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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

Free amino acid content in trunk,branches and branchlets of Araucaria angustifolia(Araucariaceae)

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Journal of Forestry Research 2018年第6期29卷 1489-1496页

作者： Crizane Hackbarth Patricia Soffiatti Fla′vio Zanette Eny Iochevet segal Floh Amanda Ferreira Macedo Henrique Aparecido Laureano Departamento de Fitotecnia e Fitossanitarismo Federal University of Parana(UFPR)Rua dos Funcionarios1540JuveveCuritibaPR 81531-990Brazil Departamento de Botanica Federal University of Parana(UFPR)Av.Cel.Francisco H.dos Santos100Jardim das AmericasCuritibaPR 81531-980Brazil Instituto de Biociencias University of Sao PauloRua do Matao277Sao PauloSP 05508-090Brazil Departamento de Estatstica Federal University of Parana(UFPR)Av.Cel.Francisco H.dos Santos100Jardim das AmericasCuritibaPR 81531-980Brazil

Araucaria angustifolia(Bertol.) O. Kuntze exhibits dimorphism in its stem structure, where the trunk is orthotropic and branches and branchlets(primary and secondary branches) are plagiotropic. These stems exhibit different behavior when used for vegetative propagation,and only segments of trunk can form a complete plant. The physiological and biochemical mechanisms that characterize these stems are still little known. The aim of this study was to describe the free amino acid profiles in trunks,branches, and branchlets of A. angustifolia. Segments of 5 cm in length were excised from young individuals below the stem apex. The needles were removed and samples were frozen and lyophilized. The determinations were made by high-performance liquid chromatography, and the results were expressed as lg/g fresh weight(FW). The trunks and branches had the highest content of total amino acids, which were 112.23 ± 20.57 lg/g FW and 111.97 ± 27.78 lg/g FW, respectively. The amino acids—glutamine, aspartate and c-aminobutyric acid and tyrosine—were noticeably higher in the three types of *** the trunk, a higher amount of asparagine and tryptophan,was also detected. Glutamic acid and glutamine were found in higher quantities in the branches. The branchlets had very low total amino acid content (30.79 ± 4.19 lg/g FW), wherein asparagine is the only amino acid not detected. Thus, it was observed that the profile of the free amino acid differs among trunks, branches, and branchlets in A. angustifolia, indicating that they perform different functions.

关键词： Brazilian pine Physiological mechanisms Stem’s dimorphism Free amino acids

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子宫骶骨韧带阴道穹隆悬吊术:5年结局

世界核心医学期刊文摘（妇产科学分册） 2006年第11期2卷 57-58页

作者： Silva W.A. Pauls R.n. segal J.L. 柳蕴 St. Francis Hospital 34503 9th Avenue South Federal Way WA 98003 United States Dr.

OBJECTIVE: To evaluate the five-year anatomic and functional outcomes of the high uterosacral vaginal vault suspension. METHODS: One hundred ten patients with advanced symptomatic uterovaginal or posthysterectomy prolapse treated between January 1997 and January 2000 were identified and 72 (65% ) consented to participate in this study. Anatomic outcomes were obtained by Pelvic Organ Prolapse Quantification. Functional results were obtained subjectively and with quality of life questionnaires, including the short-form Incontinence Impact Questionnaire (IIQ) and Urogenital Distress Inventory (UDI), and Female Sexual Function Index. RESULTS: The mean follow-up period was 5.1 years (range 3.5- 7.5 years). Vaginal hysterectomy (37.5% ), anterior colporrhaphy (58.3% ), posterior colporrhaphy (87.5% ), and suburethral slings (31.9% ) were performed as indicated. Surgical failure (symptomatic recurrent prolapse of stage 2 or greater in one or more segments) was 11 of 72 (15.3% ). Two patients (2.8% ) had recurrence of apical prolapse of stage 2 or greater. For those sexually active preoperatively and postoperatively (n=34), mean postoperative Female Sexual Function Index scores for arousal, lubrication, orgasm, satisfaction, and pain were normal, whereas the desire score was abnormal (mean= 3.2). However, 94% (n=29) were currently satisfied with their sexual activity. Postoperative IIQ/UDI scores were significantly improved in all three domains (irritative, P= .01; obstructive, P nd overall (IIQ- 7, P nction occurred 33.3% preoperatively compared with 27.8% postoperatively (P=.24). COnCLUSIOn: Uterosacral ligament vaginal vault fixation seems to be a durable procedure for vaginal repair of enterocele and vaginal vault prolapse. Lower urinary tract, bowel, and sexual function may be maintained or improved.

