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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

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

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 reproductive systems, they do differ with respect to their mating behavior （monogamy vs. polygynandry）. Past research has attributed these differences to a number of factors including： spawning densities, operational sex ratios （OSR＇s）, male condition （or age）, environmental and/or genetic factors, or a combination thereof. mating behaviors in the three Asian horseshoe crab species （Tachy-pleus gigas, T. tridentatus, and Carcinoscorpius rotundicauda） with low spawning densities and 1：1 operational sex ratios are typically monogamous. In Limuluspolyphemus, mating behavior is more variable ranging fi＇om monogamy to polygynandry. Here we provide evidence, through a long term behavioral study, that variation in mating behavior is influenced by population density in L. polyphemus. Our study population on two beaches in Connecticut （Long Island Sound） have a spawning density 400 times less than that found in Delaware Bay （0.002 females/m2 vs. 0.8 females/m2） but similar operational sex ratios. Between 90%-95% of all spawning females in CT were paired with only one male, thus exhibiting monogamous behavior. In contrast, between 30 and 60% of spawning females in Delaware Bay have more than one mate and produce clutches of eggs with multiple paternities. male condition played no role in mating behavior in CT populations. We also observed that on average 18% of the females on the spawning beaches are single. These results suggest that population density is an important condition that determines mating behavior. Also, low population density may lead to decreased mate finding ability and lost opportunities for spawning

关键词： Limulus mating behavior Population density monogamy Polygynandry

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.

Relationship between apparent redox potential discontinuity (aRPD) depth and environmental variables in soft-sediment habitats

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International Journal of Sediment Research 2017年第4期32卷 472-480页

作者： Travis G.Gerwing alyssa m.Allen Gerwing Kieran Cox Francis Juanes Sarah E.Dudas Ecosystem Science and management Program University of Northern British Columbia Department of Biology University of Victoria Department of Biology Vancouver Island University

As global temperatures increase and dissolved oxygen(DO) content decreases in marine systems, indices assessing sediment DO content in benthic habitats are becoming increasingly useful. One such measure is the depth to the apparent redox potential discontinuity(aRPD), a transition of sediment color that serves as a relative measure of sediment DO content. We examined spatiotemporal variation of aRPD depth, and the nature of the relationships between aRPD depth and biotic(infauna and epibenthic predators) and abiotic variables(sediment properties), as well as the availability of resources(chlorophyll a concentration, and organic matter content) in the intertidal mudflats of the Bay of Fundy, Canada. aRPD depth varied significantly through space and time, and a combination of biotic(sessile and errant infauna, as well as epibenthic predators), and abiotic(exposure time of a plot, sediment particle size,penetrability, and water content) variables, as well as the availability of resources(sediment organic matter content, and chlorophyll a concentration) were correlated with aRPD depth. As such, knowledge of both biotic and abiotic variables are required for a holistic understanding of sediment DO *** variables likely dictate a suite of potential aRPD depth conditions, while biota and resource availability, via bioturbation and respiration, strongly influence the observed aRPD depth. As DO conditions in marine systems will continue to change due to global climate change, elucidating these relationships are a key first step in predicting the influence decreasing DO content may have upon marine benthos.

关键词： Relationship between apparent redox potential discontinuity depth and environmental variables in soft-sediment habitats DO

Spontaneous Ca2+ oscillations in subcellular compartments of vascular smooth muscle cells rely on different Ca2+ pools

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Cell Research 2004年第5期14卷 379-388页

作者： Olesya D. FEDORYAK,Yvonne SEARLS,Irina V. SmIRNOVA,Douglas m. burns,Lisa STEHNO-BITTEL Departments of Physical Therapy and Rehabilitation Sciences University of Kansas medical Center Kansas City KS 66160 USA Departments of Physical Therapy and Rehabilitation Sciences University of Kansas medical Center Kansas City KS 66160 USA Department of Anatomy and Cell Biology University of Kansas medical Center Kansas City KS 66160 USA Departments of Physical Therapy and Rehabilitation Sciences University of Kansas medical Center Kansas City KS 66160 USA VA medical Center Kansas City mO 64128 USA Departments of Physical Therapy and Rehabilitation Sciences University of Kansas medical Center Kansas City KS 66160 USA Department of Anatomy and Cell Biology University of Kansas medical Center Kansas City KS 66160 USA

