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.
A new tool developed by researchers at the National Institutes of Health has determined, for the first time, how two distinct sets of neurons in the mouse brain work together to control movement. The method, called spectrally resolved fiber photometry (SRFP), can be used to measure the activity of these neuron groups in both healthy mice and those with brain disease. The scientists plan to use the technique to better understand what goes wrong in neurological disorders, such as Parkinson’s disease. The study appeared online in the journal Neuron.
According to Guohong Cui, M.D., Ph.D., head of the In Vivo Neurobiology Group at the National Institute of Environmental Health Sciences (NIEHS), part of NIH, the project began because he wanted to find out why patients with Parkinson’s disease have problems with movement. Typically, the disease motor symptoms include tremor, muscle stiffness, slowness of movement, and impaired balance.
Cui explained that an animal’s ability to move was controlled by two groups of neurons in the brain called the direct pathway (D1) and indirect pathway (D2). Based on clinical studies of patients with Parkinson’s and primate models, some researchers hypothesized that the loss of the neurotransmitter dopamine in the midbrain resulted in an imbalance of neural activities between D1 and D2. Since previous methods could not effectively distinguish different cell types in the brain, the hypothesis remained under debate. However, using SRFP, Cui’s team was able to label D1 and D2 neurons with green and red fluorescent sensors to report their neural activity.
"Our method allowed us to simultaneously measure neural activity of both pathways in a mouse as the animal performed tasks," Cui said. "In the future, we could potentially use SRFP to measure the activity of several cell populations utilizing various colors and sensors."
The striatum, part of the brain’s basal ganglia, is involved in movement control. Using the SRFP technique, Cui’s team found that different activity patterns in D1 (red) and D2 (green) pathways led to different types of movement.
NIH study cautions that more research is needed to determine if this small difference in weight poses a health risk
Women who experience vaginal bleeding for more than one day during the first trimester of pregnancy may be more likely to have a smaller baby, compared to women who do not experience bleeding in the first trimester, suggest researchers at the National Institutes of Health. On average, full-term babies born to women with more than one day of bleeding in the first trimester were about 3 ounces lighter than those born to women with no bleeding during this time. Additionally, infants born to women with more than a day of first trimester bleeding were roughly twice as likely to be small for gestational age, a category that includes infants who are healthy but small, as well as those whose growth has been restricted because of insufficient nutrition or oxygen or other causes.
The study appears in Obstetrics & Gynecology and was conducted by researchers at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and other U.S. research institutions.
The authors caution that the decrease in birthweight of infants born to women with vaginal bleeding was small. More studies are needed to determine if these infants are at risk for any additional health risks in infancy or later in life.
“The good news is that only one day of bleeding was not significantly associated with reduced growth,” said the study’s senior author, Katherine L. Grantz, M.D., an investigator in the NICHD Epidemiology Branch. “But our results suggest that even if bleeding stops before the second trimester, a pregnancy with more than one day of bleeding is at somewhat of a greater risk for a smaller baby.”
Early during the recent Ebola epidemic in West Africa, scientists speculated that the genetic diversity of the circulating Makona strain of virus (EBOV-Makona) would result in more severe disease and more transmissibility than prior strains. However, using two different animal models, National Institutes of Health scientists have determined that certain mutations stabilized early during the epidemic and did not alter Ebola disease presentation or outcome. Their work, published in Cell Reports, offers further evidence to support previous findings from molecular sequencing that the diversity of EBOV-Makona did not significantly impact the course of disease.
EBOV-Makona swept through Liberia, Guinea and Sierra Leone from late 2013 to early 2016. Scientists from NIH’s National Institute of Allergy and Infectious Diseases (NIAID) compared EBOV-Makona isolates from early in the outbreak—March 2014—to isolates circulating between five and nine months later, when certain mutations had emerged in the viral surface glycoprotein and elsewhere. They then infected mice and rhesus macaques with these various virus isolates to assess disease progression and viral shedding.
“We were unable to find any significant differences between early and late isolates lacking or carrying those mutations, suggesting that these mutations do not lead to alterations in the disease-causing ability in animal models,” the authors write.
NIH researchers combine two microscope technologies to create sharper, faster images
Scientists at the National Institute of Biomedical Imaging and Bioengineering (NIBIB) have combined two different microscope technologies to create sharper images of rapidly moving processes inside a cell. NIBIB is part of the National Institutes of Health.
