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1.
Zhongguo Zhong Yao Za Zhi ; 44(14): 2966-2971, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31602841

RESUMO

To study the effects of saikosaponin b2( SS-b2) on inflammatory factors and energy metabolism against lipopolysaccharide/galactosamine( LPS/Gal N) induced acute liver injury in mice. Mice were randomly divided into normal group( equal amount of normal saline),model group( 100 g·kg~(-1) LPS and 400 mg·kg~(-1) Gal N),low,medium,high dose group of SS-b2( SS-b25,10,20 mg·kg~(-1)·d-1) and positive control group( dexamethasone,10 mg·kg~(-1)). All of the groups except for the normal group were treated with LPS/Gal N though intraperitoneally injection to establish the acute liver injury model. The organ indexes were calculated. The levels of serum transaminases( ALT and AST) and the activities of ATPase( Na+-K+-ATPase,Ca2+-Mg2+-ATPase) in liver were detected. The activity of tumor necrosis factor-α( TNF-α),interleukin-1ß( IL-1ß) and interleukin-6( IL-6) were determined by the enzyme-linked immunosorbent assay( ELISA). The contents of lactate dehydrogenase( LDH) in liver were determined by micro-enzyme method. HE staining was used to observe the histopathological changes of the liver. Histochemical method was used to investigate the protein expression of liver lactate dehydrogenase-A( LDH-A). The protein expressions of Sirt-6 and NF-κB in the liver were detected by Western blot. According to the results,compared with the model group,there were significant changes in organ indexes in the high-dose group of SS-b2( P<0. 05). The level of ALT,AST,TNF-α,IL-1ß,IL-6 and the activities of LDH in serum of mice with liver injury were significantly reduced in the medium and high dose groups of SS-b2( P<0. 01). With the increase of the concentration of SS-b2,the range of hepatic lesions and the damage in mice decreased. The activities of Na+-K+-ATPase and Ca2+-Mg2+-ATPase in liver of mice were significantly enhanced in each dose group( P<0. 01). The expression of NF-κB in liver tissues was significantly down-regulated in the medium and high dose group( P<0. 01). Meanwhile,the expression of Sirt-6 protein in the liver of mice with acute liver injury was significantly increased in each dose group( P<0. 01).In summary,SS-b2 has a significant protective effect on LPS/Gal N-induced acute liver injury in mice,which may be related to the down-regulation of NF-κB protein expression and up-regulation of Sirt-6 protein expression to improve inflammatory injury and energy metabolism.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Metabolismo Energético , Inflamação/tratamento farmacológico , Ácido Oleanólico/análogos & derivados , Saponinas/farmacologia , Animais , Citocinas/metabolismo , Galactosamina , Lipopolissacarídeos , Fígado/efeitos dos fármacos , Camundongos , NF-kappa B/metabolismo , Ácido Oleanólico/farmacologia , Distribuição Aleatória , Sirtuínas/metabolismo
2.
J Alzheimers Dis ; 72(1): 301-318, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31561366

RESUMO

Most of the loci identified by genome-wide association studies (GWAS) for late-onset Alzheimer's disease (LOAD) are in strong linkage disequilibrium (LD) with nearby variants all of which could be the actual functional variants, often in non-protein-coding regions and implicating underlying gene regulatory mechanisms. We set out to characterize the causal variants, regulatory mechanisms, tissue contexts, and target genes underlying these associations. We applied our INFERNO algorithm to the top 19 non-APOE loci from the IGAP GWAS study. INFERNO annotated all LD-expanded variants at each locus with tissue-specific regulatory activity. Bayesian co-localization analysis of summary statistics and eQTL data was performed to identify tissue-specific target genes. INFERNO identified enhancer dysregulation in all 19 tag regions analyzed, significant enrichments of enhancer overlaps in the immune-related blood category, and co-localized eQTL signals overlapping enhancers from the matching tissue class in ten regions (ABCA7, BIN1, CASS4, CD2AP, CD33, CELF1, CLU, EPHA1, FERMT2, ZCWPW1). In several cases, we identified dysregulation of long noncoding RNA (lncRNA) transcripts and applied the lncRNA target identification algorithm from INFERNO to characterize their downstream biological effects. We also validated the allele-specific effects of several variants on enhancer function using luciferase expression assays. By integrating functional genomics with GWAS signals, our analysis yielded insights into the regulatory mechanisms, tissue contexts, genes, and biological processes affected by noncoding genetic variation associated with LOAD risk.

