Apoptosis induced by Staphylococcus aureus in human monocytic U937 cells involves Akt and mitogen-activated protein (MAPK) phosphorylation

Staphylococcus aureus (S. aureus) is a leading etiologic agent of nosocomial and community-acquired infectious diseases. Numerous studies have shown that, S. aureus could promote apoptosis in host cells. Unfortunately, the cellular and molecular mechanisms responsible for this phenomenon are still poorly understood. The present study aims to elucidate the signaling mechanisms involved in S. aureus-induced U937 cells apoptosis by investigating the role of phosphatidylinositol 3-kinase/Akt (PI3K/Akt), mitogen-activated protein (MAPK) and caspases. Our results showed that, i decreased the expression of phosphorylation-Akt. In contrast, S. aureus increased phosphorylation-JNK1/2, phosphorylation-ERK1/2 and phosphorylation-p38 MAPK. Treatment of U937 cells with S. aureus resulted in the activation of caspase-3 and -9. Furthermore, caspases inhibitors, SP600125 (JNK inhibitor), SB203580 (p38MAPK inhibitor) and PD98059 (ERK inhibitor) decreased apoptosis in U937 cells. However, LY294002 (Akt inhibitor) increased U937 cells apoptosis. Taken together, our study for the first time suggest that S. aureus is able to enhance apoptosis of U937 cells through inhibition of PI3K/Akt and activation of MAPK signaling pathways.Key words: Staphylococcus aureus, mitogen-activated protein (MAPK), apoptosis, U937

Detoxificación de aceites de Jatrofa curcas mediante irradiación ultravioleta combinado con lavados de etanol

Jatropha curcas oil (JCO) is non-edible due to the content of phorbolesters (PEs) which are very toxic. The aim of this study was to evaluate the potential of JCO, treated by ultraviolet irradiation combined with ethanol washing, as an edible oil. The results showed that PEs can be significantly decreased by 100% (p < 0.05), but the treatments produced no significant changes (p < 0.05) in the fatty acids composition (FAC) and triacylglycerols (TAGs) in the detoxified Jatropha curcas oil (DJCO). In addition, the quality of DJCO was improved with enhanced DPPH radical scavenging. Therefore, DJCO with good quality will become a good resource for edible oil.El aceite de Jatropha curcas (JCO) no es comestible debido a su contenido en esteres de forbol (PES) que son muy tóxicos. El objetivo de este estudio fue evaluar el potencial de JCO como aceite comestible, cuando se trató mediante irradiación ultravioleta en combinación con lavados de etanol. Los resultados mostraron que el contenido de PES puede disminuir significativamente, hasta el 100% (p < 0,05), sin embargo, no se detectaron cambios significativos (p < 0,05) en la composición de los ácidos grasos (FAC) y de los triglicéridos (TG) en el aceite de Jatropha curcas detoxificado (DJCO). Además, las cualidades de DJCO han mejorado teniendo una mayor capacidad de eliminación de radicales DPPH. Por lo tanto, DJCO con estas buenas cualidades se convertirá en un buen recurso de aceite comestible

A-6G and A-20C Polymorphisms in the Angiotensinogen Promoter and Hypertension Risk in Chinese: A Meta-Analysis

