Ashleynikolajsen7837

Cognitive flexibility, the ability to alter strategy according to changing stimulus-response-reward relationships, is critical for updating learned behavior. Attentional set-shifting, a test of cognitive flexibility, depends on the activity of prefrontal cortex (PFC). It remains unclear, however, what role PFC neurons play to support set-shifting. Using optogenetics and two-photon calcium imaging, we demonstrate that medial PFC activity does not bias sensorimotor responses during set-shifting, but rather enables set-shifting by encoding trial feedback information, a role it has been known to play in other contexts. Unexpectedly, the functional properties of PFC cells did not vary with their efferent projection targets. Instead, representations of trial feedback formed a topological gradient, with cells more strongly selective for feedback information located further from the pial surface, where afferent input from the anterior cingulate cortex was denser. These findings identify a critical role for deep PFC projection neurons in enabling set-shifting through behavioral feedback monitoring.The highly transmissible B.1.1.7 variant of SARS-CoV-2, first identified in the United Kingdom, has gained a foothold across the world. Using S gene target failure (SGTF) and SARS-CoV-2 genomic sequencing, we investigated the prevalence and dynamics of this variant in the United States (US), tracking it back to its early emergence. We found that, while the fraction of B.1.1.7 varied by state, the variant increased at a logistic rate with a roughly weekly doubling rate and an increased transmission of 40%-50%. We revealed several independent introductions of B.1.1.7 into the US as early as late November 2020, with community transmission spreading it to most states within months. We show that the US is on a similar trajectory as other countries where B.1.1.7 became dominant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality.Yu et al. (2021) demonstrate that a subset of X-linked immune genes is repressed on the inactive X chromosome (Xi) in a manner dependent on XIST RNA in B cells, and derepression of these genes upon XIST depletion could bias differentiation of naive B cells and be involved in etiology of female-biased autoimmune diseases.In this issue of Molecular Cell, Behrens et al. (2021) address a long-standing challenge in the field of tRNA regulation and develop an approach for measuring tRNA abundance at unprecedented accuracy.Using a genetic platform to generate histone mutants in Drosophila, Regadas et al. (2021) discover a novel mechanism for tissue-specific gene expression requiring a chromatin state defined by acetylation of lysine 14 of H3 but lacking other activating histone post-translational modifications.Two recent papers, Rao et al. (2021), in this issue, and Sönmezer et al. (2021), investigate transcription factor cooperativity at cis-regulatory elements. Using data from nuclease- and methyltransferase-footprinting experiments, they demonstrate that factor co-occupancy at regulatory elements commonly occurs in vivo and is conserved from fly to mouse.Anniina Vihervaara and Lea Sistonen share with us some of their experiences, including the paths to setting up their own labs and some behind-the-scenes details about their paper, "Stress-induced transcriptional memory accelerates promoter-proximal pause-release and decelerates termination over mitotic divisions."Troy McEachron, corresponding author of the technology review article "Applicability of spatial transcriptional profiling to cancer research," discusses his motivation for becoming a scientist and pursing pediatric cancer research, the challenges he faces as a Black scientist, and strategies for writing a review article.Naturalistic escape requires versatile context-specific flight with rapid evaluation of local geometry to identify and use efficient escape routes. It is unknown how spatial navigation and escape circuits are recruited to produce context-specific flight. Using mice, we show that activity in cholecystokinin-expressing hypothalamic dorsal premammillary nucleus (PMd-cck) cells is sufficient and necessary for context-specific escape that adapts to each environment's layout. In contrast, numerous other nuclei implicated in flight only induced stereotyped panic-related escape. We reasoned the dorsal premammillary nucleus (PMd) can induce context-specific escape because it projects to escape and spatial navigation nuclei. Indeed, activity in PMd-cck projections to thalamic spatial navigation circuits is necessary for context-specific escape induced by moderate threats but not panic-related stereotyped escape caused by perceived asphyxiation. Conversely, the PMd projection to the escape-inducing dorsal periaqueductal gray projection is necessary for all tested escapes. Thus, PMd-cck cells control versatile flight, engaging spatial navigation and escape circuits.How sensory evidence is transformed across multiple brain regions to influence behavior remains poorly understood. We trained mice in a visual change detection task designed to separate the covert antecedents of choices from activity associated with their execution. Wide-field calcium imaging across the dorsal cortex revealed fundamentally different dynamics of activity underlying these processes. Although signals related to execution of choice were widespread, fluctuations in sensory evidence in the absence of overt motor responses triggered a confined activity cascade, beginning with transient modulation of visual cortex and followed by sustained recruitment of the secondary and primary motor cortex. Activation of the motor cortex by sensory evidence was modulated by animals' expectation of when the stimulus was likely to change. These results reveal distinct activation timescales of specific cortical areas by sensory evidence during decision-making and show that recruitment of the motor cortex depends on the interaction of sensory evidence and temporal expectation.In the decade since the last published comprehensive report of occupational exposures in the glass wool insulation industry, many process and regulatory changes have occurred in the glass wool manufacturing sector. This paper assesses whether any significant changes in worker exposures to glass wool fibers have resulted from these process and regulatory changes. The analysis compares worker exposures to glass wool overall and across different product and job categories in the manufacturing sector prior to and after 2007, the data cutoff period for the last comprehensive update of occupational exposures in this industry. The exposure data were downloaded from the North American Insulation Manufacturers Association's synthetic vitreous fiber (SVF) exposure database, which has been continually updated with all new available SVF exposure data for the past two decades. This analysis finds no major changes in worker exposures in the glass wool manufacturing industry over the past decade, with exposures remaining well below the 1 f/cc voluntary permissible exposure limit.

