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Does the histidine-rich Ca-binding protein (HRC) interact with triadin?

['The HRC effects on RyR may be regulated by the Ca(2+)-sensitivity of its interaction with triadin.', 'In rabbit skeletal and cardiac muscles, HRC binds to sarcoplasmic reticulum (SR) membranes via triadin, a junctional SR protein. ', 'HRC may play a key role in the regulation of SR Ca cycling through its direct interactions with SERCA2 and triadin, mediating a fine cross talk between SR Ca uptake and release in the heart.', 'Histidine-rich calcium binding protein (HRC) is located in the lumen of sarcoplasmic reticulum (SR) that binds to both triadin (TRN) and SERCA affecting Ca(2+) cycling in the SR.', 'HRC is a SR luminal Ca(2+) binding protein known to associate with both triadin and the sarcoplasmic reticulum Ca(2+)-ATPase, and may thus mediate the crosstalk between SR Ca(2+) uptake and release.', 'The histidine-rich Ca(2+) binding protein (HRC) is a high capacity Ca(2+) binding protein in the sarcoplasmic reticulum (SR). Because HRC appears to interact directly with triadin, HRC may play a role in the regulation of Ca(2+) release during excitation-contraction coupling.', 'In the present study, we have performed co-immunoprecipitation experiments and show that HRC binds directly to triadin, which is an integral membrane protein of the sarcoplasmic reticulum.', 'A direct binding of HRC (histidine-rich Ca(2+)-binding protein) to triadin, the main transmembrane protein of the junctional sarcoplasmic reticulum (SR) of skeletal muscle, seems well supported.', 'The present study documents the binding interaction of skeletal muscle sarcoplasmic reticulum (SR) transmembrane protein triadin with peripheral histidine-rich, Ca(2+)-binding protein (HCP).', 'In addition, the intra-luminal histidine-rich calcium binding protein (HRC) has been shown to interact with both SERCA2a and triadin.', 'Notably, there is physical and direct interaction between these protein players, mediating a fine-cross talk between SR Ca-uptake, storage and release.', 'The histidine-rich calcium-binding protein (HRCBP) is expressed in the junctional SR, the site of calcium release from the SR. HRCBP is expressed exclusively in muscle tissues and binds calcium with low affinity and high capacity. In addition, HRCBP interacts with triadin, a protein associated with the ryanodine receptor and thought to be involved in calcium release. Its calcium binding properties, localization to the SR, and interaction with triadin suggest that HRCBP is involved in calcium handling by the SR.', 'Using a fusion protein binding assay, we further identified the histidine-rich acidic repeats of HRC as responsible for the binding of HRC to triadin. ', 'The HRC binding domain of triadin was also localized by fusion protein binding assay to the lumenal region containing the KEKE motif that was previously shown to be involved in the binding of triadin to calsequestrin. Notably, the interaction of HRC and triadin is Ca(2+)-sensitive. Our data suggest that HRC may play a role in the regulation of Ca(2+) release from the sarcoplasmic reticulum by interaction with triadin.', 'Further support for colocalization of HRC with triadin cytoplasmic domain is provided here by experiments of mild tryptic digestion of tightly sealed TC vesicles.', 'We demonstrate that HRC can be isolated as a complex with triadin, following equilibrium sucrose-density centrifugation in the presence of mM Ca(2+).', 'Here, we characterized the COOH-terminal portion of rabbit HRC, expressed and purified as a fusion protein (HRC(569-852)), with respect to Ca(2+)-binding properties, and to the interaction with triadin on blots, as a function of the concentration of Ca(2+).', 'Our results identify the polyglutamic stretch near the COOH terminus, as the Ca(2+)-binding site responsible, both for the acceleration in mobility of HRC on SDS-PAGE in the presence of millimolar concentrations of Ca(2+), and for the enhancement by high Ca(2+) of the interaction between HRC and triadin cytoplasmic segment.', 'In addition to providing further evidence that HCP coenriches with RyR1, FKBP-12, triadin and calsequestrin (CS) in sucrose-density-purified TC vesicles, using specific polyclonal antibody, we show it to be expressed as a single protein species, both in fast-twitch and slow-twitch fibers, and to identically localize to the I-band.', 'Colocalization of HCP and triadin at junctional triads is supported by the overlapping staining pattern using monoclonal antibodies to triadin. We show a specific binding interaction between digoxigenin-HCP and triadin, using ligand blot techniques.', 'Suggesting that triadin dually interacts with HCP and with CS, at distinct sites, we have found that triadin-CS interaction in overlays does not require the presence of Ca2+.', 'These differential effects form the basis for the hypothesis that HCP anchors to the junctional membrane domain of the SR, through binding to triadin short cytoplasmic domain at the NH2 terminus.', 'Although the function of this interaction, as such, is not well understood, it seems of potential biological interest within the more general context of the structural-functional role of triadin at the triadic junction in skeletal muscle.', 'BACKGROUND: Histidine-rich calcium binding protein (HRC) is located in the lumen of sarcoplasmic reticulum (SR) that binds to both triadin (TRN) and SERCA affecting Ca(2+) cycling in the SR. Chronic overexpression of HRC that may disrupt intracellular Ca(2+) homeostasis is implicated in pathogenesis of cardiac hypertrophy.', 'Interaction of HRC (histidine-rich Ca(2+)-binding protein) and triadin in the lumen of sarcoplasmic reticulum.', 'The histidine-rich Ca-binding protein (HRC) is an SR component that binds to triadin and may affect Ca release through the ryanodine receptor.', 'The histidine-rich Ca-binding protein (HRC) is an SR component that binds to triadin and may affect Ca release through the ryanodine receptor', 'Because HRC appears to interact directly with triadin, HRC may play a role in the regulation of Ca(2+) release during excitation-contraction coupling', 'A direct binding of HRC (histidine-rich Ca(2+)-binding protein) to triadin, the main transmembrane protein of the junctional sarcoplasmic reticulum (SR) of skeletal muscle, seems well supported', 'The histidine-rich Ca-binding protein (HRC) is an SR component that binds to triadin and may affect Ca release through the ryanodine receptor']

['Yes. HRC may play a key role in the regulation of SR Ca cycling through its direct interactions with SERCA2 and triadin, mediating a fine cross talk between SR Ca uptake and release in the heart. A direct binding of HRC (histidine-rich Ca(2+)-binding protein) to triadin, the main transmembrane protein of the junctional sarcoplasmic reticulum (SR) of skeletal muscle, seems well supported.', 'Histidine-rich calcium binding protein (HRC) is located in the lumen of sarcoplasmic reticulum (SR) and binds to triadin (TRN), a protein associated with the ryanodine receptor and thought to be involved in calcium release.']

['yes']

Which proteins remove H2A.Z in the yeast Saccharomyces cerevisiae?

['Removal of H2A.Z by INO80 promotes homologous recombination', 'Budding yeast INO80 can remove H2A.Z/H2B dimers from chromatin and replace them with H2A/H2B dimers.', 'Here, we show that H2A.Z in human cells is indeed rapidly removed from chromatin flanking DNA damage by INO80.', 'We also report that the histone chaperone ANP32E, which is implicated in removing H2AZ from chromatin, similarly promotes HR and appears to work on the same pathway as INO80 in these assays.', 'H2A.Z removal from chromatin is the primary function of INO80 and ANP32E in promoting homologous recombination.', 'Instead, the INO80 complex, which removes H2A.Z(Htz1) from nucleosomes, promotes the ectopic deposition of CENP-A(Cse4).']

['Removal of H2A.Z by INO80 promotes homologous recombination Budding yeast INO80 can remove H2A.Z/H2B dimers from chromatin and replace them with H2A/H2B dimers. Here, we show that H2A.Z in human cells is indeed rapidly removed from chromatin flanking DNA damage by INO80.', 'Here, we show that H2A.Z in human cells is indeed rapidly removed from chromatin flanking DNA damage by INO80. We also report that the histone chaperone ANP32E, which is implicated in removing H2AZ from chromatin, similarly promotes HR and appears to work on the same pathway as INO80 in these assays. Importantly, we demonstrate that the HR defect in cells depleted of INO80 or ANP32E can be rescued by H2A.Z co-depletion, suggesting that H2A.Z removal from chromatin is the primary function of INO80 and ANP32E in promoting homologous recombination.', 'Budding yeast INO80 can remove H2A.Z/H2B dimers from chromatin and replace them with H2A/H2B dimers. Here, we show that H2A.Z in human cells is indeed rapidly removed from chromatin flanking DNA damage by INO80. We also report that the histone chaperone ANP32E, which is implicated in removing H2AZ from chromatin, similarly promotes HR and appears to work on the same pathway as INO80 in these assays.', 'we also report that the histone chaperone anp32e, which is implicated in removing h2az from chromatin, similarly promotes hr and appears to work on the same pathway as ino80 in these assays.', 'Budding yeast INO80 can remove H2A.Z/H2B dimers from chromatin and replace them with H2A/H2B dimers. Removal of H2A.Z by INO80 promotes homologous recombination H2A.Z removal from chromatin is the primary function of INO80 and ANP32E in promoting homologous recombination.', 'Budding yeast INO80 can remove H2A.Z/H2B dimers from chromatin and replace them with H2A/H2B dimers. Removal of H2A.Z by INO80 promotes homologous recombination', 'Budding yeast INO80 can remove H2A.Z/H2B dimers from chromatin and replace them with H2A/H2B dimers. H2A.Z removal from chromatin is the primary function of INO80 and ANP32E in promoting homologous recombination.']

['INO80', 'ANP32E']

Which cells express CIDEC protein in humans?

['The expression levels of related adipocyte markers (PPARγ, C/EBPα), mature white adipose tissue specific markers (Cidec, RIP140) increased at the presence of NPY (10(-7), 10(-9), 10(-11) mol/L).', 'The cell death-inducing DNA fragmentation factor alpha-like effector c (CIDEC; also known in rodents as FSP27 or fat-specific protein 27) is a lipid droplet-associated protein that promotes intracellular triglyceride (TAG) storage. CIDEC/Fsp27 is highly expressed in adipose tissue, but undetectable in normal liver. However, its hepatic expression rises during fasting or under genetic or diet-induced hepatosteatosis in both mice and patients. ', ' Our results also suggest that patients taking fibrates likely have elevated levels of hepatic CIDEC, which may limit the efficient mobilization and catabolism of hepatic TAGs.', 'Fat-specific protein 27 (FSP27, CIDEC in humans) is a lipid-coating protein highly expressed in mature white adipocytes that contributes to unilocular lipid droplet formation.', 'We studied mouse models and human tissues to identify molecules associated with ASH progression and focused on the mouse fat-specific protein 27 (FSP-27)/human cell death-inducing DFF45-like effector C (CIDEC) protein, which is expressed in white adipose tissues and promotes formation of fat droplets.', 'Hepatic CIDEC mRNA expression was increased in patients with AH and correlated with the degree of hepatic steatosis and disease severity including mortality.', 'Hepatic expression of FSP27/CIDEC is highly up-regulated in mice following chronic-plus-binge ethanol feeding and in patients with AH; this up-regulation contributes to alcohol-induced liver damage.', 'FSP27 [cell death-inducing DFFA-like effector c (CIDEC) in humans] is a protein associated with lipid droplets that downregulates the fatty acid oxidation (FAO) rate when it is overexpressed.', 'Fsp27/CIDEC is a CREB target gene induced during early fasting in liver and regulated by FA oxidation rate.', 'Similarly, CIDEC expression was upregulated in HepG2 cells by either etomoxir or HMGCS2 interference. Our data indicate that there is a kinetic mechanism of autoregulation between short- and long-term fasting, by which free FAs delivered to the liver during early fasting are accumulated/exported by FSP27/CIDEC, whereas over longer periods of fasting, they are degraded in the mitochondria through the carnitine palmitoyl transferase system.', 'However, in adipose tissue the changes in Cidec mRNA did not correspond to the changes in Cidec protein levels, as a HFD decreased Cidec protein abundance.', 'Cell death-inducing DFFA-like effector c (CIDEC) protein, also known as fat specific protein 27 (Fsp27), is localized to lipid droplets.', 'We studied mouse models and human tissues to identify molecules associated with ASH progression and focused on the mouse fat-specific protein 27 (FSP-27)/human cell death-inducing DFF45-like effector C (CIDEC) protein, which is expressed in white adipose tissues and promotes formation of fat droplets.', 'Interestingly, in adipose tissue Cidea protein expression was significantly related to body weight (R=.725), epididymal adipose tissue (EWAT) mass (R=.475) and insulin resistance (R=.706), whereas Cidec protein expression was inversely related to body weight (R=-.787), EWAT mass (R=-.706), and insulin resistance (R=-.679).', 'Similar to adipose tissue, Cidea protein expression in liver was significantly related to body weight (R=.660), EWAT mass (R=.468), and insulin resistance (R=.599); however, unlike adipose tissue, Cidec protein levels in liver were not related to body weight or EWAT mass and only moderately associated with insulin resistance (R=-.422, P=0.051).', 'The CIDEC protein is located in lipid droplets (LDs) and the endoplasmic reticulum (ER) and is induced in fat deposition.', 'CIDEC protein is required for unilocular lipid droplet formation and optimal energy storage in addition to controlling lipid metabolism in adipocytes and hepatocytes.', 'Similarly, CIDEC expression was upregulated in HepG2 cells by either etomoxir or HMGCS2 interference.', 'The hepatic expression of the cell death-inducing DNA fragmentation factor A-like effector family (CIDEA, CIDEB, and CIDEC) genes is markedly upregulated in mouse models of obesity.', 'After the differentiation of adipocyte, the expression pattern of Cidec was similar to that of PPARgamma2.', 'This paper examined the tissue expression profile of CIDEC gene in cattle using real-time RT-PCR to suggest that bovine CIDEC is highly expressed in adipose tissue.', 'Human adipocytes express high levels of two distinct lipid droplet proteins, fat specific protein 27 (FSP27; also called CIDEC), a member of the CIDE family, and perilipin1 (PLIN1), a member of the PAT family', 'These results suggest that insulin regulates CIDEA and CIDEC expression via PI3K, and it regulates expression of each protein via Akt1/2- and JNK2-dependent pathways, respectively, in human adipocytes.', 'Differential regulation of CIDEA and CIDEC expression by insulin via Akt1/2- and JNK2-dependent pathways in human adipocytes.', 'Differential roles of CIDEA and CIDEC in insulin-induced anti-apoptosis and lipid droplet formation in human adipocytes.', 'Human adipocytes express high levels of two distinct lipid droplet proteins, fat specific protein 27 (FSP27; also called CIDEC), a member of the CIDE family, and perilipin1 (PLIN1), a member of the PAT family. ', 'Fat-specific protein 27 (FSP27, CIDEC in humans) is a lipid-coating protein highly expressed in mature white adipocytes that contributes to unilocular lipid droplet formation. ', 'Using human primary pre-adipocytes, we confirmed that the expression of CIDEC was elevated during the differentiation of pre-adipocytes, and knockdown of CIDEC in human primary pre-adipocytes resulted in differentiation defects. ', 'Cell death-inducing DFF45-like effector C (CIDEC) is a lipid droplet-coating protein that promotes triglyceride accumulation and inhibits lipolysis.', 'The cell death-inducing DNA fragmentation factor alpha-like effector c (CIDEC; also known in rodents as FSP27 or fat-specific protein 27) is a lipid droplet-associated protein that promotes intracellular triglyceride (TAG) storage.', 'Here we demonstrate that knockdown of the lipid droplet protein FSP27 (a.k.a. CIDEC) in human adipocytes increases expression of ATGL at the level of transcription, whereas overexpression of FSP27 has the opposite effect.', 'However, the transcriptional regulation of Cidec in adipocyte remains unknown.', 'Moreover, the hepatic expression of CIDEC is downregulated by marked weight loss.', 'These data demonstrate that, consistent with previous studies conducted in rodents, hepatic expression of CIDEA and CIDEC, but not CIDEB, is increased in obese humans.', 'Transcriptional activation of Cidec by PPARgamma2 in adipocyte.', 'Our data indicated additional fatty acids stimulated hepatic CIDEC expression and an increasing level of CIDEC induced hepatic LD fusion and lipid accumulation.', 'We studied mouse models and human tissues to identify molecules associated with ASH progression and focused on the mouse fat-specific protein 27 (FSP-27)/human cell death-inducing DFF45-like effector C (CIDEC) protein, which is expressed in white adipose tissues and promotes formation of fat droplets.', 'By analysis of CIDEC expression in 65 human tissues, we conclude that human CIDEC is predominantly expressed in subcutaneous adipocytes.', 'CIDEC/Fsp27 is highly expressed in adipose tissue, but undetectable in normal liver.', 'Interestingly, FSP27/CIEDC was expressed in mouse and human livers and was upregulated in obese C57BL/6J mice.', 'However, in adipose tissue the changes in Cidec mRNA did not correspond to the changes in Cidec protein levels, as a HFD decreased Cidec protein abundance.']

['The cell death-inducing DNA fragmentation factor alpha-like effector c (CIDEC) is a lipid droplet-associated protein that promotes intracellular triglyceride (TAG) storage. CIDEC is highly expressed in adipocytes, but undetectable in normal liver. However, its hepatic expression rises during fasting or under genetic or diet-induced hepatosteatosis in patients.']

[]

What is the Glasgow Coma score?

[' Injury severity was determined by the Glasgow Coma Scale (GCS) score on admission or by the duration of unconsciousness', 'Severity analysis was based on the Glasgow Coma Scale and Injury Severity Scor', 'The strongest correlations were found between the Glasgow coma score and quality of life (r\xa0= 0.236, P\xa0= 0.0001)', 'By accepting the Glasgow Coma Scale as a gold standard for classification of the level of coma, we can confirm satisfactory measuring qualities for the Vienna Vigilance Score.', 'Our aim in this study was to assess whether the new Glasgow Coma Scale, Age, and Systolic Blood Pressure (GAP) scoring system, which is a modification of the Mechanism, Glasgow Coma Scale, Age, and Arterial Pressure (MGAP) scoring system, better predicts in-hospital mortality and can be applied more easily than previous trauma scores among trauma patients in the emergency department']

['Glasgow coma sore is used to determine injury severity on admission to a hospital emergency department or by the duration of unconsciousness.']

[]

Is there association of matrix metalloproteinases with behaviour of pituitary adenomas?

['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.', 'We observed elevation of MMP-2 and -9 expression and consequent 3-D cell invasion in cells under-expressing RECK. ', ' 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. ', 'Inhibition of estrogen-induced pituitary tumor growth and angiogenesis in Fischer 344 rats by the matrix metalloproteinase inhibitor batimastat.', '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.', '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.', 'Data on the dural invasiveness of pituitary adenomas have been correlated to the expression of matrix metalloproteinases (e.g. MMP-9). ', 'We found no correlation of MMP-9 expression and tumour invasion.', 'The matrix metalloproteinases (MMPs) and their nature inhibitors-the tissue inhibitors of metalloproteinases (TIMPs) may play a central role in these processes.', 'CONCLUSIONS: TIMP-1 and TIMP-2 may play a key role in invasive pituitary adenomas to biological behavior.', '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. ', '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. ', 'Beside the digestion of the extracellular matrix during tumor invasion and metastasis, more recently, new functions for matrix metalloproteinases (MMPs) have been proposed. ', 'CONCLUSION: No correlation could be established between the invasive potential of tumors and MMP-1, -2, and -3 expression levels. ', 'Matrix metalloproteinase 2 and 9 expression correlated with cavernous sinus invasion of pituitary adenomas.', 'Data on the dural invasiveness of pituitary adenomas have been correlated to the expression of matrix metalloproteinases (e.g.', 'We found surprisingly high levels of MMP activity and low levels of tissue inhibitor of metalloproteinases, indicating a high level of extracellular matrix-degrading activity in pituitary adenomas.', 'The matrix metalloproteinases (MMPs) and their nature inhibitors-the tissue inhibitors of metalloproteinases (TIMPs) may play a central role in these processes. ', 'We found surprisingly high levels of MMP activity and low levels of tissue inhibitor of metalloproteinases, indicating a high level of extracellular matrix-degrading activity in pituitary adenomas.', 'There was an association between the invasion of pituitary adenomas and Ki-67 LI (P = 0.039) or the expression of VEGF (P &lt; 0.001) and MMP-9 (P &lt; 0.001). But c-myc LI and bcl-2 expression have no association with invasiveness of pituitary adenomas (P = 0.061 vs.', 'nm23 and MMP-9 have associations with invasiveness of pituitary adenomas,', 'Matrix metalloproteinase secreted by pituitary cells can release growth factors from the extracellular matrix that, in turn, control pituitary cell proliferation and hormone secretion. 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.', 'There was an association between the invasion of pituitary adenomas and Ki-67 LI (P = 0.039) or the expression of VEGF (P &lt; 0.001) and MMP-9 (P &lt; 0.001).', 'Although our study has shown that MVD and the expression of VEGF, Ki-67, nm23 and MMP-9 have associations with invasiveness of pituitary adenomas, they are lack of specificity.']

['Yes, there is evidence to suggest that matrix metalloproteinases are associated with more aggressive of pituitary adenomas.']

['yes']

Could Hyperthermic intraperitoneal chemotherapy (HIPEC) be effective for the treatment of recurrent ovarian cancer?

['The use of HIPEC after aggressive cytoreductive surgery in patients with ovarian cancer with peritoneal dissemination can be performed with acceptable postoperative morbidity rates. Knowledge of the factors associated with the onset of these postoperative adverse events allows better management of the same and offers the patient a safe procedure', 'These results showed that the association of HIPEC with a complete cytoreduction for recurrent ovarian cancer presents acceptable morbidity and survival', 'There is level-one evidence suggesting the benefit of postoperative adjuvant intraperitoneal chemotherapy for patients with advanced ovarian cancer after cytoreductive surgery, albeit catheter-related complications resulted after treatment discontinuation. Studies report the use of HIPEC predominantly in the setting of recurrent disease and have demonstrated encouraging results, which merits further investigation in future clinical trials', ' The combination of SCR and HIPEC seems to improve survival rate in patients suffering from platinum-sensitive EOC recurrence with respect to no-HIPEC treatments. This result further supports the need of a randomized trial', ' Cautious extrapolation of data from standard normothermic, nonintraoperative, intraperitoneal chemotherapy and data from Phase II and nonrandomized comparative studies suggest that HIPEC delivered at the time of surgery for ovarian cancer has definite potential', 'The available evidence suggests that a potential survival benefit of adding HIPEC may be largest in the settings of secondary CRS for stage III ovarian cancer and salvage CRS for recurrent ovarian cancer, two time-points representing failure of initial standard therapy. There is much less evidence for a potential benefit of HIPEC for less advanced stages (I-II) and for earlier time-points in the treatment of ovarian cancer (upfront, interval and consolidation)', 'Survival benefit of adding Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) at the different time-points of treatment of ovarian cancer', 'Patients suffering from peritoneal recurrence of ovarian cancer should be considered for radical reoperation with HIPEC in a center with expertise in multimodal therapeutic options. Organ-preserving cytoreductive surgery allows complete cytoreduction with the goal of decreasing morbidity', ' In recurrent platinum-sensitive ovarian cancer patients, the use of CRS plus HIPEC represents a safe treatment, able to significantly influence the survival rates compared to chemotherapy alone or surgery plus standard chemotherapy', ' The results of our study indicate the feasibility and the potential benefit of a protocol including systemic chemotherapy, surgical cytoreduction and HIPEC in patients with peritoneal carcinomatosis from ovarian cancer. A phase III trial to compare this approach with conventional treatment is needed', 'In selected patients with heavily pretreated recurrent ovarian cancer, cytoreduction combined with HIPEC may provide a meaningful OS with acceptable morbidity. Optimal results are achieved in patients with a macroscopically complete resection and biologically favorable disease', ' HIPEC is a complement to radical surgery/ peritonectomy, which has been shown to be a surgical procedure with high tolerability, low morbimortality, enhanced survival and prolonged disease-free interval in patients with peritoneal carcinomatosis for recurrent ovarian cancer', ' Despite the heterogeneity of the studies reviewed, current evidence suggest that complete CRS and HIPEC may be a feasible option with potential benefits that are comparable with the current standard of care. A randomized trial is required to establish the role of HIPEC in ovarian cancer', 'in the majority of patients with primary and recurrent advanced ovarian cancer, cytoreductive surgery combined with HIPEC can lead to a substantial increase in subsequent rates of disease-free and overall survival', ' Peritonectomy procedures combined with HIPEC offer promising long-term survival in patients with diffuse peritoneal ovarian carcinomatosis. They achieve high adequate primary and secondary surgical cytoreduction rates with acceptable morbidity and mortality', 'Cytoreduction surgery with hyperthermic intraperitoneal chemotherapy in recurrent ovarian cancer improves progression-free survival, especially in BRCA-positive patients- a case-control study.', 'Survival benefit of adding Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) at the different time-points of treatment of ovarian cancer: review of evidence.', 'Some encouraging results have been reported by the treatment of peritoneal carcinomatosis (PC) from ovarian cancer by complete surgical cytoreduction, peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC).', 'Although standard treatment for advanced epithelial ovarian cancer (EOC) consists of surgical debulking and intravenous platinum- and taxane-based chemotherapy, favorable oncological outcomes have been recently reported with the use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).', 'Trabectedin, Hyperthermic intraperitoneal chemotherapy (HIPEC) and chemo-immunotherapy may be become a promising therapy for the treatment of ovarian cancer.', 'Hyperthermic intraperitoneal chemotherapy (HIPEC) represents a new treatment strategy aimed to improve outcome of patients with advanced ovarian cancer.', 'Favorable oncological outcomes have been reported in several trials with the introduction of Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in the treatment of Advanced Epithelial Ovarian Cancer (EOC).', 'Based on theoretical and experimental basis, HIPEC should stand as an effective treatment for ovarian cancer.', 'Some encouraging results have been reported by the treatment of peritoneal carcinomatosis (PC) from ovarian cancer by complete surgical cytoreduction, peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC)', 'Based on theoretical and experimental basis, HIPEC should stand as an effective treatment for ovarian cancer', 'Hyperthermic intraperitoneal chemotherapy (HIPEC) represents a new treatment strategy aimed to improve outcome of patients with advanced ovarian cancer', '[Importance of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer].']

['There is level-one evidence suggesting the benefit of postoperative adjuvant intraperitoneal chemotherapy for patients with advanced ovarian cancer after cytoreductive surgery, albeit catheter-related complications resulted after treatment discontinuation. Studies report the use of HIPEC predominantly in the setting of recurrent disease and have demonstrated encouraging results, which merits further investigation in future clinical trials ', 'Yes. In the majority of patients with primary and recurrent advanced ovarian cancer, cytoreductive surgery combined with HIPEC can lead to a substantial increase in subsequent rates of disease-free and overall survival.']

['yes']

What is the mode of inheritance in Fanconi anemia?

['Fanconi anemia (FA) is a rare inherited syndrome with diverse clinical symptoms including developmental defects, short stature, bone marrow failure, and a high risk of malignancies. Fifteen genetic subtypes have been distinguished so far. The mode of inheritance for all subtypes is autosomal recessive, except for FA-B, which is X-linked', 'Fanconi anemia (FA) is a recessively inherited syndrome with predisposition to bone marrow failure and malignancies', 'Original Fanconi anemia data, for which no information about the ascertainment was available, were then analyzed, with results that confirmed a monogenic autosomal recessive mode of inheritance', "The formal genetics of Fanconi's anemia were investigated on the basis of 21 families from different European countries, and of 69 families from the literature. CONCLUSIONS: 1. The result of segregation analysis is compatible with the hypothesis of a simple autosomal recessive mode of inheritance", ' Original Fanconi anemia data, for which no information about the ascertainment was available, were then analyzed, with results that confirmed a monogenic autosomal recessive mode of inheritance.', 'X-linked inheritance of Fanconi anemia complementation group B.', 'Fanconi anemia (FA) is a rare genetic disease with both autosomal and X-linked inheritance, characterized by genomic instability.', ' X-linked inheritance has important consequences for genetic counseling of families with Fanconi anemia belonging to complementation group B.', 'Original Fanconi anemia data, for which no information about the ascertainment was available, were then analyzed, with results that confirmed a monogenic autosomal recessive mode of inheritance.', 'Fanconi anemia (FA), a recessive syndrome with both autosomal and X-linked inheritance, features diverse clinical symptoms, such as progressive bone marrow failure, hypersensitivity to DNA cross-linking agents, chromosomal instability and susceptibility to cancer.', 'X-linked inheritance has important consequences for genetic counseling of families with Fanconi anemia belonging to complementation group B. Its presence as a single active copy and essentiality for a functional Fanconi anemia-BRCA pathway make FANCB a potentially vulnerable component of the cellular machinery that maintains genomic integrity.', 'Fanconi anemia (FA) is a rare genetic disease, transmitted in an autosomal recessive mode.', 'Report of two early-onset cases with Fanconis anemia-like phenotypes suggesting an autosomal-recessive inheritance pattern.', 'In the first family, an association with Fanconis anemia was observed in three of seven pregnancies (2 boys, 1 girl) suggesting an autosomal recessive mode of transmission.', 'The mode of inheritance for all subtypes is autosomal recessive, except for FA-B, which is X-linked.', 'X-linked inheritance has important consequences for genetic counseling of families with Fanconi anemia belonging to complementation group B.', 'The mode of inheritance for all subtypes is autosomal recessive, except for FA-B, which is X-linked', "In the first family, an association with Fanconi's anemia was observed in three of seven pregnancies (2 boys, 1 girl) suggesting an autosomal recessive mode of transmission", 'X-linked inheritance has important consequences for genetic counseling of families with Fanconi anemia belonging to complementation group B', 'Fanconi anemia (FA) is a rare genetic disease, transmitted in an autosomal recessive mode']

['Fanconi anemia (FA) is a rare inherited syndrome with diverse clinical symptoms including developmental defects, short stature, bone marrow failure, and a high risk of malignancies. Fifteen genetic subtypes have been distinguished so far. The mode of inheritance for all subtypes is autosomal recessive, except for FA-B, which is X-linked ', 'Fanconi anemia (FA) is a rare inherited syndrome. So far, fifteen genetic subtypes have been distinguished. The mode of inheritance for all subtypes is autosomal recessive, except for FANCB, which is X-linked.']

['Autosomal recessive, except for FANCB, which is X-linked.']

What are the major clinical Villefranche criteria for classic Ehlers-Danlos syndrome?

['All type V collagen defects were identified within a group of 102 patients fulfilling all major clinical Villefranche criteria, that is, skin hyperextensibility, dystrophic scarring and joint hypermobility', 'All type V collagen defects were identified within a group of 102 patients fulfilling all major clinical Villefranche criteria, that is, skin hyperextensibility, dystrophic scarring and joint hypermobility']

['The major clinical Villefranche criteria for classic Ehlers-Danlos syndrome are skin hyperextensibility, dystrophic scarring, and joint hypermobility.']

['skin hyperextensibility', 'dystrophic scarring', 'joint hypermobility']

How many microorganisms are present in human normal gut?

['. A major breakthrough in understanding the etiology of neurological disorders is the recent insight on the role of the gut microbiota (GM). Human GM also referred to as the "forgotten organ" is home to 10(13-14) microorganisms', 'The gut microbiome comprises the collective genome of the trillions of microorganisms residing in our gastrointestinal ecosystem.', 'The gut microbiome (i.e. the 100 trillion symbiotic microorganisms which inhabit the mammalian gastrointestinal tract) influences numerous aspects of host metabolism, development and immunity.', 'The microorganisms inhabiting the human gut are abundant (10(14) cells) and diverse (approximately 500 species per individual).']

['Human gut microbiota is home to 10 to 100 trillions microorganisms.']

['10 to 100 trillions microorganisms.']

Can cognitive behavioral therapy improve fatigue in cancer patients?

['Physical activity, educational interventions, and cognitive-behavioral therapy have the most supportive data and can be recommended to patients with confidence. ', 'For women undergoing radiotherapy (3 RCTs), hypnosis combined with cognitive-behavioral therapy improved distress and fatigue.', 'Patients in the CBT group reported a significantly larger decrease in fatigue scores than patients in the waiting list group.', 'However, relative to VCBT-I, PCBT-I was associated with significantly greater improvements of insomnia severity, early morning awakenings, depression, fatigue, and dysfunctional beliefs about sleep. ', 'CBT-I may also improve mood, fatigue, and overall quality of life, and can be successfully delivered through a variety of treatment modalities, making it possible to reach a broader range of patients who may not have access to more traditional programs. ', 'No group differences in improvement were noted relative to QOL, fatigue, or mood. ', 'In case of persistent fatigue, personalized cognitive behavioral therapy can be considered.', 'ONCLUSION: The results support CBTH as an evidence-based intervention to control fatigue in patients undergoing radiotherapy for breast cancer. ', 'Severe fatigue after cancer treatment can be treated effectively with cognitive behavioral therapy (CBT), but it is unclear whether CBT has an effect on cognitive functioning.', 'CONCLUSION: CBT for post-cancer fatigue has already been shown to be an effective therapy. ', 'Frequently reported side effects include cancer-related fatigue, peripheral neuropathy, and psychological distress. Exercise and cognitive behavioral therapy interventions have counteracted such adverse effects in other cancer populations. ', 'There is evidence from methodologically rigorous controlled trials that exercise, psycho-educational interventions, and cognitive-behavioral therapy for insomnia are effective in the treatment of CRF, and a wide range of pharmacologic and nonpharmacologic interventions has shown initial promise in single-arm pilot studies with small, heterogeneous samples. ', 'CONCLUSIONS: Physical training combined with cognitive-behavioral therapy and physical training alone had significant and beneficial effects on fatigue compared with no intervention. Physical training was equally effective as or more effective than physical training combined with cognitive-behavioral therapy in reducing cancer-related fatigue, suggesting that cognitive-behavioral therapy did not have additional beneficial effects beyond the benefits of physical training.', 'RESULTS: Imagery/hypnosis and CBT/CST interventions have produced improvement in all the three cancer-related symptoms individually: pain, fatigue, and sleep disturbance.', "RESULTS: Multilevel modeling indicated that for weekly FACIT fatigue data, there was a significant effect of the CBTH intervention on the rate of change in fatigue (p < .05), such that on average, CBTH participants' fatigue did not increase over the course of treatment, whereas control group participants' fatigue increased linearly.", 'ONCLUSION: The results suggest that CBTH is an effective means for controlling and potentially preventing fatigue in breast cancer radiotherapy patients.', 'Results were consistent with the view that CBTH was effective in managing fatigue and skin discomfort, and increasing relaxation.', 'RESULTS: Participants in the Internet group showed significant improvements at post-assessment compared with those in the control group in overall insomnia severity (F(1,26) = 22.8; p<0.001), sleep efficiency (F(1,24) = 11.45; P = 0.002), sleep onset latency (F(1,24) = 5.18; P = 0.03), soundness of sleep (F(1,24) = 9.34; P = 0.005), restored feeling upon awakening (F(1,24) = 11.95; P = 0.002), and general fatigue (F(1,26) = 13.88; P = 0.001). ', 'Cognitive-behavior therapy (CBT) has alleviated fatigue and improved QOL of cancer patients; however, little is known about the effects of nurse-led CBT on breast cancer patients undergoing radiotherapy.', 'Physical training was equally effective as or more effective than physical training combined with cognitive-behavioral therapy in reducing cancer-related fatigue, suggesting that cognitive-behavioral therapy did not have additional beneficial effects beyond the benefits of physical training.', 'Cognitive-behavior therapy (CBT) has alleviated fatigue and improved QOL of cancer patients; however, little is known about the effects of nurse-led CBT on breast cancer patients undergoing radiotherapy.', 'Physical training was equally effective as or more effective than physical training combined with cognitive-behavioral therapy in reducing cancer-related fatigue, suggesting that cognitive-behavioral therapy did not have additional beneficial effects beyond the benefits of physical training.', 'The positive effects of cognitive behavioral therapy in adolescents with chronic fatigue syndrome are sustained after cognitive behavioral therapy']

['Yes, it has been documented that cognitive behavioral therapy reduces fatigue symptom severity in cancer patients. In addition, cognitive behavioral therapy has been also shown to improve mood and overall quality of life, and it can be successfully delivered through a variety of treatment modalities in patients with cancer.']

['yes']

To which disease does the loss of CD28 expression by liver-infiltrating T cells contribute?

['Loss of CD28 expression by liver-infiltrating T cells contributes to pathogenesis of primary sclerosing cholangitis.', 'Loss of CD28 expression by liver-infiltrating T cells contributes to pathogenesis of primary sclerosing cholangitis', 'Loss of CD28 expression by liver-infiltrating T cells contributes to pathogenesis of primary sclerosing cholangitis.']

['Loss of CD28 expression by liver-infiltrating T cells contributes to pathogenesis of primary sclerosing cholangitis.', 'Loss of CD28 expression by liver-infiltrating T cells contributes to pathogenesis of primary sclerosing cholangitis. ', 'loss of cd28 expression by liver-infiltrating t cells contributes to pathogenesis of primary sclerosing cholangitis.']

