G Protein Subunit Dissociation and Translocation Regulate Cellular Response to Receptor Stimulation

We examined the role of G proteins in modulating the response of living cells to receptor activation. The response of an effector, phospholipase C-β to M3 muscarinic receptor activation was measured using sensors that detect the generation of inositol triphosphate or diacylglycerol. The recently discovered translocation of Gβγ from plasma membrane to endomembranes on receptor activation attenuated this response. A FRET based G protein sensor suggested that in contrast to translocating Gβγ, non-translocating Gβγ subunits do not dissociate from the αq subunit on receptor activation leading to prolonged retention of the heterotrimer state and an accentuated response. M3 receptors with tethered αq induced differential responses to receptor activation in cells with or without an endogenous translocation capable γ subunit. G protein heterotrimer dissociation and βγ translocation are thus unanticipated modulators of the intensity of a cell's response to an extracellular signal

Glucose Recovery from Different Corn Stover Fractions Using Dilute Acid and Alkaline Pretreatment Techniques

Background: Limited availability of corn stover due to the competing uses (organic manure, animal feed, bio-materials, and bioenergy) presents a major concern for its future in the bio-economy. Furthermore, biomass research has exhibited different results due to the differences in the supply of enzymes and dissimilar analytical methods. The effect of the two leading pretreatment techniques (dilute acid and alkaline) on glucose yield from three corn stover fractions (cob, stalk, and leaf) sourced from a single harvest in Uganda were studied at temperatures 100, 120, 140, and 160 °C over reaction times of 5, 10, 30, and 60 min. Results: From this study, the highest glucose concentrations obtained from the dilute acid (DA) pretreated cobs, stalks, and leaves were 18.4 g/L (66.8% glucose yield), 16.2 g/L (64.1% glucose yield), and 11.0 g/L (49.5% glucose yield), respectively. The optimal pretreatment settings needed to obtain these yields from the DA pretreated samples were at a temperature of 160 °C over an incubation time of 30 min. The highest glucose concentrations obtained from the alkaline (AL) pretreated cobs, stalks, and leaves were 24.7 g/L (81.73% glucose yield), 21.3 g/L (81.23% glucose yield), and 15.0 g/L (51.92% glucose yield), respectively. To be able to achieve these yields, the optimal pretreatment settings for the cobs and stalks were 140 °C and for a retention time of 30 min, while the leaves require optimal conditions of 140 °C and for a retention time of 60 min. Conclusions: The study recommends that the leaves could be left on the field during harvesting since the recovery of glucose from the pretreated cobs and stalks is higher

American ginseng suppresses Western diet-promoted tumorigenesis in model of inflammation-associated colon cancer: role of EGFR

<p>Abstract</p> <p>Background</p> <p>Western diets increase colon cancer risk. Epidemiological evidence and experimental studies suggest that ginseng can inhibit colon cancer development. In this study we asked if ginseng could inhibit Western diet (20% fat) promoted colonic tumorigenesis and if compound K, a microbial metabolite of ginseng could suppress colon cancer xenograft growth.</p> <p>Methods</p> <p>Mice were initiated with azoxymethane (AOM) and, two weeks later fed a Western diet (WD, 20% fat) alone, or WD supplemented with 250-ppm ginseng. After 1 wk, mice received 2.5% dextran sulfate sodium (DSS) for 5 days and were sacrificed 12 wks after AOM. Tumors were harvested and cell proliferation measured by Ki67 staining and apoptosis by TUNEL assay. Levels of EGF-related signaling molecules and apoptosis regulators were determined by Western blotting. Anti-tumor effects of intraperitoneal compound K were examined using a tumor xenograft model and compound K absorption measured following oral ginseng gavage by UPLC-mass spectrometry. Effects of dietary ginseng on microbial diversity were measured by analysis of bacterial 16S rRNA.</p> <p>Results</p> <p>Ginseng significantly inhibited colonic inflammation and tumorigenesis and concomitantly reduced proliferation and increased apoptosis. The EGFR cascade was up-regulated in colonic tumors and ginseng significantly reduced EGFR and ErbB2 activation and Cox-2 expression. Dietary ginseng altered colonic microbial diversity, and bacterial suppression with metronidazole reduced serum compound K following ginseng gavage. Furthermore, compound K significantly inhibited tumor xenograft growth.</p> <p>Conclusions</p> <p>Ginseng inhibited colonic inflammation and tumorigenesis promoted by Western diet. We speculate that the ginseng metabolite compound K contributes to the chemopreventive effects of this agent in colonic tumorigenesis.</p