MESURE ET CALCUL DES DUREES DE VIE DE NIVEAUX n=3 ET 4 DE Al IV.

Les durées de vie des niveaux 3s 1P1, 3s 3P1, 4s (3/2)2 et de quelques niveaux 4p et 4d ont été mesurées par la méthode du faisceau-lame. Un calcul de probabilités de transition au second ordre est présenté. Résultats expérimentaux et théoriques sont comparés.The lifetimes of the 3s 1P1, 3s 3P1, 4s (3/2)2 levels and of several 4d and 4p lewls in Neon-like Al IV have been determined using the beam-foilmethod. Our calculation of the transition probabilities is made to the second order. Results are compared

The JAK2-STAT3 pathway is necessary and sufficient to induce reactivity in astrocytes

International audienceAstrocyte reactivity is a hallmark of neurological diseases. This response has been observed for over a century; yet, its functional consequences are still unclear, and the signaling cascades that control reactive astrocytes are not established. Several pathways are classically associated with astrocyte reactivity but their direct contribution is often not demonstrated or the reactive phenotype characterization is limited. Here, we used viral vectors targeting astrocytes to express elements or reporter systems of the JAK2-STAT3 pathway in several mouse models of neurodegenerative diseases (ND) in vivo. To explore the involvement of this cascade in astrocyte reactivity, we performed histological, biochemical analysis as well as astrocyte-specific transcriptomics. We found that STAT3 accumulated in the nucleus of reactive astrocytes in multiple animal models of ND. We developed a viral vector-based reporter system to monitor STAT3 activation in situ. Using this STAT3-reporter in selected murine models of ND, we confirmed that the JAK-STAT3 pathway is activated in reactive astrocytes. Expression of the pathway-specific inhibitor SOCS3 by viral gene transfer, prevented reactivity in mouse models of ND. SOCS3-expressing astrocytes expressed low levels of GFAP and vimentin, recovered a normal morphology and displayed a transcriptional profile of resting astrocytes. Mirror experiments were performed by overexpressing a constitutively active form of JAK2 (JAK2ca) in astrocytes of WT mice to activate the JAK2-STAT3 pathway in the absence of any pathological context. JAK2ca expression in striatal and hippocampal astrocytes activated STAT3, as demonstrated by an increased activity of the STAT3-reporter, enhanced STAT3 phosphorylation and nuclear accumulation. JAK2ca-expressing astrocytes were hypertrophic and they overexpressed GFAP along with many transcripts characteristics of reactive astrocytes. Our results show that the JAK-STAT3 pathway is necessary and sufficient for astrocyte reactivity in various disease contexts. This core cascade can be targeted to modulate reactive astrocytes and better understand their roles in ND

Targeting Neuroinflammation to Treat Alzheimer's Disease

Over the past few decades, research on Alzheimer's disease (AD) has focused on pathomechanisms linked to two of the major pathological hallmarks of extracellular deposition of beta-amyloid peptides and intra-neuronal formation of neurofibrils. Recently, a third disease component, the neuroinflammatory reaction mediated by cerebral innate immune cells, has entered the spotlight, prompted by findings from genetic, pre-clinical, and clinical studies. Various proteins that arise during neurodegeneration, including beta-amyloid, tau, heat shock proteins, and chromogranin, among others, act as danger-associated molecular patterns, that-upon engagement of pattern recognition receptors-induce inflammatory signaling pathways and ultimately lead to the production and release of immune mediators. These may have beneficial effects but ultimately compromise neuronal function and cause cell death. The current review, assembled by participants of the Chiclana Summer School on Neuroinflammation 2016, provides an overview of our current understanding of AD-related immune processes. We describe the principal cellular and molecular players in inflammation as they pertain to AD, examine modifying factors, and discuss potential future therapeutic targets.status: publishe