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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

Optical haze of transparent and conductive silver nanowire films

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nano Research 2013年第7期6卷 461-468页

作者： colin preston Yunlu Xu Xiaogang Han Jeremy n. Munday Liangbing Hu Department of Materials Science and Engineering University of Maryland College Park College Park Maryland 20742 USA Department of Electrical and Computer Engineering University of Maryland College Park Maryland 20742 USA The Institute for Research in Electronics and Applied physics University of Maryland College Park Maryland 20742 USA

Contemporary nanostructured transparent electrodes for use in solar cells require high transmittance and high conductivity, dictating nanostructures with high aspect ratios. Optical haze is an equally important yet unstudied parameter in transparent electrodes for solar cells that is also determined by the geometry of the nanostructures that compose the electrode. In this work, the effect of the silver nanowire diameter on the optical haze values in the visible spectrum was investigated using films composed of wires with either small diameters （n60 nm） or large diameters （~150 nm）. Finite difference time domain （FDTD） simulations and experimental transmittance data confirm that smaller diameter nanowires form higher performing transparent conducting electrode （TCE） films according to the current figure of merit. While maintaining near constant transmittance and conductivity for each film, however, it was observed experimentally that films composed of silver nanowires with larger diameters have a higher haze factor than films with smaller diameters. This confirms the FDTD simulations of the haze factor for single nanowires with similarly large and small diameters. This is the first record of haze properties for Ag nWs that have been simulated or experimentally measured, and also the first evidence that the current figure of merit for TCEs is insufficient to evaluate their performance in solar cell devices.

关键词： solar cell transparent conducting electrode silver nanowire haze factor light trapping

Targeted therapy for capillary-venous malformations

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3024-3039页

作者： Lola Zerbib Sophia Ladraa Antoine Fraissenon Charles Bayard Marina Firpion Quitterie Venot Sanela protic Clément Hoguin Amandine Thomas Sylvie Fraitag Jean-paul Duong Sophie Kaltenbach Estelle Balducci coline Lefevre patrick Villarese Vahid Asnafi Christine Broissand nicolas Goudin Ivan nemazanyy Gwennhael Autret Bertrand Tavitian Christophe Legendre nadia Arzouk Veronique Minard-colin Caroline Chopinet Michael Dussiot Denise MAdams Tristan Mirault Laurent Guibaud paul Isenring Guillaume Canaud Universitéparis Cité ParisFrance InSERM U1151 Institut Necker-Enfants MaladesParisFrance Service d’Imagerie pédiatrique Hôpital Femme-Mère-EnfantHCLBronFrance CREATIS UMR 5220 Villeurbanne 69100France Service de Radiologie Mère-Enfant Hôpital NordSaint EtienneFrance Service d’Anatomie pathologique Hôpital Necker-Enfants MaladesAP-HPParisFrance Laboratoire d’Oncohématologie Hôpital Necker-Enfants MaladesAP-HPParisFrance pharmacie Hôpital Necker-Enfants MaladesAP-HPParisFrance necker Bio-Image Analysis INSERM US24/CNRS UMS 3633ParisFrance platform for Metabolic Analyses Structure Fédérative de Recherche NeckerINSERM US24/CNRS UMS 3633ParisFrance plateforme Imageries du Vivant Universitéde ParisPARCCINSERMParisFrance Service de néphrologie Transplantation AdultesHôpital Necker-Enfants MaladesAP-HPParisFrance Service de Transplantation Hôpital La PitiéSalpétrièreAP-HPParisFrance Department of pediatric and Adolescent Oncology INSERM 1015Gustave RoussyUniversitéParis-SaclayVillejuifFrance Service de physiologie&Explorations Fonctionnelles Cardiovasculaires CHU de LilleLille 59000France InSERM U1163 Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic ImplicationsLaboratoire d’Excellence GR-ExParisFrance Division of Oncology Comprehensive Vascular Anomalies ProgramChildren’s Hospital of PhiladelphiaPhiladelphiaPAUSA Service de Médecine Vasculaire hôpital Européen Georges-PompidouParisFrance nephrology Research Group L’Hôtel-Dieu de Québec Research CenterDepartment of MedicineFaculty of MedicineLaval UniversityQuebecQC G1R2J6Canada Unitéde médecine translationnelle et thérapies ciblées Hôpital Necker-Enfants MaladesAP-HPParisFrance CnRS UMR8253 Institut Necker-Enfants MaladesParisFrance

