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S1P/S1PR1 signaling differentially regulates the allogeneic response of CD4 and CD8 T cells by modulating mitochondrial fission

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Cellular & molecular Immunology 2022年第11期19卷 1235-1250页

作者： Linlu Tian Yongxia Wu Hee-Jin Choi Xiaohui Sui Xinlei Li m.hanief sofi mohamed Faisal Kassir Xiao Chen Shikhar mehrotra Besim Ogretmen Xue-zhong Yu Department of microbiology&Immunology Medical University of South CarolinaCharlestonSCUSA Department of microbiology&Immunology Medical College of WisconsinMilwaukeeWIUSA Department of medicine Medical College of WisconsinMilwaukeeWIUSA Department of Biochemistry&molecular Biology Medical University of South CarolinaCharlestonSCUSA Department of Surgery Medical University of South CarolinaCharlestonSCUSA Hollings Cancer Center Medical University of South CarolinaCharlestonSCUSA The Cancer Center Medical College of WisconsinMilwaukeeWIUSA

Graft-versus-host disease (GVHD) significantly contributes to patient morbidity and mortality after allogeneic hematopoietic cell transplantation (allo-HSCT). Sphingosine-1-phosphate (S1P) signaling is involved in the biogenetic processes of different immune cells. In the current study, we demonstrated that recipient sphingosine kinase 1 (Sphk1), but not Sphk2, was required for optimal S1PR1-dependent donor T-cell allogeneic responses by secreting S1P. Using genetic and pharmacologic approaches, we demonstrated that inhibition of Sphk1 or S1PR1 substantially attenuated acute GVHD (aGVHD) while retaining the graft-versus-leukemia (GVL) effect. At the cellular level, the Sphk1/S1P/S1PR1 pathway differentially modulated the alloreactivity of CD4+ and CD8+ T cells;it facilitated T-cell differentiation into Th1/Th17 cells but not Tregs and promoted CD4+ T-cell infiltration into GVHD target organs but was dispensable for the CTL activity of allogeneic CD8+ T cells. At the molecular level, the Sphk1/S1P/S1PR1 pathway augmented mitochondrial fission and increased mitochondrial mass in allogeneic CD4+ but not CD8+ T cells by activating the AmPK/AKT/mTOR/Drp1 pathway, providing a mechanistic basis for GVL maintenance when S1P signaling was inhibited. For translational purposes, we detected the regulatory efficacy of pharmacologic inhibitors of Sphk1 and S1PR1 in GVHD induced by human T cells in a xenograft model. Our study provides novel mechanistic insight into how the Sphk1/S1P/S1PR1 pathway modulates T-cell alloreactivity and validates Sphk1 or S1PR1 as a therapeutic target for the prevention of GVHD and leukemia relapse. This novel strategy may be readily translated into the clinic to benefit patients with hematologic malignancies and disorders.

关键词： Sphk1 S1P S1PR GVHD GVL mitochondrial fission

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STING negatively regulates allogeneic T-cell responses by constraining antigen-presenting cell function

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Cellular & molecular Immunology 2021年第3期18卷 632-643页

作者： Hee-Jin ChoiTaylor Ticer Yongxia Wu Chih-Hang Anthony Tang Corey mealer David Bastian m.hanief sofi Linlu Tian Steven Schutt Hee-Jin Choi Taylor Ticer mengmeng Zhang Xiaohui Sui Lei Huang Andrew L.mellor Chih-Chi Andrew Hu Xue-Zhong Yu microbiology&Immunology Medical University of South CarolinaCharlestonSCUSA Immunology Microenvironment&Metastasis ProgramThe Wistar InstitutePhiladelphiaPAUSA Translational and Clinical Research Institute Faculty of Medical SciencesNewcastle UniversityNewcastle upon TyneUK Department of medicine Medical University of South CarolinaCharlestonSCUSA Hollings Cancer Center Medical University of South CarolinaCharlestonSCUSA

