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:
Whether you’re shedding pounds with the help of effective new medicines, slimming down after weight loss surgery or cutting calories and adding exercise, there will come a day when the numbers on the scale stop going down, and you hit the dreaded weight loss plateau.
In a recent study, Kevin Hall, a researcher at the National Institutes of Health who specializes in measuring metabolism and weight change, looked at when weight loss typically stops depending on the method people were using todrop pounds. He broke down the plateau into mathematical models using data from high-quality clinical trials of different ways to lose weight to understand why people stop losing when they do. The study published Monday in the journal Obesity.
Study in mice suggests that experimental drug may be effective against mountain sickness and other polycythemias
Researchers at the National Institutes of Health have cured mice with Chuvash polycythemia, a life-threatening disorder that involves the overproduction of red blood cells. They treated the mice using Tempol, an experimental drug being studied for treatment of diabetes, cancer and other diseases. The findings offer hope that Tempol or a similar drug may treat polycythemias that affect humans, such as mountain sickness—a serious blood complication experienced in low-oxygen, high-altitude settings. The study appears in The Journal of Clinical Investigation.
Chuvash polycythemia is a rare, inherited disorder that is endemic to the Chuvash Republic of Russia, though it does occur in other parts of the world. NIH studies rare diseases not only to help the people who have them, but also to gain insight into gene functions that may benefit people with more common conditions. Complications of Chuvash polycythemia include blood clots and cerebral hemorrhage. The condition results from a genetic mutation that makes people unable to break down hypoxia inducible factor 2α (HIF2α), a protein that helps stimulate red blood cell production. The inability to degrade HIF2α leads to higher red cell production, even under high-oxygen conditions.
Natural history investigation will deploy latest advances to identify biomarkers, targets for early therapy
A new clinical study led by the National Eye Institute (NEI), part of the National Institutes of Health, will follow 500 people over five years to learn more about the natural history of early age-related macular degeneration (AMD). By using the latest technologies to visualize structures within the eye and measure their function, researchers hope to identify biomarkers of disease progression, well before it advances to late-stage disease and causes vision loss. AMD is the leading cause of vision impairment and blindness among people age 50 and older in the United States.
“The findings will contribute to our understanding of the underlying biology driving the transition from early to late-stage disease so that therapies can be developed to halt its progression,” said the study’s lead investigator, Emily Y. Chew, M.D., deputy clinical director at NEI and director of the NEI Division of Epidemiology and Clinical Applications. “Treatments that halt the disease at its early stage would have an enormous public health impact.”
Fundus photo shows giraffe-like macular pattern in the retina of a person with reticular pseudodrusen.
National Institutes of Health scientists developing a rapid, practical test for the early diagnosis of prion diseases have modified the assay to offer the possibility of improving early diagnosis of Parkinson’s disease and dementia with Lewy bodies. The group, led by NIH’s National Institute of Allergy and Infectious Diseases (NIAID), tested 60 cerebral spinal fluid samples, including 12 from people with Parkinson’s disease, 17 from people with dementia with Lewy bodies, and 31 controls, including 16 of whom had Alzheimer’s disease. The test correctly excluded all the 31 controls and diagnosed both Parkinson’s disease and dementia with Lewy bodies with 93 percent accuracy.
Importantly, test results were available within two days, compared to related assays that require up to 13 days. The group conducted the tests using Real-Time Quaking-Induced Conversion (RT-QuIC), an assay developed and refined over the past decade at NIAID’s Rocky Mountain Laboratories. Scientists from the University of California San Diego, University of Verona in Italy, Indiana University School of Medicine, Indianapolis, and the Case Western Reserve University School of Medicine, Cleveland, collaborated on the project. The research findings were published in Acta Neuropathologica Communications.
NIAID’s Bradley Groveman, foreground, and Christina Orru using the RT-QuIC diagnostic assay, which they helped adapt to detect Parkinson’s disease and dementia with Lewy bodies.
