The airway epithelium forms the interface between the inhaled environment and the lung. The airway epithelium is dysfunctional in asthma and epigenetic mechanisms are considered a contributory factor. We hypothesised that the DNA methylation profiles of cultured primary airway epithelial cells (AECs) would differ between cells isolated from individuals with asthma (n = 17) versus those without asthma (n = 16). AECs were isolated…
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Scientists have shown that we can harness the search-and-destroy functions of cytotoxic T cells (CTLs) to help our bodies fight off cancer, but finding these cancer-fighting cells is like searching for a needle in a haystack. A new method takes advantage of the CTLs’ granzyme-mediated cell killing to identify disease antigens. To do this, the scientists generate a library of cells, each displaying a different antigen. Only a small fraction of these antigens will signal disease, and the goal is to find them.
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The authors evaluated operating characteristics, particularly specificity and positive predictive value (PPV), by mapping plasma miR371 expression to actual clinical events in patients with a history of germ cell tumour. Plasma miR371 expression predicted aGCM with high specificity and positive predictive value. Although other operating characteristics of miR371 awaited longer follow-up for more complete definition, the findings of a highly...
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The authors describe a method for the generation of blood vessel organoids from pluripotent stem cells. The protocol includes a detailed manual for the analysis of the in vitro grown and transplanted organoids. This will allow all researchers to setup vascular organoid cultures with standard cell culture lab equipment and implement this into their research of diabetes, stroke, ischemia or any other disease affecting the vasculature.
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The α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype glutamate receptors (AMPARs) mediate the fast excitatory synaptic transmission in the mammalian brain and are important for synaptic plasticity. In particular, the rapid insertion of the GluA1 homomeric (GluA1-homo) AMPARs into the postsynaptic membrane is considered to be critical in the expression of hippocampal CA1 long-term potentiation (LTP), which is important for certain forms of learning…
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Single-cell RNA sequencing has enabled the decomposition of complex tissues into functionally distinct cell types. Often, investigators wish to assign cells to cell types through unsupervised clustering followed by manual annotation or via ‘mapping’ to existing data. However, manual interpretation scales poorly to large datasets, mapping approaches require purified or pre-annotated data and both are prone to batch effects. To…
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The authors found that a well-characterized DNA repair complex, called the MRN complex, had a new role in responding to DNA replication forks that have been blocked by collisions with the transcription machinery. While the MRN complex contains a nuclease activity, their data suggested that a non-nucleolytic scaffolding role of the complex is important to promote the recruitment of downstream repair factors to conflicts during replication.
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Recent Advances in Lipid Nanoparticle-Mediated mRNA Therapy

All cells function by an intricate mechanism that converts information stored as nucleic acid sequences (DNA) into messages (messenger RNA) for translation into functional products (protein). Endogenous checks and balances exist within this information flow, which can be leveraged as therapies to treat diseases closer to their genetic origin. The significant health opportunities of gene therapies are evident in the…
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The authors identified the mechanism of action of B-Raf, a key enzyme that is mutated in 50% of melanomas. Many inhibitors, such as those used to target melanomas and other cancers, when present in low amounts end up achieving exactly the opposite result, enhancing Raf activity instead of blocking it. Using cryo-EM, they found that the active site of one of the two B-Raf molecules in the pair is closer to the 14-3-3 platform than its partner, resulting in an arrangement where the proximal B-Raf remains active, but the activity of its neighbor is blocked.
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The authors found that type 1 T-regulatory (Tr1) cells have functions outside beyond their expected ability to regulate immune cells. Specifically, Tr1 cells secreted factors which could help promote the health of cells lining the intestinal epithelium. These unique properties of Tr1 cells could make them an ideal cell therapy to treat inflammatory diseases of the gut, such as Crohn’s disease and ulcerative colitis. The Levings lab is developing humanized mouse models to test the function of these cells in models of intestinal inflammation.
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