs) are involved in the formation of multivesicular bodies and sorting of targeted proteins to the yeast vacuole. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25690770", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 191, "text": "Disassembly of the endosomal sorting complex required for transport (ESCRT) machinery from biological membranes is a critical final step in cellular processes that require the ESCRT function. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25637630", "endSection": "abstract"}, {"offsetInBeginSection": 99, "offsetInEndSection": 259, "text": "Evidence has accumulated revealing that efficient autophagic degradation requires functional endosomal sorting complex required for transport (ESCRT) machinery. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25624505", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 176, "text": "HIV-1 virions assemble at the plasma membrane of mammalian cells and recruit the endosomal sorting complex required for transport (ESCRT) machinery to enable particle release. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25099357", "endSection": "abstract"}, {"offsetInBeginSection": 213, "offsetInEndSection": 386, "text": "We found that endosomal sorting complex required for transport (ESCRT), involved previously in membrane budding and fission, plays a critical role in plasma membrane repair. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24482116", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 195, "text": "The ESCRT (endosomal sorting complex required for transport) machinery is known to sort ubiquitinated transmembrane proteins into vesicles that bud into the lumen of multivesicular bodies (MVBs). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24148098", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 301, "text": "The endosomal sorting complexes required for transport (ESCRT) are needed for three distinct cellular functions in higher eukaryotes: (i) Multivesicular body formation for the degradation of transmembrane proteins in lysosomes, (ii) midbody abscission during cytokinesis and (iii) retroviral budding. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24641493", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 274, "text": "Recently it was shown that both recycling endosome and endosomal sorting complex required for transport (ESCRT) components are required for cytokinesis, in which they are believed to act in a sequential manner to bring about secondary ingression and abscission, respectively ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24109596", "endSection": "abstract"}]}, {"body": "List functions that are evaluated with the Full Outline of Unresponsiveness score?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/24556655", "http://www.ncbi.nlm.nih.gov/pubmed/24013867", "http://www.ncbi.nlm.nih.gov/pubmed/20551672"], "ideal_answer": "The Full Outline of UnResponsiveness (FOUR) Score is a coma scale that consists of four components (eye and motor response, brainstem reflexes, and respiration).Recently, the full outline of unresponsiveness (FOUR) score was introduced, which is composed of four clinically distinct categories of evaluation: eye reaction, motor function, brainstem reflexes and respiratory pattern.The FOUR (Full Outline of UnResponsiveness) score, a new coma scale, evaluates 4 components: eye and motor responses, brainstem reflexes and respiration.The FOUR (Full Outline of UnResponsiveness) score, a new coma scale, evaluates 4 components: eye and motor responses, brainstem reflexes and respiration.The FOUR (Full Outline of UnResponsiveness) score, a new coma scale, evaluates 4 components: eye and motor responses, brainstem reflexes and respiration.The FOUR (Full Outline of UnResponsiveness) score, a new coma scale, evaluates 4 components: eye and motor responses, brainstem reflexes and respiration.", "type": "list", "id": "56c1d84cef6e394741000031", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "The Full Outline of UnResponsiveness (FOUR) Score is a coma scale that consists of four components (eye and motor response, brainstem reflexes, and respiration). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24556655", "endSection": "abstract"}, {"offsetInBeginSection": 363, "offsetInEndSection": 585, "text": "Recently, the full outline of unresponsiveness (FOUR) score was introduced, which is composed of four clinically distinct categories of evaluation: eye reaction, motor function, brainstem reflexes and respiratory pattern. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24013867", "endSection": "abstract"}, {"offsetInBeginSection": 192, "offsetInEndSection": 346, "text": "The FOUR (Full Outline of UnResponsiveness) score, a new coma scale, evaluates 4 components: eye and motor responses, brainstem reflexes and respiration. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20551672", "endSection": "abstract"}]}, {"body": "How does Foxa transcription factor exhibits its pioneering function?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/25436603", "http://www.ncbi.nlm.nih.gov/pubmed/21935353", "http://www.ncbi.nlm.nih.gov/pubmed/21502411", "http://www.ncbi.nlm.nih.gov/pubmed/20591647", "http://www.ncbi.nlm.nih.gov/pubmed/21404180", "http://www.ncbi.nlm.nih.gov/pubmed/19339686", "http://www.ncbi.nlm.nih.gov/pubmed/16909212"], "ideal_answer": "Nucleosome-binding affinity as a primary determinant of the nuclear mobility of the pioneer transcription factor FoxAInsight into the unique molecular basis of Foxa function has been obtained from recent genetic and genomic data, which identify the Foxa proteins as 'pioneer factors' whose binding to promoters and enhancers enable chromatin access for other tissue-specific transcription factorsThe Fox DNA-binding domain structurally resembles linker histone and binds nucleosomes stablyBoth EBNA1 and FoxA induce local DNA demethylation, nucleosome destabilization and bind to mitotic chromosomes.The purpose of this review is to critically examine the literature on three highly potent transcriptional activators: the herpes virus protein, VP16; the master regulator of skeletal muscle differentiation, MyoD and the \"pioneer\" factor for hepatogenesis, FoxA.Similarities between the Epstein-Barr Virus (EBV) Nuclear Protein EBNA1 and the Pioneer Transcription Factor FoxA: Is EBNA1 a \"Bookmarking\" Oncoprotein that Alters the Host Cell Epigenotype?In this overview we focus, however, on the epigenetic alterations elicited by EBNA1 by drawing a parallel between EBNA1 and the FoxA family of pioneer transcription factors.", "type": "summary", "id": "57092f9bcf1c32585100001b", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 190, "text": "Similarities between the Epstein-Barr Virus (EBV) Nuclear Protein EBNA1 and the Pioneer Transcription Factor FoxA: Is EBNA1 a \"Bookmarking\" Oncoprotein that Alters the Host Cell Epigenotype? ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25436603", "endSection": "title"}, {"offsetInBeginSection": 364, "offsetInEndSection": 537, "text": "In this overview we focus, however, on the epigenetic alterations elicited by EBNA1 by drawing a parallel between EBNA1 and the FoxA family of pioneer transcription factors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25436603", "endSection": "abstract"}, {"offsetInBeginSection": 538, "offsetInEndSection": 650, "text": "Both EBNA1 and FoxA induce local DNA demethylation, nucleosome destabilization and bind to mitotic chromosomes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25436603", "endSection": "abstract"}, {"offsetInBeginSection": 740, "offsetInEndSection": 906, "text": "In addition, EBNA1 and FoxA, when associated with mitotic chromatin may \"bookmark\" active genes and ensure their reactivation in postmitotic cells (epigenetic memory) ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25436603", "endSection": "abstract"}, {"offsetInBeginSection": 269, "offsetInEndSection": 385, "text": "about one-third of the FoxA bound sites are near silent genes, including genes without detectable RNA polymerase II. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21935353", "endSection": "abstract"}, {"offsetInBeginSection": 617, "offsetInEndSection": 779, "text": "We found one such target site at a cryptic \"shadow\" enhancer 7 kilobases (kb) downstream of the Cdx2 gene, where Rfx1 restricts transcriptional activation by FoxA ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21935353", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 125, "text": "Nuclear mobility and mitotic chromosome binding: similarities between pioneer transcription factor FoxA and linker histone H1 ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21502411", "endSection": "title"}, {"offsetInBeginSection": 1101, "offsetInEndSection": 1327, "text": "The results indicate that the \"pioneer\" features of FoxA factors involve various chromatin-binding parameters seen in linker histones and that distinguish the factors with respect to their regulatory and mechanistic functions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21502411", "endSection": "abstract"}, {"offsetInBeginSection": 215, "offsetInEndSection": 420, "text": "These discoveries followed the establishment of the conceptional framework of the mechanism of action of the FoxA proteins as 'pioneer factors' that can engage chromatin before other transcription factors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20591647", "endSection": "abstract"}, {"offsetInBeginSection": 923, "offsetInEndSection": 1184, "text": "The purpose of this review is to critically examine the literature on three highly potent transcriptional activators: the herpes virus protein, VP16; the master regulator of skeletal muscle differentiation, MyoD and the \"pioneer\" factor for hepatogenesis, FoxA. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21404180", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "Nucleosome-binding affinity as a primary determinant of the nuclear mobility of the pioneer transcription factor FoxA ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19339686", "endSection": "title"}, {"offsetInBeginSection": 420, "offsetInEndSection": 684, "text": "We find that slower nuclear mobility correlates with high nonspecific nucleosome binding, and point mutations that disrupt nonspecific binding markedly increase nuclear mobility. FoxA's distinct nuclear mobility is consistent with its pioneer activity in chromatin ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19339686", "endSection": "abstract"}, {"offsetInBeginSection": 132, "offsetInEndSection": 225, "text": "The Fox DNA-binding domain structurally resembles linker histone and binds nucleosomes stably ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19339686", "endSection": "abstract"}, {"offsetInBeginSection": 954, "offsetInEndSection": 1233, "text": "Insight into the unique molecular basis of Foxa function has been obtained from recent genetic and genomic data, which identify the Foxa proteins as 'pioneer factors' whose binding to promoters and enhancers enable chromatin access for other tissue-specific transcription factors ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16909212", "endSection": "abstract"}]}, {"body": "Which CDK targets control cytokinesis?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/25371407"], "ideal_answer": "We use phosphoproteome analysis of mitotic exit to identify Cdk targets that are dephosphorylated at the time of cytokinesis.Our results suggest that cytokinesis is coordinately controlled by the master cell cycle regulator Cdk together with its counteracting phosphatase and that it is executed by concerted dephosphorylation of Cdk targets involved in several cell biological processes.This approach identifies Aip1, Ede1 and Inn1 as cytokinetic regulators.We then apply a new and widely applicable tool to generate conditionally phosphorylated proteins to identify those whose dephosphorylation is required for cytokinesis.We then apply a new and widely applicable tool to generate conditionally phosphorylated proteins to identify those whose dephosphorylation is required for cytokinesis.We then apply a new and widely applicable tool to generate conditionally phosphorylated proteins to identify those whose dephosphorylation is required for cytokinesis.We then apply a new and widely applicable tool to generate conditionally phosphorylated proteins to identify those whose dephosphorylation is required for cytokinesis.We then apply a new and widely applicable tool to generate conditionally phosphorylated proteins to identify those whose dephosphorylation is required for cytokinesis.", "type": "list", "id": "56bf487def6e394741000011", "snippets": [{"offsetInBeginSection": 464, "offsetInEndSection": 1093, "text": "We use phosphoproteome analysis of mitotic exit to identify Cdk targets that are dephosphorylated at the time of cytokinesis. We then apply a new and widely applicable tool to generate conditionally phosphorylated proteins to identify those whose dephosphorylation is required for cytokinesis. This approach identifies Aip1, Ede1 and Inn1 as cytokinetic regulators. Our results suggest that cytokinesis is coordinately controlled by the master cell cycle regulator Cdk together with its counteracting phosphatase and that it is executed by concerted dephosphorylation of Cdk targets involved in several cell biological processes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25371407", "endSection": "abstract"}]}, {"body": "Which major signaling pathways are regulated by RIP1?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/25767797", "http://www.ncbi.nlm.nih.gov/pubmed/25391899", "http://www.ncbi.nlm.nih.gov/pubmed/24224954", "http://www.ncbi.nlm.nih.gov/pubmed/24874734", "http://www.ncbi.nlm.nih.gov/pubmed/25326752", "http://www.ncbi.nlm.nih.gov/pubmed/23674612", "http://www.ncbi.nlm.nih.gov/pubmed/24460252"], "ideal_answer": "Major signaling pathways regulated by RIP1 include necroptosis, apoptosis, and pro-survival/inflammation NF-B activation.receptor-interacting protein-1 (RIP1)-mediated necroptosisTNF-induced apoptotic signaling pathways were assessed by monitoring levels of the anti-apoptotic protein, A20, and cleavage products of the caspase-8 substrate, RIP1.Together our results reveal a specific role for the RIP1-RIP3-DRP1 pathway in RNA virus-induced activation of the NLRP3 inflammasome and establish a direct link between inflammation and cell-death signaling pathways.Necroptosis exhibits a unique signaling pathway that requires the involvement of receptor interaction protein kinases 1 and 3 (RIP1 and RIP3),Receptor-interacting protein (RIP) kinases promote the induction of necrotic cell death pathways.Receptor-interacting protein (RIP) kinases promote the induction of necrotic cell death pathways.Receptor-interacting protein (RIP) kinases promote the induction of necrotic cell death pathways.Receptor-interacting protein (RIP) kinases promote the induction of necrotic cell death pathways.Receptor-interacting protein (RIP) kinases promote the induction of necrotic cell death pathways.", "type": "list", "id": "570a922dcf1c325851000028", "snippets": [{"offsetInBeginSection": 159, "offsetInEndSection": 282, "text": "Major signaling pathways regulated by RIP1 include necroptosis, apoptosis, and pro-survival/inflammation NF-\u03baB activation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25767797", "endSection": "abstract"}, {"offsetInBeginSection": 866, "offsetInEndSection": 924, "text": "receptor-interacting protein-1 (RIP1)-mediated necroptosis ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25391899", "endSection": "abstract"}, {"offsetInBeginSection": 1090, "offsetInEndSection": 1257, "text": "TNF-induced apoptotic signaling pathways were assessed by monitoring levels of the anti-apoptotic protein, A20, and cleavage products of the caspase-8 substrate, RIP1. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24224954", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 98, "text": "Receptor-interacting protein (RIP) kinases promote the induction of necrotic cell death pathways. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24874734", "endSection": "abstract"}, {"offsetInBeginSection": 730, "offsetInEndSection": 946, "text": "Together our results reveal a specific role for the RIP1-RIP3-DRP1 pathway in RNA virus-induced activation of the NLRP3 inflammasome and establish a direct link between inflammation and cell-death signaling pathways. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25326752", "endSection": "abstract"}, {"offsetInBeginSection": 403, "offsetInEndSection": 545, "text": "Necroptosis exhibits a unique signaling pathway that requires the involvement of receptor interaction protein kinases 1 and 3 (RIP1 and RIP3), ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24460252", "endSection": "abstract"}]}, {"body": "Which pathway is activated by ficolin-3?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/25178935", "http://www.ncbi.nlm.nih.gov/pubmed/25069872", "http://www.ncbi.nlm.nih.gov/pubmed/24336142"], "ideal_answer": "OBJECTIVES: To assess the involvement of ficolin-3, the main initiator of the lectin complement pathway (LCP), in subarachnoid hemorrhage (SAH) pathology and outcome.CONCLUSION: Our data provide evidence that LCP is activated after SAH and that the actual plasma concentrations of ficolin-3 reflect the severity of brain injury as evaluated by clinical and structural parameters.Furthermore, Ficolin-3 mediated complement activation may be valuable in monitoring disease activity in SLE patients due to the high sensitivity for complement consumption in the assay independent of the Ficolin-3 concentration.This study aims to investigate whether an association exists between the ficolins that are part of the lectin complement pathway and SLE.Ficolin-3 (also called H-ficolin or Hakata antigen) is a complement-activating pattern recognition molecule, possessing a fibrinogen-like domain involved in carbohydrate binding.These results support the idea that ficolin-3-mediated functional LCP activity may be targeted to control injury progression in SAH.", "type": "factoid", "id": "56c1d856ef6e394741000032", "snippets": [{"offsetInBeginSection": 93, "offsetInEndSection": 231, "text": "This study aims to investigate whether an association exists between the ficolins that are part of the lectin complement pathway and SLE. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25069872", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 179, "text": "Ficolin-3 (also called H-ficolin or Hakata antigen) is a complement-activating pattern recognition molecule, possessing a fibrinogen-like domain involved in carbohydrate binding. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25178935", "endSection": "abstract"}, {"offsetInBeginSection": 421, "offsetInEndSection": 625, "text": "Lectin pathway activity via Ficolin-3 was measured in ELISA on acetylated bovine serum albumin (acBSA) and measured as Ficolin-3 binding and deposition of C4, C3 and the terminal complement complex (TCC). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25069872", "endSection": "abstract"}, {"offsetInBeginSection": 1458, "offsetInEndSection": 1686, "text": "Furthermore, Ficolin-3 mediated complement activation may be valuable in monitoring disease activity in SLE patients due to the high sensitivity for complement consumption in the assay independent of the Ficolin-3 concentration. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25069872", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "OBJECTIVES: To assess the involvement of ficolin-3, the main initiator of the lectin complement pathway (LCP), in subarachnoid hemorrhage (SAH) pathology and outcome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24336142", "endSection": "abstract"}, {"offsetInBeginSection": 1303, "offsetInEndSection": 1649, "text": "CONCLUSION: Our data provide evidence that LCP is activated after SAH and that the actual plasma concentrations of ficolin-3 reflect the severity of brain injury as evaluated by clinical and structural parameters. These results support the idea that ficolin-3-mediated functional LCP activity may be targeted to control injury progression in SAH. