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:
The act of cooking offers the chance to unwind and create something special, whether you’re planning to feed a crowd or just yourself. And while you may have noticed feeling good after whipping up that perfect pie or braise, there’s actually a lot of scientific data to suggest that cooking can have a positive impact on mental health.
One meta-analysis (a report of pre-existing research) from the National Institutes of Health looked at 11 studies and found that “cooking interventions” — encouraging people to follow certain recipes or giving people cooking classes — can improve a person’s mental well-being. It specifically found that people who participated in cooking interventions reported having better self-esteem and quality of life, as well as a more positive emotional state after the fact. Another study even discovered that baking can help raise a person’s confidence level.
A team of researchers from the National Library of Medicine (NLM), part of the National Institutes of Health, and collaborating academic research institutions developed a method to measure a type of gene mutation involved in the evolution of cancer. This type of mutation, called “repeat instability,” may be useful in early cancer diagnosis. Findings were published this week in the Proceedings of the National Academy of Sciences.
Cancer is primarily caused by mutations in certain genes. The most thoroughly studied cancer-associated mutations involve the substitution of one nucleotide of DNA for another in genes known as oncogenes and tumor suppressors.
In this study, the researchers identified a different type of mutation active in cancer, one that increases and/or decreases repetitive segments of DNA and protein sequences in various genes. These changes are collectively named “repeat instability.”
IRP researchers create mouse colony to address shortcomings of laboratory mice
Researchers at the National Institutes of Health developed a new mouse model that could improve the translation of research in mice into advances in human health. The mouse model, which the scientists called “wildling,” acquired the microbes and pathogens of wild mice, while maintaining the laboratory mice’s genetics that make them more useful for research. In two preclinical studies, wildlings mirrored human immune responses, where lab mice failed to do so. Led by scientists at the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the study published online in Science.
“We wanted to create a mouse model that better resembles a mouse you’d find in the wild,” said Barbara Rehermann, M.D., chief of the Immunology Section in NIDDK’s Liver Diseases Branch and senior author on the study. “Our rationale was that the immune responses and microbiota of wild mice and humans are likely shaped in a similar way — through contact with diverse microbes out in the real world.”
Microbiota refers to the trillions of tiny microbes, such as bacteria, fungi, and viruses, that live in and on the bodies of people and animals and play a critical role in keeping immune systems healthy. Unlike squeaky clean lab mice raised in artificial settings, wild mice have developed symbiotic relationships with microbes they have encountered in the outside world — just as people have done.
Structure-based candidate designed by IRP scientists
A novel experimental vaccine against respiratory syncytial virus (RSV), a leading cause of severe respiratory illness in the very young and the old, has shown early promise in a Phase 1 clinical trial. The candidate, DS-Cav1, was engineered and developed by researchers at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, who were guided by their atomic-level understanding of the shape of an RSV protein. An interim analysis of study data showed that one dose of the investigational vaccine prompted large increases in RSV-neutralizing antibodies that were sustained for several months. The findings are reported in Science.
First described in 1956 as a cause of infant pneumonia, the health burden of RSV has long been underappreciated. In fact, the virus is an important contributor to serious illness worldwide and causes as many as 118,000 deaths annually among young children. In the United States each year, RSV infections account for approximately 57,000 hospitalizations and 2 million outpatient clinic visits among children younger than 5-years-old, according to the Centers for Disease Control and Prevention. Among people older than 65, RSV is estimated to cause 14,000 annual deaths in the United States. Globally, a recent large study led by the International Vaccine Access Center found that the virus was responsible for 31% of all cases of severe pneumonia requiring hospitalization in young children in seven low- and middle-income countries.
“A vaccine to prevent RSV is a long-sought goal that has eluded us for decades,” said NIAID Director Anthony S. Fauci, M.D. “The early results of this trial suggest that this structure-based strategy for developing an RSV vaccine may bring that goal within reach.”
Scanning electron micrograph of human respiratory syncytial virus (RSV) virions (colorized blue) and labeled with anti-RSV F protein/gold antibodies (colorized yellow) shedding from the surface of human lung epithelial A549 cells.
