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.
Researchers at the National Eye Institute (NEI) report that a brain region in the superior temporal sulcus (fSTS) is crucial for processing and making decisions about visual information. The findings, which could provide clues to treating visual conditions from stroke, appear today in the journal Neuron. NEI is part of the National Institutes of Health.
“The human visual system recognizes, prioritizes, and categorizes visual objects and events to provide actionable information,” said Richard Krauzlis, Ph.D., chief of the NEI Section on Eye Movements and Selective Attention and senior author of the study. “We were surprised to learn that the fSTS is a crucial link in this story-building process, passing information from an evolutionarily ancient region in the midbrain to highly specialized regions of the visual cortex.”
While aspects of visual processing begin in the eye, crucial steps in visual attention start in the superior colliculus, a part of the midbrain that handles a variety of sensory input. Previous work in Krauzlis’ lab showed that neuronal activity in the superior colliculus is necessary for the brain to notice an event in the visual field and decide that it is significant.
Previously unknown genetic connection could be a target for gene therapy
A study led by researchers at the National Institutes of Health has made a surprising connection between frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), two disorders of the nervous system, and the genetic mutation normally understood to cause Huntington’s disease.
Several neurological disorders have been linked to “repeat expansions,” a type of mutation that results in abnormal repetition of certain DNA building blocks. For example, Huntington’s disease occurs when a sequence of three DNA building blocks that make up the gene for a protein called huntingtin repeats many more times than normal. These repeats can be used to predict whether someone will develop the illness and even when their symptoms are likely to appear, because the more repeats in the gene, the earlier the onset of disease.
“It has been recognized for some time that repeat expansion mutations can give rise to neurological disorders,” said Sonja Scholz, M.D., Ph.D., investigator, NINDS Intramural Research Program. “But screening for these mutations throughout the entire genome has traditionally been cost-prohibitive and technically challenging.”
NIH preclinical study suggests FDA-approved tetracycline-based antibiotics may slow infection and reduce neurological problems
In 2015, hundreds of children were born with brain deformities resulting from a global outbreak of Zika virus infections. Recently, National Institutes of Health researchers used a variety of advanced drug screening techniques to test out more than 10,000 compounds in search of a cure. To their surprise, they found that the widely used antibiotic methacycline was effective at preventing brain infections and reducing neurological problems associated with the virus in mice. In addition, they found that drugs originally designed to combat Alzheimer’s disease and inflammation may also help fight infections.
“Around the world, the Zika outbreak produced devastating, long-term neurological problems for many children and their families. Although the infections are down, the threat remains,” said Avindra Nath, 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 PNAS. “We hope these promising results are a good first step to preparing the world for combating the next potential outbreak.”
The study was a collaboration between scientists on Dr. Nath’s team and researchers in laboratories led by Anton Simeonov, Ph.D., scientific director at the NIH’s National Center for Advancing Translational Sciences (NCATS) and Radhakrishnan Padmanabhan, Ph.D., Professor of Microbiology & Immunology, Georgetown University Medical Center, Washington, D.C.
NIH scientists found that the commonly used antibiotic methacycline may be effective at combating the neurological problems caused by Zika virus infections. This is a picture of a Zika-infected mouse brain from the study. Image credit: Nath lab, NIH/NINDS
In a comprehensive analysis of patients with cancer who had exceptional responses to therapy, researchers have identified molecular changes in the patients’ tumors that may explain some of the exceptional responses. The results demonstrate that genomic characterizations of cancer can uncover genetic alterations that may contribute to unexpected and long-lasting responses to treatment, according to the researchers.
The results appeared in Cancer Cell on Nov. 19. Researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, conducted the study in collaboration with investigators from other institutions, including NCI-designated Cancer Centers.
“The majority of patients in this study had metastatic cancers that are typically difficult to treat, yet some of the patient responses lasted for many years,” said Louis Staudt, M.D., Ph.D., director of NCI’s Center for Cancer Genomics, who co-led the study. “Researchers and the doctors who treat these patients have long been curious about the mechanisms underlying these rare responses to treatment. Using modern genomic tools, we can now start to solve these fascinating puzzles.”