['Primary sclerosing cholangitis']

Has proteomics been used in the study of Pick's disease?

["In Pick's disease, increased AGE, CML, CEL, HNE and MDAL bands of about 50 kDa were observed in the frontal cortex (but not in the occipital cortex) in association with increased density of glial acidic protein bands.", "Thus, brain and cerebrospinal fluid (CSF) samples from patients with Alzheimer's disease, Down syndrome, Pick's disease, Parkinson's disease, schizophrenia, and other disorders as well as brain and CSF from animals serving as models of neurological disorders have been analyzed by proteomics. ", 'The present study is designed to investigate expression of peroxiredoxins (Prxs), the newly characterized family of highly conserved antioxidant enzymes, and other antioxidant enzymes in frontal cortex and cerebellum of DS, AD and PD patients using the technique of proteomics. ', 'HMT levels were measured in the frontal cortex and cerebellum of brains of patients with AD, DS, and PiD, and normal aged subjects using proteomics techniques. ']

["Yes, proteomics has been used in the study of Pick's disease."]

['yes']

Which pipelines are used for analyzing data from ChIP-nexus experiments?

['PeakXus: comprehensive transcription factor binding site discovery from ChIP-Nexus and ChIP-Exo experiments.', 'We describe a peak caller PeakXus that is specifically designed to leverage the increased resolution of ChIP-exo/Nexus and developed with the aim of making as few assumptions of the data as possible to allow discoveries of novel binding patterns. We apply PeakXus to ChIP-Nexus and ChIP-exo experiments performed both in Homo sapiens and in Drosophila melanogaster cell lines.', 'Q-nexus: a comprehensive and efficient analysis pipeline designed for ChIP-nexus.', 'Here, we present a comprehensive software package for ChIP-nexus data that exploits the random barcodes for selective removal of PCR duplicates and for quality control. Furthermore, we developed bespoke methods to estimate the width of the protected region resulting from protein-DNA binding and to infer binding positions from ChIP-nexus data. Finally, we applied our peak calling method as well as the two other methods MACE and MACS2 to the available ChIP-nexus data.', 'Q-nexus: a comprehensive and efficient analysis pipeline designed for ChIP-nexus.', 'PeakXus: comprehensive transcription factor binding site discovery from ChIP-Nexus and ChIP-Exo experiments.']

['PeakXus and Q-nexus enable comprehensive transcription factor binding site discovery from ChIP-nexus experiments.']

['PeakXus', 'Q-nexus']

Does triiodothyronine stimulate red blood cell sodium potassium pump?

['reduction in Na+,K+ATPase activity has been demonstrated in red blood cells (RBCs), as well as an inverse correlation between this enzymatic action and free triiodothyronine (FT3) levels.', 'The restoration of normal FT3 values also brings about a normalization of Na+,K+ATPase activity in erythrocytes.', 'at hyperthyroid patients have decreased red cell Na/K-ATPase activity and provide direct evidence that erythrocyte ATPase activity is increased in hypothyroid patients. The change in enzyme activity in patients with nonthyroidal illness and decreased circulating T3 levels was comparable to that in hypothyroidism.', 'The effect of triiodothyronine (T3) on Na+,K(+)-ATPase activity of K562 human erythroleukemic cell was studied to understand why the erythrocyte sodium pump activity is decreased in hyperthyroidism.', 'We conclude that T3 stimulates Na+,K(+)-ATPase activity of K562 cells and in the presence of T3 during differentiation, the enzyme activity remains high.']

['An inverse correlation between this enzymatic action and free triiodothyronine (FT3) levels.\nThe effect of triiodothyronine (T3) on Na+,K(+)-ATPase activity in red blood cells may be different in vivo and in vitro.']

['no']

List disorders that have been associated to the polymorphism rs2535629.

['A recent genome-wide analysis indicated that a polymorphism (rs2535629) of ITIH3 showed the strongest association signal with susceptibility to psychiatric disorders in Caucasian populations. ', 'he aim of the study was to replicate the association of rs2535629 with schizophrenia and major depressive disorder (MDD) in Japanese subjects. ', 'In the MDD-bipolar cross-disorder analysis, 15 SNPs exceeded genome-wide significance (P<5 × 10(-8)), and all were in a 248\u2009kb interval of high LD on 3p21.1 (chr3:52\u2009425\u2009083-53\u2009822\u2009102, minimum P=5.9 × 10(-9) at rs2535629).', 'However, there was no preferential transmission at the ITIH3 rs52535629 polymorphism (χ²=0.14, P=0.707).']

['schizophrenia and major depressive disorder. ']

['schizophrenia', 'major depressive disorder']

Is fatigue prevalent in patients receiving treatment for glioblastoma?

['By contrast, fatigue worsened over time, with a difference in mean score of 5.6 points between baseline and 4-month follow-up (P=.02).', 'In the GB cohort, the most common side effects were fatigue (56 %), diarrhea (44 %), neutropenia (31 %), and thrombocytopenia (25 %). ', 'A total of 37 patients were treated, and treatment was well tolerated: grade 3, 4 nonhematologic toxicity occurred in 30% of patients and consisted mainly of fatigue (14%) and neuropathy (5%); grade 3, 4 hematologic toxicity occurred in 37% of patients and consisted of thrombocytopenia (30%), lymphopenia (4%), and neutropenia (4%). ', 'Nonhematologic Grade 3 toxicity was rare, and included fatigue in 4 patients and cognitive disability in 1 patient.', 'The most common grade 3 events were neutropenia, thrombocytopenia, fatigue, and infection in 25, 20, 13, and 10%, respectively. ', 'Analysis of the results of the VAS Norris scale did not demonstrate an increase in emotional fatigue but did show an increase in physical fatigue that did not reach statistical significance. With regards to the MFI 20 tool, analysis of the results demonstrated a significant increase in general (P=0.0260) as well as physical (P=0.0141) fatigue but there was no difference in the other indices.', 'This study demonstrated a progressive increase in physical fatigue in patients with glioblastoma relapse treated with irinotecan-bevacizumab. ', 'One patient treated with temozolomide plus isotretinoin plus thalidomide had dose-limiting grade 3 fatigue and rash, and 1 patient receiving all 4 agents had dose-limiting grade 4 neutropenia. ', 'The toxicities observed were primarily grade 1 and 2, and the most common were fatigue, hypertension, and headache. ', 'Fatigue (41%), rash (62%), and loose stools (58%) constituted the most frequent adverse events, the majority of these being limited to Grade 1/2. ', 'The most common grades 3 and 4 nonhematologic toxicities were nausea/vomiting (6.7%) and fatigue (5.8%). ', 'Grade 3/4 toxicities included leukopenia (n = 1), lymphopenia (n = 2), thrombocytopenia (n = 1), ALT elevation (n = 3), AST elevation (n = 1), CNS hemorrhage (n = 1), fatigue (n = 1), and thrombotic/embolic events (n = 3); 8 patients required dose reduction. ', 'The most common grade 3 or greater adverse events were fatigue (7%), neutropaenia (7%), and thrombocytopaenia (7%).', 'Bevacizumab-related toxicity included fatigue (16 patients; 4 grade 3), leukopenia (9; 1 grade 3), anemia (5; 0 grade 3), hypertension (7; 1 grade 3), deep vein thrombosis (4; 1 grade 3) and wound dehiscence (2; 1 grade 3). ', 'Tiredness may be caused by the brain injury due to the tumor or the treatment in patients with glioblastoma multiforme (GBM). Some patients describe a sense of tiredness particularly after radiation or oral chemotherapy.', 'Levels of tiredness in patients with GBM were greatly affected by the radiotherapy and oral chemotherapy (temozolomide).', 'The treatment had no negative effect on HRQOL, however, fatigue (P = 0.02) and constipation (P = 0.01) scales worsened over time.', ' This regimen was well tolerated with grade 3/4 toxicities of fatigue, leukopenia, thrombocytopenia and rash requiring dose reductions. ', 'The most common atrasentan-related toxicities were grade 1 or 2 rhinitis, fatigue, and edema.', 'One patient developed Grade IV fatigue at the 100 ng/mL dose, but the MTD has not been established. ', 'Side-effects in all patients have included varying degrees of anorexia, fatigue, ipsilateral forehead dermatitis, blepharitis, and conjunctivitis. ', ' Some patients suffered from fatigue and weak concentration about three months after the end of radiotherapy, in some cases even the neurologic state was deteriorated. ', 'grade 1-2 common toxicities included fever, chills, fatigue, dizziness, nausea, vomiting and headache, neutrophilia and skin painful reactions appeared regularly at levels 3 and 4 (2.5 mg and 3.5 mg). ', 'Ten episodes of grade 3/4 adverse events were observed in nine patients, including fatigue (n = 3), thrombocytopenia (n = 4), and myelotoxicity, febrile neutropenia, and pulmonary embolism (each n = 1).', 'Common adverse events were CTCAE grade 1-2 fatigue, loss of appetite, diarrhea, and nausea.', 'The most common grade 3-4 toxicities were venous thrombosis, fatigue, skin reactions, encephalopathy, and neuropathy.']

['Yes, fatigue is a common complication of glioblastoma patients receiving chemotherapy or radiotherapy.']

['yes']

In which yeast chromosome does the rDNA cluster reside?

['Chromosome XII context is important for rDNA function in yeast', 'The rDNA cluster in Saccharomyces cerevisiae is located 450 kb from the left end and 610 kb from the right end of chromosome XII and consists of approximately 150 tandemly repeated copies of a 9.1 kb rDNA unit', 'To explore the biological significance of this specific chromosomal context, chromosome XII was split at both sides of the rDNA cluster and strains harboring deleted variants of chromosome XII consisting of 450 kb, 1500 kb (rDNA cluster only) and 610 kb were created. In the strain harboring the 1500 kb variant of chromosome XII consisting solely of rDNA, the size of the rDNA cluster was found to decrease as a result of a decrease in rDNA copy number', 'These observations suggest that the context of chromosome XII plays an important role in maintaining a constant rDNA copy number and in physiological processes related to rDNA function in S.cerevisiae.', 'Notably, strains harboring the 450 kb chromosome XII variant and/or the 1500 kb variant consisting solely of rDNA had shorter life spans than wild type and also accumulated extrachromosomal rDNA circles', 'Condensation of a unique region of chromosome XVI and the highly repetitive ribosomal DNA (rDNA) cluster from chromosome XII were also examined in budding yeast.', 'Condensation of a unique region of chromosome XVI and the highly repetitive ribosomal DNA (rDNA) cluster from chromosome XII were also examined in budding yeast.', 'To explore the biological significance of this specific chromosomal context, chromosome XII was split at both sides of the rDNA cluster and strains harboring deleted variants of chromosome XII consisting of 450 kb, 1500 kb (rDNA cluster only) and 610 kb were created.', 'In the strain harboring the 1500 kb variant of chromosome XII consisting solely of rDNA, the size of the rDNA cluster was found to decrease as a result of a decrease in rDNA copy number.', 'Apart from chromosome XII, which contains the 1-2 Mb rDNA cluster, chromosome IV is the longest S. cerevisiae chromosome.', 'We studied the largest yeast chromosome XII, which contains the rDNA locus, and we investigated its instability using cell cycle checkpoint-, DNA damage- and antioxidative defence-deficient, and lifespan-deregulated yeast mutant strains.', 'Chromosome XII context is important for rDNA function in yeast.', 'Condensation of a unique region of chromosome XVI and the highly repetitive ribosomal DNA (rDNA) cluster from chromosome XII were also examined in budding yeast. ', 'Clonal size-variation of rDNA cluster region on chromosome XII of Saccharomyces cerevisiae.', 'Using pulsed-field gel electrophoresis (PFGE), we have demonstrated clonal variation in the size of chromosome XII in a diploid strain of Saccharomyces cerevisiae X2180-2D.', 'The sizes of the two chromosome XII homologues were very different: 2600 (L-type) and 1450 kb (S-type).', 'The size variation was shown to be derived from size changes in the rDNA cluster region, which is present in chromosome XII, by digesting the chromosome with XhoI, whose cutting site is not present in a rDNA repeat unit, and hybridizing to rDNA probes.', 'Apart from chromosome XII, which contains the 1-2 Mb rDNA cluster, chromosome IV is the longest S. cerevisiae chromosome.', 'Condensation of a unique region of chromosome XVI and the highly repetitive ribosomal DNA (rDNA) cluster from chromosome XII were also examined in budding yeast.', 'Chromosome XII context is important for rDNA function in yeast.']

['Chromosome XII context is important for rDNA function in yeast', 'The rDNA cluster in Saccharomyces cerevisiae is located 450 kb from the left end and 610 kb from the right end of chromosome XII and consists of approximately 150 tandemly repeated copies of a 9.1 kb rDNA unit.', 'Condensation of a unique region of chromosome XVI and the highly repetitive ribosomal DNA (rDNA) cluster from chromosome XII were also examined in budding yeast. The rDNA cluster in Saccharomyces cerevisiae is located 450 kb from the left end and 610 kb from the right end of chromosome XII and consists of approximately 150 tandemly repeated copies of a 9.1 kb rDNA unit. However, in cells arrested in late mitosis (M) by a cdc15 mutation, the unique DNA appeared decondensed while the repetitive rDNA region appeared condensed, suggesting that the condensation state of separate regions of the genome may be regulated differently. Finally our FISH method provides a new tool to analyze centromeres, telomeres, and gene expression in budding yeast.']

['chromosome XII', 'chromosome 12']

Which mitochondrial genes are regulated by thyroid hormone?

['We used a polymerase chain reaction (PCR)-based mRNA differential display (DD) analysis to obtain a profile of thyroid hormone-responsive genes in osteoblast-like cells', 'At the 2-hour time point, 1 true-positive novel clone was identified and shown to be the mitochondrial gene, subunit 6 of ATP synthase (ATPase-6).', 'We studied the coordination of the two genomes by measuring transcript levels for nuclear (IV, Va, and VIc) and mitochondrial (II and III) subunits of cytochrome-c oxidase after altering the mitochondrial content of rat muscle and liver by altering the thyroid state of the animals. Tissue levels of these mRNAs were generally decreased in hypothyroid animals and were up-regulated again after thyroid hormone (T3) treatment.', 'Following this procedure, we now report the identification of the mitochondrial NADH dehydrogenase subunit 3 (ND3) gene as target of thyroid hormone.', 'Sequencing and electrophoretic mobility shift assays confirmed the presence of a thyroid hormone receptor (TR)/c-erbA specific binding site in the mitochondrial ND3 gene.']

['subunit 6 of ATP synthase, ATPase-6, mitochondrial II and III subunits of cytochrome-c oxidase, NADH dehydrogenase subunit 3']

['subunit 6 of ATP synthase', 'ATPase-6', 'mitochondrial II and III subunits of cytochrome-c oxidase', 'NADH dehydrogenase subunit 3', 'ND3']

Is there a phylogenetic analysis for HIV?

['The results of Burst and phylogenetic analysis suggested that the C. neoformans var. grubii strains could be separated into three nonredundant evolutionary groups (Burst group 1 to group 3). ', 'Phylogenetic trees were constructed to evaluate the relationships between the variants', 'We analyzed pol (protease/reverse transcriptase) sequences from 135 newly diagnosed HIV-1-infected patients during the years 2009-2011. For phylogenetic relationships, sequences were aligned to the most recent reference data set from the Los Alamos database using BioEdit (version 7.1.3). The resulting alignment was analyzed with the Phylip package (version 3.67) building a neighbor-joining tree based on the Kimura two-parameter substitution model', '. Phylogenetic analysis of gag gene were then performed using the MEGA 3.1 software, the gene distances were calculated by Distance program. There were three different HIV-1 subtypes including B, CRF01-AE and CRF07-BC present among twenty four MSMs in Zhengzhou', 'Phylogenetic analysis showed interpatient and intrapatient clustering of LTR nucleotide sequences.', ' We evaluated the risk factors for intrafamilial transmission of HIV-1 infection through qualitative epidemiology following pol and env gene sequencing and phylogenetic analysis', 'Phylogenetic analysis has shown that the Siberian 10.RU.6637 isolate displays the highest sequence identity to the HIV-1 subtype AG forms circulating in Uzbekistan', 'Phylogenetic analysis showed that the evolutionary relationship of Env between HIV and SIV was the closest and they appeared to descend from a common ancestor, and the relationship of HIV and EIAV was the furthest', 'DI was confirmed when maximum sequence divergence was excessive and supported by phylogenetic analysis', ' (HIV-1) dual infection (DI) has been associated with decreased CD4 T-cell counts and increased viral loads; however, the frequency of intrasubtype DI is poorly understood.', 'The aim of this study was to investigate the phylogenetic relationships of HIV-1 subtype C strains from Bangladesh and related strains from other countries, and thereby clarify when and from where subtype C was introduced in the country and how it subsequently spread within Bangladesh', ' This study characterized HCV genotype 5 sequences from South Africa, including six near full-length genomes, as well as the E1 region from an additional 12 genotype 5 samples. Phylogenetic analysis of these near full-length genome sequences revealed that all genotype 5 sequences formed a close cluster with high bootstrap support', ' The evolutionary history of the B subregion was not as clear as the C subregion, as the short length of this region yielded poor phylogenetic results', ' Finally, a phylogenetic tree was constructed to elucidate the observed pattern of HIV TDR']

['In biology, phylogenetics is the study of evolutionary relationships among groups of organisms (e.g. species, populations), which are discovered through molecular sequencing data and morphological data matrices. The result of phylogenetic studies is a hypothesis about the evolutionary history of taxonomic groups: their phylogeny. \nPhylogenetic analysis examines small differences in HIV’s genes using computational methods to calculate the genetic distance between strains. Unlike\nhuman DNA, which remains stable for a lifetime, HIV’s RNA changes very rapidly, leading to a huge amount of genetic diversity. This diversity means that scientists, using phylogenetic analysis, have been able to ascertain where HIV comes from, as well as track the various strains of HIV that exist worldwide.\nBased on results, there are found many studies on HIV phylogenetic analysis.']

['yes']

Define marine metaproteomics

["Metaproteomics is a new field within the 'omics' science which investigates protein expression from a complex biological system and provides direct evidence of physiological and metabolic activities.", 'Metaproteomic studies of whole microbial communities from environmental samples (e.g., soil, sediments, freshwater, seawater, etc.) have rapidly increased in recent years due to many technological advances in mass spectrometry (MS). ', 'Metatranscriptomics and metaproteomics are approaches based on different techniques and have recently emerged as promising techniques to describe microbial activities within a given environment at the molecular level. ', 'Culture-independent techniques such as LC-MS/MS-based metaproteomic analyses are being increasingly utilized for the study of microbial composition and function in complex environmental samples.', 'Metaproteomic analysis and protein-stable isotope probing revealed Burkholderiales, Actinomycetales, and Rhizobiales as the most active microorganisms in the groundwater communities.', 'Advances in tandem mass spectrometry (tandem MS) and sequencing have enabled the field of community proteomics, which seeks to identify expressed proteins, their sequence variability, and the physiological responses of organisms to variable environmental conditions', 'Marine community proteomic studies have verified the importance of nutrient transport, energy generation, and carbon fixation functions in bacteria and archaea and revealed spatial and temporal shifts in the expressed functions of communities. ', 'Metagenomics is the study of microbial organisms using sequencing applied directly to environmental samples. Similarly, in metatranscriptomics and metaproteomics, the RNA and protein sequences of such samples are studied. The analysis of these kinds of data often starts by asking the questions of "who is out there?", "what are they doing?", and "how do they compare?". ', 'the study of the proteins collectively expressed by all the microorganisms present within an ecosystem (metaproteomics) is not only crucial but can also provide insights into microbial functionality.', 'Metaproteomics has been employed in very diverse environments, and this review discusses the recent advances achieved in the context of human biology, soil, marine and freshwater environments as well as natural and bioengineered systems.', 'To assess the functional dynamics of microbial communities, metatranscriptomics and metaproteomics have been developed. The combination of DNA-based, mRNA-based, and protein-based analyses of microbial communities present in different environments is a way to elucidate the compositions, functions, and interactions of microbial communities and to link these to environmental processes.', 'Metaproteomics is one of a suite of new approaches providing insights into the activities of microorganisms in natural environments. ', 'We used comparative membrane metaproteomics to identify functional responses of communities to different nutrient concentrations on an oceanic scale.', 'This study describes the application of proteomic approaches (metaproteomics) to observe expressed protein profiles of natural microbial communities (metaproteomes). ', 'metaproteomics analysis of fecal samples to determine microbial gut composition and protein expression. ', 'In this study, we used metaproteomics and metabolomics to investigate the intricate network of metabolic interactions in the chemosynthetic association between Olavius algarvensis, a gutless marine worm, and its bacterial symbionts. ', 'The role of planktonic Flavobacteria in processing algal organic matter in coastal East Antarctica revealed using metagenomics and metaproteomics.']

['Marine metaproteomics is the study of the activities of whole marine microbial communities. The proteomic analyses are applied directly without the need for prior microbial culturing. The samples can be sediments,seawater, etc.']

[]

Which protein is required for Argonaute 2 recruitment to stress granules and P-bodies?

['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', 'Hsp90 regulates the function of argonaute 2 and its recruitment to stress granules and P-bodies', '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', 'Hsp90 regulates the function of argonaute 2 and its recruitment to stress granules and P-bodies.', 'Treatment with RA reduced the level of the Hsp90 client protein Argonaute 2 and the number of P-bodies.', 'Treatment with RA reduced the level of the Hsp90 client protein Argonaute 2 and the number of P-bodies. ', 'In the present study, we show that heat-shock protein (Hsp) 90 activity is required for efficient targeting of hAgo2 to PBs and SGs. ', 'To verify these observations, 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.', 'Treatment with RA reduced the level of the Hsp90 client protein Argonaute 2 and the number of P-bodies.']

['Hsp90 regulates the function of argonaute 2 and its recruitment to stress granules and P-bodies.']

['Hsp90']

Have mutations in the Polycomb group been found in human diseases?

['We identify a novel mutation in PHC1, a human orthologue of the Drosophila polyhomeotic member of polycomb group (PcG), which significantly decreases PHC1 protein expression, increases Geminin protein level and markedly abolishes the capacity to ubiquitinate histone H2A in patient cells.', 'In clinical specimens of head and neck cancer, we found that coamplification of BMI1 and AURKA correlated with poorer prognosis.', 'Mutations of EZH2, RUNX1, TP53, and ASXL1 were associated with shorter overall survival independent of the LR-PSS.', 'In this study, we show the high frequency of spontaneous γδ T-cell leukemia (T-ALL) occurrence in mice with biallelic deletion of enhancer of zeste homolog 2 (Ezh2).', 'Subsequently, analysis of deletion profiles of other PRC2 members revealed frequent losses of genes such as EZH2, AEBP2, and SUZ12; however, the deletions targeting these genes were large. We also identified two patients with homozygous losses of JARID2 and AEBP2. We observed frequent codeletion of AEBP2 and ETV6, and similarly, SUZ12 and NF1.', 'A total of 25 different EZH2 mutations were detected in 5.9% of PMF, 1.2% of PPV-MF, and 9.4% of PET-MF patients; most were exonic heterozygous missense changes.', 'In the present investigation we have focused on the candidate region in 6p23, a region that have been found linked to CL/P in several investigations, in the attempt to find out the susceptibility gene provisionally named OFC1. Gene expression experiments in mice embryo of positional candidate genes revealed that JARID2 was highly and specifically expressed in epithelial cells in merging palatal shelves.', 'High expression of EZH2 and amplification of EZH2 was found in 54.1% and 12.0% of ESCCs, respectively.', 'We also observed that HOXA9 levels were significantly inversely correlated with survival and that BMI-1 was overexpressed in cases with 11q23 rearrangements, suggesting that p19(ARF) suppression may be involved in MLL-associated leukemia.', 'We demonstrate that in multiple experimental models of metastatic prostate cancer both BMI1 and Ezh2 genes are amplified and gene amplification is associated with increased expression of corresponding mRNAs and proteins.', 'he EZH2 gene amplification was significantly (P < 0.05) associated with increased EZH2 protein expression.', 'The third tumor showed a t(6p;10q;10p) as the sole karyotypic abnormality, leading to the fusion of PHF1 with another partner, the enhancer of polycomb (EPC1) gene from 10p11; EPC1 has hitherto not been associated with neoplasia.']

['Yes, different members of the Polycomb family have been found mutated in diseases such as primary microcephaly, nonsyndromic cleft lip and several cancers (including hemotopoietic malignancies, esophageal carcinoma, head and neck cancer or prostate cancer).\n\nExact anser:\nYes']

['yes']

Describe Mozart effect.

['OBJECTIVE: Listening to Mozart K.448 has been demonstrated to improve spatial task scores, leading to what is known as the Mozart Effect.', "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. ", 'The Mozart Effect is a phenomenon whereby certain pieces of music induce temporary enhancement in "spatial temporal reasoning." ', 'OBJECTIVE: Listening to Mozart K.448 has been demonstrated to improve spatial task scores, leading to what is known as the Mozart effect.', '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". ', 'Mozart K.448 has been shown to improve cognitive function, leading to what is known as the Mozart Effect. ', "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.", "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. ", "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.", 'Listening to Mozart K.448 has been demonstrated to improve spatial task scores, leading to what is known as the Mozart effect.', 'The "Mozart effect" refers to claims that people perform better on tests of spatial abilities after listening to music composed by Mozart.', 'Listening to Mozart K.448 has been demonstrated to improve spatial task scores, leading to what is known as the Mozart Effect.', 'The Mozart effect is an increase in spatial reasoning scores detected immediately after listening to the first movement of a Mozart piano sonata.', 'The "Mozart effect" is the tendency to score higher on spatiotemporal IQ subscales following exposure to complex music such as Mozart\'s Sonata K.448.', 'Mozart K.448 has been shown to improve cognitive function, leading to what is known as the Mozart Effect.', ' Listening to Mozart K.448 has been demonstrated to improve spatial task scores, leading to what is known as the Mozart Effect. However, most of these reports only describe the phenomena but lack the scientific evidence needed to properly investigate the mechanism of Mozart Effect.', ' The Mozart effect is an increase in spatial reasoning scores detected immediately after listening to the first movement of a Mozart piano sonata. Rauscher and Shaw (1998) suggested that failure to produce a Mozart effect could arise from carryover effects of a spatial reasoning pretest which may interfere with the effect of listening to Mozart.', 'Mozart K.448 has been shown to improve cognitive function, leading to what is known as the Mozart Effect.']

["The Mozart effect implies the enhancement of reasoning skills solving spatial problems in normal subjects after listening to Mozart's piano sonata K 448."]

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What is the main component of the Lewy bodies?

["α-syn is the main component of Lewy bodies in Parkinson's disease (PD) and Lewy body dementia", "Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Majority of PD are sporadic, for which genetic causes remain largely unknown. Alpha-synuclein, the main component of Lewy bodies, plays a central role in the PD pathogenesis", "Parkinson's disease (PD) is characterized by the progressive degeneration of substantia nigra pars compacta (SNpc) dopaminergic neurones and the formation of Lewy bodies (LB) in a proportion of the remaining neurones. α-synuclein is the main component of LB, but the pathological mechanisms that lead to neurodegeneration associated with LB formation remain unclear", "α-Synuclein is the main component of Lewy bodies, the intraneuronal inclusion bodies characteristic of Parkinson's disease", "Parkinson's disease (PD) is the second most common neurodegenerative disease. The majority of PD cases are sporadic, for which genetic causes and underlying molecular mechanisms remain largely unclear. Autophagy, a highly conserved cellular process that governs the breakdown of long-lived proteins and organelles, has been involved in the degradation of α-synuclein (α-Syn), the main component of Lewy bodies", 'The main component of Lewy bodies is alpha-synuclein', 'Alpha-synuclein, a main component of Lewy bodies in synucleinopathies and senile plaques in Alzheimer disease, is centrally involved in neurodegeneration', 'alpha-Synuclein, the main component of LBs, is expressed as two main isoforms (112 and 140), but little is known about their differential expression in the brain. ', 'Amyloid precursor protein (APP) is involved in the accumulation of alpha-synuclein, the main component of Lewy bodies', "The pre-synaptic protein alpha-synuclein is the main component of Lewy bodies and Lewy neurites, the defining neuropathological characteristics of Parkinson's disease and dementia with Lewy bodies.", "Specifically, identification of Lewy bodies in fetal mesencephalic neurons transplanted in patients with Parkinson's disease raised the hypothesis that α-synuclein, the main component of Lewy bodies, could be transmitted from the host brain to a graft of healthy neurons.", 'LBD has neuropathological characteristics whereby numerous Lewy bodies are present in the central and sympathetic nervous systems, and it is a type of alpha-synucleinopathy because the main component of Lewy body is alpha-synuclein.', "In Parkinson's disease, the inclusion bodies are referred to as Lewy bodies and their main component is alpha-synuclein.", 'The main component of Lewy bodies is alpha-synuclein.', 'The main component of Lewy bodies is alpha-synuclein (AS).', 'Amyloid precursor protein (APP) is involved in the accumulation of alpha-synuclein, the main component of Lewy bodies.', 'Alpha-synuclein, a main component of Lewy bodies in synucleinopathies and senile plaques in Alzheimer disease, is centrally involved in neurodegeneration.', '�-Synuclein is the main component of Lewy bodies, the intraneuronal inclusion bodies characteristic of Parkinsons disease.', 'In the 1990s, �-synuclein was identified as the main constituent of the Lewy pathology, and its aggregation was shown to be central to PD, dementia with Lewy bodies, and multiple system atrophy.', 'Identification of protein interfaces between �-synuclein, the principal component of Lewy bodies in Parkinson disease, and the molecular chaperones human Hsc70 and the yeast Ssa1p.', 'Fibrillar �-synuclein (�-Syn) is the principal component of Lewy bodies, which are evident in individuals affected by Parkinson disease (PD).', '�-Synuclein is a major component of Lewy bodies in Parkinson disease (PD) and dementia with Lewy bodies (DLB).', 'The main component of Lewy bodies is alpha-synuclein.', "In Parkinson's disease, the inclusion bodies are referred to as Lewy bodies and their main component is alpha-synuclein.", "Specifically, identification of Lewy bodies in fetal mesencephalic neurons transplanted in patients with Parkinson's disease raised the hypothesis that α-synuclein, the main component of Lewy bodies, could be transmitted from the host brain to a graft of healthy neurons.", 'alpha-Synuclein, the main component of LBs, is expressed as two main isoforms (112 and 140), but little is known about their differential expression in the brain.', "In Parkinson's disease and Lewy body dementia, alpha-synuclein is the main component of Lewy bodies and dystrophic neurites; alpha-synuclein also accumulates in the cytoplasm of glial cells", "In Parkinson's disease, the inclusion bodies are referred to as Lewy bodies and their main component is alpha-synuclein", 'The main component of Lewy bodies is alpha-synuclein (AS)', "Specifically, identification of Lewy bodies in fetal mesencephalic neurons transplanted in patients with Parkinson's disease raised the hypothesis that α-synuclein, the main component of Lewy bodies, could be transmitted from the host brain to a graft of healthy neurons", 'alpha-Synuclein, the main component of LBs, is expressed as two main isoforms (112 and 140), but little is known about their differential expression in the brain', 'alpha-Synuclein and ubiquitin are two Lewy body protein components that may play antagonistic roles in the pathogenesis of Lewy bodies', 'Recently, the presynaptic protein alpha-synuclein was shown to be a major component of Lewy bodies and Lewy neurites', 'Alpha-synuclein (AS) is the main component of Lewy bodies and its aggregation is a key event in the pathogenesis of PD', 'The therapeutical potential of alpha-synuclein antiaggregatory agents for dementia with Lewy bodies.']

["Parkinson's disease (PD) is characterized by the progressive degeneration of substantia nigra pars compacta (SNpc) dopaminergic neurones and the formation of Lewy bodies (LB) in a proportion of the remaining neurones. Alpha-synuclein has been identified as the main component of the Lewy bodies.", 'The main component of Lewy bodies is alpha-synuclein.', 'Parkinson s disease (PD) is one of the most common neurodegenerative diseases. Majority of PD are sporadic, for which genetic causes remain largely unknown. Alpha-synuclein, the main component of Lewy bodies, plays a central role in the PD pathogenesis ']

['Alpha-synuclein']

List protein gel staining methods visualizing the entire protein set.

['DIGE requires the labelling of proteins by fluorochromes prior to their separation on 2DE gels. ', 'Stains-All (ISA) staining method for phosphoproteins in SDS-PAGE was described.', ' Pro-Q Diamond stain', 'Quantitative proteome analyses suggest that the well-established stain colloidal Coomassie Blue, when used as an infrared dye, may provide sensitive, post-electrophoretic in-gel protein detection that can rival even Sypro Ruby.', 'Several new fast staining protocols for the visualization of proteins separated by SDS-PAGE utilizing Coomassie Blue staining (CBS) have been described in literature. ', 'The CyDye family of fluorescent dyes is currently the overwhelming choice for applications in proteomic analysis, using two-dimensional difference gel electrophoresis (2D-DIGE)', 'his enables the co-detection of phosphoproteins as well as total proteins from the same gel and is accomplished by utilizing two different fluorescent stains, the ProQ-Diamond, which stains only phosphorylated proteins, and Sypro Ruby, which stains the entire subset of proteins.', 'Detection of the resulting protein maps relies on staining (i.e. colloidal coomassie blue (CCB) or SYPRO Ruby (SR), in addition to many others). Fluorescent in-gel protein stains are generally preferred for higher sensitivity, reduced background, and wider dynamic range.', 'Commonly used staining methods with excellent mass spectrometry compatibility are coomassie brilliant blue (CBB) or fluorescent dyes.', 'The typical concentration of protein loaded varies from 0.13 to 1.40 μg/μL for a classical silver staining method in 2DE gel', 'Silver staining is widely used to detect protein in polyacrylamide gels when high sensitivity is required.', 'Silver staining is used to detect proteins after electrophoretic separation on polyacrylamide gels']

['Several staining protocols for the visualization of proteins separated by SDS-PAGE have been described in literature: \nfluorescence\nSypro Ruby\nColloidal Coomassie Blue\nCoomassie Blue\nSilver staining\nCoomassie Brilliant Blue']

['fluorochromes', 'fluorescence', 'Sypro Ruby', 'Colloidal Coomassie Blue', 'Coomassie Blue', 'Silver staining', 'Coomassie Brilliant Blue']

Which is the main abnormality that arises with Sox9 locus duplication?

['Autosomal XX sex reversal caused by duplication of SOX9', 'Mutations of SOX9 leading to haploinsufficiency can cause campomelic dysplasia and XY sex reversal', 'We report here evidence supporting that SOX9 duplication can cause XX sex reversal', 'Fluorescent in situ hybridization (FISH) with a BAC clone containing the SOX9 gene demonstrated that the SOX9 gene is duplicated on the rearranged chromosome 17', 'SOX9 duplication linked to intersex in deer', 'Whole genome sequencing and quantitative real-time PCR analyses revealed a triple dose of the SOX9 gene, allowing insights into a new genetic defect in a wild animal', 'In addition, SOX9 duplication has been found to be a rare cause of 46,XX testicular DSD in humans', 'Extended pedigree with multiple cases of XX sex reversal in the absence of SRY and of a mutation at the SOX9 locus.', 'Together, these findings implicate a mutation at a sex-determining locus other than SRY and SOX9 as the cause for the XX sex reversal trait in this family.', 'Autosomal XX sex reversal caused by duplication of SOX9.', 'Sox9 duplications are a relevant cause of Sry-negative XX sex reversal dogs.', 'We report here evidence supporting that SOX9 duplication can cause XX sex reversal.', 'Mutations of SOX9 leading to haploinsufficiency can cause campomelic dysplasia and XY sex reversal.', 'Duplications of the locus DSS can lead to a failure of testicular development and a duplication of the region containing SOX9 has been implicated in XX sex reversal.', 'Extended pedigree with multiple cases of XX sex reversal in the absence of SRY and of a mutation at the SOX9 locus.', 'XX male sex reversal with genital abnormalities associated with a de novo SOX3 gene duplication.']

