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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

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DCAF1 (VprBP): emerging physiological roles for a unique dual-service E3 ubiquitin ligase substrate receptor

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Journal of Molecular Cell Biology 2019年第9期11卷 725-735页

作者： N.Max Schabla Koushik Mondal Patrick C.Swanson Department of Medical Microbiology and Immunology Creighton University2500 California PlazaOmahaNE 68178USA present address:Institute of Cellular and Molecular Immunology Georg-August-University of GottingenMedical FacultyHumboldtallee 3437073 GottingenGermany present address:Department of Ophthalmology Hamilton Eye InstituteUniversity of Tennessee Health Sciences Center930 Madison AvenueMemphisTN 38163USA

Cullin-RING ligases(CRLs)comprise a large group of modular eukaryotic E3 ubiquitin *** this family,the CRL4 ligase(consisting of the Cullin4[CUL4]scaffold protein,the Rbxl RING finger domain protein,the DNA damage-binding protein 1[DDB1],and one of many DDBl-associated substrate receptor proteins)has been intensively studied in recent years due to its involvement in regulating various cellular processes,its role in cancer development and progression,and its subversion by viral accessory *** discovered as a target for hijacking by the human immunodeficiency virus accessory protein r,the normal targets and function of the CRL4 substrate receptor protein DDBl-Cul4-associated factor 1(DCAF1;also known as VprBP)had remained elusive,but newer studies have begun to shed light on these ***,we review recent progress in understanding the diverse physiological roles of this DCAF1 in supporting various general and cell type-specific cellular processes in its context with the CRL4 E3 ligase,as well as another HECT-type E3 ligase with which DCAF1 also associates,called EDD/*** also discuss emerging questions and areas of future study to uncover the dynamic roles of DCAF1 in normal physiology.

关键词： V(D)J recombination Merlin Dicer p53 EDD/DYRK2 TET Hippo

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Measuring nanoparticles in liquid with attogram resolution using a microfabricated glass suspended microchannel resonator

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Microsystems & Nanoengineering 2022年第4期8卷 261-270页

作者： Mehdi Mollaie Daryani Tomás Manzaneque Jia Wei Murali Krishna Ghatkesar Department of Precision and Microsystems Engineering Delft University of TechnologyDelftThe Netherlands Department of Microelectronics Delft University of TechnologyDelftThe Netherlands present address:Department of Microelectronics Delft University of TechnologyDelftThe Netherlands

The use of nanoparticles has been growing in various industrial fields,and concerns about their effects on health and the environment have been ***,characterization techniques for nanoparticles are ***,we present a silicon dioxide microfabricated suspended microchannel resonator(SMR)to measure the mass and concentration of nanoparticles in a liquid as they *** measured the mass detection limits of the device using laser Doppler *** limit reached a minimum of 377 ag that correspond to a 34 nm diameter gold nanoparticle or a 243 nm diameter polystyrene particle,when sampled every 30 *** compared the fundamental limits of the measured data with an ideal noiseless measurement of the ***,we measured the buoyant mass of gold nanoparticles in real-time as they flowed through the SMR.

关键词： resonator suspended nanoparticles

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Local characterization of the COVID-19 response:the case of a lockdown in Lusaka,Zambia

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Global Health Research and Policy 2021年第1期6卷 122-129页

作者： Choolwe Muzyamba University College Utrecht Campusplein 13584 ED UtrechtThe Netherlands present address:Lusaka Zambia

Background:The onset of the COVID-19 pandemic has sparked heated debate among scholars on the relevance of *** are those in favor of the lockdown and others who are critical of ***,despite the increased interest in understanding the relevance of lockdowns,there still has not been much focus on its relevance in countries like ***,with the help of the Social Representation Theory(SRT),we set out to explore and document the local characterization of the lockdown by residents of Lusaka,***:We recruited our participants through convenient and purposive sampling *** was done through the use of the ZAMTEL public phone *** contact was made to potential participants,and they were asked of their availability and willingness to participate in the *** agreeing to participate,they were included in the sample.A total of 68 people were selected to take part in this *** age ranged from 20 to 76 years old.33 of them were male and 35 *** this,we conducted interviews with the 68 *** to COVID-19 restrictions,our interviews were conducted via telephone in conformity with the recommendations from the IRB in Lusaka and the advice of the ministry of *** anonymized the demographic characteristics and responses from our ***,thematic analysis was used to analyze the ***:The lockdown was on one hand lauded for slowing down the incidence rates,preventing fatalities,and protecting the healthcare system from *** the other hand,it was criticized for exacerbating poverty levels,unemployment rates,increasing the rate of mental health problems,aiding gender-based violence,and intensifying political repression and *** results speak to the complexity in the characterization of the lockdown as a response to COVID-19 in Lusaka,*** observation demonstrates the folly of viewing,applying and characterizing the COVID-19 lockdown as a‘one-size-fits-al

