JHM Science e-Newsletter
Vol. 2., No. 3, Feb. 14, 2002
RESEARCH HIGHLIGHTS
"Klotho" Variant Linked With Human Life Expectancy
CNGA4 Protein Acts as Brain's Nose Plug
Indirect Anti-Oxidants Protect Retinal Cells
New Findings on Aquaporins in Brain and Lung
Panic and Bipolar Disorder Frequently Co-Inherited
NEWS BRIEFS:
- Boeke Giving Dean's Lecture Feb. 18
- Epigenetics Conference Seeks Presentations
- Salary Cap Increased for NIH Awards
- Microarray Hybridization Facility Open
- JHU CAM Center Creating Database
- Monument Street Auto Center Open
AWARDS AND HONORS
Wolberger Promoted to Full HHMI Investigator
McHugh Named to President's Bioethics Council
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 410-955-4452. Information about awards and honors received by laboratory personnel and others is welcomed also.
RESEARCH HIGHLIGHTS
1/14/02
"Klotho" Variant Linked With Human Life Expectancy
"Klotho," a gene named for the Greek Fate purported to spin the thread of life, contributes to life expectancy in humans, reports a team led by Johns Hopkins scientists in the Jan. 15 online version of the Proceedings of the National Academy of Sciences.
Studying more than 2,000 anonymous samples from Bohemian Czechs and Baltimore-area Caucasians and African-Americans, the scientists found that having two copies of a less-common version of klotho is twice as prevalent in infants as in people over age 65. The results suggest that people born with two variant copies die sooner than others, the scientists say.
In these populations, a team led by HHMI investigator and pediatrics professor Hal Dietz, MD, PhD, and postdoctoral fellow Dan Arking, PhD, discovered a variant of klotho that has six changes in the gene sequence, two of which alter the protein's sequence. However, the gene's exact influence on health and aging isn't known, and neither is the variant's impact on the protein's function.
More Info
1/22/02
CNGA4 Protein Acts as Brain's Nose Plug
Scientists from Johns Hopkins and elsewhere have found that a protein called CNGA4 acts as the brain's "nose plug" - the switch in the brain that lets us stop smelling something, even though the odor is still there.
Two papers in Science show CNGA4 helps plug the "nose" of odor receptor neurons. The "nose" is really a channel in the neurons' membrane that opens when an odor is presented and closes as the neuron becomes desensitized to that smell, says Randall Reed, PhD, professor of molecular biology and genetics and neuroscience.
By measuring the signals from these odor receptor cells in genetically engineered mice, HHMI investigator Reed and his colleagues showed that mice lacking CNGA4 can't adapt to odors. In a second paper, Jonathan Bradley, now a postdoctoral fellow in neuroscience in HHMI at Johns Hopkins, and his colleagues examined the electrical behavior of CNGA4 and the odor channel in isolated cells and found that CNGA4 speeds up the "nose's" closing.
More Info
Science 2001;294(5549):2172-2175 and 2176-2178
Reed
Bradley
1/22/02
Indirect Anti-Oxidants Protect Retinal Cells
A cancer-preventing compound in broccoli, first isolated a decade ago at Hopkins, may prove to protect against a much broader spectrum of diseases, including atherosclerosis and retinal degeneration. A new study shows that the compound, sulforaphane, helps cells defend themselves for days against oxidants.
Sulforaphane does not directly neutralize oxidants, but aids cells indirectly. It turns out that sulforaphane's anti-cancer properties and its indirect anti-oxidant effects are both due to its ability to make cells create a diverse group of enzymes, called "phase 2" enzymes. Not previously considered oxidant fighters, the laboratory research increases the enzymes' value in disease prevention, says Paul Talalay, MD, J.J. Abel Distinguished Service Professor of Pharmacology.
The scientists tested three different cell types, including cancer cells and cells from the retina. When the cells were treated briefly with sulforaphane before exposure to an oxidant, all cell types defended themselves against damage. (PNAS 2001;98(26):15221-15226)
While sulforaphane was not included, last fall a multi-center clinical study in which Wilmer Eye Institute participated revealed that dietary supplements of vitamin antioxidants reduce the risk of age-related macular degeneration progressing to advanced stages or greater vision loss in certain patients. Hopkins principal investigator for the study, Susan Bressler, MD, professor of ophthalmology, says benefits were limited to people with specific versions of the dry form of the disease. The ongoing study is online.
(Arch. Ophthalmology 2001;119(10):1417-1436)
(Talalay)
(Bressler)
1/23/02
New Findings on Aquaporins in Brain and Lung
In two papers in the Proceedings of the National Academy of Sciences, scientists report that a protein involved in muscle-wasting diseases tethers the water channel protein Aquaporin-4 (AQP4) to brain cells, and that another water channel protein, Aquaporin-1 (AQP1), is involved in normal lung function. The findings may impact treatment of lethal brain swelling from injury and stroke and perhaps for some forms of asthma, pneumonia and pulmonary edema.
