There are plenty of great scientific research stories out this week. Here’s a look at just a few of them.
Why Losing Weight Can Halt Type 2 Diabetes
Clinical trial results published in the journal Cell Metabolism have identified why losing weight can fend off type 2 diabetes. It’s generally well-known that losing weight—if overweight—can help prevent the onset of type 2 diabetes and in some cases reverse it, but why this is the case hasn’t been completely understood. A recent clinical trial observed that about half of the people with type 2 diabetes in the study achieved remission to a non-diabetic state after losing weight within six years of diagnosis. And they found that the link is an early and sustained improvement in how pancreatic beta cells function.
“This observation carries potentially important implications for the initial clinical approach to management,” said Roy Taylor of Newcastle University, senior author of the study, in a statement. “At present, the early management of type 2 diabetes tends to involve a period of adjusting to the diagnosis plus pharmacotherapy with lifestyle changes, which in practice are modest. Our data suggest that substantial weight loss at the time of diagnosis is appropriate to rescue the beta cells.”
Taylor was overseeing the UK-based Diabetes Remission Clinical Trial (DiRECT). In the study, participants who were diagnosed with type 2 diabetes within six years of the beginning of the study were randomly assigned to best-practice care or an innovative primary-care-led weight-management program. A year later, 46 percent in the intervention group successfully lost weight and maintained blood sugar concentration control.
Mayo Researchers ID Genes Linked to Triple-Negative Breast Cancer
Researchers at the Mayo Clinic led by geneticist Fergus Couch identified specific genes associated with triple-negative breast cancer. Triple-negative breast cancer is generally difficult to treat and has a lower five-year survival rate than other types of breast cancer.
Triple-negative breast cancer is called that not because it’s three times as bad—although it is a very aggressive form of cancer. It is called triple-negative because the breast cancer cells test negative for estrogen receptors (ER-), progesterone receptors (PR-) and HER2 (HER2-). The results of being negative for all three means that the cancer growth is not supported by the hormones estrogen and progesterone or by the presence of too many HER2 receptors. As a result, the cancer doesn’t respond to hormonal therapy like tamoxifen or aromatase inhibitors or medications that target HER2 receptors, like Herceptin (trastuzumab).
Couch and his team conducted genetic tests on 10,901 patients with triple-negative breast cancer from two studies. They looked for 21 cancer predisposition genes in 8,753 patients and 17 genes in the remaining 2,148 patients. They discovered mutations in BARD1, BRCA1, BRCA2, PALB2 and RAD51D genes. These are associated with a high risk for triple-negative breast cancer and a higher than 20 percent lifetime overall risk of breast cancer in Caucasians. The trend was similar in African-Americans. The team also found that mutations in the BRIP1 and RAD51C genes were associated with a more moderate risk of triple-negative breast cancer.
The discovery has the potential to lead to better and broader screening and the possibility of more accurate treatment selection.
Could Stem Cells Cure Spinal Injuries?
Researchers at the University of California, San Diego School of Medicine used human pluripotent stem cells (hPSCs) to create spinal cord neural stem cells (NSCs) that can differentiate into numerous different cells that can be spread throughout the spinal cord. They also appear to stay there for sustained periods of time. The work was published in Nature Methods. It has the potential to treat spinal cord injuries and disorders.
“We established a scalable source of human spinal cord NSCs that includes all spinal cord neuronal progenitor cell types,” said Hiromi Kumamaru, first author and postdoctoral scholar at the UC San Diego Translational Neuroscience Institute, in a statement. “In grafts, these cells could be found throughout the spinal cord, dorsal to ventral. They promoted regeneration after spinal cord injury in adult rats, including corticospinal axons, which are extremely important in human voluntary motor function. In rats, they supported functional recovery.”
Identifying Ways to Improve CRISPR Gene Editing
CRISPR is the stunning new technology that allows researchers to isolate specific sections of the genome and quickly and easily snip it out and replace it. The technique uses the enzyme Cas9. However, there are other potential enzymes, and researchers are identifying some that appear to be more precise than Cas9, which sometimes edits the wrong part of the genome. Researchers at the University of Texas at Austin found evidence that Cas9 is less effective and precise than Cas12a. They published their work in the journal Molecular Cell.
