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.
Membrane-bound virus clusters provide promising target for the treatment of gastroenteritis, other diseases
Researchers have found that a group of viruses that cause severe stomach illness — including the one famous for widespread outbreaks on cruise ships — get transmitted to humans through membrane-cloaked “virus clusters” that exacerbate the spread and severity of disease. Previously, it was believed that these viruses only spread through individual virus particles. The discovery of these clusters, the scientists say, marks a turning point in the understanding of how these viruses spread and why they are so infectious. This preliminary work could lead to the development of more effective antiviral agents than existing treatments that mainly target individual particles.
The researchers studied norovirus and rotavirus — hard-to-treat viruses that are the most common cause of stomach illness, or gastroenteritis, and that afflicts millions of people each year. The viruses cause symptoms ranging from diarrhea to abdominal pain and can sometimes result in death, particularly among young children and the elderly. Their highly contagious nature has led to serious outbreaks in crowded spaces throughout many communities; most notably in cruise ships, daycare centers, classrooms, and nursing homes. Fortunately, vaccines against rotavirus are now available and are routinely given to babies in the United States.
“This is a really exciting finding in the field of virology because it reveals a mode of virus spread that has not been observed among humans and animals,” said study leader Nihal Altan-Bonnet, Ph.D., senior investigator and head of the Laboratory of Host-Pathogen Dynamics at the National Heart, Lung, and Blood Institute (NHLBI). “We hope that it will provide new clues to fighting a wide range of diseases involving many types of viruses, including those that cause gastrointestinal illnesses, heart inflammation, certain respiratory illnesses, and even the common cold.”
The National Institutes of Health’s Clinical Center has made a large-scale dataset of CT images publicly available to help the scientific community improve detection accuracy of lesions. While most publicly available medical image datasets have less than a thousand lesions, this dataset, named DeepLesion, has over 32,000 annotated lesions identified on CT images.
The images, which have been thoroughly anonymized, represent 4,400 unique patients, who are partners in research at the NIH.
Once a patient steps out of a CT scanner, the corresponding images are sent to a radiologist to interpret. Radiologists at the Clinical Center then measure and mark clinically meaningful findings with an electronic bookmark tool. Similar to a physical bookmark, radiologists save their place and mark significant findings to be able to come back to at a later time. These bookmarks are complex – they provide arrows, lines, diameters, and text that can tell the exact location and size of a lesion so experts can identify growth or new disease.
Approach could improve understanding of immune system recovery in people treated for HIV infection
Findings from an animal study suggest that a non-invasive imaging technique could, with further development, become a useful tool to assess immune system recovery in people receiving treatment for HIV infection. Researchers used single-photon emission computed tomography (SPECT) and a CD4-specific imaging probe to assess immune system changes throughout the bodies of macaques infected with SIV, a simian form of HIV, following initiation and interruption of antiretroviral therapy (ART). They evaluated pools of CD4+T cells, the main cell type that HIV infects and destroys, in tissues such as lymph nodes, spleen and gut.
Their findings illustrate that CD4+ T-cell levels in the blood — a measure of immune system health in people living with HIV — often fail to fully reflect the situation in tissues. A low blood CD4+ T-cell level indicates an immune system weakened by HIV, and the level generally increases when ART is started and the immune system begins to recover. The new research, led by scientists at the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, delineates the complexity of the immune recovery process at the level of different tissues.
Findings could inform the development of new antimalarial drugs
The vacuole, a compartment inside human red blood cells in which malaria parasites reproduce and develop, takes on a distinct spherical shape just minutes before its membrane ruptures, leading to the release of parasites into the blood stream, according to researchers at the National Institutes of Health and other institutions. Their study appears in Cellular Microbiology.
The researchers, working with red blood cells from healthy donors, were able to chemically block the sequence of events leading to this rounding of the vacuole. They note that targeting this sequence could inform new treatment strategies against Plasmodium falciparum, the species of malaria parasite that causes the most deaths worldwide and, in several areas, has become drug-resistant.
To track the rounding sequence under a microscope, researchers dyed the membrane of the vacuole with a substance that gives off green light. About 10 minutes before the membrane ruptured, the vacuole morphed from a lumpy, uneven shape to a sphere. Previous studies have shown that malaria parasites use calcium to trigger the biochemical reactions needed for their release from the cell. When the researchers treated the cells with a compound that blocks calcium’s effect, the vacuoles couldn’t transition to the spherical form, trapping the parasites inside the cell.
