Suchergebnisse

Tortajada, Agustín et alt. ; C3 glomerulopathies (C3G) are a group of severe renal diseases with distinct patterns of glomerular inflammation and C3 deposition caused by complement dysregulation. Here we report the identification of a familial C3G-associated genomic mutation in the gene complement factor H-related 1 (CFHR1), which encodes FHR1. The mutation resulted in the duplication of the N-terminal short consensus repeats (SCRs) that are conserved in FHR2 and FHR5. We determined that native FHR1, FHR2, and FHR5 circulate in plasma as homo- and hetero-oligomeric complexes, the formation of which is likely mediated by the conserved N-terminal domain. In mutant FHR1, duplication of the N-terminal domain resulted in the formation of unusually large multimeric FHR complexes that exhibited increased avidity for the FHR1 ligands C3b, iC3b, and C3dg and enhanced competition with complement factor H (FH) in surface plasmon resonance (SPR) studies and hemolytic assays. These data revealed that FHR1, FHR2, and FHR5 organize a combinatorial repertoire of oligomeric complexes and demonstrated that changes in FHR oligomerization influence the regulation of complement activation. In summary, our identification and characterization of a unique CFHR1 mutation provides insights into the biology of the FHRs and contributes to our understanding of the pathogenic mechanisms underlying C3G. Copyright © 2013, American Society for Clinical Investigation. ; Work in this report was funded by the Spanish Ministerio de Economía y Competitividad (SAF2011-26583), the Fundación Renal Iñigo Alvarez de Toledo and the 7FP European Union project EURenOmics to S. Rodríguez de Córdoba; the "Ramón Areces" Foundation, the Spanish Ministerio de Economía y Competitividad (SAF2011-22988), and the "Red Temática de Investigación Cooperativa en Cáncer(RTICC)" (RD06/0020/1001) to O. Llorca; the Spanish "Ministerio de Economía y Competitividad" (PI0900268) to P. Sánchez-Corral; the MRC UK (G0701298) to C.L. Harris; and the Spanish "Ministerio de Economía y Competitividad" (PS09/00122) to M. López Trascasa. In addition, this work was supported by a grant from the Autonomous Region of Madrid (S2010/BMD-2316) to S. Rodríguez de Córdoba, O. Llorca, M. López Trascasa, and P. Sánchez-Corral. M.C. Pickering is a Wellcome Trust Senior Fellow in Clinical Science (WT098476MA). H. Yébenes was supported by a postdoctoral contract by the RTICC, and C. Abarrategui-Garrido was supported by the "Fundación de Investigación Biomédica del Hospital Universitario La Paz." ; Peer reviewed

« Ancient history has now become a provincial branch of history... » (A. Momigliano).Le pari, en tout cas, est l'expression d'un projet : nous ne souhaitons pas réunir des articles en vue de proposer un panorama-bilan des études anciennes (prenant en compte les dix ou vingt dernières années) — cette entreprise, concevable, impliquerait un autre lieu de publication et exigerait d'autres compétences que les nôtres — mais rassembler des contributions autour d'un thème, et sans souci d'une complétude toujours hors d'atteinte. Nous avons choisi de réfléchir sur le document, non pas en vue de tracer un état des sources, ni d'écrire quelques chapitres d'une Introduction aux études historiques appliquée à l'histoire ancienne, ni de proposer des recettes (si possible inédites ?) de traitement de données, ni d'élaborer une théorie du document. Plus simplement, nous voudrions présenter quelques usages des textes — de nature diverse —, de l'archéologie — elle-même plurielle —, leur croisement aussi, toujours délicat, et interroger des traditions et des pratiques disciplinaires.

This study analyzed gender balance in the texts and illustrations of three recently published, high school US history textbooks and one alternate volume of American history. In all of the American history texts analyzed there were significantly more males than females in text content and illustrations. These textbooks focused on the contributions of those famous Americans who have been a part of the historical record. The record is skewed with regard to gender, leaving teachers and students with the arduous task of acknowledging the absence of women while attempting to fill in the gaps through their own research and resources. Standards committees and textbook publishers should change their focus and teachers and students should confront gender imbalance by integrating high quality women's history resources into the classroom with web-based resources, family and community history projects, young adult literature, history textbook analysis, and the vision of the C3 Framework.

PurposeIn both elementary schools and elementary teacher education programs, social studies is marginalized while standards require increasingly more ambitious reasoning, reading, and writing in social studies than has historically been documented in American elementary schools. The purpose of this paper is to explain the challenges that elementary social studies teacher educators face in preparing elementary school teachers to facilitate the kind of ambitious social studies envisioned in the NCSS's C3 Framework and advocate an approach to successfully address these challenges.Design/methodology/approachThis paper articulates a targeted and ambitious approach to elementary social studies teacher education. The authors describe five recommendations from the teacher education literature for supporting preservice teachers in learning disciplinary-oriented social studies teaching, recommendations that guided the redesign of the social studies methods course. The authors then highlight key aspects of the redesigned methods course and demonstrate how the authors engaged the challenges inherent in the work of elementary social studies teacher education.FindingsAlthough this paper is not arranged in such a way as to substantiate empirical findings, the purpose of the paper is to demonstrate an approach to elementary social studies education aligned with extant literature on preparing teachers to engage in reform teaching practices, specifically those disciplinary oriented practices suggested in NCSS's C3 Framework. As such, the paper should be read as a perspective on practice.Research limitations/implicationsThe type of disciplinary-oriented approach described here is increasingly under investigation in secondary teacher education research and similar approaches are under investigation in elementary math and science education research. To the authors' knowledge, the approach is novel in elementary social studies education. Furthermore, the authors believe it offers a direction for researchers interested in gaps in the literature related to practice based teacher education and disciplinary-oriented social studies teacher education.Practical implicationsThe approach described here offers specific guidance and resources for teacher educators who are struggling with the challenges of the contemporary social studies education landscape and/or who wish to focus methods courses in disciplinary ways.Social implicationsResearch in social studied education has demonstrated that when students are exposed to disciplinary practices in social studies, their literacy skills improve and they learn analytical skills that support their development as citizens (consumption of media, participation in public discourse, ability to discern arguments).Originality/valueAs noted above, the approach described here is novel in elementary social studies education. Combining a disciplinary approach with a practice-based frame in elementary social studies represents an opportunity for empirical research and offers new approaches to the practice of teacher education and early career professional development.

Spécialiste de l'histoire politique du XIXe siècle français, auteur d'une Histoire de la Libération de Paris, Adrien Dansette vient d'achever une synthèse difficile : ;l'Histoire religieuse de la France contemporaine. Il y a mis beaucoup d'habileté. N'en fallait-il pas pour enfermer en quelque douze cents pages l'histoire de cent quarante années embrouillées, disputées, passionnées, chaudes encore en nous-mêmes qui venons de les vivre? Et pour le faire dans un récit qui maintienne d'un bout à l'autre le lecteur en haleine, s'apaise quand il le faut pour un tableau d'ensemble et s'éclaire, çà et là, par des portraits vivants, équilibrés, d'où jaillissent les traits caractéristiques d'un visage ou d'une psychologie profonde.