Péptidos sintéticos o naturales que unen la proteína fosfatasa 2A, procedimiento de identificación y usos

Péptidos sintéticos o naturales que unen la proteína fosfatasa 2A, procedimiento de identificación y usos. La presente invención se refiere a nuevos péptidos, sintéticos o naturales, útiles en particular en el tratamiento de las infecciones víricas o parasitarias o en el tratamiento de tumores, siendo dicho péptidos de un tamaño inferior a 30 aminoácidos, preferentemente inferior a 20 aminoácidos, en particular de 15 a 20 aminoácidos, y caracterizados porque ligan, in vitro, de manera específica, una holoenzima proteína fosfatasa de tipo 2A o una de sus sub-unidades. La invención se refiere asimismo a un procedimiento de identificación de dichos péptidos, y a sus usos.Institut Pasteur, Institut National de la Recherche Agronomique, Consejo Superior de Investigaciones Científicas (España), Centre National de la Recherche Scientifique (CNRS)T3 Traducción de patente europe

Organoïdes hypophysaires : des outils pour caractériser le développement, la plasticité et les pathologies hypophysaires ?

L’hypophyse, glande maitresse de l’organisme, occupe une place centrale dans le système endocrinien. Composée d’un lobe antérieur (adénohypophyse) responsable de la synthèse d’hormones et d’un lobe postérieur (neurohypophyse) de structure nerveuse, elle reçoit des informations hormonales en provenance de l’hypothalamus, des organes périphériques et de ses propres cellules lui permettant de réguler les grandes fonctions physiologiques telles que la croissance, le métabolisme, la reproduction ou le stress. Constituée de plusieurs types cellulaires, chacun dédié à une fonction, l’adénohypophyse doit adapter ses sécrétions hormonales en fonction de la demande physiologique ou des modifications de son microenvironnement liées à des causes physiologiques, contextuelles ou pathologiques. Pour cela, elle fait preuve d’une grande plasticité qui met en jeu des changements dans le nombre, voire l’identité, des cellules sécrétrices. Des cellules souches/progénitrices présentes dans l’hypophyse chez l’adulte pourraient être impliquées. Les mécanismes sous-jacents à cette plasticité sont mal élucidés. Afin de mieux les comprendre, des systèmes d’étude in vitro, tels que les organoïdes capables de mimer la structure architecturale et la fonction tissulaires, offrent une opportunité intéressante. Ils permettent également d’appréhender les dysfonctionnements hypophysaires et d’envisager des approches thérapeutiques chez l’Homme et l’animal d’élevage. En outre, leur utilisation permet de contribuer au principe des 3R pour les approches expérimentales : remplacer, réduire et raffiner. Si les modèles hypophysaires actuels sont en cours d’émergence chez l’humain et les rongeurs, leur mise en place chez les espèces à intérêt agronomique représente un enjeu important. Le but de cette revue est de faire un état des lieux sur l’avancée des travaux visant à développer les modèles d’organoïdes hypophysaires en évaluant leurs avantages et leurs inconvénients. Auparavant, des éléments concernant l’histologie de l’hypophyse, son développement lors de l’embryogénèse et ses capacités d’adaptation à des variations de son environnement seront décrits

Glucose-induced posttranslational activation of protein phosphatases PP2A and PP1 in yeast

The protein phosphatases PP2A and PP1 are major regulators of a variety of cellular processes in yeast and other eukaryotes. Here, we reveal that both enzymes are direct targets of glucose sensing. Addition of glucose to glucose-deprived yeast cells triggered rapid posttranslational activation of both PP2A and PP1. Glucose activation of PP2A is controlled by regulatory subunits Rts1, Cdc55, Rrd1 and Rrd2. It is associated with rapid carboxymethylation of the catalytic subunits, which is necessary but not sufficient for activation. Glucose activation of PP1 was fully dependent on regulatory subunits Reg1 and Shp1. Absence of Gac1, Glc8, Reg2 or Red1 partially reduced activation while Pig1 and Pig2 inhibited activation. Full activation of PP2A and PP1 was also dependent on subunits classically considered to belong to the other phosphatase. PP2A activation was dependent on PP1 subunits Reg1 and Shp1 while PP1 activation was dependent on PP2A subunit Rts1. Rts1 interacted with both Pph21 and Glc7 under different conditions and these interactions were Reg1 dependent. Reg1-Glc7 interaction is responsible for PP1 involvement in the main glucose repression pathway and we show that deletion of Shp1 also causes strong derepression of the invertase gene SUC2. Deletion of the PP2A subunits Pph21 and Pph22, Rrd1 and Rrd2, specifically enhanced the derepression level of SUC2, indicating that PP2A counteracts SUC2 derepression. Interestingly, the effect of the regulatory subunit Rts1 was consistent with its role as a subunit of both PP2A and PP1, affecting derepression and repression of SUC2, respectively. We also show that abolished phosphatase activation, except by reg1Δ, does not completely block Snf1 dephosphorylation after addition of glucose. Finally, we show that glucose activation of the cAMP-PKA (protein kinase A) pathway is required for glucose activation of both PP2A and PP1. Our results provide novel insight into the complex regulatory role of these two major protein phosphatases in glucose regulation

Association of the PHACTR1/EDN1 genetic locus with spontaneous coronary artery dissection

Background: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene. Objectives: This study sought to test the association between the rs9349379 genotype and SCAD. Methods: Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD. Results: The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval [CI]: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence. Conclusions: The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Recherches sur les proteines phosphatases de l'ovocyte de Xenope. Purification d'une serine/threonine phosphatase et etude de la regulation de son activite de tyrosine phosphatase

SIGLEINIST T 76915 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Methods of screening apoptosis modulating compounds, compounds identified by said methods and use of said compounds as therapeutic agents

Filing Date: 2002-03-07.The invention relates to the modulation of apoptosis in mammalian cells. More particularly, the invention provides methods for identifying novel pro-apoptotic or anti-apoptotic cellular polypeptides, methods of screening compounds which modulate apoptosis, and method of detecting early events of the apoptotic process

Protein phosphatase 2A: a definite player in viral and parasitic regulation

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