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Myelinosome organelles in pathological retinas: ubiquitous presence and dual role in ocular proteostasis maintenance

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Neural Regeneration Research 2023年第5期18卷 1009-1016页

作者： Marina G.Yefimova Sechenov Institute of Evolutionary Physiology and Biochemistry Russian Academy of SciencesSt-PetersburgRussia Laboratoire STIM cnrs erl 7003 Universitéde PoitiersPoitiersFrance

The timely and efficient elimination of aberrant proteins and damaged organelles, formed in response to various genetic and environmental stressors, is a vital need for all cells of the body. Recent lines of evidence point out several non-classical strategies employed by ocular tissues to cope with aberrant constituents generated in the retina and in the retinal pigmented epithelium cells exposed to various stressors. Along with conventional strategies relying upon the intracellular degradation of aberrant constituents through ubiquitin-proteasome and/or lysosome-dependent autophagy proteolysis, two non-conventional mechanisms also contribute to proteostasis maintenance in ocular tissues. An exosome-mediated clearing and a myelinosome-driven secretion mechanism do not require intracellular degradation but provide the export of aberrant constituents and “waste proteins” outside of the cells. The current review is centered on the non-degradative myelinosome-driven secretion mechanism, which operates in the retina of transgenic Huntington’s disease R6/1 model mice. Myelinosome-driven secretion is supported by rare organelles myelinosomes that are detected not only in degenerative Huntington’s disease R6/1 retina but also in various pathological states of the retina and of the retinal pigmented epithelium. The intra-retinal traffic and inter-cellular exchange of myelinosomes was discussed in the context of a dual role of the myelinosome-driven secretion mechanism for proteostasis maintenance in different ocular compartments. Special focus was made on the interplay between degradative and non-degradative strategies in ocular pathophysiology, to delineate potential therapeutic approaches to counteract several vision diseases.

关键词： autophagy Huntington’s disease Müller cells myelinosome-driven secretion myelinosomes ocular pathophysiology proteostasis retina retinal pigmented epithelium ubiquitin-proteasome system

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Self-activation of Vγ9Vδ2 T cells by exogenous phosphoantigens involves TCR and butyrophilins

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Cellular & Molecular Immunology 2021年第8期18卷 1861-1870页

作者： ChloéLaplagne Laetitia Ligat Juliet Foote Frederic Lopez Jean-Jacques Fournié Camille Laurent Salvatore Valitutti Mary Poupot Inserm UMR1037 Centre de Recherches en Cancérologie de ToulouseToulouseFrance UniversitéToulouse III Paul-Sabatier ToulouseFrance erl 5294 cnrs ToulouseFrance IUCT-O ToulouseFrance

The high cytotoxic activity of Vγ9Vδ2 T lymphocytes against tumor cells makes them useful candidates in anticancer therapies.However,the molecular mechanism of their activation by phosphoantigens(PAgs)is not completely known.Many studies have depicted the mechanism of Vγ9Vδ2 T-cell activation by PAg-sensed accessory cells,such as immune presenting cells or tumor cells.In this study,we demonstrated that pure resting Vγ9Vδ2 T lymphocytes can self-activate through exogenous PAgs,involving their TCR and the butyrophilins BTN3A1 and BTN2A1.This is the first time that these three molecules,concurrently expressed at the plasma membrane of Vγ9Vδ2 T cells,have been shown to be involved together on the same and unique T cell during PAg activation.Moreover,the use of probucol to stimulate the inhibition of this self-activation prompted us to propose that ABCA-1 could be implicated in the transfer of exogenous PAgs inside Vγ9Vδ2 T cells before activating them through membrane clusters formed byγ9TCR,BTN3A1 and BTN2A1.The self-activation of Vγ9Vδ2 T cells,which leads to self-killing,can therefore participate in the failure ofγδT cell-based therapies with exogenous PAgs and should be taken into account.

