The fate of developing T cells is specified by the interaction of their antigen receptors with self-peptide-MHC complexes that are displayed by thymic antigen-presenting cells (APCs). Various subsets ...of thymic APCs are strategically positioned in particular thymic microenvironments and they coordinate the selection of a functional and self-tolerant T cell repertoire. In this Review, we discuss the different strategies that these APCs use to sample and process self antigens and to thereby generate partly unique, 'idiosyncratic' peptide-MHC ligandomes. We discuss how the particular composition of the peptide-MHC ligandomes that are presented by specific APC subsets not only shapes the T cell repertoire in the thymus but may also indelibly imprint the behaviour of mature T cells in the periphery.
Available for the first time in English, The Color of the Third Degree uncovers the still-hidden history of police torture in the Jim Crow South. Based on a wide array of previously neglected ...archival sources, Silvan Niedermeier argues that as public lynching decreased, less visible practices of racial subjugation and repression became central to southern white supremacy. In an effort to deter unruly white mobs, as well as oppress black communities, white southern law officers violently extorted confessions and testimony from black suspects and defendants in jail cells and police stations to secure speedy convictions. In response, black citizens and the NAACP fought to expose these brutal practices through individual action, local organizing, and litigation. In spite of these efforts, police torture remained a widespread, powerful form of racial control and suppression well into the late twentieth century. The first historical study of police torture in the American South, Niedermeier draws attention to the willing acceptance of violent coercion by prosecutors, judges, and juries, and brings to light the deep historical roots of police violence against African Americans, one of the most urgent and distressing issues of our time.
Overuse of antimicrobials in residents of long-term care homes is common and can result in harm. Antimicrobial stewardship interventions are needed in the long-term care (LTC) homes setting to ...improve the appropriate use of antimicrobials. Previous literature has highlighted the importance of documenting antimicrobial indication as a strategy that contributes to improve antimicrobial use; however, there is a lack of evidence in LTC homes. This study examines the prevalence, clarity, and facility-level variability of antibiotic indication documentation in this setting.
This is an observational retrospective study of oral antibiotic prescriptions dispensed to 218 homes between January 1, 2021 and December 31, 2022 in Ontario, Canada. Indication was obtained from reviewing antibiotic prescription data. Clarity was determined by comparing documented indication to the National Antimicrobial Prescribing Survey (NAPS). Descriptive analysis was performed to examine the prevalence and clarity of indication documentation. Funnel plots were generated to examine variability in prevalence of indication documentation and clarity at the home level.
Overall, 22.9% (7998/34,867) of prescriptions had an indication documented. The proportion of indications that were clear was 37% (2984/7998). The most common indications were for urinary (45%), skin and soft tissue (19.9%) and respiratory infections (15.0%). At the home level, the median prevalence of indication was 19.6% (interquartile range IQR: 10.8%-31.4%) and median prevalence of clear indications was 35.1% (IQR: 23.8%-42.9%). Funnel plots revealed substantial variability in indication prevalence with 46.3% of homes falling outside of 99% limits but minimal variability in indication clarity between homes with only 8.7% of homes outside of 99% control limits.
There is an opportunity to increase both the prevalence and clarity of antibiotic prescriptions in LTC homes. Future work should focus on determining how best to support prescription indication documentation in this setting with consideration being given to prescription workflow and most common antibiotic prescription indications.
The T cell repertoire is generated during thymic development in preparation for the response to antigens from pathogens. The T cell repertoire is shaped by positive selection, which requires ...recognition by the T cell antigen receptor (TCR) of complexes of self peptide and major histocompatibility complex proteins (self-pMHC) with low affinity, and negative selection, which eliminates T cells with TCRs that recognize self-pMHC with high affinity. This generates a repertoire with low affinity for self-pMHC but high affinity for foreign antigens. The TCR must successfully engage both of these ligands for development, homeostasis and immune responses. This review discusses mechanisms underlying the interaction of the TCR with peptide-major histocompatibility complex ligands of varying affinity and highlights signaling mechanisms that enable the TCR to generate different responses to very distinct ligands.
The intestinal microbiota is important for induction of inflammatory bowel disease (IBD). IBD is associated with complex shifts in microbiota composition, but it is unclear whether specific bacterial ...subsets induce IBD and, if so, whether their proportions in the microbiota are altered during disease. Here, we fulfilled Koch's postulates in host-genotype-specific fashion using a mouse model of IBD with human-relevant disease-susceptibility mutations. From screening experiments we isolated common commensal Bacteroides species, introduced them into antibiotic-pretreated mice, and quantitatively reisolated them in culture. The bacteria colonized IBD-susceptible and -nonsusceptible mice equivalently, but induced disease exclusively in susceptible animals. Conversely, commensal Enterobacteriaceae were >100-fold enriched during spontaneous disease, but an Enterobacteriaceae isolate failed to induce disease in antibiotic-pretreated mice despite robust colonization. We thus demonstrate that IBD-associated microbiota alterations do not necessarily reflect underlying disease etiology. These findings establish important experimental criteria and a conceptual framework for understanding microbial contributions to IBD.
