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ezQTL:A Web Platform for Interactive Visualization and Colocalization of QTLs and GWAS Loci

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Genomics, Proteomics & Bioinformatics 2022年第3期20卷 541-548页

作者： Tongwu Zhang alyssa Klein Jian Sang Jiyeon Choi Kevin m.Brown Division of Cancer Epidemiology and Genetics National Cancer InstituteBethesdaMD 20892USA

Genome-wide association studies(GWAS)have identified thousands of genomic loci associated with complex diseases and traits,including *** vast majority of common traitassociated variants identified via GWAS fall in non-coding regions of the genome,posing a challenge in elucidating the causal variants,genes,and mechanisms *** quantitative trait locus(eQTL)and other molecular QTL studies have been valuable resources in identifying candidate causal genes from GWAS loci through statistical colocalization *** QTL colocalization is becoming a standard analysis in post-GWAS investigation,an easy web tool for users to perform formal colocalization analyses with either user-provided or public GWAS and eQTL datasets has been ***,we present ezQTL,a web-based bioinformatic application to interactively visualize and analyze genetic association data such as GWAS loci and molecular QTLs under different linkage disequilibrium(LD)patterns(1000 Genomes Project,UK Biobank,or user-provided data).This application allows users to perform data quality control for variants matched between different datasets,LD visualization,and two-trait colocalization analyses using two state-of-the-art methodologies(eCAVIAR and HyPrColoc),including batch *** is a free and publicly available cross-platform web tool,which can be accessed online at https://***/ezqtl.

关键词： Genome-wide association study Expression quantitative trait locus Colocalization Linkage disequilibrium Visualization

Changes in physical activity,sedentary behavior,and self-reported cognitive function in cancer survivors before and during the COVID-19 pandemic:A cross-sectional study

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Journal of Sport and Health Science 2023年第6期12卷 653-663页

作者： Linda Trinh Allyson Tabaczynski Denise Bastas alyssa R.Neville m.Lauren Voss Alexis Whitehorn Faculty of Kinesiology&Physical Education University of TorontoTorontoOT M5S 2W6Canada

Background Physical activity(PA)and reductions in sedentary behavior(SED)may mitigate cancer-related cognitive *** purpose of this study was to examine(a)the associations between changes in PA,SED,and cognitive function in cancer survivors before and during the coronavirus disease 2019(COVID-19)pandemic;and(b)clinical subgroups that moderate this *** A cross-sectional survey was administered online to adult cancer survivors globally between July and November of *** was a secondary analysis of a cross-sectional survey examining changes in self-reported PA and quality of life in cancer survivors before and during the COVID-19 ***-reported Questionnaires assessed moderate-to-vigorous PA(mVPA)using the modified Godin Leisure Time Exercise Questionnaire,cognitive function using the Functional Assessment of Cancer Therapy-Cognitive Function(FACT-Cog)scale,and SED using the Domain-specific Sitting Time *** survivors were classified into no change in behavior,desirable change(i.e.,increase mVPA to meet PA guidelines or decrease SED by≥60 min/day),and undesirable change(i.e.,decrease mVPA tomin/week or increase SED by≥60 min/day).Analysis of covariance examined differences in FACT-Cog scores across the activity change *** contrasts compared differences in FACT-Cog scores between cancer survivors with(a)no meaningful change *** change,and(b)a desirable change *** undesirable *** There were no significant differences in FACT-Cog scores across activity-change categories in the full sample of cancer survivors(n=371;age=48.6±15.3 years(mean±SD)).However,cancer survivors who were diagnosed≥5 years ago(t(160)=–2.15,p=0.03)or who received treatment≥5 years ago(t(102)=–2.23,p=0.03)and who had a desirable change in activity reported better perceived cognitive abilities than those who had an undesirable *** PA promotion efforts should consider reducing SED in addition to mainta

关键词： Cancer-related cognitive impairment Cancer survivorship Exercise Sedentary time

A rat model of multicompartmental traumatic injury and hemorrhagic shock induces bone marrow dysfunction and profound anemia

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Animal models and Experimental medicine 2024年第3期7卷 367-376页

作者： Lauren S.Kelly Jennifer A.munley Erick E.Pons Kolenkode B.Kannan Elizabeth m.Whitley Letitia E.Bible Philip A.Efron Alicia m.mohr Department of Surgery and Sepsis and Critical Illness Research Center University of Florida College of MedicineGainesvilleFloridaUSA Pathogenesis LLCGainesvilleFloridaUSA