关键词： Vγ9Vδ2 T cells Phosphoantigen Butyrophilins T-cell receptor

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What lessons can be learned from y T cell-based cancer immunotherapy trials？

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Cellular & Molecular Immunology 2013年第1期10卷 35-41页

作者： Jean-Jacques Fournie Helene Sicard Mary Poupot Christine Bezombes Amandine Blanc Franqois-Romagne Loic Ysebaert Guy Laurent INSERM UMR1037-Cancer ResearchCenter of Toulouse Toulouse France University of Toulouse Toulouse France erl 5294 cnrs BP3028 Hospital Purpan ToulouseFrAnce lnnate Pharma Marseilles France and Department of Hematology Hospital Purpan Toulouse France

During the last several years, research has produced a significant amount of knowledge concerning the characteristics of human 76 T lymphocytes. Findings regarding the immune functions of these cells, particularly their natural killer cell-like lyric activity against tumor cells, have raised expectations for the therapeutic applications of these cells for cancer. Pharmaceutical companies have produced selective agonists for these lymphocytes, and several teams have launched clinical trials of y8 T cell-based cancer therapies. The findings from these studies include hematological malignancies （follicular lymphoma, multiple myeloma, acute and chronic myeloid leukemia）, as well as solid tumors （renal cell, breast and prostate carcinomas）, consisting of samples from more than 250 patients from Europe, Japan and the United States. The results of these pioneering studies are now available, and this short review summarizes the lessons learned and the role of y6 T cell-based strategies in the current landscape of cancer immunotherapies.

关键词： cancer cell therapy gamma-delta lymphocytes immunotherapy lymphoma trials

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3D models of dilated cardiomyopathy:Shaping the chemical,physical and topographical properties of biomaterials to mimic the cardiac extracellular matrix

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Bioactive Materials 2022年第1期7卷 275-291页

作者： Marie Camman Pierre Joanne Onnik Agbulut Christophe Helary Sorbonne Universit´e CNRSUMR 7574Laboratoire de Chimie de la Matiere Condensee de Paris4 place Jussieu(case 174)F-75005ParisFrance Sorbonne Universite Institut de Biologie Paris-Seine(IBPS)CNRS UMR 8256Inserm ERL U1164Biological Adaptation and Ageing7 quai St-Bernard(case 256)F-75005ParisFrance

The pathophysiology of dilated cardiomyopathy(DCM),one major cause of heart failure,is characterized by the dilation of the heart but remains poorly understood because of the lack of adequate in vitro models.Current 2D models do not allow for the 3D organotypic organization of cardiomyocytes and do not reproduce the ECM perturbations.In this review,the different strategies to mimic the chemical,physical and topographical properties of the cardiac tissue affected by DCM are presented.The advantages and drawbacks of techniques generating anisotropy required for the cardiomyocytes alignment are discussed.In addition,the different methods creating macroporosity and favoring organotypic organization are compared.Besides,the advances in the induced pluripotent stem cells technology to generate cardiac cells from healthy or DCM patients will be described.Thanks to the biomaterial design,some features of the DCM extracellular matrix such as stiffness,porosity,topography or chemical changes can impact the cardiomyocytes function in vitro and increase their maturation.By mimicking the affected heart,both at the cellular and at the tissue level,3D models will enable a better understanding of the pathology and favor the discovery of novel therapies.

关键词： Biomaterials Dilated cardiomyopathies Induced pluripotent stem cells Porosity Anisotropy

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The Medicago truncatula Sucrose Transporter Family： Characterization and Implication of Key Members in Carbon Partitioning towards Arbuscular Mycorrhizal Fungi

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Molecular Plant 2012年第6期5卷 1346-1358页

作者： Joan Doidy Diederik van Tuinen Olivier Lamotte Marion Corneillat Gerard Alcaraz Daniel Wipf UMR INRA 1347 Agrosup Universite de Bourgogne Agro~cologie P61e Interactions Plantes Microorganismes ERL CNRS 6300 BP 86510 21065 DijonCedex France

We identified de novo sucrose transporter （SUT） genes involved in long-distance transport of sucrose from photosynthetic source leaves towards sink organs in the model leguminous species Medicago truncatula. The iden- tification and functional analysis of sugar transporters provide key information on mechanisms that underlie carbon partitioning in plant-microorganism interactions. In that way, full-length sequences of the M. truncatula SUT （MtSUT） family were retrieved and biochemical characterization of MtSUT members was performed by heterologous expression in yeast. The MtSUT family now comprises six genes which distribute among Dicotyledonous clades. MtSUTI-1 and MtSUT4-1 are key members in regard to their expression profiles in source leaves and sink roots and were characterized as functional H~/sucrose transporters. Physiological and molecular responses to phosphorus supply and inoculation by the arbuscular mycorrhizal fungus （AMF） Glomus intraradices was studied by gene expression and sugar quantification analyses. Sucrose represents the main sugar transport form in M. truncatula and the expression profiles of MtSUTI-1, MtSUT2, and MtSUT4-1 highlight a fine-tuning regulation for beneficial sugar fluxes towards the fungal symbiont. Taken together, these results suggest distinct functions for proteins from the SUT1, SUT2, and SUT4 clades in plant and in bio- trophic interactions.

