November 2 Research Roundup: Skinny Mice, Why Weed Affects Women Differently Than Men, and How a Virus Kills Cancer Cells
There are plenty of great scientific research stories out this week. Here’s a look at just a few of them.
Protein Found that Reduces Fat in Mice by 33%
Researchers at Georgetown University, led by Anton Wellstein, professor of oncology and pharmacology at Georgetown Lombardi Comprehensive Cancer Center, were working on obese mice, forcing expression of the protein FGFBP3 (BP3 for short). The results were unexpected. The research was published in Scientific Reports.
“We found that eight BP3 treatments over 18 days was enough to reduce the fat in obese mice by over a third,” Wellstein said in a statement. “We found that BP3 exerts a striking contribution to metabolic control. When you have more BP3 chaperone available, FGF19 and FGF21 effect is increased through the increase of their signaling. That makes BP3 a strong driver of carbohydrate and lipid metabolism. It’s like having a lot more taxis available in New York City to pick up all the people who need a ride.”
The protein also cut several obesity-related disorders in the mice, including hyperglycemia (high blood sugar) and decreased the fat in their once fatty livers. And microscopic and clinical examinations didn’t turn up any side effects.
BP3 is part of a family of fibroblast growth factor (FGF) binding proteins (BP). FGFs are observed in a broad variety of living organisms, including worms and humans. They are key to numerous biological processes, including cell growth regulation, wound healing, and injury response. Some FGFs behave like hormones.
PB3 is a natural protein. That means that clinical trials of recombinant human BP3 could start after a round of preclinical studies.
Cannabis Affects Women and Men Differently
It was believed that the differences between how men and women respond to cannabis were cultural, but a review of animal studies suggest it’s biological. Researchers at the National Research Counsil of Italy published their review in Frontiers in Behavioral Neuroscience, which examined the influence of sex hormones like testosterone, estrogen and progesterone on the endocannabinoid system.
Men, for example, are up to four times more likely to try cannabis than women and use higher doses more frequently. “Male sex steroids increase risk-taking behavior and suppress the brain’s reward system, which could explain why males are more likely to try drugs, including cannabis,” stated Liana Fattore, Senior Researcher at the National Research Council of Italy and president of the Mediterranean Society of Neuroscience, the study’s co-author. “This is true for both natural male sex steroids like testosterone and synthetic steroids like nandrolone.”
On the other hand, women seem to find cannabis more addictive. It appears that sex hormones and their effects on the endocannabinoid system are the reason. “Gender-tailored detoxification treatments and relapse prevention strategies for patients with cannabis addiction are increasingly requested,” Fattore stated. “Optimizing personalized evidence-based prevention and treatment protocols demands further research on the source of sex disparities in cannabis response.”
Metformin May Protect Against Age-Related Macular Degeneration
Researchers from Taiwan presented research at the 122nd Annual Meeting of the American Academy of Ophthalmology showing that the common diabetes drug, metformin, has anti-inflammatory and anti-oxidative effects that can protect against age-related macular degeneration (AMD).
“Our study is the first to reveal the protective effect of metformin on the development of AMD,” stated lead investigator, Yu-Yen Chen. “While more study is required to determine just how metformin protects against the development of AMD, this is an exciting development for patients at risk.”
The research used data from the Taiwan National Health Insurance Research Database on patients recently diagnosed with type 2 diabetes from January 2001 to December 2013. They divided them into two groups, 45,524 that took metformin and 22,681 who did not. They followed the groups for 13 years and found that the metformin group had a significantly lower risk of developing AMD.
How a Virus Kills Cancer Cells
Using high-resolution electron microscopy, researchers at New Zealand’s University of Otago demonstrated how the Seneca Valley Virus (SVV) infects cancer cells, but not normal, healthy tissue. The research was published in the Proceedings of the National Academy of Sciences.
SVV was recently discovered. It selectively targets a cancer cell receptor found on more than 60 percent of human cancers. Mihnea Bostina from Otago and researchers at Japan’s Okinawa Institute of Science and Technology used cryo-electron microscopy to take thousands of images of the virus attached to its receptor, then reconstructed a high-resolution structure of the complex. “We can see exactly how the virus breaks into the cancer cells, while leaving other cells untouched,” Bostina stated. “This structure teaches us which part of the virus is essential for binding to the receptor and which is not. If we want to make the virus more efficient at invading cancer cells, we can leave intact the part that interacts with the cancer cells and modify the rest so the virus can escape the attack of the immune system.”
Building Synthetic Ancient Microorganisms
Classify this as “cool, but what could possibly go wrong?” Researchers at The Scripps Research Institute have created synthetic microorganisms of organisms that no longer exist today, but were alive billions of years ago. They published their work in two papers, one in the Proceedings of the National Academy of Sciences (PNAS) and another earlier this year in the Journal of the American Chemical Society (JACS).
“These engineered organisms will allow us to probe two key theories about major milestones in the evolution of living organisms—the transition from the RNA world to the DNA world and the transition from prokaryotes to eukaryotes with mitochondria,” stated Peter Schultz, senior author of both papers and president of Scripps Research. “Access to readily manipulated laboratory models enables us to seek answer to questions about early evolution that were previously intractable.”
The researchers first modified E. coli so it didn’t have the gene encoding thiamin, which makes it dependent on yeast cells for the essential vitamin. They then added a gene for ADP/ATP translocase, a transporter protein, so that ATP manufactured inside the cells would be supplied to their yeast-cell hosts. That mimics the central activity of mitochondria. They also modified the yeast so the yeast mitochondria were deficient at supplying ATP, making them dependent on the bacteria. They then will attempt to evolve the E. coli to become mitochondria-like organelles.
More Evidence CRISPR Causes Immune Reactions
Although CRISPR is revolutionizing bioscience research and potentially medicine, the more we learn, the more obstacles there seems to be that need to be overcome. A new study was published suggesting that CRISPR/Cas9 causes an immune reaction that prevents treatments from working. This new article was published in the journal Nature Medicine. The study stated, “Preexisting immunity against therapeutic gene vectors or their cargo can decrease the efficacy of a potentially curative treatment and may pose significant safety issues.”
It’s not the first time the problem has been raised. An article on bioRxiv in January advanced the topic as well. It stated, “This data demonstrates that there are pre-existing humoral and cell-mediated adaptive immune responses to Cas9 in humans, a factor which must be taken into account as the CRISPR-Cas9 system moves forward into clinical trials.”
In the new study, researchers observed that 96 percent of patients in the study had T-cell based immunity against Cas9, with 85 percent of the patients having antibodies against it. The earlier study indicated that 65 percent had antibodies against Cas9, but didn’t detect T-cell activity against it.
Michael Schmueck-Henneresse of Charite University Medicine Berlin, who led the most recent study, told Xconomy, “But it made sense because the Streptococcus pyogenes bacterium is one of the most common causes for bacterial infections in humans and we have all been through multiple infections and potentially even been colonized by it.”
CRISPR allows researchers to quickly and precisely identify gene sequences that they can then cut out and replace. But it’s not without its problems and concerns. There have been worries that the technique causes off-target cuts that could cause cancer and other disorders, and the possibility that the body’s DNA repair mechanisms kick in and reverse the changes. The new studies suggest that, because the enzymes used to cut the DNA come from common bacteria, humans have immunity against them.