December 14 Research Roundup: Lonesome George’s Genome, Alzheimer’s and Prostate Cancer Tests and More
There are plenty of great scientific research stories out this week. Here’s a look at just a few of them.
Lonesome George, the Giant Tortoise, Provides Insight into Longevity
A few years ago, in 2012, Lonesome George, the last of the Pinta Island tortoises of the Galapagos, died. The last of his kind, George was more than one hundred years old. Researchers published an article in the journal Nature Ecology & Evolution that described preliminary findings of gene variants in George associated with a strong immune system, efficient DNA repair and cancer resistance.
Adalgisa “Gisella” Caccone, a researcher at Yale University, who had been working for years on the tortoises, teamed up with Carlos Lopez-Otin, a professor at the University of Oviedo in Spain whose research focused on cancer and aging in humans. Together, with a larger team, they sequenced Lonesome George’s entire genome, as well as that of an Aldabra giant tortoise from the Seychelles, who are rumored to live up to 250 years (well, at least one did).
They then compared the tortoise genomes to other mammals, fish, birds and reptiles. They found a mutation in a gene called IGF1R, which has been linked in humans and mice to longevity. They also found that George and other tortoises had more copies of a gene associated with energy regulation, DNA repair, tumor suppression and immune defense. For example, most mammals only have a single copy of PRF1, a gene linked to immune response, but the tortoises had 12 copies.
Researchers ID Brain Genes in Primates that Differentiates Them (Us) from Other Mammals
Scientists from the University of Otago in New Zealand and the Max Planck Institute of Psychiatry in Germany identified the PLEKHG6 gene, which appears to drive specific aspects of brain development in primates compared to other mammals. They published their work in the journal Cell Reports.
“Broadly speaking, this gene can be thought of as one of the genetic factors that make us human in a neurological sense,” stated Adam O’Neill, a PhD student formerly at the University of Otago, now at Ludwig Maximilian Universität in Munich.
The researchers were looking for genes that differentiated humans from other primates, and other animals. The idea was there must have been genes that made humans have bigger brains and better functioning, even at the risk of causing other neurological or psychiatric conditions.
O’Neill stated, “Such genes have been hard to find, but using an approach where we studied children with a certain brain malformation called periventricular nodular heterotopia, we found a ‘damaged’ genomic element in a child that had the attributes of such a primate specific genetic factor.”
An error in the PLEKHG6 gene altered the ability of the gene to support the growth and proliferation of specialized stem cells that were involved in brain development.
Possible Diagnostic Tool for Alzheimer’s
Researchers at Johns Hopkins Medicine have identified radioactive “tracer” molecules in live human brains that bind to and illuminate tau tangles, one of the proteins linked to Alzheimer’s disease and other neurodegenerative diseases and dementias. They published their research in the Journal of Nuclear Medicine.
As part of a long-term project funded by F. Hoffmann-La Roche, the researchers tested a library of about 550 potential tracer molecules and found six promising tracers. They then winnowed them down to three to be tested as possible Tau PET radiopharmaceuticals. They had been tested in nonhuman primates and seemed promising for people.
They then recruited 12 Alzheimer’s patients and seven younger health controls and five older healthy controls for brain-only PET scans. Another six older healthy patients were recruited for full-body scans. Healthy brains held little to no tracer, while those with Alzheimer’s displayed tau in regions of the brain consistent with previous postmortem data on tau tangles.
Sprayable Gel Might Fend Off Cancer Recurrence
A group of researchers with the University of California, Los Angeles (UCLA) have developed a spray gel that contains immune-stimulating drugs. In a study published in the journal Nature Nanotechnology, the gel was effective about 50 percent of the time in stimulating laboratory animals’ immune systems to stop cancer from recurring and inhibiting its metastases.
“This sprayable gel shows promise against one of the greatest obstacles in curing cancer,” stated lead researcher Zhen Gu, professor of bioengineering at the UCLA Samueli School of Engineering and member of the Jonsson Comprehensive Cancer Center. “One of the trademarks of cancer is that it spreads. In fact, around 90 percent of people with cancerous tumors end up dying because of tumor recurrence or metastasis. Being able to develop something that helps lower this risk for this to occur and has low toxicity is especially gratifying.”
Zhen Gu tested the gel in mice that had advanced melanoma tumors surgically removed. The gel cut the growth of the tumors that remained post-surgery, which led to lower recurrences. After treatment, 50 percent of the mice survived for at least 60 days without tumor regrowth. The spray gel inhibited recurrence in the area of the body where the tumor was removed, but also in other parts of the body.
Why Red Meat is Linked to Heart Disease
Risks of heart disease (and cancer) have been associated with consumption of red meat, although much of it has been connected to the levels of fat in red meat. Now, researchers with the National Institutes of Health (NIH)’s National Heart, Lung, and Blood Institute have identified a gut-generated chemical called trimethylamine N-oxide (TMAO) that is associated with red meat consumption. The research was published in the European Heart Journal.
“These findings reinforce current dietary recommendations that encourage all ages to follow a heart-healthy eating plan that limits red meat,” stated Charlotte Pratt, the NHLBI project officer for the study. “This means eating a variety of foods, including more vegetables, fruits, whole grains, low-fat dairy foods, and plant-based protein sources such as beans and peas.”
TMAO is a dietary byproduct formed by gut bacteria during digestion. It is formed in part from the nutrients found in red meat. The research suggests that measuring TMAO levels, which can be done with a blood test, might be promising for individualizing diets and helping to prevent heart disease.
New Test for Prostate Cancer Metastases
In prostate cancer, about 16 percent result in metastases, and account for about eight percent of all male cancer deaths. Researchers with Albert Einstein College of Medicine in Bronx, New York, published research in The Journal of Molecular Diagnostics that described a new diagnostic test that can analyze copy number alterations (CNAs), a key biomarker of metastases, more quickly and cheaply than other available assays.
“We have demonstrated that CNAs can be detected rapidly and accurately with the new Next-Generation Copy Number Alteration (NG-CAN) assay,” stated Harry Ostrer, lead investigator. “The impact of this information is two-fold: to assure aggressive therapy at the time of diagnosis for men with metastasis-prone disease and provide a rationale for active surveillance (and not overtreatment) for men with indolent disease.”
The NG-CAN assay is able to analyze 902 genomic sites related to 194 genomic regions. Ostrer notes that the cost of DNA extraction, library prep and sequencing reagents is around $20 to $40 per sample, compared to about $1,000 for whole genome sequencing. It also can be performed on small samples.