In a paper published today in Nature Methods, Hari Shroff, Ph.D., chief of NIBIB’s lab section on High Resolution Optical Imaging (HROI), describes his new improvements to traditional Total Internal Reflection Fluorescence (TIRF) microscopy. TIRF microscopy illuminates the sample at a sharp angle so that the light reflects back, illuminating only a thin section of the sample that is extremely close to the coverslip. This process creates very high contrast images because it eliminates much of the background, out-of-focus, light that conventional microscopes pick up.
While TIRF microscopy has been used in cell biology for decades, it produces blurry images of small features within cells. In the past, super-resolution microscopy techniques applied to TIRF microscopes have been able to improve the resolution, but such attempts have always compromised speed, making it impossible to clearly image objects that move rapidly. As a result, many cellular processes remain too small or fast to observe.
The rapid movements of Rab11 particles can be clearly imaged with the new instant TIRF-SIM microscope.
Topical treatment with live Roseomonas mucosa — a bacterium naturally present on the skin — was safe for adults and children with atopic dermatitis (eczema) and was associated with reduced disease severity, according to initial findings from an ongoing early-phase clinical trial at the National Institutes of Health. Preclinical work in a mouse model of atopic dermatitis had suggested that R. mucosa strains collected from healthy skin can relieve disease symptoms. The new findings, published May 3 in JCI Insight, support further evaluation of this potential new therapy.
Atopic dermatitis is an inflammatory skin disease that can make skin dry and itchy, cause rashes and lead to skin infections. The disease is linked to an increased risk of developing asthma, hay fever and food allergy. Atopic dermatitis is common in children and sometimes resolves on its own, but it also can persist into or develop during adulthood.
“Living with atopic dermatitis can be physically and emotionally challenging. While treatment can help manage the symptoms, currently available therapies can be time-consuming — requiring multiple daily applications — and costly,” said Anthony S. Fauci, M.D., director of NIH’s National Institute of Allergy and Infectious Diseases (NIAID). “New, inexpensive therapies that require less frequent application are needed to expand the options available for atopic dermatitis treatment.”
A scientist demonstrates application of the experimental therapy to the inner elbow. For demonstration purposes, the bacteria solution has been replaced with purple dye.
Findings may help expand window for storing organs before transplantation, therapeutic hypothermia
Researchers at the National Eye Institute have discovered cellular mechanisms that help the 13-lined ground squirrel survive hibernation. Their findings could be a step to extending storage of human donor tissues awaiting transplantation and protecting traumatic brain injury patients who undergo induced hypothermia. NEI is part of the National Institutes of Health. The findings were published in the May 3 issue of Cell.
During hibernation, the 13-lined ground squirrel endures near freezing temperatures, dramatically slowing its heart rate and respiration. How the squirrel’s tissues adapt to the cold and metabolic stress has confounded researchers.
A structure in cells known to be vulnerable to cold is the microtubule cytoskeleton. This network of small tubes within a cell provides structural support and acts as a kind of inner cellular railway system, transporting organelles and molecular complexes vital for a cell’s survival.
In a series of experiments, the research team led by Wei Li, Ph.D., a senior investigator in the NEI Retinal Neurophysiology Section and Jingxing Ou, Ph.D., a postdoctoral scientist in Li’s lab, compared cells from non-hibernators to cells from the ground squirrel to determine differences in their response to cold. They found that in ground squirrel neurons the microtubule cytoskeleton remains intact while it deteriorates in the neurons of humans and other non-hibernating animals, including rats.
“By understanding the biology of cold adaptation in hibernation, we may be able to improve and broaden the applications of induced hypothermia in the future, and perhaps prolong the viability of organs prior to transplantation,” Li said. “Kidneys, for example, are typically stored for no more than 30 hours. After that, the tissue starts to deteriorate, impairing the organ’s ability to function properly after its been rewarmed and reperfused. Heart, lungs and livers have an even shorter shelf life.”
NIH study finds higher rates of dissatisfaction with family relationships
Cyberbullying, dissatisfaction with family relationships, and unmet medical needs are major contributors to the high rates of depressive symptoms seen among adolescents who are gay, lesbian, bisexual or questioning their sexual orientation, according to researchers at the National Institutes of Health. Their new study on sexual minority youth now appears in Pediatrics.
Researchers used data from the NEXT Generation Health Study, a study from 2009-2016 of 2,785 high school students in 22 states, to assess teens’ depressive symptoms beginning at age 17 and continuing for three years after they left high school. They found that almost 30 percent of sexual minority teens thought they did not have adequate medical care for a 12-month period prior to the study, compared to 19 percent for heterosexual teens. Teens questioning their sexual orientation or attracted to the same sex or both sexes may fear that providers would disclose information to parents or may be embarrassed to seek mental health services, the authors wrote.
