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Which are the major transcription factors regulating glycolysis in mammals?

['myc regulates hepatic glycolysis', 'increase in c-Myc protein was able to induce liver glucose utilization and accumulation, and suggested that c-Myc transcription factor is involved in the control in vivo of liver carbohydrate metabolism', 'STAT3 is a negative regulator of aerobic glycolysis.', 'HIF1 alpha-mediated switches in the energy production of tumor cells from OXPHOS to glycolysis', 'NF-κB organizes energy metabolism networks by controlling the balance between the utilization of glycolysis and mitochondrial respiration. NF-κB inhibition causes cellular reprogramming to aerobic glycolysis under basal conditions and induces necrosis on glucose starvation', 'Hypoxia-inducible factor-1α (HIF-1α), which is a transcription factor that enhances glycolysis in cells in response to hypoxia', 'SIRT6 appears to function as a corepressor of the transcription factor Hif1alpha, a critical regulator of nutrient stress responses', 'SIRT6-deficient cells exhibit increased Hif1alpha activity and show increased glucose uptake with upregulation of glycolysis and diminished mitochondrial respiration', 'c-Myc regulates genes involved in the biogenesis of ribosomes and mitochondria, and regulation of glucose and glutamine metabolism', 'Myc regulates gene expression either directly, such as glycolytic genes including lactate dehydrogenase A (LDHA)', 'loss of the widely expressed transcription factor Oct1 induces a coordinated metabolic shift: mitochondrial activity and amino acid oxidation are increased, while glucose metabolism is reduced.', 'PVHL is a regulator of glucose metabolism', 'Carbohydrate response element-binding protein (ChREBP) is a glucose-responsive transcription factor that plays a critical role in the glucose-mediated induction of gene products involved in hepatic glycolysis and lipogenesis', 'Activation of NF-kappaB, by loss of p53, caused an increase in the rate of aerobic glycolysis and upregulation of Glut3', 'p53 restricts activation of the IKK-NF-kappaB pathway through suppression of glycolysis', 'cells express hypoxia-inducible factor (HIF)-1alpha, a transcription factor that responds to oxygen tension and regulates glycolysis', 'The HIF-1 dependent genic products are involved in tumoral angiogenesis, in the metabolic switch to anaerobic glycolysis and in prosurvival, proliferative and apoptotic mechanisms', 'he hypoxia-inducible transcription factor (HIF) regulates the expression of genes involved in angiogenesis, erythropoiesis and glycolysis', 'hypoxia-inducible factor-1, which activates a gene program associated with angiogenesis, glycolysis, and adaptation to pH', 'ChREBP (carbohydrate response element-binding protein) was recently identified as a candidate transcription factor in the glucose-signaling pathway', 'Hypoxia-inducible factor (HIF)-1 is a master transcription factor, which up-regulates glycolysis', '(Src) express HIF-1alpha protein under normoxia, which results in the expression of multiple HIF-1alpha target genes.', 'HIF-1 alpha can then translocate to the nucleus and facilitate transcription of numerous target genes, the majority of which are involved in glycolysis and angiogenesis via heterodimerisation with the beta subunit (HIF-1 beta/ARNT)', 'We previously observed that the c-Myc oncogenic transcription factor regulates lactate dehydrogenase A and induces lactate overproduction. We, therefore, sought to determine whether c-Myc controls other genes regulating glucose metabolism', 'overexpression of the c-Myc oncoprotein deregulates glycolysis through the activation of several components of the glucose metabolic pathway', 'HNF4alpha is critical for regulating glucose transport and glycolysis and in doing so is crucial for maintaining glucose homeostasis']

['The main positive transcriptional regulator of Glycolysis in mammals is HIF1-alpha (Hypoxia Inducible Factor 1a). HIF1-alpha is upregulated by the oncogenes c-Myc and Src, which therefore also positively regulate glycolysis. Several reports have linked HIF-1α induction with STAT3 activation. SIRT6 appears to function as a corepressor of the transcription factor Hif1alpha. NF-κB also stimulates glycolysis through the inhibition of PDK4 expression. Loss of the widely expressed transcription factor Oct1 induces a coordinated metabolic shift: mitochondrial activity and amino acid oxidation are increased, while glucose metabolism is reduced. HNF4alpha is critical for regulating glucose transport and glycolysis and in doing so is crucial for maintaining glucose homeostasis.']

['HIF1-alpha', 'c-Myc', 'Src', 'STAT3', 'SIRT6', 'NF-κB', 'Oct1', 'HNF4-alpha', 'PVHL']

Is vemurafenib effective for hairy-cell leukemia?

['CONCLUSIONS: A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia.', 'Our results strongly support and inform the clinical use of BRAF and MEK inhibitors in HCL.', 'The therapeutic approach of vemurafenib in treatment-refractory hairy cell leukemia is promising and offers an additional treatment option. ', 'Successful re-treatment of a relapsed V600E mutated HCL patient with low-dose vemurafenib.', 'Recent identification of the recurrent V600E BRAF mutation in a majority of HCL patients has led some teams to evaluate the clinical potential of vemurafenib, a BRAF V600 specific inhibitor in a limited number of refractory HCL patients. Recently, we published the case of an HCL patient successfully treated with a low dose of vemurafenib.', 'We present here the successful retreatment of this patient with a second line of vemurafenib. Our data suggest for the first time that vemurafenib at the dose of 240 mg once a day could be sufficient to maintain a complete hematological remission after an initial induction treatment with low-dose vemurafenib (2 × 240 mg) daily without inducing major toxicity.', 'The discovery of the BRAF mutation has created a therapeutic target exploited by oral inhibitors like vemurafenib and dabrafenib.', '[Successful use of vemurafenib in a patient with resistant hairy cell leukemia].', 'The frequent persistence of phosphorylated ERK-positive leukemic cells in bone marrow at the end of treatment suggests bypass reactivation of MEK and ERK as a resistance mechanism.CONCLUSIONS: A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia. ', 'A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia.', 'A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia.', 'The therapeutic approach of vemurafenib in treatment-refractory hairy cell leukemia is promising and offers an additional treatment option.']

['Yes, vemurafenib is highly effective in patients with relapsed or refractory hairy-cell leukemia.']

['yes']

Dracorhodin perchlorate was tested for treatment of which cancers?

['Dracorhodin perchlorate induced human breast cancer MCF-7 apoptosis through mitochondrial pathways.', 'It was reported that DP could induce apoptosis in human prostate cancer, human gastric tumor cells and human melanoma, but the cytotoxic effect of DP on human breast cancer was not investigated.', 'CONCLUSION: Therefore DP was a candidate for anti-breast cancer, DP induced apoptosis of MCF-7 through mitochondrial pathway.', 'Dracorhodin perchlorate has been recently shown to induce apoptotic cell death in cancer cells. However, the molecular mechanisms underlying these effects are unknown in human gastric tumor cells.', 'Dracorhodin perchlorate suppresses proliferation and induces apoptosis in human prostate cancer cell line PC-3.', 'The growth inhibition and pro-apoptosis effects of dracorhodin perchlorate on human prostate cancer PC-3 cell line were examined. ', 'Dracorhodin perchlorate, an anthocyanin red pigment, induces human premyelocytic leukemia HL-60 cell death through apoptotic pathway. ', 'Dracorhodin perchlorate, an anthocyanin red pigment, induces human melanoma A375-S2 cell death through the apoptotic pathway. ', 'Dracorhodin perchlorate inhibited proliferation of several tumor cell lines. ', 'The growth inhibition and pro-apoptosis effects of dracorhodin perchlorate on human prostate cancer PC-3 cell line were examined.', 'It was reported that DP could induce apoptosis in human prostate cancer, human gastric tumor cells and human melanoma, but the cytotoxic effect of DP on human breast cancer was not investigated. ', ' Dracorhodin perchlorate (DP) was a synthetic analogue of the antimicrobial anthocyanin red pigment dracorhodin. It was reported that DP could induce apoptosis in human prostate cancer, human gastric tumor cells and human melanoma, but the cytotoxic effect of DP on human breast cancer was not investigated.', ' The growth inhibition and pro-apoptosis effects of dracorhodin perchlorate on human prostate cancer PC-3 cell line were examined. After administration of 10-80 μmol/L dracorhodin perchlorate for 12-48 h, cell viability of PC-3 cells was measured by MTT colorimetry.', 'It was reported that DP could induce apoptosis in human prostate cancer, human gastric tumor cells and human melanoma, but the cytotoxic effect of DP on human breast cancer was not investigated. This study would investigate whether DP was a candidate chemical of anti-human breast cancer.', 'Dracorhodin perchlorate (DP) was a synthetic analogue of the antimicrobial anthocyanin red pigment dracorhodin. It was reported that DP could induce apoptosis in human prostate cancer, human gastric tumor cells and human melanoma, but the cytotoxic effect of DP on human breast cancer was not investigated.', 'The growth inhibition and pro-apoptosis effects of dracorhodin perchlorate on human prostate cancer PC-3 cell line were examined. After administration of 10-80 μmol/L dracorhodin perchlorate for 12-48 h, cell viability of PC-3 cells was measured by MTT colorimetry.']

['Dracorhodin perchlorate induce apoptosis in prostate cancer, gastric tumor, melanoma and premyelocytic leukemia.']

['prostate cancer', 'gastric tumor', 'melanoma', 'premyelocytic leukemia']

List receptors of the drug Cilengitide

['Cilengitide inhibits attachment and invasion of malignant pleural mesothelioma cells through antagonism of integrins αvβ3 and αvβ5.', 'Also, this dimer bound 3650-fold stronger and inhibited tumor cell migration and proliferation compared with cilengitide, an integrin-targeting peptidomimetic that performed poorly in recent clinical trials, suggesting promise for further therapeutic development.', 'As there is evidence for expression of the integrins αvβ3 and αvβ5 in MPM, there is a rationale for investigating the effects on MPM of cilengitide, a synthetic peptide inhibitor of integrin αv heterodimer with high specificity for αvβ3 and αvβ5. ', 'Gene knockdown experiments indicated that these effects of cilengitide were, at least partly, due to antagonism of αvβ3 and αvβ5.', 'Abstract The RGD cyclic pentapetide, cilengitide, is a selective inhibitor of αvβ3 and αvβ5 integrins and was developed for antiangiogenic therapy. ', 'Cilengitide is an RGD-peptide of sequence cyclo[RGDfNMeV] that was was developed as a highly active and selective ligand for the αvβ3 and αvβ5 integrin receptors.', 'RESULTS: αvβ5 was the predominantly expressed integrin heterodimer in meningiomas, whereas αvβ3 was mainly detected in tumor blood vessels. Application of up to 100 μg/mL cilengitide resulted in only mildly reduced proliferation/survival of meningioma cell lines. ', "UW479 cells expressed only αvβ5 integrin and were not sensitive to cilengitide, suggesting that cilengitide's action largely depends on αvβ3 inhibition.", "Cilengitide's action on glioma and neuroblastoma cells appears to be dependent on αvβ3 expression and sensitivity to anoikis. ", 'METHODS: For this purpose, nude rats bearing bone metastases were treated with cilengitide, a small molecule inhibitor of αvβ3 and αvβ5 integrins, from day 30 to 55 after tumor cell inoculation of MDA-MB-231 breast cancer cells (25 mg/kg, 5 days per week; n = 8 rats) and compared to control rats (n = 8). ', 'The αVβ3/αVβ5 integrin inhibitor cilengitide augments tumor response to melphalan isolated limb perfusion in a sarcoma model.', 'Cilengitide, a cyclized Arg-Gly-Glu(RGD)-containing pentapeptide that selectively blocks activation of the αvβ3 and αvβ5 integrins has shown encouraging activity in patients with glioblastoma as single agent, and in association with standard RT and temozolomide. ', ' Aza-amino acid scanning was performed on the cyclic RGD-peptide Cilengitide, cyclo[R-G-D-f-N(Me)V] 1, and its parent peptide cyclo(R-G-D-f-V) 2, potent antagonists of the αvβ3, αvβ5, and α5β1 integrin receptors, which play important roles in human tumor metastasis and tumor-induced angiogenesis. ', 'Cilengitide (EMD121974; Merck KGaA, Darmstadt, Germany) is a new drug targeting αvβ3 and αvβ5 integrins thanks to a specific peptide called RGD sequence. ', 'Cilengitide, a cyclic RGD-mimetic peptide of αvβ3 and αvβ5 integrins is in advanced clinical development in glioblastoma.', 'The purpose of this study was the assessment of the feasibility of dynamic positron emission tomography (PET) studies with fluorine-18 fluorodeoxyglucose ((18)F-FDG) to quantify effects of the cyclic Arg-Gly-Asp peptide cilengitide, which targets the ανβ 3 and ανβ 5 integrin receptors in rats with breast cancer bone metastases. ', 'We conducted a phase II study of cilengitide, a selective antagonist of α(v)β(3) and α(v)β(5) integrins, in non-metastatic castration resistant prostate cancer with rising PSA. ', 'AlphaVbeta3 and alphaVbeta5 integrins are overexpressed on both glioma cells and tumor vasculature. Cilengitide, the most advanced specific integrin inhibitor in oncology, has shown antitumor activity against glioma in early clinical trials. ', 'The aim of this study was to investigate the effect of inhibiting αvβ(3)/α(v) β(5) integrins by cilengitide in experimentally induced breast cancer bone metastases using noninvasive imaging techniques. For this purpose, nude rats bearing established breast cancer bone metastases were treated with cilengitide, a small molecule inhibitor of αvβ(3) and αvβ(5) integrins (75 mg/kg, five days per week; n = 12 rats) and compared to vehicle-treated control rats (n = 12). ', ' In conclusion, treatment of experimental breast cancer bone metastases with cilengitide resulted in pronounced antiresorptive and antitumor effects, suggesting that αvβ(3)/αvβ(5) inhibition may be a promising therapeutic approach for bone metastases.', 'Integrin antagonists, including the alphavbeta3 and alphavbeta5 inhibitor cilengitide, have shown encouraging activity in Phase II clinical trials and cilengitide is currently being tested in a Phase III trial in patients with glioblastoma. ', 'Cilengitide (cyclic peptidic alphavbeta3 and alphavbeta5 antagonist) is currently in clinical trials for anti cancer therapy.', 'PURPOSE: Cilengitide, an inhibitor of alphavbeta3 and alphavbeta5 integrin receptors, demonstrated minimal toxicity and durable activity across a wide range of doses administered to adults with recurrent glioblastoma multiforme (GBM) in a prior phase I study. ', 'In line with this concept, peptide ligands containing the Arginine-Glycine-Aspartate (RGD) triad, which display a strong affinity and selectivity to the alpha(V)beta(3) integrin, have been developed to target the tumor-associated cells expressing the alpha (V)beta (3) receptors. Among the validated ligands, the leader compound is the cyclic pentapeptide c[-RGDf(NMe)V-] (Cilengitide) developed by kessler et al. (J. Med. Chem., 1999, 42, 3033-3040). ', 'Assessment of the biological and pharmacological effects of the alpha nu beta3 and alpha nu beta5 integrin receptor antagonist, cilengitide (EMD 121974), in patients with advanced solid tumors.', 'BACKGROUND: Cilengitide, an antiangiogenic agent that inhibits the binding of integrins alpha(nu)beta(3) and alpha(nu)beta(5) to the extracellular matrix, was studied at two dose levels in cancer patients to determine the optimal biological dose. ', 'Cilengitide (EMD121974; NSC 707544), is a potent selective alphavbeta3 and alphavbeta5 integrin antagonist. ', 'Phase I and pharmacokinetic study of continuous twice weekly intravenous administration of Cilengitide (EMD 121974), a novel inhibitor of the integrins alphavbeta3 and alphavbeta5 in patients with advanced solid tumours.', 'A single-agent dose escalating phase I and pharmacokinetic study with Cilengitide, an inhibitor of the integrins alphavbeta3 and alphavbeta5, was performed to determine its safety and toxicity. ', 'This study was designed to determine whether, and how, the cyclic Arg-Gly-Asp peptide Cilengitide (EMD 121974), which targets the alpha(v)beta(3) integrin receptor expressed on neovasculature, could increase systemic RIT efficacy of therapy in a human breast cancer tumor model having mutant p53 and expressing bcl-2. ', 'The purpose of this study was the assessment of the feasibility of dynamic positron emission tomography (PET) studies with fluorine-18 fluorodeoxyglucose ((18)F-FDG) to quantify effects of the cyclic Arg-Gly-Asp peptide cilengitide, which targets the ανβ 3 and ανβ 5 integrin receptors in rats with breast cancer bone metastases']

['Cilengitide binds αvβ3 and αvβ5 integrins. It inhibits attachment and invasion of malignant cells. Thus, cilengitide is being tested for treatment of cancer patients.']

['αvβ3 integrin', 'ανβ5 integrin', 'αvβ5', 'αvβ3']

List viral vectors used in gene therapy.

['Not only can some genetically engineered adenoviral vectors achieve remarkably efficient and specific gene delivery to target cells, but they also may act as anticancer agents by selectively replicating within cancer cells', '. Using these criteria, we then evaluate approaches made to model PD using viral vectors to date, including both adeno-associated viruses and lentiviruses', 'Recombinant AAV (rAAV) vectors are a suitable vector for gene therapy studies because of desired characteristics such as low immunogenicity, transfection of non-dividing and dividing cells, and long-term expression of the transgene.', "Over the last five years, the number of clinical trials involving AAV (adeno-associated virus) and lentiviral vectors continue to increase by about 150 trials each year. For continued success, AAV and lentiviral expression cassettes need to be designed to meet each disease's specific needs. ", 'describes commonly used gene therapeutics (herpes simplex viral vector (HSV) and adeno-associated viral vector (AAV))', 'This study examined the efficacy of gene therapy of lung adenocarcinoma using specifically controlled type I herpes simplex virus recombinant vector expressing Gibbon ape leukemia virus membrane fusion glycoprotein gene (GALV.fus)']

['adeno-associated viruses\nlentiviruses\nherpes simplex viral vector']

['adeno-associated viruses', 'lentiviruses', 'herpes simplex viral vector']

What is CRISPRi?

['CRISPR interference (CRISPRi) for sequence-specific control of gene expression.', '(CRISPRi), for targeted silencing of transcription in bacteria and human cells. The CRISPRi system is derived from the Streptococcus pyogenes CRISPR (clustered regularly interspaced palindromic repeats) pathway, requiring only the coexpression of a catalytically inactive Cas9 protein and a customizable single guide RNA (sgRNA). The Cas9-sgRNA complex binds to DNA elements complementary to the sgRNA and causes a steric block that halts transcript elongation by RNA polymerase, resulting in the repression of the target gene. ', 'CRISPRi provides a simplified approach for rapid gene repression within 1-2 weeks. The method can also be adapted for high-throughput interrogation of genome-wide gene functions and genetic interactions, thus providing a complementary approach to RNA interference, which can be used in a wider variety of organisms.', 'More recently, a new system for genome engineering based on the bacterial CRISPR-Cas9 system (Clustered Regularly Interspaced Short Palindromic Repeats), was shown to have the potential to also regulate gene expression at both transcriptional and post-transcriptional level in a more specific way.', 'CRISPR interference (CRISPRi), for targeted silencing of transcription in bacteria and human cells. ', 'RNA-seq analysis indicates that CRISPR interference (CRISPRi)-mediated transcriptional repression is highly specific.', 'Our results establish that the CRISPR system can be used as a modular and flexible DNA-binding platform for the recruitment of proteins to a target DNA sequence, revealing the potential of CRISPRi as a general tool for the precise regulation of gene expression in eukaryotic cells', 'CRISPR interference (CRISPRi) for sequence-specific control of gene expression', 'We show that delivery of the CRISPRi system is successful and can specifically repress a reporter gene in recipient cells, thereby establishing a new tool for gene regulation across bacterial cells and potentially for bacterial population control.', 'This system, which we call CRISPR interference (CRISPRi), can efficiently repress expression of targeted genes in Escherichia coli, with no detectable off-target effects. CRISPRi can be used to repress multiple target genes simultaneously, and its effects are reversible.', 'We have recently described an RNA-based method, CRISPR interference (CRISPRi), for targeted silencing of transcription in bacteria and human cells. The CRISPRi system is derived from the Streptococcus pyogenes CRISPR (clustered regularly interspaced palindromic repeats) pathway, requiring only the coexpression of a catalytically inactive Cas9 protein and a customizable single guide RNA (sgRNA).', 'CRISPR interference (CRISPRi)', ' Although the recent development of clustered regularly interspaced short palindromic repeats (CRISPR)-based screening approaches in mammalian cell culture ', 'Clustered regularly interspaced palindromic repeats interference (CRISPRi)', 'E2f8, were most highly upregulated in miR-142-deficient cells. Clustered regularly interspaced short palindromic repeat interference-mediated (CRISPRi-mediated) silencing ', ' a new system for genome engineering based on the bacterial CRISPR-Cas9 system (Clustered Regularly Interspaced Short Palindromic Repeats)', 'Sequence-specific control of gene expression on a genome-wide scale is an important approach for understanding gene functions and for engineering genetic regulatory systems.', 'Genetic screening based on loss-of-function phenotypes is a powerful discovery tool in biology']

['Clustered regularly interspaced palindromic repeats interference (CRISPRi). This discovery tool is is used for genetic screening based on loss-of-function phenotypes.', 'The Clustered Regularly Interspaced Short Palindromic Repeats interference (CRISPRi) system is used for targeted silencing of transcription in different types of cells. The CRISPRi system is derived from the Streptococcus pyogenes CRISPR pathway, requiring only the coexpression of a catalytically inactive Cas9 protein and a customizable single guide RNA (sgRNA). The Cas9-sgRNA complex binds to DNA elements complementary to the sgRNA and causes a steric block that halts transcript elongation by RNA polymerase, resulting in the repression of the target gene. CRISPRi provides a simplified approach for rapid gene repression within 1-2 weeks. The method can also be adapted for high-throughput interrogation of genome-wide gene functions and genetic interactions, thus providing a complementary approach to RNA interference, which can be used in a wider variety of organisms.']

[]

Is selenium deficiency involved in autoimmune thyroid disease?

['In areas with severe selenium deficiency higher incidence of thyroiditis has been reported due to a decreased activity of selenium-dependent glutathione peroxidase enzyme within thyroid cells', 'Of 30 patients in the selenium treated group, 6 patients were overtly hypothyroid, 15 were subclinical hypothyroid, 6 were euthyroid, and 3 were subclinical hyperthyroid. The mean TPOAb concentration decreased significantly by 49.5% (P < 0.013) in the selenium treated group versus 10.1% (P < 0.95) in the placebo-treated group', 'Selenium substitution has a significant impact on inflammatory activity in thyroid-specific autoimmune disease', "Serum selenium is low in newly diagnosed Graves' disease", 'S-Se was lower in patients with GD than in controls (mean (SD), GD: 89·9\xa0μg/l (18·4); controls: 98·8\xa0μg/l (19·7), P\xa0<\xa00·01)', 'Patients with newly diagnosed GD and AIH had significantly lower s-Se compared with random controls. Our observation supports the postulated link between inadequate selenium supply and overt autoimmune thyroid disease, especially GD', 'Selenium deficiency is likely to constitute a risk factor for a feedforward derangement of the immune system-thyroid interaction, while selenium supplementation appears to dampen the self-amplifying nature of this derailed interaction', 'The recent recognition that the essential trace element selenium is incorporated as selenocysteine in all three deiodinases has decisively confirmed the clear-cut link between selenium and thyroid function. It has additionally been established that the thyroid contains more selenium than any other tissue and that selenium deficiency aggravates the manifestation of endemic myxedematous cretinism and autoimmune thyroid disease', 'Maintenance of "selenostasis" via optimal intake not only aids preservation of general health but also contributes substantially to the prevention of thyroid disease', 'Low birth weight, iodine excess and deficiency, selenium deficiency, parity, oral contraceptive use, reproductive span, fetal microchimerism, stress, seasonal variation, allergy, smoking, radiation damage to the thyroid gland, viral and bacterial infections all play a role in the development of autoimmune thyroid disorders', 'It has additionally been established that the thyroid contains more selenium than any other tissue and that selenium deficiency aggravates the manifestation of endemic myxedematous cretinism and autoimmune thyroid disease.', 'Selenium deficiency may play an important role in the initiation and progression of autoimmune thyroid disease.', '[Selenium deficiency in celiac disease: risk of autoimmune thyroid diseases].', 'Low birth weight, iodine excess and deficiency, selenium deficiency, parity, oral contraceptive use, reproductive span, fetal microchimerism, stress, seasonal variation, allergy, smoking, radiation damage to the thyroid gland, viral and bacterial infections all play a role in the development of autoimmune thyroid disorders.', 'Some clinical studies have demonstrated that selenium-deficient patients with autoimmune thyroid disease benefit from selenium supplementation, although the data are conflicting and many parameters must still be defined.', 'Our observation supports the postulated link between inadequate selenium supply and overt autoimmune thyroid disease, especially GD.', 'Selenium deficiency in celiac disease: risk of autoimmune thyroid diseases].', 'Selenoproteins contain the essential trace element selenium whose deficiency leads to major disorders including cancer, male reproductive system failure, or autoimmune thyroid disease.', 'It has additionally been established that the thyroid contains more selenium than any other tissue and that selenium deficiency aggravates the manifestation of endemic myxedematous cretinism and autoimmune thyroid disease.', 'EVIDENCE SYNTHESIS: Evidence in support of selenium supplementation in thyroid autoimmune disease is evaluated, the results herein presented demonstrating the potential effectiveness of selenium in reducing the antithyroid peroxidase titer and improving the echostructure in the ultrasound examination.', "Some investigators suggest that selenium may be a useful adjunctive treatment for autoimmune thyroid diseases, such as Hashimoto and Graves' disease.", 'Therefore, even mild selenium deficiency may contribute to the development and maintenance of autoimmune thyroid diseases.', 'Some clinical studies have demonstrated that selenium-deficient patients with autoimmune thyroid disease benefit from selenium supplementation, although the data are conflicting and many parameters must still be defined.', 'Some clinical studies have demonstrated that selenium-deficient patients with autoimmune thyroid disease benefit from selenium supplementation, although the data are conflicting and many parameters must still be defined', 'High prevalence of hyperplastic and autoimmune diseases of thyroid in Ukrainian population is determined by endemic deficit of iodine and selenium', 'It has additionally been established that the thyroid contains more selenium than any other tissue and that selenium deficiency aggravates the manifestation of endemic myxedematous cretinism and autoimmune thyroid disease.', 'Therefore, even mild selenium deficiency may contribute to the development and maintenance of autoimmune thyroid diseases', "Some investigators suggest that selenium may be a useful adjunctive treatment for autoimmune thyroid diseases, such as Hashimoto and Graves' disease"]

['Selenium deficiency is likely to constitute a risk factor for a feedforward derangement of the immune system-thyroid interaction, while selenium supplementation appears to dampen the self-amplifying nature of this derailed interactionIn areas with severe selenium deficiency higher incidence of thyroiditis has been reported due to a decreased activity of selenium-dependent glutathione peroxidase enzyme within thyroid cells', 'The essential trace element selenium was recently recognized as being incorporated as selenocysteine in all three deiodinases of the thyroid gland. This has decisively confirmed the clear-cut link between selenium and thyroid function. Additionally, it has been established that the thyroid contains more selenium than any other tissue, and that selenium deficiency aggravates the manifestation of autoimmune thyroid disease.', 'The recent recognition that the essential trace element selenium is incorporated as selenocysteine in all three deiodinases has decisively confirmed the clear-cut link between selenium and thyroid function. It has additionally been established that the thyroid contains more selenium than any other tissue and that selenium deficiency aggravates the manifestation of endemic myxedematous cretinism and autoimmune thyroid disease ']

['yes']

List anti-amyloid-beta monoclonal antibodies that have been investigated in clinical trials for treatment of Alzheimer disease.

['The first active immunization clinical trial with AN1792 in AD patients was halted when a subset of patients developed meningoencephalitis.', 'The first passive immunotherapy trial with bapineuzumab,', 'Preliminary results of a prematurely terminated clinical trial where AD patients were actively vaccinated with aggregated Abeta ', 'strategies based on Aβ1-42 peptide induced encephalomyelitis and possible microhemorrhages.', 'Phase III trials showed that bapineuzumab failed to improve cognitive and functional performances in AD patients, and was associated with a high incidence of amyloid-related imaging abnormalities (ARIA).', "Solanezumab's two Phase III trials in AD patients failed to meet endpoints when analyzed independently. ", 'Unfortunately, the first active vaccine (AN1792, consisting of preaggregate Aβ and an immune adjuvant, QS-21) was abandoned because it caused meningoencephalitis in approximately 6% of treated patients', 'Anti-Aβ monoclonal antibodies (bapineuzumab and solanezumab) are now being developed.', 'several monoclonal and polyclonal antibodies are in clinical trials. These are bapineuzumab, solanezumab, ponezumab, gantenerumab, BAN2401, gammaguard and octagam. Since each antibody has a different antigen epitope of Abeta, anti-amyloid activities are different.', "Several types of Aβ peptide immunotherapy for Alzheimer's disease are under investigation, direct immunization with synthetic intact Aβ(42) , active immunization involving the administration of synthetic fragments of Aβ peptide conjugated to a carrier protein and passive administration with monoclonal antibodies directed against Aβ peptide", 'An active anti-Aβ vaccine preparation, AN1792, has been used in AD patients with some clues of clinical efficacy but causing meningoencephalitis in about 6% of patients and it has been abandoned', 'The most advanced of these immunological approaches is bapineuzumab, composed of humanized anti-Aβ monoclonal antibodies, that has been tested in two Phase II trials, demonstrating to reduce Aβ burden in the brain of AD patients. ', 'The results of four ongoing large Phase III trials on bapineuzumab will tell us if passive anti-Aβ immunization is able to alter the course if this devastating disease.', 'Solanezumab is a monoclonal antibody that binds to β-amyloid (Aβ), a protein that plays a key role in the pathogenesis of AD. The drug is currently being investigated in Phase III trials as a disease-modifying treatment for AD. ', 'The most advanced of these immunological approaches is bapineuzumab, which is composed of humanized anti-Aβ monoclonal antibodies that has been tested in two Phase II trials. ', 'The results of four ongoing large Phase III trials on bapineuzumab will provide answers regarding whether passive anti-Aβ immunization is able to alter the course of this devastating disease.']

['Ponezumab, solanezumab and bapineuzumab are humanized antiamyloid beta (Aβ) monoclonal antibodies that have been designed for treatment of Alzheimer disease.', 'Bapineuzumab\nSolanezumab\nPonezumab\nGantenerumab']

['Bapineuzumab', 'bapineuzumab', 'Solanezumab', 'solanezumab', 'Ponezumab', 'ponezumab', 'Gantenerumab']

Symptoms of which disorder are evaluated with the Davidson Trauma Scale?

["Besides, to study its scores' evidence of convergent, discriminant, and predictive validity in relation to other resilience questionnaires (Connor Davidson Resilience Scale 10-item version, Situated Subjective Resilience Questionnaire for Adults and Resiliency Questionnaire for Adults) and to variables such as emotions (Modified Differential Emotions Scale), coping (Person-situation Coping Questionnaire for Adults), anxiety and depression (Hospital Anxiety and Depression Scale), posttraumatic growth (Posttraumatic Growth Inventory), perceived stress (Perceived Stress Scale) and posttraumatic stress (Davidson Trauma Scale), correlation and regression analyses were conducted.", 'Using the normalized population mean of 50 on the SF-36 MH domain score as a cut-off, positive predictive values were 16 and 55% for substantial depression; 20 and 68% for substantial anxiety (Depression Anxiety Stress Scales and HADS, respectively); and 40, 44, and 67% for substantial PTSD symptoms (IES-R, IES, and Davidson Trauma Scale, respectively).', 'METHOD: A randomly selected representative sample of inmates in the Puerto Rico correctional system (N = 1,179) was assessed with the Spanish-language Wender Utah Rating Scale (WURS); the Composite International Diagnostic Interview (CIDI) modules for lifetime/current major depression disorder (MDD), generalized anxiety disorder (GAD), and SUD; the Davidson Trauma Scale (DTS; posttraumatic stress disorder [PTSD]); and self-reports of in-site high-risk behaviors.', 'After correcting for multiple comparisons, no significant effects were observed on any of the outcomes among the NHW sample; however, within the NHB sample, significant gene × environment (G × E) interactions were observed for lifetime PTSD (P = .0029) and PTSD symptom severity (P = .0009). In each case, the APOE ε4 allele had no effect on the outcomes when combat exposure was low; however, when combat exposure was high, an additive effect was observed such that ε4 homozygotes exposed to high levels of combat reported the highest rates of PTSD (92%) and the worst symptom severity scores on the Davidson Trauma Scale (M = 79.5)', 'Early prognostic screening for posttraumatic stress disorder with the Davidson Trauma Scale and the SPAN.', 'The Davidson Trauma Scale (DTS) was developed as a self-rating for use in diagnosing and measuring symptom severity and treatment outcome in post-traumatic stress disorder (PTSD); 630 subjects were identified by random digit dialing and evaluated for a history of trauma.', 'The purpose of this paper is to assess the reliability and validity of the Spanish version of the Davidson trauma scale (DTS-S) and to determine the prevalence and correlates of post-traumatic stress disorder (PTSD) symptoms in a non-clinical random sample of prison inmates.Probabilistic samples of 1,179 inmates from 26 penal institutions in Puerto Rico were selected using a multistage sampling design', 'Remission in post-traumatic stress disorder (PTSD): effects of sertraline as assessed by the Davidson Trauma Scale, Clinical Global Impressions and the Clinician-Administered PTSD scale.', 'The Davidson Trauma Scale (DTS) was developed as a self-rating for use in diagnosing and measuring symptom severity and treatment outcome in post-traumatic stress disorder (PTSD); 630 subjects were identified by random digit dialing and evaluated for a history of trauma. ', 'Symptoms were assessed at sequential time points by the Structured Interview for PTSD (SIP), a clinician interview based assessment, and a self-report scale, the Davidson Trauma Scale (DTS). ', 'The present study focused on platelet serotonin (5-HT) concentration and symptoms of comorbid depression in war veterans with or without PTSD.PTSD and depression were evaluated using Clinician Administered PTSD Scale, Davidson Trauma Scale, Montgomery-Asberg Depression Rating Scale and Hamilton Anxiety Scale.', 'Although rates of trauma and PTSD are higher in those with bipolar disorder than in the general population, little is known about differences across bipolar subtypes.Using the NIMH STEP-BD dataset (N=3158), this study evaluated whether there were baseline differences in the prevalence of PTSD between participants with bipolar disorder I (BDI) and bipolar disorder II (BDII), using the MINI and the Davidson Trauma Scale.', 'We also investigated the interaction between the genetic variants to determine whether these variables and the interactions between the variables influenced the severity of PTSD symptoms.PTSD symptoms were quantitatively assessed using the Davidson Trauma Scale (DTS) in 150 participants from an at-risk South African population.', 'Using the normalized population mean of 50 on the SF-36 MH domain score as a cut-off, positive predictive values were 16 and 55% for substantial depression; 20 and 68% for substantial anxiety (Depression Anxiety Stress Scales and HADS, respectively); and 40, 44, and 67% for substantial PTSD symptoms (IES-R, IES, and Davidson Trauma Scale, respectively).', 'The Davidson Trauma Scale was completed at 1 (n = 145), 6 (n = 106), 12 (n = 94), and 24 (n = 66) months postdischarge to assess symptoms of PTSD.', 'The Davidson Trauma Scale (DTS) is a validated, 17-item, brief global assessment scale for posttraumatic stress disorder (PTSD).', 'Evaluation of PTSD symptoms using the Davidson Trauma Scale (DTS) and General Health Questionnaire (GHQ) in a sample of 56 patients admitted to an emergency room of a general hospital, and assessment of PTSD symptoms in relatives of the patients.']