['The 46,XX testicular disorder of sex development (DSD), also known as 46,XX male syndrome, is a rare form of DSD and clinical phenotype shows complete sex reversal from female to male. A complex network of genes determines sex in mammals. Differentiation of testicular tissue in 46,XX individuals is seen either in XX males, the majority of them with SRY gene, or in individuals, usually SRY(-), with ovotesticular disorder of sex development (OT-DSD). SOX9 is one of the genes that play critical roles in male sexual differentiation.', 'Thus, SOX9 duplication is the most likely cause for the sex reversal in this case because it plays an important role in male sex determination and differentiation. The SRY-box 9 (SOX9) gene has several important functions during testis development and differentiation in males, and overexpression of SOX9 leads to the male development of 46,XX gonads in the absence of SRY.', 'Autosomal XX sex reversal caused by duplication of SOX9. Mutations of SOX9 leading to haploinsufficiency can cause campomelic dysplasia and XY sex reversal. We report here evidence supporting that SOX9 duplication can cause XX sex reversal. Fluorescent in situ hybridization (FISH) with a BAC clone containing the SOX9 gene demonstrated that the SOX9 gene is duplicated on the rearranged chromosome 17. SOX9 duplication linked to intersex in deer. ', 'SOX9 duplication can cause XX sex reversal. SOX9 duplication has been found to be a rare cause of 46,XX testicular DSD in humans.', 'Mutations of SOX9 leading to haploinsufficiency can cause campomelic dysplasia and XY sex reversal. In addition, SOX9 duplication has been found to be a rare cause of 46,XX testicular DSD in humans.', 'Autosomal XX sex reversal caused by duplication of SOX9']

['Autosomal XX sex reversal']

Do RNA:DNA hybrids preferentially form in high or low GC regions?

['Intrinsic termination signals for multisubunit bacterial RNA polymerases (RNAPs) encode a GC-rich stem-loop structure followed by a polyuridine [poly(U)] tract, and it has been proposed that steric clash of the stem-loop with the exit pore of the RNAP imposes a shearing force on the RNA in the downstream RNA:DNA hybrid, resulting in misalignment of the active site', "We have observed that transcription through the GC-rich FMR1 5'UTR region favors R-loop formation, with the nascent (G-rich) RNA forming a stable RNA:DNA hybrid with the template DNA strand, thereby displacing the non-template DNA strand.", 'Transcription termination by bacterial RNA polymerase (RNAP) occurs at sequences coding for a GC-rich RNA hairpin followed by a U-rich tract. We used single-molecule techniques to investigate the mechanism by which three representative terminators (his, t500, and tR2) destabilize the elongation complex (EC).', "In the 5' flanking region, nucleotides -234 to -213 encompass a GC-rich region which exhibits high homology (greater than 70%) to the 5' flanking regions of the genes of all the apolipoproteins published to date, namely, apo-A-II (-497 to -471), apo-A-I (approximately -196 to -179), apo-E (-409 to -391), and apo-C-III (approximately -116 to -103).", 'Recently, we demonstrated that cotranscriptional RNA•DNA hybrids are preferentially formed at GC-rich trinucleotide and tetranucleotide repeat sequences in vitro as well as in human genomic DNA.', 'Considering the extent of transcription through the human genome as well as the abundance of GC-rich and/or non-canonical DNA structure forming tandem repeats, RNA•DNA hybrids may represent a common mutagenic conformation.', 'Recently, we demonstrated that cotranscriptional RNA•DNA hybrids are preferentially formed at GC-rich trinucleotide and tetranucleotide repeat sequences in vitro as well as in human genomic DNA. ']

['Transcription through a GC-rich region favors R-loop formation, with the nascent (G-rich) RNA forming a stable RNA:DNA hybrid with the template DNA strand.']

['yes']

List Genes associated with adolescent idiopathic scoliosis

['Exome Sequencing Identifies a Rare HSPG2 Variant Associated with Familial Idiopathic Scoliosis.', 'Overall, these findings demonstrate a novel role for kif6 in spinal development and identify a new candidate gene for human idiopathic scoliosis.', 'HL1 is of interest, as it encodes an axon guidance protein related to Robo3. Mutations in the Robo3 protein cause horizontal gaze palsy with progressive scoliosis (HGPPS), a rare disease marked by severe scoliosis. Other top associations in our GWAS were with SNPs in the DSCAM gene encoding an axon guidance protein in the same structural class with Chl1 and Robo3.']

['Exome Sequencing Identifies a Rare HSPG2 Variant Associated with Familial Idiopathic Scoliosis.Overall, these findings demonstrate a novel role for kif6 in spinal development and identify a new candidate gene for human idiopathic scoliosis.', 'No genetic associations have yet been found to adolescent idiopathic scoliosis.']

['no associations found yet']

What is the reason for the narcolepsy cases developed after H1N1 influenza vaccination?

['The proposed mechanism for postvaccination narcolepsy is one in which an environmental trigger causes or enhances an antibody-mediated autoimmune response in patients with a preexisting genetic susceptibility. ', 'The loss of hypothalamic hypocretin/orexin (hcrt) producing neurons causes narcolepsy with cataplexy. An autoimmune basis for the disease has long been suspected and recent results have greatly strengthened this hypothesis. ', 'pointing towards processes such as molecular mimicry or bystander activation as crucial for disease development. ', 'Although no formal link can be established, the unusual characteristics of the reported cases and the striking temporal relationship suggests that narcolepsy may be the result of an autoimmune reaction triggered by H1N1\xa0vaccination in susceptible individuals.', 'Pandemrix vaccination is a precipitating factor for narcolepsy, especially in combination with HLA-DQB1*0602. ', 'Recently identified autoantibodies to Tribbles homologue 2 in some patients, as well as cases associated with H1N1 vaccination, support an autoimmune mechanism. ', 'n China, narcolepsy onset is highly correlated with seasonal and annual patterns of upper airway infections, including H1N1 influenza. In 2010, the peak seasonal onset of narcolepsy was phase delayed by 6 months relative to winter H1N1 infections, and the correlation was independent of H1N1 vaccination in the majority of the sample.', 'H1N1 vaccination was strongly associated with an increased risk of narcolepsy-cataplexy in both children and adults in France']

['The proposed mechanism for postvaccination narcolepsy is one in which an environmental trigger causes or enhances an antibody-mediated autoimmune response in patients with a preexisting genetic susceptibility.']

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What is the Timothy syndrome?

['A point mutation in the gene encoding Ca(V)1.2 causes Timothy syndrome, a neurodevelopmental disorder associated with autism spectrum disorders (ASDs).', 'o circumvent this issue, we have developed a method using human-induced pluripotent stem cells to generate cardiomyocytes from individuals with Timothy syndrome (TS), a genetic disorder characterized by QT prolongation, ventricular tachycardia, and autism.', 'Two de novo point mutations of Ca(v)1.2 glycine residues, G406R and G402S, cause a rare multisystem disorder called Timothy syndrome (TS).', 'Here, we discuss recent work on the mechanisms by which Ca(v)1.2 channels bearing TS mutations display slowed inactivation that leads to increased Ca(2+) influx, prolonging the cardiac AP and promoting lethal arrhythmias', 'Timothy syndrome is a human genetic disorder due to mutations in the Ca(V)1.2 gene.', 'Timothy syndrome (TS) is a disease caused by a gain-of-function mutation in the CaV1.2 channel (CaV1.2-TS) that decreases inactivation of the channel, which increases Ca(2+) influx, prolongs APs, and causes lethal arrhythmias. ', 'Recent reports suggest that parental mosaicism is involved in the heritability of type 1 Timothy syndrome (TS1), an extremely rare and life-threatening multisystem disorder characterized by severe QT interval prolongation, syndactyly, and several other complications. ', 'Timothy syndrome, long QT syndrome type 8, is highly malignant with ventricular tachyarrhythmia.', 'Timothy syndrome (TS) is a rare long-QT syndrome caused by CACNA1C mutations G406R in exon 8A (TS1) and G402S/G406R in exon 8 (TS2).', 'Timothy syndrome is caused by a missense mutation in the L-type calcium channel Ca(v)1.2 that is associated with developmental delay and autism.', 'Long QT, syndactyly, joint contractures, stroke and novel CACNA1C mutation: expanding the spectrum of Timothy syndrome.', 'Timothy syndrome (TS) is an autosomal dominant condition with the constellation of features including prolonged QT interval, hand and foot abnormalities, and mental retardation or autism.', 'Timothy syndrome type 1 (TS-1) is a rare disorder that affects multiple organ systems and has a high incidence of sudden death due to profound QT prolongation and resultant ventricular arrhythmias.', 'In some rare cases, such as Timothy syndrome (TS), a specific mutation in a single gene can be sufficient to generate autism or ASD in most patients, potentially offering insights into the etiology of autism in general. Both variants of TS (the milder TS1 and the more severe TS2) arise from missense mutations in alternatively spliced exons that cause the same G406R replacement in the Ca(V)1.2 L-type calcium channel.', 'A gain-of-function G406R mutation in a cytoplasmic loop of Ca(V)1.2 channels causes long QT syndrome 8 (LQT8), a disease also known as Timothy syndrome. ', 'A missense mutation in the L-type calcium channel Ca(V)1.2 leads to LQTS in patients with Timothy syndrome.', 'Timothy syndrome is a multisystem disorder characterized by cardiac, hand/foot, facial, and neurodevelopmental features. The two forms are type 1 (classic) and type 2, a rare form caused by mutations in a transcript variant of the same gene. Cardiac findings include a rate-corrected QT interval of between 480 ms and 700 ms and congenital heart defects (patent ductus arteriosus, patent foramen ovale, ventricular septal defect, tetralogy of Fallot, hypertrophic cardiomyopathy). Hand/foot findings are unilateral or bilateral cutaneous syndactyly variably involving fingers two (index), three (middle), four (ring), and five (little) and bilateral cutaneous syndactyly of toes two and three. Facial findings include flat nasal bridge, low-set ears, thin upper lip, and round face. Neuropsychiatric involvement includes global developmental delays and autism spectrum disorders. Ventricular tachyarrhythmia is the leading cause of death, followed by infection and complications of intractable hypoglycemia. Average age of death is 2.5 years. ', 'The gain-of-function mutations were found at two mutually exclusive exons in patients with Timothy syndrome (TS). These patients exhibit prolonged QT interval and lethal cardiac arrhythmias.', 'TS patients also suffer from multi-organ dysfunction that includes neurological disorder such as autism and mental retardation reflecting the wide tissue distribution of CaV1.2 channel.', 'Unexpectedly, TS patients may develop recurrent infections and bronchitis that suggests a role of CaV1.2 channel in the immune system.', 'Timothy syndrome (TS) is a disease of excessive cellular Ca(2+) entry and life-threatening arrhythmias caused by a mutation in the primary cardiac L-type Ca(2+) channel (Ca(V)1.2). The TS mutation causes loss of normal voltage-dependent inactivation of Ca(V)1.2 current (I(Ca)). During cellular Ca(2+) overload, the calmodulin-dependent protein kinase II (CaMKII) causes arrhythmias. ', 'Timothy syndrome is a multisystem disorder associated with the mutation of a Gly residue (G402 or G406) in the Ca(v)1.2 Ca(2+) channel. G406 is localized at the end of the IS6 segment and just before the intracellular I-II loop, which is important for the regulation of channel inactivation and the binding of the Ca(v)beta subunit.', 'Inactivation of Ca2+ channel activity is perturbed in a rare yet devastating disorder known as Timothy syndrome (TS), whose features include autism or autism spectrum disorder along with severe cardiac arrhythmia and developmental abnormalities. Most cases of TS arise from a sporadic single nucleotide change that generates a mutation (G406R) in the pore-forming subunit of the L-type Ca2+ channel Ca(V)1.2.', 'Timothy syndrome is a multisystem disorder associated with QT interval prolongation and ventricular cardiac arrhythmias. The syndrome has been linked to mutations in Ca(V)1.2 resulting in gain of function of the L-type calcium current (I(Ca,L)).']

['Timothy syndrome is a multisystem disorder characterized by cardiac, hand/foot, facial, and neurodevelopmental features. The two forms are type 1 (classic) and type 2, a rare form caused by mutations in a transcript variant of the same gene. Cardiac findings include a rate-corrected QT interval of between 480 ms and 700 ms and congenital heart defects (patent ductus arteriosus, patent foramen ovale, ventricular septal defect, tetralogy of Fallot, hypertrophic cardiomyopathy). Hand/foot findings are unilateral or bilateral cutaneous syndactyly variably involving fingers two (index), three (middle), four (ring), and five (little) and bilateral cutaneous syndactyly of toes two and three. Facial findings include flat nasal bridge, low-set ears, thin upper lip, and round face. Neuropsychiatric involvement includes global developmental delays and autism spectrum disorders. Ventricular tachyarrhythmia is the leading cause of death, followed by infection and complications of intractable hypoglycemia. Average age of death is 2.5 years.']

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What role does CRD-BP play in protecting c-myc mRNA?

['["CRD-BP shields c-myc and MDR-1 RNA from endonucleolytic attack by a mammalian endoribonuclease", "The c-myc mRNA coding region determinant-binding protein (CRD-BP) has high affinity for the coding region determinant (CRD) of c-myc mRNA. Such affinity is believed to protect c-myc CRD from endonucleolytic attack", " These results provide the first direct evidence that CRD-BP can indeed protect c-myc CRD cleavage initiated by an endoribonuclease", "CRD-BP: a c-Myc mRNA stabilizing protein with an oncofetal pattern of expression", "The Coding Region Determinant-Binding Protein (CRD-BP) is an RRM and KH-domain-containing protein that recognizes specifically at least three RNAs. It binds to one of the two c-myc mRNA instability elements", "CRD-BP has been assigned a role in stabilizing c-myc mRNA by preventing its endonucleolytic cleavage", "A 249-nucleotide coding region instability determinant (CRD) destabilizes c-myc mRNA. Previous experiments identified a CRD-binding protein (CRD-BP) that appears to protect the CRD from endonuclease cleavage", "These data suggest that c-myc mRNA is rapidly degraded unless it is (i) translated without pausing or (ii) protected by the CRD-BP when pausing occurs", "Here, we confirm that human CRD-BP/IMP-1 binds to c-myc mRNA", "The coding region determinant-binding protein (CRD-BP) binds in vitro to c-myc mRNA and is thought to stabilize the mRNA and increase c-Myc protein abundance", "Two regions within c- myc mRNA determine its short half-life. One is in the 3\'-untranslated region, the other is in the coding region. A cytoplasmic protein, the coding region determinant-binding protein (CRD-BP), binds in vitro to the c- myc coding region instability determinant. We have proposed that the CRD-BP, when bound to the mRNA, shields the mRNA from endonucleolytic attack and thereby prolongs the mRNA half-life", "Developmental regulation of CRD-BP, an RNA-binding protein that stabilizes c-myc mRNA in vitro", "We previously isolated and characterized a coding region determinant-binding protein (CRD-BP) that might regulate c-myc mRNA post-transcriptionally", "CRD-BP binds specifically to the coding region of c-myc mRNA and might stabilize c-myc mRNA in vitro by protecting it from endonucleolytic cleavage"]', '["CRD-BP shields c-myc and MDR-1 RNA from endonucleolytic attack by a mammalian endoribonuclease", "The c-myc mRNA coding region determinant-binding protein (CRD-BP) has high affinity for the coding region determinant (CRD) of c-myc mRNA. Such affinity is believed to protect c-myc CRD from endonucleolytic attack", " These results provide the first direct evidence that CRD-BP can indeed protect c-myc CRD cleavage initiated by an endoribonuclease", "CRD-BP: a c-Myc mRNA stabilizing protein with an oncofetal pattern of expression", "The Coding Region Determinant-Binding Protein (CRD-BP) is an RRM and KH-domain-containing protein that recognizes specifically at least three RNAs. It binds to one of the two c-myc mRNA instability elements", "CRD-BP has been assigned a role in stabilizing c-myc mRNA by preventing its endonucleolytic cleavage", "A 249-nucleotide coding region instability determinant (CRD) destabilizes c-myc mRNA. Previous experiments identified a CRD-binding protein (CRD-BP) that appears to protect the CRD from endonuclease cleavage", "These data suggest that c-myc mRNA is rapidly degraded unless it is (i) translated without pausing or (ii) protected by the CRD-BP when pausing occurs", "Here, we confirm that human CRD-BP/IMP-1 binds to c-myc mRNA", "The coding region determinant-binding protein (CRD-BP) binds in vitro to c-myc mRNA and is thought to stabilize the mRNA and increase c-Myc protein abundance", "Two regions within c- myc mRNA determine its short half-life. One is in the 3\'-untranslated region, the other is in the coding region. A cytoplasmic protein, the coding region determinant-binding protein (CRD-BP), binds in vitro to the c- myc coding region instability determinant. We have proposed that the CRD-BP, when bound to the mRNA, shields the mRNA from endonucleolytic attack and thereby prolongs the mRNA half-life", "Developmental regulation of CRD-BP, an RNA-binding protein that stabilizes c-myc mRNA in vitro", "We previously isolated and characterized a coding region determinant-binding protein (CRD-BP) that might regulate c-myc mRNA post-transcriptionally", "CRD-BP binds specifically to the coding region of c-myc mRNA and might stabilize c-myc mRNA in vitro by protecting it from endonucleolytic cleavage"]']

CRD-BP plays a role in protecting c-myc mRNA by preventing its endonucleolytic cleavage, shielding the mRNA from degradation and thereby stabilizing it.

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What is the role of Inn1 in cytokinesis?

['Inn1 and Cyk3 regulate chitin synthase during cytokinesis in budding yeasts', 'Our data support a model in which the C2-domain of Inn1 acts in conjunction with Cyk3 to regulate the catalytic domain of Chs2 during cytokinesis.', 'Cdc14-dependent dephosphorylation of Inn1 contributes to Inn1-Cyk3 complex formation', 'Cdc14 colocalizes with Inn1 at the cell division site and interacts with the C-terminal proline-rich domain of Inn1 that mediates its binding to the SH3-domain-containing proteins Hof1 and Cyk3. We show that phosphorylation of Inn1 by Cdk1 partially perturbs the interaction of Inn1 with Cyk3 thereby reducing the levels of Cyk3 at the cell division site. We propose that Cdc14 counteracts Cdk1 phosphorylation of Inn1 to facilitate Inn1-Cyk3 complex formation and so promote cytokinesis', 'Targeted localization of Inn1, Cyk3 and Chs2 by the mitotic-exit network regulates cytokinesis in budding yeast', 'Cyk3 acts in actomyosin ring independent cytokinesis by recruiting Inn1 to the yeast bud neck', 'Role of Inn1 and its interactions with Hof1 and Cyk3 in promoting cleavage furrow and septum formation in S. cerevisiae', 'we identified a novel factor that we call Inn1, which associates with the contractile actomyosin ring at the end of mitosis and is needed for cytokinesis. We show that Inn1 has a C2 domain at the amino terminus of the protein that is required for ingression of the plasma membrane, whereas the remainder of the protein recruits Inn1 to the actomyosin ring', ' Our data indicate that recruitment of the C2 domain of Inn1 to the contractile actomyosin ring is crucial for ingression of the plasma membrane during cytokinesis in budding yeast', 'We previously found that the C2-domain of the Saccharomyces cerevisiae Inn1 protein plays an essential but uncharacterised role at the cleavage site during cytokinesis.', 'We propose that Cdc14 counteracts Cdk1 phosphorylation of Inn1 to facilitate Inn1-Cyk3 complex formation and so promote cytokinesis.', 'Inn1 and Cyk3 regulate chitin synthase during cytokinesis in budding yeasts.', 'Cyk3 acts in actomyosin ring independent cytokinesis by recruiting Inn1 to the yeast bud neck.', 'Inn1 couples contraction of the actomyosin ring to membrane ingression during cytokinesis in budding yeast.', 'Targeted localization of Inn1, Cyk3 and Chs2 by the mitotic-exit network regulates cytokinesis in budding yeast.', 'We therefore propose that the MEN directly controls cytokinesis via targeting of Inn1, Cyk3 and Chs2 to the bud neck.', 'Our data support a model in which the C2-domain of Inn1 acts in conjunction with Cyk3 to regulate the catalytic domain of Chs2 during cytokinesis.', 'In addition to compensating for mutations in the Inn1 C2-domain, the dominant CHS2 alleles suppress cytokinesis defects produced by the lack of the Cyk3 protein.', 'We propose that Cyk3 is part of an actomyosin ring independent cytokinesis pathway, which acts as a rescue mechanism to recruit Inn1 to the bud neck.', 'We previously found that the C2-domain of the Saccharomyces cerevisiae Inn1 protein plays an essential but uncharacterised role at the cleavage site during cytokinesis.', 'We propose that Cyk3 is part of an actomyosin ring independent cytokinesis pathway, which acts as a rescue mechanism to recruit Inn1 to the bud neck.', 'The Inn1 C-terminal region is necessary for localization, and distinct PXXP motifs in this region mediate functionally important interactions with SH3 domains in the cytokinesis proteins Hof1 (an F-BAR protein) and Cyk3 (whose overexpression can restore PS formation in inn1Delta cells).', 'Role of Inn1 and its interactions with Hof1 and Cyk3 in promoting cleavage furrow and septum formation in S. cerevisiae.', 'We propose that Cdc14 counteracts Cdk1 phosphorylation of Inn1 to facilitate Inn1-Cyk3 complex formation and so promote cytokinesis.']

['Inn1 associates with the contractile actomyosin ring at the end of mitosis and is needed for cytokinesis. Inn1 has a C2 domain at the amino terminus of the protein that is required for ingression of the plasma membrane during cytokinesis in budding yeast, whereas the remainder of the protein recruits Inn1 to the actomyosin ring']

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Is there any evidence of dysregulated long non coding RNAs and Alzheimer's disease?

["lncRNAs in central nervous system (CNS) development and neurodegenerative diseases, including Alzheimer's disease (AD)", "(lncRNA) within mRNA sequences of Alzheimer's disease genes, namely, APP, APOE, PSEN1, and PSEN2", "sortilin-related receptor 1 (SORL1) is a risk gene for late-onset Alzheimer's disease (AD)", 'non-coding (nc) RNA (hereafter referred to as 51A) that maps in antisense configuration to intron 1 of the SORL1 gene', 'novel GDNF isoforms and cis-antisense GDNFOS gene and their regulation in human middle temporal gyrus of Alzheimer disease', 'GDNFOS gene has four exons that are spliced into different isoforms. GDNFOS1 and GDNFOS2 are long noncoding RNA', 'In the MTG of AD patients, the mature GDNF peptide was down-regulated; however, the transcript of GDNF isoform from human exon 2 was up-regulated', 'The findings of novel GDNF and GDNFOS isoforms and differences in tissue expression patterns dysregulated in AD brains ', 'novel non-coding (nc) RNA (named 17A) RNA polymerase (pol) III-dependent embedded in the human G-protein-coupled receptor 51 gene (GPR51, GABA B2 receptor)', '17A is expressed in human brain, and we report that it is upregulated in cerebral tissues derived from Alzheimer disease patients', "Here we identify a conserved noncoding antisense transcript for beta-secretase-1 (BACE1), a crucial enzyme in Alzheimer's disease pathophysiology.", 'the genotype of this SNP shows different distribution in normal elders, mild cognitive impairment, and Alzheimer disease subjects, suggesting that this lincRNA may have a role in physiology and pathophysiology of human brain']

['It is becoming increasingly evident that long non coding RNAs (lncRNAs) play a role on neurodegenerative diseases such as Alzheimer (AD). BACE1-AS, GDNFOS and 17A are examples of these lncRNAs. In some instances those lncRNAs are embedded or transcribed from the opposite strand of coding genes.']

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Is infertility characteristic of individuals with Fanconi anemia?

['PALB2 links BRCA1 and BRCA2 in homologous recombinational repair of DNA double strand breaks (DSBs). Mono-allelic mutations in PALB2 increase the risk of breast, pancreatic, and other cancers, and biallelic mutations cause Fanconi anemia (FA). ', 'Moreover, mutant males showed reduced fertility due to impaired meiosis and increased apoptosis in germ cells. Interestingly, mutant meiocytes showed a significant defect in sex chromosome synapsis, which likely contributed to the germ cell loss and fertility defect.', 'In females with Fanconi anemia (FA), infertility is often accompanied by diminished ovarian reserve and hypergonadotropic amenorrhea before the age of 30 years, suggesting primary ovarian insufficiency (POI).', 'Substantially reduced AMH levels in females with FA suggest a primary ovarian defect associated with reduced fertility. Measurement of AMH at the time of FA diagnosis and subsequent monitoring of AMH levels at regular intervals may be useful for the timely management of complications related to POI such as subfertility/infertility, osteoporosis, and menopausal symptoms.', 'Fanconi anemia (FA) is a human disease of bone marrow failure, leukemia, squamous cell carcinoma, and developmental anomalies, including hypogonadism and infertility. ', 'Reduced fertility is one clinical manifestation among other well known Fanconi anemia features. ', 'Fanconi anemia (FA) is a human disease of bone marrow failure, leukemia, squamous cell carcinoma, and developmental anomalies, including hypogonadism and infertility', 'Targeted disruption of exons 1 to 6 of the Fanconi Anemia group A gene leads to growth retardation, strain-specific microphthalmia, meiotic defects and primordial germ cell hypoplasia.', 'Fanconi anemia (FA) is a human disease of bone marrow failure, leukemia, squamous cell carcinoma, and developmental anomalies, including hypogonadism and infertility.', 'To potentially reduce late effects of malignancy, chronic graft-versus-host disease (GVHD), endocrinopathy, and infertility in patients with Fanconi anemia (FA) undergoing HLA-matched related donor hematopoietic cell transplantation (HCT), we developed a regimen using fludarabine (FLU), cyclophosphamide (CY), and anti-thymocyte globulin (ATG) followed by infusion of T-cell depleted (TCD) bone marrow (BM) or unmanipulated umbilical cord blood (UCB).', 'Mutations in Fanca account for the majority of cases of Fanconi anemia (FA), a recessively inherited disease identified by congenital defects, bone marrow failure, infertility, and cancer susceptibility.', 'FANCA is mutated in more than 60% of cases of Fanconi anemia (FA), a rare genetically heterogeneous autosomal recessive disorder characterized by bone marrow failure, endocrine tissue cancer susceptibility, and infertility.', 'In females with Fanconi anemia (FA), infertility is often accompanied by diminished ovarian reserve and hypergonadotropic amenorrhea before the age of 30 years, suggesting primary ovarian insufficiency (POI).', 'Fanconi anemia (FA) is a complex cancer susceptibility disorder associated with DNA repair defects and infertility, yet the precise function of the FA proteins in genome maintenance remains unclear.', 'Fanconi anemia (FA) is a genetic disease resulting in bone marrow failure, high cancer risks, and infertility, and developmental anomalies including microphthalmia, microcephaly, hypoplastic radius and thumb.']

['Yes, infertility is characteristic of individuals with Fanconi anemia.']

['yes']

What is the association between h-index and academic rank in academic neurosurgery?

[' The contemporary h-index was found to be significantly predictive of NIH funding (p<0.001). ', 'Bibliometric indices are higher for those with NIH funding compared to those without, but only the contemporary h-index was shown to be predictive of NIH funding. ', 'However, when stratified by academic rank, a trend was observed showing greater mean h-index scores for those who completed fellowships. ', 'Overall, being a senior faculty member corresponds with a greater h-index score, regardless of whether a fellowship was completed.', 'There was a positive association between the h-index, academic rank, and years posttraining.', 'Application of the h-index as a bibliometric in neurosurgery can distinguish academic productivity on the basis of academic rank, years posttraining, and neurosurgical subspecialties. ', "Overall, the authors conclude that the h index metric is a reasonable measure of academic productivity in the pediatric neurosurgery arena that provides a robust measure of an individual's contribution to the pediatric neurosurgery literature. ", 'The h index calculation also reveals the productivity of the pediatric neurosurgeons to be on par with the productivity of neurosurgeons in general.', 'The h-index frequency distribution conformed to both the log-linear variation of a power law (r (2)\u2009=\u2009.99) and the beta distribution with the same fitting exponents as previously described in a power law analysis of the productivity of neurosurgeons. ', 'The h indices increased significantly with increasing academic rank, with the median for instructors, assistant professors, associate professors, and professors being 2, 5, 10, and 19, respectively (p < 0.0001, Kruskal-Wallis; all groups significantly different from each other except the difference between instructor and assistant professor [Conover]). Departmental chairs had a median h index of 22 (range 3-55) and program directors a median of 17 (range 0-62). Plot of the log of the rank versus h index demonstrated a remarkable linear pattern (R(2) = 0.995, p < 0.0001), suggesting that this is a power-law relationship.', 'The distribution of the h index within an academic population is described for the first time and appears related to the ubiquitous power-law distribution.', 'As expected, the h index increased with academic rank and there was a statistically significant difference between each rank. ', 'Within the field of academic neurosurgery, clear differences of h indices between academic ranks exist. On average, an increase of the h index by 5 appears to correspond to the next highest academic rank, with the exception of chairperson.', 'Scopus h-index was of borderline significance in predicting physician salary (P = 0.12). ']

['Greater h-index is associated with greater academic rank in academic neurosurgery. The h indices increased significantly with increasing academic rank, with the median for instructors, assistant professors, associate professors, and professors was shown to be 2, 5, 10, and 19, respectively. In addition, h-index was shown to be predictive of NIH funding, fellowship training, academic productivity and salary.']

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Is siltuximab effective for Castleman disease?

['Siltuximab: a targeted therapy for idiopathic multicentric Castleman disease.', 'The recent approvals in North America, Europe and Brazil of siltuximab, a monoclonal antibody against IL-6, for iMCD now provide a safe and effective therapy that targets a key aspect of pathogenesis. In the first ever randomized, placebo-controlled trial in iMCD, siltuximab significantly reduced disease burden and symptoms in a large portion (34%) of patients.', 'Despite recent significant advances in our understanding of this disease and the increasing therapeutic experience with rituximab, tocilizumab and siltuximab, there are still difficult questions concerning its aetiology, prognosis and optimal treatment.', 'Emerging treatments in Castleman disease - a critical appraisal of siltuximab.', ' Siltuximab, a chimeric monoclonal antibody to IL-6, has thus emerged as a promising treatment option in a disease lacking efficacious therapy. Here, we review the findings of recent studies evaluating single-agent siltuximab treatment in CD, including the first-ever randomized clinical trial in this disease. Although much more work is needed to establish a standardized treatment approach, siltuximab appears to be a safe and effective treatment for patients with newly diagnosed and previously treated CD.', 'FDA approval: siltuximab for the treatment of patients with multicentric Castleman disease.', 'On April 22, 2014, the FDA granted full approval to siltuximab (SYLVANT for injection; Janssen Biotech, Inc.), a chimeric human-mouse monoclonal antibody to IL6, for the treatment of patients with multicentric Castleman disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative. ', '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). ', '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 for multicentric Castleman disease.', 'Siltuximab: A Review in Idiopathic (Human Herpesvirus-8-Negative) Multicentric Castleman Disease.', 'Siltuximab (IL6 antibody) is approved for the treatment of multicentric Castleman disease (MCD).', 'A phase 2, open-label, multicenter study of the long-term safety of siltuximab (an anti-interleukin-6 monoclonal antibody) in patients with multicentric Castleman disease.', 'A phase I, open-label study of siltuximab, an anti-IL-6 monoclonal antibody, in patients with B-cell non-Hodgkin lymphoma, multiple myeloma, or Castleman disease.', 'Analysis of Inflammatory and Anemia-Related Biomarkers in a Randomized, Double-Blind, Placebo-Controlled Study of Siltuximab (Anti-IL6 Monoclonal Antibody) in Patients With Multicentric Castleman Disease.', "Siltuximab (Sylvant). Castleman's disease: good symptomatic efficacy in some patients.", "Siltuximab: a new option for the management of Castleman's disease.", "Siltuximab, a novel anti-interleukin-6 monoclonal antibody, for Castleman's disease.", 'PURPOSE: To evaluate the safety and pharmacokinetics of siltuximab, an anti-interleukin-6 chimeric monoclonal antibody (mAb) in patients with B-cell non-Hodgkin lymphoma (NHL), multiple myeloma, or Castleman disease.EXPERIMENTAL DESIGN: In an open-label, dose-finding, 7 cohort, phase I study, patients with NHL, multiple myeloma, or symptomatic Castleman disease received siltuximab 3, 6, 9, or 12 mg/kg weekly, every 2 weeks, or every 3 weeks.', "Dose selection of siltuximab for multicentric Castleman's disease.", "Here, modeling and simulation of the pharmacokinetic (PK)/pharmacodynamic (PD) relationship between siltuximab and CRP were used to support dose selection for multicentric Castleman's disease (CD).METHODS: PK/PD modeling was applied to explore the relationship between siltuximab PK and CRP suppression following intravenous siltuximab infusion in 47 patients with B cell non-Hodgkin's lymphoma (n\xa0=\xa017), multiple myeloma (n\xa0=\xa013), or CD (n\xa0=\xa017).", '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)', 'Three (6%) of 53 patients had serious adverse events judged reasonably related to siltuximab (lower respiratory tract infection, anaphylactic reaction, sepsis).Siltuximab plus best supportive care was superior to best supportive care alone for patients with symptomatic multicentric Castlemans disease and well tolerated with prolonged exposure', 'Siltuximab, an anti-IL-6 monoclonal antibody, has demonstrated durable tumor and symptomatic responses in a multinational, randomized, placebo-controlled study of MCD.This preplanned safety analysis was conducted to evaluate the long-term safety of siltuximab treatment among 19 patients with MCD who had stable disease or better and were enrolled in a phase-1 study and subsequent ongoing, open-label, phase-2 extension study', 'Analysis of Inflammatory and Anemia-Related Biomarkers in a Randomized, Double-Blind, Placebo-Controlled Study of Siltuximab (Anti-IL6 Monoclonal Antibody) in Patients With Multicentric Castleman Disease', 'Siltuximab (IL6 antibody) is approved for the treatment of multicentric Castleman disease (MCD)', 'Siltuximab for multicentric Castleman disease', 'FDA approval: siltuximab for the treatment of patients with multicentric Castleman disease', 'On April 22, 2014, the FDA granted full approval to siltuximab (SYLVANT for injection; Janssen Biotech, Inc.), a chimeric human-mouse monoclonal antibody to IL6, for the treatment of patients with multicentric Castleman disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative', "Siltuximab for multicentric Castleman's disease: a randomised, double-blind, placebo-controlled trial.", 'EXPERIMENTAL DESIGN: In an open-label, dose-finding, 7 cohort, phase I study, patients with NHL, multiple myeloma, or symptomatic Castleman disease received siltuximab 3, 6, 9, or 12 mg/kg weekly, every 2 weeks, or every 3 weeks. ', '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).', 'To evaluate the safety and pharmacokinetics of siltuximab, an anti-interleukin-6 chimeric monoclonal antibody (mAb) in patients with B-cell non-Hodgkin lymphoma (NHL), multiple myeloma, or Castleman disease.In an open-label, dose-finding, 7 cohort, phase I study, patients with NHL, multiple myeloma, or symptomatic Castleman disease received siltuximab 3, 6, 9, or 12 mg/kg weekly, every 2 weeks, or every 3 weeks.', 'On April 22, 2014, the FDA granted full approval to siltuximab (SYLVANT for injection; Janssen Biotech, Inc.), a chimeric human-mouse monoclonal antibody to IL6, for the treatment of patients with multicentric Castleman disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative.', 'Clinical benefit response (CBR; composite of hemoglobin, fatigue, anorexia, fever/night sweats, weight, largest lymph node size) was also evaluated in Castleman disease.Sixty-seven patients received a median of 16 siltuximab doses for a median of 8.5 (maximum 60.5) months; 29 were treated 1 year or longer.', 'The recent approvals in North America, Europe and Brazil of siltuximab, a monoclonal antibody against IL-6, for iMCD now provide a safe and effective therapy that targets a key aspect of pathogenesis.', 'Although much more work is needed to establish a standardized treatment approach, siltuximab appears to be a safe and effective treatment for patients with newly diagnosed and previously treated CD.', 'No dose-limiting toxicity was reported, and only three patients had grade 3 or higher adverse events after a median exposure of 331 days (range, 1 to 1,148 days).These interim results strongly suggest that siltuximab is an effective treatment with favorable safety for the management of CD.', 'Siltuximab is a new anti-IL-6, chimeric monoclonal antibody with potential therapeutic benefit in patients with CD.METHODS: We report interim results from an open-label, dose-finding, seven-cohort, phase I study in which patients with symptomatic, multicentric or unresectable, unicentric CD received siltuximab at 1-, 2-, or 3-week intervals.', 'Siltuximab for multicentric Castleman disease.', 'Siltuximab: a targeted therapy for idiopathic multicentric Castleman disease.', 'Emerging treatments in Castleman disease - a critical appraisal of siltuximab.', "Siltuximab (Sylvant). Castleman's disease: good symptomatic efficacy in some patients.", "Siltuximab: a new option for the management of Castleman's disease.", "Siltuximab for multicentric Castleman's disease: a randomised, double-blind, placebo-controlled trial.", 'Siltuximab: A Review in Idiopathic (Human Herpesvirus-8-Negative) Multicentric Castleman Disease.']

['Yes, siltuximab , a chimeric human-mouse monoclonal antibody to IL6, is approved for the treatment of patients with multicentric Castleman disease who are human immunodeficiency virus negative and human herpesvirus-8 negative.']