Details could advance vaccine development for several human diseases
Virus-like particles (VLPs) are protein-based structures that mimic viruses and bind to antibodies. Because VLPs are not infectious, they show considerable promise as vaccine platforms for many viral diseases, including influenza. Realizing that fine details about influenza VLPs were scant, a team of researchers who specialize in visualizing molecular structures developed a 3D model based on the 1918 H1 pandemic influenza virus. They say their research, which appears online in Scientific Reports, could benefit VLP vaccine projects, targeting a range of viruses from HIV to Ebola and SARS coronavirus. The research was conducted by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
Other researchers had produced VLPs for 1918 H1 influenza that successfully protected animals from different influenza viruses. The NIAID group prepared hundreds of such VLP samples and analyzed their structure with a technique called cryo-electron microscopy, which quick-freezes samples with glass-like clarity. They then sliced through those VLP 3D structures—like slicing through a loaf of bread—to analyze their internal structure, using computers to document the size and placement of key molecules. After averaging all their data, the group then created a 3D 1918 influenza VLP model.
On the left is a 1918 H1 influenza virus-like particle (VLP) as seen by cryo-electron microscopy. On the right is the same VLP rendered in 3D with structural components computationally segmented and colored; hemagglutinin and membrane are light blue and internal components (molecular cargo) are red.
IRP study uses software and cameras to monitor teen driving behaviors
Teenage drivers are eight times more likely to be involved in a collision or near miss during the first three months after getting a driver’s license, compared to the previous three months on a learner’s permit, suggests a study led by the National Institutes of Health. Teens are also four times more likely to engage in risky behaviors, such as rapid acceleration, sudden braking and hard turns, during this period. In contrast, teens on a learner’s permit drove more safely, with their crash/near crash and risky driving rates similar to those of adults. The study appears in the Journal of Adolescent Health.
IRP scientists see therapeutic potential against bacteria, viruses
National Institutes of Health researchers have identified a naturally occurring lipid—a waxy, fatty acid—used by a disease-causing bacterium to impair the host immune response and increase the chance of infection. Inadvertently, they also may have found a potent inflammation therapy against bacterial and viral diseases.
Lipids are known to help Francisella tularensis bacteria, the cause of tularemia, to suppress host inflammation when infecting mouse and human cells. In a new study published in the Journal of Innate Immunity, researchers from NIH’s National Institute of Allergy and Infectious Diseases found a form of the lipid phosphatidylethanoloamine, or PE, present in the bacterium. The composition of PE found in F. tularensis differs from PE found in other bacteria. In cell-culture experiments, the researchers discovered that the natural and a synthetic form of PE reduced inflammation caused by both tularemia bacteria and dengue fever virus.
NIH and Iowa researchers shed light on molecular mechanisms of inherited form of human deafness
A small-molecule drug is the first to preserve hearing in a mouse model of an inherited form of progressive human deafness, report investigators at the University of Iowa, Iowa City, and the National Institutes of Health’s National Institute on Deafness and Other Communication Disorders (NIDCD). The study, which appears online in Cell, sheds light on the molecular mechanism that underlies a form of deafness (DFNA27), and suggests a new treatment strategy.
“We were able to partially restore hearing, especially at lower frequencies, and save some sensory hair cells,” said Thomas B. Friedman, Ph.D., chief of the Laboratory of Human Molecular Genetics at the NIDCD, and a coauthor of the study. “If additional studies show that small-molecule-based drugs are effective in treating DFNA27 deafness in people, it’s possible that using similar approaches might work for other inherited forms of progressive hearing loss.”
In mice with a mutation that induces hearing loss, treatment with HDAC inhibitors partially restored the organization and structure of hair cells (pictured above).
Young women with high body fat have a decreased chance of developing breast cancer before menopause, according to scientists at the National Institutes of Health and their collaborators. The finding, published online in the journal JAMA Oncology, may help researchers better understand the role obesity plays in breast cancer risk.
"It is well known that women who gain weight, particularly after menopause, carry an increased risk of postmenopausal breast cancer," said Dale Sandler, Ph.D., co-senior author and head of the Epidemiology Branch at the National Institute of Environmental Health Sciences (NIEHS), part of NIH. "Our finding that breast cancer risk is not increased in obese premenopausal women, and in fact decreases, points to the possibility that different biologic mechanisms are responsible for causing breast cancer in younger women."
Women in early pregnancy who have high levels of a certain thyroid hormone may be at greater risk for gestational diabetes, compared to women who have normal levels of the hormone, according to researchers at the National Institutes of Health. Their study appears in the Journal of Clinical Endocrinology and Metabolism.
The researchers found that pregnant women with the highest levels of the thyroid hormone triiodothyronine (T3), were more than four times more likely to develop gestational diabetes, compared to women with lower levels of the hormone. T3 is produced from the related hormone thyroxine (T4). The researchers also found that a high T3/T4 ratio — which indicates a high conversion rate from T4 to T3 — was strongly associated with a higher risk for gestational diabetes.
