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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

Fatty acids derived from oviposition systems guide female black soldier flies(Hermetia illucens)toward egg deposition sites

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Insect Science 2024年第4期31卷 1231-1248页

作者： Patrick Klüber Emna Arous Jeanny Jerschow Marco Fraatz Daniel Bakonyi Martin Rühl Holger Zorn Department Bioresources Fraunhofer Institute for Molecular Biology and Applied EcologyGiessenGermany institute of Food Chemistry and Food biotechnology Justus Liebig University GiessenGiessenGermany

The black soldier fly,Hermetia illucens,comes with big promises for industrial purposes since its larvae feed polyphagously on a broad spectrum of organic ***,research focusing on adult flies is scarce,which is inconsistent with their reproductive relevance within the rearing *** particular,directed oviposition is a challenge in artificial ***,decomposing organic matter is commonly used as oviposition substrate,which has extensive potential for improvement in view of the lack of standardization and the risk of microbial ***,we identified three fatty acids and one fatty acid methyl ester derived from the surface of old oviposition sites and targeted to elucidate their effect on preference behavior and oviposition site selection using Y-olfactometry and prepared oviposition sites,*** to tetradecanoic acid attracted gravid females and stimulated oviposition most strongly,while decanoic acid demonstrated a repulsive *** kept in mixed-sex populations were attracted by tetradecanoic acid,resulting in a higher egg mass found in the compound box(3.0–11.4 fold),a≥2.3 fold reduction of nonspecifically deposited eggs,and the highest total egg ***,decanoic and dodecanoic acid caused females to lay a greater proportion of eggs nonspecifically outside both *** data suggest that fatty acids,especially tetradecanoic acid,are important cues for oviposition site selection in black soldier *** order to achieve a directed oviposition behavior,the role of further short-and long-chain fatty acids as attractants should be examined.

关键词： black soldier fly Hermetia illucens fatty acids insects as food and feed oviposition oviposition site selection tetradecanoic acid

OsATL32 ubiquitinates the reactive oxygen species-producing OsRac5-OsRbohB module to suppress rice immunity

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Journal of Integrative Plant Biology 2024年第7期66卷 1459-1480页

作者： Yuqing Yan Hui Wang Yan Bi Jiajing Wang Muhammad Noman Dayong Li Fengming Song National Key Laboratory for Rice Biology and Breeding Institute of BiotechnologyZhejiang UniversityHangzhou 310058China Ministry of Agriculture Key Laboratory of molecular Biology of Crop Pathogens and Insect Pests Institute of BiotechnologyZhejiang UniversityHangzhou 310058China Key Laboratory of Biology of Crop Pathogens and Insects of Zhejiang Province Institute of BiotechnologyZhejiang UniversityHangzhou 310058China

Ubiquitination-mediated protein degradation is integral to plant immunity,with E3 ubiquitin ligases acting as key factors in this ***,we report the functions of OsATL32,a plasma membrane-localized Arabidopsis Tóxicos En Levadura(ATL)-type E3 ubiquitin ligase,in rice(Oryza sativa)immunity and its associated regulatory *** found that the expression of OsATL32 is downregulated in both compatible and incompatible interactions between rice and the rice blast fungus Magnaporthe *** OsATL32 protein level declines in response to infection by a compatible *** strain or to chitin ***32 negatively regulates rice resistance to blast and bacterial leaf blight diseases,as well as chitin-triggered *** and genetic studies revealed that OsATL32 suppresses pathogen-induced reactive oxygen species(ROS)accumulation by mediating ubiquitination and degradation of the ROS-producing OsRac5–OsRbohB module,which enhances rice immunity against *** protein phosphatase PHOSPHATASE AND TENSIN HOMOLOG enhances rice blast resistance by dephosphorylating OsATL32 and promoting its degradation,preventing its negative effect on rice *** study provides insights into the molecular mechanism by which the E3 ligase OsATL32 targets a ROS-producing module to undermine rice immunity.

关键词： E3 ligase OsATL32 OsRac5-OsRbohB module phosphatase OsPTEN reactive oxygen species rice immunity

RebL1 is required for macronuclear structure stability and gametogenesis in Tetrahymena thermophila

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Marine Life Science & Technology 2024年第2期6卷 183-197页

作者： Huijuan Hao Yinjie Lian Chenhui Ren Sitong Yang Min Zhao Tao Bo Jing Xu Wei Wang Key Laboratory of Chemical Biology and molecular Engineering of Ministry of Education Institute of BiotechnologyShanxi UniversityTaiyuan 030006China School of Life Science Shanxi UniversityTaiyuan 030006China Shanxi Key Laboratory of biotechnology Taiyuan 030006China

Histone modification and nucleosome assembly play important roles in chromatin-related *** chaperones form different complexes and coordinate histone transportation and *** histone chaperone complexes have been identified in different *** ciliate protozoa(ciliates)have various chromatin structures and different nuclear ***,histone chaperone components and functions of different subunits remain unclear in ***-rahymema thermophila contains a transcriptionally active macronucleus(MAC)and a transcriptionally inactive micronu-cleus(MIC)which exhibit multiple replication and various chromatin remodeling progresses during vegetative growth and sexual developmental ***,we found histone chaperone RebL1 not only localized evenly in the transcriptionally active MAC but also dynamically changed in the MIC during vegetative growth and sexual developmental ***1 knockdown inhibited cellular *** macronuclear morphology became bigger in growing *** abnormal macronuclear structure also occurred in the starvation ***,micronuclear meiosis was disturbed during sexual development,leading to a failure to generate new gametic ***1 potentially interacted with various factors involved in histone-modifying complexes and chromatin remodeling complexes in different developmental ***1 knockdown affected expression levels of the genes involved in chromatin organization and *** together,RebL1 plays a vital role in maintaining macronuclear structure stability and gametogenesis in ***.

