Assessment of autophagy activity has historically been limited to investigations of fixed tissue or bulk cell populations. To address questions of heterogeneity and relate measurements to functional properties of viable cells isolated from primary tissue, we created a lentiviral (RFP-GFP-MAP1LC3B) vector that allows the autophagosome and autolysosome content of transduced cells to be monitored at the single-cell level. Use of…
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Previous research from the authors identified that people with a gain-of-function DNA variant in a gene called CETP have lower levels of HDL cholesterol (the “good cholesterol”) during sepsis and a higher risk of death. In this study, they tested the hypothesis that inhibiting CETP using a drug would improve outcomes from sepsis. They performed this work in a mouse model of experimental sepsis, and showed that inhibiting CETP resulted in preservation of HDL levels and improved survival from sepsis.
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Beyond Kinases: Targeting Replication Stress Proteins in Cancer Therapy

DNA replication stress describes a state of impaired replication fork progress that triggers a cellular stress response to maintain genome stability and complete DNA synthesis. Replication stress is a common state that must be tolerated in many cancers. One promising therapeutic approach is targeting replication stress response factors such as the ataxia telangiectasia and rad 3-related kinase (ATR) or checkpoint…
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Communal Living: Glycan Utilization by the Human Gut Microbiota

Our lower gastrointestinal tract plays host to a vast consortium of microbes, known as the Human Gut Microbiota (HGM). The HGM thrives on a complex and diverse range of glycan structures from both dietary and host sources, the breakdown of which requires the concerted action of cohorts of Carbohydrate‐Active Enzymes (CAZymes), carbohydrate‐binding proteins, and transporters. The glycan utilization profile of…
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Active germ cell malignancies express high levels of specific circulating micro-RNAs (miRNAs), including miR-371a-3p (miR371), which is undetectable in teratoma. Teratoma markers are urgently needed for theselection of patients and treatments because of the risk of malignant transformation and growing teratoma syndrome. To assess the accuracy of plasma miR375 alone or in combination with miR371 in detecting teratoma, 100 germ…
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The intestinal epithelium is replenished every 3–4 days through an orderly process that maintains important secretory and absorptive functions while preserving a continuous mucosal barrier. Intestinal epithelial cells (IECs) derive from a stable population of intestinal stem cells (ISCs) that reside in the basal crypts. When intestinal injury reaches the crypts and damages IECs, a mechanism to replace them is…
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Using established culture models and CRISPR-Cas9 based gene editing, the authors uncover the surprising molecular insight that coxsackievirus B3 (CVB3) initiates autophagy independent of previously established canonical factors. The study identified the serine-threonine kinase ULK1 (ATG1) as a novel target of viral protease 3C and the PI4P lipid-kinase, PI4KIIIβ, as an important regulator of CVB3-induced non-canonical autophagy.
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Innate lymphoid cells (ILCs) are a recently identified subset of leukocytes that play a central role in pathogen surveillance and resistance, modulation of immune response, and tissue repair. They are remarkably similar to CD4+ T-helper subsets in terms of function and transcription factors required for their development but are distinguished by their lack of antigen-specific receptors. Despite their similarities, the absence…
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The authors used single-cell transcriptomics to assess the developmental origins of the three main cell types within the embryonic liver. Specifically, they characterized the emergence of previously uncharacterized mesenchymal populations, the development of liver sinusoidal endothelial cells, the specification of hepatoblasts from the endoderm, and the signaling microenvironment during liver formation. Of interest, they captured a novel cell type within the liver, which they have termed the hepatomesenchyme.
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The authors broaden the understanding of the post-translational regulation of Capicua (CIC), which has now been implicated as a tumour suppressor in multiple cancer types, including glioma. In fact, CIC has been shown to mediate EGFR signalling as well as metastatic behaviour. They also delve into non-canonical CIC regulatory pathways and identify a novel E3-ligase, TRIM25, which can regulate CIC function at a post-translational level.
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