关键词： sugar transport sucrose transporter SUT sugar partitioning Medicago truncatula Glomus intraradices.

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Extrahepatic hepcidin production:The intriguing outcomes of recent years

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World Journal of Clinical Cases 2019年第15期7卷 1926-1936页

作者： Raêd Daher Thibaud Lefebvre HervéPuy Zoubida Karim UniversitéParis Diderot Bichat siteParis 75018France Inflammation Research Center(CRI) INSERM U1149/ERL CNRS 8252Paris 75018France Laboratory of Excellence GR-ExParis 75018France

Hepcidin is the hyposideremic hormone regulating iron metabolism.It is a defensin-like disulfide-bonded peptide with antimicrobial activity.The main site of hepcidin production is the liver where its synthesis is modulated by iron,inflammation and erythropoietic signaling.However,hepcidin locally produced in several peripheral organs seems to be an important actor for the maintenance of iron homeostasis in these organs.This review highlights the presence of peripheral hepcidin and its potential functions.Understanding the role of extrahepatic hepcidin could be of great physiological and therapeutic importance for several specific pathologies.

关键词： Hepcidin Extrahepatic hepcidin Iron metabolism Bacterial infection Inflammation

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Land use in semi-free ranging Tonkean macaques Macaca tonkeana depends on environmental conditions： A geographical information system approach

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Current Zoology 2011年第1期57卷 8-17页

作者： Cedric SUEUR Paul SALZE Christiane WEBER Odile PETIT Department of Ecology and Evolutionary Biology Princeton University 08544 Princeton USA Ethologie des Primates Departement d'Ecologie Physiologie et Ethologie UMR 7178 cnrs-UdS 23 rue Becquerel 67087 Strasbourg France Laboratoire Image et Ville erl 7230 cnrs-UdS 3 rue de l'Argonne 67000 Strasbourg France

Wild animals use their habitat according to ecological pressures such as predation, resource availability or temperature, yet little is known about how individuals use their environment in semi free-ranging conditions. We assessed whether a semi-free ranging group of Tonkean macaquesMacaca tonkeanaused its wooded parkland in a heterogeneous way. GIS and GPS were used to determine whether individuals adjusted their behaviors according to variation in environmental constraints over time of day and the course of a year. We demonstrated that social and resting activities occurred in high altitude areas and areas with a high density of bushes, whereas the group foraged in areas where the density of bushes and grass was low. In general, the animals used areas exposed to the sun that were not on a slope. Semi-free ranging Tonkean macaques seemed to behave like their wild counterparts in terms of activity budget, land use per activity and thermoregulation.

关键词：地理信息系统自由放养环境变化土地使用猕猴野生动物全球定位系统高海拔地区

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Geographic and temporal variations of sulfate aerosols over the Pacific Ocean

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Acta Oceanologica Sinica 1991年第1期10卷 47-71页

作者： F.Parungo C.Nagamoto B.Kopcewicz J.Harris S.Hoyt Air Resources Laboratory NoAA/ERLBoulderColoradoU.S.A.Air Resources LaboratoryNoAA/ERLBoulderColoradoU.S.A.Air Resources LaboratoryNoAA/ERLBoulderColoradoU.S.A.Air Resources LaboratoryNoAA/ERLBoulderColoradoU.S.A.Environmental Analytical Service Inc. San Luis ObispoCaliforniaU. S. A.

To investigate the life cycle of marine sulfate aerosols, chemicophysical characteristics of marine aerosolswere measured during five cruises in the Pacific Ocean. Dimethyl sulfide concentrations in seawater and in the air were also measured. The geographic variation of sulfate-aerosol concentrations was studied in relation to biogenic and anthropogenic sources,transport with air trajectories, and chemical transformations in the atmosphere. The highest concentrations were found near Asian and American ports, indicating anthropogenic pollution is the major sulfate aerosols source. Higher concentrations were observed in the upwelling regions than in the oligotrophic areas. Along the coastal regions, both mass and number concentrations of sulfate aerosols depended on wind direction and wind speed, and land-breeze and sea-breeze oscillations; no clear diurnal variation was detected. In pelagic areas, along the equator, the concentrations of small sulfate particles showed a maximum in the afternoon and the minimum at night , indicating photo-oxidation as an important process for gas-to-particle conversion. Higher sulfate-aerosol concentrations were observed in spring than in autumn and higher concentrations were found during the La Nina anomaly than during the El Nino anomaly. Biogenic source of sulfate aerosols has an important role in the remote ocean. Case studies of sulfate-aerosol distributions are discussed.

