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.
NIH scientists discover macromolecular complexes that could enable medication development
Scientists at the National Institute on Drug Abuse (NIDA) Intramural Research Program (IRP) have uncovered evidence that shows a more complex and elaborate role for the body’s hard-working G protein-coupled receptors (GPCRs) than previously thought, suggesting a conceptual advance in the fields of biochemistry and pharmacology. With more than 800 members in the human genome, GPCRs are the largest family of proteins involved in decoding signals as they come into the cell and then adapt the cell’s function in response. NIDA is part of the National Institutes of Health.
Manipulating how cells respond to signals is key to developing new medications. Although pharmacologists have studied GPCRs for many years, there is still a debate on how they operate — are they isolated units that randomly collide with each other or are they deliberately coupled together to receive signals? The NIDA scientists conclude that GPCRs form part of very elaborate pre-coupled macromolecular complexes. Simply put, they act as little computing devices that optimally gather and process information coming into the cell, allowing the cells to adapt and change their function.
“These findings represent many years of complex and highly nuanced science, following the trail as chemical signals travel through the body at the cellular level,” said NIDA Director Nora D. Volkow, M.D. “This remarkable discovery will open new avenues for medication development for addiction, pain and other conditions, offering more precise targets with fewer side effects.”
“The specific macromolecular complex investigated in this study has therapeutic implications not only for addiction, but also for Parkinson’s disease and schizophrenia,” said Dr. Sergi Ferré, who led the team of scientists. “Discovering that these protein interact with other signals in preformed complexes gives us more precise targets for medication development.”
Diuretic therapy — commonly given to extremely preterm infants to help them overcome respiratory problems — appears to offer no benefit for this purpose, according to an analysis by researchers at the National Institutes of Health. Surprisingly, infants in the study who received diuretic therapy were more likely to require respiratory support, compared to extremely preterm infants with similar respiratory problems who did not receive the therapy. The study is published in The Journal of Pediatrics.
Diuretic medicines prompt the kidneys to make more urine. The therapy is commonly given to preterm infants to help drain fluid from the lungs, but there is little research evidence to support the practice.
Researchers at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and National Heart, Lung, and Blood Institute (NHLBI) analyzed data collected as part of the Prematurity and Respiratory Outcomes Program study, an effort to understand respiratory difficulties in extremely premature infants during the first year of life. The study included 835 infants born between 23 and 28 weeks at 13 U.S. neonatal intensive care units. An infant is considered full term at 39 weeks.
NIH discovery in mice could lead to therapies to reduce vision loss from diseases of the retina
Immune cells called microglia can completely repopulate themselves in the retina after being nearly eliminated, according to a new study in mice from scientists at the National Eye Institute (NEI). The cells also re-establish their normal organization and function. The findings point to potential therapies for controlling inflammation and slowing progression of rare retinal diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD), the most common cause of blindness among Americans 50 and older. A report on the study was published online today in Science Advances. The NEI is part of the National Institutes of Health.
“Neuroinflammation is an important driver of the death of neurons in retinal diseases,” said Wai T. Wong, M.D., Ph.D., chief of the NEI Section on Neuron-Glia Interactions in Retinal Disease, and the study’s lead investigator. “Our study is foundational for understanding ways to control the immune system in the retina.” Control of the immune system is important for developing new treatments for a variety of eye conditions, including AMD, RP, or for certain types of retinal injury.
Kinesin family member 5A (KIF5A), a gene previously linked to two rare neurodegenerative disorders, has been definitively connected to amyotrophic lateral sclerosis (ALS) by an international team from several of the world’s top ALS research labs. The findings identify how mutations in KIF5A disrupt transport of key proteins up and down long, threadlike axons that connect nerve cells between the brain and the spine, eventually leading to the neuromuscular symptoms of ALS.
The discovery, published in the March 21, 2018, issue of Neuron, was led by Bryan Traynor, M.D., Ph.D., of the Intramural Research Program of the National Institute on Aging (NIA) at the National Institutes of Health and John Landers, Ph.D., of the University of Massachusetts Medical School, Worcester, with key funding support from the NIA, the National Institute of Neurological Disorders and Stroke (NINDS) at NIH, and several public and private sector organizations. Genetic data collected by teams of scientists worldwide contributed to the project.
It took a comprehensive, collaborative effort to analyze a massive amount of genetic data to pin down KIF5A as a suspect for ALS, also known as Lou Gehrig’s disease. To zero in on KIF5A, the NIH team performed a large-scale genome-wide association study, while the University of Massachusetts team concentrated on analyzing rare variants in next generation sequence data. Over 125,000 samples were used in this study, making it by far the largest such study of ALS performed to date.
An international team of ALS researchers has proven that mutations in the neuronal transport gene KIF5A are associated with ALS.
Marijuana impairment cited most in study of recent high school graduates
Roughly a third of recent high school graduates have ridden in a motor vehicle with a substance-impaired driver, according to a study by researchers at the National Institutes of Health and other institutions. The study found that during the first two years after high school graduation, 23 percent of young adults had ridden with a marijuana-impaired driver at least once, while 20 percent had ridden with an alcohol-impaired driver, and 6 percent had ridden with a driver impaired by glue or solvents or harder, illicit drugs, such as amphetamines, opioids, cocaine.
The analysis was conducted by researchers at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Colorado State University, Fort Collins; the Colorado School of Public Health, Denver; and Yale University, New Haven, Connecticut. Their results appear in the Journal of Studies on Alcohol and Drugs.