3.
PLoS One ; 14(8): e0221217, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31412076

RESUMO

This study compares husbands' and wives' views on the person in a couple who should be responsible for preparing for hurricane hazards; it also examines whether the varying levels of agreement reached by husbands and wives regarding this responsibility are associated with actual preparedness behaviors. An online survey targeting married, heterosexual couples living in Sarasota County, Florida, USA was sent out between March and May, 2015. Both the husbands and the wives were asked to fill out the survey. A total of 170 surveys were used for analysis. Results suggested that husbands and wives felt that they had shared responsibility for most of the 19 preparedness behaviors considered. However, a few stereotypically masculine preparedness behaviors were found to typically fall to husbands. Husbands' and wives' views of perceived responsibility were not statistically different, but husbands tended to favor individual responsibility, while wives tended to favor joint responsibility. Higher levels of agreement were significantly associated with greater engagement in planning-related preparedness behaviors. Policy implications are discussed.

5.
Artigo em Chinês | MEDLINE | ID: mdl-31245947

RESUMO

OBJECTIVE: To investigate the therapeutic effects and mechanisms of Bianyanning on acute pharyngitis in rats, and to provide evidence and experimental data for its clinical application. METHODS: The acute pharyngitis of rats was induced by spraying ammonia directly to their throat. The model rats were randomly divided into model control group, the high-, medium- and low-dose group of Bianyanning, while normal rats were used as control group, 10 in each group. After the corresponding drug treatment, the symptoms and manifestations of each group were observed and recorded; 24 hours after last gavaging, blood samples of each group were collected from the abdominal aorta. The serum contents of interleukin 1-beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) were detected by ELISA. HE method was used to observe the characteristic of the lung tissues and the transmission electron microscopy method was used to observe the trachea cilia. RESULTS: After the treatment, compared with the model control group, the high-, medium- and low-dose group of Bianyanning, the symptoms of acute pharyngitis such as inflamed and congestive throat were relieved obviously. The morphological changes of lung and bronchus tissues were apparently improved. The contents of IL-1ß and TNF-α in serum were decreased significantly. CONCLUSION: Compound Bianyanning can promote the recovering process of acute pharyngitis, improve the morphology of lungs and bronchus, which may be related to inhibiting the releasing of the IL-1ß and TNF-α in serum.


Assuntos
Medicamentos de Ervas Chinesas , Faringite , Animais , Medicamentos de Ervas Chinesas/farmacologia , Interleucina-1beta/metabolismo , Faringite/tratamento farmacológico , Faringite/imunologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
6.
Nat Genet ; 51(6): 1052-1059, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31152161

RESUMO

Maize is one of the most important crops globally, and it shows remarkable genetic diversity. Knowledge of this diversity could help in crop improvement; however, gold-standard genomes have been elucidated only for modern temperate varieties. Here, we present a high-quality reference genome (contig N50 of 15.78 megabases) of the maize small-kernel inbred line, which is derived from a tropical landrace. Using haplotype maps derived from B73, Mo17 and SK, we identified 80,614 polymorphic structural variants across 521 diverse lines. Approximately 22% of these variants could not be detected by traditional single-nucleotide-polymorphism-based approaches, and some of them could affect gene expression and trait performance. To illustrate the utility of the diverse SK line, we used it to perform map-based cloning of a major effect quantitative trait locus controlling kernel weight-a key trait selected during maize improvement. The underlying candidate gene ZmBARELY ANY MERISTEM1d provides a target for increasing crop yields.


