FoxO3a overexpression prevents both glycogen overload and autophagic buildup in skeletal muscle of Pompe disease

FoxO3a overexpression prevents both glycogen overload and autophagic buildup in skeletal muscle of Pompe disease. 6eme congrès international de Myologi

Satellite cells fail to contribute to muscle repair but are functional in Pompe disease (glycogenosis type II)

Satellite cells fail to contribute to muscle repair but are functional in Pompe disease (glycogenosis type II). 6eme congrés international de Myologi

Cadeia produtiva do gengibre (Zingiber officinale ROSCOE) no estado do Paraná : análise e recomendações para melhoria da qualidade

Orientador : Raquel R.B.NegrelleCo-orientadores: Luiz Doni Filho, Neusa G.A. RuckerTese (doutorado) - Universidade Federal do Paraná. Setor de Ciências Agrárias. Curso de Pós-Graduação em Agronomia - área de concentração Produção Vegetal, Departamento de Fitotecnia e FitossanitarismoInclui bibliografia e glossárioResumo: O presente trabalho teve como objetivo o estudo prospectivo da cadeia produtiva do Zingiber officinale Roscoe no Estado do Paraná, identificando os principais agentes envolvidos e paralelamente proceder análise dos pontos de estrangulamentos, especificamente no que concerne à qualidade microbiológica deste produto em todos os níveis, desde a produção até a fase final da comercialização, visando identificar causas e propor soluções no sentido da melhoria do sistema como um todo. Este estudo foi desenvolvido no período de 2000 a 2002 englobando pesquisa de campo, entrevistas abertas com representantes de estabelecimentos de comercialização, produtores e demais atores da cadeia produtiva, além de análises laboratoriais do produto "in natura" disponível no mercado consumidor da Região Metropolitana de Curitiba - PR. Este documento está organizado em 9 capítulos, que apresentam vastas informações englobando aspectos botânicos, ecológicos, fisico-químicos e farmacológicos do gengibre, e que estão incluídas nos capítulos 1 e 2. O capítulo 3 apresenta características gerais da principal região produtora brasileira, Morretes - PR, englobando localização, aspectos sócio-econômicos, geológicos e geomorfológicos e caracterização climática. O capítulo 4 apresenta o estudo prospectivo da cadeia produtiva do gengibre no Estado do Paraná, que engloba panorama mundial, brasileiro e paranaense do volume de produção agrícola de gengibre. Inclui-se também caracterização da comunidade produtora agrícola do litoral paranaense, além da identificação e caracterização dos outros diferentes níveis da cadeia produtiva do gengibre e a detecção dos principais pontos de estrangulamento nos diferentes níveis desta cadeia produtiva. A caracterização do cultivo e beneficiamento do gengibre no litoral paranaense é apresentada no capítulo 5, evidenciando suas particularidades frente ao descrito na literatura especializada. No capítulo 6 avaliou-se as condições higiênico-sanitárias dos estabelecimentos produtores, do processo de beneficiamento pós-colheita (lavagem, limpeza, secagem e embalagem) e das condições de manipulação do gengibre "in natura" no litoral paranaense. De maneira geral, as condições de higiene e limpeza observadas foram consideradas precárias, determinando alta potencialidade de contaminação do gengibre com agentes que poderiam colocar em risco a saúde do consumidor. No capítulo 7 são apresentados os resultados dos estabelecimentos de comercialização da Região Metropolitana de Curitiba - PR, no que tange à qualidade e adequação às normas vigentes. Dos aspectos observados, as condições dos vestuários e dos equipamentos de proteção individual (manipuladores) foram considerados precários, o que pode potencializar a contaminação do produto e colocar em risco a saúde do consumidor. O capítulo 8 teve como objetivo caracterizar o perfil microbiológico do gengibre "in natura" comercializado na Região Metropolitana de Curitiba - PR, tendo como base a Resolução - CNPPA n. 12 - Brasil, 1978 e a Resolução - RDC n. 12 - Brasil, 2001. Para tanto, foram realizadas a determinação do número mais provável (NMP) de coliformes totais, coliformes a 45° C/g e Escherichia coli, e a presença de Salmonella sp em 25 gramas. Sintetizando, um conjunto de propostas e recomendações aos agentes econômicos que atuam e processam a cadeia produtiva do gengibre no Estado do Paraná, em especial o município de Morretes - PR, é apresentado no capítulo 9Abstract: Prospective studies of the productive chain of the Zingiber officinale Roscoe on Parana State identifying the main agents envolved and parallel procedure analysis of the strangulation points, in order to microbiology qualify this product in whole levels from the production until commercialization last phase, aiming identify causes and propose solutions to the improvement of the system in general. This survey developed from 2000 to 2002 involved field research, interviews with representative of the commercialization establishments, producers and others actors of the productive chain, besides made in laboratories of the quality of crude product available to the consumer market in Curitiba. This paper is organized in nine chapters that present information involving botanical, ecological, physique-chemical and pharmacological aspects of ginger that are included in chapters 1 and 2. The chapter 3 presents the characteristics of the main brazilian productive area, embody localization, social and economic aspects, geologycal, geomorphologycal and climate characterization. The chapter 4 the study of the productive chain of this product in Parana State, which includes the paranaense, the brazilian and the worldwide panoramic view of the production volume and commercialization of the ginger; characterization of the agricultural community; identification and characterization of others different levels of the productive chain and also, the main strangulation points on these different levels of the productive chain. In the chapter 5 the agricultural process of the ginger benefit and cultivation in Morretes Town, Paraná, Brazil was caracterized. In the chapter 6 the hygienic-sanitary conditions of the producers establishments, postharvest benefit system and manipulation conditions of crude ginger in the paranaense coastland, Brazil were evaluated with an aim to subsidy the ofert of the best quality product to consumer market. In general, the cleaning and hygienic conditions were precarious, determining a high potential of ginger contamination with agents that can put in risk the consumers' health. The chapter 7 presents the results of the commercialization establishments in the metropolitan area of Curitiba considering adequation to the current norm. Of the observed items, the manipulation conditions was considered precarious due to the inadequate conditions that contributes to contamination, bringing about serious problems to consumers' health. The chapter 8 aimed the microbiological quality of the ginger market in the metropolitan area of Curitiba based on the Brazilian legislation. The microbiological analysis found total coliforms, 45° C/g coliforms, Escherichia coli most probable number (MPN) and Salmonella sp presence. Synthetizing, a group of considerations and recommendations to economic agents that actuate and carry on the productive chain of the ginger in the Parana State, specially in Morretes Town, is presented in the chapter