['yes']

List FDA approved treatments for androgenetic allopecia

['Topical minoxidil 2%-5% 1 mL twice daily or finasteride 1 mg daily are recommended as first line treatments, followed by the use of Food and Drug Administration-cleared HairMax LaserComb® in patients who do not respond to first line modalities.', 'Recently, in addition to the two currently approved U.S. Food and Drug Administration (FDA) medications (minoxidil and finasteride), a novel device was FDA-approved for the treatment of hair loss, the laser hair comb.', 'In addition, low-level light therapy (LLLT) has recently been approved by the United States Food and Drug Administration (FDA) for the treatment of hair loss. ', 'Currently there are two U.S. Food and Drug Administration (FDA)-approved agents that promote hair regrowth: over-the-counter topical minoxidil solution for men and women and prescription oral finasteride tablets for men. ', 'Topical monoxidil and oral finasteride are commonly in use and have FDA approval for the treatment of male androgenetic alopecia; dutasteride, a type I and II 5-alpha-reductase inhibitor, is on hold in Phase III trials.', 'The only FDA-approved dermatological indication of finasteride is androgenetic alopecia.', 'Finasteride (Propecia) was approved by the FDA in 1998 for treating men with androgenetic alopecia.']

['Recently, in addition to the two currently approved U.S. Food and Drug Administration (FDA) medications (minoxidil and finasteride), a novel device was FDA-approved for the treatment of hair loss, the laser hair comb.']

['Minoxidil', 'Finasteride', 'Laser hair comb']

Is cadasil syndrome a hereditary disease?

[' CADASIL is the most frequent hereditary small-vessel disease of the brain. The clinical impact of various MR imaging markers has been repeatedly studied in this disorder, but alterations of contrast between gray matter and normal-appearing white matter remain unknown. The aim of this study was to evaluate the contrast alterations between gray matter and normal-appearing white matter on T1-weighted images in patients with CADASIL compared with healthy subjects', ' (CADASIL) is the most common form of hereditary cerebral angiopathy', 'Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral small vessel disease, clinically characterized by migraine, recurrent transient ischemic attacks or strokes, psychiatric disorders and cognitive decline. Strokes are typically ischemic, while hemorrhagic events have been only sporadically described', 'Mutations in the TREX1 and NOTCH3 genes cause retinal vasculopathy with cerebral leukodystrophy (RVCL) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), respectively', 'We used immunohistochemistry and immunogold electron microscopy (EM) to examine the distribution of GOM and NOTCH3 ectodomain (N3ECD) protein in microvasculature of brain gray matter and white matter in patients with CADASIL, non-CADASIL hereditary small-vessel disease and sporadic age-related degenerative disease, and comparable-age controls']

['Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral small vessel disease, clinically characterized by migraine, recurrent transient ischemic attacks or strokes, psychiatric disorders and cognitive decline. Strokes are typically ischemic, while hemorrhagic events have been only sporadically described. CADASIL is the most common form of hereditary cerebral angiopathy.']

['yes']

How does Apolipoprotein E4 contribute to the risk of cognitive decline and late onset Alzheimer's disease?

['["Apolipoprotein E4 (E4) and type 2 diabetes are major risk factors for cognitive decline and late onset Alzheimer\'s disease (AD)", "Cardiovascular risk factors, especially hypertension, are also major risk factors for Alzheimer\'s disease (AD).", "Clusterin (Apo J) is one of the major risk factors for sporadic form of AD. ", "Hypertension is one of the major risk factors for central nervous system (CNS) disorders like stroke and Alzheimer\'s disease (AD).", "Major risk factors for AD are advancing age and diabetes. Lately, obesity has been associated with an increased risk of dementia."]']

Apolipoprotein E4 (E4) is a major risk factor for cognitive decline and late onset Alzheimer's disease (AD).

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What are the clinical trial outcomes of metformin use in polycystic ovary disease?

['It has been demonstrated that by reducing hyperinsulinemia, in particular with the administration of metformin, insulin-lowering agents might improve endocrine and reproductive abnormalities in PCOS patients.', 'Metformin has failed to gain wide acceptance as a first-line treatment option for women with anovulatory infertility related to polycystic ovary syndrome. This study aimed to ascertain factors that predict fertility success with treatment that included metformin compared to standard (non-metformin) treatment. METHODS: Randomised trial data analysis by logistic regression of factors likely to have a differential influence on the likelihood of success of metformin versus non-metformin treatment amongst women with ovulation dysfunction related to polycystic ovary syndrome. RESULTS: metformin versus those receiving placebo and those with lower BMI who received metformin were more likely to become pregnant than their lower BMI counterparts who received placebo (P=0.039).', 'This study provides preliminary evidence that BMI may be an important prognostic factor in response to metformin for women with ovulation dysfunction related to polycystic ovary syndrome, suggesting that women with a lower BMI may respond better to metformin treatment versus placebo amongst women with BMI>32 kg/m(2)', 'A prospective comparative study including 63 patients with PCOS has been done during 2 years. Women were randomly allocated to clomifene + Metformin (Metformin group, Metformin took during 8 weeks, 850 mg twice a day, plus Clomifene 100 mg per day during five days) or Clomifene only (100 mg per day during five days)', 'Our conclusion is that Metformin is an effective addition to Clomifene Citrate in term of reestablishment of ovulation and full-term pregnancies achievement, excluding ART cycles.', 'A prospective, randomized, double-blind 26 week long study was undertaken in 50 women with PCOS. They all received diet and lifestyle counselling, and metformin 850 mg three times daily.', 'nti-Müllerian hormone (AMH) levels reflect the number of small antral follicles in the ovaries and are elevated in PCOS.', 'Six months of androgen suppression by either metformin or low-dose dexamethasone treatment failed to influence circulating AMH levels.', 'The effect of metformin on serum AMH concentrations, follicle number and ovarian volume was studied in 26 women (aged 20-41 years) with PCOS after 6 months of treatment', 'Serum AMH levels, the number of antral follicles and ovarian volume decreased significantly during metfromin treatment.', 'Metformin treatment before IVF/ICSI in women with polycystic ovary syndrome; a prospective, randomized, double blind study.', 'investigate the effect of pre-treatment with metformin in women with polycystic ovary syndrome (PCOS) scheduled for IVF stimulation.', 'Pre-treatment with metformin prior to conventional IVF/ICSI in women with PCOS does not improve stimulation or clinical outcome. However, among normal weight PCOS women, pre-treatment with metformin tends to improve pregnancy rates.', 'Treatment of 10 insulin-resistant PCOS women with metformin significantly increased circulating fasting ghrelin concentrations', 'double-blind, placebo-controlled approach with detailed assessment of ovarian activity', 'The effect of metformin on follicular maturation was rapid, because the E2 circulating concentration increased over the first week of treatment only in the metformin group. Significant (P < 0.01) weight loss (and leptin reduction) was recorded in the metformin group, whereas the placebo group actually increased weight (P < 0.05). A significant increase in circulating high-density lipoprotein was observed only in the metformin-treated group. Metabolic risk factor benefits of metformin treatment were not observed in the morbidly obese subgroup of patients (body mass index > 37). No change in fasting glucose concentrations, fasting insulin, or insulin responses to glucose challenge was recorded after 14-wk metformin or placebo therapy.', 'We show in a large randomized placebo-controlled trial that metformin treatment improves ovulation frequency in women with abnormal ovarian function and polycystic ovaries significantly but to a modest degree, and protracted treatment improves cardiovascular risk factors. These data support a beneficial effect of metformin in improving ovarian function in women with oligomenorrhea and polycystic ovaries.', 'studies evaluating metformin treatment in women with clomiphene citrate (CC)-resistant polycystic ovaries (PCO)', 'There was no improvement in the ovulation rate despite a significant reduction of body mass index, serum testosterone and fasting leptin concentrations in the metformin group.']

['Metformin treatment vs placebo significantly but modestly improves ovulation frequency in women with abnormal ovarian function/oligomenorrhea and polycystic ovaries, the lower BMI women were more likely to become pregnant. While in naturally conceiving normal weight PCOS women pre-treatment with metformin tends to improve pregnancy rates, pre-treatment with metformin prior to conventional IVF/ICSI in women with PCOS does not improve stimulation or clinical outcome.\nMetformin is an effective addition to Clomifene Citrate in term of reestablishment of ovulation and full-term pregnancies achievement.\nStudies on the effect of metformin on serum Anti-Mullerian Hormone levels /AMH concentrations bring conflicting results, from Metformin having no effect on AMH to Metformin treatment resulting in significant decrease of AMH levels, antral follicle numbers and ovarian volume. \nMetformin has been shown to cause significant weight loss (and leptin reduction) in PCOS.']

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Which is the prognostic impact of hypothyroidism in patients with acute myocardial infarction?

['In-hospital cardiogenic shock (15% vs 3% in the control group; p<0.01) and death (7% vs 1% in the control group; p<0.01) were more frequently observed in the thyroid dysfunction group. ', 'Thyroid dysfunction, particularly sick euthyroid syndrome, was found to be related to in-hospital and long term mortality in patients with STEMI undergoing primary percutaneous intervention.', 'A low fT3 level, a common phenomenon in patients with acute myocardial infarctions, is a strong predictor of short-term and long-term poor prognoses in patients with acute myocardial infarctions.', 'Troponin T and creatine kinase-B with an M-type subunit levels were significantly higher in the nonsurvivors when compared with survivors. Survivors in the AMI group had higher TT3, TT4, and lower FT4 levels, while the nonsurvivors in the AMI group had higher thyrotrophin and lower TT3, FT3 and FT4 levels than controls.', 'Reverse T3 levels >0.41 nmol/L were associated with an increased risk of 1-year mortality (hazard ratio = 3.0; 95% confidence interval: 1.4 to 6.3; P = 0.005), independent of age, previous myocardial infarction, prior angina, heart failure, serum creatinine level, and peak serum creatine kinase-MB fraction levels.']

['Thyroid dysfunction, particularly low T3 syndrome, is a strong predictor of short-term and long-term poor prognoses in patients with acute myocardial infarctions.']

['Low T3 Syndrome isassociatedwithpoor prognosis in patients with acute myocardial infarction']

What molecule is targeted by 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. ', '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. ', 'Crystal structure of the human OX2 orexin receptor bound to the insomnia drug suvorexant.', ' The human OX2 receptor (OX2R) belongs to the β 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. ', 'Orexin receptor antagonism for treatment of insomnia: a randomized clinical trial of suvorexant.', 'Promotion of sleep by suvorexant-a novel dual orexin receptor antagonist.', 'The neurotransmitter systems on which the development of these agents were based included serotonin for ondansetron and lorcaserin, dopamine for varenicline, substance P (or neurokinin) for aprepitant, melatonin for ramelteon, and orexin for suvorexant. The indications were chemotherapy-induced nausea and vomiting for ondansetron and aprepitant, smoking cessation for varenicline, weight loss for lorcaserin, and insomnia for suvorexant and ramelteon.', 'Suvorexant, a dual orexin receptor antagonist for the management of insomnia.', 'Suvorexant, a dual orexin receptor antagonist for the management of insomnia.', 'The orexin-1 and orexin-2 receptors are two G protein-coupled receptors that bind the neuropeptides orexin-A and orexin-B. Dual antagonism of the receptors by small molecules is clinically efficacious in the treatment of insomnia, where the most advanced molecule suvorexant has recently been approved.', 'Suvorexant helps in decreasing wakefulness by counteracting orexin activity.', ' The orexin-1 and orexin-2 receptors are two G protein-coupled receptors that bind the neuropeptides orexin-A and orexin-B. Dual antagonism of the receptors by small molecules is clinically efficacious in the treatment of insomnia, where the most advanced molecule suvorexant has recently been approved.', 'Hypnotic drug development has arguably become more focused in recent years, particularly upon the highly anticipated novel target, the orexin (hypocretin) system. Merck&apos;s suvorexant (MK-4305) is the first compound of the so-called dual orexin receptor antagonist (DORA) class expected to be submitted for FDA approval, with a new drug application anticipated in 2012.']

['Suvorexant is a dual orexin receptor antagonist for the treatment of sleep onset and sleep maintenance insomnia.']

['orexin']

How does Twinkle protein impact DNA stability near human mitochondrial DNA deletion breakpoints?

['["n this work, we performed a computational analysis of the human mitochondrial genome using the \\"Pattern Finder\\" G-quadruplex (G4) predictor algorithm to assess whether G4-forming sequences reside in close proximity (within 20 base pairs) to known mitochondrial DNA deletion breakpoints.", "Circular dichroism and UV spectral analysis demonstrated that mitochondrial G-rich sequences near deletion breakpoints prevalent in human disease form G-quadruplex DNA structures.", "Direct repeat sequences are not required at the breakpoints of age-associated mitochondrial DNA deletions in rhesus monkeys.", "Most of the analyzed deletion breakpoints showed nucleotide repeats flanking the deletions. ", "Currently, the multiple types of GQ sequences and their association with human mtDNA stability are unknown.<br><b>RESULTS</b>: Here, we show an association between human mtDNA deletion breakpoint locations (sites where DNA ends rejoin after deletion of a section) and sequences with G-quadruplex forming potential (QFP), and establish the ability of selected sequences to form GQ in vitro.", "A biochemical analysis of purified recombinant human Twinkle protein (gene product of c10orf2) showed that the mitochondrial replicative helicase inefficiently unwinds well characterized intermolecular and intramolecular G-quadruplex DNA substrates, as well as a unimolecular G4 substrate derived from a mitochondrial sequence that nests a deletion breakpoint described in human renal cell carcinoma.", "DNA sequences proximal to human mitochondrial DNA deletion breakpoints prevalent in human disease form G-quadruplexes, a class of DNA structures inefficiently unwound by the mitochondrial replicative Twinkle helicase.", "Association of G-quadruplex forming sequences with human mtDNA deletion breakpoints."]']

The Twinkle protein impacts DNA stability near human mitochondrial DNA deletion breakpoints by inefficiently unwinding G-quadruplex DNA structures formed by sequences proximal to the deletion breakpoints. This inefficient unwinding is observed for intermolecular, intramolecular, and unimolecular G4 substrates derived from mitochondrial sequences near deletion breakpoints.

[]

How many different mutations have been associated with Muenke syndrome?

['Muenke syndrome is an autosomal dominant craniosynostosis syndrome resulting from a defining point mutation in the Fibroblast Growth Factor Receptor3 (FGFR3) gene. ', 'The associated of FGFR3 mutations with craniosynostosis has been restricted to three mutations, the common p.Pro250Arg in Muenke syndrome, p.Ala391Glu in Crouzon syndrome with acanthosis nigricans, and p.Pro250Leu identified in a family with isolated craniosynostosis. ', 'The Pro250Arg mutation in the FGFR3 gene is found in patients with Muenke syndrome and is one of the most frequently encountered mutations in craniosynostosis syndromes. ', ' Fibroblasts from 10 individuals each with Apert syndrome (FGFR2 substitution S252W), Muenke syndrome (FGFR3 substitution P250R), Saethre-Chotzen syndrome (various mutations in TWIST1) and non-syndromic sagittal synostosis (no mutation detected) were cultured. ', 'The identification of the P250R mutation allowed the confirmation of the Muenke Syndrome in 9 out of the 52 cases referred. ', 'Muenke syndrome, also known as FGFR3-associated coronal synostosis, is defined molecularly by the presence of a heterozygous nucleotide transversion, c.749C>G, encoding the amino acid substitution Pro250Arg, in the fibroblast growth factor receptor type 3 gene (FGFR3). ']

['Muenke syndrome, also known as FGFR3-associated coronal synostosis, is defined molecularly by the presence of a heterozygous nucleotide transversion, c.749C>G, encoding the amino acid substitution Pro250Arg, in the fibroblast growth factor receptor type 3 gene (FGFR3).']

['One']

Has whole exome sequencing been performed in Alzheimer patients?

["Pilot whole-exome sequencing of a German early-onset Alzheimer's disease cohort reveals a substantial frequency of PSEN2 variants.", 'We performed whole-exome sequencing in early-onset Alzheimer disease (EOAD) and late-onset Alzheimer disease (LOAD) families followed by functional studies of select variants.', 'Whole-exome sequencing revealed a nonsense mutation in PRNP (NM_000311, c.C478T; p.Q160*; rs80356711) associated with homozygosity for the V allele at position 129 of the protein, further highlighting how very similar genotypes in PRNP result in strikingly different phenotypes.', "In the search for new genes in Alzheimer's disease, classic linkage-based and candidate-gene-based association studies have been supplanted by exome sequencing, genome-wide sequencing (for mendelian forms of Alzheimer's disease), and genome-wide association studies (for non-mendelian forms). ", "We performed whole exome sequencing in a Turkish patient clinically diagnosed with Alzheimer's disease from a consanguineous family ", 'Performing exome sequencing in 14 autosomal dominant early-onset Alzheimer disease (ADEOAD) index cases without mutation on known genes (amyloid precursor protein (APP), presenilin1 (PSEN1) and presenilin2 (PSEN2)), we found that in five patients, the SORL1 gene harbored unknown nonsense (n=1) or missense (n=4) mutations']

['Yes, numerous whole exome sequencing studies of ALzheimer patients have been conducted.']

['yes']

Which genes are thought to be involved in medulloblastoma development?

['Medulloblastomas, the most frequent malignant brain tumours affecting children, comprise at least 4 distinct clinicogenetic subgroups. Aberrant sonic hedgehog (SHH) signalling is observed in approximately 25% of tumours and defines one subgroup. Although alterations in SHH pathway genes (e.g. PTCH1, SUFU) are observed in many of these tumours, high throughput genomic analyses have identified few other recurring mutations', 'Mutagenesis significantly increased medulloblastoma frequency and identified 17 candidate cancer genes, including orthologs of genes somatically mutated (PTEN, CREBBP) or associated with poor outcome (PTEN, MYT1L) in the human disease. Strikingly, these candidate genes were enriched for transcription factors (p=2x10-5), the majority of which (6/7; Crebbp, Myt1L, Nfia, Nfib, Tead1 and Tgif2) were linked within a single regulatory network enriched for genes associated with a differentiated neuronal phenotype', 'Igf2, previously implicated in medulloblastoma, was the most differentially expressed gene in murine tumours with network perturbation', 'PCDH10 is a candidate tumour suppressor gene in medulloblastoma', 'The aim of this study was to investigate the genetic and epigenetic mechanisms contributing to PCDH10 down-regulation in medulloblastoma', 'We report a very focal homozygous deletion on chromosome 4q28.3 harbouring the PCDH10 gene. We demonstrate that PCDH10 transcription is down-regulated in 19/26 (73%) of medulloblastomas suggesting that other mechanisms also could be involved in gene repression', 'Our findings suggest that genetic and epigenetic deregulation of PCDH10 occurs in a significant portion of medulloblastoma patients. Failure to express PCDH10 may result in loss of inhibition of cell migration, thereby contributing to medulloblastoma progression', 'We found that the higher expression levels of BMI1 and PCGF2 genes were associated with significantly decreased patient survival', "Our analysis showed correlation between BMI1 and PCGF2 gene's expression and survival in children with medulloblastoma", 'Bmi1 is required for Hedgehog pathway-driven medulloblastoma expansion', 'These data provide the first demonstration that Bmi1 is required for spontaneous de novo development of a solid tumor arising in the brain, suggest a crucial role for Bmi1-dependent, nestin-expressing progenitor cells in medulloblastoma expansion, and implicate Bmi1 as a key factor required for Hh pathway-driven tumorigenesis', 'Genomic amplification of orthodenticle homologue 2 in medulloblastomas', 'Genomic alterations normally associated with medulloblastomas, including MYC amplification and isochromosome 17q, were easily detected. Surprisingly, analysis of only five genomes revealed novel amplicons on chromosome 14q, one of which contained the orthodenticle homologue 2 (OTX2) homeobox gene. DNA copy number analysis showed that OTX2 had undergone genomic amplification in 2 of 11 medulloblastoma cell lines and 8 of 42 primary tumors', 'Serial analysis of gene expression of 240 different human tumors or normal tissues revealed that 96% of all 783 OTX2 transcripts sequenced were in medulloblastomas or embryonic stem cells', 'OTX2 functions to specify the fate of neuroectoderm in various regions of the developing brain. This developmental role is consistent with the evidence suggesting that OTX2 is a medulloblastoma oncogene', 'Extensive hypermethylation of RASSF1A was detected frequently in medulloblastomas but not in the normal cerebellum (41/44 primary tumours versus 0/5 normal cerebella)', 'In contrast, complete methylation of HIC1 and CASP8 in a subset of primary tumours (17/44 and 14/39) occurred against a consistent background of partial methylation in the normal cerebellum', 'These data therefore indicate that extensive methylation of RASSF1A, HIC1 and CASP8 are tumour-specific events in medulloblastoma', 'We conclude that epigenetic TSG inactivation is a significant feature of medulloblastoma, and identify RASSF1A, HIC1 and CASP8 as potentially critical genes in its pathogenesis', 'Biallelic epigenetic inactivation of the RASSF1A tumor suppressor gene in medulloblastoma development', 'Seventy-nine % (27 of 34) of primary tumors and 100% (8 of 8) of medulloblastoma cell lines displayed extensive tumor-specific DNA hypermethylation across the RASSF1A promoter-associated CpG island', "Hypermethylation was associated with epigenetic silencing of RASSF1A transcription in medulloblastoma cell lines, and RASSF1A expression in these lines was restored after treatment with the DNA-methyltransferase inhibitor 5-aza-2'-deoxycytidine", 'Epigenetic inactivation by biallelic hypermethylation therefore represents the primary mechanism of RASSF1A gene inactivation in medulloblastoma', 'RASSF1A hypermethylation is a frequent event in medulloblastoma tumorigenesis detectable in adult (5 of 7) and pediatric patients (22 of 27) and in all histological variants and age and sex groupings', 'Medulloblastoma, a brain tumor, develops in about 3% of NBCCS patients, and mutations in PTCH have also been described in a subset of sporadic medulloblastomas', 'Recently, a transgenic mouse hemizygous for the Ptch gene was generated by homologous recombination. Medulloblastomas were found in about 19% of these mice within the first 25 weeks after birth', 'We also examined the mRNA expression levels for the remaining Ptch allele, as well as for Gli1, a gene known to be transcriptionally activated by Ptch inactivation. Blot analysis of RNA from the 13 tumors shows that Ptch mRNA of appropriate size is expressed in all tumors at varying levels. Expression of Gli1 was increased in tumors compared to normal cerebellum. These results suggest that deletion of one copy of Ptch may be sufficient to promote medulloblastoma development in mice']

['Medulloblastomas are the most frequent malignant brain tumors affecting children. Disease development has been suggested to be associated with a significant number of genes, such as PTCH1, SUFU, PTEN, CREBBP, PTEN, MYT1L, NFIA, NFIB, TEAD1, TGIF2, IGF2, PCDH10, BMI1, MYC, OTX2, RASSF1A, HIC1, and CASP8.']

['PTCH1', 'SUFU', 'PTEN', 'CREBBP', 'PTEN', 'MYT1L', 'NFIA', 'NFIB', 'TEAD1', 'TGIF2', 'IGF2', 'PCDH10', 'BMI1', 'MYC', 'OTX2', 'RASSF1A', 'HIC1', 'CASP8']

Which hormone abnormalities are common in Williams syndrome ?

['WS and TD participants had similar profiles in a familiar setting, while participants with WS had elevated cortisol late in the day in the novel setting when social demands were higher. The cortisol awakening response in WS was associated with parent-reported levels of somatic complaints and social difficulties. Results suggest that adults with WS have a typical diurnal cortisol profile that may be sensitive to social and activity transitions throughout the day.', 'Results revealed significantly higher median levels of OT in WS versus controls at baseline, with a less marked increase in AVP. Further, in WS, OT and AVP increased in response to music and to cold, with greater variability and an amplified peak release compared to controls. In WS, baseline OT but not AVP, was correlated positively with approach, but negatively with adaptive social behaviors. These results indicate that WS deleted genes perturb hypothalamic-pituitary release not only of OT but also of AVP, implicating more complex neuropeptide circuitry for WS features and providing evidence for their roles in endogenous regulation of human social behavior. ', 'Three quarters of the WS subjects showed abnormal glucose curves, meeting diagnostic criteria for either diabetes or the pre-diabetic state of impaired glucose tolerance. Fasting mean glucose and median insulin levels did not differ significantly in the total WS cohort versus age-gender-BMI matched controls, though the glucose area under the curve was greater in the WS subjects. ', 'Williams syndrome (WS) is characterized by cardiovascular disease (elastin arteriopathy, peripheral pulmonary stenosis, supravalvular aortic stenosis, hypertension), distinctive facies, connective tissue abnormalities, intellectual disability (usually mild), a specific cognitive profile, unique personality characteristics, growth abnormalities, and endocrine abnormalities (hypercalcemia, hypercalciuria, hypothyroidism, and early puberty).', 'In the Williams-Beuren syndrome (WBS), disorders of the thyroid function and morphology have been reported and programs of thyroid screening and surveillance are recommended. ', 'In this report we describe an infant with WBS and congenital hypothyroidism, due to an important thyroid hypoplasia. The patient, a 1-month-old female, negative at primary neonatal thyroid screening, was referred to our hospital for dyspnea. Thyroid function tests showed a raised TSH (42 mIU/l; normal range 0.5-4 mIU/l) with a low FT(4) concentration (10.21 pmol/l; normal range: 10.29-24.45 pmol/l). Ultrasound examination of the neck showed a significant thyroid hypoplasia, whereas (99m)Tc-pertechnetate thyroid scintigraphy evidenced a thyroid gland in normal position, with reduced shape and overall weak fixation. ', 'Thyroid hypoplasia is a frequent characteristic of WBS and abnormalities of thyroid function are common in patients with this feature. Therefore, the possibility of congenital hypothyroidism should always be taken into consideration too and, even if congenital hypothyroidism neonatal screening is negative, thyroid (morphology and function) evaluation should be regularly assessed when the diagnosis is made and, thereafter, every year in the first years of life.', 'As growth hormone (GH) deficiency was diagnosed by an additional GH-stimulation test, we commenced with a GH-treatment. ', 'None of our patients had overt hypothyroidism; 29 patients (31.5%) had subclinical hypothyroidism. ', 'Thyroid involvement in Williams syndrome (WS) was recently reported in two small groups of patients, both showing an increased prevalence of elevation of TSH serum concentration; in one of the two reports, 70% of the patients demonstrated a hypoplasia of thyroid gland as well. ', 'Our study confirms the increased incidence of both elevated TSH serum values (37.9% in our sample) and thyroid gland hypoplasia (74.7%).', 'A WS patient with CPP is presented, whose pubertal development and bone age progression were arrested by administration of GnRH analogues. ', ' This study confirms the presence of alterations of thyroid function in WS and also suggests the frequent occurrence of abnormalities of thyroid morphology in these patients.', 'We report a female infant with confirmed WBS who, through provocative testing, was found to have GHD and who responded satisfactorily to hGH therapy. ', 'In conclusion, GH deficiency might contribute to the growth failure in a number of patients with WBS and in such cases hGH therapy will most likely improve final height.', 'Thyrotropin level was very high (>50 microU/ml; normal value 0.2-4 microU/ml), while serum free T(3) (FT3) and free T(4) (FT4) levels were normal (FT3 3.6 pg/ml, normal value 2.8-5.6 pg/ml; FT4 11.6 pg/ml, normal value 6.6-14 pg/ml); antithyroid autoantibodies were absent. ', 'Recently a case of thyroid hemiagenesis in a child with WS has been reported; our patient underscores the association of hypothyroidism and WS. ', 'Thyroid hemiagenesis and elevated thyrotropin levels in a child with Williams syndrome.', 'A girl with Williams syndrome (WS) presented with elevated thyrotropin (TSH) levels (7.0 microU/ml), normal free thyroid hormone concentrations, and absent antithyroid autoantibodies.', 'TSH response to thyrotropin-releasing hormone (TRH) injection (200 microg/mq, i.v.) was exaggerated and prolonged, suggesting subclinical hypothyroidism. The biological activity of circulating TSH was slightly below the normal range [TSH bioactivity (B) to immunoreactivity (I) ratio (TSH B/I) = 0.4, normal: 0.6-2.2]. These abnormalities are similar to those seen in patients with hypothalamic hypothyroidism.', 'However, abnormalities of the hypothalamic-pituitary-thyroid (HPT) axis and thyroid dysgenesis have been found in other WS cases. ', 'We report a boy with confirmed Williams-Beuren syndrome, who was found to have classical growth hormone deficiency and responded well to growth hormone therapy. ', 'Although growth hormone deficiency is not likely to be a common cause of short stature in Williams-Beuren syndrome, we nevertheless recommend evaluation of the growth hormone-insulin-like growth factor I axis in all cases.', 'Endocrinological examinations revealed hypergonadotropic hypogonadism. Prolonged and exaggerated responses of adrenocorticotropin (ACTH) to insulin-induced hypoglycemia and corticotropin releasing hormone (CRH) were also noted. ', 'Involvement of the calcitonin/CGRP gene in Williams syndrome is postulated on the basis that Williams syndrome children often have infantile hypercalcemia and deficient expression of calcitonin, a hormone that lowers serum calcium levels. ', 'These findings suggest that the calcitonin deficiency might be due either to mutations elsewhere in the gene or to defects in the cellular machinery needed for calcitonin synthesis and/or secretion.', 'It has been suggested that a defect in calcitonin function may play a role in Williams syndrome. ', ' These patients were found to have significantly higher mean baseline calcium concentrations, delayed clearance of calcium after intravenous calcium loading, and blunted calcitonin responses after calcium infusion, compared with a group of seven normal children.', 'Our studies demonstrate that patients with Williams syndrome have a defect in the synthesis or release of immunoreactive calcitonin. A deficiency of calcitonin may explain the abnormalities of calcium metabolism seen in these patients and can serve as an important endocrine marker for Williams syndrome.', 'Additional periodic evaluations during childhood: serum concentration of calcium, thyroid function, hearing, and renal and bladder ultrasound examination. Periodic evaluations during adulthood: glucose tolerance; cardiac evaluation for mitral valve prolapse, aortic insufficiency, and arterial stenosis; and ophthalmologic evaluation for cataracts.', 'Subclinical hypothyroidism is a frequent but stable finding in young children with WS. The great majority of patients with WS >10 years, either with normal or hypoplastic thyroid, have normal thyroid function.', ' Three cases (15%) of subclinical hypothyroidism were identified. Overt hypothyroidism was diagnosed in two cases (10%).']

['Thyroid hormone abnormalities are common in Williams syndrome. Oxytocin and vasopressin, cortisol, growth hormone and calcitonin were also implicated in the Williams syndrome.']

['thyroid']

How could we infer functional associations from gene fusion events?

['Gene fusion is an important evolutionary process. It can yield valuable information to infer the interactions and functions of proteins.', 'We have developed a Bayesian framework to infer phosphorylation networks from time series measurements of phosphosite concentrations upon ligand stimulation. To increase the prediction accuracy we integrated different types of data, e.g., amino acid sequence data, genomic context data (gene fusion, gene neighborhood, and phylogentic profiles)', 'It is assumed that two proteins, which are found to be transcribed by a single transcript in one (or several) genomes are likely to be functionally linked, for example by acting in a same metabolic pathway or by forming a multiprotein complex. This method is of particular interest for studying genes that exhibit no, or only remote, homologies with already well-characterized proteins.', 'PLEX search results are accompanied by quantitative estimates of linkage confidence, enabling users to take advantage of coinheritance, operon and gene fusion-based methods for inferring gene function and reconstructing cellular systems and pathways.', 'While phylogenomic profiles remain the central focus of Phydbac2, it now integrates chromosomal proximity and gene fusion analyses as two additional non-similarity-based indicators for inferring pairwise gene functional relationships.', 'detection of gene fusion events can contribute towards the elucidation of functional associations of proteins within entire genomes', 'Inference of gene function based on gene fusion events: the rosetta-stone method.', 'protein domain fusions in human protein interaction networks prediction', 'Some proteins, involved in a common biological process and encoded by separate genes in one organism, can be found fused within a single protein chain in other organisms. By detecting these triplets, a functional relationship can be established between the unfused proteins.', 'These results suggest that domain fusion is an appropriate method for predicting protein complexes.', 'The detection of gene fusion events across genomes can be used for the prediction of functional associations of proteins, including physical interactions or complex formation.', 'These genomic constraints form the basis for a variety of techniques that employ systematic genome comparisons to predict functional associations among genes. The most powerful techniques to date are based on conserved gene neighborhood, gene fusion events, and common phylogenetic distributions of gene families', 'Functional links between proteins can often be inferred from genomic associations between the genes that encode them: groups of genes that are required for the same function tend to show similar species coverage, are often located in close proximity on the genome (in prokaryotes), and tend to be involved in gene-fusion events.', 'Genes linked by fusion events are generally of the same functional category', 'a functional association between two genes can be derived from the existence of a fusion of the two as one continuous sequence in another genome', 'Protein interaction maps for complete genomes based on gene fusion events', 'Because there must be selective pressure for certain genes to be fused over the course of evolution, we are able to predict functional associations of proteins.', 'We observed that gene fusion events are more related to physical interaction between proteins than to other weaker functional relationships such as participation in a common biological pathway.', 'FusionDB provides a characterization of a large number of gene fusion events at hand of multiple sequence alignments.', 'Domain fusion analysis has been proposed recently to infer the functional association of the component proteins.', 'Here we present a method that identifies gene-fusion events in complete genomes, solely based on sequence comparison.']

["The detection of gene fusion events across genomes can be used for the prediction of functional associations of proteins, based on the observation that related proteins in one organism (including physically interacting proteins/members of complexes, proteins involved in the same pathway) tend to be found in other species as a fused composite gene encoding a single multifunctional protein. For this purpose, gene fusion events may be used as the sole evidence or as independent information combined with other 'genome-aware' or similarity-based methods, and functional association may be predicted at different levels. An advantage of this approach is that it is not necessary to know the function of the composite/components to infer association."]

[]

How many clinical trials for off-label drugs in neonates are cited in the literature.

['Of the 17 Paediatric Investigation Plans submitted, 14 have resulted in an EMA Decision, 3 were withdrawn by the applicants, 8 were granted a full waiver from development, and 1 resulted in a negative opinion. Decisions as issued included 15 clinical trials, with at least 1,282 children to be recruited into studies across five different products. Neonates were included in four of the products. CONCLUSIONS: The small number of submissions indicates a lack of new drugs being developed for the management of pain. Ethical concerns that too many vulnerable children will be recruited into clinical trials must be balanced against limiting the number of off-label prescribing and obtaining age-appropriate information on paediatric use.', 'Paediatric Investigations Plans (PIPs) submitted with a Decision (outcome) reached between September 2007 and March 2010 were included in the analysis.']

['There are no reports on clinical trials of off-label drugs in neonates. An analysis of Pediatric Investigation Plans submitted between 2007 and 2010 shows that neonates were included in the study of 4 products, but it is unknown if the trial drugs are off-label and if the trials are being conducted at all.']

['none', '0', 'zero']

Is CD56 useful in Ewing sarcoma prognosis?

['Excellent prognosis in a subset of patients with Ewing sarcoma identified at diagnosis by CD56 using flow cytometry', 'There was a highly significant correlation between CD56 expression and progression-free survival (PFS; 69% in low/negative expression versus 30% in high expression groups, P = 0.024)', 'In patients with localized nonpelvic disease, those expressing low/negative CD56 had 100% PFS versus 40% in the high expressing group (P = 0.02)', 'CD56 was found to be an independent prognostic marker with an 11-fold increased risk for relapse in patients with localized disease (P = 0.006)', 'CD56 expression could be used to reveal ES patients with excellent prognosis or patients predisposed to relapse, thus improving treatment stratification and implementation of personalized therapy', 'Excellent prognosis in a subset of patients with Ewing sarcoma identified at diagnosis by CD56 using flow cytometry.', 'Three years after diagnosis the patient presented with severe respiratory difficulty and following resection, the final pathology revealed multiple tumors with foci of high grade sarcoma compatible with primitive neuroectodermal tumor/extraskeletal Ewing sarcoma based on morphology and immunohistochemistry (CD99, CD56).', 'CD56 expression could be used to reveal ES patients with excellent prognosis or patients predisposed to relapse, thus improving treatment stratification and implementation of personalized therapy.', "Identification of CD56 and CD57 by flow cytometry in Ewing's sarcoma or primitive neuroectodermal tumor.", 'CD56 expression could be used to reveal ES patients with excellent prognosis or patients predisposed to relapse, thus improving treatment stratification and implementation of personalized therapy.']

['Excellent prognosis in a subset of patients with Ewing sarcoma identified at diagnosis by CD56 using flow cytometryIn patients with localized nonpelvic disease, those expressing low/negative CD56 had 100% PFS versus 40% in the high expressing group (P = 0.02)', 'CD56 expression could be used to reveal Ewing sarcoma patients with excellent prognosis or patients predisposed to relapse, thus improving treatment stratification and implementation of personalized therapy.']

