Activating mutations in AKT1 and PIK3CA are undercharacterised in metastatic castration-resistant prostate cancer (mCRPC), but are linked to activation of phosphatidylinositol 3-kinase (PI3K) signalling and sensitivity to pathway inhibitors in other cancers. Objective: To determine the prevalence, genomic context, and clinical associations of AKT1/PIK3CA activating mutations in mCRPC. Design, setting, and participants: We analysed targeted cell-free DNA (cfDNA) sequencing data from 599…
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Host defense peptides (HDPs), also known as antimicrobial peptides, are naturally occurring polypeptides (~12–50 residues) composed of cationic and hydrophobic amino acids that adopt an amphipathic conformation upon folding usually after contact with membranes. HDPs have a variety of biological activities including immunomodulatory, anti-inflammatory, anti-bacterial, and anti-biofilm functions. Although HDPs have the potential to address the global threat of antibiotic…
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Challenges in the interpretation of whole-genome sequences leave rare disease cases undiagnosed. Cis-regulatory variants are anticipated to resolve a subset of these cases, but present a difficult problem because of their large numbers, small effect sizes, and tissue-specificity. Advancements in experimental genomics and bioinformatics approaches are rapidly revealing the locations of cis-regulatory regions. At least 46 regulatory disease variants have been reported…
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This study reveals how regulation of a microRNA links aging, inflammation and the development of myeloid malignancies. By comparing the transcriptomes of over 250 AML patients, a key player in inflammaging-associated myeloid malignancies emerged—an anti-inflammatory microRNA called miR-146a. Loss of miR-146a expression in mice promoted the development of myeloid malignancies, premature aging of hematopoietic stem cells and enhanced inflammatory signalling.
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Pseudomonas aeruginosa is a motile species that initiates swarming motility in response to specific environmental cues, i.e., a semisolid surface with amino acids as a nitrogen source (relevant to the human lung). Swarming is an intricately regulated process, but to date posttranscriptional regulation has not been extensively investigated. Small noncoding RNAs (sRNAs) are hypothesized to play posttranscriptional regulatory roles, largely through…
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The authors found that there is a ribosomal RNA hyper-modification called 1-methyl-3-α-amino-α-carboxyl-propyl pseudouridine (macpΨ) that is perturbed in human cancers. The modification is 1.5 billion years conserved (all eukaryotes have it, no exceptions). 45% of colorectal cancer (CRC) tumours have a partial loss of this modification, and the same phenotype is seen in >22 distinct types of cancers.
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Towards Stem Cell Therapies for Skeletal Muscle Repair

Skeletal muscle is an ideal target for cell therapy. The use of its potent stem cell population in the form of autologous intramuscular transplantation represents a tantalizing strategy to slow the progression of congenital muscle diseases (such as Duchenne Muscular Dystrophy) or regenerate injured tissue following trauma. The syncytial nature of skeletal muscle uniquely permits the engraftment of stem/progenitor cells…
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Detergents are not compatible with mass spectrometry, and their removal from biological samples often results in reduced protein identification. As an alternative to detergents, the authors recently developed the peptidisc membrane mimetic, which allows entrapment of the cell envelope proteome into water-soluble particles, termed a “peptidisc library”. Here, they employed a His-tagged version of the peptidisc peptide scaffold to enrich the reconstituted membrane proteome by affinity chromatography.
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To try and decipher how precisely granule cells of the dentate gyrus contribute to hippocampal function, the authors used a cell-types perspectives to see whether they could identify specific types of granule cells and relate them to function. They discovered a rare granule cell type that strikingly appeared to be selectively active across behavioral paradigms involving memory, spatial navigation, and emotion.
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The Bioinformatics Technology Lab at Canada’s Michael Smith Genome Sciences Centre (GSC) at BC Cancer has developed a new bioinformatics tool, ntJoin, which is now available for researchers to freely download and use. ntJoin is a rapid and lightweight tool for genome assembly scaffolding that leverages minimizer sketches, simultaneously making it faster while reducing the amount of memory needed in comparison to existing state-of-the-art tools.
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