Stress granules, RNA-binding proteins and polyglutamine diseases: too much aggregation?

Stress granules (SGs) are membraneless cell compartments formed in response to different stress stimuli, wherein translation factors, mRNAs, RNA-binding proteins (RBPs) and other proteins coalesce together. SGs assembly is crucial for cell survival, since SGs are implicated in the regulation of translation, mRNA storage and stabilization and cell signalling, during stress. One defining feature of SGs is their dynamism, as they are quickly assembled upon stress and then rapidly dispersed after the stress source is no longer present. Recently, SGs dynamics, their components and their functions have begun to be studied in the context of human diseases. Interestingly, the regulated protein self-assembly that mediates SG formation contrasts with the pathological protein aggregation that is a feature of several neurodegenerative diseases. In particular, aberrant protein coalescence is a key feature of polyglutamine (PolyQ) diseases, a group of nine disorders that are caused by an abnormal expansion of PolyQ tract-bearing proteins, which increases the propensity of those proteins to aggregate. Available data concerning the abnormal properties of the mutant PolyQ disease-causing proteins and their involvement in stress response dysregulation strongly suggests an important role for SGs in the pathogenesis of PolyQ disorders. This review aims at discussing the evidence supporting the existence of a link between SGs functionality and PolyQ disorders, by focusing on the biology of SGs and on the way it can be altered in a PolyQ disease context.ALG-01-0145-FEDER-29480, SFRH/BD/133192/2017, SFRH/BD/133192/2017, SFRH/BD/148533/2019info:eu-repo/semantics/publishedVersio

Genomic Characterization of Haemophilus parasuis SH0165, a Highly Virulent Strain of Serovar 5 Prevalent in China

Haemophilus parasuis can be either a commensal bacterium of the porcine respiratory tract or an opportunistic pathogen causing Glässer's disease, a severe systemic disease that has led to significant economical losses in the pig industry worldwide. We determined the complete genomic sequence of H. parasuis SH0165, a highly virulent strain of serovar 5, which was isolated from a hog pen in North China. The single circular chromosome was 2,269,156 base pairs in length and contained 2,031 protein-coding genes. Together with the full spectrum of genes detected by the analysis of metabolic pathways, we confirmed that H. parasuis generates ATP via both fermentation and respiration, and possesses an intact TCA cycle for anabolism. In addition to possessing the complete pathway essential for the biosynthesis of heme, this pathogen was also found to be well-equipped with different iron acquisition systems, such as the TonB system and ABC-type transport complexes, to overcome iron limitation during infection and persistence. We identified a number of genes encoding potential virulence factors, such as type IV fimbriae and surface polysaccharides. Analysis of the genome confirmed that H. parasuis is naturally competent, as genes related to DNA uptake are present. A nine-mer DNA uptake signal sequence (ACAAGCGGT), identical to that found in Actinobacillus pleuropneumoniae and Mannheimia haemolytica, followed by similar downstream motifs, was identified in the SH0165 genome. Genomic and phylogenetic comparisons with other Pasteurellaceae species further indicated that H. parasuis was closely related to another swine pathogenic bacteria A. pleuropneumoniae. The comprehensive genetic analysis presented here provides a foundation for future research on the metabolism, natural competence and virulence of H. parasuis

Aspect epidemiologique, etiologique et therapeutique de l’insuffisance cardiaque au service de medecine de l’hopital Somine Dolo de Mopti.: Epidemiological, etiological and therapeutic aspects of heart failure in the medical service, Somine Dolo Hospital of Mopti.

Objectif : L’insuffisance cardiaque constitue un problème majeur de santé publique. C’est une pathologie fréquente et grave. L’objectif de notre étude était de décrire les aspects épidémiologiques, étiologiques et thérapeutiques de l’insuffisance cardiaque au service de médecine de l’hôpital Sominé Dolo de Mopti. Méthodes : Une étude rétrospective descriptive a été effectuée pour décrire les aspects épidémiologiques, étiologiques et thérapeutiques de l’insuffisance cardiaque au service de médecine de l’hôpital Sominé Dolo de Mopti, portant sur la période du 1 janvier au 31 décembre 2016. Ont été inclus tous les patients hospitalisés durant cette période pour l’insuffisance cardiaque. Résultats : L’étude a concerné 164 patients sur 468 patients hospitalisés soit une prévalence hospitalière de 35,04 %. Le sexe masculin a été de (54,27 %) soit un sex ratio de 1,2.Les moins de 40 ans ont constitué 42,68% des patients. Les facteurs de risques les plus fréquents ont été : l’hypertension artérielle (39,02%), l’hypercholestérolémie (33,53%) et l’hypertriglycéridémie (20,73%).La cardiomyopathie dilatée a été la principale étiologie retrouvée 24, 40%. Plus de 60 % des patients ont été mis sous le traitement classique (IEC, Beta bloquant, Diurétique, antagoniste des récepteurs mineralocorticoide). La non observance du traitement a été la principale cause de rehospitalisation. Conclusion : L’insuffisance cardiaque est une affection grave et fréquente dans notre milieu. Les mesures de préventions doivent être mise en place à travers une formation continue des personnels de santé pour la détection et la prise en charge précoce de l’insuffisance cardiaque. ABSTRACT:Objective: Heart failure represents a major public health concern, it is a frequent and serious pathology. The objective of our work aimed at describing epidemiological, etiological and therapeutic aspects of heart failure in the medical service of Sominé Dolo hospital of Mopti. Methods: it is a descriptive retrospective study that was carried out in order to describe epidemiological, etiological and therapeutic aspects of heart failure in the medical service of Sominé Dolo hospital of Mopti from January 1st to December 31st 2016. All the patients hospitalized during that period were involved. Outcomes: the study involved 164 patients out of 468 patients hospitalized that is a hospital prevalence of 35.04%. Male patients represented 54.27% which makes a sex ratio of 1.2. 42.68% of patients were minimum 40 years old. The most frequent risk factors were high blood pressure 39.02%%, hypercholesterolemia 33.53% and hypertriglyceridemia 20.73%%. Dilated cardiomyopathy was the main etiology found 24.40%. More than 60% of the patients were under classical treatment (IEC, Beta blocking agent, diuretic, and mineralocorticoid receptor antagonists). The failure of following the treatment was the main cause of rehospitalization. Conclusion: Heart failure is a serious and frequent disease inour area. Prevention measures should be taken through the ongoing training of health personnel in the early detection and treatment of heart failure