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Proteomic analysis reveals distinctive protein profiles involved in CD8^(+) T cell-mediated murine autoimmune cholangitis

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Cellular & molecular Immunology 2018年第8期15卷 756-767页

作者： Weici Zhang Ren Zhang Jun Zhang Ying Sun Patrick SC Leung Guo-Xiang Yang Zongwen Shuai william m Ridgway m Eric Gershwin Division of Rheumatology Allergy and Clinical ImmunologyUniversity of CaliforniaDavisCaliforniaUSA Department of Pathogenic Biology and Immunology Guangzhou University of Chinese MedicineGuangzhou 510006China Center for non-infectious liver diseases Beijing 302 HospitalBeijing 100039China Department of Rheumatology and Immunology The First Affiliated Hospital of Anhui Medical UniversityHefei 230022China Division of Immunology Allergy and RheumatologyUniversity of CincinnatiCincinnatiOH 45267

Autoimmune cholangitis arises from abnormal innate and adaptive immune responses in the liver,and T cells are critical drivers in this process.However,little is known about the regulation of their functional behavior during disease development.We previously reported that mice with T cell-restricted expression of a dominant negative form of transforming growth factor beta receptor type Ⅱ(dnTGFβ RII)spontaneously develop an autoimmune cholangitis that resembles human primary biliary cholangitis(PBC).Adoptive transfer of CD8^(+) but not CD4^(+) T cells into Rag1^(−/−)mice reproduced the disease,demonstrating a critical role for CD8^(+) T cells in PBC pathogenesis.Herein,we used SOmAscan technology to perform proteomic analysis of serum samples from dnTGFβRII and B6 control mice at different ages.In addition,we analyzed CD8 protein profiles after adoptive transfer of splenic CD8^(+) cells into Rag1^(−/−)recipients.The use of the unique SOmAscan aptamer technology revealed critical and distinct profiles of CD8 cells,which are key to biliary mediation.In total,254 proteins were significantly increased while 216 proteins were significantly decreased in recipient hepatic CD8^(+) cells compared to donor splenic CD8^(+) cells.In contrast to donor splenic CD8^(+) cells,recipient hepatic CD8^(+) cells expressed distinct profiles for proteins involved in chemokine signaling,focal adhesion,T cell receptor and natural killer cell-mediated cytotoxicity pathways.

关键词： autoimmune cholangitis CD8 dnTGFβRII mice proteomic analysis

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Environmental drivers and genomic architecture of trait differentiation in fire-adapted Banksia attenuata ecotypes

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Journal of Integrative Plant Biology 2019年第4期61卷 417-432页

作者： Tianhua He Byron B.Lamont Neal J.Enright Haylee m.D'Agui william Stock School of molecular and Life Sciences Curtin University School of Veterinary and Life Sciences Murdoch University Centre for Ecosystem management Edith Cowan University

Trait divergence between populations is considered an adaptive response to different environments,but to what extent this response is accompanied by genetic differentiation is less clear since it may be phenotypic plasticity. In this study, we analyzed phenotypic variation between two Banksia attenuata growth forms, lignotuberous(shrub) and epicormic resprouting(tree), in fire-prone environments to identify the environmental factors that have driven this phenotypic divergence. We linked genotype with phenotype and traced candidate genes using differential gene expression analysis. Fire intervals determined the phenotypic divergence between growth forms in B. attenuata. A genome-wide association study identified 69 single nucleotide polymorphisms, putatively associated with growth form, whereas no growth form-or phenotype-specific genotypes were eidentified. Genomic differentiation between the two growth forms was low(F_(st)=0.024). Differential gene expression analysis identified 37 genes/transcripts that were differentially expressed in the two growth forms. A small heat-shock protein gene, associated with lignotuber presence, was differentially expressed in the two forms.We conclude that different fire regimes induce phenotypic polymorphism in B. attenuata, whereas phenotypic trait divergence involves the differential expression of a small fraction of genes that interact strongly with the disturbance regime. Thus, phenotypic plasticity among resprouters is the general strategy for surviving varying fire regimes.