关键词： COVID-19 Lockdown Zambia

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Reversible Histone H2B Monoubiquitination Fine-Tunes Abscisic Acid Signaling and Drought Response in Rice

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Molecular Plant 2019年第2期12卷 263-277页

作者： Siqi Ma Ning Tang Xu Li Yongjun Xie Denghao Xiang Jie Fu Jianqiang Shen Jun Yang Haifu Tu Xianghua Li Honghong Hu Lizhong Xiong National Key Laboratory of Crop Genetic Improvement and National Center of Plant Gene Research (Wuhan) Huazhong Agricultural University Wuhan 430070 China BPMP CNRS INRA Montpellier SupAgro Universite de Montpellier 34060 Montpellier France present address: Tobacco Research Institute of Chinese Academy of Agricultural Sciences Qingdao 266101 China present address: Department of Biology University of Pennsylvania Philadelphia PA 19104 USA

Histone H2B monoubiquitination (H2Bub1) plays important roles in several physiological and developmental processes, but its roles in the regulation of plant stress responses remain elusive. Here, we report that H2Bub1 is crucially involved in abscisic acid (ABA) signaling and drought response in rice. We found that rice HISTONE MONOUBIQUITINATION2 (OsHUB2), an E3 ligase for H2Bub1, in teracted with OsbZIP46, a key transcription factor regulating ABA signaling and drought response in rice. Genetic analyses suggest that OsHUB2, upregulated by drought and ABA, positively modulates ABA sensitivity and drought resistance. The H2Bub1 levels were in creased in the target genes of OsbZIP46 under the drought stress and ABA treat- merits, which were positively correlated with their increased expression levels. Interestingly, MODD, a reported suppressor of ABA signaling and drought resistance by mediating OsbZIP46 deactivation and degradation, could reduce the H2Bub1 levels in the target genes of OsbZIP46 by recruiting a putative deubiquitinase OsOTLD1 . Suppression of OsOTLD1in vivo resulted in increased H2Bub1 levels and expression of OsbZIP46 target genes. Collectively, these fin dings established an elaborate mecha nism of histone monoubiquitination in the fine-turning of ABA signaling and drought response by balancing H2Bub1 deposition and removal.

关键词： ABA signaling transcriptional regulation chromatin remodeling histone monoubiquitination rice

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Prefoldins Negatively Regulate Cold Acclimation in Arabidopsis thaliana by Promoting Nuclear Proteasome-Mediated HY5 Degradation

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Molecular Plant 2017年第6期10卷 791-804页

作者： Carlos Perea-Resa Miguel A. Rodriguez-Milla Elisa Iniesto Vicente Rubio Julio Salinas Departamento de Biologia Medioambiental Centro de Investigaciones Biologicas CSIC 28040 Madrid Spain Departamento de Genetica Molecular de Plantas Centro Nacional de Biotecnologia CSIC 28049 Madrid Spain present address: Department of Molecular Biology Massachusetts General Hospital Boston MA 02214 USA present address: Unidad de Biotecnologia Celular Instituto de Salud Garlos Ⅲ 28222 Madrid Spain

The process of cold acclimation is an important adaptive response whereby many plants from temperate regions increase their freezing tolerance after being exposed to low non-freezing temperatures. The correct development of this response relies on proper accumulation of a number of transcription factors that regulate expression patterns of cold-responsive genes. Multiple studies have revealed a variety of molecular mechanisms involved in promoting the accumulation of these transcription factors. Interestingly, however, the mechanisms implicated in controlling such accumulation to ensure their adequate levels remain largely unknown. In this work, we demonstrate that prefoldins （PFDs） control the levels of HY5, an Arabidopsis transcription factor with a key role in cold acclimation by activating anthocyanin biosynthesis, in response to low temperature. Our results show that, under cold conditions, PFDs accumulate into the nucleus through a DELLA-dependent mechanism, where they interact with HY5, triggering its ubiquitination and subsequent degradation. The degradation of HY5 would result, in turn, in anthocyanin biosynthesis attenuation, ensuring the accurate development of cold acclimation. These findings uncover an unanticipated nuclear function for PFDs in plant responses to abiotic stresses.