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24336142", "endSection": "abstract"}]}, {"body": "What is the application of the ASSET algorithm in C.elegans?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/21089077"], "ideal_answer": "ASSET: a robust algorithm for the automated segmentation and standardization of early Caenorhabditis elegans embryos.We illustrate how ASSET can efficiently gather quantitative data on the motion of centrosomes and precisely track cortical invaginations, revealing hitherto unnoticed differences between wild-type and saps-1(RNAi) embryos.ASSET automatically detects the eggshell and the cell cortex from DIC time-lapse recordings of live one-cell-stage embryos and can also track subcellular structures using fluorescent time-lapse microscopy.However, there is a paucity of automated methods to gather quantitative information with subcellular precision in this system.Importantly, ASSET standardizes the data into an absolute coordinate system to allow robust quantitative comparisons between embryos.We developed ASSET (Algorithm for the Segmentation and the Standardization of C. elegans Time-lapse recordings) to fill this need.The early Caenorhabditis elegans embryo is an attractive model to investigate evolutionarily conserved cellular mechanisms.In summary, we establish ASSET as a novel tool for the efficient quantification and standardization of images from early C. elegans embryos.", "type": "summary", "id": "56c06ef5ef6e39474100001e", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 117, "text": "ASSET: a robust algorithm for the automated segmentation and standardization of early Caenorhabditis elegans embryos. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21089077", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1085, "text": "The early Caenorhabditis elegans embryo is an attractive model to investigate evolutionarily conserved cellular mechanisms. However, there is a paucity of automated methods to gather quantitative information with subcellular precision in this system. We developed ASSET (Algorithm for the Segmentation and the Standardization of C. elegans Time-lapse recordings) to fill this need. ASSET automatically detects the eggshell and the cell cortex from DIC time-lapse recordings of live one-cell-stage embryos and can also track subcellular structures using fluorescent time-lapse microscopy. Importantly, ASSET standardizes the data into an absolute coordinate system to allow robust quantitative comparisons between embryos. We illustrate how ASSET can efficiently gather quantitative data on the motion of centrosomes and precisely track cortical invaginations, revealing hitherto unnoticed differences between wild-type and saps-1(RNAi) embryos. In summary, we establish ASSET as a novel tool for the efficient quantification and standardization of images from early C. elegans embryos. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21089077", "endSection": "abstract"}]}, {"body": "What enzyme is inhibied by Opicapone?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/24271646", "http://www.ncbi.nlm.nih.gov/pubmed/24148813", "http://www.ncbi.nlm.nih.gov/pubmed/24925090"], "ideal_answer": "BACKGROUND AND OBJECTIVES: Opicapone is a novel third generation catechol-O-methyltransferase (COMT) inhibitor.The purpose of this study was to compare the levodopa pharmacokinetic profile throughout a day driven by the COMT inhibition either following repeated doses of opicapone or concomitant administration with entacapone.CONCLUSIONS: Opicapone behaved as long-acting COMT inhibitor that markedly increased systemic and central levodopa bioavailability.Brain and peripheral pharmacokinetics of levodopa in the cynomolgus monkey following administration of opicapone, a third generation nitrocatechol COMT inhibitor.CONCLUSION: Opicapone, a novel third generation COMT inhibitor, when compared to entacapone, provides a superior response upon the bioavailability of levodopa associated to more pronounced, long-lasting, and sustained COMT inhibition.OBJECTIVE: The present study aimed at evaluating the effect of opicapone, a third generation nitrocatechol catechol-O-methyltransferase (COMT) inhibitor, on the systemic and central bioavailability of 3,4-dihydroxy-l-phenylalanine (levodopa) and related metabolites in the cynomolgus monkey.PURPOSE: Opicapone (OPC) is a novel catechol-O-methyltransferase (COMT) inhibitor to be used as adjunctive therapy in levodopa-treated patients with Parkinson's disease.", "type": "factoid", "id": "56c1d857ef6e394741000033", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 170, "text": "PURPOSE: Opicapone (OPC) is a novel catechol-O-methyltransferase (COMT) inhibitor to be used as adjunctive therapy in levodopa-treated patients with Parkinson's disease. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24271646", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 162, "text": "Brain and peripheral pharmacokinetics of levodopa in the cynomolgus monkey following administration of opicapone, a third generation nitrocatechol COMT inhibitor. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24148813", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 291, "text": "OBJECTIVE: The present study aimed at evaluating the effect of opicapone, a third generation nitrocatechol catechol-O-methyltransferase (COMT) inhibitor, on the systemic and central bioavailability of 3,4-dihydroxy-l-phenylalanine (levodopa) and related metabolites in the cynomolgus monkey. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24148813", "endSection": "abstract"}, {"offsetInBeginSection": 1431, "offsetInEndSection": 1563, "text": "CONCLUSIONS: Opicapone behaved as long-acting COMT inhibitor that markedly increased systemic and central levodopa bioavailability. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24148813", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 328, "text": "BACKGROUND AND OBJECTIVES: Opicapone is a novel third generation catechol-O-methyltransferase (COMT) inhibitor. The purpose of this study was to compare the levodopa pharmacokinetic profile throughout a day driven by the COMT inhibition either following repeated doses of opicapone or concomitant administration with entacapone. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24925090", "endSection": "abstract"}, {"offsetInBeginSection": 2232, "offsetInEndSection": 2467, "text": "CONCLUSION: Opicapone, a novel third generation COMT inhibitor, when compared to entacapone, provides a superior response upon the bioavailability of levodopa associated to more pronounced, long-lasting, and sustained COMT inhibition. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24925090", "endSection": "abstract"}]}, {"body": "Is the abnormal dosage of ultraconserved elements disfavored in cancer cells?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/25340765"], "ideal_answer": "Abnormal dosage of ultraconserved elements is highly disfavored in healthy cells but not cancer cells.Finally, we show that it is possible to observe the CNVs of induced pluripotent stem (iPS) cells become depleted of UCEs over time, suggesting that depletion may be established through selection against UCE-disrupting CNVs without the requirement for meiotic divisions.In striking contrast, CNVs arising specifically in cancer cells are, as a rule, not depleted for UCEs and can even become significantly enriched.This observation raises the possibility that CNVs that arise somatically and are relatively newly formed are less likely to have established a CNV profile that is depleted for UCEs.Alternatively, lack of depletion for UCEs from cancer CNVs may reflect the diseased state.We begin by showing that depletion for UCEs characterizes the most recent large-scale human CNV datasets and then find that even newly formed de novo CNVs, which have passed through meiosis at most once, are significantly depleted for UCEs.In support of this latter explanation, somatic CNVs that are not associated with disease are depleted for UCEs.", "type": "yesno", "id": "56c0708eef6e39474100001f", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 102, "text": "Abnormal dosage of ultraconserved elements is highly disfavored in healthy cells but not cancer cells. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25340765", "endSection": "title"}, {"offsetInBeginSection": 294, "offsetInEndSection": 1335, "text": "We begin by showing that depletion for UCEs characterizes the most recent large-scale human CNV datasets and then find that even newly formed de novo CNVs, which have passed through meiosis at most once, are significantly depleted for UCEs. In striking contrast, CNVs arising specifically in cancer cells are, as a rule, not depleted for UCEs and can even become significantly enriched. This observation raises the possibility that CNVs that arise somatically and are relatively newly formed are less likely to have established a CNV profile that is depleted for UCEs. Alternatively, lack of depletion for UCEs from cancer CNVs may reflect the diseased state. In support of this latter explanation, somatic CNVs that are not associated with disease are depleted for UCEs. Finally, we show that it is possible to observe the CNVs of induced pluripotent stem (iPS) cells become depleted of UCEs over time, suggesting that depletion may be established through selection against UCE-disrupting CNVs without the requirement for meiotic divisions. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25340765", "endSection": "abstract"}]}, {"body": "Is there association of matrix metalloproteinases with behaviour of pituitary adenomas?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/22822048", "http://www.ncbi.nlm.nih.gov/pubmed/18493720", "http://www.ncbi.nlm.nih.gov/pubmed/17235567", "http://www.ncbi.nlm.nih.gov/pubmed/16172741", "http://www.ncbi.nlm.nih.gov/pubmed/12904990", "http://www.ncbi.nlm.nih.gov/pubmed/12508658", "http://www.ncbi.nlm.nih.gov/pubmed/10946906", "http://www.ncbi.nlm.nih.gov/pubmed/10634397", "http://www.ncbi.nlm.nih.gov/pubmed/10598711"], "ideal_answer": "Data on the dural invasiveness of pituitary adenomas have been correlated to the expression of matrix metalloproteinases (e.g.While detailed histological subtyping remains the best independent predictor of aggressive behavior in the majority of cases, evidence suggests that the additional analyses of FGFR4, MMP, PTTG, Ki-67, p53, and deletions in chromosome 11 may contribute to decisions concerning management of aggressive pituitary adenomas.Inhibition of estrogen-induced pituitary tumor growth and angiogenesis in Fischer 344 rats by the matrix metalloproteinase inhibitor batimastat.CONCLUSIONS: TIMP-1 and TIMP-2 may play a key role in invasive pituitary adenomas to biological behavior.In addition, although there was no difference in whether MMP-9 was present or not when nonfunctioning adenomas that recurred were compared with those that did not, samples of recurrent tumor at the second presentation were more likely to express MMP-9 (P = 0.01).In summary, the differential expression of extracellular matrix components, integrins and matrix metalloproteinase contributes to the control of pituitary hormone production and cell proliferation during tumorigenesis.", "type": "yesno", "id": "56c1d85eef6e394741000035", "snippets": [{"offsetInBeginSection": 313, "offsetInEndSection": 633, "text": "While detailed histological subtyping remains the best independent predictor of aggressive behavior in the majority of cases, evidence suggests that the additional analyses of FGFR4, MMP, PTTG, Ki-67, p53, and deletions in chromosome 11 may contribute to decisions concerning management of aggressive pituitary adenomas. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22822048", "endSection": "abstract"}, {"offsetInBeginSection": 1122, "offsetInEndSection": 1236, "text": "We observed elevation of MMP-2 and -9 expression and consequent 3-D cell invasion in cells under-expressing RECK. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18493720", "endSection": "abstract"}, {"offsetInBeginSection": 133, "offsetInEndSection": 384, "text": " Based on the significance of matrix metalloproteinases (MMPs) for tumor growth and angiogenesis, we have studied the effect of batimastat (BB-94), a synthetic MMPs inhibitor (MMPI) on the progression of prolactin-secreting pituitary adenoma in rats. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17235567", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 144, "text": "Inhibition of estrogen-induced pituitary tumor growth and angiogenesis in Fischer 344 rats by the matrix metalloproteinase inhibitor batimastat. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17235567", "endSection": "title"}, {"offsetInBeginSection": 1080, "offsetInEndSection": 1258, "text": "The results of our study provide evidence for an inhibitory effect of batimastat, a synthetic MMPI, on the growth and angiogenesis in an experimental model of human prolactinoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17235567", "endSection": "abstract"}, {"offsetInBeginSection": 1528, "offsetInEndSection": 1746, "text": "In summary, the differential expression of extracellular matrix components, integrins and matrix metalloproteinase contributes to the control of pituitary hormone production and cell proliferation during tumorigenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16172741", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "Data on the dural invasiveness of pituitary adenomas have been correlated to the expression of matrix metalloproteinases (e.g. MMP-9). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12904990", "endSection": "abstract"}, {"offsetInBeginSection": 1648, "offsetInEndSection": 1712, "text": "We found no correlation of MMP-9 expression and tumour invasion. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12904990", "endSection": "abstract"}, {"offsetInBeginSection": 439, "offsetInEndSection": 599, "text": "The matrix metalloproteinases (MMPs) and their nature inhibitors-the tissue inhibitors of metalloproteinases (TIMPs) may play a central role in these processes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12508658", "endSection": "abstract"}, {"offsetInBeginSection": 1616, "offsetInEndSection": 1721, "text": "CONCLUSIONS: TIMP-1 and TIMP-2 may play a key role in invasive pituitary adenomas to biological behavior. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12508658", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 177, "text": "The matrix metalloproteinases (MMPs) are a family of zinc-containing endopeptidases that are able to degrade the extracellular matrix and allow angiogenesis and tumor invasion. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10946906", "endSection": "abstract"}, {"offsetInBeginSection": 868, "offsetInEndSection": 2039, "text": "MMP-9 expression did not differ between noninvasive tumors and normal pituitary gland, or between different sized prolactinomas. MMP-9 expression was related to aggressive tumor behavior. It was higher in invasive macroprolactinomas (P = 0.003) when compared with noninvasive macroprolactinomas or the normal anterior pituitary gland. In addition, although there was no difference in whether MMP-9 was present or not when nonfunctioning adenomas that recurred were compared with those that did not, samples of recurrent tumor at the second presentation were more likely to express MMP-9 (P = 0.01). Pituitary carcinomas were significantly more likely to be MMP-9 positive compared with normal anterior pituitary gland (P = 0.05), but there was no difference from invasive adenomas. Angiogenesis assessed by vascular density was related to MMP-9 expression (P<0.05). In summary, we have shown the presence of MMP-9 expression in some invasive and recurrent pituitary adenomas, and in the majority of pituitary carcinoma. The mechanisms whereby MMP-9 expression influences tumor recurrence and invasiveness, and its association with angiogenesis, remains to be elucidated. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10946906", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 173, "text": "Beside the digestion of the extracellular matrix during tumor invasion and metastasis, more recently, new functions for matrix metalloproteinases (MMPs) have been proposed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10634397", "endSection": "abstract"}, {"offsetInBeginSection": 892, "offsetInEndSection": 1022, "text": "CONCLUSION: No correlation could be established between the invasive potential of tumors and MMP-1, -2, and -3 expression levels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10598711", "endSection": "abstract"}]}, {"body": "Give an overview of visualizing genomes with oligopaint FISH probes.", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/24510436", "http://www.ncbi.nlm.nih.gov/pubmed/23236188"], "ideal_answer": "Oligopaint probes are fluorescently labeled, single-stranded DNA oligonucleotides that can be used to visualize genomic regions ranging in size from tens of kilobases to many megabases.Here, we describe an oligonucleotide- and PCR-based strategy for fluorescence in situ hybridization (FISH) and a bioinformatic platform that enables this technology to be extended to any organism whose genome has been sequenced.The oligonucleotide probes are renewable, highly efficient, and able to robustly label chromosomes in cell culture, fixed tissues, and metaphase spreads.We anticipate this technology will lead to an enhanced ability to visualize interphase and metaphase chromosomes.Our method gives researchers precise control over the sequences they target and allows for single and multicolor imaging of regions ranging from tens of kilobases to megabases with the same basic protocol.Our method gives researchers precise control over the sequences they target and allows for single and multicolor imaging of regions ranging from tens of kilobases to megabases with the same basic protocol.", "type": "summary", "id": "56c0ea0aef6e394741000029", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 186, "text": "Oligopaint probes are fluorescently labeled, single-stranded DNA oligonucleotides that can be used to visualize genomic regions ranging in size from tens of kilobases to many megabases. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24510436", "endSection": "abstract"}, {"offsetInBeginSection": 347, "offsetInEndSection": 1049, "text": "Here, we describe an oligonucleotide- and PCR-based strategy for fluorescence in situ hybridization (FISH) and a bioinformatic platform that enables this technology to be extended to any organism whose genome has been sequenced. The oligonucleotide probes are renewable, highly efficient, and able to robustly label chromosomes in cell culture, fixed tissues, and metaphase spreads. Our method gives researchers precise control over the sequences they target and allows for single and multicolor imaging of regions ranging from tens of kilobases to megabases with the same basic protocol. We anticipate this technology will lead to an enhanced ability to visualize interphase and metaphase chromosomes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23236188", "endSection": "abstract"}]}, {"body": "What is known about maternal smoking and brain tumor risk?