Saturday, February 18, 2017

Broad Wins CRISPR Patent Interference Case

thescientist  |   US Patent and Trademark Office’s Patent Trial and Appeal Board (PTAB) today (February 15) issued a ruling on a patent dispute regarding CRISPR gene editing. The judges declared that the work by Jennifer Doudna of the University of California, Berkeley, and colleagues (including Emmanuelle Charpentier, then at the University of Vienna) does not directly compete with the work of Feng Zhang at the Broad Institute of MIT and Harvard, which was granted the original CRISPR patent in April 2014.
“Broad has persuaded us that the parties claim patentably distinct subject matter,” the court wrote in its 51-page decision (which accompanied its two-page order). “Broad provided sufficient evidence to show that its claims, which are all limited to CRISPR-Cas9 systems in a eukaryotic environment, are not drawn to the same invention as UC’s claims, which are all directed to CRISPR-Cas9 systems not restricted to any environment.”
“It looks like Broad has the decisive victory in this case,” Jake Sherkow of New York Law School told The Scientist.
UC Berkeley said that, while it “respects” today’s ruling and is “pleased” that its patent application can now move forward, the university is considering “all options for possible next steps in this legal process, including the possibility of an appeal of the PTAB’s decision,” a statement read. “We continue to maintain that the evidence overwhelmingly supports our position that the Doudna/Charpentier team was the first group to invent this technology for use in all settings and all cell types.”
If UC Berkeley does appeal to the US Court of Appeals for the Federal Circuit, “those cases take roughly a year from soup to nuts,” said Sherkow. In that circumstance, a decision would likely come from the appellate court “sometime in February or March of next year.”

Monday, January 23, 2017

The Role of Bioactive Lipids in Cancer Metastasis

thescientist | Although metastasis is the leading cause of death among people with cancer, for the most part, researchers are stumped about which molecular signals allow malignant cells to leave primary tumors and start new ones. Two studies published in Nature this month highlight roles in metastasis for an unexpected group of molecules—lipids.
“For many years, we were studying peptides and proteins,” said Mariusz Ratajczak, a cell biologist at the University of Louisville who was not involved in the studies. “Now we are coming to bioactive lipids.”
In the first study, published January 5, researchers at the Institute for Research in Biomedicine (IRB) in Barcelona reported that, in mice, human oral cancer cells that are most likely to migrate from primary tumors are marked by the surface protein, CD36—a scavenger receptor that binds fatty acids. The researchers initially identified the cells by examining genes upregulated in non-cycling tumor cells, finding increased expression of genes involved in lipid metabolism, transport, and storage—all processes downstream of CD36.
When the researchers knocked down CD36 with short hairpin RNA before the injecting oral cancer cells into mice, they prevented the cells from seeding metastatic tumors in the lymph nodes of 80 percent to 100 percent of the animals without significantly changing the frequencies of primary tumors. “What’s really cool here is that they showed that CD36 wasn’t necessary for self-renewal, but was necessary for dissemination and metastasis,” said Justin Lathia, a cell and molecular biologist at the Cleveland Clinic who was not involved in the work. This study, he added, demonstrates that metastatic cells don’t have to be cancer stem cells.
It also suggests that metastatic cells may have their own unique metabolic regulation. The IRB team demonstrated that feeding mice a high-fat diet increased the size and number of metastatic lymph node tumors. This effect was lost when CD36 was knocked down. The researchers generated the same effect when they pretreated the cancer cells in culture with a dietary fatty acid called palmitic acid. Lathia note that while this finding could provide insight into the link between obesity and cancer, “human diets are far more complex than what we have here.”

Thursday, January 19, 2017

Effortless Weightloss For Cancer and Diabetes Fermentation Vessels...,

impactjournals |  Morbidly obese patients who accomplish substantial weight loss often display a long-term decline in their resting metabolism, causing even relatively restrained caloric intake to trigger a relapse to the obese state. Paradoxically, we observed that morbidly obese mice receiving chemotherapy for cancer experienced spontaneous weight reduction despite unabated ingestion of their high fat diet (HFD). This response to chemotherapy could also be achieved in morbidly obese mice without cancer. Optimally dosed methotrexate (MTX) or cyclophosphamide (CY) enabled the mice to completely and safely normalize their body weight despite continued consumption of obesogenic quantities of HFD. Weight reduction was not attributable to decreased HFD intake, enhanced energy expenditure or malabsorption. MTX or CY dosing significantly depleted both adipose tissue and preadipocyte progenitors. Remarkably, however, despite continued high fat feeding, a compensatory increase in hepatocyte lipid storage was not observed, but rather the opposite. Gene microarray liver analyses demonstrated that HFD mice receiving MTX or CY experienced significantly inhibited lipogenesis and lipid storage, whereas Enho (energy homeostasis) gene expression was significantly upregulated. Further metabolic studies employing a human hepatocellular line revealed that MTX treatment preserved robust oxidative phosphorylation, but also promoted mitochondrial uncoupling with a surge in proton leak. This is the first report that certain optimally dosed chemotherapeutic agents can induce weight loss in morbidly obese mice without reduced dietary intake, apparently by depleting stores of adipocytes and their progenitors, curtailment of lipogenesis, and inconspicuous disposal of incoming dietary lipid via a steady state partial uncoupling of mitochondrial oxidative phosphorylation.