A genomic study has uncovered molecular changes in patient tumors that may give rise to dramatic and long-lasting responses to cancer therapy.
NIH research findings reveal new aspects of visual processing
Researchers at the National Eye Institute (NEI) have decoded brain maps of human color perception. The findings, published today in Current Biology, open a window into how color processing is organized in the brain, and how the brain recognizes and groups colors in the environment. The study may have implications for the development of machine-brain interfaces for visual prosthetics. NEI is part of the National Institutes of Health.
“This is one of the first studies to determine what color a person is seeing based on direct measurements of brain activity,” said Bevil Conway, Ph.D., chief of NEI’s Unit on Sensation, Cognition and Action, who led the study. “The approach lets us get at fundamental questions of how we perceive, categorize, and understand color.”
The brain uses light signals detected by the retina’s cone photoreceptors as the building blocks for color perception. Three types of cone photoreceptors detect light over a range of wavelengths. The brain mixes and categorizes these signals to perceive color in a process that is not well understood.
Colored stimuli in yellow (top) and blue (bottom). Light luminance level versions are on the left; dark versions on the right. Volunteers used a variety of names for the upper stimuli, such as “yellow” for the left and “brown” for the right, but consistently used “blue” for both the lower stimuli.
An independent data and safety monitoring board (DSMB) overseeing the Phase 3 trial of the investigational COVID-19 vaccine known as mRNA-1273 reviewed trial data and shared its interim analysis with the trial oversight group on Nov. 15, 2020. This interim review of the data suggests that the vaccine is safe and effective at preventing symptomatic COVID-19 in adults. The interim analysis comprised 95 cases of symptomatic COVID-19 among volunteers. The DSMB reported that the candidate was safe and well-tolerated and noted a vaccine efficacy rate of 94.5 percent. The findings are statistically significant, meaning they are likely not due to chance. Ninety of the cases occurred in the placebo group and five occurred in the vaccinated group. There were 11 cases of severe COVID-19 out of the 95 total, all of which occurred in the placebo group.
The mRNA-1273 vaccine candidate was co-developed by the Cambridge, Massachusetts-based biotechnology company Moderna, Inc., and the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. It combines Moderna’s mRNA (messenger RNA) delivery platform with the stabilized SARS-CoV-2 spike immunogen (S-2P) developed by NIAID scientists.
The vaccine candidate transitioned from early development with NIAID to the Biomedical Advanced Research and Development Authority (BARDA), part of the Department of Health and Human Services Office of the Assistant Secretary for Preparedness and Response, for advanced development and manufacturing support, to meet the federal government’s Operation Warp Speed (OWS) goals.
3D print of a spike protein of SARS-CoV-2, the virus that causes COVID-19, in front of a 3D print of a SARS-CoV-2 virus particle. The spike protein (foreground) enables the virus to enter and infect human cells. On the virus model, the virus surface (blue) is covered with spike proteins (red) that enable the virus to enter and infect human cells.
National Institutes of Health researchers have discovered a gene in mice that controls the craving for fatty and sugary foods and the desire to exercise. The gene, Prkar2a, is highly expressed in the habenula, a tiny brain region involved in responses to pain, stress, anxiety, sleep and reward. The findings could inform future research to prevent obesity and its accompanying risks for cardiovascular disease and diabetes. The study was conducted by Edra London, Ph.D., a staff scientist in the section on endocrinology and genetics at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and colleagues. It appears in JCI Insight.
Prkar2a contains the information needed to make two subunits — molecular components — of the enzyme protein kinase A. Enzymes speed up chemical reactions, either helping to combine smaller molecules into larger molecules, or to break down larger molecules into smaller ones. Protein kinase A is the central enzyme that speeds reactions inside cells in many species. In a previous study, the NICHD team found that despite being fed a high fat diet, mice lacking functioning copies of Prkar2a were less likely to become obese than wild type mice with normally functioning Prkar2a.