Spontaneous Ca2+ oscillations in vascular smooth muscle cells have been modeled using a single Ca2+ pool. This report describes spontaneous Ca2+ oscillations dependent on two separate Ca2+ sources for the nuclear versus cytoplas- mic compartments. Changes in free intracellular Ca2+ were monitored with ratiometric Ca2+- fluorophores using confo- cal microscopy. On average, spontaneous oscillations developed in 79% of rat aortic smooth muscle cells that were synchronous between the cytoplasm and nucleus. Reduction of extracellular Ca2+ (m) decreased the frequency and amplitude of the cytoplasmic oscillations with 48% of the oscillations asynchronous between the nuclear and cytoplasmic compartments. Similar results were obtained with the Ca2+ channel blockers, nimodipine and diltiazem. Arg-vasopressin (AVP) induced a rapid release of intracellular Ca2+ stores that was greater in the nuclear compartment (4.20 ± 0.23 ratio units, n = 56) than cytoplasm (2.54 ± 0.28) in cells that had spontaneously developed prior oscillations. Conversely, cells in the same conditions lacking oscillations had a greater AVP-induced Ca2+ transient in the cytoplasm (4.99 ± 0.66, n = 17) than in the nucleus (2.67 ± 0.29). Pre-treatment with Ca2+ channel blockers depressed the AVP responses in both compartments with the cytoplasmic Ca2+ most diminished. Depletion of internal Ca2+ stores prior to AVP exposure blunted the nuclear response, mimicking the response of cells that lacked prior oscillations. Spontaneous oscillating cells had a greater sarcoplasmic reticulum network than cells that did not oscillate. We propose that sponta- neous nuclear oscillations rely on perinuclear sarcoplasmic reticulum stores, while the cytoplasmic oscillations rely on Ca2+ influx.

关键词： oscillations vascular smooth muscle cells nuclear Ca2+ vasopressin thapsigargin diltiazem nimodipine.

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

Depth to the apparent redox potential discontinuity(aRPD)as a parameter of interest in marine benthic habitat quality models

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International Journal of Sediment Research 2018年第2期33卷 149-156页

作者： Travis G.Gerwing Kieran Cox alyssa m.Allen Gerwing Charmaine N.Carr-Harris Sarah E.Dudas Francis Juanes Ecosystem Science and management Program University of Northern British Columbia Department of Biology University of Victoria Skeena Fisheries Commission 4. Department of Biology Vancouver Island University

The usefulness of the apparent redox potential discontinuity(aRPD) in assessments of marine benthic habitat quality was explored at two intertidal mudflats along the north Pacific coast of Canada. Two transects were established at each intertidal site, with three sediment biogeochemistry cores collected from each transect four times over the summer of 2016. measurements of the sediment pore water dissolved oxygen(DO) content and redox(Eh) conditions were taken at the surface of the core(measured vertically), as well as at increasing depths(1 cm between readings) into the sediment(measured horizontally through predrilled holes in the biogeochemistry corer). While oxic, anoxic, oxidized, and reduced sediment pore water was observed above and below the aRPD, in general, sediment above the aRPD had higher DO content, and higher Eh values than sediment below the aRPD. Therefore, the aRPD depth can be used as a relative indicator of sediment pore water DO and Eh conditions: sediment with a deeper aRPD depth has more available DO, and the pore water has higher Eh values(more oxidized or less reduced) than sediment with a shallower aRPD depth. As such, the aRPD depth is a useful parameter to include in models that assess the quality of marine benthic habitats.

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