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ER stress-induced aggresome trafficking of HtrA1 protects against proteotoxicity

Journal of Molecular Cell Biology 2017年第6期9卷 516-532页

作者： Maximilian J. Gerhardt Joseph A. Marsh Margaux Morrison Andrius Kazlauskas Arogya Khadka Stephan Rosenkranz Margaret M. DeAngelis magali saint-geniez Sarah Melissa P. Jacobo Department of Ophthalmology Harvard Medical School The Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary Boston MA 02114 USA Department III of Internal Medicine Cologne University Heart Center Center for Molecular Medicine University of Cologne 50931 Cologne Germany MRC Human Genetics Unit Institute of Genetics and Molecular Medicine University of Edinburgh Edinburgh EH4 2XU UK Department of Ophthalmology and Visual Sciences University of Utah and John A. Moran Eye Center Salt Lake City UT 84132 USA

High temperature requirement A1 （HtrA1） belongs to an ancient protein family that is linked to various human disorders. The pre- cise role of exon 1-encoded N-terminal domains and how these influence the biological functions of human HtrAZ remain elusive. In this study, we traced the evolutionary origins of these N-terminal domains to a single gene fusion event in the most recent common ancestor of vertebrates. We hypothesized that human HtrA1 is impticated in unfotded protein response. ｜n highly secre- tory cells of the retinal pigmented epithelia, endoplasmic reticulum （ER） stress upregulated HtrA1. HtrA1 co-localized with vimen- tin intermediate filaments in highly arborized fashion. Upon ER stress, HtrA1 tracked along intermediate filaments, which collapsed and bundled in an aggresome at the microtubule organizing center. Gene silencing of HtrA1 altered the schedule and amplitude of adaptive signaling and concomitantly resulted in apoptosis. Restoration of wild-type HtrA1, but not its protease inactive mutant, was necessary and sufficient to protect from apoptosis. A variant of HtrA1 that harbored exon 1 substitutions dis- played reduced efficacy in rescuing cells from proteotoxicity. Our results illuminate the integration of HtrA1 in the toolkit of mam- malian cells against protein misfolding and the implications of defects in HtrA1 in proteostasis.

关键词： ER stress unfolded protein response RPE HtrA1 multi-domain protein evolution proteostasis

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Umbilical Cord Prolapse Managed by Assisted Vacuum Delivery

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Case Reports in Clinical Medicine 2024年第7期13卷 234-240页

作者： Katherine magali Michael Haule Musa Faraay Eltruda Tesha Obstetrics and Gynecology Department Manyara Regional Referral Hospital Babati Tanzania Theatre and Anaesthesia Unit Manyara Regional Referral Hospital Babati Tanzania

G4P3L3 was at 40 weeks of gestation who was admitted in active stage of labor with normal fetal heart rate. At 8 cm cervical dilatation she experienced spontaneous rupture of membrane with clear liquor. Cord prolapse was detected and was prepared for caesarian section meanwhile she was kept in knee chest position and bladder was filled with normal saline 0.9%. 30 min before operation she was fully dilated with signs of Non reassuring fetal status, vacuum extraction was done to assist delivery as soon as possible. The APGAR score was 6 and 10 in the first and fifth minutes respectively. Mother and the baby were discharged the next day in good condition.

关键词： Umbilical Cord Prolapse Operative Vaginal Delivery Vacuum Extraction

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Effects of B[a]P-UVA Co-Exposure on Epigenetic Marks of Isolated Skin Cells and Impact of an Arundo donax L. Extract of These Changes

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Journal of Cosmetics, Dermatological Sciences and Applications 2024年第3期14卷 253-269页

作者： Marie M. Dorr magali Favre-Mercuret Katell Vié Richard Fitoussi Laboratoires Clarins Pontoise France