关键词：子宫骶骨韧带阴道穹隆悬吊术子宫阴道脱垂盆腔器官脱垂子宫切除阴道后壁修补术治疗指征穹隆

Investigation of androgen receptor-dependent alternative splicing has identified a unique subtype of lethal prostate cancer

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Asian Journal of Andrology 2023年第3期25卷 296-308页

作者： Sean Seltzer Paresa n Giannopoulos Tarek A Bismar Mark Trifiro Miltiadis Paliouras Lady Davis Institute for Medical Research Segal Cancer Centre-Jewish General HospitalMontrealQC H3T 1E2Canada Cumming School of Medicine Department of Pathology and Laboratory MedicineUniversity of CalgaryCalgaryAB T2N 1N4Canada Department of Medicine Division of Experimental MedicineMcGill UniversityMontrealQC H4A 3J1Canada Department of Oncology McGill UniversityMontrealQC H4A 3T2Canada

A complete proteomics study characterizing active androgen receptor(AR)complexes in prostate cancer(PCa)cells identified a diversity of protein interactors with tumorigenic annotations,including known RnA splicing ***,we chose to further investigate the functional role of AR-mediated alternative RnA splicing in PCa disease *** selected two AR-interacting RnA splicing factors,Src associated in mitosis of 68 kDa(SAM68)and DEAD(Asp-Glu-Ala-Asp)box helicase 5(DDX5)to examine their associative roles in AR-dependent alternative RnA *** assess the true physiological role of AR in alternative RnA splicing,we assessed splicing profiles of LnCaP PCa cells using exon microarrays and correlated the results to PCa clinical *** a result,we were able to highlight alternative splicing events of clinical *** use of exon-mini gene cassettes illustrated hormone-dependent AR-mediated exon-inclusion splicing events with SAM68 or exon-exclusion splicing events with DDX5 *** physiological significance in PCa was investigated through the application of clinical exon array analysis,where we identified exon-gene sets that were able to delineate aggressive disease progression profiles and predict patient disease-free outcomes independently of pathological clinical *** a clinical dataset with patients categorized as prostate cancer-specific death(PCSD),these exon gene sets further identified a select group of patients with extremely poor disease-free ***,these results strongly suggest a nonclassical role of AR in mediating robust alternative RnA splicing in ***,AR-mediated alternative spicing contributes to aggressive PCa progression,where we identified a new subtype of lethal PCa defined by AR-dependent alternative splicing.

关键词： alternative RnA splicing androgen receptor exon-gene sets lethal prostate cancer subtype prostate cancer

应用碘伏、氧氟沙星及洗必泰减少门诊患者环境中的结膜菌群

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世界核心医学期刊文摘（眼科学分册） 2005年第10期1卷 18-19页

作者： Barkana Y. Almer Z. segal O. 韩静 Department of Ophthalmology Assaf Harofe Medical Centre Beer Yaacov Zerifin 70300 Israel Dr.

Purpose: To compare the reduction of conjunctival bacterial flora by povidone -iodine 4%,ofloxacin 0.3%, and chlorhexidine 0.05%for endophthalmitis prophy laxis before corneal suture removal in an outpatient setting. Methods: In each g roup of 25 consecutive subjects who presented for outpatient ophthalmic evaluati on, one eye was treated with either povidone-iodine4%(PI), ofloxacin 0.3%(Ofl ox) or chlorhexidine 0.05%(Chex). The other eye served as a control. Three minu tes after treatment, cultures were taken from the inferior conjunctival sac in b oth eyes. Following incubation at 35°for 48 hours, the numbers of colonies were counted and compared. The difference in the numbers of colonies in each pair of treated and control eyeswas assessed for each drug and compared. Results: The r eduction in colony-formingunits was highly significant for each of the three dr ugs tested (Wilcoxon signed-ranks test; p no significant d ifference between percent reduction by the three drugs (Kruskal-Wallis test; p= 0.68). Sterile cultures following preparation by PI, Oflox and Chex were obtaine d in 52%, 68%and 52%, respectively. Conclusions: The regimens tested were sim ilarly effective in reducing conjunctival commensals. They may all be considered as options for a quick prophylaxis against infection following suture removal i n an outpatient setting.

