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.
NIH-funded study offers new path to modeling eye disease, advancing therapies
Researchers have discovered a technique for directly reprogramming skin cells into light-sensing rod photoreceptors used for vision. The lab-made rods enabled blind mice to detect light after the cells were transplanted into the animals’ eyes. The work, funded by the National Eye Institute (NEI), published April 15 in Nature. The NEI is part of the National Institutes of Health.
Up until now, researchers have replaced dying photoreceptors in animal models by creating stem cells from skin or blood cells, programming those stem cells to become photoreceptors, which are then transplanted into the back of the eye. In the new study, scientists show that it is possible to skip the stem-cell intermediary step and directly reprogram skins cells into photoreceptors for transplantation into the retina.
“This is the first study to show that direct, chemical reprogramming can produce retinal-like cells, which gives us a new and faster strategy for developing therapies for age-related macular degeneration and other retinal disorders caused by the loss of photoreceptors,” said Anand Swaroop, Ph.D., senior investigator in the NEI Neurobiology, Neurodegeneration, and Repair Laboratory, which characterized the reprogrammed rod photoreceptor cells by gene expression analysis.
Three months after transplantation, immunofluorescence studies confirmed the survival of the chemically induced photoreceptor-like cells (green). They also show integration of the cells into the layers of the mouse retina.
According to a recent analysis of data from two major eye disease studies, adherence to the Mediterranean diet — high in vegetables, whole grains, fish, and olive oil — correlates with higher cognitive function. Dietary factors also seem to play a role in slowing cognitive decline. Researchers at the National Eye Institute (NEI), part of the National Institutes of Health, led the analysis of data from the Age-Related Eye Disease Study (AREDS) and AREDS2. They published their results today in the journal Alzheimer’s and Dementia.
“We do not always pay attention to our diets. We need to explore how nutrition affects the brain and the eye,” said Emily Chew, M.D., director of the NEI Division of Epidemiology and Clinical Applications and lead author of the studies.
The researchers examined the effects of nine components of the Mediterranean diet on cognition. The diet emphasizes consumption of whole fruits, vegetables, whole grains, nuts, legumes, fish, and olive oil, as well as reduced consumption of red meat and alcohol.
A new study has begun recruiting at the National Institutes of Health in Bethesda, Maryland, to determine how many adults in the United States without a confirmed history of infection with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), have antibodies to the virus. The presence of antibodies in the blood indicates a prior infection. In this “serosurvey,” researchers will collect and analyze blood samples from as many as 10,000 volunteers to provide critical data for epidemiological models. The results will help illuminate the extent to which the novel coronavirus has spread undetected in the United States and provide insights into which communities and populations are most affected.
“This study will give us a clearer picture of the true magnitude of the COVID-19 pandemic in the United States by telling us how many people in different communities have been infected without knowing it, because they had a very mild, undocumented illness or did not access testing while they were sick,” said Anthony S. Fauci, M.D., NIAID director. “These crucial data will help us measure the impact of our public health efforts now and guide our COVID-19 response moving forward.”
Colorized scanning electron micrograph of an apoptotic cell (blue) infected with SARS-COV-2 virus particles (yellow), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland.
Autoimmunity, a condition in which the body’s immune system reacts with components of its own cells, appears to be increasing in the United States, according to scientists at the National Institutes of Health and their collaborators.
In a study published April 8 in Arthritis and Rheumatology, the researchers found that the prevalence of antinuclear antibodies (ANA), the most common biomarker of autoimmunity, was significantly increasing in the United States overall and particularly in certain groups. These groups include males, non-Hispanic whites, adults 50 years and older, and adolescents. The study is the first to evaluate ANA changes over time in a representative sampling of the U.S. population.
"The reasons for the increases in ANA are not clear, but they are concerning and may suggest a possible increase in future autoimmune disease," said corresponding and senior author Frederick Miller, M.D., Ph.D., deputy chief of the Clinical Research Branch at the National Institute of Environmental Health Sciences (NIEHS), part of NIH. "These findings could help us understand more about the causes of these immune abnormalities and possibly learn what drives development of autoimmune diseases and how to prevent them."
Immunofluorescent staining of human cells shows ANA as bright dots. Image courtesy of Edward Chan, Ph.D., University of Florida
NIH mouse study reveals key details about visual processing
Researchers at the National Eye Institute (NEI) have defined a crucial window of time that mice need to key in on visual events. As the brain processes visual information, an evolutionarily conserved region known as the superior colliculus notifies other regions of the brain that an event has occurred. Inhibiting this brain region during a specific 100-millisecond window inhibited event perception in mice. Understanding these early visual processing steps could have implications for conditions that affect perception and visual attention, like schizophrenia and attention deficit hyperactivity disorder (ADHD). The study was published online in the Journal of Neuroscience. NEI is part of the National Institutes of Health.
“One of the most important aspects of vision is fast detection of important events, like detecting threats or the opportunity for a reward. Our result shows this depends on visual processing in the midbrain, not only the visual cortex”, said Richard Krauzlis, Ph.D., chief of the Section on Eye Movements and Visual Selection at NEI and senior author of the study.
Visual perception — one’s ability to know that one has seen something — depends on the eye and the brain working together. Signals generated in the retina travel via retinal ganglion cell nerve fibers to the brain. In mice, 85% of retinal ganglion cells connect to the superior colliculus. The superior colliculus provides the majority of early visual processing in these animals. In primates, a highly complex visual cortex takes over more of this visual processing load, but 10% of retinal ganglion cells still connect to the superior colliculus, which manages basic but necessary perceptual tasks.
Slice of mouse brain showing neurons of the superior colliculus highlighted on one side.
