Archive for the ‘Michael Lutter’ Category


Joshua Neally had only been driving his Tesla Model X for a week when he found himself suffering a medical emergency.

Joshua Neally says he suffered a pulmonary embolism late last month while behind the wheel of the Tesla Model X, which features auto-driving technology, that he had purchased a week earlier.

“It was kinda getting scary. I called my wife and just said, ‘something’s wrong,’ and I couldn’t breathe, I was gasping, kind of hyperventilating,” the attorney from Springfield, Missouri, told KY3 News. “I just knew I had to get there, to the ER.”

Instead of pulling over to call 911 and wait for an ambulance, the 37-year-old father said he was able to direct his car to the nearest hospital.

Neally told Slate he doesn’t remember much after that. He said he’s fully aware, however, that the blockage in his lungs could have killed him or caused him to pass out behind the wheel.

Roughly one-third of people with an untreated or undiagnosed pulmonary embolism don’t survive, according to the Mayo Clinic.

Neally’s health scare occurred about three months after a Tesla driver in Florida was killed when his self-driving car crashed into a semi truck. The incident inspired a federal investigation into the company’s auto-piloting technology.

Neally knows about that accident, but is still grateful for his experience with the vehicle.

“It’s not going to be perfect, there’s no technology that’s perfect, but I think the measure is that it’s better and safer,” he said.

http://www.huffingtonpost.com/entry/tesla-drives-man-to-hospital_us_57a8aee8e4b0b770b1a38886

Thanks to Michael Lutter for bringing this to the It’s Interesting community.

By Rachel Feltman

If you give a mouse an eating disorder, you might just figure out how to treat the disease in humans. In a new study published Thursday in Cell Press, researchers created mice who lacked a gene associated with disordered eating in humans. Without it, the mice showed behaviors not unlike those seen in humans with eating disorders: They tended to be obsessive compulsive and have trouble socializing, and they were less interested in eating high-fat food than the control mice. The findings could lead to novel drug treatments for some of the 24 million Americans estimated to suffer from eating disorders.

In a 2013 study, the same researchers went looking for genes that might contribute to the risk of an eating disorder. Anorexia nervosa and bulimia nervosa aren’t straightforwardly inherited — there’s definitely more to an eating disorder than your genes — but it does seem like some families might have higher risks than others. Sure enough, the study of two large families, each with several members who had eating disorders, yielded mutations in two interacting genes. In one family, the estrogen-related receptor α (ESRRA) gene was mutated. The other family had a mutation on another gene that seemed to affect how well ESRRA could do its job.

So in the latest study, they created mice that didn’t have ESRRA in the parts of the brain associated with eating disorders.

“You can’t go testing this kind of gene expression in a human,” lead author and University of Iowa neuroscientist Michael Lutter said. “But in mice, you can manipulate the expression of the gene and then look at how it changes their behavior.”

It’s not a perfect analogy to what the gene mutation might do in a human, but the similarities can allow researchers to figure out the mechanism that causes the connection between your DNA and your eating habits.

The mice without ESRRA were tested for several eating-disorder-like behaviors: The researchers tested how hard they were willing to work for high fat food when they were hungry (less, it seemed, so much so that they weighed 15 percent less than their unaltered littermates), how compulsive they were, and how they behaved socially.

In general, the ESRRA-lacking mice were twitchier: They tended to overgroom, a common sign of anxiety in mice, and they were more wary of novelty, growing anxious when researchers put marbles into their cages. They also showed an inability to adapt: When researchers taught the mice how to exit a maze and then changed where the exit was, the mice without ESRRA spent way more time checking out the area where the exit should have been before looking for where it had gone.

The social changes were even more striking: Mice will usually show more interest in a new mouse than one they’ve met before, but in tests the modified mice showed the opposite preference, socializing with a familiar mouse when a new one was also presented.

They were also universally submissive to other mice, something the researchers detected with a sort of scientific game of chicken. Two mice are placed at either end of a tube, and one always plows past the other to get to the opposite side. It’s just the way mice size each other up — someone has to be on top. But every single one of the modified mice let themselves get pushed around.

“100% of the mice lacking this gene were subordinate,” Lutter said. “I’ve never seen an experiment before that produced a 0% verses 100% result.”

The avoidance of fats has an obvious connection to human disorders. But the social anxiety and rigidity are also close analogies to disordered eating in humans.