Assuntos
Estudos de Associação Genética , Genoma de Planta , Genômica , Fenótipo , Zea mays/genética , Biologia Computacional/métodos , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Endogamia , Anotação de Sequência Molecular , Melhoramento Vegetal , Plantas Geneticamente Modificadas , Polimorfismo de Nucleotídeo Único , Característica Quantitativa Herdável
8.
Sci Rep ; 9(1): 3213, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30824717

RESUMO

Paeonia ostii is a traditional ornamental and medicinal species that has attracted considerable interest for its high oil value. To facilitate the effective and rational cultivation and application of P. ostii in China, it is necessary to determine its potential spatial habitat distribution and environmental requirements. Using high-resolution environmental data for current and future climate scenarios, the potential suitable area and climatic requirements of P. ostii were modelled. Among the 11 environmental variables investigated, growing degree days, precipitation of the wettest month, mean temperature of the coldest quarter, global UV-B radiation, annual precipitation, and soil pH played major roles in determining the suitability of a habitat for the cultivation of P. ostii. Under the current environmental conditions in China, a total area of 20.31 × 105 km2 is suitable for growing P. ostii, accounting for 21.16% of the country's total land area. Under the two future climate scenario/year combinations (i.e., representative concentration pathways [RCPs], RCP2.6 and RCP8.5 in 2050), this species would increase its suitable area at high latitudes while decrease at low latitudes. These results present valuable information and a theoretical reference point for identifying the suitable cultivation areas of P. ostii.

9.
Bioinformatics ; 35(6): 1033-1039, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30668832

RESUMO

MOTIVATION: Small non-coding RNAs (sncRNAs, <100 nts) are highly abundant RNAs that regulate diverse and often tissue-specific cellular processes by associating with transcription factor complexes or binding to mRNAs. While thousands of sncRNA genes exist in the human genome, no single resource provides searchable, unified annotation, expression and processing information for full sncRNA transcripts and mature RNA products derived from these larger RNAs. RESULTS: Our goal is to establish a complete catalog of annotation, expression, processing, conservation, tissue-specificity and other biological features for all human sncRNA genes and mature products derived from all major RNA classes. DASHR (Database of small human non-coding RNAs) v2.0 database is the first that integrates human sncRNA gene and mature products profiles obtained from multiple RNA-seq protocols. Altogether, 185 tissues/cell types and sncRNA annotations and >800 curated experiments from ENCODE and GEO/SRA across multiple RNA-seq protocols for both GRCh38/hg38 and GRCh37/hg19 assemblies are integrated in DASHR. Moreover, DASHR is the first to contain both known and novel, previously un-annotated sncRNA loci identified by unsupervised segmentation (13 times more loci with 1 678 800 total). Additionally, DASHR v2.0 adds >3 200 000 annotations for non-small RNA genes and other genomic features (long-noncoding RNAs, mRNAs, promoters, repeats). Furthermore, DASHR v2.0 introduces an enhanced user interface, interactive experiment-by-locus table view, sncRNA locus sorting and filtering by biological features. All annotation and expression information directly downloadable and accessible as UCSC genome browser tracks. AVAILABILITY AND IMPLEMENTATION: DASHR v2.0 is freely available at https://lisanwanglab.org/DASHRv2. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

