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Revealed: Why the fatal Huntington’s gene takes so long to cause harm
Patterns of Klebsiella pneumoniae bacteremic dissemination from the lung
Optimal dose and type of exercise improve walking velocity in adults with Parkinson’s disease: a systematic review and Bayesian network meta-analysis
Interferon-α promotes HLA-B-restricted presentation of conventional and alternative antigens in human pancreatic β-cells
Abstract Interferon (IFN)-α is the earliest cytokine signature observed in individuals at risk for type 1 diabetes (T1D), but the effect of IFN-α on the antigen repertoire of HLA Class I (HLA-I) in pancreatic β-cells is unknown. Here we characterize the HLA-I antigen presentation in resting and IFN-α-exposed β-cells and find that IFN-α increases HLA-I expression and expands peptide repertoire to those derived from alternative mRNA splicing, protein cis-splicing and post-translational modifications. While the resting β-cell immunopeptidome is dominated by HLA-A-restricted peptides, IFN-α largely favors HLA-B and only marginally upregulates HLA-A, translating into increased HLA-B-restricted peptide presentation and activation of HLA-B-restricted CD8+ T cells. Lastly, islets of patients with T1D show preferential HLA-B hyper-expression when compared with non-diabetic donors, and islet-infiltrating CD8+ T cells reactive to HLA-B-restricted granule peptides are found in T1D donors. Thus, the inflammatory milieu of insulitis may skew the autoimmune response toward alternative epitopes presented by HLA-B, hence recruiting T cells with a distinct repertoire that may be relevant to T1D pathogenesis.
YOLOSeg with applications to wafer die particle defect segmentation
Comparative transcriptomics in serial organs uncovers early and pan-organ developmental changes associated with organ-specific morphological adaptation
Abstract Mice have evolved a new dental plan with two additional cusps on the upper molar, while hamsters were retaining the ancestral plan. By comparing the dynamics of molar development with transcriptome time series, we found at least three early changes in mouse upper molar development. Together, they redirect spatio-temporal dynamics to ultimately form two additional cusps. The mouse lower molar has undergone much more limited phenotypic evolution. Nevertheless, its developmental trajectory evolved as much as that of the upper molar and co-evolved with it. Among the coevolving changes, some are clearly involved in the new upper molar phenotype. We found a similar level of coevolution in bat limbs. In conclusion, our study reveals how serial organ morphology has adapted through organ-specific developmental changes, as expected, but also through shared changes that have organ-specific effects on the final phenotype. This highlights the important role of developmental system drift in one organ to accommodate adaptation in another.
An update on active and passive surveillance for African swine fever in the Dominican Republic
A multiprotein regulatory module, MED16–MBR1&2, controls MED25 homeostasis during jasmonate signaling
Efficient IP address retrieval using a novel octet based encoding technique for high speed lookup to improve network performance
Cola beverage reduces risk of lead poisoning from accidental ingestion of contaminated soil particles in rat and swine models
Understanding rangeland desertification through pastoralist perspectives using a grounded theory approach
Nr4a1 and Nr4a3 redundantly control clonal deletion and contribute to an anergy-like transcriptome in auto-reactive thymocytes to impose tolerance in mice
Abstract The Nr4a nuclear hormone receptors are transcriptionally upregulated in response to antigen recognition by the T cell receptor (TCR) in the thymus and are implicated in clonal deletion, but the mechanisms by which they operate are not clear. Moreover, their role in central tolerance is obscured by redundancy among the Nr4a family members and by their reported functions in Treg generation and maintenance. Here we take advantage of competitive bone marrow chimeras and the OT-II/RIPmOVA model to show that Nr4a1 and Nr4a3 are essential for the upregulation of Bcl2l11/BIM and thymic clonal deletion by self-antigen. Importantly, thymocytes lacking Nr4a1/3 acquire an anergy-like signature after escaping clonal deletion and Treg lineage diversion. We further show that the Nr4a family helps mediate a broad transcriptional program in self-reactive thymocytes that resembles anergy and may operate at the margins of canonical thymic tolerance mechanisms to restrain self-reactive T cells after thymic egress.
Understanding the role of metabolic syndrome in prostate cancer risk: A UK Biobank prospective cohort study
High-performance solid-state proton gating membranes based on two-dimensional hydrogen-bonded organic framework composites
Weave structures of polyester fabric affect the tensile strength and microplastic fiber emission during the laundry process
Increased arterial stiffness is associated with poorer social cognition in older age
Abstract It is now well established that vascular aging is a significant predictor of cognitive decline in older age. But what remains less clear is the role that vascular health plays in social cognitive aging. Therefore, we aimed to provide the first test of the relationship between arterial stiffness and theory of mind (ToM) in late adulthood. In a sample of 50 healthy older adults (Age: M = 70.08, SD = 3.93), we measured arterial stiffness via carotid-femoral pulse wave velocity and social cognition using two well validated measures of ToM (RMET, TASIT). The results revealed that arterial stiffness was a significant predictor of ToM performance when indexed via the RMET and the TASIT, accounting for 11% and 9% of unique variance in scores, respectively. These findings add to the broader literature showing that arterial stiffness is a key predictor of cognitive aging and show that this relationship extends to the domain of social cognition.