Coynebeier5516

Calpains have been implicated in heart diseases. While calpain-1 has been detrimental to the heart, the role of calpain-2 in cardiac pathology remains controversial. In this study we investigated whether sustained over-expression of calpain-2 had any adverse effects on the heart and the underlying mechanisms. Double transgenic mice (Tg-Capn2/tTA) were generated, which express human CAPN2 restricted to cardiomyocytes. The mice were subjected to echocardiography at age 3, 6, 8 and 12 months, and their heart tissues and sera were collected for analyses. We showed that transgenic mice over-expressing calpain-2 restricted to cardiomyocytes had normal heart function with no evidence of cardiac pathological remodeling at age 3 months. However, they exhibited features of dilated cardiomyopathy including increased heart size, enlarged heart chambers and heart dysfunction from age 8 months; histological analysis revealed loss of cardiomyocytes replaced by myocardial fibrosis and cardiomyocyte hypertrophy in transgenic rdiomyopathy in mice, which may be mediated through aberrant autophagy and a reduction of junctophilin-2. Thus, a sustained increase in calpain-2 may be detrimental to the heart.Nitidine chloride (NC) is a standard active component from the traditional Chinese medicine Zanthoxylum nitidum (Roxb.) DC. (ZN). NC has shown a variety of pharmacological activities including anti-tumor activity. As a number of anti-tumor drugs cause cardiotoxicity, herein we investigated whether NC exerted a cardiotoxic effect and the underlying mechanism. Aqueous extract of ZN (ZNE) was intraperitoneally injected into rats, while NC was injected into beagles and mice once daily for 4 weeks. Cardiac function was assessed using echocardiography. We showed that both ZNE administered in rats and NC administered in mice induced dose-dependent cardiac hypertrophy and dysfunction, whereas administration of NC at the middle and high dose caused death in Beagles. Consistently, we observed a reduction of cardiac autophagy levels in NC-treated mice and neonatal mouse cardiomyocytes. Furthermore, we demonstrated that autophagy-related 4B cysteine peptidase (ATG4B) may be a potential target of NC, since overexpression of ATG4B reversed the cardiac hypertrophy and reduced autophagy levels observed in NC-treated mice. We conclude that NC induces cardiac hypertrophy via ATG4B-mediated downregulation of autophagy in mice. Thus, this study provides guidance for the safe clinical application of ZN and the use of NC as an anti-tumor drug.L-BC virus persists in the budding yeast Saccharomyces cerevisiae, whereas other viruses from the family Totiviridae infect a diverse group of organisms including protists, fungi, arthropods, and vertebrates. The presence of totiviruses alters the fitness of the host organisms, for example, by maintaining the killer system in yeast or increasing the virulence of Leishmania guyanensis. Despite the importance of totiviruses for their host survival, there is limited information about Totivirus structure and assembly. Here we used cryo-electron microscopy to determine the structure of L-BC virus to a resolution of 2.9 Å. The L-BC capsid is organized with icosahedral symmetry, with each asymmetric unit composed of two copies of the capsid protein. Decamers of capsid proteins are stabilized by domain swapping of the C-termini of subunits located around icosahedral fivefold axes. We show that capsids of 9% of particles in a purified L-BC sample were open and lacked one decamer of capsid proteins. The existence of the open particles together with domain swapping within a decamer provides evidence that Totiviridae capsids assemble from the decamers of capsid proteins. Furthermore, the open particles may be assembly intermediates that are prepared for the incorporation of the virus (+) strand RNA.Background Maxillary expansion (ME) might be beneficial in improving airway dimensions and obstructive sleep apnoea syndrome (OSAS) in patients with constricted maxillae. The aim of this overview is to present clinicians with a summary of the evidence. Data from systematic reviews and meta-analyses were evaluated to investigate the effect of ME on OSAS.Methods An electronic search was commenced in five databases, in addition to a manual search until July 2021. Screening of articles started with title and abstract followed by full-text assessment. Systematic reviews with/without meta-analyses were included. Critical appraisal was done using A Measurement Tool to Assess Systematic Reviews (AMSTAR) 2, Level of Research Design scoring and criteria of body of evidence scores. The search, study selection and critical appraisal were completed by three reviewers.Results In total, 14 systematic reviews with/without meta-analyses were included. The quality of available evidence ranged between low to high, based on the overall quality evaluation.Conclusions Based on the available evidence, maxillary expansion might be able to improve the nasal airway volume and OSAS in both growing and adult patients in the short term. ME can be considered as one of the treatment options in cases with OSAS.

Recent evidence has shown associations between cardiovascular disease and a proinflammatory diet. We hypothesized that a proinflammatory diet, assessed using the Empirical Dietary Inflammatory Index (EDII), is associated with increased risk of prevalent heart failure (HF).

This analysis included 13,687 participants (44.8 ± 19.4 years; 45.7% male, 67.8% whites) from the Third National Health and Nutrition Examination Survey. EDII score was calculated from the Food Frequency Questionnaire. Prevalent HF was determined by physician-diagnosed self-report. Multivariable logistic regression analysis was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for the association between EDII score and prevalent HF across tertiles (reference group first tertile) and per 1-unit standard deviation (1-SD) increase.

