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What is Snord116?

['Further analysis with array-CGH identified a mosaic 847\u2009kb deletion in 15q11-q13, including SNURF-SNRPN, the snoRNA gene clusters SNORD116 (HBII-85), SNORD115, (HBII-52), SNORD109 A and B (HBII-438A and B), SNORD64 (HBII-13), and NPAP1 (C15ORF2).', 'All three deletions included SNORD116, but only two encompassed parts of SNURF-SNRPN, implicating SNORD116 as the major contributor to the Prader-Willi phenotype. Our case adds further information about genotype-phenotype correlation and supports the hypothesis that SNORD116 plays a major role in the pathogenesis of Prader-Willi syndrome.', 'Whereas loss of function of the SNORD116 genes appears to be responsible for the major features of PWS, the role of the other genes is less clear. ', 'Small nucleolar (sno) RNAs are a group of small RNAs located in nucleoli that modulate chemical modifications and maturation of ribosomal or other RNAs. Recent data suggest that snoRNA Snord116 is important for the pathogenesis of Prader-Willi syndrome (PWS) characterized by hyperphagia and obesity. The current study was conducted to assess a potential cellular link between Snord116 and phenotypes of PWS. Data from mice revealed Snord116 expression in the medial hypothalamus, particularly within nuclei that are part of feeding circuitry. High expression of Snord116 was evident in the paraventricular (PVN) and ventromedial (VMH) nuclei, but particularly prevalent in the arcuate nucleus (ARC) according to in situ hybridization. Snord116 expression level in ventral hypothalamic dissections including ARC was significantly greater (by 2-fold) than that in cortex; and its expression level in dorsal hypothalamic dissections including PVN was double that in cortex. The enhanced expression pattern of Snord116 in hypothalamic nuclei was observed at weaning and young adult stages, but less obvious neonatally when expression was significantly more widespread. Therefore the expression of Snord116 likely is regulated developmentally', 'The imprinted Snurf-Snrpn chromosomal domain contains two large arrays of tandemly repeated, paternally expressed box C/D small-nucleolar RNA (snoRNA) genes: the SNORD115 (H/MBII-52) and SNORD116 (H/MBII-85) gene clusters believed to play key roles in the fine-tuning of serotonin receptor (5-HT2C) pre-mRNA processing and in the etiology of the Prader-Willi Syndrome (PWS), respectively.', 'We demonstrate that the mouse C/D box snoRNA MBII-85 (SNORD116) is processed into at least five shorter RNAs using processing sites near known functional elements of C/D box snoRNAs.', 'Although the SNORD116 gene cluster has become a prime candidate for PWS, it cannot be excluded that other paternally expressed genes in the chromosomal region 15q11q13 contribute to the full phenotype.', 'In addition, recently published data provide strong evidence in support of a role for the snoRNA SNORD116 cluster (HBII-85) in PWS etiology', ' Identification and characterization of this case provide unequivocal evidence for a critical role for the SNORD116 snoRNA molecules in PWS pathogenesis. ', 'Our previous translocation studies predicted a major role for the C/D box small nucleolar RNA cluster SNORD116 (PWCR1/HBII-85) in PWS. ', 'Snord116del mice with paternally derived deletion lack expression of this snoRNA. They have early-onset postnatal growth deficiency, but normal fertility and lifespan. While pituitary structure and somatotrophs are normal, liver Igf1 mRNA is decreased. In cognitive and behavior tests, Snord116del mice are deficient in motor learning and have increased anxiety. Around three months of age, they develop hyperphagia, but stay lean on regular and high-fat diet. On reduced caloric intake, Snord116del mice maintain their weight better than wild-type littermates, excluding increased energy requirement as a cause of hyperphagia. Normal compensatory feeding after fasting, and ability to maintain body temperature in the cold indicate normal energy homeostasis regulation. Metabolic chamber studies reveal that Snord116del mice maintain energy homeostasis by altered fuel usage. Prolonged mealtime and increased circulating ghrelin indicate a defect in meal termination mechanism. Snord116del mice, the first snoRNA deletion animal model, reveal a novel role for a non-coding RNA in growth and feeding regulation.']

['SNORD116 is a small nucleolar (sno) RNA gene cluster (HBII-85) implicated as a major contributor the Prader-Willi phenotype. \nSNORD116 genes appears to be responsible for the major features of PWS. \nSNORD116 is a paternally expressed box C/D snoRNA gene cluster.\nThe mouse C/D box snoRNA MBII-85 (SNORD116) is processed into at least five shorter RNAs using processing sites near known functional elements of C/D box snoRNAs.\nSnord116 expression in the medial hypothalamus, particularly within nuclei that are part of feeding circuitry. High expression of Snord116 was evident in the paraventricular (PVN) and ventromedial (VMH) nuclei, but particularly prevalent in the arcuate nucleus (ARC) according to in situ hybridization. Snord116 expression level in ventral hypothalamic dissections including ARC was significantly greater (by 2-fold) than that in cortex; and its expression level in dorsal hypothalamic dissections including PVN was double that in cortex. The enhanced expression pattern of Snord116 in hypothalamic nuclei was observed at weaning and young adult stages, but less obvious neonatally when expression was significantly more widespread. Therefore the expression of Snord116 likely is regulated developmentally.\nSnord116del mice with paternally derived deletion lack expression of this snoRNA. They have early-onset postnatal growth deficiency, but normal fertility and lifespan. While pituitary structure and somatotrophs are normal, liver Igf1 mRNA is decreased. In cognitive and behavior tests, Snord116del mice are deficient in motor learning and have increased anxiety. Around three months of age, they develop hyperphagia, but stay lean on regular and high-fat diet. On reduced caloric intake, Snord116del mice maintain their weight better than wild-type littermates, excluding increased energy requirement as a cause of hyperphagia. Normal compensatory feeding after fasting, and ability to maintain body temperature in the cold indicate normal energy homeostasis regulation. Metabolic chamber studies reveal that Snord116del mice maintain energy homeostasis by altered fuel usage. Prolonged mealtime and increased circulating ghrelin indicate a defect in meal termination mechanism. Snord116del mice, the first snoRNA deletion animal model, reveal a novel role for a non-coding RNA in growth and feeding regulation.']

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Are ultraconserved elements often transcribed?

['Starting from a genome-wide expression profiling, we demonstrate for the first time a functional link between oxygen deprivation and the modulation of long noncoding transcripts from ultraconserved regions, termed transcribed-ultraconserved regions (T-UCRs)', 'Our data gives a first glimpse of a novel functional hypoxic network comprising protein-coding transcripts and noncoding RNAs (ncRNAs) from the T-UCRs category', 'Highly conserved elements discovered in vertebrates are present in non-syntenic loci of tunicates, act as enhancers and can be transcribed during development', "The majority of these regions map onto ultraconserved elements and we demonstrate that they can act as functional enhancers within the organism of origin, as well as in cross-transgenesis experiments, and that they are transcribed in extant species of Olfactores. We refer to the elements as 'Olfactores conserved non-coding elements'", 'We used a custom microarray to assess the levels of UCE transcription during mouse development and integrated these data with published microarray and next-generation sequencing datasets as well as with newly produced PCR validation experiments. We show that a large fraction of non-exonic UCEs is transcribed across all developmental stages examined from only one DNA strand. Although the nature of these transcripts remains a mistery, our meta-analysis of RNA-Seq datasets indicates that they are unlikely to be short RNAs and that some of them might encode nuclear transcripts', 'Our data shows that the concurrent presence of enhancer and transcript function in non-exonic UCE elements is more widespread than previously shown. Moreover through our own experiments as well as the use of next-generation sequencing datasets, we were able to show that the RNAs encoded by non-exonic UCEs are likely to be long RNAs transcribed from only one DNA strand', 'Short ultraconserved promoter regions delineate a class of preferentially expressed alternatively spliced transcripts', 'The importance of other classes of non-coding RNAs, such as long intergenic ncRNAs (lincRNAs) and transcribed ultraconserved regions (T-UCRs) as altered elements in neoplasia, is also gaining recognition.', 'Other ncRNAs, such as PIWI-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), transcribed ultraconserved regions (T-UCRs) and large intergenic non-coding RNAs (lincRNAs) are emerging as key elements of cellular homeostasis.', 'The majority of these regions map onto ultraconserved elements and we demonstrate that they can act as functional enhancers within the organism of origin, as well as in cross-transgenesis experiments, and that they are transcribed in extant species of Olfactores.', 'Transcribed ultraconserved regions (T-UCRs) are a subset of 481 sequences longer than 200 bp, which are absolutely conserved between orthologous regions of human, rat and mouse genomes, and are actively transcribed.', 'Highly conserved elements discovered in vertebrates are present in non-syntenic loci of tunicates, act as enhancers and can be transcribed during development.', 'The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator.', 'In this report, we show that the Dlx-5/6 ultraconserved region is transcribed to generate an alternatively spliced form of Evf-1, the ncRNA Evf-2.', 'These studies identify a critical role for TUC338 in regulation of transformed cell growth and of transcribed ultraconserved ncRNA as a unique class of genes involved in the pathobiology of HCC.', 'Transcribed ultraconserved region (T-UCR) transcripts are a novel class of lncRNAs transcribed from ultraconserved regions (UCRs)', 'The majority of these regions map onto ultraconserved elements and we demonstrate that they can act as functional enhancers within the organism of origin, as well as in cross-transgenesis experiments, and that they are transcribed in extant species of Olfactores', 'Transcribed ultraconserved regions (T-UCRs) are a subset of 481 sequences longer than 200 bp, which are absolutely conserved between orthologous regions of human, rat and mouse genomes, and are actively transcribed', 'Other ncRNAs, such as PIWI-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), transcribed ultraconserved regions (T-UCRs) and large intergenic non-coding RNAs (lincRNAs) are emerging as key elements of cellular homeostasis', 'Transcribed ultraconserved region in human cancers.', 'We show that a large fraction of non-exonic UCEs is transcribed across all developmental stages examined from only one DNA strand', 'Although uc.338 is partially located within the poly(rC) binding protein 2 (PCBP2) gene, the transcribed ncRNA encoding uc.338 is expressed independently of PCBP2 and was cloned as a 590-bp RNA gene, termed TUC338', 'Moreover through our own experiments as well as the use of next-generation sequencing datasets, we were able to show that the RNAs encoded by non-exonic UCEs are likely to be long RNAs transcribed from only one DNA strand.']

['Yes. Especially, a large fraction of non-exonic UCEs is transcribed across all developmental stages examined from only one DNA strand.']

['yes']

List metalloenzyme inhibitors.

[' Clinically approved inhibitors were selected as well as several other reported metalloprotein inhibitors in order to represent a broad range of metal binding groups (MBGs), including hydroxamic acid, carboxylate, hydroxypyridinonate, thiol, and N-hydroxyurea functional groups.', 'A total of 21 different raltegravir-chelator derivative (RCD) compounds were prepared that differed only in the nature of the MBG. ', 'At least two compounds (RCD-4, RCD-5) containing a hydroxypyrone MBG were found to display superior strand-transfer inhibition when compared to an abbreviated analogue of raltegravir (RCD-1). ', 'By screening a library of metalloenzyme inhibitors, the N-formyl-hydroxylamine derivative BB-3497 was identified as a potent inhibitor of Escherichia coli peptide deformylase with antibacterial activity both in vitro and in vivo.', ' The 8-hydroxyquinoline represents a promising new chelator scaffold for the development of MMP inhibitors that was discovered by use of a metalloprotein-focused chelator fragment library.', ' the metalloenzyme inhibitors VT-1129 and VT-1161 (both Viamet Pharmaceuticals)', 'Based on their ability to chelate metals, hydroxamate molecules and siderophores have been successfully used as metalloenzyme inhibitors.', " Using this model, we identified two nitrogen donor compounds--2,2'-dipyridylamine (DPA) and triazacyclononane (TACN)--as the most selective ZBGs for zinc metalloenzyme inhibitor development. ", 'Foscarnet (phosphonoformate trisodium salt), an antiviral used for the treatment of HIV and herpes virus infections, also acts as an activator or inhibitor of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1)']

['Foscarnet\nVT-1129\nVT-1161 \nBB-3497\nhydroxamate molecules\nsiderophores']

['VT-1129', 'VT-1161', 'BB-3497', 'hydroxamate molecules', 'siderophores', 'Foscarnet']

Which protein phosphatase has been found to interact with the heat shock protein, HSP20?

[' Moreover, protein phosphatase-1 activity is regulated by two binding partners, inhibitor-1 and the small heat shock protein 20, Hsp20. Indeed, human genetic variants of inhibitor-1 (G147D) or Hsp20 (P20L) result in reduced binding and inhibition of protein phosphatase-1, suggesting aberrant enzymatic regulation in human carriers. ', 'Small heat shock protein 20 interacts with protein phosphatase-1 and enhances sarcoplasmic reticulum calcium cycling.', ' Hsp20 overexpression in intact animals resulted in significant enhancement of cardiac function, coupled with augmented Ca cycling and sarcoplasmic reticulum Ca load in isolated cardiomyocytes. This was associated with specific increases in phosphorylation of phospholamban (PLN) at both Ser16 and Thr17, relieving its inhibition of the apparent Ca affinity of SERCA2a. Accordingly, the inotropic effects of Hsp20 were abrogated in cardiomyocytes expressing nonphosphorylatable PLN (S16A/T17A). Interestingly, the activity of type 1 protein phosphatase (PP1), a known regulator of PLN signaling, was significantly reduced by Hsp20 overexpression, suggesting that the Hsp20 stimulatory effects are partially mediated through the PP1-PLN axis. This hypothesis was supported by cell fractionation, coimmunoprecipitation, and coimmunolocalization studies, which revealed an association between Hsp20, PP1, and PLN.', 'Hsp20 is a novel regulator of sarcoplasmic reticulum Ca cycling by targeting the PP1-PLN axis. These findings, coupled with the well-recognized cardioprotective role of Hsp20, suggest a dual benefit of targeting Hsp20 in heart disease.', 'Moreover, protein phosphatase-1 activity is regulated by two binding partners, inhibitor-1 and the small heat shock protein 20, Hsp20.', 'Moreover, protein phosphatase-1 activity is regulated by two binding partners, inhibitor-1 and the small heat shock protein 20, Hsp20']

['Protein phosphatase-1 activity is regulated by two binding partners, inhibitor-1 and the small heat shock protein 20, Hsp20. Cell fractionation, coimmunoprecipitation, and coimmunolocalization studies, revealed an association between Hsp20 and PP1. Small heat shock protein 20 interacts with protein phosphatase-1 and enhances sarcoplasmic reticulum calcium cycling.', 'Moreover, protein phosphatase-1 activity is regulated by two binding partners, inhibitor-1 and the small heat shock protein 20, Hsp20. Small heat shock protein 20 interacts with protein phosphatase-1 and enhances sarcoplasmic reticulum calcium cycling.']

['Protein phosphatase 1', 'PP1']

Do DNA double-strand breaks play a causal role in carcinogenesis?

['The DNA non-homologous end-joining repair gene XRCC6/Ku70 plays an important role in the repair of DNA double-strand breaks (DSBs) induced by both exogenous and endogenous DNA-damaging agents. Defects in overall DSB repair capacity can lead to genomic instability and carcinogenesis.', 'The tumor suppressor breast cancer susceptibility protein 1 (BRCA1) protects our cells from genomic instability in part by facilitating the efficient repair of DNA double-strand breaks (DSBs). BRCA1 promotes the error-free repair of DSBs through homologous recombination and is also implicated in the regulation of nonhomologous end joining (NHEJ) repair fidelity.', 'The increased frequency of DSB mutagenesis and MMEJ repair in the absence of BRCA1 suggests a potential mechanism for carcinogenesis.', 'Comet assay under neutral conditions allows detection of DNA double-strand breaks (DSBs), which has consequence to genome instability and carcinogenesis.', 'Loss of p15/Ink4b accompanies tumorigenesis triggered by complex DNA double-strand breaks.', 'Although DSBs are potentially carcinogenic, it is not clear whether complex DSBs that are refractory to repair are more potently tumorigenic compared with simple breaks that can be rapidly repaired, correctly or incorrectly, by mammalian cells.', 'Zinc chromate induces chromosome instability and DNA double strand breaks in human lung cells.', 'Our study shows that zinc chromate induced concentration-dependent increases in cytotoxicity, chromosome damage and DNA double strand breaks in human lung cells.', 'Foci formation of P53-binding protein 1 in thyroid tumors: activation of genomic instability during thyroid carcinogenesis.', "Nitric oxide and acid induce double-strand DNA breaks in Barrett's esophagus carcinogenesis via distinct mechanisms.", 'DNA double-strand break repair capacity and risk of breast cancer.', 'A tumorigenic role of the non-homologous end-joining (NHEJ) pathway for the repair of DNA double-strand breaks (DSBs) has been suggested by our finding of a significant association between increased breast cancer risk and a cooperative effect of single-nucleotide polymorphisms in NHEJ genes.', 'Carcinogen-induced DNA double strand break repair in sporadic breast cancer.', 'Induction of DNA double strand breaks and alterations in the repair of these breaks is implicated in breast carcinogenesis. Prior studies have demonstrated that peripheral blood mononuclear cells (PBMC) from breast cancer patients exhibit increased numbers of DNA strand breaks after exposure to ionizing radiation, but these studies did not specifically measure DNA double strand breaks and it is not known whether chemical carcinogens produce similar effects.', 'Abnormal DNA end-joining activity in human head and neck cancer.', 'In human cells, DNA double-strand breaks (DSBs) are repaired primarily by the DNA end-joining (EJ) process and thus, abnormal DNA EJ activities lead to an accumulation of mutations and/or aneuploidy, resulting in genetic instability of cells. Since genetic instability is the hallmark of cancer cells, we studied the DNA EJ activities of normal, non-malignant immortalized and malignant human epithelial cells to investigate the association between DNA EJ and carcinogenesis.', 'Homologous recombination repair plays an important role in DSB repair and impairment of this repair mechanism may lead to loss of genomic integrity, which is one of the hallmarks of cancer. Recent research has shown that the tumor suppressor genes p53 and BRCA1 and -2 are involved in the proper control of homologous recombination, suggesting a role of this type of repair in human cancer.', 'In order to study the role of DNA damage processing in the development of cutaneous squamous cell carcinoma (SCC), we assessed the ability of six keratinocyte cell lines from a multistage-tumor progression model to repair three types of DNA damage: pyrimidine dimers, oxidative DNA lesions and DNA double strand breaks (DSB).', 'However, an acquired deficiency in repairing DNA double strand breaks can be one mechanism promoting progression towards malignancy, possibly through impairing chromosomal stability.', 'Recent findings demonstrate that accelerated carcinogenesis following liver regeneration is associated with chronic inflammation-induced double-strand DNA breaks in cells, which escaped apoptosis due to proliferative stress.', 'Although DNA double-strand breaks and apoptosis may relate to arsenite-induced damage and carcinogenesis, the mechanism of action remains obscure.']

['Yes. It has been demonstrated that induction of DNA double-strand breaks (DSBs) and defects in overall DSBs repair capacity can lead to an accumulation of mutations, resulting in genomic instability of cells. Given that genomic instability is the hallmark of cancer, DSBs play a causal role in carcinogenesis.']

['yes']

Which factor interacts with Treslin/TICRR throughout the cell cycle of human cells?

["We identified MDM two binding protein (MTBP) as a factor that interacts with Treslin/TICRR throughout the cell cycle. We show that MTBP depletion by means of small interfering RNA inhibits DNA replication by preventing assembly of the CMG (Cdc45-MCM-GINS) holohelicase during origin firing. Although MTBP has been implicated in the function of the p53 tumor suppressor, we found MTBP is required for DNA replication irrespective of a cell's p53 status. We propose that MTBP acts with Treslin/TICRR to integrate signals from cell cycle and DNA damage response pathways to control the initiation of DNA replication in human cells.", 'We identified MDM two binding protein (MTBP) as a factor that interacts with Treslin/TICRR throughout the cell cycle', 'Treslin/TICRR (TopBP1-interacting, replication stimulating protein/TopBP1-interacting, checkpoint, and replication regulator), the human ortholog of the yeast Sld3 protein, is an essential DNA replication factor that is regulated by cyclin-dependent kinases and the DNA damage checkpoint. We identified MDM two binding protein (MTBP) as a factor that interacts with Treslin/TICRR throughout the cell cycle.']

["MDM two binding protein (MTBP) is a factor that interacts with Treslin/TICRR throughout the cell cycle. MTBP depletion by means of small interfering RNA inhibits DNA replication by preventing assembly of the CMG (Cdc45-MCM-GINS) holohelicase during origin firing. Although MTBP has been implicated in the function of the p53 tumor suppressor, it is required for DNA replication irrespective of a cell's p53 status. MTBP is proposed to act with Treslin/TICRR to integrate signals from cell cycle and DNA damage response pathways to control the initiation of DNA replication in human cells."]

['MDM two binding protein (MTBP)']

Which are the newly identified DNA nucleases that can be used to treat thalassemia?

['Transcription activator-like effector nuclease (TALEN) and zinc finger nuclease (ZFN) DNA editing technology enables site-directed engineering of the genome', 'We used this opportunity to evaluate the effect of total donor homology on transcription activator-like effector nuclease (TALEN) mediated bi-allelic modification. ', 'Herein we describe our applications of site-specific nucleases, especially transcription activator-like effector nucleases, to engineer specific alterations in the genomes of pigs and cows.', 'In this study, we used zinc finger nuclease-mediated knockout of the aryl hydrocarbon receptor (AHR) or AHR nuclear translocator (ARNT) in MCF7 and AHR knockout in MDA-MB-231 human breast cancer cells to investigate cross talk among AHR, ARNT, and estrogen receptor α (ERα).', ' For example, after binding DNA, TALEs fused to transcriptional activation domains can function as robust transcription factors (TALE-TFs), while fused to restriction endonucleases (TALENs) can cut DNA. ', 'Genome editing using engineered nucleases such as transcription activator-like effector nucleases (TALENs) has become a powerful technology for reverse genetics', 'Here, we describe a robust process combining efficient generation of integration-free β-Thal iPSCs from the cells of patients and transcription activator-like effector nuclease (TALEN)-based universal correction of HBB mutations in situ.', 'We report here the correction of α-thalassemia major hydrops fetalis in transgene-free iPS cells using zinc finger-mediated insertion of a globin transgene in the AAVS1 site on human chromosome 19. ', ' Here, we review the development of Cas9 as an important tool to not only edit the genomes of a number of different prokaryotic and eukaryotic species, but also as an efficient system for site-specific transcriptional repression or activation. Additionally, a specific Cas9 protein has been observed to target an RNA substrate, suggesting that Cas9 may have the ability to be programmed to target RNA as well.', 'RNA-guided endonucleases (RGENs), derived from the prokaryotic adaptive immune system known as CRISPR/Cas, enable targeted genome engineering in cells and organisms. ', 'The CRISPR/Cas technology has been successfully used to stimulate the integration of small DNA sequences in a target locus to produce gene mutations.']

['Thalassemia is genetic diseases of the blood caused by mutations in the globin gene. Main goal for thalassemia treatment is to develop homologous recombination based gene therapy in order to cure these diseases. Zinc finger nucleases (ZFNs) and TAL effector nucleases (TALENs) are proper targets for the human globin gene. Genome editing using engineered nucleases such as ZFNs and TALENs has become a powerful technology for reverse genetics.', 'The newly identified DNA nucleases that can be used to treat thalassemia are the transcription activator-like effector nucleases (TALEN). These are engineered proteins able to stimulate targeted integration of therapeutic wild-type beta-globin cDNAs to the endogenous beta-globin locus.']

['TALEN', 'Transcription activator-like effector nucleases', 'Crispr/CAS', 'zinc-finger nucleases']

What are the applications of a Dermaroller ?

['Dermaroller along with Minoxidil treated group was statistically superior to Minoxidil treated group in promoting hair growth in men with AGA for all 3 primary efficacy measures of hair growth. Microneedling is a safe and a promising tool in hair stimulation and also is useful to treat hair loss refractory to Minoxidil therapy.', 'Microneedling with dermaroller is a new treatment modality for the treatment of scars, especially acne scars, stretch marks, wrinkles, and for facial rejuvenation. It is a simple and relatively cheap modality that also can be used for transdermal drug delivery.', 'Microneedling therapy seems to be a simple and effective treatment option for the management of atrophic facial scars.']

['Microneedling with dermaroller is a new treatment modality for the treatment of scars, especially acne scars, stretch marks, wrinkles, and for facial rejuvenation. It is a simple and relatively cheap modality that also can be used for transdermal drug delivery.\nMicroneedling is a safe and a promising tool in hair stimulation and also is useful to treat hair loss refractory to Minoxidil therapy.', 'Microneedling with dermaroller is a new treatment modality for the treatment of scars, especially acne scars, stretch marks, wrinkles, and for facial rejuvenation. It is a simple and relatively cheap modality that also can be used for transdermal drug delivery.Dermaroller along with Minoxidil treated group was statistically superior to Minoxidil treated group in promoting hair growth in men with AGA for all 3 primary efficacy measures of hair growth. Microneedling is a safe and a promising tool in hair stimulation and also is useful to treat hair loss refractory to Minoxidil therapy.', 'Microneedling therapy seems to be a simple and effective treatment option for the management of atrophic facial scars. Microneedling with dermaroller is a new treatment modality for the treatment of scars, especially acne scars, stretch marks, wrinkles, and for facial rejuvenation. It is a simple and relatively cheap modality that also can be used for transdermal drug delivery. Dermaroller along with Minoxidil treated group was statistically superior to Minoxidil treated group in promoting hair growth in men with AGA for all 3 primary efficacy measures of hair growth. Microneedling is a safe and a promising tool in hair stimulation and also is useful to treat hair loss refractory to Minoxidil therapy. ']

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What is Genomicus?

['Genomicus: a database and a browser to study gene synteny in modern and ancestral genomes.', 'Here we present Genomicus, a new synteny browser that can represent and compare unlimited numbers of genomes in a broad phylogenetic view. In addition, Genomicus includes reconstructed ancestral gene organization, thus greatly facilitating the interpretation of the data.AVAILABILITY: Genomicus is freely available for online use at http://www.dyogen.ens.fr/genomicus while data can be downloaded at ftp://ftp.biologie.ens.fr/pub/dyogen/genomicus.', 'Genomicus (http://www.dyogen.ens.fr/genomicus/) is a database and an online tool that allows easy comparative genomic visualization in>150 eukaryote genomes. It provides a way to explore spatial information related to gene organization within and between genomes and temporal relationships related to gene and genome evolution. For the specific vertebrate phylum, it also provides access to ancestral gene order reconstructions and conserved non-coding elements information. We extended the Genomicus database originally dedicated to vertebrate to four new clades, including plants, non-vertebrate metazoa, protists and fungi. This visualization tool allows evolutionary phylogenomics analysis and exploration. Here, we describe the graphical modules of Genomicus and show how it is capable of revealing differential gene loss and gain, segmental or genome duplications and study the evolution of a locus through homology relationships.', 'Genomicus update 2015: KaryoView and MatrixView provide a genome-wide perspective to multispecies comparative genomics.', 'The Genomicus web server (http://www.genomicus.biologie.ens.fr/genomicus) is a visualization tool allowing comparative genomics in four different phyla (Vertebrate, Fungi, Metazoan and Plants). It provides access to genomic information from extant species, as well as ancestral gene content and gene order for vertebrates and flowering plants. Here we present the new features available for vertebrate genome with a focus on new graphical tools. The interface to enter the database has been improved, two pairwise genome comparison tools are now available (KaryoView and MatrixView) and the multiple genome comparison tools (PhyloView and AlignView) propose three new kinds of representation and a more intuitive menu. These new developments have been implemented for Genomicus portal dedicated to vertebrates. This allows the analysis of 68 extant animal genomes, as well as 58 ancestral reconstructed genomes. The Genomicus server also provides access to ancestral gene orders, to facilitate evolutionary and comparative genomics studies, as well as computationally predicted regulatory interactions, thanks to the representation of conserved non-coding elements with their putative gene targets.', 'Genomicus: five genome browsers for comparative genomics in eukaryota.', 'Genomicus (http://www.dyogen.ens.fr/genomicus/) is a database and an online tool that allows easy comparative genomic visualization in >150 eukaryote genomes.', 'The Genomicus web server (http://www.genomicus.biologie.ens.fr/genomicus) is a visualization tool allowing comparative genomics in four different phyla (Vertebrate, Fungi, Metazoan and Plants). ', 'The Genomicus web server (http://www.genomicus.biologie.ens.fr/genomicus) is a visualization tool allowing comparative genomics in four different phyla (Vertebrate, Fungi, Metazoan and Plants).', 'The Genomicus web server (http://www.genomicus.biologie.ens.fr/genomicus) is a visualization tool allowing comparative genomics in four different phyla (Vertebrate,', 'Genomicus (http://www.dyogen.ens.fr/genomicus/) is a database and an online tool that allows easy comparative genomic visualization in >150 eukaryote genomes.', 'The Genomicus web server (http://www.genomicus.biologie.ens.fr/genomicus) is a visualization tool allowing comparative genomics in four different phyla (Vertebrate, Fungi, Metazoan and Plants).']

['Genomicus had been developed as a database and a browser to study gene synteny in modern and ancestral genomes. It allows easy comparative genomic visualization in >150 eukaryote genomes and in four different phyla (Vertebrate, Fungi, Metazoan and Plants). It provides a way to explore spatial information related to gene organization within and between genomes and temporal relationships related to gene and genome evolution. For the specific vertebrate phylum, it also provides access to ancestral gene order reconstructions and conserved non-coding elements information. The graphical modules of Genomicus show how it is capable of revealing differential gene loss and gain, segmental or genome duplications and facilitate the study of the evolution of a locus through homology relationships. The Genomicus server provides access to ancestral gene orders, as well as computationally predicted regulatory interactions, thanks to the representation of conserved non-coding elements with their putative gene targets.']

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Which proteins control the degradation of cryptic unstable transcripts (CUTs) in yeast?

['Termination of cryptic unstable transcripts is directed by yeast RNA-binding proteins Nrd1 and Nab3', 'These cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome. Yeast RNA binding proteins Nrd1 and Nab3 direct termination of sn/snoRNAs and recently have also been implicated in premature transcription termination of the NRD1 gene.', ' These results suggest that transcription termination of CUTs directed by Nrd1 and Nab3 is a prerequisite for rapid degradation by the nuclear exosome.', 'Key substrates for exosomal degradation include aberrant functional RNAs and cryptic unstable transcripts (CUTs).', 'Lack of TRAMP activity stabilises ∼ 1600 CUTs in meiotic cells, which occupy 40% of the binding capacity of the nuclear cap binding complex (CBC). CBC mutants display defects in the formation of meiotic double strand breaks (DSBs), and we see similar defects in TRAMP mutants, suggesting that a key function of the nuclear exosome is to prevent saturation of the CBC complex by CUTs', 'We find that TRAMP mutants produce high levels of CUTs during meiosis that are undetectable in wild-type cells, showing that the nuclear exosome remains functional for CUT degradation, and we further report that the meiotic exosome complex contains Rrp6.', 'The exosome component Rrp6 is required for RNA polymerase II termination at specific targets of the Nrd1-Nab3 pathway.', 'Known targets of the nuclear exosome include short (<1000 bp) RNAPII transcripts such as small noncoding RNAs (snRNAs), cryptic unstable transcripts (CUTs), and some stable unannotated transcripts (SUTs) that are terminated by an Nrd1, Nab3, and Sen1 (NNS) dependent mechanism', 'Recent work suggests Nrd1 is necessary for transcriptome surveillance, regulating promoter directionality and suppressing antisense transcription independently of, or prior to, Rrp6 activity.', 'Cryptic unstable transcripts (CUTs) were recently described as a principal class of RNA polymerase II transcripts in Saccharomyces cerevisiae. These transcripts are targeted for degradation immediately after synthesis by the action of the Nrd1-exosome-TRAMP complexes.', 'In Saccharomyces cerevisiae, non-coding RNAs, including cryptic unstable transcripts (CUTs), are subject to degradation by the exosome. The Trf4/5-Air1/2-Mtr4 polyadenylation (TRAMP) complex in S. cerevisiae is a nuclear exosome cofactor that recruits the exosome to degrade RNAs', ' The MTREC complex specifically binds to CUTs, meiotic mRNAs and unspliced pre-mRNA transcripts and targets these RNAs for degradation by the nuclear exosome, while the TRAMP complex has only a minor role in this process', 'The eukaryotic exosome exoribonuclease Rrp6 forms a complex with Rrp47 that functions in nuclear RNA quality control mechanisms, the degradation of cryptic unstable transcripts (CUTs), and in the 3 end maturation of stable RNAs', 'Nrd1 and Nab3 colocalize to regions of the genome expressing antisense CUTs, and these transcripts require yeast nuclear exosome and TRAMP components for degradation', 'Genome-wide studies have identified abundant small, noncoding RNAs, including small nuclear RNAs, small nucleolar RNAs (snoRNAs), cryptic unstable transcripts (CUTs), and upstream regulatory RNAs (uRNAs), that are transcribed by RNA polymerase II (pol II) and terminated by an Nrd1-dependent pathway', 'Nrd1 and Nab3 colocalize to regions of the genome expressing antisense CUTs, and these transcripts require yeast nuclear exosome and TRAMP components for degradation.', 'Here, by examining the overlap of stable (SUTs, stable unannotated transcripts) and unstable (CUTs, cryptic unstable transcripts) transcripts with protein-coding genes, we show that the predicted Nrd1 and Nab3-binding site sequences occur at differing frequencies.', 'Examples are the consensus binding site sequences of the RNA-binding proteins Nrd1 and Nab3 that target non-coding transcripts for degradation.', 'Termination of cryptic unstable transcripts is directed by yeast RNA-binding proteins Nrd1 and Nab3.', 'Some are designated Cryptic Unstable Transcripts (CUTs) because they are terminated by the Nrd1-Nab3-Sen1 pathway and then rapidly degraded by the nuclear exosome.']

['Termination of cryptic unstable transcripts is directed by yeast RNA-binding proteins Nrd1 and Nab3. These cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome. Key substrates for exosomal degradation include aberrant functional RNAs and cryptic unstable transcripts (CUTs). Yeast RNA binding proteins Nrd1 and Nab3 direct termination of sn/snoRNAs and recently have also been implicated in premature transcription termination of the NRD1 gene. These results suggest that transcription termination of CUTs directed by Nrd1 and Nab3 is a prerequisite for rapid degradation by the nuclear exosome. ', 'Termination of cryptic unstable transcripts is directed by yeast RNA-binding proteins Nrd1 and Nab3. Key substrates for exosomal degradation include aberrant functional RNAs and cryptic unstable transcripts (CUTs). These cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome. These transcripts are targeted for degradation immediately after synthesis by the action of the Nrd1-exosome-TRAMP complexes. Cryptic unstable transcripts (CUTs) were recently described as a principal class of RNA polymerase II transcripts in Saccharomyces cerevisiae. ', "The exosome and its nuclear specific subunit Rrp6 form a 3'-5' exonuclease complex that regulates diverse aspects of RNA biology including 3' end processing and degradation of a variety of noncoding RNAs (ncRNAs) and unstable transcripts. Known targets of the nuclear exosome include short (<1000 bp) RNAPII transcripts such as small noncoding RNAs (snRNAs), cryptic unstable transcripts (CUTs), and some stable unannotated transcripts (SUTs) that are terminated by an Nrd1, Nab3, and Sen1 (NNS) dependent mechanism. The MTREC complex physically interacts with the nuclear exosome and with various RNA-binding and RNA-processing complexes, coupling RNA processing to the RNA degradation machinery.", 'Termination of cryptic unstable transcripts is directed by yeast RNA-binding proteins Nrd1 and Nab3 These cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome. Yeast RNA binding proteins Nrd1 and Nab3 direct termination of sn/snoRNAs and recently have also been implicated in premature transcription termination of the NRD1 gene.', 'Termination of cryptic unstable transcripts is directed by yeast RNA-binding proteins Nrd1 and Nab3. Yeast RNA binding proteins Nrd1 and Nab3 direct termination of sn/snoRNAs and recently have also been implicated in premature transcription termination of the NRD1 gene. These cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome. These results suggest that transcription termination of CUTs directed by Nrd1 and Nab3 is a prerequisite for rapid degradation by the nuclear exosome. Key substrates for exosomal degradation include aberrant functional RNAs and cryptic unstable transcripts (CUTs). ', 'Termination of cryptic unstable transcripts is directed by yeast RNA-binding proteins Nrd1 and Nab3', 'Cryptic unstable transcripts (CUTs) were recently described as a principal class of RNA polymerase II transcripts in Saccharomyces cerevisiae. These transcripts are targeted for degradation immediately after synthesis by the action of the Nrd1-exosome and Trf4/5-Air1/2-Mtr4 polyadenylation (TRAMP) complexes. The termination of cryptic unstable transcripts is directed by yeast RNA-binding proteins Nrd1 and Nab3. Known targets of the nuclear exosome include short (<1000 bp) RNAPII transcripts such as small noncoding RNAs (snRNAs), cryptic unstable transcripts (CUTs), and some stable unannotated transcripts (SUTs) that are terminated by an Nrd1, Nab3, and Sen1 (NNS) dependent mechanism. Recent work suggests Nrd1 is necessary for transcriptome surveillance, regulating promoter directionality and suppressing antisense transcription independently of, or prior to, Rrp6 activity.']

['Rrp6', 'Nrd1', 'Nab3', 'TRAMP complex', 'Trf4/5-Air1/2-Mtr4 polyadenylation', 'Sen1']

Can protein coding exons originate from ALU sequences?

['The Alu element has been a major source of new exons during primate evolution. Thousands of human genes contain spliced exons derived from Alu elements.', 'More than 25% of Alu exons analyzed by RNA-Seq have estimated transcript inclusion levels of at least 50% in the human cerebellum, indicating widespread establishment of Alu exons in human genes.', 'his study presents genomic evidence that a major functional consequence of Alu exonization is the lineage-specific evolution of translational regulation.', 'Our data suggests that lineage-specific exonization events should be determined by the combination event of the formation of splicing sites and protection against site-specific mutation pressures. These evolutionary mechanisms could be major sources for primate diversification.', 'Exonization of Alu elements creates primate-specific genomic diversity', 'Our data show that, once acquired, some exonizations were lost again in some lineages. In general, Alu exonization occurred at various time points over the evolutionary history of primate lineages, and protein-coding potential was acquired either relatively soon after integration or millions of years thereafter.', 'Once integrated, they have the potential to become exapted as functional modules, e.g., as protein-coding domains via alternative splicing. This particular process is also termed exonization and increases protein versatility', 'alternative "Alu-exons" also carry the potential to greatly enhance genetic diversity by increasing the transcriptome of primates chiefly via alternative splicing.', "ere, we report a 5' exon generated from one of the two alternative transcripts in human tumor necrosis factor receptor gene type 2 (p75TNFR) that contains an ancient Alu-SINE, which provides an alternative N-terminal protein-coding domain."]