Transfert de gène dans le système nerveux central à l'aide de vecteurs recombinants dérivés de l'Adeno-associated virus dans un modèle canin de mucopolysaccharidose de type I et chez le primate

Les vecteurs dérivés de l'adéno-associated virus sont particulièrement attractifs pour un transfert de gène à long terme dans le SNC. La mucopolysaccharidose de type I est une maladie de surcharge lysosomale. La forme la plus sévère est caractérisée par des atteintes neurologiques graves pour lesquelles aucun traitement efficace n existe. Nous avons évalué le transfert de gène médié par un vecteur AAVr 5 dans le SNC d un modèle canin MPS I. Quatre injections stéréotaxiques permettent une diffusion du vecteur dans la totalité du SNC avec une correction des lésions de surcharge et des désordres biochimiques. L efficacité de transduction des sérotypes d AAV dans le SNC étant principalement évaluée chez les rongeurs, nous avons étudié le profil de transduction de 3 sérotypes d AAVr : AAVr 1, 2 et 5 dans le SNC de primates. L AAVr 1 permet le transfert de gène le plus efficace dans le SNC de primates. Ces études confirment la faisabilité du transfert de gène dans le SNC d animaux de grande taille.Adeno-associated viral vectors (AAV) are nonpathogenic for humans and allow for the long term expression of transgenes in the central nervous systeme (CNS). Mucopolysaccaridosis type I is a lysomal storage disorder. The most severe form of MPS I is characterised by severe neuronal symptoms. We evaluated the efficacy of gene replacement therapy into the CNS of a canine model of MPS I using an rAAV5 vector. Four stereotaxic injections prevented glycoaminoglycan and secondary ganglioside accumulations. The pattern of transduction of AAV serotypes has been described predominantly in rodents. In addition to this study, we evaluated the transduction pattern of three AAV serotypes after intracerebral injection in the CNS of nonhuman primates: rAAV1, rAAV2, and rAAV5. rAAV1 seems to be the most efficient serotype in the CNS of nonhuman primates. In these studies, we have shown the feasibility of gene therapy with AAV vectors in the brain of large animal models.NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Un logiciel pour l'aide à l'analyse de cartes d'acteurs réalisées à main levée