Ilya Finkelstein, assistant professor of molecular biosciences and co-author of the study, stated, “The overall goal is to find the best enzyme that nature gave us and then make it better still, rather than taking the first one that was discovered through historical accident.”
Anecdotally, many thought Cas12a was a better choice, but this is the first study that documents that Cas12a is less error-prone than Cas9.
Koala Research Helps Explain Endogenous Retroviruses in the Human Genome
There are little pieces of degraded retrovirus found in the human genome, typically dubbed “junk DNA” that has no apparent effect. They have been in the human DNA for millions of years, but researchers can’t say exactly how these bits of DNA went from virulent, disease-causing forms to their inactive forms today. Researchers from the University of Illinois College of Agricultural, Consumer and Environmental Sciences and Leibniz Institute for Zoo and Wildlife Research published research in the Proceedings of the National Academy of Sciences that might have an answer—and it’s based on koala genomes.
Koalas, unlike humans, have an ongoing invasion of the germline by a retrovirus that began more recently, although “recent” is a relative term. Retroviruses act like other viruses, attacking from the outside. They are fused into cells where they release their contents and insert pieces of their DNA into the host cells’ genetic machinery, making it manufacture copies of itself. If they make their way into sperm and egg cells, retroviral genes can be passed to the host’s offspring, becoming part of their germline. Koala retroviruses found in their genomes are relatively young, less than 50,000 years old, which allows researchers to work with them more easily. Specificaly, it’s called the koala retrovirus (KoRV).
And one thing the researchers have found is that the koala genome appears to be fighting back. Ulrike Lober, researcher at the Leibniz Institute and the study’s first author, stated, “We might have found evidence for a molecular defense mechanism of hosts against new retroviral attacks, mediated by more ancient retroviral elements.”
Alex Greenwood, who led the study, also of the Leibniz Institute, stated, “The study emphasizes how little we know about the diversity and reservoirs of retroviruses among wildlife. The koala, a species not usually associated with biomedical breakthroughs, is providing key insights into a process that has shaped 8 percent of the human genome, and likely shows us what happened millions of years ago when retroviruses invaded the human germline.”
How the Ebola Virus Enters Cells
Researchers at Texas Biomedical Research Institute published research in a supplement to The Journal of Infectious Diseases that identified how the Ebola virus enters the human cell. It looks at a cellular pathway called autophagy, which is a mechanism cells use to destroy invading foreign material or to recycle its own organelles and protein complexes. This process typically takes place inside the cell. The researchers, led by Oleena Shtanko in Tex Biomed’s Biosafety Level 4 laboratory on live Ebola viruses, found that this mechanism, autophagy, was active near the surface of the cell and was essential in the uptake of the viruses.
Ebola viruses enter cells through micropinocytosis, a process where the cell surface remodels to form membrane extensions around virus particles, which eventually close, sucking the virus into the inside of the cell. “We were stunned to find that Ebola virus is using autophagy regulators right at the surface of the cell,” Shtanko said in a statement. “Knowing that these mechanisms work together, we can start finding ways to regulate them.”
It is the interplay between micropinocytosis and autophagy that is unexpected, and may have implications for the treatment of other diseases caused by viruses. Shtanko says there’s a possibility that regulating autophagy proteins with drugs might help fight complex diseases where micropinocytosis is dysregulated, for example, in diseases like cancer and some neurodegenerative disorders like Alzheimer’s.
Researchers May Have ID’ed Solution to Treat Drug-Resistant Infections
Los Angeles-based LA BioMed published a study showing they may have found a potential vaccine for drug-resistant bacterial infections, the so-called “superbugs.” They isolated a protein found in common fungal infections which can kill the antibiotic-resistant bacteria found in hospital-acquired infections. “A scarcity of deadly bacteria-fighting therapies and the emergence of new drug-resistant bacteria increasingly threaten global and personal health,” said LA BioMed researcher Ashraf Ibrahim, in a statement, “The potential for a vaccine for drug-resistant bacteria can save lives of patients and millions of dollars in health care costs.”
The researchers conducted a study in mid using the Hry1 protein, which directed antibodies to target the bacteria.