Background: Extrinsic aging results from environmental stressors such as UVR or pollutants. While the effects of single pollutants are better understood, those of their combination remain poorly scrutinized. Objective: Building on a study showing downregulation of several processes upon co-exposure to B[a]P and UVA, we investigated changes induced by epigenetic marks. Materials and Methods: Human primary fibroblasts and HaCaT cells were exposed to B[a]P and UVA. After 24 hours, exposed and unexposed cells were compared to assess DNA methylation. Focusing on HaCaT, multiplex assays enabled quantifying histone H3 modifications and evaluating four splicing factors (SRSF1, SRSF3, SFPQ, and SF3B1) by immunohistochemical labeling. The expression of keratinocyte-/fibroblast-relevant genes was assessed by RT-qPCR. Finally, the impact of an Arundo donax L. extract added 24 hours before B[a]P-UVA co-exposure was analyzed. Results: Exposure to B[a]P-UVA raised DNA methylation (HaCaT: ×3.6, fibroblasts: ×1.9), an increase prevented by the extract. In HaCaT cells, B[a]P-UVA increases the frequency of S10P (+38%). When exposure was preceded by extract treatment, the frequency of several methylations was impacted. B[a]P-UVA only induced the expression of SRSF1 and SFPQ in HaCaT (+46% and +34%). Treatment with the extract abolished this effect. Co-exposure increases the expression of inflammation-related genes (IL-1α, IL-1β) in HaCaT cells and decreases those of AQP3, KRT15, and SOD2. The extract has little effect on these changes. In primary fibroblasts, exposure to B[a]P-UVA lowered the expression of LOXL2, LUM, and TGFBR2 (−38%, −59%, and −51%, respectively), and the extract did not affect these modifications. Conclusion: Within 24 hours, a single B[a]P-UVA co-exposure changes epigenetic marks of skin cells but has only mild effects on gene expression. An Arundo donax L. extract can prevent part of the epigenetic marks’ changes and could stimulate the expression of some genes in

关键词： Extrinsic Aging DNA Methylation Histone H3 Splicing Factors Arundo donax L.

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NONLOCAL CROWD DYNAMICS MODELS FOR SEVERAL POPULATIONS

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Acta Mathematica Scientia 2012年第1期32卷 177-196页

作者： Rinaldo M.Colombo magali Lcureux-Mercier Department of Mathematics Brescia University Department of Mathematics TechnionIsrael Institute of Technology

This paper develops the basic analytical theory related to some recently intro- duced crowd dynamics models. Where well posedness was known only locally in time, it is here extended to all of R＋. The results on the stability with respect to the equations are improved. Moreover, here the case of several populations is considered, obtaining the well posedness of systems of multi-D non-local conservation laws. The basic analytical tools are provided by the classical Kruzkov theory of scalar conservation laws in several space dimensions.

关键词： hyperbolic conservation laws nonlocal flow pedestrian traffic

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Electrochemical reactivity of In-Pb solid solution as a negative electrode for rechargeable Mg-ion batteries

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Journal of Energy Chemistry 2021年第4期30卷 124-128页

作者： Lucie Blondeau Suzy Surble Eddy Foy Hicham Khodja magali Gauthier UniversitéParis-Saclay CEACNRSNIMBELEEL91191Gif-sur-YvetteFrance UniversitéParis-Saclay CEACNRSNIMBELAPA-IRAMAT91191Gif-sur-YvetteFrance

A composite In-Pb:carbon was successfully synthetized by a two-step mechanochemical synthesis in order to obtain an adequate particles size and structure to investigate the electrochemical reactivity of the In-Pb solid solution towards Mg.A potential synergetic coupling of electroactive elements In and Pb was examined using electrochemical and ex situ X-ray diffraction *** potential profile of the solid solution indicates the formation of Mg_(2)Pb and Mg ***,the diffraction study suggests a peculiar electrochemically-driven amorphization of Mg In during the magnesiation,in strong contrast to Mg In crystallization in In-based and In Bi-based electrodes reported in the *** In and Pb favors the amorphization of Mg In and a high first magnesiation capacity of about 550 m Ah g^(-1),but is thereafter detrimental to the material’s *** results emphasize the possible influence of electrochemically-driven amorphization and crystallization processes on electrochemical performance of battery materials.