10.
Oncogene ; 2018 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-30478448

RESUMO

The poor outcomes in infant acute lymphoblastic leukemia (ALL) necessitate new treatments. Here we discover that EIF4E protein is elevated in most cases of infant ALL and test EIF4E targeting by the repurposed antiviral agent ribavirin, which has anticancer properties through EIF4E inhibition, as a potential treatment. We find that ribavirin treatment of actively dividing infant ALL cells on bone marrow stromal cells (BMSCs) at clinically achievable concentrations causes robust proliferation inhibition in proportion with EIF4E expression. Further, we find that ribavirin treatment of KMT2A-rearranged (KMT2A-R) infant ALL cells and the KMT2A-AFF1 cell line RS4:11 inhibits EIF4E, leading to decreases in oncogenic EIF4E-regulated cell growth and survival proteins. In ribavirin-sensitive KMT2A-R infant ALL cells and RS4:11 cells, EIF4E-regulated proteins with reduced levels of expression following ribavirin treatment include MYC, MCL1, NBN, BCL2 and BIRC5. Ribavirin-treated RS4:11 cells exhibit impaired EIF4E-dependent nuclear to cytoplasmic export and/or translation of the corresponding mRNAs, as well as reduced phosphorylation of the p-AKT1, p-EIF4EBP1, p-RPS6 and p-EIF4E signaling proteins. This leads to an S-phase cell cycle arrest in RS4:11 cells corresponding to the decreased proliferation. Ribavirin causes nuclear EIF4E to re-localize to the cytoplasm in KMT2A-AFF1 infant ALL and RS4:11 cells, providing further evidence for EIF4E inhibition. Ribavirin slows increases in peripheral blasts in KMT2A-R infant ALL xenograft-bearing mice. Ribavirin cooperates with chemotherapy, particularly L-asparaginase, in reducing live KMT2A-AFF1 infant ALL cells in BMSC co-cultures. This work establishes that EIF4E is broadly elevated across infant ALL and that clinically relevant ribavirin exposures have preclinical activity and effectively inhibit EIF4E in KMT2A-R cases, suggesting promise in EIF4E targeting using ribavirin as a means of treatment.

11.
Bioinformatics ; 2018 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-30351394

RESUMO

Summary: We report VCPA, our SNP/Indel Variant Calling Pipeline and data management tool used for analysis of whole genome and exome sequencing (WGS/WES) for the Alzheimer's Disease Sequencing Project. VCPA consists of two independent but linkable components: pipeline and tracking database. The pipeline, implemented using the Workflow Description Language and fully optimized for the Amazon elastic compute cloud environment, includes steps from aligning raw sequence reads, to variant calling using GATK. The tracking database allows users to view job running status in real time and visualize >100 quality metrics per genome. VCPA is functionally equivalent to the CCDG/TOPMed pipeline. Users can use the pipeline and the dockerized database to process large WGS/WES datasets on Amazon cloud with minimal configuration. Availability: VCPA is released under the MIT license and is available for academic and nonprofit use for free. The pipeline source code and step-by-step instructions are available from the National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site (http://www.niagads.org/VCPA). Supplementary information: Supplementary data are available at Bioinformatics online.

12.
Transl Stroke Res ; 2018 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-30178428

RESUMO

There is no effective biological method to classify ischemic stroke subtypes. In this study, we first performed a systematical gene array study on serum microRNAs with different ischemic stroke subtypes including 13 normal control subjects (NCs) and 87 ischemic stroke (IS) patients including 23 cardioembolism (CARD), 26 large artery atherosclerosis (LAA), 27 lacunar infarct (LAC), and 11 stroke of undetermined etiology (SUE). Validation was performed by using an independent cohort of 20 NCs and 85 IS patients including 28 CARD, 23 LAA, 18 LAC, and 16 SUE. In the pilot discovery gene array study, we found specific serum microRNA signatures between different ischemic stroke subtypes (CARD, LAA, LAC, and SUE). We further validated 6 microRNAs [miR-125b, miR-125a, let-7b, let-7e, miR-7-2-3p, miR-1908] in a different group of ischemic stroke subtypes by using an independent cohort of 20 NCs, 28 CARD, 23 LAA, 18 LAC, and 16 SUE. Moreover, these circulating miRNAs were further detected to be differentially expressed between pre- vs. post-stroke in different ischemic stroke subtypes. The ROC analysis showed that miR-125b, miR-125a, let-7b, and let-7e could discriminate CARD patients from normal controls and other subtypes. Furthermore, ROC curves shown that miR-7-2-3p and miR-1908 showed significant area-under-the-curve values in both LAA and LAC patients. In conclusion, these results demonstrated that circulating miRNAs in sera could be potentially novel risk factors that involve in the pathogenesis of ischemic stroke subtypes.

