Macroautophagy is a self-cannibalistic process that enables cells to adapt to various stresses and maintain energy homeostasis. Additionally, autophagy is an important route for turnover of misfolded proteins and damaged organelles, with important implications in cancer, neurodegenerative diseases and aging. Resveratrol and spermidine are able to induce autophagy by affecting deacetylases and acetylases, respectively, and have been found to extend the life-span of model organisms.
BACKGROUND: Regular smoking is associated with a wide variety of syndromes with prominent inflammatory components such as cancer, obesity and type 2 diabetes. Heavy regular smoking is also associated with changes in the DNA methylation of peripheral mononuclear cells. However, in younger smokers, inflammatory epigenetic findings are largely absent which suggests the inflammatory response(s) to smoking may be dose dependent.
Protein-tyrosine phosphatase 1B (PTP1B) is a physiological regulator of glucose homeostasis and adiposity and is a drug target for the treatment of obesity and diabetes. Here we identify pyruvate kinase M2 (PKM2) as a novel PTP1B substrate in adipocytes. PTP1B deficiency leads to increased PKM2 total tyrosine and Tyr(105) phosphorylation in cultured adipocytes and in vivo. Substrate trapping and mutagenesis studies identify PKM2 Tyr-105 and Tyr-148 as key sites that mediate PTP1B-PKM2 interaction.
MOTIVATION: A major challenge in post-genomic research has been to understand how physiological and pathological phenotypes arise from the networks of expressed genes. Here, we addressed this issue by developing an algorithm to mimic the behavior of regulatory networks in silico and to identify the dynamic response to disease and changing cellular conditions.
One of the major challenges in post-genomic research is to understand how physiological and pathological phenotypes arise from the networks or connectivity of expressed genes. In addressing this issue, we have developed two computational algorithms, CoExMiner and PathwayPro, to explore static features of gene co-expression and dynamic behaviors of gene networks. CoExMiner is based on B-spline approximation followed by the coefficient of determination (CoD) estimation for modeling gene co-expression patterns.
Most human diseases are complex multi-factorial diseases resulting from the combination of various genetic and environmental factors. In the KEGG database resource (http://www.genome.jp/kegg/), diseases are viewed as perturbed states of the molecular system, and drugs as perturbants to the molecular system. Disease information is computerized in two forms: pathway maps and gene/molecule lists. The KEGG PATHWAY database contains pathway maps for the molecular systems in both normal and perturbed states.
As an alternative to modern western medicine, Traditional Chinese Medicine (TCM) is receiving increasingly attention worldwide. Great efforts have been paid to TCM's modernization, which tries to bridge the gap between TCM and modern western medicine.