This in-depth analysis of the first cohort from BC Cancer’s Personalized OncoGenomics Program provides a unique, comprehensive characterization of whole genomes and transcriptomes from pre-treated, advanced cancer patients. In addition to known resistance mechanisms, the authors identified novel genomic and transcriptomic alterations associated with prior therapy and resistance. They also analyzed the immune microenvironment across the diverse cohort of mostly metastatic tumours.
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The authors performed global transcriptome profiling in leukemic stem/progenitor cells from treatment-naive chronic myeloid leukemia (CML) patients, and identified miR-185 as one of the most deregulated miRNAs. Their data indicates that miR-185 presents as a potential predictive biomarker, and dual targeting of miR-185-mediated PAK6 activity and BCR-ABL may provide a valuable strategy for overcoming drug resistance in CML patients.
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The authors investigated the role of the inflammasome effector caspases-1 and -11 during Salmonella enterica serovar Typhimurium infection of murine intestinal epithelial cells (IECs). Salmonella burdens were significantly greater in the intestines of caspase-1/11 deficient (Casp1/11−/−), Casp1−/−) and Casp11−/−) mice, as compared to wildtype mice.
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The authors have found differences in how healthy intestinal bacteria interact with the immune system in malnutrition. In malnourished mice, the probiotic bacterium Lactobacillus went into ‘starvation mode’ and stopped interacting with host antibody. This is important because there is a lot of interest right now in using Lactobacillus to treat malnourished kids, and if this bacterium stops interacting with the immune system during malnutrition, it might affect its ability to be a successful probiotic.
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The authors have shown for the first time that smoking, and having chronic obstructive pulmonary disease (COPD), increases the number of ACE-2 protein, which is the receptor that the COVID-19 virus uses to gain entry into the host. Importantly, when smokers quit smoking, ACE-2 expression normalizes to that of never smokers. They think that this finding may explain why smokers and those with COPD have relatively high rates of severe COVID-19 infection.
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The human gut microbiota (HGM) has far-reaching impacts on human health and nutrition, which are fueled primarily by the metabolism of otherwise indigestible complex carbohydrates commonly known as dietary fiber. However, the molecular basis of the ability of individual taxa of the HGM to address specific dietary glycan structures remains largely unclear. In particular, the utilization of β(1,3)-glucans, which are…
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The authors previously discovered a new form of motility in the feared nosocomial and cystic fibrosis pathogen, Pseudomonas aeruginosa, named surfing motility. In this paper, the authors show that a cystic fibrosis epidemic strain LESB58, although poorly motile in broth, is able to surf reasonably well. They show that this behaviour, which would allow Pseudomonas to move rapidly across the surface of the lung, is controlled by a universal stress response termed stringent stress response.
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Antisense Oligonucleotides for Neurodegeneration

Antisense oligonucleotides (ASOs) have the potential to reduce, restore, or modify RNA and protein expression. Thus, they can target disease pathogenesis by altering the expression of mutant proteins (1). The recent regulatory approval of ASOs for the pediatric motor neuron disease spinal muscular atrophy has provided a regulatory pathway for additional ASO therapies in other central nervous system (CNS) diseases.…
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Recent developments in understanding how the functional phenotype of the innate immune system is programmed has led to paradigm-shifting views on immunomodulation. These advances have overturned two long-held dogmas: (1) only adaptive immunity confers immunological memory; and, (2) innate immunity lacks specificity. This work describes the observation that innate immune effector cells appear to be differentially recruited to specific pathological…
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Several lines of evidence suggest that high-density lipoprotein (HDL) reduces Alzheimer’s disease (AD) risk by decreasing vascular beta-amyloid (Aβ) deposition and inflammation, however, the mechanisms by which HDL improve cerebrovascular functions relevant to AD remain poorly understood. Methods Here we use a human bioengineered model of cerebral amyloid angiopathy (CAA) to define several mechanisms by which HDL reduces Aβ deposition…
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