关键词： prefoldins cold acclimation Arabidopsis HY5 anthocyanin DELLAs

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Benchmarking the performance of Bayesian optimization across multiple experimental materials science domains

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npj Computational Materials 2021年第1期7卷 1742-1751页

作者： Qiaohao Liang Aldair E.Gongora Zekun Ren Armi Tiihonen Zhe Liu Shijing Sun James R.Deneault Daniil Bash Flore Mekki-Berrada Saif A.Khan Kedar Hippalgaonkar Benji Maruyama Keith A.Brown John Fisher III Tonio Buonassisi Massachusetts Institute of Technology CambridgeMAUnited States Boston University BostonMAUnited States Singapore-MIT Alliance for Research and Technology SingaporeSingapore Air Force Research Laboratory DaytonOhioUnited States Agency for Science Technology and Research(A*STAR)SingaporeSingapore National University of Singapore SingaporeSingapore present address:Aalto University EspooFinland present address:Northwestern Polytechincal University(NPU) Xi’anShaanxi P.R.China

Bayesian optimization(BO)has been leveraged for guiding autonomous and high-throughput experiments in materials ***,few have evaluated the efficiency of BO across a broad range of experimental materials *** this work,we quantify the performance of BO with a collection of surrogate model and acquisition function pairs across five diverse experimental materials *** defining acceleration and enhancement metrics for materials optimization objectives,we find that surrogate models such as Gaussian Process(GP)with anisotropic kernels and Random Forest(RF)have comparable performance in BO,and both outperform the commonly used GP with isotropic *** with anisotropic kernels has demonstrated the most robustness,yet RF is a close alternative and warrants more consideration because it is free from distribution assumptions,has smaller time complexity,and requires less effort in initial hyperparameter *** also raise awareness about the benefits of using GP with anisotropic kernels in future materials optimization campaigns.

关键词： optimization performance acceleration

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Relationship between species richness,taxonomic distinctness,functional diversity,and local contribution toβdiversity and effects of habitat disturbance in the riparian spider community of the Ganga River,India

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Ecological Processes 2023年第1期12卷 204-216页

作者： Kritish De Amar Paul Singh Arkojyoti Sarkar Kritika Singh Manju Siliwal Virendra Prasad Uniyal Syed Ainul Hussain Wildlife Institute of India ChandrabaniDehradun 248001India present address:Department of Life Sciences Sri Sathya Sai University for Human ExcellenceNavanihalOkali PostKamalapurKalaburagiKarnataka 585313India

Background In the riverine riparian ecosystem,particularly in India,the knowledge of the effects of habitat disturbance on taxonomic distinctness,functional diversity,and local contribution toβdiversity(LCBD)of spider community is *** present study examined the relationships between the index of taxonomic distinctness(Δ^(+)),index of variation in taxonomic distinctness(λ^(+)),functional evenness(FEve),functional divergence(FDiv),functional dispersion(FDis),and LCBD of spider community of the Ganga River and the effects of habitat disturbance on these indices.A total of 27 sampling sites were selected along the bank of the Ganga *** on the rating of the disturbance scores,the sites were classified into lowly,moderately,and highly disturbed *** understand the relationships between species richness,Δ^(+),λ^(+),FDis,FDiv,FEve,LCBD,and habitat disturbance score,Pearson’s correlation was calculated,followed by the linear regression *** one-way multivariate analysis of variance was used to find differences in taxonomic distinctness and functional diversity in the different disturbed *** Significant relationships were found betweenλ^(+)andΔ^(+),FDis andΔ^(+),FDis andλ^(+),FDiv and species richness,FEve and species richness,FEve andλ^(+),FEve and habitat disturbance,LCBD and FEve,and LCBD and habitat disturbance.A significant difference was present in the indices of functional diversity between the lowly,moderately,and highly disturbed ***,garbage dump,human settlement,and created embankment influenced the spider community’sλ^(+),FEve,and *** Unrestrained anthropogenic activities exacerbate habitat disturbance by affecting ecological ***,understanding linkages between ecosystem disturbance,taxonomic,functional,andβdiversity can be fundamental to managing and conserving natural *** work highlights the importance of including taxonomic and functional diversity to comprehend the impact of habit

