Cogan's syndrome: clinical evolution of deafness and vertigo in three patients

The aim of this study was to evaluate the clinical symptoms, the otoneurological examinations, the treatment and the clinical course of three patients suffering from Cogan's syndrome, a rare disease based on the clinical association of a non-syphilitic interstitial keratitis with a cochleo-vestibular deficit. This case series involved three patients with follow up. The clinical course of the three patients (aged 30, 48 and 49years) with Cogan's syndrome during a follow-up period of 2 to 6years is reported. All patients underwent complete otoneurological, ophthalmologic and rheumatologic examinations and were treated with immunosuppressive therapy such as glucocorticoids and cyclophosphamide in two and glucocorticoids and methotrexate in one patient. Using immunosuppressive therapy, ophthalmologic symptoms disappeared rapidly in two patients. Hearing improved only in one and stabilized in a second patient. One patient died after 6years of treatment because of complications of generalized vasculitis. Early diagnosis and rapid initiation of a combined immunosuppressive therapy such as corticosteroids and cyclophosphamide seem to be important in controlling the disease and avoiding persistent deafness. Whether systemic complications and a fatal outcome also can be prevented is still questionabl

An Iterative Genetic and Dynamical Modelling Approach Identifies Novel Features of the Gene Regulatory Network Underlying Melanocyte Development

The mechanisms generating stably differentiated cell-types from multipotent precursors are key to understanding normal development and have implications for treatment of cancer and the therapeutic use of stem cells. Pigment cells are a major derivative of neural crest stem cells and a key model cell-type for our understanding of the genetics of cell differentiation. Several factors driving melanocyte fate specification have been identified, including the transcription factor and master regulator of melanocyte development, Mitf, and Wnt signalling and the multipotency and fate specification factor, Sox10, which drive mitf expression. While these factors together drive multipotent neural crest cells to become specified melanoblasts, the mechanisms stabilising melanocyte differentiation remain unclear. Furthermore, there is controversy over whether Sox10 has an ongoing role in melanocyte differentiation. Here we use zebrafish to explore in vivo the gene regulatory network (GRN) underlying melanocyte specification and differentiation. We use an iterative process of mathematical modelling and experimental observation to explore methodically the core melanocyte GRN we have defined. We show that Sox10 is not required for ongoing differentiation and expression is downregulated in differentiating cells, in response to Mitfa and Hdac1. Unexpectedly, we find that Sox10 represses Mitf-dependent expression of melanocyte differentiation genes. Our systems biology approach allowed us to predict two novel features of the melanocyte GRN, which we then validate experimentally. Specifically, we show that maintenance of mitfa expression is Mitfa-dependent, and identify Sox9b as providing an Mitfa-independent input to melanocyte differentiation. Our data supports our previous suggestion that Sox10 only functions transiently in regulation of mitfa and cannot be responsible for long-term maintenance of mitfa expression; indeed, Sox10 is likely to slow melanocyte differentiation in the zebrafish embryo. More generally, this novel approach to understanding melanocyte differentiation provides a basis for systematic modelling of differentiation in this and other cell-types

Variabilité génétique de la ponctuation noire sur la truitelle Fario (Salmo trutta L.)

International audienc

MAPCUMBA : a fast iterative multi-grid map-making algorithm for CMB experiments

The data analysis of current Cosmic Microwave Background (CMB) experiments like BOOMERanG or MAXIMA poses severe challenges which already stretch the limits of current (super-) computer capabilities, if brute force methods are used. In this paper we present a practical solution to the optimal map making problem which can be used directly for next generation CMB experiments like ARCHEOPS and TopHat, and can probably be extended relatively easily to the full PLANCK case. This solution is based on an iterative multi-grid Jacobi algorithm which is both fast and memory sparing. Indeed, if there are N_tod data points along the one dimensional timeline to analyse, the number of operations is O(N_tod ln N_tod) and the memory requirement is O(N_tod). Timing and accuracy issues have been analysed on simulated ARCHEOPS and TopHat data, and we discuss as well the issue of the joint evaluation of the signal and noise statistical properties.Comment: 10 pages, 8 postscript and 3 jpeg figures. Submitted to AA. Code available at http://ulysse.iap.fr/download/mapcumba