['yes']

Gene silencing can be achieved by RNA interference (RNAi) in eukaryotic organisms. What is the name of the analogous process in prokaryotic organisms?

['he CRISPR-Cas (clustered regularly interspaced short palindromic repeats, CRISPR-associated genes) is an adaptive immunity system in bacteria and archaea that functions via a distinct self-non-self recognition mechanism that is partially analogous to the mechanism of eukaryotic RNA interference (RNAi).', 'RNA-guided RNA cleavage by a CRISPR RNA-Cas protein complex.', 'Compelling evidence indicates that the CRISPR-Cas system protects prokaryotes from viruses and other potential genome invaders.', 'RNA in defense: CRISPRs protect prokaryotes against mobile genetic elements.', 'n this article, we discuss our current understanding of this fascinating adaptive and heritable defense system, and describe functional similarities and differences with RNAi in eukaryotes.', 'Bacteria have developed several defense mechanisms against bacteriophages over evolutionary time, but the concept of prokaryotic RNA interference mediated defense mechanism against phages and other invading genetic elements has emerged only recently. Clustered regularly interspaced short palindromic repeats (CRISPR) together with closely associated genes (cas genes) constitute the CASS system that is believed to provide a RNAi-like defense mechanism against bacteriophages within the host bacterium.', 'In many prokaryotes, noncoding RNAs that arise from the clustered regularly interspaced short palindromic repeat (CRISPR) loci are now thought to mediate defense against viruses and other molecular invaders by an RNAi-like pathway.']

['Bacteria have developed several defense mechanisms against bacteriophages over evolutionary time, but the concept of prokaryotic RNA interference mediated defense mechanism against phages and other invading genetic elements has emerged only recently. Clustered regularly interspaced short palindromic repeats (CRISPR) together with closely associated genes (cas genes) constitute the CASS system that is believed to provide a RNAi-like defense mechanism against bacteriophages within the host bacterium.']

['CRISPR-Cas']

What are the pyknons?

['Using an unsupervised pattern-discovery method, we processed the human intergenic and intronic regions and catalogued all variable-length patterns with identically conserved copies and multiplicities above what is expected by chance. Among the millions of discovered patterns, we found a subset of 127,998 patterns, termed pyknons, which have additional nonoverlapping instances in the untranslated and protein-coding regions of 30,675 transcripts from 20,059 human genes', "In a recent paper in PNAS, Rigoutsos et al. (2006) describe a nonrandom pattern of repeated elements, called pyknons, which are found more frequently in the 3' untranslated regions of genes than in other regions of the human genome", 'Discovery of pyknons, the most frequent, variable-length DNA sequence motifs in the human genomes, suggests extensive sequence-based connectivity between non-coding and protein-coding components of human genomes', 'Short blocks from the noncoding parts of the human genome have instances within nearly all known genes and relate to biological processes.', 'Pyknons are non-random sequence patterns significantly repeated throughout non-coding genomic DNA that also appear at least once among coding genes. They are interesting because they portend an unforeseen connection between coding and non-coding DNA. Pyknons have only been discovered in the human genome, so it is unknown whether pyknons have wider biological relevance or are simply a phenomenon of the human genome', 'these data reveal that pyknons represent a biologically important link between coding and non-coding DNA', 'Pyknons are non-random sequence patterns significantly repeated throughout non-coding genomic DNA that also appear at least once among coding genes.', 'Pyknons are non-random sequence patterns significantly repeated throughout non-coding genomic DNA that also appear at least once among coding genes', 'The pyknons arrange combinatorially in the untranslated and coding regions of numerous human genes where they form mosaics']

['Using an unsupervised pattern-discovery method, the human intergenic and intronic regions were processed and all variable-length patterns with identically conserved copies and multiplicities above what is expected by chance were catalogued. Among the millions of discovered patterns, a subset of 127,998 patterns was found, termed pyknons, which have additional nonoverlapping instances in the untranslated and protein-coding regions of 30,675 transcripts from 20,059 human genes. The pyknons arrange combinatorially in the untranslated and coding regions of numerous human genes where they form mosaics. Pyknons might represent a biologically important link between coding and non-coding DNA.']

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Which genes have been found mutated in Gray platelet syndrome patients?

['We detected a nonsense mutation in the gene encoding the transcription factor GFI1B (growth factor independent 1B) that causes autosomal dominant gray platelet syndrome. ', 'The genetic defect responsible for gray platelet syndrome was recently identified in biallelic mutations in the NBEAL2 gene.', 'Here we show that mutations in NBEAL2 (neurobeachin-like 2), which encodes a BEACH/ARM/WD40 domain protein, cause GPS and that megakaryocytes and platelets from individuals with GPS express a unique combination of NBEAL2 transcripts. ', 'Linkage analysis revealed a 63 cM region on the X chromosome between markers G10578 and DXS6797, which segregated with the platelet phenotype and included the GATA1 gene. Sequencing of GATA1 revealed a G-to-A mutation at position 759 corresponding to amino acid change Arg216Gln. ', 'We identified a family with gray platelet syndrome (GPS) segregating as a sex-linked trait. ', 'X-linked gray platelet syndrome due to a GATA1 Arg216Gln mutation']

['The genetic defects responsible for gray platelet syndrome are mutations in the genes NBEAL2, GATA1 and GFI1B.', 'The genetic defect responsible for gray platelet syndrome was recently identified in biallelic mutations in the NBEAL2 gene.\nA nonsense mutation in the gene encoding the transcription factor GFI1B (growth factor independent 1B) that causes autosomal dominant gray platelet syndrome.\nX-linked gray platelet syndrome due to a GATA1 Arg216Gln mutation.']

['neurobeachin-like 2', 'NBEAL2', 'GATA1', 'GFI1B']

Is Ctf4 involved in sister chromatid cohesion establishment?

['In addition to Eco1, several other factors contribute to cohesion establishment, including Ctf4, Ctf18, Tof1, Csm3, Chl1 and Mrc1, but little is known about their roles. Here, we show that each of these factors facilitates cohesin acetylation. Moreover, the absence of Ctf4 and Chl1, but not of the other factors, causes a synthetic growth defect in cells lacking Eco1. Distinct from acetylation defects, sister chromatid cohesion in ctf4Δ and chl1Δ cells is not improved by removing Wapl', 'Thus, Ctf4 and Chl1 delineate an additional acetylation-independent pathway that might hold important clues as to the mechanism of sister chromatid cohesion establishment', 'Genetic analyses revealed that Rmi1 promoted sister chromatid cohesion in a process that was distinct from both the cohesion establishment pathway involving Ctf4, Csm3, and Chl1', 'Influence of the human cohesion establishment factor Ctf4/AND-1', ' Here, we used Xenopus egg extracts to show that AND-1 and Tim1-Tipin, homologues of Saccharomyces cerevisiae Ctf4 and Tof1-Csm3, respectively, are associated with the replisome and are required for proper establishment of the cohesion observed in the M-phase extracts', 'These data defined two cohesion pathways, one containing CSM3, TOF1, CTF4, and CHL1, and the second containing MRC1, CTF18, CTF8, and DCC1', 'Our results suggest that Chl1 and Ctf4 are directly involved in homologous recombination repair rather than acting indirectly via the establishment of sister chromatid cohesion', 'Here we show that three proteins required for sister chromatid cohesion, Eco1, Ctf4, and Ctf18, are found at, and Ctf4 travels along chromosomes with, replication forks', 'WSS1 was also found to interact genetically with SGS1, TOP3, SRS2 and CTF4, which are involved in recombination, repair of replication forks and the establishment of sister chromatid cohesion', 'The catalytic subunit of budding yeast Polalpha (Pol1p) has been shown to associate in vitro with the Spt16p-Pob3p complex, a component of the nucleosome reorganization system required for both replication and transcription, and with a sister chromatid cohesion factor, Ctf4p', 'Constituents of the replication fork, such as the DNA polymerase alpha-binding protein Ctf4, contribute to cohesion in ways that are poorly understood', 'Genetic analyses revealed that Rmi1 promoted sister chromatid cohesion in a process that was distinct from both the cohesion establishment pathway involving Ctf4, Csm3, and Chl1 and the pathway involving the acetylation of Smc3.', 'Our results suggest that Chl1 and Ctf4 are directly involved in homologous recombination repair rather than acting indirectly via the establishment of sister chromatid cohesion.', 'Ctf4/AND-1 is a highly conserved gene product required for both DNA replication and the establishment of sister chromatid cohesion.', 'Here we show that three proteins required for sister chromatid cohesion, Eco1, Ctf4, and Ctf18, are found at, and Ctf4 travels along chromosomes with, replication forks.', 'Sister-chromatid cohesion mediated by the alternative RF-CCtf18/Dcc1/Ctf8, the helicase Chl1 and the polymerase-alpha-associated protein Ctf4 is essential for chromatid disjunction during meiosis II.', 'Saccharomyces cerevisiae CTF18 and CTF4 are required for sister chromatid cohesion.', 'We find that absence of either CTF4 or CTF18 causes sister chromatid cohesion failure and leads to a preanaphase accumulation of cells that depends on the spindle assembly checkpoint.', 'We show here that CTF8, CTF4 and a helicase encoded by CHL1 are required for efficient sister chromatid cohesion in unperturbed mitotic cells, and provide evidence that Chl1 functions during S-phase.', 'In budding yeast, a specialized replication factor C called RF-C(Ctf18/Dcc1/Ctf8) and the DNA-polymerase-alpha-associated protein Ctf4 are required to maintain sister-chromatid cohesion in cells arrested for long periods in mitosis.', 'The physical and genetic interactions between CTF4, CTF18, and core components of replication fork complexes observed in this study and others suggest that both gene products act in association with the replication fork to facilitate sister chromatid cohesion.', 'Our results suggest that Chl1 and Ctf4 are directly involved in homologous recombination repair rather than acting indirectly via the establishment of sister chromatid cohesion.', 'Thus, Ctf4 and Chl1 delineate an additional acetylation-independent pathway that might hold important clues as to the mechanism of sister chromatid cohesion establishment.', 'Thus, Ctf4 and Chl1 delineate an additional acetylation-independent pathway that might hold important clues as to the mechanism of sister chromatid cohesion establishment.', 'Ctf4/AND-1 is a highly conserved gene product required for both DNA replication and the establishment of sister chromatid cohesion', 'Genetic analyses revealed that Rmi1 promoted sister chromatid cohesion in a process that was distinct from both the cohesion establishment pathway involving Ctf4, Csm3, and Chl1 and the pathway involving the acetylation of Smc3', 'Establishment of sister chromatid cohesion at the S. cerevisiae replication fork.']

['Yes. Ctf4 is associated with the replisome and is required for proper establishment of cohesion by facilitating cohesin acetylation.']

['yes']

Which is the main calcium pump of the sarcoplasmic reticulum?

['sarcoplasmic reticulum (SR) calcium pump (SERCA)', 'the sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA)', 'SERCA, an endoplasmic reticulum (ER) calcium pump, is solely responsible for transporting cytosolic calcium into the ER lumen.', 'Sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) is the pump crucial for calcium homeostasis and its impairment results in pathologies such as myopathy, heart failure or diabetes.', 'Sarcoplasmic reticulum calcium ATPase (SERCA2a), the sarcoplasmic reticulum calcium pump, was found to be a key factor in the alteration of calcium cycling.', 'The calcium pump SERCA2a (sarcoplasmic reticulum calcium ATPase 2a), which plays a central role in cardiac contraction, shows decreased expression in heart failure (HF).', 'Calcium is actively accumulated in the endoplasmic reticulum by Sarco/Endoplasmic Reticulum Calcium transport ATPases (SERCA enzymes).', 'sarco(endo)plasmic reticulum calcium pump (SERCA)', 'SERCA is a membrane protein that belongs to the family of P-type ion translocating ATPases and pumps free cytosolic calcium into intracellular stores.', 'Three different SERCA genes were identified-SERCA1, SERCA2, and SERCA3. SERCA is mainly represented by the SERCA2a isoform in the heart.', 'The sarcoplasmic reticulum Ca�z ATPase (SERCA) is a membrane-bound pump that utilizes ATP to drive calcium ions from the myocyte cytosol against the higher calcium concentration in the sarcoplasmic reticulum.']

['Sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) is the pump crucial for calcium homeostasis. SERCA is a membrane protein that belongs to the family of P-type ion translocating ATPases and pumps free cytosolic calcium into intracellular stores.']

['Sarcoplasmic reticulum Ca(2+)-ATPase', 'SERCA', 'serca2']

Is PER3 required for CHK2 activation in human cells?

['Per3, a circadian gene, is required for Chk2 activation in human cells.', 'Depletion of Per3 by siRNA almost completely abolished activation of checkpoint kinase 2 (Chk2) after inducing DNA damage in human cells.', 'Per3 overexpression induced Chk2 activation in the absence of exogenous DNA damage,', 'Per3 overexpression also led to the inhibition of cell proliferation and apoptotic cell death.', 'These combined results suggest that Per3 is a checkpoint protein that plays important roles in checkpoint activation, cell proliferation and apoptosis.', 'Depletion of Per3 by siRNA almost completely abolished activation of checkpoint kinase 2 (Chk2) after inducing DNA damage in human cells', 'Per3 overexpression induced Chk2 activation in the absence of exogenous DNA damage, and this activation depended on ATM', 'In addition, Per3 physically interacted with ATM and Chk2']

['Depletion of Per3 by siRNA almost completely abolished activation of checkpoint kinase 2 (Chk2) after inducing DNA damage in human cells.Per3, a circadian gene, is required for Chk2 activation in human cells.', 'Per3, a circadian gene, is required for Chk2 activation in human cells. ', 'Per3, a circadian gene, is required for Chk2 activation in human cells.Per3 overexpression induced Chk2 activation in the absence of exogenous DNA damage,', 'Per3 gene, involved in circadian rhythm control, is required for Chk2 activation in human cells.']

['yes']

Is the tricarboxylic acid (TCA) cycle affected in inflammation?

['In this study, the levels of amino acids and trichloroacetic acid (TCA) cycle-related molecules in the colonic tissues and sera of patients with ulcerative colitis (UC) were profiled by gas chromatography/mass spectrometry (GC/MS), with the aim of evaluating whether the clinical state induced by UC leads to variations in the amino acid profile', 'Our study raises the possibility that GC/MS-based profiling of amino acids and TCA cycle-related molecules is a useful early diagnostic tool for UC.', 'Succinate is an intermediate of the tricarboxylic acid (TCA) cycle, and plays a crucial role in adenosine triphosphate (ATP) generation in mitochondria.', 'In plasma, most metabolites in the central metabolic pathway (glycolysis and TCA cycle) were significantly downregulated after zymosan administration', 'Thus, IL-1beta+TNFalpha treated astrocytes show a marked decrease in glycogen levels, a slight but not significant decrease in lactate release as well as a massive increase in both the pentose phosphate pathway and TCA cycle activities.', 'A total of 77 and 92 metabolites were detected in serum and colon tissue, respectively, and among the metabolites the compositions of TCA cycle intermediates and amino acids changed depending on the degree of colitis', 'Extension of these findings identified a functional role for stretch-induced inhibition of succinate dehydrogenase (SDH) in mediating normoxic HIF1A stabilization, concomitant increases in glycolytic capacity, and improved tricarboxylic acid (TCA) cycle function', 'These studies reveal a surprising role for HIF1A in lung protection during ALI, where normoxic HIF1A stabilization and HIF-dependent control of alveolar-epithelial glucose metabolism function as an endogenous feedback loop to dampen lung inflammation', 'These results suggest a cataplerosis of the TCA cycle induced by phenobarbital, caused by the massive withdrawal of succinyl-CoA by ALAS induction, such that the TCA cycle is unable to supply the reduced cofactors to the RC', 'The mitochondrial respiratory chain (RC) and the tricarboxylic acid (TCA) cycle were explored in the Hmbs(-/-) mouse model. RC and TCA cycle were significantly affected in comparison to controls in mice treated with phenobarbital with decreased activities of RC complexes', 'Several changes in substrate utilization for energy homeostasis were identified in severe AAH, including increased glucose consumption by the pentose phosphate pathway, altered tricarboxylic acid (TCA) cycle activity, and enhanced peptide catabolism. ', 'Enhanced mitochondrial glucose oxidation was achieved by increased recruitment of the NOTCH1 intracellular domain (NICD1) to nuclear and mitochondrial genes that encode respiratory chain components and by NOTCH-dependent induction of pyruvate dehydrogenase phosphatase 1 (Pdp1) expression, pyruvate dehydrogenase activity, and glucose flux to the TCA cycle. ', 'Metabolic reprogramming is implicated in macrophage activation,', 'BHB blocks the NLRP3 inflammasome without undergoing oxidation in the TCA cycle, and independently of uncoupling protein-2 (UCP2), sirtuin-2 (SIRT2), the G protein-coupled receptor GPR109A or hydrocaboxylic acid receptor 2 (HCAR2). ', 'Our findings suggest that the anti-inflammatory effects of caloric restriction or ketogenic diets may be linked to BHB-mediated inhibition of the NLRP3 inflammasome.', 'Succinate: a metabolic signal in inflammation.']

['Metabolic reprogramming is implicated in macrophage activation. In many cases, intermediates of the TCA cycle are involved in the response to hypoxic conditions brought about by inflammation.']

['yes']

Willis-Ekbom disease is also known as?

['Defining the phenotype of restless legs syndrome/Willis-Ekbom disease (RLS/WED): a clinical and polysomnographic study.', 'Clinical features variability between familial and sporadic restless legs syndrome/Willis-Ekbom disease (RLS/WED) has been previously reported. With this retrospective cohort study, we aimed to determine the clinical and polysomnographic characteristics of 400 RLS/WED patients. ', '"Emplotted Narratives" and Structured "Behavioral Observations" Supporting the Diagnosis of Willis-Ekbom Disease/Restless Legs Syndrome in Children with Neurodevelopmental Conditions.', 'BACKGROUND: Willis-Ekbom disease/restless legs syndrome (WED/RLS) seems to be a frequent cause of intractable chronic insomnia (ICI) but is under-recognized in children/adolescents with neurodevelopmental conditions (NDCs), as many patients do not have the ability to express the underlying "urge-to-move". ', 'Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is a common movement disorder characterised by an uncontrollable urge to move because of uncomfortable, sometimes painful sensations in the legs with a diurnal variation and a release with movement. ', 'OBJECTIVE: In the present study, we tested the hypothesis that having migraine in middle age is related to late-life parkinsonism and a related disorder, restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED).METHODS: The AGES-Reykjavik cohort (born 1907-1935) has been followed since 1967.', 'BACKGROUND: Reported prevalence of restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), varies from country to country, and methodologic inconsistencies limit comparison of data.', 'Restless legs syndrome (RLS), also known as Willis-Ekbom disease, is a sensory-motor neurological disorder with a circadian component.', 'There is no consensus about mechanisms underlying restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED)', 'Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is a common sensorimotor disorder that can generally be effectively managed in the primary care clinic', 'Reported prevalence of restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), varies from country to country, and methodologic inconsistencies limit comparison of data', 'Restless legs syndrome (RLS), also known as Willis-Ekbom Disease (WED), is a sensorimotor disorder for which the exact pathophysiology remains unclear', 'Restless legs syndrome (RLS), also known as Willis-Ekbom disease, is a sensorimotor disorder that can result in considerable sleep disruption', 'The SP790 study (ClinicalTrials.gov, NCT00136045) showed benefits of rotigotine over placebo in improving symptom severity of restless legs syndrome (RLS), also known as Willis-Ekbom disease, on the International Restless Legs Syndrome Study Group rating scale (IRLS), Clinical Global Impression item 1 (CGI-1), RLS 6-item questionnaire (RLS-6), and the RLS-quality of life questionnaire (RLS-QoL) in patients with moderate to severe idiopathic RLS', 'In the present study, we tested the hypothesis that having migraine in middle age is related to late-life parkinsonism and a related disorder, restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED).The AGES-Reykjavik cohort (born 1907-1935) has been followed since 1967', 'Restless leg syndrome (RLS), also known as Willis-Ekbom disease, is a condition that includes sensations such as crawling, tingling, or aching in the limbs and creates an urge to move', 'Recent genome-wide association studies (GWAS) for Caucasians identified several allelic variants associated with increased risk of developing restless legs syndrome (RLS), also known as Willis-Ekbom disease', 'Since the publication of the first European Federation of Neurological Societies (EFNS) guidelines in 2005 on the management of restless legs syndrome (RLS; also known as Willis-Ekbom disease), there have been major therapeutic advances in the field', 'BACKGROUND: Reported prevalence of restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), varies from country to country, and methodologic inconsistencies limit comparison of data. ', 'OBJECTIVES: Both restless legs syndrome ([RLS], also known as Willis-Ekbom Disease [WED]) and depression are common during pregnancy. ', 'Restless legs syndrome (RLS), also known as Willis-Ekbom disease, is a sensory-motor neurological disorder with a circadian component. ', 'OBJECTIVE: In the present study, we tested the hypothesis that having migraine in middle age is related to late-life parkinsonism and a related disorder, restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED). ', 'BACKGROUND: Since the publication of the first European Federation of Neurological Societies (EFNS) guidelines in 2005 on the management of restless legs syndrome (RLS; also known as Willis-Ekbom disease), there have been major therapeutic advances in the field. ', 'STUDY OBJECTIVES: Recent genome-wide association studies (GWAS) for Caucasians identified several allelic variants associated with increased risk of developing restless legs syndrome (RLS), also known as Willis-Ekbom disease. ', 'BACKGROUND: The SP790 study (ClinicalTrials.gov, NCT00136045) showed benefits of rotigotine over placebo in improving symptom severity of restless legs syndrome (RLS), also known as Willis-Ekbom disease, on the International Restless Legs Syndrome Study Group rating scale (IRLS), Clinical Global Impression item 1 (CGI-1), RLS 6-item questionnaire (RLS-6), and the RLS-quality of life questionnaire (RLS-QoL) in patients with moderate to severe idiopathic RLS. ', 'Psychological distress in patients with restless legs syndrome (Willis-Ekbom disease): a population-based door-to-door survey in rural Ecuador.', 'Since the publication of the first European Federation of Neurological Societies (EFNS) guidelines in 2005 on the management of restless legs syndrome (RLS; also known as Willis-Ekbom disease), there have been major therapeutic advances in the field.', 'Restless leg syndrome/Willis-Ekbom disease has brain iron deficiency that produces excessive dopamine and known genetic risks, some of which contribute to the brain iron deficiency.', 'Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is a common sensorimotor disorder that can generally be effectively managed in the primary care clinic.', 'Restless legs syndrome (RLS), also known as Willis-Ekbom disease, is a sensorimotor disorder that can result in considerable sleep disruption.', 'The SP790 study (ClinicalTrials.gov, NCT00136045) showed benefits of rotigotine over placebo in improving symptom severity of restless legs syndrome (RLS), also known as Willis-Ekbom disease, on the International Restless Legs Syndrome Study Group rating scale (IRLS), Clinical Global Impression item 1 (CGI-1), RLS 6-item questionnaire (RLS-6), and the RLS-quality of life questionnaire (RLS-QoL) in patients with moderate to severe idiopathic RLS.', 'Recent genome-wide association studies (GWAS) for Caucasians identified several allelic variants associated with increased risk of developing restless legs syndrome (RLS), also known as Willis-Ekbom disease.', 'In the present study, we tested the hypothesis that having migraine in middle age is related to late-life parkinsonism and a related disorder, restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED).The AGES-Reykjavik cohort (born 1907-1935) has been followed since 1967.', 'Reported prevalence of restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), varies from country to country, and methodologic inconsistencies limit comparison of data.', 'Restless legs syndrome (RLS), also known as Willis-Ekbom disease, is characterised by abnormal sensations in the legs as well as dysaesthesia.', 'STUDY OBJECTIVES: Recent genome-wide association studies (GWAS) for Caucasians identified several allelic variants associated with increased risk of developing restless legs syndrome (RLS), also known as Willis-Ekbom disease. Although the pathogenic mechanisms of RLS are not entirely understood, it is becoming increasingly evident that many diseases such as RLS can be attributed to an epistasis.', 'OBJECTIVE: Restless legs syndrome, now called Willis-Ekbom Disease (RLS/WED), is a sensorimotor-related sleep disorder. Little is known of the effect of RLS/WED on motor function.', 'OBJECTIVE: Restless legs syndrome, now called Willis-Ekbom Disease (RLS/WED), is a sensorimotor-related sleep disorder.', 'STUDY OBJECTIVES: Recent genome-wide association studies (GWAS) for Caucasians identified several allelic variants associated with increased risk of developing restless legs syndrome (RLS), also known as Willis-Ekbom disease.', 'Upper limb function is normal in patients with restless legs syndrome (Willis-Ekbom Disease).', 'BACKGROUND: The SP790 study (ClinicalTrials.gov, NCT00136045) showed benefits of rotigotine over placebo in improving symptom severity of restless legs syndrome (RLS), also known as Willis-Ekbom disease, on the International Restless Legs Syndrome Study Group rating scale (IRLS), Clinical Global Impression item 1 (CGI-1), RLS 6-item questionnaire (RLS-6), and the RLS-quality of life questionnaire (RLS-QoL) in patients with moderate to severe idiopathic RLS.', 'Restless legs syndrome (RLS), also known as Willis-Ekbom Disease (WED), is a sensorimotor disorder for which the exact pathophysiology remains unclear.', 'Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is a common movement disorder characterised by an uncontrollable urge to move because of uncomfortable, sometimes painful sensations in the legs with a diurnal variation and a release with movement.', 'The relationship among restless legs syndrome (Willis-Ekbom Disease), hypertension, cardiovascular disease, and cerebrovascular disease.', 'Willis-Ekbom Disease or Restless Legs Syndrome?', 'Living with Restless Legs Syndrome/Willis-Ekbom Disease.', 'Restless Legs Syndrome/Willis-Ekbom Disease Morbidity: Burden, Quality of Life, Cardiovascular Aspects, and Sleep.']

['Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is a common movement disorder characterized by an uncontrollable urge to move because of uncomfortable, sometimes painful sensations in the legs with a diurnal variation and a release with movement.']

['Restless legs syndrome']

What is the cause of Phthiriasis Palpebrarum?

['Phthiriasis palpebrarum is an uncommon cause of blepharoconjunctivitis in which Pthirus pubis infest the eyelashes. We report a case of unilateral phthiriasis palpebrarum with crab louse. ', 'BACKGROUND: Pediculosis capitis is a common parasitic infestation, whereas phthiriasis palpebrarum is an uncommon infection due to Phthirus pubis (pubic lice) inoculating the eyelashes and surrounding tissues of the eye. ', "Head lice typically do not infect the eyes, and given the different morphology of the lice on the patient's head and eyes, a diagnosis of phthiriasis palpebrarum was made. ", 'P. pubis can cause pruritic eyelid margins or unusual blepharoconjunctivitis. We present a case of phthiriasis palpebrarum in a 4-year-old boy.', 'INTRODUCTION: Phthiriasis palpebrarum is an ectoparasitosis in which Phthirus pubis infest the eyelashes.', 'In all cases, the diagnosis of phthiriasis palpebrarum was confirmed by parasitological examination of eyelashes, which revealed the presence of adult and nit forms of Phthirus pubis.', ' Based on the observation of numerous nits at the base of the eyelashes and the ectoparasite in the palpebral margin, a diagnosis of phthiriasis palpebrarum was made.', 'Phthiriasis palpebrarum (lice infestation of palpabrae) is a rarely reported disorder and may present as blepharoconjuctivitis. ', 'Phthiriasis palpebrarum (PP) is a rare eyelid infestation caused by phthirus pubis.', 'Phthiriasis palpebrarum, caused by Phthirus pubis, is an uncommon cause of blepharoconjunctivitis; therefore, this condition is easily misdiagnosed', 'Phthiriasis palpebrarum, caused by the phthirus pubis, is a rare cause of blepharoconjunctivitis, and is therefore often neglected', 'Phthiriasis palpebrarum is an uncommon cause of blepharoconjunctivitis in which Pthirus pubis infest the eyelashes', 'Phthiriasis palpebrarum is an unusual cause of blepharoconjunctivitis and may easily be overlooked because of the failure of physicians to recognize Phthirus pubis', 'Phthiriasis palpebrarum (PP) is a rare eyelid infestation caused by phthirus pubis', 'Phthiriasis palpebrarum, caused by the phthirus pubis, is a rare cause of blepharoconjunctivitis, and is therefore often neglected. ', 'Phthiriasis palpebrarum is an infestation of the eyelashes caused by the louse Pthirus pubis (Linnaeus, 1758). ', 'Phthiriasis palpebrarum, caused by Phthirus pubis, is an uncommon cause of blepharoconjunctivitis; therefore, this condition is easily misdiagnosed.', 'Phthiriasis palpebrarum, caused by the phthirus pubis, is a rare cause of blepharoconjunctivitis, and is therefore often neglected.', 'Phthiriasis palpebrarum is an uncommon cause of blepharoconjunctivitis in which Pthirus pubis infest the eyelashes. We report a case of unilateral phthiriasis palpebrarum with crab louse.', 'Phthiriasis palpebrarum is an infestation of the eyelashes caused by the louse Pthirus pubis (Linnaeus, 1758). We report a case of phthiriasis palpebrarum in a 6-year-old girl, which was initially misdiagnosed as allergic blepharoconjunctivitis.', 'Phthiriasis palpebrarum is an unusual cause of blepharoconjunctivitis and may easily be overlooked because of the failure of physicians to recognize Phthirus pubis.']

['Phthiriasis palpebrarum is a rare eyelid infestation caused by phthirus pubis.']

['Pthirus pubis']

Which acetylcholinesterase inhibitors are used for treatment of myasthenia gravis?

['Pyridostigmine is the most widely used acetylcholinesterase inhibitor.', 'For more than 50 years the acetylcholinesterase inhibitor pyridostigmine bromide has been the drug of choice in the symptomatic therapy for myasthenia gravis. ', 'The switch to SR-Pyr ameliorated the total quantified myasthenia gravis (QMG) score from 0.9 ± 0.5 to 0.6 ± 0.4 (p<0.001) in all patients and in the younger subgroup. This was accompanied by a significant improvement in the quality of life parameters. The health status valued by EuroQoL questionnaire improved from 0.626 ± 0.286 to 0.782 ± 0.186 (p<0.001). ', "Our results support the usefulness of SR-Pyr in an individualized therapeutic regimen to improve quality of life regardless of the patient's age in myasthenia gravis.", 'This review focuses on treatment of MG, mainly on the use of the AChE inhibitor pyridostigmine.', 'Despite a lack of data from well controlled clinical trials to support their use, AChE inhibitors, of which pyridostigmine is the most commonly used, are recommended as first-line therapy for MG. ', 'Novel AChE inhibitors with oral antisense oligonucleotides have been developed and preliminary results appear to be promising.', 'Except for one small and inconclusive trial of intranasal neostigmine, no randomised controlled trial has been conducted on the use of acetylcholinesterase inhibitors in myasthenia gravis. Response to acetylcholinesterase inhibitors in observational studies is so clear that a randomised controlled trial depriving participants in the placebo arm of treatment would be difficult to justify.', ' Current guidelines and recommendations for MG treatment are based largely on clinical experience, retrospective analyses and expert consensus. Available therapies include oral acetylcholinesterase (AChE) inhibitors for symptomatic treatment, and short- and long-term disease-modifying treatments.', 'Pyridostigmine has been used as a treatment for MG for over 50 years and is generally considered safe. It is suitable as a long-term treatment in patients with generalized non-progressive milder disease, and as an adjunctive therapy in patients with severe disease who are also receiving immunotherapy. ', 'Acetylcholinesterase inhibitors provide temporary, symptomatic treatment for all forms of myasthenia gravis. ']

['Pyridostigmine and neostygmine are acetylcholinesterase inhibitors that are used as first-line therapy for symptomatic treatment of myasthenia gravis. Pyridostigmine is the most widely used acetylcholinesterase inhibitor. Extended release pyridotsygmine and novel acetylcholinesterase inhibitors inhibitors with oral antisense oligonucleotides are being studied.']

['neostigmine', 'pyridostigmine']

Do A-type lamins bind euchromatin or heterochromatin?

['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(Δ8-11/Δ8-11) mice', 'Lmna(Δ9/Δ9) MEFs exhibit telomere shortening and heterochromatin alterations but do not activate cathepsin L-mediated degradation of 53BP1 and maintain expression of BRCA1 and RAD51', 'Lamin A Δexon9 mutation leads to telomere and chromatin defects but not genomic instability', 'Caspase-6 gene disruption reveals a requirement for lamin A cleavage in apoptotic chromatin condensation', 'The A- and B-type nuclear lamin networks: microdomains involved in chromatin organization and transcription.', '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', 'Lamin A/C, caspase-6, and chromatin configuration during meiosis resumption in the mouse oocyte', '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', 'Histone acetylation controls, almost exclusively, euchromatin protein dynamics; lamin A expression regulates heterochromatin protein dynamics, and G9a regulates both euchromatin and heterochromatin protein dynamics.', 'Histone acetylation controls, almost exclusively, euchromatin protein dynamics; lamin A expression regulates heterochromatin protein dynamics, and G9a regulates both euchromatin and heterochromatin protein dynamics.', 'Other proteins that reversibly interact with DNA, such as the lamins and nuclear pores, may have a role in the organization of DNA into transcribable euchromatin and nontranscribable heterochromatin.', 'Histone acetylation controls, almost exclusively, euchromatin protein dynamics; lamin A expression regulates heterochromatin protein dynamics, and G9a regulates both euchromatin and heterochromatin protein dynamics.', 'Other proteins that reversibly interact with DNA, such as the lamins and nuclear pores, may have a role in the organization of DNA into transcribable euchromatin and nontranscribable heterochromatin.', 'Role for A-type lamins in herpesviral DNA targeting and heterochromatin modulation.']

['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(Δ8-11/Δ8-11) mice', '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. On the other hand, 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(Δ8-11/Δ8-11) mice']

['Both euchromatin and heterochromatin']

What is the results of inactivated ANGPLT3?

['Although it appears by now that the main lipid pathways have been uncovered, and that only modulators or adaptor proteins such as those encoded by LDLRAP1, APOA5, ANGPLT3/4, and PCSK9 are currently being discovered', 'Angptl3 knockout mice have marked hypolipidemia, and heterozygous carriers of ANGPLT3, loss-of-function mutations were found among individuals in the lowest quartile of plasma triglycerides in population studies. ', ' 4 related individuals with primary hypolipidemia were found to be compound heterozygotes for ANGPTL3 loss-of-function mutations.', 'Complete ANGPTL3 deficiency caused by loss-of-function mutations of ANGPTL3 is associated with a recessive hypolipidemia']

['Complete ANGPTL3 deficiency caused by loss-of-function mutations of ANGPTL3 is associated with a recessive hypolipidemia']

['Recessive hypolipidemia']

What is the general function of H3K79 methylation?