['Davidson Trauma Scale is used for evaluation of post-traumatic stress disorder.']

['post-traumatic stress disorder', 'PTSD']

What kind of chromatography is HILIC?

['hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC LC-MS/MS) method', 'Hydrophilic-interaction liquid chromatography (HILIC) is a widely used technique for small polar molecule analysis ', 'hydrophilic-interaction LC (HILIC)', 'A hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC LC-MS/MS) method ', 'Hydrophilic Interaction Chromatography (HILIC) ', 'n this study a hydrophilic interaction chromatographic (HILIC) method ']

['Hydrophilic Interaction Chromatography (HILIC)']

['Hydrophilic Interaction Chromatography']

Describe what is the advantage of using a stain free protein gel in a Western Blot experiment?

['V3 stain-free workflow for a practical, convenient, and reliable total protein loading control in western blotting.', 'The V3 stain-free workflow makes the western blot process faster, transparent, more quantitative\xa0and reliable.', 'Direct Blue 71 (DB71) staining-a novel, sensitive, dye-binding staining method compatible with immunodetection-may offer advantages over these traditional loading control methods.', 'Direct Blue 71 staining as a destaining-free alternative loading control method for Western blotting.', 'Stain-Free technology as a normalization tool in Western blot analysis.', 'Stain-Free technology appears to be more reliable, more robust, and more sensitive', 'tain-Free technology offers the additional advantages of providing checkpoints throughout the Western blotting process by allowing rapid visualization of gel separation and protein transfer.']

['Stain-Free technology can be used as a normalization tool in Western blot analysis.']

[]

In which isochores are Alu elements enriched?

[' the vast majority of Alu sequences were shown to have the highest density in GC-rich isochores', 'Alu sequences being unstable in the GC-poor isochores but stable in the compositionally matching GC-rich isochores,', 'Alu retrotransposons do not show a homogeneous distribution over the human genome but have a higher density in GC-rich (H) than in AT-rich (L) isochores', 'This result, together with the known higher selective disadvantage of recombination products in H isochores, points to Alu-Alu recombination as the main agent provoking the density shift of Alus toward the GC-rich parts of the genome', 'whereas GC-rich Alus are mostly present in GC-rich isochores', 'the present results on Alu and LINE stability/exclusion predict significant losses of Alu DNA from the GC-poor isochores during evolution, a phenomenon apparently due to negative selection against sequences that differ from the isochore composition', 'The frequency of Alu sequences also increases with increasing GC, but attains a maximum in H2 isochores, in agreement with previous experimental data', 'The CpG levels of both Alus and CpG islands increase with their GC levels', 'characterized as a GC-rich isochore enriched for CpG islands, genes, and Alu-like repeats', 'Microsatellites and SINES (Alu, B1, B2) are found at roughly equal frequencies in introns from all isochore classes', 'The results indicate that the short repeats of the B1 family of mouse and of the Alu I family of man are most frequent in the heavy components, whereas the long repeats of the BamHI family of mouse and of the Kpn I family of man are mainly present in the two light components.']

['Alu elements are enriched in high GC% isochores due to reduced Alu loss by recombination in these regions. The frequency of Alu sequences increases with increasing GC, but attains a maximum in H2 isochores.']

['H2', 'H3']

How does AFT1 gene in Saccharomyces cerevisiae regulate iron uptake and homeostasis, interacting with FOB transporter Arn3 and impacting chromosome stability?

['["Using a scheme for selecting mutants of Saccharomyces cerevisiae with abnormalities of iron metabolism, we have identified a gene, AFT1, that mediates the control of iron uptake", "AFT1 functions to activate transcription of target genes in response to iron deprivation and thereby plays a central role in iron homeostasis.", "Iron-regulated DNA binding by the AFT1 protein controls the iron regulon in yeast", "Iron deprivation of Saccharomyces cerevisiae induces transcription of genes required for high-affinity iron uptake. AFT1 mediates this transcriptional control.", "The AFT1 transcriptional factor is differentially required for expression of high-affinity iron uptake genes in Saccharomyces cerevisiae.", "Aft1 displays phosphorylation modifications depending on the growth stage of the cells, and it might link induction of genes for iron uptake to other metabolically dominant requirement for cell growth.", "an aft1 mutation in S. cerevisiae that makes cells dependent on iron for growth", "Subcellular localization of Aft1 transcription factor responds to iron status in Saccharomyces cerevisiae.", "The Aft1 transcription factor regulates the iron regulon in response to iron availability in Saccharomyces cerevisiae. Aft1 activates a battery of genes required for iron uptake under iron-starved conditions, whereas Aft1 function is inactivated under iron-replete conditions", "the nuclear export of Aft1 is critical for ensuring iron-responsive transcriptional activation of the Aft1 regulon and that the nuclear import/export systems are involved in iron sensing by Aft1 in S. cerevisiae.", "the Aft1 iron-responsive DNA-binding factor", "Two transcriptional activators, Aft1 and Aft2, regulate iron homeostasis in Saccharomyces cerevisiae.", "iron sensing by Aft1/Aft2 is not linked to the maturation of cytosolic/nuclear Fe-S proteins", "The yeast Saccharomyces cerevisiae contains a pair of paralogous iron-responsive transcription activators, Aft1 and Aft2. Aft1 activates the cell surface iron uptake systems in iron depletion,", "the absence of either Aft1 or Aft2 showed an iron-dependent increase in the amount of the remaining paralog", "The transcription factors Aft1 and Aft2 from Saccharomyces cerevisiae regulate the expression of genes involved in iron homeostasis.", "iron insufficiency-responsive transcription factor Aft1", "The mRNA levels of 14 proteins involved in iron homeostasis were shown to be increased by cisplatin. Interestingly, the expression of all 14 genes is known to be regulated by Aft1, a transcription factor activated in response to iron insufficiency", "Aft1 is a transcriptional activator in Saccharomyces cerevisiae that responds to iron availability and regulates the expression of genes in the iron regulon", "we found that Aft1 physically interacts with the FOB (ferrioxamine B) transporter Arn3", "These results suggest that Aft1 interacts with Arn3 and may regulate the ubiquitination of Arn3 in the cytosolic compartment", "The Saccharomyces cerevisiae transcription factor Aft1 is activated in iron-deficient cells to induce the expression of iron regulon genes, which coordinate the increase of iron uptake and remodel cellular metabolism to survive low-iron conditions", "Aft1 has been implicated in numerous cellular processes including cell-cycle progression and chromosome stability", "We demonstrate that Aft1 works in parallel with the RIM101 pH pathway and the role of Aft1 in DNA damage repair is mediated by iron. In contrast, through both directed studies and microarray transcriptional profiling, we show that the role of Aft1 in chromosome maintenance and benomyl resistance is independent of its iron regulatory role, potentially through a nontranscriptional mechanism.", "Aft1p is a major iron regulator in budding yeast Saccharomyces cerevisiae. It indirectly senses cytosolic Fe status and responds by activating or repressing iron regulon genes", "Expression of components of the high-affinity system is controlled by the Aft1 transcriptional factor", "Iron-responsive transcription factor Aft1 interacts with kinetochore protein Iml3 and promotes pericentromeric cohesin", "The Saccharomyces cerevisiae iron-responsive transcription factor, Aft1, has a well established role in regulating iron homeostasis through the transcriptional induction of iron-regulon genes", "recent studies have implicated Aft1 in other cellular processes independent of iron regulation such as chromosome stability", "Aft1 interacts with and co-localizes with kinetochore proteins", "Our work defines a new role for Aft1 in chromosome stability and transmission.", "Our genetic network reveals that', '["Using a scheme for selecting mutants of Saccharomyces cerevisiae with abnormalities of iron metabolism, we have identified a gene, AFT1, that mediates the control of iron uptake", "AFT1 functions to activate transcription of target genes in response to iron deprivation and thereby plays a central role in iron homeostasis.", "Iron-regulated DNA binding by the AFT1 protein controls the iron regulon in yeast", "Iron deprivation of Saccharomyces cerevisiae induces transcription of genes required for high-affinity iron uptake. AFT1 mediates this transcriptional control.", "The AFT1 transcriptional factor is differentially required for expression of high-affinity iron uptake genes in Saccharomyces cerevisiae.", "Aft1 displays phosphorylation modifications depending on the growth stage of the cells, and it might link induction of genes for iron uptake to other metabolically dominant requirement for cell growth.", "an aft1 mutation in S. cerevisiae that makes cells dependent on iron for growth", "Subcellular localization of Aft1 transcription factor responds to iron status in Saccharomyces cerevisiae.", "The Aft1 transcription factor regulates the iron regulon in response to iron availability in Saccharomyces cerevisiae. Aft1 activates a battery of genes required for iron uptake under iron-starved conditions, whereas Aft1 function is inactivated under iron-replete conditions", "the nuclear export of Aft1 is critical for ensuring iron-responsive transcriptional activation of the Aft1 regulon and that the nuclear import/export systems are involved in iron sensing by Aft1 in S. cerevisiae.", "the Aft1 iron-responsive DNA-binding factor", "Two transcriptional activators, Aft1 and Aft2, regulate iron homeostasis in Saccharomyces cerevisiae.", "iron sensing by Aft1/Aft2 is not linked to the maturation of cytosolic/nuclear Fe-S proteins", "The yeast Saccharomyces cerevisiae contains a pair of paralogous iron-responsive transcription activators, Aft1 and Aft2. Aft1 activates the cell surface iron uptake systems in iron depletion,", "the absence of either Aft1 or Aft2 showed an iron-dependent increase in the amount of the remaining paralog", "The transcription factors Aft1 and Aft2 from Saccharomyces cerevisiae regulate the expression of genes involved in iron homeostasis.", "iron insufficiency-responsive transcription factor Aft1", "The mRNA levels of 14 proteins involved in iron homeostasis were shown to be increased by cisplatin. Interestingly, the expression of all 14 genes is known to be regulated by Aft1, a transcription factor activated in response to iron insufficiency", "Aft1 is a transcriptional activator in Saccharomyces cerevisiae that responds to iron availability and regulates the expression of genes in the iron regulon", "we found that Aft1 physically interacts with the FOB (ferrioxamine B) transporter Arn3", "These results suggest that Aft1 interacts with Arn3 and may regulate the ubiquitination of Arn3 in the cytosolic compartment", "The Saccharomyces cerevisiae transcription factor Aft1 is activated in iron-deficient cells to induce the expression of iron regulon genes, which coordinate the increase of iron uptake and remodel cellular metabolism to survive low-iron conditions", "Aft1 has been implicated in numerous cellular processes including cell-cycle progression and chromosome stability", "We demonstrate that Aft1 works in parallel with the RIM101 pH pathway and the role of Aft1 in DNA damage repair is mediated by iron. In contrast, through both directed studies and microarray transcriptional profiling, we show that the role of Aft1 in chromosome maintenance and benomyl resistance is independent of its iron regulatory role, potentially through a nontranscriptional mechanism.", "Aft1p is a major iron regulator in budding yeast Saccharomyces cerevisiae. It indirectly senses cytosolic Fe status and responds by activating or repressing iron regulon genes", "Expression of components of the high-affinity system is controlled by the Aft1 transcriptional factor", "Iron-responsive transcription factor Aft1 interacts with kinetochore protein Iml3 and promotes pericentromeric cohesin", "The Saccharomyces cerevisiae iron-responsive transcription factor, Aft1, has a well established role in regulating iron homeostasis through the transcriptional induction of iron-regulon genes", "recent studies have implicated Aft1 in other cellular processes independent of iron regulation such as chromosome stability", "Aft1 interacts with and co-localizes with kinetochore proteins", "Our work defines a new role for Aft1 in chromosome stability and transmission.", "Our genetic network reveals that']

The AFT1 gene in Saccharomyces cerevisiae regulates iron uptake and homeostasis by activating transcription of target genes in response to iron deprivation. AFT1 mediates the transcriptional control of genes required for high-affinity iron uptake under iron-starved conditions. Additionally, AFT1 physically interacts with the FOB transporter Arn3, potentially regulating the ubiquitination of Arn3 in the cytosolic compartment. AFT1 also impacts chromosome stability and is involved in various cellular processes beyond iron regulation.

[]

Which cellular function is associated with transcription factors forkhead 1 and 2 (Fkh1 and Fkh2)?

['Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae.', 'Here we show that the yeast Forkhead transcription factors, Fkh1 and Fkh2, are global determinants of replication origin timing.', 'Instead, we show that Fkh1 and Fkh2 are required for the clustering of early origins and their association with the key initiation factor Cdc45 in G1 phase, suggesting that Fkh1 and Fkh2 selectively recruit origins to emergent replication factories. Fkh1 and Fkh2 bind Fkh-activated origins, and interact physically with ORC, providing a plausible mechanism to cluster origins.', 'Forkhead box O (FOXO) transcription factors have a conserved function in regulating metazoan lifespan. A key function in this process involves the regulation of the cell cycle and stress responses including free radical scavenging.', 'We report that the deletion of both FKH genes impedes normal lifespan and stress resistance, particularly in stationary phase cells, which are non-responsive to caloric restriction. Conversely, increased expression of the FKHs leads to extended lifespan and improved stress response.', 'This study establishes the FKHs role as evolutionarily conserved regulators of lifespan in yeast and identifies the APC as a novel component of this mechanism under certain conditions, likely through combined regulation of stress response, genomic stability, and cell cycle regulation.', 'The genome of Schizosaccharomyces pombe has four genes that code for proteins containing fork-head domains (FKH), two of which have been characterised. Here we describe the remaining two genes, fhl1 and fkh2, that code for proteins containing fork-head-associated domains (FHA) besides their FKHs.', 'Here we show that the yeast forkhead transcription factors, Fkh1p and Fkh2p, associate with the coding regions of active genes and influence, in opposing ways, transcriptional elongation and termination.', 'Our results suggest that, in addition to their documented promoter function, Fkh1p and Fkh2p coordinate early transcription elongation and pre-mRNA processing. This may reflect a general feature of gene regulation in eukaryotes.', 'Here we show that the yeast Forkhead transcription factors, Fkh1 and Fkh2, are global determinants of replication origin timing.', 'The Saccharomyces cerevisiae Forkhead Box (FOX) proteins, Fkh1 and Fkh2, regulate diverse cellular processes including transcription, long-range DNA interactions during homologous recombination, and replication origin timing and long-range origin clustering.']

['Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae. Here we show that the yeast Forkhead transcription factors, Fkh1 and Fkh2, are global determinants of replication origin timing. Forkhead box O (FOXO) transcription factors have a conserved function in regulating metazoan lifespan. Fkh1 and Fkh2 bind Fkh-activated origins, and interact physically with ORC, providing a plausible mechanism to cluster origins. Instead, we show that Fkh1 and Fkh2 are required for the clustering of early origins and their association with the key initiation factor Cdc45 in G1 phase, suggesting that Fkh1 and Fkh2 selectively recruit origins to emergent replication factories. ', 'Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae. Fkh1 and Fkh2 are required for the clustering of early origins and their association with the key initiation factor Cdc45 in G1 phase. Fkh1 and Fkh2 selectively recruit origins to emergent replication factories. They both bind Fkh-activated origins, and interact physically with ORC, providing a plausible mechanism to cluster origins.', 'Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae. Forkhead box O (FOXO) transcription factors have a conserved function in regulating metazoan lifespan. Fkh1 and Fkh2 bind Fkh-activated origins, and interact physically with ORC, providing a plausible mechanism to cluster origins. Here we describe the remaining two genes, fhl1 and fkh2, that code for proteins containing fork-head-associated domains (FHA) besides their FKHs. This may reflect a general feature of gene regulation in eukaryotes. ', 'Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae.', 'Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae. Here we show that the yeast Forkhead transcription factors, Fkh1 and Fkh2, are global determinants of replication origin timing. Fkh1 and Fkh2 bind Fkh-activated origins, and interact physically with ORC, providing a plausible mechanism to cluster origins. Instead, we show that Fkh1 and Fkh2 are required for the clustering of early origins and their association with the key initiation factor Cdc45 in G1 phase, suggesting that Fkh1 and Fkh2 selectively recruit origins to emergent replication factories. Forkhead box O (FOXO) transcription factors have a conserved function in regulating metazoan lifespan. ', 'Instead, we show that Fkh1 and Fkh2 are required for the clustering of early origins and their association with the key initiation factor Cdc45 in G1 phase, suggesting that Fkh1 and Fkh2 selectively recruit origins to emergent replication factories. Fkh1 and Fkh2 bind Fkh-activated origins, and interact physically with ORC, providing a plausible mechanism to cluster origins. Here we show that the yeast Forkhead transcription factors, Fkh1 and Fkh2, are global determinants of replication origin timing.', 'Here we show that the yeast Forkhead transcription factors, Fkh1 and Fkh2, are global determinants of replication origin timing. Forkhead box O (FOXO) transcription factors have a conserved function in regulating metazoan lifespan.', 'Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae. Here we show that the yeast Forkhead transcription factors, Fkh1 and Fkh2, are global determinants of replication origin timing.']

['DNA replication']

Is Alu hypomethylation associated with breast cancer?

['Alu and LINE-1 hypomethylation is associated with HER2 enriched subtype of breast cancer', 'In IBC, Alu hypomethylation correlated with negative estrogen receptor (ER) status', 'In survival analyses, low Alu methylation status tended to be associated with poor disease-free survival of the patients.', 'Alu hypomethylation is probably a late event during breast cancer progression', 'prominent hypomethylation of Alu and LINE-1 in HER2 enriched subtype may be related to chromosomal instability of this specific subtype.', 'DNA methylation for three repetitive elements (LINE1, Sat2 and Alu) were analyzed in invasive ductal carcinoma of the breast, paired adjacent normal tissue and WBC from 40 breast cancer patients', 'DNA methylation for the three repetitive elements was lower in tumor compared to adjacent tissue and WBC DNA.']

['Yes, Alu elements were found to be hypomethylated in breast cancer, especially in the HER2-enriched subtype. Furthermore, Alu hypomethylation was identified as a late event during breast cancer progression, and in invasive breast cancer, tended to be associated with negative estrogen receptor status and poor disease-free survival of the patients.', 'Alu and LINE-1 hypomethylation is associated with HER2 enriched subtype of breast cancer ']

['yes']

Which 2 medications are included in the Qsymia pill?

['OBJECTIVE: To quantify the incremental cost-effectiveness of Qsymia (phentermine and topiramate extended-release) for health-related quality of life improvements.', 'The intervention was diet and lifestyle advice plus the recommended dose of Qsymia (phentermine 7.5\xa0mg plus topiramate 46.0\xa0mg) vs. control, which included diet and lifestyle advice plus placebo.', 'These include combinations (at low dose) of existing drugs, e.g., bupropion + naltrexone (Contrave), phentermine + topiramate (Qsymia), higher doses of existing drugs licensed for other indications (liraglutide, 3 mg), and new entities (lorcaserin).', 'RECENT FINDINGS: Two new antiobesity drugs - naltrexone/bupropion (Contrave) and liraglutide (Saxenda) - were approved by the US Food and Drug Administration in 2014 and join four other approved obesity medications, including phentermine/topiramate XR (Qsymia) and lorcaserin (Belviq), to form the largest number of medications available for the treatment of obesity.', 'Adding to the current available pharmacotherapies for obesity, the Food and Drug Administration has recently approved 2 new combination medications known as lorcaserin (Belviq) and phentermine-topiramate (Qsymia).', 'After a long period of failure in development, two new medications (phentermine/topiramate ER - Qsymia™ and lorcaserin - Belviq®) have been approved by the US Food and Drug Administration for long-term weight management in persons with obesity (BMI ≥ 30 kg/m(2)) or in overweight persons (BMI ≥ 27 kg/m(2)) with comorbidities.', 'The intervention was diet and lifestyle advice plus the recommended dose of Qsymia (phentermine 7.5\xa0mg plus topiramate 46.0\xa0mg) vs. control, which included diet and lifestyle advice plus placebo', 'Current antiobesity medications and pharmacological strategies will be reviewed.Two new antiobesity drugs - naltrexone/bupropion (Contrave) and liraglutide (Saxenda) - were approved by the US Food and Drug Administration in 2014 and join four other approved obesity medications, including phentermine/topiramate XR (Qsymia) and lorcaserin (Belviq), to form the largest number of medications available for the treatment of obesity.', 'Almost a decade after the Food and Drug Administration approved the first weight loss medication, it recently approved two novel anti-obesity drugs Belviq (lorcaserin) and Qsymia (topiramate and phentermine), thus signalling the beginning of a new era in the pharmacotherapy of obesity.', 'Obesity is a public health crisis affecting approximately more than 33% of Americans and costing the healthcare system more than $190 billion annually.To review the 2 new drugs that were recently approved by the US Food and Drug Administration (FDA) for the treatment of obesity, lorcaserin HCl (Belviq) and phentermine/topiramate (Qsymia) and their potential impact on the treatment of obese patients.Lifestyle modification is the first and mainstay treatment for obesity.', 'Adding to the current available pharmacotherapies for obesity, the Food and Drug Administration has recently approved 2 new combination medications known as lorcaserin (Belviq) and phentermine-topiramate (Qsymia).', 'Two new antiobesity drugs - naltrexone/bupropion (Contrave) and liraglutide (Saxenda) - were approved by the US Food and Drug Administration in 2014 and join four other approved obesity medications, including phentermine/topiramate XR (Qsymia) and lorcaserin (Belviq), to form the largest number of medications available for the treatment of obesity.', 'To review the 2 new drugs that were recently approved by the US Food and Drug Administration (FDA) for the treatment of obesity, lorcaserin HCl (Belviq) and phentermine/topiramate (Qsymia) and their potential impact on the treatment of obese patients.']

['Qsymia pill includes phentermine and topiramate. It is used for treatment of obesity.']

['phentermine', 'topiramate']

What is the genetic basis of tuberous sclerosis?

['The genetic basis of this disease has been attributed to mutations in one of two unlinked genes, TSC1 and TSC2.', 'The functions of the TSC1 and TSC2 gene products, hamartin and tuberin, respectively, have remained ill defined until recently', 'Genetic, biochemical, and biologic analyses have highlighted their role as negative regulators of the mTOR signaling pathway. Tuberin, serving as a substrate of AKT and AMPK, mediates mTOR activity by coordinating inputs from growth factors and energy availability in the control of cell growth, proliferation, and survival. Emerging evidence also suggests that the TSC 1/2 complex may play a role in modulating the activity of beta-catenin and TGFbeta. These findings provide novel functional links between the TSC genes and other tumor suppressors', 'Ten years ago, a mutation in the TSC2 gene was identified in the Eker rat at Fox Chase Cancer Center by Yeung and Knudson, and in Tokyo by Kobayashi and Hino.', 'Here, we will review the clinical association of RCC in TSC, consider the factors that have led to its under-emphasis within the RCC field, address the cellular and biochemical mechanisms that may contribute to RCC in cells with TSC1 or TSC2 mutations, and finally discuss the ways in which the TSC signaling pathways may be linked to sporadic RCC in the general population.', 'Either of two genes, TSC1 or TSC2, can be mutated, resulting in the tuberous sclerosis complex phenotype.', 'The protein products of the tuberous sclerosis complex genes, hamartin (TSC1) and tuberin (TSC2), have been discovered to play important roles in several cell-signaling pathways', 'Knowledge regarding the function of the tuberin-hamartin complex has led to therapeutic intervention trials. ', 'TSC2 mutations were identified in all cyst-positive patients who were tested (n = 8), whereas both TSC1 and TSC2 mutations were found in patients with nodular disease.', 'We previously found TSC2 loss of heterozygosity in 7 of 13 (54%) of angiomyolipomas from sporadic LAM patients, suggesting that LAM and TSC could have a common genetic basis.', 'Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis', 'The disease can be caused by mutations in either of two genes, TSC2, identified in 1993, and TSC1, only recently identified.', 'Molecular genetic basis of renal carcinogenesis in the Eker rat model of tuberous sclerosis (Tsc2)', 'We have recently identified on rat chromosome 10q a germline mutation in the tuberous sclerosis gene (Tsc2), the gene predisposing to renal carcinoma (RC) in the Eker rat', 'Tuberous sclerosis complex is a genetic disorder caused by mutations in either the TSC1 or TSC2 gene that can result in the growth of hamartomas in multiple organ systems', 'Striking improvements in the understanding of the genetic basis of this autosomal dominant genetic disease are coupled to the understanding of the mechanisms that link the loss of TSC1 (9q34) or TSC2 (16p13.3) genes with the regulation of the Rheb/m-TOR/p70S6K pathway. ', 'In all these lesions, genetic alterations related to the tuberous sclerosis complex (TSC) have been demonstrated. Striking improvements in the understanding of the genetic basis of this autosomal dominant genetic disease are coupled to the understanding of the mechanisms that link the loss of TSC1 (9q34) or TSC2 (16p13.3) genes with the regulation of the Rheb/m-TOR/p70S6K pathway.', 'In all these lesions, genetic alterations related to the tuberous sclerosis complex (TSC) have been demonstrated. Striking improvements in the understanding of the genetic basis of this autosomal dominant genetic disease are coupled to the understanding of the mechanisms that link the loss of TSC1 (9q34) or TSC2 (16p13.']

['The genetic basis of tuberous sclerosis has been attributed to mutations in one of two unlinked genes, TSC1 and TSC2. The functions of the TSC1 and TSC2 gene products, hamartin and tuberin, respectively, have remained ill defined until recently. Genetic, biochemical, and biologic analyses have highlighted their role as negative regulators of the mTOR signaling pathway. Tuberin, serving as a substrate of AKT and AMPK, mediates mTOR activity by coordinating inputs from growth factors and energy availability in the control of cell growth, proliferation, and survival. Emerging evidence also suggests that the TSC 1/2 complex may play a role in modulating the activity of beta-catenin and TGFbeta. These findings provide novel functional links between the TSC genes and other tumor suppressors.', 'The genetic basis of this disease has been attributed to mutations in one of two unlinked genes, TSC1 and TSC2.', 'We previously found TSC2 loss of heterozygosity in 7 of 13 (54%) of angiomyolipomas from sporadic LAM patients, suggesting that LAM and TSC could have a common genetic basis. In this study, we report the identification of somatic TSC2 mutations in five of seven angiomyolipomas from sporadic LAM patients. Our data demonstrate that somatic mutations in the TSC2 gene occur in the angiomyolipomas and pulmonary LAM cells of women with sporadic LAM, strongly supporting a direct role of TSC2 in the pathogenesis of this disease. The study of hereditary tumor syndromes has laid a solid foundation toward understanding the genetic basis of cancer.']

['TSC1 and TSC2 genes']

List chromosomes that have been linked to Arnold Chiari syndrome in the literature.

['Consistent with a genetic hypothesis for CMI, much of the PF morphology was found to be heritable and multiple genomic regions were strongly implicated from OSA, including regions on Chromosomes 1 (LOD = 3.07, p = 3 × 10(-3) ) and 22 (LOD = 3.45, p = 6 × 10(-5) ) containing several candidates warranting further investigation.', 'Furthermore, we report the first case of documented Arnold-Chiari malformation type I and increased factor XIII activity associated with 6p trisomy. ', 'Of particular interest were two regions (Chr8, Max LOD\u200a=\u200a3.04; Chr12, Max LOD\u200a=\u200a2.09) identified within the subset of "CTD-negative" families, both of which harbor growth differentiation factors (GDF6, GDF3) implicated in the development of Klippel-Feil syndrome (KFS).', 'Moreover, the performed DNA analysis showed interstitial duplication in chromosome 5 (5q35.1). ', 'CGH microarray showed a approximately 520.7 kb microdeletion on 16p13.3 involving CREBBP, ADCY9, and SRL genes. ', 'Pentasomy 49,XXXXY associated with a Chiari type 1 malformation and cervical syrinx.', 'A 13-year-old with pentasomy 49,XXXXY and a Chiari type 1 malformation with an associated cervical syrinx is presented.', 'Phenotypic definition of Chiari type I malformation coupled with high-density SNP genome screen shows significant evidence for linkage to regions on chromosomes 9 and 15.', 'Two-point LOD scores on chromosome 15 reached 3.3 and multipoint scores in this region identified a 13 cM region with LOD scores over 1 (15q21.1-22.3). ', 'Multipoint LOD scores on chromosome 9 maximized at 3.05, identifying a 40 cM region with LOD scores over 1 (9q21.33-33.1) and a tighter region with multipoint LOD scores over 2 that was only 8.5 cM. ', 'In addition, this child had an Arnold-Chiari type I malformation that required surgical decompression. FISH studies using BAC clones spanning the 5q15 to 5q22 region revealed that these were all present in both homologues. ', 'The karyotype showed 46, XY, del(1)(q23q31.2). ', 'Karyotype analysis showed inversion of Y chromosome. ', 'The clinical features and morphological findings in 31 Japanese infants with trisomy 18 are presented. The majority were small-for-date infants. There was no sex predominance in our series, as opposed to male:female ratios of 1:3 reported in the literature. The average age at death was greater in females than in males. Cardiovascular anomalies were consistently present; ventricular septar defect and patent ductus arteriosus being the most common malformations. Various other internal malformations including the Arnold-Chiari malformation were observed.', 'An unusual heterotopia of striated skeletal muscle and glial tissue occurred in the pontine meninges of a stillborn male showing feature of trisomy 13 and an Arnold-Chiari malformation.', 'Type II Arnold-Chiari malformation with normal spine in trisomy 18.', 'A variety of anomalies of the central nervous system are observed in trisomy 18. The present case describes an infant having a type II Arnold-Chiari malformation without spina bifida. One previous case of an Arnold-Chiari malformation was reported in trisomy 18 but that infant also had a lumbar meningomyelocoele. ', 'Recently, a child was reported who presented with a 3p13-14.1 deletion of four genes, including FOXP1, and a constellation of deficits that included speech delay. In this study, we report the case of a patient with a single deletion of FOXP1. This patient presented with speech and motor developmental delays, a Chiari I malformation, and epileptiform discharges.']

['Chromosomes 1, 3, 5, 6, 8, 9, 12, 13, 15, 16, 18, 22, X and Y have been reported in association with Arnold Chiari syndrome in genetic linkage studies and individual case reports.']

['1', '3', '5', '6', '8', '9', '12', '13', '15', '16', '18', '22', 'X', 'Y']

Are there telemedicine applications for chronic pain management?

['An integrated cognitive-behavioral and physical therapy group protocol has been developed and then implemented at remote sites using videoconferencing technology to provide pain management for veterans. ', 'Tele-pain management: use of videoconferencing technology in the delivery of an integrated cognitive-behavioral and physical therapy group intervention.', 'It is feasible to provide treatment to women veterans living in rural areas by utilizing video-teleconferencing technology between larger VA medical centers and facilities at CBOCs in more rural settings', 'The results suggest that a smartphone-delivered intervention with diaries and personalized feedback can reduce catastrophizing and prevent increases in functional impairment and symptom levels in women with chronic widespread pain following inpatient rehabilitation.', ' Of the studies available, there are very few randomized trials of telehealth pain care and only one general overview of e-health and chronic pain, which dedicates just a few paragraphs to telehealth.', 'therapy adaptation and the resultant specification for the SMART2 project-a technology-based self-management system for assisting long-term health conditions, including chronic pain', 'Results showed the use of videoconferencing for this group of patients is useable and satisfactory for both patients and staff, that the patients save time and money, and that for a system where videoconferencing equipment is already in use, it is also cost effective. Staff were able to identify new patient problems. ', 'This pilot study indicates that telemedicine follow-up consultations for chronic pain patients are feasible and cost-saving. Patients and anesthesiologists were highly satisfied with telemedicine consultation.']

['Yes, telemedicine is feasible and cost-effective for education and therapy of patients with chronic pain.', 'Yes, there are.']

['yes']

What is the function of TALENs?

['Transcription activator-like effector nucleases (TALENs) are programmable nucleases that join FokI endonuclease with the modular DNA-binding domain of TALEs']

[' These chimeric enzymes can be used to introduce a double strand break at a specific genomic site which then can become the substrate for error-prone non-homologous end joining (NHEJ), generating mutations at the site of cleavage. Artificial transcription activator-like effector nucleases (TALENs) provide a powerful new approach for targeted zebrafish genome editing and functional genomic applications. Transcription Activator-Like Effector Nucleases (TALENs) consist of a nuclease domain fused to a DNA binding domain which is engineered to bind to any genomic sequence. Transcription activator-like effector nucleases (TALENs) are programmable nucleases that join FokI endonuclease with the modular DNA-binding domain of TALEs.', 'Transcription Activator-Like Effector Nucleases (TALENs) consist of a nuclease domain fused to a DNA binding domain which is engineered to bind to any genomic sequence. These chimeric enzymes can be used to introduce a double strand break at a specific genomic site which then can become the substrate for error-prone non-homologous end joining (NHEJ), generating mutations at the site of cleavage. TALENs provide a powerful new approach for targeted genome editing and functional genomic applications.']

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Which enzyme is deficient in Krabbe disease?