关键词： Environmental drivers genomic architecture trait differentiation

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Seed value influences cache pilfering rates by desert rodents

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Integrative Zoology 2019年第1期14卷 75-86页

作者： Stephen B.VANDER WALL Lindsay A.DImITRI william S.LONGLAND Joseph D.m.WHITE Department of Biology and Program in Ecology Evolution and Conservation BiologyUniversity of NevadaRenoUSA USDA Agricultural Research ServiceRenoNevadaUSA Department of Biological Sciences University of Cape TownCape TownRepublic of South Africa

Some rodents gather and store seeds.How many seeds they gather and how they treat those seeds is largely determined by seed traits such as mass,nutrient content,hardness of the seed coat,presence of secondary compounds,and germination schedule.Through their consumption and dispersal of seeds,rodents act as agents of natural selection on seed traits,and those traits influence how rodents forage.many seeds that are scatter-hoarded by rodents are pilfered,or stolen,by other rodents,and seed traits also likely influence pilfering rates and seed fates of pilfered seeds.To clarify coevolutionary relationships between rodents and the plants that they disperse,one needs to understand the role of seed traits in rodent foraging decisions.We compared how the seeds of 4 species of plants that are dispersed by scatter-hoarding animals and that differ in value(singleleaf piñon pine,Pinus monophylla;desert peach,Prunus andersonii;antelope bitterbrush,Purshia tridentata;Utah juniper,Juniperus osteosperma)were pilfered and recached by rodents.One hundred artificial caches of the 4 seed species(25 per species)were prepared,and removal by rodents was monitored.Rodents pilfered high-value seeds more rapidly than the other seeds.Desert peach seeds,which contain toxic secondary compounds,were more frequently recached.Relatively low value seeds like Utah juniper and antelope bitterbrush were pil-fered more slowly and were sometimes left at cache sites,and seeds of the latter species were transported shorter distances to new cache sites.The background density of seeds also appeared to influence the relative value of seeds.

关键词： desert rodents food storage granivory pilfering scatter-hoarding seed dispersal seed traits

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Propofol enhances the field excitatory postsynaptic potentials in CA1 hippocampal slices of young and aged mice

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Chinese medical Journal 2014年第1期127卷 137-141页

作者： Yin Yiqing william J middleton Carlos m. Florez Peter L. Carlen Hossam EI-Beheiry Department of Anesthesia Peking University China-Japan Friendship Hospital Beijing 100029 China Department of Anesthesia Toronto Westem Hospital University ofToronto University Health Network Toronto Canada Toronto Western Research Institute University of Toronto TorontoCanada Department of Anesthesia Trillium Health Centre MississaugaOntario Canada

Background Increasing age was shown to decrease the requirements for propfol.However,the mechanisms of ageing-induced potentiation of anesthetic actions have not been clearly explored.The aim of this study is to compare the effects of propofol on the field excitatory postsynaptic potentials （fEPSPs） in hippocampal slices of young and aging mice.methods Brain slices were prepared from C57BL6 male young （2 months） and aging （＞12 months） mice.The dendritic field excitatory postsynaptic potential was recorded from the CA1 stratum radiatum using patch clamp electrophysiological methods.A bipolar concentric stimulating electrode was placed along the Schaffer collateral for othodromic stimulation.The effects of clinically-relevant concentrations of propofol were studied in the young and ageing mouse tissues.Results Propofol application increased the orthodromically evoked fEPSP produced in slices taken from young and older animals.A striking feature in the I/O relationship was the decreased enhancement of the fEPSPs by propofol in slices from older mice.A clinically relevant concentration of propofol,10 μmol/L,showed more significant enhancement in amplitude and area under the curve （AUC） of fEPSP in young compared to tissues from older mice （amplitude：young （24.9±3.4）％,old （4.6±1.6）％; AUC young （30.6±5.4）％,old （2.1±1.7）％）.There was no statistically significant difference between the paired-pulse facilitation （PPF） ratios calculated for the responses obtained in tissues from young mice.In slices from older mice,in the presence of 10 μmol/L propofol,PPF was decreased and returned to baseline after washout （baseline 1.21±0.01,propofol：1.16±0.01）.Bicuculline （15 μmol/L） blocked the enhancement of propofol on fEPSP in tissues from young and old mice.Conclusion The fEPSP of slices from aging mice demonstrates diminished sensitivity to the enhancing actions of propofol.

