This is the twice-per-month electronic newsletter for basic, preclinical and translational research news related to the Johns Hopkins School of Medicine. Please forward freely. Direct comments or questions to Joanna Downer, PhD, in the Office of Corporate Communications (4-5105, jdowner1@jhmi.edu).
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IN THIS ISSUE:
+ Malonyl-CoA Appears To Be A Key Appetite Regulator
+ Scientists Find First Gene Involved in Causing Ulcerative Colitis
+ Chemical Triggers Genetic Master Switch for Bacteria's "Seafood Dinner"
NEWS BRIEFS:
Dawson Labs' PARP-1 Cell Death Paper is "Hot"
Epstein To Head Surgical Pathology
Emergency Blood Drive Jan 13 at Hopkins
AWARDS AND HONORS:
Goodman to Edit Clinical Trials Journal
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Do you have an interesting research finding about one month from publication or presentation? Send manuscripts to Joanna Downer at jdowner1@jhmi.edu or fax to 410-614-8951. Information about awards and honors received by laboratory personnel and others is welcomed also.
For more info on a story, click the accompanying hyperlink.
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RESEARCH HIGHLIGHTS:
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12/18/03
Malonyl-CoA Appears To Be A Key Appetite Regulator
In experiments with mice, scientists at Johns Hopkins have discovered the first direct evidence that malonyl-CoA, a chemical intermediate in the production of fatty acids, is a key regulator of appetite, according to a report in a recent issue of the Proceedings of the National Academy of Sciences.
In hungry mice, malonyl-CoA was almost undetectable in the brain, the researchers determined. Once fasting mice were given food, however, amounts of the chemical increased to high levels within two hours. Furthermore, chemically reducing appetite by injecting a compound called C75 into the brain quickly brought levels of malonyl-CoA up to those of mice given food.
"From this work, it appears as though malonyl-CoA levels control appetite and levels of other brain chemicals that we know go up and down with hunger and feeding," says Dan Lane, PhD, professor of biological chemistry in the Institute for Basic Biomedical Sciences. "There may be other contributors, but this is the first direct evidence that malonyl-CoA could be the body's primary appetite controller."
In previous work, Lane and his colleagues had shown that giving mice C75, which blocks conversion of malonyl-CoA into fatty acids, dramatically reduced animals' appetites. Subsequently, they found that C75 triggers changes in levels of several known appetite signals (NPY, AgRP, POMC and others).
The new experiments suggest that increasing malonyl-CoA is the first step in the process in which C75 leads animals to behave as though they are full when they should be hungry. In additional experiments, preventing formation of malonyl-CoA partially reversed the appetite-suppressing effect of C75 by keeping malonyl-CoA levels lower.
http://www.hopkinsmedicine.org/Press_releases/2003/12_18_03.html
PNAS Oct 28 2003;100(22):12624-12629.
http://www.pnas.org/cgi/content/full/100/22/12624
12/18/03
Scientists Find First Gene Involved in Causing Ulcerative Colitis
Researchers at Johns Hopkins have linked versions of two different genes with the inflammatory bowel diseases known as Crohn's disease and ulcerative colitis. The discoveries are a crucial step in developing new treatments and prevention strategies for these disabling conditions that together affect one million Americans, the scientists say.
In the Jan. 1 issue of Human Molecular Genetics, the researchers report that a version of the NFKB1 gene is an important risk factor for ulcerative colitis. In the Dec. 2003 issue of the American Journal of Human Genetics, a team led by Hopkins and University of Chicago researchers reports that a version of the MDR1 gene is strongly associated with Crohn's disease and possibly ulcerative colitis as well.
"Our greatest hope is that by identifying the gene abnormalities associated with inflammatory bowel disease (IBD), we'll be able to figure out how they contribute to causing disease and then interfere with that process to stop the disease in its tracks," says Steven Brant, MD, associate professor of medicine and director of the Meyerhoff Inflammatory Bowel Disease Genetics Laboratory at Johns Hopkins.