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/24260161", "http://www.ncbi.nlm.nih.gov/pubmed/15801484", "http://www.ncbi.nlm.nih.gov/pubmed/15191928", "http://www.ncbi.nlm.nih.gov/pubmed/12115571", "http://www.ncbi.nlm.nih.gov/pubmed/12125967", "http://www.ncbi.nlm.nih.gov/pubmed/11452935", "http://www.ncbi.nlm.nih.gov/pubmed/10620527", "http://www.ncbi.nlm.nih.gov/pubmed/8850274", "http://www.ncbi.nlm.nih.gov/pubmed/8470663", "http://www.ncbi.nlm.nih.gov/pubmed/7139628"], "ideal_answer": "Maternal smoking during pregnancy and the risk of childhood brain tumors: a meta-analysis of 6566 subjects from twelve epidemiological studies.No significant differences in risks were found to be associated with maternal or paternal smoking at any time (odds ratio (OR) = 0.92 for mothers and 1.06 for fathers), during the year of birth of the child (which included both the prenatal and postnatal periods) (ORs = 0.84 for<1 pack/day and 1.0 for>or = 1 pack/day for mothers, and 0.68 for<1 pack/day and 1.07 for>or = 1 pack/day for fathers), or 2 years before the child was born, i.e., the pre-conception period (ORs = 0.75 for<1 pack/day and 1.01 for>or = 1 pack/day for mothers, and 0.90 for<1 pack/day and 1.15 for>or = 1 pack/day for fathers).Maternal occupational exposure to PAH before conception or during pregnancy was rare, and this exposure was not associated with any type of childhood brain tumor.", "type": "summary", "id": "56c1d85fef6e394741000036", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 275, "text": "BACKGROUND: A recent meta-analysis suggested an association between exposure to paternal smoking during pregnancy and childhood brain tumor risk, but no studies have evaluated whether this association differs by polymorphisms in genes that metabolize tobacco-smoke chemicals. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24260161", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 225, "text": "OBJECTIVE: Studies of the effect of maternal smoking during pregnancy on development of brain tumors in the offspring generally have found no increase in risk but most have mainly relied on retrospective exposure assessment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15801484", "endSection": "abstract"}, {"offsetInBeginSection": 839, "offsetInEndSection": 1092, "text": "Children of women who smoked during pregnancy had an increased incidence of brain tumors (hazard ratio = 1.24; 95% confidence interval: 1.01-1.53). The increase in risk was similar for benign and malignant tumors, and was most apparent for astrocytoma. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15801484", "endSection": "abstract"}, {"offsetInBeginSection": 1199, "offsetInEndSection": 1321, "text": "CONCLUSIONS: These results support a role for maternal smoking during pregnancy in the etiology of childhood brain tumors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15801484", "endSection": "abstract"}, {"offsetInBeginSection": 1197, "offsetInEndSection": 1360, "text": "Maternal occupational exposure to PAH before conception or during pregnancy was rare, and this exposure was not associated with any type of childhood brain tumor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/15191928", "endSection": "abstract"}, {"offsetInBeginSection": 910, "offsetInEndSection": 1185, "text": "There was no association between the risk of brain tumors in the child and parental smoking prior to pregnancy, maternal smoking or regular exposure to others' cigarette smoke during pregnancy at home or at work, or passive smoking by the child during the first year of life. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12115571", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "Maternal smoking during pregnancy and the risk of childhood brain tumors: a meta-analysis of 6566 subjects from twelve epidemiological studies. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12125967", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 149, "text": "OBJECTIVE: Prior epidemiological studies suggest a possible association between maternal smoking during pregnancy and risk of childhood brain tumors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12125967", "endSection": "abstract"}, {"offsetInBeginSection": 1485, "offsetInEndSection": 1707, "text": "Pooling all twelve reports yielded an RRs of 1.05 (0.90-1.21), a non-statistically significant result suggesting no clear association between maternal smoking during pregnancy and risk of childhood brain tumor development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12125967", "endSection": "abstract"}, {"offsetInBeginSection": 1911, "offsetInEndSection": 2075, "text": ".CONCLUSION: The available epidemiological data do not support a clear association between maternal smoking during pregnancy and pediatric brain tumor development. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12125967", "endSection": "abstract"}, {"offsetInBeginSection": 654, "offsetInEndSection": 1024, "text": "We observed only few positive associations, namely, between CNS tumors and low birth weight [<2,500 g; odds ratio (OR), 1.73; 95% confidence interval (CI), 1.06-2.84], between ependymoma and maternal smoking during pregnancy (>10 cigarettes per day: OR, 4.71; 95% CI, 1.69-13.1), and between astrocytoma and exposure to wood preservatives (OR, 1.91; 95% CI, 1.22-3.01). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11452935", "endSection": "abstract"}, {"offsetInBeginSection": 879, "offsetInEndSection": 1068, "text": "The results on exposure to paternal tobacco smoke suggest an association with brain tumors (RR 1.22; CI, 1.05-1. 40; based on 10 studies) and lymphomas (RR 2.08; CI, 1.08-3.98; 4 studies). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10620527", "endSection": "abstract"}, {"offsetInBeginSection": 850, "offsetInEndSection": 1588, "text": "No association was found between the risk of CBTs and maternal or paternal smoking before pregnancy and there was no association between CBTs and maternal smoking during pregnancy [odds ratio (OR) = 0.98; 95% confidence interval (CI) = 0.72-1.3]. A slightly increased OR for CBTs was found for paternal smoking during pregnancy in the absence of maternal smoking (OR = 1.2; 95% CI = 0.90-1.5) and for maternal exposure to passive smoke from any source (OR = 1.2; 95% CI = 0.95-1.6). The results of this analysis are consistent with results from several prior epidemiological studies that showed no significant association between CBTs and maternal smoking before or during pregnancy or maternal exposure to passive smoke during pregnancy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8850274", "endSection": "abstract"}, {"offsetInBeginSection": 359, "offsetInEndSection": 1295, "text": "No significant differences in risks were found to be associated with maternal or paternal smoking at any time (odds ratio (OR) = 0.92 for mothers and 1.06 for fathers), during the year of birth of the child (which included both the prenatal and postnatal periods) (ORs = 0.84 for<1 pack/day and 1.0 for>or = 1 pack/day for mothers, and 0.68 for<1 pack/day and 1.07 for>or = 1 pack/day for fathers), or 2 years before the child was born, i.e., the pre-conception period (ORs = 0.75 for<1 pack/day and 1.01 for>or = 1 pack/day for mothers, and 0.90 for<1 pack/day and 1.15 for>or = 1 pack/day for fathers). Mothers were also specifically asked if they smoked during the pregnancy, and no association was found compared with never smokers (OR = 1.08, 95% confidence interval (CI) 0.80-1.45) or for ever-smokers who continued to smoke during pregnancy compared with those who stopped smoking during pregnancy (OR = 1.15, 95% CI 0.75-1.78). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8470663", "endSection": "abstract"}, {"offsetInBeginSection": 1489, "offsetInEndSection": 1775, "text": "The lack of an effect of parental smoking was observed for both the major histologic types and locations of brain tumors. These findings and those from earlier studies provide no support for the hypothesis that parental cigarette smoking influences the risk of brain tumors in children. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8470663", "endSection": "abstract"}, {"offsetInBeginSection": 334, "offsetInEndSection": 758, "text": "Increased risk was associated with maternal contact with nitrosamine-containing substances such as burning incense (odds ratio, 3.3; p = 0.005), sidestream cigarette smoke (odds ratio, 1.5; p = 0.03), and face makeup (odds ratio, 1.6; p = 0.02); with maternal use of diuretics (odds ratio, 2.0; p = 0.03) and antihistamines (odds ratio, 3.4; p = 0.002); and with the level of maternal consumption of cured meats (p = 0.008). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/7139628", "endSection": "abstract"}]}, {"body": "What is FINDbase?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/17135191"], "ideal_answer": "FINDbase: a relational database recording frequencies of genetic defects leading to inherited disorders worldwide.Query outputs can be either in a table or graphical format, accompanied by reference(s) on the data source.FINDbase offers a user-friendly query interface, providing instant access to the list and frequencies of the different mutations.Database records include the population and ethnic group, the disorder name and the related gene, accompanied by links to any corresponding locus-specific mutation database, to the respective Online Mendelian Inheritance in Man entries and the mutation together with its frequency in that population.The initial information is derived from the published literature, locus-specific databases and genetic disease consortia.Databaseaccess is free of charge and there are no registration requirements for data querying.Registered users from three different groups, namely administrator, national coordinator and curator, are responsible for database curation and/or data entry/correction online via a password-protected interface.", "type": "summary", "id": "56c234a4ef6e394741000059", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 114, "text": "FINDbase: a relational database recording frequencies of genetic defects leading to inherited disorders worldwide. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17135191", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1502, "text": "Frequency of INherited Disorders database (FINDbase) (http://www.findbase.org) is a relational database, derived from the ETHNOS software, recording frequencies of causative mutations leading to inherited disorders worldwide. Database records include the population and ethnic group, the disorder name and the related gene, accompanied by links to any corresponding locus-specific mutation database, to the respective Online Mendelian Inheritance in Man entries and the mutation together with its frequency in that population. The initial information is derived from the published literature, locus-specific databases and genetic disease consortia. FINDbase offers a user-friendly query interface, providing instant access to the list and frequencies of the different mutations. Query outputs can be either in a table or graphical format, accompanied by reference(s) on the data source. Registered users from three different groups, namely administrator, national coordinator and curator, are responsible for database curation and/or data entry/correction online via a password-protected interface. Databaseaccess is free of charge and there are no registration requirements for data querying. FINDbase provides a simple, web-based system for population-based mutation data collection and retrieval and can serve not only as a valuable online tool for molecular genetic testing of inherited disorders but also as a non-profit model for sustainable database funding, in the form of a 'database-journal'. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/17135191", "endSection": "abstract"}]}, {"body": "Which drugs are included in TAS-102?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/26084259", "http://www.ncbi.nlm.nih.gov/pubmed/26557901", "http://www.ncbi.nlm.nih.gov/pubmed/25750295", "http://www.ncbi.nlm.nih.gov/pubmed/25776904", "http://www.ncbi.nlm.nih.gov/pubmed/25256052"], "ideal_answer": "TAS-102 is a novel oral nucleoside antitumor agent consisting of trifluridine and tipiracil hydrochloride at a molar ratio of 1:0.5.Novel DNA synthesis inhibitors for the treatment of gastrointestinal malignancies include a combination of the antimetabolite TAS-102, which consists of trifluorothymidine with a thymidine phosphorylase inhibitor, and a novel micellar formulation of cisplatin NC-6004 that uses a nanotechnology-based drug delivery system.PURPOSE: TAS-102 is an orally administered anticancer agent composed of ,,-trifluorothymidine (FTD) and thymidine phosphorylase inhibitor (TPI).TAS-102, a combination of trifluorothymidine and the thymidine phosphorylase inhibitor TPI in a 1:0.5 ratio, is a novel oral formulation, which is active in 5FU-resistant models, both in vitro and in xenograft models.PURPOSE: Trifluridine (TFT) is an antitumor component of a novel nucleoside antitumor agent, TAS-102, which consists of TFT and tipiracil hydrochloride (thymidine phosphorylase inhibitor).PURPOSE: Trifluridine (TFT) is an antitumor component of a novel nucleoside antitumor agent, TAS-102, which consists of TFT and tipiracil hydrochloride (thymidine phosphorylase inhibitor).", "type": "list", "id": "56c1f000ef6e394741000037", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "PURPOSE: Trifluridine (TFT) is an antitumor component of a novel nucleoside antitumor agent, TAS-102, which consists of TFT and tipiracil hydrochloride (thymidine phosphorylase inhibitor). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26084259", "endSection": "abstract"}, {"offsetInBeginSection": 743, "offsetInEndSection": 960, "text": "TAS-102, a combination of trifluorothymidine and the thymidine phosphorylase inhibitor TPI in a 1:0.5 ratio, is a novel oral formulation, which is active in 5FU-resistant models, both in vitro and in xenograft models. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26557901", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "TAS-102 is a novel oral nucleoside antitumor agent consisting of trifluridine and tipiracil hydrochloride at a molar ratio of 1:0.5. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25750295", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 148, "text": "PURPOSE: TAS-102 is an orally administered anticancer agent composed of \u03b1,\u03b1,\u03b1-trifluorothymidine (FTD) and thymidine phosphorylase inhibitor (TPI). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25776904", "endSection": "abstract"}, {"offsetInBeginSection": 721, "offsetInEndSection": 1044, "text": "Novel DNA synthesis inhibitors for the treatment of gastrointestinal malignancies include a combination of the antimetabolite TAS-102, which consists of trifluorothymidine with a thymidine phosphorylase inhibitor, and a novel micellar formulation of cisplatin NC-6004 that uses a nanotechnology-based drug delivery system. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25256052", "endSection": "abstract"}]}, {"body": "What is HbVar?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/11857738"], "ideal_answer": "HbVar: A relational database of human hemoglobin variants and thalassemia mutations at the globin gene server.Extensive information is recorded for each variant and mutation, including a description of the variant and associated pathology, hematology, electrophoretic mobility, methods of isolation, stability information, ethnic occurrence, structure studies, functional studies, and references.The initial information was derived from books by Dr. Titus Huisman and colleagues [Huisman et al., 1996, 1997, 1998].Users can formulate more precise queries, such as identifying \"all beta-globin variants associated with instability and found in Scottish populations.\"The current database is updated regularly with the addition of new data and corrections to previous data.Tables of common categories of variants, such as all those involving the alpha1-globin gene (HBA1) or all those that result in high oxygen affinity, are maintained by automated queries on the database.Queries can be formulated based on fields in the database.", "type": "summary", "id": "56c23652ef6e39474100005a", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 110, "text": "HbVar: A relational database of human hemoglobin variants and thalassemia mutations at the globin gene server. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11857738", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 1281, "text": "We have constructed a relational database of hemoglobin variants and thalassemia mutations, called HbVar, which can be accessed on the web at http://globin.cse.psu.edu. Extensive information is recorded for each variant and mutation, including a description of the variant and associated pathology, hematology, electrophoretic mobility, methods of isolation, stability information, ethnic occurrence, structure studies, functional studies, and references. The initial information was derived from books by Dr. Titus Huisman and colleagues [Huisman et al., 1996, 1997, 1998]. The current database is updated regularly with the addition of new data and corrections to previous data. Queries can be formulated based on fields in the database. Tables of common categories of variants, such as all those involving the alpha1-globin gene (HBA1) or all those that result in high oxygen affinity, are maintained by automated queries on the database. Users can formulate more precise queries, such as identifying \"all beta-globin variants associated with instability and found in Scottish populations.\" This new database should be useful for clinical diagnosis as well as in fundamental studies of hemoglobin biochemistry, globin gene regulation, and human sequence variation at these loci. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/11857738", "endSection": "abstract"}]}, {"body": "Which interleukins are inhibited by Dupilumab?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/25645542", "http://www.ncbi.nlm.nih.gov/pubmed/25214796", "http://www.ncbi.nlm.nih.gov/pubmed/25006719", "http://www.ncbi.nlm.nih.gov/pubmed/25482871", "http://www.ncbi.nlm.nih.gov/pubmed/24275927", "http://www.ncbi.nlm.nih.gov/pubmed/23688323", "http://www.ncbi.nlm.nih.gov/pubmed/25584909"], "ideal_answer": "Indeed, dupilumab prevents IL-4/13 interactions with the -subunit of the IL-4 receptor complex.AThe world's first prospective controlled studies with the biologic human anti-IL4R antibody dupilumab for the indication \"atopic dermatitis\" were published in 2014.Examples include the efficacy of omalizumab in patients with severe refractory atopic asthma characterized by raised serum total IgE, mepolizumab, reslizumab, and benralizumab in patients with recurrent eosinophilic exacerbations characterized by blood and sputum eosinophilia despite high doses of corticosteroids, and lebrikizumab, pitrakinra, dupilumab, and tralokinumab that target the IL-4/IL-13 signalling pathways in patients with eosinophilic asthma or raised serum periostin.BACKGROUND: Moderate-to-severe asthma remains poorly treated.These motivated (1) to extend the studies to dupilumab and (2) to clinically test antagonization of other target molecules of TH2 polarized, atopic inflammation, e.g., IL-13, IL-31, IL-22, TSLP, and CRTH2.We evaluated the efficacy and safety of dupilumab (SAR231893/REGN668), a fully human monoclonal antibody to the alpha subunit of the interleukin-4 receptor, in patients with persistent, moderate-to-severe asthma and elevated eosinophil levels.", "type": "list", "id": "56c1f005ef6e39474100003a", "snippets": [{"offsetInBeginSection": 450, "offsetInEndSection": 822, "text": "The world's first prospective controlled studies with the biologic human anti-IL4R antibody dupilumab for the indication \"atopic dermatitis\" were published in 2014. These motivated (1) to extend the studies to dupilumab and (2) to clinically test antagonization of other target molecules of TH2 polarized, atopic inflammation, e.g., IL-13, IL-31, IL-22, TSLP, and CRTH2. A ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25645542", "endSection": "abstract"}, {"offsetInBeginSection": 564, "offsetInEndSection": 850, "text": "Among the recently developed antiasthma biologic drugs, the monoclonal antibody dupilumab is very promising because of its ability to inhibit the biological effects of both IL-4 and IL-13. Indeed, dupilumab prevents IL-4/13 interactions with the \u03b1-subunit of the IL-4 receptor complex. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25214796", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 178, "text": "BACKGROUND: Dupilumab, a fully human monoclonal antibody that blocks interleukin-4 and interleukin-13, has shown efficacy in patients with asthma and elevated eosinophil levels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25006719", "endSection": "abstract"}, {"offsetInBeginSection": 100, "offsetInEndSection": 310, "text": " In early-phase trials, dupilumab, a fully human mAb targeting IL-4 receptor \u03b1, markedly improved disease activity, but the effect of IL-4/IL-13 blockade on AD at the molecular level has not been characterized. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25482871", "endSection": "abstract"}, {"offsetInBeginSection": 888, "offsetInEndSection": 1372, "text": "Examples include the efficacy of omalizumab in patients with severe refractory atopic asthma characterized by raised serum total IgE, mepolizumab, reslizumab, and benralizumab in patients with recurrent eosinophilic exacerbations characterized by blood and sputum eosinophilia despite high doses of corticosteroids, and lebrikizumab, pitrakinra, dupilumab, and tralokinumab that target the IL-4/IL-13 signalling pathways in patients with eosinophilic asthma or raised serum periostin. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24275927", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 305, "text": "BACKGROUND: Moderate-to-severe asthma remains poorly treated. We evaluated the efficacy and safety of dupilumab (SAR231893/REGN668), a fully human monoclonal antibody to the alpha subunit of the interleukin-4 receptor, in patients with persistent, moderate-to-severe asthma and elevated eosinophil levels. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23688323", "endSection": "abstract"}, {"offsetInBeginSection": 1127, "offsetInEndSection": 1335, "text": "With respect to immune dysregulation, dupilumab, a fully human monoclonal antibody directed at the IL-4 receptor alpha subunit was recently shown to be effective in treating adults with moderate-to-severe AD. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25584909", "endSection": "abstract"}]}, {"body": "What is the vibrational theory of olfaction?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/25901328", "http://www.ncbi.nlm.nih.gov/pubmed/8985605"], "ideal_answer": "The vibrational theory of olfaction assumes that electron transfer occurs across odorants at the active sites of odorant receptors (ORs), serving as a sensitive measure of odorant vibrational frequencies, ultimately leading to olfactory perception.The evidence presented here suggests instead that olfaction, like colour vision and hearing, is a spectral sense.Elements of the tunnelling spectroscope are identified in putative olfactory receptors and their associated G-protein.It differs from previous vibrational theories (Dyson, Wright) in providing a detailed and plausible mechanism for biological transduction of molecular vibrations: inelastic electron tunnelling.It proposes that olfactory receptors respond not to the shape of the molecules but to their vibrations.It proposes that olfactory receptors respond not to the shape of the molecules but to their vibrations.It proposes that olfactory receptors respond not to the shape of the molecules but to their vibrations.It proposes that olfactory receptors respond not to the shape of the molecules but to their vibrations.It proposes that olfactory receptors respond not to the shape of the molecules but to their vibrations.", "type": "summary", "id": "56c322d750c68dd416000004", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 248, "text": "The vibrational theory of olfaction assumes that electron transfer occurs across odorants at the active sites of odorant receptors (ORs), serving as a sensitive measure of odorant vibrational frequencies, ultimately leading to olfactory perception. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25901328", "endSection": "abstract"}, {"offsetInBeginSection": 60, "offsetInEndSection": 477, "text": "It proposes that olfactory receptors respond not to the shape of the molecules but to their vibrations. It differs from previous vibrational theories (Dyson, Wright) in providing a detailed and plausible mechanism for biological transduction of molecular vibrations: inelastic electron tunnelling. Elements of the tunnelling spectroscope are identified in putative olfactory receptors and their associated G-protein. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8985605", "endSection": "abstract"}, {"offsetInBeginSection": 1017, "offsetInEndSection": 1130, "text": "The evidence presented here suggests instead that olfaction, like colour vision and hearing, is a spectral sense. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/8985605", "endSection": "abstract"}]}, {"body": "Tumor-treating fields are effective for treatment of which cancers?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/25213867", "http://www.ncbi.nlm.nih.gov/pubmed/25213870", "http://www.ncbi.nlm.nih.gov/pubmed/24884522", "http://www.ncbi.nlm.nih.gov/pubmed/23891283", "http://www.ncbi.nlm.nih.gov/pubmed/23659608", "http://www.ncbi.nlm.nih.gov/pubmed/23899985", "http://www.ncbi.nlm.nih.gov/pubmed/23095807", "http://www.ncbi.nlm.nih.gov/pubmed/21548832", "http://www.ncbi.nlm.nih.gov/pubmed/20492723", "http://www.ncbi.nlm.nih.gov/pubmed/19387848", "http://www.ncbi.nlm.nih.gov/pubmed/19133110", "http://www.ncbi.nlm.nih.gov/pubmed/18596382", "http://www.ncbi.nlm.nih.gov/pubmed/24555979"], "ideal_answer": "Response patterns of recurrent glioblastomas treated with tumor-treating fields.Tumor treating fields (TTFields) are low intensity (1 ?CONCLUSIONS: The results indicate that TTFields alone and in combination with paclitaxel and doxorubicin effectively reduce the viability of both wild type and MDR cell sub-lines and thus can potentially be used as an effective treatment of drug resistant tumors.Alternating electric fields (tumor-treating fields therapy) can improve chemotherapy treatment efficacy in non-small cell lung cancer both in vitro and in vivo.Our center was the first to apply TTField treatment to histologically proven GBM in a small pilot study of 20 individuals in 2004 and 2005, and four of those original 20 patients are still alive today.TTFields improved disease control within the treatment field and a phase III study is planned to further investigate its role as a novel treatment in NSCLC.A third patient on NovoTTF Therapy/TMZ remained stable for two years but developed a small, slow growing enhancing lesion, which was resected, and his fields were adjusted accordingly.", "type": "list", "id": "56c1f007ef6e39474100003b", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 160, "text": "Alternating electric fields (tumor-treating fields therapy) can improve chemotherapy treatment efficacy in non-small cell lung cancer both in vitro and in vivo. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25213867", "endSection": "title"}, {"offsetInBeginSection": 829, "offsetInEndSection": 1219, "text": "e evaluated the effects of combining TTFields with standard chemotherapeutic agents on several NSCLC cell lines, both in vitro and in vivo. Frequency titration curves demonstrated that the inhibitory effects of TTFields were maximal at 150 kHz for all NSCLC cell lines tested, and that the addition of TTFields to chemotherapy resulted in enhanced treatment efficacy across all cell lines. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25213867", "endSection": "abstract"}, {"offsetInBeginSection": 1647, "offsetInEndSection": 1798, "text": "Together, these findings suggest that combining TTFields therapy with chemotherapy may provide an additive efficacy benefit in the management of NSCLC. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25213867", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 80, "text": "Response patterns of recurrent glioblastomas treated with tumor-treating fields. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25213870", "endSection": "title"}, {"offsetInBeginSection": 293, "offsetInEndSection": 1152, "text": "NovoTTF Therapy is a novel and US Food and Drug Administration (FDA)-approved antimitotic treatment for recurrent GBM with potential benefits compared with other options. Recurrent GBM patients from two prior trials with demonstrated radiologic tumor response to single-agent NovoTTF Therapy were analyzed to better characterize tumor response patterns and evaluate the associations between response, compliance, and OS. In addition, a compartmental tumor growth model was developed and evaluated for its ability to predict GBM response to tumor-treating fields (TTFields). The overall response rate across both trials was 15% (4% complete responses): 14% in the phase III trial (14/120) and 20% (2/10) in a pilot study. Tumor responses to NovoTTF Therapy developed slowly (median time to response, 5.2 months) but were durable (median duration, 12.9 months). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25213870", "endSection": "abstract"}, {"offsetInBeginSection": 1645, "offsetInEndSection": 1807, "text": "NovoTTF Therapy is a novel antimitotic treatment for recurrent GBM associated with slowly developing but durable tumor responses in approximately 15% of patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25213870", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 115, "text": "The effect of field strength on glioblastoma multiforme response in patients treated with the NovoTTF\u2122-100A system. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24884522", "endSection": "title"}, {"offsetInBeginSection": 193, "offsetInEndSection": 334, "text": " An ongoing trial is assessing its efficacy for newly diagnosed glioblastoma multiforme (GBM) and it has been FDA-approved for recurrent GBM. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24884522", "endSection": "abstract"}, {"offsetInBeginSection": 595, "offsetInEndSection": 712, "text": "We present three patients with GBM in whom the fields were adjusted at recurrence and the effects of each adjustment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24884522", "endSection": "abstract"}, {"offsetInBeginSection": 837, "offsetInEndSection": 975, "text": "The first patient underwent subtotal resection, radiotherapy with temozolomide (TMZ), and then began NovoTTF Therapy with metronomic TMZ. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24884522", "endSection": "abstract"}, {"offsetInBeginSection": 1232, "offsetInEndSection": 1713, "text": " A second patient underwent two resections followed by radiotherapy/TMZ and NovoTTF Therapy/TMZ. Six months later, two new distal lesions were noted, and he underwent further resection with adjustment of his fields. He remained stable over the subsequent year on NovoTTF Therapy and bevacizumab. A third patient on NovoTTF Therapy/TMZ remained stable for two years but developed a small, slow growing enhancing lesion, which was resected, and his fields were adjusted accordingly. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24884522", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "A phase I/II trial of Tumor Treating Fields (TTFields) therapy in combination with pemetrexed for advanced non-small cell lung cancer. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23891283", "endSection": "title"}, {"offsetInBeginSection": 160, "offsetInEndSection": 466, "text": "Promising preclinical data have led to a single arm phase I/II trial in NSCLC patients.METHODS: Forty-two inoperable stage IIIB (with pleural effusion) and IV NSCLC patients who had had tumor progression received pemetrexed 500 mg/m(2) iv q3w together with daily TTFields therapy until disease progression. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23891283", "endSection": "abstract"}, {"offsetInBeginSection": 660, "offsetInEndSection": 770, "text": "The median time to in-field progression was 28 weeks and the median time to systemic progression was 22 weeks. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23891283", "endSection": "abstract"}, {"offsetInBeginSection": 989, "offsetInEndSection": 1298, "text": "CONCLUSIONS: The combination of TTFields and pemetrexed as a second line therapy for NSCLC is safe and potentially more effective than pemetrexed alone. TTFields improved disease control within the treatment field and a phase III study is planned to further investigate its role as a novel treatment in NSCLC. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23891283", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 203, "text": "Tumor treating fields (TTFields) is a noninvasive, regional antimitotic treatment modality that has been approved for the treatment of recurrent glioblastoma by the U.S. FDA and has a CE mark in Europe. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23659608", "endSection": "abstract"}, {"offsetInBeginSection": 675, "offsetInEndSection": 1227, "text": "The antimitotic effect of TTFields therapy has been demonstrated in multiple cell lines when the appropriate frequency was utilized. A phase III trial of TTFields monotherapy compared to active chemotherapy in recurrent glioblastoma patients established that TTFields therapy is associated with minimal toxicity, better quality of life, and comparable efficacy to chemotherapy. Ongoing and future trials will evaluate TTFields in newly diagnosed glioblastoma, solid tumor brain metastases, nonsmall cell lung cancer, and ovarian and pancreatic cancers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23659608", "endSection": "abstract"}, {"offsetInBeginSection": 70, "offsetInEndSection": 401, "text": "The U.S. Food and Drug Administration has approved the first device, the NovoTTF-100A\u2122, that uses this technology and is indicated for use in progressive glioblastoma multiforme after standard therapies have failed. Promising clinical trial results will likely lead to expanded uses in primary brain tumors and other cancer types. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23899985", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 105, "text": "Long-term survival of patients suffering from glioblastoma multiforme treated with tumor-treating fields. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23095807", "endSection": "title"}, {"offsetInBeginSection": 336, "offsetInEndSection": 1080, "text": "Tumor-treating fields (TTField) therapy is a novel treatment technique that has recently received CE and FDA approval for the treatment of RGBM, and is based on the principle that low intensity, intermediate frequency electric fields (100 to 300 kHz) may induce apoptosis in specific cell types. Our center was the first to apply TTField treatment to histologically proven GBM in a small pilot study of 20 individuals in 2004 and 2005, and four of those original 20 patients are still alive today. We report two cases of GBM and two cases of RGBM treated by TTField therapy, all in good health and no longer receiving any treatment more than seven years after initiating TTField therapy, with no clinical or radiological evidence of recurrence. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23095807", "endSection": "abstract"}, {"offsetInBeginSection": 113, "offsetInEndSection": 349, "text": "Tumor treating fields (TTFields) are low intensity (1 ? 2 V/cm), intermediate frequency (100 ? 200 kHz) alternating electric fields administered using insulated electrodes placed on the skin surrounding the region of a malignant tumor. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21548832", "endSection": "abstract"}, {"offsetInBeginSection": 706, "offsetInEndSection": 1113, "text": "Furthermore, it summarizes the clinical experience with TTFields, mainly in two indications: one in recurrent glioblastoma multiforme: in a large prospective randomized Phase III trial TTFields was compared with best standard care (including chemotherapy): TTFields significantly improved median overall survival (OS) compared with standard therapy (7.8 vs 6.1 months) for the patients treated per protocol. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21548832", "endSection": "abstract"}, {"offsetInBeginSection": 1182, "offsetInEndSection": 1331, "text": "The second indication was a Phase II study in second-line non-small cell lung cancer, where TTFields was administered concomitantly with pemetrexed. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21548832", "endSection": "abstract"}, {"offsetInBeginSection": 1546, "offsetInEndSection": 1711, "text": "EXPERT OPINION: The proof of concept of TTFields has been well demonstrated in the preclinical setting, and the clinical data seem promising in various tumor types. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21548832", "endSection": "abstract"}, {"offsetInBeginSection": 1568, "offsetInEndSection": 1831, "text": "CONCLUSIONS: The results indicate that TTFields alone and in combination with paclitaxel and doxorubicin effectively reduce the viability of both wild type and MDR cell sub-lines and thus can potentially be used as an effective treatment of drug resistant tumors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20492723", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 94, "text": "Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19387848", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 314, "text": "Tumor treating fields (TTFields) are low intensity, intermediate frequency, alternating electric fields used to treat cancerous tumors. This novel treatment modality effectively inhibits the growth of solid tumors in vivo and has shown promise in pilot clinical trials in patients with advanced stage solid tumors. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19387848", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 244, "text": "BACKGROUND: The present study explores the efficacy and toxicity of combining a new, non-toxic, cancer treatment modality, termed Tumor Treating Fields (TTFields), with chemotherapeutic treatment in-vitro, in-vivo and in a pilot clinical trial. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19133110", "endSection": "abstract"}, {"offsetInBeginSection": 489, "offsetInEndSection": 847, "text": "In addition, we studied the effects of combining chemotherapy with TTFields in an animal tumor model and in a pilot clinical trial in recurrent and newly diagnosed GBM patients.RESULTS: The efficacy of TTFields-chemotherapy combination in-vitro was found to be additive with a tendency towards synergism for all drugs and cell lines tested (combination index ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/19133110", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 143, "text": "A pilot study with very low-intensity, intermediate-frequency electric fields in patients with locally advanced and/or metastatic solid tumors. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18596382", "endSection": "title"}, {"offsetInBeginSection": 306, "offsetInEndSection": 555, "text": "PATIENTS AND METHODS: This open, prospective pilot study was designed to evaluate the safety, tolerability, and efficacy profile of TTFields treatment in patients with locally advanced and/or metastatic solid tumors using the NovoTTF100A(TM) device. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18596382", "endSection": "abstract"}, {"offsetInBeginSection": 848, "offsetInEndSection": 1442, "text": "Outcomes showed 1 partial response of a treated skin metastasis from a primary breast cancer, 3 cases where tumor growth was arrested during treatment, and 1 case of disease progression. One mesothelioma patient experienced lesion regression near TTFields with simultaneous tumor stability or progression in distal areas.CONCLUSION: Although the number of patients in this study is small, the lack of therapy toxicity and the efficacy observed in data gathered to date indicate the potential of TTFields as a new treatment modality for solid tumors, definitely warranting further investigation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18596382", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "Mitotic disruption and reduced clonogenicity of pancreatic cancer cells in vitro and in vivo by tumor treating fields. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24555979", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 279, "text": "OBJECTIVES: Tumor Treating Fields (TTFields) are a non-invasive cancer treatment modality approved for the treatment of patients with recurrent glioblastoma. The present study determined the efficacy and mechanism of action of TTFields in preclinical models of pancreatic cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24555979", "endSection": "abstract"}, {"offsetInBeginSection": 507, "offsetInEndSection": 1371, "text": "RESULTS: Application of TTFields in vitro showed a significant decrease in cell count, an increase in cell volume and reduced clonogenicity. Further analysis demonstrated significant increase in the number of abnormal mitotic figures, as well as a decrease in G2-M cell population. In hamsters with orthotopic pancreatic tumors, TTFields significantly reduced tumor volume accompanied by an increase in the frequency of abnormal mitotic events. TTFields efficacy was enhanced both in vitro and in vivo when combined with chemotherapy.CONCLUSIONS: These results provide the first evidence that TTFields serve as an effective antimitotic treatment in preclinical pancreatic cancer models and have a long term negative effect on cancer cell survival. These results make TTFields an attractive candidate for testing in the treatment of patients with pancreatic cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24555979", "endSection": "abstract"}]}, {"body": "Are there transposon-free regions in mammalian genomes?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/16365385"], "ideal_answer": "Transposon-free regions in mammalian genomes.Most TFRs are not associated with unusual nucleotide composition, but are significantly associated with genes encoding developmental regulators, suggesting that they represent extended regions of regulatory information that are largely unable to tolerate insertions, a conclusion difficult to reconcile with current conceptions of gene regulation.Despite the presence of over 3 million transposons separated on average by approximately 500 bp, the human and mouse genomes each contain almost 1000 transposon-free regions (TFRs) over 10 kb in length.Many human TFRs also overlap with orthologous TFRs in the marsupial opossum, indicating that these regions have remained refractory to transposon insertion for long evolutionary periods.Over 90% of the bases covered by TFRs are noncoding, much of which is not highly conserved.The majority of human TFRs correlate with orthologous TFRs in the mouse, despite the fact that most transposons are lineage specific.The majority of human TFRs correlate with orthologous TFRs in the mouse, despite the fact that most transposons are lineage specific.", "type": "yesno", "id": "56c44ce83aaba2a675000001", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 45, "text": "Transposon-free regions in mammalian genomes. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16365385", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 963, "text": "Despite the presence of over 3 million transposons separated on average by approximately 500 bp, the human and mouse genomes each contain almost 1000 transposon-free regions (TFRs) over 10 kb in length. The majority of human TFRs correlate with orthologous TFRs in the mouse, despite the fact that most transposons are lineage specific. Many human TFRs also overlap with orthologous TFRs in the marsupial opossum, indicating that these regions have remained refractory to transposon insertion for long evolutionary periods. Over 90% of the bases covered by TFRs are noncoding, much of which is not highly conserved. Most TFRs are not associated with unusual nucleotide composition, but are significantly associated with genes encoding developmental regulators, suggesting that they represent extended regions of regulatory information that are largely unable to tolerate insertions, a conclusion difficult to reconcile with current conceptions of gene regulation. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16365385", "endSection": "abstract"}]}, {"body": "Describe July Effect.", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/25860519", "http://www.ncbi.nlm.nih.gov/pubmed/25542761", "http://www.ncbi.nlm.nih.gov/pubmed/25633735", "http://www.ncbi.nlm.nih.gov/pubmed/25374038", "http://www.ncbi.nlm.nih.gov/pubmed/24578770", "http://www.ncbi.nlm.nih.gov/pubmed/24384663"], "ideal_answer": "The \"August\" or \"July effect\" describes increased errors and reduced patient safety during this transition.It is unclear, however, if this difference was related to climatological changes or inexperienced medical trainees (the July effect). Given the nonteaching nature of these hospitals, the findings demonstrate that increases in the rate of SSI during the summer are more likely related to ecological and/or environmental factors than the July effect.INTRODUCTION: There has been concern of increased emergency department (ED) length of stay (LOS) during the months when new residents are orienting to their roles.SUMMARY OF BACKGROUND DATA: The July effect is the hypothetical increase in morbidity and mortality thought to be associated with the influx of new (or newly promoted) trainees during the first portion of the academic year.This so-called \"July Effect\" has long been thought to increase LOS, and potentially contribute to hospital overcrowding and increased waiting time for patients.", "type": "summary", "id": "56c1f00fef6e394741000040", "snippets": [{"offsetInBeginSection": 325, "offsetInEndSection": 459, "text": "It is unclear, however, if this difference was related to climatological changes or inexperienced medical trainees (the July effect). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25860519", "endSection": "abstract"}, {"offsetInBeginSection": 2991, "offsetInEndSection": 3206, "text": " Given the nonteaching nature of these hospitals, the findings demonstrate that increases in the rate of SSI during the summer are more likely related to ecological and/or environmental factors than the July effect. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25860519", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 171, "text": "BACKGROUND: Lower quality of care and poorer outcomes are suspected when new trainees (eg, residents) start in July in teaching hospitals, the so-called \"the July effect.\" ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25542761", "endSection": "abstract"}, {"offsetInBeginSection": 70, "offsetInEndSection": 178, "text": "The \"August\" or \"July effect\" describes increased errors and reduced patient safety during this transition. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25633735", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 200, "text": "PURPOSE: Researchers have found mixed results about the risk to patient safety in July, when newly minted physicians enter U.S. hospitals to begin their clinical training, the so-called \"July effect.\" ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25374038", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 324, "text": "INTRODUCTION: There has been concern of increased emergency department (ED) length of stay (LOS) during the months when new residents are orienting to their roles. This so-called \"July Effect\" has long been thought to increase LOS, and potentially contribute to hospital overcrowding and increased waiting time for patients. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24578770", "endSection": "abstract"}, {"offsetInBeginSection": 140, "offsetInEndSection": 363, "text": "SUMMARY OF BACKGROUND DATA: The July effect is the hypothetical increase in morbidity and mortality thought to be associated with the influx of new (or newly promoted) trainees during the first portion of the academic year. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24384663", "endSection": "abstract"}]}, {"body": "What is the application of the Bimolecular Fluorescence Complementation (BiFC) assay in Drosophila embryos?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/25151172", "http://www.ncbi.nlm.nih.gov/pubmed/21276241"], "ideal_answer": "Bimolecular fluorescence complementation (BiFC) is a powerful method for studying protein-protein interactions in different cell types and organisms.Here we present a detailed protocol for performing BiFC with the Venus fluorescent protein in live Drosophila embryos, taking the Hox-PBC partnership as an illustrative test case.The bimolecular fluorescence complementation (BiFC) technology offers this possibility as it enables the direct visualization of protein interactions in living cells.Importantly, all BiFC parameters were established with constructs that were stably expressed under the control of endogenous promoters.This method was recently developed in the fruit fly Drosophila melanogaster, allowing analyzing protein interaction properties in a physiologically relevant developing context.We next used BiFC in a candidate interaction screen, which led to the identification of several Hox protein partners.The understanding of developmental complexity will, therefore, require the characterization of protein interactions within their proper environment.Under these physiological conditions, we showed that BiFC is specific and sensitive enough to analyse dynamic protein interactions.This protocol applies to any transcription factor and split fluorescent protein in general.", "type": "factoid", "id": "56c868a95795f9a73e000017", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 598, "text": "Bimolecular fluorescence complementation (BiFC) is a powerful method for studying protein-protein interactions in different cell types and organisms. This method was recently developed in the fruit fly Drosophila melanogaster, allowing analyzing protein interaction properties in a physiologically relevant developing context. Here we present a detailed protocol for performing BiFC with the Venus fluorescent protein in live Drosophila embryos, taking the Hox-PBC partnership as an illustrative test case. This protocol applies to any transcription factor and split fluorescent protein in general. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25151172", "endSection": "abstract"}, {"offsetInBeginSection": 101, "offsetInEndSection": 416, "text": "The understanding of developmental complexity will, therefore, require the characterization of protein interactions within their proper environment. The bimolecular fluorescence complementation (BiFC) technology offers this possibility as it enables the direct visualization of protein interactions in living cells. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21276241", "endSection": "abstract"}, {"offsetInBeginSection": 575, "offsetInEndSection": 1119, "text": "Using a Hox protein partnership as a test case, we investigated the suitability of BiFC for the study of protein interactions in the living Drosophila embryo. Importantly, all BiFC parameters were established with constructs that were stably expressed under the control of endogenous promoters. Under these physiological conditions, we showed that BiFC is specific and sensitive enough to analyse dynamic protein interactions. We next used BiFC in a candidate interaction screen, which led to the identification of several Hox protein partners. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21276241", "endSection": "abstract"}]}, {"body": "What is the mechanism of action of ocrelizumab for treatment of multiple sclerosis?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/24707333", "http://www.ncbi.nlm.nih.gov/pubmed/24001305", "http://www.ncbi.nlm.nih.gov/pubmed/24032475", "http://www.ncbi.nlm.nih.gov/pubmed/24444048", "http://www.ncbi.nlm.nih.gov/pubmed/24928997", "http://www.ncbi.nlm.nih.gov/pubmed/25732947", "http://www.ncbi.nlm.nih.gov/pubmed/25296871", "http://www.ncbi.nlm.nih.gov/pubmed/24579720", "http://www.ncbi.nlm.nih.gov/pubmed/24251808", "http://www.ncbi.nlm.nih.gov/pubmed/24832354", "http://www.ncbi.nlm.nih.gov/pubmed/22766059", "http://www.ncbi.nlm.nih.gov/pubmed/24090587", "http://www.ncbi.nlm.nih.gov/pubmed/23208729", "http://www.ncbi.nlm.nih.gov/pubmed/23448220", "http://www.ncbi.nlm.nih.gov/pubmed/23609782", "http://www.ncbi.nlm.nih.gov/pubmed/24494635", "http://www.ncbi.nlm.nih.gov/pubmed/22171583", "http://www.ncbi.nlm.nih.gov/pubmed/22229582"], "ideal_answer": "In multiple sclerosis (MS), B cell-depleting therapy using monoclonal anti-CD20 Abs, including rituximab (RTX) and ocrelizumab, effectively reduces disease activity.The main efficacy and safety results of these drugs are reviewed in this paper.Recent therapeutic advances include modifications to improve tolerability of existing products (e.g. To reduce the risk of infusion reactions and improve long-term tolerability, the human-derived components of the antibody have been increased to form humanized or human monoclonal antibodies like ocrelizumab and ofatumumab.They can be categorized according to their mode of action into compounds targeting (i) leukocyte migration into the CNS (natalizumab); (ii) cytolytic antibodies (rituximab, ocrelizumab, ofatumumab, alemtuzumab); or (iii) antibodies and recombinant proteins targeting cytokines and chemokines and their receptors (daclizumab, ustekinumab, atacicept, tabalumab [Ly-2127399], secukinumab [AIN457]).Ocrelizumab will likely also be licensed as a second-line therapy in highly active MS.rituximab, ocrelizumab or ofatumumab, in CIDP patients are currently under way.", "type": "summary", "id": "56c1f011ef6e394741000042", "snippets": [{"offsetInBeginSection": 80, "offsetInEndSection": 474, "text": "Recent therapeutic advances include modifications to improve tolerability of existing products (e.g. interferon beta and glatiramer acetate), development of novel anti-neuroinflammatory medications (e.g. fingolimod, teriflunomide and dimethyl fumarate, daclizumab, alemtuzumab, ocrelizumab) and investigation of treatments in progressive MS (e.g. natalizumab, mastinib, natalizumab, siponimod). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24707333", "endSection": "abstract"}, {"offsetInBeginSection": 630, "offsetInEndSection": 772, "text": "This review provides insights into clinical studies with the mAbs natalizumab, alemtuzumab, daclizumab, rituximab, ocrelizumab and ofatumumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24001305", "endSection": "abstract"}, {"offsetInBeginSection": 1123, "offsetInEndSection": 1456, "text": "Alemtuzumab, ocrelizumab and daclizumab respresent monoclonal antibodies in advanced stages of clinical development for their use in RRMS patients. Attempts to study the safety and efficacy of alemtuzumab and B cell-depleting anti-CD20 antibodies, i.e. rituximab, ocrelizumab or ofatumumab, in CIDP patients are currently under way. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24032475", "endSection": "abstract"}, {"offsetInBeginSection": 675, "offsetInEndSection": 940, "text": "More recently, monoclonal antibodies have been engineered to act through specific mechanisms such as blocking alpha-4 integrin interactions (natalizumab) or lysing cells bearing specific markers, for example CD52 (alemtuzumab) or CD20 (ocrelizumab and ofatumumab). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24444048", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 166, "text": "In multiple sclerosis (MS), B cell-depleting therapy using monoclonal anti-CD20 Abs, including rituximab (RTX) and ocrelizumab, effectively reduces disease activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24928997", "endSection": "abstract"}, {"offsetInBeginSection": 491, "offsetInEndSection": 738, "text": "Today, there is broad experience with natalizumab and other MOAB (alemtuzumab, daclizumab, rituximab, ocrelizumab, ofatumumab and anti-lingo-1) that are pending commercialization or are under phase II or III of development with promising results. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25732947", "endSection": "abstract"}, {"offsetInBeginSection": 1314, "offsetInEndSection": 1538, "text": " To reduce the risk of infusion reactions and improve long-term tolerability, the human-derived components of the antibody have been increased to form humanized or human monoclonal antibodies like ocrelizumab and ofatumumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25296871", "endSection": "abstract"}, {"offsetInBeginSection": 1062, "offsetInEndSection": 1149, "text": "Ocrelizumab will likely also be licensed as a second-line therapy in highly active MS. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24579720", "endSection": "abstract"}, {"offsetInBeginSection": 372, "offsetInEndSection": 814, "text": "This is because of: (i) patent expirations, (ii) the introduction of natalizumab, which targets the interaction between leukocytes and the blood-CNS barrier, (iii) the launch of three oral immunomodulatory drugs (fingolimod, dimethyl fumarate and teriflunomide), with another (laquinimod) under regulatory review and (iv) a number of immunomodulatory monoclonal antibodies (alemtuzumab, daclizumab and ocrelizumab) about to enter the market. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24251808", "endSection": "abstract"}, {"offsetInBeginSection": 1033, "offsetInEndSection": 1579, "text": "In this review, we further discuss evidence for B cell and Ig contribution to human MS and NMO pathogenesis, pro-inflammatory and regulatory B cell effector functions, impaired B cell immune tolerance, the B cell-fostering microenvironment in the CNS, and B cell-targeted therapeutic interventions for MS and NMO, including CD20 depletion (rituximab, ocrelizumab, and ofatumumab), anti-IL6-R (tocilizumab), complement-blocking (eculizumab), inhibitors of AQP4-Ig binding (aquaporumab, small molecular compounds), and BAFF/BAFF-R-targeting agents. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24832354", "endSection": "abstract"}, {"offsetInBeginSection": 669, "offsetInEndSection": 979, "text": "The main efficacy and safety results of these drugs are reviewed in this paper. They can be classified into 2 groups: oral (fingolimod, laquinimod, teriflunomide, BG-12 [dimethyl fumarate], oral cladribine, dalfampridine) and monoclonal antibodies (rituximab, ocrelizumab, ofatumumab, daclizumab, alemtuzumab). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22766059", "endSection": "abstract"}, {"offsetInBeginSection": 700, "offsetInEndSection": 883, "text": "Daclizumab and ocrelizumab are monoclonal antibodies that have shown efficacy and acceptable safety profiles in phase 2 trials; both are under investigation in ongoing phase 3 trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24090587", "endSection": "abstract"}, {"offsetInBeginSection": 408, "offsetInEndSection": 585, "text": " As such, humoral targeted immunotherapies that are being developed for MS are discussed herein: rituximab, ocrelizumab, and ofatumumab show promise as B-cell depleting agents. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23208729", "endSection": "abstract"}, {"offsetInBeginSection": 889, "offsetInEndSection": 1052, "text": " The section on anti-CD20 antibodies reviews Phase II results on ocrelizumab and ofatumumab, and discusses current perspectives of these antibodies for MS therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23448220", "endSection": "abstract"}, {"offsetInBeginSection": 1655, "offsetInEndSection": 1858, "text": "Rituximab is unlikely to be developed further as its license will expire, but ocrelizumab, another monoclonal antibody directly targeting B cells, is currently in phase 2 development and looks promising. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23609782", "endSection": "abstract"}, {"offsetInBeginSection": 1228, "offsetInEndSection": 1439, "text": "In addition, oral laquinimod, several monoclonal antibodies (eg, alemtuzumab, daclizumab, and ocrelizumab), and other agents have shown preliminary beneficial results in relapsing MS in phase 3 clinical trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24494635", "endSection": "abstract"}, {"offsetInBeginSection": 614, "offsetInEndSection": 1010, "text": "They can be categorized according to their mode of action into compounds targeting (i) leukocyte migration into the CNS (natalizumab); (ii) cytolytic antibodies (rituximab, ocrelizumab, ofatumumab, alemtuzumab); or (iii) antibodies and recombinant proteins targeting cytokines and chemokines and their receptors (daclizumab, ustekinumab, atacicept, tabalumab [Ly-2127399], secukinumab [AIN457]). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22171583", "endSection": "abstract"}, {"offsetInBeginSection": 731, "offsetInEndSection": 933, "text": "The second concept is to deplete T cells and/or B cells from the peripheral circulation using highly specific monoclonal antibodies such as alemtuzumab (anti-CD52) or rituximab/ocrelizumab (anti-CD20). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22229582", "endSection": "abstract"}]}, {"body": "Which genome browser database for DNA shape annotations is available?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/25326329"], "ideal_answer": "GBshape: a genome browser database for DNA shape annotations.As biological applications, we illustrate the periodicity of DNA shape features that are present in nucleosome-occupied sequences from human, fly and worm, and we demonstrate structural similarities between transcription start sites in the genomes of four Drosophila species.Our Genome Browser for DNA shape annotations (GBshape; freely available at http://rohslab.cmb.usc.edu/GBshape/) provides minor groove width, propeller twist, roll, helix twist and hydroxyl radical cleavage predictions for the entire genomes of 94 organisms.GBshape can be used to visualize DNA shape annotations qualitatively in a genome browser track format, and to download quantitative values of DNA shape features as a function of genomic position at nucleotide resolution.Additional genomes can easily be added using the GBshape framework.Additional genomes can easily be added using the GBshape framework.Additional genomes can easily be added using the GBshape framework.Additional genomes can easily be added using the GBshape framework.Additional genomes can easily be added using the GBshape framework.Additional genomes can easily be added using the GBshape framework.", "type": "factoid", "id": "56c8f4615795f9a73e00001a", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 61, "text": "GBshape: a genome browser database for DNA shape annotations. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25326329", "endSection": "title"}, {"offsetInBeginSection": 531, "offsetInEndSection": 1353, "text": "Our Genome Browser for DNA shape annotations (GBshape; freely available at http://rohslab.cmb.usc.edu/GBshape/) provides minor groove width, propeller twist, roll, helix twist and hydroxyl radical cleavage predictions for the entire genomes of 94 organisms. Additional genomes can easily be added using the GBshape framework. GBshape can be used to visualize DNA shape annotations qualitatively in a genome browser track format, and to download quantitative values of DNA shape features as a function of genomic position at nucleotide resolution. As biological applications, we illustrate the periodicity of DNA shape features that are present in nucleosome-occupied sequences from human, fly and worm, and we demonstrate structural similarities between transcription start sites in the genomes of four Drosophila species. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25326329", "endSection": "abstract"}]}, {"body": "What is targeted by Palbociclib?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/26045340", "http://www.ncbi.nlm.nih.gov/pubmed/25636162", "http://www.ncbi.nlm.nih.gov/pubmed/25701171", "http://www.ncbi.nlm.nih.gov/pubmed/24216225", "http://www.ncbi.nlm.nih.gov/pubmed/23300028", "http://www.ncbi.nlm.nih.gov/pubmed/21109448", "http://www.ncbi.nlm.nih.gov/pubmed/21815704", "http://www.ncbi.nlm.nih.gov/pubmed/21679088", "http://www.ncbi.nlm.nih.gov/pubmed/21806477", "http://www.ncbi.nlm.nih.gov/pubmed/20197484"], "ideal_answer": "BACKGROUND: Necitumumab is a second-generation, recombinant, human immunoglobulin G1 EGFR antibody. A Southwest Oncology Group study currently prospectively evaluates the predictive biomarkers for cetuximab.Joining cetuximab, sorafenib, afatinib, intedanib, and crizotinib in phase III development for non-small cell lung cancer (NSCLC) are ramucirumab (developed by ImClone, a subsidiary of Lilly), necitumumab (developed by ImClone and Bristol-Myers Squibb), and tivantinib (ARQ 197, developed by ArQule and Daiichi Sankyo).Numerous other drugs are in earlier stages of development for HNSCC treatment, including novel anti-EGFR mAbs (MEHD7945A, necitumumab, and RO5083945), small-molecule TKIs (vandetanib, icotinib, and CUDC-101), EGFR antisense, various add-on therapies to radiation and chemotherapy (bevacizumab, interleukin-12, lenalidomide, alisertib, and VTX-2337), and drugs (temsirolimus, everolimus, OSI-906, dasatinib, and PX-866) intended to overcome resistance to anti-EGFR agents.Epidermal growth factor receptor-directed monoclonal antibodies in nonsmall cell lung cancer: an update.Necitumumab is a second-generation anti-EGFR monoclonal antibody (mAb) similar to cetuximab.", "type": "factoid", "id": "56c1f01cef6e394741000044", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "BACKGROUND: Necitumumab is a second-generation, recombinant, human immunoglobulin G1 EGFR antibody. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26045340", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 104, "text": "Epidermal growth factor receptor-directed monoclonal antibodies in nonsmall cell lung cancer: an update. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25636162", "endSection": "title"}, {"offsetInBeginSection": 505, "offsetInEndSection": 762, "text": " A Southwest Oncology Group study currently prospectively evaluates the predictive biomarkers for cetuximab. In the SQUIRE phase III trial, necitumumab added to cisplatin and gemcitabine increased the survival in patients with advanced squamous cell NSCLC. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25636162", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "BACKGROUND: Necitumumab is a second-generation recombinant human immunoglobulin G1 EGFR monoclonal antibody that competitively inhibits ligand binding. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25701171", "endSection": "abstract"}, {"offsetInBeginSection": 1231, "offsetInEndSection": 1703, "text": "Numerous other drugs are in earlier stages of development for HNSCC treatment, including novel anti-EGFR mAbs (MEHD7945A, necitumumab, and RO5083945), small-molecule TKIs (vandetanib, icotinib, and CUDC-101), EGFR antisense, various add-on therapies to radiation and chemotherapy (bevacizumab, interleukin-12, lenalidomide, alisertib, and VTX-2337), and drugs (temsirolimus, everolimus, OSI-906, dasatinib, and PX-866) intended to overcome resistance to anti-EGFR agents. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24216225", "endSection": "abstract"}, {"offsetInBeginSection": 1072, "offsetInEndSection": 1233, "text": "Necitumumab, a fully human monoclonal antibody, is currently evaluated in combination with chemotherapy in two phase III trials in patients with advanced NSCLC. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23300028", "endSection": "abstract"}, {"offsetInBeginSection": 1188, "offsetInEndSection": 1291, "text": "Necitumumab is currently evaluated in combination with chemotherapy in two randomized phase III trials. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21109448", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 412, "text": "Joining cetuximab, sorafenib, afatinib, intedanib, and crizotinib in phase III development for non-small cell lung cancer (NSCLC) are ramucirumab (developed by ImClone, a subsidiary of Lilly), necitumumab (developed by ImClone and Bristol-Myers Squibb), and tivantinib (ARQ 197, developed by ArQule and Daiichi Sankyo). Necitumumab is a second-generation anti-EGFR monoclonal antibody (mAb) similar to cetuximab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21815704", "endSection": "abstract"}, {"offsetInBeginSection": 332, "offsetInEndSection": 564, "text": "Necitumunab is a fully human IgG1 monoclonal antibody targeting EGFR, having the potential benefit of lower hypersensitivity reaction risk as compared with cetuximab and also equivalent antibody-dependent cell-mediated cytotoxicity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21679088", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 123, "text": "Necitumumab, a monoclonal antibody directed against EGFR, is currently under development as a treatment for advanced NSCLC. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21806477", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 163, "text": "A phase I pharmacologic study of necitumumab (IMC-11F8), a fully human IgG1 monoclonal antibody directed against EGFR in patients with advanced solid malignancies. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20197484", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 362, "text": "PURPOSE: This study aimed to determine a maximum tolerated dose (MTD) and recommended dose for disease-directed studies of necitumumab (IMC-11F8), a fully human IgG(1) monoclonal antibody directed at the epidermal growth factor receptor, and to characterize the safety profile, pharmacokinetics, preliminary antitumor activity, and immunogenicity of necitumumab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/20197484", "endSection": "abstract"}]}, {"body": "What is DNAshape?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/23703209"], "ideal_answer": "The DNAshape web server is freely available at http://rohslab.cmb.usc.edu/DNAshape/.The results of rigorous validations of the HT predictions based on DNA structures solved by X-ray crystallography and NMR spectroscopy, hydroxyl radical cleavage data, statistical analysis and cross-validation, and molecular dynamics simulations provide strong confidence in this approach.It requires only nucleotide sequence as input and instantly predicts multiple structural features of DNA (minor groove width, roll, propeller twist and helix twist).DNAshape: a method for the high-throughput prediction of DNA structural features on a genomic scale.This approach provides the framework for the integration of DNA sequence and shape analyses in genome-wide studies.The HT methodology uses a sliding-window approach to mine DNA structural information obtained from Monte Carlo simulations.We present a method and web server for predicting DNA structural features in a high-throughput (HT) manner for massive sequence data.We present a method and web server for predicting DNA structural features in a high-throughput (HT) manner for massive sequence data.", "type": "summary", "id": "56c8f7445795f9a73e00001b", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 100, "text": "DNAshape: a method for the high-throughput prediction of DNA structural features on a genomic scale. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23703209", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 914, "text": "We present a method and web server for predicting DNA structural features in a high-throughput (HT) manner for massive sequence data. This approach provides the framework for the integration of DNA sequence and shape analyses in genome-wide studies. The HT methodology uses a sliding-window approach to mine DNA structural information obtained from Monte Carlo simulations. It requires only nucleotide sequence as input and instantly predicts multiple structural features of DNA (minor groove width, roll, propeller twist and helix twist). The results of rigorous validations of the HT predictions based on DNA structures solved by X-ray crystallography and NMR spectroscopy, hydroxyl radical cleavage data, statistical analysis and cross-validation, and molecular dynamics simulations provide strong confidence in this approach. The DNAshape web server is freely available at http://rohslab.cmb.usc.edu/DNAshape/. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23703209", "endSection": "abstract"}]}, {"body": "Is olaparib effective for prostate cancer?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/26510020", "http://www.ncbi.nlm.nih.gov/pubmed/25616434", "http://www.ncbi.nlm.nih.gov/pubmed/25583815", "http://www.ncbi.nlm.nih.gov/pubmed/25366685", "http://www.ncbi.nlm.nih.gov/pubmed/24789362", "http://www.ncbi.nlm.nih.gov/pubmed/24225019", "http://www.ncbi.nlm.nih.gov/pubmed/25127709"], "ideal_answer": "Prostate cancer cells cotreated with the HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA) and the PARPi, olaparib, demonstrated a synergistic decrease in cell viability compared with single-agent treatment (combination index<0.9), whereas normal prostatic cells did not.Eligibility included ovarian cancer resistant to prior platinum; breast cancer with  three chemotherapy regimens for metastatic disease; pancreatic cancer with prior gemcitabine treatment; or prostate cancer with progression on hormonal and one systemic therapy.CONCLUSIONS: Treatment with the PARP inhibitor olaparib in patients whose prostate cancers were no longer responding to standard treatments and who had defects in DNA-repair genes led to a high response rate. In addition, phase III trials in breast, gastric and pancreatic cancer are underway/planned, and phase I/II investigation is being conducted in other malignancies, including prostate cancer, non-small cell lung cancer, Ewing's sarcoma and advanced cancer.Olaparib, one of the most studied PARPis, has demonstrated activity in BRCA1/2(MUT+) and BRCA-like sporadic ovarian and breast cancers, and looks promising in prostate and pancreatic cancers.", "type": "yesno", "id": "56c1f01eef6e394741000046", "snippets": [{"offsetInBeginSection": 122, "offsetInEndSection": 496, "text": "We hypothesized that metastatic, castration-resistant prostate cancers with DNA-repair defects would respond to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibition with olaparib.METHODS: We conducted a phase 2 trial in which patients with metastatic, castration-resistant prostate cancer were treated with olaparib tablets at a dose of 400 mg twice a day. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26510020", "endSection": "abstract"}, {"offsetInBeginSection": 2035, "offsetInEndSection": 2244, "text": "CONCLUSIONS: Treatment with the PARP inhibitor olaparib in patients whose prostate cancers were no longer responding to standard treatments and who had defects in DNA-repair genes led to a high response rate. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26510020", "endSection": "abstract"}, {"offsetInBeginSection": 511, "offsetInEndSection": 768, "text": " In addition, phase III trials in breast, gastric and pancreatic cancer are underway/planned, and phase I/II investigation is being conducted in other malignancies, including prostate cancer, non-small cell lung cancer, Ewing's sarcoma and advanced cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25616434", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 236, "text": "In a phase II study, researchers found that the PARP inhibitor olaparib led to stable disease or tumor regressions in patients with advanced breast, ovarian, pancreatic, and prostate cancers who had germline mutations in BRCA1 or BRCA2. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25583815", "endSection": "abstract"}, {"offsetInBeginSection": 383, "offsetInEndSection": 647, "text": "Eligibility included ovarian cancer resistant to prior platinum; breast cancer with \u2265 three chemotherapy regimens for metastatic disease; pancreatic cancer with prior gemcitabine treatment; or prostate cancer with progression on hormonal and one systemic therapy. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25366685", "endSection": "abstract"}, {"offsetInBeginSection": 825, "offsetInEndSection": 1427, "text": "The tumor response rate was 26.2% (78 of 298; 95% CI, 21.3 to 31.6) overall and 31.1% (60 of 193; 95% CI, 24.6 to 38.1), 12.9% (eight of 62; 95% CI, 5.7 to 23.9), 21.7% (five of 23; 95% CI, 7.5 to 43.7), and 50.0% (four of eight; 95% CI, 15.7 to 84.3) in ovarian, breast, pancreatic, and prostate cancers, respectively. Stable disease \u2265 8 weeks was observed in 42% of patients (95% CI, 36.0 to 47.4), including 40% (95% CI, 33.4 to 47.7), 47% (95% CI, 34.0 to 59.9), 35% (95% CI, 16.4 to 57.3), and 25% (95% CI, 3.2 to 65.1) of those with ovarian, breast, pancreatic, or prostate cancer, respectively. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25366685", "endSection": "abstract"}, {"offsetInBeginSection": 698, "offsetInEndSection": 1301, "text": "It is increasingly clear that there are molecularly distinct subtypes of various common cancers, with different therapeutic approaches required for each subtype, for example, the use of the monoclonal antibodies (trastuzumab and cetuximab) in HER2-positive breast cancer and wild-type KRAS colorectal cancer; tyrosine kinase inhibitors (imatinib, gefitinib, erlotinib and crizotinib) in chronic myeloid leukaemia, gastrointestinal stromal tumours and non-small-cell lung cancer and intracellular agents (vemurafenib and olaparib) in metastatic malignant melanoma and ovarian, breast and prostate cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24789362", "endSection": "abstract"}, {"offsetInBeginSection": 512, "offsetInEndSection": 703, "text": "Olaparib, one of the most studied PARPis, has demonstrated activity in BRCA1/2(MUT+) and BRCA-like sporadic ovarian and breast cancers, and looks promising in prostate and pancreatic cancers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24225019", "endSection": "abstract"}, {"offsetInBeginSection": 552, "offsetInEndSection": 828, "text": "Prostate cancer cells cotreated with the HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA) and the PARPi, olaparib, demonstrated a synergistic decrease in cell viability compared with single-agent treatment (combination index<0.9), whereas normal prostatic cells did not. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25127709", "endSection": "abstract"}]}, {"body": "Describe the usefulness of Macrostomum lignano in ion channel and stem cell research", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/23024658"], "ideal_answer": "Here we introduce the flatworm Macrostomum lignano as a versatile model organism for addressing these topics.While the importance of membrane potential in stem cell maintenance, proliferation, and differentiation is evident, the mechanisms of this bioelectric control of stem cell activity are still not well understood, and the role of specific ion channels in these processes remains unclear.Together with ion transporters and gap junction complexes, ion channels form steady-state voltage gradients across the cell membranes in nonexcitable cells.We discuss biological and experimental properties of M. lignano, provide an overview of the recently developed experimental tools for this animal model, and demonstrate how manipulation of membrane potential influences regeneration in M. lignano.Some ion channels are directly implemented in chemical signaling pathways, the others are involved in regulation of cytoplasmic or vesicular ion concentrations, pH, cell volume, and membrane potentials.Bioelectrical signals generated by ion channels play crucial roles in many cellular processes in both excitable and nonexcitable cells.", "type": "summary", "id": "56c904745795f9a73e00001c", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 1314, "text": "Bioelectrical signals generated by ion channels play crucial roles in many cellular processes in both excitable and nonexcitable cells. Some ion channels are directly implemented in chemical signaling pathways, the others are involved in regulation of cytoplasmic or vesicular ion concentrations, pH, cell volume, and membrane potentials. Together with ion transporters and gap junction complexes, ion channels form steady-state voltage gradients across the cell membranes in nonexcitable cells. These membrane potentials are involved in regulation of such processes as migration guidance, cell proliferation, and body axis patterning during development and regeneration. While the importance of membrane potential in stem cell maintenance, proliferation, and differentiation is evident, the mechanisms of this bioelectric control of stem cell activity are still not well understood, and the role of specific ion channels in these processes remains unclear. Here we introduce the flatworm Macrostomum lignano as a versatile model organism for addressing these topics. We discuss biological and experimental properties of M. lignano, provide an overview of the recently developed experimental tools for this animal model, and demonstrate how manipulation of membrane potential influences regeneration in M. lignano. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23024658", "endSection": "abstract"}]}, {"body": "Galassi classification is used for which disorder?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/18704305", "http://www.ncbi.nlm.nih.gov/pubmed/14676729", "http://www.ncbi.nlm.nih.gov/pubmed/12922037", "http://www.ncbi.nlm.nih.gov/pubmed/10663819", "http://www.ncbi.nlm.nih.gov/pubmed/16096939", "http://www.ncbi.nlm.nih.gov/pubmed/12218836"], "ideal_answer": "According to Galassi classification they were subdivided into 3 groups.We are led to conclude that Fenestration is suitable for cysts of types I and II (Galassi classification), cysto-peritoneal shunting is better for cysts of type III.The authors present CT and MRI of a patient with an extremely large arachnoidal cyst (Galassi classification type III). All these patients were divided into three subgroups according to Galassi classification.All cysts were type II according to Galassi classification.On follow-up CT scan and MRI, cysts of types I and II (Galassi classification) exhibited a steady tendency to reduction or obliteration.Chronic subdural hemorrhage into a giant arachnoidal cyst (Galassi classification type III).According to Galassi classification they were subdivided in three groups.According to Galassi classification they were subdivided in three groups.According to Galassi classification they were subdivided in three groups.", "type": "factoid", "id": "56c1f021ef6e394741000048", "snippets": [{"offsetInBeginSection": 282, "offsetInEndSection": 373, "text": " All these patients were divided into three subgroups according to Galassi classification. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18704305", "endSection": "abstract"}, {"offsetInBeginSection": 655, "offsetInEndSection": 820, "text": "We are led to conclude that Fenestration is suitable for cysts of types I and II (Galassi classification), cysto-peritoneal shunting is better for cysts of type III. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/18704305", "endSection": "abstract"}, {"offsetInBeginSection": 509, "offsetInEndSection": 580, "text": "According to Galassi classification they were subdivided into 3 groups. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/14676729", "endSection": "abstract"}, {"offsetInBeginSection": 502, "offsetInEndSection": 575, "text": "According to Galassi classification they were subdivided in three groups. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12922037", "endSection": "abstract"}, {"offsetInBeginSection": 2052, "offsetInEndSection": 2188, "text": "On follow-up CT scan and MRI, cysts of types I and II (Galassi classification) exhibited a steady tendency to reduction or obliteration. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/10663819", "endSection": "abstract"}, {"offsetInBeginSection": 754, "offsetInEndSection": 813, "text": "All cysts were type II according to Galassi classification. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/16096939", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 92, "text": "Chronic subdural hemorrhage into a giant arachnoidal cyst (Galassi classification type III). ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12218836", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 120, "text": "The authors present CT and MRI of a patient with an extremely large arachnoidal cyst (Galassi classification type III). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/12218836", "endSection": "abstract"}]}, {"body": "Is there a package in R/bioconductor for classification of alternative splicing?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/24655717"], "ideal_answer": "spliceR: an R package for classification of alternative splicing and prediction of coding potential from RNA-seq data.For each transcript isoform fraction values are calculated to identify transcript switching between conditions.For each of these events spliceR also annotates the genomic coordinates of the differentially spliced elements, facilitating downstream sequence analysis.spliceR uses the full-length transcript output from RNA-seq assemblers to detect single or multiple exon skipping, alternative donor and acceptor sites, intron retention, alternative first or last exon usage, and mutually exclusive exon events.Lastly, spliceR predicts the coding potential, as well as the potential nonsense mediated decay (NMD) sensitivity of each transcript.Recent software improvements in full-length transcript deconvolution prompted us to develop spliceR, an R package for classification of alternative splicing and prediction of coding potential.Recent software improvements in full-length transcript deconvolution prompted us to develop spliceR, an R package for classification of alternative splicing and prediction of coding potential.Recent software improvements in full-length transcript deconvolution prompted us to develop spliceR, an R package for classification of alternative splicing and prediction of coding potential.", "type": "yesno", "id": "56d19ffaab2fed4a47000001", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 118, "text": "spliceR: an R package for classification of alternative splicing and prediction of coding potential from RNA-seq data. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24655717", "endSection": "title"}, {"offsetInBeginSection": 153, "offsetInEndSection": 345, "text": "Recent software improvements in full-length transcript deconvolution prompted us to develop spliceR, an R package for classification of alternative splicing and prediction of coding potential. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24655717", "endSection": "abstract"}, {"offsetInBeginSection": 354, "offsetInEndSection": 999, "text": "spliceR uses the full-length transcript output from RNA-seq assemblers to detect single or multiple exon skipping, alternative donor and acceptor sites, intron retention, alternative first or last exon usage, and mutually exclusive exon events. For each of these events spliceR also annotates the genomic coordinates of the differentially spliced elements, facilitating downstream sequence analysis. For each transcript isoform fraction values are calculated to identify transcript switching between conditions. Lastly, spliceR predicts the coding potential, as well as the potential nonsense mediated decay (NMD) sensitivity of each transcript. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24655717", "endSection": "abstract"}]}, {"body": "Describe Mozart effect.", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/25383198", "http://www.ncbi.nlm.nih.gov/pubmed/25060169", "http://www.ncbi.nlm.nih.gov/pubmed/23154636", "http://www.ncbi.nlm.nih.gov/pubmed/23540417", "http://www.ncbi.nlm.nih.gov/pubmed/23724071", "http://www.ncbi.nlm.nih.gov/pubmed/23304207", "http://www.ncbi.nlm.nih.gov/pubmed/21292560", "http://www.ncbi.nlm.nih.gov/pubmed/21689988"], "ideal_answer": "Mozart K.448 has been shown to improve cognitive function, leading to what is known as the Mozart Effect.The Mozart Effect is a phenomenon whereby certain pieces of music induce temporary enhancement in \"spatial temporal reasoning.\"According to the first publication in 1993 by Rauscher et al.In the absence of cerebellar cTBS, music listening did not influence either MR task, thus not revealing a \"Mozart Effect\".[Nature 1993;365:611], the Mozart effect implies the enhancement of reasoning skills solving spatial problems in normal subjects after listening to Mozart's piano sonata K 448.Here, we investigated the cerebellar role in the association between spatial and musical domains, by testing performances in embodied (EMR) or abstract (AMR) mental rotation tasks of subjects listening Mozart Sonata K.448, which is reported to improve spatial-temporal reasoning, in the presence or in the absence of continuous theta burst stimulation (cTBS) of the left cerebellar hemisphere.", "type": "summary", "id": "56c1f027ef6e394741000049", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "OBJECTIVE: Listening to Mozart K.448 has been demonstrated to improve spatial task scores, leading to what is known as the Mozart Effect. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25383198", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 239, "text": "According to the first publication in 1993 by Rauscher et al. [Nature 1993;365:611], the Mozart effect implies the enhancement of reasoning skills solving spatial problems in normal subjects after listening to Mozart's piano sonata K 448. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25060169", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 128, "text": "The Mozart Effect is a phenomenon whereby certain pieces of music induce temporary enhancement in \"spatial temporal reasoning.\" ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23154636", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 137, "text": "OBJECTIVE: Listening to Mozart K.448 has been demonstrated to improve spatial task scores, leading to what is known as the Mozart effect. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23540417", "endSection": "abstract"}, {"offsetInBeginSection": 195, "offsetInEndSection": 712, "text": "Here, we investigated the cerebellar role in the association between spatial and musical domains, by testing performances in embodied (EMR) or abstract (AMR) mental rotation tasks of subjects listening Mozart Sonata K.448, which is reported to improve spatial-temporal reasoning, in the presence or in the absence of continuous theta burst stimulation (cTBS) of the left cerebellar hemisphere. In the absence of cerebellar cTBS, music listening did not influence either MR task, thus not revealing a \"Mozart Effect\". ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23724071", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 106, "text": "Mozart K.448 has been shown to improve cognitive function, leading to what is known as the Mozart Effect. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23304207", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 154, "text": "Mozart's Sonata for two pianos in D major, K.448 (Mozart K.448), has been shown to improve mental function, leading to what is known as the Mozart effect. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21292560", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 155, "text": "Mozart's Sonata for Two Pianos in D major, K.448 (Mozart K.448), has been shown to improve mental function, leading to what is known as the Mozart Effect. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21689988", "endSection": "abstract"}]}, {"body": "What is TOPAZ1?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/22069478"], "ideal_answer": "TOPAZ1 protein is highly conserved in vertebrates and specifically expressed in mouse and sheep gonads.Further characterization of TOPAZ1 may elucidate the mechanisms involved in gametogenesis, and particularly in the RNA silencing process in the germ line.The expression pattern of TOPAZ1, and its high degree of conservation, suggests that it may play an important role in germ cell development.It is localized in the cytoplasm of germ cells from the sheep fetal ovary and mouse adult testis.TOPAZ1, a novel germ cell-specific expressed gene conserved during evolution across vertebrates.We have identified a novel PAZ-domain protein that is abundantly expressed in the gonads during germ cell meiosis.We have identified a novel PAZ-domain protein that is abundantly expressed in the gonads during germ cell meiosis.We have identified a novel PAZ-domain protein that is abundantly expressed in the gonads during germ cell meiosis.We have identified a novel PAZ-domain protein that is abundantly expressed in the gonads during germ cell meiosis.We have identified a novel PAZ-domain protein that is abundantly expressed in the gonads during germ cell meiosis.", "type": "summary", "id": "56d1a9baab2fed4a47000002", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 96, "text": "TOPAZ1, a novel germ cell-specific expressed gene conserved during evolution across vertebrates. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22069478", "endSection": "title"}, {"offsetInBeginSection": 829, "offsetInEndSection": 1030, "text": "TOPAZ1 protein is highly conserved in vertebrates and specifically expressed in mouse and sheep gonads. It is localized in the cytoplasm of germ cells from the sheep fetal ovary and mouse adult testis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22069478", "endSection": "abstract"}, {"offsetInBeginSection": 1043, "offsetInEndSection": 1453, "text": "We have identified a novel PAZ-domain protein that is abundantly expressed in the gonads during germ cell meiosis. The expression pattern of TOPAZ1, and its high degree of conservation, suggests that it may play an important role in germ cell development. Further characterization of TOPAZ1 may elucidate the mechanisms involved in gametogenesis, and particularly in the RNA silencing process in the germ line. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22069478", "endSection": "abstract"}]}, {"body": "Which interleukin is blocked by Siltuximab?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/26392750", "http://www.ncbi.nlm.nih.gov/pubmed/25655379", "http://www.ncbi.nlm.nih.gov/pubmed/25294016", "http://www.ncbi.nlm.nih.gov/pubmed/25873122", "http://www.ncbi.nlm.nih.gov/pubmed/25784388"], "ideal_answer": "PURPOSE: Siltuximab is a monoclonal antibody that binds to interleukin (IL)-6 with high affinity and specificity; C-reactive protein (CRP) is an acute-phase protein induced by IL-6.This review also summarizes the biologics targeting either IL-6 or the IL-6 receptor, including tocilizumab, sarilumab, sirukumab, olokizumab, clazakizumab, and siltuximab.A phase 2, randomized, double-blind, placebo-controlled study of siltuximab (anti-IL-6 mAb) and bortezomib versus bortezomib alone in patients with relapsed or refractory multiple myeloma.Currently, there are more effective therapeutic alternatives in multicentric Castleman disease: treatment with monotherapy of rituximab or in combination therapy with immunomodulatory drugs (thalidomide or lenalidomide, treatment with anti-IL-6 (siltuximab) or against its receptor (tocilizumab).Siltuximab, a chimeric monoclonal antibody with high affinity and specificity for interleukin-6, has been shown to enhance anti-multiple myeloma activity of bortezomib and corticosteroid in vitro.", "type": "factoid", "id": "56c1f02aef6e39474100004b", "snippets": [{"offsetInBeginSection": 510, "offsetInEndSection": 683, "text": "This review also summarizes the biologics targeting either IL-6 or the IL-6 receptor, including tocilizumab, sarilumab, sirukumab, olokizumab, clazakizumab, and siltuximab. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/26392750", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 196, "text": "Siltuximab, a chimeric monoclonal antibody with high affinity and specificity for interleukin-6, has been shown to enhance anti-multiple myeloma activity of bortezomib and corticosteroid in vitro. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25655379", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 188, "text": "A phase 2, randomized, double-blind, placebo-controlled study of siltuximab (anti-IL-6 mAb) and bortezomib versus bortezomib alone in patients with relapsed or refractory multiple myeloma. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25294016", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 235, "text": "We compared the safety and efficacy of siltuximab (S), an anti-interleukin-6 chimeric monoclonal antibody, plus bortezomib (B) with placebo (plc) + B in patients with relapsed/refractory multiple myeloma in a randomized phase 2 study. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25294016", "endSection": "abstract"}, {"offsetInBeginSection": 1460, "offsetInEndSection": 1757, "text": "Currently, there are more effective therapeutic alternatives in multicentric Castleman disease: treatment with monotherapy of rituximab or in combination therapy with immunomodulatory drugs (thalidomide or lenalidomide, treatment with anti-IL-6 (siltuximab) or against its receptor (tocilizumab). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25873122", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 182, "text": "PURPOSE: Siltuximab is a monoclonal antibody that binds to interleukin (IL)-6 with high affinity and specificity; C-reactive protein (CRP) is an acute-phase protein induced by IL-6. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25784388", "endSection": "abstract"}]}, {"body": "Is there any role for long noncoding RNAs in adipogenesis?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/23401553"], "ideal_answer": "Long noncoding RNAs regulate adipogenesis.Many lncRNAs are adipose-enriched, strongly induced during adipogenesis, and bound at their promoters by key transcription factors such as peroxisome proliferator-activated receptor  (PPAR) and CCAAT/enhancer-binding protein  (CEBP).Here we profiled the transcriptome of primary brown and white adipocytes, preadipocytes, and cultured adipocytes and identified 175 lncRNAs that are specifically regulated during adipogenesis.RNAi-mediated loss of function screens identified functional lncRNAs with varying impact on adipogenesis.Collectively, we have identified numerous lncRNAs that are functionally required for proper adipogenesis.Collectively, we have identified numerous lncRNAs that are functionally required for proper adipogenesis.Collectively, we have identified numerous lncRNAs that are functionally required for proper adipogenesis.Collectively, we have identified numerous lncRNAs that are functionally required for proper adipogenesis.Collectively, we have identified numerous lncRNAs that are functionally required for proper adipogenesis.Collectively, we have identified numerous lncRNAs that are functionally required for proper adipogenesis.", "type": "yesno", "id": "56d1d56b67f0cb3d66000004", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 42, "text": "Long noncoding RNAs regulate adipogenesis. