Natural anti-phytopathogenic fungi compound phenol, 2, 4-bis (1, 1-dimethylethyl) from Pseudomonas fluorescens TL-1

A strain was isolated from tobacco phylloplane and preliminarily identified as Pseudomonas fluorescens TL-1, which had the visible inhibition against ten plant pathogenic fungi, viz., Curvularia lunata, Bipolaris maydis, Valsa mali, Rhizoctonia solani, Colletotrichum gloeosporioides, Sclerotinia sclerotiorum, Botrytis cinerea, Alternaria alternate, Fusarium oxysporum and Verticillium dahlia in dual culture experiments. The ethyl acetate extract of nutrient broth seeded with Pseudomonas fluorescens TL-1 suspension was separated into fifty-nine fractions by the Sephadex LH-20 column and the antifungal activity of each fraction was tested with paper disc diffusion method against Curvularia lunata. The results showed that fraction 1 to 3 had the strongest inhibitory effects on Curvularia lunata. Furthermore, GC/MS analysis of the constituents of fraction 1 to 59 confirmed that phenol, 2, 4-bis (1, 1-dimethylethyl) was the active compound for the antifungal activity from Pseudomonas fluorescens TL-1

A UML and Petri Nets Integrated Modeling Method for Business Processes in Virtual Enterprises

Abstract Virtual Enterprise is an important organization pattern for future enterprises, one of whose major functions is the distributed and parallel business process execution. This paper aims at the study on business process modeling in virtual enterprises. Based on the object-oriented description of business processes in virtual enterprises, we propose a UML and Petri nets integrated modeling method for business processes in virtual enterprises. The method provides an integrative framework supporting requirement description, model specification and design, model analysis and simulation, and model implementation

Lipin1 Regulates Skeletal Muscle Differentiation through Extracellular Signal-regulated Kinase (ERK) Activation and Cyclin D Complex-Regulated Cell Cycle Withdrawal

Lipin1, an intracellular protein, plays critical roles in controlling lipid synthesis and energy metabolism through its enzymatic activity and nuclear transcriptional functions. Several mouse models of skeletal muscle wasting are associated with lipin1 mutation or altered expression. Recent human studies have suggested that children with homozygous null mutations in the LPIN1 gene suffer from rhabdomyolysis. However, the underlying pathophysiologic mechanism is still poorly understood. In the present study we examined whether lipin1 contributes to regulating muscle regeneration. We characterized the time course of skeletal muscle regeneration in lipin1-deficient fld mice after injury. We found that fld mice exhibited smaller regenerated muscle fiber cross-sectional areas compared with wild-type mice in response to injury. Our results from a series of in vitro experiments suggest that lipin1 is up-regulated and translocated to the nucleus during myoblast differentiation and plays a key role in myogenesis by regulating the cytosolic activation of ERK1/2 to form a complex and a downstream effector cyclin D3-mediated cell cycle withdrawal. Overall, our study reveals a previously unknown role of lipin1 in skeletal muscle regeneration and expands our understanding of the cellular and molecular mechanisms underlying skeletal muscle regeneration

Semi-parametric Bayesian variable selection for gene-environment interactions

Many complex diseases are known to be affected by the interactions between genetic variants and environmental exposures beyond the main genetic and environmental effects. Study of gene-environment (G$\times$E) interactions is important for elucidating the disease etiology. Existing Bayesian methods for G$\times$E interaction studies are challenged by the high-dimensional nature of the study and the complexity of environmental influences. Many studies have shown the advantages of penalization methods in detecting G$\times$E interactions in "large p, small n" settings. However, Bayesian variable selection, which can provide fresh insight into G$\times$E study, has not been widely examined. We propose a novel and powerful semi-parametric Bayesian variable selection model that can investigate linear and nonlinear G$\times$E interactions simultaneously. Furthermore, the proposed method can conduct structural identification by distinguishing nonlinear interactions from main-effects-only case within the Bayesian framework. Spike and slab priors are incorporated on both individual and group levels to identify the sparse main and interaction effects. The proposed method conducts Bayesian variable selection more efficiently than existing methods. Simulation shows that the proposed model outperforms competing alternatives in terms of both identification and prediction. The proposed Bayesian method leads to the identification of main and interaction effects with important implications in a high-throughput profiling study with high-dimensional SNP data

Association between daily screen time and risk of stroke among middle-aged and elderly people: research based on China health and nutrition survey

BackgroundWe aimed to explore the independent associations between screen time and the risk of stroke among Chinese adults based on the China Health and Nutrition Survey (CHNS).MethodsData on Chinese adults aged older than 40 years from the CHNS in during 2004–2009 were selected. A total of 4,587 individuals were included in 2009, including screen time and the risk of stroke. Simultaneously, we traced the previous screen time to 2004 for those with outcome measures in 2009 (n = 2,100). Basic information, lifestyle, and screen behavior were obtained through face-to-face interviews and self-completed questionnaires. Anthropometric data collected included blood pressure, body weight, height, hip circumference, and waist circumference. Fasting blood was obtained for measurements of lipid and glucose levels. Cross-sectional analysis and cohort analysis were both performed using multivariate logistic regression.ResultsOf all participants, 3,004 (65.49%) participants spent more than 2 h per day on screen time. Taking the men who spent less than 2 h on screen per day as reference, the crude odds ratio (OR) of the high risk of stroke was 1.53 [95% confidence interval (CI), 1.20–1.95] for the men who spent 2–3 h per day on screen and 2.37 (95% CI, 1.78–3.16) for the men who spent more than 3 h per day on screen. This difference remained significant after adjusting for confounding factors. No association was observed among women. However, in the cohort analysis with screen time in 2006 as the independent variable, the association between screen time and stroke risk was found both in men [OR, 1.83 (95% CI, 1.19–2.82)] and women [OR, 1.48 (95% CI, 1.10–1.99)]).ConclusionWe found that the high screen time was associated with an increased stroke risk, which was pronounced in men, warranting a universal need to limit screen time in order to improve health