关键词： Habitat disturbance Taxonomic distinctness Functional evenness Functional divergence Functional dispersion Local contribution to beta diversity Spider community Riparian area Ganga River

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Non-invasive photoacoustic computed tomography of rat heart anatomy and function

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Light(Science & Applications) 2023年第1期12卷 109-117页

作者： Li Lin Xin Tong Susana Cavallero Yide Zhang Shuai Na Rui Cao Tzung K.Hsiai Lihong V.Wang Caltech Optical Imaging Laboratory Andrew and Peggy Cherng Department of Medical EngineeringDepartment of Electrical EngineeringCalifornia Institute of TechnologyPasadenaCAUSA Department of Bioengineering UCLALos AngelesCAUSA Division of Cardiology Department of MedicineUCLALos AngelesCAUSA present address:College of Biomedical Engineering and Instrument Science Zhejiang UniversityHangzhouChina present address:The First Affiliated Hospital Zhejiang University School of MedicineHangzhouChina

Complementary to mainstream cardiac imaging modalities for preclinical research,photoacoustic computed tomography(PACT)can provide functional optical contrast with high imaging speed and ***,PACT has not been demonstrated to reveal the dynamics of whole cardiac anatomy or vascular system without surgical procedure(thoracotomy)for tissue ***,we achieved non-invasive imaging of rat hearts using the recently developed three-dimensional PACT(3D-PACT)platform,demonstrating the regulated illumination and detection schemes to reduce the effects of optical attenuation and acoustic distortion through the chest wall;thereby,enabling unimpeded visualization of the cardiac anatomy and intracardiac hemodynamics following rapidly scanning the heart within 10 *** further applied 3D-PACT to reveal distinct cardiac structural and functional changes among the healthy,hypertensive,and obese rats,with optical contrast to uncover differences in cardiac chamber size,wall thickness,and ***,3D-PACT provides high imaging speed and nonionizing penetration to capture the whole heart for diagnosing the animal models,holding promises for clinical translation to cardiac imaging of human neonates.

关键词： anatomy hypertensive illumination

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Ecological succession following forest decline in a xeric oak forest of south-central United States

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Journal of Plant Ecology 2016年第4期9卷 402-409页

作者： Devin P.Bendixsen Stephen W.Hallgren Jesse A.Burton Department of Natural Resource Ecology and Management Oklahoma State University008 Ag HallStillwaterOK 74074USA present address:Department of Biomolecular Sciences Boise State University1357 S.Brady St.BoiseID 83725USA present address:National Park Service 2680 Natchez Trace PkwyTupeloMS 38804USA

Aims The loss of canopy trees associated with forest decline can greatly influence the species composition and structure of a forest and have major impacts on the *** studied the changes in forest composition and structure 1 and 5 years following nearly total canopy mortality on several hundreds of hectares of xeric oak forests in south-central United *** the forests were within an ecotonal vegetation type composed of a mosaic of forest,savanna and grassland,we sought to learn whether forest decline areas would recover to forest or change to more open savanna and grassland conditions in the landscape pattern of *** low intensity fire shaped the vegetation type,we sought to learn whether fire would keep the decline areas *** The study was conducted in a xeric oak forest in east-central Oklahoma,*** located vegetation and regeneration surveys were conducted in decline and non-decline stands 1 and 5 years following nearly total canopy *** at breast height(DBH),regeneration and sprout origin were recorded for all woody *** FindingsThe major canopy species post oak(Quercus stellata Wangenh.),blackjack oak(Quercus marilandica Muenchh.)and black hickory(Carya texana Buckl.)suffered 85-92%mortality;however,minor canopy components experienced limited *** affected all size classes of canopy trees except those below 5 cm breast height *** was abundant regeneration of all species and fire seemed to maintain a high level of *** appeared to decrease the relative importance of stump sprouting and increase other types including root *** areas had abundant true seedlings,with stem origin from a root with the same diameter as the stem,which is very unusual for xeric oak *** height in decline areas was twice that of non-decline *** findings suggest that forest decline may lead to:(i)reduced oak dominance and species change in t

关键词： oak decline prescribed fire seedling stump sprouts drought

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