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.
Compound targets essential viral enzyme and prevents replication in cells
The experimental drug TEMPOL may be a promising oral antiviral treatment for COVID-19, suggests a study of cell cultures by researchers at the National Institutes of Health. TEMPOL can limit SARS-CoV-2 infection by impairing the activity of a viral enzyme called RNA replicase. The work was led by researchers at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The study appears in Science.
“We urgently need additional effective, accessible treatments for COVID-19,” said Diana W. Bianchi, M.D., NICHD Director. “An oral drug that prevents SARS-CoV-2 from replicating would be an important tool for reducing the severity of the disease.”
The study team was led by Tracey A. Rouault, M.D., head of the NICHD Section on Human Iron Metabolism. It discovered TEMPOL’s effectiveness by evaluating a more basic question on how the virus uses its RNA replicase, an enzyme that allows SARS-CoV-2 to replicate its genome and make copies of itself once inside a cell.
The small spherical structures in the center of the image are SARS-CoV-2 virus particles. The string-like protrusions extending from the cells are cell projections or pseudopodium.
A healthy diet around the time of conception through the second trimester may reduce the risk of several common pregnancy complications, suggests a study by researchers at the National Institutes of Health. Expectant women in the study who scored high on any of three measures of healthy eating had lower risks for gestational diabetes, pregnancy-related blood pressure disorders and preterm birth. The study was conducted by Cuilin Zhang, M.D., Ph.D., and colleagues at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). It appears in the American Journal of Clinical Nutrition.
The researchers analyzed dietary data collected multiple times during pregnancy from the NICHD Fetal Growth Study. Nearly 1,900 women responded to questionnaires on their diets at eight to 13 weeks of pregnancy and were asked to estimate what they ate in the previous three months. At 16 to 22 weeks and 24 to 29 weeks, the women identified what they ate in the previous 24 hours. Their responses were scored according to three measures of healthy eating: the Alternate Healthy Eating Index (AHEI), Alternate Mediterranean Diet (AMED), and Dietary Approaches to Stop Hypertension (DASH) diet. All three measures emphasize consumption of fruits, vegetables, whole grain, nuts and legumes while limiting red and processed meat.
Overall, the researchers found that following any of the diets around the time of conception through the second trimester was associated with a lower risk of gestational diabetes, hypertension, preeclampsia and preterm delivery. For example, women with a high AHEI score at 16 to 22 weeks had a 32% lower risk for gestational diabetes than women with a low AHEI score. Women with a high DASH score at eight to 12 weeks and 16 to 22 weeks had a 19% lower risk for pregnancy-related high blood pressure disorders. A high AMED score at 24 to 29 weeks or a high DASH score at 24 to 29 weeks was associated with a 50% lower risk for preterm birth.
NIH- and USU-led study links ALS to a fat manufacturing gene and maps out a genetic therapy
In a study of 11 medical-mystery patients, an international team of researchers led by scientists at the National Institutes of Health and the Uniformed Services University (USU) discovered a new and unique form of amyotrophic lateral sclerosis (ALS). Unlike most cases of ALS, the disease began attacking these patients during childhood, worsened more slowly than usual, and was linked to a gene, called SPTLC1, that is part of the body’s fat production system. Preliminary results suggested that genetically silencing SPTLC1 activity would be an effective strategy for combating this type of ALS.
“ALS is a paralyzing and often fatal disease that usually affects middle-aged people. We found that a genetic form of the disease can also threaten children. Our results show for the first time that ALS can be caused by changes in the way the body metabolizes lipids,” said Carsten Bönnemann, M.D., senior investigator at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and a senior author of the study published in Nature Medicine. “We hope these results will help doctors recognize this new form of ALS and lead to the development of treatments that will improve the lives of these children and young adults. We also hope that our results may provide new clues to understanding and treating other forms of the disease.”
Dr. Bönnemann leads a team of researchers that uses advanced genetic techniques to solve some of the most mysterious childhood neurological disorders around the world. In this study, the team discovered that 11 of these cases had ALS that was linked to variations in the DNA sequence of SPLTC1, a gene responsible for manufacturing a diverse class of fats called sphingolipids.