Atelier Démo associé à la conférence SAGEO, Rouen, 6 novembre 2017A software for automatic recognition of various shapes on hand sketch maps drawn on a shelf or sheet is described. Sketches are collected during socio-geographical surveys in villages subjected to risks of muddy flows. The chosen method uses several image processings in order to achieve a geometric classification of the elements detected in the sketches. An interaction with the user allows to assign a type of spatial object to each shape. Then, the software computes statistics on the labelled shapes of several sketches, by taking as criteria the different parameters describing the persons who have drawn the sketchs. MOTS-CLÉS : cartes à main levée, reconnaissance de formes, segmentation, ensembles flous, C++Un logiciel permettant la reconnaissance automatique de différentes formes présentes dans des esquisses faites à la main sur tablette ou sur feuille est décrit. Les esquisses sont produites dans le cadre d'enquêtes socio-géographiques dans des villages soumis à des risques de coulées d'eau boueuse. L'approche développée utilise plusieurs traitements d'images afin de parvenir à une classification géométrique des éléments détectés dans les esquisses. Une interaction avec l'utilisateur permet d'attribuer à chaque élément un type d'objet spatial. Le logiciel peut alors calculer des statistiques sur les objets présents dans un ensemble d'esquisses, en prenant comme critères les différents paramètres décrivant les personnes ayant dessiné les esquisses

Long-range connectivity of mouse primary somatosensory barrel cortex

The primary somatosensory barrel cortex processes tactile vibrissae information, allowing rodents to actively perceive spatial and textural features of their immediate surroundings. Each whisker on the snout is individually represented in the neocortex by an anatomically identifiable 'barrel' specified by the segregated termination zones of thalamocortical axons of the ventroposterior medial nucleus, which provide the primary sensory input to the neocortex. The sensory information is subsequently processed within local synaptically connected neocortical microcircuits, which have begun to be investigated in quantitative detail. In addition to these local synaptic microcircuits, the excitatory pyramidal neurons of the barrel cortex send and receive long-range glutamatergic axonal projections to and from a wide variety of specific brain regions. Much less is known about these long-range connections and their contribution to sensory processing. Here, we review current knowledge of the long-range axonal input and output of the mouse primary somatosensory barrel cortex. Prominent reciprocal projections are found between primary somatosensory cortex and secondary somatosensory cortex, motor cortex, perirhinal cortex and thalamus. Primary somatosensory barrel cortex also projects strongly to striatum, thalamic reticular nucleus, zona incerta, anterior pretectal nucleus, superior colliculus, pons, red nucleus and spinal trigeminal brain stem nuclei. These long-range connections of the barrel cortex with other specific cortical and subcortical brain regions are likely to play a crucial role in sensorimotor integration, sensory perception and associative learning

PGC-1 alpha activity in nigral dopamine neurons determines vulnerability to alpha-synuclein

