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  • Barry Outzen posted an update 1 day, 9 hours ago

    These findings provide a step toward developing biological markers of social emotions, which could serve as important tools to investigate guilt-related brain processes in both healthy and clinical populations. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.BACKGROUND Dietary supplementation with carotenoids can have beneficial health effects, but carotenoids are poorly absorbed. OBJECTIVES We aimed to evaluate how milk fermented by lactic acid bacteria affects dietary carotenoid bioavailability in humans and rats and to investigate mechanisms by which active components in milk fermented by Lactobacilli enhance dietary carotenoid absorption. METHODS Male rats (n = 8/group) were administered β-carotene or β-carotene + fermented milk. Rats (n = 6/group) were also pretreated with ezetimibe, a cholesterol absorption inhibitor, to investigate β-carotene transport mechanisms. In humans, 3 studies were conducted using a randomized crossover method. Subjects (n = 16/study) consumed a vegetable (carrot, tomato, or spinach) drink alone or with a fermented milk drink. Blood samples were collected at various time points after consumption. RESULTS In rats, the serum β-carotene area under the concentration-time curve (AUC) was significantly higher for the β-carotene + fermentβ-carotene bioavailability in humans and rats. EPSs could affect the physical properties of fermented milk to enhance dietary β-carotene absorption mediated by simple diffusion mechanisms. These findings may be relevant for methods to increase dietary carotenoid bioavailability.This trial was registered at umin.ac.jp/ctr as UMIN000034838, UMIN000034839, and UMIN000034840. Copyright © The Author(s) 2020.AIMS  Left ventricular (LV) myocardial crypts are considered a subtle marker of hypertrophic cardiomyopathy. However, crypts have also been observed in seemingly healthy individuals and it is unknown whether myocardial crypts are associated with adverse outcome. METHODS AND RESULTS  Myocardial crypts were defined as invaginations traversing >50% of the myocardial wall and assessed using contrast-enhanced cardiac computed tomography in 10 097 individuals from the Copenhagen General Population Study. Number of crypts, location, shape, penetrance, and volume were assessed. The endpoint was a composite of major adverse cardiovascular events and defined as death, myocardial infarction, heart failure, or stroke. Cox regression models were adjusted for clinical variables, medical history, electrocardiographic parameters, and cardiac chamber sizes. A total of 1199 LV myocardial crypts were identified in 915 (9.1%) individuals. Hedgehog antagonist Seven hundred (6.9%) had one crypt and 215 (2.1%) had multiple crypts. During a median follow-up of 4.0 years (interquartile range 1.5-6.7), major adverse cardiovascular events occurred in 619 individuals. Individuals with one or multiple crypts had a hazard ratio for major adverse cardiovascular events of 1.00 [95% confidence interval (CI) 0.72-1.40; P = 0.98] and 0.90 (95% CI 0.47-1.75; P = 0.76), respectively, compared with those with no crypts. No specific pattern of crypt location, shape, penetrance, or volume was associated to an increased hazard ratio for major adverse cardiovascular events. CONCLUSION  LV myocardial crypts are frequent in the general population and are not associated with intermediate-term major adverse cardiovascular events. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email journals.permissions@oup.com.Cytokines can trigger multiple signaling pathways, including Janus Tyrosine kinases (JAK) and signal transducers and activators of transcription (STATS) pathways. JAKs are cytoplasmic proteins that, following the binding of cytokines to their receptors, transduce the signal by phosphorylating STAT proteins, which enter the nuclei and rapidly target gene promoters to regulate gene transcription. Due to the critical involvement of JAK proteins in mediating innate and adaptive immune responses, these family of kinases have become desirable pharmacological targets in inflammatory diseases, including ulcerative colitis and Crohn’s disease. In this review we provide an overview of the main cytokines that signal through the JAK/STAT pathway, the available in vivo evidence on mutant or deleted JAK proteins and discuss the implications of pharmacologically targeting this kinase family in the context of inflammatory diseases. © European Crohn’s and Colitis Organisation (ECCO) 2019.SUMMARY We present an R-Shiny package, netGO, for novel network-integrated pathway enrichment analysis. The conventional Fisher’s exact test (FET) considers the extent of overlap between target genes and pathway gene-sets, while recent network-based analysis tools consider only network interactions between the two. netGO implements an intuitive framework to integrate both the overlap and networks into a single score, and adaptively resamples genes based on network degrees to assess the pathway enrichment. In benchmark tests for gene expression and genome-wide association study (GWAS) data, netGO captured the relevant gene-sets better than existing tools, especially when analyzing a small number of genes. Specifically, netGO provides user-interactive visualization of the target genes, enriched gene-set and their network interactions for both netGO and FET results for further analysis. For this visualization, we also developed a standalone R-Shiny package shinyCyJS to connect R-shiny and the JavaScript version of cytoscape. AVAILABILITY AND IMPLEMENTATION netGO R-Shiny package is freely available from github, https//github.com/unistbig/netGO. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.Severe acute respiratory syndrome coronavirus is the causative agent of a respiratory disease with a high case fatality rate. During the formation of the coronaviral replication/transcription complex, essential steps include processing of the conserved polyprotein nsp7-10 region by the main protease Mpro and subsequent complex formation of the released nsp’s. Here, we analyzed processing of the coronavirus nsp7-10 region using native mass spectrometry showing consumption of substrate, rise and fall of intermediate products and complexation. Importantly, there is a clear order of cleavage efficiencies, which is influenced by the polyprotein tertiary structure. Furthermore, the predominant product is an nsp7+8(2  2) hetero-tetramer with nsp8 scaffold. In conclusion, native MS, opposed to other methods, can expose the processing dynamics of viral polyproteins and the landscape of protein interactions in one set of experiments. Thereby, new insights into protein interactions, essential for generation of viral progeny, were provided, with relevance for development of antivirals.

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