• Frederick Houston posted an update 1 day, 11 hours ago

    t of human lung adenocarcinoma.Recent evidence suggests that fibrotic liver injury in patients with chronic hepatitis C correlates with cellular senescence in damaged liver tissue. However, it is still unclear how senescence can affect replication of the hepatitis C virus (HCV). find more In this work, we report that an inhibitor of cyclin-dependent kinases 4/6, palbociclib, not only induced in hepatoma cells a pre-senescent cellular phenotype, including G1 arrest in the cell cycle, but also accelerated viral replicon multiplication. Importantly, suppression of HCV replication by direct acting antivirals (DAAs) was barely affected by pre-senescence induction, and vice versa, the antiviral activities of host-targeting agents (HTAs), such as inhibitors of human histone deacetylases (HDACi), produced a wide range of reactions-from a dramatic reduction to a noticeable increase. It is very likely that under conditions of the G1 arrest in the cell cycle, HDACi exhibit their actual antiviral potency, since their inherent anticancer activity that complicates the interpretation of test results is minimized.The high tensile strength and irradiation resistance of oxide dispersion strengthened (ODS) ferritic steels is attributed to the ultrafine and dispersed oxides within the matrix. The high content of oxygen and yttrium is critical for the formation of dense Y-rich oxides. However, only few studies have reported the effect of oxygen content on the microstructure and mechanical properties of ODS steels. Herein, we employed gas atomization reactive synthesis to prepare pre-alloy powders and then hot isostatic pressing (HIP) to consolidate two 22Cr-5Al ODS steels with different oxygen content. Our results showed Y-rich precipitates at and near grain boundaries of the as-HIPed alloys. Moreover, with the oxygen content increasing from 0.04 to 0.16 wt%, more precipitates precipitated in the as-HIPed alloy, and the ultimate tensile strength of the alloy was improved. However, increasing the oxygen content to 0.16 wt% led to formation of stripe and chain precipitates at and near grain boundaries, which caused a partial intergranular fracture of the as-HIPed alloy.Extracellular vesicles (EVs) and their contents (proteins, lipids, messenger RNA, microRNA, and DNA) are viewed as intercellular signals, cell-transforming agents, and shelters for viruses that allow both diagnostic and therapeutic interventions. EVs circulating in the blood of individuals infected with human immunodeficiency virus (HIV-1) may provide insights into pathogenesis, inflammation, and disease progression. However, distinguishing plasma membrane EVs from exosomes, exomeres, apoptotic bodies, virions, and contaminating proteins remains challenging. We aimed at comparing sucrose and iodixanol density and velocity gradients along with commercial kits as a means of separating EVs from HIV particles and contaminating protein like calprotectin; and thereby evaluating the suitability of current plasma EVs analysis techniques for identifying new biomarkers of HIV-1 immune activation. Multiple analysis have been performed on HIV-1 infected cell lines, plasma from HIV-1 patients, or plasma from HIV-negative her use as biomarkers. By revealing a new population of EVs enriched in miR-155 and mitochondrial DNA, this study paves a way to increase our understanding of HIV-1 pathogenesis.Neuronal nitric oxide synthase (nNOS) has various roles as a neurotransmitter. However, studies to date have produced insufficient data to fully support the correlation between nNOS and bowel motility. This study aimed to investigate the correlation between nNOS expression and gastrointestinal (GI) tract motility using a stress-induced neonatal maternal separation (NMS) mouse model. In this study, we generated a genetically modified mouse with the HiBiT sequence knock-in into the nNOS gene using CRISPR/Cas9 for analyzing accurate nNOS expression. nNOS expression was measured in the stomach, small intestine, large intestine, adrenal gland, and hypothalamus tissues after establishing the NMS model. The NMS model exhibited a significant increase in nNOS expression in large intestine, adrenal gland, and hypothalamus. Moreover, a significant positive correlation was observed between whole gastrointestinal transit time and the expression level of nNOS. We reasoned that NMS induced chronic stress and consequent nNOS activation in the hypothalamic-pituitary-adrenal (HPA) axis, and led to an excessive increase in intestinal motility in the lower GI tract. These results demonstrated that HiBiT is a sensitive and valuable tool for analyzing in vivo gene activation, and nNOS could be a biomarker of the HPA axis-linked lower intestinal tract dysfunction.The present study aimed to develop predictive models of calf birth weight (CBW) from liveweight (LW) data collected remotely and individually using an automated in-paddock walk-over-weighing scale (WOW). Twenty-eight multiparous Charolais cows were mated with two Brahman bulls. The WOW was installed at the only watering point to capture LW over five months. Calf birth date and weight were manually recorded, and the liveweight change experienced by a dam at calving (ΔLWC) was calculated as pre-LW minus post-LW calving. Cow non-foetal weight loss at calving (NFW) was calculated as ΔLWC minus CBW. Pearson’s correlational analysis and simple linear regressions were used to identify associations between all variables measured. No correlations were found between ΔLWC and pre-LW (p = 0.52), or post-LW (p = 0.14). However, positive associations were observed between ΔLWC and CBW (p less then 0.001, R2 = 0.56) and NFW (p less then 0.001, R2 = 0.90). Thus, the results suggest that 56% of the variation in ΔLWC is attributed to the calf weight, and consequently could be used as an indicator of CBW. Remote, in-paddock weighing systems have the potential to provide timely and accurate LW data of breeding cows to improve calving management and productivity.The SARS-CoV-2 outbreak was declared a worldwide pandemic in 2020. Infection triggers the respiratory tract disease COVID-19, which is accompanied by serious changes in clinical biomarkers such as hemoglobin and interleukins. The same parameters are altered during hemolysis, which is characterized by an increase in labile heme. We present two computational-experimental approaches aimed at analyzing a potential link between heme-related and COVID-19 pathophysiologies. Herein, we performed a detailed analysis of the common pathways induced by heme and SARS-CoV-2 by superimposition of knowledge graphs covering heme biology and COVID-19 pathophysiology. Focus was laid on inflammatory pathways and distinct biomarkers as the linking elements. In a second approach, four COVID-19-related proteins, the host cell proteins ACE2 and TMPRSS2 as well as the viral proteins 7a and S protein were computationally analyzed as potential heme-binding proteins with an experimental validation. The results contribute to the understanding of the progression of COVID-19 infections in patients with different clinical backgrounds and may allow for a more individual diagnosis and therapy in the future.