The obesity epidemic has become a major public health concern. The phenomenon is typically attributed to changes in diet and lifestyle, and socioeconomic factors like poverty and poor education.

Genetic factors have been known play a role as well, but a recent study by UK-based scientists suggests they play much more prominent role, at least in a subset of people who become morbidly obese at a young age.

In the study, Sadaf Farooqi of the University of Cambridge and colleagues showed that many such kids are missing a large chunk of DNA, known as SH2B1, from chromosome 16.

The missing genetic code had been known to play a role in regulating weight and blood sugar levels. Kids with the chromosomal abnormality tended to overeat on a massive scale, and gain weight easily. 

To reach these conclusions, the scientists scanned the genomes of 300 morbidly obese kids in search of copy number variants (CNVs), which are lengthy strands of DNA that are either duplicated or missing.
The scientists compared their findings with information from healthy controls.

In their write-up, which appears in Nature, the scientists wrote, “we identified several rare copy number variants that were recurrent in patients but absent or at much lower prevalence in controls.”

“Part of chromosome 16 can be deleted in some families. People with this deletion have severe obesity from a young age,” Farooqi told Medical News Today: “One particular gene on chromosome 16 called SH2B1 plays a key role.”

The finding may have broad social implications, since it is common to blame parents or guardians for morbid obesity in kids. The scientists noted for example, that some kids in the study had been handed over to Social Services because their parents were assumed to have been deliberately overfeeding them.

Cal Tech scientists may have figured out why some people have a notably annoying tendency to get too close during conversations, on subway trains or in restrooms.

The culprit turns out to be a malfunction in an almond-sized structure known as the amygdala, which is located in both temporal lobes of the brain. The amygdala processes negative emotions like anger and fear, but its role in social interaction had not previously been studied.

Daniel Kennedy, Ralph Adolphs and colleagus made the association by studying a 42-year-old woman known as SM, who has severe, isolated damage to her amygdala.

The scientists had known that SM couldn’t recognize fear in the expressions of others, or judge their trustworthiness, and had shown these abnormalities to be caused by her amygdala lesions.
 
While observing SM over time, Adolphs also noticed that she seemed to be too friendly, and frequently violated what others perceived to be their own personal space.

“She is extremely friendly, and she wants to approach people more than normal. It’s something that immediately becomes apparent as you interact with her,” Kennedy told BurrillReport.
 
So the scientists decided to compare SM’s sense of personal space to normal volunteers using the stop-distance technique, in which subjects approach a person until they reach a point where they feel most comfortable, and this distance is recorded.

www.youtube.com/watch?v=OM59nSkjEWU

Among the normal volunteers, the mean preferred distance was about 2 feet, but SM came in much tighter than that, about a foot. And unlike normal subjects who reported feeling uncomfortable when the experimenter approached to a distance within their preferred range, SM never became uncomfortable.

Even cheek to cheek, she was relaxed, and her feelings changed not a whit regardless of who the experimenter was or how well she knew them.

The write-up appears in Nature Neuroscience.

A multinational group of scientists has concluded that about a third of the genetic underpinnings of schizophrenia are caused by the interactions of many thousand common genetic variants. While each variant may be harmless on its own, the combined impact vastly increases the risk of both schizophrenia and bipolar disorder.

The results imply that the genetic basis of the 2 common psychoses  are more complex than had been thought, and that the conditions can develop not just from a rare, devastating genetic variant, but from dozens or hundreds of common ones.

The write-up is in Nature.
 
“This is an enormous first for our field,” co-author Patrick Sullivan told BurrillReport. “We now have the outline of the puzzle, we just need to… see how (the pieces) fit together,” added the professor of psychiatry at the UNC School of Medicine.
 
Although scientists have long recognized that schizophrenia has a genetic basis, it’s only recently that they’ve started pinpointing offending genetic loci.
 
To reach their conclusions, Sullivan and colleagues isolated 30,000 genetic variants that occurred more frequently in 3,000 people having schizophrenia than in a control group without the condition. The team confirmed the differences in 2 other populations of schizophrenic patients and 2 groups with bipolar disorder.

The genetic link between schizophrenia and bipolar disorder had not previously been recognized.
 
“While our study finds a surprising number of genetic effects, we expect that future work will assemble them into meaningful pathways that will teach us about the biology of schizophrenia and bipolar disorder,” senior author Pamela Sklar told Burrill.
 
The scientists also found that a particular HLA haplotype increased the risk for both psychoses. Since HLA proteins are involved in the immune response to infections, they speculated that an infectious agent might be an etiologic factor.

Just weeks after scientists blew up the dogma that new heart muscle cells can’t be generated after birth, other investigators have followed suit for the eggs of mammalian females.

A familiar tenet of reproductive medicine held that women were on a biological clock: they were born with a full complement of eggs that were gradually used up during reproductive years.

These losses, combined with alterations in hormone production, led to the loss of childbearing capacity by the late 50s.

Not so, say Ji Wu and colleagues from Shanghai Jiao Tong University, who have shown that adult female mice harbor stem cell-like cells in their ovaries that can be coaxed to become fully functional eggs.