Scientists using an experimental treatment have slowed the progression of scrapie, a degenerative central nervous disease caused by prions, in laboratory mice and greatly extended the rodents’ lives, according to a new report in JCI Insight. The scientists used antisense oligonucleotides (ASOs), synthetic compounds that inhibit the formation of specific proteins.
Prion diseases occur when normally harmless prion protein molecules become abnormal and gather in clusters and filaments in the body, including the brain. The diseases are thought to be always fatal. Scrapie, which affects sheep and goats and can be adapted to rodents, is closely related to human prion diseases such as Creutzfeldt-Jakob disease, which is currently untreatable. Thus, scrapie is a valuable experimental model for the development of human prion disease therapies.
In the studies, National Institutes of Health scientists and their colleagues injected ASOs into the spinal fluid of mice already infected with scrapie or that were challenged with scrapie proteins within weeks of the injection. Ionis Pharmaceuticals specifically designed ASO1 and ASO2 to reduce the rodents’ supply of normal prion protein. Rodent studies using different dosages of ASO1 and ASO2 were conducted at Rocky Mountain Laboratories (RML) in Hamilton, Montana, (part of the NIH’s National Institute of Allergy and Infectious Diseases) and at the Broad Institute of Cambridge, Massachusetts.
Prion protein, shown in red, can become infectious and cause neurodegenerative disease. Here four nerve cells in a mouse illustrate how infectious prion protein moves within cells along neurites — wire-like connections the nerve cells use for communicating with adjacent cells.
Novel imaging biomarker could track interventions on coronary artery disease
Researchers have found that anti-inflammatory biologic therapies used to treat moderate to severe psoriasis can significantly reduce coronary inflammation in patients with the chronic skin condition. Scientists said the findings are particularly notable because of the use of a novel imaging biomarker, the perivascular fat attenuation index (FAI), that was able to measure the effect of the therapy in reducing the inflammation.
The study published online in JAMA Cardiology, has implications not just for people with psoriasis, but for those with other chronic inflammatory diseases, such as lupus and rheumatoid arthritis. These conditions are known to increase the risk for heart attacks and strokes. The study was funded by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health,
“Coronary inflammation offers important clues about the risk of developing heart artery disease,” said study’s senior author Nehal N. Mehta, M.D., a cardiologist and head of the Lab of Inflammation and Cardiometabolic Diseases at NHLBI. “Our findings add to the growing body of research that shows treating underlying inflammatory conditions may reduce the risk of cardiovascular diseases."
Coronary CT angiography image of the coronary arteries depicting the perivascular fat attenuation index before and after biologic therapy at one-year follow-up for patients with excellent response to biologic therapy.
Researchers show critical association between diabetes and previously unlinked ZRANB3 gene
National Institute of Health researchers have reported the largest genomic study of type 2 diabetes (T2D) in sub-Saharan Africans, with data from more than 5,000 individuals from Nigeria, Ghana and Kenya. Researchers confirmed known genomic variants and identified a novel gene ZRANB3, which may influence susceptibility to the disease in sub-Saharan African populations. The gene could also influence the development of T2D in other populations and inform further research.
In a study published in the journal Nature Communications, researchers analyzed genomic data available on participants through the Africa America Diabetes Mellitus study, the single largest diabetes genomic association study conducted on the continent. Using the information available from 5,231 people, they found many genomic variants to be significantly associated with T2D.
“Africa is the original cradle of all humanity, to which all humans can trace their genetic origin,” said Francis S. Collins, M.D., Ph.D., co-author of the paper and senior investigator with the NHGRI Medical Genomics and Metabolic Genetics Branch. “Thus, studying the genomes of Africans offers important opportunities to understand genetic variation across all human populations.”
Infants born to women exposed to high levels of air pollution in the week before delivery are more likely to be admitted to a newborn intensive care unit (NICU), suggests an analysis by researchers at the National Institutes of Health. Depending on the type of pollution, chances for NICU admission increased from about 4% to as much as 147%, compared to infants whose mothers did not encounter high levels of air pollution during the week before delivery. The study was led by Pauline Mendola, Ph.D., of the Epidemiology Branch at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development. It appears in Annals of Epidemiology.