关键词： Gametogenesis Histone chaperone Macronuclear structure RebL1 Tetrahymena thermophilaIntroduction

Transcriptomic and pathological profiling of a new congenic mouse model with Lepr mutation:Evaluating susceptibility to the development of obesity and NAFLD

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Genes & Diseases 2024年第3期11卷 34-38页

作者： MJ Mahesh Kumar Shailendra Arindkar Masum Saini Perumal Nagarajan National institute of Immunology New Delhi 100067India Center for Cellular and molecular Biology Hyderabad 500007India Regional Center for biotechnology Faridabad 121001India

Non-alcoholic fatty liver disease(NAFLD)and type 2 diabetes mellitus(T2DM)are two disease conditions for which obesity is a risk factor.^(1)Due to the close relationship between the three pathologies,researchers frequently use the same mouse models to identify the underlying processes of obesity,NAFLD,and *** instance,leptin(Lep)-null(ob/ob)and leptin receptor(Lepr)-deficient(db/db)mice spontaneously develop NAFLD and show different phenotypes of extreme obesity and diabetes,respectively.

关键词： obesity NAFLD Lep

Two distinct subpopulations of marginal zone B cells exhibit differential antibody-producing capacities and radioresistance

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Cellular & molecular Immunology 2024年第4期21卷 393-408页

作者： Sujin Lee Yeunjung Ko Hyun Woo Lee Won Joon Oh Hun Gi Hong Dinuka Ariyaratne Se Jin Im Tae Jin Kim Department of Immunology Graduate School of Basic Medical ScienceSungkyunkwan University School of MedicineSuwon16419Republic of Korea Department of Immunology and molecular Medicine Faculty of Medical SciencesUniversity of Sri JayewardenepuraNugegodaSri Lanka present address:Immunology and Microbiology Graduate Program Baylor College of MedicineHoustonTX77030USA

Marginal zone(MZ)B cells,which are splenic innate-like B cells that rapidly secrete antibodies(Abs)against blood-borne pathogens,are composed of heterogeneous ***,we showed that MZ B cells can be divided into two distinct subpopulations according to their CD80 expression ***80^(high)MZ B cells exhibited greater Ab-producing,proliferative,and IL-10-secreting capacities than did CD80^(low)MZ B ***,CD80^(high)MZ B cells survived 2-Gy whole-body irradiation,whereas CD80^(low)MZ B cells were depleted by irradiation and then repleted with one month after *** of CD80^(low)MZ B cells led to accelerated development of type II collagen(CII)-induced arthritis upon immunization with bovine ***80^(high)MZ B cells exhibited higher expression of genes involved in proliferation,plasma cell differentiation,and the antioxidant ***80^(high)MZ B cells expressed more autoreactive B cell receptors(BCRs)that recognized double-stranded DNA or CII,expressed more immunoglobulin heavy chain sequences with shorter complementarity-determining region 3 sequences,and included more clonotypes with no N-nucleotides or with B-1a BCR sequences than CD80^(low)MZ B *** transfer experiments showed that CD21^(+)CD23^(+)transitional 2 MZ precursors preferentially generated CD80^(low)MZ B cells and that a proportion of CD80^(low)MZ B cells were converted into CD80^(high)MZ B cells;in contrast,CD80^(high)MZ B cells stably remained CD80^(high)MZ B *** summary,MZ B cells can be divided into two subpopulations according to their CD80 expression levels,Ab-producing capacity,radioresistance,and autoreactivity,and these findings may suggest a hierarchical composition of MZ B cells with differential stability and BCR specificity.

关键词： Marginal Zone B Cell CD80 Autoreactivity Radioresistance

Oxygen is an essential gasotransmitter directly sensed via protein gasoreceptors

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Animal Models and Experimental Medicine 2024年第2期7卷 189-193页

作者： Savani Anbalagan Faculty of Biology Institute of Molecular Biology and BiotechnologyAdam Mickiewicz UniversityPoznańPoland