Ebola virus can infect the reproductive organs of male and female macaques, according to a study published in The American Journal of Pathology, suggesting that humans could be similarly infected. Prior studies of survivors of the 2014-2016 Ebola outbreak in West Africa have revealed sexual transmission of Ebola virus, and that viral RNA (Ebola virus genetic material) can persist in semen following recovery. While little is known about viral persistence in female reproductive tissues, pregnant women with Ebola virus disease have a maternal death rate of more than 80 percent and a fetal death rate of nearly 100 percent.
In this study, investigators from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and from Thomas Jefferson University infected four female and eight male macaques with the Makona variant of Ebola virus, the variant responsible for the recent West Africa outbreak. All the macaques succumbed to Ebola virus disease and were euthanized six to nine days after infection. The scientists then took reproductive tissue samples from each macaque and analyzed the samples for signs of Ebola virus infection, organ and tissue damage, and immune responses. They found widespread Ebola virus infection of reproductive organs with minimal tissue immune response or signs of disease.
Colorized transmission electron micrograph of the ovary from a nonhuman primate infected with Ebola virus. Characteristic filamentous Ebola virus particles are present between cells (bright red). Intracytoplasmic Ebola virus inclusion bodies forming crystalline arrays can be seen within ovarian stromal cells (darker red).
Preliminary results suggest strokes also affect the eye
Research into curious bright spots in the eyes on stroke patients’ brain images could one day alter the way these individuals are assessed and treated. A team of scientists at the National Institutes of Health found that a chemical routinely given to stroke patients undergoing brain scans can leak into their eyes, highlighting those areas and potentially providing insight into their strokes. The study was published in Neurology.
“We were kind of astounded by this – it’s a very unrecognized phenomenon,” said Richard Leigh, M.D., an assistant clinical investigator at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and the paper’s senior author. “It raises the question of whether there is something we can observe in the eye that would help clinicians evaluate the severity of a stroke and guide us on how best to help patients.”
Eyes yield information about strokes: MRI scans revealed that a chemical called gadolinium, used to improve images, leaked into the eyes of stroke patients.
NIH study in rats suggests that support cells modulate brain circuit activity
Traditionally, scientists thought that star-shaped brain cells called astrocytes were steady, quiet supporters of their talkative, wire-like neighbors, called neurons. Now, an NIH study suggests that astrocytes may also have their say. It showed that silencing astrocytes in the brain’s breathing center caused rats to breathe at a lower rate and tire out on a treadmill earlier than normal. These were just two examples of changes in breathing caused by manipulating the way astrocytes communicate with neighboring cells.
“For decades we thought that breathing was exclusively controlled by neurons in the brain. Our results suggest that astrocytes actively help control the rhythm of breathing,” said Jeffrey C. Smith, Ph.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 Communications. “These results add to the growing body of evidence that is changing the way we think about astrocytes and how the brain works.”
A fresh look at the brain and breathing: NIH study in rats shows that star-shaped brain cells, called astrocytes (red), may play an active role in breathing.
Mouse nicotinamide riboside study shows potential for human research
The supplement nicotinamide riboside (NR) – a form of vitamin B3 – prevented neurological damage and improved cognitive and physical function in a new mouse model of Alzheimer’s disease. The results of the study, conducted by researchers at the National Institute on Aging (NIA) part of the National Institutes of Health, suggest a potential new target for treating Alzheimer’s disease. The findings appear in the Feb. 5, 2018, issue of Proceedings of the National Academy of Sciences.
NR acts on the brain by normalizing levels of nicotinamide adenine dinucleotide (NAD+), a metabolite vital to cellular energy, stem cell self-renewal, resistance to neuronal stress and DNA repair. In Alzheimer’s disease, the brain’s usual DNA repair activity is impaired, leading to mitochondrial dysfunction, lower neuron production, and increased neuronal dysfunction and inflammation.
The international team of scientists was led by Vilhelm A. Bohr, M.D., Ph.D., senior investigator and chief of the Laboratory of Molecular Gerontology of the NIA’s Intramural Research Program, with Dr. Yujun Hou, a postdoctoral investigator in the laboratory.
In a mouse model of Alzheimer’s disease, amyloid beta clusters (red) build up among neurons (green) in a memory-related area of the brain. With support from the National Center for Advancing Translational Sciences, scientists have found that a compound originally developed as a cancer therapy potentially could be used to treat Alzheimer’s disease.