Background:Severe trauma is associated with systemic inflammation and organ *** rodent trauma models are the mainstay of postinjury research but have been criticized for not fully replicating severe human *** aim of this study was to create a rat model of multicompartmental injury which recreates profound traumatic ***:male Sprague-Dawley rats were subjected to unilateral lung contusion and hemorrhagic shock(LCHS),multicompartmental polytrauma(PT)(unilateral lung contusion,hemorrhagic shock,cecectomy,bifemoral pseudofracture),or na?ve ***,plasma toll-l ike receptor 4(TLR4),hemoglobin,spleen to body weight ratio,bone marrow(Bm)erythroid progenitor(CFU-GEmm,BFU-E,and CFU-E)growth,plasma granulocyte colony-stimulating factor(G-CSF)and right lung histologic injury were assessed on day 7,with significance defined as p valuesma resulted in markedly more profound inhibition of weight gain compared to LCHS(p=0.0002)along with elevated plasma TLR4(pmoglobin(pmonstrated suppression of CFU-E and BFU-E growth compared to naive(pma G-CSF was elevated in PT compared to both na?ve and LCHS(pmonstrated significant histologic right lung injury with poor alveolar wall integrity and interstitial ***:multicompartmental injury as described here establishes a reproducible model of multicompartmental injury with worsened anemia,splenic tissue enlargement,weight loss,and increased inflammatory activity compared to a less severe *** may serve as a more effective model to recreate profound traumatic injury to replicate the human inflammatory response postinjury.

关键词： anemia i nflammation polytrauma pseudofracture shock

EEG/ERP evidence of possible hyperexcitability in older adults with elevated beta-amyloid

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Translational Neurodegeneration 2022年第1期11卷 835-844页

作者： Hannes Devos Kathleen Gustafson Ke Liao Pedram Ahmadnezhad Bradley Estes Laura E.martin Jonathan D.mahnken William m.Brooks Jeffrey m.burns Department of Physical Therapy Rehabilitation Scienceand Athletic TrainingUniversity of Kansas Medical CenterKansas CityKS 66160USA Department of Neurology University of Kansas Medical CenterKansas CityKS 66160USA Hoglund Biomedical Imaging Center University of Kansas Medical CenterKansas CityKS 66160USA Department of Population Health University of Kansas Medical CenterKansas CityKS 66160USA Department of Biostatistics and Data Science University of Kansas Medical CenterKansas CityKS 66160USA University of Kansas Alzheimer’s Disease Center University of Kansas Medical CenterKansas CityKS 66160USA.

Background: Although growing evidence links beta-amyloid (Aβ) and neuronal hyperexcitability in preclinical mouse models of Alzheimer’s disease (AD), a similar association in humans is yet to be established. The first aim of the study was to determine the association between elevated Aβ (Aβ+) and cognitive processes measured by the P3 event-related potential (ERP) in cognitively normal (CN) older adults. The second aim was to compare the event- related power between CNAβ+ and CNAβ−. methods: Seventeen CNAβ+ participants (age: 73 ± 5, 11 females, montreal Cognitive Assessment [moCA] score 26 ± 2) and 17 CNAβ- participants group-matched for age, sex, and mOCA completed a working memory task (n-back with n = 0, 1, 2) test while wearing a 256-channel electro-encephalography net. P3 peak amplitude and latency of the target, nontarget and task difference effect (nontarget−target), and event-related power in the delta, theta, alpha, and beta bands, extracted from Fz, Cz, and Pz, were compared between groups using linear mixed models. P3 ampli-tude of the task difference effect at Fz and event-related power in the delta band were considered main outcomes. Correlations of mean Aβ standard uptake value ratios (SUVR) using positron emission tomography with P3 amplitude and latency of the task difference effect were analyzed using Pearson Correlation Coefficient r. Results: The P3 peak amplitude of the task difference effect at Fz was lower in the CNAβ+ group (P = 0.048). Simi-larly, power was lower in the delta band for nontargets at Fz in the CNAβ+ participants (P = 0.04). The CNAβ+ partici-pants also demonstrated higher theta and alpha power in channels at Cz and Pz, but no changes in P3 ERP. Strong correlations were found between the mean Aβ SUVR and the latency of the 1-back (r = − 0.69;P = 0.003) and 2-back (r = − 0.69;P = 0.004) of the task difference effect at channel Fz in the CNAβ+ group. Conclusions: Our data suggest that the elevated amyloid in cognitively normal ol

