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Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that controls blood phosphate levels by increasing renal phosphate excretion and reducing 1,25-dihydroxyvitamin [D.sub.3] [1,25[(OH).sub.2]D] production. Disorders of FGF23 homeostasis are associated with significant morbidity and mortality, but a fundamental understanding of what regulates FGF23 production is lacking. Because the kidney is the major end organ of FGF23 action, we hypothesized that it releases a factor that regulates FGF23 synthesis. Using aptamer-based proteomics and liquid chromatography-mass spectrometry-based (LC-MS-based) metabolomics, we profiled more than 1600 molecules in renal venous plasma obtained from human subjects. Renal vein glycerol-3-phosphate (G-3-P) had the strongest correlation with circulating FGF23. In mice, exogenous G-3-P stimulated bone and bone marrow FGF23 production through local G-3-P acyltransferase-mediated (GPAT-mediated) lysophosphatidic acid (LPA) synthesis. Further, the stimulatory effect of G-3-P and LPA on FGF23 required LPA receptor 1 (LPAR1). Acute kidney injury (AKI), which increases FGF23 levels, rapidly increased circulating G-3-P in humans and mice, and the effect of AKI on FGF23 was abrogated by GPAT inhibition or Lpar1 deletion. Together, our findings establish a role for kidney-derived G-3-P in mineral metabolism and outline potential targets to modulate FGF23 production during kidney injury., Introduction Fibroblast growth factor-23 (FGF23) levels increase with both acute and chronic kidney disease (CKD) (1) and are a strong independent risk factor for adverse renal outcomes and mortality in [...]

The responses of Escherichia coli central carbon metabolism to knockout mutations in phosphoglucose isomerase and glucose-6-phosphate (G6P) dehydrogenase genes were investigated by using glucose- and ammonia-limited chemostats. The metabolic network structures and intracellular carbon fluxes in the wild type and in the knockout mutants were characterized by using the complementary methods of flux ratio analysis and metabolic flux analysis based on [[U-.sup.13]C]glucose labeling and two-dimensional nuclear magnetic resonance (NMR) spectroscopy of cellular amino acids, glycerol, and glucose. Disruption of phosphoglucose isomerase resulted in use of the pentose phosphate pathway as the primary route of glucose catabolism, while flux rerouting via the Embden-Meyerhof-Parnas pathway and the nonoxidative branch of the pentose phosphate pathway compensated for the G6P dehydrogenase deficiency. Furthermore, additional, unexpected flux responses to the knockout mutations were observed. Most prominently, the glyoxylate shunt was found to be active in phosphoglucose isomerase-deficient E. coli. The Entner-Doudoroff pathway also contributed to a minor fraction of the glucose catabolism in this mutant strain. Moreover, although knockout of G6P dehydrogenase had no significant influence on the central metabolism under glucose-limited conditions, this mutation resulted in extensive overflow metabolism and extremely low tricarboxylic acid cycle fluxes under ammonia limitation conditions.

Research has been conducted on the conditional expression system used in Bacillus subtilis. The precise deletion of a teichoic acid biosynthesis gene based on the use of this conditional expression system has been carried out and investigated and the results are described.

Research has been conducted on the Myxococcus xanthus gene with the similarities to the glycerol 3-phosphate permease of the other bacteria. The cloning of this gene has been carried out and the results demonstrate that the gene expression has increase during the starvation hours.

Research has been conducted on Oct-1 coactivator OCA-S which is important for histone H2B transcription. The authors have investigated the functional identification and purification of OCA-S activity, and they report that the characterization of this cofactor has identified the role for the p38 subunit which is identical to glyceraldehyde-3-phosphate dehydrogenase, and that p38 mediates S phase-inducible H2B promoter activation.

Research has been conducted on cobra cardiotoxin which causes membrane leakage in human erythrocytes. The authors report that this cardiotoxin can cause leakage of vesicle contents in phosphatidylglycerol and phosphatidylserine which contain membrane bilayers.