Saturday, December 3, 2016

The Collapse of the Body's Ecosystem?

thescientist |  Many people with Parkinson’s disease have digestive symptoms like constipation years before they have neurological symptoms, and scientists have found differences in the gut microbiome compositions of patients with Parkinson’s disease and healthy controls. But whether and how gut microbes contribute to the pathology and symptoms of the disease has been an open question.

In a study published today (December 1) in Cell, a team led by Timothy Sampson and Sarkis Mazmanian of Caltech demonstrate that gut microbiota promote neuroinflammation and motor deficits in a mouse model of Parkinson’s disease. The researchers also identify a possible mechanism for the influence of intestinal microbes and on the development of the disease in mice.

“It’s a beautiful study,” Justin Sonnenburg of Stanford University School of Medicine, who did not participate in the work, told The Scientist. “It’s really a first in establishing that gut microbes can not only contribute, but appear to play a causal role in neurodegenerative disease in this mouse model,” he added.

Sampson, Mazmanian, and colleagues used transgenic mice that overexpress human α-synuclein, the protein that forms the insoluble aggregates that are a hallmark of Parkinson’s disease. These mice exhibit deficits in motor function and gut motility.

Transgenic animals raised germ-free or treated with antibiotics performed better at motor tasks and maintained fecal output, as compared to those with typical microbiota, the researchers reported. Mice without intestinal microbes or those receiving antibiotic treatment also developed fewer α-synuclein aggregates in their brains than did their counterparts with intestinal microbes. In other words, in transgenic mice without intestinal bacteria and in those treated with antibiotics, both Parkinson’s-like symptoms and brain pathology decreased.

Saturday, November 26, 2016

You Are What You Eat: Diet-Biota-Epigenetics

sciencenewsline |  You are what you eat, the old saying goes, but why is that so? Researchers have known for some time that diet affects the balance of microbes in our bodies, but how that translates into an effect on the host has not been understood. Now, research in mice is showing that microbes communicate with their hosts by sending out metabolites that act on histones--thus influencing gene transcription not only in the colon but also in tissues in other parts of the body. The findings publish November 23 in Molecular Cell.

"This is the first of what we hope is a long, fruitful set of studies to understand the connection between the microbiome in the gut and its influence on host health," says John Denu, a professor of biomolecular chemistry at the University of Wisconsin, Madison, and one of the study's senior authors. "We wanted to look at whether the gut microbiota affect epigenetic programming in a variety of different tissues in the host." These tissues were in the proximal colon, the liver, and fat tissue.

In the study, the researchers first compared germ-free mice with those that have active gut microbes and discovered that gut microbiota alter the host's epigenome in several tissues. Next, they compared mice that were fed a normal chow diet to mice fed a Western-type diet--one that was low in complex carbohydrates and fiber and high in fat and simple sugars. Consistent with previous studies from other researchers, they found that the gut microbiota of mice fed the normal chow diet differed from those fed the Western-type diet.

"When the host consumes a diet that's rich in complex plant polysaccharides (such as fiber), there's more food available for microbes in the gut, because unlike simple sugars, our human cells cannot use them," explains Federico Rey, an assistant professor of bacteriology at UW-Madison and the study's other senior author.

Why it's Easier to Change a Man's Religion

theatlantic |  In 2009, Danny Cahill won the eighth season of The Biggest Loser, a reality TV show in which contestants compete to lose the most weight. Over the program’s seven months, Cahill’s weight dropped from 430 pounds to just 191. But since then, he has regained 100. The same is true for most of the show’s contestants, several of whom are now heavier than they were before they took part.

Their story is all too common. Even when people successfully manage to lose weight, in the majority of cases, the vanished pounds return within a year—and often with reinforcements. For many people, weight loss isn’t just hard, it’s Sisyphean.

No one really understands the reasons behind this “weight cycling”, this so-called “yo-yo effect”. It seems to happen no matter your starting weight, or how much exercise you do. As my colleague Julie Beck noted earlier this year, the speed at which people lose weight might be important—but even that’s controversial. “There’s a lot of speculation but very little knowledge,” says Eran Elinav from the Weizmann Institute of Science in Israel.

Thursday, November 24, 2016

It is Easier to Change a Man's Religion than to Change his Diet

cnsnews |  Soft drinks were the top commodity bought by food stamp recipients shopping at outlets run by a single U.S. grocery retailer.

That is according to a new study released by the Food and Nutrition Service, the federal agency responsible for running the Supplemental Nutrition Assistance Program (SNAP), commonly known as the food stamp program.

By contrast, milk was the top commodity bought from the same retailer by customers not on food stamps.

In calendar year 2011, according to the study, food stamp recipients spent approximately $357,700,000 buying soft drinks from an enterprise the study reveals only as “a leading U.S. grocery retailer.”

That was more than they spent on any other “food” commodity—including milk ($253,700,000), ground beef ($201,000,000), “bag snacks” ($199,300,000) or “candy-packaged” ($96,200,000), which also ranked among the top purchases.