Stimulator of interferon genes(STING)-mediated innate immune activation plays a key role in tumor-and self-DNA-elicited antitumor immunity and ***,STING can also suppress tumor immunity and *** signaling In host nonhematopoietic cells was reported to either protect against or promote graft-versus-host disease(GVHD),a major complication of allogeneic hematopoietic cell transplantation(allo-HCT).Host hematopoietic antigen-presenting cells(APCs)play key roles in donor T-cell priming during GVHD ***,how STING regulates host hematopoietic APCs after allo-HCT remains *** utilized murine models of allo-HCT to assess the role of STING in hematopoietic ***-deficient recipients developed more severe GVHD after major histocompatibility complex-mismatched *** bone marrow chimeras,we found that STING deficiency in host hematopoietic cells was primarily responsible for exacerbating the ***,STING on host CD11c+cells played a dominant role in suppressing allogeneic T-cell ***,STING deficiency resulted in increased survival,activation,and function of APCs,including macrophages and dendritic ***,constitutive activation of STING attenuated the survival,activation,and function of APCs isolated from STING V154m knock-in ***-deficient APCs augmented donor T-cell expansion,chemokine receptor expression,and migration into intestinal tissues,resulting in accelerated/exacerbated *** pharmacologic approaches,we demonstrated that systemic administration of a STING agonist(bis-(3'-5')-cyclic dimeric guanosine monophosphate)to recipient mice before transplantation significantly reduced GVHD *** conclusion,we revealed a novel role of STING in APC activity that dictates T-cell allogeneic responses and validated STING as a potential therapeutic target for controlling GVHD after allo-HCT.

关键词： Stimulator of interferon genes antigen-presenting cells allogeneic hematopoietic cell transplantation graft-versushost diseases hematopoietic stem-cell transplantation T cells

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Assessment of above- and belowground carbon pools in a semi-arid forest ecosystem of Delhi, India

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Ecological Processes 2019年第1期8卷 93-103页

作者： Archana meena Ankita Bidalia m.hanief JDinakaran K.S.Rao Department of Botany University of RajasthanJaipurRajasthan 302004India Natural Resource management Laboratory Department of BotanyUniversity of DelhiNorth CampusDelhi 110007India Department of Botany Baba Ghulam Shah Badshah UniversityRajouriJ&K 185234India

Background:Assessment of carbon pools in semi-arid forests of India is crucial in order to develop a better action plan for management of such ecosystems under global climate change and rapid *** study,therefore,aims to assess the above-and belowground carbon storage potential of a semi-arid forest ecosystem of ***:For the study,two forest sites were selected,i.e.,north ridge(NRF)and central ridge(CRF).Aboveground tree biomass was estimated by using growing stock volume equations developed by Forest Survey of India and specific wood *** biomass was determined by harvest sampling ***(root)biomass was determined by using a developed *** soil organic carbon(SOC),soil samples were collected at 0–10-cm and 10–20-cm depth and carbon content was ***:The present study estimated 90.51 mg ha−1 biomass and 63.49 mg C ha−1 carbon in the semi-arid forest of Delhi,*** lower diameter classes showed highest tree density,i.e.,240 and 328 individuals ha−1(11–20 cm),basal area,i.e.,8.7(31–40 cm)and 6.08m2 ha−1(11–20 cm),and biomass,i.e.,24.25 and 23.57 mg ha−1(11–20 cm)in NRF and CRF,***,a significant contribution of biomass(7.8 mg ha−1)in DBH class 81–90 cm in NRF suggested the importance of mature trees in biomass and carbon *** forests were predominantly occupied by Prosopis juliflora(Sw.)DC which also showed the highest contribution to the(approximately 40%)tree *** allocation was maximum in aboveground(40–49%),followed by soil(29.93–37.7%),belowground or root(20–22%),and litter(0.27–0.59%).Conclusion:Our study suggested plant biomass and soils are the potential pools of carbon storage in these ***,carbon storage in tree biomass was found to be mainly influenced by tree density,basal area,and species *** belonging to lower DBH classes are the major carbon sinks in these *** the study,native trees contributed to the significan

关键词： Semi-arid forest Carbon pool Forest management Species composition Basal area Carbon allocation pattern

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Soil moisture controls the spatio-temporal pattern of soil respiration under different land use systems in a semi-arid ecosystem of Delhi,India

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Ecological Processes 2020年第1期9卷 172-184页

作者： Archana meena m.hanief J.Dinakaran K.S.Rao Department of Botany University of RajasthanJaipurRajasthan 302004India Department of Botany Baba Ghulam Ghulam Shah Badshah UniversityRajouriJammu and Kashmir 185234India Department of Botany Bhaskaracharya College of Applied SciencesUniversity of DelhiDwarkaDelhi 110007India Department of Botany University of DelhiDelhi 110007India