['Saccharomyces cerevisiae cells lacking Dot1 exhibit a complete loss of H3K79 methylation and defects in heterochromatin-mediated silencing', 'Furthermore, an acidic patch at the C terminus of Dot1 is required for histone H4 tail binding in vitro, histone H3K79 di- and trimethylation in vivo, and proper telomere silencing', 'Recently, we demonstrated that in Drosophila spermatids, H3K79 methylation accompanies histone H4 hyperacetylation during chromatin reorganization', 'In human and mice spermatids, di- and tri-methylated H3K79 temporally overlapped with hyperacetylated H4 and thus accompanied chromatin reorganization.', 'Our results indicated that H3K79 methylation is a histone modification conserved in Drosophila, mouse, rat and human spermatids and may be a prerequisite for proper chromatin reorganization.', 'Here, we report the cytological distribution of the evolutionarily conserved DOT1L methyltransferase and the different H3K79 methylation states resulting from its activity (mono-, di- and tri-methylation; H3K79me1, me2 and me3, respectively) during meiotic prophase I in mouse spermatocytes. ', 'The heterochromatic centromeric regions and the sex body are enriched for H3K79me3', 'H3K79me patterns, combined with the cytological analysis of the H3.3, γH2AX, macroH2A and H2A.Z histone variants, are consistent with a differential role for these epigenetic marks in male mouse meiotic prophase I', 'We propose that H3K79me2 is related to transcriptional reactivation on autosomes during pachynema, whereas H3K79me3 may contribute to the maintenance of repressive chromatin at centromeric regions and the sex body.', 'We demonstrate that H3K79 dimethylation (H3K79me2) is converted to monomethylation (H3K79me1) at HOX loci as hematopoietic cells mature, thus coinciding with a decrease in HOX gene expression', 'H3K79 methylation: a new conserved mark that accompanies H4 hyperacetylation prior to histone-to-protamine transition in Drosophila and rat', 'Here we show for the first time that H3K79 methylation is a conserved feature preceding the histone-to-protamine transition in Drosophila melanogaster and rat.', 'The corresponding H3K79 methylation is a histone modification that precedes the histone-to-protamine transition and correlates with histone H4 hyperacetylation', 'In rat, H3K79 methylation also correlates with H4 hyperacetylation but not with active RNA polymerase II, which might point towards a conserved function in chromatin remodeling during the histone-to-protamine transition in both Drosophila and rat.', 'Methylation of histones H3 at positions K4 and K79 is involved in the initiation of recombination and the recombination checkpoint, respectively, during meiosis in the budding yeast. ', 'We confirmed the role of Set1-dependent H3K4 methylation in the formation of double-strand breaks (DSBs) in meiosis for the initiation of meiotic recombination, and we showed the involvement of Dot1 (H3K79 methylation) in DSB formation in the absence of Set1-dependent H3K4 methylation', 'Together, our studies identified the evolutionarily conserved YEATS domain as a novel acetyllysine-binding module and established a direct link between histone acetylation and DOT1L-mediated H3K79 methylation in transcription control.', 'Here, we unveil the role of Dot1-dependent histone H3 methylation at lysine 79 (H3K79me) in this meiotic surveillance mechanism.', 'Moreover, by genetically manipulating Dot1 catalytic activity, we find that the status of H3K79me modulates the meiotic checkpoint response.', 'Methylation of H3K79 is associated with chromatin at expressed genes, though it is unclear if this histone modification is required for transcription of all genes.', 'Thus, H3K79 methylation is not essential for transcription of Wnt-responsive or other intestinal genes, and intestinal toxicity is not imperative when DOT1L is rendered inactive in vivo.', 'Whereas mono-, di- and trimethylation states of lysines on histones typically have specific functions, no specific functions have been attributed so far to the different methylation states of histone H3 Lysine 79 (H3K79) generated by Dot1.', 'Indeed, gene silencing in yeast, which is dependent on Dot1, relied on global H3K79 methylation levels and not on one specific methylation state. Furthermore, our findings suggest that histone H2B ubiquitination affects H3K79 trimethylation by enhancing synthesis of all H3K79 methylation states. Our results suggest that multiple methylation of H3K79 leads to a binary code, which is expected to limit the possibilities for regulation by putative demethylases or binding proteins.', 'ChIP-chip analysis demonstrated histone H3 lysine 79 (H3K79) methylation profiles that correlated with Mll-AF4-associated gene expression profiles in murine ALLs and in human MLL-rearranged leukemias', 'To elucidate the mechanisms of genome reprogramming, we investigated histone H3 lysine 79 dimethylation (H3K79me2) and trimethylation (H3K79me3) in oocytes and preimplantation embryos via immunocytochemistry', 'n somatic cells and oocytes, H3K79me2 was observed throughout the genome, whereas H3K79me3 was localized in the pericentromeric heterochromatin regions in which there are no active genes.', 'Because H3K79me2 is considered an active gene marker, H3K79 methylation seems to have differing functions depending on the number of methyl groups added on the same residues. Both H3K79me2 and H3K79me3 decreased soon after fertilization, and the hypomethylated state was maintained at interphase (before the blastocyst stage), except for a transient increase in H3K79me2 at mitosis (M phase)', 'ChIP-chip tiling arrays revealed that levels of all degrees of genic H3K79 methylation correlate with mRNA abundance and dynamically respond to changes in gene activity.', 'Conversion of H3K79 monomethylation into di- and trimethylation correlated with the transition from low- to high-level gene transcription. We also observed enrichment of H3K79 monomethylation at intergenic regions occupied by DNA-binding transcriptional activators. Our findings highlight several similarities between the patterning of H3K4 methylation and that of H3K79 methylation in mammalian chromatin, suggesting a widespread mechanism for parallel or sequential recruitment of DOT1L and MLL to genes in their normal "on" state.', 'URA3 reporter assays also indicated that H3K79 methylation is required for HM silencing. Surprisingly, a genome-wide expression analysis of H3K79 methylation-defective mutants identified only a few telomeric genes, such as COS12 at TEL-VII-L, to be subject to H3K79 methylation-dependent natural silencing.', 'Furthermore, H3K79 methylation by Dot1 did not play a role in the maintenance of natural HML silencing', 'Since the discovery ∼10 years ago that Dot1 and its mammalian homolog, DOT1L (DOT1-Like), possess histone methyltransferase activity toward histone H3 Lys 79, great progress has been made in characterizing their enzymatic activities and the role of Dot1/DOT1L-mediated H3K79 methylation in transcriptional regulation, cell cycle regulation, and the DNA damage response', 'The histone 3 lysine 79 (H3K79) methyltransferase Dot1l has been implicated in the development of leukemias bearing translocations of the Mixed Lineage Leukemia (MLL) gene', 'Inhibition of histone H3K79 methylation selectively inhibits proliferation, self-renewal and metastatic potential of breast cancer', 'H3K79 methylation directly precedes the histone-to-protamine transition in mammalian spermatids and is sensitive to bacterial infections', 'in Drosophila spermatids, H3K79 methylation accompanies histone H4 hyperacetylation during chromatin reorganization', 'In human and mice spermatids, di- and tri-methylated H3K79 temporally overlapped with hyperacetylated H4 and thus accompanied chromatin reorganization', 'Our results indicated that H3K79 methylation is a histone modification conserved in Drosophila, mouse, rat and human spermatids and may be a prerequisite for proper chromatin reorganization', 'During spermiogenesis, haploid spermatids undergo extensive chromatin remodeling events in which histones are successively replaced by more basic protamines to generate highly compacted chromatin. Here we show for the first time that H3K79 methylation is a conserved feature preceding the histone-to-protamine transition in Drosophila melanogaster and rat', 'When acetylation was inhibited in cultured Drosophila testes, nuclei were smaller and chromatin was compact, Gpp was little synthesized, H3K79 methylation was strongly reduced, and protamines were not synthesized', 'Deficiency of H3K79 histone methyltransferase Dot1-like protein (DOT1L) inhibits cell proliferation', 'Dot1-like protein (DOT1L) is an evolutionarily conserved histone methyltransferase that methylates lysine 79 of histone H3 (H3K79). Mammalian DOT1L participates in the regulation of transcription, development, erythropoiesis, differentiation, and proliferation of normal cells', 'H3K79 methylation is a critical histone modification that regulates cell proliferation and would be a novel histone mark for aging and cancer', 'In rat, H3K79 methylation also correlates with H4 hyperacetylation but not with active RNA polymerase II, which might point towards a conserved function in chromatin remodeling during the histone-to-protamine transition in both Drosophila and rat']

['ChIP-chip tiling arrays revealed that levels of all degrees of genic H3K79 methylation correlate with mRNA abundance and dynamically respond to changes in gene activity. ', 'ChIP-chip tiling arrays revealed that levels of all degrees of genic H3K79 methylation correlate with mRNA abundance and dynamically respond to changes in gene activity. Conversion of H3K79 monomethylation into di- and trimethylation correlated with the transition from low- to high-level gene transcription. Findings highlight several similarities between the patterning of H3K4 methylation and that of H3K79 methylation in mammalian chromatin.\nMethylation of H3K79 is associated with chromatin at expressed genes, though it is unclear if this histone modification is required for transcription of all genes.', 'H3K79 methylation is a histone modification that correlates with histone H4 hyperacetylation prior to histone-to-protamine transition, and is accompanied by chromatin reorganization, playing an important role in the regulation of cell proliferation.']

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What is DeepCAGE?

["The cap analysis of gene expression (CAGE) technology has been established to detect transcriptional starting sites (TSSs) and expression levels by utilizing 5' cDNA tags and PCR. It has been reported that the amount of templates is proportional to the amplification efficiency of PCR. CAGE has been used as a key technique for analyzing promoter activity and finding new transcripts including alternative spliced products and noncoding transcripts. Here, we introduce more powerful tools such as deepCAGE, which can be utilized for high-throughput next-generation sequencing technology. DeepCAGE can produce much deeper transcriptome datasets and can reveal more details of the regulatory network.", "Here, we present a new method for high-throughput sequencing of 5' cDNA tags-DeepCAGE: merging the Cap Analysis of Gene Expression method with ultra-high-throughput sequence technology. ", 'DeepCAGE can also detect promoters used only in a small subset of cells within the complex tissue', 'DeepCAGE can produce much deeper transcriptome datasets and can reveal more details of the regulatory network.', 'DeepCAGE can also detect promoters used only in a small subset of cells within the complex tissue.', 'Here, we introduce more powerful tools such as deepCAGE, which can be utilized for high-throughput next-generation sequencing technology.', "Mammalian cells have at least 5-10 magnitudes more TSS than previously believed, and deeper sequencing is necessary to detect all active promoters in a given tissue. Here, we present a new method for high-throughput sequencing of 5' cDNA tags-DeepCAGE: merging the Cap Analysis of Gene Expression method with ultra-high-throughput sequence technology. ", 'Here, we introduce more powerful tools such as deepCAGE, which can be utilized for high-throughput next-generation sequencing technology. ', 'Using these data, we present evidence indicating a key role for the Arnt2 transcription factor in hippocampus gene regulation. DeepCAGE can also detect promoters used only in a small subset of cells within the complex tissue.', 'Here, we introduce more powerful tools such as deepCAGE, which can be utilized for high-throughput next-generation sequencing technology. DeepCAGE can produce much deeper transcriptome datasets and can reveal more details of the regulatory network.']

["The cap analysis of gene expression (CAGE) technology has been established to detect transcriptional starting sites (TSSs) and expression levels by utilizing 5' cDNA tags and PCR. It has been reported that the amount of templates is proportional to the amplification efficiency of PCR. CAGE has been used as a key technique for analyzing promoter activity and finding new transcripts including alternative spliced products and noncoding transcripts. DeepCAGE can be utilized for high-throughput next-generation sequencing technology. DeepCAGE can produce much deeper transcriptome datasets and can reveal more details of the regulatory network."]

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How many genes are imprinted in the human genome?

['Among approximately 70 known imprinted genes are some causing disorders affecting growth, metabolism and cancer predisposition. ', '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. ', '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.', 'To date, however, fewer than 100 imprinted genes have been identified in the human genome.', '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.', ' 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.', '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.', 'Our findings suggest that there are at most several hundred genes in the human genome that are universally imprinted.', 'To date, however, fewer than 100 imprinted genes have been identified in the human genome.', 'The Imprinted Gene Catalogue now has more than 200 genes listed, and estimates based on mouse models suggest many more may exist in humans. ', 'Our findings suggest that there are at most several hundred genes in the human genome that are universally imprinted. With samples of mRNA from appropriate tissues and a collection of informative cSNPs, a genome-wide search using this methodology could expand the list of genes that undergo genomic imprinting in a tissue- or temporal-specific manner.', 'We confirmed that PEG10 is paternally expressed, identified one gene (ZNF331) with multiple lines of data indicating it is imprinted, and predicted several additional imprinting candidate genes. Our findings suggest that there are at most several hundred genes in the human genome that are universally imprinted.', 'Our findings suggest that there are at most several hundred genes in the human genome that are universally imprinted.']

['Among approximately 70 known imprinted genes are some causing disorders affecting growth, metabolism and cancer predisposition. ', '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. To date, fewer than 100 imprinted genes have been identified in the human genome.']

[' fewer than 100']

Could hypophosphatemic rickets cause craniosynostosis?

['This study examines a series of patients with hypophosphatemic rickets and craniosynostosis to characterize the clinical course and associated craniofacial anomalies. ', 'Hypophosphatemic rickets and craniosynostosis: a multicenter case series.', 'A 20-year retrospective review identified patients with hypophosphatemic rickets and secondary craniosynostosis at 3 major craniofacial centers. ', 'Secondary craniosynostosis develops postnatally due to metabolic or mechanical factors. The most common metabolic cause is hypophosphatemic rickets, which has a variety of etiologies. Head shape changes occur later and with a more heterogeneous presentation compared with that of primary craniosynostosis.', 'Patients with multisutural involvement or X-linked hypophosphatemic rickets had a significant delay in presentation for craniosynostosis. ', 'Craniosynostosis can be gene-linked, or caused by metabolic diseases, such as rickets, which results from a deficiency or impaired metabolism of vitamin D, magnesium, phosphorus or calcium leading to hypomineralization of the bone. X-linked dominant hypophosphatemic rickets (XLHR) is the most prevalent genetic type of hypophosphatemic rickets and is caused by germ line mutations in the PHEX-gene. In XLHR, only few case reports of craniosynostosis were described.', 'Papilledema in the setting of x-linked hypophosphatemic rickets with craniosynostosis.', 'Case report of a 3-year-old female presenting with papilledema resulting from craniosynostosis secondary to XLH.', 'X-linked hypophosphatemic rickets and craniosynostosis.', 'X-linked hypophosphatemic (XLH) rickets is the most common form of metabolic rickets, and there have been reports linking XLH rickets to craniosynostosis. A clinical report of a patient with XLH rickets and craniosynostosis is presented with a review of literature. ', 'This may be the reason for the common association of craniosynostosis and XLH rickets. ', 'Craniosynostosis and associated craniofacial deformities, such as frontal bossing, often occur as symptoms of vitamin D-resistant rickets in children. Similar skull deformities develop in mice with X-linked dominant hypophosphatemia, the most common form of vitamin D-resistant rickets. ', 'The x-linked hypophosphatemic mouse is an animal model that can be used to study the role of vitamin D-resistant rickets in the development of craniosynostosis, to relate craniosynostosis to the development of associated skull deformities, and to test new treatment procedures.', 'Craniosynostosis secondary to rickets is rarely reported, but since neither rickets nor craniosynostosis is a reportable disease, the exact incidence of both diseases is unknown.', 'X-linked hypophosphatemic (XLH) rickets is the most common form of metabolic rickets, and there have been reports linking XLH rickets to craniosynostosis.', 'A clinical report of a patient with XLH rickets and craniosynostosis is presented with a review of literature.', 'METHODS A 20-year retrospective review identified patients with hypophosphatemic rickets and secondary craniosynostosis at 3 major craniofacial centers.', 'Bilateral coronal and sagittal synostosis in X-linked hypophosphatemic rickets: a case report.', 'X-linked hypophosphatemic rickets and sagittal craniosynostosis: three patients requiring operative cranial expansion: case series and literature review', 'X-linked hypophosphatemic rickets and craniosynostosis', 'X-linked hypophosphatemic (XLH) rickets is the most common form of metabolic rickets, and there have been reports linking XLH rickets to craniosynostosis', 'The recent observations of two new cases of X-linked hypophosphatemic rickets associated with premature closure of the sagittal suture prompted a review of similar cases seen in this institution.To review the clinical records and skull radiographs of 28 children with hypophosphatemic rickets in order to investigate the frequency and type of craniosynostosis and other cranial vault changes seen in these conditions and to review the literature for relevant findings.Clinical and imaging records were reviewed on 28 patients with hypophosphatemic rickets, all younger than 18 years', 'Those with multisutural synostosis presented at a significantly older age than patients with sagittal or bicoronal synostosis.Patients with multisutural involvement or X-linked hypophosphatemic rickets had a significant delay in presentation for craniosynostosis', 'Papilledema in the setting of x-linked hypophosphatemic rickets with craniosynostosis', 'INTRODUCTION TO THE OPHTHALMIC LITERATURE OF AN UNUSUAL CAUSE OF PAPILLEDEMA AND SUBSEQUENT OPTIC ATROPHY: X-linked hypophosphatemic rickets (XLH).Case report of a 3-year-old female presenting with papilledema resulting from craniosynostosis secondary to XLH.Early intervention with craniofacial surgery prevented the development of optic atrophy.Children with XLH should be screened for ophthalmic evidence of elevated intracranial pressure to aid early intervention and prevention of permanent loss of vision', 'CONCLUSIONS: Patients with multisutural involvement or X-linked hypophosphatemic rickets had a significant delay in presentation for craniosynostosis. ', 'Craniosynostosis can be gene-linked, or caused by metabolic diseases, such as rickets, which results from a deficiency or impaired metabolism of vitamin D, magnesium, phosphorus or calcium leading to hypomineralization of the bone. ', 'Similar skull deformities develop in mice with X-linked dominant hypophosphatemia, the most common form of vitamin D-resistant rickets.', 'Craniosynostosis in vitamin D-resistant rickets.', 'Craniosynostosis can be gene-linked, or caused by metabolic diseases, such as rickets, which results from a deficiency or impaired metabolism of vitamin D, magnesium, phosphorus or calcium leading to hypomineralization of the bone.', 'X-linked hypophosphatemic rickets and craniosynostosis.', 'X-linked hypophosphatemic (XLH) rickets is the most common form of metabolic rickets, and there have been reports linking XLH rickets to craniosynostosis.', 'Hypophosphatemic rickets and craniosynostosis: a multicenter case series.']

['Yes, hypophosphatemic rickets could cause craniosynostosis.']

['yes']

Is Lysine-specific demethylase 1 (LSD1) a critical regulator of hematopoiesis?

['Histone lysine-specific demethylase 1 (LSD1) protein is involved in Sal-like protein 4 (SALL4)-mediated transcriptional repression in hematopoietic stem cells', 'shRNA-mediated knockdown of LSD1 in hematopoietic precursor cells resulted in altered SALL4 downstream gene expression and increased cellular activity', 'our data revealed that histone demethylase LSD1 may negatively regulate SALL4-mediated transcription, and the dynamic regulation of SALL4-associated epigenetic factors cooperatively modulates early hematopoietic precursor proliferation', 'Lysine-specific demethylase 1 restricts hematopoietic progenitor proliferation and is essential for terminal differentiation', ' LSD1 represents a central regulator of hematopoietic stem and progenitor cells', ' LSD1-kd led to an extensive expansion of granulomonocytic, erythroid and megakaryocytic progenitors', 'LSD1-kd was associated with the upregulation of key hematopoietic genes', 'our findings distinguish LSD1 as a critical regulator of hematopoiesis', 'A short Gfi-1B isoform controls erythroid differentiation by recruiting the LSD1-CoREST complex through the dimethylation of its SNAG domain', 'Dynamic interaction between TAL1 oncoprotein and LSD1 regulates TAL1 function in hematopoiesis and leukemogenesis', 'Here, we reported that protein kinase A (PKA)-mediated phosphorylation regulates TAL1 interaction with the lysine-specific demethylase (LSD1) that removes methyl group from methylated Lys 4 on histone H3 tails. Phosphorylation of serine 172 in TAL1 specifically destabilizes the TAL1-LSD1 interaction leading to promoter H3K4 hypermethylation and activation of target genes that have been suppressed in normal and malignant hematopoiesis', 'LSD1-mediated epigenetic modification is required for TAL1 function and hematopoiesis', 'we show that TAL1 is associated with histone demethylase complexes containing lysine-specific demethylase 1 (LSD1), RE1 silencing transcription factor corepressor (CoREST), histone deacetylase 1 (HDAC1), and histone deacetylase 2 in erythroleukemia and T cell leukemia cells', 'we demonstrate that the TAL1-associated LSD1, HDAC1, and their enzymatic activities are coordinately down-regulated during the early phases of erythroid differentiation', 'TAL1 recruits LSD1 to the silenced p4.2 promoter in undifferentiated, but not in differentiated, murine erythroleukemia (MEL) cells', 'the dynamic regulation of TAL1-associated LSD1/HDAC1 complex may determine the onset of erythroid differentiation programs', 'Epigenetic regulation of hematopoietic differentiation by Gfi-1 and Gfi-1b is mediated by the cofactors CoREST and LSD1', 'Inhibition of CoREST and LSD1 perturbs differentiation of erythroid, megakaryocytic, and granulocytic cells as well as primary erythroid progenitors', 'we show that chromatin regulatory proteins CoREST and LSD1 mediate transcriptional repression by Gfi proteins. Lineage-restricted deployment of these cofactors through interaction with Gfi proteins controls hematopoietic differentiation', 'Taken together, our findings distinguish LSD1 as a critical regulator of hematopoiesis and point to severe, but reversible, side effects of a LSD1-targeted therapy.', 'LSD1-mediated epigenetic modification is required for TAL1 function and hematopoiesis.', 'Dynamic interaction between TAL1 oncoprotein and LSD1 regulates TAL1 function in hematopoiesis and leukemogenesis.', 'Phosphorylation of serine 172 in TAL1 specifically destabilizes the TAL1-LSD1 interaction leading to promoter H3K4 hypermethylation and activation of target genes that have been suppressed in normal and malignant hematopoiesis.', 'Histone lysine-specific demethylase 1 (LSD1) protein is involved in Sal-like protein 4 (SALL4)-mediated transcriptional repression in hematopoietic stem cells.', 'Taken together, our findings distinguish LSD1 as a critical regulator of hematopoiesis and point to severe, but reversible, side effects of a LSD1-targeted therapy.']

['Yes. Lysine-specific demethylase 1 restricts hematopoietic progenitor proliferation and is essential for terminal differentiation of erythroid, granulomonocytic and megakaryocytic progenitors.']

['yes']

Are Ultra-conserved elements (UCEs) enriched in segmental duplications?

['Here we address the process by which CNVs become depleted of UCEs.', '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.', 'Alternatively, lack of depletion for UCEs from cancer CNVs may reflect the diseased state. ', 'ULEs are located in intergenic or intronic regions and are depleted from segmental duplications.', 'Interestingly, human UCEs have been reported to be strongly depleted among segmental duplications and benign copy number variants (CNVs).', 'In addition, here we show that these elements are preferentially found in pathogenic deletions (enrichment ratio 3.6 vs. 0.5 in duplications), and that this association is not related with a higher content of genes.', 'In contrast, pathogenic CNVs lacking UCEs showed almost a threefold higher content in genes', 'We have demonstrated that nonexonic UCEs are depleted among segmental duplications (SDs) and copy number variants (CNVs) and proposed that their ultraconservation may reflect a mechanism of copy counting via comparison.', 'Mammalian ultraconserved elements are strongly depleted among segmental duplications and copy number variants.', 'Here, we show that UCEs are significantly depleted among segmental duplications and copy number variants. Notably, of the UCEs that are found in segmental duplications or copy number variants, the majority overlap exons, indicating, along with other findings presented, that UCEs overlapping exons represent a distinct subset.', 'Ultraconserved elements (UCEs) are strongly depleted from segmental duplications and copy number variations (CNVs) in the human genome, suggesting that deletion or duplication of a UCE can be deleterious to the mammalian cell.', 'Here, we show that UCEs are significantly depleted among segmental duplications and copy number variants.', 'We have demonstrated that nonexonic UCEs are depleted among segmental duplications (SDs) and copy number variants (CNVs) and proposed that their ultraconservation may reflect a mechanism of copy counting via comparison.', 'Here, we show that UCEs are significantly depleted among segmental duplications and copy number variants.', 'Ultraconserved elements (UCEs) are strongly depleted from segmental duplications and copy number variations (CNVs) in the human genome, suggesting that deletion or duplication of a UCE can be deleterious to the mammalian cell', 'melanogaster genome revealed depletion of the P-element and piggyBac insertions in and around the Sophophora UCEs.', 'Mammalian ultraconserved elements are strongly depleted among segmental duplications and copy number variants.', 'Here, we show that UCEs are significantly depleted among segmental duplications and copy number variants.', 'Interestingly, human UCEs have been reported to be strongly depleted among segmental duplications and benign copy number variants (CNVs).']

['ULEs are located in intergenic or intronic regions and are depleted from segmental duplications. In addition, here we show that these elements are preferentially found in pathogenic deletions (enrichment ratio 3.6 vs. 0.5 in duplications), and that this association is not related with a higher content of genes.', '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.', 'Ultraconserved elements (UCEs) are strongly depleted from segmental duplications and copy number variations (CNVs) in the human genome, suggesting that deletion or duplication of a UCE can be deleterious to the mammalian cell. These elements are most often located either overlapping exons in genes involved in RNA processing or in introns or nearby genes involved in the regulation of transcription and development.', 'Mammalian ultraconserved elements are strongly depleted among segmental duplications and copy number variants. Notably, of the UCEs that are found in segmental duplications or copy number variants, the majority overlap exons, indicating, along with other findings presented, that UCEs overlapping exons represent a distinct subset.', 'Here we address the process by which CNVs become depleted of UCEs. 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.', 'Mammalian ultraconserved elements are strongly depleted among segmental duplications and copy number variants.']

['no']

What is the mechanism of DNA replication termination in vertebrates?

['Eukaryotic DNA replication terminates when replisomes from adjacent replication origins converge. Termination involves local completion of DNA synthesis, decatenation of daughter molecules and replisome disassembly.', 'We show that DNA synthesis does not slow detectably as forks approach each other, and that leading strands pass each other unhindered before undergoing ligation to downstream lagging strands. Dissociation of the replicative CMG helicase (comprising CDC45, MCM2-7 and GINS) occurs only after the final ligation step, and is not required for completion of DNA synthesis, strongly suggesting that converging CMGs pass one another and dissociate from double-stranded DNA. This termination mechanism allows rapid completion of DNA synthesis while avoiding premature replisome disassembly']

['Eukaryotic DNA replication terminates when replisomes from adjacent replication origins converge. Termination involves local completion of DNA synthesis, decatenation of daughter molecules and replisome disassembly. DNA synthesis does not slow detectably as forks approach each other, and leading strands pass each other unhindered before undergoing ligation to downstream lagging strands. Dissociation of the replicative CMG helicase (comprising CDC45, MCM2-7 and GINS) occurs only after the final ligation step, and is not required for completion of DNA synthesis, strongly suggesting that converging CMGs pass one another and dissociate from double-stranded DNA. This termination mechanism allows rapid completion of DNA synthesis while avoiding premature replisome disassembly.']

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Describe ATR-16 syndrome.

['ATR-16 syndrome is due to alterations on chromosome 16p13.3, and is usually accompanied by alpha-thalassemia, mild-moderate mental retardation, dysmorphic facial features, skeletal and genitourinary malformations.', 'Alpha thalassemia retardation associated with chromosome16 (ATR-16 syndrome) is defined as a contiguous gene syndrome resulting from haploinsufficiency of the alpha-globin gene cluster and genes involved in mental retardation (MR). ', 'This is the fifth reported case of the ATR-16 syndrome (alpha-thalassemia retardation-16) not complicated by duplication or deletion of other chromosomes.', 'Familial mental retardation syndrome ATR-16 due to an inherited cryptic subtelomeric translocation, t(3;16)(q29;p13.3).']

['ATR-16 syndrome is due to alterations on chromosome 16p13.3, and is usually accompanied by alpha-thalassemia, mild-moderate mental retardation, dysmorphic facial features, skeletal and genitourinary malformations.']

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What gene is mutated in Sickle Cell Anemia?

['Sickle cell anemia (SCA) is an inherited blood disorder. SCA patients present clinical and hematologic variability that cannot be only explained by the single mutation in the beta-globin gene.', 'Sickle cell anemia (SCA) is an autosomal recessive disease caused by the HBB:c.20A>T mutation that leads to hemoglobin S synthesis.', 'Sickle cell anemia is caused by a single type of mutation, a homozygous A→T substitution in the ß globin gene.', 'Implementation of this approach for disorders resulting from mutations affecting the beta-globin gene (e.g., beta-thalassemia and sickle cell anemia), however, has been hampered by the inability to generate recombinant viruses able to efficiently and faithfully transmit the necessary sequences for appropriate gene expression.', "The allele-specific PCR approach has been modified by introducing a second mismatch at the 3'-penultimate link of the primer and used to identify the sickle cell anemia mutation (A-->T transversion in the sixth codon of the human beta-globin gene causing Glu-->Val substitution in the protein), thus obviating the problem of an interpretationally ambiguous 3'-terminal mismatch including T residue.", 'Sickle-cell anemia results from an A leads to T transversion in the second nucleotide of codon 6 of the beta-globin gene.', 'Sickle cell anemia is a genetic blood disorder arising from a point mutation in the beta-globin gene that leads to the replacement of glutamic acid residue by valine at the sixth position of the beta--chain of hemoglobin.', 'Sickle cell anemia is a genetic blood disease resulting from production of mutant beta-globin (beta(S)) and has severe clinical consequences. ']

['Sickle cell anemia (SCA) is an autosomal recessive disease caused by by the HBB:c.20A>T mutation that leads to hemoglobin S synthesis.', ' sca patients present clinical and hematologic variability that cannot be only explained by the single mutation in the beta-globin gene.']

['HBB']

Describe the mechanism of action of aliskiren.

['Preliminary assignment a direct renin inhibitor aliskiren enhances the diuretic, natriuretic and kaliyuretic effects of the drug. ', 'Aliskiren: An orally active renin inhibitor.', 'Optimization of this compound by Novartis led to the development of aliskiren - the only direct renin inhibitor which is clinically used as an antihypertensive drug.', 'Aliskiren is a new renin inhibitor of a novel structural class that has recently been shown to be efficacious in hypertensive patients after once-daily oral dosing.', 'Aliskiren is a direct renin inhibitor that interrupts the renin-angiotensin-aldosterone system (RAAS) at its rate-limiting step.', 'THE READER WILL GAIN: Aliskiren, the first approved renin inhibitor to reach the market, is a low-molecular-weight, orally active, hydrophilic non-peptide molecule that blocks angiotensin I generation. ', 'TAKE HOME MESSAGE: The DRI aliskiren is an effective antihypertensive agent that preliminary data suggests has a beneficial effect in CVD and CKD. ', 'Aliskiren is a novel molecule which blocks the renin-angiotensin-aldosterone system in its rate limiting step by renin inhibition.', 'After discovery of the first direct renin inhibitor, aliskiren, which blocks the renin-angiotensin-aldosterone system in the first rate limiting step, in addition to angiotensin-converting enzymes (ACE) and angiotensin-receptor blockers (ARB), renin has become an important target nowadays. ', 'Aliskiren, the first orally effective direct renin inhibitor, is an effective antihypertensive agent with distinctive properties including placebo-like tolerability, pharmacologic effects that persist after drug discontinuation, and a unique mechanism of action.', 'Aliskiren, the first direct renin inhibitor to reach the market, is a low-molecular-weight, orally active, hydrophilic nonpeptide. Aliskiren blocks Ang I generation, while plasma renin concentration increases because the drugs blocks the negative feed-back exerted by Ang II on renin synthesis.', 'Pharmacokinetics and pharmacodynamics of aliskiren, an oral direct renin inhibitor.', 'One drug that emerged from this effort is aliskiren, a direct human renin inhibitor that blocks the conversion of angiotensinogen to angiotensin I (Ang I).', 'With its unique mechanism of action, combining aliskiren with another RAAS-blocking agent that has a different mechanism of action may provide more comprehensive blockade of the RAAS, potentially conferring additional clinical benefits.', 'In the ALTITUDE trial the use of the direct renin inhibitor, aliskiren, was associated with hypotensive episodes and an excess of ischaemic stroke', 'Renin is the rate limiting enzyme of the RAAS and aliskiren is a highly potent and selective inhibitor of the human renin', 'Aliskiren, the first direct renin inhibitor to be approved for the treatment of hypertension, blocks the RAAS at its point of activation', 'With its unique mechanism of action, combining aliskiren with another RAAS-blocking agent that has a different mechanism of action may provide more comprehensive blockade of the RAAS, potentially conferring additional clinical benefits']

['Aliskiren is a low-molecular-weight, orally active, hydrophilic non-peptide molecule that blocks renin and consequential angiotensin I generation. Renin inhibition interrupts the renin-angiotensin-aldosterone system (RAAS).']

[]

Which disease phenotypes are associated to PRPS1 mutations?

['X-linked Charcot-Marie-Tooth disease, Arts syndrome, and prelingual non-syndromic deafness form a disease continuum: evidence from a family with a novel PRPS1 mutation', 'X-linked Charcot-Marie-Tooth disease type 5 (CMTX5), Arts syndrome, and non-syndromic sensorineural deafness (DFN2) are allelic syndromes, caused by reduced activity of phosphoribosylpyrophosphate synthetase 1 (PRS-I) due to loss-of-function mutations in PRPS1', 'Our findings demonstrate that CMTX5, Arts syndrome and DFN2 are phenotypic clusters on an intrafamilial continuum, including overlapping phenotypes even within individuals. The respective phenotypic presentation seems to be determined by the exact PRPS1 mutation and the residual enzyme activity, the latter being largely influenced by the degree of skewed X-inactivation', 'Mutations in PRPS1 are associated with a spectrum of non-syndromic to syndromic hearing loss', 'Gain of function mutations in PRPS1 cause a superactivity of the PRS-I protein whereas the loss-of-function mutations result in X-linked nonsyndromic sensorineural deafness type 2 (DFN2), or in syndromic deafness including Arts syndrome and X-linked Charcot-Marie-Tooth disease-5 (CMTX5)', 'X-linked Charcot-Marie-Tooth disease, Arts syndrome, and prelingual non-syndromic deafness form a disease continuum: evidence from a family with a novel PRPS1 mutation.', 'Mutations described thus far in PRPS1 are all missense mutations that result in PRS-I superactivity or in variable levels of decreased activity, resulting in X-linked Charcot-Marie-Tooth disease-5 (CMTX5), Arts syndrome, and X-linked nonsyndromic sensorineural deafness (DFN2).', 'Mutations described thus far in PRPS1 are all missense mutations that result in PRS-I superactivity or in variable levels of decreased activity, resulting in X-linked Charcot-Marie-Tooth disease-5 (CMTX5), Arts syndrome, and X-linked nonsyndromic sensorineural deafness (DFN2)', 'X-linked Charcot-Marie-Tooth disease type 5 (CMTX5), Arts syndrome, and non-syndromic sensorineural deafness (DFN2) are allelic syndromes, caused by reduced activity of phosphoribosylpyrophosphate synthetase 1 (PRS-I) due to loss-of-function mutations in PRPS1', 'X-linked Charcot-Marie-Tooth disease type 5 (CMTX5) is caused by mutations in the gene encoding phosphoribosyl pyrophosphate synthetase I (PRPS1)', 'Gain of function mutations in PRPS1 cause a superactivity of the PRS-I protein whereas the loss-of-function mutations result in X-linked nonsyndromic sensorineural deafness type 2 (DFN2), or in syndromic deafness including Arts syndrome and X-linked Charcot-Marie-Tooth disease-5 (CMTX5).', 'The spectrum of PRPS1-related disorders associated with reduced activity includes Arts syndrome, Charcot-Marie-Tooth disease-5 (CMTX5) and X-linked non-syndromic sensorineural deafness (DFN2).', 'X-linked Charcot-Marie-Tooth disease, Arts syndrome, and prelingual non-syndromic deafness form a disease continuum: evidence from a family with a novel PRPS1 mutation.']

['X-linked Charcot-Marie-Tooth disease type 5 (CMTX5), Arts syndrome, and non-syndromic sensorineural deafness (DFN2) are allelic syndromes, caused by reduced activity of phosphoribosylpyrophosphate synthetase 1 (PRS-I) due to loss-of-function mutations in PRPS1.']

['X-linked Charcot-Marie-Tooth disease type 5 (CMTX5)', 'Arts syndrome', 'Non-syndromic sensorineural deafness (DFN2)']

Does cucumber lower blood sugar in diabetics?