['Yes. Intronic ALUs can evolve into exons by the activation of splice signals residing within the ALU sequence. While most ALU exons do not add or modify the coding capacity of the resulting transcript, examples have been identified of ALU exons becoming protein coding.']

['yes']

List adenosine A2A receptor antagonists that are used for Parkinson's disease treatment.

['Adenosine A2A antagonists, such as istradefylline, improve motor function in PD, but their effect on cognitive impairment has not been determined.', 'Both istradefylline and preladenant have demonstrated moderate efficacy in reducing off time in PD patients with motor fluctuations. ', " The available data also suggest that caffeine can improve the motor deficits of PD and that adenosine A2A receptor antagonists such as istradefylline reduces OFF time and dyskinesia associated with standard 'dopamine replacement' treatments. ", "Istradefylline (KW-6002) is the first of several adenosine A2A receptor antagonists in development for PD to advance to phase III clinical trials. Initial studies indicate that in patients with motor fluctuations on levodopa, addition of istradefylline reduces 'off' time. ", 'These include alpha2 adrenergic receptor antagonists (eg, fipamezole), adenosine A2A receptor antagonists (eg, istradefylline), AMPA receptor antagonists (eg, talampanel), neuronal synchronization modulators (eg, levetiracetam) and agents that interact with serotonergic systems such as 5-hydroxytryptamine (5-HT)1A agonists (eg, sarizotan) and 5-HT2A antagonists (eg, quetiapine). ', 'BACKGROUND: We evaluated the efficacy and safety of istradefylline, a selective adenosine A2A receptor antagonist administered as adjunctive treatment to levodopa for 12 weeks in a double-blind manner in Parkinsons disease patients with motor complications in Japan.', 'Istradefylline, a novel adenosine A2A receptor antagonist, for the treatment of Parkinsons disease.', "Istradefylline, a novel adenosine A2A receptor antagonist, for the treatment of Parkinson's disease.", "In this article, the author discusses the potential role of A2A adenosine receptor antagonists in the treatment of Parkinson's disease through the evaluation of istradefylline", "Suitability of the adenosine antagonist istradefylline for the treatment of Parkinson's disease: pharmacokinetic and clinical considerations."]

["Istradefylline and preladenant are adenosine A2A receptor antagonists that are used for Parkinson's disease treatment."]

['istradefylline', 'preladenant']

Are microtubules marked by glutamylation?

["Together with detyrosination, glutamylation and other modifications, tubulin acetylation may form a unique 'language' to regulate microtubule structure and function.", 'Glutamylation, the most prevalent tubulin posttranslational modification, marks stable microtubules and regulates recruitment and activity of microtubule- interacting proteins.', 'Enzymes of the tubulin tyrosine ligase-like (TTLL) family posttranslationally modify and thereby mark microtubules by glutamylation, generating specific recognition sites for microtubule-interacting proteins.', ' PTMs of the cytoskeleton, including phosphorylation, glycosylation, ubiquitination, detyrosination/tyrosination, (poly)glutamylation and (poly)glycylation, acetylation, sumoylation, and palmitoylation, will be addressed in this chapter.', 'The tubulin posttranslational modifications: acetylation, detyrosination, polyglutamylation, and polyglycylation play important roles in microtubule functions', 'In most eukaryotic cells, tubulin is subjected to posttranslational glutamylation, a conserved modification of unclear function.']

['Yes, glutamylation is the most prevalent tubulin posttranslational modification and marks stable microtubules.']

['yes']

Albumin depletion is a common first step for proteomic analysis of CSF fluid. What is the advantage and disadvantage of this procedure?

['However, albumin binds peptides and proteins, which raises concerns as to how the removal of albumin could impact the outcome of the biomarker study while ignoring the possibility that this could be a biomarker subproteome itself.', 'This study demonstrates that reduction of sample complexity by albumin depletion of CSF can be performed without CV impairment.', 'We have utilized albumin depletion prior to 2D gel electrophoresis to enhance glycoprotein concentration for image analysis as well as structural glycoprotein determination without glycan release using mass spectrometry (MS).', 'The albumin depletion method is the most suitable as prefractionation method of CSF prior to 2-DE for structural determination of glycoproteins in the study of neurodegenerative disorders.', 'A proper sample preparation, in particular, abundant protein removal is crucial in the characterization of low-abundance proteins including those harboring post-translational modifications. In human cerebrospinal fluid (CSF), approximately 80% of proteins originate from serum, and removal of major proteins is necessary to study brain-derived proteins that are present at low concentrations for successful biomarker and therapeutic target discoveries for neurological disorders.', 'The most abundant component in human body fluids, human serum albumin (HSA), is present at concentrations corresponding to approximately 50% of the total protein content in, e.g., plasma and cerebrospinal fluid (CSF). If this component could be selectively removed, then the chances of observing lower-abundance component of clinical interest would be greatly improved.', ', and the identification of lower abundant components was clearly facilitated.', 'Two different depletion strategies for removing albumin from human cerebrospinal fluid (CSF), Microcon Centrifugal Filter vs. Montage Albumin Deplete kit, were evaluated for improving protein profiling pattern and reproducibility in SELDI analysis. METHODS: Pooled CSF was divided into 20 aliquots and these aliquots were subjected to SELDI analysis ei', 'Enhanced identification of lower-abundance components was observed in the depleted fraction, in terms of more detected peptides per protein.']

['Depletion of the high abundant protein Albumin from CSF samples is improving the detection of lower abundant proteins but may also lead to the potential loss of non-target proteins.']

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What is "Epitranscriptome analysis"?

['The simultaneous detection of all the post-transcriptional modifications (PTMs) that decorate cellular RNA can provide comprehensive information on the effects of changing environmental conditions on the entire epitranscriptome. ', 'The advent of high-throughput sequencing technologies coupled with new detection methods of RNA modifications has enabled investigation of a new layer of gene regulation - the epitranscriptome.', ' Other mRNA modifications, including N1-methyladenosine (m1A), 5-methylcytosine (m5C) and pseudouridine, together with m6A form the epitranscriptome and collectively code a new layer of information that controls protein synthesis.', ' the utility of mass spectrometry approaches for discovery-based analyses of RNA modifications, such as are required for studies of the epitranscriptome.', 'Despite the intriguing advancements, little is known so far about the dynamic landscape of RNA methylome across different cell types and how the epitranscriptome is regulated at the system level by enzymes, i.e., RNA methyltransferases and demethylases.', "Modified nucleotides in messenger RNA (mRNA) have been discovered over 40 years ago, but until recently little was known about which transcripts contain them and what their function is. High-throughput sequencing approaches revealed a dynamic landscape of the 'Epitranscriptome' for many mRNA modifications in various organisms from yeast to humans. "]

["Modified nucleotides in messenger RNA (mRNA) have been discovered over 40 years ago, but until recently little was known about which transcripts contain them and what their function is. High-throughput sequencing approaches revealed a dynamic landscape of the 'Epitranscriptome' for many mRNA modifications in various organisms from yeast to humans.\t\t\nThe detection methods of RNA modifications has enabled investigation of a new layer of gene regulation - the epitranscriptome."]

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Is Fibroblast Growth Factor 23 a phosphaturic hormone?

['PTH can induce skeletal synthesis of another potent phosphaturic hormone, fibroblast growth factor 23 (FGF23), ', ' Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that has recently been identified as a CKD-related factor affecting CRS. ', ' circulating phosphaturic hormone fibroblast growth factor-23 levels', ' Fibroblast growth factor (FGF) 23 is one of the most recently discovered FGFs. This phosphaturic hormone produced in bones is a risk factor for cardiovascular diseases and thus mortality.', 'fibroblast growth factor 23 (FGF23), a phosphaturic hormone and regulator of 1,25(OH)2 vitamin D3 (1,25VitD3). ', 'fibroblast growth factor-23 (FGF23), a bone-derived phosphaturic hormone.', ' the phosphaturic hormone fibroblast growth factor 23 (FGF23) and soluble Klotho with all-cause mortality.', 'In particular, diseases caused by changes in the expression and proteolytic control of the phosphaturic hormone fibroblast growth factor-23 (FGF23) have come to the forefront in terms of directing new models explaining mineral metabolism', 'serum levels of a phosphaturic hormone, fibroblast growth factor 23 (Fgf23), ']

['Yes, fbroblast growth factor 23 (FGF23) is a phosphaturic hormone.']

['yes']

Which are the components of the pre-replication complex (pre-RC) in eukaryotes?

[' The first step of replication initiation is the assembly of pre-replication complex (pre-RC). Since 1973, four proteins, Cdc6/Cdc18, MCM, ORC and Cdt1, have been extensively studied and proved to be pre-RC components. Recently, a novel pre-RC component called Sap1/Girdin was identified. Sap1/Girdin is required for loading Cdc18/Cdc6 to origins for pre-RC assembly in the fission yeast and human cells, respectively. ', 'In eukaryotes, the pre-replication complex is composed of the Origin Recognition Complex (ORC), Cdc6 and the MCM replicative helicase in conjunction with Cdt1. Eukaryotic ORC is considered to be composed of six subunits, named Orc1-6, and monomeric Cdc6 is closely related in sequence to Orc1.', 'The sequencing of the Plasmodium genome has also revealed the apparent absence of many key components (e.g. Cdt1, DDK and Cdc45) of the eukaryotic cell cycle machinery that are responsible for the formation of the pre-replication complex (pre-RC). We have characterized the Plasmodium falciparum minichromosome maintenance complex (MCM) that plays a key role in the transition of pre-RC to the RC. Similar to other eukaryotes, the Plasmodium genome encodes six MCM subunits. ', 'During pre-replication complex (pre-RC) formation, origin recognition complex (ORC), Cdc6, and Cdt1 cooperatively load the 6-subunit mini chromosome maintenance (MCM2-7) complex onto DNA.', 'ORC1 is an essential component of the pre-replicative complex (pre-RC) that licenses eukaryote DNA replication origins.', 'In higher eukaryotes, the pre-replication complex (pre-RC) component Cdt1 is the major regulator in licensing control for DNA replication.', 'The sequencing of the Plasmodium genome has also revealed the apparent absence of many key components (e.g. Cdt1, DDK and Cdc45) of the eukaryotic cell cycle machinery that are responsible for the formation of the pre-replication complex (pre-RC)', 'We examined the mRNA expression of the components of pre-replication complex (Pre-RC), CDC6, CDT1, and MCM2-7', 'Replication initiation is a multi-step process involving many factors including ORC, Cdt1p, Mcm2-7p and other proteins that bind to replication origins to form a pre-replicative complex (pre-RC)', 'The sequencing of the Plasmodium genome has also revealed the apparent absence of many key components (e.g. Cdt1, DDK and Cdc45) of the eukaryotic cell cycle machinery that are responsible for the formation of the pre-replication complex (pre-RC).', 'Different components of the ORC complex and Cdc6 stimulated prereplicative complex (pre-RC) formation and replication initiation when fused to the GAL4 DNA-binding domain and recruited to plasmid DNA containing a tandem array of GAL4-binding sites.', 'Cdt1, DDK and Cdc45) of the eukaryotic cell cycle machinery that are responsible for the formation of the pre-replication complex (pre-RC).', 'Recently, a novel pre-RC component called Sap1/Girdin was identified.', 'MCM2-7 is a key component of the prereplicative complex (pre-RC), which is loaded onto chromatin by the concerted action of origin recognition complex, Cdc6, and Cdt1.', 'The pre-replicative complex (pre-RC) is formed at all potential origins of replication through the action of the origin recognition complex (ORC), Cdc6, Cdt1, and the Mcm2-7 complex.']

['The components of the pre-replication complex (pre-RC) in eukaryotes are:\n1) Cdc6/Cdc18, \n2) MCM, \n3) ORC1-6,\n4) Cdt1 and\n5) Sap1/Gi.']

['Cdc6/Cdc18', 'MCM', 'ORC1-6', 'Cdt1', 'Sap1/Gi']

What organism causes woolsorter's disease

["Today, woolsorters' disease and other industrial manifestations of anthrax are extremely rare, ", "Working independently of their more famous counterparts (Robert Koch and Louis Pasteur), Anglo-American anthrax investigators used visual representations of anthrax bacilli to persuade their peers that a specific, identifiable cause produced all forms of anthrax-malignant pustule (cutaneous anthrax), intestinal anthrax, and woolsorter's disease (pneumonic anthrax). ", "Today, woolsorters' disease and other industrial manifestations of anthrax are extremely rare, but the increasing threat of bioterrorism means that the international dread and historical lessons of this significant condition should never be forgotten. ", "Today, woolsorters' disease and other industrial manifestations of anthrax are extremely rare, but the increasing threat of bioterrorism means that the international dread and historical lessons of this significant condition should never be forgotten."]

["Woolsorter's disease is caused by the same organism as Anthrax, bacillus Anthrax. "]

['Bacillus Anthracis']

List drugs included in the DHAP-R chemotherapy regiment.

['Standard treatment of transplant-eligible patients with relapsed diffuse large B-cell lymphoma (DLBCL) consists of rituximab and platinum-based chemotherapy, either ifosfamide, carboplatin, and etoposide (ICE) or dexamethasone, cytarabine, and cisplatin (DHAP), with autologous transplant consolidation for those with chemosensitive disease.', 'The intergroup Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) set the limits for this standard of treatment after first comparing 2 salvage regimens: rituximab, ifosfamide, etoposide, and carboplatin (R-ICE) and rituximab, dexamethasone, aracytine, and cisplatin (R-DHAP). ', 'The response rate (RR) to first salvage chemotherapy was 23% (RR by regimen: dexamethasone, cytosine arabinoside and cisplatin [DHAP] 15%, etoposide, Solu-Medrol, cytosine arabinoside and cisplatin [ESHAP] 36%, and gemcitabine, dexamethasone and cisplatin [GDP] 45%); 25% (n = 28) of patients underwent ASCT. ', 'PURPOSE: To evaluate the prognostic value of the cell of origin (COO) in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBLC), prospectively treated by rituximab, dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP) versus rituximab, ifosfamide, carboplatin, and etoposide and followed by intensive therapy plus autologous stem-cell transplantation on the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) trial. ', 'The aim of this study was to evaluate the efficacy and toxicity of two chemotherapy regimens based on platinum and cytarabine in association with etoposide and methylprednisolone (ESHAP) or with dexamethasone (DHAP) with or without Rituximab (± R) in patients with refractory or a relapsed Primary Central Nervous System Lymphoma (PCNSL). ', 'R-DHAP combines rituximab with cisplatin, cytarabine, and dexamethasone. ', 'PATIENTS AND METHODS: Patients with CD20(+) DLBCL in first relapse or who were refractory after first-line therapy were randomly assigned to either rituximab, ifosfamide, etoposide, and carboplatin (R-ICE) or rituximab, dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP).', 'Because of the inability to safely administer unattenuated doses of anthracycline-based regimens, dexamethasone, high-dose cytarabine, and cisplatin (DHAP) was used at full doses (along with rituximab for the DLBCL patient) until hepatic function normalized (1-5 cycles). ', 'Randomized to DHAP (cisplatin-cytarabine-dexamethasone)-VIM (etoposide-ifosfamide-methotrexate)-DHAP (cisplatin-cytarabine-dexamethasone) chemotherapy with rituximab (R; R-DHAP arm) were 119 patients (113 evaluable) and to chemotherapy without rituximab (DHAP arm) 120 patients (112 evaluable). ', 'Patients are first randomised between ICE (ifosfamide, carboplatin, etoposide) and DHAP (dexamethasone, ara-C and cisplatin), both combined with rituximab (R-ICE or R-DHAP).', "BACKGROUND AND OBJECTIVE: The treatment of the patients with relapsed and refractory non-Hodgkin's lymphoma(NHL) remains difficult. It was reported that DHAP regimen(cisplatin + Ara-C + dexamthsone) was an effective salvage therapy, but there was no report about it in China. ", 'Randomized to DHAP (cisplatin-cytarabine-dexamethasone)-VIM (etoposide-ifosfamide-methotrexate)-DHAP (cisplatin-cytarabine-dexamethasone) chemotherapy with rituximab (R; R-DHAP arm) were 119 patients (113 evaluable) and to chemotherapy without rituximab (DHAP arm) 120 patients (112 evaluable).', 'Randomized to DHAP (cisplatin-cytarabine-dexamethasone)-VIM (etoposide-ifosfamide-methotrexate)-DHAP (cisplatin-cytarabine-dexamethasone) chemotherapy with rituximab (R; R-DHAP arm) were 119 patients (113 evaluable) and to chemotherapy without rituximab (DHAP arm) 120 patients (112 evaluable)']

['Dexamethasone (a steroid hormone), cytarabine (ara-C), cisplatin (platinum agent) and rituximab are included in the DHAP-R chemotherapy protocol.']

['dexamethasone', 'cytarabine', 'cisplatin', 'rituximab']

What is the treatment of interferon-induced thyroiditis?

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['An altered thyroid function is frequently observed during interferon treatment with a pattern similar to Hashimoto Thyroiditis or Graves disease.\nVery frequently the alterations of thyroid hormones related to interferon-induced thyroiditis spontaneosly diseapper in a few months\nTreatment when necessary is propanolol and antithyroid drugs for the Graves like form and thyroxine for chronic hypothyroidism indiced by interferon']

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Has the protein GFP been used in transgenesis for live protein imaging?

['we review recent advancement in the functional studies of the three different GnRH neuron systems, mainly focusing on the electrophysiological analysis of the GnRH-green fluorescent protein (GFP) transgenic animals.', 'founders were found to be transgenic for GFP.', 'GFP expression was detected in a wide range of murine tissues', 'Transgenic Xenopus laevis for live imaging in cell and developmental biology.', 'The stable transgenesis of genes encoding functional or spatially localized proteins, fused to fluorescent proteins such as green fluorescent protein (GFP) or red fluorescent protein (RFP), is an extremely important research tool in cell and developmental biology.', 'GFP-transgenic animals for in vivo imaging: rats, rabbits, and pigs.', 'We have further extended the techniques of genetic engineering to rats, rabbits, and pigs, and have created corresponding GFP-transgenic animals.', 'The results revealed that the 3.6-GFP transgenic animals provide a unique model for direct analysis of cellular and molecular mechanisms of pulp repair and tertiary dentinogenesis in vivo.', 'Long-term effects of PERV-specific RNA interference in transgenic pigs.', 'green fluorescent protein (GFP) as reporter of the vector system were consistently expressed in transgenic animals.', 'The ability to specify the expression levels of exogenous genes inserted in the genomes of transgenic animals is critical for the success of a wide variety of experimental manipulations. ', 'Welfare assessment in transgenic pigs expressing green fluorescent protein (GFP).', 'transgenic animals expressing GFP with wildtype animals along various stages of post natal development', 'Production of transgenic chickens expressing a tetracycline-inducible GFP gene.', 'transgenic animals can be readily created to express fluorescently tagged proteins or reporters', 'These findings suggest that mhc2dab:GFP and cd45:DsRed transgenic lines will be instrumental in elucidating the immune response in the zebrafish.', 'f 33 mice born, 28 (81%) carried the transgene DNA and 15 (55.5%) were GFP-positive.', 'Lentiviral vectors containing the green fluorescent protein gene have been successfully used to select transgenic embryos before transfer to a surrogate mother', 'Typically transgenes are generated by placing a promoter upstream of a GFP reporter gene or cDNA of interest, and this often produces a representative expression pattern.', 'Survival and immunogenicity of mesenchymal stem cells from the green fluorescent protein transgenic rat in the adult rat brain.', 'This problem has been lessened by the availability of transgenic animals that express "reporter" genes, such as green fluorescent protein (GFP)', ' full-length GFP fusion proteins was examined, in transgenic animals, ', 'Two stable transgenic lines express GFP prior to hair-bundle formation', 'we generated two transgenic pigs by somatic cell nuclear transfer (SCNT) that express green fluorescent protein (GFP) driven by cytomegalovirus (CMV).', 'Fluorescent proteins such as the green fluorescent protein (GFP) have widely been used in transgenic animals as reporter genes. ', 'Green Fluorescent Protein (GFP) is used extensively as a reporter for transgene expression in Drosophila and other organisms.']

['Yes, the stable transgenesis of genes encoding functional or spatially localized proteins, fused to fluorescent proteins such as green fluorescent protein (GFP) or red fluorescent protein (RFP), is an extremely important research tool in cell and developmental biology.']

['yes']

What is the causative agent of the "Panama disease" affecting bananas?

['Fusarium oxysporum f. sp. cubense (Foc), the causal agent of Fusarium wilt (Panama disease), is one of the most devastating diseases of banana (Musa spp.)', 'avendish, the most widely grown banana cultivar, is relatively resistant to Race 1 of Fusarium oxysporum f. sp. cubense (Foc1) which caused widespread Panama disease during the first half of the 20th century but is susceptible to Tropical Race 4 of Foc (Foc TR4) which is threatening world banana production. ', 'Fusarium oxysporum f. sp. cubense race 4 (FOC), the causal agent of Panama disease in banana,', 'Fusarium oxysporum f.sp. cubense, a causative agent of Panama disease', 'Fusarium wilt of banana (also known as Panama disease) is caused by Fusarium oxysporum f. sp. cubense', ' inoculated with Fusarium oxysporum f.sp. cubense (FOC), Race 4, the causal agent of Panama disease', 'the fungus causing Panama disease of banana', 'Panama disease of banana, caused by the fungus Fusarium oxysporum f. sp. cubense, is a serious constraint both to the commercial production of banana and cultivation for subsistence agriculture']

['Panama disease of banana is caused by the fungus Fusarium oxysporum f. sp. cubense.']

['Fusarium oxysporum f. sp. cubense']

Can NXY-059 be used for treatment of acute ischemic stroke patients?

['Even when the international recommendations for preclinical stroke research, the Stroke Academic Industry Roundtable (STAIR) criteria, were followed, we have still seen limited success in the clinic, examples being NXY-059 and haematopoietic growth factors which fulfilled nearly all the STAIR criteria', 'This occurred during 1993-2006, when the 2,4-disulfonylphenyl PBN derivative, called NXY-059 in the stroke studies, was shown to be safe in humans and was taken all the way through clinical phase 3 trials and then was deemed to be ineffective. ', 'The nitrone-based compound NXY-059, which is the first drug to reach clinical trials for the treatment of acute ischemic stroke, has provided promise for the development of more robust pharmacological agents. ', 'OKN-007 is a proprietary compound that has had extensive commercial development (designated as NXY-059) for another indication, acute ischemic stroke, and after extensive clinical studies was shown to lack efficacy for this indication but was shown to be very safe for human use. ', 'NXY-059, a polar compound with limited transport across the blood-brain barrier, has demonstrated neuroprotection in several animal models of acute ischemic stroke but failed to confirm clinical benefit in the second phase III trial (SAINT-II).', 'NXY-059 is no longer in development following a lack of efficacy found in a Phase III trial in patients with acute ischemic stroke. ', 'We analyzed the quality and adequacy of animal studies supporting the efficacy of NXY-059 and other neuroprotective agents that are currently being investigated in phase II/III trials', ' In the aftermath of the failed stroke clinical trials with the nitrone spin trap/radical scavenger, NXY-059, a number of articles raised the question: are we doing the right thing? ', ' In 2006, the first positive trial of neuroprotection was published: the SAINT I (Stroke-Acute Ischemic NXY Treatment) study. In February 2008, the SAINT II study was published, indicating that NXY-059 was not effective for AIS treatment.', 'CONCLUSIONS: NXY-059 is ineffective for treatment of AIS within 6 hours of symptom onset. ', 'BACKGROUND AND PURPOSE: The SAINT I trial that showed a significant benefit of the neuroprotectant NXY-059 used a novel outcome for acute ischemic stroke trials: a shift toward good functional outcome on the 7-category modified Rankin scale (mRS).', 'BACKGROUND: The free-radical-trapping agent NXY-059 showed promise as a neuroprotectant in the Stroke-Acute Ischemic NXY Treatment I (SAINT I) trial, reducing disability when given to patients who had acute ischemic stroke. ', 'CONCLUSIONS: NXY-059 is ineffective for the treatment of acute ischemic stroke within 6 hours after the onset of symptoms.', 'The continued failure in approving new drugs for treatment of acute stroke has been recently set back by the failure of the NXY-059 (Stroke-Acute Ischemic NXY Treatment (SAINT) II) trial.', 'The SAINT II Trial, a large randomized multicenter clinical trial of the putative neuroprotectant, NXY-059, failed to demonstrate a treatment benefit in acute ischemic stroke. ', 'The positive results from the first Stroke-Acute-Ischaemic-NXY-Treatment (SAINT-I) trial of the free-radical spin-trap drug, NXY-059, which followed many of the STAIR guidelines, reinvigorated enthusiasm in neuroprotection, but the SAINT-II trial did not replicate the positive effect on the same primary prespecified outcome measure. ', 'NXY-059, a free radical spin trap agent, was felt by many to have followed these criteria and it was recently shown to improve outcome in AIS patients in the SAINT I trial. However, the repeat, SAINT II trial was a neutral study, the results of which cast doubt on neuroprotection as a viable strategy for AIS. ', 'NXY-059 is a novel free radical-trapping neuroprotectant that reduces infarct size and preserves brain function in animal models of acute ischemic stroke. It is the first neuroprotectant to demonstrate a reduction in global disability in a phase III clinical trial, as measured by the modified Rankin Scale.', 'BACKGROUND AND PURPOSE: NXY-059 is a free radical-trapping neuroprotectant demonstrated to reduce disability from ischemic stroke.', 'CONCLUSIONS: NXY-059 within 6 hours of acute ischemic stroke significantly reduced disability. ', 'CONCLUSIONS: The administration of NXY-059 within six hours after the onset of acute ischemic stroke significantly improved the primary outcome (reduced disability at 90 days), but it did not significantly improve other outcome measures, including neurologic functioning as measured by the NIHSS score. Additional research is needed to confirm whether NXY-059 is beneficial in ischemic stroke. ', 'BACKGROUND: The free-radical-trapping agent NXY-059 showed promise as a neuroprotectant in the Stroke-Acute Ischemic NXY Treatment I (SAINT I) trial, reducing disability when given to patients who had acute ischemic stroke.', 'NXY-059 is no longer in development following a lack of efficacy found in a Phase III trial in patients with acute ischemic stroke.', 'The free-radical-trapping agent NXY-059 showed promise as a neuroprotectant in the Stroke-Acute Ischemic NXY Treatment I (SAINT I) trial, reducing disability when given to patients who had acute ischemic stroke', 'The continued failure in approving new drugs for treatment of acute stroke has been recently set back by the failure of the NXY-059 (Stroke-Acute Ischemic NXY Treatment (SAINT) II) trial']

['No. 2,4-disulfonylphenyl PBN derivative, called NXY-059 in the stroke studies, was shown to be safe in humans and was taken all the way through clinical phase 3 trials and then was deemed to be ineffective.']

['no']

What are the molecular characteristics of the FAA (FANCA) cDNA?

['Here we report the isolation of a cDNA representing the FAA gene, following an expression cloning method similar to the one used to clone the FAC gene. The 5.5-kb cDNA has an open reading frame of 4,368 nucleotides. In contrast to the 63-kD cytosolic protein encoded by the FAC gene, the predicted FAA protein (M(r) 162, 752) contains two overlapping bipartite nuclear localization signals and a partial leucine zipper consensus, which are suggestive of a nuclear localization']

['The 5.5-kb cDNA of the FAA (FANCA) gene has an open reading frame of 4,368 nucleotides, whereas the FAA protein is predicted to have a molecular weight of approximately 163 kDa.']

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Is there a genetic component for happiness?

['inally, a systematic review performed based on existing information. Results of studies on genetic factors indicated an average effectiveness of genetic about 35 -50 percent on happiness. ', 'The MAOA gene predicts happiness in women.', 'Although twin studies estimate that genetic factors account for 35-50% of the variance in human happiness, knowledge of specific genes is limited.', 'This investigation examines association between happiness and monoamine oxidase A (MAOA) genotype. ', 'Those with the syndrome have a predisposition toward apparent happiness and paroxysms of laughter, and this finding helps distinguish Angelman syndrome from other ones involving severe developmental handicap. ', 'The heritability of happiness was estimated at 22% for males and 41% in females. ', 'Biometric studies have shown that happiness is strongly affected by genes.', 'The clustering of the four different measures (quality of life in general, satisfaction with life, quality of life at present, and subjective happiness) was explained by an underlying additive genetic factor and an underlying non-additive genetic factor. ', ' happiness and the environment are influenced by genetic factors and family upbringing', 'The results suggest that many putative indicators of the environment are highly heritable and, indeed, that the same genes that affect the environment may affect happiness as well.']

['Results of studies on genetic factors indicated an average effectiveness of genetic about 35 -50 percent on happiness. The MAOA gene predicts happiness in women. The heritability of happiness was estimated at 22% for males and 41% in females.']

[]

What is being measured with an accelerometer in back pain patients

['accelerometer assessment measuring overall physical activity (PAL), constant strain postures (CSP), standing time (ST) and lying time (LT)', 'Physical activity was measured for 7 days at both baseline and at 3 months with an RT3 accelerometer', 'wearing an accelerometer to assess physical activity in daily life', 'An accelerometer was used to objectively assess their activity level ', 'objective activity data to determine whether patients with chronic lower back pain report their activity levels as accurately as controls do. DESIGN: A cross-sectional study was performed in patients and controls. SETTING: The study was carried out in the daily environment of the subjects. SUBJECTS: Thirty-two chronic lower back pain patients with symptoms more than three months and 20 healthy controls from the Netherlands, aged 18-65 years. MAIN MEASURES: A tri-axial accelerometer was worn for five weekdays', 'During 14days physical activity in daily life was measured, with both an electronic diary and an accelerometer', 'physical activity in daily life was measured with an accelerometer', 'physical activity (PA) in individuals with chronic low back pain (CLBP). Thirty-eight participants with non-specific CLBP (29=distressed; 9=non-distressed) were recruited. PA levels were measured using an accelerometer (activPAL activity monitor) over a one week period. The following parameters of physical activity were recorded: time upright (standing or walking), time standing, time walking, and step count.', 'Physical activity levels will be measured by self report, RT3 triaxial accelerometer,', 'to study the time spent in different static trunk postures which was recorded by a biaxial accelerometer attached to the T12 level', 'Daily activities were assessed by measuring body movement with a tri-axial accelerometer', 'nighttime activity data from 18 patients diagnosed with chronic back pain. The patients were followed for 6 days and 5 nights. Pain levels were collected every 90 min between 0800 hours and 2,200 hours using a computerized electronic diary. Activity levels were collected using a wrist accelerometer (Actiwatch AW-64). The Actiwatch sampled activity counts every 1 min. Patients were asked to wear the Actiwatch on their non-dominant arm.', ' 8-h accelerometer assessment in their daily life (physical activity level (PAL), number of constant postures (CP)', 'The activity levels were collected automatically using a wrist accelerometer and were sampled every minute.', 'Physical activity in daily life, expressed as whole-body acceleration measured with a triaxial accelerometer (Tracmor),']

['Accelerometer assessment measuring overall physical activity (PAL), constant strain postures (CSP), standing time (ST) and lying time (LT)...\nThe following parameters of physical activity were recorded: time upright (standing or walking), time standing, time walking, and step count.']

['Physical activity', 'PA', 'PAL', 'Constant Strain Postures', 'CSP', 'constant postures', 'Standing time', 'ST', 'Lying time', 'LT']

What disease is small bowel lymphoma commonly associated with

['Marginal zone B-cell lymphoma of MALT in small intestine associated with amyloidosis: a rare association.', 'This is the first case of marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) in the small intestine associated with amyloidosis in Korea', 'MR enterography of small-bowel lymphoma: potential for suggestion of histologic subtype and the presence of underlying celiac disease.', 'We describe the characteristics of small-bowel lymphoma on MR enterography, identifying a number of key features that may help the interpreting radiologist in suggesting the underlying histologic subtype and whether the presence of underlying celiac disease is likely.', 'Celiac disease is an autoimmune disorder triggered by ingestion of gluten-containing foods. Epidemiologic studies dating from the 1950s established its association with gastrointestinal malignancies, particularly small bowel lymphoma.', 'An association between untreated coeliac disease and intestinal malignancy is well described so it is possible that patients with undiagnosed coeliac disease constitute a significant reservoir of preventable gastrointestinal malignancy.', 'An increased incidence of small bowel lymphoma in patients with long-standing celiac sprue is well documented in the literature.']

['Small bowel lymphoma is commonly associated with celiac disease.']

['Celiac disease', 'gluten-associated enteropathy', 'CELIAC SPRU', 'Non tropical spru', 'Gluten Sensitive Enteropath']

In which cells are gasdermins expressed?

['Members of the novel gene family Gasdermin (Gsdm) are exclusively expressed in a highly tissue-specific manner in the epithelium of skin and the gastrointestinal tract. ', 'These results indicate that the mouse Gsdma and Gsdma3 genes share common function to regulate epithelial maintenance ', 'Gasdermin (GSDM or GSDMA), expressed in the upper gastrointestinal tract but frequently silenced in gastric cancers (GCs), regulates apoptosis of the gastric epithelium.', '. Immunohistochemical analysis revealed that gasdermins are expressed specifically in cells at advanced stages of differentiation in the upper epidermis, the differentiating inner root sheath and hair shaft and in the most mature sebocytes of the sebaceous gland and preputial, meibomium, ceruminous gland, and anal glands. This expression pattern suggests a role for gasdermins in differentiation of the epidermis and its appendages.']

['Members of the novel gene family Gasdermin (Gsdm) are exclusively expressed in a highly tissue-specific manner in the epithelium of skin and the gastrointestinal tract.']

['epithelial cells']

What is the name of the stem loop present in the 3' end of genes encoding for selenoproteins?

['stem-loop structure called the selenocysteine incorporating sequence (SECIS)', "3'-UTR mRNA stem-loop termed SElenoCysteine Insertion Sequence (SECIS)", 'Sec is inserted by a specific translational machinery that recognizes a stem-loop structure, the SECIS element', "Selenocysteine Insertion Sequence (SECIS) element in the 3'UTR of the transcript.", 'The proximal stem-loop promotes Sec insertion ', 'Selenocysteine is encoded by an in-frame UGA codon specified by a stem-loop structure, the Sec insertion sequence element (SECIS)', "3' untranslated region RNA stem loop called a SEC incorporation sequence (SECIS)", "recoding of UGA as Sec depends on the selenocysteine insertion sequence (SECIS) element, a stem-loop structure in the 3' untranslated region of the transcript", "this requires a dedicated machinery comprising a stem-loop structure in the 3' UTR RNA (the SECIS element)", 'RNA stem-loop structure, the SECIS element in the 3 untranslated region of (UTR) selenoprotein mRNAs', "recoding of the UGA stop codon to selenocysteine. In eukaryotes, this requires an RNA stem loop structure in the 3'-untranslated region, termed a selenocysteine insertion sequence (SECIS),", ' insertion into proteins is directed by translational recoding of specific UGA codons located upstream of a stem-loop structure known as Sec insertion sequence (SECIS) element', "In eukaryotes, incorporation of Sec requires a Sec insertion sequence (SECIS) element, a stem-loop structure located in the 3'-untranslated regions of selenoprotein mRNAs", "selenocysteine insertion requires a cis-acting selenocysteine insertion sequence (SECIS) usually located in the 3'UTR of selenoprotein mRNAs", "The Sec insertion sequence (SECIS) element, which is the stem-loop structure present in 3' untranslated regions (UTRs) of eukaryotic selenoprotein-encoding genes", "For eukaryotic selenoprotein mRNAs, it has been proposed that a conserved stem-loop structure designated the Sec insertion sequence (SECIS) in the 3'-untranslated (3'-UTR) region is required for recognition of UGA as a Sec codon", "3'-untranslated regions of selenoprotein genes contain a common stem-loop structure, selenocysteine insertion sequence (SECIS) element, that is necessary for decoding UGA as selenocysteine", 'Analyses of eukaryotic selenocysteine insertion sequence (SECIS) elements via computer folding programs, mutagenesis studies, and chemical and enzymatic probing has led to the derivation of a predicted consensus structural model for these elements. This model consists of a stem-loop or hairpin', "ECIS elements form stem-loop structures in the 3' untranslated regions (UTR) of eukaryotic mRNAs that encode selenoproteins", 'We report a detailed experimental study of the secondary structures of the SECIS elements ', 'It is characterized by a stem-loop structure', " in eukaryotic selenoprotein mRNAs, this stem-loop structure, the selenocysteine insertion sequence (SECIS) element, resides in the 3'-untranslated region", "ECIS elements are stem-loop structures located in the 3' untranslated regions (UTRs) of eukaryotic selenoprotein mRNAs", "eukaryotic selenocysteine UGA codons requires a stem-loop structure in the 3'UTR of mRNAs, the selenocysteine insertion sequence (SECIS) element", 'stem-loops and critical nucleotides similar to those in the SECIS elements ']

['SECIS (selenocysteine insertion sequence)']

['SECIS']

List interaction partners for the protein GATA1.

