Research advances from the National Institutes of Health (NIH) Intramural Research Program (IRP) often make headlines. Read the news releases that describe our most recent findings:
Whether you’re shedding pounds with the help of effective new medicines, slimming down after weight loss surgery or cutting calories and adding exercise, there will come a day when the numbers on the scale stop going down, and you hit the dreaded weight loss plateau.
In a recent study, Kevin Hall, a researcher at the National Institutes of Health who specializes in measuring metabolism and weight change, looked at when weight loss typically stops depending on the method people were using todrop pounds. He broke down the plateau into mathematical models using data from high-quality clinical trials of different ways to lose weight to understand why people stop losing when they do. The study published Monday in the journal Obesity.
NIH study shows specific set of immune cells can harm and also help brain after injury
Researchers from the National Institutes of Health have discovered Jekyll and Hyde immune cells in the brain that ultimately help with brain repair but early after injury can lead to fatal swelling, suggesting that timing may be critical when administering treatment. These dual-purpose cells, which are called myelomonocytic cells and which are carried to the brain by the blood, are just one type of brain immune cell that NIH researchers tracked, watching in real-time as the brain repaired itself after injury. The study, published in Nature Neuroscience, was supported by the National Institute of Neurological Disorders and Stroke (NINDS) Intramural Research Program at NIH.
“Fixing the brain after injury is a highly orchestrated, coordinated process, and giving a treatment at the wrong time could end up doing more harm than good,” said Dorian McGavern, Ph.D., NINDS scientist and senior author of the study.
Cerebrovascular injury, or damage to brain blood vessels, can occur following several conditions including traumatic brain injury or stroke. Dr. McGavern, along with Larry Latour, M.D., NINDS scientist, and their colleagues, observed that a subset of stroke patients developed bleeding and swelling in the brain after surgical removal of the blood vessel clot responsible for the stroke. The swelling, also known as edema, results in poor outcomes and can even be fatal as brain structures become compressed and further damaged.
NIH researchers tracked the progression of brain blood vessel repair after injury. At day 1 after injury (left panel), the brain had areas of bleeding and broken vessels. Ten days later (right panel) the vessels were almost completely rebuilt.
Taurine, which helps the body digest fats and oils, could offer treatment benefit
Scientists studying the body’s natural defenses against bacterial infection have identified a nutrient — taurine — that helps the gut recall prior infections and kill invading bacteria, such as Klebsiella pneumoniae (Kpn). The finding, published in the journal Cell by scientists from five institutes of the National Institutes of Health, could aid efforts seeking alternatives to antibiotics.
Scientists know that microbiota — the trillions of beneficial microbes living harmoniously inside our gut — can protect people from bacterial infections, but little is known about how they provide protection. Scientists are studying the microbiota with an eye to finding or enhancing natural treatments to replace antibiotics, which harm microbiota and become less effective as bacteria develop drug resistance.
The scientists observed that microbiota that had experienced prior infection and transferred to germ-free mice helped prevent infection with Kpn. They identified a class of bacteria — Deltaproteobacteria — involved in fighting these infections, and further analysis led them to identify taurine as the trigger for Deltaproteobacteria activity.
Colorized scanning electron micrograph showing carbapenem-resistant Klebsiella pneumoniae interacting with a human neutrophil.
DNA-based “liquid biopsy” could help save lives and reduce health disparities
Researchers have developed a blood test that could make it possible for doctors to detect — then quickly prevent or slow down — acute heart transplant rejection, a potentially deadly condition that occurs in the early months after a patient has received a donor heart. They estimate that the test could eliminate up to 80 percent of invasive heart tissue biopsies currently used to detect rejection.
In studies of a group of nearly 200 heart transplant recipients, the new blood test performed better than tissue biopsies, as it signaled problems even when no outward signs of rejection were evident.
The study was primarily funded by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health. The study’s findings are scheduled to appear January 13 in Circulation, a publication of the American Heart Association.
“There’s an urgent need for an alternative method to monitor patients for acute heart transplant rejection,” said Sean Agbor-Enoh, M.D., Ph.D., study co-author and chief of the NHLBI’s Laboratory of Applied Precision Omics.