A new study by researchers at the National Institutes of Health and their colleagues has found that SARS-CoV-2, the virus that causes COVID-19, does not appear to pose a threat to the safety of the nation’s blood supply. The analysis, published in Transfusion, supports current donor screening guidelines, including those used by the U.S. Food and Drug Administration, that do not require testing blood samples for the SARS-CoV-2 virus but do require that donors be screened for physical symptoms of COVID-19 and for infections that occurred within 14 days of the blood donation. The blood of donors with recent COVID-19 infections, or who develop infections after recent donations, cannot be used.
After reviewing test results for the presence of SARS-CoV-2 in thousands of blood donations across the country, researchers found no reason to alter the current blood donor screening practices that are in place because of the COVID-19 pandemic.
“This finding is good news for thousands of patients who may need a blood transfusion because of surgery or a disease that causes anemia, such as a rare blood-related condition or leukemia,” said Simone Glynn, M.D., M.P.H., chief of the Blood Epidemiology and Clinical Therapeutics Branch at the National Heart, Lung, and Blood Institute (NHLBI), which conducted the study along with National Institute of Allergy and Infectious Diseases (NIAID).
An environment in which family members support one another and express their feelings can reduce the effects of social deprivation on cognitive ability and development among adopted children, suggests a small study by researchers at the National Institutes of Health. In contrast, rule-driven households where family members are in conflict may increase an adopted child’s chances for cognitive, behavioral and emotional difficulties.
Researchers enrolled children who had spent at least eight months in Eastern European orphanages before their adoption by American families. The children ranged from 14 to 40 months of age and were evaluated with physical, psychological and developmental tests twice during the following two years. Families also responded to questionnaires on the children’s development and on various aspects of their home lives. The study included 10 adopted children and 19 similar children born to American families.
The immune system’s attempt to eliminate Salmonella bacteria from the gastrointestinal (GI) tract instead facilitates colonization of the intestinal tract and fecal shedding, according to National Institutes of Health scientists. The study, published in Cell Host & Microbe, was conducted by National Institute of Allergy and Infectious Diseases (NIAID) scientists at Rocky Mountain Laboratories in Hamilton, Montana.
Salmonella Typhimurium bacteria (hereafter Salmonella) live in the gut and often cause gastroenteritis in people. The Centers for Disease Control and Prevention estimates Salmonella bacteria cause about 1.35 million infections, 26,500 hospitalizations and 420 deaths in the United States every year. Contaminated food is the source for most of these illnesses. Most people who get ill from Salmonella have diarrhea, fever and stomach cramps but recover without specific treatment. Antibiotics typically are used only to treat people who have severe illness or who are at risk for it.
Salmonella bacteria also can infect a wide variety of animals, including cattle, pigs and chickens. Although clinical disease usually resolves within a few days, the bacteria can persist in the GI tract for much longer. Fecal shedding of the bacteria facilitates transmission to new hosts, especially by so-called “super shedders” that release high numbers of bacteria in their feces.
Two clusters of brain cells compete to promote either the persistence or disappearance of traumatic memories, according to a new study conducted in mice. The findings could provide important insights into human conditions such as post-traumatic stress disorder (PTSD), anxiety disorders, and associated problems such as alcohol use disorder (AUD) that can arise from the persistence of traumatic memories. The new research, led by scientists at the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health, and their colleagues in Switzerland, is reported in the journal Nature.
“Over time, the distress of having experienced trauma will subside for some people, as memories of the trauma cease to provoke a fearful response,” says NIAAA Director Dr. George F. Koob. “For other people who have experienced trauma, however, the fearful memories persist, and can adversely affect their ability to engage in everyday activities. These fearful memories can continue even though a person may repeatedly encounter cues associated with a traumatic experience without a harm. The current study sheds light on the specific neural circuits that may underlie the persistence and the extinction of fearful memories associated with trauma.”
