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Scientists Say They've Identified a Gene Linked to Anorexia

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People with anorexia nervosa have a distorted body image and severely restrict their food to the point of emaciation and sometimes death. It's long been treated as a psychological disorder, but that approach has had limited results; the condition has one of the highest mortality rates among psychiatric conditions. But recently, neuroscience researchers at the UC San Diego School of Medicine who study the genetic underpinnings of psychiatric disorders have identified a possible gene that appears to contribute to the onset of the disease, giving scientists a new tool in the effort to understand the molecular and cellular mechanisms of the illness.

The study, published in Translational Psychiatry, was led by UC San Diego's Alysson Muotri, a professor at the School of Medicine’s departments of pediatrics and cellular and molecular medicine and associate co-director of the UCSD Stem Cell Program. His team took skin cells known as fibroblasts from seven young women with anorexia nervosa who were receiving treatment at UCSD’s outpatient Eating Disorders Treatment and Research Center, as well as from four healthy young women (the study's controls). Then the team initiated the cells to become induced pluripotent stem cells (iPSCs). 

The technique, which won researcher Shinya Yamanaka the Nobel Prize in 2012, takes any nonreproductive cell in the body and reprograms it by activating genes on those cells. “You can push the cells back into the development stage by capturing the entire genome in a pluripotent stem cell state, similar to embryonic stem cells,” Muotri tells mental_floss. Like natural stem cells, iPSCs have the unique ability to develop into many different types of cells.

Once the fibroblasts were induced into stem cells, the team differentiated the stem cells to become neurons. This is the most effective way to study the genetics of any disorder without doing an invasive brain biopsy, according to Muotri. Also, studying animal brains for this kind of disorder wouldn’t have been as effective. “At the genetic level as well as the neural network, our brains are very different from any other animal. We don’t see chimpanzees, for example, with anorexia nervosa. These are human-specific disorders,” he says.

Once the iPSCs had become neurons, they began to form neural networks and communicate with one another in the dish similar to the way neurons work inside the brain. “Basically what we have is an avatar of the patient’s brain in the lab,” Muotri says.

His team then used genetic analysis processes known as whole transcriptome pathway analysis to identify which genes were activated, and which might be associated with the anorexia nervosa disorder specifically.

They found unusual activity in the neurons from the patients with anorexia nervosa, helping them identify a gene known as TACR1, which uses a neurotransmitter pathway called the tachykinin pathway. The pathway has been associated with other psychiatric conditions such as anxiety disorders, but more pertinent to their study, says Mutori, is that “tachykinin works on the communication between the brain and the gut, so it seems relevant for an eating disorder—but nobody has really explored that.” Prior research on the tachykinin system has shown that it is responsible for “the sensation of fat. So if there are misregulations in the fat system, it will inform your brain that your body has a lot of fat.”

Indeed, they found that the AN-derived neurons had a greater number of tachykinin receptors on them than the healthy control neurons. “This means they can receive more information from this neurotransmitter system than a normal neuron would,” Muotri explains. “We think this is at least partially one of the mechanisms that explains why [those with anorexia] have the wrong sensation that they have enough fat.”

In addition, among the misregulated genes, connective tissue growth factor (CTGF), which is crucial for normal ovarian follicle development and ovulation, was decreased in the AN samples. They speculate that this result may explain why many female anorexia patients stop menstruating.

Muotri next wants to understand what he calls “the downstream effect” of those neurons with too many TACR1 receptors. In other words, how does it affect the neurons at a molecular level, and what information do those neurons receive from the gut? “This link between the brain and the gut is unclear, so we want to follow up on that,” he says.

He also wants to look into the potential to design a drug that could compensate for the large amount of TACR1 receptors, and the over-regulation of that receptor in the brain—which would be a huge development for the notoriously difficult-to-treat disease.

While Muotri is excited about new avenues of research that can follow from this work, he doesn't see it as a panacea for the disease, but a way to begin to understand it more fully. He says, “It’s a good start, but arguably you have to understand what are the other environmental factors that contribute.”

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Stones, Bones, and Wrecks
The 'Alien' Mummy Is of Course Human—And Yet, Still Unusual
Emery Smith
Emery Smith

Ata has never been an alien, but she's always been an enigma. Discovered in 2003 in a leather pouch near an abandoned mining town in Chile's Atacama Desert, the tiny, 6-inch mummy's unusual features—including a narrow, sloped head, angled eyes, missing ribs, and oddly dense bones—had both the “It's aliens!” crowd and paleopathologists intrigued. Now, a team of researchers from Stanford University School of Medicine and UC-San Francisco has completed a deep genomic analysis that reveals why Ata looks as she does.

