Weill Cornell Science Briefs: April 2008
Apr 17, 2008
It's All in the Eyes
Training People With Autism to Recognize Faces
Researchers might have gained insight into why people with autism have difficulty remembering faces and distinguishing facial emotion. In an ongoing study, Dr. Nim Tottenham, assistant professor of psychology in psychiatry at Weill Cornell Medical College, is examining how normal and autistic brains behave when viewing a face. While their brain is scanned in an fMRI machine, subjects look at a computer screen displaying different faces with various facial expressions. Each subject is motivated by a visual cue — a star symbol — to draw his or her attention to either the eyes or mouth on each face. Facial recognition areas in the brain are recorded by the fMRI, and eye movements are tracked with a camera. Early data in both healthy and autistic subjects show that only when a subject looks at the eyes does the facial recognition area of the brain become active. The research team hopes that early intervention with this behavioral technique in autistic children might help to train the brain to focus on others' eyes in order to improve facial recognition and facial emotion early in life.
Antioxidant Therapy Shows Early Promise Against Alzheimer's Disease
Improved Blood Flow Boosted Cognition and Behavior in Mice With AD-Like Illness, Researchers Report
For the first time, new research demonstrates that curbing harmful antioxidant processes in the brain's vasculature can reverse some of the cognitive decline associated with Alzheimer's disease. A natural enzyme of the immune system — NADPH oxidase — has been found to have toxic side effects, producing free radicals in the brains of mice. Identification of the enzyme's role in dementia might translate into a new drug target for Alzheimer's disease in humans, according to new findings published in a recent issue of the Proceedings of the National Academy of Sciences. After the offending enzyme was genetically "switched off," mice with a type of dementia mimicking Alzheimer's regained important cognitive abilities, even though the amount of Alzheimer's-linked amyloid plaques in their brains remained unchanged. These results suggest that the enzyme independently influences the progression of dementia.
The researchers, led by Dr. Costantino Iadecola, the George C. Cotzias Distinguished Professor of Neurology and Neuroscience at Weill Cornell Medical College and chief of the Division of Neurobiology at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, also genetically engineered mice that produced a mutated form of NADPH enzyme that did not produce the toxic free radicals. The result: The formerly "demented" mice regained their healthy, exploratory behaviors, just as non-demented mice do. According to the authors, the findings suggest that neurological damage from Alzheimer's may not be permanent and might even be reversed through antioxidant treatment.
New Malaria Target
Researchers Discover Weakness in Malaria-Causing Parasite
Scientists may have found a promising new drug target on the parasite that causes malaria — P. falciparum. To survive, the parasite creates a tiny pore called an anion channel, through which it takes in nutrients from outside the host cell's membrane and excretes its waste. In a recent paper published in PLoS Pathogens, the authors describe for the first time how this channel functions and how to possibly impair that function — thereby sickening and killing the parasite. The researchers discovered an important regulatory subunit enzyme, called PfPKA-R, which is encoded in the parasite's genome, and appears to be key to the proper function of the anion channel. Medications to treat malaria exist but the parasite gradually develops resistance, making the ongoing search for new and better treatments imperative. The study was an international collaboration — led by Dr. Kirk Deitsch of Weill Cornell Medical College in New York City and Stéphane Egée of Université Pierre et Marie Curie, in Roscoff, France.
The "Therapeutic Misconception": An Issue of Trust as Well as Research Integrity
What People Should Know When Enrolling in Clinical Trials
An article published in the March 2008 issue of the Journal of Medical Ethics explores often-neglected aspects of the "therapeutic misconception," an ethical problem present in many clinical research studies. This misunderstanding arises when research subjects believe they will be receiving optimal medical care as opposed to being participants in an experimental trial whose main goal is the benefit of future patients. Such misconception can lead subjects to underestimate risks and overestimate benefits.
Discussions on the therapeutic misconception usually center on whether it invalidates the consent of subjects. But lead author Dr. Inmaculada de Melo-Martín of the Department of Public Health at Weill Cornell Medical College and co-author Dr. Anita Ho of the Department of Philosophy at the University of British Columbia argue that focusing only on how the therapeutic misconception affects informed consent doesn't capture the ethical complexity of the problem. Equally significant are negative consequences to subjects, researchers and others resulting from misplaced trust, especially if this trust is exploited in order to recruit and retain subjects. The manipulation of subjects' misplaced trust, whether intentional or not, can undermine the trustworthiness of the research enterprise. It is therefore crucial for investigators and institutions to make efforts and employ strategies that are likely to dispel the therapeutic misconception and not to enroll those who still suffer from the misconception.
How Cells Generate Asymmetry
Protein Coating Tiny Vesicles May Play Key Role
Most common tools are intrinsically asymmetric, which is necessary for their function. For example, knives and forks have handles for grabbing and tips designed for cutting or punching. Likewise, most cells are asymmetrically shaped. This "polarity" is necessary to perform vital functions for the body. For example, neurons feature dendrites and axons to receive and relay electric signals, and epithelial cells display apical (top) and basal (bottom) poles to ingest nutrients and remove waste from the body. Research published in the journal Nature reveals how clathrin, a protein long known for its role in assembling tiny vesicles at the cell surface that bring nutrients into cells, orchestrates the production of tiny vesicles deep inside the cell that are necessary to build asymmetric cell architecture.
Dr. Enrique Rodriguez-Boulan, professor of cell and developmental biology in ophthalmology at Weill Cornell Medical College, and his team removed clathrin from cultured epithelial cells and found that, as expected from the known function of clathrin, their outside-in routes (endocytosis) were disrupted. Surprisingly, clathrin-depleted cells also showed a dramatic disruption of their inside-out routes (exocytosis). The researchers showed that the cells were defective in packaging proteins destined to the basal pole into tiny vesicles at two intracellular sites, the Golgi complex and the recycling endosomes. They believe this is an important discovery because it explains a long-sought mechanism for the generation of cell polarity. They also speculate that it may have practical consequences because 90 percent of human cancers are caused by epithelial cells that have lost their polarity. Hence, clathrin might become a useful target for some cancer therapies.
NewYork-Presbyterian Hospital/Weill Cornell Medical Center
NewYork-Presbyterian Hospital/Weill Cornell Medical Center, located in New York City, is one of the leading academic medical centers in the world, comprising the teaching hospital NewYork-Presbyterian and Weill Cornell Medical College, the medical school of Cornell University. NewYork-Presbyterian/Weill Cornell provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine, and is committed to excellence in patient care, education, research and community service. Weill Cornell physician-scientists have been responsible for many medical advances — from the development of the Pap test for cervical cancer to the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial for gene therapy for Parkinson's disease, the first indication of bone marrow's critical role in tumor growth, and, most recently, the world's first successful use of deep brain stimulation to treat a minimally-conscious brain-injured patient. NewYork-Presbyterian, which is ranked sixth on the U.S.News & World Report list of top hospitals, also comprises NewYork-Presbyterian Hospital/Columbia University Medical Center, Morgan Stanley Children's Hospital of NewYork-Presbyterian, NewYork-Presbyterian Hospital/Westchester Division and NewYork-Presbyterian Hospital/The Allen Pavilion. Weill Cornell Medical College is the first U.S. medical college to offer a medical degree overseas and maintains a strong global presence in Austria, Brazil, Haiti, Tanzania, Turkey and Qatar. For more information, visit www.nyp.org and www.med.cornell.edu.
Andrew Klein [email protected]