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23401553", "endSection": "title"}, {"offsetInBeginSection": 366, "offsetInEndSection": 1008, "text": "Here we profiled the transcriptome of primary brown and white adipocytes, preadipocytes, and cultured adipocytes and identified 175 lncRNAs that are specifically regulated during adipogenesis. Many lncRNAs are adipose-enriched, strongly induced during adipogenesis, and bound at their promoters by key transcription factors such as peroxisome proliferator-activated receptor \u03b3 (PPAR\u03b3) and CCAAT/enhancer-binding protein \u03b1 (CEBP\u03b1). RNAi-mediated loss of function screens identified functional lncRNAs with varying impact on adipogenesis. Collectively, we have identified numerous lncRNAs that are functionally required for proper adipogenesis. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23401553", "endSection": "abstract"}]}, {"body": "GV1001 vaccine targets which enzyme?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/24411674", "http://www.ncbi.nlm.nih.gov/pubmed/24919654", "http://www.ncbi.nlm.nih.gov/pubmed/24954781", "http://www.ncbi.nlm.nih.gov/pubmed/24439482", "http://www.ncbi.nlm.nih.gov/pubmed/24815142", "http://www.ncbi.nlm.nih.gov/pubmed/22841437", "http://www.ncbi.nlm.nih.gov/pubmed/23827187"], "ideal_answer": "GV1001 is a 16-amino-acid vaccine peptide derived from the human telomerase reverse transcriptase sequence.BACKGROUND: We aimed to assess the efficacy and safety of sequential or simultaneous telomerase vaccination (GV1001) in combination with chemotherapy in patients with locally advanced or metastatic pancreatic cancer.Based on this review, the most promising current telomerase targeting therapeutics are the antisense oligonucleotide inhibitor GRN163L and immunotherapies that use dendritic cells (GRVAC1), hTERT peptide (GV1001) or cryptic peptides (Vx-001).Together, these results suggest that GV1001 possesses neuroprotective effects against A oligomer in NSCs and that these effects are mediated through mimicking the extra-telomeric functions of human telomerase reverse transcriptase, including the induction of cellular proliferation, anti-apoptotic effects, mitochondrial stabilization, and anti-aging and anti-oxidant effects.A reverse-transcriptase-subunit of telomerase (hTERT) derived peptide, GV1001, has been developed as a vaccine against various cancers.Telomerase vaccination (GV1001) in combination with chemotherapy appeared to be safe but the immune responses were weak and transient.", "type": "factoid", "id": "56c1f02cef6e39474100004c", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 136, "text": "A reverse-transcriptase-subunit of telomerase (hTERT) derived peptide, GV1001, has been developed as a vaccine against various cancers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24411674", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 97, "text": "Telomerase (GV1001) vaccination together with gemcitabine in advanced pancreatic cancer patients. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24919654", "endSection": "title"}, {"offsetInBeginSection": 120, "offsetInEndSection": 365, "text": "A study was conducted to investigate safety and immunogenicity in non-resectable pancreatic carcinoma patients using a 16-amino acid telomerase peptide (GV1001) for vaccination in combination with GM-CSF and gemcitabine as first line treatment. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24919654", "endSection": "abstract"}, {"offsetInBeginSection": 1461, "offsetInEndSection": 1596, "text": "Telomerase vaccination (GV1001) in combination with chemotherapy appeared to be safe but the immune responses were weak and transient. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24919654", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 197, "text": "Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac): an open-label, randomised, phase 3 trial. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24954781", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 216, "text": "BACKGROUND: We aimed to assess the efficacy and safety of sequential or simultaneous telomerase vaccination (GV1001) in combination with chemotherapy in patients with locally advanced or metastatic pancreatic cancer. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24954781", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 152, "text": "Novel vaccine peptide GV1001 effectively blocks \u03b2-amyloid toxicity by mimicking the extra-telomeric functions of human telomerase reverse transcriptase. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24439482", "endSection": "title"}, {"offsetInBeginSection": 0, "offsetInEndSection": 107, "text": "GV1001 is a 16-amino-acid vaccine peptide derived from the human telomerase reverse transcriptase sequence. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24439482", "endSection": "abstract"}, {"offsetInBeginSection": 997, "offsetInEndSection": 1379, "text": "Together, these results suggest that GV1001 possesses neuroprotective effects against A\u03b2\u2082\u2085\u208b\u2083\u2085 oligomer in NSCs and that these effects are mediated through mimicking the extra-telomeric functions of human telomerase reverse transcriptase, including the induction of cellular proliferation, anti-apoptotic effects, mitochondrial stabilization, and anti-aging and anti-oxidant effects. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24439482", "endSection": "abstract"}, {"offsetInBeginSection": 101, "offsetInEndSection": 307, "text": "Peptide GV1001 is a peptide vaccine representing a 16-amino acid human telomerase reverse transcriptase sequence, which has been reported to possess potential antineoplastic and anti-inflammatory activity. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24815142", "endSection": "abstract"}, {"offsetInBeginSection": 990, "offsetInEndSection": 1232, "text": "Based on this review, the most promising current telomerase targeting therapeutics are the antisense oligonucleotide inhibitor GRN163L and immunotherapies that use dendritic cells (GRVAC1), hTERT peptide (GV1001) or cryptic peptides (Vx-001). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22841437", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 135, "text": "A reverse-transcriptase-subunit of telomerase (hTERT) derived peptide, GV1001, has been developed as a vaccine against various cancers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23827187", "endSection": "abstract"}]}, {"body": "How many periods of regulatory innovation led to the evolution of vertebrates?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/21852499"], "ideal_answer": "Three periods of regulatory innovation during vertebrate evolution.These putative regulatory regions are conserved nonexonic elements (CNEEs), which are evolutionarily conserved yet do not overlap any coding or noncoding mature transcript.To investigate the gain of regulatory elements throughout vertebrate evolution, we identified genome-wide sets of putative regulatory regions for five vertebrates, including humans.We then inferred the branch on which each CNEE came under selective constraint.Early vertebrate evolution was characterized by regulatory gains near transcription factors and developmental genes, but this trend was replaced by innovations near extracellular signaling genes, and then innovations near posttranslational protein modifiers.Our analysis identified three extended periods in the evolution of gene regulatory elements.Our analysis identified three extended periods in the evolution of gene regulatory elements.Our analysis identified three extended periods in the evolution of gene regulatory elements.Our analysis identified three extended periods in the evolution of gene regulatory elements.Our analysis identified three extended periods in the evolution of gene regulatory elements.", "type": "factoid", "id": "56d1da3b67f0cb3d66000006", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 67, "text": "Three periods of regulatory innovation during vertebrate evolution. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21852499", "endSection": "title"}, {"offsetInBeginSection": 141, "offsetInEndSection": 927, "text": "To investigate the gain of regulatory elements throughout vertebrate evolution, we identified genome-wide sets of putative regulatory regions for five vertebrates, including humans. These putative regulatory regions are conserved nonexonic elements (CNEEs), which are evolutionarily conserved yet do not overlap any coding or noncoding mature transcript. We then inferred the branch on which each CNEE came under selective constraint. Our analysis identified three extended periods in the evolution of gene regulatory elements. Early vertebrate evolution was characterized by regulatory gains near transcription factors and developmental genes, but this trend was replaced by innovations near extracellular signaling genes, and then innovations near posttranslational protein modifiers. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/21852499", "endSection": "abstract"}]}, {"body": "List features of the DEND syndrome.", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/24150202", "http://www.ncbi.nlm.nih.gov/pubmed/23783767", "http://www.ncbi.nlm.nih.gov/pubmed/23382304", "http://www.ncbi.nlm.nih.gov/pubmed/23462667", "http://www.ncbi.nlm.nih.gov/pubmed/22326206", "http://www.ncbi.nlm.nih.gov/pubmed/22694282", "http://www.ncbi.nlm.nih.gov/pubmed/22768671", "http://www.ncbi.nlm.nih.gov/pubmed/22145471"], "ideal_answer": "Developmental delay was noted on follow-up which raised the possibility of intermediate DEND syndrome.We have verified a lack of clinical response for both glycemic control and neurological features in an infant with permanent neonatal diabetes mellitus and DEND syndrome due to a V59A mutation in the KCNJ11 gene.They also may cause neurologic symptoms such as mental retardation and motor problems (iDEND syndrome) and epilepsy (DEND syndrome).Approximately 20% have associated neurologic features: the most severe form, which includes epilepsy and developmental delay, is called developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome and the milder form, with less severe developmental delay and without epilepsy, is designated intermediate DEND syndrome. The patient with the V59M mutation successfully switched from insulin injections to oral glibenclamide; 2 years of follow-up revealed that the patient had intermediate developmental delay, epilepsy and neonatal diabetes (DEND) syndrome. Wide phenotype variability is associated with single ABCC8 mutations, ranging from transient or permanent neonatal diabetes (ND) with or without developmental delay (DEND syndrome) to very mild phenotypes.", "type": "list", "id": "56c1f030ef6e39474100004d", "snippets": [{"offsetInBeginSection": 116, "offsetInEndSection": 252, "text": "Some mutations in this gene, including p.Q52R, are associated with the developmental delay, epilepsy, neonatal diabetes (DEND) syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24150202", "endSection": "abstract"}, {"offsetInBeginSection": 657, "offsetInEndSection": 759, "text": "Developmental delay was noted on follow-up which raised the possibility of intermediate DEND syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23783767", "endSection": "abstract"}, {"offsetInBeginSection": 223, "offsetInEndSection": 436, "text": "We have verified a lack of clinical response for both glycemic control and neurological features in an infant with permanent neonatal diabetes mellitus and DEND syndrome due to a V59A mutation in the KCNJ11 gene. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23382304", "endSection": "abstract"}, {"offsetInBeginSection": 149, "offsetInEndSection": 282, "text": "They also may cause neurologic symptoms such as mental retardation and motor problems (iDEND syndrome) and epilepsy (DEND syndrome). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23462667", "endSection": "abstract"}, {"offsetInBeginSection": 294, "offsetInEndSection": 501, "text": " Wide phenotype variability is associated with single ABCC8 mutations, ranging from transient or permanent neonatal diabetes (ND) with or without developmental delay (DEND syndrome) to very mild phenotypes. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22326206", "endSection": "abstract"}, {"offsetInBeginSection": 124, "offsetInEndSection": 353, "text": "Specific uncommon mutations KCNJ11give rise to a syndrome defined as developmental delay, epilepsy, and neonatal diabetes (DEND), or - more frequently - to a milder sub-type lacking epilepsy, denoted as intermediate-DEND (iDEND). ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22694282", "endSection": "abstract"}, {"offsetInBeginSection": 429, "offsetInEndSection": 756, "text": "Approximately 20% have associated neurologic features: the most severe form, which includes epilepsy and developmental delay, is called developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome and the milder form, with less severe developmental delay and without epilepsy, is designated intermediate DEND syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22768671", "endSection": "abstract"}, {"offsetInBeginSection": 426, "offsetInEndSection": 664, "text": " The patient with the V59M mutation successfully switched from insulin injections to oral glibenclamide; 2 years of follow-up revealed that the patient had intermediate developmental delay, epilepsy and neonatal diabetes (DEND) syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/22145471", "endSection": "abstract"}]}, {"body": "What is the functionality of the Triplex R/bioconductor package?", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/23709494"], "ideal_answer": "Triplex: an R/Bioconductor package for identification and visualization of potential intramolecular triplex patterns in DNA sequences.Leveraging the power of Biostrings and GRanges classes, the results get fully integrated into the existing Bioconductor framework, allowing their passage to other Genome visualization and annotation packages, such as GenomeGraphs, rtracklayer or Gviz.Functions producing 2D and 3D diagrams of the identified triplexes allow instant visualization of the search results.The new package provides functions that can be used to search Bioconductor genomes and other DNA sequence data for occurrence of nucleotide patterns capable of forming intramolecular triplexes (H-DNA).The new package provides functions that can be used to search Bioconductor genomes and other DNA sequence data for occurrence of nucleotide patterns capable of forming intramolecular triplexes (H-DNA).The new package provides functions that can be used to search Bioconductor genomes and other DNA sequence data for occurrence of nucleotide patterns capable of forming intramolecular triplexes (H-DNA).", "type": "summary", "id": "56d1ddd267f0cb3d66000008", "snippets": [{"offsetInBeginSection": 0, "offsetInEndSection": 134, "text": "Triplex: an R/Bioconductor package for identification and visualization of potential intramolecular triplex patterns in DNA sequences. ", "beginSection": "title", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23709494", "endSection": "title"}, {"offsetInBeginSection": 258, "offsetInEndSection": 829, "text": "The new package provides functions that can be used to search Bioconductor genomes and other DNA sequence data for occurrence of nucleotide patterns capable of forming intramolecular triplexes (H-DNA). Functions producing 2D and 3D diagrams of the identified triplexes allow instant visualization of the search results. Leveraging the power of Biostrings and GRanges classes, the results get fully integrated into the existing Bioconductor framework, allowing their passage to other Genome visualization and annotation packages, such as GenomeGraphs, rtracklayer or Gviz. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23709494", "endSection": "abstract"}]}, {"body": "List symptoms of the IFAP syndrome.", "documents": ["http://www.ncbi.nlm.nih.gov/pubmed/25685152", "http://www.ncbi.nlm.nih.gov/pubmed/24313295", "http://www.ncbi.nlm.nih.gov/pubmed/24090718"], "ideal_answer": "The IFAP syndrome is a rare X-linked genetic disorder characterized by the triad of follicular ichthyosis, atrichia, and photophobia.We report a recurrent intronic mutation in MBTPS2 (c.671-9T>G) in a Chinese patient with the typical triad of IFAP syndrome (i.e.Mutations in MBTPS2 have been reported to cause a broad phenotypic spectrum of X-linked genodermatoses, including IFAP (ichthyosis follicularis; atrichia and photophobia) syndrome (OMIM 308205) with or without BRESHECK (brain anomalies, retardation of mentality and growth, ectodermal dysplasia, skeletal malformations, Hirschsprung disease, ear deformity and deafness, eye hypoplasia, cleft palate, cryptorchidism, and kidney dysplasia/hypoplasia) syndrome, keratosis follicularis spinulosa decalvans (KFSD; OMIM 308800) and an X-linked form of Olmsted syndrome.ichthyosis, atrichia and photophobia), along with pachyonychia, palmoplantar and periorificial keratoderma, which were reminiscent of Olmsted syndrome.This patient presented with a severe IFAP/BRESHECK phenotype including ichthyosis follicular, atrichia, photophobia, brain anomalies, global developmental delay, Hirschsprung disease and kidney hypoplasia.", "type": "list", "id": "56c1f038ef6e394741000051", "snippets": [{"offsetInBeginSection": 14, "offsetInEndSection": 147, "text": "The IFAP syndrome is a rare X-linked genetic disorder characterized by the triad of follicular ichthyosis, atrichia, and photophobia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/25685152", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 846, "text": "Mutations in MBTPS2 have been reported to cause a broad phenotypic spectrum of X-linked genodermatoses, including IFAP (ichthyosis follicularis; atrichia and photophobia) syndrome (OMIM 308205) with or without BRESHECK (brain anomalies, retardation of mentality and growth, ectodermal dysplasia, skeletal malformations, Hirschsprung disease, ear deformity and deafness, eye hypoplasia, cleft palate, cryptorchidism, and kidney dysplasia/hypoplasia) syndrome, keratosis follicularis spinulosa decalvans (KFSD; OMIM 308800) and an X-linked form of Olmsted syndrome. We report a recurrent intronic mutation in MBTPS2 (c.671-9T>G) in a Chinese patient with the typical triad of IFAP syndrome (i.e. ichthyosis, atrichia and photophobia), along with pachyonychia, palmoplantar and periorificial keratoderma, which were reminiscent of Olmsted syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24313295", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 133, "text": "The ichthyosis follicular with atrichia and photophobia syndrome (IFAP) is a rare X-linked multiple congenital malformation syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24090718", "endSection": "abstract"}, {"offsetInBeginSection": 644, "offsetInEndSection": 850, "text": "This patient presented with a severe IFAP/BRESHECK phenotype including ichthyosis follicular, atrichia, photophobia, brain anomalies, global developmental delay, Hirschsprung disease and kidney hypoplasia. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/24090718", "endSection": "abstract"}, {"offsetInBeginSection": 0, "offsetInEndSection": 291, "text": "Missense mutations affecting membrane-bound transcription factor protease site 2 (MBTPS2) have been associated with Ichthyosis Follicularis with Atrichia and Photophobia (IFAP) syndrome with or without BRESHECK syndrome, with keratosis follicularis spinulosa decalvans, and Olmsted syndrome. ", "beginSection": "abstract", "document": "http://www.ncbi.nlm.nih.gov/pubmed/23316014", "endSection": "abstract"}]}]}