BACKGROUND: Numerous studies in Chinese populations have evaluated the association between the A-6G and A-20C polymorphisms in the promoter region of angiotensinogen gene and hypertension. However, the results remain conflicting. We carried out a meta-analysis for these associations. METHODS AND RESULTS: Case-control studies in Chinese and English publications were identified by searching the MEDLINE, EMBASE, CNKI, Wanfang, CBM, and VIP databases. The random-effects model was applied for dichotomous outcomes to combine the results of the individual studies. We finally selected 24 studies containing 5932 hypertensive patients and 5231 normotensive controls. Overall, we found significant association between the A-6G polymorphism and the decreased risk of hypertension in the dominant genetic model (AA+AG vs. GG: P=0.001, OR=0.71, 95%CI 0.57-0.87, P(heterogeneity)=0.96). The A-20C polymorphism was significantly associated with the increased risk for hypertension in the allele comparison (C vs. A: P=0.03, OR=1.14, 95%CI 1.02-1.27, P(heterogeneity)=0.92) and recessive genetic model (CC vs. CA+AA: P=0.005, OR=1.71, 95%CI 1.18-2.48, P(heterogeneity)=0.99). In the subgroup analysis by ethnicity, significant association was also found among Han Chinese for both A-6G and A-20C polymorphisms. A borderline significantly decreased risk of hypertension between A-6G and Chinese Mongolian was seen in the allele comparison (A vs. G: P=0.05, OR=0.79, 95%CI 0.62-1.00, P(heterogeneity)=0.84). CONCLUSION: Our meta-analysis indicated significant association between angiotensinogen promoter polymorphisms and hypertension in the Chinese populations, especially in Han Chinese

Integration of decision support systems to improve decision support performance

Decision support system (DSS) is a well-established research and development area. Traditional isolated, stand-alone DSS has been recently facing new challenges. In order to improve the performance of DSS to meet the challenges, research has been actively carried out to develop integrated decision support systems (IDSS). This paper reviews the current research efforts with regard to the development of IDSS. The focus of the paper is on the integration aspect for IDSS through multiple perspectives, and the technologies that support this integration. More than 100 papers and software systems are discussed. Current research efforts and the development status of IDSS are explained, compared and classified. In addition, future trends and challenges in integration are outlined. The paper concludes that by addressing integration, better support will be provided to decision makers, with the expectation of both better decisions and improved decision making processes

Synergistic Association of PTGS2 and CYP2E1 Genetic Polymorphisms with Lung Cancer Risk in Northeastern Chinese

BACKGROUND: Lung cancer is the most common cause of cancer-related deaths worldwide. The aim of this study was to investigate the association of five extensively-studied polymorphisms in PTGS2 (rs689466, rs5275, rs20417) and CYP2E1 (rs2031920, rs6413432) genes with lung cancer risk in a large northeastern Chinese population. METHODOLOGY/PRINCIPAL FINDINGS: This is a hospital-based case-control study involving 684 patients with lung cancer and 604 cancer-free controls. Genotyping was performed using the PCR-LDR method. Data were analyzed using Haplo.stats and MDR programs. There were significant differences between patients and controls in allele/genotype distributions of rs5275 (P = 0.002/0.003) and rs6413432 (P = 0.037/0.044), as well as in genotype distributions of rs689466 (P = 0.02). The risk for lung cancer associated with the rs5275-C mutant allele was decreased by 60% (95% CI [confidence interval]: 0.21-0.74; P = 0.004) under the recessive model. Carriers of rs689466-G mutant allele had a 28% (95% CI: 0.57-0.92; P = 0.008) reduced risk of developing lung cancer relative to the AA genotype carriers. In haplotype analysis, haplotype G-C-C-T (in order of rs689466, rs5275, rs2031920 and rs6413432) decreased the odds of lung cancer by 28% (95% CI: 0.51-0.93; P = 0.019) after adjusting for confounding factors, whereas haplotype A-T-T-T had 1.49-fold (95% CI: 1.21-1.79; P = 0.012) increased risk for lung cancer. Using MDR method, the overall best model including rs5275, rs689466 and rs6413432 polymorphisms was identified with a maximal testing accuracy of 66.1% and a maximal cross-validation consistency of 10 out of 10 (P = 0.003). CONCLUSIONS/SIGNIFICANCE: Our findings demonstrated a potentially synergistic association of PTGS2 and CYP2E1 polymorphisms with the underlying cause of lung cancer in northeastern Chinese

Relationship between Reproductive Allocation and Relative Abundance among 32 Species of a Tibetan Alpine Meadow: Effects of Fertilization and Grazing

