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  • Through population screening on the island of Kosrae, Rockefeller scientists discover a mutant gene that controls dietary cholesterol absorption | Newswire
    derived cholesterol like molecules called plant sterols as a proxy measure for dietary cholesterol absorption Sehayek measured plant sterol levels from Kosraean blood samples which were obtained as part of a long term study conducted by Rockefeller University scientists and study co authors Jeffrey M Friedman M D Ph D Markus Stoffel M D Ph D and Jan L Breslow M D and the island s Department of Health Sehayek then was able to correlate plasma plant sterol levels to genetic markers in Kosraens which had been determined as part of a general effort to pinpoint errant genes that contribute to the high incidence of obesity diabetes high blood pressure and high cholesterol among the people who live on the island of Kosrae The Kosraean islanders have been studied for 10 years because of their genetic history In the 1800s the Micronesian islanders of Kosrae married European Caucasians and about 120 years ago because of western diseases the population of the island was reduced to a few survivors The modern population has resulted from a relatively few individuals founders who were a mixture of the two genetic backgrounds This population structure is very favorable for finding genes for common diseases and in 1994 Friedman Stoffel and Breslow began a study to find genes for Syndrome X an umbrella term for the clustering of conditions including obesity diabetes blood pressure and high cholesterol which dramatically increases the risk of heart attacks In two population screenings in 1994 and 2001 more than 90 percent of the population was studied This has provided scientists with an invaluable database of blood samples a virtual living genetic library that Sehayek and his colleagues used to test plasma plant sterol levels against genetic profiles to determine a link Using the living library of samples and genetic data Sehayek measured plasma plant sterols as a surrogate marker for dietary cholesterol absorption and genotyped the DNA of over 1 000 Kosraean islanders to find genes that control cholesterol absorption In the course of this study three Kosraens were identified who had plasma plant sterol levels 25 to 50 times normal This finding suggested they had a disease called ßsitosterolemia This is a rare genetic disease that causes high plasma plant sterol levels cholesterol bumps in the skin and early heart attacks The disease is caused by mutations in one of two genes ABCG5 and ABCG8 Affected individuals have two mutant copies one from their mother and the other from their father All the affected Kosraens inherited the same two bad copies of the ABCG8 gene but did not have cholesterol bumps in their skin or early heart attacks This indicates that this disorder may be more common than previously thought says Sehayek because the presence of the disease without the symptoms may mean it goes undiagnosed Sehayek was able to trace genealogical data showing that two of the individuals who inherited two copies of the mutant gene were siblings born to a married couple who were second cousins

    Original URL path: http://newswire.rockefeller.edu/2004/07/30/through-population-screening-on-the-island-of-kosrae-rockefeller-scientists-discover-a-mutant-gene-that-controls-dietary-cholesterol-absorption/ (2016-02-13)
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  • Fat hormone leptin alters brain architecture and activity, which in turn shapes feeding behavior | Newswire
    The malleability of these feeding circuits by leptin suggest the possibility that the brain s wiring may be different in lean versus obese individuals Friedman added In March 2004 the U S Centers for Disease Control and Prevention announced that obesity is now the second leading cause of death in the United States Poor diet and inactivity now account for more than 400 000 deaths a year second only to tobacco as a preventable cause of death Pinto and her colleagues have shown for the first time that leptin induces visible changes in the synaptic connections and recordable changes in the electrical activity of specific brain cells Other researchers have shown that brain maps of cells can be quite plastic or changeable Pinto whose scientific training is in the area of learning and memory wanted to know if the same was true when it came to feeding behavior Feeding turns out to be a really good model to test plasticity because it s much simpler to study than the system that controls learning or memory said Pinto For her research Pinto used a famous mouse strain that resembles obesity in some humans These mice lack leptin and grow to twice the size of a normal mouse with a body that contains five times the fat Using the obese mice Pinto and her colleagues were able to show effects of the hormone on two particular sets of neurons NPY and POMC These neurons are found in the hypothalamus an area of the brain that controls appetite NPY stimulates food intake and increases body weight while one of the active products of POMC a peptide called alpha MSH has the opposite effect Pinto and colleagues discovered that leptin changes the number of connections that either excite or inhibit NPY and POMC neurons in the hypothalamus Led by Roseberry the researchers also showed that leptin alters the electrical activity of the connections to NPY and POMC neurons These effects are consistent with what the researchers found on the structural level In other words leptin inhibits NPY neurons that encourage the animal to eat and reserve energy At the same time the hormone activates POMC neurons that curtail feeding And it does this by altering the synaptic inputs of these cells the points where the cells connect and communicate The Rockefeller scientists suggest that these leptin induced structural and functional changes are responsible for changes in the animal s behavior too Six hours after administering leptin to obese mice changes could be seen in their synaptic connections Forty eight hours later they were eating less and at 12 days the mice had lost weight Finally the researchers also discovered that the same brain wiring system could be influenced with a separate substance a peptide called ghrelin found in the stomach and the brain In contrast to leptin ghrelin stimulates appetite Application of ghrelin was associated with an increase in the numbers of inhibitory synapses on the POMC neurons suggesting that the effects of ghrelin