['Krabbe disease is a lethal, demyelinating condition caused by genetic deficiency of galactocerebrosidase (GALC) and resultant accumulation of its cytotoxic substrate, psychosine (galactosylsphingosine), primarily in oligodendrocytes (OLs).', 'In this study, we report that accumulation of endogenous psychosine under GALC deficient Krabbe conditions impedes OL differentiation process both by decreasing the expression of myelin lipids and protein and by inducing the cell death of maturating OLs.', 'In almost all individuals with Krabbe disease, galactocerebrosidase (GALC) enzyme activity is deficient (0%-5% of normal activity) in leukocytes isolated from whole heparinized blood or in cultured skin fibroblasts.', 'This chapter describes in detail a practical procedure for the preparation of radiolabeled galactocerebroside and its use in the assay of galactocerebrosidase (GalCase), the enzyme deficient in globoid cell leukodystrophy (Krabbe disease).', 'Globoid cell leukodystrophy (Krabbe disease) is an inherited neurological disorder caused by the pathogenomic accumulation of psychosine (galactosylsphingosine), a substrate for the deficient enzyme galactocerebroside beta-galactosidase.', 'Krabbe disease is an extremely rare condition with an incidence of 1 in 1,00,000 live births. It is caused by deficient activity of the Iysosomal hydrolase galactosylceramide beta-galactosidase.', 'Globoid cell leukodystrophy (Krabbe disease) is characterized by the accumulation of a toxic metabolite, psychosine (galactosylsphingosine), which is a substrate for the deficient enzyme (galactocerebroside beta-galactosidase).', 'Krabbe disease (globoid-cell leukodystrophy; GLD) is caused by mutations in the GALC gene. Beta-galactocerebrosidase (GALC) is a specific beta-galactosidase which is defective in GLD.', 'Both galactosylceramide beta-galactosidase (GALC-GC) and GALC-PS activities were reduced by at least 85% of the normal in all but 2 of the 10 GLD patients studied.', 'Krabbe disease, or globoid cell leukodystrophy, is an autosomal recessive disorder caused by the deficiency of galactocerebrosidase (GALC) activity.', 'The disease can be diagnosed by detecting the deficiency of GALC activity (less than 5% of normal) in any available tissue sample.', 'Globoid cell leukodystrophy, or Krabbe disease, is a severe disorder of the peripheral and central nervous system myelin caused by deficient galactocerebrosidase (GALC) activity.', 'Globoid cell leukodystrophy (GCL or Krabbe disease) is a recessive disease caused by mutations of the lysosomal enzyme galactocerebrosidase (GALC) and twitcher is the murine model of GCL.', 'Galactocerebrosidase (GALC) is the lysosomal enzyme deficient in human and certain animal species with globoid cell leukodystrophy (GLD) or Krabbe disease.', 'Globoid-cell leukodystrophy (GLD) is an autosomal recessive inherited disorder caused by the deficiency of galactocerebrosidase, the lysosomal enzyme responsible for the degradation of the myelin glycolipid galactocerebroside.', 'Krabbe disease is an autosomal recessive inherited demyelinating disease, which is deficient in lysosomal enzyme, galactocerebrosidase.', 'Galactocerebrosidase (GALC) activity is deficient in all patients with globoid cell leukodystrophy (GLD).', 'Human galactocerebrosidase, the enzyme deficient in Krabbe disease, was purified, through several hydrophobic column steps and gel filtration, 22,650-fold from human lymphocytes', 'Globoid cell leukodystrophy (Krabbe disease) is an autosomal recessive disorder resulting from the deficiency of galactocerebrosidase (GALC) activity.', '6-Hexadecanoylamino-4-methylumbelliferyl-beta-D-galactopyranoside (HMGal) has been shown to be a specific fluorogenic substrate of galactocerebrosidase and to facilitate the simple enzymatic diagnosis of Krabbe disease in human patients and in twitcher mice.', 'The inherited deficiency of galactosylceramide beta-galactosidase (E.C. 3.2.1.46: galactocerebrosidase) activity results in globoid cell leukodystrophy in humans (Krabbe disease) and in mice (twitcher mutant).', 'The lack of complementation between Krabbe disease patient and twitcher mutant mouse cells provides further evidence that the twitcher mouse is an authentic murine model for Krabbe disease and supports the hypothesis that the mutations in both species are within the structural gene for the galactocerebrosidase enzyme.', 'Galactosylceramide beta-galactosidase cross reacting material was demonstrated in brain, liver, and skin fibroblasts from patients with Krabbe disease.', '. In this study, LRs in the brain of the twitcher (TWI) mouse, a bona-fide model for infant variants of human globoid cell leukodystrophy or Krabbe disease, were investigated. This mouse has deficient activity of GALC (beta-galactosylceramidase) that leads to a progressive accumulation of some galactosyl-sphingolipids in the brain.', 'A GALC genotype with one deleted and one polymorphic GALC activity-reducing allele can lead to enzymatic and clinical signs of LOGLD in the absence of marked GALC-PS deficiency.', 'Galactocerebrosidase (GALC) is deficient in all tissues from human patients and animal models with globoid cell leukodystrophy (GLD) or Krabbe disease.', 'The purification of GALC and the securing of amino acid sequence information will aid in the cloning of the GALC gene. This enzyme is deficient in human patients with Krabbe disease and several animal species.']

['Galactocerebrosidase is an enzyme that is deficient in Krabbe disease (also known as globoid-cell leukodystrophy). This leads to accumulation of psychosine (galactosylsphingosine) primarily in oligodendrocytes.']

['galactocerebrosidase']

Is rivaroxaban metabolized in kidneys?

['The novel oral anticoagulants (i.e., dabigatran, apixaban, rivaroxaban) all undergo renal metabolism to varying degrees, and hence dosing, efficacy, and safety require special consideration in CKD patients.', 'The new oral anticoagulants have relatively little data in patients with severe renal impairment, and all have an element of renal excretion.', 'Now new anticoagulant drugs(dabigatran and rivaroxaban) can become available. Therefore, we have to learn how to use those drugs. They have to carefully be used because they discharge from kidney and old aged patients have potential renal dysfunction. ', 'In the everyday practice it will be necessary to be very cautious in patients with impaired renal function, as all these drugs are eliminated by kidneys.', 'Dabigatran etexilate and rivaroxaban carry the highest risk due to a high degree of renal excretion, whereas the risk for apixaban, edoxaban and betrixaban seems lower.', 'However, all these agents undergo renal clearance to varying degrees, and hence dosing, efficacy, and safety require special consideration in patients with CKD. ', 'Rivaroxaban being excreted via kidney and liver, some precautions should apply in case of liver insufficiency. ', 'Rivaroxaban elimination is mainly renal, but also through faecal matter and by hepatic metabolism. ']

['rivaroxaban undergoes renal metabolism']

['yes']

Can the Micro-C XL method achieve mononucleosome resolution?

['We present Micro-C XL, an improved method for analysis of chromosome folding at mononucleosome resolution', 'We present Micro-C XL, an improved method for analysis of chromosome folding at mononucleosome resolution.', 'Micro-C XL: assaying chromosome conformation from the nucleosome to the entire genome.', 'Micro-C XL provides a single assay to interrogate chromosome folding at length scales from the nucleosome to the full genome.']

['Yes. Micro-C XL is an improved method for analysis of chromosome folding at mononucleosome resolution.']

['yes']

What is the role of SERCA in diabetic cardiomyopathy?

['Compared with control group, [Ca(2+)](i) and the expression of CaSR, RyR and SERCA/PLN were decreased, while PKC-α and PLN were significantly increased in a time-dependent manner in diabetic group', 'Diabetic rats showed impaired cardiac structure and function compared with control rats. The expression of PKC, PLB increased significantly, while the PPI-1, SERCA-2 and RyR expression decreased. Treatment with breviscapine could reverse the cardiac dysfunction and structure changes in diabetic cardiomyopathy rats, and decrease the expression of PKC and PLB, as well as increase the expression of PPI-1, SERCA-2 and RyR.', 'Diabetic Ren-2 rats developed impairment of both active and passive phases of diastole, accompanied by reductions in SERCA-2a ATPase and phospholamban along with activation of the fetal gene program.', 'The levels of SERCA and GLUT4, but not PLB, were significantly reduced in diabetic hearts compared with controls.', 'CONCLUSIONS: CASQ2, FKBP12.6 and SERCA2a were down-regulated in diabetic cardiomyopathy.', 'Reduced sarcoplasmic calcium ATPase (SERCA2a) expression has been shown to play a significant role in the cardiac dysfunction in diabetic cardiomyopathy.', 'Depressed sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA2a) and Ca(2+)-release channels (ryanodine receptor RyR2) are involved in diabetic cardiomyopathy, however, the implication of intracellular calcium handling proteins in SR is undefined.', 'The depressed sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a) and Ca2+-release channels (ryanodine receptor RyR2) are involved in the diabetic cardiomyopathy.', 'Slowed relaxation in diabetic cardiomyopathy (CM) is partially related to diminished expression of the sarcoplasmic reticulum (SR) Ca2+-ATPase SERCA2a.']

['Diabetic cardiomyopathy is accompanied by reduced SERCA levels and activity in later stages. The up-regulation of SERCA2a in the early phase of type 2 diabetes is an important physiological adaptation of the heart.']

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ROSIER scale is used for which disorder?

['Validation of the use of the ROSIER scale in prehospital assessment of stroke.', 'MATERIALS AND METHODS: Compared with the Cincinnati Prehospital Stroke Scale (CPSS), emergency physicians prospectively used the ROSIER as a stroke recognition tool on suspected patients in the prehospital setting.', "CONCLUSIONS: The ROSIER is a sensitive and specific stroke recognition tool for health providers' use among Chinese patients in the prehospital setting.", 'Can the FAST and ROSIER adult stroke recognition tools be applied to confirmed childhood arterial ischemic stroke?', ' Two adult stroke recognition tools; ROSIER (Recognition of Stroke in the Emergency Room) and FAST (Face Arm Speech Test) scales were applied retrospectively to all patients to determine test sensitivity. ', ' DIAGNOSTIC SCALES: The results of an assessment with the Recognition of Stroke in the Emergency Room (ROSIER) scale, the Face Arm Speech Test (FAST) scale and the diagnosis of definite or probable stroke by an emergency department.', 'CONCLUSIONS: The simpler FAST scale could replace the more complex ROSIER for the initial assessment of patients with suspected acute stroke in the emergency department.', 'The Recognition of Stroke in the Emergency Room (ROSIER) scale: development and validation of a stroke recognition instrument.', 'We designed and validated a stroke recognition tool-the Recognition of Stroke in the Emergency Room (ROSIER) scale-for use by ER physicians.', 'INTERPRETATION: The ROSIER scale was effective in the initial differentiation of acute stroke from stroke mimics in the ER.', 'DIAGNOSTIC SCALES: The results of an assessment with the Recognition of Stroke in the Emergency Room (ROSIER) scale, the Face Arm Speech Test (FAST) scale and the diagnosis of definite or probable stroke by an emergency department.', 'The ROSIER scale had greater sensitivity than existing stroke recognition instruments in this population.', 'If the ROSIER scale is to be clinically useful in Chinese suspected stroke patients, it requires further refinement.', 'Evaluation of the Recognition of Stroke in the Emergency Room (ROSIER) scale in Chinese patients in Hong Kong.', 'The ROSIER scale was effective in the initial differentiation of acute stroke from stroke mimics in the ER.', 'We designed and validated a stroke recognition tool-the Recognition of Stroke in the Emergency Room (ROSIER) scale-for use by ER physicians.', 'The simpler FAST scale could replace the more complex ROSIER for the initial assessment of patients with suspected acute stroke in the emergency department.', 'The ROSIER scale was effective in the initial differentiation of acute stroke from stroke mimics in the ER.', 'DIAGNOSTIC SCALES: The results of an assessment with the Recognition of Stroke in the Emergency Room (ROSIER) scale, the Face Arm Speech Test (FAST) scale and the diagnosis of definite or probable stroke by an emergency department', 'The ROSIER scale had greater sensitivity than existing stroke recognition instruments in this population.', 'The ROSIER scale was effective in the initial differentiation of acute stroke from stroke mimics in the ER', 'We designed and validated a stroke recognition tool-the Recognition of Stroke in the Emergency Room (ROSIER) scale-for use by ER physicians.', 'To determine the utility of the Recognition of Stroke in the Emergency Room (ROSIER) scale as a stroke recognition tool among Chinese patients in the prehospital setting.']

['ROSIER (Recognition of Stroke in the Emergency Room) scale was developed as a stroke recognition tool on suspected patients in the prehospital setting.']

['stroke']

Which is the major phytoalexin in alfalfa (Medicago sativa L.)?

['Medicarpin, the major phytoalexin in alfalfa, is synthesized via the isoflavonoid branch of phenylpropanoid metabolism.', 'Medicarpin, the major phytoalexin in alfalfa, is synthesized by way of the isoflavonoid branch of phenylpropanoid metabolism.', 'The major phytoalexin in alfalfa is the isoflavonoid (-)-medicarpin (or 6aR, 11aR)-medicarpin.', 'The isoflavonoid conjugates medicarpin-3-O-glucoside-6-O-malonate (MGM), afrormosin-7-O-glucoside (AG), and afrormosin-7-O-glucoside-6-O-malonate (AGM) were isolated and characterized from cell suspension cultures of alfalfa (Medicago sativa L.), where they were the major constitutive secondary metabolites.', 'Alfalfa (Medicago sativa L.) cell suspension cultures accumulated high concentrations of the pterocarpan phytoalexin medicarpin, reaching a maximum within 24 hours after exposure to an elicitor preparation from cell walls of the phytopathogenic fungus Colletotrichum lindemuthianum.', "The isoflavonoid conjugates medicarpin-3-O-glucoside-6''-O-malonate (MGM), afrormosin-7-O-glucoside (AG), and afrormosin-7-O-glucoside-6''-O-malonate (AGM) were isolated and characterized from cell suspension cultures of alfalfa (Medicago sativa L.), where they were the major constitutive secondary metabolites", 'The major phytoalexin in alfalfa is the isoflavonoid (-)-medicarpin (or 6aR, 11aR)-medicarpin', 'Medicarpin, the major phytoalexin in alfalfa, is synthesized via the isoflavonoid branch of phenylpropanoid metabolism', 'Medicarpin, the major phytoalexin in alfalfa, is synthesized by way of the isoflavonoid branch of phenylpropanoid metabolism']

['The major phytoalexin in alfalfa (Medicago sativa L.) is the isoflavonoid (-)-medicarpin (or 6aR, 11aR)-medicarpin. Medicarpin is synthesized via the isoflavonoid branch of phenylpropanoid metabolism.']

['medicarpin']

List common symptoms of patients with the DOORS syndrome.

['Deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures (DOORS) syndrome is a rare autosomal recessive disorder of unknown cause. ', 'Through a search of available case studies and communication with collaborators, we identified families that included at least one individual with at least three of the five main features of the DOORS syndrome: deafness, onychodystrophy, osteodystrophy, intellectual disability, and seizures. ']

['DOORS syndrome is a constellation of deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures. It is a rare autosomal recessive disorder of unknown cause.']

['deafness', 'onychodystrophy', 'osteodystrophy', 'mental retardation', 'seizures']

What is the relationship between TailorX and Oncotype?

['The TAILORx trial uses the Oncotype DX recurrence score to assign estrogen receptor-positive (ER+), node-negative patients to chemotherapy plus hormonal therapy versus hormonal therapy alone. ', 'A cohort study was undertaken, including consecutive patients with early node-negative, ER-positive breast cancer diagnosed between 2006 and May 2013, including a period of prospective clinical trial (Trial Assigning Individualised Options for Treatment (TAILORx)) recruitment.', 'Data were collected regarding patient demographics, tumour clinico-pathological features, Oncotype DX use and recurrence score and chemotherapy use. ', 'Oncotype DX testing began on a trial basis in 2007 and until October 2011, only patients enrolled on TAILORx availed of genomic profiling.', '479 consecutive patients were included in the study, of whom 241 (50%) underwent Oncotype DX testing, 97 as part of the TAILORx clinical trial.', 'To evaluate the ability to guide treatment decisions in the group with a mid-range recurrence score, the North American Cooperative Groups developed the Trial Assessing IndiviuaLized Options for Treatment for breast cancer, a randomized trial of chemotherapy followed by hormonal therapy versus hormonal therapy alone on invasive disease-free survival-ductal carcinoma in situ (IDFS-DCIS) survival in women with node-negative, estrogen-receptor-positive breast cancer with a recurrence score of 11-25.', 'One of these tests, Oncotype DXtrade mark, is a diagnostic test comprised of a 21-gene assay applied to paraffin-embedded breast cancer tissue, which allows physicians to predict subgroups of hormone-receptor-positive, node-negative patients who may benefit from hormonal therapy alone or require adjuvant chemotherapy to attain the best survival outcome.', 'We tested if Oncotype DX and TAILORx risk categories could be predicted by standard pathological features and protein markers corresponding to 10 genes in the assay (ER, PR, Ki67, HER2, BCL2, CD68, Aurora A kinase, survivin, cyclin B1 and BAG1) on 52 patients who enrolled on TAILORx', 'The TAILORx trial uses the Oncotype DX recurrence score to assign estrogen receptor-positive (ER+), node-negative patients to chemotherapy plus hormonal therapy versus hormonal therapy alone', 'Prediction of Oncotype DX and TAILORx risk categories using histopathological and immunohistochemical markers by classification and regression tree (CART) analysis', 'Each patient is stratified into a risk category based on a recurrence score (RS) and the TAILORx trial is determining the benefit of chemotherapy for patients with mid-range RSs. We tested if Oncotype DX and TAILORx risk categories could be predicted by standard pathological features and protein markers corresponding to 10 genes in the assay (ER, PR, Ki67, HER2, BCL2, CD68, Aurora A kinase, survivin, cyclin B1 and BAG1) on 52 patients who enrolled on TAILORx.', '479 consecutive patients were included in the study, of whom 241 (50%) underwent Oncotype DX testing, 97 as part of the TAILORx clinical trial. Oncotype DX testing began on a trial basis in 2007 and until October 2011, only patients enrolled on TAILORx availed of genomic profiling.', 'The TAILORx trial uses the Oncotype DX recurrence score to assign estrogen receptor-positive (ER+),']

['The TAILORx trial uses the Oncotype DX recurrence score to assign estrogen receptor-positive (ER+), node-negative patients to chemotherapy plus hormonal therapy versus hormonal therapy alone.']

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What role do mutations in the histone methyltransferase EZH2 play in causing Weaver syndrome?

['["Loss-of-function mutations of EZH2, a catalytic component of polycomb repressive complex 2 (PRC2), are observed in ~\\\\n10% of patients with myelodysplastic syndrome (MDS), but are rare in acute myeloid leukaemia (AML)", "We describe the use of an oligo-SNP array for genomic profiling of aCNA and cnLOH, together with sequence analysis of recurrently mutated genes, in a patient with myelodysplastic syndrome (MDS) presenting with normal karyotype and FISH result", " Conditionally deleting Ezh2 in mature T cells dramatically reduced the production of BM-destructive Th1 cells in vivo, decreased BM-infiltrating Th1 cells, and rescued mice from BM failure.", "Acquired aplastic anemia (AA) is a potentially fatal bone marrow (BM) failure syndrome", "Constitutional NSD1 and EZH2 mutations cause Sotos and Weaver syndromes respectively, overgrowth syndromes with considerable phenotypic overlap.", "EZH2 mutations that cause Weaver syndrome are primarily missense variants and the rare truncating mutations reported to date are in the last exon, suggesting that simple haploinsufficiency is unlikely to be generating the overgrowth phenotype although the exact mechanism has not yet been determined", "Weaver syndrome and EZH2 mutations", "In 2011, mutations in the histone methyltransferase, EZH2, were shown to cause Weaver syndrome", "The identification of an EZH2 mutation can therefore provide an objective means of confirming a subtle presentation of Weaver syndrome and/or distinguishing Weaver and Sotos syndromes. ", "Mutations in EZH2 cause Weaver syndrome", "These data show that mutations in EZH2 cause Weaver syndrome", "The EZH2 mutation spectrum in Weaver syndrome shows considerable overlap with the inactivating somatic EZH2 mutations recently reported in myeloid malignancies", "EZH2 mutations as the cause of Weaver syndrome and provide further links between histone modifications and regulation of human growth.", "Mutations at tyrosine 641 (Y641F, Y641N, Y641S and Y641H) in the SET domain of EZH2 have been identified in patients with certain subtypes of non-Hodgkin lymphoma (NHL)", "The EZH2 gene was previously reported to be located on chromosome 21q22 and was proposed as a candidate gene for some characteristics of the Down syndrome phenotype", "Recent extensive mutation analyses of the myeloid malignancies have revealed that inactivating somatic mutations in PcG genes such as EZH2 and ASXL1 occur frequently in patients with myelodysplastic disorders including myelodysplastic syndromes (MDSs) and MDS/myeloproliferative neoplasm (MPN) overlap disorders (MDS/MPN).", "EZH2 is frequently overexpressed and considered to be an oncogene in cancers; nevertheless, EZH2 is considered as a candidate tumor suppressor gene in MDS due to EZH2 mutations associated with poor survival.", "In 2011, mutations in the histone methyltransferase, EZH2, were shown to cause Weaver syndrome.", "Among them, Sotos and Weaver syndromes are clinically well defined and due to heterozygous mutations in NSD1 and EZH2, respectively.", "Weaver syndrome and EZH2 mutations: Clarifying the clinical phenotype.", "Constitutional NSD1 and EZH2 mutations cause Sotos and Weaver syndromes respectively, overgrowth syndromes with considerable phenotypic overlap.", "The identification of an EZH2 mutation can therefore provide an objective means of confirming a subtle presentation of Weaver syndrome and/or distinguishing Weaver and Sotos syndromes.", "We postulated that mutations in writers of these two chromatin marks could cause overgrowth conditions, resembling Sotos or Weaver syndromes, in patients with no NSD1 or EZH2 abnormalities.", "Recent extensive mutation analyses of the myeloid malignancies have revealed that inactivating somatic mutations in PcG genes such as EZH2 and ASXL1 occur frequently in patients with myelodysplastic disorders including myelodysplastic syndromes (MDSs) and MDS/myeloproliferative neoplasm (MPN) overlap disorders (MDS/MPN). ", "Somatic mutations of epigenetic gene regulators are common in patients with myelodysplastic syndromes (MDS) and correlate with some clinical and laboratory features. ", "Recently, the advent of next generation sequencing (NGS) techniques has helped identify somatic gene mutations in 75-']

Mutations in the histone methyltransferase EZH2 cause Weaver syndrome and provide further links between histone modifications and regulation of human growth.

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How functional connectivity of the default mode network changes in patients with disorders of consciousness?

['Functional connectivity in the default mode network (DMN) is known to be reduced in patients with disorders of consciousness, to a different extent depending on their clinical severity.', 'Patients showed significant impairments in all of the pathways connecting cortical regions within this network, as well as the pathway connecting the posterior cingulate cortex/precuneus with the thalamus, relative to the healthy volunteers.', "Moreover, the structural integrity of this pathway, as well as that of those connecting the posterior areas of the network, was correlated with the patients' behavioral signs for awareness, being higher in EMCS patients than those in the upper and lower ranges of the MCS patients, and lowest in VS patients.", 'These results provide a possible neural substrate for the functional disconnection previously described in these patients, and reinforce the importance of the DMN in the genesis of awareness and the neural bases of its disorders.', 'Although the functional significance of the default-mode network remains a matter of debate, it has been suggested to be a candidate for the network subserving basic functions related to consciousness.', 'Despite resolution of corpus callosum lesion on magnetic resonance imaging (MRI) within 1 week, the patient persistently presented disturbance of consciousness. Resting-state functional MRI revealed that the posterior cingulate cortex/precuneus was functionally disconnected from other brain regions within the default-mode network.', 'Our case report suggests that assessment of the functional connectivity in the resting-state default-mode network could be a useful marker of consciousness disturbance even in the presence of a reversible brain lesion.', 'A present and intact DMN was observed in controls and those patients who subsequently regained consciousness, but was disrupted in all patients who failed to regain consciousness.', 'The results suggest that the DMN is necessary but not sufficient to support consciousness.', 'Clinically, DMN connectivity may serve as an indicator of the extent of cortical disruption and predict reversible impairments in consciousness.', 'Recent studies on resting state activity in DOC, measured with functional magnetic resonance imaging (fMRI) techniques, show that functional connectivity is disrupted in the task-negative or the default mode network.', 'This report shows for the first time, in three patients, that the persistent vegetative state (PVS) is marked by a dysfunctional default mode network, with decreased connectivity in several brain regions, including the dorsolateral prefrontal cortex and anterior cingulated cortex, especially in the right hemisphere.']

['Functional connectivity in the default mode network (DMN) is reduced in patients with different disorders of consciousness, and correlates with the level of consciousness. \nSpecifically, functional connectivity in the default mode network was shown to be absent in brain death patients, extremely low in vegetative state patients and slightly decreased in minimally conscious state patients when compared to healthy subjects. Therefore, functional connectivity in the default mode network was suggested to be valuable in differentiating patients with different disorders of consciousness. Clinically, functional connectivity in the default mode network was also shown to be an indicator of the extent of cortical disruption and predict reversible impairments in consciousness.']

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Which phenotypes are associated with heterozygous mutations of the BSCL2 gene?

['Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2) gene have been associated with different clinical phenotypes including Silver syndrome/spastic paraplegia 17, distal hereditary motor neuropathy type V, and Charcot-Marie-Tooth disease type 2 (CMT2) with predominant hand involvement', 'Distal hereditary motor neuropathy type V (dHMN-V) and Charcot-Marie-Tooth syndrome (CMT) type 2 presenting with predominant hand involvement, also known as CMT2D and Silver syndrome (SS) are rare phenotypically overlapping diseases which can be caused by mutations in the Berardinelli-Seip Congenital Lipodystrophy 2 (BSCL2) and in the glycyl-tRNA synthetase encoding (GARS) genes', 'Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2) gene have been associated with different clinical phenotypes including Silver syndrome/spastic paraplegia 17, distal hereditary motor neuropathy type V, and Charcot-Marie-Tooth disease type 2 (CMT2) with predominant hand involvement.', 'In 2004, heterozygous mutations (N88S, S90L) in the Seipin/BSCL2 gene were identified in two autosomal dominant motor neuron diseases, distal hereditary motor neuropathy type V (OMIM #182960) and Silver syndrome (OMIM #270685).', 'We recently found heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2, seipin) gene causing SPG17 and distal hereditary motor neuropathy type V (distal HMN V).', 'Distal hereditary motor neuropathy type V (dHMN-V) and Silver syndrome are rare phenotypically overlapping diseases which can be caused by mutations in the Berardinelli-Seip Congenital Lipodystrophy 2 (BSCL2) gene or Seipin.', 'Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome.', "Heterozygous mutations in the Seipin/BSCL2 gene have recently been identified in two autosomal dominant motor neuron diseases, distal hereditary motor neuropathy type V and Silver's syndrome.", 'We recently found heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2, seipin) gene causing SPG17 and distal hereditary motor neuropathy type V (distal HMN V)', 'Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome', 'In 2004, heterozygous mutations (N88S, S90L) in the Seipin/BSCL2 gene were identified in two autosomal dominant motor neuron diseases, distal hereditary motor neuropathy type V (OMIM #182960) and Silver syndrome (OMIM #270685)', 'Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2) gene have been associated with different clinical phenotypes including Silver syndrome/spastic paraplegia 17, distal hereditary motor neuropathy type V, and Charcot-Marie-Tooth disease type 2 (CMT2) with predominant hand involvement. ', 'Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2) gene have been associated with different clinical phenotypes including Silver syndrome/spastic paraplegia 17,', 'We recently found heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2, seipin) gene causing SPG17 and distal hereditary motor neuropathy type V (distal HMN V). Here we report the clinical features of two families with heterozygous BSCL2 mutations.', 'Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2) gene have been associated with different clinical phenotypes including Silver syndrome/spastic paraplegia 17, distal hereditary motor neuropathy type V, and Charcot-Marie-Tooth disease type 2 (CMT2) with predominant hand involvement.', 'Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome.', 'We recently found heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2, seipin) gene causing SPG17 and distal hereditary motor neuropathy type V (distal HMN V).', 'In 2004, heterozygous mutations (N88S, S90L) in the Seipin/BSCL2 gene were identified in two autosomal dominant motor neuron diseases, distal hereditary motor neuropathy type V (OMIM #182960) and Silver syndrome (OMIM #270685).', "Heterozygous mutations in the Seipin/BSCL2 gene have recently been identified in two autosomal dominant motor neuron diseases, distal hereditary motor neuropathy type V and Silver's syndrome."]

['Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2) gene have been associated with different clinical phenotypes including Silver syndrome/spastic paraplegia 17, distal hereditary motor neuropathy type V, and Charcot-Marie-Tooth disease type 2 (CMT2) with predominant hand involvement.', 'Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2) gene have been associated with different clinical phenotypes including Silver syndrome/spastic paraplegia 17, distal hereditary motor neuropathy type V, and Charcot-Marie-Tooth disease type 2 (CMT2) with predominant hand involvement']

['Silver syndrome/spastic paraplegia 17', 'Distal hereditary motor neuropathy type V', 'Charcot-Marie-Tooth disease type 2 (CMT2) with predominant hand involvement']

Which SLC family is FLVCR1 a member of?

['Feline leukemia virus subgroup C receptor (FLVCR1), a member of the SLC49 family of four paralogous genes, is a cell surface heme exporter, essential for erythropoiesis and systemic iron homeostasis.', 'Feline leukemia virus subgroup C receptor (FLVCR1), a member of the SLC49 family of four paralogous genes, is a cell surface heme exporter, essential for erythropoiesis and systemic iron homeostasis.', 'Feline leukemia virus subgroup C receptor (FLVCR1), a member of the SLC49 family of four paralogous genes, is a cell surface heme exporter, essential for erythropoiesis and systemic iron homeostasis. Disruption of FLVCR1 function blocks development of erythroid progenitors, likely due to heme toxicity.', ' Heme is critical for a variety of cellular processes, but excess intracellular heme may result in oxidative stress and membrane injury. Feline leukemia virus subgroup C receptor (FLVCR1), a member of the SLC49 family of four paralogous genes, is a cell surface heme exporter, essential for erythropoiesis and systemic iron homeostasis.', 'Heme is critical for a variety of cellular processes, but excess intracellular heme may result in oxidative stress and membrane injury. Feline leukemia virus subgroup C receptor (FLVCR1), a member of the SLC49 family of four paralogous genes, is a cell surface heme exporter, essential for erythropoiesis and systemic iron homeostasis.']

['Feline leukemia virus subgroup C receptor (FLVCR1) is a member of the SLC49 family.']

['SLC49']

Does NADPH oxidase 5 require any subunit for function?

['Nox5 forms a functional oligomer mediated by self-association of its dehydrogenase domain.', ' While Nox1-4 require regulatory subunits, including p22phox, Nox5 activity does not depend on any subunits. ', ' Thus, Nox5 forms a catalytically active oligomer in the membrane that is mediated by its dehydrogenase domain. ', 'Coexpression of specific Nox catalytic subunits (Nox1, Nox2, Nox3, Nox4, or Nox5) along with their corresponding regulatory subunits (NOXO1/NOXA1 for Nox1; p47phox/p67phox/Rac for Nox2; NOXO1 for Nox3; no subunits for Nox4 or Nox5) resulted in marked production of reactive oxygen. ']

['No, NADPH oxidase 5 (NOX5) does not require any subunits for function.']

['no']

Are there any functional differences between Mfd and its human Cocaine syndrome protein B (CSB) homolog?

['In humans, the TCR coupling factor, CSB, plays a critical role in restoring transcription following both UV-induced and oxidative DNA damage. It also contributes indirectly to the global repair of some forms of oxidative DNA damage. The Escherichia coli homolog, Mfd, is similarly required for TCR of UV-induced lesions.', 'Mfd may be functionally distinct from its human CSB homolog in that it does not detectably contribute to the recovery of gene expression or global repair following oxidative damage.', 'CSB has an ATPase activity that is stimulated strongly by DNA; however, it neither acts as a helicase nor does it dissociate stalled RNA polymerase II, suggesting a coupling mechanism in humans different from that in prokaryotes. ', 'In addition, these findings imply that Mfd may be functionally distinct from its human CSB homolog in that it does not detectably contribute to the recovery of gene expression or global repair following oxidative damage.', 'In addition, these findings imply that Mfd may be functionally distinct from its human CSB homolog in that it does not detectably contribute to the recovery of gene expression or global repair following oxidative damage.', 'In contrast, no difference was detected in the rate of transcription recovery in mfd, uvrA, fpg, nth, or polB dinB umuDC mutants relative to wild-type cells following oxidative damage']

['Both Cockayne syndrome protein B (CSB) and Mfd are involved in transcription-coupled repair. CSB is the human TCR coupling factor and Mfd is the bacterial TCR coupling factor. However, unlike Mfd, CSB does not act as a helicase nor does it dissociate stalled RNA polymerase II, suggesting a coupling mechanism in humans different from that in prokaryotes. Moreover, Mfd may be functionally distinct from its human CSB homolog in that it does not detectably contribute to the recovery of gene expression or global repair following oxidative damage.']

['yes']

Which receptors can be evaluated with the [18F]altanserin?

