Vitamin D and Cardiovascular Disease: The Final Chapter?

Vitamin D deficiency is globally prevalent and has been associated with the pathogenesis and complications of cardiovascular disease (CVD) and its risk factors. Defining these relationships has been challenging, and the clinical applications of vitamin D screening and supplementation for CVD risk prevention and modification have only recently become clearer. Most of the available evidence includes large observational studies and smaller randomized trials that scarcely evaluate CV outcomes as primary endpoints. Additionally, these studies include methodological inconsistencies, making it difficult to ascertain the benefits of vitamin D supplementation. However, more recently, randomized trials have been conducted which utilize CVD outcomes as primary endpoints, while assessing the effects of high dose vitamin D supplementation on CV health. Despite observational evidence as well as a conventional consensus that vitamin D supplementation improves CV health, these studies suggest that vitamin D supplementation likely has no benefit in this regard, at least in the follow-up period and populations evaluated

iPLA2-VIA is Required for Healthy Aging of Neurons, Muscle, and the Female Germline in Drosophila melanogaster

Neurodegenerative disease (ND) is a growing health burden worldwide, but its causes and treatments remain elusive. Although most cases of ND are sporadic, rare familial cases have been attributed to single genes, which can be investigated in animal models. We have generated a new mutation in the calcium-independent phospholipase A2 (iPLA2) VIA gene CG6718, the Drosophila melanogaster ortholog of human PLA2G6/PARK14, mutations in which cause a suite of NDs collectively called PLA2G6-associated neurodegeneration (PLAN). Our mutants display age-related loss of climbing ability, a symptom of neurodegeneration in flies. Although phospholipase activity commonly is presumed to underlie iPLA2VIA function, locomotor decline in our mutants is rescued by a transgene carrying a serine-to-alanine mutation in the catalytic residue, suggesting that important functional aspects are independent of phospholipase activity. Additionally, we find that iPLA2-VIA knockdown in either muscle or neurons phenocopies locomotor decline with age, demonstrating its necessity in both neuronal and non-neuronal tissues. Furthermore, RNA in situ hybridization shows high endogenous iPLA2-VIA mRNA expression in adult germ cells, and transgenic HA-tagged iPLA2-VIA colocalizes with mitochondria there. Mutant males are fertile with normal spermatogenesis, while fertility is reduced in mutant females. Mutant female germ cells display age-related mitochondrial aggregation, loss of mitochondrial potential, and elevated cell death. These results suggest that iPLA2-VIA is critical for mitochondrial integrity in the Drosophila female germline, which may provide a novel context to investigate its functions with parallels to PLAN

Turning Cancer Stem Cells Inside Out: An Exploration of Glioma Stem Cell Signaling Pathways*

Tumors are complex collections of heterogeneous cells with recruited vasculature, inflammatory cells, and stromal elements. Neoplastic cells frequently display a hierarchy in differentiation status. Recent studies suggest that brain tumors have a limited population of neoplastic cells called cancer stem cells with the capacity for sustained self-renewal and tumor propagation. Brain tumor stem cells contribute to therapeutic resistance and tumor angiogenesis. In this minireview, we summarize recent data regarding critical signaling pathways involved in brain tumor stem cell biology and discuss how targeting these molecules may contribute to the development of novel anti-glioma therapies