关键词： Event-related potentials Electro-encephalography Working memory Older adults Preclinical Beta-amyloid

Daily genetic profiling indicates JAK/STAT signaling promotes early hepatic stellate cell transdifferentiation

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World Journal of Gastroenterology 2010年第40期16卷 5047-5056页

作者： Ashley m Lakner Cathy C moore alyssa A Gulledge Laura W Schrum Department of Biology University of North Carolina at Charlotte Digestive and metabolic Disorders Laboratory Carolinas Medical Center

AIm: To identify signaling pathways and genes that initiate and commit hepatic stellate cells (HSCs) to transdifferentiation. mETHODS: Primary HSCs were isolated from male Sprague-Dawley rats and cultured on plastic for 0-10 d. Gene expression was assessed daily (quiescent to day 10 culture-activation) by real time polymerase chain reaction and data clustered using AmADA software. The significance of JAK/STAT signaling to HSC transdifferentiation was determined by treating cells with a JAK2 inhibitor. RESULTS: Genetic cluster analyses, based on expression of these 21 genes, showed similar expression profiles on days 1-3, days 5 and 6, and days 7-10, while freshly isolated cells (day Q) and day 4 cells were genotypically distinct from any of the other days. Additionally, gene expression clustering revealed strong upregulation of interleukin-6, JAK2 and STAT3 mRNA in the early stages of activation. Inhibition of the JAK/STAT signaling pathway impeded the morphological transdifferentiation of HSCs which correlated with decreased mRNA expression of several profibrotic genes including collagens, α-SmA, PDGFR and TGFβR. CONCLUSION: These data demonstrate unique clustered genetic profiles during the daily progression of HSC transdifferentiation and that JAK/STAT signaling may be critical in the early stages of transdifferentiation.

关键词： Cluster analysis Fibrosis Genetic profile Hepatic stellate cell Interleukin-6

A bio-instructive parylene-based conformal coating suppresses thrombosis and intimal hyperplasia of implantable vascular devices

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Bioactive materials 2023年第10期28卷 467-479页

作者： Dake Hao Jonathan Lin Ruiwu Liu Christopher Pivetti Kaeli Yamashiro Linda m.Schutzman Junichiro Sageshima mimmie Kwong Nataliya Bahatyrevich Diana L.Farmer misty D.Humphries Kit S.Lam alyssa Panitch Aijun Wang Department of Surgery School of MedicineUniversity of California DavisSacramentoCA95817United States Institute for Pediatric Regenerative medicine Shriners Hospitals for ChildrenSacramentoCA95817United States Department of Biochemistry and molecular medicine School of MedicineUniversity of California DavisSacramentoCA95817United States Wallace H.Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory UniversityAtlant1GA30332United States Department of Biomedical Engineering University of California DavisDavisCA95616United States

Implantable vascular devices are widely used in clinical treatments for various vascular diseases. However, current approved clinical implantable vascular devices generally have high failure rates primarily due to their surface lacking inherent functional endothelium. Here, inspired by the pathological mechanisms of vascular device failure and physiological functions of native endothelium, we developed a new generation of bioactive parylene (poly(p-xylylene))-based conformal coating to address these challenges of the vascular devices. This coating used a polyethylene glycol (PEG) linker to introduce an endothelial progenitor cell (EPC) specific binding ligand LXW7 (cGRGDdvc) onto the vascular devices for preventing platelet adhesion and selectively capturing endogenous EPCs. Also, we confirmed the long-term stability and function of this coating in human serum. Using two vascular disease-related large animal models, a porcine carotid artery interposition model and a porcine carotid artery-jugular vein arteriovenous graft model, we demonstrated that this coating enabled rapid generation of self-renewable “living” endothelium on the blood contacting surface of the expanded polytetrafluoroethylene (ePTFE) grafts after implantation. We expect this easy-to-apply conformal coating will present a promising avenue to engineer surface properties of “off-the-shelf” implantable vascular devices for long-lasting performance in the clinical settings.