The P2Y(12) antagonists, 2MeSAMP and cangrelor, inhibit platelet activation through P2Y(12)/G(i)-dependent mechanism

BACKGROUND: ADP is an important physiological agonist that induces integrin activation and platelet aggregation through its receptors P2Y(1) (Gα(q)-coupled) and P2Y(12) (Gα(i)-coupled). P2Y(12) plays a critical role in platelet activation and thrombosis. Adenosine-based P2Y(12) antagonists, 2-methylthioadenosine 5\u27-monophosphate triethylammonium salt hydrate (2MeSAMP) and Cangrelor (AR-C69931MX) have been widely used to demonstrate the role of P2Y(12) in platelet function. Cangrelor is being evaluated in clinical trials of thrombotic diseases. However, a recent study reported that both 2MeSAMP and Cangrelor raise intra-platelet cAMP levels and inhibit platelet aggregation through a P2Y(12)-independent mechanism. METHODOLOGY/PRINCIPAL FINDINGS: The present work, using P2Y(12) deficient mice, sought to clarify previous conflicting reports and to elucidate the mechanisms by which 2MeSAMP and Cangrelor inhibit platelet activation and thrombosis. 2MeSAMP and Cangrelor inhibited aggregation and ATP release of wild-type but not P2Y(12) deficient platelets. 2MeSAMP and Cangrelor neither raised intracellular cAMP concentrations nor induced phosphorylation of vasodilator-stimulated phosphoprotein (VASP) in washed human or mouse platelets. Furthermore, unlike the activators (PGI(2) and forskolin) of the cAMP pathway, 2MeSAMP and Cangrelor failed to inhibit Ca(2+) mobilization, Akt phosphorylation, and Rap1b activation in P2Y(12) deficient platelets. Importantly, while injection of Cangrelor inhibited thrombus formation in a FeCl(3)-induced thrombosis model in wild-type mice, it failed to affect thrombus formation in P2Y(12) deficient mice. CONCLUSIONS: These data together demonstrate that 2MeSAMP and Cangrelor inhibit platelet function through the P2Y(12)-dependent mechanism both in vitro and in vivo

Long-Term Exposure of Fine Particulate Matter Causes Hypertension by Impaired Renal D1 Receptor-Mediated Sodium Excretion via Upregulation of G-Protein-Coupled Receptor Kinase Type 4 Expression in Sprague-Dawley Rats.

BACKGROUND: Epidemiological evidence supports an important association between air pollution exposure and hypertension. However, the mechanisms are not clear. METHODS AND RESULTS: Our present study found that long-term exposure to fine particulate matter (PM2.5) causes hypertension and impairs renal sodium excretion, which might be ascribed to lower D1 receptor expression and higher D1 receptor phosphorylation, accompanied with a higher G-protein-coupled receptor kinase type 4 (GRK4) expression. The in vivo results were confirmed in in vitro studies (ie, PM2.5 increased basal and decreased D1 receptor mediated inhibitory effect on Na+-K+ ATPase activity, decreased D1 receptor expression, and increased D1 receptor phosphorylation in renal proximal tubule cells). The downregulation of D1 receptor expression and function might be attributable to a higher GRK4 expression after the exposure of renal proximal tubule cells to PM2.5, because downregulation of GRK4 by small-interfering RNA reversed the D1 receptor expression and function. Because of the role of reactive oxygen species on D1 receptor dysfunction and its relationship with air pollution exposure, we determined plasma reactive oxygen species and found the levels higher in PM2.5-treated Sprague-Dawley rats. Inhibition of reactive oxygen species by tempol (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl) reduced blood pressure and increased sodium excretion in PM2.5-treated Sprague-Dawley rats, accompanied by an increase in the low D1 receptor expression, and decreased the hyperphosphorylated D1 receptor and GRK4 expression. CONCLUSIONS: Our present study indicated that long-term exposure of PM2.5 increases blood pressure by decreasing D1 receptor expression and function; reactive oxygen species, via regulation of GRK4 expression, plays an important role in the pathogenesis of PM2.5-induced hypertension

USP7: Novel Drug Target in Cancer Therapy

Ubiquitin specific protease 7 (USP7) is one of the deubiquitinating enzymes (DUB) that erases ubiquitin and protects substrate protein from degradation. Full activity of USP7 requires the C-terminal Ub-like domains fold back onto the catalytic domain, allowing the remodeling of the active site to a catalytically competent state by the C-terminal peptide. Until now, numerous proteins have been identified as substrates of USP7, which play a key role in cell cycle, DNA repair, chromatin remodeling, and epigenetic regulation. Aberrant activation or overexpression of USP7 may promote oncogenesis and viral disease, making it a target for therapeutic intervention. Currently, several synthetic small molecules have been identified as inhibitors of USP7, and applied in the treatment of diverse diseases. Hence, USP7 may be a promising therapeutic target for the treatment of cancer