Excitation-contraction coupling in vertebrate hearts is underpinned by calcium (Ca
) release from Ca
release units (CRUs). CRUs are formed by clusters of channels called ryanodine receptors on the ...sarcoplasmic reticulum (SR) within the cardiomyocyte. Distances between CRUs influence the diffusion of Ca
, thus influencing the rate and strength of excitation-contraction coupling. Avian myocytes lack T-tubules, so Ca
from surface CRUs (peripheral couplings, PCs) must diffuse to internal CRU sites of the corbular SR (cSR) during centripetal propagation. Despite this, avian hearts achieve higher contractile rates and develop greater contractile strength than many mammalian hearts, which have T-tubules to provide simultaneous activation of the Ca
signal through the myocyte. We used 3D electron tomography to test the hypothesis that the intracellular distribution of CRUs in the avian heart permits faster and stronger contractions despite the absence of T-tubules. Nearest edge-edge distances between PCs and cSR, and geometric information including surface area and volume of individual cSR, were obtained for each cardiac chamber of the white leghorn chicken. Computational modelling was then used to establish a relationship between CRU distance and cell activation time in the avian heart. Our data suggest that cSR clustered close together along the Z-line is vital for rapid propagation of the Ca
signal from the cell periphery to the cell centre, which would aid in the strong and fast contractions of the avian heart.
Objective:The purpose of this study was to assess the impact of the Virtual Hope Box (VHB), a smartphone app to improve stress coping skills, suicidal ideation, and perceived reasons for living among ...patients at elevated risk of suicide and self-harm.Methods:The authors conducted a parallel-group randomized controlled trial with two groups of U.S. service veterans in active mental health treatment who had recently expressed suicidal ideation. Between March 2014 and April 2015, 118 patients were enrolled in the study. Participants were assigned to use the VHB (N=58) or to a control group that received printed materials about coping with suicidality (N=60) to supplement treatment as usual over a 12-week period. Three measures—the Coping Self-Efficacy Scale, Beck Scale for Suicidal Ideation, and Brief Reasons for Living Inventory—were collected at baseline (before randomization) and three, six, and 12 weeks. Secondary measures—the Interpersonal Needs Questionnaire, Perceived Stress Scale, and Columbia-Suicide Severity Rating Scale—were collected at baseline and 12 weeks.Results:VHB users reported significantly greater ability to cope with unpleasant emotions and thoughts (Coping Self-Efficacy Scale) at three (b=2.41, 95% confidence interval CI=.29–4.55) and 12 weeks (b=2.99, 95% CI=.08–5.90) compared with the control group. No significant advantage was found on other outcome measures for treatment augmented by the VHB.Conclusions: The VHB is a demonstrably useful accessory to treatment—an easily accessible tool that can increase stress coping skills. Because the app is easily disseminated across a large population, it is likely to have broad, positive utility in behavioral health care.
Variation in susceptibility is ubiquitous in multi‐host, multi‐parasite assemblages, and can have profound implications for ecology and evolution in these systems. The extent to which susceptibility ...to parasites is phylogenetically conserved among hosts can be revealed by analysing diverse regional communities. We screened for haemosporidian parasites in 3983 birds representing 40 families and 523 species, spanning ~ 4500 m elevation in the tropical Andes. To quantify the influence of host phylogeny on infection status, we applied Bayesian phylogenetic multilevel models that included a suite of environmental, spatial, temporal, life history and ecological predictors. We found evidence of deeply conserved susceptibility across the avian tree; host phylogeny explained substantial variation in infection status, and results were robust to phylogenetic uncertainty. Our study suggests that susceptibility is governed, in part, by conserved, latent aspects of anti‐parasite defence. This demonstrates the importance of deep phylogeny for understanding present‐day ecological interactions.
Participants in an underserved minority population in the United States were randomly assigned to receive a polypill that included low doses of atorvastatin, amlodipine, losartan, and ...hydrochlorothiazide or to receive usual care. At 12 months, systolic blood pressure and LDL cholesterol levels were significantly lower in the polypill group.
Multiple roles of reactive oxygen species (ROS) and their consequences for health and disease are emerging throughout biological sciences. This development has led researchers unfamiliar with the ...complexities of ROS and their reactions to employ commercial kits and probes to measure ROS and oxidative damage inappropriately, treating ROS (a generic abbreviation) as if it were a discrete molecular entity. Unfortunately, the application and interpretation of these measurements are fraught with challenges and limitations. This can lead to misleading claims entering the literature and impeding progress, despite a well-established body of knowledge on how best to assess individual ROS, their reactions, role as signalling molecules and the oxidative damage that they can cause. In this consensus statement we illuminate problems that can arise with many commonly used approaches for measurement of ROS and oxidative damage, and propose guidelines for best practice. We hope that these strategies will be useful to those who find their research requiring assessment of ROS, oxidative damage and redox signalling in cells and in vivo.