Now that Lutter and his colleagues know that the gene does something similar in mice, they can start looking for the actual mechanism that’s tripping these switches in the brain. They know that the gene’s pathway is very important for energy metabolism, especially in the breakdown of glucose. It’s possible that mutations in the gene cause some kind of impairment in neurons’ ability to get and process energy, but they can’t be sure yet.

They’ll see if they can pinpoint affected neurons and fix them. They’re also going to test some drugs that are known to affect this gene and its pathways. It’s possible that they’ll land on a treatment that helps calm these negative behaviors in affected mice, leading to treatments for humans with the mutation.

http://www.washingtonpost.com/news/speaking-of-science/wp/2015/04/09/scientists-manage-to-give-mice-eating-disorders-by-knocking-out-one-gene/

Open Access Article here: http://www.cell.com/cell-reports/abstract/S2211-1247(15)00301-0

Lutter,Michael

Eating-1

Eating disorders like anorexia nervosa and bulimia often run in families, but identifying specific genes that increase a person’s risk for these complex disorders has proved difficult.

Now scientists from the University of Iowa and University of Texas Southwestern Medical Center have discovered — by studying the genetics of two families severely affected by eating disorders — two gene mutations, one in each family, that are associated with increased risk of developing eating disorders.

Moreover, the new study shows that the two genes interact in the same signaling pathway in the brain, and that the two mutations produce the same biological effect. The findings suggest that this pathway might represent a new target for understanding and potentially treating eating disorders.

“If you’re considering two randomly discovered genes, the chance that they will interact is small. But, what really sealed the deal for us that the association was real was that the mutations have the same effect,” says Michael Lutter, M.D., Ph.D., UI assistant professor of psychiatry and senior author of the study.

Overall, the study, published Oct. 8 in the Journal of Clinical Investigation, suggests that mutations that decrease the activity of a transcription factor — a protein that turns on the expression of other genes — called estrogen-related receptor alpha (ESRRA) increase the risk of eating disorders.

Anorexia nervosa and bulimia nervosa are fairly common, especially among women. They affect between 1 and 3 percent of women. They also are among the most lethal of all psychiatric diseases; about 1 in 1,000 women will die from anorexia.

Finding genes associated with complex diseases like eating disorders is challenging. Scientists can analyze the genetics of thousands of people and use statistics to find common, low-risk gene variations, the accumulation of which causes complex disorders from psychiatric conditions like eating disorders to conditions like heart disease or obesity.

On the other end of the spectrum are very rare gene variants, which confer an almost 100 percent risk of getting the disease. To track down these variants, researchers turn to large families that are severely affected by an illness.

Lutter and his colleagues were able to work with two such families to identify the two new genes associated with eating disorders.

“It’s basically a matter of finding out what the people with the disorder share in common that people without the disease don’t have,” Lutter explains. “From a theoretical perspective, it’s straightforward. But the difficulty comes in having a large enough group to find these rare genes. You have to have large families to get the statistical power.”

In the new study, 20 members from three generations of one family (10 affected individuals and 10 unaffected), and eight members of a second family (six affected and two unaffected) were analyzed.

The gene discovered in the larger family was ESRRA, a transcription factor that turns on the expression of other genes. The mutation associated with eating disorders decreases ESSRA activity.

The gene found in the second family is a transcriptional repressor called histone deacetylase 4 (HDAC4), which turns off transcription factors, including ESRRA. This mutation is unusual in the sense that it increases the gene’s activity — most mutations decrease or destroy a gene’s activity.

Importantly, the team also found that the two affected proteins interacted with one another; HDAC4 binds to ESRRA and inhibits it.

“The fact that the HDAC4 mutation happens to increase the gene activity and happens to increase its ability to repress the ESSRA protein we found in the other family was just beyond coincidence,” Lutter says.

The two genes are already known to be involved in metabolic pathways in muscle and fat tissue. They also are both regulated by exercise.

In the brain, HDAC4 is very important for regulating genes that form connections between neurons. However, there’s almost nothing known about ESRRA in the brain, although it is expressed in many brain regions that are disrupted in anorexia.

Lutter and his colleagues plan to study the role of these genes in mice and in cultured neurons to find out exactly what they are doing in the brain. They will also look for ways to modify the genes’ activity, with the long-term goal of finding small molecules that might be developed into therapies for eating disorders.

They also plan to study patients with eating disorders and see if other genes associated with the ESSRA/HDAC4 brain pathway are affected in humans.

http://www.sciencedaily.com/releases/2013/10/131008122443.htm