Role of Ubiquilins for Brown Adipocyte Proteostasis and Thermogenesis.

The acclimatization of brown adipose tissue (BAT) to sustained cold exposure requires an adaptive increase in proteasomal protein quality control. Ubiquilins represent a recently identified family of shuttle proteins with versatile functions in protein degradation, such as facilitating substrate targeting and proteasomal degradation. However, whether ubiquilins participate in brown adipocyte function has not been investigated so far.

Fuse your mitochondria, lose appetite: an anorexic, anti-obesity sphingolipid.

Aberrant production of ceramides, the precursors of complex sphingolipids, is a hallmark of obesity and strongly linked to metabolic dysfunction (Meikle and Summers 2017). Ceramides are formed by recycling or de novo synthesis from sphingosine and a fatty acid side chain moiety. The side chain length determines lipotoxicity of ceramides, as those composed of C16:0 or C18:0 side chains are toxic whereas those with C24:0 or C24:1 are not (Meikle and Summers 2017).

Methylglyoxal Drives a Distinct, Nonclassical Macrophage Activation Status.

Metabolic complications in diabetic patients are driven by a combination of increased levels of nutrients and the presence of a proinflammatory environment. Methylglyoxal (MG) is a toxic byproduct of catabolism and has been strongly associated with the development of such complications. Macrophages are key mediators of inflammatory processes and their contribution to the development of metabolic complications has been demonstrated.

Survey of ex vivo drug combination effects in chronic lymphocytic leukemia reveals synergistic drug effects and genetic dependencies.

Drug combinations that target critical pathways are a mainstay of cancer care. To improve current approaches to combination treatment of chronic lymphocytic leukemia (CLL) and gain insights into the underlying biology, we studied the effect of 352 drug combination pairs in multiple concentrations by analysing ex vivo drug response of 52 primary CLL samples, which were characterized by "omics" profiling. Known synergistic interactions were confirmed for B-cell receptor (BCR) inhibitors with Bcl-2 inhibitors and with chemotherapeutic drugs, suggesting that this approach can identify clinically useful combinations.