Sporadic venous malformations are genetic conditions primarily caused by somatic gain-of-function mutation of pIK3CA or TEK,an endothelial transmembrane receptor signaling through *** malformations are associated with pain,bleedings,thrombosis,pulmonary embolism,esthetic deformities and,in severe cases,life-threatening *** authorized medical treatment exists for patients with venous ***,we created a genetic mouse model of pIK3CA-related capillary venous malformations that replicates patient *** showed that these malformations only partially signal through AKT *** compared the efficacy of different drugs,including rapamycin,a mTORC1 inhibitor,miransertib,an AKT inhibitor and alpelisib,a pI3Kαinhibitor at improving the lesions seen in the mouse *** demonstrated the effectiveness of alpelisib in preventing vascular malformations’occurrence,improving the already established ones,and prolonging *** these findings,we were authorized to treat 25 patients with alpelisib,including 7 children displaying pIK3CA(n=16)or TEK(n=9)-related capillary venous malformations resistant to usual therapies including sirolimus,debulking surgical procedures or percutaneous *** assessed the volume of vascular malformations using magnetic resonance imaging(MRI)for each *** demonstrated improvement in all 25 *** malformations previously considered intractable were reduced and clinical symptoms were *** showed a decrease of 33.4%and 27.8%in the median volume of pIK3CA and TEK malformations respectively,over 6 months on *** conclusion,this study supports pI3Kαinhibition as a promising therapeutic strategy in patients with pIK3CA or TEK-related capillary venous malformations.

关键词： pIK3CA malformations venous

participation in cooperative prey capture and the benefits gained from it are associated with individual personality

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Current Zoology 2017年第5期63卷 561-567页

作者： James L.L. LICHTEnSTEIn colin M. WRIGHT Lauren p. LUSCUSKIE Graham A. MOnTGOMERY pInTER-WOLLMAn Jonathan n. pRUITT Department of Biological Sciences University of Pittsburgh Pittsburgh PA 15260 USA Department of Ecology and Evolutionary Biology University of California Los Angeles CA 90095 USA Department of Ecology Evolution and Marine Biology University of California Santa Barbara Santa Barbara CA 93106 USA

In animal societies, behavioral idiosyncrasies of the individuals often guide which tasks theyshould perform. Such personality-specific task participation can increase individual task efficiency,thereby improving group performance. While several recent studies have documented group-levelbenefits of within-group behavioral （i.e., personality） diversity, how these benefits are realized atthe individual level is unclear. Here we probe the individual-level benefits of personality-driven taskparticipation in the social spider Stegodyphus dumicola. In S. dumicola, the presence of at leastone highly bold individual catalyzes foraging behavior in shy colony members, and all group con-stituents heavily compete for prey. We assessed boldness by examining how quickly spidersresumed normal movement after a simulated predator attack. We test here whether （1） participantsin collective foraging gain more mass from prey items and （2） whether bold individuals are less re-sistant to starvation than shy spiders, which would motivate the bold individuals to forage ***, we assembled colonies of shy spiders with and without a bold individual, added one preyitem, and then tracked the mass gain of each individual spider after this single feeding event. Wefound that spiders that participated in prey capture （whether bold or shy） gained more mass thannonparticipators, and colonies containing a single bold spider gained more total mass than purelyshy colonies. We also found that bold spiders participated in more collective foraging events andwere more susceptible to starvation than shy spiders, suggesting that the aggressive foraging ofbold individuals may represent a strategy to offset starvation risk. These findings add to the bodyof evidence that animal personality can shape social organization, individual performance, andgroup success.

关键词： animal personality, keystone individuals, social behaviour, task allocation.

near-bed hydrodynamics associated with the entrainment of coarse particles at different protrusion heights

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Journal of Hydrodynamics 2022年第6期34卷 1067-1080页

作者： Yushu Xie Bruce W.Melville Asaad Y.Shamseldin colin n.Whittaker Yifan Yang Department of Civil and Environmental Engineering The University of AucklandAucklandNew Zealand School of Engineering The University of WaikatoHamiltonNew Zealand

This paper presents an investigation of near-bed hydrodynamics for a protruding coarse particle over a regular roughened *** laboratory experiments were undertaken at the threshold flow condition,which induced dislodgement of the protruding *** different protrusion heights,the experimental results show that the protruding particle substantially changed the spatial distributions of time-averaged velocities,turbulent kinetic energy,and Reynolds shear stress when compared with those obtained from a flat rough *** spatial distribution pattern of the flow characteristics shows a reasonable degree of similarity at different protrusion heights examined in this *** the target particle,a zone of low Reynolds shear stress was *** analysis was conducted along the main flow direction,at an elevation close to the top of the target particle.A prevalence of sweep(Quadrant 4)and outwards interaction(Quadrant 1)events were associated with the dislodgement of the protruding *** findings imply that the drag force related to strong streamwise velocities may play a more significant role in protruding particle entrainment than the shear stress.

