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Opposing regulatory functions of the TIM3 (HAVCR2) signalosome in primary effector T cells as revealed by quantitative interactomics

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Cellular & Molecular Immunology 2021年第6期18卷 1581-1583页

作者： Yunhao Zhai Javier Celis-Gutierrez Guillaume Voisinne Daiki Mori laura Girard Odile Burlet-Schiltz Anne Gonzalez de Peredo Romain Roncagalli Bernard Malissen Centre d’Immunologie de Marseille-Luminy Aix Marseille UniversitéINSERMCNRS13288MarseilleFrance Centre d’Immunophénomique Aix Marseille UniversitéINSERMCNRSMarseilleFrance Institut de Pharmacologie et de Biologie Structurale Département Biologie Structurale BiophysiqueProtéomique Génopole Toulouse Midi Pyrénées CNRS UMR 5089ToulouseFrance

deciphering how T-cell antigen receptor signals are modulated by coinhibitors is a fundamental goal in immunology and of considerable clinical interest because blocking coinhibitory signals via therapeutic antibodies have become a standard cancer immunotherapeutic *** of the attention devoted to T-cell immunoglobulin and mucin domain-3(TIM3;also known as HAVCR2 or CD366)molecules stems from their expression on exhausted T cells in settings of chronic viral infection and ***,T cells expressing high levels of both PD-1 and TIM3 coinhibitors appear more dysfunctional than those expressing PD-1 *** therapies intending to block both PD-1 and TIM3 are thus actively being explored in the cancer treatment *** interaction with Galectin-9(GAL-9)and carcinoembryonic antigen-related cell adhesion molecule 1(CEACAM-1),the tyrosines found in the TIM3 cytoplasmic tail are phosphorylated.1 Because these conserved tyrosines do not form a recognizable inhibitory signaling motif,the mechanism by which TIM3 transmits inhibitory signals has not been ***,TIM3 also has costimulatory activity in T cells.2,3 Published biochemical studies attempting to unveil the mode of action of TIM3 have relied on approaches addressing one candidate effector at a time with limited quantitative insight,and most used transformed *** mice expressing an affinity Twin-Strep-tag(OST)at the TIM3-protein C-terminus(TIM3OST mice)(Figs.1a and S1a)and affinity purification coupled with mass spectrometry(AP-MS),we herein defined the composition and dynamics of the signaling protein complex(signalosome)used by TIM3 in primary effector T *** results provide a more complete model of TIM3 signaling and explain its paradoxical coinhibitory and costimulatory functions.

关键词： TIM3 expressing devoted

Sensitivity analysis of sediment flux derived by laser diffraction and acoustic backscatter within a reservoir

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International Journal of Sediment Research 2018年第1期33卷 18-26页

作者： Stefan Haun laura Lizano Institute for Modelling Hydraulic and Environmental Systems University of Stuttgart department of Hydraulic and Environmental Engineering Norwegian University of Science and Technology Ministry of Environment and Energy

A combination of two indirect methods to measure sediment flux is presented in this study to evaluate suspended sediment transport in a hydropower reservoir. The acoustic backscatter signal(ABS)from an Acoustic Doppler Current Profiler(ADCP) is therefore applied in pre-defined transects within the reservoir in combination with a Laser In-Situ Scattering Transmissometry-stream lined device(LISSTSL). The stationary LISST-SL derived suspended sediment concentration(SSC) measurements are used to calibrate the ABS. From the LISST-SL measurements a time series of SSC is obtained. This enables, in addition, a comprehensive data analysis to evaluate the influence of natural fluctuations of the SSC on the calculated sediment flux, which should be taken into account when assessing sediment transport. Furthermore SSC measurements are done with the LISST-SL close to the reservoir bed. In areas close to the bed no information regarding the ABS is available from the ADCP measurements due to the side-lobe interference. In various studies the information from the last three valid cells is used for ***, as result of a comparison of the LISST-SL measurements with extrapolated SSC values from the ADCP measurements it can be seen that, especially in deep reservoirs, this method has to be adapted to the in-situ conditions.