Scientists led by Andrew Holmes, Ph.D., chief of NIAAA’s Laboratory of Behavioral and Genomic Neuroscience, examined clusters of neurons, known as intercalated cells or ITCs, that are packed tightly around the mouse amygdala. Found deep within the temporal lobes of mammals’ brains, the amygdala is well-known as a hub for processing emotions. It is therefore a likely actor in the brain systems that underlie the formation of fearful memories associated with certain environmental cues and the successful extinction of those memories when the same cues later predict no harm.
Pregnant women made only modest dietary changes after being diagnosed with gestational diabetes, according to a study by researchers at the National Institutes of Health. Women with gestational diabetes are generally advised to reduce their carbohydrate intake, and the women in the study did cut their daily intake of juice and added sugars. They also increased their intake of cheese and artificially sweetened beverages. However, certain groups of women did not reduce their carbohydrate intake, including women with obesity, had more than one child, were Hispanic, had a high school degree or less, or were between the ages of 35-41 years.
Patients with gestational (or pregnancy-related) diabetes have a higher risk of maternal high blood pressure, larger babies, cesarean delivery, low blood sugar in newborns, and development of chronic diabetes later in life.
“The improvements in diet that we observed were not equitable across all groups of women,” said Dr. Hinkle. “This research highlights the importance of creating individualized programs to ensure that all women with gestational diabetes are successful at modifying their diet and optimizing their health.”
Scientists at the National Institutes of Health determined that stomach inflammation is regulated differently in male and female mice after finding that androgens, or male sex hormones, play a critical role in preventing inflammation in the stomach. The finding suggests that physicians could consider treating male patients with stomach inflammation differently than female patients with the same condition. The study was published in Gastroenterology.
Researchers at NIH’s National Institute of Environmental Health Sciences (NIEHS) made the discovery after removing adrenal glands from mice of both sexes. Adrenal glands produce glucocorticoids, hormones that have several functions, one of them being suppressing inflammation. With no glucocorticoids, the female mice soon developed stomach inflammation. The males did not. However, after removing androgens from the males, they exhibited the same stomach inflammation seen in the females.
"The fact that androgens are regulating inflammation is a novel idea," said co-corresponding author John Cidlowski, Ph.D., deputy chief of the NIEHS Laboratory of Signal Transduction and head of the Molecular Endocrinology Group. "Along with glucocorticoids, androgens offer a new way to control immune function in humans."
Glucocorticoids and androgens promote a healthy stomach pit by inhibiting inflammation, left, while their absence promotes inflammation and SPEM seen in a diseased pit, right. SPEM glands are also much larger than healthy stomach glands.
Researchers at the National Institutes of Health have devised a four-part small-molecule cocktail that can protect stem cells called induced pluripotent stem cells (iPSCs) from stress and maintain normal stem cell structure and function. The researchers suggest that the cocktail could enhance the potential therapeutic uses of stem cells, ranging from treating diseases and conditions — such as diabetes, Parkinson’s disease and spinal cord injury — to genome editing.
Human pluripotent stem cells are cells that, in theory, can grow forever and serve as an inexhaustible source for specialized cells, such as brain, kidney and heart cells. But stem cells are sensitive, and their potential uses in medicine are hampered by the stress of growing in a cell culture dish, which can damage their DNA and lead to cell death.
In a series of experiments, scientists led by Ilyas Singeç, M.D., Ph.D., director of the Stem Cell Translation Laboratory at NIH’s National Center for Advancing Translational Sciences (NCATS), used high-throughput screening to systematically test thousands of compounds and drugs to identify a unique combination that greatly improved stem cell survival and reduced cell culture stress. Singeç and his co-investigators described how they developed the cocktail, called CEPT, and its potential applications May 3 in Nature Methods.
“The small-molecule cocktail is safeguarding cells and making stem cell use more predictable and efficient. In preventing cellular stress and DNA damage that typically occur, we’re avoiding cell death and improving the quality of surviving cells,” said Singeç. “The cocktail will become a broadly used staple of the stem cell field and boost stem cell applications in both research and the clinic.”