关键词：洗必泰氧氟沙星眼科检查眼内炎秩和检验 allis 无菌培养

SARS-CoV-2 interaction with Siglec-1 mediates trans-infection by dendritic cells

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Cellular & Molecular Immunology 2021年第12期18卷 2676-2678页

作者： Daniel Perez-Zsolt Jordana Muñoz-Basagoiti Jordi Rodon Marc Elosua-Bayes Dàlia Raïch-Regué Cristina Risco Martin Sachse Maria Pino Sanjeev Gumber Mirko Paiardini Jakub Chojnacki Itziar Erkizia Xabier Muñiz-Trabudua Ester Ballana Eva Riveira-Muñoz Marc noguera-Julian Roger Paredes Benjamin Trinité Ferran Tarrés-Freixas Ignacio Blanco Victor Guallar Jorge Carrillo JuliàBlanco Amalio Telenti Holger Heyn Joaquim segalés Bonaventura Clotet Javier Martinez-Picado Júlia Vergara-Alert nuria Izquierdo-Useros IrsiCaixa AIDS Research Institute 089BadalonaSpain IRTA Centre de Recerca en Sanitat Animal(CReSAIRTA-UAB)Campus de la UAB08193Bellaterra(Cerdanyola del Vallès)Spain CnAG-CRG Centre for Genomic Regulation(CRGBarcelona Institute of Science and Technology(BIST)08028BarcelonaSpain Centro nacional de Biotecnología CSIC28049MadridSpain Division of Microbiology and Immunology Yerkes National Primate Research CenterEmory UniversityAtlantaGAUSA Department of Pathology and Laboratory Medicine School of MedicineEmory UniversityAtlantaGeorgiaUSA Division of Pathology Yerkes National Primate Research CenterEmory UniversityAtlantaGeorgiaUSA Germans Trias i Pujol Research Institute(IGTP) Can Ruti Campus089BadalonaSpain Barcelona Supercomputing Center(BSC) 08034BarcelonaSpain Catalan Institution for Research and Advanced Studies(ICREA) 08010BarcelonaSpain University of Vic-Central University of Catalonia(UVic-UCC) Vic08500Spain Department of Integrative Structural and Computational Biology Scripps ResearchLa JollaCA92037USA Universitat Pompeu Fabra(UPF) BarcelonaSpain UAB CReSA(IRTA-UAB)Campus de la UAB08193Bellaterra(Cerdanyola del Vallès)Spain Departament de Sanitat i Anatomia Animals Facultat de VeterinàriaUAB08193Bellaterra(Cerdanyola del Vallès)Spain

Antigen-presenting cells(APCs)may be resistant to SARS-CoV-2 infection but still contribute to viral *** such as sialic acid-binding Ig-like lectin 1(Siglec-1/CD169)mediate the attachment of viruses to ***,we show that APCs effectively capture SARS-CoV-2 within compartments via recognition of *** receptor interacts with sialylated gangliosides on membranes of SARS-CoV-2 variants.

关键词： infection Antigen media

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克罗恩病的不完全性急性炎症:一项临床调查

世界核心医学期刊文摘（胃肠病学分册） 2006年第8期2卷 2-3页

作者： Marks D. J. Harbord M. W. MacAllister R. A.W. segal 陈云茹(译) 史敏(校) 不详 Department of Medicine University College London London WC1E 6JJ United Kingdom

Background: The cause of Crohn’s disease has not been mechanistically proven. We tested the hypothesis that the disease is a form of immunodeficiency caused by impaired innate immunity. Methods: We investigated inflammatory responses in patients and controls by quantifying neutrophil recruitment and cytokine production after acute trauma, interleukin 8 secretion by cultured monocyte-derived macrophages after exposure to inflammatory mediators, and local inflammatory and vascular changes in response to subcutaneous injection of heat-killed Escherichia coli. Findings: In patients with Crohn’s disease, trauma to rectum, ileum, or skin led to abnormally low neutrophil accumulation (differences from healthy individuals of 79% , n = 8, p =0.0003; 57%, n = 3, p=0.05; 50%, n = 13, pnd lower production of proinflammatory interleukin 8 (63%, n=7, p= 0.003; 63%, n = 3, p = 0.05; 45%, n = 8, pnd interleukin 1β (50%, n = 8, p =0.0005). Interleukin 8 secretion by cultured macrophages was reduced after exposure to acute wound fluid (38%, n =50, p n=41, p = 0.0005), or tumour necrosis factor α (52%, n = 27, p nflammatory reaction to inoculation with E coli was attenuated, as quantified by changes in bloodflow (ileal disease 50%, n = 6, p = 0. 01; colonic disease 77%, n=6, p=0.0003).This response was mediated by nitric oxide in controls, was increased by sildenafil in patients, and was not related to CARD15 genotype. Interpretation: In Crohn’s disease, a constitutionally weak immune response predisposes to accumulation of intestinal contents that breach the mucosal barrier of the bowel wall, resulting in granuloma formation and chronic inflammation. Polymorphisms in CARD15 do not underlie this phenotype, but incapacitate the nOD2 pathway that can compensate for impairment of innate inflammation. Current treatment of secondary chronic inflammation might exaggerate the underlying lesion and promote chronic di