关键词： Reservoir Suspended sediment concentrations Sediment flux Laser diffraction Acoustic backscatter signal

Implications of metabolism-driven myeloid dysfunctions in cancer therapy

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Cellular & Molecular Immunology 2021年第4期18卷 829-841页

作者： laura Strauss Valentina Guarneri Alessandra Gennari Antonio Sica department of Immunopharmacology and Immuno Oncology EMD Serono Research&Development InstituteInc.80119545A Middlesex TurnpikeBillericaMA 01821USA department of Surgery Oncology and GastroenterologyUniversity of PadovaPadovaItaly Veneto Institute of Oncology-IRCCS PaduaItalyPadovaItaly Division of Oncology Department of Translational MedicineUniversity of Eastern PiedmontNovaraItaly department of Pharmaceutical Sciences University of Eastern PiedmontA.Avogadrovia Bovio 6NovaraItaly Humanitas Clinical and Research Center IRCCSVia Manzoni 56RozzanoMilanItaly

Immune homeostasis is maintained by an adequate balance of myeloid and lymphoid *** chronic inflammatory states,including cancer,this balance is lost due to dramatic expansion of myeloid progenitors that fail to mature to functional inflammatory neutrophils,macrophages,and dendritic cells(DCs),thus giving rise to a decline in the antitumor effector lymphoid ***-related inflammation orchestrates the production of hematopoietic growth factors and cytokines that perpetuate recruitment and activation of myeloid precursors,resulting in unresolved and chronic *** pathologic inflammation creates profound alterations in the intrinsic cellular metabolism of the myeloid progenitor pool,which is amplified by competition for essential nutrients and by hypoxia-induced metabolic rewiring at the tumor ***,persistent myelopoiesis and metabolic dysfunctions contribute to the development of cancer,as well as to the severity of a broad range of diseases,including metabolic syndrome and autoimmune and infectious *** aims of this review are to(1)define the metabolic networks implicated in aberrant myelopoiesis observed in cancer patients,(2)discuss the mechanisms underlying these clinical manifestations and the impact of metabolic perturbations on clinical outcomes,and(3)explore new biomarkers and therapeutic strategies to restore immunometabolism and differentiation of myeloid cells towards an effector phenotype to increase host antitumor *** propose that the profound metabolic alterations and associated transcriptional changes triggered by chronic and overactivated immune responses in myeloid cells represent critical factors influencing the balance between therapeutic efficacy and immune-related adverse effects(irAEs)for current therapeutic strategies,including immune checkpoint inhibitor(ICI)therapy.

关键词： Myelopoiesis Tumor-associated macrophages Myeloid-derived suppressor cells Metabolism Cancer therapy

The HEPD particle detector of the CSES satellite mission for investigating seismo-associated perturbations of the Van Allen belts

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Science China(Technological Sciences) 2018年第5期61卷 643-652页

作者： AMBROSI Giovanni BARTOCCI Simona BASARA Laurent BATTISTON Roberto BURGER William J. CARFORA luca CASTELLINI Guido CIPOLLONE Piero CONTI Livio CONTIN Andrea de DONATO Cinzia de SANTIS Cristian FOLLEGA Francesco M. GUANDALINI Cristina IONICA Maria IUPPA Roberto LAURENTI Giuliano LAZZIZZERA Ignazio LOLLI Mauro MANEA Christian MARCELLI laura MASCIANTONIO Giuseppe MERGE Matteo OSTERIA Giuseppe PACINI Lorenzo PALMA Francesco PALMONARI Federico PANICO Beatrice PATRIZII laura PERFETTO Francesco PICOZZA Piergiorgio POZZATO Michele PUEL Matteo RASHEVSKAYA Irina RICCI Ester RICCI Marco RICCIARINI Sergio Bruno SCOTTI Valentina SOTGIU Alessando SPARVOLI Roberta SPATARO Bruno VITALE Vincenzo Istituto Nazionale di Fisica Nucleare (INFN) Sezione di Perugia Perugia 06123 Italy Uninettuno University Rome 00186 Italy Istituto Nazionale di Fisica Nucleare (INFN) Sezione di Roma Tor Vergata Rome 00133 Italy Istituto Nazionale di Fisica Nucleare (INFN) TIFPA Povo (TN) 38123 Italy Dipartimento di Fisica Universita di Trento Povo (TN) 38123 Italy Dipartimento di Fisica Universita di Roma Tor Vergata Rome 00133 Italy IFAC-CNR Sesto Fiorentino (FI) 50019 Italy Dipartimento di Fisica e Astronomia Universita di Bologna Bologna 40127 Italy Istituto Nazionale di Fisica Nucleare (INFN) Sezione di Bologna Bologna 40127 Italy Istituto Nazionale di Fisica Nucleare (INFN) Sezione di Napoli Naples 80126 Italy Istituto Nazionale di Fisica Nucleare (INFN) LNE Frascati (RM) 00044 Italy Agenzia Spaziale Italiana (ASI) SSDC Rome 00133 Italy