['PURPOSE: While the selective 5-hydroxytryptamine type 2a receptor (5-HT2AR) radiotracer [18F]altanserin is well established in humans, the present study evaluated its suitability for quantifying cerebral 5-HT2ARs with positron emission tomography (PET) in albino rats.', 'CONCLUSION: [18F]Altanserin PET is a reliable tool for in vivo quantification of 5-HT2AR availability in albino rats.', 'Imaging the cerebral serotonin 2A (5-HT2A ) receptors with positron emission tomography (PET) has been carried out in humans with [(11) C]MDL 100907 and [(18) F]altanserin.', 'The cortical binding of [(18) F]MH.MZ and [(18) F]altanserin was blocked by ketanserin supporting that both radioligands bind to 5-HT2A receptors in the pig brain.', 'We investigated 94 healthy individuals (60 men, mean age 47.0±18.7, range 23-86) to determine if trait aggression and trait impulsivity were related to frontal cortex 5-HT2A receptor binding (5-HT2AR) as measured with [18F]-altanserin PET imaging. ', 'Two hours after placebo/drug administration, 250 MBq of the 5-HT(2A) receptor selective PET-radiotracer [(18)F]altanserin was administered intravenously as a 30s bolus.', 'These data suggest that the combination of a dexfenfluramine-induced 5-HT release and subsequent assessment of 5-HT(2A) receptor availability with [(18)F]altanserin PET is suitable to measure cortical 5-HT release capacity in the human brain.', 'The 5-hydroxytryptamine type 2a (5-HT(2A)) selective radiotracer [(18)F]altanserin has been subjected to a quantitative micro-positron emission tomography study in Lister Hooded rats.', '[(18)F]altanserin is suitable for quantification of 5-HT(2A) receptor availability in rats.', 'Altanserin, a fluorobenzoyl derivative related to ketanserin, was reported to be a potent antagonist of 5-HT2A receptors with >100-fold selectivity over D2/3 receptors, 5-HT1A, 5-HT6, and 5-HT7 (9, 10). This led to the development of 3-{2-[4-(4-[(18)F]fluorobenzoyl)-1-piperidyl]ethyl}-2-sulfanyl-3H-quinazolin-4-one ([(18)F]altanserin) as a useful tool for 5-HT2A receptor PET imaging in vivo (11). ', 'Altanserin, a fluorobenzoyl derivative related to ketanserin, was reported to be a potent antagonist of 5-HT2A receptors with >100-fold selectivity over D2/3 receptors, 5-HT1A, 5-HT6, and 5-HT7 (9, 10). This led to the development of 3-{2-[4-(4-[(18)F]fluorobenzoyl)-1-piperidyl]ethyl}-2-sulfanyl-3H-quinazolin-4-one ([(18)F]altanserin) as a useful tool for 5-HT2A receptor PET imaging in vivo (11). 5-HT2A antagonists bind to the total pool of receptors, whereas 5-HT2A agonists bind only to the high-affinity functional state of the receptor but may be more important in disease states because the high affinity sites are the ones that transmit the intracellular signals. ', 'Baseline and follow-up partial volume corrected levels of 5-HT2A in four neocortical lobes and the posterior cingulate gyrus were investigated using [18F]altanserin positron emission tomography with a bolus-infusion approach.', 'Altanserin, a fluorobenzoyl derivative related to ketanserin, was reported to be a potent inhibitor of 5-HT2A receptors with >100-fold selectivity over D2/3 receptors, 5-HT1A, 5-HT6, and 5-HT7 (8, 9). This led to the development of 3-[2-[4-(4-[(18)F]fluorobenzoyl)-1-piperidyl]ethyl]-2-sulfanyl-3H-quinazolin-4-one ([(18)F]altanserin) as a useful tool for 5-HT2A receptor PET imaging in vivo (10).', 'We investigated the relationships of gender, mood, impulsivity, aggression and temperament to 5HT(2A) receptor binding in 21 healthy subjects using [18F]altanserin and PET neuroimaging.', 'We, therefore, studied the binding potential of the serotonin 2A (5-HT(2A)) receptor ligand [18F]altanserin in 8 patients with clinically probable PSP and 13 healthy controls using positron emission tomography. ', '[(18)F]altanserin is the preferred radiotracer for in-vivo labeling of serotonin 2A receptors by positron emission tomography (PET). ', 'Twenty-one healthy subjects underwent PET scanning with the 5-HT(2A) antagonist, [(18)F]altanserin.', 'METHODS: [(18)F]-Altanserin PET was used to quantify 5-HT(2A) receptors in 12 healthy elderly individuals at baseline and at 2 years in six volumes of interest. ', 'The aim of this feasibility study was to examine whether acute ketamine-induced 5-HT release interferes with the binding of the 5-HT(2A) receptor (5-HT(2A)R) radioligand [(18)F]altanserin and positron emission tomography (PET)', 'METHODS: Fifteen women ill with AN (ILL AN) were compared with 29 healthy control women (CW); PET and [11C]WAY100635 were used to assess binding potential (BP) of the 5-HT1A receptor, and [18F]altanserin was used to assess postsynaptic 5-HT2A receptor BP.', 'In summary, these results demonstrate that the test-retest variability of [18F]altanserin-specific binding is comparable to that of other PET radiotracers and that the regional specific binding of [18F]altanserin in human brain was correlated with the known regional distribution of 5-HT2A receptors.', '[18F]altanserin binding to human 5HT2A receptors is unaltered after citalopram and pindolol challenge.', 'Our data confirmed that [18F]altanserin is a valid tracer for 5HT2 receptors binding studies.', 'PET quantification of 5-HT2A receptors in the human brain: a constant infusion paradigm with [18F]altanserin.', 'In vivo binding of [18F]altanserin to rat brain 5HT2 receptors: a film and electronic autoradiographic study.', 'We used [18F]altanserin and positron emission tomography (PET) to image serotonin 5-HT2A receptors in humans.', 'Quantification of 5-HT2A receptors in the human brain using [18F]altanserin-PET and the bolus/infusion approach.', 'These findings support the usefulness of [18F]altanserin as a radioligand for PET studies of 5-HT2A receptors.', 'This study was performed to identify and characterize the radiometabolites of the serotonin 5-HT2A receptor ligand [18F]altanserin in supporting quantification of the target receptors by positron emission tomography.', 'PURPOSE: To determine the reproducibility of measurements of brain 5-HT2A receptors with an [18F]altanserin PET bolus/infusion approach.', '18F]altanserin binding to human 5HT2A receptors is unaltered after citalopram and pindolol challenge.', 'Influence of synaptic serotonin level on [18F]altanserin binding to 5HT2 receptors in man.', 'The aim of the present study is to describe and validate a method for accurate quantification of 5-hydroxytryptamine (5-HT)(2A) receptors using [18F]altanserin-positron emission tomography (PET) and the bolus/infusion approach.', 'The regional [18F]altanserin DV values using both of these methods were significantly correlated with literature-based values of the regional concentrations of 5-HT2A receptors determined by postmortem autoradiographic studies (r2 = 0.95, P < 0.001 for the 4C model and r2 = 0.96, P < 0.001 for the Logan method).', 'In summary, these results demonstrate that the test-retest variability of [18F]altanserin-specific binding is comparable to that of other PET radiotracers and that the regional specific binding of [18F]altanserin in human brain was correlated with the known regional distribution of 5-HT2A receptors.', 'These findings support the usefulness of [18F]altanserin as a radioligand for PET studies of 5-HT2A receptors.', 'Reduced binding of [18F]altanserin to serotonin type 2A receptors in aging: persistence of effect after partial volume correction.', 'Visualisation of loss of 5-HT2A receptors with age in healthy volunteers using [18F]altanserin and positron emission tomographic imaging.', 'Imaging the cerebral serotonin 2A (5-HT2A ) receptors with positron emission tomography (PET) has been carried out in humans with [(11) C]MDL 100907 and [(18) F]altanserin', '[(18)F]altanserin showed sufficient brain uptake in a distribution pattern consistent with the known distribution of 5-HT(2A) receptors', 'This controlled cross-over PET study aimed to identify brain regions with WM-induced changes in the binding potential (BP(nd)) of the 5-HT2aR antagonist [(18)F]altanserin', 'MZ and [(18) F]altanserin was blocked by ketanserin supporting that both radioligands bind to 5-HT2A receptors in the pig brain', "PET was performed by using [18F]altanserin to evaluate 5-HT2A receptor binding in 11 elderly patients with depression (four men, seven women; mean age = 65.0 years, SD = 5.5); nine Alzheimer's disease patients, including three with concurrent depression (two men, seven women; mean age = 69.7 years, SD = 5.0); and 10 age-matched healthy subjects (four men, six women; mean age = 69.8 years, SD = 5.0)", 'While the selective 5-hydroxytryptamine type 2a receptor (5-HT2AR) radiotracer [18F]altanserin is well established in humans, the present study evaluated its suitability for quantifying cerebral 5-HT2ARs with positron emission tomography (PET) in albino rats.', 'This study was performed to identify and characterize the radiometabolites of the serotonin 5-HT2A receptor ligand [18F]altanserin in supporting quantification of the target receptors by positron emission tomography', 'To this end, the regional distribution and intrasubject test-retest variability of the binding of [18F]altanserin were measured as important steps in the further development of [18F]altanserin as a radiotracer for positron emission tomography (PET) studies of the serotonin 5-HT2A receptor', 'Our data confirmed that [18F]altanserin is a valid tracer for 5HT2 receptors binding studies.', 'In summary, these results demonstrate that the test-retest variability of [18F]altanserin-specific binding is comparable to that of other PET radiotracers and that the regional specific binding of [18F]altanserin in human brain was correlated with the known regional distribution of 5-HT2A receptors', 'Characterization of radioactive metabolites of 5-HT2A receptor PET ligand [18F]altanserin in human and rodent.', 'We used [18F]altanserin and positron emission tomography (PET) to image serotonin 5-HT2A receptors in humans']

['5-HT2A (5-hydroxytryptamine type 2a) receptor can be evaluated with the [18F]altanserin.']

['5-HT2A']

How is oprozomib administered?

['Further, new orally administered second-generation PI oprozomib is being investigated. ', 'Carfilzomib and its orally bioavailable structural analog oprozomib are second-generation, highly-selective, proteasome inhibitors.', 'This review provides an overview of the role of oral proteasome inhibitors including Marizomib, Oprozomib, Delanzomib, chemical proteasome inhibitors, and cinnabaramides, in the therapy of MM, focusing on developments over the past five years. ', 'In addition, novel drug classes have shown promising activity in RR MM, including the orally-administered proteasome inhibitors ixazomib and oprozomib; monoclonal antibodies such as the anti-CS1 monoclonal antibody elotuzumab and anti-CD38 monoclonal antibody daratumumab; and histone deacetylase inhibitors such as panobinostat and rocilinostat.', 'Further, new orally administered second-generation PI oprozomib is being investigated.', 'In addition, novel drug classes have shown promising activity in RR MM, including the orally-administered proteasome inhibitors ixazomib and oprozomib; monoclonal antibodies such as the anti-CS1 monoclonal antibody elotuzumab and anti-CD38 monoclonal antibody daratumumab; and histone deacetylase inhibitors such as panobinostat and rocilinostat.', 'We concluded that based on its activity and oral bioavailability, oprozomib merits further investigation in an animal GvHD prevention model.', 'Carfilzomib and its orally bioavailable analog oprozomib, effectively decreased MM cell viability following continual or transient treatment mimicking in vivo pharmacokinetics.', 'Carfilzomib and its orally bioavailable structural analog oprozomib are second-generation, highly-selective, proteasome inhibitors.', 'Further, new orally administered second-generation PI oprozomib is being investigated', 'In addition, novel drug classes have shown promising activity in RR MM, including the orally-administered proteasome inhibitors ixazomib and oprozomib; monoclonal antibodies such as the anti-CS1 monoclonal antibody elotuzumab and anti-CD38 monoclonal antibody daratumumab; and histone deacetylase inhibitors such as panobinostat and rocilinostat', 'The epoxyketone-based proteasome inhibitors carfilzomib and orally bioavailable oprozomib have anti-resorptive and bone-anabolic activity in addition to anti-myeloma effects.', 'Carfilzomib and its orally bioavailable structural analog oprozomib are second-generation, highly-selective, proteasome inhibitors. However, the mechanisms of acquired resistance to carfilzomib and oprozomib are incompletely understood, and effective strategies for overcoming this resistance are needed. ', 'Carfilzomib and its orally bioavailable analog oprozomib, effectively decreased MM cell viability following continual or transient treatment mimicking in vivo pharmacokinetics. ', 'Carfilzomib and its orally bioavailable structural analog oprozomib are second-generation, highly-selective, proteasome inhibitors. ', 'new orally administered second-generation PI oprozomib is being investigated.', 'including the orally-administered proteasome inhibitors ixazomib and oprozomib; monoclonal antibodies such as the anti-CS1 monoclonal antibody elotuzumab and anti-CD38 monoclonal antibody daratumumab; and histone deacetylase inhibitors such as panobinostat and rocilinostat.', 'Carfilzomib and its orally bioavailable structural analog oprozomib are second-generation, highly-selective, proteasome inhibitors. However, the mechanisms of acquired resistance to carfilzomib and oprozomib are incompletely understood, and effective strategies for overcoming this resistance are needed.', 'Finally, we found that DC incubation with the drug(s) enhanced IκB expression and that oprozomib inhibited NF-κB expression. We concluded that based on its activity and oral bioavailability, oprozomib merits further investigation in an animal GvHD prevention model.']

['Oprozomib is administered orally.']

['Orally']

Is Wnt16b secreted in response to chemotherapy?

[' In this study, we found WNT16B could be expressed and secreted into the microenvironment by human ovarian fibroblasts after DNA damage-associated treatment, including chemotherapy drugs and radiation.', 'In a recent article in Nature Medicine, Sun et al. show that increased expression of Wnt family member wingless-type MMTV integration site family member 16B (WNT16B) by the tumor microenvironment in response to cytotoxic damage and signals through the canonical Wnt pathway to promote tumor growth and chemotherapy resistance. ', 'Using a genome-wide analysis of transcriptional responses to genotoxic stress induced by cancer therapeutics, we identified a spectrum of secreted proteins derived from the tumor microenvironment that includes the Wnt family member wingless-type MMTV integration site family member 16B (WNT16B).']

['Yes, WNT16B is secreted into the microenvironment by human ovarian fibroblasts after DNA damage-associated treatment, including chemotherapy drugs and radiation.']

['yes']

Which proteins compose the error prevention GO (8-oxo-G) system in Pseudomonas putida?

['the GO repair enzymes MutY, MutM, and MutT are involved in the prevention of base substitution mutations in carbon-starved P. putida.', 'Our results demonstrated that the GO repair enzymes MutY, MutM, and MutT are involved in the prevention of base substitution mutations in carbon-starved P. putida.']

['In P. putida (Pseudomonas putida) the error prevention GO (8-oxo-G) system is composed of MutY, MutM, and MutT enzymes.']

['MutY', 'MutM', 'MutT']

Is rucaparib used for ovarian cancer treatment?

['While olaparib is the first PARP inhibitor to receive approval for ovarian cancer treatment, others including rucaparib and niraparib are clearly effective in this disease and, within the next year or two, the results of ongoing randomised trials will clarify their respective roles. ', 'Similar trials with other PARP inhibitors (rucaparib, niraparib and veliparib) are in progress and include non-BRCA-mutated ovarian cancer. ', 'IMPLICATIONS FOR PRACTICE: The poly(ADP-ribose) polymerase (PARP) inhibitor olaparib has recently received approval from the Food and Drug Administration (FDA) and European Medicines Agency (EMA), with a second agent (rucaparib) likely to be approved in the near future.', 'Ovarian Cancers Harbour Defects in Non-Homologous End Joining Resulting in Resistance to Rucaparib.', 'There are a number of other PARP inhibitors in late phase clinical development in ovarian cancer including rucaparib, niraparib, veliparib, and talazoparib. ', 'Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial.', 'INTERPRETATION: In patients with BRCA mutant or BRCA wild-type and LOH high platinum-sensitive ovarian carcinomas treated with rucaparib, progression-free survival was longer than in patients with BRCA wild-type LOH low carcinomas. Our results suggest that assessment of tumour LOH can be used to identify patients with BRCA wild-type platinum-sensitive ovarian cancers who might benefit from rucaparib. ', 'Genomic LOH May Predict Rucaparib Response in Ovarian Cancer.', 'High LOH is associated with response to the PARP inhibitor rucaparib in BRCA wild-type ovarian cancer.', 'Therapeutic potential of the poly(ADP-ribose) polymerase inhibitor rucaparib for the treatment of sporadic human ovarian cancer.', 'While olaparib is the first PARP inhibitor to receive approval for ovarian cancer treatment, others including rucaparib and niraparib are clearly effective in this disease and, within the next year or two, the results of ongoing randomised trials will clarify their respective roles.', 'These results support further clinical evaluation of rucaparib either as a single agent or as an adjunct to chemotherapy for the treatment of sporadic ovarian cancer.', 'Here, we investigate the potential role of the PARP inhibitor rucaparib (CO-338, formerly known as AG014699 and PF-01367338) for the treatment of sporadic ovarian cancer.', 'Rucaparib received US FDA Breakthrough Therapy designation for treatment of platinum-sensitive BRCA-mutated advanced ovarian cancer patients who received greater than two lines of platinum-based therapy.', 'These results support further clinical evaluation of rucaparib either as a single agent or as an adjunct to chemotherapy for the treatment of sporadic ovarian cancer.', 'Ongoing clinical trials are assessing the efficacy of rucaparib alone or in combination with other cytotoxic drugs, mainly in breast and ovarian cancer patients with mutations in the breast cancer associated (BRCA) genes.PURPOSE: We aimed to establish whether the multidrug efflux transporters ABCG2 (BCRP) and ABCB1 (P-gp, MDR1) affect the oral availability and brain penetration of rucaparib in mice.RESULTS: In vitro, rucaparib was efficiently transported by both human ABCB1 and ABCG2, and very efficiently by mouse Abcg2.', 'Therapeutic potential of the poly(ADP-ribose) polymerase inhibitor rucaparib for the treatment of sporadic human ovarian cancer', 'Here, we investigate the potential role of the PARP inhibitor rucaparib (CO-338, formerly known as AG014699 and PF-01367338) for the treatment of sporadic ovarian cancer', 'These results support further clinical evaluation of rucaparib either as a single agent or as an adjunct to chemotherapy for the treatment of sporadic ovarian cancer.<CopyrightInformation>©2013 AACR</', 'Ongoing clinical trials are assessing the efficacy of rucaparib alone or in combination with other cytotoxic drugs, mainly in breast and ovarian cancer patients with mutations in the breast cancer associated (BRCA) genes.We aimed to establish whether the multidrug efflux transporters ABCG2 (BCRP) and ABCB1 (P-gp, MDR1) affect the oral availability and brain penetration of rucaparib in mice.In vitro, rucaparib was efficiently transported by both human ABCB1 and ABCG2, and very efficiently by mouse Abcg2', 'Here, we investigate the potential role of the PARP inhibitor rucaparib (CO-338, formerly known as AG014699 and PF-01367338) for the treatment of sporadic ovarian cancer. ', 'While olaparib is the first PARP inhibitor to receive approval for ovarian cancer treatment, others including rucaparib and niraparib are clearly effective in this disease and, within the next year or two, the results of ongoing randomised trials will clarify their respective roles.', 'We investigated the efficacy and safety of single-agent rucaparib in germline (g) BRCA mutation carriers with advanced breast and ovarian cancers.Phase II, open-label, multicentre trial of rucaparib in proven BRCA-1/2 mutation carriers with advanced breast and or ovarian cancer, WHO PS 0-1 and normal organ function.', 'These results support further clinical evaluation of rucaparib either as a single agent or as an adjunct to chemotherapy for the treatment of sporadic ovarian cancer.<CopyrightInformation>©2013 AACR</C', 'Similar trials with other PARP inhibitors (rucaparib, niraparib and veliparib) are in progress and include non-BRCA-mutated ovarian cancer.', 'Rucaparib received US FDA Breakthrough Therapy designation for treatment of platinum-sensitive BRCA-mutated advanced ovarian cancer patients who received greater than two lines of platinum-based therapy.', 'Therapeutic potential of the poly(ADP-ribose) polymerase inhibitor rucaparib for the treatment of sporadic human ovarian cancer.', 'These results support further clinical evaluation of rucaparib either as a single agent or as an adjunct to chemotherapy for the treatment of sporadic ovarian cancer..']

['Yes, rucaparib is a PARP inhibitor that is used for ovarian cancer treatment.']

['yes']

What is the role of photodynamic therapy for meningioma treatment?

['CONCLUSIONS: Efficacy of 5-ALA PDT could be increased by adjunction of ciprofloxacin in conventional clinical dosing and by prolongation of ALA incubation time. ', 'CONCLUSION: Gefitinib can inhibit ABCG2-mediated PpIX efflux from malignant brain tumor cells to increase the intracellular PpIX and thereby enhance the PDT effect.', 'CONCLUSION: ALA-PDT was more effective in killing U-105MG glioma cells than CH-157MN meningioma cells.', 'These data indicate unique features of AlPc which suggests its application as a potent, non-toxic photosensitizer in the photodynamic therapy of human meningiomas.', 'Photodynamic therapy is being investigated as an adjuvant treatment for intracranial neoplasms. ', 'It was found that PDT using haematoporphyrin derivative as a photosensitizing drug showed dose-dependent activity against a variety of histological subtypes of meningioma. ', 'Photodynamic therapy is a promising treatment for human brain tumors because of the selective retention of certain compounds by tumor cells. ', 'Susceptibility to 5-aminolevulinic acid based photodynamic therapy in WHO I meningioma cells corresponds to ferrochelatase activity.', 'We conclude that differences in intracellular PpIX concentrations between HBL-52 and BEN-MEN-1 benign meningioma cells were mainly due to differences in FECH activity and that these differences correspond to their susceptibility to 5-ALA-induced PDT.', 'Photodynamic therapy (PDT) has been employed in the management of recurrent cerebral gliomas but its activity against meningiomas has not been specifically studied.', 'Enhancing the effect of 5-aminolevulinic acid based photodynamic therapy in human meningioma cells.', 'An in vitro study of the effect of photodynamic therapy on human meningiomas.', 'Photodynamic therapy (PDT) has been employed in the management of recurrent cerebral gliomas but its activity against meningiomas has not been specifically studied. ']

['Photodynamic therapy was shown to have activity againt meningioma treatment. Gefitinib and ciprofloxacin enhance efficacy of photodynamic therapy.']

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Do IEG create a ripple effect of transcription?

['Rapid induction of immediate-early genes (IEGs) in response to growth factor stimulations is accompanied by co-upregulation of their neighbouring genes.', 'Even in surrounding intergenic regions, transcriptional activation took place at the same time. ', 'Here we show that intensive transcription at one locus frequently spills over into its physical neighbouring loci.', 'Ripples from neighbouring transcription.', 'Ripples from neighbouring transcription.']

['Rapid induction of immediate-early genes (IEGs) in response to growth factor stimulations is accompanied by co-upregulation of their neighbouring genes. Profiling the primary transcripts in the nucleus with whole-genome tiling arrays delineated simultaneous activation of transcription centred on IEGs.', 'rapid induction of immediate-early genes (iegs) in response to growth factor stimulations is accompanied by co-upregulation of their neighbouring genes.', 'Rapid induction of immediate-early genes (IEGs) in response to growth factor stimulations is accompanied by co-upregulation of their neighbouring genes. Even in surrounding intergenic regions, transcriptional activation took place at the same time.', 'Rapid induction of immediate-early genes (IEGs) in response to growth factor stimulations is accompanied by co-upregulation of their neighbouring genes.', 'Here we show that intensive transcription at one locus frequently spills over into its physical neighbouring loci. Rapid induction of immediate-early genes (IEGs) in response to growth factor stimulations is accompanied by co-upregulation of their neighbouring genes.']

['yes']

What congenital anomalies are commonly found in Mowat-Wilson syndrome, particularly regarding heart defects and male genitourinary issues?

[' genitourinary anomalies (in particular hypospadias in males), congenital heart defects, agenesis of the corpus callosum and eye anomalies.", "Mowat-Wilson syndrome is a mental retardation-multiple congenital anomaly syndrome characterized by a typical facies, developmental delay, epilepsy, and variable congenital malformations, including Hirschsprung disease, urogenital anomalies, congenital heart disease, and agenesis of the corpus callosum. ", "Mowat-Wilson syndrome (MWS) is a recently delineated mental retardation (MR)-multiple congenital anomaly syndrome, characterized by typical facies, severe MR, epilepsy, and variable congenital malformations, including Hirschsprung disease (HSCR), genital anomalies, congenital heart disease (CHD), and agenesis of the corpus callosum (ACC). ", "Medical issues in our cohort of patients included seizures (75%) with no predeliction for any particular seizure type; agenesis of the corpus callosum (60% of our patients studied); congenital heart defects (75%), particularly involving the pulmonary arteries and/or valves; hypospadias (55% of males); severely impaired or absent speech (100% of individuals over 1 year of age) with relatively spared receptive language; and Hirschsprung disease (50%) or chronic constipation (25%). ", "Mowat-Wilson syndrome (MWS) is a mental retardation syndrome associated with distinctive facial features, microcephaly, epilepsy, and a variable spectrum of congenital anomalies, including Hirschsprung disease (HSCR), agenesis of the corpus callosum, genitourinary abnormalities, and congenital heart disease.", "ACC is found in 40% of the cases of Mowat-Wilson syndrome (MWS), a polytopic embryonic defect including a distinctive facial gestalt, severe mental retardation, epilepsy and postnatal microcephaly as constant features. ", "However, analysis of MWS should be considered in the differential diagnosis of ACC, especially when the facial features raise the possibility of MWS.", "Frameshift mutation of the zinc finger homeo box 1 B gene in syndromic corpus callosum agenesis (Mowat-Wilson syndrome).", "We report a girl who had Hirschsprung disease in association with distinct facial appearance, microcephaly, agenesis of the corpus callosum and mental retardation (Mowat-Wilson syndrome).", "Congenital anomalies, including Hirschsprung disease (HSCR), congenital heart disease, hypospadias, genitourinary anomalies, agenesis of the corpus callosum, and short stature are common. "]', ' genitourinary anomalies (in particular hypospadias in males), congenital heart defects, agenesis of the corpus callosum and eye anomalies.", "Mowat-Wilson syndrome is a mental retardation-multiple congenital anomaly syndrome characterized by a typical facies, developmental delay, epilepsy, and variable congenital malformations, including Hirschsprung disease, urogenital anomalies, congenital heart disease, and agenesis of the corpus callosum. ", "Mowat-Wilson syndrome (MWS) is a recently delineated mental retardation (MR)-multiple congenital anomaly syndrome, characterized by typical facies, severe MR, epilepsy, and variable congenital malformations, including Hirschsprung disease (HSCR), genital anomalies, congenital heart disease (CHD), and agenesis of the corpus callosum (ACC). ", "Medical issues in our cohort of patients included seizures (75%) with no predeliction for any particular seizure type; agenesis of the corpus callosum (60% of our patients studied); congenital heart defects (75%), particularly involving the pulmonary arteries and/or valves; hypospadias (55% of males); severely impaired or absent speech (100% of individuals over 1 year of age) with relatively spared receptive language; and Hirschsprung disease (50%) or chronic constipation (25%). ", "Mowat-Wilson syndrome (MWS) is a mental retardation syndrome associated with distinctive facial features, microcephaly, epilepsy, and a variable spectrum of congenital anomalies, including Hirschsprung disease (HSCR), agenesis of the corpus callosum, genitourinary abnormalities, and congenital heart disease.", "ACC is found in 40% of the cases of Mowat-Wilson syndrome (MWS), a polytopic embryonic defect including a distinctive facial gestalt, severe mental retardation, epilepsy and postnatal microcephaly as constant features. ", "However, analysis of MWS should be considered in the differential diagnosis of ACC, especially when the facial features raise the possibility of MWS.", "Frameshift mutation of the zinc finger homeo box 1 B gene in syndromic corpus callosum agenesis (Mowat-Wilson syndrome).", "We report a girl who had Hirschsprung disease in association with distinct facial appearance, microcephaly, agenesis of the corpus callosum and mental retardation (Mowat-Wilson syndrome).", "Congenital anomalies, including Hirschsprung disease (HSCR), congenital heart disease, hypospadias, genitourinary anomalies, agenesis of the corpus callosum, and short stature are common. "]']

Congenital anomalies commonly found in Mowat-Wilson syndrome include agenesis of the corpus callosum, congenital heart defects, hypospadias in males, and genitourinary anomalies.

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Which gene mutations cause the Marfan syndrome?

['The diagnostic criteria of Marfan syndrome (MFS) highlight the importance of a FBN1 mutation test in diagnosing MFS. ', 'A marked decrease in heart rate variability in Marfan syndrome patients with confirmed FBN1 mutations.', 'The studies on heart rate variability (HRV), a key predictor of all-cause mortality, in Marfan syndrome (MS), up to now have not been reported, especially in patients with FBN1 mutations.', 'Among 18 MS patients with the phenotype of MS meeting inclusion criteria 15 have had a FBN1 gene mutation. ', 'Heart rates in MS patients with the FBN1 mutation were increased in both the supine position and orthostatic test (p<0.001).', 'A marked decrease in HRV, documented in the study, may be an important clinical feature in MS patients with confirmed FBN1 gene mutations.', 'Evaluating the quality of Marfan genotype-phenotype correlations in existing FBN1 databases.', 'Genetic FBN1 testing is pivotal for confirming the clinical diagnosis of Marfan syndrome. ', 'Novel FBN1 gene mutation and maternal germinal mosaicism as the cause of neonatal form of Marfan syndrome.', 'Marfan syndrome (MFS) is an autosomal dominant disorder caused by mutations in the fibrillin 1 gene (FBN1). ', 'While mutations causing classic manifestations of Marfan syndrome have been identified throughout the FBN1 gene, the six previously characterized mutations resulting in the severe, perinatal lethal form of Marfan syndrome have clustered in exons 24-32 of the gene.', '[Screening of FBN1 gene mutations in a family with Marfan syndrome].', 'To identify FBN1 gene mutations in a Chinese family with Marfan syndrome.', 'Identification of fibrillin-1 gene mutations in Marfan syndrome by high-resolution melting analysis.', 'Three diagnostic classifications comprising first, Marfan genotype with a causative FBN1 gene mutation; second, Marfan phenotype with clinical criteria of the original Ghent nosology (Ghent-1); and third, phenotype with clinical criteria of its current revision (Ghent-2) in 300 consecutive persons referred for confirmation or exclusion of Marfan syndrome (150 men, 150 women aged 35 ± 13 years) were used.', 'Prevalence of dural ectasia in 63 gene-mutation-positive patients with features of Marfan syndrome type 1 and Loeys-Dietz syndrome and report of 22 novel FBN1 mutations.', 'Marfan syndrome type 1 (MFS1) is caused by mutations in the FBN1 gene.', 'Fibrillin gene (FBN1) mutations in Japanese patients with Marfan syndrome.', 'Mutations in FBN1, TGFBR1, TGFBR2 are known to cause Marfan syndrome (MIM 154700), a pleiotropic disorder.', 'Classic, atypically severe and neonatal Marfan syndrome: twelve mutations and genotype-phenotype correlations in FBN1 exons 24-40.', 'We conclude that fibrillin gene defects cause familial Marfan syndrome, that mutations in the EGF-like motif of the fibrillin gene are not uniformly associated with severe disease, and that fibrillin genotype is not the sole determinant of Marfan phenotype.', "Mutations of the fibrillin gene (FBN1) are known to cause classical Marfan's syndrome, ectopia lentis and neonatal Marfan's syndrome.", 'Severe Marfan syndrome due to FBN1 exon deletions.', 'BACKGROUND: Mutations in the FBN1 gene are the cause of the Marfan syndrome, an autosomal dominant disorder with skeletal, ocular, and cardiovascular complications.', 'It is still difficult to use modern genetic testing for diagnosis because Marfan syndrome can be caused by many different mutations in FBN1, a large gene with 65 coding segments, while mutations in other genes can cause overlapping phenotypes', 'The studies on heart rate variability (HRV), a key predictor of all-cause mortality, in Marfan syndrome (MS), up to now have not been reported, especially in patients with FBN1 mutations.Among 18 MS patients with the phenotype of MS meeting inclusion criteria 15 have had a FBN1 gene mutation', 'Mutations in the gene encoding fibrillin-1 (FBN1), a component of the extracellular microfibril, cause Marfan syndrome (MFS)', 'Mutations in the fibrillin-1 (FBN1) gene cause Marfan syndrome (MFS) and have been associated with a wide range of overlapping phenotypes', 'Mutations in the gene encoding fibrillin-1 (FBN1) cause Marfan syndrome (MFS) and other related connective tissue disorders', 'Mutations in the FBN1 gene cause Marfan syndrome (MFS) and have been associated with a wide range of milder overlapping phenotypes', 'The aim of this study was to establish a national database of mutations in the fibrillin-1 (FBN1) gene that cause Marfan syndrome (MFS) in the Taiwanese population', 'Fibrillin-1 gene (FBN1) mutations cause Marfan syndrome (MFS), an inherited connective tissue disorder with autosomal dominant transmission', 'Mutations in the gene encoding fibrillin 1 (FBN1) cause Marfan syndrome (MFS), and related connective tissue disorders', 'Acute mitral regurgitation due to chordal rupture in a patient with neonatal Marfan syndrome caused by a deletion in exon 29 of the FBN1 gene.', 'Neonatal Marfan syndrome caused by an exon 25 mutation of the fibrillin-1 gene.', 'Functional pulmonary atresia in a patient with neonatal Marfan syndrome caused by a c.3602G>A mutation in exon 29 of the FBN1 gene.', 'Mutations in the gene for fibrillin-1 (FBN1) cause Marfan syndrome, an autosomal dominant disorder of connective tissue with prominent manifestations in the skeletal, ocular, and cardiovascular system. ', 'It has been firmly established that mutations in the gene for fibrillin 1, FBN1, cause Marfan syndrome (MFS).', 'Mutations in the fibrillin-1 gene (FBN1) cause Marfan syndrome and related connective tissue disorders (fibrillinopathies) that show autosomal dominant inheritance.', 'It is known that mutations in the fibrillin gene cause a heterogenous connective tissue disease called Marfan syndrome [2], so information on mechanical properties of microfibrils or their role in tissue function would be useful.', 'Mutations in the fibrillin gene located on human chromosome 15 have been strongly implicated as the cause of the Marfan syndrome.', 'Mutations in the FBN1 gene cause Marfan syndrome (MFS) and have been associated with a wide range of milder overlapping phenotypes.', 'Mutations within the fibrillin-1 gene cause Marfan syndrome (MFS), a heritable disease of connective tissue.', 'These data speak against the hypothesis that mutations in one or more of these 3 fibrillar collagens cause the classic Marfan syndrome.', 'By WES and filtering with a mining tool, a novel FBN1 missense variant was found in patient 1 and his mother, who both showed clinical features of Marfan syndrome by thorough anthropometric assessment, and a novel EYA1 missense variant as a probable cause of the renal malformation in the patient.', 'Mutations in the fibrillin-1 (FBN1) gene cause Marfan syndrome (MFS) and have been associated with a wide range of overlapping phenotypes.', 'FBN1 mutations cause Marfan syndrome, whose major cardiovascular complication is TAAD.', 'Marfan syndrome is a multisystem disorder of connective tissue that is inherited in an autosomal dominant fashion, and results from mutation of the FBN1 gene on human chromosome 15.', 'Mutations in the gene for fibrillin-1 (FBN1) cause Marfan syndrome, an autosomal dominant disorder of connective tissue with prominent manifestations in the skeletal, ocular, and cardiovascular system.', 'We here report 22 novel and 9 recurrent mutations in the FBN1 gene in 36 patients with clinical features of Marfan syndrome.', "The fibrillin gene is the site of mutations causing Marfan's syndrome.", 'Fibrillin-1 gene (FBN1) mutations cause Marfan syndrome (MFS), an inherited connective tissue disorder with autosomal dominant transmission.', 'FBN1 at 15q21.1 was found to cause Marfan syndrome in 1991, and in 2004 TGFBR2 at 3p24.1 was newly identified as the Marfan syndrome type II gene.', 'Fifteen novel FBN1 mutations causing Marfan syndrome detected by heteroduplex analysis of genomic amplicons.', 'Mutations in the gene encoding fibrillin-1 (FBN1) cause Marfan syndrome (MFS) and other related connective tissue disorders.', 'Mutations in the gene coding for fibrillin-1, FBN1, are known to cause Marfan syndrome, and have been identified in almost all exons of FBN1.', 'Mutations in the gene encoding fibrillin-1 (FBN1), a component of the extracellular microfibril, cause the Marfan syndrome (MFS).', 'The aim of this study was to establish a national database of mutations in the fibrillin-1 (FBN1) gene that cause Marfan syndrome (MFS) in the Taiwanese population.', 'While mutations causing classic manifestations of Marfan syndrome have been identified throughout the FBN1 gene, the six previously characterized mutations resulting in the severe, perinatal lethal form of Marfan syndrome have clustered in exons 24-32 of the gene.', 'Mutations in the fibrillin-1 (FBN1) gene, on chromosome 15q21.1, have been found to cause Marfan syndrome, a dominantly inherited disorder characterised by clinically variable skeletal, ocular, and cardiovascular abnormalities.', 'Mutations in the gene for fibrillin-1 (FBN1) have been shown to cause Marfan syndrome, an autosomal dominant disorder of connective tissue characterised by pleiotropic manifestations involving primarily the ocular, skeletal, and cardiovascular systems.', 'Through a number of investigational approaches, the gene encoding for fibrillin, the FBN1 gene on chromosome 15, has been identified as the defective gene causing the Marfan syndrome.']

['Marfan syndrome (MFS) is an autosomal dominant disorder caused by mutations in the fibrillin 1 gene (FBN1).']

['fibrillin 1 gene', 'FBN1']

Which is the protein that is encoded by the gene GLT8D1?

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['The GLT8D1 gene codes for the protein named glycosyltransferase 8 domain containing 1']

['glycosyltransferase 8 domain containing 1']

How are protein biomarkers used to study the impact of genetic and lifestyle factors on plasma protein profiles?

['[" To study the impact of genetic and lifestyle factors on protein biomarkers and develop personally normalized plasma protein profiles (PNPPP) controlling for non-disease-related variance."]']

Protein biomarkers are used to study the impact of genetic and lifestyle factors on plasma protein profiles by developing personally normalized plasma protein profiles (PNPPP) that control for non-disease-related variance.

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What do studies show about the effect of Induced hypothermia in premature babies?

['Therapeutic hypothermia is a recognized treatment for term infants with hypoxic-ischemic encephalopathy (HIE) in reducing rate of death or neurodevelopmental disabilities. Little is known about applications of this treatment to preterm newborns.', 'Randomised studies have demonstrated the efficacy of hypothermia for the treatment of perinatal hypoxic-ischaemic encephalopathy (HIE) in term or late preterm infants.', 'We aimed to establish the feasibility and safety of mild hypothermia in preterm neonates with NEC and MODS as a prelude to a randomized trial. METHODS: This was a prospective, nonrandomized pilot study of 15 preterm infants who were referred for surgical intervention of advanced NEC and failure of at least 3 organs. Whole-body cooling was achieved by ambient temperature adjustment with or without cooling mattress', 'Mild hypothermia for 48 hours in preterm neonates with severe NEC seems both feasible and safe. Additional investigation of the efficacy of this therapeutic intervention in this population is warranted.']

['Randomised studies have demonstrated the efficacy of hypothermia for the treatment of perinatal hypoxic-ischaemic encephalopathy (HIE) in reducing rate of death or neurodevelopmental disabilities in term or late preterm infants. It remains unclear to what degree preterm infants were included in these studies.\nA prospective non-randomised pilot study reported that mild hypothermia for 48 hours in preterm neonates with severe NEC (necrotising enterocolitis) seems both feasible and safe.']

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How can physical performance improve in patients with chronic heart failure and subclinical hypothyroidism by achieving normal TSH levels with T(3) replacement therapy?