The current restrictive criteria for gasotransmitters exclude oxygen(O_(2))as a gasotransmitter in *** this manuscript,I propose a revision of gasotransmitter criteria to include O_(2) per se as a signaling molecule and'essential gasotransmitter'for *** revision would enable us to search for protein-based O_(2)-binding sensors(gasoreceptors)in all cells in the brain or other tissues rather than specialized tissues such as the carotid body or *** microorganisms have protein-based O_(2)-binding sensors or gasoreceptors such as DosP or FixL or FNR with diverse signaling domains,then eukaryotic cells must also have O_(2)-binding sensors or *** as there are proteinbased receptor(s)for nitric oxide(GUCY1A,GUCY1B,CLOCK,NR1D2)in cells of diverse tissues,it is reasonable to consider that there are protein-based receptors for O_(2) in cells of diverse tissues as *** mammals,O_(2) must be acting as a gasotransmitter or gaseous signaling molecule via protein-based gasoreceptors such as androglobin that very likely mediate acute sensing of O_(2).Accepting O_(2) as an essential gasotransmitter will enable us to search for gasoreceptors not only for O_(2) but also for other nonessential gasotransmitters such as hydrogen sulfide,ammonia,methane,and *** will also allow us to investigate the role of environment-derived metal ions in acute gas(or solute)sensing within and between ***,accepting O_(2) per se as a signaling molecule acting via gasoreceptors will open up the field of gasocrinology.

关键词： essential gasotransmitter gasocrine gasoreceptor gasocrinology

Drosophila X virus-like particles as delivery carriers for improved oral insecticidal efficacy of scorpion Androctonus australis peptide against the invasive fruit fly,Drosophila suzukii

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Insect Science 2024年第3期31卷 847-858页

作者： Qi Xue Luc Swevers Clauvis Nji Tizi Taning Faculty of Bioscience Engineering Department of Plants and CropsGhent UniversityGhentBelgium Insect molecular Genetics and biotechnology Institute of Biosciences and ApplicationsNational Centre for Scientific Research"Demokritos"AthensGreece

Insect-specific neurotoxic peptides derived from the venoms of scorpions and spiders can cause acute paralysis and death when injected into insects,offering a promising insecticidal component for insect pest ***,effective delivery systems are required to help neurotoxic peptides pass through the gut barrier into the hemolymph,where they can ***,we investigated the potential of a novel nanocarrier,Drosophila X virus-like particle(DXV-VLP),for delivering a neurotoxin from the scorpion Androctonus australis Hector(AaIT)against the invasive pest fruit fly,Drosophila *** results show that the fusion proteins of DXV polyproteins with AalT peptide at their Ctermini could be sufficiently produced in Lepidoptera Hi5 cells in a soluble form using the recombinant baculovirus expression system,and could self-assemble into VLPs with similar particle morphology and size to authentic DXV *** addition,the AalT peptides displayed on DXV-VLPs retained their toxicity,as demonstrated in injection bioassays that resulted in severe mortality(72%)in adults after 72 *** fed to adults,mild mortality was observed in the group treated with DXV-AalT(38%),while no mortality occurred in the group treated with AaIT peptide,thus indicating the significant role of DXV-VLPs in delivering AalT ***,this proof-of-concept study demonstrates for the first time that VLPs can be exploited to enhance oral delivery of insect-specific neurotoxic peptides in the context of pest ***,it provides insights for further improvements and potentially the development of neurotoxin-based bioinsecticides and/or transgenic crops for insect pest control.

关键词： AalT Drosophila suzuki nanocarrier neurotoxic peptides pest control virus-like particle(VLP)

Immune response to inactivated bacterial vector carrying the recombinant K39 antigen of Leishmania infantum in mice

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Asian Pacific Journal of Tropical Biomedicine 2024年第5期14卷 199-206页

作者： Lucelina S.Araújo Bruno B.Silva Eduarda N.F.N.Santos Arnaldo S.Bezerra Samuel S.Frota Assis R.Montenegro Eridan O.P.T.Florean Maurício Fvan Tilburg Maria Izabel F.Guedes Laboratory of biotechnology and molecular Biology Northeast Biotechnology NetworkState University of CearáFortalezaBrazil Faculty of Veterinary Medicine State University of CearáFortalezaBrazil

Objective:To evaluate the immunological response elicited by an inactivated bacterial vector carrying the K39 antigen of Leishmania infantum,and a purified ***:Mice were subjected to the following treatments:(1)Purified recombinant K39(rK39)protein at a 20μg dose with complete Freund’s adjuvant;(2)Inactivated Escherichia coli(BL21 DE3)carrying the K39 protein at an equivalent total protein content of 200μg;(3)Inactivated bacteria lacking the K39 protein;(4)Non-immunized control *** monitoring was *** groups were challenged by intraperitoneal injection of 10^(7) Leishmania infantum *** euthanasia,the liver and spleen were collected to analyze the levels of TNF,IFN-γ,IL-12,IL-4,and ***:Mice immunized with purified rK39 or the inactivated bacterial vector carrying the K39 antigen of Leishmania infantum showed a long-lasting immune response with high levels of polyclonal antibodies specifically recognizing the recombinant *** IgG1 subclass was the predominant immunoglobulin;however,the induction of IgG2a and the profile of cytokines produced were indicative of the induction of a mixed-type ***:The inactivated bacterial vector carrying the K39 antigen,as well as the purified antigen can induce a long-lasting immune response in immunized mice,predominantly favouring a Th2 profile response.

关键词： Visceral leishmaniasis K39 Inactivated bacterial vector Vaccine Immune response Th1 Th2 Leishmania infantum