CSES(China Seismo-Electromagnetic Satellite) is a mission developed by CNSA(Chinese National Space Administration) and ASI(Italian Space Agency), to investigate the near-Earth electromagnetic, plasma and particle environment, for studying the seismo-associated disturbances in the ionosphere-magnetosphere transition zone. The anthropogenic and electromagnetic noise,as well as the natural non-seismic electromagnetic emissions is mainly due to tropospheric activity. In particular, the mission aims to confirming the existence of possible temporal correlations between the occurrence of earthquakes for medium and strong magnitude and the observation in space of electromagnetic perturbations, plasma variations and precipitation of bursts with highenergy charged particles from the inner Van Allen belt. In this framework, the high energy particle detector(HEPD) of the CSES mission has been developed by the Italian LIMADOU Collaboration. HEPD is an advanced detector based on a tower of scintillators and a silicon tracker that provides good energy and angular resolution and a wide angular acceptance, for electrons of 3–100 Me V, protons of 30–200 Me V and light nuclei up to the oxygen. CSES satellite has been launched on February 2^(nd), 2018 from the Jiuquan Satellite Launch Center(China).

关键词： earthquake seismic-precursors particle detector Van Allen belts magnetosphere ionosphere space weather cosmic rays

Partially defatted black soldier fly larva meal inclusion in piglet diets: effects on the growth performance, nutrient digestibility,blood profile, gut morphology and histological features

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Journal of Animal Science and Biotechnology 2019年第3期10卷 708-718页

作者： Ilaria Biasato Manuela Renna Francesco Gai Sihem Dabbou Marco Meneguz Giovanni Perona Silvia Martinez Ana Cristina Barroeta Lajusticia Stefania Bergagna luca Sardi Maria Teresa Capucchio Enrico Bressan Andrea Dama Achille Schiavone laura Gasco department of Agricultural Forest and Food SciencesUniversity of TurinLargo P.Braccini 210095 Grugliasco(TO)Italy department of Veterinary Sciences University of TurinLargo P.Braccini 210095 Grugliasco(TO) TurinItaly National Research Council Institute of Science of Food ProductionLargo P.Braccini 210095 Grugliasco(TO)Italy SDSV-Teaching Structure of Veterinary Medicine University of TurinLargo P.Braccini 210095 Grugliasco(TO)Italy department of Animal Production University of MurciaCampus de Espinardo30071 MurciaSpain department of Animal and Food Science Autonomous University of BarcelonaCerdanyola del Vallès08193 BellaterraBarcelonaSpain Veterinary Medical Research Institute for Piemonte Liguria and the Valle D’AostaVia Bologna 14810154 TurinItaly department of Veterinary Medical Sciences University of BolognaVia Tolara di Sopra 5040064 Ozzano dell’Emilia(BO)Italy