关键词： DMS Geographic and temporal variations of sulfate aerosols over the Pacific Ocean over

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The ABA-Deficiency Suppressor Locus HAS2 Encodes the PPR Protein LOI1/MEF11 Involved in Mitochondrial RNA Editing

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Molecular Plant 2015年第4期8卷 644-656页

作者： Julien Sechet Camille Roux Anne Plessis Delphine Effroy Anne Frey Francois Perreau Catherine Biniek Anja Krieger-Liszkay David Macherel Helen M. North Hakim Mireau Annie Marion-Poll INRA Institut Jean-Pierre Bourgin UMR 1318 ERL CNRS 3559 Saclay Plant Sciences RD10 F-78026 Versailles France AgroParisTech Institut Jean-Pierre Bourgin UMR 1318 ERL CNRS 3559 Saclay Plant Sciences RD10 F-78026 Versailles France CEA Saclay IBiTec-S CNRS UMR 8221 Serv Bioenerget Biol Struct & Mecanisme F-91191 Gif Sur Yvette France Universite d'Angers UMR IRHS 1345 INRA Agrocampus Ouest F-49045 Angers France Institut Jean-Pierre Bourgin INRA Bat 2 F-78026 Versailles Cedex France Institut Jean-Pierre Bourgin INRA Bat 7 F-78026 Versailles Cedex France Department of Biology New York University 1009 Main Building 100 Washington Square East New York NY 10003-6688 USA

The hotABA-deficiency suppressor2 （has2） mutation increases drought tolerance and the ABA sensitivity of stomata closure and seed germination. Here we report that the HAS2 locus encodes the MITOCHONDRIAL EDITING FACTOR11 （MEF11）, also known as LOVASTATIN INSENSITIVE1. has21mef11 mutants exhibited phenotypes very similar to the ABA-hypersensitive mutant, hail-1 pp2ca-1 hab 1-1 abil-2, which is impaired in four genes encoding type 2C protein phosphatases （PP2C） that act as upstream negative regulators of the ABA signaling cascade. Like pp2c, mef11 plants were more resistant to progressive water stress and seed germination was more sensitive to paclobutrazol （a gibberellin biosynthesis inhibitor） as well as mannitol and NaCI, compared with the wild-type plants. Phenotypic alterations in mef11 were associated with the lack of editing of transcripts for the mitochondrial cytochrome c maturation FN2 （cCmFN2） gene, which encodes a cytochrome c-heme lyase subunit involved in cytochrome c biogenesis. Although the abundance of electron transfer chain complexes was not affected, their dysfunction could be deduced from increased respiration and altered production of hydrogen peroxide and nitric oxide in reef11 seeds. As minor defects in mitochondrial respiration affect ABA signaling, this suggests an essential role for ABA in mitochondrial retrograde regulation.

关键词： abscisic acid mitochondria pentatricopeptide repeat protein RNA editing drought tolerance germination

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COMPUTER DEMODULATION TECHNIQUE FOR A DUAL-CHANNEL MICROWAVE RADIOMETER

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Advances in Atmospheric Sciences 1986年第2期3卷 189-198页

作者：赵从龙,J. B. Snider,D. C. Hogg Colourado U.S.A. Institute of Atmospheric Physics Academia Sinica Beijing NOAA/erl/Wave Propagation Laboratory Boulder Colourado U.S.A. NOAA/erl/Wave Propagation Laboratory Boulder

The three stairstep output of the video amplifier has now been designed for the NOAA/WPL dual-channel radiometer in order to provide an analog input to one A/D converter instead of to two phase-detectors, and the synchronous detection for data and AGC is done in software. We put the new system into the dual-channel radiometer which was set in Boulder Atmospheric Observatory (BAO) to make experiments for three weeks and found the processor reliable and flexible.

关键词： COMPUTER DEMODULATION TECHNIQUE FOR A DUAL-CHANNEL MICROWAVE RADIOMETER

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