['["Patients with chronic heart failure and subclinical hypothyroidism significantly improved their physical performance when normal TSH levels were reached.", "Early and sustained physiological restoration of circulating L-T3 levels after MI halves infarct scar size and prevents the progression towards heart failure. This beneficial effect is likely due to enhanced capillary formation and mitochondrial protection.", "These data indicate that T(3) replacement to euthyroid levels improves systolic function and tends to improve diastolic function, potentially through changes in myocardial gene expression.", "In these patients, the administration of synthetic triiodothyronine (T(3)) was well tolerated and induced significant improvement in cardiac function without increased heart rate and metabolic demand.", "In DC patients, short-term synthetic L-T(3) replacement therapy significantly improved neuroendocrine profile and ventricular performance.", "Triiodothyronine was well tolerated without episodes of ischemia or clinical arrhythmia. There was no significant change in heart rate or metabolic rate and there was minimal increase in core temperature. Cardiac output increased with a reduction in systemic vascular resistance in patients receiving the largest dose, consistent with a peripheral vasodilatory effect."]', '["Patients with chronic heart failure and subclinical hypothyroidism significantly improved their physical performance when normal TSH levels were reached.", "Early and sustained physiological restoration of circulating L-T3 levels after MI halves infarct scar size and prevents the progression towards heart failure. This beneficial effect is likely due to enhanced capillary formation and mitochondrial protection.", "These data indicate that T(3) replacement to euthyroid levels improves systolic function and tends to improve diastolic function, potentially through changes in myocardial gene expression.", "In these patients, the administration of synthetic triiodothyronine (T(3)) was well tolerated and induced significant improvement in cardiac function without increased heart rate and metabolic demand.", "In DC patients, short-term synthetic L-T(3) replacement therapy significantly improved neuroendocrine profile and ventricular performance.", "Triiodothyronine was well tolerated without episodes of ischemia or clinical arrhythmia. There was no significant change in heart rate or metabolic rate and there was minimal increase in core temperature. Cardiac output increased with a reduction in systemic vascular resistance in patients receiving the largest dose, consistent with a peripheral vasodilatory effect."]']

Patients with chronic heart failure and subclinical hypothyroidism can significantly improve their physical performance by achieving normal TSH levels with T(3) replacement therapy. This improvement is observed when normal TSH levels are reached, indicating the importance of thyroid hormone balance in enhancing physical performance in these patients.

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What is the mechanism of action of geldanamycin?

['Geldanamycin (HSP90 inhibitor)', 'Geldanamycin is an antibiotic originally discovered based on its ability to bind heat-shock protein 90. This interaction can lead to the disruption of heat-shock protein 90-containing multimolecular complexes. It can also induce the inhibition or even degradation of partner proteins dissociated from the 90 kDa chaperone and, eventually, can cause apoptosis, for instance, in PC12 cells.', 'An Hsp90 ATPase inhibitor, geldanamycin, inhibits luciferase reactivation demonstrating the importance of the ATP-dependent chaperone activity of E. coli Hsp90 during client protein remodeling.', 'Unique proteome patterns were observed in HeLa cells treated with the HSP90 inhibitor geldanamycin, and were similar to the patterns induced by radicicol, a structurally different HSP90 inhibitor.', 'the Hsp90 inhibitor geldanamycin', 'The molecular chaperone heat-shock protein (Hsp) 90 is an important anticancer drug target because it maintains the conformation, stability, and function of many important oncogenic client proteins, including those involved with signal transduction, cell proliferation, survival, differentiation, motility angiogenesis, and metastasis. Using the standard inhibitors of the adenosine triphosphatase (ATPase) activity of Hsp90, geldanamycin (GA) and 17-allylamino-17- demethoxygeldanamycin (17AAG), novel solid-phase immunoassays have been validated using a time-resolved fluorescence (TRF) end point. Their utility for confirming the mechanism of action of Hsp90 inhibition in secondary cell-based assays has been shown and applied to the novel Hsp90 inhibitor CCT018159.', 'A recent crystal structure of the NH2-terminal domain of yeast Hsp90 established the presence of a conserved nucleotide binding site that is identical with the binding site of geldanamycin, a specific inhibitor of Hsp90.', 'The functional significance of nucleotide binding by Hsp90 has remained unclear. Here we present evidence for a slow but clearly detectable ATPase activity in purified Hsp90.']

['Geldanamycin is an ansamycin antibiotic which holds the ability to bind heat-shock protein 90. This interaction can lead to the disruption of heat-shock protein 90-containing multimolecular complexes. Additionally, it can induce inhibition or even degradation of partner proteins dissociated from the 90 kDa chaperone and, eventually, cause apoptosis in a variety of cell types.']

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The secreted frizzled-related protein 3 (sFPR3) is altered in human cancers. Are its level found to increase or to decrease?

['We performed tissue microarray and found that the level of sFRP3 protein was high in normal kidney, low in primary renal cancer tissues, and high in metastatic renal cancer tissues.', 'In conclusion, this is the first report to show that sFRP3 expression promotes cell growth, invasion, and inhibition of apoptosis in renal cancer cells.', 'secreted frizzled-related protein-3 were produced by multiple myeloma cells.', 'these data suggest a tumor-suppressive potential for FRZB/sFRP3 in OGS.', 'The ability of Frzb/secreted Frizzled-related protein 3 (sFRP3) to inhibit Wnt signaling and the localization of Frzb/sFRP3 on chromosome 2q to a region frequently deleted in cancers have led some investigators to hypothesize that Frzb/sFRP3 is a tumor suppressor gene.', 'Together, these data suggest that Frzb/sFRP3 and DN-LRP5 exhibit antitumor activity through the reversal of epithelial-to-mesenchymal transition and inhibition of MMP activities in a subset of prostate cancer.', 'secreted frizzled related protein (hsFRP) was found to be down-regulated in some cancer.', 'hsFRP is a potential tumor suppressor gene.', 'All these cases were associated with either up-regulation of FzE3 or down-regulation of hsFRP', 'Since modified Wnt signaling and down-regulation of frizzled-related proteins have been observed in many human cancers, this variant may also affect the susceptibility to other cancers.']

['SFRPs are down-regulated in several cancers and this is often correlated with poor prognosis, as has been shown for breast, colorectal, and a number of other cancers. (PMID: 21494614) We performed tissue microarray and found that the level of sFRP3 protein was high in normal kidney, low in primary renal cancer tissues, and high in metastatic renal cancer tissues. (PMID: 20160027)', 'Secreted frizzled-related protein 3 is potentially acting as a tumor suppressor gene, thus it is down-regulated (decreased) in some cancers.']

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What is the effect of CRD-BP on the stability of 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']

['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.', '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 ']

['To protect c-myc CRD from endonucleolytic attack.']

What is the incidence of new cases of X-linked adrenoleukodystrophy (ALD) in Australian and New Zealand in the late 1990's?

['cases of ALD diagnosed in Australia and New Zealand between 1981 and 1996 and their families. We estimate that the combined incidence of ALD and its variants in Australasia is at least 1.6 per 100,000. ']

['cases of ALD diagnosed in Australia and New Zealand between 1981 and 1996 and their families. We estimate that the combined incidence of ALD and its variants in Australasia is at least 1.6 per 100,000. ', 'cases of ALD diagnosed in Australia and New Zealand between 1981 and 1996 and their families. We estimate that the combined incidence of ALD and its variants in Australasia is at least 1.6 per 100,000.', 'When looking cases of ALD diagnosed in Australia and New Zealand between 1981 and 1996, it was estimated that the combined incidence of ALD and its variants in Australasia is at least 1.6 per 100,000.']

['1.6 per 100,000 people']

Which is the receptor for the immunosuppressive drug cyclosporin A (CsA)?

['hemical modification of CsA has led to analogs with distinct biological activities associated with its protein receptor family, cyclophilins', ' the CsA receptor, cyclophilin', 'These results would support cyclophilin as the major, if not only, intracellular receptor protein for CsA. ']

['Cyclophilin is the intracellular receptor protein for cyclosporin A (CsA).']

['cyclophilin']

Could BRCA gene test used for breast and ovarian cancer risk?

['Participation of Korean families at high risk for hereditary breast and ovarian cancer in BRCA1/2 genetic testing.', 'The prevalence of BRCA1/2 mutations in Korean ovarian cancer patients irrespective of the family history was significantly higher than previously reported. Possible founder mutations in Korean ovarian cancer patients were identified.', 'Germline Mutations of BRCA1 and BRCA2 in Korean Ovarian Cancer Patients: Finding Founder Mutations.', 'The assessment of BRCA1 and BRCA2 coding sequences to identify pathogenic mutations associated with inherited breast/ovarian cancer syndrome has provided a method to identify high-risk individuals, allowing them to seek preventative treatments and strategies. ', 'Maximising survival: the main concern of women with hereditary breast and ovarian cancer who undergo genetic testing for BRCA1/2.', ' Little is known about how women with hereditary breast and/or ovarian cancer who test positive for a BRCA gene manage the impact of a positive test result on their everyday lives and in the longer term. This study defined the experience and needs of women with hereditary breast and ovarian cancer and a positive BRCA test over time.', 'The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7 × 10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 × 10(-3)).', 'Female BRCA (breast cancer gene)-1 and BRCA-2 mutations are significantly associated with risk of developing breast and ovarian cancers, in turn, associated with female infertility. ', 'Large BRCA1 and BRCA2 genomic rearrangements in Polish high-risk breast and ovarian cancer families.', 'BRCA1 and BRCA2 are two major genes associated with familial breast and ovarian cancer susceptibility.', 'Until 2006, she supervised a diagnostic unit for BRCA gene testing at the Interdisciplinary Center for Hereditary Breast Cancer (Max Delbrück Center, Berlin, Germany). ', 'Inherited BRCA gene mutations convey a high risk for breast and ovarian cancer, but current guidelines limit BRCA mutation testing to women with early-onset cancer and relatives of mutation-positive cases. ', 'Women who carry a BRCA1 or BRCA2 gene mutation face a risk of developing breast or ovarian cancer at an earlier age than women without such a mutation.', 'In 2006, participants were recruited from Web sites for women with breast cancer or BRCA gene mutations. ', 'About 20 % of hereditary breast cancers are caused by mutations in BRCA1 and BRCA2 genes. Since BRCA1 and BRCA2 mutations may be spread throughout the gene, genetic testing is usually performed by direct sequencing of entire coding regions.', 'Suggestion of an association between BRCA2 c.7806-2A>G and risk of breast cancer in males has emerged. ', 'The presence of deleterious mutations in breast cancer (BRCA)-1 or BRCA-2 gene has a decisive influence on the development of various types of neoplasms, such as breast, ovarian, tubal, and peritoneal cancers. ', 'OBJECTIVE: Female BRCA (breast cancer gene)-1 and BRCA-2 mutations are significantly associated with risk of developing breast and ovarian cancers, in turn, associated with female infertility.', 'BRCA1 and BRCA2 genes are responsible for 5-10% of breast and ovarian cancer cases.', 'She was daughter of a woman, a carrier of BRCA 1 gene mutation, with early onset of breast cancer and positive family history.CONCLUSIONS: BRCA 1 and BRCA 2 gene mutations are of particular importance in the increasing risk of ovarian cancer and early onset of breast cancer as well as some other malignancies.', 'BACKGROUND: Women who are diagnosed with a deleterious mutation in either breast cancer (BRCA) gene have a high risk of developing breast and ovarian cancers at young ages.', 'We identified AJ individuals with breast and/or ovarian cancer undergoing hereditary breast/ovarian cancer risk assessment since 2006 without evidence of a deleterious mutation on BRCA gene sequencing who were screened for major gene rearrangements in BRCA1 and BRCA2.', 'Germline BRCA gene mutations are reportedly associated with hereditary breast and ovarian cancers.', '[Detection and occurrence of BRCA 1 gene mutation in patients with carcinoma of the breast and ovary].', 'We investigated the relationship between BRCA mutations and the distribution of familial cancers other than breast or ovary in high-risk breast cancer patients.PATIENTS WITH BREAST CANCER WHO HAD AT LEAST ONE OF THE FOLLOWING RISK FACTORS WERE ENROLLED: reported family history of breast or ovarian cancer; 40 years of age or younger age at diagnosis; bilateral breast cancer; or male gender', 'Mutations in breast cancer susceptibility genes (BRCA1 and BRCA2) are associated with increased risks for breast, ovarian, and other types of cancer.To review new evidence on the benefits and harms of risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women.MEDLINE and PsycINFO between 2004 and 30 July 2013, the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews from 2004 through the second quarter of 2013, Health Technology Assessment during the fourth quarter of 2012, Scopus, and reference lists.English-language studies about accuracy of risk assessment and benefits and harms of genetic counseling, genetic testing, and interventions to reduce cancer incidence and mortality.', 'The objective of this study was to assess the incidence of primary breast cancer (PBC) and contralateral breast cancer (CBC) in patients who had BRCA1/BRCA2-associated epithelial ovarian cancer (OC).From the database of the Rotterdam Family Cancer Clinic, patients who had BRCA-associated OC without a history of unilateral breast cancer (BC) (at risk of PBC; n = 79) or with a history of unilateral BC (at risk of CBC; n = 37) were selected', 'Statistically significant earlier ages at diagnosis also were observed within subgroups of BRCA1 and BRCA2 mutations, maternal inheritance, paternal inheritance, breast cancer only, and breast cancer-identified and ovarian cancer-identified families.Breast and ovarian cancers in BRCA mutation carriers appeared to be diagnosed at an earlier age in later generations', 'The USPSTF also reviewed interventions aimed at reducing the risk for BRCA-related cancer in women with potentially harmful BRCA mutations, including intensive cancer screening, medications, and risk-reducing surgery.This recommendation applies to asymptomatic women who have not been diagnosed with BRCA-related cancer.The USPSTF recommends that primary care providers screen women who have family members with breast, ovarian, tubal, or peritoneal cancer with 1 of several screening tools designed to identify a family history that may be associated with an increased risk for potentially harmful mutations in breast cancer susceptibility genes (BRCA1 or BRCA2)', 'If a woman bearing a mutation develops cancer in one breast, her risk of developing cancer in the other breast depends on the particular gene that is mutated and on her age at the onset of disease.About half of all monogenically determined carcinomas of the breast and ovary are due to a mutation in one or the other of the highly penetrant BRCA genes (BRCA1 and BRCA2)', 'A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk.Mutations of BRCA1 or BRCA2.Breast and ovarian cancer risks.Among BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317 (12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer', 'This study defined the experience and needs of women with hereditary breast and ovarian cancer and a positive BRCA test over time.METHODS: A grounded theory approach was taken using qualitative interviews (n = 49) and reflective diaries. ', 'Little is known about how women with hereditary breast and/or ovarian cancer who test positive for a BRCA gene manage the impact of a positive test result on their everyday lives and in the longer term.', 'This study defined the experience and needs of women with hereditary breast and ovarian cancer and a positive BRCA test over time.A grounded theory approach was taken using qualitative interviews (n = 49) and reflective diaries.', 'Women with a harmful mutation in the BReast CAncer (BRCA) gene are at significantly increased risk of developing hereditary breast and ovarian cancer (HBOC) during their lifetime, compared to those without.', 'Genetic testing for BRCA genes, associated with hereditary breast-ovarian cancer risk, is an accepted cancer control strategy.', 'Younger patients, those with a family history of breast or ovarian cancer, and those diagnosed more recently were more likely to be BRCA tested.', 'Mutations in BRCA genes elevate risk for breast and ovarian cancer.', 'Observational studies of prophylactic surgeries report reduced risks for breast and ovarian cancer in mutation carriers.No data describe the range of risk associated with BRCA mutations, genetic heterogeneity, and moderating factors; studies conducted in highly selected populations contain biases; and information on adverse effects is incomplete.A primary care approach to screening for inherited breast and ovarian cancer susceptibility has not been evaluated, and evidence is lacking to determine benefits and harms for the general population.', 'We identified AJ individuals with breast and/or ovarian cancer undergoing hereditary breast/ovarian cancer risk assessment since 2006 without evidence of a deleterious mutation on BRCA gene sequencing who were screened for major gene rearrangements in BRCA1 and BRCA2. For each proband, the pre-test probability of identifying a deleterious BRCA mutation was estimated using the Myriad II model. We identified 108 affected individuals who underwent large rearrangement testing (80 breast cancer, 19 ovarian cancer, nine both breast and ovarian cancer).', 'Truncated proteins are easily discriminated from full size.RESULTS: Three BRCA 1 gene alterations were identified in the investigated group of women suffering from ovarian or breast cancer. One asymptomatic person--carrier of BRCA 1 gene mutation--was identified in this study. She was daughter of a woman, a carrier of BRCA 1 gene mutation, with early onset of breast cancer and positive family history.CONCLUSIONS: BRCA 1 and BRCA 2 gene mutations are of particular importance in the increasing risk of ovarian cancer and early onset of breast cancer as well as some other malignancies.', 'Germline BRCA gene mutations are reportedly associated with hereditary breast and ovarian cancers. Identification of BRCA mutations greatly improves the preventive strategies and management of breast cancer.', 'Statistically significant earlier ages at diagnosis also were observed within subgroups of BRCA1 and BRCA2 mutations, maternal inheritance, paternal inheritance, breast cancer only, and breast cancer-identified and ovarian cancer-identified families.CONCLUSIONS: Breast and ovarian cancers in BRCA mutation carriers appeared to be diagnosed at an earlier age in later generations.', 'Truncated proteins are easily discriminated from full size.RESULTS: Three BRCA 1 gene alterations were identified in the investigated group of women suffering from ovarian or breast cancer.', 'However, some single risk factors without family histories (early-onset breast cancer, male breast cancer, or multiple organ cancers) may limit the utility of BRCA gene testing in the Korean population.', 'BRCA Mutations Increase Fertility in Families at Hereditary Breast/Ovarian Cancer Risk.', 'Because infertility is associated with breast and ovarian cancer risks, we hypothesized that the mutations in the BRCA gene may be associated with low response to fertility treatments.', "Moreover, in families of breast cancer patients without BRCA mutations, breast cancer risk depends on the patient's age at diagnosis.", 'Among the 554 women who underwent genetic testing for BRCA mutation, 78 were found to have a deleterious mutation in the BRCA1 gene, and 54 had a mutation in the BRCA 2 gene.', 'Frequent recurrent mutations in the breast and ovarian cancer susceptibility (BRCA) genes BRCA1 and BRCA2 among Hispanics, including a large rearrangement Mexican founder mutation (BRCA1 exon 9-12 deletion [ex9-12del]), suggest that an ancestry-informed BRCA-testing strategy could reduce disparities and promote cancer prevention by enabling economic screening for hereditary breast and ovarian cancer in Mexico.', 'Individuals who carry a BRCA gene mutation have increased lifetime risks of developing hereditary breast and ovarian cancer syndrome-related cancers.', 'BRCA gene mutations have been well described to carry an increased risk of both breast and ovarian cancer.', 'Ovarian cancer among 8,005 women from a breast cancer family history clinic: no increased risk of invasive ovarian cancer in families testing negative for BRCA1 and BRCA2.', 'Women who were BRCA carriers, women who had a history of breast cancer, DCIS, or breast biopsy, or had a family history of ovarian cancer were more likely to have undergone surgery for cancer risk reduction.', 'Genetic testing for breast cancer susceptibility became a reality after two cancer predisposition genes, BRCA1 and BRCA2, were identified.', 'Germline mutations in BRCA genes are associated with breast and ovarian cancer susceptibility.', 'We used person-years at risk to assess ovarian cancer rates in the study population, subdivided by genetic status (BRCA1, BRCA2, BRCA negative, BRCA untested) compared with the general population.']

['Yes, BRCA gene test could be used for breast and ovarian cancer risk, as female BRCA1 and BRCA2 mutations are significantly associated with risk of developing breast and ovarian cancers.']

['yes']

List the classical triad of symptoms of the Melkersson–Rosenthal syndrome.

['The Melkersson-Rosenthal syndrome consists of a triad of recurrent lip and/or face swelling, fissured tongue, and intermittent facial palsy. ', 'The patient has a typical for Melkersson-Rosenthal syndrome triad of symptoms: bilateral facial nerve palsy, lingua plicata and facial oedema. ', 'Melkersson-Rosenthal syndrome (MRS) is a rare disorder of unknown cause. The classical triad of MRS is orofacial edema, recurrent facial paralysis, and a fissured tongue.', 'Melkersson-Rosenthal syndrome (MRS) is a rare granulomatous inflammatory disease characterised by the triad of orofacial oedema, facial nerve palsy and furrowed tongue.', 'Melkersson-Rosenthal syndrome (MRS) is a rare neuro-mucocutaneous granulomatous disorder of unknown etiology, characterized by the triad of facial palsy, lingua plicata (fissured tongue), and orofacial edema. ', 'Melkerrson-Rosenthal syndrome is a rare disorder of unknown etiology. The classical triad of recurrent facial paralysis, swelling of the face, lips and deep furrowed tongue (Lingua Plicata) is seen in very few cases, majority of the patients often present with one or two symptoms only, which often leads to misdiagnosis and mismanagement. ', 'Melkersson-Rosenthal syndrome (MRS) is a rare neuromucocutaneous syndrome marked by the triad of recurrent nonpitting orofacial edema, fissured dorsal tongue (lingua plicata), and lower motoneuron facial paralysis.', 'Recurrent facial nerve palsy, facial swelling, and fissured tongue are the symptoms and signs of this condition. However, this triad is not typical in all patients as patients may present with one or more of the symptoms, which makes management of this condition difficult. ', 'Melkersson-Rosenthal syndrome may manifest as the classical triad (orofacial edema, facial nerve palsy and stable lingua plicata) but monosymptomatic manifestations or combinations of typical symptoms are not infrequent.', 'Melkersson-Rosenthal Syndrome (MRS) is a systemic neuro-mucocutaneous granulomatous disease, characterized in its classical form by a triad of recurrent facial nerve paralysis, swelling of the lips and lingua plicata.', 'Melkersson-Rosenthal syndrome is classically described as a triad of orofacial swelling, facial palsy, and fissured tongue.', 'Melkersson-Rosenthal syndrome is a rare disorder consisting of the triad of persistent or recurrent orofacial edema, relapsing facial paralysis and fissured tongue.', 'The Melkersson-Rosenthal syndrome consists of a triad of recurrent lip and/or face swelling, fissured tongue, and intermittent facial palsy.', 'The Melkersson-Rosenthal syndrome consists of a triad of symptoms: peripheral facial nerve paralysis, congenital "lingua plicata" and noninflammatory facial oedema.', 'The Melkersson-Rosenthal syndrome consists of triad of symptoms: recurrent oedema of lips, recurrent facial nerve paralysis and lingua plicata.', 'Melkersson-Rosenthal syndrome is characterised by a triad of recurrent orofacial swelling, relapsing facial paralysis, and fissured tongue.', 'The Melkersson-Rosenthal syndrome consists of triad of symptoms: recurrent oedema of lips, recurrent facial nerve paralysis and lingua plicata', 'Melkersson-Rosenthal syndrome may manifest as the classical triad (orofacial edema, facial nerve palsy and stable lingua plicata) but monosymptomatic manifestations or combinations of typical symptoms are not infrequent', 'Melkersson-Rosenthal syndrome (MRS) is a rare disorder of unknown etiology characterized by a triad of symptoms: recurrent orofacial swelling, relapsing facial palsy. and a fissured tongue', 'The Melkersson-Rosenthal syndrome consists of a triad of symptoms: peripheral facial nerve paralysis, congenital "lingua plicata" and noninflammatory facial oedema', 'Melkersson-Rosenthal syndrome (MRS) is characterized by the triad of facial paralysis, facial oedema, and lingua plicata in association with other symptoms, such as headache and mental changes', 'Peripheral facial nerve palsy, recurrent or persistent oral or facial swelling, and fissured tongue constitute a triad of symptoms known as Melkersson-Rosenthal syndrome', 'Melkersson-Rosenthal (MRS) syndrome is characterized by a classical triad of recurrent or persistent orofacial swelling, peripheral facial nerve paralysis and lingua plicata. ', 'BACKGROUND: Melkersson-Rosenthal syndrome may manifest as the classical triad (orofacial edema, facial nerve palsy and stable lingua plicata) but monosymptomatic manifestations or combinations of typical symptoms are not infrequent. ', 'The syndrome is classically characterized by a triad of signs consisting of facial edema, recurrent peripheral facial nerve paralysis, and congenital fissured tongue, although it may also present in a mono- or oligosymptomatic form. ', 'The classic triad of signs includes recurrent orofacial edema, recurrent facial nerve palsy, and lingua plicata. ', 'Melkersson-Rosenthal syndrome (MRS) is characterized by the triad of facial paralysis, facial oedema, and lingua plicata in association with other symptoms, such as headache and mental changes.', 'The patient has a typical for Melkersson-Rosenthal syndrome triad of symptoms: bilateral facial nerve palsy, lingua plicata and facial oedema.', 'Peripheral facial nerve palsy, recurrent or persistent oral or facial swelling, and fissured tongue constitute a triad of symptoms known as Melkersson-Rosenthal syndrome.', 'Classical signs include recurrent facial palsy, lingua plicata and orofacial edema.', 'The classical triad includes recurrent orofacial oedema involving predominantly the lips (macrocheilitis), intermittent peripheral facial palsy and scrotal tongue.', 'The patient has a typical for Melkersson-Rosenthal syndrome triad of symptoms: bilateral facial nerve palsy, lingua plicata and facial oedema.']

['The Melkersson-Rosenthal syndrome consists of the classical triad of symptoms:\n1) orofacial oedema \n2) fissured tongue (lingua plicata) and\n3) facial paralysis.']

['orofacial oedema', 'lip and face swelling', 'fissured tongue', 'lingua plicata', 'facial paralysis', 'facial palsy']

Which cyclin- dependent kinase inhibitor is regulated by Bmi-1?

['the knockdown of BMI-1 expression could lead to significant up-regulation of p16INK4a', 'In EC9706 cells transfected by Bmi-1 siRNA, the expression levels of p16 ', 'One important pathway regulated by Bmi-1 is that involving two cyclin-dependent kinase inhibitors, p16(Ink4a) and p19(Arf)', 'We also observe that ROS-induced up-regulation of p16(Ink4a) occurs correlatively with ERK1/2-dependent down-regulation and subsequent dissociation from chromatin of Bmi-1', 'Bmi-1 is important for postnatal, but not embryonic, neural stem cell (NSC) self-renewal and have identified the cell-cycle inhibitors p16/p19 as molecular targets', 'Bmi-1 function in stem cells during development that, surprisingly, seems to involve regulation of the cell-cycle inhibitor p21', 'Our data therefore implicate p21 as an important Bmi-1 target in NSCs', 'Bmi-1-mediated repression of Cdkn2A', 'decreased expression of proliferating cell nuclear antigen and Bmi-1; upregulation of p16(INK4a)', 'BMI-1 promotes self-renewal of stem cells largely by interfering with two central cellular tumor suppressor pathways, p16(Ink4a)', 'p16INK4a and p14ARF tumor suppressors, human telomerase reverse transcriptase (h-TERT), and oncoprotein c-Myc have been implicated in the regulation of the cell cycle and proliferation mediated by PcG proteins, mainly Bmi-1', 'involving the polycomb group repressor Bmi-1 and the cyclin-dependent kinase inhibitor p16(INK4a)', 'increased frequency to a telomere-independent senescent state mediated by the cyclin-dependent kinase inhibitor p16(INK4a). p16(INK4a) expression was regulated by the Polycomb group repressor Bmi-1', 'The antisense Bmi-1 gene can inhibit the growth of K562 cell and upgrade expression of p16 in K562 cells', 'overexpression of BMI-1, a transcriptional repressor of the p16(INK4a) locus,', 'experimental model systems indicate that p16 is a downstream target of Bmi', 'In the absence of Bmi-1, the cyclin-dependent kinase inhibitor gene p16Ink4a is upregulated in neural stem cells, reducing the rate of proliferation', 'A gene expression analysis revealed that the expression of stem cell associated genes, cell survival genes, transcription factors, and genes modulating proliferation including p16Ink4a and p19Arf was altered in bone marrow cells of the Bmi-1-/- mice', 'polycomb protein Bmi-1 represses the INK4a locus, which encodes the tumor suppressors p16 and p14(ARF)', 'Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus', 'in bmi-1-deficient lymphocytes, the expression of the tumour suppressors p16 and p19Arf, which are encoded by ink4a, is raised markedly', 'BMI-1-mediated INK4a/ARF pathway ', ' expression of the polycomb protein BMI-1 and its downstream targets p16(Ink4a)', 'reduced expression of Bmi-1, OC, DSP, and BSP compared with rapidly proliferating cells, whereas p16(INK4A) level increased.', '16Ink4a suppression of lung adenocarcinoma by Bmi-1', 'The suppression of p16Ink4a occurred in parallel with an increase in Bmi-1', 'Bmi-1 overexpression reduced p16(INK4a) promoter activity ', 'mi-1 regulates the Ink4a/Arf locus', 'derepression of the Ink4a/Arf locus is associated with decreased Bmi-1 binding,', 'pronounced effects of Bmi-1 over-expression in culture were largely attributable to the attenuated induction of p16(Ink4a) ', 'BMI-1 is a transcriptional repressor of the Ink4a/Arf locus encoding p16(ink4a)', 'introduction of Bmi-1 can inhibit p16(INK4a) expression', 'Bmi-1 promotes stem cell self-renewal partly by repressing the expression of Ink4a ', 'Overexpression of Bmi-1 in NPECs led to the induction of human telomerase reverse transcriptase activity and reduction of p16(INK4a) expression', 'Bmi-1 thus prevents the premature senescence of neural stem cells by repressing Ink4a', 'overexpression of the polycomb-group gene BMI-1 might also down-regulate p16 expression', 'Bmi-1 oncoprotein is overexpressed in human colorectal cancer and correlates with the reduced p16INK4a/p14ARF', 'modulation of Bmi-1 protein might be involved in human colorectal carcinogenesis by repressing the INK4a/ARF protein', 'mi-1 regulation of INK4A-ARF', 'expression of BMI-1, a lymphoid oncogene whose product functions as a transcriptional repressor of the INK4A-ARF tumor suppressor locu', 'bmi-1 oncoprotein is differentially expressed in non-small cell lung cancer and correlates with INK4A-ARF locus expression', 'bmi-1 overexpression induces immortalization due to repression of p16/p19ARF']

['p16INK4 (also known as CDKN2A)']

['p16INK4']

What is the role of Laser Interstitial Thermal Therapy in glioma treatment?

['OBJECTIVE MR-guided laser-induced thermal therapy (MRgLITT) can be used to treat intracranial tumors, epilepsy, and chronic pain syndromes. ', 'Eight patients had glioblastoma multiforme (GBM), 1 had a previously treated GBM with radiation necrosis, and 1 had a melanoma brain metastasis. ', 'CONCLUSIONS Laser interstitial thermal therapy followed by minimally invasive transsulcal resection, reported here for the first time, is a novel option for patients with large, DTA, malignant brain neoplasms.', 'MRI-guided laser interstitial thermal therapy is currently used as a minimally invasive treatment for brain metastases, radiation necrosis, glioma, and epilepsy. ', 'The role of laser interstitial thermal therapy in enhancing progression-free survival of difficult-to-access high-grade gliomas: a multicenter study.', 'We report our multicenter results of laser interstitial thermal therapy (LITT) in DTA-HGGs. We retrospectively reviewed 34 consecutive DTA-HGG patients (24 glioblastoma, 10 anaplastic) who underwent LITT at Cleveland Clinic, Washington University, and Wake Forest University (May 2011-December 2012) using the NeuroBlate(®) System. ', 'LITT can be used effectively for treatment of DTA-HGGs. More complete coverage of tumor by TDT lines improves PFS which can be translated as the extent of resection concept for surgery.', 'Stereotactic laser ablation of high-grade gliomas.', 'Recent advances in intraoperative imaging have spurred the use of stereotactic laser ablation (laser interstitial thermal therapy [LITT]) for intracranial lesions. Among other targets, laser ablation has been used in the focal treatment of high-grade gliomas (HGGs). ', 'Results of the NeuroBlate System first-in-humans Phase I clinical trial for recurrent glioblastoma: clinical article.', 'OBJECT: Laser interstitial thermal therapy has been used as an ablative treatment for glioma; however, its development was limited due to technical issues. ', 'CONCLUSIONS: NeuroBlate represents new technology for delivering laser interstitial thermal therapy, allowing controlled thermal ablation of deep hemispheric rGBM. ', 'Ongoing researches concern the adjunction of local treatments within the surgical field (photodynamic therapy, chemotherapy, convection immunotherapy...), but also the development of minimal invasive procedures (radiosurgery, high intensity focalized ultrasounds, laser interstitial thermal therapy).', 'Current commercially available LITT systems have been used for the treatment of neurosurgical soft-tissue lesions, including difficult to access brain tumors, malignant gliomas, and radiosurgery-resistant metastases, as well as for the ablation of such lesions as epileptogenic foci and radiation necrosis.', ' The authors report a Phase I, thermal dose-escalation trial assessing the safety and efficacy of NeuroBlate in recurrent glioblastoma multiforme (rGBM).', 'MRI-guided laser interstitial thermal therapy is currently used as a minimally invasive treatment for brain metastases, radiation necrosis, glioma, and epilepsy.', 'Laser interstitial thermal therapy has been used as an ablative treatment for glioma; however, its development was limited due to technical issues.', 'MRI-guided laser interstitial thermal therapy for the treatment of low-grade gliomas in children: a case-series review, description of the current technologies and perspectives.', 'MRI-guided laser interstitial thermal therapy is currently used as a minimally invasive treatment for brain metastases, radiation necrosis, glioma, and epilepsy', 'Laser interstitial thermal therapy has been used as an ablative treatment for glioma; however, its development was limited due to technical issues', 'Thermal ablation (radiofrequency, microwave, cryosurgery, laser interstitial thermal therapy) is being used more frequently as a local treatment of secondary but also primary cancers and benign lesions', 'The role of laser interstitial thermal therapy in enhancing progression-free survival of difficult-to-access high-grade gliomas: a multicenter study', 'Current Applications of MRI-Guided Laser Interstitial Thermal Therapy in the Treatment of Brain Neoplasms and Epilepsy: A Radiologic and Neurosurgical Overview', 'Magnetic resonance imaging-guided laser interstitial thermal therapy (LITT) is a minimally invasive treatment modality with recent increasing use to ablate brain tumors', 'Further study is needed to assess the role of laser-induced thermal therapy for the treatment of intracranial tumors', 'OBJECT: Laser interstitial thermal therapy has been used as an ablative treatment for glioma; however, its development was limited due to technical issues.', 'Three had Grade 3 adverse events at the highest dose.CONCLUSIONS: NeuroBlate represents new technology for delivering laser interstitial thermal therapy, allowing controlled thermal ablation of deep hemispheric rGBM.', 'The role of laser interstitial thermal therapy in enhancing progression-free survival of difficult-to-access high-grade gliomas: a multicenter study.', 'Stereotactic Laser Interstitial Thermal Therapy for Recurrent High-Grade Gliomas.', 'MRI-guided laser interstitial thermal therapy for the treatment of low-grade gliomas in children: a case-series review, description of the current technologies and perspectives.', 'MRI-guided laser interstitial thermal therapy is currently used as a minimally invasive treatment for brain metastases, radiation necrosis, glioma, and epilepsy.', 'NeuroBlate represents new technology for delivering laser interstitial thermal therapy, allowing controlled thermal ablation of deep hemispheric rGBM.', 'Laser interstitial thermal therapy followed by minimal-access transsulcal resection for the treatment of large and difficult to access brain tumors.']