关键词： Magnesium battery Negative electrode Alloy Amorphization

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Can subjective sleep quality, evaluated at the age of 73, have an influence on successful aging? The PROOF study

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Open Journal of Preventive Medicine 2014年第2期4卷 51-56页

作者： Emilie Crawford-Achour Virginie Dauphinot magali saint Martin magali Tardy Regis Gonthier Jean Claude Barthelemy Frederic Roche Laboratoire de Physiologie de l’exercice Equipe SNA Epis EA 4607Universite Jean MonnetFaculte de Medecine J.LisfrancHopital UniversitaireSaint EtienneFrance Departement de Gerontologie Clinique Universite Jean MonnetFaculte de Medecine J.LisfrancHopital UniversitaireSaint EtienneFrance Centre Memoire de Ressources et de Recherche de Lyon Hopital des CharpennesHospices Civils de LyonVilleurbanneFrance Centre VISAS Universite Jean MonnetFaculte de Medecine J.LisfrancHopital UniversitaireSaint EtienneFrance Departement de Gérontologie Clinique Universite Jean MonnetFaculte de Medecine J.LisfrancHopital GeneralSaint ChamondFrance

Objective: Sleep complaints are recurrent in Geriatrics and are often attributed to physiological aging. The aim of this work is to describe subjective sleep quality and its impact on successful aging. Methods: Subjective sleep quality was evaluated by using the Pittsburgh subjective sleep quality questionnaire. Two visual analogical scales (graduate from 0 to 10) were used to quantify perceived state of health and life satisfaction. Objective respiratory sleep parameters were also collected. Results: 370 data were analysed (46.2% of males). The average age was 73.2 +/- 1. The level of perceived state of health was 6.9 +/- 2, and life satisfaction level was 7.7 +/-2. Subjective sleep quality was significantly related to perceived health status (p = 0.034) and life satisfaction (p = 0.005). There was no significant association between sleep quality and objective respiratory sleep parameters. Conclusion: The assessment of sleep quality plays an important role in the management of elderly persons and can help them to age more successfully.

关键词： Successful Aging Sleep Complaint Pittsburgh Sleep Quality Index

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An optimized use of limited ground based topographic data for river applications

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International Journal of Sediment Research 2019年第3期34卷 216-225页

作者： Mohamed Jaballah Benoit Camenen ANDré Paquier magali Jodeau Irstea UR River Ly centre de Lyon-Villeurbanne EDF R&D

A prime requirement for hydrological applications, such as sediment budgeting or numerical modelling,is that produced Digital Terrain Models(DTMs) accurately represent the shape of landforms, especially for river reaches where data are not homogeneous. DTM error is a function of data point measurement accuracy and density and also of the field survey strategy when limited amounts of data will be *** paper aims to advance the importance of the field survey strategy for the specific, but common cases, where only limited topographic data will be available. This methodology is based on the idea that any feature can be properly described by a set of cross sections and breaklines describing both main and secondary directions of the flow. Then, a longitudinal linear interpolation can be applied to the defined homogeneous zones. This morphologically oriented(MO) method that includes data acquisition strategy and interpolation, was validated using a reference DTM derived from Li DAR measurements. An estimation of the uncertainties also is suggested based on the distance of the nearest point and the local slope using a geographically weighted regression. The proposed MO method is typically applicable to Alpine river reaches characterized by multiple channels that may always be underwater and not navigable such as an alternate bar system with secondary and transverse channels.

关键词： Digital Terrain Model Survey strategy Interpolation DTM error Gravel bar

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The Sulfate Transporter Family in Wheat： Tissue-Specific Gene Expression in Relation to Nutrition

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Molecular Plant 2010年第2期3卷 374-389页

作者： Peter Buchner Saroj Parmar Anne Kriegel magali Carpentier Malcolm J. Hawkesford Rothamsted Research Plant Science Department West Common Harpenden Hertfordshire AL5 2JQ UK Molecular Plant Nutrition University of Hohenheim Stuttgart Germany

Sulfate uptake and distribution in plants are managed by the differential expression of a family of transporters, developmentally, spatially, and in response to sulfur nutrition. Elucidation of the signaling pathways involved requires a knowledge of the component parts and their interactions. Here, the expression patterns of the full complement of sulfate transporters in wheat, as influenced by development and sulfur nutrition, are described. The 10 wheat sulfate transporters characterized here are compared to the gene families for both rice and Brachypodium, for whom full genome information is available. Expression is reported in young seedlings with a focus on roles in uptake from nutrient solution and differential expression in relation to sulfate deprivation. In addition, patterns of expression in all organs at the grain filling stage are reported and indicate differential responses to nutritional signals of the individual transporters in specific tissues and an overall coordination of uptake, storage, and remobilization to deliver sulfur to the developing grain.

