An imaging technique lets scientists peer through the skin of a whole mouse or rat to examine its organs after death. Ali Ertürk of the Ludwig Maximilians University of Munich in Germany and his colleagues created a technique called ultimate DISCO (uDISCO), which removes pigments and lipids from the tissues of dead animals using an organic solvent. This leaves the organs and skin intact but transparent, while preserving genetically encoded fluorescent proteins. The method revealed the nervous system of a mouse in stark detail. uDISCO also shrinks bodies by up to 65%, making it possible to image whole animals using light-sheet microscopy, which excels at imaging smaller samples. Nature Methods http://dx.
Amino acid metabolism is a critical regulator of the immune response, and its modulating becomes a promising approach in various forms of immunotherapy. Insufficient concentrations of essential amino acids restrict T-cells activation and proliferation. However, only arginases, that degrade L-arginine, as well as enzymes that hydrolyze L-tryptophan are substantially increased in cancer. Two arginase isoforms, ARG1 and ARG2, have been found to be present in tumors and their increased activity usually correlates with more advanced disease and worse clinical prognosis. Nearly all types of myeloid cells were reported to produce arginases and the increased numbers of various populations of myeloid-derived suppressor cells and macrophages correlate with inferior clinical outcomes of cancer patients. Here, we describe the role of arginases produced by myeloid cells in regulating various populations of immune cells, discuss molecular mechanisms of immunoregulatory processes involving L-arginine metabolism and outline therapeutic approaches to mitigate the negative effects of arginases on antitumor immune response. Development of potent arginase inhibitors, with improved pharmacokinetic properties, may lead to the elaboration of novel therapeutic strategies based on targeting immunoregulatory pathways controlled by L-arginine degradation.
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