['Laser Interstitial Thermal Therapy (LITT) is used in treatment of gliomas. LITT can be used effectively for treatment of difficult-to-access high-grade gliomas. More complete coverage of tumor improves progression free survival which can be translated as the extent of resection concept for surgery.']

[]

Are the genes for marneral biosynthesis scattered in the genome of A. thaliana?

['Here we characterize a second operon-like triterpene cluster (the marneral cluster) from A. thaliana, compare the features of these two clusters, and investigate the evolutionary events that have led to cluster formation', 'Here we characterize a second operon-like triterpene cluster (the marneral cluster) from A. thaliana, compare the features of these two clusters, and investigate the evolutionary events that have led to cluster formation.', 'Previously in thale cress (Arabidopsis thaliana) we identified an operon-like gene cluster that is required for the synthesis and modification of the triterpene thalianol.', 'Prediction of operon-like gene clusters in the Arabidopsis thaliana genome based on co-expression analysis of neighboring genes', 'Here we characterize a second operon-like triterpene cluster (the marneral cluster) from A. thaliana, compare the features of these two clusters, and investigate the evolutionary events that have led to cluster formation. ', 'Here we characterize a second operon-like triterpene cluster (the marneral cluster) from A.', 'the cyclic hydroxamic acid pathways in maize, the avenacin biosynthesis gene clusters in oat, the thalianol pathway in Arabidopsis thaliana, and the diterpenoid momilactone cluster in rice.', 'Prediction of operon-like gene clusters in the Arabidopsis thaliana genome based on co-expression analysis of neighboring genes.']

['These clusters are unlikely to have arisen by horizontal gene transfer, and the mechanisms behind their formation are poorly understood. Here we characterize a second operon-like triterpene cluster (the marneral cluster) from A. thaliana, compare the features of these two clusters, and investigate the evolutionary events that have led to cluster formation.', 'Here we characterize a second operon-like triterpene cluster (the marneral cluster) from A. thaliana, compare the features of these two clusters, and investigate the evolutionary events that have led to cluster formation. ', 'Genes for marneral synthesis are organized in an operon-like gene cluster in thale cress (A. thaliana).']

['no']

Orteronel was developed for treatment of which cancer?

['Pooled-analysis was also performed, to assess the effectiveness of agents targeting the androgen axis via identical mechanisms of action (abiraterone acetate, orteronel).', 'The experimental interventions tested in these studies were enzalutamide, ipilimumab, abiraterone acetate, orteronel and cabazitaxel. ', ' Pooled analysis of androgen synthesis inhibitors orteronel and abiraterone resulted in significantly increased overall and progression-free survival for anti-androgen agents, compared to placebo (hazard ratio for death: 0.76, 95% CI 0.67 to 0.87, P<0.0001; hazard ratio for radiographic progression: 0.7, 95% CI 0.63 to 0.77, P<0.00001). ', 'Agents targeting the androgen axis (enzalutamide, abiraterone, orteronel) significantly prolonged rPFS, compared to placebo. ', 'Orteronel plus prednisone in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (ELM-PC 4): a double-blind, multicentre, phase 3, randomised, placebo-controlled trial.', 'BACKGROUND: Orteronel is an investigational, partially selective inhibitor of CYP 17,20-lyase in the androgen signalling pathway, a validated therapeutic target for metastatic castration-resistant prostate cancer. We assessed orteronel in chemotherapy-naive patients with metastatic castration-resistant prostate cancer.', 'NTERPRETATION: In chemotherapy-naive patients with metastatic castration-resistant prostate cancer, radiographic progression-free survival was prolonged with orteronel plus prednisone versus placebo plus prednisone.', 'On the basis of these and other data, orteronel is not undergoing further development in metastatic castration-resistant prostate cancer.', 'Phase III, randomized, double-blind, multicenter trial comparing orteronel (TAK-700) plus prednisone with placebo plus prednisone in patients with metastatic castration-resistant prostate cancer that has progressed during or after docetaxel-based therapy: ELM-PC 5.', 'This study examined orteronel in patients with metastatic castration-resistant prostate cancer that progressed after docetaxel therapy.', 'Longer rPFS and a higher PSA50 rate with orteronel-prednisone indicate antitumor activity.', 'A phase 1 multiple-dose study of orteronel in Japanese patients with castration-resistant prostate cancer.', 'We evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor effect of orteronel with or without prednisolone in Japanese patients with castration-resistant prostate cancer (CRPC).', 'CONCLUSIONS: Orteronel at doses up to 400 mg BID was tolerable in Japanese CRPC patients.', 'Orteronel for the treatment of prostate cancer.', 'Orteronel (also known as TAK-700) is a novel hormonal therapy that is currently in testing for the treatment of prostate cancer.', 'Orteronel is a nonsteroidal, selective inhibitor of 17,20-lyase that was recently in phase 3 clinical development as a treatment for castration-resistant prostate cancer.', 'Early reports of clinical studies demonstrate that orteronel treatment leads to reduced prostate-specific antigen levels, a marker of prostate cancer tumor burden, and more complete suppression of androgen synthesis than conventional androgen deprivation therapies that act in the testes alone.', 'Discovery of orteronel (TAK-700), a naphthylmethylimidazole derivative, as a highly selective 17,20-lyase inhibitor with potential utility in the treatment of prostate cancer.', 'Therefore, (+)-3c (termed orteronel [TAK-700]) was selected as a candidate for clinical evaluation and is currently in phase III clinical trials for the treatment of castration-resistant prostate cancer.', 'We assessed orteronel in chemotherapy-naive patients with metastatic castration-resistant prostate cancer.', 'Orteronel is a nonsteroidal, selective inhibitor of 17,20-lyase that was recently in phase 3 clinical development as a treatment for castration-resistant prostate cancer. ', 'Phase I/II trial of orteronel (TAK-700)--an investigational 17,20-lyase inhibitor--in patients with metastatic castration-resistant prostate cancer.', 'On the basis of these and other data, orteronel is not undergoing further development in metastatic castration-resistant prostate cancer.FUNDING: Millennium Pharmaceuticals, Inc, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.', 'New androgen biosynthesis inhibitors have been developed, such as orteronel (TAK-700), but also new antiandrogens (enzalutamide, ARN-509, ODM-201) or even agents with a dual mechanism of action (galeterone). In this review the development of new hormonal therapies following the arrival of abiraterone for the treatment of prostate cancer will be summarized.']

['Orteronel was developed for treatment of castration-resistant prostate cancer.']

['castration-resistant prostate cancer']

Which trinucleotide repeat disorders are affecting the nervous system?

['The discovery that expansion of unstable repeats can cause a variety of neurological disorders has changed the landscape of disease-oriented research for several forms of mental retardation, Huntington disease, inherited ataxias, and muscular dystrophy.', "Expansion of trinucleotide repeats is now recognized as a major cause of neurological disease. At least seven disorders result from trinucleotide repeat expansion: X-linked spinal and bulbar muscular atrophy (SBMA), two fragile X syndromes of mental retardation (FRAXA and FRAXE), myotonic dystrophy, Huntington's disease, spinocerebellar ataxia type 1 (SCA1), and dentatorubral-pallidoluysian atrophy (DRPLA).", "Fragile X and myotonic dystrophy are multisystem disorders usually associated with large expansions of untranslated repeats, while the four neurodegenerative disorders, SBMA, Huntington's disease, SCA1, and DRPLA, are caused by smaller expansions of CAG repeats within the protein coding portion of the gene."]

["At least six neudegenerative disorders result from trinucleotide repeat expansion: X-linked spinal and bulbar muscular atrophy (SBMA), two fragile X syndromes of mental retardation (FRAXA and FRAXE), Huntington's disease (HD), spinocerebellar ataxia type 1 (SCA1), and dentatorubral-pallidoluysian atrophy (DRPLA)."]

['X-linked spinal and bulbar muscular atrophy (SBMA)', 'Fragile X syndrome of mental retardation (FRAXA)', 'Fragile X syndrome of mental retardation (FRAXE)', "Huntington's disease (HD)", 'Spinocerebellar ataxia type 1 (SCA1)', 'Dentatorubral-pallidoluysian atrophy (DRPLA)']

Which disease of the central nervous system is characterized by the presence of Lewy bodies?

["Parkinson's disease (PD) is one of the most common degenerative disorders of the central nervous system that produces motor and non-motor symptoms. The majority of cases are idiopathic and characterized by the presence of Lewy bodies containing fibrillar α-synuclein", "Parkinson's disease is characterized by α-synuclein pathology in the form of Lewy bodies and Lewy neurites", "Parkinson's disease is characterized by neuronal death in the substantia nigra and the presence of intracellular inclusions of α-synuclein in the Lewy bodies", "Parkinson's disease, also known as paralysis agitans, is a progressive degenerative disorder of the central nervous system, with onset usually between the ages of 50 and 65 years, and is associated with loss of dopaminergic neurons in the subsantia nigra and the presence of Lewy bodies", 'The protein α-synuclein is well recognized to contribute to the pathogenesis of Parkinson disease and is the major component of Lewy bodies and Lewy neurites', "Parkinson's disease (PD) and related Lewy body diseases are characterized by deposition of α-synuclein aggregates in both the central nervous system and peripheral nervous system.", 'Parkinsons disease (PD) and dementia with Lewy bodies are common disorders of the aging population and characterized by the progressive accumulation of �-synuclein (�-syn) in the central nervous system.', 'AF-LB and Parkinsons disease (PD) share the neuropathological findings characterized by widely distributed Lewy bodies in the central nervous system including the substantia nigra and locus coeruleus.', 'Parkinsons disease (PD) and dementia with Lewy bodies (DLB) are characterized by abnormal deposition of �-synuclein aggregates in many regions of the central and peripheral nervous systems.', 'A number of neurodegenerative diseases including Parkinsons disease, dementia with Lewy bodies (DLB) and multiple system atrophy are characterized by the formation and intraneuronal accumulation of fibrillar aggregates of alpha-synuclein (alpha-syn) protein in affected brain regions.', 'They have been a long time the hallmark of Parkinsons disease, but in recent years it has emerged that a small group of rare disorders or rare variants of common degenerative diseases are also sometimes associated with Lewy bodies in the nervous system.', 'BACKGROUND: Lewy body disease is a heterogeneous group of neurodegenerative disorders characterized by alpha-synuclein accumulation that includes dementia with Lewy bodies (DLB) and Parkinsons Disease (PD).', 'Although Parkinsons disease with later dementia (PDD) and dementia with Lewy bodies (DLB) are pathologically characterized by the presence of intraneuronal Lewy inclusion bodies, amyloid deposition is also associated to varying degrees with both these disorders.', 'Parkinsons disease (PD) is a neurodegnerative disorder that is pathologically characterized by the presence of Lewy bodies in the brain.', 'However, it seems that Braak staging can not explain difference in severity of autonomic failure between DLB and PD. As a possibility, in DLB patients with significant autonomic failure, Lewy bodies may have been localized to the peripheral autonomic nervous system in a long time before onset of dementia or parkinsonism, and propagation of Lewy bodies into the central nervous system may be initiated by apparition of certain promotion factor, such as ageing and amyloid-�.', "Parkinson's disease (PD) is the second most common neurodegenerative disorder that is characterized by two major neuropathological hallmarks: the degeneration of dopaminergic neurons in the substantia nigra (SN) and the presence of Lewy bodies in the surviving SN neurons, as well as other regions of the central and peripheral nervous system", 'These include multiple system atrophy (MSA), characterized by accumulation of glial cytoplasmic inclusions, and Lewy body disorders, including Parkinson disease (PD), dementia with Lewy bodies, and the so-called "pure" autonomic failure']

['Parkinson s disease (PD) is one of the most common degenerative disorders of the central nervous system that produces motor and non-motor symptoms. The majority of cases are idiopathic and characterized by the presence of Lewy bodies containing fibrillar α-synuclein ', "Parkinson's disease (PD) is one of the most common degenerative disorders of the central nervous system that produces motor and non-motor symptoms. The majority of cases are idiopathic and characterized by the presence of Lewy bodies containing fibrillar α-synuclein.", 'Parkinsons disease (PD) is one of the most common degenerative disorders of the central nervous system that produces motor and non-motor symptoms. The protein α-synuclein is well recognized to contribute to the pathogenesis of Parkinson disease and is the major component of Lewy bodies and Lewy neurites']

["Parkinson's disease (PD)"]

What are the roles of Smyd3 in zebrafish?

['Smyd3 is required for the development of cardiac and skeletal muscle in zebrafish', 'We here show that transcripts of smyd3 were expressed in zebrafish embryos at all developmental stages examined and that knockdown of smyd3 in embryos resulted in pericardial edema and defects in the trunk structure. In addition, these phenotypes were associated with abnormal expression of three heart-chamber markers including cmlc2, amhc and vmhc, and abnormal expression of myogenic regulatory factors including myod and myog. These data suggest that Smyd3 plays an important role in the development of heart and skeletal muscle.', 'We here show that transcripts of smyd3 were expressed in zebrafish embryos at all developmental stages examined and that knockdown of smyd3 in embryos resulted in pericardial edema and defects in the trunk structure.', 'We find both smyd3 and setd7 are highly expressed within developing zebrafish heart and knock-down of these genes led to severe defects in cardiac morphogenesis without altering the expressions pattern of heart markers, including cmlc2, vmhc, and amhc.', 'Smyd3 is required for the development of cardiac and skeletal muscle in zebrafish.', 'SMYD1, SMYD2, SMYD3, and SMYD4 have been found to play critical roles in carcinogenesis and/or the development of heart and skeletal muscle.', 'SMYD1, SMYD2, SMYD3, and SMYD4 have been found to play critical roles in carcinogenesis and/or the development of heart and skeletal muscle.', 'Smyd3 is required for the development of cardiac and skeletal muscle in zebrafish.', 'These data suggest that Smyd3 plays an important role in the development of heart and skeletal muscle..']

['Smyd3 is required for the development of cardiac and skeletal muscle in zebrafish. Transcripts of smyd3 are expressed in zebrafish embryos at all developmental stages and knockdown of smyd3 in embryos resulted in pericardial edema and defects in the trunk structure. In addition, these phenotypes are associated with abnormal expression of three heart-chamber markers including cmlc2, amhc and vmhc, and abnormal expression of myogenic regulatory factors including myod and myog.']

['The development of cardiac muscle', 'The development of skeletal muscle']

Is there any involvement of the long non-coding RNA Gomafu in schizophrenia?

['The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing.', 'Here, we profile these transcriptomic responses and show that long non-coding RNAs (lncRNAs) are dynamically regulated by neuronal activation, including acute downregulation of the lncRNA Gomafu, previously implicated in brain and retinal development. Moreover, we demonstrate that Gomafu binds directly to the splicing factors QKI and SRSF1 (serine/arginine-rich splicing factor 1) and dysregulation of Gomafu leads to alternative splicing patterns that resemble those observed in SZ for the archetypal SZ-associated genes DISC1 and ERBB4. Finally, we show that Gomafu is downregulated in post-mortem cortical gray matter from the superior temporal gyrus in SZ. These results functionally link activity-regulated lncRNAs and alternative splicing in neuronal function and suggest that their dysregulation may contribute to neurological disorders.', 'Gomafu/MIAT/Rncr2 is a long noncoding RNA that has been proposed to control retinal cell specification, stem cell differentiation and alternative splicing of schizophrenia-related genes.', 'The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing', 'Moreover, we demonstrate that Gomafu binds directly to the splicing factors QKI and SRSF1 (serine/arginine-rich splicing factor 1) and dysregulation of Gomafu leads to alternative splicing patterns that resemble those observed in SZ for the archetypal SZ-associated genes DISC1 and ERBB4. ', 'Finally, we show that Gomafu is downregulated in post-mortem cortical gray matter from the superior temporal gyrus in SZ. ', 'The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing.']

['Yes. The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing.']

['yes']

Can siRNA affect response to afatinib treatment?

['On the other hand, miR-146a enhanced the inhibition of cell proliferation by drugs targeting EGFR, including both TKIs (gefitinib, erlotinib, and afatinib) and a monoclonal antibody (cetuximab)', 'These effects were independent of the EGFR mutation status (wild type, sensitizing mutation or resistance mutation), but were less potent compared to the effects of siRNA targeting of EGFR', 'Among the anti-EGFR agents tested, the strongest biological effect was observed when afatinib was combined with T790M-specific-siRNAs', 'The combination of a potent, irreversible kinase inhibitor such as afatinib, with T790M-specific-siRNAs should be further investigated as a new strategy in the treatment of lung cancer containing the resistant T790M mutation.', 'The strongest biological effect was observed when afatinib was combined with an EGFR-specific siRNA', 'The addition of EGFR siRNA to either TKIs or cetuximab additively enhanced growth inhibition and induction of apoptosis in all five cell lines, independent of the EGFR mutation status (wild-type or sensitizing mutation or resistant mutation).', 'The combination of a potent, irreversible kinase inhibitor such as afatinib, with EGFR-specific siRNAs should be further investigated as a new strategy in the treatment of lung cancer and other EGFR dependent cancers, including those with downstream resistance mutations.']

['When afatinib was combined with an EGFR-specific siRNA there was a strong biological effect on growth inhibition and induction of apoptosis.']

['yes']

What are some common congenital anomalies associated with Mowat-Wilson syndrome, including hypospadias, agenesis of the corpus callosum, and what else?

[' genitourinary anomalies (in particular hypospadias in males), congenital heart defects, agenesis of the corpus callosum and eye anomalies.", "Mowat-Wilson syndrome is a mental retardation-multiple congenital anomaly syndrome characterized by a typical facies, developmental delay, epilepsy, and variable congenital malformations, including Hirschsprung disease, urogenital anomalies, congenital heart disease, and agenesis of the corpus callosum. ", "Mowat-Wilson syndrome (MWS) is a recently delineated mental retardation (MR)-multiple congenital anomaly syndrome, characterized by typical facies, severe MR, epilepsy, and variable congenital malformations, including Hirschsprung disease (HSCR), genital anomalies, congenital heart disease (CHD), and agenesis of the corpus callosum (ACC). ", "Medical issues in our cohort of patients included seizures (75%) with no predeliction for any particular seizure type; agenesis of the corpus callosum (60% of our patients studied); congenital heart defects (75%), particularly involving the pulmonary arteries and/or valves; hypospadias (55% of males); severely impaired or absent speech (100% of individuals over 1 year of age) with relatively spared receptive language; and Hirschsprung disease (50%) or chronic constipation (25%). ", "Mowat-Wilson syndrome (MWS) is a mental retardation syndrome associated with distinctive facial features, microcephaly, epilepsy, and a variable spectrum of congenital anomalies, including Hirschsprung disease (HSCR), agenesis of the corpus callosum, genitourinary abnormalities, and congenital heart disease.", "ACC is found in 40% of the cases of Mowat-Wilson syndrome (MWS), a polytopic embryonic defect including a distinctive facial gestalt, severe mental retardation, epilepsy and postnatal microcephaly as constant features. ", "However, analysis of MWS should be considered in the differential diagnosis of ACC, especially when the facial features raise the possibility of MWS.", "Frameshift mutation of the zinc finger homeo box 1 B gene in syndromic corpus callosum agenesis (Mowat-Wilson syndrome).", "We report a girl who had Hirschsprung disease in association with distinct facial appearance, microcephaly, agenesis of the corpus callosum and mental retardation (Mowat-Wilson syndrome).", "Congenital anomalies, including Hirschsprung disease (HSCR), congenital heart disease, hypospadias, genitourinary anomalies, agenesis of the corpus callosum, and short stature are common. "]']

Congenital anomalies commonly associated with Mowat-Wilson syndrome include hypospadias, agenesis of the corpus callosum, genitourinary anomalies, congenital heart defects, Hirschsprung disease, and microcephaly.

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What is DNAshape?

['DNAshape: a method for the high-throughput prediction of DNA structural features on a genomic scale.', 'We present a method and web server for predicting DNA structural features in a high-throughput (HT) manner for massive sequence data. This approach provides the framework for the integration of DNA sequence and shape analyses in genome-wide studies. The HT methodology uses a sliding-window approach to mine DNA structural information obtained from Monte Carlo simulations. It requires only nucleotide sequence as input and instantly predicts multiple structural features of DNA (minor groove width, roll, propeller twist and helix twist). The results of rigorous validations of the HT predictions based on DNA structures solved by X-ray crystallography and NMR spectroscopy, hydroxyl radical cleavage data, statistical analysis and cross-validation, and molecular dynamics simulations provide strong confidence in this approach. The DNAshape web server is freely available at http://rohslab.cmb.usc.edu/DNAshape/.']

['DNAshape is a method and web server for predicting DNA structural features in a high-throughput (HT) manner for massive sequence data. This approach provides the framework for the integration of DNA sequence and shape analyses in genome-wide studies. The HT methodology uses a sliding-window approach to mine DNA structural information obtained from Monte Carlo simulations. It requires only nucleotide sequence as input and instantly predicts multiple structural features of DNA (minor groove width, roll, propeller twist and helix twist). The results of rigorous validations of the HT predictions based on DNA structures solved by X-ray crystallography and NMR spectroscopy, hydroxyl radical cleavage data, statistical analysis and cross-validation, and molecular dynamics simulations provide strong confidence in this approach. The DNAshape web server is freely available at http://rohslab.cmb.usc.edu/DNAshape/.']

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Are there any specific antidotes for rivaroxaban?

['Novel oral anticoagulants (NOACs)--apixaban, dabigatran, and rivaroxaban--have a significantly smaller risk of intracerebral hemorrhage (ICH). However, two facts make this situation complicated: First, the risk of hematoma expansion is unknown for NOACs. Second, there is no specific antidote for neither of the NOACs.', 'he new oral anticoagulants dabigatran etexilate (Pradaxa), rivaroxaban (Xarelto), and apixaban (Eliquis) have predictable pharmacokinetic and pharmacodynamic profiles and are alternatives to warfarin. However, many physicians are wary of these drugs, since there is limited evidence on how to manage bleeding in patients taking them, and since no specific antidote is known to reverse their anticoagulant effect. ', 'Given the absence of a specific antidote, the action to be taken in these situations must be defined. ', 'The fact that there is no specific antidote to reverse the anticoagulant action of the new anticoagulants can impair management of hemorrhagic complications; ', 'Like any new therapy, the potential benefits must be weighed against the potential challenges and one of the most concerning aspects of the new target-specific oral anticoagulants is the lack of a proven method to reverse their effect. Unlike the vitamin K antagonist, i.e. warfarin, there is no specific antidote for these medications. ', 'Two major drawbacks are on the one hand the risk of drug accumulation in kidney and/or liver disease and, on the other hand, the lack of specific antidotes.', 'NOA also have other unresolved problems: drug interactions are still possible, specific coagulation test to assess them must be developed, and no specific antidote is currently available in case of hemorrhagic complication.', 'But they have disadvantages also, they depend on renal clearance, they can interact with other medicaments and they lack a specific antidote. ', 'While these trial data are extremely encouraging, several practical issues (e.g., lack of specific antidote, safety of long-term treatment or cost-effectiveness in "real-life" clinical practice) still need to be elucidated.', 'In case of massive bleeding, management is unclear and none of these newer agents has a specific antidote that completely reverses its anticoagulant effect.', 'The short half-life of these new agents compensates for the lack of any specific antidote in many instances. ', 'Currently, none of these new agents has a specific antidote, and little advise can be given on how to manage a major bleeding event.', 'Rivaroxaban, which inhibits activated factor X (Xa), is currently in clinical trials and is the most advanced factor Xa inhibitor. The drug offers once-daily oral dosing, with no need for injections, dose titration, or frequent blood tests to monitor the international normalised ratio. It has a rapid onset of action and, although there is no specific antidote, it has a short plasma elimination half-life (about 5-9 hours). ', 'Increased use of dabigatran, rivaroxaban, and apixaban as oral anticoagulants for the treatment of atrial fibrillation and acute deep venous thrombosis has increased despite the lack of known antidotes to these medications.', 'There is no antidote for reversal and no reliable laboratory monitoring of the anticoagulant effect for emergency situations. ', 'Further concerns about the use of NOAC in the elderly are the high prevalence of renal insufficiency in AF patients >75 years of age, the largely unknown risk of drug-drug and drug-food interactions, the lack of easily available laboratory monitoring tests of anticoagulant activity and the lack of an antidote.', 'Specific antidotes for the reversal of the anticoagulant effect of these drugs, such as monoclonal antibodies against the direct thrombin inhibitor dabigatran or recombinant Xa-analog in the case of factor Xa inhibitors, are still being investigated in early clinical trials.', 'In early 2013 there is no antidote for dabigatran, rivaroxaban or apixaban, nor any specific treatment with proven efficacy for severe bleeding linked to these drugs. ']

['Currently, there is no specific antidote for rivaroxaban']

['no']

Which is the most common genetic lesion among patients with Joubert Syndrome and a cerebello-oculo-renal phenotype?

['Nephronophthisis (NPHP) is the major cause of pediatric renal failure, yet the disease remains poorly understood, partly due to the lack of appropriate animal models. Joubert syndrome (JBTS) is an inherited ciliopathy giving rise to NPHP with cerebellar vermis aplasia and retinal degeneration. Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion', 'Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion.', 'Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion', 'Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion. ', 'Joubert syndrome (JBTS) is an inherited ciliopathy giving rise to NPHP with cerebellar vermis aplasia and retinal degeneration. Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion.', 'Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion. We present a Cep290 gene trap mouse model of JBTS that displays the kidney, eye, and brain abnormalities that define the syndrome.', 'Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion.']

['Joubert syndrome (JBTS) is an inherited ciliopathy giving rise to NPHP with cerebellar vermis aplasia and retinal degeneration. Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion.', 'Nephronophthisis (NPHP) is the major cause of pediatric renal failure, yet the disease remains poorly understood, partly due to the lack of appropriate animal models. Joubert syndrome (JBTS) is an inherited ciliopathy giving rise to NPHP with cerebellar vermis aplasia and retinal degeneration. Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion']

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Is Migalastat used for treatment of Fabry Disease?

['Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease: 18-month results from the randomised phase III ATTRACT study.', 'BACKGROUND: Fabry disease is an X-linked lysosomal storage disorder caused by GLA mutations, resulting in α-galactosidase (α-Gal) deficiency and accumulation of lysosomal substrates. Migalastat, an oral pharmacological chaperone being developed as an alternative to intravenous enzyme replacement therapy (ERT), stabilises specific mutant (amenable) forms of α-Gal to facilitate normal lysosomal trafficking.', 'CONCLUSIONS: Migalastat offers promise as a first-in-class oral monotherapy alternative treatment to intravenous ERT for patients with Fabry disease and amenable mutations.', 'Migalastat (Galafold™)-a small molecule drug developed by Amicus Therapeutics that restores the activity of specific mutant forms of α-galactosidase-has been approved for the treatment of Fabry disease in the EU in patients with amenable mutations.', 'This article summarizes the milestones in the development of migalastat leading to this first approval in the EU for the long-term treatment of adults and adolescents aged ≥16 years with a confirmed diagnosis of Fabry disease.', "Treatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat.", "BACKGROUND: Fabry's disease, an X-linked disorder of lysosomal α-galactosidase deficiency, leads to substrate accumulation in multiple organs. Migalastat, an oral pharmacologic chaperone, stabilizes specific mutant forms of α-galactosidase, increasing enzyme trafficking to lysosomes.", 'Oral Migalastat HCl Leads to Greater Systemic Exposure and Tissue Levels of Active α-Galactosidase A in Fabry Patients when Co-Administered with Infused Agalsidase.', 'UNLABELLED: Migalastat HCl (AT1001, 1-Deoxygalactonojirimycin) is an investigational pharmacological chaperone for the treatment of α-galactosidase A (α-Gal A) deficiency, which leads to Fabry disease, an X-linked, lysosomal storage disorder. ', 'Migalastat HCl reduces globotriaosylsphingosine (lyso-Gb3) in Fabry transgenic mice and in the plasma of Fabry patients.', 'migalastat for Fabry disease) and inhibitors of glucosylceramide synthesis (e.g.', 'A Phase 2 study of migalastat hydrochloride in females with Fabry disease: selection of population, safety and pharmacodynamic effects.', 'Migalastat HCl (AT1001, 1-Deoxygalactonojirimycin) is an investigational pharmacological chaperone for the treatment of α-galactosidase A (α-Gal A) deficiency, which leads to Fabry disease, an X-linked, lysosomal storage disorder', 'Migalastat HCl is an investigational, oral treatment for Fabry disease, an X-linked lysosomal storage disorder', 'Oral administration of migalastat HCl reduces tissue GL-3 in Fabry transgenic mice, and in urine and kidneys of some FD patients. ', 'Migalastat HCl is an investigational, oral treatment for Fabry disease, an X-linked lysosomal storage disorder.', 'Migalastat HCl (AT1001, 1-Deoxygalactonojirimycin) is an investigational pharmacological chaperone for the treatment of α-galactosidase A (α-Gal A) deficiency, which leads to Fabry disease, an X-linked, lysosomal storage disorder.', 'Molecular chaperones (e.g. migalastat for Fabry disease) and inhibitors of glucosylceramide synthesis (e.g. eliglustat tartrate for Gaucher disease) are currently under investigation in various clinical trials.<CopyrightInformation>Copyright © 2010 Elsevier Masson SAS.', 'Migalastat HCl was well tolerated.Migalastat HCl is a candidate pharmacological chaperone that provides a novel genotype-specific treatment for FD.', 'Additionally, these three patients all demonstrated decreases in GL-3 inclusions in kidney peri-tubular capillaries.Migalastat HCl is a candidate oral pharmacological chaperone that provides a potential novel genotype-specific treatment for FD.', 'migalastat for Fabry disease) and inhibitors of glucosylceramide synthesis (e.g. eliglustat tartrate for Gaucher disease) are currently under investigation in various clinical trials.', 'Molecular chaperones (e.g. migalastat for Fabry disease) and inhibitors of glucosylceramide synthesis (e.g. eliglustat tartrate for Gaucher disease) are currently under investigation in various clinical trials.', "Treatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat.", 'The GLP HEK assay is a clinically validated method of identifying male and female Fabry patients for treatment with migalastat.Genet Med advance online publication 22 September 2016Genetics in Medicine (2016); doi:10.1038/gim.2016.122..', 'A Phase 2 study of migalastat hydrochloride in females with Fabry disease: selection of population, safety and pharmacodynamic effects.', 'Migalastat offers promise as a first-in-class oral monotherapy alternative treatment to intravenous ERT for patients with Fabry disease and amenable mutations.']

['Yes, Migalastat is approved for treatment of Fabry disease. Migalastat is an oral pharmacological chaperone developed as an alternative to intravenous enzyme replacement therapy (ERT), stabilises specific mutant (amenable) forms of α-Gal to facilitate normal lysosomal trafficking.']

['yes']

Which population has a high frequency of the HLA-B*1502 allele?

['A strong association between human leukocyte antigen (HLA)-B*1502 and CBZ-induced SJS/TEN has been reported in Han Chinese, Thai, Malaysian and Indian populations, but not in Caucasian or Japanese populations.', 'found a strong association between HLA-B*1502 and CBZ-induced SJS/TEN in the Han Chinese population from central and northern China. Combined with previous studies of the southern Han Chinese subpopulation, our results suggest that HLA-B*1502 is strongly associated with CBZ-induced SJS/TEN in the whole Han Chinese population.', 'A strong association between HLA-B*1502 and carbamazepine-induced SJS/TEN has been identified in Chinese and Thai.', 'In the present study, we conducted a pilot study to detect a possible association of oxcarbazepine (OXC)-induced MPE with HLA-B*1502 allele in Chinese Han population.', 'observed an increased frequency of HLA-B*1502 allele in patients (44.44%) compared with tolerant controls (11.11%), although it failed to reach statistical significance (P=0.294). CONCLUSIONS: Our findings indicate that HLA-B*1502 allele may contribute to the genetic susceptibility to OXC-induced MPE in Chinese Han population.', 'A strong association between HLA-B*1502 and CBZ-induced SJS/TEN has been reported in Han Chinese but not in Caucasian and Japanese populations. A case-control study was conducted to determine whether HLA-B*1502 is a valid pharmacogenetic test for SJS/TEN caused by CBZ in a Thai population.', 'Results from this study suggest that HLA-B*1502 may be a useful pharmacogenetic test for screening Thai individuals who may be at risk for CBZ-induced SJS and TEN.', 'A strong association has been reported between human leucocyte antigen (HLA)-B*1502 and carbamazepine-induced SJS in Han Chinese patients. European studies suggested that HLA-B*1502 is not a universal marker but is ethnicity-specific for Asians.', 'the human leukocyte antigen HLA-B*1502 is associated with Stevens-Johnson syndrome (SJS) induced by CBZ in Han Chinese.', 'the HLA allele B*1502 as a marker for carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese,', 'This allele is seen in high frequency in many Asian populations other than Han Chinese, but there are few data on whether the allele is a marker for this severe outcome in anyone other than Han Chinese.', 'a strong association between HLA-B*1502 and carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS) in Han Chinese, but not in Caucasian populations.', 'A very strong association of carbamazepine-induced SJS with HLA-B*1502 has recently been described in the Han Chinese population.', 'there is a strong association in Han Chinese between a genetic marker, the human leukocyte antigen HLA-B*1502, and Stevens-Johnson syndrome induced by carbamazepine, a drug commonly prescribed for the treatment of seizures']

['HLA-B*1502 has a high frequency in Han Chinese and other Asian populations, except Japanese. (There is a strong association between human leucocyte antigen (HLA)-B*1502 and carbamazepine-induced Stevens-Johnson syndrome (SJS)).']

['Han Chinese and other Asian populations, except Japanese']

What is the mode of action of Hsp90 inhibitors?

['In vitro, we show that pharmacologic inhibition of Hsp90 by IPI-504 exerts antiproliferative effects in a panel of pancreatic cancer cells in a dose- and time-dependent manner.', 'In pancreatic cancer xenografts obtained directly from patients with pancreas cancer, the agent resulted in a marked suppression of tumor growth.', 'Using a proteomic profiling analysis with isotope tags for relative and absolute quantitation labeling technique, we have identified 20 down-regulated proteins and 42 up-regulated proteins on IPI-504 treatment.tumor growth Identical changes were observed in the expression of the genes coding for these proteins in a subset of proteins including HSPA1B, LGALS3, CALM1, FAM84B, FDPS, GOLPH2, HBA1, HIST1H1C, HLA-B, and MARCKS. The majority of these proteins belong to the functional class of intracellular signal transduction, immune response, cell growth and maintenance, transport, and metabolism.', 'Dicoumarol, a long-established oral anticoagulant, is a new Hsp90 inhibitor that represses PTTG1/Securin gene expression and provokes apoptosis through a complex trait involving both intrinsic and extrinsic pathways.', 'Dicoumarol activity as an Hsp90 inhibitor is confirmed by smaller levels of Hsp90 clients in treated cells and inhibition of in vivo heat shock luciferase activity recovery assays.', 'Likewise, established Hsp90 inhibitors (17-allylamino-geldanamycin and novobiocin) repress PTTG1/Securin gene expression. ', 'However, effects on PTTG1/Securin could be partially ascribed to inhibition of the Ras/Raf/extracellular signal-regulated kinase pathway.', 'To document this field, we have studied two Hsp90 inhibitors (radicicol and geldanamycin), known to interact with the ATP-binding site of Hsp90 (the Bergerat fold),', 'One of these is the novel agent 17-allylamino-17-demethoxygeldanamycin that acts to inhibit the hsp90 molecular chaperone. Treatment of four human colon cancer cell lines with iso-effective concentrations of this agent resulted in depletion of c-raf-1 and akt and inhibition of signal transduction.', 'The expression of hsp90 client protein genes was not affected, but hsc hsp70, hsp90beta, keratin 8, keratin 18 and caveolin-1 were deregulated following treatment.']