“The study shows that adolescence is a critical window for interventions to address depressive symptoms experienced by sexual minority youth,” said Jeremy Luk, Ph.D., first author of the study and postdoctoral researcher at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development. “Without appropriate screening and intervention, these disparities may likely persist into young adulthood.”
IRP scientists report single dose elicited long-term protection
Two genetically modified broadly neutralizing antibodies (bNAbs) protected rhesus macaques from an HIV-like virus, report scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. After introducing genetic mutations into two potent HIV bNAbs, researchers prepared intravenous infusions of two bNAbs known as 3BNC117-LS and 10-1074-LS. Single infusions of each modified bNAb protected two groups of six monkeys each against weekly exposures to simian-human immunodeficiency virus (SHIV) for up to 37 weeks, compared with a median of three weeks in 12 monkeys receiving no antibody. SHIV is a manmade virus commonly used in HIV nonhuman primate studies.
The study, led by Malcolm A. Martin, M.D., chief of the NIAID Laboratory of Molecular Microbiology, also assessed the efficacy of injecting a combination of both modified bNAbs into six monkeys subcutaneously — a route of administration considered more feasible in resource-limited clinical settings. This bNAb mixture, administered at a three-fold lower concentration than the individual antibodies infused intravenously, protected this group of monkeys for a median of 20 weeks.
This human T cell (blue) is under attack by HIV (yellow), the virus that causes AIDS. The virus specifically targets T cells, which play a critical role in the body's immune response against invaders like bacteria and viruses.
Study provides insights into the immune system’s role in recovery after concussion in mice
Following head injury, the protective lining that surrounds the brain may get a little help from its friends: immune cells that spring into action to assist with repairs. In a new study, scientists from the National Institutes of Health watched in real-time as different immune cells took on carefully timed jobs to fix the damaged lining of the brain, also known as meninges, in mice. These results may help provide clues to the discovery that the meninges in humans may heal following mild traumatic brain injury (mTBI) and why additional hits to the head can be so devastating.
“The lining of the brain, with help from the immune system, has a remarkable ability to put itself back together again after injury,” said Dorian McGavern, Ph.D., scientist at the NIH’s National Institute of Neurological Disorders and Stroke and the senior author of the study published in Nature Immunology. “As we learn more about all the cells involved in the repair process, we may be able to identify potential targets for therapy that lead to better outcomes for patients.”
The study came about from an observation on MRI scans of adult patients who experienced a concussion or mTBI. Around half of patients with mTBI show evidence of injury to blood vessels in the meninges, which appears on MRI scans as a vascular dye leaking out of the damaged vessels.
One day after head injury (left), bright dye along the edge of the brain suggests damage to the meninges, or the brain’s protective lining. After 35 days (right), the dye no longer appears, indicating the meninges may have healed.
Preliminary IRP study shows increased levels of beta-amyloid
Losing just one night of sleep led to an immediate increase in beta-amyloid, a protein in the brain associated with Alzheimer’s disease, according to a small, new study by researchers at the National Institutes of Health. In Alzheimer’s disease, beta-amyloid proteins clump together to form amyloid plaques, a hallmark of the disease.
While acute sleep deprivation is known to elevate brain beta-amyloid levels in mice, less is known about the impact of sleep deprivation on beta-amyloid accumulation in the human brain. The study is among the first to demonstrate that sleep may play an important role in human beta-amyloid clearance.
“This research provides new insight about the potentially harmful effects of a lack of sleep on the brain and has implications for better characterizing the pathology of Alzheimer's disease,” said George F. Koob, Ph.D., director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health, which funded the study.
Beta-amyloid is a metabolic waste product present in the fluid between brain cells. In Alzheimer’s disease, beta-amyloid clumps together to form amyloid plaques, negatively impacting communication between neurons.
Led by Drs. Ehsan Shokri-Kojori and Nora D. Volkow of the NIAAA Laboratory of Neuroimaging, the study is now online in the Proceedings of the National Academy of Sciences. Dr. Volkow is also the director of the National Institute on Drug Abuse at NIH.
Brain imaging after one night of sleep deprivation revealed beta-amyloid accumulation in the hippocampus and thalamus, regions affected by Alzheimer’s disease.
