Datasets:

nirantk

/

geneticsQA-train

like 0

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.']

[]

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. ']

[]

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.']

[]

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.']

[]

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."]

[]

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?

[]

['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']

[]

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.']

[]

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).']

[]

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.']

[]

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.']

[]

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. ']

[]

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.

[]

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.']

[]

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.']

[]

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.

[]

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']