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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 determined.In this study,we investigated the influence of the nuclear cap-binding complex(CBC)adaptor protein ARS2 on mature T cells.In doing so,we discovered a novel signaling axis that endows activated CD8+T cells with flexibility of glucose catabolism.ARS2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing events.Among 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 function.Importantly,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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Coal rib response during bench mining: A case study

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International Journal of mining Science and Technology 2018年第1期28卷 107-113页

作者： morgan m.Sears John Rusnak mark Van Dyke Gamal Rashed Khaled mohamed m.chael sloan Ground Control Branch NIOSH Pittsburgh Mining Research Division

In 2016, room-and-pillar mining provided nearly 40% of underground coal production in the United States.Over the past decade, rib falls have resulted in 12 fatalities, representing 28% of the ground fall fatalities in U.S.underground coal mines.Nine of these 12 fatalities(75%) have occurred in room-andpillar mines.The objective of this research is to study the geomechanics of bench room-and-pillar mining and the associated response of high pillar ribs at overburden depths greater than 300 m.This paper provides a definition of the bench technique, the pillar response due to loading, observational data for a case history, a calibrated numerical model of the observed rib response, and application of this calibrated model to a second site.

关键词： Deep cover Bench mining Thick seam Retreat mining Rib response Rib support

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A case study of multi-seam coal mine entry stability analysis with strength reduction method

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矿业科学技术学报：英文版 2016年第2期26卷 193-198页

作者： Tulu Ihsan Berk Esterhuizen Gabriel S. Klemetti Ted murphy m.chael m. Sumner James sloan m.chael Ground Control Branch NIOSH Office of Mine Safety and Health Research Pittsburgh PA 15216 USA Lone mountain Processing Inc. St. Charles VA 24282 USA

In this paper,the advantage of using numerical models with the strength reduction method(SRm) to evaluate entry stability in complex multiple-seam conditions is demonstrated.A coal mine under variable topography from the Central Appalachian region is used as a case study.At this mine,unexpected roof conditions were encountered during development below previously mined panels.Stress mapping and observation of ground conditions were used to quantify the success of entry support systems in three room-and-pillar panels.Numerical model analyses were initially conducted to estimate the stresses induced by the multiple-seam mining at the locations of the affected entries.The SRm was used to quantify the stability factor of the supported roof of the entries at selected locations.The SRm-calculated stability factors were compared with observations made during the site visits,and the results demonstrate that the SRm adequately identifies the unexpected roof conditions in this complex case.It is concluded that the SRm can be used to effectively evaluate the likely success of roof supports and the stability condition of entries in coal mines.

关键词：稳定性分析强度折减煤层巷道多煤层开采实例数值模型煤矿井下应力影响

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The effect of tailing lipidation on the bioactivity of antimicrobial peptides and their aggregation tendency Special Issue:Emerging Investigators

聚集体(英文)

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聚集体(英文) 2023年第4期4卷 195-209页

作者： Bruce Lin Andrew Hung William Singleton Kevion K.Darmawan Rachael moses Bicheng Yao Hongkang Wu Anders Barlow marc-Antoine Sani Alastair J.sloan mohammed Akhter Hossain John D.Wade Yuning Hong Neil m.O’Brien-Simpson Wenyi Li The Bio21 Institute of molecular Science and Biotechnology University of MelbourneMelbourneVictoriaAustralia ACTV Research group Melbourne Dental SchoolCentre for Oral Health ResearchUniversity of MelbourneMelbourneVictoriaAustralia School of Science RMIT UniversityMelbourneVictoriaAustralia melbourne Dental School Division of Basic and Clinical Oral SciencesUniversity of MelbourneMelbourneVictoriaAustralia Department of Biochemistry and Chemistry La Trobe Institute for Molecular ScienceLa Trobe UniversityMelbourneVictoriaAustralia Florey Institute of Neuroscience and mental Health University of MelbourneMelbourneVictoriaAustralia School of Chemistry University of MelbourneMelbourneVictoriaAustralia materials Characterisation and Fabrication Platform University of MelbourneMelbourneVictoriaAustralia

Antimicrobial peptides(AmPs)are potentially powerful alternatives to conven-tional antibiotics in combating multidrug resistance,given their broad spectrum of activity.They mainly interact with cell membranes through surface electrostatic potentials and the formation of secondary structures,resulting in permeability and destruction of target microorganism membranes.Our earlier work showed that two leading AmPs,mSI-78(4–20)and pardaxin(1–22),had potent antimicrobial activ-ity against a range of bacteria.It is known that the attachment of moderate-length lipid carbon chains to cationic peptides can further improve the functionality of these peptides through enhanced interactions with the membrane lipid bilayer,inducing membrane curvature,destabilization,and potential leakage.Thus,in this work,we aimed to investigate the antimicrobial activity,oligomerization propensity,and lipid-membrane binding interactions of a range of N-terminal lipidated analogs of mSI-78(4–20)and pardaxin(1–22).molecular modeling results suggest that aggregation of the N-lipidated AmPs may impart greater structural stability to the peptides in solu-tion and a greater depth of lipid bilayer insertion for the N-lipidated AmPs over the parental peptide.Our experimental and computationalfindings provide insights into how N-terminal lipidation of AmPs may alter their conformations,with subsequent effects on their functional properties in regard to their self-aggregation behavior,membrane interactions,and antimicrobial activity.

