Le souvenir de Loti en Turquie

Taha Toros Arşivi, Dosya Adı: Pierre Lotiİstanbul Kalkınma Ajansı (TR10/14/YEN/0033) İstanbul Development Agency (TR10/14/YEN/0033

Rapid effects of 17beta-estradiol on TRPV5 epithelial Ca2+ channels in rat renal cells.

The renal distal tubules and collecting ducts play a key role in the control of electrolyte and fluid homeostasis. The discovery of highly calcium selective channels, Transient Receptor Potential Vanilloid 5 (TRPV5) of the TRP superfamily, has clarified the nature of the calcium entry channels. It has been proposed that this channel mediates the critical Ca(2+) entry step in transcellular Ca(2+) re-absorption in the kidney. The regulation of transmembrane Ca(2+) flux through TRPV5 is of particular importance for whole body calcium homeostasis.In this study, we provide evidence that the TRPV5 channel is present in rat cortical collecting duct (RCCD(2)) cells at mRNA and protein levels. We demonstrate that 17beta-estradiol (E(2)) is involved in the regulation of Ca(2+) influx in these cells via the epithelial Ca(2+) channels TRPV5. By combining whole-cell patch-clamp and Ca(2+)-imaging techniques, we have characterized the electrophysiological properties of the TRPV5 channel and showed that treatment with 20-50nM E(2) rapidly (\u3c5min) induced a transient increase in inward whole-cell currents and intracellular Ca(2+) via TRPV5 channels. This rise was significantly prevented when cells were pre-treated with ruthenium red and completely abolished in cells treated with siRNA specifically targeting TRPV5.These data demonstrate for the first time, a novel rapid modulation of endogenously expressed TRPV5 channels by E(2) in kidney cells. Furthermore, the results suggest calcitropic effects of E(2). The results are discussed in relation to present concepts of non-genomic actions of E(2) in Ca(2+) homeostasis

Progressive Structural Defects in Canine Centronuclear Myopathy Indicate a Role for HACD1 in Maintaining Skeletal Muscle Membrane Systems

Mutations in HACD1/PTPLA cause recessive congenital myopathies in humans and dogs. Hydroxyacyl-coA dehydratases are required for elongation of very long chain fatty acids, and HACD1 has a role in early myogenesis, but the functions of this striated muscle-specific enzyme in more differentiated skeletal muscle remain unknown. Canine HACD1 deficiency is histopathologically classified as a centronuclear myopathy (CNM). We investigated the hypothesis that muscle from HACD1-deficient dogs has membrane abnormalities in common with CNMs with different genetic causes. We found progressive changes in tubuloreticular and sarcolemmal membranes and mislocalized triads and mitochondria in skeletal muscle from animals deficient in HACD1. Furthermore, comparable membranous abnormalities in cultured HACD1-deficient myotubes provide additional evidence that these defects are a primary consequence of altered HACD1 expression. Our novel findings, including T-tubule dilatation and disorganization, associated with defects in this additional CNM-associated gene provide a definitive pathophysiologic link with these disorders, confirm that dogs deficient in HACD1 are relevant models, and strengthen the evidence for a unifying pathogenesis in CNMs via defective membrane trafficking and excitation-contraction coupling in muscle. These results build on previous work by determining further functional roles of HACD1 in muscle and provide new insight into the pathology and pathogenetic mechanisms of HACD1 CNM. Consequently, alterations in membrane properties associated with HACD1 mutations should be investigated in humans with related phenotypes

Creación adolescente y mundo contemporáneo

Adolescence, as a paradigm of creation, is defined by the awing that givesplace to inspiration, by sublimation and by the encounter with alterity. This encounter of the other with the social aspect has institutions that accompany the adolescent. Among them the family, as the closest of the institutions, carries out dialectic functions as a place of sublimation and as a place of fascination. The adolescence is described from the adult institutions, granting them a value that marks a difference between the adolescent creation and the processes of the adults. The recognition of the similitude between these fields is fundamental in a clinical position for the adolescence.    La adolescencia, como paradigma de la creación, es definida por el sobrecogimiento que da lugar a la inspiración, por la sublimación y por el encuentro con la alteridad. Este encuentro con el otro en lo social, dispone de instituciones que acompañan al adolescente. Entre ellas la familia como la más cercana de las instituciones, cumple funciones dialécticas como lugar de sublimación y como lugar de arrobamiento. La adolescencia es descrita desde las instituciones adultas, otorgándole un valor que marca una diferencia entre la creación adolescente y los procesos del adulto. El reconocimiento de la similitud entre estos campos es fundamental en una posición clínica para la adolescencia

David BUISSERET, Ingénieurs et fortifications avant Vauban. L’organisation d’un service royal aux XVIe-XVIIIe siècles, Paris, Édition du Comité des travaux historiques et scientifiques, 2002, 142 p.

L'historien de Sully et d'Henri IV, qui enseigne maintenant à l’université du Texas, avoue avoir mis plus de quarante ans à réaliser ce volume, dont la publication avait d'ailleurs été préparée par plusieurs articles. Le résultat de ce travail d'érudition impeccable, mise au service de l’histoire d'un important thème de l’administration monarchique, est remarquable. Le livre s'intéresse à ceux qui portent le titre de “ commissaires des fortifications ”, puis, à partir du milieu du XVIe siècle..

David BUISSERET, Ingénieurs et fortifications avant Vauban. L’organisation d’un service royal aux XVIe-XVIIIe siècles, Paris, Édition du Comité des travaux historiques et scientifiques, 2002, 142 p.

L'historien de Sully et d'Henri IV, qui enseigne maintenant à l’université du Texas, avoue avoir mis plus de quarante ans à réaliser ce volume, dont la publication avait d'ailleurs été préparée par plusieurs articles. Le résultat de ce travail d'érudition impeccable, mise au service de l’histoire d'un important thème de l’administration monarchique, est remarquable. Le livre s'intéresse à ceux qui portent le titre de “ commissaires des fortifications ”, puis, à partir du milieu du XVIe siècle..

HACD1, a regulator of membrane composition and fluidity, promotes myoblast fusion and skeletal muscle growth

The reduced diameter of skeletal myofibres is a hallmark of several congenital myopathies, yet the underlying cellular and molecular mechanisms remain elusive. In this study, we investigate the role of HACD1/PTPLA, which is involved in the elongation of the very long chain fatty acids, in muscle fibre formation. In humans and dogs, HACD1 deficiency leads to a congenital myopathy with fibre size disproportion associated with a generalized muscle weakness. Through analysis of HACD1-deficient Labradors, Hacd1-knockout mice, and Hacd1-deficient myoblasts, we provide evidence that HACD1 promotes myoblast fusion during muscle development and regeneration. We further demonstrate that in normal differentiating myoblasts, expression of the catalytically active HACD1 isoform, which is encoded by a muscle-enriched splice variant, yields decreased lysophosphatidylcholine content, a potent inhibitor of myoblast fusion, and increased concentrations of ≥C18 and monounsaturated fatty acids of phospholipids. These lipid modifications correlate with a reduction in plasma membrane rigidity. In conclusion, we propose that fusion impairment constitutes a novel, non-exclusive pathological mechanism operating in congenital myopathies and reveal that HACD1 is a key regulator of a lipid-dependent muscle fibre growth mechanism