13.
Nucleic Acids Res ; 46(17): 8740-8753, 2018 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-30113658

RESUMO

The majority of variants identified by genome-wide association studies (GWAS) reside in the noncoding genome, affecting regulatory elements including transcriptional enhancers. However, characterizing their effects requires the integration of GWAS results with context-specific regulatory activity and linkage disequilibrium annotations to identify causal variants underlying noncoding association signals and the regulatory elements, tissue contexts, and target genes they affect. We propose INFERNO, a novel method which integrates hundreds of functional genomics datasets spanning enhancer activity, transcription factor binding sites, and expression quantitative trait loci with GWAS summary statistics. INFERNO includes novel statistical methods to quantify empirical enrichments of tissue-specific enhancer overlap and to identify co-regulatory networks of dysregulated long noncoding RNAs (lncRNAs). We applied INFERNO to two large GWAS studies. For schizophrenia (36,989 cases, 113,075 controls), INFERNO identified putatively causal variants affecting brain enhancers for known schizophrenia-related genes. For inflammatory bowel disease (IBD) (12,882 cases, 21,770 controls), INFERNO found enrichments of immune and digestive enhancers and lncRNAs involved in regulation of the adaptive immune response. In summary, INFERNO comprehensively infers the molecular mechanisms of causal noncoding variants, providing a sensitive hypothesis generation method for post-GWAS analysis. The software is available as an open source pipeline and a web server.

14.
J Stroke Cerebrovasc Dis ; 27(10): 2840-2842, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30068478

RESUMO

Our objective is to reported a Chinese CARASIL patient caused by novel compound heterozygous mutations in HTRA1. Detailed clinical and neuroimaging examination were conducted in proband and her available family members. Sanger sequencing of NOTCH3 and HTRA1 was used to investigate causative mutations. The patient was born in an outbred family. She experienced recurrent transient ischemic attacks, hair loss, and low back pain. Brain magnetic resonance imaging showed multiple lacunar infarctions, diffuse leukoencephalopathy, and multiple microbleeds of white matter. A compound heterozygous mutation, c.958G > A (p.D320N) and c.1021G > A (p.G341J), were identified in the proband. This report highlights that screening of HTRA1 should be considered in young SVD patient despite from outbred families.


Assuntos
Alopecia/genética , Grupo com Ancestrais do Continente Asiático/genética , Infarto Cerebral/genética , Serina Peptidase 1 de Requerimento de Alta Temperatura A/genética , Leucoencefalopatias/genética , Mutação , Doenças da Coluna Vertebral/genética , Adulto , Alopecia/diagnóstico por imagem , Alopecia/etnologia , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/etnologia , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença , Hereditariedade , Heterozigoto , Humanos , Hemorragias Intracranianas/diagnóstico por imagem , Hemorragias Intracranianas/genética , Ataque Isquêmico Transitório/diagnóstico por imagem , Ataque Isquêmico Transitório/genética , Leucoencefalopatias/diagnóstico por imagem , Leucoencefalopatias/etnologia , Imagem por Ressonância Magnética , Linhagem , Fenótipo , Doenças da Coluna Vertebral/diagnóstico por imagem , Doenças da Coluna Vertebral/etnologia , Acidente Vascular Cerebral Lacunar/diagnóstico por imagem , Acidente Vascular Cerebral Lacunar/genética
15.
Bioinformatics ; 34(14): 2349-2355, 2018 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-29992253