    Original URL path: http://newswire.rockefeller.edu/2004/04/02/fat-hormone-leptin-alters-brain-architecture-and-activity-which-in-turn-shapes-feeding-behavior/ (2016-02-13)
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  • “Gene therapy” in worms identifies protein that plays role in controlling water balance, sense of touch in live animals | Newswire
    generate the electrical impulses underlying information transfer in the nervous system This year s Nobel Prize in Chemistry was shared by Roderick MacKinnon M D a Rockefeller University professor and HHMI investigator who was the first scientist to visualize an ion channel the potassium channel at the level of its atomic structure The TRPV4 ion channel was found to play similar roles in roundworms and mammals suggesting the protein harbors an ancient highly conserved biological principle that allows a cell membrane to maintain a certain tension just like a balloon filled with a certain amount of air or water say the researchers In multicellular organisms this property forms the basis of sensitivity to touch as well as changes in osmotic pressure which is sensed by specialized cells they say Friedman and Liedtke had identified the trpv4 gene in 2000 in collaboration with Rockefeller University scientist A James Hudspeth also an HHMI investigator and now say the new findings report a crucial role of the trpv4 gene in living animals Their earlier findings reported in the journal Cell were a result of their search for genes involved in controlling constancy of the internal milieu of mammals like temperature and osmotic pressure The Rockefeller researchers focused on a master regulatory region of the brain called the hypothalamus The hypothalamus is the place where the actual level of osmotic pressure is sensed and also where counterregulatory measures drinking and secretion of ADH anti diuretic hormone that tells the kidney to preserve water are coordinated They didn t find a temperature regulator but discovered a gene that appeared to be involved in a physiological process at least as fundamental the regulation of osmotic pressure Osmotic pressure in mammals including humans is maintained with exquisite precision within the animal says Friedman TRPV4 had been detected in osmoregulatory cells in the hypothalamus as well as in cells sensitive to mechanical stimuli such as the trigeminal nerve cells that are sensitive to touch and pain and the inner ear hair cells that sense sound and change in posture The type of cells in which TRPV4 had been found led to speculation about the role of TRPV4 in live animals To determine the protein s actual function Liedtke and Friedman designed a set of in vivo experiments In the first study Liedtke and Friedman generated knockout mice that lacked the trpv4 gene and thus did not express TRPV4 protein They found that the engineered mice secreted less anti diuretic hormone and drank less water compared to normal or wild type mice The results suggest that TRPV4 functions as an osmotic sensor in the central nervous system says Friedman and that there must be other systems involved in maintaining osmotic pressure otherwise the engineered mice would not have been able to survive There are likely redundant mechanisms at work to maintain normal osmotic pressure he says The companion study by the Rockefeller scientists in collaboration with the UCSF researchers Cornelia Bargmann Ph D and David Tobin Ph D studied