Microbes interact with the host immune system via several potential mechanisms. One essential step for each mechanism is the method by which intestinal microbes or their antigens access specific host ...immune cells. Using genetically susceptible mice (dnKO) that develop spontaneous, fulminant colitis, triggered by Bacteroides thetaiotaomicron (B. theta), we investigated the mechanism of intestinal microbial access under conditions that stimulate colonic inflammation. B. theta antigens localized to host immune cells through outer membrane vesicles (OMVs) that harbor bacterial sulfatase activity. We deleted the anaerobic sulfatase maturating enzyme (anSME) from B. theta, which is required for post-translational activation of all B. theta sulfatase enzymes. This bacterial mutant strain did not stimulate colitis in dnKO mice. Lastly, access of B. theta OMVs to host immune cells was sulfatase dependent. These data demonstrate that bacterial OMVs and associated enzymes promote inflammatory immune stimulation in genetically susceptible hosts.
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•B. thetaiotaomicron antigen localizes to host mucosa in colitis-susceptible mice•Host-penetrant B. thetaiotaomicron antigen localizes to sulfatase-active OMVs•A sulfatase-deficient B. thetaiotaomicron mutant strain is not colitogenic•B. thetaiotaomicron OMVs access host immune cells in a sulfatase-dependent manner
Microbes interact with the host to influence physiology and pathophysiology by poorly understood mechanisms. Hickey et al. show that Bacteroides thetaiotaomicron, a colitogenic bacterium of the gut flora, generates numerous bacterial antigen-containing outer membrane vesicles that access host immune cells in a sulfatase-dependent manner.
Subjecting verses Miller, Paul Allen; Miller, Paul Allen
2004., 20090110, 2009, 2003
eBook
The elegy flared into existence, commanded the cultural stage for several decades, then went extinct. This book accounts for the swift rise and sudden decline of a genre whose life span was ...incredibly brief relative to its impact. Examining every major poet from Catullus to Ovid, Subjecting Verses presents the first comprehensive history of Latin erotic elegy since Georg Luck's. Paul Allen Miller harmoniously weds close readings of the poetry with insights from theoreticians as diverse as Jameson, Foucault, Lacan, and Zizek. In welcome contrast to previous, thematic studies of elegy--efforts that have become bogged down in determining whether particular themes and poets were pro- or anti-Augustan--Miller offers a new, "symptomatic" history. He asks two obvious but rarely posed questions: what historical conditions were necessary to produce elegy, and what provoked its decline? Ultimately, he argues that elegiac poetry arose from a fundamental split in the nature of subjectivity that occurred in the late first century--a split symptomatic of the historical changes taking place at the time.
► We developed a hyperspectral imaging system to assess beef chemical composition. ► We developed a band and difference ratio approach for fat pixels segmentation. ► We tested PLS regression for ...prediction and selecting the optimum wavelengths. ► We developed image processing algorithm for building chemical images of beef.
Developing a rapid and non-destructive method for food safety and quality monitoring has become a crucial request from the meat industry. Hyperspectral imaging technique provides extraordinary advantages over the traditional imaging and spectroscopy techniques in food quality evaluation due to the spatial and spectral information that it can offer. In this study, a laboratory-based pushbroom hyperspectral imaging system in reflectance mode was developed in the near infrared (NIR) range (900–1700nm) for non-invasive determination of the major chemical compositions of beef. Beef samples collected from different breeds were scanned by the system followed by traditional assessment of their chemical composition by using the ordinary wet-chemical methods. The extracted spectral data and the measured quality parameters were modeled by partial least squares regression (PLSR) for predicting water, fat and protein contents yielding a reasonable accuracy with determination coefficients (RP2) of 0.89, 0.84 and 0.86 concomitant with standard error of prediction (SEP) of 0.46%, 0.65% and 0.29%, respectively. Some image processing algorithms were developed and the most relevant wavelengths were selected to visualize the predicted chemical constituents in each pixel of the hyperspectral image yielding the spatially distributed visualizations of the sample contents. The results were promising and implied that hyperspectral imaging technique associated with appropriate chemometric multivariate analyses has a great potential for simultaneous assessment of various chemical constituents without using hazardous chemical reagents.
The disconnection hypothesis suggests that the core symptoms of schizophrenia (SZ) are related to aberrant, or 'dys-', connectivity between distinct brain regions. A proliferation of functional and ...structural neuroimaging studies have been conducted to investigate this hypothesis, across the full course of the disorder; from people at Ultra-High-Risk of developing psychosis to patients with chronic SZ. However the results of these studies have not always been consistent, and to date, there have been no attempts to summarise the results of both methodologies in conjunction. In this article, we systematically review both the structural and functional connectivity literature in SZ. The main trends to emerge are that schizophrenia is associated with connectivity reductions, as opposed to increases, relative to healthy controls, and that this is particularly evident in the connections involving the frontal lobe. These two trends appear to apply across all stages of the disorder, and to be independent of the neuroimaging methodology employed. We discuss the potential implications of these trends, and identify possible future investigative directions.
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