Introduction: Mitochondrial dysfunction and oxidative stress are critical factors in the pathogenesis of age-dependent neurodegenerative diseases. PGC-1 alpha, a master regulator of mitochondrial biogenesis and cellular antioxidant defense, has emerged as a possible therapeutic target for Parkinson's disease, with important roles in the function and survival of dopaminergic neurons in the substantia nigra. The objective of this study is to determine if the loss of PGC-1 alpha activity contributes to alpha-synuclein-induced degeneration. Results: We explore the vulnerability of PGC-1 alpha null mice to the accumulation of human alpha-synuclein in nigral neurons, and assess the neuroprotective effect of AAV-mediated PGC-1 alpha expression in this experimental model. Using neuronal cultures derived from these mice, mitochondrial respiration and production of reactive oxygen species are assessed in conditions of human alpha-synuclein overexpression. We find ultrastructural evidence for abnormal mitochondria and fragmented endoplasmic reticulum in the nigral dopaminergic neurons of PGC-1 alpha null mice. Furthermore, PGC-1 alpha null nigral neurons are more prone to degenerate following overexpression of human alpha-synuclein, an effect more apparent in male mice. PGC-1 alpha overexpression restores mitochondrial morphology, oxidative stress detoxification and basal respiration, which is consistent with the observed neuroprotection against alpha-synuclein toxicity in male PGC-1 alpha null mice. Conclusions: Altogether, our results highlight an important role for PGC-1 alpha in controlling the mitochondrial function of nigral neurons accumulating alpha-synuclein, which may be critical for gender-dependent vulnerability to Parkinson's disease

Efficient CNS targeting in adult mice by intrathecal infusion of single-stranded AAV9-GFP for gene therapy of neurological disorders

Adeno-associated virus (AAV) gene therapy constitutes a powerful tool for the treatment of neurodegenerative diseases. While AAVs are generally administered systemically to newborns in preclinical studies of neurological disorders, in adults the maturity of the blood-brain barrier (BBB) must be considered when selecting the route of administration. Delivery of AAVs into the cerebrospinal fluid (CSF) represents an attractive approach to target the central nervous system (CNS) and bypass the BBB. In this study, we investigated the efficacy of intra-CSF delivery of a single-stranded (ss) AAV9-CAG-GFP vector in adult mice via intracisternal (iCist) or intralumbar (it-Lumb) administration. It-Lumb ssAAV9 delivery resulted in greater diffusion throughout the entire spinal cord and green fluorescent protein (GFP) expression mainly in the cerebellum, cortex and olfactory bulb. By contrast, iCist delivery led to strong GFP expression throughout the entire brain. Comparison of the transduction efficiency of ssAAV9-CAG-GFP versus ssAAV9-SYN1-GFP following it-Lumb administration revealed widespread and specific GFP expression in neurons and motoneurons of the spinal cord and brain when the neuron-specific synapsin 1 (SYN1) promoter was used. Our findings demonstrate that it-Lumb ssAAV9 delivery is a safe and highly efficient means of targeting the CNS in adult mice

New polyclonal antibodies, inhibit selectively tumor growth and invasion and synergize with immune checkpoint inhibitors

International audienceHeterologous polyclonal antibodies (pAb) were shown to possess oncolytic properties a century ago with reported clinical responses. More recent pre-clinical models confirm pAb efficacy though their ability to tackle complex target antigens, which reduces susceptibility to tumor escape. Owing to the recent availability of glyco-humanized pAbs with acceptable clinical safety profile, we revisited use of pAbs in oncology and highlighted their therapeutic potential against multiple cancer types.Murine anti-tumor pAbs were generated after repeated immunization of rabbits with murine tumor cell lines from hepatocarcinoma, melanoma, and colorectal cancers. Anti-tumor pAbs recognized and showed cytotoxicity against their targets without cross-reactivity with healthy tissues. In vivo, pAbs are effective alone, moreover, these pAbs synergize with, immune checkpoints inhibitors like anti-PDL-1 in several cancer models. They elicited an anti-tumor host immune response and prevented metastases.The anticancer activity of pAbs was also confirmed in xenografted NMRI nude mice using glyco-humanized pAbs (GH-pAbs) produced by repeated immunization of pigs with human tumor cell lines.In conclusion, the availability of bioengineered GH-pAb allows to revisit passive immunotherapy with oncolytic pAb to fight against solid tumor and cancer metastasis

FoxO3a overexpression prevents both glycogen overload and autophagic buildup in skeletal muscle of Pompe disease.

International audienc