Background:Soil respiration(S_(R))is a critical process for understanding the impact of climatic conditions and land degradation on the carbon cycle in terrestrial *** measured the S_(R) and soil environmental factors over 1 year in four land uses with varying levels of disturbance and different vegetation types viz.,mixed forest cover(mFC),Prosopis juliflora(Sw.)forest cover(PFC),agricultural field(AF),and vegetable field(VF),in a semi-arid area of Delhi,*** primary aim was to assess the effects of soil moisture(S_(m)),soil temperature(S_(T)),and soil microbial activity(S_(mA))on the S_(R).methods:The S_(R) was measured monthly using an LI-6400 with an infrared gas analyser and a soil *** S_(m) was measured using the gravimetric *** S_(T)(10 cm)was measured with a probe attached to the *** S_(mA) was determined by fluorescein diacetate ***:The S_(R) showed seasonal variations,with the mean annual S_(R) ranging from 3.22 to 5.78μmol m^(−2) s^(−1) and higher S_(R) rates of~15-55%in the cultivated fields(AF,VF)than in the forest sites(mFC,PFC).The VF had significantly higher S_(R)(PmFC),which did not vary significantly from one another in S_(R)(Pmeasures ANOVA evaluated the significant differences(Pmonths(July,August,September,February).The S_(m) as a single factor showed a strong significant relationship in all the land uses(R^(2)=0.67-0.91,PmFC,and AF(R^(2)=0.14-0.31;P>0.05).Contrasting results were observed in the VF,which showed high S_(R) during summer(may;11.21μmol m^(−2) s^(−1))and a significant exponential relationship with the S_(T)(R^(2)=0.52;PmA(R2=0.44-0.5;Pm),S_(T),and S_(mA) explained 91-95

关键词： Soil respiration Soil moisture Soil microbes Soil temperature Precipitation Land use change Semi-arid ecosystems

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management of needle blight (Lophodermium pinastri) disease in Blue pine trees in Kashmir,India

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Journal of Forestry Research 2016年第1期27卷 185-192页

作者： Farooq A.Ahanger Gh.Hassan Dar m.A.Beig T.A.sofi Division of Plant Pathology Sher-e-Kashmir University of Agricultural Sciences & Technology of Kashmir

Evaluation of various fungicides against needle blight disease of pine was carried out at Shed Kashmir University of Agriculture Sciences and Technology of Kashmir （India） during the year 2008 and 2009. Applica- tion of various fungicides were evaluated in vivo at dif- ferent concentrations. However in both, mist-chamber and poly-chamber, the Blue pine （Pinus wallichiana Jackson） seedlings treated with hexaconazole 5EC （@ 0.03 %） or carbendazim 50WP （@ 0.1%） depicted significantly less disease incidence and intensity. The seedlings treated with mancozeb 75WP （@ 0.3 %） and chlorothalonil 75WP （@ 0.3 %） exhibited less disease incidence and intensity. Increase in relative humidity from 60 to 100 % signifi- cantly enhanced needle blight disease incidence and intensity. In field trial the fungitoxicants used either as single spray or protectant followed by systemic fungitoxi- cant spray significantly reduced disease incidence in Blue pine compared to check. The mean disease incidence in fungitoxicant treated plants varied from 11.82 to 25.51% as compared to 36.03 % in control.

关键词： Needle blight disease Fungicides - Bluepine Lophodermium pinastri

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Anthelmintic, antimicrobial, antioxidant and cytotoxic activity of Caltha palustris var. alba Kashmir, India

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Chinese Journal of Natural medicines 2014年第8期12卷 567-572页

作者： sofi mubashir mohd Yousuf Dar Bashir A.Lone m.Iqbal Zargar Wajaht A.Shah Department of Chemistry University of Kashmir Centre of Research for Development University of Kashmir Department of Pharmaceutical Sciences University of Kashmir

The methanolic extract obtained from the root portion of Caltha palustris var. alba was evaluated for its anthelmintic efficacy against gastrointestinal nematodes of sheep under both in vitro and in vivo conditions using worm motility inhibition(WmI) assay and fecal egg count reduction(FECR) assay, respectively. The extract was subjected to antimicrobial activity using agar-well diffusion method against different bacterial strains. In addition the extract was evaluated for cytotoxic and antioxidant activity against cultured THP-1(Leukemia), A-549(Lung), HCT-15(Colon), Cervix(HeLa) and PC-3(Prostrate) cell lines by SRB and DPPH radical scavenging assays. The extract used resulted in mean %WmI of 94.44%, as observed when the worms were put in lukewarm buffer for 30 min after exposure to different treatments. The mean mortality index of the sample was 0.95. The lethal concentration(LC50) was 0.11 mg·mL-1. Cell lines were exposed to concentration of 100 μg·mL-1 of extract for 48 h, which reduced the viability of these cell lines. The same plant extract also showed 55.58% DPPH radical scavenging activity.