['Our work describes, for the first time, distinct GATA-1 interactions with the essential hematopoietic factor Gfi-1b, the repressive MeCP1 complex, and the chromatin remodeling ACF/WCRF complex, in addition to the known GATA-1/FOG-1 and GATA-1/TAL-1 complexes. We also provide evidence that distinct GATA-1 complexes are associated with specific GATA-1 functions in erythroid differentiation, for example, GATA-1/Gfi-1b with the suppression of cell proliferation and GATA-1/FOG-1/MeCP1 with the repression of other hematopoietic transcription programs. We next applied the biotinylation tag to Ldb-1, a known partner of GATA-1, and characterized a number of novel interaction partners that are essential in erythroid development, in particular, Eto-2, Lmo4, and CdK9. ', 'Endogenous GATA1 and LDB1 proteins were confirmed to bind to LMO2-C by MBP pull down analysis. ', 'LMO2-C can bind endogenous GATA1 and LDB1 protein in K562 cells and down regulates the expression of GPA.', 'We identify novel transcription factor binding partners for PIAS3 including ETS, EGR1, NR1I2, and GATA1.', 'At other differentiation stages, additional combinatorial interactions occurred between RUNX1 and its coregulators, GATA1 and ETS. ', 'Ldb1, a ubiquitously expressed LIM domain binding protein, is essential in a number of tissues during development. It interacts with Gata1, Tal1, E2A and Lmo2 to form a transcription factor complex regulating late erythroid genes. ', 'Using a biotinylation tagging/proteomics approach in erythroid cells, we describe distinct GATA-1 interactions with the essential hematopoietic factor Gfi-1b, the repressive MeCP1 complex and the chromatin remodeling ACF/WCRF complex, in addition to the known GATA-1/FOG-1 and GATA-1/TAL-1 complexes. Importantly, we show that FOG-1 mediates GATA-1 interactions with the MeCP1 complex, thus providing an explanation for the overlapping functions of these two factors in erythropoiesis.', "Here we show that Ski interacts with GATA1, a transcription factor essential in erythropoiesis. Using a Ski mutant deficient in GATA1 binding, we show that this Ski-GATA1 interaction is critical for Ski's ability to repress GATA1-mediated transcription and block erythroid differentiation. ", 'The zinc finger transcription factor GATA-1, a central mediator of erythroid gene expression, interacts with multiple proteins including FOG-1, EKLF, SP1, CBP/p300 and PU.1. ', 'tudies involving point mutants of GATA-1 have shown that a direct physical interaction between GATA-1 and FOG-1 is essential for normal human erythroid and megakaryocyte maturation in vivo. In addition, evidence has emerged that physical interaction between GATA-1 and the myeloid/lymphoid specific factor PU.1, an oncogene implicated in murine erythroleukemia, acts to functionally cross-antagonize one another. ']

['GATA-1 interact with factor Gfi-1b, the repressive MeCP1 complex, the chromatin remodeling ACF/WCRF complex, FOG-1, TAL-1, Ldb-1 and LMO2-C.', 'GATA1 interacts with the essential hematopoietic factor Gfi-1b, the repressive MeCP1 complex, the chromatin remodeling ACF/WCRF complex, in addition to the known GATA-1/FOG-1 and GATA-1/TAL-1 complexes. Ldb1 is a known partners of GATA1. LMO2-C can bind endogenous GATA1. Novel transcription factor binding partners for PIAS3 include GATA1. Combinatorial interactions occurre between RUNX1 and its coregulator GATA1. Ski interacts with GATA1. GATA-1 interacts with multiple proteins including FOG-1, EKLF, SP1, CBP/p300 and PU.1.']

['Gfi-1b', 'MeCP1', 'MeCP1 complex', 'ACF/WCRF complex', 'FOG-1', 'TAL-1', 'Ldb1', 'Ldb-1', 'LMO2-C', 'PIAS3', 'RUNX1', 'Ski', 'EKLF', 'SP1', 'CBP/p300', 'PU.1']

Are long non coding RNAs as conserved in sequence as protein coding genes?

['Most lncRNAs are under lower sequence constraints than protein-coding genes and lack conserved secondary structures, making it hard to predict them computationally.', 'hey are under stronger selective pressure than neutrally evolving sequences-particularly in their promoter regions, which display levels of selection comparable to protein-coding genes.', 'bout one-third seem to have arisen within the primate lineage.']

['No. Most long non coding RNAs (lncRNAs) are under lower sequence constraints than protein-coding genes.']

['no']

Which miRNAs could be used as potential biomarkers for epithelial ovarian cancer?

['Finally, five promising differentially miRNAs (miR-200a, miR-100, miR-141, miR-200b, and miR-200c) were reported with the consistent direction in four or more studies. MiR-200a, miR-200b, miR-200c, and miR-141, all of them belong to miR-200 family, were reported with consistently up-regulated in at least 4 studies, whereas miR-100 was reported with down-regulated in 4 studies', 'Upregulation of microRNA-203 is associated with advanced tumor progression and poor prognosis in epithelial ovarian cancer', 'multivariate analysis showed that the status of miR-203 expression was an independent predictor for both overall survival and progression-free survival in EOC. These findings provide the convincing evidence for the first time that the upregulation of miR-203 may serve as a novel molecular marker to predict the aggressive tumor progression and unfavorable prognosis of EOC patients', 'Some, but not all, of the data indicated that the miR-200 family was dysregulated in a variety of malignancies. In this study, we demonstrated that miR-200a and E-cadherin were significantly upregulated in EOC compared to benign epithelial ovarian cysts and normal ovarian tissues', 'There was a significantly positive correlation between miR-200a and E-cadherin in EOC. The biphasic expression pattern suggested that miR-200a levels may serve as novel biomarkers for the early detection of EOC, and miR-200a and E-cadherin are candidate targets for the development of new treatment modalities against ovarian cancer', 'Kaplan-Meier analysis showed low miR-510 expression, low miR-509-5p expression, and advanced FIGO stage, and chemotherapy resistance were significantly associated with poorer overall survival (P < 0.05). Our results suggest that miRNAs may play a role in the progression of OSC, and miR-510 and miR-509-5p may be considered novel-candidate clinical biomarkers for predicting OSC outcome', 'The qRT-PCR results showed that miR-510, miR-509-5p, and miR-508-3p were significantly downregulated and that miR-483-5p was upregulated in stage III OSC compared with stage I, which was consistent with the microarray results', 'In this study, we examined serum miR-21 levels in epithelial ovarian cancer (EOC) patients, and explored its association with clinicopathological factors and prognosis. The results showed significantly higher serum miR-21 levels in EOC patients than in healthy controls. In addition, increased serum miR-21 expression was correlated with advanced FIGO stage, high tumor grade, and shortened overall survival. These findings indicate that serum miR-21 may serve as a novel diagnostic and prognostic marker, and be used as a therapeutic target for the treatment of EOC', 'Identification of serum microRNA-21 as a biomarker for early detection and prognosis in human epithelial ovarian cancer', 'Serum miR-132, miR-26a, let-7b, and miR-145 could be considered as potential candidates as novel biomarkers in serous ovarian cancer.', 'Among the miRNAs that showed a consistent regulation tendency through all specimens and showed more than a 2-fold difference in serum, 5 miRNAs (miR-132, miR-26a, let-7b, miR-145, and miR-143) were determined as the 5 most markedly down-regulated miRNAs in the serum from ovarian cancer patients with respect to those of controls. Four miRNAs (miR-132, miR-26a, let-7b, and miR-145) out of 5 selected miRNAs were significantly underexpressed in the serum of ovarian cancer patients in qRT-PCR', ' microRNA (miR)-182, miR-200a, miR-200b and miR-200c were highly overexpressed in the SEOC cell lines relative to normal human ovarian surface epithelial cells and were assessed in RNA extracted from serum as candidate biomarkers', 'Together, these results suggest that low miR-100 expression may be an independent poor prognostic factor and miR-100 can function as a tumor suppressor by targeting PLK1 in human EOCs', 'Prognostic implications of microRNA-100 and its functional roles in human epithelial ovarian cancer', 'Taken together, miR-152 and miR-148a may be involved in the carcinogenesis of ovarian cancer through deregulation of cell proliferation. They may be novel biomarkers for early detection or therapeutic targets of ovarian cancer', 'MicroRNA let-7a: a potential marker for selection of paclitaxel in ovarian cancer management', ' The study suggests that the beneficial impact of the addition of paclitaxel on EOC survival was significantly linked to let-7a levels, and that miRNAs such as let-7a may be a useful marker for selection of chemotherapeutic agents in EOC management', 'miR-200c has potential as a predictor of survival, and is a biomarker of relapse, in stage I EOC', 'MicroRNA microarray identifies Let-7i as a novel biomarker and therapeutic target in human epithelial ovarian cancer', ' our results strongly suggest that let-7i might be used as a therapeutic target to modulate platinum-based chemotherapy and as a biomarker to predict chemotherapy response and survival in patients with ovarian cancer', 'miRNAs-21, 92 and 93 are known oncogenes with therapeutic and biomarker potential', 'Serum miR-132, miR-26a, let-7b, and miR-145 could be considered as potential candidates as novel biomarkers in serous ovarian cancer']

['miR-200a, miR-100, miR-141, miR-200b, miR-200c, miR-203, miR-510, miR-509-5p, miR-132, miR-26a, let-7b, miR-145, miR-182, miR-152, miR-148a, let-7a, let-7i, miR-21, miR-92 and miR-93 could be used as potential biomarkers for epithelial ovarian cancer.']

['let-7a', 'let-7b', 'let-7i', 'miR-21', 'miR-26a', 'miR-92', 'miR-93', 'miR-100', 'miR-132', 'miR-141', 'miR-145', 'miR-148a', 'miR-152', 'miR-182', 'miR-200a', 'miR-200b', 'miR-200c', 'miR-203', 'miR-509-5p', 'miR-510']

Do Conserved noncoding elements act as enhancers?

['The aCNEs are rich in tissue-specific enhancers', 'Transgenic zebrafish assay of some human CNE enhancers that have been lost in teleosts', 'Conserved noncoding elements (CNEs) in vertebrate genomes often act as developmental enhancers,', 'In all four cases where the zebra fish and human CNE display a similar expression pattern in zebra fish, the human CNE also displays a similar expression pattern in mouse. This suggests that the endogenous enhancer activity of ∼30% of human CNEs can be determined from experiments in zebra fish', 'If these ancient CNEs are indeed enhancers directing tissue-specific expression of Hox genes, divergence of their sequences in vertebrate lineages might have led to altered expression patterns and presumably the functions of their associated Hox genes.', 'Comparisons of noncoding sequences of the elephant shark and human Hox clusters have identified a large number of conserved noncoding elements (CNEs), which represent putative cis-regulatory elements that may be involved in the regulation of Hox genes.', 'Animal genomes possess highly conserved cis-regulatory sequences that are often found near genes that regulate transcription and development.', 'We test 42 of our PCNEs in transgenic zebrafish assays--including examples from vertebrates and amphioxus--and find that the majority are functional enhancers.', 'The genomes of vertebrates, flies, and nematodes contain highly conserved noncoding elements (CNEs). CNEs cluster around genes that regulate development, and where tested, they can act as transcriptional enhancers.', ', we identified 17 highly conserved noncoding elements, 9 of which revealed specific acetylation marks in chromatin-immunoprecipitation and microarray (ChIP-chip) assays performed across 250 kb of the Lmo2 locus in 11 cell types covering different stages of hematopoietic differentiation. All candidate regulatory regions were tested in transgenic mice. An extended LMO2 proximal promoter fragment displayed strong endothelial activity, while the distal promoter showed weak forebrain activity. Eight of the 15 distal candidate elements functioned as enhancers,', 'Pan-vertebrate developmental cis-regulatory elements are discernible as highly conserved noncoding elements (HCNEs) and are often dispersed over large areas around the pleiotropic genes whose expression they control.', 'HCNEs of both human and zebrafish function as specific developmental enhancers in zebrafish.', 'several transcriptional enhancers are conserved between amphioxus and vertebrates--a very wide phylogenetic distance.', 'We recently described GRBs in vertebrates, where most HCNEs function as enhancers', 'Besides developmental regulators that are likely targets of HCNE enhancers', 'We identify and characterize highly conserved noncoding elements flanking the TNF gene, which undergo activation-dependent intrachromosomal interactions. These elements, hypersensitive site (HSS)-9 and HSS+3 (9 kb upstream and 3 kb downstream of the TNF gene, respectively), contain DNase I hypersensitive sites in naive, T helper 1, and T helper 2 primary T cells. Both HSS-9 and HSS+3 inducibly associate with acetylated histones, indicative of chromatin remodeling, bind the transcription factor nuclear factor of activated T cells (NFAT)p in vitro and in vivo, and function as enhancers', 'We used the sequence signatures identified by this approach to successfully assign tissue-specific predictions to approximately 328,000 human-mouse conserved noncoding elements in the human genome. By overlapping these genome-wide predictions with a data set of enhancers validated in vivo, in transgenic mice, we were able to confirm our results with a 28% sensitivity and 50% precision.', 'Fish-mammal genomic comparisons have proved powerful in identifying conserved noncoding elements likely to be cis-regulatory in nature, and the majority of those tested in vivo have been shown to act as tissue-specific enhancers associated with genes involved in transcriptional regulation of development.', 'uncovered two anciently conserved noncoding sequences (CNS) upstream of COUP-TFII (CNS-62kb and CNS-66kb). Testing these two elements using reporter constructs in liver cells (HepG2) revealed that CNS-66kb, but not CNS-62kb, yielded robust in vitro enhancer activity.']

['An important percentage of noncoding elements conserved across distant species shows enhancer activity and other forms of regulatory functionality.']

['yes']

For what is Protein A from Staphylococcus aureus used in biochemistry?

['Staphylococcal protein A (SpA) binds Fcγ and VH3 clan Fab domains of human and animal immunoglobulin (Ig) with each of its five Ig binding domains (IgBDs),', 'Protein A from Staphylococcus aureus plays one key role as an immobilized affinity ligand for the purification of antibodies. ', 'The recombinant SpA is also widely used in biotechnology to purify polyclonal and monoclonal immunoglobulin G antibodies.', 'Staphylococcus aureus protein A (SpA) is the most popular affinity ligand for immunoglobulin G1 (IgG1).', 'Staphylococcal Protein A (SPA), a cell wall protein of Staphylococcus aureus, is in high demand because of its ability to bind immunoglobulins.', 'Protein A from the bacterium Staphylococcus aureus (SpA) has been widely used as an affinity ligand for purification of immunoglobulin G (IgG). ', 'Affinity chromatography with protein A from Staphylococcus aureus (SpA) is the most widespread and accepted methodology for antibody capture during the downstream process of antibody manufacturing', 'Affinity chromatography using protein A from Staphylococcus aureus as the ligand has been widely used for the isolation of immunoglobulin G (IgG) from various species.']

['Protein A from the bacterium Staphylococcus aureus (SpA) is used as an affinity ligand for purification of immunoglobulin G (IgG).']

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What is evaluated using the EORTC QLQ – INFO25 questionnaire?

['The EORTC QLQ-INFO25 was used to evaluate the perceived level of and satisfaction with information. ', 'METHODS: The EORTC information questionnaire, EORTC QLQ-INFO25, was administered during the treatment process.', 'The EORTC information questionnaire, EORTC QLQ-INFO25. Validation study for Spanish patients.', 'INTRODUCTION: The EORTC QLQ-INFO25 evaluates the information received by cancer patients. ', 'Information disclosure to cancer patients: EORTC QLQ-INFO25 questionnaire.', "We highlight the need to assess patients' characteristics and desires through questionnaires and interviews and present the European Organisation for Research and Treatment of Cancer Quality of Life Group information questionnaire (EORTC QLQ-INFO 25). This instrument evaluates the level of information patients have received in different areas of their disease, treatment and care, and evaluates qualitative aspects. ", 'AIM: The EORTC Quality of Life (QOL) Group has developed an instrument to evaluate the information received by cancer patients. This study assessed the psychometric characteristics of the EORTC INFO module in a large international/multi-cultural sample of cancer patients. ', 'An international validation study of the EORTC QLQ-INFO25 questionnaire: an instrument to assess the information given to cancer patients.', 'The EORTC QLQ-INFO25 was used to evaluate the perceived level of and satisfaction with information.', 'The EORTC QLQ-INFO25 evaluates the information received by cancer patients', 'The EORTC QLQ-INFO25 was used to evaluate the perceived level of and satisfaction with information']

['The European Organisation for Research and Treatment of Cancer Quality of Life Group information questionnaire (EORTC QLQ-INFO 25) evaluates the level of information patients have received in different areas of their disease, treatment and care, and evaluates qualitative aspects together with satisfaction with information.']

[]

What is an approximate number of CTCF binding sites in the human genome?

['To study CTCF multivalency in\xa0vivo, we define ZF binding requirements at ∼50,000 genomic sites in primary lymphocytes. ', 'However, only ~3,700 out of the ~5,700 CTCFL- and ~31,000 CTCF-binding sites overlap.']

['The number of CTCF binding sites in the human genome lies between 31,000 and 50,000.']

['30,000-50,000']

Which miRNA is targeted by SRY/Sox9?

['Does the linear Sry transcript function as a ceRNA for miR-138?', 'Recently, the sex determining region Y ( Sry) and the cerebellar degeneration-related protein 1 ( CDR1as) RNA transcripts have been described to function as a new class of post-transcriptional regulatory RNAs that behave as circular endogenous RNA sponges for the micro RNAs (miRNAs) miR-138 and miR-7, respectively. ', ' it is reasonable to think that the linear Sry sense transcript could additionally act as a miRNA sponge, or as an endogenous competing RNA for miR-138.', 'Results indicated that miR-138 directly targeted SRY-related high mobility group box 4 (SOX4) and hypoxia-inducible factor-1α (HIF-1α), and overexpression of SOX4 and HIF-1α effectively reversed the miR-138-mediated suppression of cell invasion.', 'We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. ']

['The testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon', 'Does the linear Sry transcript function as a ceRNA for miR-138?. Recently, the sex determining region Y ( Sry) and the cerebellar degeneration-related protein 1 ( CDR1as) RNA transcripts have been described to function as a new class of post-transcriptional regulatory RNAs that behave as circular endogenous RNA sponges for the micro RNAs (miRNAs) miR-138 and miR-7, respectively. it is reasonable to think that the linear Sry sense transcript could additionally act as a miRNA sponge, or as an endogenous competing RNA for miR-138. Results indicated that miR-138 directly targeted SRY-related high mobility group box 4 (SOX4) and hypoxia-inducible factor-1 (HIF-1), and overexpression of SOX4 and HIF-1 effectively reversed the miR-138-mediated suppression of cell invasion. We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. ', ', the sex determining region y ( sry) and the cerebellar degeneration-related protein 1 ( cdr1as) rna transcripts have been described to function as a new class of post-transcriptional regulatory rnas that behave as circular endogenous rna sponges for the micro rnas (mirnas) mir-138 and mir-7 , respectively . ', 'Recently, the sex determining region Y ( Sry) and the cerebellar degeneration-related protein 1 ( CDR1as) RNA transcripts have been described to function as a new class of post-transcriptional regulatory RNAs that behave as circular endogenous RNA sponges for the micro RNAs (miRNAs) miR-138 and miR-7, respectively. it is reasonable to think that the linear Sry sense transcript could additionally act as a miRNA sponge, or as an endogenous competing RNA for miR-138.', 'Recently, the sex determining region Y ( Sry) and the cerebellar degeneration-related protein 1 ( CDR1as) RNA transcripts have been described to function as a new class of post-transcriptional regulatory RNAs that behave as circular endogenous RNA sponges for the micro RNAs (miRNAs) miR-138 and miR-7, respectively.', 'Does the linear Sry transcript function as a ceRNA for miR-138?. Results indicated that miR-138 directly targeted SRY-related high mobility group box 4 (SOX4) and hypoxia-inducible factor-1 (HIF-1), and overexpression of SOX4 and HIF-1 effectively reversed the miR-138-mediated suppression of cell invasion. We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. it is reasonable to think that the linear Sry sense transcript could additionally act as a miRNA sponge, or as an endogenous competing RNA for miR-138. Recently, the sex determining region Y ( Sry) and the cerebellar degeneration-related protein 1 ( CDR1as) RNA transcripts have been described to function as a new class of post-transcriptional regulatory RNAs that behave as circular endogenous RNA sponges for the micro RNAs (miRNAs) miR-138 and miR-7, respectively. ', 'recently, the sex determining region y ( sry) and the cerebellar degeneration-related protein 1 ( cdr1as) rna transcripts have been described to function as a new class of post-transcriptional regulatory rnas that behave as circular endogenous rna sponges for the micro rnas (mirnas) mir-138 and mir-7, respectively.', 'Recently, the sex determining region Y ( Sry) and the cerebellar degeneration-related protein 1 ( CDR1as) RNA transcripts have been described to function as a new class of post-transcriptional regulatory RNAs that behave as circular endogenous RNA sponges for the micro RNAs (miRNAs) miR-138 and miR-7, respectively. Metastasis is the major factor affecting patient survival in ovarian cancer. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that act by direct base pairing to target sites within untranslated regions of messenger RNAs.', 'Results indicated that miR-138 directly targeted SRY-related high mobility group box 4 (SOX4) and hypoxia-inducible factor-1α (HIF-1α), and overexpression of SOX4 and HIF-1α effectively reversed the miR-138-mediated suppression of cell invasion. We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon.', 'Does the linear Sry transcript function as a ceRNA for miR-138? Recently, the sex determining region Y ( Sry) and the cerebellar degeneration-related protein 1 ( CDR1as) RNA transcripts have been described to function as a new class of post-transcriptional regulatory RNAs that behave as circular endogenous RNA sponges for the micro RNAs (miRNAs) miR-138 and miR-7, respectively.', 'Recently, the sex determining region Y ( Sry) and the cerebellar degeneration-related protein 1 ( CDR1as) RNA transcripts have been described to function as a new class of post-transcriptional regulatory RNAs that behave as circular endogenous RNA sponges for the micro RNAs (miRNAs) miR-138 and miR-7, respectively. Epidermal growth factor receptor acted as the downstream molecule of SOX4 by way of direct transcriptional control, whereas Slug was the downstream molecule of HIF-1α by way of proteasome-mediated degradation.', 'Results indicated that miR-138 directly targeted SRY-related high mobility group box 4 (SOX4) and hypoxia-inducible factor-1α (HIF-1α), and overexpression of SOX4 and HIF-1α effectively reversed the miR-138-mediated suppression of cell invasion. We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. ']

['mir-138']

What kind of analyses are performed with the software tool "unipept"

['Unipept is an open source web application that is designed for metaproteomics analysis with a focus on interactive datavisualization. ', 'The Unique Peptide Finder (http://unipept.ugent.be/peptidefinder) is an interactive web application to quickly hunt for tryptic peptides that are unique to a particular species, genus, or any other taxon.', 'Computations are extremely fast since they are underpinned by the Unipept database, the lowest common ancestor algorithm implemented in Unipept and modern web technologies that facilitate in-browser data storage and parallel processing.', 'Unipept (http://unipept.ugent.be) is a web application that offers a user-friendly way to explore the biodiversity of complex metaproteome samples by providing interactive visualizations.', 'Outputted results are compatible with tools for taxonomic and functional characterization (e.g. Unipept, MEGAN5)', 'The Unipept web application (http://unipept.ugent.be) supports biodiversity analysis of large and complex metaproteome samples using tryptic peptide information obtained from shotgun MS/MS experiments.']

['The Unipept web application (http://unipept.ugent.be) supports biodiversity analysis of large and complex metaproteome samples using tryptic peptide information obtained from shotgun MS/MS experiments. The application designed for metaproteomics analysis with a focus on interactive datavisualization.']

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Is vemurafenib used for thyroid cancer?

['Vemurafenib in patients with BRAF(V600E)-positive metastatic or unresectable papillary thyroid cancer refractory to radioactive iodine: a non-randomised, multicentre, open-label, phase 2 trial.', 'Vemurafenib, an oncogenic BRAF kinase inhibitor approved for BRAF-positive melanoma, showed clinical benefit in three patients with BRAF(V600E)-positive papillary thyroid cancer in a phase 1 trial.', 'INTERPRETATION: Vemurafenib showed antitumour activity in patients with progressive, BRAF(V600E)-positive papillary thyroid cancer refractory to radioactive iodine who had never been treated with a multikinase inhibitor. ', 'CONTEXT: Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.', 'Efficacy and tolerability of vemurafenib in patients with BRAF(V600E) -positive papillary thyroid cancer: M.D. Anderson Cancer Center off label experience.', 'CONCLUSIONS: Vemurafenib is a potentially effective and well-tolerated treatment strategy in patients with advanced PTC harboring the BRAF(V600E) mutation.', 'The US Food and Drug Administration-approved BRAF inhibitors, vemurafenib and dabrafenib, have demonstrated superior efficacy in patients with BRAF-mutant melanomas but have limited efficacy in BRAF-mutant colorectal cancer. Little is known at this time regarding BRAF inhibitors in thyroid cancer. Initial reports in patients with progressive, radioactive iodine-refractory BRAF-mutant papillary thyroid cancer suggest response rates of approximately 30-40%.', 'Use of vemurafenib in anaplastic thyroid carcinoma: a case report.', 'Finally, we found that propranolol can amplify the cytotoxicity of vemurafenib and sensitize thyroid cancer cells to cytotoxic effect of vemurafenib.', 'CONTEXT: Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.OBJECTIVE: To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.DESIGN: A retrospective review at MD Anderson Cancer Center.METHODS: The best responses were evaluated using RECIST v1.1.', 'Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.A retrospective review at MD Anderson Cancer Center.The best responses were evaluated using RECIST v1.1', 'CONTEXT: Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.OBJECTIVE: To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.DESIGN: A retrospective review at MD Anderson Cancer Center.METHODS: The best responses were evaluated using RECIST v1.1. ', 'Finally, we found that propranolol can amplify the cytotoxicity of vemurafenib and sensitize thyroid cancer cells to cytotoxic effect of vemurafenib.', 'Metformin or rapamycin adjuvant treatment may provide clinical benefits with minimal side effects to BRAFV600E-positive advanced thyroid cancer patients treated with vemurafenib.', 'Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.A retrospective review at MD Anderson Cancer Center.The best responses were evaluated using RECIST v1.1.', 'Our data demonstrate that vemurafenib induces ER stress response-mediated autophagy in thyroid cancer and autophagy inhibition may be a beneficial strategy to sensitize BRAF-mutant thyroid cancer to vemurafenib..', 'Combination of vemurafenib and metformin decreased cell viability and increased apoptosis in both BCPAP papillary thyroid cancer cells and 8505c anaplastic thyroid cancer cells.', 'Targeting autophagy sensitizes BRAF-mutant thyroid cancer to vemurafenib.', 'Propranolol sensitizes thyroid cancer cells to cytotoxic effect of vemurafenib.', 'mTOR inhibitors sensitize thyroid cancer cells to cytotoxic effect of vemurafenib.', 'Vemurafenib induced a high level of autophagy in BRAF-mutant thyroid cancer cells.']

['Yes. Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.']

['yes']

What is the role of per genes in circadian rhythm control?

['Temporal expression of genes involved in cell cycle regulation and tumor suppression, such as c-Myc, Cyclin D1, Cyclin A, Mdm-2 and Gadd45alpha is deregulated in mPer2 mutant mice.', 'The Period (Per) genes are key circadian rhythm regulators in mammals. Expression of the mouse Per (mPer) genes have diurnal pattern in the suprachiamstic nuclei and in peripheral tissues. Genetic ablation mPER1 and mPER2 function results in a complete loss of circadian rhythm control based on wheel running activity in mice. In addition, these animals also display apparent premature aging and significant increase in neoplastic and hyperplastic phenotypes.', 'Period (Per) genes are key circadian rhythm regulators in mammals. Expression of mouse Per (mPer) genes has a diurnal pattern in the suprachiasmatic nucleus and in peripheral tissues. Genetic ablation mPER1 and mPER2 function results in a complete loss of circadian rhythm control based on wheel-running activity in mice. In addition, these animals also display apparent premature aging and a significant increase in neoplastic and hyperplastic phenotypes.', 'The temporal expression of genes involved in cell cycle regulation and tumor suppression, such as c-Myc, Cyclin D1, Cyclin A, Mdm-2, and Gadd45alpha, is deregulated in mPer2 mutant mice.']

['PER1 and PER2 genes are involved in cell cycle regulation and tumor suppression, controlling expression of genes such as c-Myc, Cyclin D1, Cyclin A, Mdm-2 and Gadd45alpha.']

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What are prions?

['Prion diseases are protein conformation disorders and neither caused by viroid or virus but is a transmissible particle labeled a prion by Pruisner. Normal prion protein becomes infectious by a different folding, but the triggers are not known. ', 'Prions are proteins most commonly associated with fatal neurodegenerative diseases in mammals but are also responsible for a number of harmless heritable phenotypes in yeast. These states arise when a misfolded form of a protein appears and, rather than be removed by cellular quality control mechanisms, persists. The misfolded prion protein forms aggregates and is capable of converting normally folded protein to the misfolded state through direct interaction between the two forms.', 'Prion diseases or transmissible spongiform encephalopathies are fatal neurodegenerative diseases characterized by the aggregation and deposition of the misfolded prion protein in the brain. ', "Several neurodegenerative diseases such as transmissible spongiform encephalopathies, Alzheimer's and Parkinson's diseases are caused by the conversion of cellular proteins to a pathogenic conformer. ", 'Prions are self-propagating infectious protein isoforms.', 'Prions are units of propagation of an altered state of a protein or proteins; prions can propagate from organism to organism, through cooption of other protein copies']

['Prion diseases are protein conformation disorders and neither caused by viroid or virus but is a transmissible particle labeled a prion by Pruisner. Normal prion protein becomes infectious by a different folding, but the triggers are not known. ', 'A prion is an infectious agent composed entirely of protein and is responsible for a number of neurodegenerative diseases. Prions are self-propagating infectious protein isoforms. ']

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How can transcranial sonography assist in the placement of electrodes into the subthalamic nucleus for patients with Parkinson's disease?

['["After measuring thermal effects of TCS and imaging artefact sizes of DBS lead using a skull phantom, we prospectively enrolled 34 patients with DBS of globus pallidus internus, ventro-intermediate thalamic or subthalamic nucleus. TCS had no influence on lead temperature, electrical parameters of DBS device or clinical state of patients. TCS measures of lead coordinates agreed with MRI measures in anterior-posterior and medial-lateral axis. Lead dislocation requiring reinsertion was reliably detected.", "TCS may therefore become a first-choice modality to monitor lead location.", "Two pilot studies have demonstrated that the intraoperative visualization with TCS and the TCS-assisted insertion of deep-brain stimulation (DBS) electrodes into the subthalamic nucleus and the globus pallidus interna are feasible and safe provided there is exact knowledge on the extent of electrode TCS imaging artifacts. ", "Peroperative transcranial sonography for electrode placement into the targeted subthalamic nucleus of patients with Parkinson disease: technical note", "The correct anatomic position of the electrode tip could be indirectly assessed thanks to the topographic relationship of the STN with the hyperechogenic substantia nigra and the nucleus ruber.", "CONCLUSIONS: Transcranial sonography is easily feasible during stereotactic surgery. In combination with the clinical effects of electrostimulation on the symptoms of Parkinson\'s disease and with stereotactic x-ray images, it enables the assessment and the documentation of the correct position of implanted STN electrodes in real time.", "After measuring thermal effects of TCS and imaging artefact sizes of DBS lead using a skull phantom, we prospectively enrolled 34 patients with DBS of globus pallidus internus, ventro-intermediate thalamic or subthalamic nucleus", "Two pilot studies have demonstrated that the intraoperative visualization with TCS and the TCS-assisted insertion of deep-brain stimulation (DBS) electrodes into the subthalamic nucleus and the globus pallidus interna are feasible and safe provided there is exact knowledge on the extent of electrode TCS imaging artifacts"]']

Transcranial sonography can assist in the placement of electrodes into the subthalamic nucleus for patients with Parkinson's disease by providing intraoperative visualization and TCS-assisted insertion of deep-brain stimulation electrodes. It helps in detecting lead dislocation requiring reinsertion and allows for the assessment and documentation of the correct position of implanted STN electrodes in real time, in combination with clinical effects of electrostimulation and stereotactic x-ray images.

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Is the number of described human nuclear mutations less than 50000?

['The number of known mutations in human nuclear genes, underlying or associated with human inherited disease, has now exceeded 100,000 in more than 3700 different genes (Human Gene Mutation Database).', 'The Human Gene Mutation Database (HGMD®) is a comprehensive collection of germline mutations in nuclear genes that underlie, or are associated with, human inherited disease. By June 2013, the database contained over 141,000 different lesions detected in over 5,700 different genes, with new mutation entries currently accumulating at a rate exceeding 10,000 per annum.', 'By March 2012, the database contained in excess of 123,600 different lesions (HGMD Professional release 2012.1) detected in 4,514 different nuclear genes, with new entries']

['No, The number of known mutations in human nuclear genes, underlying or associated with human inherited disease, has now exceeded 100,000 in more than 3700 different genes (Human Gene Mutation Database).']

['no']

Which are the main functions of G3BP1 and G3BP2 proteins?

['Both G3BP1 and G3BP2 contribute to stress granule formation', 'G3BP1, G3BP2 and CAPRIN1 are required for translation of interferon stimulated mRNAs and are targeted by a dengue virus non-coding RNA', 'We examined three conserved host RNA-binding proteins (RBPs) G3BP1, G3BP2 and CAPRIN1 in dengue virus (DENV-2) infection and found them to be novel regulators of the interferon (IFN) response against DENV-2', 'Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is a component of SGs that initiates the assembly of SGs by forming a multimer', 'Although single knockdown of either G3BP1 or G3BP2 in 293T cells partially reduced the number of SG-positive cells induced by arsenite, the knockdowns of both genes significantly reduced the number', 'like G3BP1, the overexpression of G3BP2 induced SGs even without stress stimuli', 'Collectively, these results suggest that both G3BP1 and G3BP2 play a role in the formation of SGs in various human cells and thereby recovery from these cellular stresses', 'Regulation of PMP22 mRNA by G3BP1 affects cell proliferation in breast cancer cells', 'G3BP has been reported to both stabilize and induce degradation of specific mRNAs', 'Global gene expression analyses of G3BP1- and G3BP2-depleted cells indicate that primarily G3BP1, and much less G3BP2, influences mRNA expression levels. Peripheral myelin protein 22 (PMP22) was one gene that was significantly influenced by G3BP1 depletion which led to a 2-3 fold increased expression', 'Depletion of PMP22 resulted in increased proliferation and the G3BP1-mediated effect on proliferation was not seen upon PMP22-depletion', 'Ras-GTPase-activating protein SH3 domain-binding proteins (G3BP) are overexpressed in various human tumors and participate in several signaling pathways involved in growth, differentiation and apoptosis', 'Two related proteins found in association with nsP4 at both times of infection, GTPase-activating protein (SH3 domain) binding protein 1 (G3BP1) and G3BP2 were also previously identified as associated with SINV nsP2 and nsP3. We demonstrate a likely overlapping role for these host factors in limiting SINV replication events', 'Modulation of p53 and MDM2 activity by novel interaction with Ras-GAP binding proteins (G3BP)', 'we have found that members of the Ras network of proteins, Ras-GTPase activating protein-SH3-domain-binding proteins 1 and 2 (G3BP1 and 2), bind to p53 in vitro and in vivo. Our data show that expression of G3BPs leads to the redistribution of p53 from the nucleus to the cytoplasm. The G3BP2 isoform additionally associated with murine double minute 2 (MDM2), a negative regulator of p53. G3BP2 expression resulted in significant reduction in MDM2-mediated p53 ubiquitylation and degradation. Interestingly, MDM2 was also stabilized in G3BP2-expressing cells and its ability to ubiquitylate itself was compromised', 'We identified several proteins, including DDX6, G3BP1, G3BP2, Caprin1, and USP10, implicated in P body (PB) and stress granule (SG) function, and not previously known to bind DENV RNAs.', "Additional experiments demonstrate that, in contrast to DDX6, the SG proteins G3BP1, G3BP2, Caprin1 and USP10 bind to the variable region (VR) in the 3' UTR.", 'G3BP1, G3BP2 and CAPRIN1 are required for translation of interferon stimulated mRNAs and are targeted by a dengue virus non-coding RNA.', 'Both G3BP1 and G3BP2 contribute to stress granule formation.', 'Although single knockdown of either G3BP1 or G3BP2 in 293T cells partially reduced the number of SG-positive cells induced by arsenite, the knockdowns of both genes significantly reduced the number. ', 'Collectively, these results suggest that both G3BP1 and G3BP2 play a role in the formation of SGs in various human cells and thereby recovery from these cellular stresses.', 'Furthermore, expression of shRNA targeting either G3BP1 or G3BP2 in human cancer cell lines resulted in marked upregulation of p53 levels and activity. ', 'Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is a component of SGs that initiates the assembly of SGs by forming a multimer.', 'Although single knockdown of either G3BP1 or G3BP2 in 293T cells partially reduced the number of SG-positive cells induced by arsenite, the knockdowns of both genes significantly reduced the number.', 'Moreover, like G3BP1, the overexpression of G3BP2 induced SGs even without stress stimuli.', 'We found that HDAC6 interacts with another SG protein, G3BP (Ras-GTPase-activating protein SH3 domain-binding protein 1), and localizes to SGs under all stress conditions tested.', 'Dengue virus (DENV) is a rapidly re-emerging flavivirus that causes dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), diseases for which there are no available therapies or vaccines.\xa0 The DENV-2 positive-strand RNA genome contains 5\' and 3\' untranslated regions (UTRs) that have been shown to form secondary structures required for virus replication and interaction with host cell proteins.\xa0 In order to comprehensively identify host cell factors that bind the DENV-2 UTRs, we performed RNA chromatography, using the DENV-2 5\' and 3\' UTRs as "bait", combined with quantitative mass spectrometry.\xa0 We identified several proteins, including DDX6, G3BP1, G3BP2, Caprin1, and USP10, implicated in P body (PB) and stress granule (SG) function, and not previously known to bind DENV RNAs.', "\xa0Additional experiments demonstrate that, in contrast to DDX6, the SG proteins G3BP1, G3BP2, Caprin1 and USP10 bind to the variable region (VR) in the 3' UTR."]

['The main functions of G3BP1 and/or G3BP2 include translation of interferon stimulated mRNAs during dengue virus infection, initiation of assembly of stress granules, regulation of PMP22 mRNA which was found to affect cell proliferation in breast cancer cells, participation in several signaling pathways involved in growth, differentiation and apoptosis in human tumor cells after overexpression, limit viral replication events during Sindbis virus (SINV) infection, and modulation of p53 and MDM2 activity.']

['Translation of interferon stimulated mRNAs during dengue virus infection', 'Initiation of assembly of stress granules', 'Regulation of PMP22 mRNA which was found to affect cell proliferation in breast cancer cells', 'Participation in several signaling pathways involved in growth, differentiation and apoptosis in human tumor cells after overexpression', 'Limit viral replication events during Sindbis virus (SINV) infection', 'Modulation of p53 and MDM2 activity']

What was the aim of the COSS (Carotid Occlusion Surgery Study) clinical trial?