关键词： propofol field excitatory postsynaptic potentials CA1 hippocampal slice aging patch clamp

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Analytical strategies for studying stem cell metabolism

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Frontiers in Biology 2015年第2期10卷 141-153页

作者： James m. Arnold william T. Choi Arun Sreekumar mirjana maletic-Savatic Department of molecular and Cell Biology Baylor College of Medicine Houston TX 77030 USA Program in Developmental Biology and medical Scientist Training Program Baylor College of Medicine Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital Houston TX 77030 USA Departments of Pediatrics-Neurology and Neuroscience and Program in Structural and Computational Biology and Molecular Biophysics Baylor College of Medicine Houston TX 77030 USA

Owing to their capacity for self-renewal and pluripotency, stem cells possess untold potential for revolutionizing the field of regenerative medicine through the development of novel therapeutic strategies for treating cancer, diabetes, cardiovascular and neurodegenerative diseases. Central to developing these strategies is improving our understanding of biological mechanisms responsible for governing stem cell fate and self-renewal. Increasing attention is being given to the significance of metabolism, through the production of energy and generation of small molecules, as a critical regulator of stem cell functioning. Rapid advances in the field of metabolomics now allow for in-depth profiling of stem cells both in vitro and in vivo, providing a systems perspective on key metabolic and molecular pathways which influence stem cell biology. Understanding the analytical platforms and techniques that are currently used to study stem cell metabolomics, as well as how new insights can be derived from this knowledge, will accelerate new research in the field and improve future efforts to expand our understanding of the interplay between metabolism and stem cell biology.

关键词： stem cell metabolism NmR mass spectrometry mRS flux analysis

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An adjusted ELISpot-based immunoassay for evaluation of SARS-CoV-2-specific T-cell responses

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Biosafety and Health 2022年第3期4卷 179-185页

作者： Hao Lin Jie Zhang Shaobo Dong Yaning Liu Peipei Liu George F.Gao william J.Liu Guizhen Wu National Health Commission Key Laboratory of Biosafety Research Units of Adaptive Evolution and Control of Emerging VirusesChinese Academy of Medical SciencesNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and Prevention(China CDC)Beijing 102206China macheng Center for Disease Control and Prevention Huanggang 438300China Center for Biosafety mega-Science Chinese Academy of SciencesWuhan 430071China

Like antibody evaluation,using an effective antigen‐specific T‐cell immunity assessment method in coronavirus disease 2019(COVID‐19)patients,survivors and vaccinees is crucial for understanding the immune persistence,prognosis assessment,and vaccine development for COVID‐19.This study evaluated an empirically adjusted enzyme‐linked immunospot assay for detecting severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2)‐specific T‐cell immunity in 175 peripheral blood samples from COVID‐19 convalescents and healthy individuals.Results of viral nucleic acid were used as the gold standard of infection confirmation.The SARS‐CoV‐2m peptide pool had higher sensitivity of 85%and specificity of 71%for the single peptide pool.For combined peptide pools,the parallel evaluation(at least one of the peptide pools is positive)of total peptide pools(S1&S2&m&N)had higher sensitivity(up to 93%),and the serial evaluation(all peptide pools are positive)of total peptide pools had higher specificity(up to 100%).The result of the serial evaluation was better than that of the parallel evaluation as a whole.The detection efficiency of m and N peptide pool serial evaluation appeared the highest,with a sensitivity of 80%and specificity of 93%.This T‐cell immunity detection assay introduced in this report can achieve high operability and applicability.Therefore,it can be an effective SARS‐CoV‐2‐specific cellular immune function evaluation method.