关键词： Caltha palustris var.alba Anthelmintic activity(in vivo and in vitro) Antimicrobial activity Cytotoxic activity Radical scavenging activity

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A Generalization of Eneström-Kakeya Theorem and a Zero Free Region of a Polynomial

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Journal of Applied mathematics and Physics 2021年第6期9卷 1271-1277页

作者： mushtaq Ahmad Shah Ram Swroop Humayun mohd sofi Insha Nisar G.C.E.T Safapora Ganderbal Kashmir Jammu and Kashmir India NImS University Jaipur India mewar University Rajasthan India

For the polynomial P (z) = ajzj, aj ≥ aj-1, a0 > 0, j = 1, 2, …, n, an > 0, a classical result of Eneström-Kakeya says that all the zeros of P (z) lie in |z|≤ 1. This result was generalised by A. Joyall and G. Labe... 详细信息

For the polynomial m>Pm> (m>zm>) = mg src="Edit_***" alt="" />m>ajzjm>, m>am>m>j m>≥ m>am>m>jm>-1, m>am>0 > 0, m>jm> = 1, 2, …, m>nm>, m>anm> > 0, a classical result of Eneström-Kakeya says that all the zeros of m>Pm> (m>zm>) lie in |m>zm>|≤ 1. This result was generalised by A. Joyall and G. Labelle, where they relaxed the non-negativity condition on coefficients. It was further generalized by m.A Shah by relaxing the monotonicity of some coefficients. In this paper, we use some known techniques and provide some more generalizations of the above results by giving more relaxation to the conditions.

关键词： Polynomial Zeros Eneström-Kakeya Theorem

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Innate-like CD4 T cells selected by thymocytes suppress adaptive immune responses against bacterial infections

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Open Journal of Immunology 2012年第1期2卷 25-39页

作者： Yu Qiao Brian m. Gray mohammed H. sofi Laura D. Bauler Kathryn A. Eaton mary X. D. O’Riordan Cheong-Hee Chang Department of microbiology and Immunology University of Michigan Ann Arbor USA Unit for Lab Animal medicine Medical School University of Michigan Ann Arbor USA

We have reported a new innate-like CD4 T cell population that expresses cell surface makers of effector/memory cells and produce Th1 and Th2 cytokines immediately upon activation. Unlike conventional CD4 T cells that are selected by thymic epithelial cells, these CD4 T cells, named T-CD4 T cells, are selected by mHC class II expressing thymocytes. Previously, we showed that the presence of T-CD4 T cells protected mice from airway inflammation suggesting an immune regulatory role of T-CD4 T cells. To further understand the function of T-CD4 T cells, we investigated immune responses mediated by T-CD4 T cells during bacterial infection because the generation of antigen specific CD4 T cells contributes to clearance of infection and for the development of immune memory. The current study shows a suppressive effect of T-CD4 T cells on both CD8 and CD4 T cell-mediated immune responses during Listeria and Helicobacter infections. In the mouse model of Listeria monocytogenes infection, T-CD4 T cells resulted in decreasedfrequency of Listeria-specific CD8 T cells and the killing activity of them. Furthermore, mice with T-CD4 T cells developed poor immune memory, demonstrated by reduced expansion of antigen-specific T cells and high bacterial burden upon re-infection. Similarly, the presence of T-CD4 T cells suppressed the generation of antigen-specific CD4 T cells in Helicobacter pylori infected mice. Thus, our studies reveal a novel function of T-CD4 T cells in sup-pressing anti-bacterial immunity.

