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CD8+T cell metabolic flexibility elicited by CD28-ARS2 axisdriven alternative splicing of PKm supports antitumor immunity

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Cellular & molecular Immunology 2024年第3期21卷 260-274页

作者： G.Aaron Holling Colin A.Chavel Anand P.Sharda mackenzie m.Lieberman Caitlin m.James Shivana m.Lightman Jason H.Tong Guanxi Qiao Tiffany R.Emmons Thejaswini Giridharan Shengqi Hou Andrew m.Intlekofer Richard m.Higashi teresa W.m.Fan Andrew N.Lane Kevin H.Eng Brahm H.Segal Elizabeth A.Repasky Kelvin P.Lee Scott H.Olejniczak Department of Immunology Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Department of medicine Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Center for Environmental Systems Biochemistry Department of Toxicology and Cancer Biology and Markey Cancer CenterLexingtonKY 40536USA Department of Cancer Genetics and Genomics Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Present address:University of Colorado Boulder BoulderCO 80309USA Present address:Dana Farber Cancer Institute BostonMA 02215USA Present address:massachusetts Institute of Technology BostonMA 02139USA Present address:melvin and Bren Simon Comprehensive Cancer Center Indiana University School of MedicineIndianapolisIN 46202USA

metabolic flexibility has emerged as a critical determinant of CD8+T-cell antitumor activity,yet the mechanisms driving the metabolic flexibility of T cells have not been *** this study,we investigated the influence of the nuclear cap-binding complex(CBC)adaptor protein ARS2 on mature T *** doing so,we discovered a novel signaling axis that endows activated CD8+T cells with flexibility of glucose ***2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing *** these effects,the CD28-ARS2 axis suppressed the expression of the m1 isoform of pyruvate kinase in favor of PKm2,a key determinant of CD8+T-cell glucose utilization,interferon gamma production,and antitumor effector ***,PKm alternative splicing occurred independently of CD28-driven PI3K pathway activation,revealing a novel means by which costimulation reprograms glucose metabolism in CD8+T cells.

关键词： Immunometabolism mRNA splicing CD8 T cells ARS2 PKm2

Himalayas as a global hot spot of springtime stratospheric intrusions:Insight from isotopic signatures in sulfate aerosols

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Research in Cold and Arid Regions 2024年第1期16卷 5-13页

作者： Kun Wang ShiChang Kang mang Lin PengFei Chen ChaoLiu Li XiuFeng Yin Shohei Hattori teresa L.Jackson JunHua Yang YiXi Liu Naohiro Yoshida mark HThiemens State Key Laboratory of Cryospheric Science Northwest Institute of Eco-Environment and ResourcesChinese Academy of Sciences(CAS)LanzhouGansu 730000China State Key Laboratory of Isotope Geochemistry Guangzhou Institute of GeochemistryCASGuangzhouGuangdong 510640China University of Chinese Academy of Sciences Beijing 100049China International Center for Isotope Effects Research(ICIER) School of Earth Sciences and EngineeringNanjing UniversityNanjingJiangsu 210023China Frontiers Science Center for Critical Earth material Cycling State Key Laboratory for Mineral Deposits ResearchSchool of Earth Sciences and EngineeringNanjing UniversityNanjingJiangsu 210023China Department of Chemical Science and Engineering School of Materials and Chemical TechnologyTokyo Institute of Technology4259 Nagatsuta-choMidori-kuYokohamaKanagawa 226-8502Japan Department of Chemistry and Biochemistry University of California San DiegoLa JollaCA 92093-0021USA Earth-Life Science Institute Tokyo Institute of TechnologyMeguro-kuTokyo 152-8551Japan National Institute of Information and Communications Technology KoganeiTokyo 184-8795Japan