The researchers determined that Prkar2a-negative mice ate less high-fat food than their counterparts, not only when given unlimited access to the food, but also after a fast. Similarly, the Prkar2a-negative mice also drank less of a sugar solution than the wild type mice. The Prkar2a-negative mice were also more inclined to exercise, running two to three times longer than wild type mice on a treadmill. Female Prkar2a-negative mice were less inclined to consume high fat foods than Prkar2-negative males, while Prkar2-negative males showed less preference for the sugar solution than Prkar2-negative females.
Gut-trained immune cells at CNS borders guard against meningitis and other infections
The membranes surrounding our brains are in a never-ending battle against deadly infections, as germs constantly try to elude watchful immune cells and sneak past a special protective barrier called the meninges. In a study involving mice and human autopsy tissue, researchers at the National Institutes of Health and Cambridge University have shown that some of these immune cells are trained to fight these infections by first spending time in the gut.
“This finding opens a new area of neuroimmunology, showing that gut-educated antibody-producing cells inhabit and defend regions that surround the central nervous system,” said Dorian McGavern, Ph.D., senior investigator at NINDS and co-senior author of the study, which was published in Nature.
The central nervous system (CNS) is protected from pathogens both by a three-membrane barrier called the meninges and by immune cells within those membranes. The CNS is also walled off from the rest of the body by specialized blood vessels that are tightly sealed by the blood brain barrier. This is not the case, however, in the dura mater, the outermost layer of the meninges. Blood vessels in this compartment are not sealed, and large venous structures, referred to as the sinuses, carry slow moving blood back to the heart. The combination of slow blood flow and proximity to the brain requires strong immune protection to stop potential infections in their tracks.
Targeting cells’ ‘trash compactor’ could lead to new antiviral strategy to fight COVID-19
Researchers at the National Institutes of Health have discovered a biological pathway that the novel coronavirus appears to use to hijack and exit cells as it spreads through the body. A better understanding of this important pathway may provide vital insight in stopping the transmission of the virus — SARS-CoV-2 — which causes COVID-19 disease.
In cell studies, the researchers showed for the first time that the coronavirus can exit infected cells through the lysosome, an organelle known as the cells’ “trash compactor.” Normally the lysosome destroys viruses and other pathogens before they leave the cells. However, the researchers found that the coronavirus deactivates the lysosome’s disease-fighting machinery, allowing it to freely spread throughout the body.
Targeting this lysosomal pathway could lead to the development of new, more effective antiviral therapies to fight COVID-19. The findings, published today in the journal Cell, come at a time when new coronavirus cases are surging worldwide, with related U.S. deaths nearing 225,000.
Illustration shows components of the lysosome exocytosis pathway, which coronaviruses use to exit cells. Also shown are components of the normal biosynthetic secretory pathway. Image credit: NIH Medical Arts
NIH study suggests women with mood disorders, gestational diabetes may have a higher risk
A National Institutes of Health study of 5,000 women has found that approximately 1 in 4 experienced high levels of depressive symptoms at some point in the three years after giving birth. The rest of the women experienced low levels of depression throughout the three-year span. The study was conducted by researchers at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). It appears in the journal Pediatrics.
The American Academy of Pediatrics recommends that pediatricians screen mothers for postpartum depression at well-child visits at one, two, four and six months after childbirth. Researchers identified four trajectories of postpartum depressive symptoms and the factors that may increase a woman’s risk for elevated symptoms. The findings suggest that extending screening for postpartum depressive symptoms for at least two years after childbirth may be beneficial, the authors write.
“Our study indicates that six months may not be long enough to gauge depressive symptoms,” said Diane Putnick, Ph.D., the primary author and a staff scientist in the NICHD Epidemiology Branch. “These long-term data are key to improving our understanding of mom’s mental health, which we know is critical to her child’s well-being and development.”