['The Carotid Occlusion Surgery Study (COSS) was conducted to determine if superficial temporal artery-middle cerebral artery (STA-MCA) bypass, when added to the best medical therapy, would reduce subsequent ipsilateral stroke in patients with complete internal carotid artery (ICA) occlusion and an elevated oxygen extraction fraction (OEF) in the cerebral hemisphere distal to the occlusion.', 'Extracranial-intracranial bypass surgery for stroke prevention in hemodynamic cerebral ischemia: the Carotid Occlusion Surgery Study randomized trial.', 'To test the hypothesis that extracranial-intracranial (EC-IC) bypass surgery, added to best medical therapy, reduces subsequent ipsilateral ischemic stroke in patients with recently symptomatic AICAO and hemodynamic cerebral ischemia. ', 'The Carotid Occlusion Surgery Study (COSS) was a large, prospective clinical trial that examined whether superficial temporal artery-middle cerebral artery (STA-MCA) bypass, in addition to best medical therapy, reduced the risk of ipsilateral ischemic stroke in patients with carotid artery occlusion and hemodynamic cerebral ischemia.']

['The Carotid Occlusion Surgery Study (COSS) was conducted to determine if superficial temporal artery-middle cerebral artery (STA-MCA) bypass, when added to the best medical therapy, would reduce subsequent ipsilateral stroke in patients with complete internal carotid artery (ICA) occlusion and an elevated oxygen extraction fraction (OEF) in the cerebral hemisphere distal to the occlusion.']

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What is Desomorphine?

['Desomorphine is the semi-synthetic opioid claimed to be the main component of krokodil', 'Desomorphine is an opioid misused as "crocodile", a cheaper alternative to heroin', '"Krokodil" is the street name for the semi-synthetic opioid derivative desomorphine.', 'Desomorphine is an opioid misused as "crocodile", a cheaper alternative to heroin.', 'ince Soviet period the most popular injective narcotics have been opioids: home-made opium, heroine, buprenorphine and home-made desomorphine ("Krokodile") replacing each other on the black market. ', 'ous increase in the number of addicted individuals since then. The psychoactive core agent of Krokodil is desomorphine, an opioid-analogon that can be manufactured by boiling tablets containing codeine and other ingredients', 'The core agent of "Krokodil" is desomorphine, an opioid-analogue that can be easily and cheaply manufactured by oneself.']

['Desomorphine is an opioid misused as "crocodile", a cheaper alternative to heroin Desomorphine is the semi-synthetic opioid claimed to be the main component of krokodil', 'Desomorphine is an opioid misused as "crocodile", a cheaper alternative to heroin', 'Desomorphine is the semi-synthetic opioid claimed to be the main component of krokodil', '"Krokodil" is the street name for the homemade injectable mixture that has been used as a cheap substitute for heroin. Desomorphine is an opioid misused as "crocodile", a cheaper alternative to heroin.', 'Desomorphine is the semi-synthetic opioid claimed to be the main component of krokodil Desomorphine is an opioid misused as "crocodile", a cheaper alternative to heroin', 'Desomorphine is an opioid drug which is often synthsised using a combination of readily available ingredients and is often available on the "street" as a cheaper alternative to heroin.']

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What is the relationship between serum miR-21 levels, clinicopathological factors, prognosis in ovarian cancer patients, and the role of miR-100?

['["Finally, five promising differentially miRNAs (miR-200a, miR-100, miR-141, miR-200b, and miR-200c) were reported with the consistent direction in four or more studies. MiR-200a, miR-200b, miR-200c, and miR-141, all of them belong to miR-200 family, were reported with consistently up-regulated in at least 4 studies, whereas miR-100 was reported with down-regulated in 4 studies", "Upregulation of microRNA-203 is associated with advanced tumor progression and poor prognosis in epithelial ovarian cancer", "multivariate analysis showed that the status of miR-203 expression was an independent predictor for both overall survival and progression-free survival in EOC. These findings provide the convincing evidence for the first time that the upregulation of miR-203 may serve as a novel molecular marker to predict the aggressive tumor progression and unfavorable prognosis of EOC patients", "Some, but not all, of the data indicated that the miR-200 family was dysregulated in a variety of malignancies. In this study, we demonstrated that miR-200a and E-cadherin were significantly upregulated in EOC compared to benign epithelial ovarian cysts and normal ovarian tissues", "There was a significantly positive correlation between miR-200a and E-cadherin in EOC. The biphasic expression pattern suggested that miR-200a levels may serve as novel biomarkers for the early detection of EOC, and miR-200a and E-cadherin are candidate targets for the development of new treatment modalities against ovarian cancer", "Kaplan-Meier analysis showed low miR-510 expression, low miR-509-5p expression, and advanced FIGO stage, and chemotherapy resistance were significantly associated with poorer overall survival (P < 0.05). Our results suggest that miRNAs may play a role in the progression of OSC, and miR-510 and miR-509-5p may be considered novel-candidate clinical biomarkers for predicting OSC outcome", "The qRT-PCR results showed that miR-510, miR-509-5p, and miR-508-3p were significantly downregulated and that miR-483-5p was upregulated in stage III OSC compared with stage I, which was consistent with the microarray results", "In this study, we examined serum miR-21 levels in epithelial ovarian cancer (EOC) patients, and explored its association with clinicopathological factors and prognosis. The results showed significantly higher serum miR-21 levels in EOC patients than in healthy controls. In addition, increased serum miR-21 expression was correlated with advanced FIGO stage, high tumor grade, and shortened overall survival. These findings indicate that serum miR-21 may serve as a novel diagnostic and prognostic marker, and be used as a therapeutic target for the treatment of EOC", "Identification of serum microRNA-21 as a biomarker for early detection and prognosis in human epithelial ovarian cancer", "Serum miR-132, miR-26a, let-7b, and miR-145 could be considered as potential candidates as novel biomarkers in serous ovarian cancer.", "Among the miRNAs that showed a consistent regulation tendency through all specimens and showed more than a 2-fold difference in serum, 5 miRNAs (miR-132, miR-26a, let-7b, miR-145, and miR-143) were determined as the 5 most markedly down-regulated miRNAs in the serum from ovarian cancer patients with respect to those of controls. Four miRNAs (miR-132, miR-26a, let-7b, and miR-145) out of 5 selected miRNAs were significantly underexpressed in the serum of ovarian cancer patients in qRT-PCR", " microRNA (miR)-182, miR-200a, miR-200b and miR-200c were highly overexpressed in the SEOC cell lines relative to normal human ovarian surface epithelial cells and were assessed in RNA extracted from serum as candidate biomarkers", "Together, these results suggest that low miR-100 expression may be an independent poor prognostic factor and miR-100 can function as a tumor suppressor by targeting PLK1 in human EOCs", "Prognostic implications of microRNA-100 and its functional roles in human epithelial ovarian cancer", "Taken together, miR-152 and miR-148a may be involved ']

The relationship between serum miR-21 levels, clinicopathological factors, and prognosis in ovarian cancer patients is that increased serum miR-21 expression is correlated with advanced FIGO stage, high tumor grade, and shortened overall survival. Serum miR-21 may serve as a novel diagnostic and prognostic marker in epithelial ovarian cancer. On the other hand, miR-100 expression levels may be an independent poor prognostic factor and function as a tumor suppressor by targeting PLK1 in human EOCs.

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What is saxagliptin's role in diabetes treatment trials compared to vildagliptin and sitagliptin?

[' up to October 1st, 2013.", "Saxagliptin.", "Vildagliptin.", "an extensive Medline, Embase and Cochrane Database search for \'vildagliptin\', \'sitagliptin\', \'saxagliptin\', \'alogliptin\', \'linagliptin\' and \'dutogliptin\' was performed up to 1 March 2013.", "An extensive Medline and Embase search for \'vildagliptin\', \'sitagliptin\', \'saxagliptin\', \'alogliptin\', \'linagliptin\', and \'dutogliptin\' was performed, collecting all randomized clinical trials on humans up to March 1, 2011.", "An extensive Medline, Embase, and Cochrane Database search for \\"vildagliptin\\", \\"sitagliptin\\", \\"saxagliptin\\", \\"alogliptin\\", \\"linagliptin\\", and \\"dutogliptin\\" was performed, collecting all randomized clinical trials on humans up to October 1st, 2013.", "the words \\"sitagliptin,\\" \\"vildagliptin,\\" \\"saxagliptin,\\" \\"alogliptin,\\" \\"linagliptin,\\" and/or \\"dutogliptin.\\" Completed but unpublished trials were identified through a search of the ClinicalTrials.gov website,", "Sitagliptin (MK- 0431), Saxagliptin, Melogliptin, Linagliptin (BI-1356), Dutogliptin, Carmegliptin, Alogliptin and Vildagliptin (LAF237).", "Of these, two have been approved for clinical use in the United States: sitagliptin and saxagliptin. Additionally, linagliptin, vildagliptin and alogliptin are currently in phase III development in the United States while studies with another DPP IV inhibitor, dutogliptin, have been terminated (2).", "We conducted a search on MEDLINE, Embase and Cochrane Collaborative database for randomized controlled trials (RCTs) of DPP-4 inhibitors and metformin as initial combination therapy or as monotherapy in patients with T2DM by the end of December 2012, using the key words \'alogliptin\', \'dutogliptin\', \'linagliptin\', \'saxagliptin\', \'sitagliptin\', \'vildagliptin\' and \'metformin\'.", "Given as monotherapy, linagliptin, sitagliptin, and vildagliptin (but not saxagliptin) met the equivalence criterion when compared with one another. Given in combination with metformin, linagliptin, saxagliptin, sitagliptin, and vildagliptin showed an equivalent effect whereas alogliptin did not satisfy the equivalence criterion.", "Additionally, linagliptin, vildagliptin and alogliptin are currently in phase III development in the United States while studies with another DPP IV inhibitor, dutogliptin, have been terminated (2). Alogliptin was approved for use in Japan under the trade name Nesina\\u00ae in April 2010 (3).", "Any DPP-4 inhibitor (vildagliptin, sitagliptin, saxagliptin, linagliptin or alogliptin).", "An extensive search of Medline and the Cochrane Library (any date up to December 31, 2010, restricted to randomized clinical trials, published in English) was performed for all trials containing, in any field, the words \\"sitagliptin,\\" \\"vildagliptin,\\" \\"saxagliptin,\\" \\"alogliptin,\\" \\"linagliptin,\\" and/or \\"dutogliptin.\\" Completed but unpublished trials were identified through a search of the ClinicalTrials.gov website, using the same keywords as above.", "A systematic review and meta-analysis of randomised controlled trials (RCTs) of DPP-4 inhibitors (vildagliptin, sitagliptin, saxagliptin, linagliptin and alogliptin) on HbA1c were conducted.", "Several clinical trials have studied the addition of GLP-1 receptor agonists [exenatide BID (twice daily), lixisenatide, albiglutide] or DPP-4 inhibitors (vildagliptin, sitagliptin, saxagliptin, alogliptin, linagliptin) to ongoing insulin therapy or adding insulin to ongoing therapy with a GLP-1 receptor agonist (liraglutide).", "Testing the therapeutic equivalence of alogliptin, linagliptin, saxagliptin, sit']

[]

Is the gene MAOA epigenetically modified by methylation?

['Evidence that the methylation state of the monoamine oxidase A (MAOA) gene predicts brain activity of MAO A enzyme in healthy men.', 'We found significant interindividual differences in methylation status and methylation patterns of the core MAOA promoter. ', 'In the present study, DNA methylation patterns in the MAOA regulatory and exon 1/intron 1 region were investigated for association with panic disorder with particular attention to possible effects of gender and environmental factors. ', ' The present pilot data suggest a potential role of MAOA gene hypomethylation in the pathogenesis of panic disorder particularly in female patients, possibly mediating a detrimental influence of negative life events. ', 'The MAOA promoter was hypermethylated immediately upstream of the start codon in cholangiocarcinoma samples and cell lines but not in nonmalignant counterparts. ', 'MAOA promoter methylation and susceptibility to carotid atherosclerosis: role of familial factors in a monozygotic twin sample.', 'Because twins reared together share early life experience, which may leave a long-lasting epigenetic mark, aberrant MAOA methylation may represent an early biomarker for unhealthy familial environment.', 'Effects of MAOA promoter methylation on susceptibility to paranoid schizophrenia.', 'In conclusion, abnormalities of DNA methylation at the MAOA promoter may be associated with schizophrenia in males.', 'In our study we analyzed DNA methylation patterns of 14 neuropsychiatric genes (COMT, DAT1, GABRA1, GNB3, GRIN2B, HTR1B, HTR2A, 5-HTT, MAOA, MAOB, NOS1, NR3C1, TPH1 and TH). D', 'Our data suggest that aberrant epigenetic regulation of neuropsychiatric genes may contribute to the pathogenesis of BPD.', 'We conclude that smoking reliably decreases MAOA methylation, but exact characterization of effects on level of methylation depend on genotype, smoking history, current smoking status, gender, and region of the promoter-associated CpG Island examined.', 'Given that DNA methylation is linked to the regulation of gene expression, we hypothesized that epigenetic mechanisms factor into the MAOA expression', ' the extended MAOA regulatory region contains two CpG islands (CGIs), one of which overlaps with the canonical MAOA promoter and the other is located further upstream; both CGIs exhibit sensitivity to differential methylation.', 'Identification and characterization of putative methylation targets in the MAOA locus using bioinformatic approaches.', 'DNA methylation is a key epigenetic mechanism involved in the developmental regulation of gene expression. ', 'MAOA methylation is associated with nicotine and alcohol dependence in women.', 'In recent years, the role of epigenetic phenomenon, such as methylation, in mediating vulnerability to behavioral illness has become increasingly appreciated. One prominent locus at which epigenetic phenomena are thought to be in play is the monoamine oxidase A (MAOA) locus. ', 'We conclude that methylation of MAOA may play a significant role in common psychiatric illness and that further examination of epigenetic processes at this locus is in order.', 'Analysis of CpG methylation in the MAOA promoter region revealed substantial methylation in females but not in males.', 'Therefore, allelic mRNA expression is affected by genetic and epigenetic events, both with the potential to modulate biogenic amine tone in the CNS.']

['In recent years, the role of epigenetic phenomenon, such as methylation, in mediating vulnerability to behavioral illness has become increasingly appreciated. One prominent locus at which epigenetic phenomena are thought to be in play is the monoamine oxidase A (MAOA) locus.\nWe conclude that methylation of MAOA may play a significant role in common psychiatric illness and that further examination of epigenetic processes at this locus is in order.']

['yes']

Which drug should be used as an antidote in benzodiazepine overdose?

['Benzodiazepine (BZD) overdose (OD) continues to cause significant morbidity and mortality in the UK. Flumazenil is an effective antidote but there is a risk of seizures, particularly in those who have co-ingested tricyclic antidepressants.', 'Flumazenil was administered to 80 patients in 4504 BZD-related enquiries, 68 of whom did not have ventilatory failure or had recognised contraindications to flumazenil.', 'Flumazenil is used infrequently in the management of BZD OD in the UK.', 'Flumazenil is a benzodiazepine antagonist. It is widely used as an antidote in comatose patients suspected of having ingested a benzodiazepine overdose.', 'Flumazenil is very useful in reversing benzodiazepine-induced sedation as well as to diagnose or treat benzodiazepine overdose.', 'Flumazenil is indicated for reversal of sedation from benzodiazepines administered during therapeutic or diagnostic procedures and during induction or maintenance of general anesthesia, as well as for benzodiazepine overdose.', "When measures are required to ensure adequate recovery of a patient's respiratory function and mental awareness, such as in patients with benzodiazepine toxicity, consideration of continuous-infusion flumazenil is warranted.", 'Flumazenil is a potent benzodiazepine antagonist that competitively blocks the central effects of benzodiazepines. It can reverse the sedative effects of benzodiazepines occurring after diagnostic or therapeutic procedures or after benzodiazepine overdose.', 'A 54-y-old man ingested 2 g of bulk laboratory diazepam and was treated with activated charcoal, enhanced diuresis and flumazenil infusion.', 'Flumazenil is a specific and competitive antagonist at the central benzodiazepine receptor, reversing all effects of benzodiazepine agonists without tranquillising or anticonvulsant actions.', 'Incremental intravenous bolus injections of flumazenil 0.1 to 0.3 mg are the most effective and well tolerated in the diagnosis and treatment of pure benzodiazepine overdose; additional boluses or an infusion (0.3 to 0.5 mg/h) can be given to prevent patients from relapsing into coma.', 'Flumazenil is a competitive benzodiazepine antagonist that acts to reverse their sedative and hypnotic effects. It is indicated in the management of benzodiazepine overdose, but its role in the routine reversal of endoscopic conscious sedation has not been defined.', 'To develop clinical rules for the safe and effective use of flumazenil in suspected benzodiazepine overdose.', 'Unconscious patients (n = 110) suspected of benzodiazepine overdose, graded 2 to 4 on the Matthew and Lawson coma scale, were treated with flumazenil, the specific benzodiazepine receptor antagonist.', 'Fourteen of 17 double-blind, flumazenil-treated patients woke after a mean of 0.8 +/- 0.3 (SD) mg vs. one of 14 placebo patients (p < .001). Seventy-five percent of the aggregated controlled and uncontrolled patients awoke from coma scores of 3.1 +/- 0.6 to 0.4 +/- 0.5 (p < .01) after the injection of 0.7 +/- 0.3 mg of flumazenil. These patients had high benzodiazepine serum blood concentrations.', 'Flumazenil is effective in preventing recurrence of benzodiazepine-induced coma.', 'Flumazenil is best left for reversal of therapeutic conscious sedation and rare select cases of benzodiazepine overdose.', 'Flumazenil interacts at the central benzodiazepine receptor to antagonize or reverse the behavioral, neurologic, and electrophysiologic effects of benzodiazepine agonists and inverse agonists.', 'It improves the level of consciousness in patients with benzodiazepine overdose; however, resedation may occur within one to two hours after administration, so repeated doses or a continuous infusion may be required to maintain therapeutic efficacy.', 'Flumazenil has been shown to reverse sedation caused by intoxication with benzodiazepines alone or benzodiazepines in combination with other agents, but it should not be used when cyclic antidepressant intoxication is suspected.', 'Flumazenil, a specific benzodiazepine antagonist, was evaluated as adjunctive therapy in the management of benzodiazepine overdose.', 'The mean CGIS score at 10 minutes for benzodiazepine-positive patients treated with flumazenil was 1.95 versus 3.58 for those given placebo.', 'Among the benzodiazepine-positive patients, 9 (53%) of 17 patients from the flumazenil group responded to the additional flumazenil, and 58 (81%) of patients previously given placebo responded.', 'The results of this study confirm published reports of the efficacy of flumazenil in reversing benzodiazepine-induced sedation in patients with benzodiazepine overdose.', 'Flumazenil, a specific benzodiazepine antagonist, is useful in reversing the sedation and respiratory depression that often occur when benzodiazepines are administered to patients undergoing anesthesia or when patients have taken an intentional benzodiazepine overdose.', 'Flumazenil rapidly and effectively reverses the clinical signs and symptoms of a BDZ overdose.', 'Flumazenil is a benzodiazepine antagonist that is highly effective in reversing the central nervous system effects of benzodiazepine overdose.', 'In the setting of isolated benzodiazepine overdose, flumazenil is capable of completely reversing coma within one to two minutes, with this effect lasting between one and five hours.', 'Fifteen comatous patients with suspected sedatives/hypnotics overdose were included in this study and flumazenil 0.25 mg per dose was administrated intravenously. The average score of Glasgow Coma Scale increased from 7.13 +/- 2.92 to 10.93 +/- 3.67 after one dose of flumazenil. Clear consciousness was restored after multiple doses of flumazenil administration.', 'We concluded that flumazenil is an excellent antidote for benzodiazepine overdose and valuable for differentiating the patients in comatose.', 'Patients with benzodiazepine overdose who received 5 mg flumazenil regained consciousness about 1-2 min after the end of injection.', 'We conclude that flumazenil is an effective and safe drug in the treatment of benzodiazepine overdose.', 'Flumazenil is the first benzodiazepine antagonist which can be used in humans and is a well established for treatment of benzodiazepine overdose.', 'Flumazenil, a 1,4-imidazobenzodiazepine, is a highly effective, specific benzodiazepine antagonist which is indicated for use when the effect of a benzodiazepine must be attenuated or terminated at short notice.', 'Thus, flumazenil provides a safe and effective means of attenuating or reversing the CNS-depressant effects of benzodiazepines whenever indicated, e.g. following benzodiazepine-induced general anaesthesia, conscious sedation, or after benzodiazepine overdose, either alone or in combination with other agents.', 'Flumazenil is safe when administered cautiously, even in patients with coma caused by a mixed overdose of benzodiazepine plus tricyclic antidepressants.', 'The mean +/- SD CGIS score at ten minutes for BDZ-positive patients was 1.41 +/- 0.72 for patients who received flumazenil and 3.41 +/- 0.91 for the placebo group (P < .01). There was no difference in the mean CGIS score between the flumazenil (3.25 +/- 1.15) and placebo (3.75 +/- 0.69) groups in BDZ-negative patients. The GCS and NAS were also significantly better in patients who were BDZ-positive and received flumazenil.', 'In 23 patients admitted to the Intensive Care Unit with coma due to overdose with benzodiazepines or other sedatives, flumazenil i.v. (up to 2 mg or placebo) was given. In 13 patients given flumazenil the Glasgow Coma Scale (GCS) increased significantly from 4.9 to 7.8 (p less than 0.05). Six of these 13 patients, including mainly benzodiazepine mono-intoxications, needed only one series of injections (up to 1.0 mg flumazenil); the GCS increased thereby from 4.5 to 10.7 within a maximum of 5 min (p less than 0.01).', 'The efficacy and safety of flumazenil were assessed in comparison to placebo in a double-blind randomised study of 31 adults intoxicated with benzodiazepines. The criteria of efficacy were the degree of sedation, and orientation in time and space. Patients who received flumazenil awoke within minutes but central depression returned partly one hour later, which reflects the short elimination half-life of the drug.', 'Side effects were few and the results indicate that flumazenil is effective in the primary management of benzodiazepine overdose and in states where benzodiazepines have been taken with other drugs.', 'Flumazenil (Ro 15-1788) proved to be a very efficacious competitive antagonist of benzodiazepines that reliably counteracts their pharmacological actions within 1-2 min as could be demonstrated in clinical and EEG studies.', 'In intensive care medicine, the antagonist may be used in the treatment of benzodiazepine overdose as well as in the differential diagnosis of a coma of unknown origin.']

['Flumazenil should be used in all patients presenting with suspected benzodiazepine overdose. Flumazenil is a potent benzodiazepine receptor antagonist that competitively blocks the central effects of benzodiazepines and reverses behavioral, neurologic, and electrophysiologic effects of benzodiazepine overdose. Clinical efficacy and safety of flumazenil in treatment of benzodiazepine overdose has been confirmed in a number of rigorous clinical trials. In addition, flumazenil is also useful to to reverse benzodiazepine induced sedation and to and to diagnose benzodiazepine overdose.']

['flumazenil']

What chromosome is affected in Turner's syndrome?

["Turner's syndrome (TS) is a chromosomal defect with partial or total absence of the X chromosome. ", 'Turner syndrome is a genetic disorder caused by the complete or partial absence of an X chromosome in affected women', 'Turner syndrome (TS) is a chromosomal disorder caused by complete or partial X chromosome monosomy that manifests various clinical features depending on the karyotype and on the genetic background of affected girls', 'CONTEXT: Turner syndrome (TS) is the most common genetic problem affecting women and occurs when an X chromosome is completely deleted, portions of an X chromosome are deleted, or chromosomal mosaicism occurs. ', "Turner's syndrome (TS) is a chromosomal disorder that results from the loss of the entire or a part of the X-chromosome and occurs in 1/2,500 female births.", 'Women with Turner\'s syndrome (TS), who lack a complete X-chromosome, show an impairment in remembering faces and in classifying "fear" in face images.', "The proposition that finger print variability between individuals might be reduced by the absence of an X-chromosome in Turner's syndrome was rejected.", "While the classic karyotype related to Turner's syndrome is 45,X, the majority of those affected actually have a mosaic chromosomal complement, most often with a second normal cell line (46,XX).", "45,X Turner's syndrome in monozygotic twin sisters.", "Monosomy for the X chromosome is the most frequent cause of Turner's syndrome, a common clinical syndrome associated with particular physical and neurobehavioral features.", 'Turner syndrome is a chromosomal abnormality in which there is complete or partial absence of the X chromosome.', ' To identify the origin and study the morphology of small supernumerary marker chromosome (sSMC) in Turner syndrome with 45, X/46, X, + mar karyotype.', 'Turner syndrome is a chromosomal disorder in which all or part of one X chromosome is missing', 'urner phenotype in this family is the result of deletion of the entire short arm of one X chromosome.', 'X monosomic mice (39,XO) have a remarkably mild phenotype when compared to women with Turner syndrome (45,XO).', 'X-monosomy is a form of Turner syndrome (TS) in which an entire X chromosome is missing. ', "Turner's syndrome is defined as a congenital disease determining by quantitative and/or structural aberrations of one from two X chromosomes with frequent presence of mosaicism"]

["Turner's syndrome (TS) is a chromosomal defect with partial or total absence of the X chromosome", "Turner's syndrome (TS) is a chromosomal defect with partial or total absence of the X chromosome.", "Turner's syndrome (TS) is a chromosomal defect with partial or total absence of the X chromosome. ", "turner's syndrome (ts) is a chromosomal defect with partial or total absence of the x chromosome."]

['X']

Are there Conserved Noncoding Elements (CNEs) in plant genomes?

['Conservation and functional element discovery in 20 angiosperm plant genomes', 'The detailed view of conservation across angiosperms revealed not only high coding-sequence conservation but also a large set of previously uncharacterized intergenic conservation', 'Conserved noncoding sequences highlight shared components of regulatory networks in dicotyledonous plants', 'Using a comparative genomics approach with four dicotyledonous plant species (Arabidopsis thaliana, papaya [Carica papaya], poplar [Populus trichocarpa], and grape [Vitis vinifera]), we detected hundreds of CNSs upstream of Arabidopsis genes', 'Long identical multispecies elements in plant and animal genomes.', 'Using an alignment-free information-retrieval approach, we have comprehensively identified all long identical multispecies elements (LIMEs), which include both syntenic and nonsyntenic regions, of at least 100 identical base pairs shared by at least two genomes', 'In contrast, among six plant genomes, we only found nonsyntenic LIMEs', ' Although complex LIMEs were found in both animal and plant genomes, they differed significantly in their composition and copy number', 'Ultraconserved elements between the genomes of the plants Arabidopsis thaliana and rice', 'We consequently compared the genomes of Arabidopsis thaliana and rice, which diverged about 200 million years ago, and identified 25 ultraconserved elements that are longer than 100 bp', 'ultraconserved elements in plants tend to occur in clusters and locate at noncoding regions', 'the functions of these plant ultraconserved elements and the reasons why they are practically frozen during the evolution of millions of years remain a mystery', 'Conserved noncoding sequences in the grasses', ' Using a local sequence alignment set to deliver only significant alignments, we found one or more CNSs in the noncoding regions of the majority of genes studied. Grass genes have dramatically fewer and much smaller CNSs than mammalian genes', 'Conserved noncoding sequences among cultivated cereal genomes identify candidate regulatory sequence elements and patterns of promoter evolution', 'Surveys for conserved noncoding sequences (CNS) among genes from monocot cereal species were conducted to assess the general properties of CNS in grass genomes and their correlation with known promoter regulatory elements', 'Comparisons of orthologous maize-rice and maize-sorghum gene pairs identified 20 bp as a minimal length criterion for a significant CNS among grass genes, with few such CNS found to be conserved across rice, maize, sorghum, and barley']

['The detailed view of conservation across angiosperms revealed not only high coding-sequence conservation but also a large set of previously uncharacterized intergenic conservation. Grass genes have dramatically fewer and much smaller CNSs than mammalian genes. Using an alignment-free information-retrieval approach, we have comprehensively identified all long identical multispecies elements (LIMEs), which include both syntenic and nonsyntenic regions, of at least 100 identical base pairs shared by at least two genomes. Using a comparative genomics approach with four dicotyledonous plant species (Arabidopsis thaliana, papaya [Carica papaya], poplar [Populus trichocarpa], and grape [Vitis vinifera]), we detected hundreds of CNSs upstream of Arabidopsis genes. We consequently compared the genomes of Arabidopsis thaliana and rice, which diverged about 200 million years ago, and identified 25 ultraconserved elements that are longer than 100 bp. Using a local sequence alignment set to deliver only significant alignments, we found one or more CNSs in the noncoding regions of the majority of genes studied. ', 'Grass genes have dramatically fewer and much smaller CNSs than mammalian genes. The detailed view of conservation across angiosperms revealed not only high coding-sequence conservation but also a large set of previously uncharacterized intergenic conservation. Using an alignment-free information-retrieval approach, we have comprehensively identified all long identical multispecies elements (LIMEs), which include both syntenic and nonsyntenic regions, of at least 100 identical base pairs shared by at least two genomes. Using a comparative genomics approach with four dicotyledonous plant species (Arabidopsis thaliana, papaya [Carica papaya], poplar [Populus trichocarpa], and grape [Vitis vinifera]), we detected hundreds of CNSs upstream of Arabidopsis genes. We consequently compared the genomes of Arabidopsis thaliana and rice, which diverged about 200 million years ago, and identified 25 ultraconserved elements that are longer than 100 bp. Using a local sequence alignment set to deliver only significant alignments, we found one or more CNSs in the noncoding regions of the majority of genes studied. ', 'Yes. Conserved, UltraConserved and other classes of Constrained Noncoding Sequences have been found in plant genomes.']

['yes']

Do lincRNAs play a role in human cancer?

['Long non-coding RNA H19 increases bladder cancer metastasis', 'These data suggest that upregulated H19 enhances bladder cancer metastasis by associating with EZH2 and inhibiting E-cad expression', 'lncRNA H19 is essential for human tumor growth', 'Previous reports have demonstrated that HOTAIR associates with chromatin modifications in cooperation with the Polycomb complex PRC2, and promotes breast and colorectal cancer metastasis', 'although the clinical significance of HOTAIR expression in HCC may not be as pronounced as that in breast and colorectal cancers, the current study demonstrates that HOTAIR expression is associated with HCC progression, warranting further studies.', 'Long non-coding RNA HOTAIR is an independent prognostic marker for nasopharyngeal carcinoma progression and survival', 'Long non-coding RNA influences radiosensitivity of colorectal carcinoma cell lines by regulating cyclin D1 expression', 'Long non-coding RNA urothelial carcinoma associated 1 (UCA1) promotes human bladder cancer cell proliferation, but the underlying mechanism remains unknown', 'UCA1 regulated cell cycle through CREB via PI3K-AKT dependent pathway in bladder cancer.', 'Long non-coding RNA UCA1 regulated cell cycle distribution via CREB through PI3-K dependent pathway in bladder carcinoma cells', 'overexpression of Yiya promotes cell cycle progression at the G1/S transition, therefore identifying Yiya as a cell-cycle-associated long non-coding RNA', 'The long noncoding RNA HOTAIR has been reported as a poor prognostic biomarker in patients with breast cancer. The aim of the present study is to examine the expression pattern of HOTAIR in hepatocellular carcinoma (HCC) and its clinical significance as well as its biological role in tumor progression', 'The high expression level of HOTAIR in HCC could be a candidate biomarker for predicting tumor recurrence in HCC patients who have undergone liver transplant therapy and might be a potential therapeutic target', 'Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene', 'A 42\u2009kb region on human chromosome 9p21 encodes for three distinct tumor suppressors, p16(INK4A), p14(ARF) and p15(INK4B), and is altered in an estimated 30-40% of human tumors', 'These results advance our understanding of the role of lncRNA-LET as a regulator of hypoxia signaling and\xa0offer new avenues for therapeutic intervention against cancer progression.', 'Silencing MALAT1 is a potential novel therapeutic approach for this cancer.']

['Long non-coding RNAs (lncRNAs) are pervasively transcribed in the genome and are emerging as new players in tumorigenesis due to their various functions in transcriptional, posttranscriptional and epigenetic mechanisms of gene regulation. The best-studied examples include HOTAIR, a negative prognostic factor that exhibits pro-oncogenic activity in a variety of human cancers, CRNDE the gene symbol for Colorectal Neoplasia Differentially Expressed (non-protein-coding), a long non-coding RNA (lncRNA) gene that expresses multiple splice variants and displays a very tissue-specific pattern of expression and ANRIL, a lincRNA that is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene.']

['yes']

Is there alternative polyadenylation during zebrafish development?

['Extensive alternative polyadenylation during zebrafish development.', "At 2 h post-fertilization, thousands of unique poly(A) sites appear at locations lacking a typical polyadenylation signal, which suggests a wave of widespread cytoplasmic polyadenylation of mRNA degradation intermediates. Our insights into the identities, formation, and evolution of zebrafish 3' UTRs provide a resource for studying gene regulation during vertebrate development.", 'Extensive alternative polyadenylation during zebrafish development.']

['Yes. There is extensive alternative polyadenylation during zebrafish development.']

['yes']

What is the mechanism of cementogenesis in pulp regeneration?

['New vital tissues can be regenerated in permanent canine teeth after pulpectomy and enlargement of the apical foramen', 'The loss of dental pulp may weaken teeth, rendering them susceptible to reinfection, fracture, and subsequent tooth loss. Therefore, regeneration of pulp is considered an ideal treatment to preserve teeth.', 'Constitutive stabilization of ß-catenin in the dental mesenchyme leads to excessive dentin and cementum formation', 'Wnt/ß-catenin signaling plays an important role in morphogenesis and cellular differentiation during development. Essential roles of Wnt/ß-catenin signaling in tooth morphogenesis have been well known', 'Our results indicate that persistent stabilization of ß-catenin in the dental mesenchyme leads to premature differentiation of odontoblasts and differentiation of cementoblasts, and induces excessive dentin and cementum formation in vivo. These results suggest that temporospatial regulation of Wnt/ß-catenin signaling plays critical roles in the differentiation of odontoblasts and cementoblasts, and that inhibition of Wnt/ß-catenin signaling may be important for the formation of dentin and cementum during tooth development', 'Local modulation of Wnt/ß-catenin signaling has therapeutic potential to improve the regeneration of dentin and periodontium', 'It is known that the dental follicle (DF) consists of progenitor cells that give rise to the cementum, periodontal ligament, and alveolar bone', " but little information is available about the regulation of DF cell differentiation into either cementogenic or osteogenic cell lineages for the regeneration of diseased periodontal tissue. Here, we investigated the roles of DF, Hertwig's epithelial root sheath (HERS), and pulp cells in the cementum", 'These results suggest that the combined use of DF, HERS, and pulp cells could direct DF cell differentiation into cementoblasts and/or osteoblasts in vivo, thus providing a novel strategy for the successful repair and regeneration of diseased periodontal tissue', ' HERS cells played a role in the induction and maturation of cementum-like tissues formed by DF cells', ' implants of DF cells in the presence of pulp cells led to the formation of bone-like tissues', 'Interestingly, in the presence of both HERS and pulp cells, DF cells formed both cementum-like and bone-like tissues. We demonstrated that while HERS cells are able to induce DF cell differentiation into cementoblasts and promote cementum formation, pulp cells could direct DF cell differentiation into osteoblasts and enhance alveolar bone formation', 'Periodontal ligament (PDL) and cementum complex and dentin pulp complex have been tissue engineered using human dental pulp stem cells and PDL stem cells', 'Histological, immunohistochemical, and scanning electronic microscopy examinations results showed that bioengineered dentin could induce cementogenesis and PDL formation, and condense PDL arranged perpendicularly on the dentin surface via a layer of cementum-like tissue']

["The dental follicle (DF) consists of progenitor cells that give rise to the cementum, periodontal ligament, and alveolar bone. Dental follicle cells attach to Hertwig's epithelial root sheath (HERS), and pulp cells in the cementum promoting cementogenesis. The temporospatial regulation of Wnt/ß-catenin signaling plays critical roles in the differentiation of odontoblasts and cementoblasts.", 'Our results indicate that persistent stabilization of ß-catenin in the dental mesenchyme leads to premature differentiation of odontoblasts and differentiation of cementoblasts, and induces excessive dentin and cementum formation in vivo. It is known that the dental follicle (DF) consists of progenitor cells that give rise to the cementum, periodontal ligament, and alveolar bone. Wnt/ß-catenin signaling plays an important role in morphogenesis and cellular differentiation during development. New vital tissues can be regenerated in permanent canine teeth after pulpectomy and enlargement of the apical foramen. Constitutive stabilization of ß-catenin in the dental mesenchyme leads to excessive dentin and cementum formation. These results suggest that temporospatial regulation of Wnt/ß-catenin signaling plays critical roles in the differentiation of odontoblasts and cementoblasts, and that inhibition of Wnt/ß-catenin signaling may be important for the formation of dentin and cementum during tooth development. HERS cells played a role in the induction and maturation of cementum-like tissues formed by DF cells. Essential roles of Wnt/ß-catenin signaling in tooth morphogenesis have been well known. ']

[]

Is the Wnt protein modified by notum?

['Notum deacylates Wnt proteins to suppress signalling activity.', 'Kinetic and mass spectrometric analyses of human proteins show that Notum is a carboxylesterase that removes an essential palmitoleate moiety from Wnt proteins and thus constitutes the first known extracellular protein deacylase.', 'the Wnt inhibitor notum', 'the WNT-inhibitor notum.']

['Yes, \tNotum deacylates Wnt proteins to suppress signalling activity.']

['yes']

Does HuR bind to the untranslated regions (UTRs) of mRNAs?

["HuR is also overexpressed during tumourigenesis and is abnormally present within the cytoplasm, where it binds to AU-rich elements in the 3'UTRs of target mRNA and post-transcriptionally regulates the expression of its target genes.", "Human antigen R (HuR) is a ubiquitous 32 kDa protein comprising three RNA Recognition Motifs (RRMs), whose main function is to bind Adenylate and uridylate Rich Elements (AREs) in 3' UnTranslated Regions (UTRs) of mRNAs.", 'Human antigen R (HuR) is a ubiquitously expressed RNA-binding protein that modulates gene expression at the post-transcriptional level.', "The RNA-binding protein HuR binds at 3' untranslated regions (UTRs) of target transcripts, thereby protecting them against degradation. ", 'ELAV/Hu proteins bind to AU-rich elements (ARE) in mRNAs and regulate their stability from splicing to translation, and the ubiquitous HuR protein has been implicated in cancerous cell growth. ', "This is achieved by altered expression of the proteins TTP and HuR, which bind 3' untranslated region (UTR) elements in cancer-related genes."]

["Yes, the RNA-binding protein HuR binds at 3' untranslated regions (UTRs) of target transcripts, thereby protecting them against degradation."]

['yes']

Can beans induce apoptosis?

