Turning Foes to Friends: Knocking Down Diabetes Associated SGLT2 Transporters and Sustaining Life.

Background: The discovery of Sodium-Glucose co-transporter-2 (SGLT2) inhibitors had rewritten the treatment of diabetes mellitus with an impressive fall in the incidence of death and associated complications.

Introduction: The SGLT2 inhibitors by inhibiting the SGLT2 in the proximal nephron, helps in reducing the reabsorption of approximately 90% of the filtered glucose and increased urinary glucose excretion (UGE).

Methods: The literature related to SGLT2 inhibitors has been thoroughly explored from various available public domains and reviewed extensively for this article.

Combinatorial regulation by a novel arrangement of FruA and MrpC2 transcription factors during Myxococcus xanthus development.

Myxococcus xanthus is a gram-negative soil bacterium that undergoes multicellular development upon nutrient limitation. Intercellular signals control cell movements and regulate gene expression during the developmental process. C-signal is a short-range signal essential for aggregation and sporulation.

A combination of unusual transcription factors binds cooperatively to control Myxococcus xanthus developmental gene expression.

Myxococcus xanthus is a bacterium that undergoes multicellular development requiring coordinate regulation of multiple signaling pathways. One pathway governs aggregation and sporulation of some cells in a starving population and requires C-signaling, whereas another pathway causes programmed cell death and requires the MazF toxin. In response to starvation, the levels of the bifunctional transcription factor/antitoxin MrpC and its related proteolytic fragment MrpC2 are increased, inhibiting the cell death pathway via direct interaction of MrpC with MazF.

A Three Stage Integrative Pathway Search (TIPS) framework to identify toxicity relevant genes and pathways.

Background: The ability to obtain profiles of gene expressions, proteins and metabolites with the advent of high throughput technologies has advanced the study of pathway and network reconstruction. Genome-wide network reconstruction requires either interaction measurements or large amount of perturbation data, often not available for mammalian cell systems. To overcome these shortcomings, we developed a Three Stage Integrative Pathway Search (TIPS(c)) approach to reconstruct context-specific active pathways involved in conferring a specific phenotype, from limited amount of perturbation data.

A hierarchical approach employing metabolic and gene expression profiles to identify the pathways that confer cytotoxicity in HepG2 cells.

Background: Free fatty acids (FFA) and tumor necrosis factor alpha (TNF-alpha) have been implicated in the pathogenesis of many obesity-related metabolic disorders. When human hepatoblastoma cells (HepG2) were exposed to different types of FFA and TNF-alpha, saturated fatty acid was found to be cytotoxic and its toxicity was exacerbated by TNF-alpha. In order to identify the processes associated with the toxicity of saturated FFA and TNF-alpha, the metabolic and gene expression profiles were measured to characterize the cellular states.

Phosphorylation of the VP16 transcriptional activator protein during herpes simplex virus infection and mutational analysis of putative phosphorylation sites.

VP16 is a virion phosphoprotein of herpes simplex virus and a transcriptional activator of the viral immediate-early (IE) genes. We identified four novel VP16 phosphorylation sites (Ser18, Ser353, Ser411, and Ser452) at late times in infection but found no evidence of phosphorylation of Ser375, a residue reportedly phosphorylated when VP16 is expressed from a transfected plasmid. A virus carrying a Ser375Ala mutation of VP16 was viable in cell culture but with a slow growth rate.