METABOLISM: Energy Equation Proposes Patterns of Weight Gain and Loss
HMS researchers (from left) Rakesh Jain, Joshua Tam, and Dai Fukumura have devised a mathematical model of energy balance and body weight that suggests a possible explanation for intractable obesity. The model, based on results from experiments with mice and reported in the January Cell Metabolism, predicts that leptin resistance causes mice to have multiple stable body weights. Switching from a higher weight to a lower weight involves more than simply cutting calories. The model indicates that dieting may cause internal control systems to kick in with a magnetlike hold that pulls body weight back up. This hypothesis opens the door to new research that may help validate the predictions and determine if similar equations apply to humans.

GENOMICS: Predicting Heart Trouble
Diabetes is a major risk factor for coronary artery disease, which can lead to heart attacks, stroke, and premature death. Alesssandro Doria and his colleagues discovered that a single nucleotide polymorphism that increases risk of coronary artery disease in the general population confers an even greater risk in diabetic patients with poor glycemic control. It is not yet clear how the two risk factors synergize, but the researchers speculate that their findings may aid in understanding the development of atherosclerosis in diabetes and in designing more effective prevention strategies through early identification of individuals at high risk of coronary artery disease. Their study appears in the Nov. 26 Journal of the American Medical Association.

BIOLOGICAL CHEMISTRY: Lagging Steps Traced in DNA Replication
To pass along genes, dividing cells must duplicate their genomes. Complicating this everyday routine, the strands are replicated in a lopsided process. Researchers in the lab of Antoine van Oijen (center), including Samir Hamdan (left) and Joe Loparo, have observed the dynamic loop-and-release exploits of lagging-strand replication by studying hundreds of duplicating DNA strands, one at a time. Their single-molecule analysis, reported online Nov. 23 in Nature, establishes the molecular events that regulate loop growth and release, revealing new feats of timing and technique in a famously thorny aspect of DNA replication.

HEMATOLOGY: Therapeutic Target Found for Sickle Cell Anemia
A hurdle blocking the way to treatment for sickle cell anemia and beta-thalassemia has been understanding how humans switch from fetal to adult hemoglobin as they develop. Now Vijay Sankaran (left), Stuart Orkin, and their colleagues have a new lead. As reported in the Dec. 19 Science, they have found evidence that the transcription factor BCL11A directly downregulates expression of fetal hemoglobin (HbF); because keeping HbF expression “on” reduces symptoms, knocking down BCL11A might be a good therapeutic strategy. The researchers were tipped off by earlier genomewide association studies, so the work provides hope that this new generation of human genetic studies will yield clinically valuable returns.

Copyright 2009 by the President and Fellows of Harvard College