September 7 Research Roundup: Antibiotics, Human Genes, ALS, Sherpas and More
There are plenty of great scientific research stories out this week. Here’s a look at just a few of them.
Potentially 8,000 New Antibiotic Combinations
Researchers at the University of California, Los Angeles (UCLA) identified thousands of combinations of four and five antibiotics that appear to be more effective than previously thought. They published their research in the journal npj Systems Biology and Applications.
“There is a tradition of using just one drug, maybe two,” stated Pamela Yeh, one of the study’s senior authors and an assistant professor of ecology and evolutionary biology at UCLA. “We’re offering an alternative that looks very promising. We shouldn’t limit ourselves to just single drugs or two-drug combinations in our medical toolbox. We expect several of these combinations, or more, will work much better than existing antibiotics.”
The team worked with eight antibiotics, analyzing every possible four- and five-drug combination, including varying dosages, for a total of 18,278 combinations, against E. coli. They first predicted how effective they thought each combination would be. Of the four-drug combinations, 1,676 combos performed better than expected, and in the five-drug combos, 6,443 performed better.
“I was blown away by how many effective combinations there are as we increased the number of drugs,” said Van Savage, the study’s other co-author and professor of ecology and evolutionary biology, and of biomathematics at UCLA, in a statement. “People may think they know how drug combinations will interact, but they really don’t.”
Cue the New Fad Diet: The 10-Hour Window Diet
Scientists at the Salk Institute, working on mice without the biological clocks needed for a healthy metabolism, found that by restricting the mice’s eating to a 10-hour window, they were protected against obesity and metabolic diseases. The research was published in the journal Cell Metabolism.
“For many of us, the day begins with a cup of coffee first thing in the morning and ends with a bedtime snack 14 or 15 hours later,” stated Satchidananda Panda, professor in Salk’s Regulatory Biology Laboratory and the senior author of the research. “But restricting food intake to 10 hours a day, and fasting the rest, can lead to better health, regardless of our biological clock.”
Mammalian cells operate on a 24-hour cycle dubbed the circadian rhythm. These cycles influence gene activity. In humans, for instance, genes for digestion are more active earlier in the day and genes for cellular repair are more active at night. In Panda’s lab, earlier research found that mice given 24-hour access to a high-fat diet became obese and developed metabolic diseases like high cholesterol, fatty liver and diabetes. But when the mice were restricted to an 8- to 10-hour eating window, became “lean, fit and healthy.” The lab postulates that this is because it kept the mice in better sync with their cellular clocks.
Even Fewer Human Genes than Thought
Prior to the completion of the Human Genome Project, the primary thinking was that each protein was coded for by a single gene. As a result of that thinking, it was believed that the human genome contained well over 100,000 genes. But when the Human Genome Project was completed, only around 20,000 genes were observed, but numerous alternative ways of transcribing the genome were discovered, explaining how this was accomplished. A new study led by the Spanish National Cancer Research Center (CNIO) now found that up to 20 percent of the genes classified as coding may not actually be coding. They have characteristics usually observed in non-coding or pseudogenes, which are obsolete coding genes. Their research was published in the journal Nucleic Acids Research.
Federico Abascal, first author of the research, of the Wellcome Trust Sanger Institute in the UK, stated, “Our evidence suggests that humans may only have 19,000 coding genes, but we still do not know which 19,000 genes they are.”
David Juan, of the Pompeu Fabra University and a participant in the study, stated, “Surprisingly, some of these unusual genes have been well studied and have more than 100 scientific publications based on the assumption that the gene produces a protein.”
The research was funded by the U.S. National Institutes of Health (NIH). The study suggests that the final number of coding genes could be anywhere from 2,000 more or 2,000 fewer than it is now.
Mothers with Gestational Diabetes More Likely to Have Postpartum Depression
Researchers with the University of Eastern Finland published research in the Journal of Affective Disorders linking gestational diabetes mellitus (GDM) with having an elevated risk of developing symptoms of postpartum depression. About 10 to 15 percent of women experience symptoms of postpartum depression after childbirth. The research utilized the Edinburgh Postnatal Depression Scale to evaluate depression symptoms during the third trimester of pregnancy and eight weeks after delivery. Symptoms were observed in 16 percent of mothers after childbirth who had been diagnosed with GDM, and in about 9 percent of mothers without GDM.
The research was conducted by the University of Eastern Finland, Kuopio University Hospital, and the Finnish National Institute for Health and Welfare using pooled data from Kuopio Birth Cohort, an ongoing follow-up of women from the beginning of their pregnancy. In total, 1,066 mothers with no previous mental health issues were chosen for the study.
“Psychological mechanisms may partially explain the observed association between GDM and postpartum depression symptoms,” stated Aleksi Ruohamaki, the first author of the study and a doctoral student at the university. “Being diagnosed during pregnancy with a disease that might harm the fetus can be a stressful experience, which may predispose to depression symptoms.”
Soili Lehto, Group Leader of Kuopio Birth Cohort’s mental well-being section, stated, “Furthermore, physiological mechanisms may also contribute to this association. Impaired glucose metabolism may increase cytokine-mediated low-grade inflammation, which has also been associated with depression. Previous studies have also shown that type 2 diabetes predisposes to depression, and depression to type 2 diabetes.”
Mechanism Behind Amyotrophic Lateral Sclerosis Identified
Researchers at Umea University in Sweden identified a mechanism for how amyotrophic lateral sclerosis (ALS) evolves. “We’ve been able to identify two different types of protein aggregates with different structures and propagation abilities,” said Johan Bergh, a doctoral student at the Department of Medical Biosciences at Umea University, in a statement. “One type gave rise to a more aggressive disease progression, which shows that these aggregates are the driving force in the development of ALS.”
Bergh and the ALS group at the university invented a method of analyzing protein aggregates formed in ALS. The protein targeted is superoxide dismutase-1 (SOD1), which has long been linked to mutations in the protein that can cause ALS. The researchers were attempting to determine how the protein contributes to ALS. In various CNS diseases, like Alzheimer’s and Parkinson’s disease, some proteins misfold, causing them to clump, which then stimulates other proteins to take on the same shape, which spreads throughout the nervous system. The work is the center of Bergh’s doctoral dissertation research.
Why Nepalese Sherpas Can Handle the Thin Air on Mount Everest
Physiologically, populations of people who live at high altitudes, such as Andeans and Ethiopians, deal with reduced oxygen levels at high altitude by developing higher hemoglobin levels. However, studies of the Sherpas that help mountain climbers take on Mount Everest, don’t. University College London’s Centre for Altitude, Space, and Extreme Environmental Medicine conducted research that compared the Sherpas and an altitude naïve population of Lowlanders to determine the physiological differences. The results were published in the journal Experimental Physiology.
The researcher found that as the environmental oxygen levels drop, Sherpas can maintain a greater degree of blood flow and oxygen delivery to the working tissues. High hemoglobin levels make blood thick and viscous, which decreases blood flow through the body and increases the risks of a blood clot in the lungs. So the researchers believe it might be possible that the Sherpas’ physiological strategy provides adequate oxygen to tissues while minimizing the risk of fatal side effects.
“The mechanisms identified in this study, such as increased blood flow and oxygen delivery to working tissue, feasibly describe an alternative means to aid oxygen delivery in critically ill patients,” stated Edward Gilbert-Kawai, co-author of the research. “Future research should establish the underlying cellular mechanisms behind this response. Identifying such differences and mimicking those in humans most highly adapted to reduced environmental oxygen may thus reveal novel target pathways that are amenable to drug treatment in the critically ill, and could provide new directions in critical care medicine.”