关键词： aggregation antimicrobial peptide lipidation membrane active peptide

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The overview of antimicrobial peptide-coated implants against oral bacterial infections

聚集体(英文)

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聚集体(英文) 2023年第3期4卷 3-18页

作者： Zhe Sun Li ma Xiaodong Sun Alastair J.sloan Neil m.O’Brien-Simpson Wenyi Li Department of Stomatology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandongChina Department of Endodontics Gaoxin branch of Jinan Stomatological HospitalJinanShandongChina melbourne Dental School Division of Basic and Clinical Oral SciencesThe University of MelbourneCarltonVictoriaAustralia ACTV Research Group Melbourne Dental SchoolDivision of Basic and Clinical Oral SciencesThe Bio21 Institute of Molecular Science and BiotechnologyThe University of MelbourneCarltonVictoriaAustralia

Dental implants are the most common therapeutic approach for resolving tooth loss and damage.Despite technical advances in treatment,implant failure rates can be as high as 23%with the major cause of peri-implantitis:a multi-species bacterial infection.With an annual growth rate in implant placements of 8.78%per annum,implant failure caused by bacterial infection is a significant oral and general health issue.The rise in antibiotic resistance in oral bacteria further adds pressure to implant failure;thus,there is a need for adjunctive therapy to improve implant outcomes.Due to the broad spectrum of activity and a low risk of inducing bacterial resistance,peptide antibiotics are emerging as a promising implant coating material to reduce/prevent peri-implantitis and improve dental implant success rates.In this review,we summarised the current strategies of coating antimicrobial peptides(AmPs)onto dental implant material surfaces with multi-functional properties to enhance osteoblast growth and prevent bacterial infections.This review compared the recent reported literature on dental implant coating with AmPs,which will provide an overview of the current dental implant coating strategies using AmPs and insights for future clinical applications.

关键词： antimicrobial coating antimicrobial peptides dental implants implant-associated infection peptide release peri-implant disease

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Systemic-to-pulmonary artery pressure ratio as a predictor of patient outcome following liver transplantation

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World Journal of Hepatology 2016年第32期8卷 1384-1391页

作者： Annette Rebel Dung Nguyen Brooke Bauer Paul A sloan Amy DiLorenzo Zaki-Udin Hassan Department of Anesthesiology and Surgery Medical Center N 202University of Kentucky

AIm To assess the value of the mean systemic-to-pulmonary artery pressure(mAP/m PAP) ratio for predicting outcomes following orthotopic liver transplant(OLT). mETHODS A retrospective data analysis was performed and data(mean arterial blood pressure, mean pulmonary artery pressure and Cardiac Index) were collected at several points during OLT. Outcomes evaluated were duration of postoperative endotracheal intubation [ET; minutes after intensive care unit(ICU) arrival], length of ICU stay, total hospitalization and frequency of immediate postoperative complications. A total of 91 patients were included in the data analysis. Based on the intraoperative course of the mAP/m PAP ratio, 2 hemodynamic responses were identified: Group 1(mAP/m PAP ratio increase during anhepatic period with postreperfusion recovery, n = 66); and Group 2(mAP/m PAP ratio with no change during anhepatic period or decreased without recovery, n = 25). RESULTS The main finding was that the lack of increased mAP/m PAP ratio in the anhepatic period was associated with:(1) longer intubation times; and(2) prolonged ICU stays and total hospitalization time, when compared to patients with an increase in mAP/m PAP ratio during the anhepatic period. CONCLUSION The data from this retrospective study should raise awareness to the mean systemic to pulmonary artery pressure ratio as a potential indicator for poor outcome after OLT. Further prospective studies are needed for validation.