The authors analyzed data from NICHD’s NEXT Generation Health Study, a seven-year study of more than 2,700 U.S. adolescents starting at grade 10. Its goal is to identify the social, behavioral and genetic factors linked to health and healthy behaviors. Along with NICHD, funding for the NEXT Generation Health Study was provided by NIH’s National Heart, Lung, and Blood Institute and the Maternal and Child Health Bureau of the Health Resources and Services Administration.
Scientists have discovered a human antibody that protected mice from infection with the deadliest malaria parasite, Plasmodium falciparum. The research findings provide the basis for future testing in humans to determine if the antibody can provide short-term protection against malaria, and also may aid in vaccine design. Investigators at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, led the research with colleagues at the Fred Hutchinson Cancer Research Center in Seattle. Currently, there is no highly effective, long-lasting vaccine to prevent malaria, a mosquito-spread disease that causes some 430,000 deaths each year, primarily among young children in sub-Saharan Africa.
The research team isolated the antibody, called CIS43, from the blood of a volunteer who had received an experimental vaccine made from whole, weakened malaria parasites (PfSPZ Vaccine-Sanaria). The volunteer was later exposed to infectious malaria-carrying mosquitoes under carefully controlled conditions and did not become infected. In two different models of malaria infection in mice, CIS43 was highly effective at preventing malaria infection. If confirmed through additional studies in people, CIS43 could be developed as a prophylactic measure to prevent infection for several months after administration, the researchers say. Such a prophylactic antibody could be useful for tourists, health care workers, military personnel or others who travel to areas where malaria is common. Moreover, if the antibody prevented malaria infection for up to six months, it might be combined with antimalarial drugs and be deployed as part of mass drug administration efforts that potentially could eliminate the disease in malaria-endemic regions.
Promising concept may lead to an alternative to antibiotics
Researchers are developing a promising alternative to antibiotic treatment for infections caused by Klebsiella pneumoniae bacteria resistant to carbapenem antibiotics. The approach uses antibodies to target the K. pneumoniae protective capsule polysaccharide, allowing immune system cells called neutrophils to attack and kill the bacteria. The early stage, in vitro research was conducted by scientists at the National Institute of Allergy and Infectious Diseases’ (NIAID) Rocky Mountain Laboratories and the New Jersey Medical School-Rutgers University.
Klebsiella bacteria cause about 10 percent of all hospital-acquired infections in the United States. A carbapenem-resistant K. pneumoniae strain known as multilocus sequence type 258 (ST258) is one of the antibiotic-resistant organisms labeled an urgent threat by the Centers for Disease Control and Prevention. ST258 is particularly concerning because it is resistant to most antibiotics. It is a significant cause of mortality among people with bloodstream infections.
Study of flies suggests neurodegenerative disorders may speed up aging process
To understand the link between aging and neurodegenerative disorders such as Alzheimer’s disease, scientists from the National Institutes of Health compared the genetic clocks that tick during the lives of normal and mutant flies. They found that altering the activity of a gene called Cdk5 appeared to make the clocks run faster than normal, and the flies older than their chronological age. This caused the flies to have problems walking or flying later in life, to show signs of neurodegeneration, and to die earlier.
“We tried to untangle the large role aging appears to play in some of the most devastating neurological disorders,” said Edward Giniger, Ph.D., senior investigator at the NIH’s National Institute of Neurological Disorders and Stroke and the senior author of the study published in Disease Models & Mechanisms. “Our results suggest that neurodegenerative disorders may accelerate the aging process.”
On average, the normal flies in this study lived for 47 days. To create a genetic clock, Dr. Giniger’s team measured the levels of every gene encoded in messenger RNA molecules from cells from the heads and bodies of flies at 3, 10, 30, and 45 days after birth. This allowed the researchers to use advanced analysis techniques to search for the genes that seemed to be sensitive to aging, and create a standard curve, or timeline, that described the way they changed.
Monoclonal antibodies (mAbs) — preparations of a specific type of antibody designed to bind to a single target — have shown promise in the fight against cancer and autoimmune diseases. They also may play a critical role in future battles against emerging infectious disease outbreaks, according to a new article by scientists from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The article is published online this week by the New England Journal of Medicine and outlines the potential uses for mAbs as treatments for infectious diseases and as a prevention tool for protecting individuals at risk of infection and slowing disease outbreaks.
The article, written by NIAID Director Anthony S. Fauci, M.D., and colleagues Hilary D. Marston, M.D., M.P.H., and Catharine I. Paules, M.D., highlights the research advances that could allow for rapid, strategic deployment of mAbs to prevent and treat emerging infectious diseases and, potentially, alter the course of epidemics.
Ebola virus particles (red) on a larger cell. ZMAPP, a potential treatment for Ebola, includes a cocktail of monoclonal antibodies.
Familial human prion diseases are passed within families and are associated with 34 known prion protein mutations. To determine whether three of the unstudied mutations are transmissible, scientists from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, exposed research mice to brain samples from three people who died from a familial prion disease. After observing the mice for about two years, they found two of the mutations, Y226X and G131V, are transmissible.
Perhaps more interesting, the Y226X patient sample had previously been preserved in formaldehyde for three days, embedded in wax, and dried on glass specimen slides for several years before being rehydrated for the study. Yet, the sample infected four of eight mice.
The finding illustrates the hardiness of prion infectivity and the potential risks associated with prion transmission, potentially through surgery, blood transfusion or tissue donation. Samples for the other two mutations studied were taken from frozen brain tissue that was thawed.