As they lay out in a paper published this week in Genome Research, the researchers found a host of genetic mutations that doomed the fetus—some of which have never been seen before.

Stanford professor of microbiology and immunology Garry Nolan first analyzed Ata back in 2012; the mummy had been purchased by a Spanish businessman and studied by a doctor named Steven Greer, who made her a star of his UFO/ET conspiracy movie Sirius. Nolan was also given a sample of her bone marrow; his DNA analysis confirmed she was, of course, human. But Nolan's study, published in the journal Science, also found something very odd: Though she was just 6 inches long when she died—a typical size for a midterm fetus—her bones appeared to be 6 to 8 years old. This did not lead Nolan to hypothesize an alien origin for Ata, but to infer that she may have had a rare bone disorder.

The current analysis confirmed that interpretation. The researchers found 40 mutations in several genes that govern bone development; these mutations have been linked to "diseases of small stature, rib anomalies, cranial malformations, premature joint fusion, and osteochondrodysplasia (also known as skeletal dysplasia)," they write. The latter is commonly known as dwarfism. Some of these mutations are linked to conditions including Ehlers-Danlos syndrome, which affects connective tissue, and Kabuki syndrome, which causes a range of physical deformities and cognitive issues. Other mutations known to cause disease had never before been associated with bone growth or developmental disorders until being discovered in Ata.

scientist measures the the 6-inch-long mummy called Ata, which is not an alien
Emery Smith

"Given the size of the specimen and the severity of the mutations … it seems likely the specimen was a pre-term birth," they write. "While we can only speculate as to the cause for multiple mutations in Ata's genome, the specimen was found in La Noria, one of the Atacama Desert's many abandoned nitrate mining towns, which suggests a possible role for prenatal nitrate exposure leading to DNA damage."

Though the researchers haven't identified the exact age of Ata's remains, they're estimated to be less than 500 years old (and potentially as young as 40 years old). Genomic analysis also confirms that Ata is very much not only an Earthling, but a local; her DNA is a nearest match to three individuals from the Chilote people of Chile.

In a press statement, study co-lead Atul Butte, director of the Institute for Computational Health Sciences at UC-San Francisco, stressed the potential applications of the study to genetic disorders. "For me, what really came of this study was the idea that we shouldn't stop investigating when we find one gene that might explain a symptom. It could be multiple things going wrong, and it's worth getting a full explanation, especially as we head closer and closer to gene therapy," Butte said. "We could presumably one day fix some of these disorders."

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Health
Just Two Cans of Soda a Day May Double Your Risk of Death From Heart Disease
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If you've been stocking your refrigerator full of carbonated corn syrup in anticipation of warmer weather, the American Heart Association has some bad news. The advocacy group on Wednesday released results of research that demonstrate a link between consumption of sugary drinks—including soda, fruit juices, and other sweetened beverages—and an increased risk of dying from heart disease.

Study participants who reported consuming 24 ounces or more of sugary drinks per day had twice the risk of death from coronary artery disease of those who averaged less than 1 ounce daily. There was also an increased risk of death overall, including from other cardiovascular conditions.

The study, led by Emory University professor Jean Welsh, examined data taken from a longitudinal study of 17,930 adults over the age of 45 with no previous history of heart disease, stroke, or diabetes. Researchers followed participants for six years, and examined death records to determine causes. They observed a greater risk of death associated with sugary drinks even when they controlled for other factors, including race, income, education, smoking habits, and physical activity. The study does not show cause and effect, the researchers said, but does illuminate a trend.

The study also noted that while it showed an increased risk of death from heart disease, consumption of sugary foods was not shown to carry similar risk. One possible explanation is that the body metabolizes the sugars differently: Solid foods carry other nutrients, like fat and protein, that slow metabolism, while sugary drinks provide an undiluted influx of carbohydrates that the body must process.

The news will likely prove troublesome for the beverage industry, which has long contended with concerns that sugary drinks contribute to type 2 diabetes and tooth decay. Some cities, including Seattle, have introduced controversial "soda tax" plans that raise the sales tax on the drinks in an effort to discourage consumption.

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