Reconceptualizing the Republic: Diversity and Education in France, 1945–2008

Since the nineteenth century, France, not unlike the United States, has experienced significant immigration and, as a result, great flux. Yet, the French public discourse and policy instruments concerned with ethnic and racial diversities evolved in sharp contrast to those in the United States. Whereas U.S. nation-building incorporated the recognition of ethnoracial identities, with all of its trials and tribulations, the French nation's trajectory assumed a unitary form. Recent developments, however, point to changes in the Republic's projection of its identity and its citizenry. An analysis of school teaching finds that the Republic is now re-envisioned as open and tolerant of diversity, though more from a universalistic, normative perspective—increasingly indexed at the transnational level—than from a perspective that privileges France's immigrant and colonial past. </jats:p

Small-Molecule Activators of Insulin-Degrading Enzyme Discovered through High-Throughput Compound Screening

Background: Hypocatabolism of the amyloid β-protein (Aβ) by insulin-degrading enzyme (IDE) is implicated in the pathogenesis of Alzheimer disease (AD), making pharmacological activation of IDE an attractive therapeutic strategy. However, it has not been established whether the proteolytic activity of IDE can be enhanced by drug-like compounds. Methodology/Principal Findings: Based on the finding that ATP and other nucleotide polyphosphates modulate IDE activity at physiological concentrations, we conducted parallel high-throughput screening campaigns in the absence or presence of ATP and identified two compounds—designated Ia1 and Ia2—that significantly stimulate IDE proteolytic activity. Both compounds were found to interfere with the crosslinking of a photoaffinity ATP analogue to IDE, suggesting that they interact with a bona fide ATP-binding domain within IDE. Unexpectedly, we observed highly synergistic activation effects when the activity of Ia1 or Ia2 was tested in the presence of ATP, a finding that has implications for the mechanisms underlying ATP-mediated activation of IDE. Notably, Ia1 and Ia2 activated the degradation of Aβ by ∼700% and ∼400%, respectively, albeit only when Aβ was presented in a mixture also containing shorter substrates. Conclusions/Significance: This study describes the first examples of synthetic small-molecule activators of IDE, showing that pharmacological activation of this important protease with drug-like compounds is achievable. These novel activators help to establish the putative ATP-binding domain as a key modulator of IDE proteolytic activity and offer new insights into the modulatory action of ATP. Several larger lessons abstracted from this screen will help inform the design of future screening campaigns and facilitate the eventual development of IDE activators with therapeutic utility

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Regulation du cycle cellulaire : roles respectifs de la synthese et de la phosphorylation des proteines

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Elaboration et caracterisation d'une membrane minerale conductrice a base d'un melange d'oxydes TiO2-RuO2

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Rôle de la traduction locale de CaMKIIalpha dans la plasticité et le développement du bulbe olfactif adulte

Thèse Marie Néant-Fery - Résumé La traduction locale dendritique de CaMKIIa a été mise en évidence notamment dans l hippocampe (HC), où elle contribue à la plasticité synaptique et à l élaboration de certaines formes de mémoire. Nous avons étudié son rôle dans le bulbe olfactif (BO) de la souris, région du cerveau hautement plastique en réponse à l activité olfactive. Nous avons montré que l ARNm de CaMKIIa est localisé dans les dendrites et enrichi aux synapses des cellules granulaires (CG), où il peut être traduit localement. Sa localisation synaptique dépend de l activité olfactive et semble être régulée par les récepteurs NMDA. Dans des souris mutantes dépourvues du 3 UTR de l ARNm de CaMKIIa (critique pour la localisation dendritique du messager), cette localisation dendritique est dramatiquement réduite, et ces souris présentent des défauts d apprentissage olfactif. Cette étude indique donc un rôle nouveau pour la traduction locale de CaMKIIa dans la plasticité olfactive. Le BO possède de plus une forme de métaplasticité conférée par le renouvellement permanent des CG chez l adulte. Nous avons utilisé cette neurogénèse adulte dans le BO comme un nouveau modèle d étude de la traduction locale de CaMKIIa. Dans le GC néoformées, l ARNm de CaMKIIa est également transporté dans les dendrites et enrichi aux synapses. Chez les mutants 3 UTR, ces néoneurones présentent des anomalies de développement de l arborisation dendritique. Les conséquences fonctionnelles de ces anomalies restent à être élucidées, mais cette seconde étude révèle pour la première fois le rôle de la traduction locale de CaMKIIa dans le développement dendritiquePARIS-BIUSJ-Biologie recherche (751052107) / SudocSudocFranceF