About 1.4% (n = 190) of the participants reported a history of HF. Each 1-SD increase in EDII score (0.276) conferred 25% increased odds of prevalent HF (OR (95% CI) 1.25 (1.07-1.46); p value = 0.006). Odds of HF increased as EDII tertile increased, indicating a dose-response relationship (OR (95% CI) for 2nd and 3rd tertiles compared to 1st tertile 1.42 (0.99-2.04), 1.68 (1.15-2.46), respectively). These results were consistent in subgroups of the participants stratified by demographics and comorbidities.

Proinflammatory dietary patterns are associated with an increased risk of HF. The risk of HF could potentially be reduced by avoiding proinflammatory dietary patterns.

Proinflammatory dietary patterns are associated with an increased risk of HF. The risk of HF could potentially be reduced by avoiding proinflammatory dietary patterns.

Exposure to lead (Pb), arsenic (As) and copper (Cu) may cause significant health issues including harmful neurological effects, cancer or organ damage. Determination of human exposure-relevant concentrations of these metal(loids) in drinking water, therefore, is critical.

We sought to characterize exposure-relevant Pb, As, and Cu concentrations in drinking water collected from homes participating in the American Healthy Homes Survey II, a national survey that monitors the prevalence of Pb and related hazards in United States homes.

Drinking water samples were collected from a national survey of 678 U.S. homes where children may live using an exposure-based composite sampling protocol. Relationships between metal(loid) concentration, water source and house age were evaluated.

18 of 678 (2.6%) of samples analyzed exceeded 5 µg Pb L



(Mean = 1.0 µg L



). 1.5% of samples exceeded 10 µg As L



(Mean = 1.7 µg L



) and 1,300 µg Cu L



(Mean = 125 µg L



). Private well samples were more likely toampling protocol. Therefore, assessing public health impacts from metal(loids) in drinking water remains challenging. Results presented in this study represent the largest effort to date to test for exposure-relevant concentrations of Pb, As and Cu in US household drinking water, providing a critical step toward improved understanding of metal(loid) exposure risk.Postmating-prezygotic (PMPZ) reproductive isolation is hypothesized to result from divergent coevolutionary trajectories of sexual selection and/or sexual conflict in isolated populations. However, the genetic basis of PMPZ incompatibilities between species is poorly understood. Here, we use a comparative framework to compare global gene expression in con- and heterospecifically mated Drosophila mojavensis and D. arizonae female reproductive tracts. We find striking divergence between the species in the female postmating transcriptional response to conspecific mating, including differences in differential expression (DE), alternative splicing (AS), and intron retention (IR). As predicted, heterospecific matings produce disrupted transcriptional profiles, but the overall patterns of misregulation are different between the reciprocal crosses. Moreover, we find a positive correlation between postmating transcriptional divergence between species and levels of transcriptional disruption in heterospecific crosses. Bcl2 inhibitor This result indicates that mating responsive genes that have diverged more in expression also have more disrupted transcriptional profiles in heterospecifically mated females. Overall, our results provide insights into the evolution of PMPZ isolation and lay the foundation for future studies aimed at identifying specific genes involved in PMPZ incompatibilities and the evolutionary forces that have contributed to their divergence in closely related species.In the search for biological markers after a large-scale exposure of the human population to radiation, gene expression is a sensitive endpoint easily translatable to in-field high throughput applications. Primarily, the ex-vivo irradiated healthy human blood model has been used to generate available gene expression datasets. This model has limitations i.e., lack of signaling from other irradiated tissues and deterioration of blood cells cultures over time. In vivo models are needed; therefore, we present our novel approach to define a gene signature in mouse blood cells that quantitatively correlates with radiation dose (at 1 Gy/min). Starting with available microarray datasets, we selected 30 radiation-responsive genes and performed cross-validation/training-testing data splits to downselect 16 radiation-responsive genes. We then tested these genes in an independent cohort of irradiated adult C57BL/6 mice (5050 both sexes) and measured mRNA by quantitative RT-PCR in whole blood at 24 h. Dose reconstruction using net signal (difference between geometric means of top 3 positively correlated and top 4 negatively correlated genes with dose), was highly improved over the microarrays, with a root mean square error of ± 1.1 Gy in male and female mice combined. There were no significant sex-specific differences in mRNA or cell counts after irradiation.A major roadblock to the development of photonic sensors is the scattering associated with many biological systems. We show the conservation of photonic states through optically self-arranged biological waveguides, for the first time, which can be implemented to transmit light through scattering media. The conservation of optical properties of light through biological waveguides allows for the transmission of high bandwidth information with low loss through scattering media. Here, we experimentally demonstrate the conservation of polarization state and orbital angular momentum of light through a self-arranged biological waveguide, several centimeters long, in a sheep red blood cell suspension. We utilize nonlinear optical effects to self-trap cells, which form waveguides at 532 nm and 780 nm wavelengths. Moreover, we use the formed waveguide channels to couple and guide probe beams without altering the information. The formed biological waveguides are in a sub-diffusive scattering regime, so the photons' information degrades insignificantly over several centimeters of propagation through the scattering media.