Functional genomics with libraries of knockout alleles is limited to non-essential genes and convoluted by the potential accumulation of suppressor mutations in knockout backgrounds, which can lead to erroneous functional annotations. To address these limitations, we constructed genome-wide libraries of conditional alleles based on the auxin-inducible degron (AID) system for inducible degradation of AID-tagged proteins in the budding yeast Saccharomyces cerevisiae. First, we determined that N-terminal tagging is at least twice as likely to inadvertently impair protein function across the proteome.
View Article and Find Full Text PDFThe onset of degenerative joint diseases such as post-traumatic osteoarthritis (PTOA) are associated with joint injury, biomechanical changes, and synovial biochemical anomalies. Sex and reproductive endocrinology have been emerging as potential risk factors, with epidemiological evidence revealing that female's exhibit higher PTOA risk and poorer outcomes post-injury compared to males. Sex hormones, including estradiol, progesterone, and testosterone, have been shown to regulate inflammatory signaling in immune and synovial cells, yet their collective impact on injury-induced joint inflammation and catabolism is poorly understood.
View Article and Find Full Text PDFBackground: Blast-induced spinal cord injury (bSCI) is prevalent among military populations and frequently leads to irreversible spinal cord tissue damage that manifests as sensorimotor and autonomic nervous system dysfunction. Clinical recovery from bSCI has been proven to be multifactorial, as it is heavily dependent on the function of numerous cell populations in the tissue environment, as well as extensive ongoing inflammatory processes. This varied recovery process is thought to be due to irreversible spinal cord damage after 72 hours post-injury.
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