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Klebsiella pneumoniae represents a growing clinical threat, given its rapid development of antibiotic resistance, necessitating new therapeutic strategies. Existing live-infection models feature high mortality rates, limiting their utility in the study of natural adaptive immune response to this pathogen. We developed a preclinical model of pneumonia with low overall mortality, in which previously exposed mice are protected from subsequent respiratory tract challenge with K. pneumoniae Histologic analyses of infected murine lungs demonstrate lymphocytic aggregates surrounding vasculature and larger airways. Initial exposure in RAG1 knockout mice (lacking functional B and T cells) failed to confer protection against subsequent K. pneumoniae challenge. While administration of isolated K. pneumoniae capsule was sufficient to provide protection, we also found that initial inoculation with K. pneumoniae mutants lacking capsule (Δcps), O-antigen (ΔwecA) or both conferred protection from subsequent wild-type infection and elicited K. pneumoniae-specific antibody responses, indicating that non-capsular antigens may also elicit protective immunity. Experiments in this model will inform future development of multivalent vaccines to prevent invasive K. pneumoniae infections. © 2020. Published by The Company of Biologists Ltd.Regulation of protein synthesis makes a major contribution to post-transcriptional control pathways. During disease, or under stress, cells initiate processes to reprogramme protein synthesis and thus orchestrate the appropriate cellular response. Recent data show that the elongation stage of protein synthesis is a key regulatory node for translational control in health and disease. There is a complex set of factors that individually affect the overall rate of elongation and, for the most part, these influence either transfer RNA (tRNA)- and eukaryotic elongation factor 1A (eEF1A)-dependent codon decoding, and/or elongation factor 2 (eEF2)-dependent ribosome translocation along the mRNA. Decoding speeds depend on the relative abundance of each tRNA, the cognatenear-cognate tRNA ratios and the degree of tRNA modification, whereas eEF2-dependent ribosome translocation is negatively regulated by phosphorylation on threonine-56 by eEF2 kinase. Additional factors that contribute to the control of the elongation rate include epigenetic modification of the mRNA, coding sequence variation and the expression of eIF5A, which stimulates peptide bond formation between proline residues. Importantly, dysregulation of elongation control is central to disease mechanisms in both tumorigenesis and neurodegeneration, making the individual key steps in this process attractive therapeutic targets. Here, we discuss the relative contribution of individual components of the translational apparatus (e.g. tRNAs, elongation factors and their modifiers) to the overall control of translation elongation and how their dysregulation contributes towards disease processes. AICAR molecular weight © 2020. Published by The Company of Biologists Ltd.Sarcopenia - the accelerated age-related loss of muscle mass and function - is an under-diagnosed condition, and is central to deteriorating mobility, disability and frailty in older age. There is a lack of treatment options for older adults at risk of sarcopenia. Although sarcopenia's pathogenesis is multifactorial, its major phenotypes - muscle mass and muscle strength - are highly heritable. Several genome-wide association studies of muscle-related traits were published recently, providing dozens of candidate genes, many with unknown function. Therefore, animal models are required not only to identify causal mechanisms, but also to clarify the underlying biology and translate this knowledge into new interventions. Over the past several decades, small teleost fishes had emerged as powerful systems for modeling the genetics of human diseases. Owing to their amenability to rapid genetic intervention and the large number of conserved genetic and physiological features, small teleosts - such as zebrafish, medaka and killifish - have become indispensable for skeletal muscle genomic studies. The goal of this Review is to summarize evidence supporting the utility of small fish models for accelerating our understanding of human skeletal muscle in health and disease. We do this by providing a basic foundation of the (zebra)fish skeletal muscle morphology and physiology, and evidence of muscle-related gene homology. We also outline challenges in interpreting zebrafish mutant phenotypes and in translating them to human disease. Finally, we conclude with recommendations on future directions to leverage the large body of tools developed in small fish for the needs of genomic exploration in sarcopenia. © 2020. Published by The Company of Biologists Ltd.BACKGROUND In the U.S., racial disparities in birth outcomes persist and have been widening. Interpersonal and structural racism are leading explanations for the continuing racial disparities in birth outcomes but research to confirm the role of racism and evaluate trends in the impact of racism on health outcomes has been hampered by the challenge of measuring racism. Most research on discrimination relies on self-reported experiences of discrimination, and few studies have examined racial attitudes and bias at the U.S. national level. OBJECTIVE Investigate associations between state-level Twitter-derived sentiment related to racial/ethnic minorities and birth outcomes. METHODS We utilized Twitter's Streaming Application Programming Interface (API) to collect 26,027,740 tweets from June 2015 to December 2017 containing at least one race-related term. Sentiment analysis was performed using Support Vector Machines (SVM), a supervised machine learning model. We constructed overall indicators of sentiment towardpared to mothers living in the lowest tertile. More negative tweets referencing minorities was associated with adverse birth outcomes among the total population, including non-Hispanic Whites and racial/ethnic minorities. In stratified subgroup analyses, more negative tweets referencing specific racial/ethnic minority groups --Blacks and Middle Easterners--was associated with poor birth outcomes for Blacks and minorities, respectively. CONCLUSIONS More negative social context related to race was associated with worse birth outcomes for racial/ethnic minorities as well as non-Hispanic White people. CLINICALTRIAL
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