['A 60-kDa glucosamine binding lectin, white kidney bean lectin (WKBL), was purified from Phaseolus vulgaris cv. white kidney beans, by application of anion exchange chromatography on Q-Sepharose, affinity chromatography on Affi-gel blue gel, and FPLC-size exclusion on Superdex 75. The anti-proliferative activity of WKBL on HONE1 cells and HepG2 cells was stronger than the activity on MCF7 cells and WRL68 cells ', 'Treatment of human stomach cancer KATO III cells with hot-water extracts from adzuki beans led to their growth inhibition as well as apoptosis induction.', 'Stimulation of dendritic cell maturation and induction of apoptosis in leukemia cells by a heat-stable extract from azuki bean (Vigna angularis), a promising immunopotentiating food and dietary supplement for cancer prevention.', 'Human gut flora-fermented nondigestible fraction from cooked bean ( Phaseolus vulgaris L.) modifies protein expression associated with apoptosis, cell cycle arrest, and proliferation in human adenocarcinoma colon cancer cells.', 'This paper reports the effect of fermentation products (FP) by hgf (FP-hgf) from NDF of cooked beans on survival and protein expression associated with apoptosis, cell cycle arrest, and proliferation in human adenocarcinoma colon cancer cells.', 'PHA-E is a natural product extracted from red kidney beans, and it has been reported to induce cell apoptosis by blocking EGFR in lung cancer cells', 'A Glucosamine-Specific Lectin from Green Dragon No. 8 Beans (Phaseolus vulgaris) Induced Apoptosis on Nasopharyngeal Carcinoma Cells', 'PHA-E is a natural product extracted from red kidney beans, and it has been reported to induce cell apoptosis by blocking EGFR in lung cancer cells.', 'The anticancer activity of δ-tocotrienol, a bioactive vitamin E present in whole grain cereals, annatto beans and palm fruit, is strongly dependent on its effect on the induction of apoptosis. δ-Tocotrienol-induced apoptosis is associated with consistent induction in the expression of the proapoptotic protein Bcl-2-associated X protein (Bax).', 'NDF of cooked common beans inhibited colon carcinogenesis at an early stage by inducing cell cycle arrest of colon cells and morphological changes linked to apoptosis, thus confirming previous results obtained with gene expression studies.', 'Azuki extract also inhibited the growth of human leukemia U937 cells, leading to induction of apoptosis.', 'Fermentation product of soybean, black bean, and green bean mixture induces apoptosis in a wide variety of cancer cells.', 'A non-digestible fraction of the common bean (Phaseolus vulgaris L.) induces cell cycle arrest and apoptosis during early carcinogenesis.']

['White kidney bean lectin has been shown to exert anti-proliferative and apoptotic effects on cancer cells']

['yes']

Are there clinical trials on stem cells in multiple sclerosis

['Cells are generally given intravenously. Multiple sclerosis, rheumatoid arthritis and lupus have been successfully treated in human clinical trials', "Human multipotent mesenchymal stem cell (MSC) therapies are currently being tested in clinical trials for Crohn's disease, multiple sclerosis, graft-versus-host disease, type 1 diabetes, bone fractures, cartilage damage, and cardiac diseases.", 'Based on these results, several small pilot clinical trials in subjects with advanced MS have demonstrated that MSC administration is safe and provided an early signal of clinical effectiveness. The current aim of clinicians and scientists interested in the development of MSC-based strategies for the treatment of MS is to have the ultimate demonstration in large clinical trials that MSC can inhibit CNS inflammation and foster tissue repair', 'Mesenchymal stem cells (MSC) promote functional recovery in experimental models of central nervous system (CNS) pathology and are currently being tested in clinical trials for stroke, multiple sclerosis and CNS injury.', 'Autologous bone marrow stromal cells (BMSCs) offer significant practical advantages for potential clinical applications in multiple sclerosis (MS). Based on recent experimental data, a number of clinical trials have been designed for the intravenous (IV) and/or intrathecal (ITH) administration of BMSCs in MS patients.', 'Fingolimod is a S1P receptor modulator in MS clinical trials due to systemic anti-inflammatory properties, yet may impact cells within the CNS by crossing the blood-brain barrier.', 'Their development in vitro and their use in vivo in animal models of degenerative neurological disease and recent first efforts in human clinical trials were the topics of a recent international meeting sponsored by the Multiple Sclerosis International Federation and the National Multiple Sclerosis Society on "Stem Cells & MS: Prospects and Strategies"', 'Here we discuss key observations and questions emerging from clinical trials of hematopoietic stem cell transplantation for MS', 'Another possibility to achieve remyelination is the transplantation of myelinating cells into the central nervous system. Proof of principle and demonstration of the functionality were shown in numerous experiments, and a first clinical trial in patients with MS has started', 'This first trial will show if cell transplantation is a feasible concept in MS and whether the transplanted cells will survive and form new myelin.']

['Yes. Human multipotent mesenchymal stem cell (MSC) therapies are currently being tested in clinical trials for multiple sclerosis. Several small pilot clinical trials in subjects with advanced MS have demonstrated that MSC administration is safe and provided an early signal of clinical effectiveness. The current aim of clinicians and scientists interested in the development of MSC-based strategies for the treatment of MS is to have the ultimate demonstration in large clinical trials that MSC can inhibit CNS inflammation and foster tissue repair.']

['yes']

Does melanoma occur in people of African origin ?

['ALM is the most common type of melanoma amongst Asians, Africans,', 'ALM develops on palmar, plantar, and subungual skin, and its biology is different from that of other cutaneous melanomas, where sunlight is the major known environmental determinant', 'We present four albinos with histologic diagnoses of skin cancer', 'Four Nigerian albinos (two men and two women) with skin cancer', 'The sites of the lesions included the head [squamous cell carcinoma (SCC) in two patients and basal cell carcinoma (BCC) in one patient] and the upper limb (melanoma', 'wenty-nine patients (18 males and 11 females) with skin cancer were identified', 'Kaposi sarcoma associated with HIV represented 81.8 percent of KS cases found. Squamous cell carcinoma (SCC) ranked second and malignant melanoma third', 'Earlier studies have shown frequent mutations in the BRAF and NRAS genes in cutaneous melanoma, but these alterations have not been examined in the rare category of melanoma from black Africans.', 'In a series of melanomas from black Africans (n=26), only two BRAF mutations (8%) were found, both being different from the common T1799A substitution. Moreover, melanomas from black Africans exhibited mutations in NRAS exon 1 only (12%), whereas NRAS exon 2 mutations were predominant in melanomas from Caucasians. Thus, the frequencies of BRAF and NRAS mutations were particularly low in melanomas from black Africans, supporting a different pathogenesis of these tumors.', 'Malignant melanoma (MM) remains a pediatric rarity world-wide, but perhaps more so in black Africans. To the best of our knowledge, the current report of MM in a two-and-a-half-year-old Nigerian who had a pre-existing congenital giant hairy nevus is probably the first (in an accessible literature) in a black African child.', 'Malignant melanomas in black Africans are predominantly located on the lower extremities', 'Thus, our findings indicate that melanomas located on the lower extremities in black Africans show several features of aggressiveness; in particular, the proliferative activity was high, and p16 alterations was frequent as evidenced by loss of protein staining. Our findings also indicated that the diagnosis is delayed among black Africans.', 'Africans with dark skin have a reduced risk of getting all types of skin cancer as compared with Caucasians, but the ratio of their incidence rates of cutaneous malignant melanoma to that of squamous cell carcinoma is larger than the corresponding ratio for Caucasians. (', 'Albino Africans, as compared with normally pigmented Africans, seem to have a relatively small risk of getting cutaneous malignant melanomas compared to nonmelanomas. This is probably also true for albino and normally pigmented Caucasians.', 'Scant data exists on melanoma in blacks from Africa', 'The mean age at presentation of the 39 women and 24 men was 60.5 years (range of 30 to 85 years), with a peak incidence in the sixth decade. The foot was the most common site of disease (45 patients). Seven patients had subungual melanoma, seven had primary mucosal lesions, and in six, the primary lesion could not be found.', 'The poor prognosis in black patients in South Africa is the result of delayed presentation with thick primary lesions and advanced disease', 'The outcome of treatment in 40 black patients (27 women, 13 men; mean age 62.9 years) with plantar melanoma over a 13-year period was analysed', 'Delay in presentation and locally advanced disease may explain the poor prognosis of plantar melanoma in black South Africans.', 'Eighteen cases of malignant skin tumors seen at the University of Port Harcourt Teaching Hospital over 3 years (1984 to 1987) were analyzed for diagnoses, site of tumors, sex, and age. Seven patients (39%) had malignant melanomas affecting only the soles of the feet, while the same number had squamous cell carcinomas widely distributed in various parts of the body', 'Non-white populations experienced in general a much lower incidence of melanoma although there was some overlap of white and non-white rates.', 'Populations of African descent were found to have a higher incidence than those of Asiatic origin, but it was concluded that this was due largely to the high frequency of tumours among Africans on the sole of the foot.', 'Pathological features of twenty-one cases of malignant melanoma studied in the University of Nigeria Teaching Hospital, Enugu during the period January, 1974 to December, 1975 are presented. Malignant melanoma accounted for 2.4% of all tumours and 4.5% of all malignant tumours, greatest age incidence being in the fifth to seventh decades.', '81% melanomas occurred on the sole of feet validating the hypothesis that the pigmented skin in Africans is resistant to malignant melanoma.', 'This paper reports the incidence of this lesion in association with invasive malignant melanomas of the feet and hands of Black Africans.', 'Follow-up data (over a 3-year period) and the histological appearances of primary lesion were studied and related in 40 Black patients with malignant melanoma.', 'Malignant melanoma of the skin in Blacks in formidable and sinister tumour.', 'The incidence of malignant melanoma in Johannesburg Black was 1,2 per 100 000 and accounted for 2% of all cancers. The largest number of cases occurred in the 50- 70-year age group and there was a female preponderance. As in previous studies, the sites predominantly affected were the foot and the hand, mainly on the plantar and palmar surfaces.', 'Twenty-one cases of malignant melanoma occurring in the Igbos of Nigeria have been analysed. The site of predilection is the sole of the foot. This result supports the conclusion that Negroes tend to have the disease in the non-pigmented parts.', 'A case of leptomeningeal melanoma in an African child of 7 years is presented together with a survey of pigmentation in the normal African brain.']

['Yes. Africans with dark skin have a reduced risk of getting all types of skin cancer as compared with Caucasians. The incidence of malignant melanoma in Johannesburg Black was 1,2 per 100 000 and accounted for 2% of all cancers. The largest number of cases occurred in the 50- 70-year age group and there was a female preponderance. As in previous studies, the sites predominantly affected were the foot and the hand, mainly on the plantar and palmar surfaces.']

['yes']

What is the incidence of cystic fibrosis in the caucasian population?

['Estimates of the newborn frequency of cystic fibrosis in different Caucasian groups range from 4 times more to 40 times less common than the generally accepted figure of 1:2000.', 'Current meconium screening trials which may be effective in populations with the incidence equal to or greater than 1:2000, may be useful for populations with an incidence as low as 1:7000 only after maximum improvement of the methods', 'Studies on migrant Indian population in United States and United Kingdom estimate frequency of CF as 1:10,000 to 1:40,000', 'The frequency of common mutation F508del in Indian children is between 19% and 34%. Other mutations are heterogeneous', 'The delta F508 mutation was found in 9 cases (60%), of which 5 were homozygous for the disorder.', 'The disease frequency varies considerably among the latter. Among Ashkenazi Jews, the frequency of CF is 1:3300, which is similar to the frequency in most Caucasian populations', 'Although no careful scientific study had ever been done the impression was that CF was extremely rare among the Greek-Cypriots, with an incidence estimated at around 1:30,000', 'The incidence of cystic fibrosis (CF) in Finland, 1:25,000 newborn, is one of the lowest in Caucasian populations', 'Cystic fibrosis (CF) is the most common severe autosomal recessive genetic disorder in Caucasian populations, with an incidence of about 1 in 2000 live births, implying a carrier frequency of about 1 in 22', 'The incidence of cystic fibrosis (CF) in Finland is one tenth that in other Caucasian populations', 'In Denmark the incidence of cystic fibrosis is 1:4700, which is quite low compared to other European countries.', 'Cystic fibrosis is the most frequent autosomal recessive disease in the Caucasian population, with an incidence of 1:2500 newborn', 'Cystic fibrosis (CF) is the commonest autosomal recessive condition among Caucasian populations, affecting 1 in 2500 live births.', 'Cystic fibrosis (CF) is the most common severe autosomal recessive genetic disorder in Caucasian populations, with an incidence of about 1 in 2000 live births', 'Cystic fibrosis (CF) is the most common autosomal recessive disorder in the Caucasian population, affecting approximately 1 in 2,000 newborns but the actual estimate varies with the geographic location. ', 'Cystic fibrosis (CF) is an autosomal recessive disorder with a prevalence at birth estimated at 1/2000-1/2500 livebirths in Caucasian populations', 'Cystic fibrosis is one of the most common autosomal recessive hereditary diseases in the Caucasian population, with an incidence of 1:2000 to 1:3500 liveborns', 'Cystic fibrosis (CF) is the most common autosomal recessive disease in the European (Caucasian) population, with an incidence of 1:2000 to 1:8000', 'Cystic fibrosis (CF) is the most common genetic disease in Caucasian populations, with an incidence of 1 in 2,000 live births in the United Kingdom, and a carrier frequency of approximately 1 in 20', 'Current meconium screening trials which may be effective in populations with the incidence equal to or greater than 1:2000, may be useful for populations with an incidence as low as 1:7000 only after maximum improvement of the methods. Once the true incidence or the variable incidence is proven for Caucasian populations, screening trails in Negro, Oriental and Indian populations will be required.', 'Cystic fibrosis (CF) is the most common lethal genetic disease among Caucasian populations. The generally accepted incidence of CF in the United States is 1 in 3,200 in the Caucasian population.', 'In this region, it has been documented that the incidence of cystic fibrosis reached 1/902 live births between 1975 and 1988, three times higher than the average incidence of 1/2500 live births reported in other Caucasian populations.', 'Cystic fibrosis (CF) is the most common autosomal recessive disorder in the Caucasian population, affecting approximately 1 in 2,000 newborns but the actual estimate varies with the geographic location. The incidence of CF in non-Caucasian populations is low.', 'Cystic fibrosis is the most frequent autosomal recessive disease in the Caucasian population, with an incidence of 1:2500 newborn and a frequency of 1:25', 'Cystic fibrosis (CF) is the most common lethal inherited disease in the Caucasian population with an incidence of approximately 1 in 2,500 live births', 'Cystic Fibrosis (CF) is the most common and severe autosomal recessive disease in Caucasian populations, with an incidence of 1 in 2500 live births. ']

['Estimates of the newborn frequency of cystic fibrosis in different Caucasian groups range from 4 times more to 40 times less common than the generally accepted figure of 1:2000.', 'Cystic fibrosis (CF) is the most common autosomal recessive disorder in the Caucasian population, affecting approximately 1 in 2,000-1/2,500 live births, but the actual estimate varies with the geographic location.']

['1:2000']

Is pregabalin effective for treatment of patients with restless leg syndrome?

['CONCLUSIONS: This study demonstrated improvements in objective and subjective measures of sleep maintenance and sleep architecture with pregabalin compared with placebo and pramipexole. Effects of pregabalin on periodic limb movement arousal index were comparable to pramipexole. ', 'CONCLUSIONS: Pregabalin provided significantly improved treatment outcomes as compared with placebo, and augmentation rates were significantly lower with pregabalin than with 0.5 mg of pramipexole.', 'The alpha-2-delta ligands, including gabapentin, gabapentin enacarbil, and pregabalin, are effective for RLS without known occurrence of augmentation or impulse control disorders, although sedation and dizziness can occur. ', 'Pregabalin has been established as effective for up to 1 year in treating RLS/WED (Level A evidence). ', 'In the group of anticonvulsants, only the trials performed with α₂δ ligands such as gabapentin, gabapentin enacarbil, and pregabalin showed good efficacy. ', 'Alternative or additional pharmacologic treatment with a lower level of overall quality of evidence includes opioids (codeine, tramadol, and oxycodone) and anticonvulsants (gabapentin, gabapentin enacarbil, and pregabalin). ', 'There is sufficient evidence to conclude that dopamine agonists such as rotigotine transdermal patch, pramipexole, ropinirole, gabapentin enacarbil, pregabalin and gabapentin are effective in the short-term treatment of RLS and rotigotine, followed by gabapentin enacarbil, ropinirole, pramipexole and gabapentin for long-term treatment.', 'Calcium channel alpha-2-delta ligands (gabapentin, gabapentin enacarbil, and pregabalin) provide alternative therapies for RLS especially in patients with augmentation, impulse control disorders, or hypersomnia induced by dopamine agonists. ', 'Alpha-2-delta ligands (gabapentin enacarbil, gabapentin, and pregabalin) increased the number of IRLS responders (RR=1.66; [95% CI: 1.33 to 2.09], k=3, high strength of evidence) and mean change in IRLS symptom scores (k=3, high strength of evidence). ', 'RECOMMENDATIONS: Level A recommendations can be made for rotigotine, ropinirole, pramipexole, gabapentin enacarbil, gabapentin and pregabalin, which are all considered effective for the short-term treatment for RLS.', 'Therapies with an OPTION level of recommendation include carbamazepine, gabapentin, pregabalin, clonidine, and for patients with low ferritin levels, iron supplementation.', 'CONCLUSIONS: In this 6-week phase 2b study, pregabalin reduced RLS symptoms in patients with moderate-to-severe idiopathic RLS', 'CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that pregabalin is effective for the treatment of restless legs syndrome and improves sleep architecture and periodic limb movements in placebo-unresponsive patients.', 'In severe, refractory or neuropathy-associated RLS, antiepileptic (gabapentin, pregabalin) or opioid (oxycodone, tramadol) drugs can be used.', 'The alpha-2-delta ligands, including gabapentin, gabapentin enacarbil, and pregabalin, are effective for RLS without known occurrence of augmentation or impulse control disorders, although sedation and dizziness can occur', 'This study provides Class II evidence that pregabalin is effective for the treatment of restless legs syndrome and improves sleep architecture and periodic limb movements in placebo-unresponsive patients.', 'Level A recommendations can be made for rotigotine, ropinirole, pramipexole, gabapentin enacarbil, gabapentin and pregabalin, which are all considered effective for the short-term treatment for RLS']

['Yes, numerous evidence from clinical trials indicate that pregabalic is effective for treatment of patients diagnosed with restless leg syndrome.']

['yes']

What is the function of calcium-sensing receptor (CaSR)?

['The calcium-sensing receptor (CaSR) is a G-protein-coupled receptor that plays an essential role in maintaining calcium homeostasis. ', 'The calcium-sensing receptor (CaSR) plays a pivotal role in systemic calcium metabolism by regulating parathyroid hormone secretion and urinary calcium excretion. The CaSR is ubiquitously expressed, implying a wide range of functions regulated by this receptor.', 'The CaSR is a key regulator for such diverse processes as hormone secretion, gene expression, inflammation, proliferation, differentiation, and apoptosis. Due to this pleiotropy, the CaSR is able to regulate cell fate and is implicated in the development of many types of benign or malignant tumours of the breast, prostate, parathyroid, and colon.', 'Extracellular calcium-sensing receptor (CaSR) and ovarian cancer gene receptor 1 (OGR1) are two GPCRs that sense extracellular Ca(2+) and H(+), respectively. ', ' The calcium-sensing receptor (CASR) plays a key role in maintaining calcium homeostasis']

['The calcium-sensing receptor (CaSR) is a G-protein-coupled receptor that plays an essential role in maintaining calcium homeostasis.\nThe CaSR is a key regulator for such diverse processes as hormone secretion, gene expression, inflammation, proliferation, differentiation, and apoptosis. Due to this pleiotropy, the CaSR is able to regulate cell fate and is implicated in the development of many types of benign or malignant tumours of the breast, prostate, parathyroid, and colon.']

['The calcium-sensing receptor (CaSR) is a G-protein-coupled receptor that plays an essential role in maintaining calcium homeostasis.']

Describe Hot water reflex epilepsy.

['In this review we assess our currently available knowledge about reflex seizures with special emphasis on the difference between "generalized" reflex seizures induced by visual stimuli, thinking, praxis and language tasks, and "focal" seizures induced by startle, eating, music, hot water, somatosensory stimuli and orgasm.', 'CONCLUSIONS: Intermittent clobazam prophylaxis prior to head water bath might be a preferred mode of treatment of pure HWE. ', 'Different types of reflex epilepsy such as eating, startle myoclonus, and hot water epilepsy were included in the study. ', 'Hot water epilepsy was triggered by contact with hot water either in the bath or by hand immersion, and VEEG showed fronto-parietal involvement.', 'Hot water epilepsy is rarely described in European countries, where bathing epilepsy in younger children is more common and often confused with this type of epilepsy.', 'We studied the anatomical correlates of reflex hot water epilepsy (HWE) using multimodality investigations viz. magnetic resonance imaging (MRI), electroencephalography (EEG), and single photon emission computed tomography (SPECT). ', 'The clinical and SPECT studies suggested temporal lobe as the seizure onset zone in some of the patients with HWE.', 'Hot water epilepsy (HWE) refers to a specific type of reflex epilepsy precipitated by the stimulus of bathing in hot water. Pathogenesis is still unknown and temporal lobe has been thought to take part in the epileptogenesis. HWE can be symptomatic of focal cortical malformation, and few cases were reported. ', 'Hot water epilepsy is a reflex or sensory epilepsy in which seizures are triggered by the stimulus of bathing in hot water', 'Hot water epilepsy (HWE) refers to a specific type of reflex epilepsy precipitated by the stimulus of bathing in hot water', 'Hot water epilepsy was triggered by contact with hot water either in the bath or by hand immersion, and VEEG showed fronto-parietal involvement', 'Hot water epilepsy: A rare form of reflex epilepsy', 'Hot water epilepsy is a form of reflex epilepsy in childhood', 'We studied the anatomical correlates of reflex hot water epilepsy (HWE) using multimodality investigations viz. magnetic resonance imaging (MRI), electroencephalography (EEG), and single photon emission computed tomography (SPECT)', 'Hot water epilepsy is a reflex or sensory epilepsy in which seizures are triggered by the stimulus of bathing in hot water. ', 'The diagnosis of hot water epilepsy was supported by an ictal EEG. Hot water epilepsy, also known as bathing epilepsy or water-immersion epilepsy is, in the Caucasian population, a rare form of benign epilepsy, where seizures are provoked by immersion in a hot or even just a warm bath. This is the first comprehensive video publication of a seizure provoked by water-immersion in a Caucasian child. ', 'Hot water epilepsy (HWE) is a form of reflex or sensory epilepsy wherein seizures are precipitated by an unusual stimulus, the contact of hot water over the head and body. ', 'Hot water epilepsy (HWE) is a rare form of reflex epilepsy caused by bathing with hot water. In this paper, we describe three cases with hot water epilepsy.', '&quot;Hot water epilepsy&quot; (HWE), precipitated by a bath or shower in hot water, has been described infrequently in the literature.', 'A video-EEG recording was taken while hot water was poured onto his chest. Hot water epilepsy is rarely described in European countries, where bathing epilepsy in younger children is more common and often confused with this type of epilepsy.', 'Hot water epilepsy (HWE) or bathing epilepsy is one of the reflex epilepsies induced by hot water pouring over the head,', 'These two patients are the youngest reported cases of reflex hot water seizures, and the only reported cases in which reflex hot water seizures subsequently manifested episodes of alternating hemiplegia.', 'Hot water epilepsy is a reflex epilepsy. Seizures are provoked by hot water, and result from the association of both cutaneous and heat stimuli.', 'Hot water epilepsy belongs to the group of reflex epilepsies. Seizures are provoked by hot water, due to the association of both cutaneous and heat stimuli.', 'A patient with reflex epilepsy is described, in whom seizures were induced by bathing in hot water.']

['Hot water epilepsy (HWE) refers to a specific type of reflex epilepsy precipitated by the stimulus of bathing in hot water. Pathogenesis is still unknown and temporal lobe has been thought to take part in the epileptogenesis. HWE can be symptomatic of focal cortical malformation, and few cases were reported. Intermittent clobazam prophylaxis prior to head water bath might be a preferred mode of treatment of pure HWE.']

[]

Which gene controls the expression of GATA-1 isoforms?

['Mutations in exon 2 interfere with the synthesis of the full-length isoform of GATA-1 and lead to the production of a shortened isoform, GATA-1s.', 'In this study, we report a transcriptional network in which PU.1 positively regulates GATA-1 expression in mast cell development. ', 'This isoform contains an alternatively spliced first exon (IB) that is distinct from the first exon (IE) incorporated in the major erythroid mRNA transcript.', 'Reintroduction of PU.1 restores variant IB isoform and upregulates total GATA-1 protein expression, which is concurrent with mast cell differentiation.', 'Novel combinatorial interactions of GATA-1, PU.1, and C/EBPepsilon isoforms regulate transcription of the gene encoding eosinophil granule major basic protein.', 'Furthermore, we observe that in PU.1(-/-) fetal liver cells, low levels of the IE GATA-1 isoform is expressed, but the variant IB isoform is absent.', 'Our findings identify novel combinatorial protein-protein interactions for GATA-1, PU.1, and C/EBPepsilon isoforms in eosinophil gene transcription that include GATA-1/PU.1 synergy and repressor activity for C/EBPepsilon(27)..']

['In this study, we report a transcriptional network in which PU.1 positively regulates GATA-1 expression in mast cell development. This isoform contains an alternatively spliced first exon (IB) that is distinct from the first exon (IE) incorporated in the major erythroid mRNA transcript.', 'A transcriptional network has been reported, in which PU.1 positively regulates GATA-1 expression in mast cell development.', 'In this study, we report a transcriptional network in which PU.1 positively regulates GATA-1 expression in mast cell development. Reintroduction of PU.1 restores variant IB isoform and upregulates total GATA-1 protein expression, which is concurrent with mast cell differentiation.', 'Mutations in exon 2 interfere with the synthesis of the full-length isoform of GATA-1 and lead to the production of a shortened isoform, GATA-1s. In this study, we report a transcriptional network in which PU.1 positively regulates GATA-1 expression in mast cell development.', 'Mutations in exon 2 interfere with the synthesis of the full-length isoform of GATA-1 and lead to the production of a shortened isoform, GATA-1s. In this study, we report a transcriptional network in which PU.1 positively regulates GATA-1 expression in mast cell development. This isoform contains an alternatively spliced first exon (IB) that is distinct from the first exon (IE) incorporated in the major erythroid mRNA transcript. Reintroduction of PU.1 restores variant IB isoform and upregulates total GATA-1 protein expression, which is concurrent with mast cell differentiation. ', 'Reintroduction of PU.1 restores variant IB isoform and upregulates total GATA-1 protein expression, which is concurrent with mast cell differentiation. Mutations in exon 2 interfere with the synthesis of the full-length isoform of GATA-1 and lead to the production of a shortened isoform, GATA-1s.']

['PU.1']

What is the function of Oseltamivir when administered during flu?

['All patients were given specific antiviral therapy (oseltamivir).', "Oseltamivir (has known by its brand name 'Tamiflu') is a prodrug, requiring ester hydrolysis for conversion to the active form, Oseltamivir carboxylate. Oseltamivir was the first orally active neuraminidase inhibitor commercially developed by US based Gilead Sciences and is currently marketed by F. Hoffmann-La Roche (Roche). Oseltamivir is an antiviral drug which works by blocking the function of the viral neuraminidase protein. US FDA approved Oseltamivir for prophylaxis of uncomplicated influenza A and B. Currently, Oseltamivir is the only first line defense drug available for the treatment of Swine Flu. ", 'The latter is the binding cavity for 3 currently used neuraminidase inhibitors: oseltamivir (Tamiflu), zanamivir (Relenza) and peramivir; thus, the drugs should remain effective for treatment. ', 'Though therapeutic dose of oseltamivir was given as antiviral treatment for the early therapy, and other therapeutic measures such as energetic respiratory and circulatory support, and immunosuppressant therapy were given', 'Oseltamivir (Tamiflu), a neuraminidase inhibitor, is widely used for treatment of influenza.', 'Oseltamivir (Tamiflu), a neuraminidase inhibitor, is effective for treating both seasonal flu and H5N1 influenza A virus infection.', 'BACKGROUND: Oseltamivir phosphate (OP; Tamiflu) is a prodrug of the anti-influenza neuraminidase inhibitor oseltamivir carboxylate (OC) and has been developed for the treatment and prevention of both A and B strains of influenza.', 'Oseltamivir (Tamiflu) is currently the frontline antiviral drug employed to fight the flu virus in infected individuals by inhibiting neuraminidase, a flu protein responsible for the release of newly synthesized virions.', 'Oseltamivir (Tamiflu) is the most important antiviral drug available and a cornerstone in the defence against a future influenza pandemic.', 'The country where oseltamivir is used most is Japan, where it is used to treat seasonal flu.', 'Oseltamivir safety and tolerability were verified in patients with new variant infection A/H1N1.', 'To investigate oseltamivir and oseltamivir carboxylate pharmacokinetics in critically ill patients who were receiving continuous venovenous hemodialysis (CVVHD) and/or extracorporeal membrane oxygenation (ECMO).Prospective, open-label, pharmacokinetic study.Intensive care units of an academic medical center.Thirteen critically ill patients aged 13\xa0years or older with suspected or confirmed H1N1 influenza who had a prescription for oseltamivir and were concurrently receiving CVVHD and/or ECMO between October 2009 and January 2010.Oseltamivir 150\xa0mg was administered nasogastrically or nasoenterically every 12\xa0hours', 'The study included 3351 patients in whom influenza had been diagnosed by use of an antigen detection test kit.Oseltamivir was administered to 1818 patients with influenza A and 1485 patients with influenza B. No anti-influenza drugs were administered to 21 patients with influenza A or to 27 patients with influenza B. Patients receiving oseltamivir therapy were divided into 4 groups according to the time between the onset of fever (temperature, > or = 37.5 degrees C) and administration of the first dose of oseltamivir (0-12 h, 13-24 h, 25-36 h, and 37-48 h)', 'To clarify the usefulness of oseltamivir in the elderly we administered oseltamivir to all residents when an influenza A outbreak occurred in a nursing home.Sixty-eight residents in the nursing home were investigated in which the influenza A outbreak occurred; 32 residents had fever and 28 residents were positive for influenza A with direct enzyme immunoassay.Oseltamivir was administered at 75 mg twice daily for 5 days to all residents.Oseltamivir almost inhibited symptom onset in the influenza A-positive afebrile group', 'Oseltamivir was administered to patients with influenza like illness and confirmed influenza, while their close contacts were given oseltamivir prophylactically', 'Insights from investigating the interaction of oseltamivir (Tamiflu) with neuraminidase of the 2009 H1N1 swine flu virus.', 'Evaluation of treatment with Oseltamivir during the 2009 H1N1 (swine flu) pandemic: the problem of incomplete clinical information.', 'Immunological effects of the orally administered neuraminidase inhibitor oseltamivir in influenza virus-infected and uninfected mice.', 'Oral oseltamivir improves pulmonary function and reduces exacerbation frequency for influenza-infected children with asthma.', 'Oseltamivir (Tamiflu) is a potent and selective antiviral drug employed to fight the flu virus in infected individuals by inhibiting neuraminidase (NA), a flu protein responsible for the release and spread of the progeny virions.', 'Oseltamivir is an antiviral drug which works by blocking the function of the viral neuraminidase protein.', 'Neuraminidase (NA) inhibitors (Oseltamivir and Zanamivir) are presently used as an anti-flu drugs.', 'US FDA approved Oseltamivir for prophylaxis of uncomplicated influenza A and B. Currently, Oseltamivir is the only first line defense drug available for the treatment of Swine Flu.', 'Oseltamivir and Zanamivir have good number of interactions with H1N1 2009 virus and the scoring function also support to this result.', 'The number of interaction and scoring function shows that Oseltamivir and Zanamivir will be able to effectively control the present pandemic H1N1 virus 2009.', 'Oseltamivir (Tamiflu), a neuraminidase inhibitor, is effective for treating both seasonal flu and H5N1 influenza A virus infection. Oseltamivir is generally well tolerated, and its most common adverse effects are nausea and vomiting.', 'Oseltamivir (Tamiflu) is currently the frontline antiviral drug employed to fight the flu virus in infected individuals by inhibiting neuraminidase, a flu protein responsible for the release of newly synthesized virions. However, oseltamivir resistance has become a critical problem due to rapid mutation of the flu virus.', 'Approximately 1.4% of tested isolates are oseltamivir resistant. We report a patient with an underlying hematological malignancy who was hospitalized with influenza A (H1N1) swine-origin and whose strain developed oseltamivir resistance during therapy.', 'Oseltamivir (Tamiflu), a neuraminidase inhibitor, is widely used for treatment of influenza. Because abnormal behaviors have been observed in some Japanese teenagers following oseltamivir use, its safety has been questioned. Oseltamivir is known to alter neuronal function and behavior in animals, particularly when administered in combination with ethanol.', 'Oseltamivir (Tamiflu), a neuraminidase inhibitor, is effective for treating both seasonal flu and H5N1 influenza A virus infection. Oseltamivir is generally well tolerated, and its most common adverse effects are nausea and vomiting. However, neuropsychiatric behaviors including jumping and falling from balconies by young patients being treated by oseltamivir have been reported from Japan; this has led to warnings against its prescribing by many authorities.', 'However, oseltamivir resistance has become a critical problem due to rapid mutation of the flu virus.', 'We observed also 10 infections A/H1N1 influenza during pregnancy, with good oseltamivir tolerance and without recent perinathal complications.CONCLUSIONS: Among 109 individuals with swine flu influenza, 67% have not complicated clinical manifestation and they recovered during 3-4 days.', 'The number of interaction and scoring function shows that Oseltamivir and Zanamivir will be able to effectively control the present pandemic H1N1 virus 2009..', 'Most reported that oseltamivir was an effective treatment for the flu.', 'It is needed to perform surveillance on oseltamivir resistance in swine flu.', 'The neuraminidase (NA) of influenza virus is the target of anti-flu drugs oseltamivir and zanamivir.', "According to one trial, oseltamivir was moderately effective as a prophylactic for close contacts of 'flu cases (6.6% in absolute values).", 'Oseltamivir: a first line defense against swine flu.', 'Oseltamivir administered daily for six weeks by the oral route is safe and effective for the prevention of influenza..']

["Oseltamivir (has known by its brand name 'Tamiflu') is a prodrug, requiring ester hydrolysis for conversion to the active form, Oseltamivir carboxylate. Oseltamivir is the first orally active neuraminidase inhibitor and it is an antiviral drug for the treatment of Swine Flu."]

[]

Is there any software for automated analysis of FISH images?

['he study demonstrated the feasibility of automated FISH signal analysis that applying a CAD scheme to the automated generated 2-D projection images.', 'A color imaging technique, multiplex fluorescent in situ hybridization (M-FISH), has been developed to ease the analysis of the process. Using an M-FISH technique each chromosome class (1,2, …,22,X,Y) is stained with a unique color. However, significant variations between images are observed due to a number of factors such as uneven hybridization and spectral overlap among channels. These types of variations influence the pixel classification accuracy of image classification methods which are supervised and require a set of annotated images for training. In this paper, we present a fully unsupervised M-FISH chromosome image classification methodology. Our main contributions are 1) the assumption that the intensity of a chromosome pixel is sampled from multiple Gaussian components [Gaussian mixture model (GMM)] such that each component corresponds to one chromosome class, and 2) the initialization of the GMM model using the emission information of each chromosome class. This is feasible since prior to the M-FISH image acquirement, we already know which chromosome class is emitting to each of the five M-FISH image channels. The method has been tested on a large number of M-FISH images and an overall accuracy of 89.85% is reported. Our method is unsupervised and presents higher classification accuracy even when it is compared with common supervised based methods.', 'hybridization (FISH) tests provide promising molecular imaging biomarkers to more accurately and reliably detect and diagnose cancers and genetic disorders. Since current manual FISH signal analysis is low-efficient and inconsistent, which limits its clinical utility, developing automated FISH image scanning systems and computer-aided detection (CAD) schemes has been attracting research interests. To acquire high-resolution FISH images in a multi-spectral scanning mode, a huge amount of image data with the stack of the multiple three-dimensional (3-D) image slices is generated from a single specimen. Automated preprocessing these scanned images to eliminate the non-useful and redundant data is important to make the automated FISH tests acceptable in clinical applications. In this study, a dual-detector fluorescence image scanning system was applied to scan four specimen slides with FISH-probed chromosome X. A CAD scheme was developed to detect analyzable interphase cells and map the multiple imaging slices recorded FISH-probed signals into the 2-D projection images. CAD scheme was then applied to each projection image to detect analyzable interphase cells using an adaptive multiple-threshold algorithm, identify FISH-probed signals using a top-hat transform, and compute the ratios between the normal and abnormal cells. To assess CAD performance, the FISH-probed signals were also independently visually detected by an observer. The Kappa coefficients for agreement between CAD and observer ranged from 0.69 to 1.0 in detecting/counting FISH signal spots in four testing samples.', ' In this paper we developed a sparse representation-based classification (SRC) algorithm based on L1-norm minimization for classifying chromosomes from multicolor fluorescence in situ hybridization (M-FISH) images. The algorithm has been tested on a comprehensive M-FISH database that we established, demonstrating improved performance in classification. When compared with other pixel-wise M-FISH image classifiers such as fuzzy c-means (FCM) clustering algorithms and adaptive fuzzy c-means (AFCM) clustering algorithms that we proposed earlier the current method gave the lowest classification error. In order to evaluate the performance of different SRC for M-FISH imaging analysis, three different sparse representation methods, namely, Homotopy method, Orthogonal Matching Pursuit (OMP), and Least Angle Regression (LARS), were tested and compared. Results from our statistical analysis have shown that Homotopy based method is significantly better than the other two methods. ', 'Fluorescence in situ hybridization (FISH) is used to study the organization and the positioning of specific DNA sequences within the cell nucleus. Analyzing the data from FISH images is a tedious process that invokes an element of subjectivity. Automated FISH image analysis offers savings in time as well as gaining the benefit of objective data analysis. While several FISH image analysis software tools have been developed, they often use a threshold-based segmentation algorithm for nucleus segmentation. As fluorescence signal intensities can vary significantly from experiment to experiment, from cell to cell, and within a cell, threshold-based segmentation is inflexible and often insufficient for automatic image analysis, leading to additional manual segmentation and potential subjective bias. To overcome these problems, we developed a graphical software tool called FISH Finder to automatically analyze FISH images that vary significantly. By posing the nucleus segmentation as a classification problem, compound Bayesian classifier is employed so that contextual information is utilized, resulting in reliable classification and boundary extraction. This makes it possible to analyze FISH images efficiently and objectively without adjustment of input parameters. Additionally, FISH Finder was designed to analyze the distances between differentially stained FISH probes.', 'The simultaneous detection of protein expression and gene copy number changes in patient samples, like paraffin-embedded tissue sections, is challenging since the procedures of immunohistochemistry (IHC) and Fluorescence in situ Hybridization (FISH) negatively influence each other which often results in suboptimal staining. Therefore, we developed a novel automated algorithm based on relocation which allows subsequent detection of protein content and gene copy number changes within the same cell. METHODS: Paraffin-embedded tissue sections of colorectal cancers were stained for CD133 expression. IHC images were acquired and image coordinates recorded. Slides were subsequently hybridized with fluorescently labeled DNA probes. FISH images were taken at the previously recorded positions allowing for direct comparison of protein expression and gene copy number signals within the same cells/tissue areas. Relocation, acquisition of the IHC and FISH images, and enumeration of FISH signals in the immunophenotyped tumour areas were done in an automated fashion. RESULTS: Automated FISH analysis was performed on 13 different colon cancer samples that had been stained for CD133; each sample was scored for MYC, ZNF217 and Chromosome 6 in CD133 positive and negative glands. From the 13 cases four (31%) showed amplification for the MYC oncogene and seven of 13 (54%) cases were amplified for ZNF217.', 'The simultaneous detection of protein expression and gene copy number changes in patient samples, like paraffin-embedded tissue sections, is challenging since the procedures of immunohistochemistry (IHC) and Fluorescence in situ Hybridization (FISH) negatively influence each other which often results in suboptimal staining.Therefore, we developed a novel automated algorithm based on relocation which allows subsequent detection of protein content and gene copy number changes within the same cell. METHODS: Paraffin-embedded tissue sections of colorectal cancers were stained for CD133 expression. IHC images were acquired and image coordinates recorded. Slides were subsequently hybridized with fluorescently labeled DNA probes. FISH images were taken at the previously recorded positions allowing for direct comparison of protein expression and gene copy number signals within the same cells/tissue areas. Relocation, acquisition of the IHC and FISH images, and enumeration of FISH signals in the immunophenotyped tumour areas were done in an automated fashion. RESULTS: Automated FISH analysis was performed on 13 different colon cancer samples that had been stained for CD133; each sample was scored for MYC, ZNF217 and Chromosome 6 in CD133 positive and negative glands. From the 13 cases four (31%) showed amplification for the MYC oncogene and seven of 13 (54%) cases were amplified for ZNF217. There was no significant difference between CD133 positive tumour and CD133 negative tumour cells. ', 'The simultaneous detection of protein expression and gene copy number changes in patient samples, like paraffin-embedded tissue sections, is challenging since the procedures of immunohistochemistry (IHC) and Fluorescence in situ Hybridization (FISH) negatively influence each other which often results in suboptimal staining.Therefore, we developed a novel automated algorithm based on relocation which allows subsequent detection of protein content and gene copy number changes within the same cell.Methods: Paraffin-embedded tissue sections of colorectal cancers were stained for CD133 expression. IHC images were acquired and image coordinates recorded. Slides were subsequently hybridized with fluorescently labeled DNA probes. FISH images were taken at the previously recorded positions allowing for direct comparison of protein expression and gene copy number signals within the same cells/tissue areas. Relocation, acquisition of the IHC and FISH images, and enumeration of FISH signals in the immunophenotyped tumour areas were done in an automated fashion.Results: Automated FISH analysis was performed on 13 different colon cancer samples that had been stained for CD133; each sample was scored for MYC, ZNF217 and Chromosome 6 in CD133 positive and negative glands. From the 13 cases four (31%) showed amplification for the MYC oncogene and seven of 13 (54%) cases were amplified for ZNF217. There was no significant difference between CD133 positive tumour and CD133 negative tumour cells.']

