C-fos and c-jun Proto-Oncogene Expression Is Decreased in Psoriasis: an In Situ Quantitative Analysis

Psoriasis is a common, sometimes sevcre, non-malignant skin disease characterized by hyperproliferation and abnormal differentiation of keratinocytes. Because proto-oncogenes are implicated in both cell proliferation and differentiation, their expression could be modified in skin diseases such as psoriasis. The c-fos and c-jun proto-oncogenes, whose products associate to form a heterodimeric transcription factor, are among the first genes to be expressed when certain cells are stimulated to either proliferate or differentiate. Recent studies in our laboratory have shown that the c-fos protooncogene is highly expressed in normal human adult skin. In the present study, we used in situ hybridization with RNA to compare the expression and localization of c-fos and c-jun transcripts in 15 lesional and non-lesional psoriatic skin samples. Two clinical variants of psoriasis were studied: the most severe and chronic form or plaque-type psoriasis (N = 10) and rapidly resolutive guttate-type psoriasis (N = 5). Quantitative analysis was performed using a semi-automatic image analyzer and the “Starwise grain” software program. Our control samples included 10 normal skins and eight specimens from other benign hyperproliferative non-psoriatic skin diseases, consisting of three with inflammation (seborrheic dermatitis and atopic dermatitis), and 5 without inflammation (seborrheic keratoses). Control genes we used for in situ hybridization and RNA integrity were keratin 14, which is expressed in the epidermis and was normally expressed in all tissue analyzed, and ribosomal RNA. Our data showed that c-fos and c-jun were expressed to an equivalent extent, both spatially and quantitatively, in all specimens tested. Expression was significantly decreased in plaque-type but not in guttate-type psoriasis. It was also decreased in the three other benign inflammatory cutaneous hyperproliferative disorders, but not in the five non-inflammatory cases. These results were surprising because hyperproliferation was here associated with a decrease in proto-oncogene expression, thus suggesting that c-fos and c-jun do not play a crucial role in the control of keratinocyte proliferation in vivo. However, their reduced expression in some abnormally differentiated skins indicates that both c-fos and c-jun proto-oncogenes may play a key role in keratinocyte differentiation. Their altered expression correlated with severity of the disease and the presence of an inflammatory infiltrate. These data offer a new insight into the role and regulation of these proto-oncogenes in vivo in humans

Synthèse et caractérisation de nouveaux complexes aryloxy à base de tungstène

International audienc

Beyond PrPres Type 1/Type 2 Dichotomy in Creutzfeldt-Jakob Disease

Sporadic Creutzfeldt-Jakob disease (sCJD) cases are currently subclassified according to the methionine/valine polymorphism at codon 129 of the PRNP gene and the proteinase K (PK) digested abnormal prion protein (PrPres) identified on Western blotting (type 1 or type 2). These biochemically distinct PrPres types have been considered to represent potential distinct prion strains. However, since cases of CJD show co-occurrence of type 1 and type 2 PrPres in the brain, the basis of this classification system and its relationship to agent strain are under discussion. Different brain areas from 41 sCJD and 12 iatrogenic CJD (iCJD) cases were investigated, using Western blotting for PrPres and two other biochemical assays reflecting the behaviour of the disease-associated form of the prion protein (PrPSc) under variable PK digestion conditions. In 30% of cases, both type 1 and type 2 PrPres were identified. Despite this, the other two biochemical assays found that PrPSc from an individual patient demonstrated uniform biochemical properties. Moreover, in sCJD, four distinct biochemical PrPSc subgroups were identified that correlated with the current sCJD clinico-pathological classification. In iCJD, four similar biochemical clusters were observed, but these did not correlate to any particular PRNP 129 polymorphism or western blot PrPres pattern. The identification of four different PrPSc biochemical subgroups in sCJD and iCJD, irrespective of the PRNP polymorphism at codon 129 and the PrPres isoform provides an alternative biochemical definition of PrPSc diversity and new insight in the perception of Human TSE agents variability

Pour une démocratie socio-environnementale : cadre pour une plate-forme participative « transition écologique »

Contribution publiée in Penser une démocratie alimentaire Volume II – Proposition Lascaux entre ressources naturelles et besoins fondamentaux, F. Collart Dutilleul et T. Bréger (dir), Inida, San José, 2014, pp. 87-111.International audienceL’anthropocène triomphant actuel, avec ses forçages environnementaux et sociaux, est à l’origine de l’accélération des dégradations des milieux de vie sur Terre et de l’accentuation des tensions sociales et géopolitiques. Passer à un anthropocène de gestion équitable, informé et sobre vis-à-vis de toutes les ressources et dans tous les secteurs d’activité (slow anthropocene), impose une analyse préalable sur l’ensemble des activités et des rapports humains. Cette transition dite « écologique », mais en réalité à la fois sociétale et écologique, est tout sauf un ajustement technique de secteurs dits prioritaires et technocratiques. Elle est avant tout culturelle, politique et philosophique au sens propre du terme. Elle est un horizon pour des trajectoires de développement humain, pour des constructions sociales et économiques, censées redéfinir socialement richesse, bien-être, travail etc. La dénomination « transition écologique » est largement véhiculée, mais ses bases conceptuelles ne sont pas entièrement acquises ni même élaborées. Dans ce contexte, les étudiants en première année de Master BioSciences à l’Ecole Normale Supérieure (ENS) de Lyon ont préparé une première étude analytique de ce changement radical et global de société pour mieux comprendre dans quelle société ils souhaitent vivre, en donnant du sens aux activités humaines présentes et à venir. Une trentaine de dossiers sur divers secteurs d’activités et acteurs de la société ont été produits et ont servis de support à cette synthèse. Plus largement, le but est de construire un socle conceptuel et une plate-forme de travail sur lesquels les questions de fond, mais aussi opérationnelles, peuvent être posées et étudiées en permanence. Cette démarche participative est ouverte à la collectivité sur le site http://institutmichelserres.ens-lyon.fr/