Rivaroxaban and Apixaban Induce Clotting Factor Xa Fibrinolytic Activity

In previous years, the Canadian Blood Services’ Pryzdial lab at the UBC Centre for Blood Research identified a new role for clotting factor Xa (FXa) in a completely opposite activity, clot dissolution (i.e. fibrinolysis). This function is acquired through specific cleavages that turn FXa into an accelerator of plasmin, the physiological scissors tasked with cutting and removing clots...
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High-throughput expression analyses of postmortem brain tissue have been widely used to study bipolar disorder and schizophrenia. However, despite the extensive efforts, no consensus has emerged as to the functional interpretation of the findings. We hypothesized that incorporating information on cell type–specific expression would provide new insights. Methods We reanalyzed 15 publicly available bulk tissue expression datasets on schizophrenia and…
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The Rennie and Cherkasov labs have a long history of developing therapeutics to target the function of transcription factors that drive advanced and metastatic forms of endocrine cancers. Currently, our main focus is to use Computer-Aided Drug Design (CADD) to create small-molecule inhibitors of the androgen receptor (AR), a hormone inducible transcription factor that is responsible for the disease progression of prostate cancer (PCa)...
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Cell autonomous immunity is the ability of individual cells to initiate a first line of host defense against invading microbes, such as viruses. Autophagy receptors, a diverse family of multivalent proteins, play a key role in this host response by detecting, sequestering, and eliminating virus in a process termed virophagy. To counteract this, positive-stranded RNA viruses, such as enteroviruses, have…
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Mechanical Anisotropy in GNNQQNY Amyloid Crystals

Mapping the nanomechanical properties of amyloids can provide valuable insights into structure and assembly mechanisms of protein aggregates that underlie the development of various human diseases. Although it is well-known that amyloids exhibit an intrinsic stiffness comparable to that of silk (1-10 GPa), a detailed understanding of the directional dependence (anisotropy) of the stiffness of amyloids and how it relates…
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In this study, we characterized the role of a specific class of repetitive elements in the genome, known as long-terminal repeat (LTR) retrotransposons, in directing the establishment of DNA methylation in oocytes, and how they may influence the expression of nearby genes in the offspring. Notably, a subset of LTR elements are particularly active, ie transcribed at high levels, in both rodent and human oocytes. To study the implications of expression of such parasitic elements and their relics, we utilized genome-wide approaches to study the relationship between such LTR-initiated transcription units (LITs)...
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Remyelination occurs after spinal cord injury (SCI) but its functional relevance is unclear. We assessed the necessity of myelin regulatory factor (Myrf) in remyelination after contusive SCI by deleting the gene from platelet-derived growth factor receptor alpha positive (PDGFRα-positive) oligodendrocyte progenitor cells (OPCs) in mice prior to SCI. While OPC proliferation and density are not altered by Myrf inducible knockout…
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Mechanism-based glycoside hydrolase inhibitors are carbohydrate analogs that mimic the natural substrate’s structure. Their covalent bond formation with the glycoside hydrolase makes these compounds excellent tools for chemical biology and potential drug candidates. Here we report the synthesis of cyclohexene-based α-galactopyranoside mimics and the kinetic and structural characterization of their inhibitory activity toward an α-galactosidase from Thermotoga maritima (TmGalA). By…
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Synapses are fundamental units of communication in the brain. The prototypical synapse-organizing complex neurexin-neuroligin mediates synapse development and function and is central to a shared genetic risk pathway in autism and schizophrenia. Neurexin’s role in synapse development is thought to be mediated purely by its protein domains, but we reveal a requirement for a rare glycan modification. Mice lacking heparan…
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New fundamental discoveries in stem cell biology have yielded potentially transformative regenerative therapeutics. However, widespread implementation of stem-cell-derived therapeutics remains sporadic. Barriers that impede the development of these therapeutics can be linked to our incomplete understanding of how the regulatory networks that encode stem cell fate govern the development of the complex tissues and organs that are ultimately required for restorative…
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