关键词： SARS‐CoV‐2 COVID‐19 T‐cell response ELISpot assay Sensitivity Specificity

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Experimental and modeling Study of Forest Fire Effect on Soil Thermal Conductivity

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Pedosphere 2016年第4期26卷 462-473页

作者： Kathleen m.SmITS Elizabeth KIRBY william J.mASSmAN Larry Scott BAGGETT Center for the Experimental Study of Subsurface Environmental Processes Department of Civil and Environmental EngineeringColorado School of Mines USDA Forest Service Rocky Mountain Research Station

An understanding of soil thermal conductivity after a wildfire or controlled burn is important to land management and post-fire recovery efforts. Although soil thermal conductivity has been well studied for non-fire heated soils, comprehensive data that evaluate the long-term effect of extreme heating from a fire on the soil thermal conductivity are limited. The purpose of this study was to evaluate the long-term impact of fire on the effective thermal conductivity of soils by directly comparing fire-heated and no-fire control soils through a series of laboratory studies. The thermal conductivity was measured for ten soil samples from two sites within the manitou Experimental Forest, Colorado, USA, for a range of water contents from saturation to the residual degree of saturation. The thermal conductivity measured was compared with independent estimates made using three empirical models from literature, including the Campbell et al.(1994), Cté and Konrad(2005), and massman et al.(2008) models. Results demonstrate that for the test soils studied, the thermal conductivity of the fire-heated soils was slightly lower than that of the control soils for all observed water contents.modeling results show that the Campbell et al.(1994) model gave the best agreement over the full range of water contents when proper fitting parameters were employed. Further studies are needed to evaluate the significance of including the influence of fire burn on the thermal properties of soils in modeling studies.

关键词：土壤有效森林火灾热导率实验室模拟经验模型水含量恢复工作

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Engineering cannabidiol synergistic carbon monoxide nanocomplexes to enhance cancer therapy via excessive autophagy

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Acta Pharmaceutica Sinica B 2023年第11期13卷 4591-4606页

作者： Chang Xiao Yue Sun Jialong Fan william Nguyen Simin Chen Ying Long Wei Chen Aiguo Zhu Bin Liu College of Biology Hunan UniversityChangsha 410082China General Hospital of Ningxia medical University School of Public Health and ManagementNingxia Medical UniversityYinchuan 750004China Institute of Bast Fiber Crops Chinese Academy of Agricultural SciencesChangsha 410205China Department of Physics the University of Texas at ArlingtonArlingtonTX 76019USA

Although carbon monoxide(CO)-based treatments have demonstrated the high cancer efficacy by promoting mitochondrial damage and core-region penetrating ability,the efficiency was often compromised by protective autophagy(mitophagy).Herein,cannabidiol(CBD)is integrated into biomimetic carbon monoxide nanocomplexes(HmPOC@m)to address this issue by inducing excessive autophagy.The biomimetic membrane not only prevents premature drugs leakage,but also prolongs blood circulation for tumor enrichment.After entering the acidic tumor microenvironment,carbon monoxide(CO)donors are stimulated by hydrogen oxide(H_(2)O_(2))to disintegrate into CO and mn^(2+).The comprehensive effect of CO/mn^(2+)and CBD can induce ROS-mediated cell apoptosis.In addition,HmPOC@mmediated excessive autophagy can promote cancer cell death by increasing autophagic flux via classⅢPI3K/BECN1 complex activation and blocking autolysosome degradation via LAmP1 downregulation.Furthermore,in vivo experiments showed that HmPOC@m+laser strongly inhibited tumor growth and attenuated liver and lung metastases by downregulating VEGF and mmP9 proteins.This strategy may highlight the pro-death role of excessive autophagy in TNBC treatment,providing a novel yet versatile avenue to enhance the efficacy of CO treatments.Importantly,this work also indicated the applicability of CBD for triple-negative breast cancer(TNBC)therapy through excessive autophagy.

