Malfunction of a protein has been linked to form of mental retardation that affects one in 500 males

Friday 4 October 2013

Islamabad, Oct 5 (Newswire): Malfunction of a protein has been linked to a form of mental retardation that affects up to one out of every 500 males, says Nasser K. Yaghi, a Texas A&M University magna cum laude biology graduate who was selected to participate in a medical research project at Harvard that has been published in the journal Nature.

The results of the study suggest that if the condition is detected early in fetal development a treatment could possibly be developed to correct the problem.

"X-linked mental retardation (XLMR) is a human genetic disease affecting up to 2 out of 1,000 males and causes significant reduction in intellectual development characterized by an IQ less than 70," Yaghi says. "Many of these patients also have deficits in craniofacial (head and face) development such as cleft lip and cleft palate."

The double helix of DNA spools around proteins called histones, whose activities regulate gene expression, and PHF8, an enzyme in the family of histone demethylases, regulates some of these histones, he explains.

"Mutations in PHF8 have been found in patients with XLMR and craniofacial malformations," Yaghi adds. "Importantly, these mutations compromised PHF8's catalytic function."

Biological function of PHF8 was tested in zebrafish, which have an evolutionarily conserved PHF8 called zPHF8. Expression of zPHF8 was found in the developing zebrafish embryo mostly in the head region and was also able to be detected in the jaw, Yaghi notes.

When zPHF8's expression was inhibited, delay in brain development and the neural tube was observed. In addition, "when zPHF8 is not present in the developing zebrafish embryo, there are very noticeable differences in craniofacial development early in development when compared to normal embryos," he adds.

"Although this study was largely basic science research, I can hypothesize that when XLMR can be detected early in fetal development through genetic screening, then possibly a treatment could be created that would target the mutated PHF8 gene or introduce a new way to allow for proper histone demethylation in the absence of nonfunctional PHF8, and this would possibly correct the defect and allow proper development to continue," he explains.

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Homes of the poor and the affluent both have high levels of endocrine disruptors

Islamabad, Oct 5 (Newswire): Homes in low-income and affluent communities in California both had similarly high levels of endocrine disruptors, and the levels were higher in indoor air than outdoor air, according to a new study believed to be the first that paired indoor and outdoor air samples for such wide range (104) of these substances.

Ruthann Rudel and colleagues note concern about the reproductive and other health effects of endocrine disrupting compounds (EDCs), which are found in many products used in the home. Examples include phthalates, which are found in vinyl and other plastics, and polychlorinated biphenyls (PCBs), which are found in older paints, electrical equipment, and building materials. EDCs also are among the ingredients in some pesticides, fragrances, and other materials.

The scientists analyzed indoor and outdoor air samples as well as house dust in homes from two different communities in the San Francisco Bay area for the presence of 104 compounds, including 70 suspected EDCs.

The sampling, which took place in 2006, included 40 homes in Richmond, Calif., an urban, industrial, low-income area, and 10 homes in Bolinas, Calif., an affluent, coastal community. Levels were generally higher indoors than outdoors -- 32 of the compounds occurred in higher concentrations indoors and only 2 were higher outdoors.

The scientists expressed surprise at finding higher concentrations of some phthalates outdoors near urban homes contributing to higher indoor levels as well, but concluded that EDCs "are ubiquitously common across socioeconomic groups."

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One high-fat diet, two different outcomes: the path to obesity becomes clearer

Islamabad, Oct 5 (Newswire): Why is it that two people can consume the same high fat, high-calorie Western diet and one becomes obese and prone to diabetes while the other maintains a slim frame?

This question has long baffled scientists, but a study by Yale School of Medicine researchers provides a simple explanation: weight is set before birth in the developing brain.

The results are reported online the week of August 2 in the Proceedings of the National Academy of Sciences.

Led by Tamas Horvath, chair and professor of comparative medicine and professor of neurobiology and obstetrics & gynecology at Yale School of Medicine, the research team analyzed the same question in specific groups of rats. These animals have been bred so that their vulnerability to diet-induced obesity is known before they would be put on high-fat, high-calorie diet diets.

Horvath said animals that become obese already had a significant difference in the feeding center of the brain. Neurons that are supposed to signal when you've eaten enough and when to burn calories, are much more sluggish in these animals because they are inhibited by other cells. In animals resistant to obesity, these satiety signaling neurons are much more active and ready to signal to the rest of the brain and peripheral tissues when enough food has been consumed.

"It appears that this base wiring of the brain is a determinant of one's vulnerability to develop obesity," said Horvath, who is also co-director of the Yale Program in Integrative Cell Signaling and Neurobiology of Metabolism. "These observations add to the argument that it is less about personal will that makes a difference in becoming obese, and, it is more related to the connections that emerge in our brain during development."

Horvath points to other unwanted consequences of these brain mechanisms. "Those who are vulnerable to diet-induced obesity also develop a brain inflammation, while those who are resistant, do not," he said. "This emerging inflammatory response in the brain may also explain why those who once developed obesity have a harder time losing weight."

Diet-induced obesity has become one of the most critical medical problems in the United States. In particular, the incidence of childhood obesity has reached unprecedented levels. Since genetics alone cannot explain the surge of obesity in society, investigators have been trying to determine the primary underpinnings of the vulnerability to develop obesity on a Western diet.

"What genetic, epigenetic and environmental factor determines this base wiring in the brain is a very important issue to address," said Horvath. "Specifically, the emerging view is that besides genetics, maternal impact on the developing brain is likely to be critical to imprint these feeding circuits thereby determining one's vulnerability or resistance to obesity."

The study was supported by the National Institutes of Health and the American Diabetes Association.

Other Yale authors include Beatrix Sarman, Peter Sotonyi, Marya Shanabrough, Erzsebet Borok and Sabrina Diano. The study also included authors from the following institutions: Monash University, University of Cincinnati, German Institute of Human Nutrition Potsdam-Rehbrücke, Department of Veterans Affairs New Jersey Health Care System and University of Medicine and Dentistry New Jersey.

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