Downward transport of stratospheric air into the troposphere(identified as stratospheric intrusions)could potentially modify the radiation budget and chemical of the Earth's surface *** the highest and largest plateau on earth,the Tibetan Plateau including the Himalayas couples to global climate,and has attracted widespread attention due to rapid warming and cryospheric *** studies recognized strong stratospheric intrusions in the Himalayas but are poorly understood due to limited direct evidences and the complexity of the meteorological dynamics of the third ***^(35)S is a radioactive isotope predominately produced in the lower stratosphere and has been demonstrated as a sensitive chemical tracer to detect stratospherically sourced air mass in the planetary boundary ***,we report 6-month(April–September 2018)observation of^(35)S in atmospheric sulfate aerosols(^(35)SO_(4)^(2-))collected from a remote site in the Himalayas to reveal the stratospheric intrusion phenomenon as well as its potential impacts in this *** the sampling campaign,the^(35)SO_(4)^(2-)concentrations show an average of 1,070±980 atoms/m^(3).In springtime,the average is 1,620±730 atoms/m^(3),significantly higher than the global existing data measured so *** significant enrichments of^(35)SO_(4)^(2-)measured in this study verified the hypothesis that the Himalayas is a global hot spot of stratospheric intrusions,especially during the springtime as a consequence of its unique geology and atmospheric *** combined with the ancillary evidences,e.g.,oxygen-17 anomaly in sulfate and modeling results,we found that the stratospheric intrusions have a profound impact on the surface ozone concentrations over the study region,and potentially have the ability to constrain how the mechanisms of sulfate oxidation are affected by a change in plateau atmospheric properties and *** study provides new observational constraints on stra

关键词： Himalayas Stratospheric intrusions Cosmogenic^(35)SO_(4)^(2-) Ozone Atmospheric oxidation

Repeatability of decision-making behaviour in male threespine stickleback Gasterosteus aculeatus： Effects of dummy vs. live stimuli

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Current Zoology 2011年第1期57卷 101-108页

作者： teresa L. DZIEWECZYNSKI Lindsay m. FORRETTE Department of Psychology University of New England 11 Hills Beach Rd Biddeford ME 04005 USA

Individuals select from a number of behaviours when responding to various situations and the decisions they make may affect their fitness. The costs and benefits of these responses vary among individuals causing them to differ even in identical situations. One example of this type of situation is when territorial males encounter both a male and female simultaneously, gene- rating a trade-off that likely leads to individual differences due to differing costs of various actions among males. This situation commonly occurs in threespine stickleback, Gasterosteus aculeatus. However, for selection to act effectively, individuals must behave in a consistent manner and measuring repeatability can aid in understanding how selection may shape such trade-offs. males of this species exhibit consistent individual differences in their response to dummy males and females but it is unknown ff patterns are similar when feedback from the stimuli is present. To assess this, male threespine stickleback were tested with dummy and live male and female conspecifics, presented separately and simultaneously. While the same trends were found re- gardless of stimulus type, males were more aggressive towards the live conspecifics than to the dummies. Repeatability values were similar within a treatment regardless of whether live or dummy conspecifics were used, suggesting that individuals show the same level of consistency. This study adds to our understanding of consistent individual differences by demonstrating that feed- back may not affect responses to conflicting stimuli and that male threespine stickleback respond in a consistent manner to both dummy and live stimuli

关键词： Decision-making Stimulus efficacy Behavioural consistency Repeatability Threespine stickleback

Assessment of aerobic biodegradation of lower-chlorinated benzenes in contaminated groundwater using field-derived microcosms and compound-specific carbon isotope fractionation

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Journal of Environmental Sciences 2022年第8期34卷 204-213页

作者： Alba Trueba-Santiso Jordi Palau Jesica m.Soder-Walz teresa Vicent Ernest marco-Urrea Department of Chemical Biological and Environmental EngineeringUniversitat Autonoma de Barcelona(UAB)08193 BellaterraSpain mAimA group SGR Applied MineralogyGeochemistry and GeomicrobiologyDepartment of MineralogyPetrology and Applied GeologyFaculty of Earth SciencesUniversitat de Barcelona(UB)MartiFranques s/n08028 BarcelonaSpain