RESUMO

Motivation: Copy number variations (CNVs) are gains and losses of DNA segments and have been associated with disease. Many large-scale genetic association studies are performing CNV analysis using whole exome sequencing (WES) and whole genome sequencing (WGS). In many of these studies, previous single-nucleotide polymorphism (SNP)-array data are available. An integrated cross-platform analysis is expected to improve resolution and accuracy, yet there is no tool for effectively combining data from sequencing and array platforms. The detection of CNVs using sequencing data alone can also be further improved by the utilization of allele-specific reads. Results: We propose a statistical framework, integrated CNV (iCNV) detection algorithm, which can be applied to multiple study designs: WES only, WGS only, SNP array only, or any combination of SNP and sequencing data. iCNV applies platform-specific normalization, utilizes allele specific reads from sequencing and integrates matched NGS and SNP-array data by a hidden Markov model. We compare integrated two-platform CNV detection using iCNV to naïve intersection or union of platforms and show that iCNV increases sensitivity and robustness. We also assess the accuracy of iCNV on WGS data only and show that the utilization of allele-specific reads improve CNV detection accuracy compared to existing methods. Availability and implementation: https://github.com/zhouzilu/iCNV. Supplementary information: Supplementary data are available at Bioinformatics online.

16.
Mol Neurodegener ; 13(1): 37, 2018 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-29986742

RESUMO

BACKGROUND: Progressive supranuclear palsy (PSP) is a parkinsonian neurodegenerative tauopathy affecting brain regions involved in motor function, including the basal ganglia, diencephalon and brainstem. While PSP is largely considered to be a sporadic disorder, cases with suspected familial inheritance have been identified and the common MAPT H1haplotype is a major genetic risk factor. Due to the relatively low prevalence of PSP, large sample sizes can be difficult to achieve, and this has limited the ability to detect true genetic risk factors at the genome-wide statistical threshold for significance in GWAS data. With this in mind, in this study we genotyped the genetic variants that displayed the strongest degree of association with PSP (P<1E-4) in the previous GWAS in a new cohort of 533 pathologically-confirmed PSP cases and 1172 controls, and performed a combined analysis with the previous GWAS data. RESULTS: Our findings validate the known association of loci at MAPT, MOBP, EIF2AK3 and STX6 with risk of PSP, and uncover novel associations with SLCO1A2 (rs11568563) and DUSP10 (rs6687758) variants, both of which were classified as non-significant in the original GWAS. CONCLUSIONS: Resolving the genetic architecture of PSP will provide mechanistic insights and nominate candidate genes and pathways for future therapeutic intervention strategies.

17.
Sci Data ; 5: 180130, 2018 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-30015804

RESUMO

Sustained observations of microbial dynamics are rare, especially in southern hemisphere waters. The Australian Marine Microbial Biodiversity Initiative (AMMBI) provides methodologically standardized, continental scale, temporal phylogenetic amplicon sequencing data describing Bacteria, Archaea and microbial Eukarya assemblages. Sequence data is linked to extensive physical, biological and chemical oceanographic contextual information. Samples are collected monthly to seasonally from multiple depths at seven sites: Darwin Harbour (Northern Territory), Yongala (Queensland), North Stradbroke Island (Queensland), Port Hacking (New South Wales), Maria Island (Tasmania), Kangaroo Island (South Australia), Rottnest Island (Western Australia). These sites span ~30° of latitude and ~38° longitude, range from tropical to cold temperate zones, and are influenced by both local and globally significant oceanographic and climatic features. All sequence datasets are provided in both raw and processed fashion. Currently 952 samples are publically available for bacteria and archaea which include 88,951,761 bacterial (72,435 unique) and 70,463,079 archaeal (24,205 unique) 16 S rRNA v1-3 gene sequences, and 388 samples are available for eukaryotes which include 39,801,050 (78,463 unique) 18 S rRNA v4 gene sequences.