关键词： Parylene coating Integrin ligand Thrombosis Intimal hyperplasia Implantable vascular devices

Ⅱ度烧伤创面治疗专家共识(2024版)Ⅱ:手术治疗和感染防治

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中华烧伤与创面修复杂志 2024年第2期40卷 101-118页

作者：中华医学会烧伤外科学分会海峡两岸医药卫生交流协会暨烧创伤组织修复专委会夏照帆不详海军军医大学第一附属医院烧伤外科全军烧伤研究所中国医学科学院烧伤暨烧创复合伤救治关键技术创新单元上海200433

Ⅱ度烧伤是临床中最为常见但处理十分棘手的烧伤类型,其治疗不仅需要考虑换药或手术处置方式本身可能产生的不同影响,还需评估烧伤部位、患者年龄及烧伤面积等多方面的因素。目前对于Ⅱ度烧伤创面治疗的手术方式以及感染诊断、分级等尚... 详细信息

Ⅱ度烧伤是临床中最为常见但处理十分棘手的烧伤类型,其治疗不仅需要考虑换药或手术处置方式本身可能产生的不同影响,还需评估烧伤部位、患者年龄及烧伤面积等多方面的因素。目前对于Ⅱ度烧伤创面治疗的手术方式以及感染诊断、分级等尚未形成统一的标准和规范,严重影响临床治疗方案的制订。本共识编写组以循证医学证据为基础,结合专家意见,制订《Ⅱ度烧伤创面治疗专家共识(2024版)Ⅱ:手术治疗和感染防治》。本共识从Ⅱ度烧伤创面的手术治疗及感染防治2个方面提出29条具体推荐意见,旨在形成规范化的Ⅱ度烧伤临床治疗方案。

关键词：烧伤外科手术清创术感染

Reproductive behavior in horseshoe crabs:Does density matter?

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Current Zoology 2010年第5期56卷 634-642页

作者： Jennifer H.mATTEI mark A.BEEKEY Adam RUDmAN alyssa WORONIK Department of Biology Sacred Heart University Department of Biology Southern Connecticut State University

While the four species of horseshoe crabs share many common reproductive traits with respect to their reproductivesystems,they do differ with respect to their mating behavior (monogamy ***).Past research has attributed thesedifferences to a number of factors including:spawning densities,operational sex ratios (OSR's),male condition (or age),environmentaland/or genetic factors,or a combination *** behaviors in the three Asian horseshoe crab species (Tachypleusgigas,***,and Carcinoscorpius rotundicauda) with low spawning densities and 1:1 operational sex ratios aretypically *** Limulus polyphemus,mating behavior is more variable ranging from monogamy to *** provide evidence,through a long term behavioral study,that variation in mating behavior is influenced by population densityin *** study population on two beaches in Connecticut (Long Island Sound) have a spawning density 400 timesless than that found in Delaware Bay (0.002 females/m^2 vs.0.8 females/m^2) but similar operational sex *** 90%-95%of all spawning females in CT were paired with only one male,thus exhibiting monogamous *** contrast,between 30and 60% of spawning females in Delaware Bay have more than one mate and produce clutches of eggs with multiple *** condition played no role in mating behavior in CT *** also observed that on average 18% of the females on thespawning beaches are *** results suggest that population density is an important condition that determines mating ***,low population density may lead to decreased mate finding ability and lost opportunities for

关键词：生殖行为卵密度一夫一妻制交配行为交配产卵人口密度物质鲎

Apparent redox potential discontinuity(aRPD) depth as a relative measure of sediment oxygen content and habitat quality

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International Journal of Sediment Research 2015年第1期30卷 74-80页

作者： Travis G.GERWING alyssa m.ALLEN GERWING Diana J.HAmILTON myriam A.BARBEAU Department of Biology University of New Brunswick Department of Biology Mount Allison University

As hypoxic conditions spread in our oceans,indices that quickly and efficiently assess oxygen content in sediment pore water,and habitat quality are increasingly becoming *** to the apparent redox potential discontinuity(aRPD) in sediment is one such index;however,the relationship between aRPD depth and oxygen content is still *** quantified oxygen content in sediment pore water with a dissolved oxygen(DO) probe,utilizing luminescent technology,to determine how DO concentration varies with depth in the sediment,and with position relative to the aRPD(above versus below) on an intertidal mudflat in the Bay of Fundy,*** on generalized linear regression models,we found that depth in the sediment was a poor predictor of pore water DO concentration,while position in the sediment relative to the aRPD was a good ***,sediment above the aRPD had higher DO content than sediment *** maintain that aRPD depth is a good measure of relative oxygen content in sediment pore water,as well as habitat ***,we recommend caution as the factors that influence aRPD depth arc numerous and variable;therefore,the relationship between aRPD depth and DO content should be experimentally confirmed in any system of interest before aRPD depth is used as an indicator.

关键词： Anoxia Apparent redox potential discontinuity(aRPD) Dissolved oxygen Habitat quality Hypoxia Intertidal marine benthos Sediment pore water.