“If you are looking to disprove that females cannot make new eggs, this paper proves it. This is the smoking gun,” Jonathan Tilly, a Harvard-based OB/GYN professor told the Washington Post.

The scientists removed ovaries from mice and isolated from them some cells that appeared to be germline stem cells.

They stimulated the cells to differentiate in petri dishes, labeled them with a fluorescent protein and injected them into the ovaries of mice that had been rendered infertile using chemotherapy drugs.

These mice soon became proud mothers to offspring that glowed in the dark proving they had been conceived from the fluorescent labeled eggs.

The offspring were normal in every way, reported the authors in Nature.

The findings raise hope for women who need to delay childbearing or who are facing possible sterilization secondary to surgery or chemotherapy.

Yet some researchers remained cautious, “The aging process of the human egg differs fundamentally from that of the mouse egg,” said David Keefe, an OB/GYN professor at the University of South Florida.

“Except at Disney World, humans are not large mice,” he reminded the Post.

Autistic 2 year-olds respond differently to visual and auditory cues presented in cartoons, an observation that could help diagnose the condition earlier and perhaps encourage development of interventions that favorably alter the course of the disease.

To reach this conclusion, Ami Klin and colleagues at Yale showed specially prepared animations to 21 toddlers with autistic-spectrum disorders, 39 normally developing children and 16 that had developmental problems other than autism.

The cartoons were specially designed versions children’s games like ‘peek-a-boo’ and ‘pat-a-cake.’

In some versions, the images appeared upside-down. In others, they were not.

In addition, some versions featured audio cues like the sounds of clapping hands, while others were silent. 

The Yale scientists showed that normally developing toddlers and those with non-autism related developmental problems showed a clear preference for the upright animations whether or not audio cues were present.

Toddlers with ASD did not demonstrate this preference when shown silent versions of the cartoons, but when audio cues were added, they did prefer the upright versions over the upside-down versions 66% of the time.

Apparently, sound helped grab their attention.

The write-up appears in Nature.

“In autism, genetic predispositions are exacerbated by atypical experience from a very early age, altering brain development,” Klin told the BBC.

“Attention to biological motion is a fundamental mechanism of social engagement. We need to understand how this process is derailed in autism, starting in the first weeks and months of life,” he added.

“This line of research holds promise for development of new therapies based on redirecting visual attention in children with (autism),” said Thomas Insel, director of the National Institute of Mental Health.

Playing fast action video games, including first-person shooter games can boost ones’ ability to perceive subtle differences in shades of gray.

Contrast sensitivity like this is the primary factor that determines how well a person can see.

Daphne Bavelier and colleagues at the University of Rochester and the Eye Institute at Tel Aviv University probably had no problem rounding up 22 young adult volunteers for her study of these matters.

After assessing the participants’ visual contrast sensitivity, the scientists randomized them into 2 groups and asked them to play assigned video games for 50 hours during a 9 week intervention.

The test group played 2 action video games, “Unreal Tournament 2004″ and “Call of Duty 2.” Controls played “The Sims 2″ which was visually complex, but had a slower pace and did not require precise, visually guided aiming activity.

After the volunteers had skipped the light fandango and turned cartwheels ‘cross the floor for 9 weeks, action game players were found to have improved by 43% their ability to discern between shades of pale. There was no change in the Sims group.

www.youtube.com/watch?v=PbWULu5_nXI

 “Normally, improving contrast sensitivity means getting glasses or eye surgery—somehow changing the optics of the eye,” Bavelier told BurrillReport. “But we’ve found that action video games train the brain to process the existing visual information more efficiently.”

The improvements held true for 2 years after the “training” had ended. The write-up is in Nature Neuroscience.
 
The scientists’ findings extended Bavelier’s earlier research showing that action video games reduce visual crowding and increase visual attention.

They concluded that action video game training may complement standard eye-correction techniques by teaching the visual cortex to better use the information it receives.

Scientists at Dana-Farber Cancer Institute and the CDC have produced monoclonal antibodies that can destroy most strains of flu virus, a new line of attack that promises to overcome the virus’ maddening ability to mutate and thus fool today’s vaccines.

Such antibodies “could provide broad protection against all seasonal and pandemic influenza A viruses,” according to Wayne Marasco of Harvard Medical School and colleagues.

The potion targets the flu virus near its base, a region that turns out to be genetically stable.

The base mediates viral entry into cells, Marasco’s team wrote in Nature Structural & Molecular Biology.

Today’s vaccines stimulate antibody production against the viral head, a region that demonstrates extraordinary genetic polymorphism. That’s why flu vaccines are useless after one year at best and queueing-up for a jab has become an annual ritual for millions.

Coauthor Ruben Donis of the CDC is confident his group has flu by the short hairs, pointing out to MedpageToday that “By mutating (at the base, the flu virus) commits suicide.” 

The monoclonal antibodies appear to work against multiple strains of flu, including H5N1 avian flu and the H1N1 Spanish flu strain that killed 50 million people in 1918.