关键词： Entrainment particle protrusion flow structure shear stress quadrant analysis

phage-mediated horizontal gene transfer and its implications for the human gut microbiome

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Gastroenterology Report 2022年第1期10卷 78-89页

作者： Tatiana Borodovich Andrey n.Shkoporov R.paul Ross colin Hill ApC Microbiome Ireland University College CorkCorkIreland School of Microbiology University College CorkCorkIreland

Horizontal gene transfer(HGT)in the microbiome has profound consequences for human health and *** spread of antibiotic resistance genes,virulence,and pathogenicity determinants predominantly occurs by way of *** exists of extensive horizontal transfer in the human gut *** transduction is a type of HGT event in which a bacteriophage transfers non-viral DnA from one bacterial host cell to *** abundance of tailed bacteriophages in the human gut suggests that transduction could act as a significant mode of HGT in the gut *** we review in detail the known mechanisms of phage-mediated HGT,namely specialized and generalized transduction,lateral transduction,gene-transfer agents,and molecular piracy,as well as methods used to detect phage-mediated HGT,and discuss its potential implications for the human gut microbiome.

关键词： gut phageome horizontal gene transfer gene transduction phage-mediated gene transfer

Smart Sediment particle: A novel approach to investigating fluvial bed entrainment using instrumented sensors

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International Journal of Sediment Research 2023年第1期38卷 66-82页

作者： Yushu Xie Bruce W.Melville Asaad Y.Shamseldin colin n.Whittaker Yifan Yang Department of Civil and Environmental Engineering The University of Auckland School of Engineering The University of Waikato

The Smart Sediment particle(SSp) instrumented with multiple sensors to obtain tri-axial linear accelerations is used for studying the mechanism of coarse grain entrainment. Three bed arrangements are tested to examine their influences on entrainment processes and the threshold force and impulse conditions. The SSp shows satisfactory precision to capture the imperceptible movement tendencies immediately(e.g., 0.15 s) after the dislodgement. The experimental results show that bed packing can significantly affect the particle’s entrainment threshold and the path of movement. Lateral movement is predominant for some cases because the entrainment path is based on the least work done by the flow,even if the direction is not aligned with the flow. The concept of effective protrusion height is proposed to quantify the effect of local bed arrangement on entrainment. The mean velocity field around the SSp is also measured together with the acceleration data. The mean threshold velocity and resultant impulse show consistent dependence on the bed arrangement. In general, the SSp shows a good prospect of being used to study small-scale entrainment mechanism.

关键词： Smart Sediment particle Instrumented sensors Entrainment behaviours Tri-axial acceleration Hydrodynamic force impulse

A review of hydrogen technologies and engineering solutions for railway vehicle design and operations

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Railway Engineering Science 2021年第3期29卷 212-232页

作者： Yan Sun M.Anwar n.M.S.Hassan Maksym Spiryagin colin Cole Centre for Railway Engineering Central Queensland UniversityRockhamptonQLDAustralia

Interest in hydrogen-powered rail vehicles has gradually increased worldwide over recent decades due to the global pressure on reduction in greenhouse gas emissions,technology availability,and multiple options of power *** the past,research and development have been primarily focusing on light rail and regional trains,but the interest in hydrogen-powered freight and heavy haul trains is also *** review shows that some technical feasibility has been demonstrated from the research and experiments on proof-of-concept *** rail vehicles powered by hydrogen either are currently operating or are the subject of experimental *** paper identifies that fuel cell technology is well developed and has obvious application in providing electrical traction power,while hydrogen combustion in traditional IC engines and gas turbines is not yet well *** need for on-board energy storage is discussed along with the benefits of energy management and control systems.

关键词： Hydrogen Fuel cells Hybrid power Rail vehicles Greenhouse gas emissions

Coupler force and fatigue assessments with stochasticdraft gear frictions

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Journal of Traffic and Transportation Engineering(English Edition) 2023年第1期10卷 1-12页

作者： Qing Wu colin Cole Maksym Spiryagin Centre for Railway Engineering Central Queensland UniversityRockhamptonQLD 4701Australia

Train dynamics and component fatigue assessments are important steps towards successful operations of long heavy haul *** train dynamics(LTD)simulation is an effective and efficient approach in this *** gear friction has been known to have a strong stochastic ***,relevant train dynamics simulations have not been reported in open *** paper uses experimental data to extract the stochastic feature of draft gear *** stochastic feature is then introduced into LTD *** force and fatigue damage assessments were conducted by simulating a heavy haul train that has 244 vehicles and weighs nearly 30,000 *** results show that average in-train force variations due to stochastic friction were 55 and 40 kn for the traction and air brake cases respectively;maximum force variations were 207 and 98 kn for the traction and air brake cases *** fatigue calculations are even more sensitive to stochastic draft gear friction;the largest variations can be up to 700 times different due to the strong nonlinearity of fatigue calculation *** friction is an unavoidable nature in friction draft *** using stochastic draft gear friction can deliver results that are more robust and reliable.

关键词： Stochastic friction Draft gear Train dynamics Coupler fatigue Laboratory testing