Hepatitis C virus (HCV) infection is an important cause of a variety of otherwise unexplained heart diseases and myocardial injury. A high prevalence of HCV infection has been noted in patients with hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular dysplasia/cardiomyopathy and myocarditis. Various arrhythmias, conduction disturbances and QT prolongation were also associated with HCV infection. A possible role of HCV infection in the pathogenesis of diabetes and atherosclerosis, and the role of immunogenetics of HCV cardiomyopathies is discussed. Recent studies suggest that mononuclear cells may be the major target of HCV, and clinical applications to test this new hypothesis are discussed.

In this review, we will evaluate the evidence that HCV causes various cardiovascular diseases, and discuss on the pathogenesis of these disorders.

HCV is the cause of many different forms of heart disease worldwide, but their existence has not been recognized by most of cardiologists. The recognition and diagnosis are indispensable for the early treatment of these diseases. The diverse clinical manifestation of HCV infection and the presence of multiple extrahepatic disease syndromes could be explained by a new hypothesis that the target of HCV is leukocytes.

HCV is the cause of many different forms of heart disease worldwide, but their existence has not been recognized by most of cardiologists. The recognition and diagnosis are indispensable for the early treatment of these diseases. The diverse clinical manifestation of HCV infection and the presence of multiple extrahepatic disease syndromes could be explained by a new hypothesis that the target of HCV is leukocytes.The coronavirus pandemic has taken a detrimental toll on the lives of individuals globally. In addition to the direct effect (e.g., being infected with the virus), this pandemic has negatively ravaged many industries, particularly food retail, food services, and hospitality. Given the novelty of the disease, the true impact of COVID-19 remains to be determined. Because of the nature of their work, and the characteristics of the workers, individuals in the food retail, food service, and hospitality industries are a group whose vulnerability is at its most fragile state during this pandemic. Through this qualitative study, we explored workers' perspectives on the impact of COVID-19 on their mental health and coping, including screening for post-traumatic stress disorder (PTSD) and alcohol use disorder symptoms. Twenty-seven individual interviews were conducted, audio-recorded, transcribed, and analyzed using qualitative content analysis. Four key themes emerged being infected and infecting others, the unknown, isolation, and work and customer demands. Considering the many uncertainties of COVID-19, workers in these three industries were experiencing heightened levels of mental distress because of where they worked and the already existing disparities they faced on a daily basis before the pandemic started. Yet they remained hopeful for a better future. More studies are needed to fully understand the magnitude, short-term, and long-term effects of COVID-19. Based on this study's findings, programs are critically needed to promote positive coping behaviors among at-risk and distressed workers. Recommendations for employers, occupational health and safety professionals, and policy stakeholders to further support these service workers are discussed.Chronic cough is very common in respiratory clinics, and no effective drugs are available. Schisandra chinensis (Turcz.) Baill. (S. chinensis), an important traditional Chinese medicine, has been extensively prescribed for patients with a persistent cough. Preliminary research indicated that 95% ethanol extracts (EE) of S. chinensis showed remarkable antitussive activity in guinea pigs exposed to cigarette smoke (CS). To find out the antitussive ingredients of S. chinensis, EE was divided into four fractions according to the polarity petroleum ether extract (PEE), ethyl acetate extract (ECE), n-butyl alcohol extract, and residue extract. The antitussive, antioxidant, and anti-inflammatory effects of the four fractions were evaluated in a guinea pig model of cough hypersensitivity induced by CS exposure. Eighteen main constituents of the two effective fractions, PEE and ECE, were identified using ultra-high-pressure liquid chromatography electronic spray ion time-of-flight mass spectrometry. The cough inhibition activities of compound 1, 3, 9, 10, 17 were evaluated on citric acid induced acute cough guinea pigs.