['Pharmacologic inhibition of Hsp90 involves interaction with the ATP-binding site of the chaperone. This exerts antiproliferative effects resulting in a marked suppression of tumor growth. Following treatment with a Hsp90 inhibitor, expression of a number of proteins is affected, and most notably the Hsp90 clients, leading to dysregulation of intracellular signal transduction, immune response, cell growth and maintenance, transport, and metabolism, finally resulting in cancer cell death through activation of both intrinsic and extrinsic apoptotic pathways.']

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Is intraoperative radiotherapy used for treatment of glioblastoma?

[' 1) Intraoperative radiotherapy ( IOR , 1,000-2,000 rad) was applied in 13 cases; the 2-year survival was 41.6%. ', 'The median survival time after IORT was 12 months for 9 patients with glioblastoma or anaplastic astrocytoma, while it was 51 months for 8 patients with less infiltrative tumors (ependymoma, anaplastic ependymoma, and anaplastic oligodendroglioma). ', 'It is concluded that IORT combined with extensive tumor removal has an acceptable toxicity in previously irradiated patients and can be effective for selected recurrent malignant brain tumors.', 'CONCLUSIONS: The results of this study indicate that IORT can contribute to successful tumor treatment while neither increasing peri-operative morbidity nor subacute sequelae.', 'This review compiles preclinical and clinical evidence for a dedicated treatment of both residual cancer cells and regional microenvironment using intraoperative radiotherapy (IORT).', ' Intraoperative radiotherapy (IORT) is a pragmatic and effective approach to sterilize the margins from persistent tumor cells, abrogate post-injury proliferative stimuli and to bridge the therapeutic gap between surgery and radiochemotherapy. ', '[Surgical treatment and radiation therapy for glioblastoma multiforme, with special reference to intraoperative radiotherapy].', 'Rationale for intraoperative radiotherapy in glioblastoma.', 'Intraoperative radiotherapy (IORT) was performed in 20 of 36 patients with glioma; 11 glioblastomas, 7 malignant astrocytomas, 2 benign astrocytomas.', '[Surgical treatment and radiation therapy for glioblastoma multiforme, with special reference to intraoperative radiotherapy]', 'INTRAGO: intraoperative radiotherapy in glioblastoma multiforme—a phase I/II dose escalation study', 'Intraoperative cobalt-60 treatment of glioblastoma multiforme', 'An intraoperative remote afterloading endocurietherapy (ECT) technique with high-activity 60cobalt (60Co) for the treatment of glioblastoma multiforme (GM) is described', '[Surgical treatment and radiation therapy for glioblastoma multiforme, with special reference to intraoperative radiotherapy].', 'Rationale for intraoperative radiotherapy in glioblastoma.', 'Intraoperative cobalt-60 treatment of glioblastoma multiforme.', 'INTRAGO: intraoperative radiotherapy in glioblastoma multiforme—a phase I/II dose escalation study.', 'Intraoperative remote afterloading endocurietherapy with high-activity 60cobalt for treatment of glioblastoma multiforme.', 'Combining intraoperative carmustine wafers and Stupp regimen in multimodal first-line treatment of primary glioblastomas.', 'The intraoperative use of carmustine wafers in combination with Stupp regimen is a viable first-line treatment option of glioblastomas.', 'An intraoperative remote afterloading endocurietherapy (ECT) technique with high-activity 60cobalt (60Co) for the treatment of glioblastoma multiforme (GM) is described.', 'The study investigated if intraoperative use of carmustine wafers, particularly in combination with Stupp regimen, is a viable and safe first-line treatment option of glioblastomas.']

['Yes, intraoperative radiotherapy (IORT) is being used for treatment of glioblastoma. IORT combined with extensive tumor removal has an acceptable toxicity in previously irradiated patients and can be effective for selected recurrent malignant brain tumors.']

['no']

How does lncRNA Gomafu respond to neuronal activation and what is its role in schizophrenia-related alternative splicing, given its interaction with splicing factors QKI and SRSF1 and its downregulation in post-mortem cortical gray matter from the superior temporal gyrus in SZ?

['["The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing.", "Here, we profile these transcriptomic responses and show that long non-coding RNAs (lncRNAs) are dynamically regulated by neuronal activation, including acute downregulation of the lncRNA Gomafu, previously implicated in brain and retinal development. Moreover, we demonstrate that Gomafu binds directly to the splicing factors QKI and SRSF1 (serine/arginine-rich splicing factor 1) and dysregulation of Gomafu leads to alternative splicing patterns that resemble those observed in SZ for the archetypal SZ-associated genes DISC1 and ERBB4. Finally, we show that Gomafu is downregulated in post-mortem cortical gray matter from the superior temporal gyrus in SZ. These results functionally link activity-regulated lncRNAs and alternative splicing in neuronal function and suggest that their dysregulation may contribute to neurological disorders.", "Gomafu/MIAT/Rncr2 is a long noncoding RNA that has been proposed to control retinal cell specification, stem cell differentiation and alternative splicing of schizophrenia-related genes.", "The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing", "Moreover, we demonstrate that Gomafu binds directly to the splicing factors QKI and SRSF1 (serine/arginine-rich splicing factor 1) and dysregulation of Gomafu leads to alternative splicing patterns that resemble those observed in SZ for the archetypal SZ-associated genes DISC1 and ERBB4. ", "Finally, we show that Gomafu is downregulated in post-mortem cortical gray matter from the superior temporal gyrus in SZ. ", "The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing."]']

The long non-coding RNA Gomafu is acutely downregulated in response to neuronal activation. It is involved in schizophrenia-associated alternative splicing by binding directly to the splicing factors QKI and SRSF1. Dysregulation of Gomafu leads to alternative splicing patterns similar to those observed in schizophrenia for genes DISC1 and ERBB4. Additionally, Gomafu is downregulated in post-mortem cortical gray matter from the superior temporal gyrus in schizophrenia.

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What are Degrons?

['Specific signals (degrons) regulate protein turnover mediated by the ubiquitin-proteasome system.', 'Portable degradation sequences, or degrons, have the ability to bind to E3 ligases and promote substrate ubiquitination when the sequence is presented in isolation or appended to other entities such as fluorescent peptide-based reporters. ', "The N-degrons, a set of degradation signals recognized by the N-end rule pathway, comprise a protein's destabilizing N-terminal residue and an internal lysine residue.", "The ubiquitin-proteasome system degrades an enormous variety of proteins that contain specific degradation signals, or 'degrons'.", 'Degron refers to an amino acid sequence that encodes a protein degradation signal, which is oftentimes a poly-ubiquitin chain that can be transferred to other proteins. ', 'Degradation signals (degrons) that are targeted by the N-end rule pathway include a set called N-degrons. The main determinant of an N-degron is a destabilizing N-terminal residue of a protein', 'The N-end rule pathway is a proteolytic system in which destabilizing N-terminal amino acids of short lived proteins are recognized by recognition components (N-recognins) as an essential element of degrons, called N-degrons', 'The N-end rule pathway is a regulated proteolytic system that targets proteins containing destabilizing N-terminal residues (N-degrons) for ubiquitination and proteasomal degradation in eukaryotes', 'More than 25 years ago, the first degradation signal was discovered and defined as destabilizing N-terminal amino-acid residue (or N-degron) of protein substrates', 'A protein domain called "degron", which induces rapid proteolysis by the proteasome, can be used for this purpose. Degron-based technologies for the conditional depletion of POI--degron fusion proteins have been developed by exploiting various pathways leading to proteasomal degradation.']

['Specific signals (degrons) regulate protein turnover mediated by the ubiquitin-proteasome system.', 'Portable degradation sequences, or degrons, have the ability to bind to E3 ligases and promote substrate ubiquitination when the sequence is presented in isolation or appended to other entities such as fluorescent peptide-based reporters.', 'portable degradation sequences, or degrons, have the ability to bind to e3 ligases and promote substrate ubiquitination when the sequence is presented in isolation or appended to other entities such as fluorescent peptide-based reporters.']

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What personality traits can be evaluated with the Ten Item Personality Inventory.

['Analyses included correlations and a regression analysis between depressive symptoms and unmet expectations with the Five-Factor Model personality traits (extraversion, agreeableness, conscientiousness, emotional stability, openness to experience) as measured by the Ten-Item Personality Inventory.', 'The questionnaire measures each of the five major facets of personality: openness, extroversion, conscientiousness, agreeableness and neuroticism.', 'DESIGN: Adoptive mothers (N = 136) were surveyed for depressive symptoms using the Center for Epidemiologic Studies-Depression Scale (CES-D) and the Edinburgh Postnatal Depression Scale (EPDS). Analyses included correlations and a regression analysis between depressive symptoms and unmet expectations with the Five-Factor Model personality traits (extraversion, agreeableness, conscientiousness, emotional stability, openness to experience) as measured by the Ten-Item Personality Inventory. ', 'Analyses included correlations and a regression analysis between depressive symptoms and unmet expectations with the Five-Factor Model personality traits (extraversion, agreeableness, conscientiousness, emotional stability, openness to experience) as measured by the Ten-Item Personality Inventory. ']

['The Ten Item Personality Inventory measures each of the five major facets of personality: openness, extroversion, conscientiousness, agreeableness and neuroticism.']

['openness', 'extroversion', 'conscientiousness', 'agreeableness', 'neuroticism']

How are G-quadruplex forming sequences associated with human mitochondrial DNA deletion breakpoints in disease?

['["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."]']

G-quadruplex forming sequences are associated with human mitochondrial DNA deletion breakpoints in disease by residing in close proximity (within 20 base pairs) to known deletion breakpoints. Circular dichroism and UV spectral analysis have shown that G-rich sequences near deletion breakpoints form G-quadruplex DNA structures. Nucleotide repeats flanking the deletions are also observed at most analyzed deletion breakpoints. The ability of selected sequences to form G-quadruplexes in vitro has been established, and these structures are inefficiently unwound by the mitochondrial replicative Twinkle helicase.

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Describe mechanism of action of PLX3397 drug.

['Following the 25 d lesion, we administered PLX3397, a CSF1R inhibitor, for 30 d to eliminate microglia. ', '.METHODS: Using x-ray co-crystallography to guide our drug-discovery research, we generated a potent, selective CSF1R inhibitor, PLX3397, that traps the kinase in the autoinhibited conformation.', 'Treatment with PLX3397, a small molecule inhibitor of the CSF1 receptor CSF1R and related kinases, decreases microglial numbers by promoting microglial apoptosis in both CSF1 overexpressing and control mice.', 'Sustained inhibition of receptor tyrosine kinases and macrophage depletion by PLX3397 and rapamycin as a potential new approach for the treatment of MPNSTs.', 'We hypothesized that PLX3397, which inhibits KIT and colony-stimulating-factor-1 receptor (CSF1R), would be more efficacious than imatinib in GIST by also depleting tumor-associated macrophages, which are generally thought to support tumor growth.', 'The cytokine CSF-1 (or M-CSF) is an important factor of TAM recruitment and differentiation and several pharmacological agents targeting the CSF-1 receptor (CSF-1R) have been developed to regulate TAM in solid cancers. We show that the kinase inhibitor PLX3397 strongly dampened the systemic and local accumulation of macrophages driven by B16F10 melanomas, without affecting Gr-1(+) myeloid derived suppressor cells. ', 'The CSF-1 receptor (CSF-1R) is a tyrosine kinase that is targetable by small molecule inhibitors such as PLX3397.', 'In conclusion, CSF-1R blockade with PLX3397 improved the efficacy of ACT immunotherapy by inhibiting the intratumoral accumulation of immunosuppressive macrophages.', 'The CSF-1 receptor (CSF-1R) is a tyrosine kinase that is targetable by small molecule inhibitors such as PLX3397.', 'In conclusion, CSF-1R blockade with PLX3397 improved the efficacy of ACT immunotherapy by inhibiting the intratumoral accumulation of immunosuppressive macrophages.', 'The CSF-1 receptor (CSF-1R) is a tyrosine kinase that is targetable by small molecule inhibitors such as PLX3397. ']

['PLX3397 works by inhibiting colony-stimulating-factor-1 receptor (CSF1R).']

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What is the mechanism of action of Pictilisib?

['EXPERIMENTAL DESIGN: Antiestrogen-sensitive and antiestrogen-resistant ER(+) human breast cancer cell lines and mice bearing PIK3CA-mutant xenografts were treated with the antiestrogen fulvestrant, the PI3K inhibitor GDC-0941 (pictilisib; varied doses/schedules that provided similar amounts of drug each week), or combinations. ', 'These strategies include first-line therapy with high-dose fulvestrant or everolimus (in combination with exemestane or letrozole or with other endocrine therapies), use of the PI3K inhibitors (e.g., buparlisib, alpelisib, pictilisib, taselisib), entinostat, CDK 4/6 inhibitors (e.g., palbociclib, ribociclib, abemaciclib), and novel selective estrogen receptor degradation agents that may enhance the targeting of acquired mutations in the ESR1 gene.', 'Phase II Randomized Preoperative Window-of-Opportunity Study of the PI3K Inhibitor Pictilisib Plus Anastrozole Compared With Anastrozole Alone in Patients With Estrogen Receptor-Positive Breast Cancer.', 'This preoperative window study assessed whether adding the PI3K inhibitor pictilisib (GDC-0941) can increase the antitumor effects of anastrozole in primary breast cancer and aimed to identify the most appropriate patient population for combination therapy.', 'In contrast to parental cells, resistant cells were sensitive to growth inhibition and apoptosis induced by the class I PI3K inhibitor, GDC-0941 (pictilisib), which also induced FOXO1 nuclear translocation.', 'Using a mass spectrometry-based metabolomics platform, we discovered that plasma concentrations of 26 metabolites, including amino acids, acylcarnitines, and phosphatidylcholines, were decreased in mice bearing PTEN-deficient tumors compared with non-tumor-bearing controls and in addition were increased following dosing with class I PI3K inhibitor pictilisib (GDC-0941).', 'The PI3K inhibitor pictilisib plus anastrozole suppresses luminal B breast cancer proliferation.', 'Pictilisib is an oral inhibitor of multiple PI3K isoforms.', 'Pictilisib (GDC-0941) is an oral class I phosphatidylinositol-3-phosphate kinase inhibitor.', 'Distribution of the phosphatidylinositol 3-kinase inhibitors Pictilisib (GDC-0941) and GNE-317 in U87 and GS2 intracranial glioblastoma models-assessment by matrix-assisted laser desorption ionization imaging.', 'First-in-human phase I study of pictilisib (GDC-0941), a potent pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor, in patients with advanced solid tumors.', 'PURPOSE: This first-in-human dose-escalation trial evaluated the safety, tolerability, maximal-tolerated dose (MTD), dose-limiting toxicities (DLT), pharmacokinetics, pharmacodynamics, and preliminary clinical activity of pictilisib (GDC-0941), an oral, potent, and selective inhibitor of the class I phosphatidylinositol-3-kinases (PI3K).PATIENTS AND METHODS: Sixty patients with solid tumors received pictilisib at 14 dose levels from 15 to 450 mg once-daily, initially on days 1 to 21 every 28 days and later, using continuous dosing for selected dose levels. ', 'The PI3K inhibitor pictilisib plus anastrozole suppresses luminal B breast cancer proliferation. <CopyrightInformation>©2016 American Association for Cancer Research.</C', 'Understanding the temporal response and pharmacodynamic effects of PI3K inhibition in ER(+) breast cancer will provide a rationale for treatment scheduling to maximize therapeutic index.Antiestrogen-sensitive and antiestrogen-resistant ER(+) human breast cancer cell lines and mice bearing PIK3CA-mutant xenografts were treated with the antiestrogen fulvestrant, the PI3K inhibitor GDC-0941 (pictilisib; varied doses/schedules that provided similar amounts of drug each week), or combinations.', 'The objectives of these studies were to visualize and compare by matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry the brain and tumor distribution of the phosphatidylinositol 3-kinase (PI3K) inhibitors pictilisib (GDC-0941, 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine) and GNE-317 [5-(6-(3-methoxyoxetan-3-yl)-7-methyl-4-morpholinothieno[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine] in U87 and GS2 orthotopic models of GBM, models that exhibit differing blood-brain barrier characteristics.', 'Treating Mx1-Cre, Kras(D12) mice with GDC-0941 (also referred to as pictilisib), an orally bioavailable inhibitor of class I PI3K isoforms, reduced leukocytosis, anemia and splenomegaly while extending survival.', 'These strategies include first-line therapy with high-dose fulvestrant or everolimus (in combination with exemestane or letrozole or with other endocrine therapies), use of the PI3K inhibitors (e.g., buparlisib, alpelisib, pictilisib, taselisib), entinostat, CDK 4/6 inhibitors (e.g., palbociclib, ribociclib, abemaciclib), and novel selective estrogen receptor degradation agents that may enhance the targeting of acquired mutations in the ESR1 gene. <CopyrightInformation>Copyright © 2015.', 'Pictilisib is an oral inhibitor of multiple PI3K isoforms.']

['Pictilisib acts by inhibiting PI3K. It is used for breast cancer treatment.']

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Which are the coactivators of the Yes-associated protein (yap)?

['ndependent research, often in the context of muscle biology, described Tead (TEA domain) transcription factors, which bind CATTCC DNA motifs to regulate gene expression. These two research areas were joined by the finding that the Hippo pathway regulates the activity of Tead transcription factors mainly through phosphorylation of the transcriptional coactivators Yap and Taz, which bind to and activate Teads.', 'TEADs on their own are unable to activate transcription and they require the help of coactivators. Several TEAD-interacting coactivators are known and they can be classified into three groups: (1) YAP and its paralog TAZ;', 'YAP and TAZ are transcription coactivators and effectors of the Hippo pathway, which play a key role in organ size control. Through interaction with transcription factors such as TEADs, they activate gene transcription and thus promote cell proliferation, inhibit apoptosis, and regulate cell differentiation. ', 'The YAP/TAZ-TEAD complex also upregulates several other proliferation-promoting genes and also promotes anchorage-independent cell proliferation.', 'hree-dimensional structure of the YAP-TEAD complex']

['The Yap protein forms complex with Tead (TEA domain) transcription factors.']

['Tead (TEA domain) transcription factors.']

Can administration of the thyrotropin releasing hormone reduce fatigue in cancer patients?

['TRH administration was associated with significant improvement (p < 0.05) in fatigue levels as measured by the Visual Analog Scale-Energy (VAS-E), was associated with significant (p < 0.05) improvement in sleep disturbances and improved quality of life. ', 'This decrease in CRP level with TRH administration was associated with improvement in energy levels as measured by the VAS-E. ', 'In the present pilot, randomized, placebo-controlled, crossover study, we investigated the efficacy and safety of TRH as a treatment for CF.', 'TRH administration was associated with significant improvement in fatigue level as measured by the VAS-E, the fatigue and vigor subscales of the POMS, and the fatigue subscale of FACIT-F (p < 0.05). ', 'TRH administration was efficacious, safe, and tolerable in the treatment of CF with a positive impact on quality of life. These results provide a crucial impetus for pursuing TRH therapeutics to treat CF.', 'Thyrotropin-releasing hormone can relieve cancer-related fatigue: hypothesis and preliminary observations.', 'Global assessment using both subjective and objective parameters showed that TRH exerted clear anti-fatigue effects in four of the six TRH treatments. ', 'These initial findings support the proposal that TRH can ameliorate cancer-related fatigue.']

['yes, in cancer patients, thyrotropin releasing hormone (TRH) administration was associated with significant improvement in cancer related fatigue levels as measured by the Visual Analog Scale-Energy, fatigue and vigor subscales of the POMS, and the fatigue subscale of FACIT-F. TRH administration was safe and tolerable in the treatment of cancer-related with a positive impact on quality of life, suggesting the need for further studies investigating TRH for treatment of fatigue in cancer patients.']

['yes']

What is the association between NT-proBNP and cognitive function?

['RESULTS: Measures of cognitive decline were significantly associated with stroke, NT-proBNP, ABI, and cIMT, but not with nonstroke vascular events. ', 'SCI was present at baseline more often in NYHA IV patients compared with NYHA II [odds ratio 2.94; 95% confidence interval (CI) 1.15-7.51, P = 0.025], but it was not related to NT-proBNP levels. ', "Comparing extreme quintiles of NT-proBNP, subjects in the highest quintile were more likely to have reduced cognitive ability (within the lowest tertile of 'g') and 'possible' depression (HADS depression ≥8) (OR 1.80; 95% CI: 1.20, 2.70; p\u200a=\u200a0.005 and OR 2.18; 95% CI: 1.28, 3.71; p\u200a=\u200a0.004, respectively). Associations persisted when pre-morbid ability was adjusted for, but as expected were no longer statistically significant following the adjustment for diabetes-related and vascular co-variates (β -0.02, 95% CI -0.07 to 0.03, p>0.05 for 'g'; β 0.03, 95% CI -0.02 to 0.07, p>0.05 for depression scores). CONCLUSION: Raised plasma NT-proBNP was weakly but statistically significantly associated with poorer cognitive function and depression. The prospective phases of the ET2DS will help determine whether or not NT-proBNP can be considered a risk marker for subsequent cognitive impairment and incident depression and whether it provides additional information over and above traditional risk factors for these conditions.", 'RESULTS AND CONCLUSION: Patients with vascular disease and elevated serum NT-proBNP level had a lower cognition level, shorter survival time, lower renal function and a higher percentage of pathological brain imaging than patients with vascular disease and normal NT-proBNP level. ', 'BACKGROUND: Natriuretic peptides have prognostic value across a wide spectrum of cardiovascular diseases and may predict cognitive dysfunction in patients with cardiovascular disease, even in the absence of previous stroke. ', 'In unadjusted analyses, all 3 cognitive function test scores were significantly associated with NT-proBNP levels (P<.001). After adjusting for age, sex, education, hypertension, body mass index, exercise, alcohol use, smoking, low density lipoprotein cholesterol, creatinine clearance, and previous cardiovascular disease, elevated NT-proBNP levels remained independently associated with poor cognitive performance on MMSE (odds ratio [OR] 2.0; 95% confidence interval [CI], 1.1-3.6; P=.02) and Trails B (OR 1.7; 95% CI, 1.2-2.7; P=.01), but not Category Fluency (OR 1.4; 95% CI, 0.9-2.2; P=.19). ', ' CONCLUSIONS: NT-proBNP levels were strongly and independently associated with poor cognitive function in community-dwelling older adults.', 'However, NT-proBNP level did not predict cognition as assessed by MMSE score. ', 'However, N-terminal pro-brain natriuretic peptide (NT-proBNP) was significantly enhanced both in MCI and AD patients (1', 'In a second analysis of a sample of 110 subjects including younger healthy controls, we confirmed that NT-proBNP has the potential to be a stable candidate protein for both diagnosis and AD disease progression', 'Raised plasma NT-proBNP was weakly but statistically significantly associated with poorer cognitive function and depression', 'In unadjusted analyses, all 3 cognitive function test scores were significantly associated with NT-proBNP levels (P<.001)', 'NT-proBNP levels were strongly and independently associated with poor cognitive function in community-dwelling older adults.']

['Greater NT-proBNP serum concentration is associated with poorer cognitive function and cognitive decline. In community-dwelling older adults, greater NT-proBNP levels were strongly associated with poor cognitive function independently from age, sex, education, hypertension, body mass index, exercise, alcohol use, smoking, low density lipoprotein cholesterol, creatinine clearance, and previous cardiovascular disease. However, other authors did not find an association between NT-proBNP and severe cognitive impairment (SCI).']

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Is transcapillary albumin escape altered in diabetic patients?

['On the contrary, altered TERalb and increased carotid artery intimal thickness are shown by all hypertensive type 2 diabetic patients, both with normal and altered patterns of AER.', 'Altered systemic capillary permeability characterizes insulin-resistant hypertensive patients with Metabolic Syndrome.', 'TERalb is increased in normo-albuminuric type 1 diabetic patients. ']

['An altered TERalb is present in type 2 diabetic patients, both with normal and altered patterns of AER.\nTERalb is increased also in normo-albuminuric type 1 diabetic patients.']

['yes']

Does the Oncotype DX test work with paraffin embedded tissues?

['The Oncotype-DX Breast Cancer Assay (Genomic Health, Redwood City, CA) quantifies gene expression for 21 genes in breast cancer tissue by performing reverse transcription polymerase chain reaction (RT-PCR) on formalin-fixed paraffin-embedded (FFPE) tumour blocks that are obtained during initial surgery (lumpectomy, mastectomy, or core biopsy) of women with early breast cancer that is newly diagnosed.', 'Oncotype DXtrade mark, is a diagnostic test comprised of a 21-gene assay applied to paraffin-embedded breast cancer tissue, which allows physicians to predict subgroups of hormone-receptor-positive, node-negative patients who may benefit from hormonal therapy alone or require adjuvant chemotherapy to attain the best survival outcome.', 'Oncotype DX is a clinically validated, high-complexity, multianalyte reverse transcription-PCR genomic test that predicts the likelihood of breast cancer recurrence in early-stage, node-negative, estrogen receptor-positive breast cancer. ', 'We therefore investigated the analytical performance of the assay.', 'Assays used a pooled RNA sample from fixed paraffin-embedded tissues to evaluate the analytical performance of a 21-gene panel with respect to amplification efficiency, precision, linearity, and dynamic range, as well as limits of detection and quantification.', 'One such strategy is the 21-gene assay (Oncotype DX), which is currently in commercial use in the USA. One advantage of this test is the use of paraffin-embedded blocks instead of previous methods, which required fresh frozen tissue. ', 'We used paraffin-embedded core biopsies from a completed phase II trial to identify genes that correlate with response to primary chemotherapy. ', 'In addition to the individual genes, the correlation of the Oncotype DX Recurrence Score with pCR was examined', 'RNA was extracted from paraffin blocks', 'to develop the 21-gene Recurrence Score assay (Oncotype DX)']

['Yes, the Oncotype DX test works with paraffin embedded tissue.']

['yes']

For which diseases members of the 2-aminobenzamide class of histone deacetylase (HDAC) inhibitors show promise as therapeutics?

["Members of the 2-aminobenzamide class of histone deacetylase (HDAC) inhibitors show promise as therapeutics for the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD)", "Histone deacetylase (HDAC) inhibitors have received considerable attention as potential therapeutics for a variety of cancers and neurological disorders. Recent publications on a class of pimelic diphenylamide HDAC inhibitors have highlighted their promise in the treatment of the neurodegenerative diseases Friedreich's ataxia and Huntington's disease, based on efficacy in cell and mouse models", "We recently identified a novel class of pimelic o-aminobenzamide histone deacetylase (HDAC) inhibitors that show promise as therapeutics in the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD)", "We recently identified a class of pimelic diphenylamide histone deacetylase (HDAC) inhibitors that show promise as therapeutics in the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease", "Members of the 2-aminobenzamide class of histone deacetylase (HDAC) inhibitors show promise as therapeutics for the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD).", "We recently identified a novel class of pimelic o-aminobenzamide histone deacetylase (HDAC) inhibitors that show promise as therapeutics in the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD).", 'Rationale for the development of 2-aminobenzamide histone deacetylase inhibitors as therapeutics for Friedreich ataxia.', 'While it is clear that HDAC3 is one of the important targets of the 2-aminobenzamide HDAC inhibitors, inhibition of other class I HDACs (HDACs 1 and 2) may also be involved in the beneficial effects of these compounds in FRDA and HD, and other HDAC interacting proteins may be impacted by the compound.', "The authors' laboratories have identified a novel class of histone deacetylase inhibitors (2-aminobenzamides) that reverses heterochromatin-mediated silencing of the frataxin (FXN) gene in Friedreich ataxia.", 'Members of the 2-aminobenzamide class of histone deacetylase (HDAC) inhibitors show promise as therapeutics for the neurodegenerative diseases Friedreich&apos;s ataxia (FRDA) and Huntington&apos;s disease (HD)', 'While it is clear that HDAC3 is one of the important targets of the 2-aminobenzamide HDAC inhibitors, inhibition of other class I HDACs (HDACs 1 and 2) may also be involved in the beneficial effects of these compounds in FRDA and HD, and other HDAC interacting proteins may be impacted by the compound', "Members of the 2-aminobenzamide class of histone deacetylase (HDAC) inhibitors show promise as therapeutics for the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD). ", "We recently identified a novel class of pimelic o-aminobenzamide histone deacetylase (HDAC) inhibitors that show promise as therapeutics in the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD). ", "We recently identified a novel class of pimelic o-aminobenzamide histone deacetylase (HDAC) inhibitors that show promise as therapeutics in the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD).", "The authors' laboratories have identified a novel class of histone deacetylase inhibitors (2-aminobenzamides) that reverses heterochromatin-mediated silencing of the frataxin (FXN) gene in Friedreich ataxia.", "Members of the 2-aminobenzamide class of histone deacetylase (HDAC) inhibitors show promise as therapeutics for the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD). While it is clear that HDAC3 is one of the important targets of the 2-aminobenzamide HDAC inhibitors, inhibition of other class I HDACs (HDACs 1 and 2) may also be involved in the beneficial effects of these compounds in FRDA and HD, and other HDAC interacting proteins may be impacted by the compound.", "We recently identified a novel class of pimelic o-aminobenzamide histone deacetylase (HDAC) inhibitors that show promise as therapeutics in the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD).", "However, histone deacetylase inhibitors tested to date either are highly cytotoxic or have very low specificities for different histone deacetylase enzymes. The authors' laboratories have identified a novel class of histone deacetylase inhibitors (2-aminobenzamides) that reverses heterochromatin-mediated silencing of the frataxin (FXN) gene in Friedreich ataxia.", "Members of the 2-aminobenzamide class of histone deacetylase (HDAC) inhibitors show promise as therapeutics for the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD).", 'Rationale for the development of 2-aminobenzamide histone deacetylase inhibitors as therapeutics for Friedreich ataxia.', "The authors' laboratories have identified a novel class of histone deacetylase inhibitors (2-aminobenzamides) that reverses heterochromatin-mediated silencing of the frataxin (FXN) gene in Friedreich ataxia."]

["Members of the 2-aminobenzamide class of histone deacetylase (HDAC) inhibitors show promise as therapeutics for the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD).", "Members of the 2-aminobenzamide class of histone deacetylase (HDAC) inhibitors show promise as therapeutics for the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD)"]

["Friedreich's ataxia (FRDA)", "Huntington's disease (HD)"]

Where does TORC1 sequester during heat stress?

['Transient sequestration of TORC1 into stress granules during heat stress.', 'Here we report that TORC1 signaling upon heat stress is regulated by stress granules (SGs), which are cytoplasmic foci formed under certain stresses. Ectopic formation of SGs achieved by Pbp1 overexpression in unstressed cells sequesters TORC1 in this compartment, thereby blunting TORC1 signaling', 'Upon heat stress, a physiological SG-inducing condition, TORC1 is also recruited to SGs, which delays reactivation of TORC1 signaling during recovery from heat stress', 'TORC1 reactivation is directed through SG disassembly, suggesting that SGs act as a key determinant for TORC1 reactivation during recovery from heat stress', 'Upon heat stress, a physiological SG-inducing condition, TORC1 is also recruited to SGs, which delays reactivation of TORC1 signaling during recovery from heat stress.', 'Here we report that TORC1 signaling upon heat stress is regulated by stress granules (SGs), which are cytoplasmic foci formed under certain stresses.', 'Here we report that TORC1 signaling upon heat stress is regulated by stress granules (SGs), which are cytoplasmic foci formed under certain stresses. Ectopic formation of SGs achieved by Pbp1 overexpression in unstressed cells sequesters TORC1 in this compartment, thereby blunting TORC1 signaling. Upon heat stress, a physiological SG-inducing condition, TORC1 is also recruited to SGs, which delays reactivation of TORC1 signaling during recovery from heat stress. ', 'Ectopic formation of SGs achieved by Pbp1 overexpression in unstressed cells sequesters TORC1 in this compartment, thereby blunting TORC1 signaling. Upon heat stress, a physiological SG-inducing condition, TORC1 is also recruited to SGs, which delays reactivation of TORC1 signaling during recovery from heat stress.', 'Here we report that TORC1 signaling upon heat stress is regulated by stress granules (SGs), which are cytoplasmic foci formed under certain stresses. Ectopic formation of SGs achieved by Pbp1 overexpression in unstressed cells sequesters TORC1 in this compartment, thereby blunting TORC1 signaling.', 'Upon heat stress, a physiological SG-inducing condition, TORC1 is also recruited to SGs, which delays reactivation of TORC1 signaling during recovery from heat stress. Moreover, TORC1 reactivation is directed through SG disassembly, suggesting that SGs act as a key determinant for TORC1 reactivation during recovery from heat stress.', 'Although TORC1 signaling is repressed by various stresses in yeast, the underlying mechanisms remain elusive. Here we report that TORC1 signaling upon heat stress is regulated by stress granules (SGs), which are cytoplasmic foci formed under certain stresses.', 'Here we report that TORC1 signaling upon heat stress is regulated by stress granules (SGs), which are cytoplasmic foci formed under certain stresses.', 'Upon heat stress, a physiological SG-inducing condition, TORC1 is also recruited to SGs, which delays reactivation of TORC1 signaling during recovery from heat stress.']

['Upon heat stress, TORC1 is recruited to stress granules.']

[]

Which drugs may interfere thyroxine absorption?

['ommonly used drugs, such as bile acid sequestrants, ferrous sulphate, sucralfate, calcium carbonate, aluminium-containing antacids, phosphate binders, raloxifene and proton-pump inhibitors, have also been shown to interfere with the absorption of levothyroxine', 'Hypothyroid patients taking sevelamer hydrochloride or chromium picolinate should be advised to separate the time of ingestion of these drugs from their thyroid hormone preparation by several hours.']

['bile acid sequestrants, ferrous sulphate, sucralfate, calcium carbonate, aluminium-containing antacids, phosphate binders, raloxifene and proton-pump inhibitors, have also been shown to interfere with the absorption of levothyroxine\nsevelamer hydrochloride or chromium picolinate should be advised to separate the time of ingestion of these drugs from their thyroid hormone preparation by several hours']

['bile acide sequestrant', 'ferrous sulphate', 'sucralfate', 'Calcium carbonate', 'aluminium-containing antacids', 'raloxifene', 'proton pump inhibithors', 'sevelamer', 'chromium picolinate']

Which gene test can be used for the X-linked myotubular myopathy?

