Mécanismes et conséquences des mutations

L’identification des mutations à l’origine de maladies génétiques chez l’homme a pris ces dernières années un essor considérable. Il est devenu possible d’établir le spectre des mutations délétères pour une maladie génétique donnée, et des bases de données internationales sont aujourd’hui accessibles via le réseau Internet. Le diagnostic génotypique des maladies héréditaires occupe actuellement une place prépondérante en matière de conseil génétique et de diagnostic prénatal. La connaissance du type de mutation délétère et des mécanismes en cause est essentielle pour déterminer la stratégie de diagnostic moléculaire adaptée à chaque situation. Cet article a pour objectif de présenter les différents types de mutations responsables de maladies génétiques (substitutions nucléotidiques, délétions ou insertions de petite taille, mutations dynamiques, grands remaniements…) et de récapituler les connaissances actuelles concernant les mécanismes moléculaires à l’origine de ces mutations. Leurs conséquences sur l’expression du gène (transcription et maturation du transcrit) et sur la fonction de la protéine sont également abordées dans cet article.The identification of mutations leading to human genetic diseases has grown into an intensive research field during the last few years. Through novel DNA analysis progress, it is now possible to determine the mutational spectrum for a given genetic disease and international databases are now available online. Genetic diagnosis of hereditary diseases has become an essential tool in genetic counselling and prenatal diagnosis. The knowledge of the deleterious mutation type and the molecular associated mechanism is fundamental in order to devise the optimal molecular diagnosis strategy. This review aims to present the various mutation categories involved in genetic diseases (single base-pair substitutions, small deletions or insertions, dynamic mutations, gross DNA lesions…) and to summarize our current knowledge about the main molecular mechanisms responsible for these mutations. Their deleterious consequences on gene expression, including transcription and transcript maturation, and protein loss or gain of function are also discussed in this review

Study on Investment in Agricultural Research: Review for Switzerland

This report forms part of the deliverables from a project called "IMPRESA" which has been awarded financial support by the European Commission under the 7th Framework Programme. The project aims to evaluate the impact of research on agriculture performed in the EU, collecting data on recent trends in investment in agricultural research, and developing a framework combining case studies, econometric analysis and modelling for assessing its impact. A first task is to prepare country-level analysis of the agricultural research expenditures and an assessment of the availabilities of data regarding public and private investments in agricultural research. Agricultural research covers all research on the promotion of agriculture, forestry, fisheries and foodstuff production. It includes: research on chemical fertilisers, biocides, biological pest control and the mechanisation of agriculture; research on the impact of agricultural and forestry activities on the environment; research in the field of developing food productivity and technology

Sensory Cell Proliferation within the Olfactory Epithelium of Developing Adult Manduca sexta (Lepidoptera)

BACKGROUND: Insects detect a multitude of odors using a broad array of phenotypically distinct olfactory organs referred to as olfactory sensilla. Each sensillum contains one to several sensory neurons and at least three support cells; these cells arise from mitotic activities from one or a small group of defined precursor cells. Sensilla phenotypes are defined by distinct morphologies, and specificities to specific odors; these are the consequence of developmental programs expressed by associated neurons and support cells, and by selection and expression of subpopulations of olfactory genes encoding such proteins as odor receptors, odorant binding proteins, and odor degrading enzymes. METHODOLOGY/PRINCIPAL FINDINGS: We are investigating development of the olfactory epithelium of adult M. sexta, identifying events which might establish sensilla phenotypes. In the present study, antennal tissue was examined during the first three days of an 18 day development, a period when sensory mitotic activity was previously reported to occur. Each antenna develops as a cylinder with an outward facing sensory epithelium divided into approximately 80 repeat units or annuli. Mitotic proliferation of sensory cells initiated about 20–24 hrs after pupation (a.p.), in pre-existing zones of high density cells lining the proximal and distal borders of each annulus. These high density zones were observed as early as two hr. a.p., and expanded with mitotic activity to fill the mid-annular regions by about 72 hrs a.p. Mitotic activity initiated at a low rate, increasing dramatically after 40–48 hrs a.p.; this activity was enhanced by ecdysteroids, but did not occur in animals entering pupal diapause (which is also ecdysteroid sensitive). CONCLUSIONS/SIGNIFICANCE: Sensory proliferation initiates in narrow zones along the proximal and distal borders of each annulus; these zones rapidly expand to fill the mid-annular regions. These zones exist prior to any mitotic activity as regions of high density cells which form either at or prior to pupation. Mitotic sensitivity to ecdysteroids may be a regulatory mechanism coordinating olfactory development with the developmental choice of diapause entry

Platelet-Activating Factor Induces Th17 Cell Differentiation

Th17 cells have been implicated in a number of inflammatory and autoimmune diseases. The phospholipid mediator platelet-activating factor (PAF) is found in increased concentrations in inflammatory lesions and has been shown to induce IL-6 production. We investigated whether PAF could affect the development of Th17 cells. Picomolar concentrations of PAF induced IL-23, IL-6, and IL-1β expression in monocyte-derived Langerhans cells (LCs) and in keratinocytes. Moreover, when LC were pretreated with PAF and then cocultured with anti-CD3- and anti-CD28-activated T cells, the latter developed a Th17 phenotype, with a significant increase in the expression of the transcriptional regulator RORγt and enhanced expression of IL-17, IL-21, and IL-22. PAF-induced Th17 development was prevented by the PAF receptor antagonist WEB2086 and by neutralizing antibodies to IL-23 and IL-6R. This may constitute a previously unknown stimulus for the development and persistence of inflammatory processes that could be amenable to pharmacologic intervention

El hermanito diferente

Victoria Rodrigo, PhD- Serie Leamos’ EditorProfessor of Spanish World Languages and Cultures DepartmentGeorgia State Universityhttps://scholarworks.gsu.edu/wcl_leamos/1021/thumbnail.jp

Large increase in bloodstream infections with carbapenem-resistant Acinetobacter species during the first 2 years of the COVID-19 pandemic, EU/EEA, 2020 and 2021

EARS-Net Study Group (Portugal: Manuela Caniça).EARS-Net Study Group participants: Reinhild Strauss, Karl Mertens, Stefana Sabtcheva, Arjana Tambic Andrasevic, Panagiota Maikanti, Helena Žemličková, Henrik Hasman, Marina Ivanova, Kati Räisänen, Sylvie Maugat, Ines Noll, Kassiani Mellou, Ákos Tóth, Kristján Orri Helgason, Stephen Murchan, Giulia Errico, Ieva Voita, Esther Walser-Domjan, Jolanta Miciulevičienė, Monique Perrin, Elizabeth Anne Scicluna, Sjoukje Hs Woudt, Ørjan Samuelsen, Dorota Żabicka, Manuela Caniça, Gabriel Adrian Popescu, Eva Schréterová, Helena Ribič, Maria Belén Aracil García, Hanna Billström.Bloodstream infections (BSIs) with Acinetobacter species commonly have poor outcomes, especially in intensive care unit (ICU) patients [1]. Acinetobacter spp. is intrinsically resistant to many antimicrobials, and additional acquired resistance further complicates the treatment of serious infections in already vulnerable patient groups. Recent data from the European Antimicrobial Resistance Surveillance Network (EARS-Net) show a large and statistically significant increase in reports of Acinetobacter spp. BSIs in the European Union (EU) and European Economic Area (EEA) during the period from 2017 to 2021 [2]. Most of this increase occurred in 2020 and 2021, the first years of the coronavirus disease (COVID-19) pandemic. Here we further explore this trend in a subset of data from laboratories that continuously reported data during that period.info:eu-repo/semantics/publishedVersio