['FISH is a popular molecular cytogenetic method. The output of a single FISH analysis is a set of several tens or hundreds microscopic images — a single evaluated sample is of roughly 20mm diameter. The goal of an automated evaluation is to replace the subjective evaluation of images by the laboratory technician to achieve higher uniformity of results. Following explanation of the principle of the method and the typical contents of images, the processing flow of image segmentation is outlined and the results are presented on several example images. Based on results there are software for automated analysis of FISH images.']

['yes']

What is the function of the AtxA pleiotropic regulator?

['The atxA gene product activates transcription of the anthrax toxin genes and is essential for virulence.', 'The atxA-null mutant is avirulent in mice', 'These data suggest that the atxA gene product also regulates toxin gene expression during infection.', 'Thus, we conclude that the pX01 influence on capsule synthesis is mediated by AtxA, the pXO1-encoded trans-activator of the toxin gene expression.', 'atxA, the gene encoding the trans-activator of anthrax toxin synthesis', 'The genes atxA, located on pXO1, and acpA, located on pXO2, encode positive trans-acting proteins that are involved in bicarbonate-mediated regulation of toxin and capsule production, respectively', ' Transcription initiated from P1 and P2 was activated by both atxA and acpA, and activation appeared to be stimulated by bicarbonate.', 'In atxA+ strains, toxin gene expression is increased 5- to 20-fold in cells grown in 5% CO2 relative to cells grown in air.', 'Our data indicate a clear association of atxA with CO2-enhanced gene expression in B. anthracis and provide evidence that atxA regulates genes other than the structural genes for the anthrax toxin proteins.', ' Our data strongly suggest that an additional factor(s) is involved in regulation of pag and that the relative amounts of such a factor(s) and AtxA are important for optimal toxin gene expression.', 'Two regulatory genes, acpA and atxA, have been reported to control expression of the Bacillus anthracis capsule biosynthesis operon capBCAD', 'The atxA gene is located on the virulence plasmid pXO1, while pXO2 carries acpA and the cap genes', 'Dual promoters control expression of the Bacillus anthracis virulence factor AtxA.', 'Here we report that transcription of the atxA gene occurs from two independent promoters, P1 (previously described by Dai et al. [Z. Dai, J. C. Sirard, M. Mock, and T. M. Koehler, Mol. Microbiol. 16:1171-1181, 1995]) and P2, whose transcription start sites are separated by 650 bp.', 'AtxA controls the expression of more than a hundred genes belonging to all genetic elements, the chromosome and both virulence plasmids, including those encoding the major virulence factors. AtxA can activate or repress gene expression. ', "Here we employ 5' and 3' deletion analysis and site-directed mutagenesis of the atxA control region to demonstrate that atxA transcription from the major start site P1 is dependent upon a consensus sequence for the housekeeping sigma factor SigA and an A+T-rich upstream element for RNA polymerase.", 'We also show that an additional trans-acting protein(s) binds specifically to atxA promoter sequences located between -13 and +36 relative to P1 and negatively impacts transcription. Deletion of this region increases promoter activity up to 15-fold.', 'A majority of genes on the virulence plasmid pXO1 that are regulated by the presence of either CO2 or AtxA separately are also regulated synergistically in the presence of both. These results also elucidate novel pXO1-encoded small RNAs that are associated with virulence conditions.', 'This response requires the presence of the pXO1 virulence plasmid-encoded pleiotropic regulator AtxA.', 'Transcriptome analysis identifies Bacillus anthracis genes that respond to CO2 through an AtxA-dependent mechanism', 'The majority of the regulated genes responded to both AtxA and carbon dioxide rather than to just one of these factors. Interestingly, we identified two previously unrecognized small RNAs that are highly expressed under physiological carbon dioxide concentrations in an AtxA-dependent manner', 'This response requires the presence of the pXO1 virulence plasmid-encoded pleiotropic regulator AtxA.', 'As a similar organization is found in transcription regulators in many other pathogens, AtxA might become the paradigm of a new class of virulence regulators.', 'AtxA, a Bacillus anthracis global virulence regulator.', 'Bacillus anthracis virulence regulator AtxA: oligomeric state, function and CO(2) -signalling.', 'The accumulation of the global virulence regulator AtxA protein was strongly reduced in the mutant strain.', 'This response requires the presence of the pXO1 virulence plasmid-encoded pleiotropic regulator AtxA', 'This response requires the presence of the pXO1 virulence plasmid-encoded pleiotropic regulator AtxA. ', 'Opposing effects of histidine phosphorylation regulate the AtxA virulence transcription factor in Bacillus anthracis.', 'The B. anthracis pleiotropic regulator CodY activates toxin gene expression by post-translationally regulating the accumulation of the global regulator AtxA. ', 'Cross-talk to the genes for Bacillus anthracis capsule synthesis by atxA, the gene encoding the trans-activator of anthrax toxin synthesis.', 'AtxA, a unique regulatory protein of unknown molecular function, positively controls expression of the major virulence genes of Bacillus anthracis. ', 'Consistent with the role of atxA in virulence factor expression, a B. anthracis atxA-null mutant is avirulent in a murine model for anthrax. ', 'This response requires the presence of the pXO1 virulence plasmid-encoded pleiotropic regulator AtxA.', 'PlcR is the first example described of a pleiotropic regulator involved in the control of extracellular virulence factor expression in pathogenic Bacillus spp.', 'Bacillus anthracis virulence regulator AtxA: oligomeric state, function and CO(2) -signalling.', 'AtxA, a unique regulatory protein of unknown molecular function, positively controls expression of the major virulence genes of Bacillus anthracis.']

['AtxA is the gene encoding the trans-activator of anthrax toxin synthesis and is essential for virulence of B. anthracis. It is located on the resident 185-kb plasmid pXO1 and its activation is stimulated by bicarbonate. AtxA controls the expression of more than a hundred genes belonging to all genetic elements, the chromosome and both virulence plasmids, including those encoding the major virulence factors. AtxA can activate or repress gene expression. In atxA+ strains, toxin gene expression is increased 5- to 20-fold in cells grown in 5% CO2 relative to cells grown in air. Dual promoters control expression of AtxA. Transcription of the atxA gene occurs from two independent promoters, P1 and P2, whose transcription start sites are separated by 650 bp.', 'Comparison of the resulting protein patterns indicated that synthesis of non-toxin proteins is influenced by growth in elevated CO2 and the toxin gene regulator, atxA. The AtxA virulence regulator of Bacillus anthracis is required for toxin and capsule gene expression. DNA sequence analysis of transposon insertion sites in 17 mutants carrying CO2- and atxA-regulated fusions revealed 10 mutants carrying independent insertions on the 185-kb toxin plasmid pXO1 which did not map to the toxin genes. We purified histidine-tagged AtxA [AtxA(His)] from Escherichia coli and used anti-AtxA(His) serum to detect AtxA in protein preparations from B. anthracis cells.', 'The atxA gene product activates transcription of the anthrax toxin genes and is essential for virulence.']

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What is the indication for prophylactic use of antibiotics in COPD?

['Yet recent well-designed studies have demonstrated that prophylactic antibiotic use is of significant benefit to patients prone to developing infections. Study patients suffered from recurrent urinary tract infections, COPD or were mechanically ventilated in intensive care units. In the first 2 populations, use of antibiotics was associated with an increase in carriage of antibiotic-resistant bacteria, but in intensive care patients the opposite was documented', 'Guidelines do not recommend the use of prophylactic antibiotics in COPD but there is preliminary evidence to suggest that they may reduce the number of exacerbations.', 'A short prophylactic treatment course with azithromycin is a good alternative in the management of patients with severe, advanced COPD, and could lead to an improvement in social and healthcare costs']

['In a subset of patients with severe disease and prone to developing infections prophylactic use of antibiotics may reduce number of exacerbations and improve social and health care costs.']

['Reduction of number of exacerbations']

Is amantadine effective for treatment of disorders conciousness?

['We here provide a systematic overview of the therapeutic effects of amantadine, apomorphine and zolpidem in patients recovering from coma. Evidence from clinical trials using these commonly prescribed pharmacological agents suggests positive changes in the neurological status in patients, leading sometimes to dramatic improvements.', 'Pharmaceuticals that act in the oxygen based amino acid systems of the brain include the GABAergic medications zolpidem and baclofen, while those that act in the monoamine axes include the dopaminergic medications L Dopa, amantadine, bromocriptine, apomorphine and methylphenidate, and the noradrenergic and serotonergic medications desipramine, amitriptyline, protriptyline and fluoxetine. ', 'Sporadic cases of recovery from a DOC have been reported after the administration of various pharmacological agents (baclofen, zolpidem, amantadine etc.).', 'Amantadine hydrochloride is one of the most commonly prescribed medications for patients with prolonged disorders of consciousness after traumatic brain injury. Preliminary studies have suggested that amantadine may promote functional recovery.', ' During the 4-week treatment period, recovery was significantly faster in the amantadine group than in the placebo group, as measured by the DRS score (difference in slope, 0.24 points per week; P=0.007), indicating a benefit with respect to the primary outcome measure. ', 'Amantadine accelerated the pace of functional recovery during active treatment in patients with post-traumatic disorders of consciousness.', 'Sporadic cases of dramatic recovery from DOC after the administration of various pharmacological agents, such as baclofen, zolpidem and amantadine, have been recently supported by intriguing scientific observations. ', 'According to the 16 eligible studies, medical management by dopaminergic agents (levodopa, amantadine), zolpidem and median nerve stimulation, or surgical management by deep brain stimulation, extradural cortical stimulation, spinal cord stimulation and intrathecal baclofen have shown to improve the level of consciousness in certain cases. ', 'Higher exposure of amantadine (average concentration of amantadine during 6 mg/kg/day > 1.5 mg/L) may be associated with better recovery of consciousness. ', 'Based on the preliminary data, higher dosing may be considered in the setting of brain injury.', 'Patients treated with PK-Merz exhibited the more significant restoration of consciousness and better dynamics (regress) of neurological deficit with the most intensive restoration of neurological deficit in the first day that allows to recommend the use of amantadine sulfate in the first hours of ischemic stroke and for the prevention of reperfusion damage in recanalisation therapy of ischemic stroke.', 'There was no significant difference in the slopes of recovery during either arm for the Coma/Near-Coma Scale (P = 0.24) or the Coma Recovery Scale-Revised (P = 0.28), although improvements in consciousness were noted by the physician during weeks when amantadine was given (P = 0.02). ', 'This study suggests that amantadine facilitates recovery of consciousness in pediatric acquired brain injury and provides important information necessary to design future more definitive studies.', 'The study has shown a positive effect of this drug at coma emergence, which manifested itself as clinical improvement and a better outcome of the disease.', "This article will review the evidence for the use of psychostimulants (methylphenidate), antidepressants (amitriptyline, selective serotonin reuptake inhibitors, and buproprion), Parkinson's medications (amantadine, bromocriptine, carbidopa/levodopa), anticonvulsants (valproic acid), modafinil (Provigil), lactate, hyperbaric oxygen chamber, electroconvulsive therapy, and transmagnetic stimulation, in patients following a head injury.", 'Of the psychoactive medications, amantadine hydrochloride was associated with greater recovery and dantrolene sodium was associated with less recovery, in terms of the DRS score at 16 weeks but not the time until commands were followed.']

['Amantadine, a dopaminergic agent, has been shown to be effective for induction of recovery from disorders of consciousness. Amantadine is a commonly prescribed medication for patients with prolonged disorders of consciousness after traumatic brain injury. Amantadine accelerates the pace of functional recovery during active treatment in patients with post-traumatic disorders of consciousness. Higher dosing of amantadine may be considered in the setting of brain injury.']

['yes']

How histone deacetylation causes transcriptional gene silencing?

['Lysine acetylation of histones is one of the major epigenetic regulators of chromatin conformation and gene expression. The dynamic nature of histone acetylation is determined by the counterbalancing activity of histone acetyltransferase and histone deacetylase (HDAC) enzymes. Acetylation of histones is generally associated with open and transcriptionally active chromatin, whereas the activity of HDACs leads to histone deacetylation, condensation of chromatin, and inhibition of transcription.', 'Abnormal activity of HDACs has been implicated in tumorigenesis and therefore considerable effort has been put into the development of HDAC inhibitors as a means of modifying histone acetylation status and reexpressing aberrantly silenced tumor suppressor genes.', 'Histone acetylation and deacetylation play essential roles in eukaryotic gene regulation. Reversible modifications of core histones are catalyzed by two intrinsic enzymes, histone acetyltransferase and histone deacetylase (HD). In general, histone deacetylation is related to transcriptional gene silencing, whereas acetylation correlates with gene activation.', 'The reversible nature of deregulated chromatin structure by DNA methylation and histone deacetylation inhibitors, leading to re-expression of tumor suppressor genes, makes chromatin-remodeling pathways as promising therapeutic targets.', 'Furthermore, the histone deacetylase inhibitor, trichostatin A (TSA), recovered the expression and function of NEO1 in the silenced lines, suggesting that histone deacetylation is essential for the direct suppression of target genes by DNAi.', 'We had previously shown that in anergic CD4(+) T cells, Ikaros participates in the transcriptional repression of the Il2 gene by recruiting histone deacetylases that cause core histone deacetylation at the Il2 promoter. Here we show that deacetylation at the Il2 promoter is the initial step in a process that leads to the stable silencing of the Il2 gene transcription in anergic T cells.', 'We demonstrate that HP1 forms distinct DNA methylation and histone deacetylation complexes that work in parallel to assemble silent chromatin in N. crassa.', 'These results indicated that histone deacetylation is a silencing mechanism for GATA4 expression in AFP-producing gastric cancer cells.', 'We found that histone deacetylase 1 (HDAC1) increases the expression levels of mature miRNAs despite repressing the transcription of host genes.', 'Promoter methylation and histone deacetylation were studied as possible mechanisms for klotho silencing.', 'Taken together, these data indicate loss of klotho expression as an early event in breast cancer development, and suggest a role for DNA methylation and histone deacetylation in klotho silencing.', 'DNA methylation and histone acetylation/deacetylation are distinct biochemical processes that control gene expression. While DNA methylation is a common epigenetic signal that inhibits gene transcription, histone deacetylation similarly represses transcription but can be both an epigenetic and nonepigenetic phenomenon', 'DNA methylation and histone acetylation/deacetylation are distinct biochemical processes that control gene expression. While DNA methylation is a common epigenetic signal that inhibits gene transcription, histone deacetylation similarly represses transcription but can be both an epigenetic and nonepigenetic phenomenon.', 'Because DNA hypermethylation-based silencing may couple with and depend on histone deacetylation, our study suggests that endogenous HDAC inhibition by maspin may prevent pathologic gene silencing in prostate tumor progression.', 'Epigenetic regulation of the IL-13-induced human eotaxin-3 gene by CREB-binding protein-mediated histone 3 acetylation.', 'Heterochromatin impacts various nuclear processes by providing a recruiting platform for diverse chromosomal proteins. In fission yeast, HP1 proteins Chp2 and Swi6, which bind to methylated histone H3 lysine 9, associate with SHREC (Snf2/HDAC repressor complex) and Clr6 histone deacetylases (HDACs) involved in heterochromatic silencing.', 'We established that the silencing of these genes in UVB-exposed epidermis and UVB-induced skin tumors is associated with a network of epigenetic modifications, including hypoacetylation of histone H3 and H4 and increased histone deacetylation, as well as recruitment of methyl-binding proteins, including MeCP2 and MBD1, to the methylated CpGs.', 'Histone deacetylation directs DNA methylation in survivin gene silencing.', 'Next, we investigated the roles of histone acetylation and DNA methylation in survivin silencing after blockade of histone deacetylation with Trichostatin A (TSA).', 'The results showed that histone deacetylation blocked by TSA reversed the increasing effect of histone deacetylation on the expression of survivin mRNA.', 'Aberrant hypermethylation at CpG sites within the CDKN2A gene is associated with silencing and has been proposed as a target for reactivation using both DNA methylation and histone deacetylation inhibitors.', 'Mechanisms of HDA6-mediated rRNA gene silencing: suppression of intergenic Pol II transcription and differential effects on maintenance versus siRNA-directed cytosine methylation.', 'The Arabidopsis histone deacetylase HDA6 is required to silence transgenes, transposons, and ribosomal RNA (rRNA) genes subjected to nucleolar dominance in genetic hybrids.', 'Distinct and temporal roles of nucleosomal remodeling and histone deacetylation in the repression of the hTERT gene.', 'Surprisingly, inhibition of histone deacetylation at the hTERT promoter did not prevent hTERT repression or nucleosomal deposition, indicating that nucleosomal deposition at the core promoter, but not histone deacetylation, was the cause of transcriptional repression. Our data also suggested that succeeding nucleosomal remodeling and histone deacetylation worked in parallel to establish the stable repressive status of hTERT gene in human somatic cells.', 'Reconstitution of heterochromatin-dependent transcriptional gene silencing.', 'Silencing requires all three Sir proteins, even with fully deacetylated chromatin, and involves the specific association of Sir3 with deacetylated H4K16. These results define a minimal set of components that mediate heterochromatic gene silencing and demonstrate distinct contributions for histone deacetylation and nucleosome binding in the silencing mechanism.', 'Silencing requires all three Sir proteins, even with fully deacetylated chromatin, and involves the specific association of Sir3 with deacetylated H4K16. These results define a minimal set of components that mediate heterochromatic gene silencing and demonstrate distinct contributions for histone deacetylation and nucleosome binding in the silencing mechanism', 'Inhibition of histone deacetylase suppresses EGF signaling pathways by destabilizing EGFR mRNA in ER-negative human breast cancer cells.', 'Our previous studies demonstrate that histone deacetylation plays a key role in ER gene silencing, and ER expression can be restored with histone deacetylase (HDAC) inhibitors in ER-negative human breast cancer cells.', 'This chromatin pattern, and particularly H3K4me2 levels, crisply separates DNA-hypermethylated genes from those where histone deacetylation is responsible for transcriptional silencing.', 'Loss of gene expression is not due to structural mutations, but to regulatory changes including epigenetic deacetylation of histones.', 'We found that these PERV families are differentially up- or downregulated upon chemical inhibition of DNA methylation and histone deacetylation in cultured porcine cells.', 'The class IIa histone deacetylases (HDACs) act as transcriptional repressors by altering chromatin structure through histone deacetylation.', "The Set3 histone deacetylase complex (Set3C) binds histone H3 dimethylated at lysine 4 (H3K4me2) to mediate deacetylation of histones in 5'-transcribed regions.", 'Core histone modifications play an important role in chromatin remodeling and transcriptional regulation.', 'These results demonstrate that the acetylation/deacetylation balance strongly influences the expression of arginase-1, a gene of alternative activation of macrophages.', 'MTA1 acts as part of a nucleosome remodelling and histone deacetylation complex, which is involved in transcriptional regulation.', 'The ectopic expression of ThPOK resulted in increased recruitment of histone deacetylases at Cd8 loci; the enhanced deacetylation of Cd8 genes eventually led to impaired Cd8 transcription.', 'Sirt-1, a nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase, has been linked to transcriptional silencing and appears to play a key role in inflammation.', 'OBJECTIVE: Histone deacetylation regulates chromatin remodeling and transcriptional down-regulation of specific genomic regions; it is altered in many types of cancer cells.', "Histone acetylations affect the regulation of gene transcription, and the loss of learning induced deacetylation at specific histone sites may represent biomarkers for memory loss and Alzheimer's disease (AD).", 'Increasing chromatin accessibility via inhibition of histone deacetylation or DNA methylation lowered the induction threshold, demonstrating that chromatin accessibility sets the level of RelA required to activate gene expression.', 'The NAD-dependent histone deacetylase Sirt1 antagonizes p53 transcriptional activity to regulate cell-cycle progression and apoptosis.', 'These studies reveal a new mechanism by which acetyltransferase activity induces gene expression through targeted destruction of a transcriptional repressor.', 'Further studies indicated that GR recruited histone deacetylase 1 to the Runx2 P2 promoter which then mediated the deacetylation of histone H4 and down-regulated Runx2 expression.', 'RUNX2 cofactors such as histone deacetylases (HDACs) play a key role in chromatin remodeling and regulation of gene transcription.', 'In some cell lines latently infected with EBV, an HDAC inhibitor alone can induce BZLF1 transcription, while the treatment does not enhance expression in other cell lines, such as B95-8 or Raji cells, suggesting unknown suppressive mechanisms besides histone deacetylation in those cells.', 'Furthermore, the deacetylation of p53 by EWS-Fli1 suppressed its transcriptional activity and enhanced mdm2-mediated p53 degradation.', 'This finding suggests that HDACs have two arms for gene silencing: transcriptional repression by promoter histone deacetylation and post-transcriptional inhibition by increasing miRNA abundance.', 'Promoter-localized deacetylation of H3 tails is a prerequisite for VprBP to tether and act as a bona fide inhibitor at p53 target genes.', 'CONCLUSIONS: These findings imply an important role for histone deacetylation in the downregulation of E-cadherin in human pancreatic cancer.', 'Inhibition of transcription results from the release of p300 coactivator from NF-κB target gene promoters and subsequent histone deacetylation.', 'In fungi in general, gene expression is often partially controlled at the chromatin level in secondary metabolism; when this is the case, the deacetylation and acetylation (and other posttranslational modifications) of histones are usually crucial in the regulation of transcription.', 'For the first time, we provide direct evidence that CREMα mediates silencing of the IL2 gene in SLE T cells though histone deacetylation and CpG-DNA methylation.', 'The downregulation of CD43 mRNA is caused by p53-dependent transrepression, at least in part, via a histone deacetylation mechanism.', 'DNA methylation and histone acetylation/deacetylation are distinct biochemical processes that control gene expression.', 'Acetylation of histones is generally associated with open and transcriptionally active chromatin, whereas the activity of HDACs leads to histone deacetylation, condensation of chromatin, and inhibition of transcription.', 'This study demonstrates that a mutual cross-talk mechanism exists between histone chaperones and histone deacetylation in transcriptional regulation.', 'FVE is a homologue of the mammalian retinoblastoma-associated protein (RbAp), one component of a histone deacetylase (HDAC) complex involved in transcriptional repression, and has been shown to be involved in the deacetylation of the FLOWERING LOCUS C (FLC) chromatin encoding for a repressor of flowering.', 'Thus, our data illustrate the orchestration of a sequential epigenetic mechanism including the histone deacetylation and methylation, and the DNA methylation processes.', 'Histone deacetylases (HDACs) mediate histone deacetylation and act in concert with histone acetyltransferases to regulate dynamic and reversible histone acetylation which modifies chromatin structure and function, affects gene transcription, thus, controlling multiple cellular processes.', 'We hypothesized that the episomal nature of IDLVs turns them into preferential targets for epigenetic silencing involving chromatin-remodeling histone deacetylation.', 'Silencing involves epigenetic mechanisms, including histone deacetylation.', 'Jmjd3 transcription is not induced in Atf4-knock-out cells, but the AAR-dependent activation was rescued by inhibition of histone deacetylation with trichostatin A (TSA).', 'We conclude that histone deacetylation is specifically required for the earliest events in appendage regeneration in amphibians, and suggest that this may act as a switch to trigger re-expression of developmental genes.', "Inhibition of DNA methylation with 5-aza-2'-deoxycytidine (5aza) and histone deacetylation with Trichostatin A (TSA) resulted in upregulation of EP2 mRNA in all cell lines with varying influences of each epigenetic process observed.", 'During cancer development, tumor suppressor genes were silenced by promoter methylation or histone deacetylation.', 'Histone deacetylases (HDACs) are important to maintain histone deacetylation.', 'Suppression of histone deacetylation and DNA methylation normalized Pomc expression and functional abnormalities.']

['Histone deacetylation, catalyzed by the histone deacetylase (HDAC) enzymes, is an epigenetic modification. Histone deacetylation leads to the formation of a condensed and transcriptionally repressive chromatin structure which inhibits gene transcription. ']

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How does phospholamban affect the biological activity of the calcium ATPase SERCA?

['Phospholamban (PLN) is a small integral membrane protein, which binds and inhibits in a yet unknown fashion the Ca(2+)-ATPase (SERCA) in the sarcoplasmic reticulum.', 'SR calcium uptake is mediated by a Ca(2+)-ATPase (SERCA2), whose activity is reversibly regulated by phospholamban (PLN). Dephosphorylated PLN is an inhibitor of SERCA and phosphorylation of PLN relieves this inhibition. ', 'Regulation of the SERCA calcium pump by phospholamban (PLB) is largely due to interactions between their respective transmembrane domains. In spite of numerous mutagenesis and kinetic studies, we still do not have a clear mechanistic picture of how PLB influences the calcium transport cycle of SERCA. ', 'Phospholamban (PLN) regulates cardiac contractility via its modulation of sarco(endo)plasmic reticulum calcium ATPase (SERCA) activity. Impairment of this regulatory process causes heart failure.', 'Based on structural and dynamics data, we propose a model in which PLN undergoes allosteric activation upon encountering SERCA.', 'The membrane protein complex between the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and phospholamban (PLN) controls Ca(2+) transport in cardiomyocytes, thereby modulating cardiac contractility. β-Adrenergic-stimulated phosphorylation of PLN at Ser-16 enhances SERCA activity via an unknown mechanism.', 'We found that the allosteric regulation of SERCA depends on the conformational equilibrium of PLN, whose cytoplasmic regulatory domain interconverts between three different states: a ground T state (helical and membrane associated), an excited R state (unfolded and membrane detached), and a B state (extended and enzyme-bound), which is noninhibitory. Phosphorylation at Ser-16 of PLN shifts the populations toward the B state, increasing SERCA activity.', 'Phospholamban (PLN) is a type II membrane protein that inhibits the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA), thereby regulating calcium homeostasis in cardiac muscle.']

['SR calcium uptake is mediated by a Ca(2+)-ATPase (SERCA2), whose activity is reversibly regulated by phospholamban (PLN). Dephosphorylated PLN is an inhibitor of SERCA and phosphorylation of PLN relieves this inhibition. Phospholamban (PLN) is a small integral membrane protein, which binds and inhibits in a yet unknown fashion the Ca(2+)-ATPase (SERCA) in the sarcoplasmic reticulum. Based on structural and dynamics data, a model in which PLN undergoes allosteric activation upon encountering SERCA has been proposed. The allosteric regulation of SERCA depends on the conformational equilibrium of PLN, whose cytoplasmic regulatory domain interconverts between three different states: a ground T state (helical and membrane associated), an excited R state (unfolded and membrane detached), and a B state (extended and enzyme-bound), which is noninhibitory. Phosphorylation of PLN shifts the populations toward the B state, increasing SERCA activity. Phospholamban (PLN) regulates cardiac contractility via its modulation of sarco(endo)plasmic reticulum calcium ATPase (SERCA) activity. Impairment of this regulatory process causes heart failure.']

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Which receptor(s) recognize lysosomal hydrolases in trans-Golgi network (TGN)?

['The majority of the enzymes leave the TGN after modification with mannose-6-phosphate (M6P) residues, which are specifically recognized by M6P receptors (MPRs), ensuring their transport to the endosomal/lysosomal system.', 'M6P receptors play a major role in the intracellular transport of newly synthesized lysosomal enzymes in mammalian cells', 'Mannose 6-phosphate receptors (MPRs) are known to be shuttled between the trans-Golgi network (TGN) and endosomes, thereby several lysosomal hydrolases are delivered through the endocytic pathway into lysosomes.', 'Most soluble lysosomal hydrolases are sorted in the trans-Golgi network (TGN) and delivered to the lysosomes by the mannose 6-phosphate receptor (M6PR).', 'certain soluble lysosomal hydrolases, is sorted and trafficked to the lysosomes by sortilin.', 'Mannose-6-phosphate receptors (MPRs) transport lysosomal hydrolases from the trans Golgi network (TGN) to endosomes. Recently, the multi-ligand receptor sortilin has also been implicated in this transport', 'A shortcut to the lysosome: the mannose-6-phosphate-independent pathway', 'several lines of evidence suggest the existence of alternative processes of lysosomal targeting. Among them, the two that are mediated by the M6P alternative receptors, lysosomal integral membrane protein (LIMP-2) and sortilin, have gained unequivocal support.', 'delivery of mannose 6-phosphate receptors carrying lysosomal hydrolases from the trans-Golgi network (TGN) to the endosomal system', 'The cation-independent mannose 6-phosphate receptor (CI-MPR) mediates sorting of lysosomal hydrolase precursors from the TGN to endosomes.', 'mannose 6-phosphate (Man-6-P) recognition marker on lysosomal hydrolases.', 'The delivery of mannose 6-phosphate receptors carrying lysosomal hydrolases from the trans-Golgi network (TGN) to the endosomal system is mediated by selective incorporation of the receptor-hydrolase complexes into vesicular transport carriers (TCs) that are coated with clathrin and the adaptor proteins, GGA and AP-1.', 'Mannose-6-phosphate receptors (MPRs) transport lysosomal hydrolases from the trans Golgi network (TGN) to endosomes.', 'Mannose 6-phosphate receptors carry newly synthesized lysosomal hydrolases from the trans-Golgi network to endosomes, then return to the trans-Golgi network for another round of enzyme delivery.', 'In this way, the M6P receptors help package the hydrolases into vesicles that bud from the trans-Golgi network to deliver their contents to endosomes that ultimately will develop into mature lysosomes, where recently-delivered hydrolases may start digesting the endocyted material.', 'However, LS fibroblasts displayed reduced mannose 6-phosphate receptor (MPR)-mediated re-uptake of the lysosomal enzyme arylsulfatase B. In addition, endosome-to-trans Golgi network (TGN) transport of MPRs was decreased significantly, leading to higher levels of cell surface MPRs and their enrichment in enlarged, retromer-positive endosomes in OCRL-depleted HeLa cells.', 'The M6P groups are then recognized by two independent transmembrane M6P receptors, present in the trans-Golgi network: the cation-independent M6P receptor and/or the cation-dependent M6P receptor.', 'Two related mannose 6-phosphate receptors (MPRs) recognize this feature in the trans Golgi network (TGN) and deliver the hydrolases to the late endosome.', 'The cation-independent mannose 6-phosphate receptor (CIMPR) cycles between the trans-Golgi network (TGN) and endosomes to mediate sorting of lysosomal hydrolases.', 'The M6P groups are then recognized by two independent transmembrane M6P receptors, present in the trans-Golgi network: the cation-independent M6P receptor and/or the cation-dependent M6P receptor', 'Mannose-6-phosphate receptors (MPRs) transport lysosomal hydrolases from the trans Golgi network (TGN) to endosomes', 'The delivery of mannose 6-phosphate receptors carrying lysosomal hydrolases from the trans-Golgi network (TGN) to the endosomal system is mediated by selective incorporation of the receptor-hydrolase complexes into vesicular transport carriers (TCs) that are coated with clathrin and the adaptor proteins, GGA and AP-1', 'Mannose 6-phosphate receptors (MPRs) are known to be shuttled between the trans-Golgi network (TGN) and endosomes, thereby several lysosomal hydrolases are delivered through the endocytic pathway into lysosomes', 'The cation-independent mannose 6-phosphate receptor (CIMPR) cycles between the trans-Golgi network (TGN) and endosomes to mediate sorting of lysosomal hydrolases', 'Two related mannose 6-phosphate receptors (MPRs) recognize this feature in the trans Golgi network (TGN) and deliver the hydrolases to the late endosome']

['The majority of lysosomal hydrolases in trans-Golgi network (TGN) are specifically recognized by mannose 6-phosphate (M6P) receptors (MPRs), which ensure their transport to the endosomal/lysosomal system. Other receptors can also carry lysosomal hydrolases from the trans-Golgi network (TGN) to the endosomal system. These M6P alternative receptors are the lysosomal integral membrane protein (LIMP-2) and the multi-ligand receptor sortilin. These reseptors enable a mannose-6-phosphate-independent pathway from TGN to lysosomes.']

['mannose 6-phosphate receptors (MPRs)', 'sortilin', 'lysosomal integral membrane protein (LIMP-2)', 'cation-independent mannose 6-phosphate receptor (CI-MPR)']

The antibodies MK-3475 and CT-011 have shown promising results in treating malignancies. Which protein are they targeting?

['we find that using an anti-PD-1 antibody (CT-011)', 'PD-1 blockade by CT-011, anti-PD-1 antibody,', '. Presence of CT-011, an anti-PD1 antibody,', 'CT-011, a novel monoclonal anti-PD-1 antibody', 'CT-011, a humanized antibody interacting with PD-1,', 'Anti-PD1 (nivolumab and MK-3475)', 'anti-PD-1 antibodies MK-3475']

['Modulation of the immune system by targeting coinhibitory and costimulatory receptors has become a promising new approach of immunotherapy for cancer. OBJECTIVE: CT-011 is a humanized IgG1 monoclonal antibody that modulates the immune response through interaction with PD-1, a protein belonging to the B7 receptor family present on lymphocytes. The objectives of this phase I study were to assess the dose-limiting toxicities, to determine the maximum tolerated dose, and to study the pharmacokinetics of CT-011 administered once to patients with advanced hematologic malignancies. We have developed a cancer vaccine in which autologous tumor is fused with dendritic cells resulting in the presentation of tumor antigens in the context of DC-mediated costimulation. The median t1/2 of CT-011 ranged from 217 to 410 hours. The PD1/PDL1 pathway is an important element contributing to tumor-mediated immune suppression. The recent approval of the CTLA-4-blocking antibody ipilimumab for the treatment of melanoma was a watershed event, opening up a new era in the field of immunotherapy. T-cell expression of programmed death receptor-1 down-regulates the immune response against malignancy by interacting with cognate ligands ( eg, PD-L1 ) on tumor cells; however, little is known regarding PD-1 and natural killer ( NK ) cells. ', 'PD-1']

['PD-1']

How does mTORC1 signaling impact Notch1 expression via STAT3 activation?