The mRNA-1273 vaccine was approved for emergency use in December 2020; trial participants who received placebo were informed of the results and offered vaccination. At the close of the blinded phase ...of the trial, the vaccine efficacy in preventing Covid-19 illness was 93.2%, and the efficacy against severe disease was 98.2%. No new safety issues were identified.
Type 2 immunity is critical for defense against cutaneous infections but also underlies the development of allergic skin diseases. We report the identification in normal mouse dermis of an abundant, ...phenotypically unique group 2 innate lymphoid cell (ILC2) subset that depended on interleukin 7 (IL-7) and constitutively produced IL-13. Intravital multiphoton microscopy showed that dermal ILC2 cells specifically interacted with mast cells, whose function was suppressed by IL-13. Treatment of mice deficient in recombination-activating gene 1 (Rag1(-/-)) with IL-2 resulted in the population expansion of activated, IL-5-producing dermal ILC2 cells, which led to spontaneous dermatitis characterized by eosinophil infiltrates and activated mast cells. Our data show that ILC2 cells have both pro- and anti-inflammatory properties and identify a previously unknown interactive pathway between two innate populations of cells of the immune system linked to type 2 immunity and allergic diseases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives:
We examine whether individuals engage in crime across a variety of different settings (contextual generality). Specifically, we assess whether individuals who engage in workplace crime ...will engage in street crime and whether certain individuals have a greater tendency to engage in workplace crime relative to street crime. We are guided by trait-based theories, learning theories, and strain theories to guide our expectations related to the contextual generality of criminal behavior.
Methods:
We analyze data from the National Youth Survey and conduct multinomial logistic regressions, item response theory, and ordinary least squares regressions. We supplement this with the Youth Development Survey and the Pathways to Desistance Study.
Results:
There is a small overlap between workplace crime and street crime. Participation in each context is related to context-specific perceived coworker/peer disapproval and deviant workplace definitions. There is a tendency for some respondents to specialize in workplace crime relative to street crime.
Conclusions:
Contextual generality in criminal behavior is a fruitful avenue to study theoretical debates between theories of population heterogeneity and theories that allow for specific types of offending. More studies are needed to extend this line of inquiry.
Germline pathogenic variants in BRCA1 and BRCA2 predispose to an increased lifetime risk of breast cancer. However, the relevance of germline variants in other genes from multigene hereditary cancer ...testing panels is not well defined.
To determine the risks of breast cancer associated with germline variants in cancer predisposition genes.
A study population of 65 057 patients with breast cancer receiving germline genetic testing of cancer predisposition genes with hereditary cancer multigene panels. Associations between pathogenic variants in non-BRCA1 and non-BRCA2 predisposition genes and breast cancer risk were estimated in a case-control analysis of patients with breast cancer and Exome Aggregation Consortium reference controls. The women underwent testing between March 15, 2012, and June 30, 2016.
Breast cancer risk conferred by pathogenic variants in non-BRCA1 and non-BRCA2 predisposition genes.
The mean (SD) age at diagnosis for the 65 057 women included in the analysis was 48.5 (11.1) years. The frequency of pathogenic variants in 21 panel genes identified in 41 611 consecutively tested white women with breast cancer was estimated at 10.2%. After exclusion of BRCA1, BRCA2, and syndromic breast cancer genes (CDH1, PTEN, and TP53), observed pathogenic variants in 5 of 16 genes were associated with high or moderately increased risks of breast cancer: ATM (OR, 2.78; 95% CI, 2.22-3.62), BARD1 (OR, 2.16; 95% CI, 1.31-3.63), CHEK2 (OR, 1.48; 95% CI, 1.31-1.67), PALB2 (OR, 7.46; 95% CI, 5.12-11.19), and RAD51D (OR, 3.07; 95% CI, 1.21-7.88). Conversely, variants in the BRIP1 and RAD51C ovarian cancer risk genes; the MRE11A, RAD50, and NBN MRN complex genes; the MLH1 and PMS2 mismatch repair genes; and NF1 were not associated with increased risks of breast cancer.
This study establishes several panel genes as high- and moderate-risk breast cancer genes and provides estimates of breast cancer risk associated with pathogenic variants in these genes among individuals qualifying for clinical genetic testing.
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