Biodegradation of lower chlorinated benzenes(tri-, di-and monochlorobenzene) was assessed at a coastal aquifer contaminated with multiple chlorinated aromatic hydrocarbons. Field-derived microcosms, established with groundwater from the source zone and amended with a mixture of lower chlorinated benzenes, evidenced biodegradation of monochlorobenzene(mCB) and 1,4-dichlorobenzene(1,4-DCB) in aerobic microcosms,whereas the addition of lactate in anaerobic microcosms did not enhance anaerobic reductive dechlorination. Aerobic microcosms established with groundwater from the plume consumed several doses of mCB and concomitantly degraded the three isomers of dichlorobenzene with no observable inhibitory effect. In the light of these results, we assessed the applicability of compound stable isotope analysis to monitor a potential aerobic remediation treatment of mCB and 1,4-DCB in this site. The carbon isotopic fractionation factors(ε) obtained from field-derived microcosms were-0.7‰ ± 0.1 ‰ and-1.0‰ ± 0.2 ‰ for mCB and1,4-DCB, respectively. For 1,4-DCB, the carbon isotope fractionation during aerobic biodegradation was reported for the first time. The weak carbon isotope fractionation values for the aerobic pathway would only allow tracing of in situ degradation in aquifer parts with high extent of biodegradation. However, based on the carbon isotope effects measured in this and previous studies, relatively high carbon isotope shifts(i.e., Δδ13C > 4.0 ‰) of mCB or 1,4-DCB in contaminated groundwater would suggest that their biodegradation is controlled by anaerobic reductive dechlorination.

关键词： Groundwater Isotope fractionation Chlorobenzenes Aerobic biodegradation Anaerobic reductive dehalogenation Natural attenuation

metabolic reprogramming in tumors:Contributions of the tumor microenvironment

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Genes & Diseases 2020年第2期7卷 185-198页

作者： Andrew N.Lane Richard m.Higashi teresa W-m.Fan Center for Environmental and Systems Biochemistry Markey Cancer CenterDepartment of Toxicology and Cancer BiologyUniversity of KentuckyUSA

The genetic alterations associated with cell transformation are in large measure expressed in the metabolic phenotype as cancer cells proliferate and change their local environment,and prepare for ***,the fundamental biochemistry of cancer cells is generally the same as in the untransformed cells,but the cancer cells produce a local environment,the TmE,that is hostile to the stromal cells,and compete for *** order to proliferate,cells need sufficient nutrients,either those that cannot be made by the cells themselves,or must be made from simpler ***,in solid tumors,the nutrient supply is often limiting given the potential for rapid proliferation,and the poor quality of the ***,cancer cells may employ a variety of strategies to obtain nutrients for survival,growth and *** much has been learned using established cell lines in standard culture conditions,it is becoming clear from in vivo metabolic studies that this can also be misleading,and which nutrients are used for energy production versus building blocks for synthesis of macromolecules can vary greatly from tumor to tumor,and even within the same *** we review the operation of metabolic networks,and how recent understanding of nutrient supply in the TmE and utilization are being revealed using stable isotope tracers in vivo as well as in vitro.

关键词： Cancer metabolism Nutrient supply Stable isotope resolved metabolomics Tumor microenvironment metabolic flux

XBAT35, a Novel Arabidopsis RING E3 Ligase Exhibiting Dual Targeting of Its Splice Isoforms, Is Involved in Ethylene-mediated Regulation of Apical Hook Curvature

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molecular Plant 2012年第6期5卷 1295-1309页

作者： Sofia D. Carvalho Rita Saraiva teresa m. maia Isabel A. Abreu Paula Duquea Instituto Gulbenkian de Ciencia Rua da Quinta Grande 6 2780-156 Oeiras Portugal Instituto de Tecnologia Quimica e Biologica Universidade Nova de Lisboa Av. da Republica 2780-157 Oeiras Portugal