NIH study provides insight into one mechanism underlying the higher prevalence of males in some cases of autism
A new study in Neuron offers clues to why autism spectrum disorder (ASD) is more common in boys than in girls. National Institutes of Health scientists found that a single amino acid change in the NLGN4 gene, which has been linked to autism symptoms, may drive this difference in some cases. The study was conducted at NIH’s National Institute of Neurological Disorders and Stroke (NINDS).
Researchers led by Katherine Roche, Ph.D., a neuroscientist at NINDS, compared two NLGN4 genes, (one on the X chromosome and one on the Y chromosome), which are important for establishing and maintaining synapses, the communication points between neurons.
Every cell in our body contains two sex chromosomes. Females have two X chromosomes; males have one X and one Y chromosome. Until now, it was assumed that the NLGN4X and NLGN4Y genes, which encode proteins that are 97% identical, functioned equally well in neurons.
New findings suggest that a single mutation may contribute to increased prevalence of autism in boys than in girls.
Findings provide insight that may inform search for treatments
Researchers at the National Institutes of Health have discovered a second gene that causes melorheostosis, a rare group of conditions involving an often painful and disfiguring overgrowth of bone tissue. The gene, SMAD3, is part of a pathway that regulates cell development and growth. The researchers are now working to develop an animal model with a mutant version of SMAD3 to test potential treatments for the condition. The study appears in the Journal of Experimental Medicine.
Melorheostosis affects about 1 in 1 million people. Its causes have long been unknown. DNA tests of blood and skin could not identify a mutation. The key to finding the gene was to biopsy the affected bone directly and compare it to unaffected bone. Earlier, the researchers used this method to discover the gene for “dripping candle wax bone disease,” a form of melorheostosis in which excess bone growth appears to drip from the bone surface like hot wax. In that study, mutations in the gene MAP2K1 accounted for eight cases of the disease among 15 patients.
In the current study, researchers scanned the exome — the part of the genome that codes for proteins — and found mutations in the affected bone. These mutations occurred during the patient’s lifetime rather than being inherited from parents and are not present in all the cells of the body.
The researchers found SMAD3 mutations in four of the patients who did not have mutations in MAP2K1. SMAD3 is involved in a pathway crucial for skeletal development both before and after birth. The SMAD3 mutations increase the maturation of bone-forming cells and are involved in a cellular pathway distinct from the MAPK2K1 pathway.
Findings may have implications for understanding epilepsy, autism spectrum disorders
Researchers at the National Institutes of Health have discovered in mice what they believe is the first known genetic mutation to improve cognitive flexibility — the ability to adapt to changing situations. The gene, KCND2, codes for a protein that regulates potassium channels, which control electrical signals that travel along neurons. The electrical signals stimulate chemical messengers that jump from neuron to neuron. The researchers were led by Dax Hoffman, Ph.D., chief of the Section on Neurophysiology at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). It appears in Nature Communications.
The KCND2 protein, when modified by an enzyme, slows the generation of electrical impulses in neurons. The researchers found that altering a single base pair in the KCND2 gene enhanced the ability of the protein to dampen nerve impulses. Mice with this mutation performed better than mice without the mutation in a cognitive task. The task involved finding and swimming to a slightly submerged platform that had been moved to a new location. Mice with the mutation found the relocated platform much faster than their counterparts without the mutation.
The researchers plan to investigate whether the mutation will affect neural networks in the animals’ brains. They added that studying the gene and its protein may ultimately lead to insights on the nature of cognitive flexibility in people. It also may help improve understanding of epilepsy, schizophrenia, Fragile X syndrome, and autism spectrum disorder, which all have been associated with other mutations in KCND2.
In a new study, higher daily step counts were associated with lower mortality risk from all causes. The research team, which included investigators from the National Cancer Institute (NCI) and the National Institute on Aging (NIA), both parts of the National Institutes of Health, as well as from the Centers for Disease Control and Prevention, also found that the number of steps a person takes each day, but not the intensity of stepping, had a strong association with mortality.
The findings were published March 24, 2020, in the Journal of the American Medical Association.
“While we knew physical activity is good for you, we didn’t know how many steps per day you need to take to lower your mortality risk or whether stepping at a higher intensity makes a difference,” said Pedro Saint-Maurice, Ph.D., of NCI’s Division of Cancer Epidemiology and Genetics, first author of the study. “We wanted to investigate this question to provide new insights that could help people better understand the health implications of the step counts they get from fitness trackers and phone apps.”
A study by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, offers new insight into genetic alterations associated with osteosarcoma, the most common cancerous bone tumor of children and adolescents. The researchers found that more people with osteosarcoma carry harmful, or likely harmful, variants in known cancer-susceptibility genes than people without osteosarcoma. This finding has implications for genetic testing of children with osteosarcoma, as well as their families.
The study was published March 19, 2020, in JAMA Oncology.
“With this study, we wanted to find out how many people with osteosarcoma may have been at high risk for it because of their genetics,” said Lisa Mirabello, Ph.D., of NCI’s Division of Cancer Epidemiology and Genetics (DCEG), who led the research. “We not only learned that at least a quarter of the people in the study with osteosarcoma had a variant in a gene known to predispose someone to cancer, we also uncovered variants that had never before been associated with this cancer.”
In the study, the researchers looked for harmful (or likely harmful) variants in 238 known cancer-susceptibility genes in DNA samples from 1,244 people with osteosarcoma and compared the frequency of such variants with that in people in a cancer-free control group. They identified a harmful or likely harmful variant in a known cancer-susceptibility gene in 28% of the people with osteosarcoma. By contrast, only 12% of people in the cancer-free control group had such a variant.
An x-ray of a femur (thigh bone) from a patient with osteosarcoma.