['The ethanolic extract of Cucumis sativus Linn, Cucumis melo utilissimum Roxb, Cucumis melo Linn, Benincasa hispida Thunb Cogn and Tricosanthes anguina Nees, when administered in 250 mg/kg dose, orally to rats failed to lower blood sugar or to depress the peak value, after glucose load.', 'Ethanolic extract of Tricosanthes dioica Roxb plant caused a significant lowering of blood sugar in fasted rats and depressed the peak value in glucose loaded single and longterm fed groups of rats. The ethanolic extract of the aerial part of T. dioica also induced significant depression in the peak values in the glucose loaded models.', 'The amount of sucrose in ordinary marinated foods, such as herring, cucumber, and common beet was negligible', 'Dietary saponins of sea cucumber ameliorate obesity, hepatic steatosis, and glucose intolerance in high-fat diet-fed mice.', 'In this study, we investigated the effects of saponins of sea cucumber (SSC) on high-fat diet-induced obesity, insulin resistance, and fatty liver in mice.', 'Mice administrated with 0.1% SSC had significantly decreased serum glucose and insulin levels, lower homeostatic model assessment for insulin resistance index, and area under the blood glucose curve, suggesting that insulin sensitivity is enhanced by dietary SSC.', '[Effects of sea cucumber cerebroside and its long-chain base on lipid and glucose metabolism in obese mice].', 'OBJECTIVE: To investigate the effect of sea cucumber cerebroside(SCC) and its long-chain base(LCB) on lipid and glucose metabolism in obese mice.', 'CONCLUSIONS: Sea cucumber cerebroside and its long-chain base can improve the glucose and lipid metabolism in obese mice.', 'The hitherto unknown glucose regulating role of three vegetable peels from cucurbitaceae family was evaluated. In a preliminary study, effects of ethanolic extracts of Cucurbita pepo, Cucumis sativus and Praecitrullus fistulosus peels were studied at 250 and 500\xa0mg\xa0kg(-1)\xa0d(-1) for 15\xa0days in the alterations in serum glucose and in hepatic lipid peroxidation (LPO) in male mice.', 'All the three peel extracts nearly reversed most of these changes induced by alloxan suggesting their possible role in ameliorating diabetes mellitus and related changes in serum lipids.', 'Antidiabetic activity of aqueous fruit extract of Cucumis trigonus Roxb. in streptozotocin-induced-diabetic rats.', 'Cucumis trigonus Roxb. (Cucurbitaceae) fruit is used in the Indian traditional medicine for the treatment of diabetes. Based on a number of reports on the blood glucose level reduction and the other complications of diabetes associated with some Cucurbitaceae plants, the antidiabetic effect of Cucumis trigonus fruit was investigated.', 'The antidiabetic activity of aqueous extract of Cucumis trigonus fruit was evaluated by using normal and streptozotocin-induced-diabetic rats.', 'The aqueous fruit extract of Cucumis trigonus has had beneficial effects in reducing the elevated blood glucose level and lipid profile of STZ-induced-diabetic rats.', 'Possible amelioration of atherogenic diet induced dyslipidemia, hypothyroidism and hyperglycemia by the peel extracts of Mangifera indica, Cucumis melo and Citrullus vulgaris fruits in rats.', 'Hitherto unknown efficacy of the peel extracts of Mangifera indica (MI), Cucumis melo (CM) and Citrullus vulgaris (CV) fruits in ameliorating the diet-induced alterations in dyslipidemia, thyroid dysfunction and diabetes mellitus have been investigated in rats.', 'Rats, treated simultaneously with either of the peel extracts reversed the CCT-diet induced increase in the levels of tissue LPO, serum lipids, glucose, creatinine kinase-MB and decrease in the levels of thyroid hormones and insulin indicating their potential to ameliorate the diet induced alterations in serum lipids, thyroid dysfunctions and hyperglycemia/diabetes mellitus.', 'Role of pectin from cucumber (Cucumis sativus) in modulation of protein kinase C activity and regulation of glycogen metabolism in rats.', 'The regulatory role of protein kinase C (PKC) in glycogen metabolism in pectin fed rats was investigated. Administration of pectin (5 g/kg body wt/day) from cucumber (Cucumis sativius L.) led to inhibitory effects on PKC activity in the liver of rats. In the brain and pancreas, PKC activity was significantly higher in pectin-treated rats as compared to the control group. Level of blood glucose was significantly lowered and the level of glycogen in the liver was significantly increased in pectin-administered rats.', 'Addition of fermented milk (yogurt) and pickled cucumber to a breakfast with a high-glycemic index bread significantly lowered postprandial glycemia and insulinemia compared with the reference meal. In contrast, addition of regular milk and fresh cucumber had no favorable effect on the metabolic responses.', 'Tolbutamide, Cucurbita ficifolia, Phaseolus vulgaris, Opuntia streptacantha, Spinacea oleracea, Cucumis sativus and Cuminum cyminum decrease significantly the area under the glucose tolerance curve and the hyperglycemic peak.', 'Two unsaturated fatty acids with potent α-glucosidase inhibitory activity purified from the body wall of sea cucumber (Stichopus japonicus).', 'In this study, 2 fatty acids with strong α-glucosidase-inhibitory activity, 7(Z)-octadecenoic acid and 7(Z),10(Z)-octadecadienoic acid, were purified and identified from sea cucumber. Therefore, sea cucumber fatty acids can potentially be developed as a novel natural nutraceutical for the management of type-2 diabetes.']

['Yes. Based on several scientific reports, ethanolic extract of cucumber and some other Cucurbitaceae plants are associated with a significant reduction of elevated blood glucose level, suggesting that cucumber could have antidiabetic activity.']

['yes']

Is the JNK pathway activated during liver regeneration?

['analysis of the role of JNK signaling pathway in regulating cell proliferation and apoptosis of rat liver regeneration', 'paths of JNK signaling pathway regulate cell proliferation and apoptosis in both LR', 'c-jun is not mandatory for mouse hepatocyte proliferation ', 'Mice lacking c-jun in the liver display impaired regeneration after partial hepatectomy (PH)', 'initial activity of the JNK pathway', 'use of Drosophila for the study of regeneration ', 'Loss of macroautophagy led to overactivation of the c-Jun N-terminal kinase (JNK)/c-Jun signaling pathway that induced cell death.', 'stress induced during intermittent selective clamping accelerates rat liver regeneration through JNK pathway', 'JNK2 promotes injury after mouse LT via the MPT', 'Jun N-terminal kinase 2 promotes graft injury via the mitochondrial permeability transition after mouse liver transplantation', 'add45beta promotes hepatocyte survival during liver regeneration in mice by modulating JNK signaling', 'basis for JNK suppression during liver regeneration and identify Gadd45beta as a potential therapeutic target in liver diseases', ' genetic inactivation of the JNK pathway results in impaired proliferation of fetal hepatoblasts in vitro and defective adult liver regeneration in vivo', 'enhancement of the activation of Jun N-terminal kinase and p38 mitogen-activated protein kinase caused by partial hepatectomy', ' arsenite induced apoptosis in the hepatocytes in vivo, through the enhancement of the activation of JNK and p38 MAPK caused by partial hepatectomy', 'Jun N-terminal kinase and p38 MAPK, but not Akt, was altered.', 'Although mechanical stress has been implicated in hepatic cirrhosis and liver regeneration following hepatectomy, the signaling pathway(s) that may be activated in hepatocytes in response to mechanical stress have not been determined', ' JNK, ERK and JAK2 inhibitors partially abrogated apoptosis and when used in combination reduced it to basal levels', 'induction of CD40-mediated cholangiocyte apoptosis requires JAK2-mediated phosphorylation of STAT3 as well as sustained JNK1/2, ERK1/2 activation', 'Jun-N-terminal kinase drives cyclin D1 expression and proliferation during liver regeneration', 'c-Jun-N-terminal kinase (JNK) pathway is strongly activated after partial hepatectomy (PH)', 'growth factors and cytokines are involved in liver regeneration', 'JAB1 (Jun activation domain-binding protein 1), a co-activator of AP-1, which is essential for liver regeneration, specifically interacts with intracellular HPO']

['Yes, the Jun-N-terminal kinase (JNK) pathway is strongly activated after partial hepatectomy.']

['yes']

Which are the main features of CREST and other ALS-linked proteins?

['Similar to several proteins implicated in ALS, CREST contains a prion-like domain and was reported to be a component of paraspeckles.', 'Like several other ALS-associated proteins, CREST is recruited to induced stress granules.', 'CREST and certain other ALS-linked proteins share several features implicated in ALS pathogenesis, namely the ability to aggregate, be recruited to stress granules and alter paraspeckle integrity.', 'Similar to several proteins implicated in ALS, CREST contains a prion-like domain and was reported to be a component of paraspeckles', ' Like several other ALS-associated proteins, CREST is recruited to induced stress granules', 'Our data indicate that CREST and certain other ALS-linked proteins share several features implicated in ALS pathogenesis, namely the ability to aggregate, be recruited to stress granules and alter paraspeckle integrity.', 'Similar to several proteins implicated in ALS, CREST contains a prion-like domain and was reported to be a component of paraspeckles', 'Our data indicate that CREST and certain other ALS-linked proteins share several features implicated in ALS pathogenesis, namely the ability to aggregate, be recruited to stress granules and alter paraspeckle integrity. A change in CREST levels in neurons which might occur under pathological conditions would have a profound negative effect on neuronal homeostasis.', 'Calcium-responsive transactivator (CREST) protein shares a set of structural and functional traits with other proteins associated with amyotrophic lateral sclerosis.', 'calcium-responsive transactivator (CREST) encoding gene have been recently linked to ALS.', 'A de novo mutation in the SS18L1 (also known as CREST or KIAA0693) gene encoding the calcium-responsive transactivator and/or neuronal chromatin remodeling complex subunit has recently been identified by exome sequencing of 47 sporadic ALS trios.', 'Here we report that profilin 1 and related protein profilin 2 are novel stress granule-associated proteins in mouse primary cortical neurons and in human cell lines and that ALS-linked mutations in profilin 1 alter stress granule dynamics, providing further evidence for the potential role of stress granules in ALS pathogenesis', 'Aggregation of ALS-linked FUS mutant sequesters RNA binding proteins and impairs RNA granules formation', 'In the present study, we examined the effects of ALS-linked FUS mutants on ALS-associated RNA binding proteins and RNA granules', 'Aggregation of ALS-linked FUS mutant sequesters RNA binding proteins and impairs RNA granules formation.']

['CREST and certain other ALS-linked proteins share several features implicated in ALS pathogenesis, namely the ability to aggregate, be recruited to stress granules and alter paraspeckle integrity.', 'Similar to several proteins implicated in ALS, CREST contains a prion-like domain and was reported to be a component of paraspeckles. Like several other ALS-associated proteins, CREST is recruited to induced stress granules. Our data indicate that CREST and certain other ALS-linked proteins share several features implicated in ALS pathogenesis, namely the ability to aggregate, be recruited to stress granules and alter paraspeckle integrity.', 'Like several other ALS-associated proteins, CREST is recruited to induced stress granules. ']

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Has Denosumab (Prolia) been approved by FDA?

['Denosumab is a RANK-ligand antibody that was approved by the FDA in 2010 for the prevention of skeletal fractures in patients with bone metastases from solid tumors.', ' The authors present the imaging findings and technical report of an attempted percutaneous vertebroplasty in the only patient found to be actively under treatment with denosumab after a retrospective review of the databank of patients with pathological fractures referred to the Department Radiology of the Ohio State University for percutaneous vertebroplasty (a total sample of 20 patients) since the FDA approval of denosumab (November 2010) until June of 2013 (a 30-month period).', 'On the basis of this data, the FDA approved denosumab for the treatment of patients whose GCTB is unresectable, or when surgery is likely to result in severe morbidity.', 'Denosumab (Prolia®) is a fully human monoclonal antibody for RANKL, which selectively inhibits osteoclastogenesis, being recently approved for the treatment of postmenopausal osteoporosis in women at a high or increased risk of fracture by the FDA in the United Sates and by the European Medicines Agency in Europe since June 2010.', 'Recent phase II clinical trials with denosumab in skeletally mature adolescents over age 12 years and adults with GCTB, have shown both safety and efficacy, leading to its accelerated US FDA approval on 13 June 2013. ', 'Zoledronic acid (ZA), an intravenously administered bisphosphonate, and Denosumab, a subcutaneously administered inhibitor of nuclear factor B ligand (RANKL), have already been approved by Food and Drug Administration (FDA) for their use in treatment of bone metastases.', 'These results led to the approval of denosumab by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA), for the prevention of SREs in adults with bone metastases from solid tumors, including breast cancer.', 'Alendronate, risedronate, zoledronic acid, denosumab, and teriparatide are Food and Drug Administration (FDA)-approved therapeutic options. ', 'Several of these therapies have recently been approved by the FDA to treat bone cancer pain (bisphosphonates, denosumab) and others are currently being evaluated in human clinical trials (tanezumab).', 'A fourth agent, denosumab (bone targeted therapy) was also recently approved by the FDA for patients with bone metastasis after showing a reduction in the occurrence of skeletal-related events. ', 'AHRQ published an updated review in March 2012 that summarized the benefits and risks of osteoporosis medications in treatment and prevention of osteoporosis, including bisphosphonates (aledronate, risedronate, ibandronate, zoledronic acid), parathyroid hormone, teriparatide, calcitonin, estrogens (for prevention in postmenopausal women), selective estrogen receptor modulators (raloxifene), and denosumab(approved by the FDA in 2010). ', 'Four new drugs have received U.S. Food and Drug Administration (FDA)-approval in 2010 and 2011: sipuleucel-T, an immunotherapeutic agent; cabazitaxel, a novel microtubule inhibitor; abiraterone acetate, a new androgen biosynthesis inhibitor; and denosumab, a bone-targeting agent. ', 'Recently, the US FDA and the EMA approved denosumab (a fully human monoclonal antibody) to treat skeletal-related events in bone-metastatic prostate cancer.', 'In addition to these new and emerging therapeutic agents, denosumab was approved for the prevention of skeletal complications in patients with bone metastases due to solid tumor malignancies, providing an alternative to zoledronic acid. ', 'Recently, denosumab was FDA-approved for prevention of SREs in patients with bone metastases from solid tumors. ', 'In the 2010s to date, an additional 3 antibodies (denosumab, belimumab, ipilimumab) have been approved and one antibody-drug conjugate (brentuximab vedotin) is undergoing regulatory review and may be approved in the US by August 30, 2011.', "We also review the evidence supporting the FDA's approval of denosumab (bone-targeted therapy) as a treatment option for men with CRPC and bony metastases. ", ' It has been approved for clinical use by the FDA in the US and by the European Medicines Agency in Europe since June 2010 (trade name Prolia(™), Amgen, Thousand Oaks, CA, USA). ', 'The fully human monoclonal antibody denosumab (Prolia(®)) has been recently approved by the European Medical Agency (EMEA) and the Food and Drug Administration (FDA) for the treatment of postmenopausal osteoporosis. ', 'Raloxifene and denosumab are only FDA approved for postmenopausal osteoporosis.', 'The new antiresorptive drug, denosumab, although FDA-approved only for postmenopausal women, has been shown in a study of men on ADT to increase bone density in spine, hip, and forearm and decrease vertebral fractures on x-ray. ', ' Since then, an additional six human mAbs have received FDA approval: panitumumab, golimumab, canakinumab, ustekinumab, ofatumumab and denosumab. ']

['Yes, Denosumab was approved by the FDA in 2010.']

['yes']

The MMR vaccine protects against what 3 viruses?

[' measles, mumps and rubella (MMR) vaccine ', 'Measles, mumps, rubella (MMR) vaccine is a live vaccine preparation containing attenuated strains of all 3 viruses.']

['The MMR vaccine provides immunity to measles, mumps and rubella.', ' measles, mumps and rubella (mmr) vaccine .']

['Measles', 'Mumps', 'Rubella']

Patients of which disease could be treated by utilizing knowledge obtained from experiments suppressing TDP-43 toxicity in yeast?

['Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease primarily affecting motor neurons. Mutations in the gene encoding TDP-43 cause some forms of the disease, and cytoplasmic TDP-43 aggregates accumulate in degenerating neurons of most individuals with ALS. Thus, strategies aimed at targeting the toxicity of cytoplasmic TDP-43 aggregates may be effective', 'The strongest suppressor of TDP-43 toxicity was deletion of DBR1, which encodes an RNA lariat debranching enzyme. We show that, in the absence of Dbr1 enzymatic activity, intronic lariats accumulate in the cytoplasm and likely act as decoys to sequester TDP-43, preventing it from interfering with essential cellular RNAs and RNA-binding proteins. Knockdown of Dbr1 in a human neuronal cell line or in primary rat neurons is also sufficient to rescue TDP-43 toxicity. Our findings provide insight into TDP-43-mediated cytotoxicity and suggest that decreasing Dbr1 activity could be a potential therapeutic approach for ALS']

['Amyotrophic lateral sclerosis (ALS).', 'The strongest suppressor of TDP-43 toxicity was deletion of DBR1, which encodes an RNA lariat debranching enzyme. We show that, in the absence of Dbr1 enzymatic activity, intronic lariats accumulate in the cytoplasm and likely act as decoys to sequester TDP-43, preventing it from interfering with essential cellular RNAs and RNA-binding proteins. Knockdown of Dbr1 in a human neuronal cell line or in primary rat neurons is also sufficient to rescue TDP-43 toxicity. Our findings provide insight into TDP-43-mediated cytotoxicity and suggest that decreasing Dbr1 activity could be a potential therapeutic approach for ALS ']

['Amyotrophic lateral sclerosis (ALS)']

What is the purpose of the Tokuhashi scoring system?

[' Those referring to representative scoring systems about predicting the survival of patients with metastatic spine tumors were used. The significance and limits of these scoring systems, and the future perspectives were described. Tokuhashi score, Tomita score, Baur score, Linden score, Rades score, and Katagiri score were introduced. ', 'BACKGROUND: We sought to identify preoperative factors significantly correlated with survival. We also aimed to evaluate the validity of the prognostic scores in the Tomita and Tokuhashi systems and discuss several aspects to improve the predictive accuracy of these systems. ', 'Accuracy of the revised Tokuhashi score in predicting survival in patients with metastatic spinal cord compression (MSCC).', 'PURPOSE: The revised Tokuhashi score has been widely used to evaluate indications for surgery and predict survival in patients with metastatic spinal disease.', 'CONCLUSION: We would conclude that although the predictive value of the Tokuhashi score in terms of survival time is at best modest (66 %), the fact that there were statistically significant differences in survival between the groups looked at in this paper indicates that the scoring system, and the components which it consists of, are important in the evaluation of these patients when considering surgery.', 'Tokuhashi Scoring System has limited applicability in the majority of patients with spinal cord compression secondary to vertebral metastasis.', 'The Tokuhashi Scoring System (TSS) is a widely used prognostic tool. ', 'Predictive value of Tokuhashi scoring systems in spinal metastases, focusing on various primary tumor groups: evaluation of 448 patients in the Aarhus spinal metastases database.', 'OBJECTIVE: To determine the specific predictive value of the Tokuhashi scoring system (T12) and its revised version (T15) in spinal metastases of various primary tumors.', 'Is Tokuhashi score suitable for evaluation of life expectancy before surgery in Iranian patients with spinal metastases?', 'BACKGROUND: One of the most important selection criteria for spinal metastases surgery is life expectancy and the most important system for this prediction has been proposed by Tokuhashi. The aim of this study was to evaluate predictive value of the Tokuhashi score for life expectancy in Iranian patients with spinal metastases one year after diagnosis.', 'CONCLUSIONS: Present study showed that the Tokuhashi revised scoring system may be practicable and highly predictive preoperative scoring system for patients with spinal metastases in Iran.', 'This study was to evaluate Tomita and Tokuhashi scoring systems in selecting surgical procedure and predicting prognosis of extradural spinal metastases.', 'Analysis of the predictive role and new proposal for surgical strategies based on the modified Tomita and Tokuhashi scoring systems for spinal metastasis.', 'We compared the Tokuhashi and Tomita scoring systems, two commonly used scoring systems for prognosis in spinal metastases.', '[The predictive value of the Tokuhashi revised scoring system for the survival time of patients with spinal metastases].', 'To evaluate the predictive value of the Tokuhashi revised scoring system for the life expectancy of patients with spinal metastases.', 'To determine the specific predictive value of the Tokuhashi scoring system (T12) and its revised version (T15) in spinal metastases of various primary tumors.', 'To evaluate the predictive values of Tokuhashi score, revised Tokuhashi score and Tomita score systems for life expectancy and treatment options in patients with spinal metastasis.', 'Tokuhashi Scoring System has limited applicability in the majority of patients with spinal cord compression secondary to vertebral metastasis', '[The predictive value of the Tokuhashi revised scoring system for the survival time of patients with spinal metastases]', 'To evaluate the predictive value of the Tokuhashi revised scoring system for the life expectancy of patients with spinal metastases', 'We compared the Tokuhashi and Tomita scoring systems, two commonly used scoring systems for prognosis in spinal metastases', 'PURPOSE: The revised Tokuhashi score has been widely used to evaluate indications for surgery and predict survival in patients with metastatic spinal disease. ']

['Tokuhashi scoring system was developed to predict life expectancy of patients with spinal metastases. The revised Tokuhashi score has been widely used to evaluate indications for surgery and predict survival in patients with metastatic spinal disease.']

[]

What is the number of long non coding RNAs in the human genome

['The recent ENCODE (Encyclopedia of DNA Elements) study reported 9,640 lncRNA loci in the human genome, which corresponds to around half the number of protein-coding genes. ', 'Over 18,000 transcripts are presently annotated as lncRNA, and encompass previously annotated classes of noncoding transcripts including large intergenic noncoding RNA, antisense RNA and processed pseudogenes', 'BACKGROUND: Over 10,000 long intergenic non-coding RNAs (lincRNAs) have been identified in the human genome.']

['Different estimates put currently the number of human long non coding RNAs between 10,000 and 20,000']

['between 10,000 and 20,000']

Which are the typical symptoms of Ménière's disease?

["To evaluate the onset of vertigo, hearing loss and tinnitus in Ménière's disease and the associated endolymphatic hydrops (EH) of the inner ear.", 'We suggest that a 3T MRI measurement should be carried out in patients with sensory-neural hearing loss, vertigo and tinnitus, 4 h after the intravenous injection of a gadolinium-contrast agent to verify the inner ear pathology. ', "Eleven of the 17425 veterans appeared to have typical Ménière's Disease. Their symptoms included attacks of vertigo, lasting between half an hour and a few hours and no more than 24 hours; the sensation of aural fullness; and tinnitus accompanied by a fluctuating or permanent low-tone hearing loss. ", "Diagnosis of Menière's Disease is based upon the wellknown labyrinthic syndrome (hypoacusia, tinnitus and dizziness) which manifests with the typical abscessual, recurrent and unforeseeable course. ", "Typical clinical manifestations of Ménière's disease (vertigo, sensorineural hearing loss and tinnitus) were found in 6/11 patients (54.5%) in the Lyme disease group.", "Among 93 patients presenting the typical symptoms of a Ménière's disease associating an unilateral fluctuating hearing loss of sensorineural type, tinnitus and vertiginous attacks lasting minutes to hours, 40 patients (43%) presented in their personal history a particular otologic insult in the ear which later on developed into the full Ménière's symptomatology, or a particular systemic disease with otologic manifestations. ", "Fourteen children (aged 14 years or younger) with typical Ménière's triad with cochlear sensorineural hearing loss, tinnitus, and intermittent vertigo attacks lasting from minutes to hours were investigated in four different neuro-otologic centers. ", "Among 93 patients presenting the typical symptoms of a Ménière's disease associating an unilateral fluctuating hearing loss of sensorineural type, tinnitus and vertiginous attacks lasting minutes to hours, 40 patients (43%) presented in their personal history a particular otologic insult in the ear which later on developed into the full Ménière's symptomatology, or a particular systemic disease with otologic manifestations.", 'To evaluate the onset of vertigo, hearing loss and tinnitus in Ménières disease and the associated endolymphatic hydrops (EH) of the inner ear.Multicentre evaluation of three patient groups.Disease-specific symptoms were reviewed among referred patients in a tertiary referral hospital in Finland and in members of a Finnish Ménière Association in Finland', 'In monosymptomatic patients with vertigo, tinnitus or hearing loss; EH was demonstrated in 55-90% of the patients either in the cochlea and/or the vestibulum of the symptomatic ear.Ménières disease often shows bilateral EH and comprises a continuum from a monosymptomatic disease to the typical symptom complex of the disease', "Typical clinical manifestations of Ménière's disease (vertigo, sensorineural hearing loss and tinnitus) were found in 6/11 patients (54.5%) in the Lyme disease group. ", 'Nine children, labeled as having "idiopathic Ménière\'s disease," developed the auditory and vestibular symptoms without any detectable causative factor.', "To evaluate the onset of vertigo, hearing loss and tinnitus in Ménière's disease and the associated endolymphatic hydrops (EH) of the inner ear.Multicentre evaluation of three patient groups.Disease-specific symptoms were reviewed among referred patients in a tertiary referral hospital in Finland and in members of a Finnish Ménière Association in Finland.", "In each twin pair, one twin had migraine and Ménière's disease, whereas the other experienced migraine and episodic vertigo without auditory symptoms.The frequent association of episodic vertigo, migraine, and Ménière's disease in closely related individuals, including identical twins supports the heritability of a migraine-Ménière's syndrome, with variable expression of the individual features of hearing loss, episodic vertigo, and migraine headaches.", "There has been literature, beginning with Ménière himself, suggesting a relationship between Ménière's disease and migraine-associated dizziness.", "In the characterizations of the migraine-associated dizziness, the signs and symptoms show overlap with those characterizing Meniere's disease."]

["The typical symptoms of Ménière's disease are:\n1) sensorineural hearing loss, \n2) vertigo and \n3) tinnitus."]

['sensorineural hearing loss', 'hypoacusia', 'vertigo', 'dizziness', 'tinnitus']

Is there an association between c-reactive protein concentrations and outcomes of subarachnoid hemorrhage patients?

['Besides the baseline characteristics, daily interleukin-6 (IL-6), procalcitonin, C-reactive protein levels, and leukocyte counts were prospectively measured until day 14 after subarachnoid hemorrhage. Occurrence of infectious complications and application of therapeutic hypothermia were assessed as confounding factors. The primary end point was outcome after 3 months, assessed by Glasgow Outcome Scale; the secondary end point was the occurrence of DINDs. RESULTS: : During a 3-year period, a total of 138 patients were included. All inflammatory parameters measured were higher in patients with unfavorable outcome (Glasgow Outcome Scale score, 1-3).', 'Twenty-three and 28 patients showed poor outcome and symptomatic vasospasm after SAH, respectively. Both preoperative and postoperative CRP levels were significantly higher in patients with a poor outcome compared with patients with a good outcome (P<0.05).', 'e area under the receiver operating characteristic curve of CRP measured on postoperative day 1 or 2 (CRP POD1-2) for predicting a poor clinical outcome was 0.870, and its cutoff point of 4 mg/dL had a sensitivity of 0.826 and a specificity of 0.843.', 'A high CRP level after aneurysm treatment was associated with severe neurological deterioration on admission, cerebral infarction, intracerebral hemorrhage, and surgical decompression (P<0.05).', 'CRP POD1-2, and not the preoperative CRP, was an independent factor in predicting symptomatic vasospasm (P<0.05). In patients with symptomatic vasospasm, an increase in the postoperative CRP was associated with the time profile of developing symptomatic vasospasm.', 'Postoperative CRP, especially CRP POD1-2, can be a useful prognostic factor for both poor outcome and symptomatic vasospasm in patients with aneurysmal SAH.', 'Serum CRP levels were related to severity of aSAH. Patients with lower GCS scores and higher Hunt and Hess and Fisher grades presented statistically significant higher serum CRP levels. Patients with higher serum CRP levels had a less favorable prognosis.', 'Increased serum CRP levels were strongly associated with worse clinical prognosis in this study.', 'After SAH, the value of C-reactive protein (CRP)--an acute phase sensitive inflammatory marker--as a prognostic factor has been poorly studied, with conflicting results.', 'Admission (18.0\u2009±\u200935.7 vs 8.5\u2009±\u20098.4 mg/l) and postoperative (41.0\u2009±\u200940.2 vs 21.1\u2009±\u200924.1 mg/l) CRP levels were higher (p\u2009<\u20090.001) in those with a poor outcome than in those with a favourable outcome, but CRP values did not predict delayed cerebral ischaemia or cerebral infarction.', 'Higher increase in CRP level between admission and postoperative morning, however, independently predicted poor outcome (p\u2009=\u20090.004).', 'CRP levels correlate with outcome but do not seem to predict delayed cerebral ischaemia or infarction after SAH.', 'Systemic oxygen consumption is associated with hsCRP levels in the first 14 days after SAH and is an independent predictor of DCI.', 'Intracranial hypertension was associated with an inflammatory response, indicating activation of the inflammatory cascade in the brain (ECF) and systemic circulation with high IL-6 and C-reactive protein (CRP) plasma levels after SAH, the latter associated with unfavourable outcome.', 'Patients with angiographic vasospasm had higher CRP measurements in serum and CSF, in a statistically significant fashion (p < 0.0001). Additionally, patients with higher CRP levels in serum and CSF had less favorable outcome in this cohort.', 'Furthermore, patients developing angiographically proven vasospasm demonstrated significantly elevated CRP levels in serum and CSF, and increased CRP measurements were strongly associated with poor clinical outcome in this cohort.', 'Finally, serum concentrations of ICAM-1, VCAM-1, and hsCRP during the early (P = .0055, P = .0266, and P = .0266) and late (P = .0423, P = .0041, and P = .0004) period were significantly higher in patients with DIND than in patients without DIND. CONCLUSIONS: Serum levels of ICAM-1, VCAM-1 and hsCRP during the early and late period following SAH correlate with DIND', 'CRP levels on days 5, 6, 7, and 8 were statistically significantly higher in the group of patients developing a DIND (P < 0.025, P < 0.016, P < 0.011, P < 0.0002).', 'Overall CRP values were higher with increasing severity of the initial ictus according to the Hunt and Hess Scale and to the outcome according to the Glasgow Outcome Scale from day 3 on.', 'The presented data do not prove that WBCs and CRP values have a direct contribution to the pathogenesis of ischemic complications following SAH, but it supports the assertion that inflammation may present a common pathogenic pathway in the development of such complications.', 'The CRP and TGF-beta1 levels in CSF are strongly concerned with communicating hydrocephalus after SAH.']

['Yes. Higher concentrations of C-reactive protein are associated with worse outcomes of subarachnoid hemorrhage patients.']

['yes']

Which deiodinases are best known to be present in brain?

['In brain, the presence of type III iodothyronine deiodinase (D3) seems to be important to maintain homeostasis of T(3) levels.', 'We were able to detect a protein fragment corresponding to the expected molecular mass (30 kDa) for type III deiodinase by means of Western blot analysis. RT-PCR as well as Northern blot analysis confirmed the presence of D3 mRNA in the cerebellum.', "The presence of 5D (type-III) together with our previous report of 5'-deiodinase (type-I in euthyroidism and type-II in hypothyroidism) shows that the isozymes of deiodinases in the neurohypophysis are quite similar to those in the brain."]

['All the 3 deiodinases (Type 1, Type 2 and Type 3 deiodinase) are present in the "brain" but Type 1 deiodinase is only found in neurohypophysis that cannot be actually considered true "brain tissue".']

['Type 2 deiodinase', 'Type 3 deiodinase']

What is promoted by ERAP1-ERAP2 dimerization?

['ERAP1-ERAP2 dimerization increases peptide-trimming efficiency.', 'In this study, we produced stabilized ERAP1-ERAP2 heterodimers and found that they produced several mature epitopes more efficiently than a mix of the two enzymes unable to dimerize. Physical interaction with ERAP2 changes basic enzymatic parameters of ERAP1 and improves its substrate-binding affinity. Thus, by bringing the two enzymes in proximity and by producing allosteric effects on ERAP1, dimerization of ERAP1/2 creates complexes with superior peptide-trimming efficacy. Such complexes are likely to enhance Ag presentation by cells displaying coordinated expression of the two enzymes.', 'In this study, we produced stabilized ERAP1-ERAP2 heterodimers and found that they produced several mature epitopes more efficiently than a mix of the two enzymes unable to dimerize.', 'Formation of heterodimers by ERAP1 and ERAP2 has been proposed to facilitate trimming of epitope precursor peptides, but the effects of dimerization on ERAP function remain unknown.', 'ERAP1-ERAP2 dimerization increases peptide-trimming efficiency', 'In this study, we produced stabilized ERAP1-ERAP2 heterodimers and found that they produced several mature epitopes more efficiently than a mix of the two enzymes unable to dimerize. ', 'In this study, we produced stabilized ERAP1-ERAP2 heterodimers and found that they produced several mature epitopes more efficiently than a mix of the two enzymes unable to dimerize.', 'ERAP1-ERAP2 dimerization increases peptide-trimming efficiency.']

['ERAP1-ERAP2 dimerization increases peptide-trimming efficiency.', 'ERAP1-ERAP2 dimerization increases peptide-trimming efficiency. ERAP1-ERAP2 heterodimers produce several mature epitopes more efficiently than a mix of the two enzymes unable to dimerize. Physical interaction with ERAP2 changes basic enzymatic parameters of ERAP1 and improves its substrate-binding affinity. Thus, by bringing the two enzymes in proximity and by producing allosteric effects on ERAP1, dimerization of ERAP1/2 creates complexes with superior peptide-trimming efficacy. Such complexes are likely to enhance Ag presentation by cells displaying coordinated expression of the two enzymes.', 'The endoplasmic reticulum aminopeptidases (ERAP)1 and ERAP2 play a critical role in the production of final epitopes presented by MHC class I molecules.']

[]

What is the function of R-spondin 1 and noggin in non-damaged gallbladders?

['R-spondin 1 and noggin facilitate expansion of resident stem cells from non-damaged gallbladders.', 'R-spondin 1 and noggin facilitate expansion of resident stem cells from non-damaged gallbladders.']

['R-spondin 1 and noggin facilitate expansion of resident stem cells from non-damaged gallbladders.']

['The expansion of resident stem cells.']

Is there any research that relates the function of Notch Signaling with Alzheimer Disease?

["RIP regulates signaling pathways by abrogating or releasing signaling molecules. Since the discovery, already >15 years ago, of its catalytic component, presenilin, and even much earlier with the identification of amyloid precursor protein as its first substrate, γ-secretase has been commonly associated with Alzheimer's disease. However, starting with Notch and thereafter a continuously increasing number of novel substrates, γ-secretase is becoming linked to an equally broader range of biological processes.", "In the last decade, increasing evidence has pointed out an important role of this pathway beyond embryonic development, indicating that Notch also displays a critical function in the mature brain of vertebrates and invertebrates. This pathway appears to be involved in neural progenitor regulation, neuronal connectivity, synaptic plasticity and learning/memory. In addition, Notch appears to be aberrantly regulated in neurodegenerative diseases, including Alzheimer's disease and ischemic injury", "Along with β-secretase, this enzyme produces the amyloid β-protein of Alzheimer's disease (AD) from the amyloid β-protein precursor. Because of its key role in the pathogenesis of AD, γ-secretase has been a prime target for drug discovery, and many inhibitors of this protease have been developed. The therapeutic potential of these inhibitors is virtually negated by the fact that γ-secretase is an essential part of the Notch signaling pathway, rendering the compounds unacceptably toxic upon chronic exposure", "High physiological concentrations of Aβ monomer induced angiogenesis by a conserved mechanism that blocks γ-secretase processing of a Notch intermediate, NEXT, and reduces the expression of downstream Notch target genes. Our findings allude to an integration of signaling pathways that utilize γ-secretase activity, which may have significant implications for our understanding of Alzheimer's pathogenesis vis-à-vis vascular changes that set the stage for ensuing neurodegeneration.", 'Aggregated forms of Aβ have a pathogenic role in Alzheimer disease and, thus, reducing the Aβ levels by inhibiting γ-secretase is a possible treatment strategy for Alzheimer disease. Regrettably, clinical trials have shown that inhibition of γ-secretase results in Notch-related side effects. Therefore, it is of great importance to find ways to inhibit amyloid precursor protein (APP) processing without disturbing vital signaling pathways such as Notch. Nicastrin (Nct) is part of the γ-secretase complex and has been proposed to be involved in substrate recognition and selection']

["Notch signaling is an evolutionarily conserved pathway, which is fundamental for neuronal development and specification. In the last decade, increasing evidence has pointed out an important role of this pathway beyond embryonic development, indicating that Notch also displays a critical function in the mature brain of vertebrates and invertebrates. This pathway appears to be involved in neural progenitor regulation, neuronal connectivity, synaptic plasticity and learning/memory. In addition, Notch appears to be aberrantly regulated in neurodegenerative diseases, including Alzheimer's disease and ischemic injury"]

['yes']

List proteins of lipids droplets

['The perilipins are a multi-protein family that targets lipid droplet surfaces and regulates lipid storage and hydrolysis.', 'or the abundance of the lipid droplet coat proteins (perilipins 2, 3, 4, and 5) between treatments. ', 'This study investigated the lipid droplet coat proteins perilipin 1 (PLIN1) and perilipin 2 (PLIN2) localization in pig skeletal muscle and their relationship with intramuscular fat (IMF) content.', 'Lipid droplets of mammalian cells are coated with one or more members of the PAT protein family, which serve important functions in regulating lipolysis. In this study, we investigate the mechanisms by which PAT family members, perilipin A, adipose differentiation-related protein (ADFP), and LSDP5, control lipolysis catalyzed by hormone-sensitive lipase (HSL), a major lipase in adipocytes and several non-adipose cells.', 'The coordination of lipid storage and utilization is regulated by the perilipin family of lipid droplet coat proteins [perilipin, adipophilin/adipocyte differentiation-related protein (ADRP), S3-12, tail-interacting protein of 47 kilodaltons (TIP47), and myocardial lipid droplet protein (MLDP)/oxidative tissues-enriched PAT protein (OXPAT)/lipid storage droplet protein 5 (LSDP5)].', ' Perilipin is a member of the evolutionarily related family of PAT proteins (Perilipin, Adipophilin, TIP47), which is defined by sequence similarity and association with lipid droplets. ']

['perilipins\nadipose differentiation-related protein\nlipid storage droplet protein 5 \ntail-interacting protein of 47 kilodaltons \nS3-12']

['perilipins', 'adipose differentiation-related protein', 'ADFP', 'LSDP5', 'lipid storage droplet protein 5', 'tail-interacting protein of 47 kilodaltons', 'TIP47', 'S3-12']

Which are the cardiac effects of thyronamines?