    Original URL path: http://newswire.rockefeller.edu/2003/10/28/gene-therapy-in-worms-identifies-protein-that-plays-role-in-controlling-water-balance-sense-of-touch-in-live-animals/ (2016-02-13)
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  • gene therapy | Newswire
    mice and mutant roundworms researchers at The Rockefeller University and the University of California San Francisco have identified a protein that helps control water balance in the body and underlies the sensation of touch functions basic to life that have long eluded explanation More Tags gene therapy Jeffrey M Friedman TRPV4 Search for Categories Science News Awards and Honors Campus News Grants Gifts Topics Video Archive 2015 2014 2013 2012

    Original URL path: http://newswire.rockefeller.edu/tag/gene-therapy/ (2016-02-13)
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  • TRPV4 | Newswire
    and mutant roundworms researchers at The Rockefeller University and the University of California San Francisco have identified a protein that helps control water balance in the body and underlies the sensation of touch functions basic to life that have long eluded explanation More Tags gene therapy Jeffrey M Friedman TRPV4 Search for Categories Science News Awards and Honors Campus News Grants Gifts Topics Video Archive 2015 2014 2013 2012 2011

    Original URL path: http://newswire.rockefeller.edu/tag/trpv4/ (2016-02-13)
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  • Obesity not a personal failing, says leptin discoverer Jeffrey Friedman, but a battle against biology | Newswire
    have such a significant effect on the incidence of obesity As Friedman explains the reported incidence of obesity is rooted in the definition of obesity which is described by the body mass index or BMI BMI is a measure of body fat based on height and weight that applies to both adult men and women A BMI calculator can be found at http nhlbisupport com bmi bmicalc htm Obesity is diagnosed when BMI passes a defined threshold People are said to be overweight if their BMI is greater than 25 and obese if their BMI exceeds 30 According to Friedman since obesity is defined as a threshold an increase in average weight has a disproportionate effect on the increasing incidence of obesity Friedman suggests that there is a bright side small achievable decrease in the average weight of the U S population could have an enormous benefit to public health In addition Freidman cites a statistical analysis of BMI trends by Katherine Flegal Ph D an expert in the epidemiology of obesity and overweight at the U S Centers for Disease Control and Prevention which shows that in addition to an increase in average BMI the distribution of BMI in our population is also becoming increasingly skewed at the higher end Thus in modern times some individuals have manifested a much greater increase of BMI than others strongly Friedman writes suggesting the possibility that in our population there is a subgroup that is genetically susceptible to obesity and a different subgroup that is relatively resistant Many factors have been cited as contributors to the rise in obesity a shift in American eating habits toward more fast food increased consumption of soft drinks decreased physical activity and increased inactivity But even with these environmental changes Friedman poses a basic question how can anyone be thin in an environment where virtually everyone has unfettered access to calories The answer lies in the interaction of the environment with the biological system that our genes comprise In 1995 Friedman and his colleagues discovered the hormone leptin which is produced by fat tissue and signals the brain when to stop eating As body fat increases more leptin is produced which acts to reduce food intake As body fat decreases less leptin is produced which stimulates food intake and reduces energy expenditure Research by Friedman and other scientists has shown that genetic mutations that lead to a full or partial loss of leptin are associated with obesity in some humans In addition to leptin Friedman and other scientists have identified a number of hormones and genes that play a role in appetite and weight These hormones orchestrate the unconscious urge to eat a basic biological drive that is difficult to fight with the conscious desire to eat less Those who doubt the power of basic drives however might note that while one can hold one s breath this conscious act is soon overcome by the compulsion to breathe notes Friedman The feeling of hunger is intense

