Diacylglycerol kinase ζ controls diacylglycerol metabolism at the immunological synapse

DGKα and DGKζ negatively regulate the DAG/RasGRP1/Ras pathway in T cells. Study of the specific contribution of each isoform to DAG metabolism during immune synapse formation by use of a combination of RNAi and videomicroscopy techniques identifies DGKζ as mainly responsible for DAG consumption at the immunological synapse

Dairy Products, Vitamin D, and Bone Health

Osteoporosis is a major public health problem affecting over 200 million people worldwide. Dairy foods such as milk, cheese, and yogurt provide a unique set of nutrients, such as calcium, protein, vitamin D (in fortified dairy), magnesium, and potassium, which are thought to be beneficial for bone health. There is strong evidence for a positive association between milk and areal bone mineral density (aBMD), and limited evidence for yogurt intake with BMD looks promising. However, data on cheese and cream is very limited. Vitamin D is involved in calcium homeostasis, suggesting that both adequate levels of calcium and vitamin D are needed to ensure optimal calcium absorption. Results from the Framingham Study demonstrated that a higher intake of dairy foods (milk, milk + yogurt, and milk + yogurt + cheese) was protective against bone loss among vitamin D supplement users but not among nonusers. This suggests that adequate vitamin D levels may provide bone-protective benefits with higher dairy intakes. Only few studies have examined the association of dairy food intake with novel measures of bone, derived using quantitative computed tomography (QCT) and high-resolution peripheral QCT (HR-pQCT). These studies show positive associations at the radius, tibia, and spine with high dairy intakes. Future studies of dairy products should focus on (1) novel measures of bone beyond aBMD and (2) specific dairy foods (3) and should consider vitamin D status

p75 neurotrophin receptor mediates apoptosis in transit-amplifying cells and its overexpression restores cell death in psoriatic keratinocytes

p75 neurotrophin receptor (p75NTR) belongs to the TNF-receptor superfamily and signals apoptosis in many cell settings. In human epidermis, p75NTR is mostly confined to the transit-amplifying (TA) sub-population of basal keratinocytes. Brain-derived neurotrophic factor (BDNF) or neurotrophin-4 (NT-4), which signals through p75NTR, induces keratinocyte apoptosis, whereas β-amyloid, a ligand for p75NTR, triggers caspase-3 activation to a greater extent in p75NTR transfected cells. Moreover, p75NTR co-immunoprecipitates with NRAGE, induces the phosphorylation of c-Jun N-terminal kinase (JNK) and reduces nuclear factor kappa B (NF-κB) DNA-binding activity. p75NTR also mediates pro-NGF-induced keratinocyte apoptosis through its co-receptor sortilin. Furthermore, BDNF or β-amyloid cause cell death in TA, but not in keratinocyte stem cells (KSCs) or in p75NTR silenced TA cells. p75NTR is absent in lesional psoriatic skin and p75NTR levels are significantly lower in psoriatic than in normal TA keratinocytes. The rate of apoptosis in psoriatic TA cells is significantly lower than in normal TA cells. BDNF or β-amyloid fail to induce apoptosis in psoriatic TA cells, and p75NTR retroviral infection restores BDNF- or β-amyloid-induced apoptosis in psoriatic keratinocytes. These results demonstrate that p75NTR has a pro-apoptotic role in keratinocytes and is involved in the maintenance of epidermal homeostasis