High exposure to radiofrequency radiation (RFR) in rodents resulted in tumors in tissues surrounding nerves in the hearts of male rats, but not female rats or any mice, according to draft studies from the National Toxicology Program (NTP). The exposure levels used in the studies were equal to and higher than the highest level permitted for local tissue exposure in cell phone emissions today. Cell phones typically emit lower levels of RFR than the maximum level allowed. NTP’s draft conclusions were released today as two technical reports, one for rat studies and one for mouse studies. NTP will hold an external expert review of its complete findings from these rodent studies March 26-28.
The incidence of tumors, called malignant schwannomas, that were observed in the heart increased in male rats as they were exposed to increasing levels of RFR beyond the allowable cell phone emissions. Researchers also noted increases in an unusual pattern of cardiomyopathy, or damage to heart tissue, in exposed male and female rats. Overall, there was little indication of health problems in mice related to RFR.
The reports also point out statistically significant increases in the number of rats and mice with tumors found in other organs at one or more of the exposure levels studied, including the brain, prostate gland, pituitary gland, adrenal gland, liver, and pancreas. However, the researchers determined that these were equivocal findings, meaning it was unclear if any of these tumor increases were related to RFR.
“The levels and duration of exposure to RFR were much greater than what people experience with even the highest level of cell phone use, and exposed the rodents’ whole bodies. So, these findings should not be directly extrapolated to human cell phone usage,” said John Bucher, Ph.D., NTP senior scientist. “We note, however, that the tumors we saw in these studies are similar to tumors previously reported in some studies of frequent cell phone users.”
Scientists looking for jobs after completing their training may soon have a new tool that helps them evaluate various career paths. The new tool uses a method that was developed by scientists at the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health. The method differs from others in that it separates employment trends in biomedical science by sector, type, and job specifics. The creators hope this novel approach will be useful throughout NIH, as well as for academic and research institutions around the world.
Led by Tammy Collins, Ph.D., director of the NIEHS Office of Fellows’ Career Development, team members collected detailed career outcomes for more than 900 NIEHS postdoctoral fellows over the past 15 years. Postdoctoral fellows, or postdocs, are scientists who have received their doctoral degrees and are participating in a program that offers additional training.
Lead author and NIEHS computer scientist Hong Xu analyzed the data using the R Project for Statistical Computing, a free online program that displays data using graphs and charts. Shyamal Peddada, Ph.D., former NIEHS head of the Biostatistics and Computational Biology Branch, served as key advisor. The study appeared online in the journal Nature Biotechnology, and is the first standardized method for categorizing career outcomes of NIEHS postdocs.
The study categorized career outcomes for NIEHS postdocs by sector, type, and job specifics. The authors envision that this approach will help young scientists make career decisions based on data and not anecdotal evidence.
NIH clinical trial is testing antibody against the protein in people with HIV.
For the first time, scientists have shown a relationship between the proportion of key immune cells that display high levels of a gut-homing protein called alpha-4 beta-7 at the time of HIV infection and health outcomes. Previous research illustrated this relationship in monkeys infected with a simian form of HIV.
The new study found that women who had more CD4+ T cells displaying high levels of alpha-4 beta-7 on their surface were more likely to become infected with HIV, and the virus damaged their immune systems more rapidly, than women with fewer such cells. The National Institutes of Health co-funded the study with the South African Medical Research Council as part of the U.S.–South Africa Program for Collaborative Biomedical Research. In addition, NIH scientists collaborated on the study. The report appears online today in the journal Science Translational Medicine.
“Our findings suggest that having a high frequency of alpha-4 beta-7-expressing CD4+ T cells, which HIV preferentially infects, leads to more HIV-infected CD4+ T cells moving to the gut, which in turn leads to extensive damage to gut-based immune cells,” said Anthony S. Fauci, M.D. Dr. Fauci co-authored the paper as chief of the Laboratory of Immunoregulation at the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH. He also is director of NIAID.
Scanning electron micrograph of a human T lymphocyte (also called a T cell) from the immune system of a healthy donor.