关键词： Bacterial Infection Innate-Like CD4 T Cells Immune Suppression

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High-throughput multiplexed fluorescence-activated droplet sorting

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microsystems & Nanoengineering 2018年第1期4卷 95-104页

作者： Ouriel Caen Simon Schütz m.S.Suryateja Jammalamadaka Jérémy Vrignon Philippe Nizard Tobias m.Schneider Jean-Christophe Baret Valérie Taly INSERm UmR-S1147 CNRS SNC5014Paris Descartes UniversityEquipe labellisée Ligue Nationale contre le cancerParisFrance Emergent Complexity in Physical Systems Laboratory(ECPS) Ecole Polytechnique Fédérale de Lausanne1015 LausanneSwitzerland CNRS University BordeauxCRPPUMR 5031115 Avenue Schweitzer33600 PessacFrance

Fluorescence-activated droplet sorting(FADS)is one of the most important features provided by droplet-based ***,to date,it does not allow to compete with the high-throughput multiplexed sorting capabilities offered by flow ***,we demonstrate the use of a dielectrophoretic-based FADS,allowing to sort up to five different droplet populations *** system provides means to select droplets of different phenotypes in a single experimental run to separate initially heterogeneous *** experimental results are rationalized with the help of a numerical model of the actuation of droplets in electric fields providing guidelines for the prediction of sorting designs for upscaled or downscaled microsystems.

关键词： rational initially sorting

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Douglas-fi r(Pseudotsuga menziesii(mirb.)Franco)in Europe:an overview of management practices

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Journal of Forestry Research 2023年第4期34卷 871-888页

作者： Valeriu-Norocel Nicolescu William Lmason Jean-Charles Bastien Torsten Vor Krasimira Petkova Vilém Podrázský martina Đodan Sanja Perić Nicola La Porta Robert Brus Siniša Andrašev martin Slávik Juraj modranský michal Pástor Károly Rédei Branislav Cvjetkovic Ahmet Sivacioğlu Vasyl Lavnyy Cornelia Buzatu-Goanță Gheorghe mihăilescu Faculty of Silviculture and Forest Engineering Transylvania University of BrasovBrasovRomania Forest Research Northern Research StationRoslinMidlothianUK INRAe Centre Val de Loire ArdonOrléansFrance Faculty of Forest Sciences and Forest Ecology University Georg-AugustGöttingenGermany University of Forestry Sofi aBulgaria Department of Silviculture Faculty of Forestry and Wood SciencesCzech University of Life SciencesPragueCzech Republic Croatian Forest Research Institute JastrebarskoCroatia Foundation Edmund mach San Michele all’AdigeItaly Biotechnical Faculty University of LjubljanaLjubljanaSlovenia Institute of Lowland Forestry and Environment Novi SadSerbia National Forest Centre Forest Research InstituteZvolenSlovakia Faculty of Ecology and Environmental Sciences Technical University in ZvolenZvolenSlovakia Faculty of Agricultural and Food Sciences and Environmental management University of DebrecenDebrecenHungary Faculty of Forestry University of Banja LukaBanja LukaBosnia and Herzegovina Department of Silviculture Faculty of ForestryKastamonu UniversityKastamonuTurkey Department of Silviculture Ukrainian National Forestry UniversityLvivUkraine Faculty of Horticulture and Forestry Banat’s University of Agricultural Sciences and Veterinary MedicineTimisoaraRomania Vâlcea County Branch National Forest Administration-ROMSILVARâmnicu-VâlceaRomania

Douglas-fir(Pseudotsuga menziesii(mirb.)Franco),one of the most commercially important tree species in western North America and one of the most valuable timber trees worldwide,was introduced to Europe in *** became a major species for aff orestation in Western Europe after WWII,currently grows in 35 countries on over 0.83 million ha and is one of the most widespread nonnative tree species across the continent.A lower sensitivity to drought makes Douglas-fi r a potential alternative to the more drought-sensitive Norway spruce so its importance in Europe is expected to increase in the *** is one of the fastest growing conifer species cultivated in Europe,with the largest reported dimensions of 2.3 m in diameter and 67.5 m in *** stands have high productivity(up to 20 m 3 ha−1 a−1)and production(over 1000 m 3 ha−1).The species is generally regenerated by planting(initial stocking density from less than 1000 seedlings ha−1 to more than 4000 ha−1),using seedlings of European provenance derived from seed orchards or certifi ed seed *** the range of end-uses of its wood is very wide,the rotation period of Douglas-fi r is highly variable and ranges between 40 and 120 *** the production of large-sized,knotfree timber is targeted,thinnings are always coupled with pruning up to 6 *** is an increasing interest in growing Douglas-fi r in mixtures and managing stands through close-to-nature silviculture,but the species’intermediate shade tolerance means that it is best managed through group selection or shelterwood systems.

关键词： Douglas-fi r Ecological requirements Growth and yield Timber Climate change

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