Illustration shows DNA fragments (yellow) derived from a transplanted heart alongside the patient’s own DNA (blue). A new blood test measures donor DNA fragments and detects acute heart transplant rejection earlier than current methods. Image credit: Erina He, NIH Medical Arts
Salmonella enterica serovar Typhimurium bacteria (S. Typhimurium) commonly cause human gastroenteritis, inflammation of the lining of the intestines. The bacteria live inside the gut and can infect the epithelial cells that line its surface. Many studies have shown that Salmonella use a “run-and-tumble” method of short swimming periods (runs) punctuated by tumbles when they randomly change direction, but how they move within the gut is not well understood.
National Institutes of Health scientists and their colleagues believe they have identified a S. Typhimurium protein, McpC (Methyl-accepting chemotaxis protein C), that allows the bacteria to swim straight when they are ready to infect cells. This new study, published in Nature Communications, describes S. Typhimurium movement and shows that McpC is required for the bacteria to invade surface epithelial cells in the gut.
The study authors suggest that McpC is a potential target for developing new antibacterial treatments to hinder the ability of S. Typhimurium to infect intestinal epithelial cells and colonize the gut. National Institute of Allergy and Infectious Diseases scientists at Rocky Mountain Laboratories in Hamilton, Montana, led the study. Collaborators included groups from the University of Texas A&M campuses in College Station and Kingsville.
Salmonella bacteria (pink), a common cause of foodborne disease, invade a human epithelial cell (yellow).
Women who use marijuana could have a more difficult time conceiving a child than women who do not use marijuana, suggests a study by researchers at the National Institutes of Health. Marijuana use among the women’s partners — which could have influenced conception rates — was not studied. The researchers were led by Sunni L. Mumford, Ph.D., of the Epidemiology Branch in NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development. The study appears in Human Reproduction.
The women were part of a larger group trying to conceive after one or two prior miscarriages. Women who said they used cannabis products — marijuana or hashish — in the weeks before pregnancy, or who had positive urine tests for cannabis use, were around 40 percent less likely to conceive per monthly cycle than women who did not use cannabis. The authors noted that although the findings suggest cannabis could affect women’s fertility, they should be tempered with caution as the study observed a relatively small number of cannabis users. However, the authors say their results suggest that women trying to conceive should exercise caution with cannabis use until more definitive evidence is available.
The researchers analyzed data from a broader study of more than 1,200 women ages 18 to 40 with one or two pregnancy losses. The women participated in the study for up to six monthly cycles while attempting pregnancy and throughout pregnancy if conception occurred. After enrolling in the study, the women responded to a questionnaire asking if they had used marijuana, pot, or hashish in the past 12 months, with responses ranging from never, rarely, occasionally, sometimes, often, to daily. Each woman also provided urine samples for analysis when they first entered the study and after six months if they did not conceive or at the time of positive pregnancy test if they conceived.
Using a recently developed DNA base-editing technique, researchers correct accelerating aging disorder
Researchers have successfully used a DNA-editing technique to extend the lifespan of mice with the genetic variation associated with progeria, a rare genetic disease that causes extreme premature aging in children and can significantly shorten their life expectancy. The study was published in the journal Nature, and was a collaboration between the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health; Broad Institute of Harvard and MIT, Boston; and the Vanderbilt University Medical Center, Nashville, Tennessee.
DNA is made up of four chemical bases — A, C, G and T. Progeria, which is also known as Hutchinson-Gilford progeria syndrome, is caused by a mutation in the nuclear lamin A (LMNA) gene in which one DNA base C is changed to a T. This change increases the production of the toxic protein progerin, which causes the rapid aging process.
Approximately 1 in 4 million children are diagnosed with progeria within the first two years of birth, and virtually all of these children develop health issues in childhood and adolescence that are normally associated with old age, including cardiovascular disease (heart attacks and strokes), hair loss, skeletal problems, subcutaneous fat loss and hardened skin.
Results from a study of 19 deceased patients suggests brain damage is a byproduct of a patient’s illness
In an in-depth study of how COVID-19 affects a patient’s brain, National Institutes of Health researchers consistently spotted hallmarks of damage caused by thinning and leaky brain blood vessels in tissue samples from patients who died shortly after contracting the disease. In addition, they saw no signs of SARS-CoV-2 in the tissue samples, suggesting the damage was not caused by a direct viral attack on the brain. The results were published as a correspondence in the New England Journal of Medicine.
