Revealing the importance of carrier-cargo association in delivery of insulin and lipidated insulin.

Delivery of therapeutic peptides upon oral administration is highly desired and investigations report that the cell-penetrating peptide (CPP) penetratin and its analogues shuffle and penetramax show potential as carriers to enhance insulin delivery. Exploring this, the specific aim of the present study was to understand the impact that their complexation with a lipidated or non-lipidated therapeutic cargo would have on the delivery, to evaluate the effect of differences in membrane interactions in vitro and in vivo, as well as to deduce the mode of action leading to enhanced delivery. Fundamental biophysical aspects were studied by a range of orthogonal methods.

Dysregulated Expression of microRNA-21 and Disease-Related Genes in Human Patients and in a Mouse Model of Alport Syndrome.

Alport syndrome is a genetic disease caused by mutations in type IV collagen and is characterized by progressive kidney disease. The mouse model recapitulates the main features of human Alport syndrome. Previously, it was reported that kidney microRNA-21 (miR-21) expression is significantly increased in mice, and administration of anti-miR-21 oligonucleotides (anti-miR-21) attenuates kidney disease progression in mice, indicating that miR-21 is a viable therapeutic target for Alport syndrome.

Regulation of all members of the antizyme family by antizyme inhibitor.

ODC (ornithine decarboxylase) is the rate-limiting enzyme in polyamine biosynthesis. Polyamines are essential for cellular growth and differentiation but enhanced ODC activity is associated with cell transformation. Post-translationally, ODC is negatively regulated through members of the antizyme family.

CDC42 is required for polarized growth in human pathogen Candida albicans.

Cdc42p is a member of the RAS superfamily of GTPases and plays an essential role in polarized growth in many eukaryotic cells. We cloned the Candida albicans CaCDC42 by functional complementation in Saccharomyces cerevisiae and analyzed its function in C. albicans.

Generation of conditional lethal Candida albicans mutants by inducible deletion of essential genes.

The yeast Candida albicans is the most important fungal pathogen of humans and a model organism for studying fungal virulence. Sequencing of the C. albicans genome will soon be completed, allowing systematic approaches to analyse gene function.