Scientists led by biological chemistry professor Peter Agre, MD, and medical student John Neely, PhD, discovered that alpha-Syntrophin protein keeps AQP4 on the tips of brain cells called astrocytes. Without Syntrophin, part of the complex that fails in muscular dystrophy, the water channels are everywhere on the brain cells except where they are supposed to be. (PNAS 98(24):14108-14113)
Following Agre's discovery in the early 1990s of water channels, others began studying the proteins' roles in rare people born without them. A study led by Landon King, MD, assistant professor of pulmonary medicine, and Robert Brown, MD, associate professor of anesthesiology and critical care medicine, shows that another water channel protein, AQP1, regulates water flow into and out of cells in the lung.
(PNAS 2001;99(2):1059-1063)
(Agre)
(King)
From the Clinic: 1/23/02
Panic and Bipolar Disorder Frequently Co-Inherited
The inheritance patterns of panic disorder and bi-polar disorder shows that they are probably different forms of a shared and complex biological condition, rather than separate diseases, report Hopkins scientists in the ?? issue of the American Journal of Psychiatry.
"We've shown that panic attacks and panic disorder are related genetically to bipolar disorder and therefore likely share a common cause," says Dean MacKinnon, MD, assistant professor of psychiatry.
The researchers examined the disease pedigrees of 203 families in which at least one family member had bipolar disorder. Interviews with family members led to the identification of symptoms characteristic of major mood disorders and other psychiatric conditions in relatives.
If one family member had both panic disorder and bipolar disorder, the risk of panic disorder in other relatives was greatly increased, says MacKinnon. The particular genes responsible in these families have not been identified.
More Info
(Am. J. Psychiatry. 2002;159:30-35 )
NEWS BRIEFS:
Boeke Giving Dean's Lecture Feb. 18 -- Jef Boeke, PhD, DSc, professor of molecular biology and genetics, will be giving the third Dean's Lecture of the year on Monday, Feb. 18, at 5 pm in Hurd Hall. The title of his talk is "How retrotransposons shape the genomes of yeast and man." Boeke is co-director of the JHMI Microarray Core Facility (see brief below).
Epigenetics Conference Seeks Presentations -- An International Conference on "Epigenetic Mechanisms in Human Disease" will be held May 30?31 at the Natcher Conference Center on the NIH campus in Bethesda. According to the organizers, including Andy Feinberg of Johns Hopkins, the conference is a forum for basic and clinical aspects of research on epigenetic mechanisms in human diseases involving epigenetic modifiers, complex traits, model organisms, stem cells, basic mechanisms and cancer. For general information, preliminary agenda, registration and abstracts see the conference web site . The deadline for abstracts is March 15, but space is limited.
Salary Cap Increased for NIH Awards -- The amount of direct salary that individuals may charge to NIH awards is restricted to Executive Level I of the Federal Executive Pay Scale, which was increased to $166,700 effective Jan. 1. The complete announcement and further details regarding this salary cap can be found online .
Microarray Hybridization Facility Open -- Half of the new JHMI Microarray Core Facility is now open, kicked off by a lecture and reception Jan. 30 in Mountcastle Auditorium. Directed by Jef Boeke, PhD, DSc,professor of molecular biology and genetics, the Hybridization Unit will provide fee-for-service RNA expression profiling . The Analysis Unit, directed by Forrest Spencer, PhD, of the McKusick-Nathans Institute of Genetic Medicine, is due to open in the next few months.
JHU CAM Center Creating Database -- The JHU Complementary and Alternative Medicine (CAM) Center is creating a database of research projects on CAM modalities underway at Hopkins. If you are conducting or participating in such research, contact Rachel Schwartz at rschwart@mail.jhmi.edu and include your name, title, department, division, study title, patient population (if applicable), funding source and any publications.
Monument Street Auto Center Open -- In the Hopkins parking facility at 3700 Monument Street, the former Tower Ford facility, a full service auto center is now open. Just make an appointment, drop off the vehicle and take the shuttle to work. Parking at the site is free the day of service. For wash-and-wax services, call 410-889-4496. For guaranteed service for all makes and models by factory-trained technicians, call 410-522-3737. Read more about the new service in Dome, online.
AWARDS AND HONORS:
Wolberger Promoted to Full HHMI Investigator -- Cynthia Wolberger, PhD, professor of biophysics and biophysical chemistry, has been promoted to full Investigator of the Howard Hughes Medical Institute at Hopkins. Her research focus is understanding at the molecular level how transcriptional regulators modulate mRNA transcription, using x-ray crystallography to study both protein-DNA and protein-protein interactions.
McHugh Named to President's Bioethics Council -- Paul McHugh, MD, psychiatrist in chief at Hopkins Hospital and University Distinguished Professor of Psychiatry, has been named to the President's Council on Bioethics. The 18-member council, created by executive order of the president late last year, will advise President Bush on ethical and social issues related to biomedical and other scientific research.
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