Prolyl and lysyl hydroxylases in collagen synthesis

Collagens are the most abundant proteins in the extracellular matrix. They provide a framework to build organs and tissues and give structural support to make them resistant to mechanical load and forces. Several intra‐ and extracellular modifications are needed to make functional collagen molecules, intracellular post‐translational modifications of proline and lysine residues having key roles in this. In this article, we provide a review on the enzymes responsible for the proline and lysine modifications, that is collagen prolyl 4‐hydroxylases, 3‐hydroxylases and lysyl hydroxylases, and discuss their biological functions and involvement in diseases.     

Genomic variants within chromosome 14q32.32 regulate bone mass through MARK3 signaling in osteoblasts

Bone mineral density (BMD) is a highly heritable predictor of osteoporotic fracture. GWAS have identified hundreds of loci influencing BMD, but few have been functionally analyzed. In this study, we show that SNPs within a BMD locus on chromosome 14q32.32 alter splicing and expression of PAR-1a/microtubule affinity regulating kinase 3 (MARK3), a conserved serine/threonine kinase known to regulate bioenergetics, cell division, and polarity. Mice lacking Mark3 either globally or selectively in osteoblasts have increased bone mass at maturity. RNA profiling from Mark3-deficient osteoblasts suggested changes in the expression of components of the Notch signaling pathway. Mark3-deficient osteoblasts exhibited greater matrix mineralization compared with controls that was accompanied by reduced Jag1/Hes1 expression and diminished downstream JNK signaling. Overexpression of Jag1 in Mark3-deficient osteoblasts both in vitro and in vivo normalized mineralization capacity and bone mass, respectively. Together, these findings reveal a mechanism whereby genetically regulated alterations in Mark3 expression perturb cell signaling in osteoblasts to influence bone mass.     

Improving Lesbian,Gay, Bisexual,Transgender, Queer and Two-Spirit Content in a Radiation Therapy Undergraduate Curriculum

Lesbian, gay, bisexual, transgender, queer and two-spirit plus (LGBTQ2S+) people have distinct healthcare needs that may be unaddressed in many undergraduate healthcare curricula. The Radiation Therapy Program (RADTH) at the University of Alberta underwent a review of the three-year didactic curriculum using an online survey. The survey sought to ascertain if, where and how topics related to LGBTQ2S + healthcare are taught. Results indicated that out of 10 RADTH program faculty respondents, three teach related topics. The total time dedicated within the three-year curriculum was approximately three and a half hours. Other findings showed that faculty are interested in receiving more education in this area and would favour discussions about how to incorporate these themes into appropriate courses. This preliminary investigation demonstrated that there has been some initial work in this area, but there is more to be done.