Mullinssaleh8953

MOTIVATION Polyproline II (PPII) is a common conformation, comparable to α-helix and β-sheet and is a candidate for being the most prevalent secondary structure. PPII, recently termed with a more generic name - κ-helix, adopts a left-handed structure with 3-fold rotational symmetry. Lately, a new type of binding mechanism - the helical lock and key model was introduced in SH3-domain complexes, where the interaction is characterized by a sliding helical pattern. However, whether this binding mechanism is unique only to SH3 domains is unreported. RESULTS Here, we show that the helical binding pattern is a universal feature of the κ-helix conformation, present within all the major target families - SH3, WW, profilin, MHC-II, EVH1, and GYF domains. Based on a geometric analysis of 255 experimentally solved structures, we found that they are characterized by a distinctive rotational angle along the helical axis. Furthermore, we found that the range of helical pitch varies between different protein domains or peptide orientations and that the interaction is also represented by a rotational displacement mimicking helical motion. The discovery of rotational interactions as a mechanism, reveals a new dimension in the realm of protein-protein interactions, which introduces a new layer of information encoded by the helical conformation. Due to the extensive involvement of the conformation in functional interactions, we anticipate our model to expand the current molecular understanding of the relationship between protein structure and function. AVAILABILITY We have implemented the proposed methods in an R package freely available at https//github.com/Grantlab/bio3d. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online. © The Author(s) (2020). Published by Oxford University Press. All rights reserved. For Permissions, please email journals.permissions@oup.com.BACKGROUND Some religious dimensions have been associated with different health-related outcomes over many years. Attending religious services is one of these dimensions that were associated with hypertension, with inconsistent results. And religious involvement seems to be closely influenced by sociodemographic factors, such as education. Therefore, this study aimed to investigate the association between religious service attendance and hypertension according to levels of education. METHODS We analyzed baseline data of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Frequency of religious service attendance and presence of hypertension were assessed in all 15,105 participants at baseline. The analyses were stratified by two levels of education (less than high school and high school or more). Logistic regression models were used to obtain the association between religious service attendance and hypertension in both groups. RESULTS For those with high school or more, attending religious services was positively associated with hypertension (adjusted odds ratio [OR] = 1.14, 95% confidence interval [CI] 1.02-1.28). In contrast, for those with less than high school, attending services was inversely associated with presence of hypertension (adjusted OR = 0.73, 95% CI 0.55-0.96). CONCLUSIONS There seems to be a paradox in the association of religious service attendance and hypertension depending on the level of education. Proteasome function © American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email journals.permissions@oup.com.AIMS Patients with heart failure (HF) have high costs, morbidity and mortality, but it is not known if appropriate pharmacotherapy (AP), defined as compliance with international evidence-based guidelines, is associated with improved. The purpose of this study was to evaluate HF patients' health care utilization, cost and outcomes in Region Halland (RH), Sweden, and if AP was associated with costs. METHODS AND RESULTS 5 987 residents of RH in 2016 carried HF diagnoses. Costs were assigned to all healthcare utilization (inpatient, outpatient, emergency department, primary health care and medications) using a Patient Encounter Costing methodology. Care of HF patients cost €58.6M, (€9 790/patient) representing 8.7% of RH's total visit expenses and 14.9% of inpatient care expenses. Inpatient care represented 57.2% of this expenditure, totaling €33.5M (€5,601/patient). Receiving AP was associated with significantly lower costs, by €1 130 per patient (p  less then  0.001, 95% Confidence Interval 574,1 687) Comorbidities such as renal failure, diabetes, COPD and cancer were significantly associated with higher costs. CONCLUSION HF patients are heavy users of healthcare, particularly inpatient care. Receiving AP is associated with lower costs even adjusting for comorbidities, although causality cannot be proven from an observational study. There may be an opportunity to decrease overall costs and improve outcomes by improving prescribing patterns and associated high-quality care. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions please email journals.permissions@oup.com.AIM Cardiac dysfunction is a prevalent comorbidity of disrupted inflammatory homeostasis observed in conditions such as sepsis (acute) or obesity (chronic). Secreted and transmembrane protein 1a (Sectm1a) has previously been implicated to regulate inflammatory responses, yet its role in inflammation-associated cardiac dysfunction is virtually unknown. METHODS AND RESULTS Using the CRISPR/Cas9 system, we generated a global Sectm1a-knockout (KO) mouse model and observed significantly increased mortality and cardiac injury after LPS injection, when compared to wild-type (WT) control. Further analysis revealed significantly increased accumulation of inflammatory macrophages in hearts of LPS-treated KO mice. Accordingly, ablation of Sectm1a remarkably increased inflammatory cytokines levels both in vitro [from bone marrow-derived macrophages (BMDMs)] and in vivo (in serum and myocardium) after LPS challenge. RNA-sequencing results and bioinformatics analyses showed that the most significantly downregulated genes in KO-BMDMs were modulated by LXRα, a nuclear receptor with robust anti-inflammatory activity in macrophages.