关键词： Carbon monoxide therapy Cannabidiol Reactive oxygen species Excessive autophagy Autophagic flux Autolysosome degradation metastases Triple-negative breast cancer

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Eight decades of compositional change in a managed northern hardwood landscape

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Forest Ecosystems 2023年第3期10卷 398-410页

作者： mark J.Ducey Olivia L.Fraser mariko Yamasaki Ethan P.Belair william B.Leak University of New Hampshire Department of Natural Resources and the Environment114 James HallDurhamNH03824USA U.S.D.A.Forest Service White Mountain National Forest71 White Mountain DriveCamptonNH03223USA U.S.D.A.Forest Service Northern Research Station271 Mast RoadDurhamNH03824USA The Nature Conservancy Natural Climate SolutionsAfrica Regional Portland Office45 Exchange StSuite 303PortlandME04101USA

We analyzed over 8 decades of change in forest composition(represented by species proportion of basal area)and size class from more than 400 permanent plots located on the Bartlett Experimental Forest in the White mountains of New Hampshire.These data represent one of the longest-term landscape-scale records of forest change based on permanent plots in North America.We analyzed the plots based on elevation class,land type indicating assumed successional direction(grouped into coniferous and deciduous),and inventory period within managed and unmanaged portions of the forest.An ongoing shift from small-to large-diameter stems is clear across all species,in response to the overall aging of the forest following exploitative harvesting in the 19th century.major compositional changes include a continuing decline in shade-intolerant species(paper birch and aspen),along with the mid-tolerant yellow birch.An increase in red maple abundance through the early 1990s has leveled off or reversed.Among shade-tolerant species,increases in beech and red spruce were largely consistent with assumed land type on unmanaged plots,but heavy marking against diseased beech on managed plots restricted increase of that species.Sugar maple declined in abundance except where silvicultural intervention helped maintain it.By contrast,eastern hemlock showed a continuing expansion at all elevations below 600 m.The data continue to show little or no evidence of upward migration of species,despite evidence of recent regional change in climate.However,the BEF is poised for substantial changes when emerald ash borer and hemlock woolly adelgid,both of which are known to infest nearby areas,do arrive.

关键词： Northern hardwoods Succession Stand dynamics Silviculture

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High-resolution sea surface wind speeds of Super Typhoon Lekima (2019) retrieved by Gaofen-3 SAR

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Frontiers of Earth Science 2022年第1期16卷 90-98页

作者： He FANG william PERRIE Gaofeng FAN Zhengquan LI Juzhen CAI Yue HE Jingsong YANG Tao XIE Xuesong ZHU Zhejiang Climate Centre Hangzhou 310017China State Key Laboratory of Satellite Ocean Environment Dynamics Second Institute of OceanographyMinistry of Natural ResourcesHangzhou 310012China Shanghai Typhoon Institute and Key Laboratory of Numerical Modeling for Tropical Cyclone of China Meteorological AdministrationShanghai 200030China Fisheries&Oceans Canada Bedford Institute of OceanographyDartmouth B2Y4A2Canada School of Remote Sensing and Geomatics Engineering Nanjing University of Information Science and TechnologyNanjing 210044China

Gaofen-3(GF-3)is the first Chinese spaceborne multi-polarization synthetic aperture radar(SAR)instrument at C-band(5.43 GHz).In this paper,we use data collected from GF-3 to observe Super Typhoon Lekima(2019)in the East China Sea.Using a VH-polarized wide ScanSAR(WSC)image,ocean surface wind speeds at 100m horizontal resolution are obtained at 21:56:59 UTC on 8 August 2019,with the maximum wind speed,38.9 m·s^(-1).Validating the SAR-retrieved winds with buoymeasured wind speeds,we find that the root mean square error(RmSE)is 1.86 m·s^(-1),and correlation coefficient,0.92.This suggests that wind speeds retrieved from GF-3 SAR are reliable.Both the European Centre for mediumRange Weather Forecasts(ECmWF)fine grid operational forecast products with spatial resolution,and China Global/Regional Assimilation and Prediction Enhance System(GRAPES)have good performances on surface wind prediction under weak wind speed condition(m·s^(-1)),but underestimate the maximum wind speed when the storm is intensified as a severe tropical storm(>24m·s^(-1)).With respect to SAR-retrieved wind speeds,the RmSEs are 5.24 m·s^(–1) for ECmWF and 5.17 m·s^(–1) for GRAPES,with biases of 4.16 m·s^(–1) for ECmWF and 3.84 m·s^(-1)for GRAPES during Super Typhoon Lekima(2019).

关键词： synthetic aperture radar wind speed numerical weather predication(NWP) typhoon

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