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:
BETHESDA, Md. (AP) — Sam Srisatta, a 20-year-old Florida college student, spent a month living inside a government hospital here last fall, playing video games and allowing scientists to document every morsel of food that went into his mouth.
From big bowls of salad to platters of meatballs and spaghetti sauce, Srisatta noshed his way through a nutrition study aimed at understanding the health effects of ultraprocessed foods, the controversial fare that now accounts for more than 70% of the U.S. food supply. He allowed The Associated Press to tag along for a day.
“Today my lunch was chicken nuggets, some chips, some ketchup,” said Srisatta, one of three dozen participants paid $5,000 each to devote 28 days of their lives to science. “It was pretty fulfilling.”
Examining exactly what made those nuggets so satisfying is the goal of the widely anticipated research led by National Institutes of Health nutrition researcher Kevin Hall.
“What we hope to do is figure out what those mechanisms are so that we can better understand that process,” Hall said.
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.
Researchers at the National Eye Institute (NEI) report that a brain region in the superior temporal sulcus (fSTS) is crucial for processing and making decisions about visual information. The findings, which could provide clues to treating visual conditions from stroke, appear today in the journal Neuron. NEI is part of the National Institutes of Health.
“The human visual system recognizes, prioritizes, and categorizes visual objects and events to provide actionable information,” said Richard Krauzlis, Ph.D., chief of the NEI Section on Eye Movements and Selective Attention and senior author of the study. “We were surprised to learn that the fSTS is a crucial link in this story-building process, passing information from an evolutionarily ancient region in the midbrain to highly specialized regions of the visual cortex.”
While aspects of visual processing begin in the eye, crucial steps in visual attention start in the superior colliculus, a part of the midbrain that handles a variety of sensory input. Previous work in Krauzlis’ lab showed that neuronal activity in the superior colliculus is necessary for the brain to notice an event in the visual field and decide that it is significant.
Previously unknown genetic connection could be a target for gene therapy
A study led by researchers at the National Institutes of Health has made a surprising connection between frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), two disorders of the nervous system, and the genetic mutation normally understood to cause Huntington’s disease.
Several neurological disorders have been linked to “repeat expansions,” a type of mutation that results in abnormal repetition of certain DNA building blocks. For example, Huntington’s disease occurs when a sequence of three DNA building blocks that make up the gene for a protein called huntingtin repeats many more times than normal. These repeats can be used to predict whether someone will develop the illness and even when their symptoms are likely to appear, because the more repeats in the gene, the earlier the onset of disease.
“It has been recognized for some time that repeat expansion mutations can give rise to neurological disorders,” said Sonja Scholz, M.D., Ph.D., investigator, NINDS Intramural Research Program. “But screening for these mutations throughout the entire genome has traditionally been cost-prohibitive and technically challenging.”
