Biochemical adaptations of the retina and retinal pigment epithelium support a metabolic ecosystem in the vertebrate eye

Here we report multiple lines of evidence for a comprehensive model of energy metabolism in the vertebrate eye. Metabolic flux, locations of key enzymes, and our finding that glucose enters mouse and zebrafish retinas mostly through photoreceptors support a conceptually new model for retinal metabolism. In this model, glucose from the choroidal blood passes through the retinal pigment epithelium to the retina where photoreceptors convert it to lactate. Photoreceptors then export the lactate as fuel for the retinal pigment epithelium and for neighboring Mu ̈ ller glial cells. We used human retinal epithelial cells to show that lactate can suppress consumption of glucose by the retinal pigment epithelium. Suppression of glucose consumption in the retinal pigment epithelium can increase the amount of glucose that reaches the retina. This framework for understanding metabolic relationships in the vertebrate retina provides new insights into the underlying causes of retinal disease and age-related vision loss

The SUrvey for Pulsars and Extragalactic Radio Bursts - III. Polarization properties of FRBs 160102 and 151230

We report on the polarization properties of two fast radio bursts (FRBs): 151230 and 160102 discovered in the SUrvey for Pulsars and Extragalactic Radio Bursts (SUPERB) at the Parkes Radio Telescope. FRB 151230 is observed to be 6 ± 11 per cent circularly polarized and 35 ± 13 per cent linearly polarized with a rotation measure (RM) consistent with zero. Conversely, FRB160102 is observed to have a circular polarization fraction of 30±11 per cent, linear polarization fraction of 84 ± 15 per cent for RM = -221(6) radm-2, and the highest measured dispersion measure (2596.1±0.3 pc cm-3) for an FRB to date.We examine possible progenitor models for FRB 160102 in extragalactic, non-cosmological and cosmological scenarios. After accounting for the Galactic foreground contribution, we estimate the intrinsic RM to be -256(9) rad m-2in the low-redshift case and ~-2.4×102rad m-2in the highredshift case. We assess the relative likeliness of these scenarios and how each can be tested. We also place constraints on the scattering measure and study the impact of scattering on the signal's polarization position angle

GCN2 adapts protein synthesis to scavenging-dependent growth

Pancreatic cancer cells with limited access to free amino acids can grow by scavenging extracellular protein. In a murine model of pancreatic cancer, we performed a genome-wide CRISPR screen for genes required for scavenging-dependent growth. The screen identified key mediators of macropinocytosis, peripheral lysosome positioning, endosome-lysosome fusion, lysosomal protein catabolism, and translational control. The top hit was GCN2, a kinase that suppresses translation initiation upon amino acid depletion. Using isotope tracers, we show that GCN2 is not required for protein scavenging. Instead, GCN2 prevents ribosome stalling but without slowing protein synthesis; cells still use all of the limiting amino acids as they emerge from lysosomes. GCN2 also adapts gene expression to the nutrient-poor environment, reorienting protein synthesis away from ribosomes and toward lysosomal hydrolases, such as cathepsin L. GCN2, cathepsin L, and the other genes identified in the screen are potential therapeutic targets in pancreatic cancer.UPPERSA