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.

British scientists reported last week that genetically engineered tomatoes, rendered purple by an abundance of cancer-fighting chemicals normally found in dark berries, helped prevent cancer in mice.

In the British study, a special breed of cancer prone mice lived an average of 182 days on a diet containing the purple tomatoes, whereas the same breed of mice lived only 142 days on a standard diet.

Cathie Martin and her team carried out the research at the John Innes Center in the UK, and published their findings in Nature Biotechnology. The study supports the theory that vegetables can be genetically modified to enhance their health promoting characteristics.

“The effect was much bigger than we expected,” Martin told Reuters.

The cancer preventing ingredients in the purple tomatoes are anthocyanins which are normally found in blueberries, blackberries, raspberries, cranberries and concord grapes. The antioxidant compounds have been shown to reduce the risk of cancer, heart disease and certain neurological diseases.

For this study, Martin’s team spliced anthocyanin-producing genes from a snapdragon flower (pictured) into the DNA of a tomato. The resulting phenotype was a purple tomato that contained three times the antioxidant capacity of red tomatoes.

While the results are exciting, Dr. Lara Bennett, a science information officer at Cancer Research UK told Reuters, “It’s too early to say whether anthocyanins obtained through diet could help reduce the risk of cancer” in humans.

It’s also too early to say whether the world is ready for purple pizza.

Scientists reported in Nature this week that monkeys could overcome a temporarily paralyzed wrist in order to continue playing a computer game, a finding that could point towards new treatments for people that have sustained spinal cord injuries or a stroke.

Amazingly, the animals pulled off the feat by controlling the activity of a single cell in their brains.

Chet Moritz and colleagues at the University of Washington tested two pigtail macaques (see picture) in their study. The monkeys had learned to play a game in which they manipulated their wrists up and down in order to move a cursor towards a target on a computer screen.

The scientists then implanted probes to track firing patterns in the monkeys’ brain cells and observed as the monkeys played the game. They noted that certain brain cells fired at different frequencies when the monkeys raised or lowered their wrists.

The researchers then used anesthetic to temporarily block nerves that normally activate wrist the monkeys’ wrist muscles, and connected the brain cell probe directly to an electrical stimulator affixed to the monkeys’ wrist muscles.  In no time, the monkeys learned to use the artificial bypass tract to move their wrists so they could continue playing the game.

The finding is, “an important step forward.” Case Western Reserve scientist Dawn Taylor told the Associated Press. Taylor works in the field but was not involved in this study.

But Moritz cautioned that human applications are at best a decade away. “There’s no way to say with confidence that it will work,” he added.

Is the world finally getting serious about malaria, a disease that strickens half a billion people every year, killing 1-3 million of them? Just maybe, yes.

Last week an alliance of celebrities, businesses and big donors began to implement an affordable, scalable action plan for the disease. Coincidentally, scientists shed new light on the genetics of two malaria-causing parasites.

The Global Malaria Action Plan aims to reduce the incidence of malaria from 2000 levels by 75% in seven years, and reduce mortality from the disease to nearly zero over the same time period. The United Nations supports the malaria control plan, and donors recently committed $3 billion to it, a promising start although more money is required. 

The Action Plan relies on three tactics: artemisinin-based anti-malarial drugs to treat the disease, insecticide-impregnated nets to prevent mosquitoes from biting people in bed, and pesticide spraying inside buildings. The strategy has proven to be effective during recent trials in Rwanda, Ethiopia and elsewhere.

Eradication will be harder. For that we need new tools such as a vaccine, and that does not exist right now. Enter a pair of scientific advances published in Nature this week, in which scientists in the US and England report having sequenced the entire genomes for the malaria-causing parasites Plasmodium vivax and Plasmodium knowlesi respectively. These breakthroughs may well accelerate development of vaccines or drug therapies against them.