['X-linked myotubular myopathy (MTM) is a severe neuromuscular disease of infancy caused by mutations of MTM1, which encodes the phosphoinositide lipid phosphatase, myotubularin', 'As a gene for X linked MTM was recently identified in Xq28, we screened the obligatory carrier mothers for mutation. We found a 4 bp deletion in exon 4 of the MTM1 gene,', 'X-linked Myotubular Myopathy has clearly shown the benefits to be gained from a multinational research consortium with a common interest in identifying and cloning the MTM1 gene.', 'Myotubular myopathy (MTM1) is an X-linked disease, characterized by severe neonatal hypotonia and generalized muscle weakness, with pathological features suggesting an impairment in maturation of muscle fibres. The MTM1 gene encodes a protein (myotubularin) with a phosphotyrosine phosphatase consensus.', 'myotubular myopathy (XLMTM), a severe congenital muscular disorder due to loss-of-function mutations in the MTM1 gene,', 'We established a colony of dogs that harbor an X-linked MTM1 missense mutation.Muscle from affected male dogs exhibits reduction and altered localization of the MTM1 gene product, myotubularin, and provides a model analogous to X-linked myotubular myopathy (XLMTM)', 'X-linked myotubular myopathy (XLMTM) is a rare congenital myopathy, usually characterized by severe hypotonia and respiratory insufficiency at birth, in affected, male infants. The disease is causally associated with mutations in the MTM1 gene, coding for phosphatase myotubularin.', 'Mutations in the MTM1 gene encoding myotubularin cause X-linked myotubular myopathy (XLMTM), a well-defined subtype of human centronuclear myopathy.', 'MTM1 gene sequencing revealed a unique exon 7 variant in all seven affected males, causing a nonconservative missense change, p.N155K, which haplotype data suggest derives from a recent founder in the local population.', 'X-linked centronuclear myopathy (XLMTM), also called myotubular myopathy, is a severe congenital myopathy characterized by generalized hypotonia and weakness at birth and the typical histological finding of centralization of myo-nuclei. It is caused by mutations in the MTM1 gene encoding the 3-phosphoinositides phosphatase myotubularin.', 'sequencing all MTM1 exons', 'X-linked myotubular myopathy (XLMTM), a severe congenital disorder due to loss of function mutations in the MTM1 gene, encoding myotubularin, a phosphoinositide phosphatase thought to have a role in plasma membrane homeostasis and endocytosis.', 'Mutations in the gene encoding the phosphoinositide phosphatase myotubularin 1 protein (MTM1) are usually associated with severe neonatal X-linked myotubular myopathy (XLMTM). However, mutations in MTM1 have also been recognized as the underlying cause of "atypical" forms of XLMTM in newborn boys, female infants, female manifesting carriers and adult men.', 'X-linked myotubular myopathy (XLMTM), a recessive disorder, is caused by mutations affecting the myotubulatin (MTM1) gene located on the X chromosome. Most of the affected males die in the early postnatal period whereas female carriers are usually asymptomatic.', 'The authors present a patient with the most severe X-linked recessive type (XLMTM).', 'The diagnosis was confirmed and further specified by genetic analysis, revealing a novel frameshift mutation (1314-1315insT) of the myotubularin-coding MTM1 gene.', 'X-linked myotubular myopathy (XLMTM) is a congenital muscle disorder caused by mutations in the MTM1 gene.', 'MTM1, the gene encoding myotubularin (MTM1), is mutated in the X-linked myotubular myopathy (XLMTM), a severe genetic muscular disorder', 'Myotubularin is a ubiquitously expressed phosphatase that acts on phosphatidylinositol 3-monophosphate [PI(3)P], a lipid implicated in intracellular vesicle trafficking and autophagy. It is encoded by the MTM1 gene, which is mutated in X-linked myotubular myopathy (XLMTM), a muscular disorder characterized by generalized hypotonia and muscle weakness at birth leading to early death of most affected males.', 'The entire coding sequence of the gene was screened in 10 XLMTM patients using this technique.', 'X-linked myotubular myopathy (XLMTM; OMIM# 310400) is a severe congenital muscle disease caused by mutations in the myotubularin (MTM1) gene.', 'Mutations in the MTM1 gene cause X-linked recessive myotubular myopathy (XLMTM; MIM310400).', 'We screened 29 independant patients with XLMTM phenotype and four with centronuclear myopathy. 87% (21/24) of patients with known MTM1 mutations showed abnormal myotubularin levels, including some with missense mutations.', 'X-linked myotubular myopathy (XLMTM) characteristically causes severe or fatal muscle weakness in male infants. Mutations in the gene MTM1, encoding the protein myotubularin, can be identified in most families.', 'X-linked myotubular myopathy (XLMTM) is a congenital muscular disease characterized by severe hypotonia and generalized muscle weakness, leading in most cases to early postnatal death. The gene responsible for the disease, MTM1, encodes a dual specificity phosphatase, named myotubularin, which is highly conserved throughout evolution.', 'X-linked recessive myotubular myopathy (XLMTM) is a muscle disorder usually affecting newborn males. In the majority of cases, muscle weakness and hypotonia lead to a rapid demise at neonatal age. The responsible MTM1 gene is located in proximal Xq28.', 'X-linked myotubular myopathy (XLMTM) is a severe congenital muscle disorder due to mutations in the MTM1 gene.', 'X-linked recessive myotubular myopathy (XLMTM) is characterized by severe hypotonia and generalized muscle weakness, with impaired maturation of muscle fibres. The gene responsible, MTM1, was identified recently by positional cloning, and encodes a protein (myotubularin) with a tyrosine phosphatase domain (PTP).', 'X-linked recessive myotubular myopathy (XLMTM; MTM1) is a severe neonatal disorder often causing perinatal death of the affected males. The responsible gene, designated MTM1, was localized to proximal Xq28 and recently isolated. The characterization of MTM1 allowed us to screen for causing mutations in three families, previously investigated by linkage analysis. Using exon amplification, single strand conformation polymorphism, and subsequent sequencing analysis, three new mutations and their mutational origin were characterized by analyzing 10 exons.']

['Genetic testing of the MTM1 gene can be used for the X-linked myotubular myopathy.']

['MTM1 gene test']

What is the Shelterin complex?

['Human telomeres are associated with the shelterin complex which consists of six telomere-associated proteins that specifically bind to telomeric DNA. Alterations or removal of individual shelterin components would lead to telomere uncapping and telomere dysfunction, resulting in cellular senescence and transformation to a malignant state.', 'Telomeres interact with numerous proteins, including components of the shelterin complex, whose alteration, similarly to proliferation-induced telomere shortening, initiates cellular senescence.', 'Telomere repeat binding factor TRF2 is a member of shelterin complex with an important role in protecting and stabilizing chromosomal ends.', 'In human, the shelterin complex binds TTAGGG DNA repeats and provides capping to chromosome ends.', 'Shelterin Protects Chromosome Ends by Compacting Telomeric Chromatin.', 'Telomeres, repetitive DNA sequences at chromosome ends, are shielded against the DNA damage response (DDR) by the shelterin complex. ', 'Telomeres need to be protected by the shelterin complex to avoid junctions occurring between chromosomes while failing topoisomerases or clustered DNA damage processing may produce double-strand breaks, thus requiring swift repair to avoid cell death.', 'A multiprotein complex known as shelterin prevents recognition of telomeric sequences as sites of DNA damage. ']

['Human telomeres are associated with the shelterin complex which consists of six telomere-associated proteins that specifically bind to telomeric DNA. Alterations or removal of individual shelterin components would lead to telomere uncapping and telomere dysfunction, resulting in cellular senescence and transformation to a malignant state.']

[]

Which are the best treatment options to treat Helicobacter pylori?

['Triple therapy, which has been the mainstay of treatment in many countries over the last decade, now has suboptimal results in many parts of the world.', 'equential therapy and quadruple therapy (either bismuth-based or non-bismuth-based) are the best current options to replace initial treatment with triple therapy.', 'olecular tests can be used to detect H. pylori and clarithromycin and/or fluoroquinolone resistance in gastric biopsies without necessitating culture. In regions of high clarithromycin resistance, such as France, sequential treatment or bismuth-containing quadruple therapies are replacing standard triple therapies for the first-line empirical treatment.', 'The evidence in favour of bismuth compounds for treating infected children is still not clear.', 'Chitosan microspheres with multiple Eudragit L100 cores were easily prepared by a new emulsification/coagulation encapsulating method.', 'the multi-core chitosan microspheres could serve as a satisfactory vehicle for stomach-specific delivery of hydrophilic antibiotics.', 'Treatment consisted of a one-week regimen containing a PPI twice daily, amoxicillin (A) 1 g twice daily and rifabutin (R) 300 mg once daily (PPI-AR).', 'Pretreatment antibiotic susceptibility to metronidazole, clarithromycin and A was evaluated using a validated epsilometer test.', 'four different strategies for prevention of rebleeding in patients with peptic ulcer hemorrhage: 1) test for H. pylori and treatment, if positive; 2) proton pump inhibitor maintenance; 3) no preventive treatment; 4) empirical H. pylori eradication immediately after bleeding.', 'Empirical H. pylori eradication was the dominant strategy: its estimated rate of recurrent bleeding was lower (6.1%) than those of strategies 1 (7.4%), 2 (11.1%), and 3 (18.4%) and it was the least expensive strategy. The results remained stable when variables were changed inside a wide range of plausible values.', 'In patients with bleeding peptic ulcer, empirical treatment of H. pylori infection immediately after feeding is restarted is the most cost-effective strategy for preventing recurrent hemorrhage.']

['The best treatment options for eradication of Helicobacter pylori involve triple or quadruple drugs therapy with different types of antibiotics.\nBismuth may be also an additional option. Proton pump inhibitors are also included in treatment.\nThe more effective drug list includes: amoxicillin, claritromycin, metronidazole rifabutin.\nAlso chitosan microspheres with Eudragit L100 have been tested.']

['amoxicillin', 'metronidazole', 'claritromycin', 'Proton pump inhibithors', 'rifabutin', 'Eudragit L100']

To what extent does HPV vaccination reduce the risk for cervical cancer?

['The success of HPV vaccination as a major public health prevention opportunity, however, will entirely depend on efficient infrastructures to deliver the vaccines and on the acceptance by individuals, parents and health care providers.', 'The most effective strategy therein was vaccination of 12-year-olds, plus a temporary 12-24-year-old catch-up program covering both sexes; whereby HPV 6/11/16/18-related cervical cancer, high-grade cervical precancer, and genital wart incidence was reduced by 84-98% during year 50 following vaccine introduction', 'the introduction of cervical screening programs, the incidence and mortality of cervical cancer has been drastically reduced', 'On the assumption that the vaccine provided lifelong immunity, the cost-effectiveness ratio of vaccination of 12-year-old girls was $43,600 per quality-adjusted life-year (QALY) gained, as compared with the current screening practice', 'Vaccine efficacy in prevention of CIN 2 or higher lesions in HPV 16 or HPV 18 negative women, who received all vaccination doses, ranges between 98% and 100%', 'Life expectancy gained from vaccination is 13.04 years and average Quality Adjusted Life Years saved (QALYs) is 24.4 in vaccinated vs 6.29 in unvaccinated', 'Organized vaccination programs against HPV have the potential to prevent about 70% of cervical cancers and the vast majority of the other HPV-related conditions. ', 'However, existing data strongly suggests that as many as 440,000 cervical cancer cases and 220,000 deaths due to this malignancy will be prevented with the establishment of an effective worldwide HPV immunization program', 'Prophylactic HPV vaccination against HPV 16 and 18 has been shown to be highly effective in preventing HPV related malignancy in clinical trials', 'Nevertheless women up to 45 years of age have been shown to exhibit strong immune responses to the bivalent HPV vaccine which might be expected to reduce the risk of HPV re-infection and address the second peak of HPV related malignancy in later life, evident over 45 years of age', 'Reduced costs, simple vaccine regimes and strengthening vaccine delivery platforms for adolescents should eventually facilitate HPV vaccine introduction in developing countries.', 'Besides cost, there are several socio-cultural and ethical issues involved with the implementation of already developed vaccines including the acceptability of HPV vaccination by preadolescent girls and their parents in India.']

['The most effective strategy therein was vaccination of 12-year-olds, plus a temporary 12-24-year-old catch-up program covering both sexes; whereby HPV 6/11/16/18-related cervical cancer, high-grade cervical precancer, and genital wart incidence was reduced by 84-98% during year 50 following vaccine introduction. Vaccine efficacy in prevention of CIN 2 or higher lesions in HPV 16 or HPV 18 negative women, who received all vaccination doses, ranges between 98% and 100%']

['Cervical precancer and similar neoplasias were reduced by 84-100%']

List signaling molecules (ligands) that interact with the receptor EGFR?

['the epidermal growth factor receptor (EGFR) ligands, such as epidermal growth factor (EGF) and amphiregulin (AREG)', ' EGFR ligands epidermal growth factor (EGF), amphiregulin (AREG) and transforming growth factor alpha (TGFα)', ' EGFR and its ligand EGF ', 'Among EGFR ligands, heparin-binding EGF-like growth factor, TGF-α and Betacellulin (BTC) are produced in the tumor microenvironment of FDC-S at RNA level. ', '. Plasma amphiregulin (AR), epidermal growth factor (EGF), transforming growth factor-α, and heparin binding-EGF were assessed by ELISA in 45 chemorefractory mCRC patients', 'Among EGFR ligands, heparin-binding epidermal growth factor (HB-EGF)', ' Of the six known EGFR ligands, transforming growth factor alpha (TGFα) was expressed more highly in triple-negative breast tumors than in tumors of other subtypes.', 'the 7 known EGFR ligands (EGF, betacellulin, epiregulin, heparin-binding EGF, transforming growth factor-α [TGF-α], amphiregulin, and epigen) ', 'EGFR ligands based on the two affinity classes: EGF>HB-EGF>TGF-α>BTC>EPR>EPG>AR', 'In this article, however, we demonstrate that PEPD directly binds to and activates epidermal growth factor receptor (EGFR),', 'four EGFR ligands (AR, HB-EGF, TGF-α, and EREG) ', 'Epidermal growth factor (EGF) family peptides are ligands for the EGF receptor (EGFR). ', 'oluble amphiregulin (AR), transforming growth factor alpha (TGFα), neuregulin 2 beta, and epigen stimulate greater EGFR coupling to cell proliferation and DNA synthesis than do EGF, betacellulin, heparin-binding EGF-like growth factor, and epiregulin', 'Here, we demonstrate that histamine releases 2 EGFR ligands, amphiregulin and heparin-binding epidermal growth factor-like growth factor (HB-EGF), from airway epithelial cells.', 'mammalian EGFR ligands including EGF, TGF-α (TGFα), amphiregulin (AREG), heparin-binding EGF-like growth factor (HB-EGF), betacellulin, epiregulin, and epigen.']

['The 7 known EGFR ligands are: epidermal growth factor (EGF), betacellulin (BTC), epiregulin (EPR), heparin-binding EGF (HB-EGF), transforming growth factor-α [TGF-α], amphiregulin (AREG) and epigen (EPG).']

['epidermal growth factor', 'betacellulin', 'epiregulin', 'heparin-binding epidermal growth factor', 'transforming growth factor-α', 'amphiregulin', 'epigen']

Which genes code for the alpha subunit of the DNA polymerase III in most Firmicutes?

['PolC co-evolves with RNA degradation enzymes that are present only in the A+T-rich Firmicutes clade', 'Bacterial genomes displaying a strong bias between the leading and the lagging strand of DNA replication encode two DNA polymerases III, DnaE and PolC, rather than a single one.', 'SGD, PAS, and polC are all features associated with a group of low-GC, gram-positive bacteria (Firmicutes)', 'PAS is a characteristic of organisms with a heterodimeric DNA polymerase III alpha-subunit constituted by polC and dnaE', 'Bacterial DNA polymerase III, the primary complex of DNA replication, consists of PolC and DnaE. PolC is conserved in Gram-positive bacteria, especially in the Firmicutes with low GC content, whereas DnaE is widely conserved in most Gram-negative and Gram-positive bacteria.', 'PolC-PolE DNA polymerases', 'We conclude that PAS is a characteristic of organisms with a heterodimeric DNA polymerase III alpha-subunit constituted by polC and dnaE, which may play a direct role in the maintenance of SGD.', 'Furthermore, SGD, PAS, and polC are all features associated with a group of low-GC, gram-positive bacteria (Firmicutes)', 'In contrast, PolC co-evolves with RNA degradation enzymes that are present only in the A+T-rich Firmicutes clade, suggesting at least two origins for the degradosome.', 'A method for the construction of in frame substitutions in operons: deletion of the essential Escherichia coli holB gene coding for a subunit of the DNA polymerase III holoenzyme.']

['Bacterial DNA polymerase III is the primary complex of DNA replication. In most Firmicutes, which are low-GC, gram-positive bacteria, the alpha subunit of their DNA polymerase III is encoded by polC and dnaE. DnaE is widely conserved in most bacteria, while PolC is present mainly in Firmicutes clade.']

['dnaE', 'polC']

Which is the transcript responsible for X-chromosome inactivation?

['Xist, a gene responsible for X chromosome inactivation (XCI)', 'X inactivation-specific transcript (XIST) is a long ncRNA that mediates X chromosome inactivation', 'the X inactive specific transcript (Xist) gene, which is known now to represent the master switch locus regulating X inactivation', 'IST, a long non-coding RNA, plays an important role in triggering X chromosome inactivation in eutherians', 'X inactive-specific transcript (XIST) gene in humans', 'Xist (X-inactive specific transcript) is a major effector of the X-inactivation process', 'efforts have been focused on the X inactive-specific transcript (Xist) locus, discovered to be the master regulator of X-inactivation', 'X-inactivation specific transcript (Xist) RNA', 'transcriptional silencing of one of the female X-chromosomes is a finely regulated process that requires accumulation in cis of the long non-coding RNA X-inactive-specific transcript (Xist)', 'the X-inactivated-specific transcript (Xist) gene, whose gene product consists of RNA which coats and thereby inactivates one of the X chromosomes', 'the X inactivation center (Xic). Xic contains many of the regulatory elements for the mutual interplay of X-inactive specific transcript (Xist', 'chromosome inactivation (XCI) in female mammals depends on the noncoding RNA X inactivation specific transcript (Xist)', ' One of the striking features that characterize the Xic landscape is the abundance of loci transcribing non-coding RNAs (ncRNAs), including Xist, the master regulator of the inactivation process', 'The process is mediated by the non-coding RNA X inactive specific transcript (Xist) that binds in cis and propagates along the inactive X chromosome elect, triggering chromosome-wide silencing', 'the X chromosome of paternal origin (Xp) is silenced during early embryogenesis owing to imprinted expression of the regulatory RNA, Xist (X-inactive specific transcript)', 'X-inactive-specific transcript (Xist) gene ', 'expression of the non-coding X-inactive specific transcript (Xist) RNA and depends on specific cellular contexts, in which essential silencing factors are expressed', 'Xist (X-inactive specific transcript) and Tsix gene pair, which is pivotal in X-inactivation.', 'In eutherian mammals X inactivation is regulated by the X-inactive specific transcript (Xist), a cis-acting non-coding RNA that triggers silencing of the chromosome from which it is transcribed', ' inactivation in female mammals involves transcriptional silencing of an entire chromosome in response to a cis-acting noncoding RNA, the X inactive-specific transcript (Xist)', 'chromosome inactivation (XCI) depends on a noncoding sense-antisense transcript pair, Xist', ' The key regulatory molecule that triggers silencing is the Xist transcrip', 'chromosome inactivation begins when a novel chromosomal RNA (cRNA) from the imprinted mouse Xist or human XIST locus coats or "paints" one X chromosome in cis and initiates a cascade of chromosome remodeling events', 'X-inactive-specific transcript (Xist) locus is a cis-acting switch that regulates X chromosome inactivation in mammals', ' In X chromosome inactivation (XCI), unfavorable XCI ratios promote X-linked disease penetrance in females. During XCI, one X is randomly silenced by Xist', ' imprinted mouse Xist (X-inactive specific transcript) gene is involved in the initiation of X-chromosome inactivation', 'initiation of X-chromosome inactivation are critically dependent on the expression of the X-inactive specific transcript (Xist)', 'X chromosome inactivation requires the presence, in cis, of the X inactivation center (XIC). The Xist gene, which lies within the XIC region in both human and mouse', 'inactive-specific transcript (Xist', ' X inactive-specific transcript (Xist) is thought to be essential for the initiation of X chromosome inactivation and dosage compensation during female embryo development', 'deletions of the X inactivation center (XIC/Xic) and/or the X inactive specific transcript (XIST/Xist) gene result in failure of cis X-inactivation', 'Xist (X inactive specific transcript) gene plays an essential role in X chromosome inactivation.', 'expression of the Xist (X inactive specific transcript) gene correlates with X inactivation ', 'XIST (X inactive specific transcript) gene ', 'one of the two X chromosomes in somatic cells of the female becomes inactivated through a process that is thought to depend on a unique initiator region, the X-chromosome inactivation center (Xic). The recently characterized Xist sequence (X-inactive-specific transcript) is thought to be a possible candidate for Xic', 'human XIST gene, a candidate for a role in X chromosome inactivation,']

['The long non- coding RNA Xist (X inactive specific transcript)']

['Xist']

Which cellular processes are regulated by Nanog?

['critical for the regulation of cancer stem cells.', 'the effect of FAK and Nanog cross-regulation on cancer cell morphology, invasion, and growth that plays a significant role in carcinogenesis', 'Nanog-like regulates endoderm formation', 'In mammalian embryonic stem cells, the acquisition of pluripotency is dependent on Nanog', 'we identified a zebrafish Nanog ortholog and found that its\xa0knockdown impaired endoderm formation', 'establishes a role for Nanog-like in regulating the formation of the extraembryonic tissue required for endoderm induction', 'Nanog regulates molecules involved in stemness and cell cycle-signaling pathway for maintenance of pluripotency', 'Nanog, a key transcription factor in the maintenance of pluripotency of embryonic stem (ES) and embryonal carcinoma (EC) cells', 'Nanog, a positive regulator of ESC proliferation and G1/S transition', 'Nanog is a stem cell transcription factor required for self-renewal and for maintaining pluripotency', 'NANOG regulates glioma stem cells', 'We find that NANOG modulates gliomasphere clonogenicity, CD133(+) stem cell cell behavior and proliferation', 'NANOG is essential for GBM tumourigenicity', 'Nanog regulates primordial germ cell migration', 'Nanog mediates PGC migration by regulating Cxcr4b expression', 'Nanog regulates proliferation during early fish development.', 'Nanog is necessary for S-phase transition and proliferation in the developing embryo', 'our results demonstrate that NANOG, a cell-fate regulatory molecule known to be important for ESC self-renewal, also plays a novel role in tumor development', 'the self-renewal gene NANOG regulates human tumor development', 'The emerging picture is one in which Oct4 and Nanog control a cascade of pathways that are intricately connected to govern pluripotency, self-renewal, genome surveillance and cell fate determination', 'the pluripotency sustaining factor nanog']

['The pluripotency sustaining factor Nanog, controls a cascade of pathways that are intricately connected to govern pluripotency, self-renewal, genome surveillance and cell fate determination. Elevated expression of Nanog has also been reported to result in clonal expansion of murine ESCs, but it also plays a role in tumor development. A positive regulator of cell proliferation, it is essential for G1 to S transition in human embryonic stem cells while it regulates primordial germ cell migration.']

['cell proliferation', 'pluripotency', 'cell fate determination', 'G1 to S transition', 'germ cell migration', 'tumour development']

Which protein is associated with hyperemesis gravidarum during pregrancy?

['Maternal smoking, BMI, parity, ethnicity, fetal gender, placental weight and hyperemesis gravidarum symptoms were associated with total hCG. ', 'First trimester maternal serum PAPP-A and free β-HCG levels in hyperemesis gravidarum.', 'HG is associated with elevated levels of PAPP-A and free β-hCG, and such changes are independent of serum indicators of thyroid and liver function.', "hCG promotes progesterone production by corpus luteal cells; promotes angiogenesis in uterine vasculature; promoted the fusion of cytotrophoblast cell and differentiation to make syncytiotrophoblast cells; causes the blockage of any immune or macrophage action by mother on foreign invading placental cells; causes uterine growth parallel to fetal growth; suppresses any myometrial contractions during the course of pregnancy; causes growth and differentiation of the umbilical cord; signals the endometrium about forthcoming implantation; acts on receptor in mother's brain causing hyperemesis gravidarum, and seemingly promotes growth of fetal organs during pregnancy. "]

['Human chorionic gonadotropin (hCG) is associated with hyperemesis gravidarum during pregrancy.']

['Human chorionic gonadotropin', 'hCG']

Which viruses are best known to cause myocarditis?

['Enteroviruses (EV) are an important cause of neonatal disease including hepatitis, meningoencephalitis, and myocarditis that can lead to death or severe long-term sequelae', 'Enteroviruses have been considered to be the most common cause of acute myocarditis and possible consequence of dilated cardiomyopathy.', 'n our study the adenovirus genome was found to be the most frequent virus genome in explanted heart tissues.', 'Coxsackie B viruses (types 1 to 5) are the most frequent reported cause of acute viral myocarditis.']

['The most frequent viruses causing myocarditis are Enterovirus, Adenovirus and Coxsackie B viruses.']

['Enterovirus', 'Adenovirus', 'Coxsackie B virus']

Which diseases are involved in the severe cutaneous reactions (SCAR) spectrum?

['Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are diseases within the spectrum of severe cutaneous adverse reactions affecting skin and mucous membranes. ', 'Toxic epidermal necrolysis (TEN) and Stevens Johnson Syndrome (SJS) are severe adverse cutaneous drug reactions that predominantly involve the skin and mucous membranes.', 'Currently, TEN and SJS are considered to be two ends of a spectrum of severe epidermolytic adverse cutaneous drug reactions, differing only by their extent of skin detachment. ', 'Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are considered part of a spectrum of adverse cutaneous drug reactions showing severe and extensive skin detachment.', 'Our aim was to study patch testing in severe cutaneous adverse drug reactions (ADRs) (Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis (AGEP), and other cutaneous ADRs)', 'However, allopurinol is also one of the most common causes of severe cutaneous adverse reactions (SCARs), which include drug hypersensitivity syndrome, Stevens–Johnson syndrome, and toxic epidermal necrolysis.', 'Drug eruptions range from transient erythema to the life threatening severe cutaneous adverse reactions (SCAR) that encompass Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms complex (DRESS).To study the clinical and epidemiological aspects of cutaneous adverse drug reactions (CADR).Ethical clearance was obtained from the institutional ethics committee', 'Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) are severe cutaneous adverse reactions (SCAR) which are majorly caused by drugs', 'This study investigated the association between the HLA class I genotype and carbamazepine-induced severe cutaneous adverse reaction (SCAR) in Koreans.Twenty-four patients who had developed carbamazepine-induced SCAR (7 Stevens-Johnson syndrome (SJS), 17 drug hypersensitivity syndrome (HSS)), 50 carbamazepine-tolerant controls from the Korean Pharmacogenetic Adverse Drug Reaction Research Network and data of 485 Korean general population from a previously published study were recruited', 'Severe cutaneous adverse reactions (SCARs) include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS)', 'Severe Cutaneous Adverse Reaction (SCAR) represents the spectrum of adverse drug reactions from erythema multiforme, Stevens - Johnson syndrome (SJS) to Toxic Epidermal Necrolysis (TEN). ', 'Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are uncommon but extremely serious and often life-threatening mucocutaneous reactions characterized by extensive epithelial sloughing and systemic symptoms. There is no effective evidence-based treatment for severe cutaneous adverse reactions (SCAR) to drugs and no consensus on how to treat these patients.', 'However, allopurinol is also one of the most common causes of severe cutaneous adverse reactions (SCARs), which include drug hypersensitivity syndrome, Stevens–Johnson syndrome, and toxic epidermal necrolysis. A variant allele of the human leukocyte antigen (HLA)-B, HLA-B*58:01, associates strongly with allopurinolinduced SCAR.', 'The skin is often involved in ADRs and although most cutaneous ADRs have a favorable course, they may present as severe adverse cutaneous drug reactions (SCARs), such as Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (also referred to as drug-induced hypersensitivity syndrome), and acute generalized exanthematous pustulosis.', 'By comparison, Stevens-Johnson syndrome (SJS) is a life-threatening severe cutaneous adverse reaction (SCAR), mainly caused by drugs.', "The study sought to identify the magnitude and characteristic of severe cutaneous adverse reactions (SCAR's) like Steven-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN).", 'Allopurinol, an antihyperuricaemic agent, is one of the common causes of life-threatening severe cutaneous adverse reactions (SCAR), including drug rash with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN).']

['The diseases that are involved in the severe cutaneous reactions (SCAR) spectrum are:\n1) Stevens-Johnson syndrome (SJS)\n2) Toxic epidermal necrolysis (TEN)\n3) Acute generalized exanthematous pustulosis (AGEP).']

['Stevens-Johnson syndrome', 'SJS', 'Toxic epidermal necrolysis', 'TEN', 'Acute generalized exanthematous pustulosis', 'AGEP']

Which variables are included in the SPAN-100 score?

['Furthermore, MR-proADM levels significantly improved reclassification of patients in the prediction of outcome by the Stroke Prognostication using Age and NIHSS-100 (SPAN-100; NRI\u200a=\u200a0.175; p\u200a=\u200a0.04). ', 'Stroke Prognostication using Age and NIH Stroke Scale: SPAN-100.', 'METHODS: We created the Stroke Prognostication using Age and NIH Stroke Scale (SPAN) index by combining age in years plus NIH Stroke Scale (NIHSS) ≥100. ', 'The SPAN-100 index is considered positive if the sum of the age and the NIH Stroke Scale (a 15-item neurological examination scale with scores ranging from 0 to 42, with higher scores indicating more severe strokes) score is greater than or equal to 100', 'The Stroke Prognostication using Age and the NIH Stroke Scale index, created by combining age in years plus a National Institutes of Health (NIH) Stroke Scale score of 100 or higher (and hereafter referred to as the SPAN-100 index), is a simple risk score for estimating clinical outcomes for patients with acute ischemic stroke (AIS)']

["SPAN-100 score includes patient's age and NIH Stroke Scale score. SPAN-100 is used for prognostication of stroke patients."]

['Age', 'NIH Stroke Scale score']

List the main proteases used for sample digestion in proteomics.

['the consecutive use of endoproteinases LysC and trypsin', ' Asp-N to trypsin ', ' tryptic digestion', 'tryptic digest', 'enzymatic digestion is most commonly performed using trypsin', 'chymotrypsin/trypsin digestion', "In this method, chymotrypsin, single or in combination with trypsin, was used, which enabled to obtain proteolytic peptides from the hydrophobic regions and to identify new oil bodies' proteins.", 'proteins were digested by thermolysin', 'tryptic digestion', 'protein digestion by trypsin', 'Trypsin is an endoprotease commonly used for sample preparation in proteomics experiments', 'tryptic digestion ', 'direct tryptic digestion', ' trypsin digestion', 'Tryptic digestion is an important component of most proteomics experiments', 'We evaluated nine trypsin-based digestion protocols, based on standard in-solution or on spin filter-aided digestion', 'Getting intimate with trypsin, the leading protease in proteomics.', 'sample preparation via trypsin digestion', ' in-gel digested with trypsin, chymotrypsin, Asp-N, or trypsin plus Asp-N in triplicate. ', 'In this study, we examined the use of multiple proteases (trypsin, LysC, tandem LysC/trypsin) on both protein identification and quantification ', 'digested with LysC and trypsin, ', 'In-gel trypsin digestion', 'Magnetic bead cellulose activated with divinyl sulfone was used for the immobilization of Staphylococcus aureus endoproteinase Glu-C (EC 3.4.21.19).', 'protease digestion with AspN or trypsin']

['Trypsin is the main protease used in proteomics followed by Asp-N, chymotrypsin, LysC, GluC and thermolysin.']

['trypsin', 'Asp-N', 'chymotrypsin', 'LysC', 'Glu-C', 'thermolysin']

What was the purpose of the FANTOM5 project?

['The FANTOM5 and ENCODE projects represent two independent large scale efforts to map regulatory and transcriptional features to the human genome.', 'The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research', 'The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.', 'The online FANTOM5 enhancer atlas represents a unique resource for studies on cell-type-specific enhancers and gene regulation.', 'The FANTOM5 and ENCODE projects represent two independent large scale efforts to map regulatory and transcriptional features to the human genome.', 'The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.', 'The FANTOM5 and ENCODE projects represent two independent large scale efforts to map regulatory and transcriptional features to the human genome. ', 'The online FANTOM5 enhancer atlas represents a unique resource for studies on cell-type-specific enhancers and gene regulation.', 'Here we use the FANTOM5 panel of samples, covering the majority of human tissues and cell types, to produce an atlas of active, in vivo-transcribed enhancers. ', 'The FANTOM5 and ENCODE projects represent two independent large scale efforts to map regulatory and transcriptional features to the human genome. Here we investigate chromatin features around a comprehensive set of transcription start sites in four cell lines by integrating data from these two projects. ', 'The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.', 'The FANTOM5 and ENCODE projects represent two independent large scale efforts to map regulatory and transcriptional features to the human genome.']

['The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research. The FANTOM5 and ENCODE projects represent two independent large scale efforts to map regulatory and transcriptional features to the human genome.']

['To provide comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.']

Which is the E3 ubiquitin ligase which ubiquitinates IkB leading to its proteasomal degradation?

['IKK activation and IκB degradation involve different ubiquitination modes; the latter is mediated by a specific E3 ubiquitin ligase SCF(β-TrCP) . The F-box component of this E3, β-TrCP, recognizes the IκB degron formed following phosphorylation by IKK and thus couples IκB phosphorylation to ubiquitination. SCF(β-TrCP) -mediated IκB ubiquitination and degradation is a very efficient process, often resulting in complete degradation of the key inhibitor IκBα within a few minutes of cell stimulation. In vivo ablation of β-TrCP results in accumulation of all the IκBs and complete NF-κB inhibition. ', 'Sequence comparison analysis showed sequence motif identity between CLU and beta-transducin repeat-containing protein (beta-TrCP), a main E3 ubiquitin ligase involved in IkappaB-alpha degradation.', 'IkappaB degradation is dependent upon its phosphorylation by the IkappaB kinase (IKK) complex and subsequent ubiquitination facilitated by beta-Trcp E3 ubiquitin ligase.', 'Here we show that beta-catenin stabilizes the mRNA encoding the F-box protein betaTrCP1, and identify the RNA-binding protein CRD-BP (coding region determinant-binding protein) as a previously unknown target of beta-catenin/Tcf transcription factor. CRD-BP binds to the coding region of betaTrCP1 mRNA. Overexpression of CRD-BP stabilizes betaTrCP1 mRNA and elevates betaTrCP1 levels (both in cells and in vivo), resulting in the activation of the Skp1-Cullin1-F-box protein (SCF)(betaTrCP) E3 ubiquitin ligase and in accelerated turnover of its substrates including IkappaB and beta-catenin.', ' The multisubunit IkappaB kinase (IKK) responsible for inducible IkappaB phosphorylation is the point of convergence for most NF-kappaB-activating stimuli. IKK contains two catalytic subunits, IKKalpha and IKKbeta, both of which are able to correctly phosphorylate IkappaB. Gene knockout studies have shed light on the very different physiological functions of IKKalpha and IKKbeta. After phosphorylation, the IKK phosphoacceptor sites on IkappaB serve as an essential part of a specific recognition site for E3RS(IkappaB/beta-TrCP), an SCF-type E3 ubiquitin ligase, thereby explaining how IKK controls IkappaB ubiquitination and degradation. ']

['IκB degradation involves ubiquitination mediated by a specific E3 ubiquitin ligase SCF(β-TrCP). SCF(β-TrCP) -mediated IκB ubiquitination and degradation is a very efficient process, often resulting in complete degradation of the key inhibitor IκBα within a few minutes of cell stimulation.', 'IkappaB degradation is dependent upon its phosphorylation by the IkappaB kinase (IKK) complex and subsequent ubiquitination facilitated by beta-Trcp E3 ubiquitin ligase.Sequence comparison analysis showed sequence motif identity between CLU and beta-transducin repeat-containing protein (beta-TrCP), a main E3 ubiquitin ligase involved in IkappaB-alpha degradation.', 'IkappaB degradation is dependent upon its phosphorylation by the IkappaB kinase (IKK) complex and subsequent ubiquitination facilitated by beta-Trcp E3 ubiquitin ligase. SCF(β-TrCP) -mediated IκB ubiquitination and degradation is a very efficient process, often resulting in complete degradation of the key inhibitor IκBα within a few minutes of cell stimulation.']

['SCF(β-TrCP)', 'SCF beta-transducin repeat-containing protein (beta-TrCP)', 'beta-Trcp']