关键词： Sulfate transporter wheat transcriptional regulation sulfur nutrition grain filling.

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Experimental manipulation of reproductive tactics in Seba’s short-tailed bats:consequences on sperm quality and oxidative status

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Current Zoology 2019年第6期65卷 609-616页

作者： magali MENIRI Florence GOHON Ophelie GNING Gaetan GLAUSER Armelle VALLAT Nicolas JFASEL Fabrice HELFENSTEIN Laboratory of Evolutionary Ecophysiology Institute of BiologyUniversity of NeuchatelSwitzerland Neuchatel Platform of Analytical Chemistry University of NeuchatelSwitzerland Leibniz Institute for Zoo and Wildlife Research Germany

To reproduce,males have to fertilize the female’s eggs,sometimes in competition with ejaculates of other *** species where males display alternative reproductive tactics,whereby territorial males secure mating and non-territorial males have to sneak copulations,the latter might be expected to invest relatively more resources towards sperm quality compared with the territorial *** cells are especially vulnerable to oxidative stress,which reduces male ***,antioxidant resources are expected to modulate sperm quality,and might be allocated differently between reproductive *** test the link between reproductive tactics,redox profile and sperm quality,we experimentally induced changes in the reproductive tactics of 39 captive males Seba's short-tailed bats Carollia *** monitored the blood and ejaculate oxidative balance,and the sperm quality before,7 days and 21 days after the manipulation of reproductive *** ejaculates'oxidative damage was negatively related to sperm velocity,males exhibited similar blood and ejaculates redox profiles and similar sperm quality,regardless of their reproductive ***,these results arise as a consequence of some constraints having been lifted during the *** results also suggest that,in Seba's short-tailed bats,the expression of alternative reproductive tactics is not subjected to strong oxidative ***,our results could reflect an absence of trade-off between pre-and post-copulatory traits in harem males,as they could be selected to invest both in female attraction and sperm quality,as a consequence of their inability to fully monopolize females.

关键词： oxidative stress sperm competition alternative reproductive tactics Carollia perspicillata

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Colorectal cancer and immunity:what we know and perspectives

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World Journal of Gastroenterology 2014年第14期20卷 3738-3750页

作者： Simon Pernot magali Terme Thibault Voron Orianne Colussi Elie Marcheteau Eric Tartour Julien Taieb Service d’Hépatogastro-entérologie et d’oncologie digestive H?pital Européen Georges-PompidouUniversité Paris DescartesSorbonne Paris Cité INSERM U970 Paris Cardiovascular Research CenterUniversité Paris-Descartes Service d’Immunologie biologique H?pital Européen Georges-PompidouUniversité Paris Descartes

Strong evidence supports the concept of immunosurveillance and immunoediting in colorectal cancer. In particular, the density of T CD8+ and CD45+ lymphocyte infiltration was recently shown to have a better prognostic value than the classic tumor node metastasis classification factor. Other immune subsets, as macrophages, natural killer cells or unconventionnal lymphocytes, seem to play an important role. Induction of regulatory T cells (Tregs) or immunosuppressive molecules such as PD-1 or CTLA-4 and downregulation of antigen-presenting molecules are major escape mechanisms to antitumor immune response. The development of these mechanisms is a major obstacle to the establishment of an effective immune response, but also to the use of immunotherapy. Although immunotherapy is not yet routinely used in colorectal cancer, we now know that most treatments used (chemotherapy and biotherapy) have immunomodulatory effects, such as induction of immunogenic cell death by chemotherapy, inhibition of immunosuppression by antiangiogenic agents, and antibody-dependent cytotoxicity induced by cetuximab. Finally, many immunotherapy strategies are being developed and tested in phase I to III clinical trials. The most promising strategies are boosting the immune system with cytokines, inhibition of immunoregulatory checkpoints, vaccination with vectorized antigens, and adoptive cell therapy. Comprehension of antitumor immune response and combination of the different approaches of immunotherapy may allow the use of effective immunotherapy for treatment of colorectal cancer in the near future.

关键词： Colorectal cancer Immunotherapy Immunity Immunoregulation Vaccination

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