The new discoveries may also prove useful to researchers working on other diseases in which the genes play a role, he says.
http://www.hopkinsmedicine.org/Press_releases/2003/12_19_03c.html
Hum Mol Genet 2004;13(1);35-45.
http://hmg.oupjournals.org/cgi/content/full/13/1/35
AJHG 2003;73(6):1282-1292.
http://www.journals.uchicago.edu/AJHG/journal/issues/v73n6/40175/40175.html
From Homewood:
12/29/03
Chemical Triggers Genetic Master Switch for Bacteria's "Seafood Dinner"
Two Johns Hopkins University biologists have made a key discovery about how and when armies of bacteria launch their cleanup of chitin (pronounced KITE-in), a cousin to cellulose and a major component of the skeletal debris discarded daily by crustaceans in the world's oceans.
In the Advance Online section of the Proceedings of the National Academy of Sciences, Xibing Li and Saul Roseman report finding a genetic master switch that reacts to the presence of nearby chitin and sets off a biological chain reaction that triggers the bacteria's feast. The master switch controls at least 50 and perhaps up to 300 other genes involved in the chitin sensing and consumption process, the researchers say.
To pinpoint the master switch, the scientists separated and tested mutant strains of Vibrios, the ocean's most common bacteria, according to their ability to detect and break down chitin, then they analyzed the bacteria's genetic structure. When Vibrios aren't in their feeding mode, this master switch remains in the "off" position, locked in place by a binding protein, Roseman says.
"When the bacteria are starving, however, they secrete an enzyme called chitinase into the water," says Roseman. "When chitinase touches the discarded shell material, it begins breaking down chitin, releasing a partially degraded soluble form into the water. These molecules are the signals to the bacteria that chitin is nearby. Diffusing through the ocean near the bacteria, these dissolved fragments of degraded chitin bind to the binding protein and remove the 'lock' [on the master switch]."
When the switch is on, the bacteria's genes get to work, moving the organisms along the trail of partially degraded chitin back to its source material. In the ocean, the bacteria follow a gradient stream of degraded chitin until they reach the solid shell material. The bacteria then latch on and begin their feast.
http://www.jhu.edu/news_info/news/home03/dec03/roseman.html
PNAS (published online Dec 29, 2003)
http://www.pnas.org/cgi/content/abstract/0307645100v1
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Dawson Labs' PARP-1 Cell Death Paper is "Hot" -- A paper from the laboratories of Valina Dawson, PhD, and Ted Dawson, MD, PhD, has recently joined the list of highly cited papers as determined by Thompson ISI, an organization that tracks scientific citations and measures research impact. The July 12, 2002, paper in Science describes an alternate cell death program that involves apoptosis-inducing factor (AIF) and is PARP-1 dependent. PARP-1, or poly-ADP ribose polymerase, dependent cell death is critically important in a number of experimental disease models, including diabetes, inflammation, arthritis, myocardial infarction, Parkinson's disease and cerebral ischemia, says Valina Dawson.
Science July 12 2002;297(5579):259-263.
http://www.sciencemag.org/cgi/content/full/297/5579/259
http://www.hopkinsmedicine.org/press/2002/July/020716.htm
http://www.esi-topics.com/nhp/2003/november-03-ValinaLDawson.html
Epstein To Head Surgical Pathology -- Jonathan Epstein, MD, has been named Director of the Division of Surgical Pathology, effective Jan. 1. The first recipient of The Reinhard Endowed Chair of Urologic Pathology, Epstein is renowned for his expertise in prostate cancer. He is a graduate of the six-year BA-MD program at the Boston University School of Medicine and did his anatomical pathology residency training at Johns Hopkins. After a one year fellowship in Oncological Pathology at Memorial Sloan Kettering Cancer Center, Epstein returned to Hopkins as chief resident. He joined the Hopkins faculty as instructor in 1985 and attained the rank of professor in 1994.
Emergency Blood Drive Jan 13 at Hopkins -- To assist the Red Cross in meeting the blood needs of patients throughout the Baltimore region, an emergency Blood Drive has been scheduled for Tuesday, Jan. 13, 7 am until 4 pm on the ground level of the Broadway Research Building, accessible via the Turner Concourse. Call your departmental recruiter or 4-0513 or email johnshopkinsblooddrive@jhmi.edu to schedule an appointment.
http://www.insidehopkinsmedicine.org/news/news_detail_page.cfm?id=1609
Goodman to Edit Clinical Trials Journal -- Steven Goodman, MD, PhD, associate professor of oncology, pediatrics, biostatistics and epidemiology, has been selected to become the editor in chief of Clinical Trials: The Journal of the Society for Clinical Trials. His five year term will run from 2004 2008.
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