The Arabidopsis XBAT35 is one of five structurally related ankyrin repeat-containing Really Interesting New Gene （RING） E3 ligases involved in ubiquitin-mediated protein degradation, which plays key roles in a wide range of cel- lular processes. Here, we show that the XBAT35 gene undergoes alternative splicing, generating two transcripts that are constitutively expressed in all plant tissues. The two splice variants derive from an exon skipping event that excludes an in-frame segment from the XBAT35 precursor mRNA, giving rise to two protein isoforms that differ solely in the presence of a nuclear localization signal （NLS）. Transient expression assays indicate that the isoform lacking the NLS localizes in the cytoplasm of plant cells, whereas the other is targeted to the nucleus, accumulating in nuclear speckles. Both isoforms are functional E3 ligases, as assessed by in vitro ubiquitination assays. Two insertion mutant alleles and RNA-interference （RNAi） silencing lines for XBAT35 display no evident phenotypes under normal growth conditions, but exhibit hyper- sensitivity to the ethylene precursor 1-aminocyclopropane-l-carboxylate （ACC） during apical hook exaggeration in the dark, which is rescued by an inhibitor of ethylene perception. Independent expression of each XBAT35 splice variant in the mutant background indicates that the two isoforms may differentially contribute to apical hook formation but are both functional in this ethylene-mediated response. Thus, XBAT35 defines a novel player in ethylene signaling involved in negatively regulating apical hook curvature, with alternative splicing controlling dual targeting of this E3 ubiquitin ligase to the nuclear and cytoplasmic compartments.

关键词： alternative splicing apical hook Arabidopsis thaliana ethylene signaling RiNG E3 ligase ubiquitination.

Past,present,and future of long-term treatment for hepatitis B virus

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World Journal of Gastroenterology 2023年第25期29卷 3964-3983页

作者： teresa Broquetas José A Carrión Liver Section Gastroenterology DepartmentHospital del MarBarcelona 08003Spain Institut Hospital del mar D’Investigacions mèdiques PSMARBarcelona 08003Spain Universitat Pompeu Fabra Facultat de Ciències de la Salut i de la VidaBarcelona 08003Spain

The estimated world prevalence of hepatitis B virus(HBV)infection is 316 *** infection was identified in 1963 and nowadays is a major cause of cirrhosis and hepatocellular carcinoma(HCC)despite universal vaccination programs,and effective antiviral ***-term administration of nucleos(t)ide analogues(NA)has been the treatment of choice for chronic hepatitis B during the last *** NA has shown a good safety profile and high efficacy in controlling viral replication,improving histology,and decreasing the HCC incidence,decompensation,and ***,the low probability of HBV surface antigen seroclearance made necessary an indefinite *** knowledge,in recent years,about the different phases of the viral cycle,and the new insights into the role of the immune system have yielded an increase in new therapeutic ***,several clinical trials evaluating combinations of new drugs with different mechanisms of action are ongoing with promising *** integrative literature review aims to assess the knowledge and major advances from the past of hepatitis B,the present of NA treatment and withdrawal,and the future perspectives with combined molecules to achieve a functional cure.

关键词： Hepatitis B Therapy Antigen Functional cure Antiviral agents Drug development

Geomorphic indices and relative tectonic uplift in the Guerrero sector of the mexican forearc

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Geoscience Frontiers 2017年第4期8卷 885-902页

作者： Krzysztof Gaidzik maría teresa Ramírez-Herrera Laboratorio Universitario de Geofísica Ambiental & Instituto de Geografía Universidad Nacional Autónoma de MéxicoCiudad Universitaria Berkeley Seismological Laboratory Department of Earth and Planetary ScienceUniversity of California Berkeley

