https://cancerbiologyprogram.med.wayne.edu/pdfs/hallmarks_cancer_article.pdf

Hallmarks of cancer: the next generation.

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

https://staff.blog.ui.ac.id/hsuryadi/files/2012/02/ROS_RNS.pdf

Free radicals and antioxidants in normal physiological functions and human disease

Pathogen Recognition and Innate Immunity

Several reactive oxygen species (ROS) are continuously produced in plants as byproducts of aerobic metabolism. Depending on the nature of the ROS species, some are highly toxic and rapidly detoxified by various cellular enzymatic and nonenzymatic mechanisms. Whereas plants are surfeited with mechanisms to combat increased ROS levels during abiotic stress conditions, in other circumstances plants appear to purposefully generate ROS as signaling molecules to control various processes including pathogen defense, programmed cell death, and stomatal behavior. This review describes the mechanisms of ROS generation and removal in plants during development and under biotic and abiotic stress conditions. New insights into the complexity and roles that ROS play in plants have come from genetic analyses of ROS detoxifying and signaling mutants. Considering recent ROS-induced genome-wide expression analyses, the possible functions and mechanisms for ROS sensing and signaling in plants are compared with those in animals and yeast.

REACTIVE OXYGEN SPECIES: Metabolism, Oxidative Stress, and Signal Transduction

Erratum: The commonly used antimicrobial additive triclosan is a liver tumor promoter (Proc Natl Acad Sci USA (2014) 111 (17200-17205) DOI: 10.1073/pnas.1419119111)

https://www.cell.com/cell-metabolism/pdf/S1550-4131(13)00505-6.pdf

NCOA5, IL-6, type 2 diabetes, and HCC: The deadly quartet.

IjB kinase a (IKKa), one of the two catalytic subunits ofthe IKK complex involved in nuclear factor jB (NF-jB)activation, also functions as a molecular switch that con-trols epidermal differentiation. This unexpected functionrequires IKKa nuclear translocation but does not dependon its kinase activity, and is independent of NF-jB signal-ling. Ikka

New EMBO Member's Review IKKa, a critical regulator of epidermal differentiation and a suppressor of skin cancer

P38alpha Inhibits Liver Fibrogenesis and Consequent Hepatocarcinogenesis by Curtailing Accumulation of Reactive Oxygen Species

Severe neonatal hyperbilirubinemia (SNH) and the onset of bilirubin encephalopathy and kernicterus result in part from delayed expression of UDP-glucuronosyltransferase 1A1 (UGT1A1) and the inability to metabolize bilirubin. Although there is a good understanding of the early events after birth that lead to the rapid increase in serum bilirubin, the events that control delayed expression of UGT1A1 during development remain a mystery. Humanized UGT1 (hUGT1) mice develop SNH spontaneously, which is linked to repression of both liver and intestinal UGT1A1. In this study, we report that deletion of intestinal nuclear receptor corepressor 1 (NCoR1) completely diminishes hyperbilirubinemia in hUGT1 neonates because of intestinal UGT1A1 gene derepression. Transcriptomic studies and immunohistochemistry analysis demonstrate that NCoR1 plays a major role in repressing developmental maturation of the intestines. Derepression is marked by accelerated metabolic and oxidative phosphorylation, drug metabolism, fatty acid metabolism, and intestinal maturation, events that are controlled predominantly by H3K27 acetylation. The control of NCoR1 function and derepression is linked to IKKβ function, as validated in hUGT1 mice with targeted deletion of intestinal IKKβ. Physiological events during neonatal development that target activation of an IKKβ/NCoR1 loop in intestinal epithelial cells lead to derepression of genes involved in intestinal maturation and bilirubin detoxification. These findings provide a mechanism of NCoR1 in intestinal homeostasis during development and provide a key link to those events that control developmental repression of UGT1A1 and hyperbilirubinemia.

https://www.pnas.org/content/pnas/114/8/E1432.full.pdf

Michael Karin

Papers

Erratum: The commonly used antimicrobial additive triclosan is a liver tumor promoter (Proc Natl Acad Sci USA (2014) 111 (17200-17205) DOI: 10.1073/pnas.1419119111)

NCOA5, IL-6, type 2 diabetes, and HCC: The deadly quartet.

New EMBO Member's Review IKKa, a critical regulator of epidermal differentiation and a suppressor of skin cancer

P38alpha Inhibits Liver Fibrogenesis and Consequent Hepatocarcinogenesis by Curtailing Accumulation of Reactive Oxygen Species

Intestinal NCoR1, a regulator of epithelial cell maturation, controls neonatal hyperbilirubinemia