Systematic reduction of the dimensionality of natural scenes allows accurate predictions of retinal ganglion cell spike outputs.

The mammalian retina engages a broad array of linear and nonlinear circuit mechanisms to convert natural scenes into retinal ganglion cell (RGC) spike outputs. Although many individual integration mechanisms are well understood, we know less about how multiple mechanisms interact to encode the complex spatial features present in natural inputs. Here, we identified key spatial features in natural scenes that shape encoding by primate parasol RGCs.

Genome Profiling for Aflatoxin B Resistance in Reveals a Role for the CSM2/SHU Complex in Tolerance of Aflatoxin B-Associated DNA Damage.

Exposure to the mycotoxin aflatoxin B1 (AFB) strongly correlates with hepatocellular carcinoma (HCC). P450 enzymes convert AFB into a highly reactive epoxide that forms unstable 8,9-dihydro-8-(7-guanyl)-9-hydroxyaflatoxin B1 (AFB--Gua) DNA adducts, which convert to stable mutagenic AFB formamidopyrimidine (FAPY) DNA adducts. In CYP1A2-expressing budding yeast, AFB is a weak mutagen but a potent recombinagen.

An in vitro system for measuring genotoxicity mediated by human CYP3A4 in Saccharomyces cerevisiae.

P450 activity is required to metabolically activate many chemical carcinogens, rendering them highly genotoxic. CYP3A4 is the most abundantly expressed P450 enzyme in the liver, accounting for most drug metabolism and constituting 50% of all hepatic P450 activity. CYP3A4 is also expressed in extrahepatic tissues, including the intestine.

CYP1A1 I462V polymorphism is associated with reduced genotoxicity in yeast despite positive association with increased cancer risk.

CYP1A1 functions in detoxifying xenobiotics but occasionally converts compounds into potent genotoxins. CYP1A1 activates polyaromatic hydrocarbons, such as benzo[a]pyrene 7,8 dihydrodiol (BaP-DHD), rendering them genotoxic. Particular alleles of CYP1A1, such as CYP1A1 I462V have been correlated with a higher incidence of breast and lung cancer, but it is unknown whether these variants express enzymes in vivo that are more potent in generating genotoxins.