They also were shown to prevent flu symptoms in animals even when given 24 hours after exposure to flu virus, so long as they’re given in higher but “achievable” doses, according to the scientists.

The next step is to see whether the antibodies work in ferrets, which strangely enough have immunologic responses to flu virus more like humans than any other species.

Clinical trials could begin in 2 years.
 
The Dana-Farber holds patents on the discovery of the static region and the monoclonal antibodies against it.

Reykjavik-based Decode Genetics, which is a lot better at personal genomics than selecting investment advisors, is back in the news now that its scientists have determined that 57% of all thyroid cancer is attributable to 2 genetic variations.

Julius Gudmundsson and colleagues report in Nature Genetics that the variants are simple base-pair substitutions occurring in genes residing near those controlling thyroid gland development, one on Chromosome 9 and the other on Chromosome 14.

Compared with those having neither variant, “the risk associated with these variants was almost six-fold, which is quite extraordinary,” Erich Sturgis, a head and neck surgeon at Houston’s MD Anderson Cancer told the New York Times.

Each year in the US, about 35,000 cases of thyroid cancer are diagnosed. Treatment generally includes surgical resection of the gland followed by lifelong thyroid replacement. It’s quite effective and only 1,500 people die from thyroid cancer each year.

The Decode breakthroughs are thus not going to trigger interest in population-wide screening programs, but the information would be useful in the assessment of people at high risk, such as those with a positive family history of the disease. 

Gudmundsson’s group reached its conclusions by performing a genome-wide association study involving 192 positive cases and a large control group.

They showed that people having both genetic variants had low levels of thyroid-stimulating hormone, which is produced normally by the pituitary gland.

TSH helps thyroid cells mature, so the authors postulate that chronically low TSH levels might impede their differentiation and thus increase the risk of malignant transformation.

If this theory proves correct, TSH supplementation might reduce the risk of developing thyroid cancer in affected individuals.

Scientists at UC Berkeley have found that mice with a genetically engineered defect in a fat tissue enzyme remained thin despite gorging to their heart’s content on a high-fat diet.
 
The enzyme is adipose-specific phospholipase A2 or AdPLA. It normally catalyzes a biochemical process that produces prostaglandin E2. High PGE2 levels suppress fat metabolism. The AdPLA-deficient mice had low PGE2 levels and broke down fat like crazy.
 
Kathy Jaworski and her colleagues bred mice that produced an inactive form of AdPLA and offered them and a control group a continuous, all-you-can-eat fatty-food fiesta for life.
 
The two groups ate the same amount of food, so the enzyme does not impact appetite. But by 64 weeks, the AdPLA-deficient mice weighed in at a svelte 39 grams, while controls tipped the scales at 74.
 
For kicks the scientists then repeated the experiment in leptin-deficient mice, with leptin being the hormone that tells your brain you’re full so stop eating. Leptin-deficient mice eat like pigs and put on weight faster than a sumo wrestler on the Oprah Winfrey diet.
 
Seventeen weeks after this study began, the leptin-deficient mice weighed 75 grams, whereas mice lacking both leptin and functional AdPLA weighed 35 soaking wet.
 
 “This means that local signals in fat tissue allow fat cells to regulate fuel provision for the body, which changes our fundamental understanding of how the body regulates fat breakdown,” Maryam Ahmadian, a study co-author told BurrillReports.
 
Studies of murine fat metabolism don’t always translate to the human condition, but rest assured that before long someone will take a peek at AdPLA gene expression in humans.

Oh and the AdPLA-deficient mice had significant insulin resistance and a marked increase in liver fat. Somebody needs to get on that, too.

Scientists in St. Louis have decoded the entire genome of a woman who died of leukemia and in the process, they identified several mutations that probably caused the disease, accelerated its progression or rendered it resistant to chemotherapeutic agents.

The researchers sequenced DNA from the woman’s leukemia cells and her non-cancerous skin cells, and then compared them side-by-side. The comparison revealed 10 mutations that were present only in the cancer cells.

“This is the first of many of these whole cancer genomes to be sequenced,” Richard K. Wilson told the New York Times. Wilson is Director of the Genome Sequencing Center at Washington University and a senior author on the paper published in Nature. “They’ll give us a whole bunch of clues about what’s going on in the DNA when cancer starts to bloom,” he added.

The scientists’ strategy to sequence the entire genome of a human cancer cell represents a break from previous approaches that had focused on a few hundred “likely suspect” genes. The strategy has been enabled by recent advances that make it far cheaper and quicker to sequence large amounts of DNA. The advantage of the new strategy is that it eliminates the possibility that the genes actually associated with cancer are not among the “likely suspects.”

Indeed Wilson’s group found that 8 of the 10 mutations in their study were not considered likely suspect genes.

The woman’s sequenced DNA will be made available for other research projects. Before her donation, the only fully sequenced human genomes had come from Craig Venter, the founder of the Institute for Genomic Research, and Nobel Prize winning molecular biologist James Watson.