A curated online resource for SOX10 and pigment cell molecular genetic pathways

We describe the creation of a specialized web-accessible database named the Pigment Cell Gene Resource, which contains information on the genetic pathways that regulate pigment cell development and function. This manually curated database is comprised of two sections, an annotated literature section and an interactive transcriptional network diagram. Initially, this database focuses on the transcription factor SOX10, which has essential roles in pigment cell development and function, but the database has been designed with the capacity to expand in the future, allowing inclusion of many more pigmentation genes

PAX2 Regulates ADAM10 Expression and Mediates Anchorage-Independent Cell Growth of Melanoma Cells

PAX transcription factors play an important role during development and carcinogenesis. In this study, we investigated PAX2 protein levels in melanocytes and melanoma cells by Western Blot and immunofluorescence analysis and characterized the role of PAX2 in the pathogenesis of melanoma. In vitro we found weak PAX2 protein expression in keratinocytes and melanocytes. Compared to melanocytes increased PAX2 protein levels were detectable in melanoma cell lines. Interestingly, in tissue sections of melanoma patients nuclear PAX2 expression strongly correlated with nuclear atypia and the degree of prominent nucleoli, indicating an association of PAX2 with a more atypical cellular phenotype. In addition, with chromatin immunoprecipitation assay, PAX2 overexpression and PAX2 siRNA we present compelling evidence that PAX2 can regulate ADAM10 expression, a metalloproteinase known to play important roles in melanoma metastasis. In human tissue samples we found co-expression of PAX2 and ADAM10 in melanocytes of benign nevi and in melanoma cells of patients with malignant melanoma. Importantly, the downregulation of PAX2 by specific siRNA inhibited the anchorage independent cell growth and decreased the migratory and invasive capacity of melanoma cells. Furthermore, the downregulation of PAX2 abrogated the chemoresistance of melanoma cells against cisplatin, indicating that PAX2 expression mediates cell survival and plays important roles during melanoma progression

Genome-wide association analysis reveals QTL and candidate mutations involved in white spotting in cattle

International audienceAbstractBackgroundWhite spotting of the coat is a characteristic trait of various domestic species including cattle and other mammals. It is a hallmark of Holstein–Friesian cattle, and several previous studies have detected genetic loci with major effects for white spotting in animals with Holstein–Friesian ancestry. Here, our aim was to better understand the underlying genetic and molecular mechanisms of white spotting, by conducting the largest mapping study for this trait in cattle, to date.ResultsUsing imputed whole-genome sequence data, we conducted a genome-wide association analysis in 2973 mixed-breed cows and bulls. Highly significant quantitative trait loci (QTL) were found on chromosomes 6 and 22, highlighting the well-established coat color genes KIT and MITF as likely responsible for these effects. These results are in broad agreement with previous studies, although we also report a third significant QTL on chromosome 2 that appears to be novel. This signal maps immediately adjacent to the PAX3 gene, which encodes a known transcription factor that controls MITF expression and is the causal locus for white spotting in horses. More detailed examination of these loci revealed a candidate causal mutation in PAX3 (p.Thr424Met), and another candidate mutation (rs209784468) within a conserved element in intron 2 of MITF transcripts expressed in the skin. These analyses also revealed a mechanistic ambiguity at the chromosome 6 locus, where highly dispersed association signals suggested multiple or multiallelic QTL involving KIT and/or other genes in this region.ConclusionsOur findings extend those of previous studies that reported KIT as a likely causal gene for white spotting, and report novel associations between candidate causal mutations in both the MITF and PAX3 genes. The sizes of the effects of these QTL are substantial, and could be used to select animals with darker, or conversely whiter, coats depending on the desired characteristics

Fluid modeling of radio frequency and direct currents in a biased magnetized plasma

Équipe 107 : Physique des plasmas chaudsInternational audienceThis model aims at simulating a magnetized plasma column connected on one side to a probe and on the other side to an ICRH (Ion Cyclotron Resonant Heating) antenna. This is a double probe modeling of a plasma flux tube exchanging perpendicular currents: rf polarization current and dc currents (inertia, viscous, and friction) perpendicular to the magnetic field. A self consistent solution for the rectified potential and the density is obtained under the assumptions of flute hypothesis, inertialess electrons, and no collision in parallel direction. The main effect of rf biasing on the antenna side is to shift the IV characteristic so that the floating potential can be increased up to ln(I-0(eV(rf)/(k(B)T(e)))), with I-0 the modified Bessel function of the first kind. On the contrary, the effect of dc currents is to decrease the plasma potential and the sheath potential which can be lower than 3k(B)T(e)/e or even be negative. Experimental characteristics are well matched by the 1D fluid code and exhibit very high negative currents (more than 30j(i) the ion saturation current) for high positive biasing of the probe and for long flux tube (10 m). The non-saturation of the electron current is here due to high transverse transport enhanced by convective fluxes and dc currents able to bring an amount of density around the biased flux tube. During comparisons with experiments, the floating potential measured by a reciprocating probe is recovered by the code revealing that for a 120V measured peak potential on the probe, the rf potential on the ICRH antenna is twice this value. Finally, the density profile can be flattened or steepened as a function of the transverse dc current direction