L’état des droits de l’homme au Tadjikistan

Pour Amnesty International, la situation régnant au Tadjikistan, depuis le début des violences factieuses en mai 1992, est une catastrophe du point de vue des droits de l’homme. De plus, c’est une catastrophe qui a dans une grande mesure été passée sous silence par le reste du monde. Durant tout le conflit et encore aujourd’hui, il a été fait état d’effroyables violations des droits de l’homme commises par les parties en conflit. Cependant, les informations concernant l’étendue de ces violati..

Human Rights Watch world report 2008 : events of 2007

Ian Gorvin [u.a.

Mice with a Brd4 Mutation Represent a New Model of Nephrocalcinosis

Nephrolithiasis (NL) and nephrocalcinosis (NC), which comprise renal calcification of the collecting system and parenchyma, respectively, have a multifactorial etiology with environmental and genetic determinants and affect similar to 10% of adults by age 70 years. Studies of families with hereditary NL and NC have identified >30 causative genes that have increased our understanding of extracellular calcium homeostasis and renal tubular transport of calcium. However, these account for 80% penetrance in 152 progeny. The calcification consisted of calcium phosphate deposits in the renal papillae and was associated with the presence of the urinary macromolecules osteopontin and Tamm-Horsfall protein, which are features found in Randall's plaques of patients with NC. Genome-wide mapping located the disease locus to a similar to 30 Mbp region on chromosome 17A3.3-B3 and whole-exome sequence analysis identified a heterozygous mutation, resulting in a missense substitution (Met149Thr, M149T), in the bromodomain-containing protein 4 (BRD4). The mutant heterozygous (Brd4(+/M149T)) mice, when compared with wild-type (Brd4(+/+)) mice, were normocalcemic and normophosphatemic, with normal urinary excretions of calcium and phosphate, and had normal bone turnover markers. BRD4 plays a critical role in histone modification and gene transcription, and cDNA expression profiling, using kidneys from Brd4(+/M149T) and Brd4(+/+) mice, revealed differential expression of genes involved in vitamin D metabolism, cell differentiation, and apoptosis. Kidneys from Brd4(+/M149T) mice also had increased apoptosis at sites of calcification within the renal papillae. Thus, our studies have established a mouse model, due to a Brd4 Met149Thr mutation, for inherited NC. (c) 2019 American Society for Bone and Mineral Research