['["Mechanistically, mTORC1 mediated IL-6-induced Stat3 activation in intestinal epithelial cells to stimulate the expression of downstream targets essential for cell proliferation and tissue regeneration. Therefore, mTORC1 signaling critically protects against inflammatory bowel disease through modulation of inflammation-induced Stat3 activity.", "we demonstrated that STAT3 is directly phosphorylated by mTORC1 on Ser727 during hypoxia, promoting HIF-1\\u03b1 mRNA transcription", "Mechanistically, mTORC1 signaling was activated by excess amino acids, which then positively regulated Notch1 expression through the activation of the signal transducer and activator of transcription 3 (STAT3).", "Here we present evidence for the involvement of STAT3, a known mTORC1 regulated transcription factor, in this process", "Furthermore, we demonstrated that STAT3 is directly phosphorylated by mTORC1 on Ser727 during hypoxia, promoting HIF-1\\u03b1 mRNA transcription. mTORC1 also regulates HIF-1\\u03b1 synthesis on a translational level via co-operative regulation of both initiation factor 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase-1 (S6K1), whereas\\u00a0HIF-1\\u03b1 degradation remains unaffected", "Here we present evidence for the involvement of STAT3, a known mTORC1 regulated transcription factor, in this process. ", "TSC1/TSC2 inactivation inhibits AKT through mTORC1-dependent up-regulation of STAT3-PTEN cascade.", "Mechanistically, mTORC1 signaling was activated by excess amino acids, which then positively regulated Notch1 expression through the activation of the signal transducer and activator of transcription 3 (STAT3). ", "Suppression of the mTORC1/STAT3/Notch1 pathway by activated AMPK prevents hepatic insulin resistance induced by excess amino acids.", "Here, we review the connections between mTORC1 and gene transcription by focusing on its impact in regulating the activation of specific transcription factors including including STAT3, SREBPs, PPAR\\u03b3, PPAR\\u03b1, HIF1\\u03b1, YY1\\u2013PGC1\\u03b1 and TFEB. We also discuss the importance of these transcription factors in mediating the effects of mTORC1 on various cellular processes in physiological and pathological contexts."]', '["Mechanistically, mTORC1 mediated IL-6-induced Stat3 activation in intestinal epithelial cells to stimulate the expression of downstream targets essential for cell proliferation and tissue regeneration. Therefore, mTORC1 signaling critically protects against inflammatory bowel disease through modulation of inflammation-induced Stat3 activity.", "we demonstrated that STAT3 is directly phosphorylated by mTORC1 on Ser727 during hypoxia, promoting HIF-1\\u03b1 mRNA transcription", "Mechanistically, mTORC1 signaling was activated by excess amino acids, which then positively regulated Notch1 expression through the activation of the signal transducer and activator of transcription 3 (STAT3).", "Here we present evidence for the involvement of STAT3, a known mTORC1 regulated transcription factor, in this process", "Furthermore, we demonstrated that STAT3 is directly phosphorylated by mTORC1 on Ser727 during hypoxia, promoting HIF-1\\u03b1 mRNA transcription. mTORC1 also regulates HIF-1\\u03b1 synthesis on a translational level via co-operative regulation of both initiation factor 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase-1 (S6K1), whereas\\u00a0HIF-1\\u03b1 degradation remains unaffected", "Here we present evidence for the involvement of STAT3, a known mTORC1 regulated transcription factor, in this process. ", "TSC1/TSC2 inactivation inhibits AKT through mTORC1-dependent up-regulation of STAT3-PTEN cascade.", "Mechanistically, mTORC1 signaling was activated by excess amino acids, which then positively regulated Notch1 expression through the activation of the signal transducer and activator of transcription 3 (STAT3). ", "Suppression of the mTORC1/STAT3/Notch1 pathway by activated AMPK prevents hepatic insulin resistance induced by excess amino acids.", "Here, we review the connections between mTORC1 and gene transcription by focusing on its impact in regulating the activation of specific transcription factors including including STAT3, SREBPs, PPAR\\u03b3, PPAR\\u03b1, HIF1\\u03b1, YY1\\u2013PGC1\\u03b1 and TFEB. We also discuss the importance of these transcription factors in mediating the effects of mTORC1 on various cellular processes in physiological and pathological contexts."]']

mTORC1 signaling impacts Notch1 expression by positively regulating it through the activation of STAT3.

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List all the available databases of super enhancers

['dbSUPER: a database of super-enhancers in mouse and human genome', 'We developed dbSUPER (http://bioinfo.au.tsinghua.edu.cn/dbsuper/), the first integrated and interactive database of super-enhancers, with the primary goal of providing a resource for assistance in further studies related to transcriptional control of cell identity and disease. dbSUPER provides a responsive and user-friendly web interface to facilitate efficient and comprehensive search and browsing. The data can be easily sent to Galaxy instances, GREAT and Cistrome web-servers for downstream analysis, and can also be visualized in the UCSC genome browser where custom tracks can be added automatically. The data can be downloaded and exported in variety of formats. Furthermore, dbSUPER lists genes associated with super-enhancers and also links to external databases such as GeneCards, UniProt and Entrez. dbSUPER also provides an overlap analysis tool to annotate user-defined regions. We believe dbSUPER is a valuable resource for the biology and genetic research communities', 'SEA: a super-enhancer archive', 'Here, we present a specifically designed web-accessible database, Super-Enhancer Archive (SEA, http://sea.edbc.org). SEA focuses on integrating super-enhancers in multiple species and annotating their potential roles in the regulation of cell identity gene expression. The current release of SEA incorporates 83 996 super-enhancers computationally or experimentally identified in 134 cell types/tissues/diseases, including human (75 439, three of which were experimentally identified), mouse (5879, five of which were experimentally identified), Drosophila melanogaster (1774) and Caenorhabditis elegans (904). To facilitate data extraction, SEA supports multiple search options, including species, genome location, gene name, cell type/tissue and super-enhancer name. The response provides detailed (epi)genetic information, incorporating cell type specificity, nearby genes, transcriptional factor binding sites, CRISPR/Cas9 target sites, evolutionary conservation, SNPs, H3K27ac, DNA methylation, gene expression and TF ChIP-seq data. Moreover, analytical tools and a genome browser were developed for users to explore super-enhancers and their roles in defining cell identity and disease processes in depth', 'SEA focuses on integrating super-enhancers in multiple species and annotating their potential roles in the regulation of cell identity gene expression. ', 'SEA incorporates 83 996 super-enhancers computationally or experimentally identified in 134 cell types/tissues/diseases, including human (75 439, three of which were experimentally identified), mouse (5879, five of which were experimentally identified), Drosophila melanogaster (1774) and Caenorhabditis elegans (904).', 'We developed dbSUPER (http://bioinfo.au.tsinghua.edu.cn/dbsuper/), the first integrated and interactive database of super-enhancers, with the primary goal of providing a resource for assistance in further studies related to transcriptional control of cell identity and disease', 'Furthermore, dbSUPER lists genes associated with super-enhancers and also links to external databases such as GeneCards, UniProt and Entrez. dbSUPER also provides an overlap analysis tool to annotate user-defined regions', 'We developed dbSUPER (http://bioinfo.au.tsinghua.edu.cn/dbsuper/), the first integrated and interactive database of super-enhancers, with the primary goal of providing a resource for assistance in further studies related to transcriptional control of cell identity and disease. dbSUPER provides a responsive and user-friendly web interface to facilitate efficient and comprehensive search and browsing', 'dbSUPER: a database of super-enhancers in mouse and human genome.']

['dbSUPER and SEA are the available databases of super enhancers.', 'dbSUPER and SEA are the most well-known and widely used Super-Enhancer Databases.']

['dbSUPER', 'SEA']

How does Foxa transcription factor exhibits its pioneering function?

['Similarities between the Epstein-Barr Virus (EBV) Nuclear Protein EBNA1 and the Pioneer Transcription Factor FoxA: Is EBNA1 a "Bookmarking" Oncoprotein that Alters the Host Cell Epigenotype?', 'In this overview we focus, however, on the epigenetic alterations elicited by EBNA1 by drawing a parallel between EBNA1 and the FoxA family of pioneer transcription factors.', 'Both EBNA1 and FoxA induce local DNA demethylation, nucleosome destabilization and bind to mitotic chromosomes. ', 'In addition, EBNA1 and FoxA, when associated with mitotic chromatin may "bookmark" active genes and ensure their reactivation in postmitotic cells (epigenetic memory)', 'about one-third of the FoxA bound sites are near silent genes, including genes without detectable RNA polymerase II.', 'We found one such target site at a cryptic "shadow" enhancer 7 kilobases (kb) downstream of the Cdx2 gene, where Rfx1 restricts transcriptional activation by FoxA', 'Nuclear mobility and mitotic chromosome binding: similarities between pioneer transcription factor FoxA and linker histone H1', 'The results indicate that the "pioneer" features of FoxA factors involve various chromatin-binding parameters seen in linker histones and that distinguish the factors with respect to their regulatory and mechanistic functions.', "These discoveries followed the establishment of the conceptional framework of the mechanism of action of the FoxA proteins as 'pioneer factors' that can engage chromatin before other transcription factors.", 'The purpose of this review is to critically examine the literature on three highly potent transcriptional activators: the herpes virus protein, VP16; the master regulator of skeletal muscle differentiation, MyoD and the "pioneer" factor for hepatogenesis, FoxA.', 'Nucleosome-binding affinity as a primary determinant of the nuclear mobility of the pioneer transcription factor FoxA', "We find that slower nuclear mobility correlates with high nonspecific nucleosome binding, and point mutations that disrupt nonspecific binding markedly increase nuclear mobility. FoxA's distinct nuclear mobility is consistent with its pioneer activity in chromatin", 'The Fox DNA-binding domain structurally resembles linker histone and binds nucleosomes stably', "Insight into the unique molecular basis of Foxa function has been obtained from recent genetic and genomic data, which identify the Foxa proteins as 'pioneer factors' whose binding to promoters and enhancers enable chromatin access for other tissue-specific transcription factors", 'Nucleosome-binding affinity as a primary determinant of the nuclear mobility of the pioneer transcription factor FoxA.', 'FOXO proteins represent a hybrid subclass having dual roles as pioneering factors and transcription factors. A subset of FOX proteins interacts with condensed mitotic chromatin and may function as &apos;bookmarking&apos; agents to maintain transcriptional competence at specific genomic sites.', 'There exists a hierarchy by which transcription factors can engage their target sites in chromatin, in that a subset of factors can bind transcriptionally silent, nucleosomal DNA, whereas most factors cannot, and this hierarchy is reflected, at least in part, in the developmental function of the factors.']

['The conceptional framework of the mechanism of action of the FoxA proteins is that these \'pioneer factors\' that can engage chromatin before other transcription factors. The Fox DNA-binding domain structurally resembles linker histone and binds nucleosomes stably. FoxA induces local DNA demethylation, nucleosome destabilization and binds to mitotic chromosomes. When associated with mitotic chromatin, FoxA may "bookmark" active genes and ensure their reactivation in postmitotic cells (epigenetic memory). About one-third of the FoxA bound sites are near silent genes, including genes without detectable RNA polymerase II. The "pioneer" features of FoxA factors involve various chromatin-binding parameters seen in linker histones and distinguish the factors with respect to their regulatory and mechanistic functions.', "FoxA proteins are pioneer transcription factors, among the first to bind chromatin domains in development and enable gene activity. There exists a hierarchy by which transcription factors can engage their target sites in chromatin, in that a subset of factors can bind transcriptionally silent, nucleosomal DNA, whereas most factors cannot, and this hierarchy is reflected, at least in part, in the developmental function of the factors. These discoveries followed the establishment of the conceptional framework of the mechanism of action of the FoxA proteins as 'pioneer factors' that can engage chromatin before other transcription factors. Such sites are enriched in motifs for transcriptional repressors, including for Rfx1 and type II nuclear hormone receptors."]

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Where is Akkermansia muciniphila found?

['Akkermansia muciniphila is a Gram-negative mucin-degrading bacterium that resides in the gastrointestinal tracts of humans and animals. ', 'Individuals with obesity and type 2 diabetes differ from lean and healthy individuals in their abundance of certain gut microbial species and microbial gene richness. Abundance of Akkermansia muciniphila, a mucin-degrading bacterium, has been inversely associated with body fat mass and glucose intolerance in mice, but more evidence is needed in humans.']

['Akkermansia muciniphila is a Gram-negative mucin-degrading bacterium that resides in the gastrointestinal tracts of humans and animals.', 'RYGB led to altered relative abundances of 31 species (P\u2009<\u20090.05, q\u2009<\u20090.15) within the first 3\xa0months, including those of Escherichia coli, Klebsiella pneumoniae, Veillonella spp., Streptococcus spp., Alistipes spp., and Akkermansia muciniphila. Main findings are as follows: (1) gut microbiota compositions of cecal and fecal samples were altered in BTBR compared to control mice, indicating that this model may be of utility in understanding gut-brain interactions in ASD; (2) KD consumption caused an anti-microbial-like effect by significantly decreasing total host bacterial abundance in cecal and fecal matter; (3) specific to BTBR animals, the KD counteracted the common ASD phenotype of a low Firmicutes to Bacteroidetes ratio in both sample types; and (4) the KD reversed elevated Akkermansia m However, faeces from the UC cohort had lower proportions of Akkermansia muciniphila and increased diversity within Clostridium cluster XIVa compared to controls.Gut fermentation of NSP and starch is diminished in patients with UC. Specific members of the microbiota such as Akkermansia muciniphila might be decreased in diabetes and when administered to murines exerted antidiabetic effects. In parallel, the antibiotic susceptibility of Akkermansia muciniphila Muc(T) strain was studied and this strain was observed by electron microscopy.']

['Akkermansia muciniphila resides in the gastrointestinal tracts of humans and animals.']

What enzyme is inhibied by Opicapone?

["PURPOSE: Opicapone (OPC) is a novel catechol-O-methyltransferase (COMT) inhibitor to be used as adjunctive therapy in levodopa-treated patients with Parkinson's disease. ", 'Brain and peripheral pharmacokinetics of levodopa in the cynomolgus monkey following administration of opicapone, a third generation nitrocatechol COMT inhibitor.', 'OBJECTIVE: The present study aimed at evaluating the effect of opicapone, a third generation nitrocatechol catechol-O-methyltransferase (COMT) inhibitor, on the systemic and central bioavailability of 3,4-dihydroxy-l-phenylalanine (levodopa) and related metabolites in the cynomolgus monkey.', 'CONCLUSIONS: Opicapone behaved as long-acting COMT inhibitor that markedly increased systemic and central levodopa bioavailability. ', 'BACKGROUND AND OBJECTIVES: Opicapone is a novel third generation catechol-O-methyltransferase (COMT) inhibitor. The purpose of this study was to compare the levodopa pharmacokinetic profile throughout a day driven by the COMT inhibition either following repeated doses of opicapone or concomitant administration with entacapone.', 'CONCLUSION: Opicapone, a novel third generation COMT inhibitor, when compared to entacapone, provides a superior response upon the bioavailability of levodopa associated to more pronounced, long-lasting, and sustained COMT inhibition. ', 'Pharmacokinetics, pharmacodynamics and tolerability of opicapone, a novel catechol-O-methyltransferase inhibitor, in healthy subjects: prediction of slow enzyme-inhibitor complex dissociation of a short-living and very long-acting inhibitor.', 'Opicapone is a novel catechol-O-methyltransferase (COMT) inhibitor.', 'Opicapone is a novel third generation catechol-O-methyltransferase (COMT) inhibitor.', 'The purpose of this study was to evaluate the tolerability, pharmacokinetics (including the effect of food) and pharmacodynamics (effect on COMT activity) following single oral doses of opicapone in young healthy male volunteers. ', 'AIMS: The aim of this study was to assess the tolerability, pharmacokinetics and inhibitory effect on erythrocyte soluble catechol-O-methyltransferase (S-COMT) activity following repeated doses of opicapone. ', 'CONCLUSION: Despite its short elimination half-life, opicapone markedly and sustainably inhibited erythrocyte S-COMT activity making it suitable for a once daily regimen.', 'Opicapone demonstrated marked and sustained inhibition of erythrocyte soluble COMT activity.', 'The long duration of COMT inhibition by opicapone, however, tended to be independent from the dose taken.']

["Opicapone is a novel catechol-O-methyltransferase (COMT) inhibitor to be used as adjunctive therapy in levodopa-treated patients with Parkinson's disease"]

['catechol-O-methyltransferase']

How does benralizumab's mechanism differ from other IL-5 biotherapeutics for severe asthma?

['["Since IL-5 plays an important role in the maturation, survival and migration of eosinophils, hence the pathogenesis of eosinophilic asthma, biotherapeutics targeting IL-5/IL-5R\\u03b1 have been developed and/or marketed, including Mepolizumab, Reslizumab, and Benralizumab.", "Mepolizumab, reslizumab, and benralizumab target IL-5, a key cytokine for eosinophils.", "Benralizumab is a humanized, afucosylated, anti-interleukin-5 receptor \\u03b1, immunoglobulin G (IgG)1\\u03ba monoclonal antibody.", "A global meta-analysis was first conducted followed by an indirect comparison of each IL-5-targeting drug: benralizumab, reslizumab and mepolizumab. ", "These include monoclonal antibodies against IL-5 or IL-5 receptor alpha (mepolizumab, reslizumab, and benralizumab), IL-13 (lebrikizumab and tralokinumab), IL-4 receptor alpha (dupilumab), IgE (omalizumab), and anti-thymic stromal lymphopoietin (tezepelumab) and small molecule therapies such as prostaglandin D2blockers (fevipiprant and timapiprant).", "However, there is research underway investigating interleukin-based monoclonal antibodies such as benralizumab, an anti-IL-5R monoclonal antibody which is currently in phase III clinical development. ", "BACKGROUND: Benralizumab is a humanised, anti-interleukin 5 receptor \\u03b1 monoclonal antibody that directly and rapidly depletes eosinophils, reduces asthma exacerbations, and improves lung function for patients with severe eosinophilic asthma. ", ". We investigated whether benralizumab, a monoclonal antibody directed against the alpha subunit of the interleukin-5 receptor that significantly reduces the incidence of asthma exacerbations, was also effective as an oral glucocorticoid-sparing therapy in patients relying on oral glucocorticoids to manage severe asthma associated with eosinophilia.", "Benralizumab--a humanized mAb to IL-5R\\u03b1 with enhanced antibody-dependent cell-mediated cytotoxicity--a novel approach for the treatment of asthma.", "Benralizumab is a monoclonal antibody that binds the \\u03b1 subunit of the receptor to IL-5.", "We assessed the safety and efficacy of benralizumab, a monoclonal antibody against interleukin-5 receptor \\u03b1 that depletes eosinophils by antibody-dependent cell-mediated cytotoxicity, for patients with severe, uncontrolled asthma with eosinophilia.", "While previous monoclonal antibodies against the IL-5 ligand resulted in inconsistent improvements in asthma outcomes, benralizumab has shown promise.", "Benralizumab is a monoclonal antibody against IL-5 receptor, and has an enhanced antibody dependent cell-mediated cytotoxicity function.", "Anti-IL-5-based therapies (mepolizumab and reslizumab are humanized monoclonal antibodies (hmAbs) that recognize free IL-5, benralizumab is a hmAb directed at the \\u03b1 subunit of the IL-5R) target the IL-5-signaling in eosinophilic asthma.", "Benralizumab is a humanised, afucosylated, anti-interleukin-5 receptor \\u03b1 monoclonal antibody that induces direct, rapid, and nearly complete depletion of eosinophils.", "Benralizumab is a humanized anti-IL5 receptor \\u03b1 (IL5R\\u03b1) monoclonal antibody (mAb) with enhanced (afucosylation) antibody-dependent cell-mediated cytotoxicity (ADCC) function.", "BACKGROUND: Benralizumab is a humanised, afucosylated, anti-interleukin-5 receptor \\u03b1 monoclonal antibody that induces direct, rapid, and nearly complete depletion of eosinophils.", "Benralizumab is a monoclonal antibody that targets interleukin-5 receptor \\u03b1 to de', '["Since IL-5 plays an important role in the maturation, survival and migration of eosinophils, hence the pathogenesis of eosinophilic asthma, biotherapeutics targeting IL-5/IL-5R\\u03b1 have been developed and/or marketed, including Mepolizumab, Reslizumab, and Benralizumab.", "Mepolizumab, reslizumab, and benralizumab target IL-5, a key cytokine for eosinophils.", "Benralizumab is a humanized, afucosylated, anti-interleukin-5 receptor \\u03b1, immunoglobulin G (IgG)1\\u03ba monoclonal antibody.", "A global meta-analysis was first conducted followed by an indirect comparison of each IL-5-targeting drug: benralizumab, reslizumab and mepolizumab. ", "These include monoclonal antibodies against IL-5 or IL-5 receptor alpha (mepolizumab, reslizumab, and benralizumab), IL-13 (lebrikizumab and tralokinumab), IL-4 receptor alpha (dupilumab), IgE (omalizumab), and anti-thymic stromal lymphopoietin (tezepelumab) and small molecule therapies such as prostaglandin D2blockers (fevipiprant and timapiprant).", "However, there is research underway investigating interleukin-based monoclonal antibodies such as benralizumab, an anti-IL-5R monoclonal antibody which is currently in phase III clinical development. ", "BACKGROUND: Benralizumab is a humanised, anti-interleukin 5 receptor \\u03b1 monoclonal antibody that directly and rapidly depletes eosinophils, reduces asthma exacerbations, and improves lung function for patients with severe eosinophilic asthma. ", ". We investigated whether benralizumab, a monoclonal antibody directed against the alpha subunit of the interleukin-5 receptor that significantly reduces the incidence of asthma exacerbations, was also effective as an oral glucocorticoid-sparing therapy in patients relying on oral glucocorticoids to manage severe asthma associated with eosinophilia.", "Benralizumab--a humanized mAb to IL-5R\\u03b1 with enhanced antibody-dependent cell-mediated cytotoxicity--a novel approach for the treatment of asthma.", "Benralizumab is a monoclonal antibody that binds the \\u03b1 subunit of the receptor to IL-5.", "We assessed the safety and efficacy of benralizumab, a monoclonal antibody against interleukin-5 receptor \\u03b1 that depletes eosinophils by antibody-dependent cell-mediated cytotoxicity, for patients with severe, uncontrolled asthma with eosinophilia.", "While previous monoclonal antibodies against the IL-5 ligand resulted in inconsistent improvements in asthma outcomes, benralizumab has shown promise.", "Benralizumab is a monoclonal antibody against IL-5 receptor, and has an enhanced antibody dependent cell-mediated cytotoxicity function.", "Anti-IL-5-based therapies (mepolizumab and reslizumab are humanized monoclonal antibodies (hmAbs) that recognize free IL-5, benralizumab is a hmAb directed at the \\u03b1 subunit of the IL-5R) target the IL-5-signaling in eosinophilic asthma.", "Benralizumab is a humanised, afucosylated, anti-interleukin-5 receptor \\u03b1 monoclonal antibody that induces direct, rapid, and nearly complete depletion of eosinophils.", "Benralizumab is a humanized anti-IL5 receptor \\u03b1 (IL5R\\u03b1) monoclonal antibody (mAb) with enhanced (afucosylation) antibody-dependent cell-mediated cytotoxicity (ADCC) function.", "BACKGROUND: Benralizumab is a humanised, afucosylated, anti-interleukin-5 receptor \\u03b1 monoclonal antibody that induces direct, rapid, and nearly complete depletion of eosinophils.", "Benralizumab is a monoclonal antibody that targets interleukin-5 receptor \\u03b1 to de']

Benralizumab's mechanism differs from other IL-5 biotherapeutics for severe asthma in that it directly and rapidly depletes eosinophils through antibody-dependent cell-mediated cytotoxicity, reduces asthma exacerbations, and improves lung function for patients with severe eosinophilic asthma.

[]

Which are the mains risk factors of metabolic syndrome?

["tigated the association between circulating levels of 60 and 70 kDa heat-shock proteins (HSP60 and 70) and cardiovascular risk factors in postmenopausal women with or without metabolic syndrome (MetS). This cross-sectional study included 311 Brazilian women (age ≥45 years with amenorrhea ≥12 months). Women showing three or more of the following diagnostic criteria were diagnosed with MetS: waist circumference (WC) ≥88 cm, blood pressure ≥130/85 mmHg, triglycerides ≥150 mg/dl, high-density lipoprotein (HDL) <50 mg/dl, and glucose ≥100 mg/dl. Clinical, anthropometric, and biochemical parameters were collected. HSP60, HSP70, antibodies to HSP60 and HSP70, and C-reactive protein (CRP) levels were measured in serum. Student's t test, Kruskal-Wallis test, chi-square test, and Pearson correlation were used for statistical analysis. Of the 311 women, 30.9 % (96/311) were diagnosed with MetS. These women were, on average, obese with abdominal fat deposition and had lower HDL values as well as higher triglycerides and glucose levels. Homeostasis model assessment-insulin resistant (HOMA-IR) test values in these women were compatible with insulin resistance (P\u2009<\u20090.05). CRP and ", ' is associated with an increased risk for cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). Several', 'alence of the metabolic syndrome (MetS), a cluster of cardiovascular risk factors associated with obesity and insulin resistance, is dramatically increasing in Western and developing countries. This disorder is not only associated with a higher risk of appearance of type 2 diabetes and cardiovascular events, but impacts on the liver in different ways. Nonalc', 'bolic syndrome (MS) components, such as dyslipidemia, prothrombotic status, and increased blood pressure, are risk factors for patients with renal disease. Visceral fat mass is closely related to the MS and atherosclerosis. We investigated the effects of body compositions and MS on anemia parameters and recombinant human erythropoietin (rHuEPO) requirements in maintenance hemodialysis patients. METHODS: Body composition (body mass index and bioimpedance analysis) and laboratory data were obtained from 110 dialysis patients. The MS was identified according to ATP-III criteria. Anemia parameters, hemoglobin (Hgb), albumin, C-reactive protein (CRP), calcium, phosphorus, parathormone levels, and rHuEPO requirements over the last 6 months were retrospectively analyzed. RESULTS: Patients with the MS seem to reach target Hgb levels more frequently (10-12 g/dL; 66.3% vs 84.8%; P = .03) without any difference in total intravenous iron therapy dosage. MS patients also required lower rHuEPO for reaching similar Hgb levels compared with patients without MS (2679.3 ± 1936.1 vs 3702.5 ± 2213.0 U/kg/6 mo; P = .02). There we', 'bolic syndrome (MetS) is typically diagnosed based on abnormalities in specific clustered clinical measures that are associated with increased risk for coronary heart disease (CHD) and Type 2 diabetes mellitus (T2DM). However, current MetS criteria result in racial/ethnic discrepancies. Our goals were to use confirmatory factor analysis (CFA) to delineate differential contributions to MetS by sub-group, and if contributions were discovered, develop sex and racial/ethnic-specific equations to calculate MetS severity. RESEARCH DESIGN AND METHODS: Using data on adults from the National Health and Nutrition Examination Survey 1999-2010, we performed a CFA of a single MetS factor that allowed differential loadings across groups, resulting in a sex and race/ethnicity-specific continuous MetS severity score. RESULTS: Loadings to the single MetS factor differed by sub-group for each MetS component (p<0.001), with lower factor loadings among non-Hispanic-blacks for triglycerides and among Hispanics for waist circumference. Systolic blood pressure exhibited low factor loadings among all groups. MetS severity scores were correlated with biomarkers of future disease (high-sensitivity C-reactive-protein, uric acid, insulin resistance). Non-Hispanic-black-males with diabetics had a low prevalence of MetS but high MetS severity scores that were not significantly different from other racial/ethnic groups. CONCLUSIONS: This analysis among adults uniquely demonstrated differences between sexes and racial/ethnic groups regarding contributions of traditional MetS components to an assumed single factor. The resulting equations provide a clinically-accessible and interpretable continuous measure of MetS for potential use in identifying adults at higher risk for MetS-related diseases and following changes within individuals over time. These eq', ' study, we aim to examine the associations of obesity related loci with risk of metabolic syndrome (MetS) in a children population from China. A tota', 'alence of obesity is on the increase, and consequently metabolic syndrome is also becoming a serious health problem in children and adolescents all over the world. This rev', 'ciation between alopecia areata (AA), psoriasis, and other autoimmune diseases has been well reported in the literature, an association with metabolic syndrome has not been reported. We present two young women with the combination of severe psoriasis, androgen excess, metabolic syndrome, thyroiditis, and AA. Both w']

['Metabolic syndrome is a disorder of energy utilization and storage, diagnosed by a co-occurrence of three out of five of the following medical conditions: abdominal (central) obesity, elevated blood pressure, elevated fasting plasma glucose, high serum triglycerides, and low high-density cholesterol (HDL) levels. Metabolic syndrome increases the risk of developing cardiovascular disease, particularly heart failure, and diabetes.']

['Obesity', 'High blood pressure', 'Hypertension', 'High serum triglycerides', 'Low high-density cholesterol (HDL) levels', 'Diabetes type 2', 'Dyslipidaemia']

List symptoms of Gradenigo's syndrome.

["INTRODUCTION: Gradenigo's syndrome is nowadays a rare condition characterized by a triad of otorrhea, facial pain with trigeminal nerve involvement and abducens nerve palsy.", "Gradenigo's syndrome is a rare but life threatening complication of acute otitis media (AOM), which includes a classic triad of otitis media, deep facial pain and ipsilateral abducens nerve paralysis. ", "We report a case of typical Gradenigo's syndrome, including left abducens nerve palsy, left facial pain and paresthesia in V1 and V2 distribution of trigeminal nerve caused by solitary osseous plasmacytoma of the left petrous apex.", "BACKGROUND: Gradenigo's syndrome is a rare disease, which is characterized by the triad of the following conditions: suppurative otitis media, pain in the distribution of the first and the second division of trigeminal nerve, and abducens nerve palsy.", 'RESULTS: It was after Gradenigo that the well-known syndrome consisting of diplopia and facial pain due to a middle ear infection was named.', "Gradenigo's syndrome, the triad of suppurative otitis media, abducens nerve palsy and pain in the ophthalmic division of the trigeminal nerve, remains a rare complication of otitis media.", 'In 1904, Giuseppe Gradenigo published his case series on the triad of ipsilateral abducens nerve palsy, facial pain in the trigeminal nerve distribution, and suppurative otitis media, which would subsequently be referred to as Gradenigo syndrome']

["Gradenigo's syndrome is a rare but life threatening complication of acute otitis media, which includes a classic triad of otitis media, deep facial pain and ipsilateral abducens nerve paralysis."]

['otitis media', 'deep facial pain', 'abducens nerve paralysis']

Is CD99 encoded by MIC2 gene?

['We report 2 unusual cytogenetic findings in a pediatric Ewing sarcoma, an insertion of the MIC2 gene encoding CD99 from Xp to 10p and a submicroscopic deletion of the well-known tumor supressor gene KLF6', 'We obtained the final diagnosis of ES/PNET by immunohistochemical molecular study with positive staining for the MIC2 gene product (CD99) and a Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangement', 'CD99, a transmembrane protein encoded by MIC2 gene is involved in multiple cellular events including cell adhesion and migration, apoptosis, cell differentiation and regulation of protein trafficking either in physiological or pathological conditions', 'CD99 is a 32-kDa transmembrane glycoprotein that is encoded by the MIC2 gene', 'The surgical specimens showed small round cell tumor with positive staining for MIC2 gene product (CD99)', 'CD99 is a 32-kDa transmembrane glycoprotein that is encoded by the MIC2 gene.', 'The leukocyte surface molecule CD99 is an integral membrane glycoprotein encoded by the E2/MIC2 gene.', 'Human CD99, which is encoded by the mic2 gene, is a ubiquitous 32 kDa transmembrane protein.', 'Human CD99 is a 32-kDa cell surface protein that is encoded by the MIC2 gene localized to the PAR1.', 'The tumors displayed intense immunoreactivity in a membranous pattern for CD99, the cell surface glycoprotein encoded by the MIC2 gene.', 'CD99, a transmembrane protein encoded by MIC2 gene is involved in multiple cellular events including cell adhesion and migration, apoptosis, cell differentiation and regulation of protein trafficking either in physiological or pathological conditions.', 'CD99, the product of the MIC2 gene, exhibits an erythroid-specific quantitative polymorphism coregulated with the polymorphism of the XG blood group gene.', 'CD99, the product of the MIC2 gene, exhibits an erythroid-specific quantitative polymorphism co-regulated with the Xga blood group polymorphism.', 'Homology searches resulted in finding homologous sequences (totally about 40% homology) in the human MIC2 gene product (CD99; 32-kDa) of T lymphocytes.', "Although considered a specific marker for Ewing's sarcoma/peripheral neuroectodermal tumour, the MIC2 gene product (CD99) has been immunolocalised in a variety of human tumours.", 'MIC2, the gene encoding the CD99 antigen, is found in the pseudoautosomal region of both the X and Y chromosomes.', 'Human CD99 is a 32-kDa cell surface protein that is encoded by the MIC2 gene localized to the PAR1.', 'The tumors displayed intense immunoreactivity in a membranous pattern for CD99, the cell surface glycoprotein encoded by the MIC2 gene.', 'CD99 (MIC2) regulates the LFA-1/ICAM-1-mediated adhesion of lymphocytes, and its gene encodes both positive and negative regulators of cellular adhesion.', 'Relation of neurological marker expression and EWS gene fusion types in MIC2/CD99-positive tumors of the Ewing family.', 'The Ewing family of tumors (EFT) is characterized by high MIC2/CD99 expression and specific EWS/ETS gene rearrangements, resulting in different chimeric transcripts.', 'The tumors displayed intense immunoreactivity in a membranous pattern for CD99, the cell surface glycoprotein encoded by the MIC2 gene.', "Monoclonal antibody (MAb) HBA71, which was raised against Ewing's sarcoma cells, recognizes a cell-surface glycoprotein, p30/32MIC2, that is encoded by the MIC2 gene in the pseudoautosomal region of human chromosomes X and Y.", 'Monoclonal antibodies (mAbs) directed against E2, a 32-kDa transmembrane protein encoded by the MIC2 gene located in the pseudoautosomal region, induce a transbilayer movement of phosphatidylserine and, to a lesser extent, phosphatidylethanolamine in human thymocytes and a Jurkat T lymphocytes.', 'Homology searches resulted in finding homologous sequences (totally about 40% homology) in the human MIC2 gene product (CD99; 32-kDa) of T lymphocytes.', 'CD99 is a 32-kDa transmembrane glycoprotein that is encoded by the MIC2 gene', 'CD99, a transmembrane protein encoded by MIC2 gene is involved in multiple cellular events including cell adhesion and migration, apoptosis, cell differentiation and regulation of protein trafficking either in physiological or pathological conditions', 'The surgical specimens showed small round cell tumor with positive staining for MIC2 gene product (CD99)', 'We report 2 unusual cytogenetic findings in a pediatric Ewing sarcoma, an insertion of the MIC2 gene encoding CD99 from Xp to 10p and a submicroscopic deletion of the well-known tumor supressor gene KLF6', 'MIC2, the gene encoding the CD99 antigen, is found in the pseudoautosomal region of both the X and Y chromosomes', 'Immunohistochemical analysis showed weak to moderate and partial staining for MIC2 (CD99) and WT1, respectively', 'Human CD99, which is encoded by the mic2 gene, is a ubiquitous 32 kDa transmembrane protein', 'The leukocyte surface molecule CD99 is an integral membrane glycoprotein encoded by the E2/MIC2 gene', 'The tumors displayed intense immunoreactivity in a membranous pattern for CD99, the cell surface glycoprotein encoded by the MIC2 gene', 'Human CD99 is a 32-kDa cell surface protein that is encoded by the MIC2 gene localized to the PAR1', 'MIC2, the gene encoding the CD99 antigen, is found in the pseudoautosomal region of both the X and Y chromosomes', 'CD99, the product of the MIC2 gene, exhibits an erythroid-specific quantitative polymorphism co-regulated with the Xga blood group polymorphism']

['CD99 is a 32-kDa transmembrane glycoprotein that is encoded by the MIC2 gene ', 'CD99 is a transmembrane protein encoded by MIC2 gene. It is involved in multiple cellular functions, including cell adhesion and migration, apoptosis, cell differentiation, and regulation of protein trafficking, in either physiological or pathological conditions.']

['yes']

What is targeted by Palbociclib?

['BACKGROUND: Necitumumab is a second-generation, recombinant, human immunoglobulin G1 EGFR antibody. ', 'Epidermal growth factor receptor-directed monoclonal antibodies in nonsmall cell lung cancer: an update.', ' A Southwest Oncology Group study currently prospectively evaluates the predictive biomarkers for cetuximab. In the SQUIRE phase III trial, necitumumab added to cisplatin and gemcitabine increased the survival in patients with advanced squamous cell NSCLC. ', 'BACKGROUND: Necitumumab is a second-generation recombinant human immunoglobulin G1 EGFR monoclonal antibody that competitively inhibits ligand binding. ', 'Numerous other drugs are in earlier stages of development for HNSCC treatment, including novel anti-EGFR mAbs (MEHD7945A, necitumumab, and RO5083945), small-molecule TKIs (vandetanib, icotinib, and CUDC-101), EGFR antisense, various add-on therapies to radiation and chemotherapy (bevacizumab, interleukin-12, lenalidomide, alisertib, and VTX-2337), and drugs (temsirolimus, everolimus, OSI-906, dasatinib, and PX-866) intended to overcome resistance to anti-EGFR agents. ', 'Necitumumab, a fully human monoclonal antibody, is currently evaluated in combination with chemotherapy in two phase III trials in patients with advanced NSCLC. ', 'Necitumumab is currently evaluated in combination with chemotherapy in two randomized phase III trials.', 'Joining cetuximab, sorafenib, afatinib, intedanib, and crizotinib in phase III development for non-small cell lung cancer (NSCLC) are ramucirumab (developed by ImClone, a subsidiary of Lilly), necitumumab (developed by ImClone and Bristol-Myers Squibb), and tivantinib (ARQ 197, developed by ArQule and Daiichi Sankyo). Necitumumab is a second-generation anti-EGFR monoclonal antibody (mAb) similar to cetuximab.', 'Necitumunab is a fully human IgG1 monoclonal antibody targeting EGFR, having the potential benefit of lower hypersensitivity reaction risk as compared with cetuximab and also equivalent antibody-dependent cell-mediated cytotoxicity.', 'Necitumumab, a monoclonal antibody directed against EGFR, is currently under development as a treatment for advanced NSCLC.', 'A phase I pharmacologic study of necitumumab (IMC-11F8), a fully human IgG1 monoclonal antibody directed against EGFR in patients with advanced solid malignancies.', 'PURPOSE: This study aimed to determine a maximum tolerated dose (MTD) and recommended dose for disease-directed studies of necitumumab (IMC-11F8), a fully human IgG(1) monoclonal antibody directed at the epidermal growth factor receptor, and to characterize the safety profile, pharmacokinetics, preliminary antitumor activity, and immunogenicity of necitumumab.']

['Necitumumab is a fully human IgG(1) monoclonal antibody directed at the epidermal growth factor receptor (EGFR). It is used for treatment of nonsmall cell lung cancer.']

['epidermal growth factor receptor']

Which computational frameworks are available for predicting enhancers?