关键词：麻醉学肝移植正确的心功能结果病态

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Landscape of global urban environmental resistome and its association with local socioeconomic and medical status

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Science China(Life Sciences) 2024年第6期67卷 1292-1301页

作者： Jun Wu Yige Hu m.chael H Perlin David Danko Jun Lu manuela Oliveira Johannes Werner maria m Zambrano maria A Sierra Olayinka O Osuolale PawełŁabaj Nicolás Rascovan Nur Hazlin Hazrin-Chong Soojin Jang Haruo Suzuki marina Nieto-Caballero Bharath Prithiviraj Patrick K H Lee Agnieszka Chmielarczyk Anna Różańska Yongxiang Zhao Lan Wang Christopher E mason Tieliu Shi Center for Bioinformatics and Computational Biology and the Institute of Biomedical SciencesSchool of Life SciencesEast China Normal UniversityShanghai 200241China Department of Biology Program on Disease EvolutionUniversity of LouisvilleLouisville 40292USA Weill Cornell medicine New York 10065USA The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine New York 10065USA Department of Pulmonary medicine Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghai 200025China i3S-Instituto de Investiga玢o e Inova玢o em Saúde Universidade do PortoPorto 4050-290Portugal Ipatimup-Instituto de Patologia e Imunologia molecular da Universidade do Porto Porto 4200-465Portugal Departamento de Biologia Faculdade de CiênciasUniversidade do PortoPorto 4050-290Portugal High Performance and Cloud Computing Group Zentrum für Datenverarbeitung(ZDV)Eberhard Karls University of TübingenW鋍hterstra遝7672074TübingenGermany Corporación Corpogen Research Center Bogotá110311Colombia Applied Environmental metagenomics and Infectious Diseases Research(AEmIDR) Department of Biological SciencesElizade UniversityIlara-Mokin 340271Nigeria maopolska Centre of Biotechnology Jagiellonian UniversityKraków 30-005Poland Aix-marseille Université Mediterranean Institute of OceanologyUniversitéde ToulonCNRSIRDUM 110Marseille 83041France Department of Biological Sciences and Biotechnology Faculty of Science and TechnologyUniversiti Kebangsaan Malaysia43600 UKM BangiSelangor Institut Pasteur Korea Seoul 13488Republic of Korea Faculty of Environment and Information Studies Keio UniversityFujisawaKanagawa 252-0882Japan University of Colorado at Boulder CivilEnvironmental and Architectural DepartmentBoulder 80303USA Brooklyn College of the City University of New York Brooklyn 11210USA School of Energy and Environment City University of Hong KongHong Kong 999077China Department of microbiology Faculty of MedicineJagiellonian UniversityKraków 30-005Poland Biological Targeting Diagnosis and The

Antimicrobial resistance(AmR)poses a critical threat to global health and development,with environmental factors—particularly in urban areas—contributing significantly to the spread of antibiotic resistance genes(ARGs).However,most research to date has been conducted at a local level,leaving significant gaps in our understanding of the global status of antibiotic resistance in urban environments.To address this issue,we thoroughly analyzed a total of 86,213 ARGs detected within 4,728 metagenome samples,which were collected by the meta SUB International Consortium involving diverse urban environments in 60 cities of 27 countries,utilizing a deep-learning based methodology.Our findings demonstrated the strong geographical specificity of urban environmental resistome,and their correlation with various local socioeconomic and medical conditions.We also identified distinctive evolutionary patterns of ARG-related biosynthetic gene clusters(BGCs)across different countries,and discovered that the urban environment represents a rich source of novel antibiotics.Our study provides a comprehensive overview of the global urban environmental resistome,and fills a significant gap in our knowledge of large-scale urban antibiotic resistome analysis.

关键词： urban environment metagenome antibiotic resistance resistance diversity biosynthetic gene clusters

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Effect of oxygen and nitrogen functionalization on the physical and electronic structure of graphene

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Nano Research 2015年第8期8卷 2620-2635页

作者： Alexander J. marsden Peter Brommer James J. mudd m. Adam Dyson Robert Cook maria Asensio Jose Avila Ana Levy Jeremy sloan David Quigley Gavin R. Bell Neil R. Wilson Department of Physics University of Warwick Coventry UK Centre for Scientific Computing University of Warwick Coventry UK Synchrotron SOLEIL L'Orme des Merisiers Saint Aubin-BP 48 91192 Gifsur Yvette Cedex France

graphene 的共有原子价 functionalization 为定制它的性质提供机会并且是一些 graphene 合成技术的不可避免的后果。然而， functionalization 导致的变化很好没被理解。由使用原子来源控制氧和氮 functionalization 的程度，我们在原... 详细信息

graphene 的共有原子价 functionalization 为定制它的性质提供机会并且是一些 graphene 合成技术的不可避免的后果。然而， functionalization 导致的变化很好没被理解。由使用原子来源控制氧和氮 functionalization 的程度，我们在原子规模在结构和性质学习了进化。虽然，原子氧 reversibly 介绍 epoxide 组，在类似的条件下面，原子氮不可逆转地创造包括的多样的功能代理， pyridinic，和 pyrrolic 氮。原子氧在迪拉克点离开费密能量(即， undoped ) ，虽然原子氮导致网做 n；然而，试验性的结果与为两是转变从的主导的电子效果一致去除到局部性的状态，和因此签名的损失 graphene 的电子结构。

关键词：电子结构环氧基团氮原子功能化石墨物理合成技术原子尺度

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