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.     

Outcomes of patients with non-small cell lung cancer and poor performance status treated with immune checkpoint inhibitors in the real-world setting

International Journal of Clinical Oncology - Immune-checkpoint inhibitors (ICIs) are standard treatments for metastatic non-small cell lung cancer (NSCLC). Patients with poor performance status...     

Comparison of multiple methods of assessing parental emotion language discourse and their effects on Preschooler’s emotion understanding

The current study explored the influence of three methods of parental emotion discourse (structured story-telling, reminiscing, and picture book) and their relation to preschoolers’ emotion understanding. Thirty-seven families participated in the study. Analyses showed that the structured story-telling method produced more emotion words, was high in unique emotion words, and was high for both emotion labelling and explanations. All three methods showed some potential to predict preschooler’s emotion understanding. Structured story-telling was best at predicting role-taking, while reminiscing and the picture book both were better at predicting situation knowledge. Additional studies are needed to further explore the influence of different methods of assessing emotion discourse to enhance validity and reliability of research in this field.     

The proteome microenvironment determines the protective effect of preconditioning in cisplatin-induced acute kidney injury

1. Download high-res image (341KB)
2. Download full-size image