["In this study we developed DEEP, a novel ensemble prediction framework. DEEP integrates three components with diverse characteristics that streamline the analysis of enhancer's properties in a great variety of cellular conditions. In our method we train many individual classification models that we combine to classify DNA regions as enhancers or non-enhancers. DEEP uses features derived from histone modification marks or attributes coming from sequence characteristics. Experimental results indicate that DEEP performs better than four state-of-the-art methods on the ENCODE data. We report the first computational enhancer prediction results on FANTOM5 data where DEEP achieves 90.2% accuracy and 90% geometric mean (GM) of specificity and sensitivity across 36 different tissues. We further present results derived using in vivo-derived enhancer data from VISTA database. DEEP-VISTA, when tested on an independent test set, achieved GM of 80.1% and accuracy of 89.64%.", 'Our novel PRISM (predicting regulatory information from single motifs) approach obtains 2543 TF function predictions in a large variety of contexts, at a false discovery rate of 16%. The predictions are highly enriched for validated TF roles, and 45 of 67 (67%) tested binding site regions in five different contexts act as enhancers in functionally matched cells.', 'DEEP: a general computational framework for predicting enhancers', 'We report the first computational enhancer prediction results on FANTOM5 data where DEEP achieves 90.2% accuracy and 90% geometric mean (GM) of specificity and sensitivity across 36 different tissues', 'DEEP: a general computational framework for predicting enhancers.']

["DEEP integrates three components with diverse characteristics that streamline the analysis of enhancer's properties in a great variety of cellular conditions. DEEP uses features derived from histone modification marks or attributes coming from sequence characteristics. Experimental results indicate that DEEP performs better than four state-of-the-art methods on the ENCODE data. The PRISM (predicting regulatory information from single motifs) approach obtains 2543 TF function predictions in a large variety of contexts, at a false discovery rate of 16%. The predictions are highly enriched for validated TF roles, and 45 of 67 (67%) tested binding site regions in five different contexts act as enhancers in functionally matched cells."]

['DEEP', 'PRISM']

How do septins contribute to cell asymmetry in fungi and animals?

['["discover that septins, a component of the cytoskeleton, recognize membrane curvature at the micron scale, a common morphological hallmark of eukaryotic cellular processes.", "Septins are an evolutionarily conserved family of GTP-binding proteins. They are involved in diverse processes including cytokinesis, apoptosis, infection, neurodegeneration and neoplasia. ", "eptins are a family of cytoskeletal GTP-binding proteins that assemble into membrane-associated hetero-oligomers and organize scaffolds for recruitment of cytosolic proteins or stabilization of membrane proteins. Septins have been implicated in a diverse range of cancers, including gastric cancer, but the underlying mechanisms remain unclear. ", "nidulans septins contain the highly conserved GTP binding and coiled-coil domains seen in other septins.", "The septins: roles in cytokinesis and other processes.", "The septins are a novel family of proteins that were first recognized in yeast as proteins associated with the neck filaments.", "Septin9 is involved in septin filament formation and cellular stability.", "Here, we review these findings and discuss emerging mechanisms by which septins promote cell asymmetry in fungi and animals.<CopyrightInformation>\\u00a9 2011 John Wiley & Sons A/S.</C", "These observations together with conserved sequence motifs identify the septins as members of the GTPase superfamily.", "BACKGROUND: Septins belong to the GTPase superclass of proteins and have been functionally implicated in cytokinesis and the maintenance of cellular morphology.", "Septins are important components of the cytoskeleton that are highly conserved in eukaryotes and play major roles in cytokinesis, patterning, and many developmental processes.", "The septins also appear to be involved in various other aspects of the organization of the cell surface.", "Septins are a family of eukaryotic GTP binding proteins conserved from yeasts to humans.", "Septins are a highly conserved family of GTP-binding proteins involved in multiple cellular functions, including cell division and morphogenesis.", "Septin proteins are conserved structural proteins that often demarcate regions of cell division.", "Septins are GTP-binding proteins that form filaments and higher-order structures on the cell cortex of eukaryotic cells and associate with actin and microtubule cytoskeletal networks.", "Septins are guanosine-5\'-triphosphate-binding proteins involved in wide-ranging cellular processes including cytokinesis, vesicle trafficking, membrane remodelling and scaffolds, and with diverse binding partners", "Septins are a group of GTP-binding proteins that can organize into heteromeric complexes and then into large filaments. ", "Septins are a conserved family of GTPases that regulate important cellular processes such as cell wall integrity, and septation in fungi.", "Septins are a cytosolic GTP-binding protein family first characterized in yeast, but gaining increasing recognition as critical protagonists in higher eukaryotic cellular events. Mammalian septins have been associated with cytokinesis and exocytosis, along with contributing to the development of neurological disorder", "Septins are a family of proteins that assemble a ring structure at the mother-daughter neck during vegetative growth, where they control cytokinesis. ", "Septins are a class of GTP-binding proteins conserved throughout many eukaryotes. Individual septin subunits associate with one another and assemble into heteromeric complexes that form filaments and higher-order structures in vivo. ", "The septins are a conserved family of GTP-binding, filament-forming proteins. I", "The septins are filament-forming, GTP-binding proteins that are conserved from yeast to humans. Septins assemble into higher-order structures such as rings, bars, and gauzes with diverse functions including serving as membrane diffusion barriers and scaffolds for cell signaling. ", "Septins are a family of 14 cytoskeletal proteins that dynamically form hetero-oligomers and organize membrane microdomains for protein complexes", "Septins are highly conserved and essential eukaryotic cytoskeletal proteins that interact with the inner plasma membrane. They are involved in essential functions requiring cell membrane remodeling and compartmentalization, such as cell division and dendrite morphogenesis, and have been implicated in numerous diseases", "Septins are conserved GTP-binding proteins that assemble into heteromeric complexes that form filaments and higher-order structures in cells.", " Septins are members of a conserved family of GTPases found in organisms as diverse as budding yeast and mammal", "Septins are a family of conserved proteins that are essential for cytokinesis in a wide range of organisms including fungi, Drosophila and mammals.']

Septins contribute to cell asymmetry in fungi and animals by promoting cell asymmetry through mechanisms that involve septin filament formation and cellular stability. These findings suggest that septins play a crucial role in establishing and maintaining cell polarity and asymmetry in various organisms.

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Is delayed enhancement documented in patients with non-ischemic dilated cardiomyopathy?

['Myocardial fibrosis was present in 30% of patients, the majority of which was mid-myocardial (63%). ', ' DCM patients frequently have myocardial fibrosis detected on CE-CMR, the majority of which is mid-myocardial.', 'Fifty (40%) patients showed myocardial DE, representing 12±7% of LV mass.', 'one case was dilated cardiomyopathy, in which the delayed enhancement was diffuse small midwall spots ', 'In the dilated cardiomyopathy group, only seven (29%) patients showed delayed enhancement and its pattern was characterized by mid-wall, patchy or diffuse location.', 'Patterns of delayed enhancement are different in dilated cardiomyopathy and ischemic cardiomyopathy, reflecting the presence of scarring or various degrees of fibrosis in left ventricular myocardium. The presence of subendocardial or transmural delayed enhancement at contrast-enhanced cardiovascular magnetic resonance allowed distinction between dilated cardiomyopathy and ischemic cardiomyopathy with high sensitivity (88%) and specificity (100%).']

['Delayed enhancement is documented in almost 30% of patients with non-ischemic dilated cardiomyopathy and its pattern is characterized by mid-wall, patchy or diffuse location.']

['yes']

Does PU.1 (SPI1) affect NF-kB binding?

['Recent data demonstrate that developmental transcription factors like the macrophage fate-determining Pu.1 set the stage for the activity of ubiquitous transcription factors activated by inflammatory stimuli, like NF-kB, AP-1, and interferon regulatory factors (IRFs).', 'Within 1217 bp of upstream sequence, 3 sites for NF-kB, 10 sites for NF-IL6, 15 sites for AP1, 6 sites for AP4, 2 sites for CHOP/CEBP alpha and 1 site for SP1 and PU.1 were identified.', 'As little as 82 bp of upstream sequence gave relatively strong luciferase activity, a region containing both a PU.1 and NF-kB site.', 'Potential transcription regulatory elements, AP1, AP2, AP3, NF-kB and GATA recognition sequences, are located within 523 bp upstream of the p35 gene; however, no TATA box was identified. The p40 subunit gene consists of eight exons. A TATA box is located 30 bp upstream from the transcription start site, and AP1, AP3, GATA, and Pu.1 recognition sequences are located within 690 bp upstream of the p40 gene.', 'Several putative binding sequences for ubiquitous (Sp1, AP-1, AP-2, and NF-kB) and leukocyte-specific (PU.1) transcription factors have been identified in the proximal region of the CD11c promoter which may participate in the regulation of the expression of p150,95.', 'PU.1 is regulated by NF-kappaB through a novel binding site in a 17 kb upstream enhancer element.']

['Recent data demonstrate that developmental transcription factors like the macrophage fate-determining Pu.1 set the stage for the activity of ubiquitous transcription factors activated by inflammatory stimuli, like NF-kB, AP-1, and interferon regulatory factors (IRFs). Within 1217 bp of upstream sequence, 3 sites for NF-kB, 10 sites for NF-IL6, 15 sites for AP1, 6 sites for AP4, 2 sites for CHOP/CEBP alpha and 1 site for SP1 and PU.1 were identified.', 'Recent data demonstrate that developmental transcription factors like the macrophage fate-determining Pu.1 set the stage for the activity of ubiquitous transcription factors activated by inflammatory stimuli, like NF-kB, AP-1, and interferon regulatory factors (IRFs).']

['yes']

What is known about the role of mHealth in the prevention of disease?

['mHealth approaches to child obesity prevention', 'Daily text messaging for weight control among racial and ethnic minority women', 'text messaging intervention for weight loss among predominantly black women. ', 'Given the increasing penetration of mobile devices, text messaging may be a useful self-monitoring tool for weight control, particularly among populations most in need of intervention', 'The review revealed evidence that mHealth tools support HIV programmatic priorities, including: linkage to care, retention in care, and adherence to antiretroviral treatment. In terms of technical features, mHealth tools facilitate alerts and reminders, data collection, direct voice communication, educational messaging, information on demand, and more', 'Mobile health messages help sustain recent weight loss.', ' A clinically significant decrease in mean weight, higher rate of sustained weight loss, and medium-to-large effects on sustained weight loss occurred in the promotion and prevention interventions', 'A mobile health intervention for weight management among young adults:', 'HIV prevalence in Uganda has leveled off, however trends indicate that incidence is on the rise and disproportionately affects certain vulnerable groups, such as women. There is growing support for using mobile health (mHealth) programs to reach vulnerable populations. ', 'We successully designed and implemented a mobile phone SMS-based system to track pregnancy and maternal and child outcomes in limited resources setting.', 'The purpose of the study, Project ACTION (Adult smoking Cessation Treatment through Innovative Outreach to Neighborhoods), is to utilize a mobile clinic model, a network of community sites (i.e., community centers and churches) and an interactive mobile messaging system to reach and deliver smoking cessation treatment to underserved, low-income communities.', 'Participants were randomized to usual prenatal care plus text messaging or usual care alone. The evaluation has a theoretical model of behavior change and measures mediators as well as behavioral outcomes. Results will inform how behavioral theory works within mobile health programs.']

['Most reported uses of mHealth are for treatment, we identified report on approaches to child obesity prevention.']

[]

Which is the most well-accepted method for Down syndrome non-invasive prenatal diagnosis?

['Potential of syncytiotrophoblasts isolated from the cervical mucus for early non-invasive prenatal diagnosis', 'Maternal serum protein profile and immune response protein subunits as markers for non-invasive prenatal diagnosis of trisomy 21, 18, and 13', 'Maternal serum protein profiling using proteomics may allow non-invasive diagnostic testing for the most common trisomies and may complement ultrasound-based methods to more accurately determine pregnancies with fetal aneuploidies', 'The presence of foetal DNA in the plasma of pregnant women has opened up new possibilities for non-invasive prenatal diagnosis. The use of circulating foetal DNA for the non-invasive prenatal detection of foetal chromosomal aneuploidies is challenging as foetal DNA represents a minor fraction of maternal plasma DNA', 'Using massively parallel sequencing, foetal trisomies 21, 13 and 18 have been detected from maternal plasma.', 'These developments suggest that the analysis of foetal DNA in maternal plasma would play an increasingly important role in future obstetrics practice.', 'Currently, two applications for NIPD of Down syndrome have been developed with potential and have displayed positive results; the NIPD using next-generation sequencing technologies and the NIPD using the methylated DNA immunoprecipitation (MeDIP) real-time quantitative polymerase chain reaction (qPCR)', 'Cell-free fetal RNA was extracted from the plasma of peripheral blood from 121 women 9-20 weeks of pregnancy. Five single nucleotide polymorphism (SNP) loci in PLAC4 gene were analyzed by reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA), followed by capillary electrophoresis', 'Non-invasive prenatal diagnosis of trisomy 21 by dosage ratio of fetal chromosome-specific epigenetic markers in maternal plasma', 'This study examined the methylation difference in AIRE and RASSF1A between maternal and placental DNA, and the implication of this difference in the identification of free fetal DNA in maternal plasma and in prenatal diagnosis of trisomy 21.', 'Diagnosis of trisomy 21 was established according to the ratio of fetal-specific AIRE to RASSF1A in maternal plasma. Both methods confirmed that AIRE and RASSF1A were hypomethylated in maternal blood cells but hypermethylated in placental or chorionic villus tissues.', 'It was concluded that hypermethylated AIRE and RASSF1A may serve as fetal-specific markers for the identification of fetal DNA in maternal plasma and may be used for noninvasive prenatal diagnosis of trisomy 21.', 'Preliminary reports indicate that the detection of fetal aneuploidies might be possible using epigenetically modified genes, e.g. maspin on chromosome 18. Additionally, an exiting recent development is that it might be feasible to detect Down syndrome via the quantitative assessment of placentally derived cell-free mRNA of chromosome-21-specific genes such as PLAC4', 'Candidate epigenetic biomarkers for non-invasive prenatal diagnosis of Down syndrome', 'Next, it was shown that the methylation status of chorionic villus sample DNA from first trimester pregnancies matched the hypermethylated state of term placenta.', 'Non-invasive prenatal diagnosis of trisomy 21 by reverse transcriptase multiplex ligation-dependent probe amplification.', 'To study whether pregnant women would like to be informed if sex chromosomal abnormalities (SCA) were suspected with the non-invasive prenatal diagnosis of fetal Down syndrome (the NIFTY) test.']

['Currently, two applications for NIPD of Down syndrome have been developed with potential and have displayed positive results; the NIPD using next-generation sequencing technologies and the NIPD using the methylated DNA immunoprecipitation (MeDIP) real-time quantitative polymerase chain reaction (qPCR). This study examined the methylation difference in AIRE and RASSF1A between maternal and placental DNA, and the implication of this difference in the identification of free fetal DNA in maternal plasma and in prenatal diagnosis of trisomy 21. Diagnosis of trisomy 21 was established according to the ratio of fetal-specific AIRE to RASSF1A in maternal plasma. Both methods confirmed that AIRE and RASSF1A were hypomethylated in maternal blood cells but hypermethylated in placental or chorionic villus tissues. It was concluded that hypermethylated AIRE and RASSF1A may serve as fetal-specific markers for the identification of fetal DNA in maternal plasma and may be used for noninvasive prenatal diagnosis of trisomy 21.', 'This study examined the methylation difference in AIRE and RASSF1A between maternal and placental DNA, and the implication of this difference in the identification of free fetal DNA in maternal plasma and in prenatal diagnosis of trisomy 21. Similarly, cell-free fetal DNA can be reliably recovered from maternal plasma and assessed by quantitative PCR to detect fetal trisomy 21 and paternally derived single gene mutations. The presence of foetal DNA in the plasma of pregnant women has opened up new possibilities for non-invasive prenatal diagnosis. Moreover, the differential methylation for each locus could be seen during the whole pregnant period.']

[]

Does Apolipoprotein E (ApoE) have anti-inflammatory activity?

[' have previously reported that apolipoprotein E (apoE), a protein component of very-low-density lipoproteins (VLDL) and high-density lipoproteins and a potent plasma-borne atheroprotective factor, exerts anti-inflammatory activity in macrophages by switching the activation profile from M1 ("classic") to M2 ("alternative") in a process involving signaling via low-density lipoprotein receptor ', 'anti-inflammatory activity in macrophages ', 'Small peptides corresponding to the receptor-binding region of apoE mimic the anti-inflammatory activity of the apoE ', 'Apolipoprotein (apo) E-containing high-density lipoprotein (HDL) has antioxidant, anti-inflammatory and anti-atherogenic properties']

['Yes. ApoE has anti-inflammatory activity']

['yes']

List fluorescent reporter proteins.

['Fluorescent Timer, or DsRed1-E5, is a mutant of the red fluorescent protein, dsRed, in which fluorescence shifts over time from green to red as the protein matures.', 'green fluorescent protein (Gfp)', 'Characterization of flavin-based fluorescent proteins: an emerging class of fluorescent reporters.', 'Flavin-based fluorescent proteins (FbFPs)', 'mCherry was employed as a reporter protein ', 'yellow fluorescent protein', 'red cytoplasmic fluorescent reporter protein. ', 'red fluorescent reporter protein', ' enhanced green fluorescent reporter protein', 'Fluorescent and luminescent reporter genes have become popular tools for the real-time monitoring of gene expression in living cells. ', ' fluorescent reporter protein [green fluorescent protein (GFP) and DsRed2]', 'coral fluorescent reporter protein ', 'driving a cassette for the enhanced green "live" fluorescent reporter protein (eGFP) ', 'GFP as a fluorescent reporter protein', ' protein', 'red fluorescent reporter protein (RFP) gene. ', 'The red fluorescent protein eqFP611', 'the green fluorescent reporter protein gene ', ' red fluorescent reporter protein', 'beta-phycoerythrin, a fluorescent reporter protein derived from algae', ' live-cell fluorescent reporter protein, Timer', 'red fluorescent reporter protein']

['Fluorescent and luminescent reporter genes have become popular tools for the real-time monitoring of gene expression in living cells:\ngreen fluorescent protein\nTimer\nred fluorescent protein\nyellow fluorescent protein\nbeta-phycoerythrin\ncoral fluorescent reporter protein\nenhanced green fluorescent reporter protein\nmCherry']

['green fluorescent protein', 'Gfp', 'Timer', 'DsRed1-E5', 'red fluorescent protein', 'dsRed', 'yellow fluorescent protein', 'beta-phycoerythrin', 'coral fluorescent reporter protein', 'enhanced green fluorescent reporter protein', 'mCherry']

Which hormone receptor function is altered in patients with Donohue syndrome?

['This disease is caused by a defective insulin receptor and features abnormal glucose metabolism and retarded intrauterine and postnatal growth.', 'Biallelic insulin receptor (INSR) gene mutations cause congenital syndromes of severe insulin resistance (SIR) known as Donohue syndrome (DS) and Rabson-Mendenhall syndrome (RMS). ', 'Severe progressive obstructive cardiomyopathy and renal tubular dysfunction in Donohue syndrome with decreased insulin receptor autophosphorylation due to a novel INSR mutation.', 'Donohue syndrome (leprechaunism; OMIM *246200) is a rare, recessively inherited disorder of extreme insulin resistance due to mutations in the insulin receptor gene (INSR) causing either defects in insulin binding or receptor autophosphorylation and tyrosine kinase activity.', 'Leprechaunism (Donohue syndrome): a case bearing novel compound heterozygous mutations in the insulin receptor gene.', 'Leprechaunism (Donohue syndrome) is the most severe type of insulin receptor (INSR) gene anomaly with the majority of patients surviving for only 2 years.', 'A novel mutation of the insulin receptor gene in a preterm infant with Donohue syndrome and heart failure.', 'Donohue syndrome (DS) is a rare autosomal recessive condition caused by mutations in the gene encoding the insulin receptor.', 'Any dysfunction of insulin signalling pathway as a result of insulin receptor gene mutations is linked with various forms of insulin resistance, including insulin resistance type A, Donohue or Rabson-Mendenhall syndrome, which differ in the level of severity. ', 'Donohue syndrome in a neonate with homozygous deletion of exon 3 of the insulin receptor gene.', 'Donohue syndrome describes the clinical consequences of the most severe genetic loss of insulin receptor function.', 'Homozygous or compound heterozygous mutations within the insulin binding domain of the human insulin receptor (INSR) are usually associated with severe impairment of insulin binding leading to Donohue syndrome ("Leprechaunism"), which is characterized by excessive hyperglycemia with hyperinsulinism, pre- and postnatal growth retardation, distinct dysmorphism and early death. ', 'The former mutation has been described in homozygous form in Donohue syndrome, while the latter is novel. ']

['Donohue syndrome (leprechaunism) is a rare, recessively inherited disorder of extreme insulin resistance due to mutations in the insulin receptor gene causing either defects in insulin binding or receptor autophosphorylation and tyrosine kinase activity. This syndrome is characterized by excessive hyperglycemia with hyperinsulinism, pre- and postnatal growth retardation, distinct dysmorphism and early death. Progressive obstructive cardiomyopathy and renal tubular dysfunction have been described in patients with Donohue syndrome. Milder form of insulin resistance due to insulin receptor gene mutation is coined as Rabson-Mendenhall syndrome.']

['insulin receptor']

Which mutated enzyme is responsible for oculocutaneous 1 (OCA1)-type albinism?

['An overview of oculocutaneous albinism: TYR gene mutations in five Colombian individuals', 'To date, 230 mutations in the TYR gene have been reported as responsible for oculocutaneus albinism type 1 worldwide. TYR gene encodes the enzyme tyrosinase involved in the metabolic pathway of melanin synthesis.', 'Mutations were identified in the TYR gene as responsible for oculocutaneous albinism type 1 in five Colombian individuals, and a new ophthalmic system was tested that corrected visual defects and symptoms in a patient with oculocutaneous albinism.', 'Mutations in the gene for tyrosinase, the key enzyme in melanin synthesis, are responsible for oculocutaneous albinism type 1, and more than 100 mutations of this gene have been identified.', 'The Q402 allele has been associated with autosomal recessive ocular albinism when it is in trans with a tyrosinase gene mutation associated with oculocutaneous albinism type 1.', 'The disruption of tyrosinase trafficking occurs at the level of the endoplasmic reticulum (ER) in OCA1 and OCA3, but at the post-Golgi level in OCA2. ', 'Mutations at a single N-glycosylation sequon of tyrosinase have been reported to be responsible for oculocutaneous albinism type IA in humans, characterized by inactive tyrosinase and the total absence of pigmentation. ', 'Mutations of the human tyrosinase gene associated with tyrosinase related oculocutaneous albinism (OCA1). ', 'Mutations in the human tyrosinase gene produce tyrosinase-related oculocutaneous albinism (OCA1, MIM #203100). Tyrosinase is a copper containing enzyme and is responsible for catalyzing the rate limiting step in melanin biosynthesis, the hydroxylation of tyrosine to dopaquinone. We report 13 new mutations in the tyrosinase gene associated with OCA1A (without pigment) and OCA1B (with pigment) including 9 missense mutations (H19Q, R521, R77C, G97R, C289R, L312V, P313R, F340L and H404P), two nonsense mutations (W80X and R116X) and two frameshift mutations (53delG and 223 delG). ', 'Mutations of the TYR gene lead to Oculocutaneous Albinism type 1 (OCA1), the most common type of albinism in humans (OMIM accession number 203100).', 'Mutations of the tyrosinase gene associated with a partial or complete loss of enzymatic activity are responsible for tyrosinase related oculocutaneous albinism (OCA1).', 'Oculocutaneous albinism type 1 (OCA1), resulting from mutations of the tyrosinase gene, is genetically and biochemically the best understood type of albinism.', 'Mutations in six genes have been reported to be responsible for different types of oculocutaneous and ocular albinism, including the tyrosinase gene (TYR) and OCA1 (MIM# 203100), the OCA2 gene and OCA2 (MIM# 203200), the tyrosinase-related protein-1 gene (TYRP1) and OCA3 (MIM# 203290), the HPS gene and Hermansky-Pudlak syndrome (MIM# 203300), the CHS gene (CHS1), and Chediak-Higashi syndrome (MIM# 214500), and the X-linked ocular albinism gene and OA1 (MIM#300500).', 'Defects in the tyrosinase gene (TYR) cause a common type of OCA, known as oculocutaneous albinism type 1 (OCA1).', 'Oculocutaneous albinism (OCA) in man may be caused by mutations within the tyrosinase gene (TYR) resulting in OCA1.', 'Two novel tyrosinase (TYR) gene mutations with pathogenic impact on oculocutaneous albinism type 1 (OCA1).', 'BACKGROUND: Tyrosinase (TYR) catalyzes the rate-limiting, first step in melanin production and its gene (TYR) is mutated in many cases of oculocutaneous albinism (OCA1), an autosomal recessive cause of childhood blindness.', 'Mutation analysis and prenatal gene diagnosis for the mutated tyrosinase (TYR) gene in two families with oculocutaneous albinism type I (OCA1).To define the fetus genotypes and gene mutation sites, the PCR and sequencing techniques were applied to amplify and analyze the regions of exon, exon-intron and promoter of TYR gene in probands and their parents of 2 families.The patient or proband of family 1 showed as a compound heterozygote with mutants R278X and 929insC', 'Mutations in the gene for tyrosinase, the key enzyme in melanin synthesis, are responsible for oculocutaneous albinism type 1, and more than 100 mutations of this gene have been identified', 'TYR gene encodes the enzyme tyrosinase involved in the metabolic pathway of melanin synthesis.Mutations were identified in the TYR gene as responsible for oculocutaneous albinism type 1 in five Colombian individuals, and a new ophthalmic system was tested that corrected visual defects and symptoms in a patient with oculocutaneous albinism.Samples were taken from 5 individuals, four of whom belong to a single family, along with a fifth individual not related to the family', 'Oculocutaneous albinism type 1 (OCA1) results from mutations in the tyrosinase gene, which lead to partial or complete loss of activity of the corresponding enzyme', 'Disrupting mutations in the tyrosinase (TYR) gene are known to cause recessive albinisms in humans (oculocutaneous albinism Type 1; OCA1) and other species', 'To explore the patients genotypes and the mutation spectrum of Tyrosinase (TYR) gene and the effects on protein structure and function in oculocutaneous albinism type 1 (OCA1).The polymerase chain reaction (PCR) and sequencing techniques were applied to amplify and analyze the regions of exon, exonintron and promoter of TYR gene of 15 OCA1 probands and some of their parents', 'Genetic analysis of oculocutaneous albinism type 1 (OCA1) in Indian families: two novel frameshift mutations in the TYR Gene', 'Mutations of the TYR gene lead to Oculocutaneous Albinism type 1 (OCA1), the most common type of albinism in humans (OMIM accession number 203100). ', 'Mutations of the tyrosinase gene associated with a partial or complete loss of enzymatic activity are responsible for tyrosinase related oculocutaneous albinism (OCA1). ', 'Oculocutaneous albinism (OCA) is a heterogeneous group of autosomal recessive disorders resulting from mutations of the tyrosinase (TYR) gene and presents with either complete or partial absence of pigment in the skin, hair and eyes due to a defect in an enzyme involved in the production of melanin. ', 'Oculocutaneous albinism type 1 (OCA1) results from mutations in the tyrosinase gene, which lead to partial or complete loss of activity of the corresponding enzyme. ', 'OCA1 (MIM 203100) is associated with mutations of the TYR gene encoding tyrosinase (the rate-limiting enzyme in the production of melanin pigment) and accounts for approximately 40% of OCA worldwide. ', 'Tyrosinase (EC 1.14.18.1) is a copper-containing enzyme that catalyzes several reactions in the biosynthesis of melanin pigments and is deficient in patients with type I oculocutaneous albinism (OCA1).', 'Oculocutaneous albinism type 1 (OCA1) results from mutations in the tyrosinase gene, which lead to partial or complete loss of activity of the corresponding enzyme.', 'Mutations of the TYR gene lead to Oculocutaneous Albinism type 1 (OCA1), the most common type of albinism in humans (OMIM accession number 203100).', 'In humans mutations in the TYR gene are associated with type 1 oculocutaneous albinism (OCA1) that leads to reduced or absent pigmentation of skin, hair and eye.', 'Oculocutaneous albinism type 1 (OCA1) is an autosomal recessive disease resulting from mutations of the tyrosinase gene (TYR).', 'Tyrosinase (TYR) catalyzes the rate-limiting, first step in melanin production and its gene (TYR) is mutated in many cases of oculocutaneous albinism (OCA1), an autosomal recessive cause of childhood blindness.', 'Mutations in six genes have been reported to be responsible for different types of oculocutaneous and ocular albinism, including the tyrosinase gene (TYR) and OCA1 (MIM# 203100), the OCA2 gene and OCA2 (MIM# 203200), the tyrosinase-related protein-1 gene (TYRP1) and OCA3 (MIM# 203290), the HPS gene and Hermansky-Pudlak syndrome (MIM# 203300), the CHS gene (CHS1), and Chediak-Higashi syndrome (MIM# 214500), and the X-linked ocular albinism gene and OA1 (MIM#300500).', 'Therapeutic research for OCA1 has been hampered, in part, by the absence of purified, active, recombinant wild-type and mutant human enzymes.The intra-melanosomal domain of human tyrosinase (residues 19-469) and two OCA1B related temperature-sensitive mutants, R422Q and R422W were expressed in insect cells and produced in T. ni larvae.', 'The tyrosinase gene family of proteins (tyrosinase, TRP1, and TRP2) regulate the type of eumelanin synthesized and mutations affecting them result in OCA1, OCA3, and slaty (in the murine system), respectively.', 'Genetic analysis of oculocutaneous albinism type 1 (OCA1) in Indian families: two novel frameshift mutations in the TYR Gene.', 'Oculocutaneous albinism (OCA) is a heterogeneous group of autosomal recessive disorders resulting from mutations of the tyrosinase (TYR) gene and presents with either complete or partial absence of pigment in the skin, hair and eyes due to a defect in an enzyme involved in the production of melanin.', 'Mutation analysis and prenatal gene diagnosis for the mutated tyrosinase (TYR) gene in two families with oculocutaneous albinism type I (OCA1).', 'Oculocutaneous albinism type 1 (OCA1), resulting from mutations of the tyrosinase gene, is genetically and biochemically the best understood type of albinism.', 'Two novel tyrosinase (TYR) gene mutations with pathogenic impact on oculocutaneous albinism type 1 (OCA1).', 'Oculocutaneous albinism Type 1 (OCA1) is an autosomal recessive disorder caused by mutations in the tyrosinase gene.', 'The mutation of the tyrosinase (TYR) gene results in oculocutaneous albinism type 1 (OCA1), an autosomal recessive genetic disorder.', 'The tyrosinase gene and oculocutaneous albinism type 1 (OCA1): A model for understanding the molecular biology of melanin formation.', 'Genetic analysis of oculocutaneous albinism type 1 (OCA1) in Indian families: two novel frameshift mutations in the TYR Gene.']

['Mutations in the gene for tyrosinase (TYR), the key enzyme in melanin synthesis, are responsible for oculocutaneous 1 (OCA1)-type albinism.']

['tyrosinase', 'TYR']

Is airplane stroke syndrome a common disease.

['Only 37 cases of stroke during or soon after long-haul flights have been published to our knowledge. ', 'Our centre admitted 5727 stroke patients, of whom 42 (0.73%) had flight-related strokes.', 'The authors report three cases of ischemic stroke in young adults that occurred during or after an airplane flight.']

['No. Only 37 cases of stroke during or soon after long-haul flights have been published. A single center study reported that 42 out of 5727 stroke admissions (0.73%) were flight-related strokes.']

['no']

Have thyronamines effects on fat tissue?

['In conclusion, trace amines and thyronamines are negative inotropic agents.', 'Their in vivo administration induces effects opposite to those induced by thyroid hormone, including lowering of body temperature.']

['There is not clear evidence that thyronamines have direct effect on adipose tissue']

['no']

What is the mode of inheritance of Facioscapulohumeral muscular dystrophy (FSHD)?

['autosomal dominant FSHD1', 'Facioscapulohumeral muscular dystrophy (FSHD) is a neuromuscular disease, characterized by an autosomal dominant mode of inheritance, facial involvement, and selectivity and asymmetry of muscle involvement.', 'Facioscapulohumeral dystrophy (FSHD) is an autosomal-dominant disorder characterized by weakness of the face, upper arm, shoulder, and lower limb musculature, with an onset between the first and third decades. ', 'Clinical diagnosis is made from the distinctive pattern of weakness, autosomal-dominant inheritance, and confirmed by genetic testing.', ' In one family together with prenatal diagnosis founder mutation in FSHD A1 gene was detected, according to the autosomal dominant (AD) inheritance.', 'Facioscapulohumeral muscular dystrophy (FSHD) is a primary muscle disorder with autosomal dominant inheritance.', 'Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive myopathy with autosomal dominant inheritance remarkable for its early involvement of facial musculature.', 'Consensual diagnostic criteria for facioscapulohumeral dystrophy (FSHD) include onset of the disease in facial or shoulder girdle muscles, facial weakness in more than 50% of affected family members, autosomal dominant inheritance in familial cases, and evidence of myopathic disease in at least one affected member without biopsy features specific to alternative diagnoses', 'Facioscapulohumeral dystrophy (FSHD) is an autosomal-dominant muscular disorder associated with a short (<35 kb) EcoRI/BlnI fragment resulting from deletion of an integral number of units of a 3.3-kb repeat located at 4q35.', 'In 139 families, dominant inheritance was observed in 97, a pattern compatible with germline mosaicism in 6, while sporadic cases were found in 36 families. ', 'In 139 families, dominant inheritance was observed in 97, a pattern compatible with germline mosaicism in 6, while sporadic cases were found in 36 families.']

['Facioscapulohumeral muscular dystrophy has an autosomal dominant inheritance pattern.']

['autosomal dominant']

Which tool is available for predicting regulatory interactions from ChIP-seq data?

['CisMapper: predicting regulatory interactions from transcription factor ChIP-seq data', "We present CisMapper, which predicts the regulatory targets of a TF using the correlation between a histone mark at the TF's bound sites and the expression of each gene across a panel of tissues.", 'Using both chromatin conformation capture and differential expression data, we show that CisMapper is more accurate at predicting the target genes of a TF than the distance-based approaches currently used, and is particularly advantageous for predicting the long-range regulatory interactions typical of tissue-specific gene expression', ' CisMapper also predicts which TF binding sites regulate a given gene more accurately than using genomic distance. Unlike distance-based methods, CisMapper can predict which transcription start site of a gene is regulated by a particular binding site of the TF', 'CisMapper: predicting regulatory interactions from transcription factor ChIP-seq data.', 'CisMapper: predicting regulatory interactions from transcription factor ChIP-seq data.', 'Using both chromatin conformation capture and differential expression data, we show that CisMapper is more accurate at predicting the target genes of a TF than the distance-based approaches currently used, and is particularly advantageous for predicting the long-range regulatory interactions typical of tissue-specific gene expression.']

["CisMapper predicts the regulatory targets of a TF using the correlation between a histone mark at the TF's bound sites and the expression of each gene across a panel of tissues. CisMapper is more accurate at predicting the target genes of a TF than the distance-based approaches currently used, and is particularly advantageous for predicting the long-range regulatory interactions typical of tissue-specific gene expression. CisMapper also predicts which TF binding sites regulate a given gene more accurately than using genomic distance. Unlike distance-based methods, CisMapper can predict which transcription start site of a gene is regulated by a particular binding site of the TF."]

['CisMapper']

What does the SAGA complex acronym stands for?

['SAGA (Spt-Ada-Gcn5 Acetyltransferase)', 'SAGA (Spt-Ada-Gcn5-acetyltransferase)', 'Spt-Ada-Gcn5-acetyltransferase (SAGA) ', 'Spt-Ada-Gcn5-acetyltransferase (SAGA) complex is a transcription coactivator ', 'the yeast transcriptional coactivator Spt-Ada-Gcn5 acetyltransferase (SAGA)']

['SAGA stands for Spt-Ada-Gcn5-acetyltransferase (SAGA)']

['Spt-Ada-Gcn5-acetyltransferase']

Is there any involvement of L1 retrotransposition in the Rett syndrome?

['Using neuronal progenitor cells derived from human induced pluripotent stem cells and human tissues, we revealed that patients with Rett syndrome (RTT), carrying MeCP2 mutations, have increased susceptibility for L1 retrotransposition. Our data demonstrate that L1 retrotransposition can be controlled in a tissue-specific manner and that disease-related genetic mutations can influence the frequency of neuronal L1 retrotransposition. Our findings add a new level of complexity to the molecular events that can lead to neurological disorders.', 'Furthermore, some neurological diseases, such as Rett syndrome and ataxia telangiectasia, misregulate L1 retrotransposition, which could contribute to some pathological aspects. ', 'Recent studies indicate that long interspersed nuclear element-1 (L1) are mobilized in the genome of human neural progenitor cells and enhanced in Rett syndrome and ataxia telangiectasia. ', 'In addition, recent data indicate that engineered human L1s can undergo somatic retrotransposition in human neural progenitor cells and that an increase in human-specific L1 DNA content can be detected in the brains of normal controls, as well as in Rett syndrome patients.', 'Furthermore, some neurological diseases, such as Rett syndrome and ataxia telangiectasia, misregulate L1 retrotransposition, which could contribute to some pathological aspects.', 'Using neuronal progenitor cells derived from human induced pluripotent stem cells and human tissues, we revealed that patients with Rett syndrome (RTT), carrying MeCP2 mutations, have increased susceptibility for L1 retrotransposition.', 'In addition, recent data indicate that engineered human L1s can undergo somatic retrotransposition in human neural progenitor cells and that an increase in human-specific L1 DNA content can be detected in the brains of normal controls, as well as in Rett syndrome patients.', 'Using neuronal progenitor cells derived from human induced pluripotent stem cells and human tissues, we revealed that patients with Rett syndrome (RTT), carrying MeCP2 mutations, have increased susceptibility for L1 retrotransposition', 'Furthermore, some neurological diseases, such as Rett syndrome and ataxia telangiectasia, misregulate L1 retrotransposition, which could contribute to some pathological aspects', 'Using neuronal progenitor cells derived from human induced pluripotent stem cells and human tissues, we revealed that patients with Rett syndrome (RTT), carrying MeCP2 mutations, have increased susceptibility for L1 retrotransposition.', 'Furthermore, some neurological diseases, such as Rett syndrome and ataxia telangiectasia, misregulate L1 retrotransposition, which could contribute to some pathological aspects.', 'Recent studies indicate that long interspersed nuclear element-1 (L1) are mobilized in the genome of human neural progenitor cells and enhanced in Rett syndrome and ataxia telangiectasia.']

['Yes. Recent studies indicate that long interspersed nuclear element-1 (L1) are mobilized in the genome of human neural progenitor cells and enhanced in Rett syndrome and ataxia telangiectasia.']

['yes']