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JCI early table of contents for March 8, 2013

Enhanced brain acetate metabolism may reward heavy drinkers

In addition to its well-known effects on the CNS, alcohol consumption has a significant impact on metabolism. After consumption, the body rapidly begins converting ethanol to acetate, which can serve as an energy source for the brain and other organs. Lihong Jiang and colleagues at Yale University used a brain imaging technique, magnetic resonance spectroscopy, to track acetate uptake and metabolism in the brains of heavy drinkers (consumed at least 8 drinks/week) and light drinkers (consumed less than 2 drinks/week). In this issue of the Journal of Clinical Investigation, they report that heavy drinkers had greater, more rapid acetate uptake and metabolism compared to light drinkers. Because ethanol consumption can cause acute drops in blood glucose levels, acetate has the potential to provide a compensatory energetic reward. Additionally, acetate metabolism produces adenosine, which has a sedating effect similar to alcohol. These findings suggest that the provision of acetate and/or enhancement of adenosine during alcohol detoxification could help alleviate withdrawal symptoms.

Increased brain uptake and oxidation of acetate in heavy drinkers

Lihong Jiang
Yale School of Medicine, New Haven, CT, USA
Phone: 203-785-2953; E-mail:

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Fully wired: planar cell polarity genes guide gut neurons

The enteric nervous system (ENS), the "little brain" that resides within the gut wall, governs motility, secretion, and blood flow in the human gastrointestinal tract. Failure of the ENS to develop normally leads to congenital megacolon (Hirschsprung Disease) while loss of normal gut innervation is thought to contribute to debilitating motility disorders, such as irritable bowel syndrome. In order to prevent and treat these conditions, it is necessary to understand the molecular mechanisms that control the formation and function of the ENS. In this issue of the Journal of Clinial Investigation, Vassilis Pachnis and colleagues at the MRC National Institute for Medical Research in London found that the planar cell polarity (PCP) genes, Celsr3 and Fzd3 are required for the formation of the complex neural networks within the guts of mice. Inactivation of these genes resulted in disorganization of neuronal projections, slower gut transit time and abnormal colonic motility, indicating for the first time that improper ENS wiring contributes to gastrointestinal motility disorders. Future studies will be required to determine if mutations or dysfunction of these genes contributes to human gut motility disorders.

Planar cell polarity genes control the connectivity of enteric neurons

Vassilis Pachnis
MRC National Institute for Medical Research, London, GBR
Phone: 00442088162113; E-mail:

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GSK3β regulates physiological migration of stem/progenitor cells via cytoskeletal rearrangement

Tsvee Lapidot
Weizmann Inst. of Science, Rehovot, ISR
Phone: 972-8-9342481; Fax: 972-8-9344141; E-mail:

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The ubiquitin ligase Mindbomb 1 coordinates gastrointestinal secretory cell maturation

Jason Mills
Washington University School of Medicine, St. Louis, MO, USA
Phone: 314-362-4213;

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Activation of inflammasome signaling mediates pathology of acute P. aeruginosa pneumonia

Alice S. Prince
Columbia University, New York, NY, USA
Phone: 212/305-4193; Fax: 212-305-2284; E-mail:

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Rapamycin-treated human endothelial cells preferentially activate allogeneic regulatory T cells

Chen Wang
Yale University School Of Medicine, New Haven, CT, USA
Phone: 7202177392;

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Chronic activation of a designer Gq-coupled receptor improves β-cell function

Jrgen Wess
NIH-NIDDK, Bethesda, MD, USA
Phone: 301-402-3589; Fax: 301-480-3447; E-mail:

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Biochemical correlates of neuropsychiatric disorders in maple syrup urine disease

Emilie Muelly
The Pennsylvania State University, Hershey, PA, USA
Phone: 412-983-0410; E-mail:

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Contact: Jillian Hurst
Journal of Clinical Investigation

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