关键词：克罗恩病急性炎症临床调查不完全性中性粒细胞聚集细胞因子产物单核细胞衍生操作特征分析白介素-8 免疫缺陷

“猪Ⅱ型圆环病毒”专栏六:西班牙和丹麦受感染猪场的猪个体感染断奶后多系统衰竭综合征的风险因素

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国外畜牧学（猪与禽） 2013年第5期33卷 27-28页

作者：陶莉 Grau-Roma L Stockmarr A Kristensen CS Enφe C López-Soria S nofrarías M Bille-Hansen V Hjulsager CK Sibila M Jorsal SE Fraile L Baekbo P Vigre H segalés J Larsen LE

研究人员对来自西班牙（n=3）和丹麦（n=10）13家感染断奶后多系统衰竭综合征（Postweaning Multisystemic Wasting Syndrome,PMWS）的猪场进行了2项前瞻性纵向研究。

关键词：断奶后多系统衰竭综合征猪Ⅱ型圆环病毒西班牙风险因素感染猪场丹麦个体

原发性免疫缺陷病患者肿瘤发生情况:美国免疫缺陷网络注册患者肿瘤发病率分析

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中华临床免疫和变态反应杂志 2018年第2期12卷 236-246页

作者： Paul C.Mayor Kevin H.Eng Kelly L.Singel Scott I.Abrams Kunle Odunsi Kirsten B.Moysich Ramsay Fuleihan Elizabeth Garabedian Patricia Lugar Hans D.Ochs Francisco A.Bonilla Rebecca H.Buckley Kathleen E.Sullivan Zuhair K.Ballas Charlotte Cunningham-Rundles Brahm H.segal 白炜曾小峰中国医学科学院北京协和医学院北京协和医院风湿免疫科

研究背景评估了在美国免疫缺陷网络(USIDnET)注册的原发性免疫缺陷病(PIDDs)患者的总体和器官特异性肿瘤发病率,并与监测、流行病学和最终结果项目(SEER)数据库中经年龄校正的人群的肿瘤发病率进行比较。目的假设PIDD患者由于免疫功能受... 详细信息

研究背景评估了在美国免疫缺陷网络(USIDnET)注册的原发性免疫缺陷病(PIDDs)患者的总体和器官特异性肿瘤发病率,并与监测、流行病学和最终结果项目(SEER)数据库中经年龄校正的人群的肿瘤发病率进行比较。目的假设PIDD患者由于免疫功能受损,肿瘤发病率会增加。方法将2003年至2015年在USIDnET注册中心注册的PIDD (n=3658)患者的总体和器官特异性肿瘤发病率进行评估,并与SEER数据库中经年龄校正的人群发病率进行比较。结果与年龄相匹配的SEER人群相比,观察到PIDD患者罹患肿瘤的相对危险率为1. 42倍(P<0. 001)。PIDD的男性患癌症的风险是年龄校正的男性人群的1. 91倍(P<0. 001),而PIDD女性患者的总体肿瘤发病率与经年龄校正的女性人群相比并无差异。对SEER数据库中最常见的4个恶性肿瘤——肺癌、结肠癌、乳腺癌和前列腺癌的发病率进行分析,PIDD患者中这些肿瘤的发病没有显著增加。男性和女性PIDD患者的淋巴瘤发病率均显著增加(男性10倍,P<0. 001;女性8. 34倍,P<0. 001)。结论 PIDD患者的肿瘤发病率较高。在特定的PIDD人群中淋巴瘤发病率的增高是导致总体肿瘤发病率提高的主要原因,而常见的实体肿瘤的风险没有增加。这些数据表明免疫系统在预防特定肿瘤方面有一定的作用。

关键词：原发性免疫缺陷病普通变异性免疫缺陷病肿瘤白血病淋巴瘤美国免疫缺陷网络