18.
Genomics ; 2018 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-29857119

RESUMO

The Alzheimer's Disease Sequencing Project (ADSP) performed whole genome sequencing (WGS) of 584 subjects from 111 multiplex families at three sequencing centers. Genotype calling of single nucleotide variants (SNVs) and insertion-deletion variants (indels) was performed centrally using GATK-HaplotypeCaller and Atlas V2. The ADSP Quality Control (QC) Working Group applied QC protocols to project-level variant call format files (VCFs) from each pipeline, and developed and implemented a novel protocol, termed "consensus calling," to combine genotype calls from both pipelines into a single high-quality set. QC was applied to autosomal bi-allelic SNVs and indels, and included pipeline-recommended QC filters, variant-level QC, and sample-level QC. Low-quality variants or genotypes were excluded, and sample outliers were noted. Quality was assessed by examining Mendelian inconsistencies (MIs) among 67 parent-offspring pairs, and MIs were used to establish additional genotype-specific filters for GATK calls. After QC, 578 subjects remained. Pipeline-specific QC excluded ~12.0% of GATK and 14.5% of Atlas SNVs. Between pipelines, ~91% of SNV genotypes across all QCed variants were concordant; 4.23% and 4.56% of genotypes were exclusive to Atlas or GATK, respectively; the remaining ~0.01% of discordant genotypes were excluded. For indels, variant-level QC excluded ~36.8% of GATK and 35.3% of Atlas indels. Between pipelines, ~55.6% of indel genotypes were concordant; while 10.3% and 28.3% were exclusive to Atlas or GATK, respectively; and ~0.29% of discordant genotypes were. The final WGS consensus dataset contains 27,896,774 SNVs and 3,133,926 indels and is publicly available.

19.
Nucleic Acids Res ; 46(W1): W36-W42, 2018 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-29733404

RESUMO

The introduction of new high-throughput small RNA sequencing protocols that generate large-scale genomics datasets along with increasing evidence of the significant regulatory roles of small non-coding RNAs (sncRNAs) have highlighted the urgent need for tools to analyze and interpret large amounts of small RNA sequencing data. However, it remains challenging to systematically and comprehensively discover and characterize sncRNA genes and specifically-processed sncRNA products from these datasets. To fill this gap, we present Small RNA-seq Portal for Analysis of sequencing expeRiments (SPAR), a user-friendly web server for interactive processing, analysis, annotation and visualization of small RNA sequencing data. SPAR supports sequencing data generated from various experimental protocols, including smRNA-seq, short total RNA sequencing, microRNA-seq, and single-cell small RNA-seq. Additionally, SPAR includes publicly available reference sncRNA datasets from our DASHR database and from ENCODE across 185 human tissues and cell types to produce highly informative small RNA annotations across all major small RNA types and other features such as co-localization with various genomic features, precursor transcript cleavage patterns, and conservation. SPAR allows the user to compare the input experiment against reference ENCODE/DASHR datasets. SPAR currently supports analyses of human (hg19, hg38) and mouse (mm10) sequencing data. SPAR is freely available at https://www.lisanwanglab.org/SPAR.

20.
Neurosci Lett ; 678: 110-117, 2018 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-29733976

RESUMO

Ebselen is a fat-soluble small molecule and organic selenium compound that regulates the activity of glutathione peroxidase to alleviate mitochondrial oxidative stress and improve mitochondrial function. In the present study, we aimed to investigate the effects of ebselen on mitochondrial oxidative stress response, mitochondrial apotosis, and motor behaviors after spinal cord injury (SCI). We found that ebselen significantly increased the BBB score in motor behavior, thus suggesting a rescue effect of ebselen on motor function after SCI in rats. Meanwhile, we revealed that ebselen can increase glutathione (GSH) content as well as superoxide dismutase (SOD) and catalase (CAT) activities after SCI-this suggests ebselen has an antioxidant effect. Furthermore, the ATP content and Na+-K+-ATPase activity in mitochondria were increased by ebselen after SCI, while the mitochondrial membrane potential (MMP) was decreased by ebselen. The Cytochrome C and Smac release from mitochondria were reduced by ebselen after SCI, thus indicating improved membrane permeability by ebselen. Moreover, the alterations in caspase-3, Bax and Bcl-2 protein expression, as well as the proportion of cell apoptosis were improved by ebselen treatment, which together suggested that ebselen has an inhibitory effect on mitochondrial apotosis pathways after SCI. Taken together, our results suggest that ebselen can inhibit secondary damage caused by spinal cord injury. Indeed it plays a neuroprotective role in spinal cord injury perhaps by improving mitochondrial function and inhibiting the mitochondrial apoptosis pathway.

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