Tectonically active areas,such as forearc regions,commonly show contrasting relief,differential tectonic uplift,variations in erosion rates,in river incision,and in channel gradient produced by ongoing tectonic ***,information on the tectonic activity of a defined area could be derived via landscape *** study uses topography and geomorphic indices to extract signals of ongoing tectonic deformation along the mexican subduction forearc within the Guerrero *** this purpose,we use field data,topographical data,knickpoints,the ratio of volume to area（Rva）.the stream-length gradient index（St）,and the normalized channel steepness index（k_（sn））.The results of the applied landscape analysis reveal considerable variations in relief,topography and geomorphic indices values along the Guerrero sector of the mexican subduction *** argue that the reported differences are indicative of tectonic deformation and of variations in relative tectonic uplift along the studied forearc.A significant drop from central and eastern parts of the study area towards the west in values of R_（VA）（from ~500 to^300）,St（from ~500 to ca.400）,maximum St（from ~1500-2500 to ~ 1000） and k_（sn）（from ~150 to ~100） denotes a decrease in relative tectonic uplift in the same *** suggest that applied geomorphic indices values and forearc topography are independent of climate and *** mechanisms responsible for the observed variations and inferred changes in relative forearc tectonic uplift call for further studies that explain the physical processes that control the forearc along strike uplift variations and that determine the rates of *** proposed methodology and results obtained through this study could prove useful to scientists who study the geomorphology of forearc regions and active subduction zones.

关键词： Relative tectonic uplift Forearc Active tectonics Geomorphic index Drainage network mexican subduction zone

morphometric and kinematic sperm subpopulations in split ejaculates of normozoospermic men

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Asian Journal of Andrology 2016年第6期18卷 831-834页

作者： Pilar Santolaria Caries Soler Pilar Recreo teresa Carretero Araceli Bono Jose m Berne Jesus L Yaniz TECNOGAm research group Environmental Sciences Institute (IUCA) Department of Animal Production and Food Sciences University of Zaragoza Huesca Spain Department of Functionat 8iotogy and Physical Anthropology University of Valencia 46100 Burjassot Valencia Spain R+D Department Proiser R+D Scientific Park University of Valencia 46980 Paterna Valencia Spain TECNOGAm research group Environmental Sciences Institute (IUCA) Departament of Human Anatomy and Histolosy Faculty of Health and Sport Sciences of Huesca PLaza Universidad 3 22002 Huesca Spain TECNOGAm research group Environmental Sciences Institute (IUCA) Hospital General San Jorge de Huesca Area de Urologia Av. Martinez de Velasco 36 22004 Huesca Spain

This study was designed to analyze the sperm kinematic and morphometric subpopulations in the different fractions of the ejaculate in normozoospermic men. Ejaculates from eight normozoospermic men were collected by masturbation in three fractions after 3-5 days of sexual abstinence. Analyses of sperm motility by computer-assisted sperm analysis （CASA-mot）, and of sperm morphometry by computer-assisted sperm morphometry analysis （CASA-morph） using fluorescence were performed. Clustering and discriminant procedures were performed to identify sperm subpopulations in the kinematic and morphometric data obtained. Clustering procedures resulted in the classification of spermatozoa into three kinematic subpopulations （slow with low ALH [35.6% of all motile spermatozoa], with circular trajectories [32.0%], and rapid with high ALH [32.4%]）, and three morphometric subpopulations （large-round [33.9% of all spermatozoa], elongated [32.0%], and small [34.10%]）. The distribution of kinematic sperm subpopulations was different among ejaculate fractions （P 〈 0.001）, with higher percentages of spermatozoa exhibiting slow movements with low ALH in the second and third portions, and with a more homogeneous distribution of kinematic sperm subpopulations in the first portion. The distribution of morphometric sperm subpopulations was also different among ejaculate fractions （P〈 0.001）, with more elongated spermatozoa in the first, and of small spermatozoa in the third, portion. It is concluded that important variations in the distribution of kinematic and morphometric sperm subpopulations exist between ejaculate fractions, with possible functional implications.

关键词： man sperm morphometry by computer-assisted sperm morphometry analysis sperm motility by computer-assisted spermanalysis sperm subpopulations split ejaculate