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Inhibition of 4NQO-induced nitrosative stress by BK3C231 was observed through a decrease in nitric oxide (NO) level and an increase in glutathione (GSH) level. These new findings elucidate the cytoprotective potential of BK3C231 in human colon fibroblast CCD-18Co cell model which warrants further investigation into its chemopreventive role.Biological systems are acknowledged to be robust to perturbations but a rigorous understanding of this has been elusive. In a mathematical model, perturbations often exert their effect through parameters, so sizes and shapes of parametric regions offer an integrated global estimate of robustness. Here, we explore this "parameter geography" for bistability in post-translational modification (PTM) systems. We use the previously developed "linear framework" for timescale separation to describe the steady-states of a two-site PTM system as the solutions of two polynomial equations in two variables, with eight non-dimensional parameters. Importantly, this approach allows us to accommodate enzyme mechanisms of arbitrary complexity beyond the conventional Michaelis-Menten scheme, which unrealistically forbids product rebinding. We further use the numerical algebraic geometry tools Bertini, Paramotopy, and alphaCertified to statistically assess the solutions to these equations at ∼109 parameter points in total. Subje now permit insights into parameter geography to be uncovered by high-dimensional, data-centric analysis.Plasmodium vivax and P. falciparum, the parasites responsible for most human malaria worldwide, exhibit striking biological differences, which have important clinical consequences. Unfortunately, P. vivax, unlike P. falciparum, cannot be cultivated continuously in vitro, which limits our understanding of its biology and, consequently, our ability to effectively control vivax malaria. Here, we describe single-cell gene expression profiles of 9,215 P. vivax parasites from bloodstream infections of Aotus and Saimiri monkeys. Our results show that transcription of most P. vivax genes occurs during short periods of the intraerythrocytic cycle and that this pattern of gene expression is conserved in other Plasmodium species. However, we also identify a strikingly high proportion of species-specific transcripts in late schizonts, possibly associated with the specificity of erythrocyte invasion. Our findings provide new and robust markers of blood-stage parasites, including some that are specific to the elusive P. vivax male gametocytes, and will be useful for analyzing gene expression data from laboratory and field samples.In music education, women are present in great numbers. In professional settings, however, women musicians are not as predominant. With some exceptions, such as Scandinavian countries, women still pursue gender equality in professional music practice. To inquire about the causes of this, we considered if gender-differences in amotivation in conservatoire instrument practice could be associated with aspects of learning environment. Self-determination theory (SDT) posits that learning environments may influence motivation, by satisfying or thwarting students' psychological needs and by selectively endorsing specific extrinsic goals. Thus, we analysed if-women and men-amotivation variations could be explained by differences in behavioural regulations and satisfaction of their psychological needs for competence and autonomy. Participants (67 women and 74 men, 18-47 years old) completed validated scales for amotivation, behavioural regulations, and needs satisfaction. Students exhibited high intrinsic and introjected regulations, and high autonomy and competence needs satisfaction. Students' identified regulation levels were modest, and external regulation and amotivation levels were low. Women students' perceived competence was lower, and their amotivation was higher than men's. Amotivation variations were explained positively by identified regulation and negatively by context-derived satisfaction of the psychological needs for competence (and autonomy, only among women). Results suggest that internalization of extrinsic goals can pose difficulties and that psychological needs satisfaction may counteract amotivation (autonomy being potentially more important for women musicians).BACKGROUND Intensive care unit (ICU) patients with the most severe forms of acute coronary syndrome (ACS) require invasive therapies such as extracorporeal life support. The risk of bleeding in ICU patients with ACS treated with a dual antiplatelet therapy of aspirin and ticagrelor is unknown. The primary objective of this study was to compare the bleeding risk of ticagrelor and clopidogrel in ICU patients with ACS. METHODS AND FINDINGS We conducted a retrospective study based on a propensity score and a proportional hazards model. All patients with ACS hospitalized in the ICU of a French university hospital between January 2013 and January 2017 were included in the study. Bleeding during ICU stay was defined as all Thrombolysis in myocardial infarction (TIMI) major or minor events. A total of 155 patients were included in the study. According to propensity score matching, 57 patients treated with aspirin and ticagrelor were matched with 57 patients treated with aspirin and clopidogrel. Median (first-third quartile) Simplified Acute Physiology Score II was 61.5 (41.0-85.0). Bleeding during ICU stay occurred in 12 patients (21.1%) treated with clopidogrel and in 35 patients (61.4%) treated with ticagrelor (p less then 0.0001). This significant association was found for both TIMI major bleeding (12.3% vs. NSC 640488 35.1%, p = 0.004) and TIMI minor bleeding (8.8% vs. 26.3%, p = 0.01). The relative risk of bleeding occurrence during ICU stay was 2.60 (confidence interval 95% 1.55-4.35) for ticagrelor compared to clopidogrel. No significant difference in ICU mortality was found between the two groups (45.6% in the clopidogrel group vs. 29.8% in the ticagrelor group, p = 0.08). CONCLUSIONS Bleeding complications are frequent and serious in ICU patients with ACS. A dual antiplatelet therapy of aspirin and ticagrelor is associated with a higher risk of bleeding compared to a dual antiplatelet therapy of aspirin and clopidogrel.
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