Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses

Control of intracellular reactive oxygen species (ROS) concentrations is critical for cancer cell survival. We show that, in human lung cancer cells, acute increases in intracellular concentrations of ROS caused inhibition of the glycolytic enzyme pyruvate kinase M2 (PKM2) through oxidation of Cys(358). This inhibition of PKM2 is required to divert glucose flux into the pentose phosphate pathway and thereby generate sufficient reducing potential for detoxification of ROS. Lung cancer cells in which endogenous PKM2 was replaced with the Cys(358) to Ser(358) oxidation-resistant mutant exhibited increased sensitivity to oxidative stress and impaired tumor formation in a xenograft model. Besides promoting metabolic changes required for proliferation, the regulatory properties of PKM2 may confer an additional advantage to cancer cells by allowing them to withstand oxidative stress.     

A possible relativistic jetted outburst from a massive black hole fed by a tidally disrupted star

Gas accretion onto some massive black holes (MBHs) at the centers of galaxies actively powers luminous emission, but most MBHs are considered dormant. Occasionally, a star passing too near an MBH is torn apart by gravitational forces, leading to a bright tidal disruption flare (TDF). Although the high-energy transient Sw 1644+57 initially displayed none of the theoretically anticipated (nor previously observed) TDF characteristics, we show that observations suggest a sudden accretion event onto a central MBH of mass about 10(6) to 10(7) solar masses. There is evidence for a mildly relativistic outflow, jet collimation, and a spectrum characterized by synchrotron and inverse Compton processes; this leads to a natural analogy of Sw 1644+57 to a temporary smaller-scale blazar.     

Assembly mechanism of the contractile ring for cytokinesis by fission yeast

Animals and fungi assemble a contractile ring of actin filaments and the motor protein myosin to separate into individual daughter cells during cytokinesis. We used fluorescence microscopy of live fission yeast cells to observe that membrane-bound nodes containing myosin were broadly distributed around the cell equator and assembled into a contractile ring through stochastic motions, after a meshwork of dynamic actin filaments appeared. Analysis of node motions and numerical simulations supported a mechanism whereby transient connections are established when myosins in one node capture and exert force on actin filaments growing from other nodes.     

Phenolic Composition,Antioxidant and Enzyme Inhibitory Activities of Eryngium bornmuelleri leaf

Eryngium bornmuelleri Nab. (Tusî) is an endemic botanical from the Eastern Anatolia region of Turkey traditionally used for preparation of herbal tea. Within this study, phenolic composition, antioxidant capacities and inhibitory activities towards selected digestive enzymes of E. bornmuelleri leaf were investigated. Sequential extracts, obtained by extraction of plant tissue by ethanol, acetone and water exhibited pronounced antioxidant capacities and in a dose-dependent manner suppressed the metabolic syndrome related enzymes: α-amylase, α-glucosidase and pancreatic lipase. All extracts contained high levels of phenolic compounds. Flavonoid glycosides were the main phytochemicals detected, with rutin as the major compound (70 % of total phenolics). Chlorogenic, hydroxybenzoic and caftaric acids as well as traces of caffeic, ferulic and rosmarinic acids were also detected. Correlation analysis indicated that phenolic compounds were the major sources of the enzyme-inhibitory activities. This study suggests that E. bornmuelleri leaf extracts can modulate the metabolism of sugars and fats through inhibition of the relevant digestive enzymes.     

Influence of soil physicochemical and biological properties on the degradation and adsorption of the nematicide fosthiazate

The degradation and adsorption of the organophosphorus nematicide fosthiazate were investigated in nine soils with various physicochemical and biological characteristics. Fosthiazate was more persistent in acidic soils (pH <6), with half-life (t1/2) values ranging from 53.3 to 57.7 days, compared to soils with higher pH (pH >7), with t1/2 ranging from 14.1 to 20.7 days. Application of antibacterial and antifungal antibiotics to soil samples resulted in a significant inhibition of fosthiazate degradation only in two of the three acidic soils. In contrast, soil autoclaving resulted in doubling the t1/2 of fosthiazate in all studied soils, suggesting that both microbial and abiotic processes contribute to fosthiazate degradation. Statistical analysis indicated a significant negative correlation (P < 0.01) between soil pH and t1/2. Fosthiazate was generally weakly adsorbed with Freundlich adsorption coefficient (Kf) values ranging from 1.23 to 2.74 mL/g. Fosthiazate concentration was strongly correlated with soil organic matter content with higher Kf values in soils with higher organic matter content (P < 0.01). The mean t1/2 and Kf values derived from the laboratory studies were used to parametrize the FOCUS groundwater (GW) models PRZM, PELMO, PEARL, and MACRO for nematicide application in potato and tomato crops. Predicted environmental concentrations produced by the models PEARL and MACRO suggested a potential risk for GW in several scenarios, unlike PELMO and PRZM, which predicted low risk for GW. These findings suggest that the environmental fate of fosthiazate is strongly influenced by soil characteristics and that this nematicide should be used with care in acidic, light soils with low organic matter content.