    Original URL path: http://newswire.rockefeller.edu/2003/02/06/obesity-not-a-personal-failing-says-leptin-discoverer-jeffrey-friedman-but-a-battle-against-biology/ (2016-02-13)
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  • Leslie B. Vosshall | Newswire | Page 2
    called SNMP and its mechanism of action have been implicated in pheromone detection the mechanism also appears to underlie the diverse biological functions regulated by CD36 proteins ranging from how we taste fats to how our immune system detects and responds to foreign invaders More Tags Leslie B Vosshall olfactory pheromones September 16 2007 Science News Gene determines whether male body odor smells pleasant Up to one third of the adult human population does not perceive an odor in androstenone a component of male body odor that has been shown to induce physiological responses in both men and women To those who do androstenone either takes on a pleasant sweet odor or a repulsive urine like one New research from Rockefeller University and Duke University traces this variability to point mutations in a single odorant receptor gene a finding that raises questions of how people detect other people s body odor More Tags androstenone Leslie B Vosshall olfactory March 23 2007 Science News Humans flies smell alike neurobiologists find While it would seem that how a fruit fly judges odors should differ from how a human smells new research from Rockefeller University finds that at the neurobiological level the two organisms have more in common than one might expect More Tags Andreas Keller Leslie B Vosshall olfactory December 13 2006 Science News Identification of carbon dioxide detectors in insects may help fight infectious disease Blood feeding insects like mosquitoes use the carbon dioxide in your breath to hone in on their targets But in a finding that could have implications for fighting infectious disease new research from Rockefeller University pinpoints the molecules these insects use to detect carbon dioxide More Tags carbon dioxide Leslie B Vosshall January 20 2006 Science News Study shows a fundamental difference between how insects mammals detect odors Contrary to what has been widely believed the molecular basis of insect olfaction is not related to the mammalian system but is an extraordinary case of the two types of organisms evolving along similar but separate lines what scientists term convergent evolution says Rockefeller s Leslie Vosshall More Tags Leslie B Vosshall olfactory January 9 2006 Awards and Honors Three Rockefeller scientists receive 2005 Mayor s awards Rockefeller faculty members Jan Breslow Mitchell Feigenbaum and Leslie Vosshall were among recipients of the 2005 New York City Mayor s Awards for Excellence in Science and Technology announced today at Gracie Mansion More Tags Jan Breslow Leslie B Vosshall Mayor s Award Mitchell Feigenbaum December 21 2005 Science News Watching fruit fly larvae crawl towards odors provides clues to how smells are detected In new research published this month in Current Biology Rockefeller scientists provide evidence that a combinatorial code is the mechanism by which fruit flies and most likely other animals distinguish one odor from another More Tags Leslie B Vosshall olfactory September 9 2005 Science News In flies odorant receptors work together By tracing the location of nerve cells that produce specific odorant receptors scientists have linked dozens

    Original URL path: http://newswire.rockefeller.edu/tag/leslie-b-vosshall/page/2/ (2016-02-13)
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  • Sniff study suggests humans can distinguish more than 1 trillion scents | Newswire
    number of colors we can distinguish at between 2 3 and 7 5 million and audible tones at about 340 000 To overcome this complexity Keller combined odors and asked volunteers whether they could distinguish between mixtures with some components in common Our trick is we use mixtures of odor molecules and we use the percentage of overlap between two mixtures to measure the sensitivity of a person s sense of smell Keller says To create his mixtures Keller drew upon 128 odor molecules responsible for scents such as orange anise and spearmint He mixed these in combinations of 10 20 and 30 with different proportions of components in common The volunteers received three vials two of which contained identical mixes and they were asked to pick out the odd one This approach was inspired by previous work at the Weizmann Institute in Israel in which researchers combined odors at similar intensities to create neutral smelling olfactory white In that experiment and in Keller s study the researchers were interested in the perception of odor qualities such as fishy floral or musky not their intensity But since intensity can interfere with the perceived qualities both had to account for it The results published this week in Science show that while individual volunteers performance varied greatly on average they could tell the difference between mixtures containing as much as 51 percent of the same components Once the mixes shared more than half of their components fewer volunteers could tell the difference between them This was true for mixes of 10 20 and 30 odors By analyzing the data the researchers could calculate the total number of distinguishable mixtures It turns out that the resolution of the olfactory system is not extraordinary you need to change a fair fraction of the components

    Original URL path: http://newswire.rockefeller.edu/2014/03/20/sniff-study-suggests-humans-can-distinguish-more-than-1-trillion-scents/ (2016-02-13)
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