The index below is a selection of new studies and review articles by researchers from across the HMS community. It represents a small sample of research.
Low-Density Lipoproteins Containing Apolipoprotein C-III and the Risk of Coronary Heart Disease
Mendivil CO, Rimm EB, Furtado J, Chiuve SE, Sacks FM. Harvard School of Public Health, Department of Nutrition.
Low-density lipoprotein (LDL) that contains apolipoprotein (apo) C-III makes up only 10% to 20% of plasma LDL but has a markedly altered metabolism and proatherogenic effects on vascular cells. The authors examined the association between plasma LDL with apoC-III and coronary heart disease in 320 women and 419 men initially free of cardiovascular disease who developed a fatal or nonfatal myocardial infarction during 10 to 14 years of follow-up and matched controls who remained free of coronary heart disease; they conclude that the risk of coronary heart disease contributed by LDL appeared to result to a large extent from LDL that contains apoC-III. Circulation. 2011 Nov. 8;124(19):2065-72.
The three-dimensional architecture of a bacterial genome and its alteration by genetic perturbation.
Umbarger MA, Toro E, Wright MA, Porreca GJ, Baù D, Hong SH, Fero MJ, Zhu LJ, Marti-Renom MA, McAdams HH, Shapiro L, Dekker J, Church GM. Department of Genetics, Harvard Medical School.
The authors have determined the three-dimensional (3D) architecture of the Caulobacter crescentus genome by combining genome-wide chromatin interaction detection, live-cell imaging, and computational modeling. Using chromosome conformation capture carbon copy (5C), the authors derive ∼13 kb resolution 3D models of the Caulobacter genome. The resulting models illustrate that the genome is ellipsoidal with periodically arranged arms. The parS sites, a pair of short contiguous sequence elements known to be involved in chromosome segregation, are positioned at one pole, where they anchor the chromosome to the cell and contribute to the formation of a compact chromatin conformation. Collectively, the data suggest that genome folding is globally dictated by the parS sites and chromosome segregation. Molecular Cell. 2011 Oct. 21;44(2):252-64.
Inhibition of Pyruvate Kinase M2 by Reactive Oxygen Species Contributes to Antioxidant Responses.
Anastasiou D, Poulogiannis G, Asara JM, Boxer MB, Jiang JK, Shen M, Bellinger G, Sasaki AT, Locasale JW, Auld DS, Thomas CJ, Vander Heiden MG, Cantley LC. Beth Israel Deaconess Medical Center.
Control of intracellular reactive oxygen species (ROS) concentrations is critical for cancer cell survival. The authors show that, in human lung cancer cells, acute increases in intracellular concentrations of ROS caused inhibition of the glycolytic enzyme pyruvate kinase M2 (PKM2) through oxidation of Cys(358). Besides promoting metabolic changes required for proliferation, the regulatory properties of PKM2 may confer an additional advantage to cancer cells by allowing them to withstand oxidative stress. Science. 2011 Nov. 3.