Regulation of TRPC6 ion channels in podocytes - Implications for focal segmental glomerulosclerosis and acquired forms of proteinuric diseases.

The glomerular filtration barrier is a highly specialized tri-layer structure with unique functional properties. Podocyte dysfunction and cytoskeletal disorganization leads to disruption of the slit diaphragma, and proteinuria. Inflammatory diseases involving the kidney as well as inherited podocytopathies or diabetic nephropathy cause injury of the podocyte network. Focal segmental glomerulosclerosis (FSGS) is a pathologic entity that is a common cause of nephrotic syndrome with severe proteinuria in both adults and children. Several causative genes have been identified in the pathogenesis of FSGS. Mutations of the transient receptor potential canonical-6 (TRPC6), a non-selective cation channel that is directly activated by diacylglycerol (DAG), cause a particularly aggressive form of FSGS. Angiotensin II, acting through its AT1 receptor, plays a critical role in generation of proteinuria and progression of kidney injury in a number of kidney diseases, including FSGS. Mounting evidence suggest the central role of TRPC6 and perhaps other TRPC channels in the pathogenesis of FSGS as well as of acquired forms of proteinuria such as diabetic nephropathy or hypertension. Identification of signaling pathways downstream of TRPC6 may provide novel targets for the treatment of proteinuria and prevent progression of podocyte injury.

Biological diversity of Saccharomyces yeasts of spontaneously fermenting wines in four wine regions: comparative genotypic and phenotypic analysis.

Combination of molecular genetic analysis (karyotyping, PCR-RFLP of MET2, the ITS1-ITS2 region and the NTS region) and physiological examination (melibiose and mannitol utilization, sugar-, ethanol- and copper tolerance, killer activity, fermentation vigor and production of metabolites) of yeasts isolated from spontaneously fermenting wines in four wine regions revealed very high diversity in the Saccharomyces cerevisiae populations. Practically each S. cerevisiae isolate showed a unique pattern of properties. Although the strains originating from the same wine were quite similar in certain traits, they showed diversity in other properties. These results indicate that alcoholic fermentation in grape wines is performed by highly diverse yeast consortia rather than by one or two dominating strains. The less frequent Saccharomyces uvarum strains were less diverse, showed lower karyotype variability, were Mel(+), Man(+), more sensitive to 60% sugar, and ethanol or copper in the medium. They produced less acetic acid and fermented better at 14 degrees C than most of the S. cerevisiae isolates, but certain S. cerevisiae strains showed comparably high fermentation rates at this temperature, indicating that it is not a general rule that S. uvarum ferments better than S. cerevisiae at low temperatures. The segregation of certain traits (melibiose utilization, mannitol utilization and copper resistance) in both species indicates that the genomes can easily change during vegetative propagation. The higher diversity among the S. cerevisiae isolates suggests that the S. cerevisiae genome may be more flexible than the S. uvarum genome and may allow more efficient adaptation to the continuously changing environment in the fermenting wine.