“We found that the brains of patients who contract infection from SARS-CoV-2 may be susceptible to microvascular blood vessel damage. Our results suggest that this may be caused by the body’s inflammatory response to the virus” said Avindra Nath, M.D., clinical director at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and the senior author of the study. “We hope these results will help doctors understand the full spectrum of problems patients may suffer so that we can come up with better treatments.”
Although COVID-19 is primarily a respiratory disease, patients often experience neurological problems including headaches, delirium, cognitive dysfunction, dizziness, fatigue, and loss of the sense of smell. The disease may also cause patients to suffer strokes and other neuropathologies.
NIH researchers consistently found blood vessel damage in the brains of COVID-19 patients but no signs of SARS-CoV-2 infections. Arrows point to light and dark spots that are indicative of blood vessel damage observed in the study.
Psoriasis, a chronic inflammatory skin disease, has long been known to increase the risk of cardiovascular disease, which includes heart attack and stroke. Now, researchers have identified a key culprit: the presence of metabolic syndrome (MetSyn), a condition that includes obesity, diabetes, high cholesterol, and hypertension, and is highly prevalent among psoriasis patients.
The findings, which could lead to new ways to help prevent cardiovascular disease among people with psoriasis, appear online today in the Journal of the American Association of Dermatology (JAAD). The study was funded by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health.
“Metabolic syndrome, so common among our psoriasis patients, drives up coronary artery disease in this population by increasing the plaque buildup that clogs the heart’s arteries,” said Nehal N. Mehta, M.D., MSCE, preventive cardiologist and head of the NHLBI’s Lab of Inflammation and Cardiometabolic Diseases. “Our study shows that, of the MetSyn components, hypertension and obesity contribute the most to coronary plaque buildup, and hence can be good targets for intervention.”
Preliminary results suggest anti-COVID19 nanobodies may be effective at preventing and diagnosing infections
National Institutes of Health researchers have isolated a set of promising, tiny antibodies, or “nanobodies,” against SARS-CoV-2 that were produced by a llama named Cormac. Preliminary results published in Scientific Reports suggest that at least one of these nanobodies, called NIH-CoVnb-112, could prevent infections and detect virus particles by grabbing hold of SARS-CoV-2 spike proteins. In addition, the nanobody appeared to work equally well in either liquid or aerosol form, suggesting it could remain effective after inhalation. SARS-CoV-2 is the virus that causes COVID-19.
The study was led by a pair of neuroscientists, Thomas J. “T.J.” Esparza, B.S., and David L. Brody, M.D., Ph.D., who work in a brain imaging lab at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS).
“For years TJ and I had been testing out how to use nanobodies to improve brain imaging. When the pandemic broke, we thought this was a once in a lifetime, all-hands-on-deck situation and joined the fight,” said Dr. Brody, who is also a professor at Uniformed Services University for the Health Sciences and the senior author of the study. “We hope that these anti-COVID-19 nanobodies may be highly effective and versatile in combating the coronavirus pandemic.”
Scientists isolated nanobodies against COVID-19 from a llama named Cormac. Image credit: Triple J Farms, Bellingham, Washington
Reston ebolavirus (RESTV) should be considered a livestock pathogen with potential to affect other mammals, including people, according to National Institutes of Health scientists. The caution comes from a study published in Proceedings of the National Academy of Sciences in which the scientists found that experimental piglets infected with RESTV developed severe respiratory disease and shed the virus from the upper respiratory tract. RESTV can infect humans but is not known to cause disease. Now the scientists express concern that pigs could serve as an “interim or amplifying host for ebolaviruses.”
“The emergence of RESTV in pigs is a wake-up call as transmission into humans through direct contact with pigs or the food chain is a possibility,” they state in their study report. Scientists from NIH’s National Institute of Allergy and Infectious Diseases (NIAID) conducted the work at Rocky Mountain Laboratories in Hamilton, Montana.
Scientists first identified RESTV in 1989 in research monkeys shipped from the Philippines to Reston, Virginia. The virus also gained attention in 2008 when an outbreak swept through pigs in the Philippines. That outbreak led to the first association of pig-to-human RESTV transmission, prompting the World Health Organization to issue a global alert in February 2009. RESTV sequences also have been identified in pigs in China, and the scientists suggest officials monitor pigs for disease throughout the Philippines and Southeast Asia.
This colorized transmission electron micrograph shows a slice of Reston virus particles (blue) in the lung of an infected pig.