['Most recently, thyroid hormone derivatives were identified, the thyronamines which are decarboxylated thyroid hormones initiating physiological actions like lowering body temperature and heart rate, thereby acting in opposite direction to the classical thyroid hormones.', 'Intraperitoneal or central injection of 3-T(1)AM or T(0)AM into mice, rats, or Djungarian hamsters caused various prompt effects, such as metabolic depression, hypothermia, negative chronotropy, negative inotropy, hyperglycemia, reduction of the respiratory quotient, ketonuria, and reduction of fat mass. ', 'Functional effects have been observed after administration of exogenous T(1)AM: in the isolated heart, a negative inotropic and chronotropic action was produced, and the resistance to ischemic injury was increased, possibly as a consequence of an action on intracellular calcium homeostasis.', 'Octopamine, beta-phenylethylamine, and tryptamine produced a dose-dependent negative inotropic effect as shown by reduced cardiac output (IC(50)=109 microM, 159 microM, and 242 microM, respectively). In the same preparation a similar effect was produced by thyronamine and 3-iodothyronamine, with IC(50)=94 microM and 27 microM, respectively. ', 'A class of thyroid hormone metabolites has dramatic physiological effects on metabolism and heart rate by still-unknown mechanisms of action. ', 'In the mouse, thyronamines act rapidly in a nongenomic fashion to initiate hypothermia and decrease cardiac output and heart rate.']

['Thyronamines have negative chronotropy, negative inotropy; in particular thyronamines are considered negative inotropic agents', 'In the heart, thyronamines cause negative chronotropy, negative inotropy,reduced cardiac output and resistance to ischemic injury.']

['negative chronotropy', 'lower heart rate', 'negative inotropy', 'negative inotropism', 'resistance to ischemic injury', 'reduced cardiac output']

Are retroviruses used for gene therapy?

['Several immunodeficiencies have been treated successfully by stem cell-targeted, retroviral-mediated gene transfer with reconstitution of the immune system following infusion of the transduced cells.', 'In this work we have developed and tested a self-inactivating (SIN) gammaretroviral vector (SINfes.gp91s) containing a codon-optimized transgene (gp91(phox)) under the transcriptional control of a myeloid promoter for the gene therapy of the X-linked form of CGD (X-CGD).', ' We used a lentiviral vector encoding functional WASP to genetically correct HSPCs from three WAS patients and reinfused the cells after a reduced-intensity conditioning regimen', 'We used a lentiviral vector to transfer a functional ARSA gene into hematopoietic stem cells (HSCs) from three presymptomatic patients who showed genetic, biochemical, and neurophysiological evidence of late infantile MLD. ', 'We assessed lentiviral vectors (LVs) targeted to the EC surface marker CD105 for in vivo gene delivery.', 'gef and apoptin genes were cloned into a doxycycline-regulated retrovirus-mediated gene expression system.']

['Gene therapy is one of the most promising and active fields in therapeutic research. Gene therapy is a treatment option that introduces genetic material in vivo or ex vivo into the cells of an affected organism in order to: exchange a defective gene; manipulate a disease-related gene; or introduce an additional gene copy for overexpression of the encoded protein to generate a curative biological effect. Somatic gene therapy is gene transfer by a specific vector to a somatic cell; in contrast to germline gene therapy, the modification of the cell is restricted to the recipient and cannot be passed to her/his progeny. High efficiency of gene transfer, high specificity for the target cells, long-lasting expression of the transgene and safety without adverse reactions are the desired characteristics of an ideal vector for gene transfer.\nRetroviral (gretroviral and lentiviral) vectors have now been used in more than 350 gene-therapy studies. Retroviral vectors are particularly suited for gene-correction of cells due to long-term and stable expression of the transferred transgene(s), and also because little effort is required for their cloning and production. Several monogenic inherited diseases, mostly immunodeficiencies, can now be successfully treated.']

['yes']

What is the extracellular core "matrisome"?

['Over 300 ECM molecules have been defined as comprising the "core matrisome" in mammals through the analysis of whole genome sequences. ', 'Completion of genome sequences for many organisms allows a reasonably complete definition of the complement of extracellular matrix (ECM) proteins. In mammals this "core matrisome" comprises ∼300 proteins. ', 'we have developed a bioinformatic approach to predict the in silico "matrisome" defined as the ensemble of ECM proteins and associated factors. ']

['The "matrisome" is defined as the ensemble of extracellular matrix proteins (ECM) proteins and associated factors. The core matrisome have been defined in mammals through the analysis of whole genome sequences and comprises of ~ 300 proteins.']

[]

Is there any relationship between histone ubiquitylation and splicing?

['histone H2B-specific deubiquitinase and demonstrate that H2B deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons.', 'H2B monoubiquitylation (H2BK123ub1) marks introns in Saccharomyces cerevisiae', 'H2B ubiquitination by facilitating splicing', 'pre-mRNA splicing plays a critical role in histone H2B ubiquitination', 'unanticipated functional link between histone H2B ubiquitination and pre-mRNA splicing']

['Yes, in the case of histone H2B']

['yes']

What is the target of daratumumab?

['Dominantly daratumumab (anti-CD38) and elotuzumab (anti-CS1) showed extraordinary effectiveness in phase I/II trials.', 'In the last few weeks, the FDA approved three new therapies for multiple myeloma: ixazomib, the first oral proteasome inhibitor; and daratumumab and elotuzumab, two monoclonal antibodies that target CD38 and SLAMF7, respectively.', 'Of these agents, CD38-targeting antibodies have marked single agent activity in extensively pretreated MM, and preliminary results from studies with relapsed/refractory patients have shown enhanced therapeutic efficacy when daratumumab and isatuximab are combined with other agents', 'Furthermore, daratumumab, and probably also other CD38-targeting antibodies, interfere with blood compatibility testing and thereby complicate the safe release of blood products. Neutralization of the therapeutic CD38 antibody or CD38 denaturation on reagent red blood cells mitigates daratumumab interference with transfusion laboratory serologic tests. ', 'Daratumumab is a fully human anti-CD38 IgG1-κ monoclonal antibody (mAb) currently being evaluated in several Phase 2 and 3 clinical studies for the treatment of multiple myeloma (MM). ', 'In this study, we describe the cytotoxic mechanisms of action of daratumumab, a novel, high-affinity, therapeutic human mAb against a unique CD38 epitope.', 'This article focuses on the basic and clinical aspects of several emerging and promising novel MoAbs for MM, such as elotuzumab which targets CS1 and daratumumab which targets CD38.', 'Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors.', 'Daratumumab is a novel human CD38 monoclonal antibody which kills CD38+ multiple myeloma cells via antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity and apoptosis.To explore the effect of lenalidomide combined with daratumumab, we first carried out standard antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity assays in which the CD38+ multiple myeloma cell line UM-9 and primary multiple myeloma cells isolated from patients were used as target cells', 'However, we discovered, next to an expected effect of effector (natural killer cells/monocytes) to target (MM cells) ratio on ADCC, a significant association between CD38 expression and daratumumab-mediated ADCC (127 patients), as well as CDC (56 patients)', 'Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma.', 'Towards effective immunotherapy of myeloma: enhanced elimination of myeloma cells by combination of lenalidomide with the human CD38 monoclonal antibody daratumumab.', 'We studied daratumumab, a CD38-targeting, human IgG1� monoclonal antibody, in a phase 1-2 trial involving patients with relapsed myeloma or relapsed myeloma that was refractory to two or more prior lines of therapy.METHODS: In part 1, the dose-escalation phase, we administered daratumumab at doses of 0.005 to 24 mg per kilogram of body weight. ', 'Antibodies targeting CS-1 (elotuzumab) and CD38 (daratumumab) in particular are currently undergoing advanced clinical phase II/III trials.', 'In this study, we describe the cytotoxic mechanisms of action of daratumumab, a novel, high-affinity, therapeutic human mAb against a unique CD38 epitope. ', 'Daratumumab is a novel human CD38 monoclonal antibody which kills CD38+ multiple myeloma cells via antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity and apoptosis.To explore the effect of lenalidomide combined with daratumumab, we first carried out standard antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity assays in which the CD38+ multiple myeloma cell line UM-9 and primary multiple myeloma cells isolated from patients were used as target cells.', 'However, we discovered, next to an expected effect of effector (natural killer cells/monocytes) to target (MM cells) ratio on ADCC, a significant association between CD38 expression and daratumumab-mediated ADCC (127 patients), as well as CDC (56 patients).', "These mechanisms may also target nonplasma cells that express CD38, which prompted evaluation of daratumumab's effects on CD38-positive immune subpopulations.", 'In the last few weeks, the FDA approved three new therapies for multiple myeloma: ixazomib, the first oral proteasome inhibitor; and daratumumab and elotuzumab, two monoclonal antibodies that target CD38 and SLAMF7, respectively. <CopyrightInformation>©2016 American Association for Cancer Research.</C', 'This review focuses on the basic and clinical aspects of two emerging and promising novel MoAbs for MM, elotuzumab which targets CS1 and daratumumab which targets CD38.', 'In this regard, some of these novel agents seem promising, such as monoclonal antibodies (anti-CD38 - daratumumab or anti-CS1 - elotuzumab) or the kinesin protein inhibitor Arry-520.', 'This is likely to change within the next few years with a number of mAb therapies being assessed in late stage clinical trials, most notably, the anti-CS-1 mAb, elotuzumab, and the anti-CD38 mAb, daratumumab, which are currently being evaluated in Phase III clinical trials for MM.', 'CD38, a type II transmembrane glycoprotein highly expressed in hematological malignancies including multiple myeloma (MM), represents a promising target for mAb-based immunotherapy. In this study, we describe the cytotoxic mechanisms of action of daratumumab, a novel, high-affinity, therapeutic human mAb against a unique CD38 epitope.', 'CD38, a type II transmembrane glycoprotein highly expressed in hematological malignancies including multiple myeloma (MM), represents a promising target for mAb-based immunotherapy. In this study, we describe the cytotoxic mechanisms of action of daratumumab, a novel, high-affinity, therapeutic human mAb against a unique CD38 epitope. Daratumumab induced potent Ab-dependent cellular cytotoxicity in CD38-expressing lymphoma- and MM-derived cell lines as well as in patient MM cells, both with autologous and allogeneic effector cells.', 'One of novel fields for anti-MM therapeutic strategy is the development of immunotherapy using monoclonal antibodies (MoAbs) against myeloma-specific antigens. This article focuses on the basic and clinical aspects of several emerging and promising novel MoAbs for MM, such as elotuzumab which targets CS1 and daratumumab which targets CD38.', 'One of novel fields for anti-MM therapeutic strategy is the development of immunotherapy using monoclonal antibodies (MoAbs) against myeloma-specific antigens. This article focuses on the basic and clinical aspects of several emerging and promising novel MoAbs for MM, such as elotuzumab which targets CS1 and daratumumab which targets CD38. Both antigens are highly expressed in more than 90% of MM patients, and the clinical trials have shown promising anti-MM effects, especially in combination with immunomodulatory agent lenalidomide.', 'Multiple myeloma (MM) remains mostly incurable despite the recent progress in the treatment strategy. One of novel fields for anti-MM therapeutic strategy is the development of immunotherapy using monoclonal antibodies (MoAbs) against myeloma-specific antigens. This article focuses on the basic and clinical aspects of several emerging and promising novel MoAbs for MM, such as elotuzumab which targets CS1 and daratumumab which targets CD38.', 'In this study, we describe the cytotoxic mechanisms of action of daratumumab, a novel, high-affinity, therapeutic human mAb against a unique CD38 epitope. Daratumumab induced potent Ab-dependent cellular cytotoxicity in CD38-expressing lymphoma- and MM-derived cell lines as well as in patient MM cells, both with autologous and allogeneic effector cells.', 'In this study, we describe the cytotoxic mechanisms of action of daratumumab, a novel, high-affinity, therapeutic human mAb against a unique CD38 epitope. Daratumumab induced potent Ab-dependent cellular cytotoxicity in CD38-expressing lymphoma- and MM-derived cell lines as well as in patient MM cells, both with autologous and allogeneic effector cells. Daratumumab stood out from other CD38 mAbs in its strong ability to induce complement-dependent cytotoxicity in patient MM cells.', 'This article focuses on the basic and clinical aspects of several emerging and promising novel MoAbs for MM, such as elotuzumab which targets CS1 and daratumumab which targets CD38. Both antigens are highly expressed in more than 90% of MM patients, and the clinical trials have shown promising anti-MM effects, especially in combination with immunomodulatory agent lenalidomide.', 'Daratumumab is a novel human CD38 monoclonal antibody which kills CD38+ multiple myeloma cells via antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity and apoptosis.DESIGN AND METHODS: To explore the effect of lenalidomide combined with daratumumab, we first carried out standard antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity assays in which the CD38+ multiple myeloma cell line UM-9 and primary multiple myeloma cells isolated from patients were used as target cells.', 'Daratumumab stood out from other CD38 mAbs in its strong ability to induce complement-dependent cytotoxicity in patient MM cells.', 'We studied daratumumab, a CD38-targeting, human IgG1ê monoclonal antibody, in a phase 1-2 trial involving patients with relapsed myeloma or relapsed myeloma that was refractory to two or more prior lines of therapy.METHODS: In part 1, the dose-escalation phase, we administered daratumumab at doses of 0.005 to 24 mg per kilogram of body weight.', 'Collectively, our results show the versatility of daratumumab to effectively kill CD38-expressing tumor cells, including patient MM cells, via diverse cytotoxic mechanisms.', 'Amongst these antibodies, elotuzumab which targets SLAMF-7 and daratumumab which targets CD38, have been recently approved by FDA for patients with relapsed/refractory MM.', '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.', 'Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma.', 'We assessed daratumumab, a novel CD38-targeted monoclonal antibody, in patients with refractory multiple myeloma.', 'Daratumumab is a human monoclonal antibody that targets CD38, a cell surface protein that is overexpressed on multiple myeloma (MM) cells.', 'Furthermore, daratumumab, and probably also other CD38-targeting antibodies, interfere with blood compatibility testing and thereby complicate the safe release of blood products.', 'Daratumumab, a human IgGκ monoclonal antibody that targets CD38, induces direct and indirect antimyeloma activity and has shown substantial efficacy as monotherapy in heavily pretreated patients with multiple myeloma, as well as in combination with bortezomib in patients with newly diagnosed multiple myeloma.', 'Importantly, IFNγ was able to up-regulate CD38, the target of the therapeutic antibody daratumumab.']

['Daratumumab is a fully human anti-CD38 IgG1-κ monoclonal antibody. It is approved for treatment of multiple myeloma.']

['CD38']

List features of the Kaufman Oculocerebrofacial Syndrome.

['A pair of sisters was ascertained for multiple congenital defects, including marked craniofacial dysmorphisms with blepharophimosis, and severe psychomotor delay. ', 'Genetic syndromes involving both brain and eye abnormalities are numerous and include syndromes such as Warburg micro syndrome, Kaufman oculocerebrofacial syndrome, Cerebro-oculo-facio-skeletal syndrome, Kahrizi syndrome and others. ', 'Biallelic mutations of UBE3B have recently been shown to cause Kaufman oculocerebrofacial syndrome (also reported as blepharophimosis-ptosis-intellectual disability syndrome), an autosomal recessive condition characterized by hypotonia, developmental delay, intellectual disability, congenital anomalies, characteristic facial dysmorphic features, and low cholesterol levels.', 'BACKGROUND: Kaufman oculocerebrofacial syndrome (KOS) is a developmental disorder characterised by reduced growth, microcephaly, ocular anomalies (microcornea, strabismus, myopia, and pale optic disk), distinctive facial features (narrow palpebral fissures, telecanthus, sparse and laterally broad eyebrows, preauricular tags, and micrognathia), mental retardation, and generalised hypotonia. ', 'Kaufman oculocerebrofacial syndrome (KOS) is a rare autosomal recessive disorder characterized by severe mental retardation, microcephaly, long narrow face, ocular anomalies, and long thin hands and feet. ', 'Both showed psychomotor retardation, microcephaly, blepharophimosis and delayed growth as the main features; the infant also presented preauricular tags and large clitoris. ', 'Kaufman oculocerebrofacial syndrome (KOS) is a developmental disorder characterised by reduced growth, microcephaly, ocular anomalies (microcornea, strabismus, myopia, and pale optic disk), distinctive facial features (narrow palpebral fissures, telecanthus, sparse and laterally broad eyebrows, preauricular tags, and micrognathia), mental retardation, and generalised hypotonia.', 'Biallelic mutations of UBE3B have recently been shown to cause Kaufman oculocerebrofacial syndrome (also reported as blepharophimosis-ptosis-intellectual disability syndrome), an autosomal recessive condition characterized by hypotonia, developmental delay, intellectual disability, congenital anomalies, characteristic facial dysmorphic features, and low cholesterol levels', 'Kaufman oculocerebrofacial syndrome (KOS) is a developmental disorder characterised by reduced growth, microcephaly, ocular anomalies (microcornea, strabismus, myopia, and pale optic disk), distinctive facial features (narrow palpebral fissures, telecanthus, sparse and laterally broad eyebrows, preauricular tags, and micrognathia), mental retardation, and generalised hypotonia', 'Kaufman oculocerebrofacial syndrome (KOS) is a rare autosomal recessive disorder characterized by severe mental retardation, microcephaly, long narrow face, ocular anomalies, and long thin hands and feet', 'Kaufman oculocerebrofacial syndrome (KOS) is a rare autosomal recessive disorder characterized by severe mental retardation, microcephaly, long narrow face, ocular anomalies, and long thin hands and feet.']

['Clinical features of the Kaufman Oculocerebrofacial Syndrome include hypotonia, developmental delay, intellectual disability, low cholesterol levels, microcephaly, long narrow face, ocular anomalies, and long thin hands and feet.']

['hypotonia', 'developmental delay', 'intellectual disability', 'low cholesterol levels', 'microcephaly', 'long narrow face', 'ocular anomalies', 'long thin hands and feet']

Which is the defective protein causing the lysosomal storage disease Fabry?

['The lysosomal storage disorder Fabry disease is characterized by excessive globotriaosylceramide (Gb3) accumulation in major organs such as the heart and kidney. Defective lysosomal alpha-galactosidase A (Gla) is responsible for excessive Gb3 accumulation, and one cell sensitive to the effects of Gb3 accumulation is vascular endothelium.', 'Anderson-Fabry disease (referred to as Fabry disease) is an X-linked disorder characterized by a deficiency of the lysosomal enzyme alpha-galactosidase A and the subsequent accumulation in various tissues of globotriaosylceramide (Gb(3)), the main substrate of the defective enzyme.', 'Human alpha-galactosidase A (EC 3.2.1.22; alpha-Gal A) is the lysosomal exoglycosidase responsible for the hydrolysis of terminal alpha-galactosyl residues from glycoconjugates and is the defective enzyme causing Fabry disease (McKusick 301500).', 'Transgenic mice expressing a human mutant alpha-galactosidase with an R301Q substitution, which was found in a patient with a variant form of Fabry disease, were established.']

['Anderson-Fabry disease (referred to as Fabry disease) is an X-linked disorder characterized by a deficiency of the lysosomal enzyme alpha-galactosidase A and the subsequent accumulation in various tissues of globotriaosylceramide (Gb(3)), the main substrate of the defective enzyme.']

['alpha-galactosidase A']

What is Sotos syndrome?

['Sotos syndrome is a well-known overgrowth syndrome characterized by excessive growth during childhood, macrocephaly, distinctive facial appearance and learning disability', 'Sotos syndrome (SoS) is a multiple anomaly, congenital disorder characterized by overgrowth, macrocephaly, distinctive facial features and variable degree of intellectual disability', 'Sotos syndrome is a rare genetic disorder with a distinct phenotypic spectrum including overgrowth and learning difficulties', 'Sotos syndrome is an overgrowth syndrome with characteristic facial gestalt and mental retardation of variable severity.', 'Sotos syndrome (OMIM #117550) is a congenital syndrome characterized by overgrowth with advanced bone age, macrocephaly, and learning difficulties.', 'Sotos syndrome is a well-described multiple anomaly syndrome characterized by overgrowth, distinctive craniofacial appearance, and variable learning disabilities.', 'Sotos syndrome is an overgrowth syndrome characterised by pre- and postnatal overgrowth, macrocephaly, advanced bone age, and typical facial features.', 'Sotos syndrome is an autosomal dominant condition characterized by pre- and postnatal overgrowth (tall stature and macrocephaly), a typical facial appearance, advanced bone age, and developmental delay', 'Sotos syndrome is characterised by excessive pre and postnatal growth, a variable degree of learning difficulties and a recognisable facial appearance', "Sotos' syndrome, or cerebral gigantism, is a disorder of growth regulation.", 'Initial descriptions of Sotos syndrome included severe to mild mental retardation.', 'Sotos syndrome is another genetic and neurodevelopmental syndrome that can be associated with autistic as well as communication and language disorders.', 'Sotos syndrome is an overgrowth syndrome with characteristic facial gestalt and mental retardation of variable severity.', 'Sotos syndrome (OMIM #117550) is a congenital syndrome characterized by overgrowth with advanced bone age, macrocephaly, and learning difficulties.', 'Sotos syndrome is a well-described multiple anomaly syndrome characterized by overgrowth, distinctive craniofacial appearance, and variable learning disabilities.']

['Sotos syndrome is a well-known overgrowth syndrome characterized by excessive growth during childhood, macrocephaly, distinctive facial appearance and learning disability', 'Sotos syndrome is a rare genetic disorder with a distinct phenotypic spectrum including excessive growth during childhood, macrocephaly, distinctive facial appearance and learning disability.']

[]

What is the aim of the TRAP assay?

['Positive activity by the telomerase repeat amplification protocol (TRAP) was identified in cell extracts of Escherichia coli expressing a sequence-optimized hTERT gene', 'The regulatory role of PCDH10 in telomerase activity was confirmed by a telomeric repeat amplification protocol (TRAP) assay, and the biological functions of it were characterized by in vitro proliferation, migration, and invasion assays.', 'TRAP assay is a standard method for detecting telomerase activity in various tissues or cell lines. ', 'Telomerase activity was determined by TRAP assay.', 'The telomerase activity was evaluated by TRAP assay. ', 'The telomeric repeat amplification protocol (TRAP) represents an easy and rapid method for detection of telomerase activity in cells. A non-telomeric TS primer is extended by telomerase in the first step followed by the PCR amplification of the products. The PCR step renders this protocol very sensitive to detect telomerase activity at the single cell level making it compatible with the analysis of tumor samples. When run on a polyacrylamide gel, the PCR product is a characteristic ladder of bands due to the repetitive nature of telomeric DNA sequence. The densitometric analysis of the ladder allows the TRAP assay to be used for comparative quantification of telomerase activity in different samples.', 'Telomerase enzyme activity can be detected in whole cell lysates by a polymerase chain reaction (PCR)-based method referred to as the telomeric repeat amplification protocol (TRAP). ']

['Telomerase enzyme activity can be detected in whole cell lysates by a polymerase chain reaction (PCR)-based method referred to as the telomeric repeat amplification protocol (TRAP).']

['Telomerase enzyme activity can be detected in whole cell lysates by a polymerase chain reaction (PCR)-based method referred to as the telomeric repeat amplification protocol (TRAP).']

In which cells are A-type lamins expressed?

['Antibodies specific for mouse A/C lamins, human A/C lamins, or B lamins have been used to define the lamin complement as a function of time in culture and of cell type. ', 'dramatic increase in lamin A/C-positive cells was observed in the first 3 days of culture with both accessory cells and macrophages expressing lamins A/C as soon as such cell types could be identified. Parallel in vivo experiments showed that treatment with thioglycollate caused the percentage of lamin A/C-positive peritoneal macrophages to increase from 5 to 80% between Days 0 and 6.', 'Early embryonic cells and stem cells of mammals generally possess only lamin B while lamins A and C appear later during differentiation. ', 'Northern analysis and immunoblotting demonstrated that lamin A/C mRNA and protein were not detectable in some human cell lines whereas lamin B1 was always present', 'In the rat brain, lamin A and C are expressed in relatively equal amounts, while the expressions of lamin B1 and B2 vary depending on the cell type.', 'Hemopoietic cells from blood and bone marrow of mammals usually do not express lamins A/C but only lamin B, and this feature distinguishes these cells from the vast majority of somatic cells of the adult animal, which reveal lamins A/C as well as lamin B', 'These results demonstrated that EC cells devoid of lamins A and C nevertheless possessed the appropriate mechanisms for the localization and mitotic redistribution of exogenous lamins A and C.', 'Spermatogonia and seminoma cells, which follow a differentiation pathway along the spermatogenic lineage and show characteristics of germ cells, do not express A-type lamins.', 'While B-type lamins are expressed in almost all cell types, no A-type lamins are present in early vertebrate embryos or undifferentiated embryonal carcinoma cell lines.', 'B-type lamins are present in almost all cell types, but A-type lamins are expressed predominantly in differentiated cells, suggesting a role in maintenance of the differentiated state.', 'The expression of A-type lamins coincides with cell differentiation and as A-type lamins specifically interact with chromatin, a role in the regulation of differential gene expression has been suggested for A-type lamins.', 'In the literature it is conveyed that only B-type lamins are required in these early stages of development and that A-type lamins are not present or required until differentiation of specific cell types associated with specialized tissue is initiated.', 'B-type lamins are present in almost all cell types, but A-type lamins are expressed predominantly in differentiated cells, suggesting a role in maintenance of the differentiated state', 'The nuclear lamina is a meshwork of intermediate filaments adjacent to the inner nuclear membrane that in mammalian cells is predominantly composed of three proteins: lamin A, lamin B, and lamin C. Because lamin A and C (A-type lamins) expression has been shown to be lacking in several types of undifferentiated or rapidly proliferating cells, we investigated lamin expression in the human liver in conditions with hepatocellular regeneration (cirrhosis of various etiologies and macroregenerative nodules) and in hepatocellular carcinomas of various grades of differentiation', 'Our results identify the absence of A-type lamin expression as a novel marker for undifferentiated ES cells and further support a role for nuclear lamins in cell maintenance and differentiation', 'In an attempt to provide an additional meaning to lamin-genome contacts, a recent study characterized the association of gene promoters with A-type lamins in progenitor and differentiated cells', 'Previous studies have shown that lamin A/C is not expressed during mouse development before day 9, nor in undifferentiated mouse embryonic carcinoma cells. ', 'Ectopic expression of an A-type lamin does not interfere with differentiation of lamin A-negative embryonal carcinoma cells.', 'Intriguingly, expression of A-type lamins occurs concomitant with cell differentiation and embryonic development. ', 'While B-type lamins are expressed in almost all cell types, no A-type lamins are present in early vertebrate embryos or undifferentiated embryonal carcinoma cell lines. Intriguingly, expression of A-type lamins occurs concomitant with cell differentiation and embryonic development.', 'B-type lamins are present in almost all cell types, but A-type lamins are expressed predominantly in differentiated cells, suggesting a role in maintenance of the differentiated state. Previous studies have shown that lamin A/C is not expressed during mouse development before day 9, nor in undifferentiated mouse embryonic carcinoma cells.', 'On the basis of biochemical properties and sequence criteria, vertebrate lamin proteins are classified as either A- or B-type. While B-type lamins are expressed in almost all cell types, no A-type lamins are present in early vertebrate embryos or undifferentiated embryonal carcinoma cell lines.']

['In the rat brain, lamin A and C are expressed in relatively equal amounts, while the expressions of lamin B1 and B2 vary depending on the cell type. Human cells with reduced expression of the major B-type lamin protein, lamin B1, were generated using RNA interference. In addition, horizontal cells and a subpopulation of retinal ganglion cells expressed lamin A and C, while photoreceptor cells expressed neither lamin A nor C, and all other retinal neurons expressed lamin C only. Parallel in vivo experiments showed that treatment with thioglycollate caused the percentage of lamin A/C-positive peritoneal macrophages to increase from 5 to 80% between Days 0 and 6.', 'Early embryonic cells and stem cells of mammals generally possess only lamin B while lamins A and C appear later during differentiation. Northern analysis and immunoblotting demonstrated that lamin A/C mRNA and protein were not detectable in some human cell lines whereas lamin B1 was always present. Hemopoietic cells from blood and bone marrow of mammals usually do not express lamins A/C but only lamin B, and this feature distinguishes these cells from the vast majority of somatic cells of the adult animal, which reveal lamins A/C as well as lamin B.']

['late differentiating primary cells']

List algorithms suitable for predicting protein complexes

['Protein complexes are basic cellular entities that carry out the functions of their components', 'we have designed several features characterizing heterodimeric protein complexes based on genomic data sets, and proposed a supervised-learning method for the prediction of heterodimeric protein complexes. This method learns the parameters of the features, which are embedded in the naïve Bayes classifier', ' non-interacting proteins (NIPs) is important for training the algorithms to predict protein-protein interactions (PPIs) and for assessing the false positive rates of PPI detection efforts. We present the second version of Negatome,', 'Negatome is derived by manual curation of literature and by analyzing three-dimensional structures of protein complexes.', 'Identification of protein-ligand binding site is an important task in structure-based drug design and docking algorithms', 'Support Vector Machine (SVM) is used to cluster the pockets that are most likely to bind ligands with the attributes of geometric characteristics, interaction potential, offset from protein, conservation score and properties surrounding the pockets', 'Predicting protein complexes from protein-protein interaction data is becoming a fundamental problem in computational biology. The identification and characterization of protein complexes implicated are crucial to the understanding of the molecular events under normal and abnormal physiological conditions', 'a novel graph mining algorithm (PEWCC) to identify such protein complexes. Firstly, the algorithm assesses the reliability of the interaction data, then predicts protein complexes based on the concept of weighted clustering coefficient. To demonstrate the effectiveness of the proposed method, the performance of PEWCC was compared to several methods', 'We developed a novel PTM refinement algorithm, iPTMClust, which extends a recently introduced PTM refinement algorithm PTMClust and uses a non-parametric Bayesian model to better account for uncertainties in the quantity and identity of PTMs in the input data. The use of this new modeling approach enables iPTMClust to provide a confidence score per modification site that allows fine-tuning and interpreting resulting PTM predictions', 'We develop an algorithm for identifying protein complexes by considering these two types of complexes separately. We test our algorithm on a few yeast protein interaction networks, and show that our algorithm is able to identify complexes more accurately than existing algorithms. A software program NDComplex', 'Studying protein complexes is very important in biological processes since it helps reveal the structure-functionality relationships in biological networks and much attention has been paid to accurately predict protein complexes from the increasing amount of protein-protein interaction (PPI) data', ' To provide an investigation of the roles of edges in PPI networks, we show that the edges connecting less similar vertices in topology are more significant in maintaining the global connectivity, indicating the weak ties phenomenon in PPI networks', 'Identification of protein complexes in protein-protein interaction (PPI) networks is the first step in understanding the organization and dynamics of cell function.', 'We have developed an algorithm PROCOMOSS (Protein Complex Detection using Multi-objective Evolutionary Approach based on Semantic Similarity) for partitioning the whole PPI network into clusters, which serve as predicted protein complexes.', 'With the exponentially growing amount of protein sequence data, an exploration of new methods that predict protein interaction sites based solely on sequence information is becoming increasingly urgent', 'This paper describes a new method that predicts interaction sites based on protein sequences by integrating five different algorithms employing meta-method, Majority Vote and SVMhmm Regression techniques', "The 'metaPIS' web-server was implemented for meta-prediction.", ' In this paper, a novel protein complex identifying method, named EPOF, is proposed, using essential proteins and the local metric of vertex fitness', 'We compare the performances of EPOF to other ten previous algorithms, including EAGLE, NFC, MCODE, DPClus, IPCA, CPM, MCL, CMC, SPICi, and Core-Attachment.', ' We compare the performance of ProRank to some of the well known protein complex prediction methods (ClusterONE, CMC, CFinder, MCL, MCode and Core) in terms of precision and recall', 'In this paper we evaluated four different clustering algorithms using six different interaction datasets. We parameterized the MCL, Spectral, RNSC and Affinity Propagation algorithms and applied them to six PPI datasets produced experimentally by Yeast 2 Hybrid (Y2H) and Tandem Affinity Purification (TAP) methods', 'this paper, we present a new topology-based algorithm, HKC, to detect protein complexes in genome-scale PPI networks. HKC mainly uses the concepts of highest k-core and cohesion to predict protein complexes by identifying overlapping clusters. ', ' Protein complexes are important entities to organize various biological processes in the cell, like signal transduction, gene expression, and molecular transmission. In most cases, proteins perform their intrinsic tasks in association with their specific interacting partners, forming protein complexe', 'Macropol et al. proposed a protein complex prediction algorithm, called RRW, which repeatedly expands a current cluster of proteins according to the stationary vector of a random walk with restarts with the cluster whose proteins are equally weighted. In the cluster expansion, all the proteins within the cluster have equal influences on determination of newly added protein to the cluster. In this paper, we extend the RRW algorithm by introducing a random walk with restarts with a cluster of proteins, each of which is weighted by the sum of the strengths of supporting evidence for the direct physical interactions involving the protein. The resulting algorithm is called NWE (Node-Weighted Expansion of clusters of proteins). ', 'In this paper, we propose a new topological model by extending the definition of k-clique community of algorithm CPM and introduced distance restriction, and develop a novel algorithm called CP-DR based on the new topological model for identifying protein complexes', 'This paper also describes a random forest classifier which can effectively combine the structure-based prediction results and other functional annotations together to predict protein interactions', 'Here we explain the development and implementation of a novel Protein-Protein Interaction Prediction Engine termed PIPE. This tool is capable of predicting protein-protein interactions for any target pair of the yeast Saccharomyces cerevisiae proteins from their primary structure and without the need for any additional information or predictions about the proteins']

['Protein-Protein interactions (PPI) play a key role in determining the outcome of most cellular processes. The correct identification and characterization of protein interactions and the networks, which they comprise, is critical for understanding the molecular mechanisms within the cell. Large-scale techniques such as pull down assays and tandem affinity purification are used in order to detect protein interactions in an organism. Today, relatively new high-throughput methods like yeast two hybrid, mass spectrometry, microarrays, and phage display are also used to reveal protein interaction networks. Some suitable algorithms for predicting protein complexes are Naive Bayes Classifier, Negatome, Support Vector Machine, PEWCC, iPTMClust, NDComplex, PROCOMOSS, PPI network, metaPIS, EPOF, EAGLE, NFC, MCODE, DPClus, IPCA, CPM, MCL, CMC, SPICi, Core-Attachment, ProRank, ClusterONE, CFinder, Spectral, RNSC, Affinity Propagation, HKC, NWE, CP-DR, Struct2net and PIPE.']

['Naïve Bayes Classifier', 'Negatome', 'Support Vector Machine', 'PEWCC', 'iPTMClust', 'NDComplex', 'PROCOMOSS', 'PPI network', 'metaPIS', 'EPOF', 'EAGLE', 'NFC', 'MCODE', 'DPClus', 'IPCA', 'CPM', 'MCL', 'CMC', 'SPICi', 'Core-Attachment', 'ProRank', 'ClusterONE', 'CFinder', 'Spectral', 'RNSC', 'Affinity Propagation', 'HKC', 'NWE', 'CP-DR', 'Struct2net', 'PIPE']

Is zolpidem an antibiotic?

['Zolpidem is a short-acting imidazopyridine hypnotic drug that is metabolized mainly by CYP3A4.', 'FGIN-1-27 and alpidem, like the neurosteroid 3 alpha,21-dehydroxy-5 alpha-pregnane-20-one (THDOC), clonazepam and zolpidem (the direct allosteric modulators of gamma-aminobutyric acidA receptors) delay the onset of isoniazid and metrazol-induced convulsions.', 'olpidem is a new, short-acting hypnotic of imidazopyridine structure which binds selectively to a subpopulation of receptors involved in the action of benzodiazepines [omega 1 (BZ1) sites of the gamma-aminobutyric acidA receptors]', 'lpidem is a new, short-acting hypnotic of imidazopyridine structure which binds selectively to a subpopulation of receptors involved in the action of benzodiazepines [omega 1 (BZ1) sites of the gamma-aminobutyric acidA receptors]', 'In contrast, after repeated treatment with zolpidem, there was no change in its ability to produce sedative and anticonvulsant effects.', 'Zolpidem, a novel nonbenzodiazepine hypnotic. I. Neuropharmacological and behavioral effects.', 'Zolpidem [N,N,6-trimethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine-3-acetamide hemitartrate] is reported to be a rapid onset, short duration hypnotic that interacts at the benzodiazepine recognition site.', 'The imidazopyridine zolpidem is a short-acting hypnotic chemically distinct from benzodiazepines (BZs).', 'According to its peculiar neuropharmacologic activity (selectivity for the omega 1-BZ receptors), zolpidem is expected to be a pure hypnotic, without the other effects of BZs.']

['No, zolpidem is a short-acting imidazopyridine hypnotic drug']

['no']