Background:The aim of this trial was to investigate the effects of different inclusion levels of a partially defatted black soldier fly (BSF,Hermetia illucens L.) larva meal on the growth performance,nutrient digestibility,blood profile,gut morphology and histological features of piglets.A total of 48 newly weaned piglets were individually weighed (initial body weight (IBW):6.1 ± 0.16 kg) and randomly allocated to 3 dietary treatments (4 boxes as replicates/treatment and 4 animals/box).BSF larva meal was included at increasing levels (0% [BSF0],5% [BSFS] and 10% [BSF10]) in isonitrogenous and isoenergetic diets formulated for two feeding phases:Ⅰ (from d 1 to d 23) and Ⅱ (from d 24 to d 61).The weight gain (WG),average daily gain (ADG),average daily feed intake (ADFI) and feed conversion ratio (FCR) were calculated for each feeding phase and for the whole *** haematochemical parameters and nutrient digestibility of the piglets were also evaluated.A total of 3 piglets per box were slaughtered on d 61 and the slaughtered piglets were submitted to morphometric investigations and histopathological ***:No overall significant differences were observed for growth performance (P > 0.05),except for the ADFI of phase Ⅱ,which showed a linear response to increasing BSF meal levels (P 0.05).Conclusions:The obtained results show that a partially defatted BSF larva meal can be used as a feed ingredient in diets for weaned piglets without negatively affecting their growth performance,nutrient digestibilit

关键词： Hermetia il ucens L. Histopathology Insect meal Performance Weaning pigs

Longitudinal bending stiffness does not affect running economy in Nike Vaporfly Shoes

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Journal of Sport and Health Science 2022年第3期11卷 285-292页

作者： laura A.Healey Wouter Hoogkamer Integrative Locomotion Laboratory Department of KinesiologyUniversity of MassachusettsAmherstMA 01003-9258USA

Purpose This study aimed to determine the independent effect of the curved carbon-fiber plate in the Nike Vaporfly 4%shoe on running economy and running *** Fifteen healthy male runners completed a metabolic protocol and a biomechanics *** both protocols participants wore 2 different shoes,an intact Nike Vaporfly 4%(VF_(intact))and a cut Nike Vaporfly 4%(VF_(cut)).The VF_(cut) had 6 medio-lateral cuts through the carbon-fiber plate in the forefoot to reduce the effectiveness of the *** the metabolic protocol,participants ran at 14 km/h for 5 min,twice with each shoe,on a force-measuring treadmill while we measured metabolic *** the biomechanics protocol,participants ran across a runway with embedded force plates at 14 km/*** calculated running economy,kinetics,and lower limb joint *** Running economy did not significantly differ between shoe conditions(on average,0.55%±1.77%(mean±SD))worse in the VF_(cut) compared to the VF_(intact);95%confidence interval(-1.44%to 0.40%).Biomechanical differences were only found in the metatarsophalangeal(MTP)joint with increased MTP dorsiflexion angle,angular velocity,and negative power in the VF_(cut).Contact time was 1%longer in the VF_(intact).Conclusion Cutting the carbon-fiber plate and reducing the longitudinal bending stiffness did not have a significant effect on the energy savings in the Nike Vaporfly 4%.This suggests that the plate's stiffening effect on the MTP joint plays a limited role in the reported energy savings,and instead savings are likely from a combination and interaction of the foam,geometry,and plate.

关键词： Biomechanics Footwear Mechanical doping Metabolic rate Performance

Therapeutic potential of α7 nicotinic receptor agonists to regulate neuroinflammation in neurodegenerative diseases

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Neural Regeneration Research 2017年第9期12卷 1418-1421页

作者： laura Foucault-Fruchard Daniel Antier UMR INSERM U930 Université Fran?ois Rabelais CHRU de Tours H?pital Bretonneau

Neurodegenerative diseases, such as Alzheimer＇s, Parkinson＇s and Huntington＇s diseases, are all character- ized by a component of innate immunity called neuroinflammation. Neuronal loss and neuroinflammation are two phenomena closely linked. Hence, the neuroinflammation is a relevant target for the management of the neurodegenerative diseases given that, to date, there is no treatment to stop neuronal loss. Several studies have investigated the potential effects of activators of alpha 7 nicotinic acetylcholine receptors in animal models of neurodegenerative diseases. These receptors are widely distributed in the central nervous system. After activation, they seem to mediate the cholinergic anti-inflammatory pathway in the brain. This anti-inflammatory pathway, first described in periphery, regulates activation of microglial cells considered as the resident macrophage population of the central nervous system. In this article, we shortly review the agonists of the alpha 7 nicotinic acetylcholine receptors that have been evaluated in vivo and we focused on the selective positive allosteric modulators of these receptors. These compounds represent a key element to enhance receptor activity only in the presence of the endogenous agonist.