“Short-term exposure to most types of air pollutants may increase the risk for NICU admission,” Dr. Mendola said. “If our findings are confirmed, they suggest that pregnant women may want to consider limiting their time outdoors when air quality advisories indicate unhealthy conditions.”
Previous studies have linked elevated levels of certain kinds of air pollutants to higher risks for gestational diabetes and preeclampsia, a blood pressure disorder of pregnancy. Earlier research also has shown that infants born to women exposed to high levels of air pollutants are at risk for preterm birth, of being small for their gestational age at birth and of growing more slowly than normal in the uterus. Given these associations, the study authors sought to determine whether prenatal exposure to air pollution might increase the chance for NICU admission.
Small study suggests botulinum toxin may be potential treatment
Pelvic pain associated with endometriosis often becomes chronic and can persist (or recur) following surgical and hormonal interventions. According to results published in Regional Anesthesia & Pain Medicine, treating pelvic floor muscle spasm with botulinum toxin may relieve pain and improve quality of life. The study was conducted by scientists at the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.
“The botulinum toxin injections were incredibly effective in decreasing pain levels, as well as patients’ use of pain medications, including opioids,” said Pamela Stratton, M.D., a gynecologist and scientist at NINDS, who co-led the study with Barbara Karp, M.D., a neurologist and program director at NINDS. “Many of the women in our study reported that the pain had a profound effect on their quality of life, and this treatment may be able to help them get their lives back.”
Endometriosis occurs when the uterine tissue lining grows outside of the uterus and is estimated to affect up to 176 million women worldwide. It is an inflammatory condition that can lead to infertility and cause chronic pain. The usual gynecologic treatments include hormonal therapy and surgery to remove the growths. However, in many cases, pain returns after the interventions.
IRP study research uncovers specialized networks in the brain for processing face color
Anyone who has ever sensed that a person is sick simply by looking at their face has experienced the wealth of information conveyed by face color. A new study by the National Eye Institute (NEI), part of the National Institutes of Health, provides evidence that the human brain’s visual system is especially sensitive to the color of faces compared to the colors of other objects or things. Study results were published today in Nature Communications.
“The findings underscore the complexity of color perception. Far from operating as a reflex, color perception involves a set of sophisticated brain operations that ultimately assign value and meaning to what we see,” said the study’s lead investigator, Bevil Conway, Ph.D., head of the NEI Unit on Sensation, Cognition, and Action.
The findings also suggest that social communication cues from faces factored into evolutionary selective pressures that gave rise to trichromatic color vision in our ancestors 23 million years ago.
These face images illustrate how color plays a key role in how faces are read. Both images are manipulated away from normal, by about the same units in color (green in one direction, red in the other). Both color directions may be deemed meaningful in terms of indicating blushing or sickness.
Variants in the gene ARMC5 may be associated with high blood pressure among blacks, according to a National Institutes of Health study led by researchers at the Eunice Kennedy ShriverNational Institute of Child Health and Human Development (NICHD). The study team identified 17 variants in the ARMC5 gene that were associated with high blood pressure by analyzing genetic research databases that include those of African descent. The study is published in the July 3, 2019, issue of the Journal of the American Heart Association.
“High blood pressure increases a person’s risk for heart disease and stroke,” said Constantine A. Stratakis, M.D., D. Sc., NICHD Scientific Director and the study’s senior author. “The condition is more common among blacks, who also tend to get it at a younger age than whites do, and we are studying the underlying causes of this health disparity.”
Earlier work by the NICHD group linked some variants of ARMC5 to primary aldosteronism, a hormonal disorder that causes high blood pressure, among black patients. In the current study, the researchers analyzed datasets containing genetic information from large numbers of people, including NIH’s Minority Health Genomics and Translational Research Bio-Repository Database and the Genomics, Environmental Factors and Social Determinants of Cardiovascular Disease in African-Americans Study, which are based in the United States, as well as the UK Biobank.