Background: Understanding the relationship between species traits and species abundance is an important goal in ecology and biodiversity science. Although theoretical studies predict that traits related to performance (e.g. reproductive allocation) are most directly linked to species abundance within a community, empirical investigations have rarely been done. It also remains unclear how environmental factors such as grazing or fertilizer application affect the predicted relationship. Methodology: We conducted a 3-year field experiment in a Tibetan alpine meadow to assess the relationship between plant reproductive allocation (RA) and species relative abundance (SRA) on control, grazed and fertilized plots. Overall, the studied plant community contained 32 common species. Principal Findings: At the treatment level, (i) RA was negatively correlated with SRA on control plots and during the first year on fertilized plots. (ii) No negative RA–SRA correlations were observed on grazed plots and during the second and third year on fertilized plots. (iii) Seed size was positively correlated with SRA on control plots. At the plot level, the correlation between SRA and RA were not affected by treatment, year or species composition. Conclusions/Significance: Our study shows that the performance-related trait RA can negatively affect SRA within communities, which is possibly due to the tradeoffs between clonal growth (for space occupancy) and sexual reproduction. We propose that if different species occupy different positions along these tradeoffs it will contribute to biodiversity maintenance in local communities or even at lager scale

Multivalency-Driven Formation of Te-Based Monolayer Materials: A Combined First-Principles and Experimental study

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GA-based multi-objective optimization of active nonlinear quarter car suspension system—PID and fuzzy logic control

Background The primary function of a suspension system is to isolate the vehicle body from road irregularities thus providing the ride comfort and to support the vehicle and provide stability. The suspension system has to perform conflicting requirements; hence, a passive suspension system is replaced by the active suspension system which can supply force to the system. Active suspension supplies energy to respond dynamically and achieve relative motion between body and wheel and thus improves the performance of suspension system. Methods This study presents modelling and control optimization of a nonlinear quarter car suspension system. A mathematical model of nonlinear quarter car is developed and simulated for control and optimization in Matlab/Simulink® environment. Class C road is selected as input road condition with the vehicle traveling at 80 kmph. Active control of the suspension system is achieved using FLC and PID control actions. Instead of guessing and or trial and error method, genetic algorithm (GA)-based optimization algorithm is implemented to tune PID parameters and FLC membership functions’ range and scaling factors. The optimization function is modeled as a multi-objective problem comprising of frequency weighted RMS seat acceleration, Vibration dose value (VDV), RMS suspension space, and RMS tyre deflection. ISO 2631-1 standard is adopted to assess the ride and health criterion. Results The nonlinear quarter model along with the controller is modeled and simulated and optimized in a Matlab/Simulink environment. It is observed that GA-optimized FLC gives better control as compared to PID and passive suspension system. Further simulations are validated on suspension system with seat and human model. Parameters under observation are frequency-weighted RMS head acceleration, VDV at the head, crest factor, and amplitude ratios at the head and upper torso (AR_h and AR_ut). Simulation results are presented in time and frequency domain. Conclusion Simulation results show that GA-based FLC and PID controller gives better ride comfort and health criterion by reducing RMS head acceleration, VDV at the head, CF, and AR_h and AR_ut over passive suspension system

MicroRNAs in pulmonary arterial remodeling

Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH

Human cell dedifferentiation in mesenchymal condensates through controlled autophagy

Tissue and whole organ regeneration is a dramatic biological response to injury that occurs across different plant and animal phyla. It frequently requires the dedifferentiation of mature cells to a condensed mesenchymal blastema, from which replacement tissues develop. Human somatic cells cannot regenerate in this way and differentiation is considered irreversible under normal developmental conditions. Here, we sought to establish in vitro conditions to mimic blastema formation by generating different three-dimensional (3D) condensates of human mesenchymal stromal cells (MSCs). We identified specific 3D growth environments that were sufficient to dedifferentiate aged human MSCs to an early mesendoderm-like state with reversal of age-associated cell hypertrophy and restoration of organized tissue regenerating capacity in vivo. An optimal auophagic response was required to promote cytoplasmic remodeling, mitochondrial regression, and a bioenergetic shift from oxidative phosphorylation to anaerobic metabolism. Our evidence suggests that human cell dedifferentiation can be achieved through autonomously controlled autophagic flux