关键词： α7 nicotinic receptors cholinergic anti-inflammatory pathway Alzheimer's disease Huntington's disease Parkinson's disease neuroinflammation neurodegeneration positive allosteric modulators

The intestinal epithelial response to damage

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Science China(Life Sciences) 2018年第10期61卷 1205-1211页

作者： laura Weichselbaum Ophir D.Klein Program in Craniofacial Biology and department of Orofacial Sciences University of CaliforniaSan Francisco CA 94143USA Institute for Medical Immunology Université Libre de BruxellesGosselies 6041Belgium Laboratory of Experimental Gastroenterology Université libre de BruxellesBrussels 1070Belgium department of Pediatrics and Institute for Human Genetics University of CaliforniaSan FranciscoCA 94143 USA

The constant renewal of the intestinal epithelium is fueled by intestinal stem cells(ISCs) lying at the base of crypts, and these ISCs continuously give rise to transit-amplifying progenitor cells during homeostasis. Upon injury and loss of ISCs, the epithelium has the ability to regenerate by the dedifferentiation of progenitor cells that then regain stemness and repopulate the pool of ISCs. Epithelial cells receive cues from immune cells, mesenchymal cells and the microbiome to maintain *** review focuses on the response of the epithelium to damage and the interplay between the different intestinal compartments.

关键词： intestine regeneration microenvironment

Collecting Ophiocordyceps sinensis:an emerging livelihood strategy in the Garhwal,Indian Himalaya

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Journal of Mountain Science 2017年第2期14卷 390-402页

作者： laura CAPLINS Sarah J.HALVORSON department of Society and Conservation College of Forestry and ConservationUniversity of MontanaMissoulaMontana59812USA department of Geography College of Arts and SciencesUniversity of MontanaMissoulaMontana59812USA

In the Garhwal of Uttarakhand, India, the Bhotiya, an ethnically and culturally distinct tribal group, were historically engaged in seasonal migration(i.e. transhumance) to take advantage of scarce mountain resources and trade relations with Tibet. This livelihood practice has all but *** are adapting to these changing circumstances by engaging in the collection and sale of the valuable alpine medicinal fungus Ophiocordyceps sinensis, widely known as Cordyceps. The collection of this fungus has exploded, emerging as a lucrative yet high-risk livelihood strategy for many Bhotiya *** Bhotiyas' historic herding and trade-based interactions and knowledge of these alpine environments where Cordyceps are found uniquely positions them to access this valuable biological resource. Elsewhere in the Himalayan region, some households are earning as much as two-thirds of their income from the collection of Cordyceps; in China Cordyceps is now listed as an endangered species due to intense over-exploitation in the Tibetan *** paper seeks to fill the void in the scientific literature on the social, ecological and economic aspects of the emerging Cordyceps trade in the Garhwal. Our study investigates the socio-spatial dimensions of Cordyceps collection in the high alpine meadows. We document how a fusion of local knowledge and practice with alpine mountain systems has served to reinvigorate the economic integrity of mountain communities at a time of rapid socioeconomic change and to reimagine a new relationship between alpine resources and community *** article offers suggestions to address the sustainability of both Cordyceps collection and livelihood activities which hinge on this fungus population. We find a need for(1) community-based conservation measures that are rooted in(2) secure resource access rights for local communities to continue sustainable collection and sale of Cordyceps and(3) participatory-and science-based proc

关键词： Cordyceps ( Ophiocordyceps sinensis) Garhwal Himalaya Livelihood Alpine meadows Bhotiya Sustainability