New susceptibility Loci associated with kidney disease in type 1 diabetes

Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genome-wide association studies (GWAS) of T1D DN comprising ~2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P?=?1.2×10(-8)) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P?=?2.0×10(-9)). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-ß1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P?=?2.1×10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.

Composer in Interview: Pierre Boulez

Interview with composer Pierre Boulez

'Michel Blondi'

Highlights the significance of this dancer-choreographer to musicologists.

Predictors and dynamics of postpartum relapses in women with multiple sclerosis

Several studies have shown that pregnancy reduces multiple sclerosis (MS) relapses, which increase in the early postpartum period. Postpartum relapse risk has been predicted by pre-pregnancy disease activity in some studies.

New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Research in Progress: Medical Research Council United Kingdom Refractory Asthma Stratification Programme (RASP-UK)

The UK Refractory Asthma Stratification Programme(RASP-UK) will explore novel biomarker stratificationstrategies in severe asthma to improve clinicalmanagement and accelerate development of newtherapies. Prior asthma mechanistic studies have notstratified on inflammatory phenotype and theunderstanding of pathophysiological mechanisms inasthma without Type 2 cytokine inflammation is limited.RASP-UK will objectively assess adherence tocorticosteroids (CS) and examine a novel compositebiomarker strategy to optimise CS dose; this will alsoaddress what proportion of patients with severe asthmahave persistent symptoms without eosinophilic airwaysinflammation after progressive CS withdrawal. There will be interactive partnership with the pharmaceutical industry to facilitate access to stratified populations for novel therapeutic studies.

Review of Michel Cahen, Les bandits. Un historien au Mozambique.

Book review of Michel Cahen, Les bandits. Un historien au Mozambique, 1994, Paris : Centre Culturel Calouste Gulbenkian, 2002, 351p., cartes, ISBN : 972-8462-28-X

Wilkinson, Joseph Brooke (1870–1948)

Profile and biographical entry of Joseph Brooke Wilkinson, early film Censor

Création littéraire sous contexte médiatisé: l'œuvre de Michel Houellebecq, Amélie Nothomb et Jacques Chessex

Partindo da análise dos processos de legitimação e de consagração que regem, a partir da segunda metade do século XX, a mediatização do campo literário, propomo-nos estudar os peri-fenómenos consequentes, tal como a correlação possível entre essa circunstância e a própria criação. O objeto deste estudo focaliza-se na produção de três escritores paradigmáticos das letras de expressão francesa europeias contemporâneas, cuja mediatização acompanha a popularidade: o francês Michel Houellebecq, a belga Amélie Nothomb e o suíço romando Jacques Chessex. Interrogamo-nos sobre as relações possíveis entre os instrumentos dessa mediatização e os seus efeitos nas opções de escrita destes três escritores. Atenta à projeção transfronteiriça de autores e de obras, resultado de uma convergência de alguns fatores de mediatização, mas também às particularidades da memória cultural e literária onde se inscrevem as literaturas respectivas (num percurso de legitimação progressiva das literaturas de periferia face à centralidade franco-francesa), a nossa reflexão visa também contribuir para uma recontextualização do cânone da literatura francesa no contexto globalizado da sociedade mediática contemporânea na qual os autores visados estão comprometidos.

Coloquio Michel Foucault, reflexiones sobre el saber, el poder, la verdad y las prácticas de sí

En este libro se encuentran distintas posturas acerca de los dos grandes temas de Foucault: el saber y el poder. Temas que, por otra parte, marcan derroteros de búsqueda, de formulación, interrogantes que se vertieron en investigaciones que comprometen la escritura misma de las cosas. Todos los aquí presentes son estudiantes de posgrado de la carrera de filosofía, alumnos de dos seminarios que extendieron, como prácticas de formación y discusión sus trabajos en el “Coloquio Reflexiones sobre el saber, el poder, la verdad y las prácticas de sí”. Hoy, parte de estos trabajos, en los que los estudiantes arriesgaron sus propias tesis, sus pesquisas, la entrañable cualidad de quedar comprometidos con el discurso y haciendo “uso” de lo que el propio Foucault deseaba, cada uno hace de sí una parte de esa obra que es la estética de sí. En este libro queda el testimonio