In the News

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:

Featured Article

Here’s when your weight loss will plateau, according to science

Monday, April 22, 2024

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 to drop 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.

For childhood cancer survivors, inherited genetic factors influence risk of cancers later in life

NIH-led study sheds light on the causes of new cancers among childhood cancer survivors and could have implications for their screening and follow-up

Common inherited genetic factors that predict cancer risk in the general population may also predict elevated risk of new cancers among childhood cancer survivors, according to a study led by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health. The findings, published in Nature Medicine, provide additional evidence that genetics may play an important role in the development of subsequent cancers in survivors of childhood cancer and suggest that common inherited variants could potentially inform screening and long-term follow-up of those at greatest risk.

Childhood cancer survivors are known to have a higher risk of developing a new cancer later in life due to adverse effects of cancer treatment or rare inherited genetic factors. In the new study, the researchers evaluated the combined effect of common variants with history of radiation treatment and found the resulting elevated cancer risk was greater than the sum of the individual associations for treatment and genetic factors alone.

“Knowledge about a person’s genetic makeup could potentially be useful in managing their risk of subsequent cancers,” said lead investigator Todd M. Gibson, Ph.D., of NCI’s Division of Cancer Epidemiology and Genetics. “The hope would be that, in the future, we can incorporate genetics along with treatment exposures and other risk factors to provide a more complete picture of a survivor’s risk of subsequent cancers to help guide their long-term follow-up care.”

New antibodies target “dark side” of influenza virus protein

NIH researchers explore hidden, vulnerable region of influenza neuraminidase

Researchers at the National Institutes of Health have identified antibodies targeting a hard-to-spot region of the influenza virus, shedding light on the relatively unexplored “dark side” of the neuraminidase (NA) protein head. The antibodies target a region of the NA protein that is common among many influenza viruses, including H3N2 subtype viruses, and could be a new target for countermeasures. The research, led by scientists at the National Institute of Allergy and Infectious Diseases’ Vaccine Research Center, part of NIH, was published today in Immunity.

Influenza, or flu, sickens millions of people across the globe each year and can lead to severe illness and death. While vaccination against influenza reduces the burden of the disease, updated vaccines are needed each season to provide protection against the many strains and subtypes of the rapidly evolving virus. Vaccines that provide protection against a broad range of influenza viruses could prevent outbreaks of new and reemerging flu viruses without the need for yearly vaccine reformulation or vaccinations.

One way to improve influenza vaccines and other countermeasures is to identify new targets on the virus’s surface proteins in “conserved” regions — portions that tend to be relatively unchanged between different strains of the virus. Influenza NA is a surface protein containing a globular head portion and a narrow stalk portion. The underside of the NA head contains a highly conserved region with targets for antibodies — known as epitopes — that make it vulnerable to antibody binding and inhibition of the virus, as well as not being impacted by mutations common in drug-resistant strains. This region is termed the “dark side” due to its partially hidden location and relatively unexplored characteristics.

IRP study offers new clues into the causes of post-infectious ME/CFS

In-depth study finds brain, immune, and metabolic abnormalities linked to debilitating chronic disease

In a detailed clinical study, researchers at the National Institutes of Health have found differences in the brains and immune systems of people with post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS). They also found distinct differences between men and women with the disease. The findings were published in Nature Communications.

“People with ME/CFS have very real and disabling symptoms, but uncovering their biological basis has been extremely difficult,” said Walter Koroshetz, M.D., director of NIH’s National Institute of Neurological Disorders and Stroke (NINDS). “This in-depth study of a small group of people found a number of factors that likely contribute to their ME/CFS. Now researchers can test whether these findings apply to a larger patient group and move towards identifying treatments that target core drivers of the disease.”

A team of multidisciplinary researchers discovered how feelings of fatigue are processed in the brains of people with ME/CFS. Results from functional magnetic resonance imaging (fMRI) brain scans showed that people with ME/CFS had lower activity in a brain region called the temporal-parietal junction (TPJ), which may cause fatigue by disrupting the way the brain decides how to exert effort.

Researchers identify brain hub with key role in learned response to direct and indirect threats

NIH-supported study in mice could inform treatments of trauma- and stress-related psychiatric conditions

Scientists have identified an area within the brain’s frontal cortex that may coordinate an animal’s response to potentially traumatic situations. Understanding where and how neural circuits involving the frontal cortex regulate such functions, and how such circuits could malfunction, may provide insight about their role in trauma-related and stress-related psychiatric disorders in people. The study, led by scientists at the National Institute on Alcohol Abuse and Alcoholism (NIAAA), a part of the National Institutes of Health, was published in Nature.

“Experiencing traumatic events is often at the root of trauma-related and stress-related psychiatric conditions, including alcohol use disorder (AUD),” said the study’s senior author, Andrew Holmes, Ph.D., senior investigator in NIAAA’s Laboratory of Behavioral and Genomic Neuroscience. “Additionally, witnessing others experience traumatic events can also contribute to these disorders.”

In animal models of stress and trauma, learning about potential sources of threat by observing how others deal with danger can be an effective way to avoid harm. Understanding the differences in how the brain processes direct experience of a threat compared to observing another’s response to a threat may shed light on factors that predispose humans to trauma- and stress-related psychiatric disorders.

Diagram of mouse prefrontal cortex showing neural projections to the midbrain (purple) and the amygdala (green), pathways involved in learning about threat

Diagram of mouse prefrontal cortex showing neural projections to the midbrain (purple) and the amygdala (green), pathways involved in learning about threat.

NIH selects Dr. Sean Mooney as director of the Center for Information Technology

National Institutes of Health Director Monica M. Bertagnolli, M.D., has named Sean Mooney, Ph.D., as director of NIH’s Center for Information Technology (CIT). Dr. Mooney is expected to join NIH in mid-March.

“Dr. Mooney has spent his career developing effective and collaborative computing systems to support biomedical research. His background in bioinformatics and expertise in the implementation and governance of a multi-faceted research IT department make him particularly suited to lead NIH CIT,” said Dr. Bertagnolli. “I look forward to welcoming Dr. Mooney to the NIH leadership team and extend my gratitude to Ivor D’Souza who is serving as acting director of CIT following the retirement of former director Andrea Norris in September 2022.”

As CIT director, Dr. Mooney will oversee an approximately $400 million portfolio that includes a world-renowned supercomputer that allows researchers to conduct large-scale data analyses; a state-of-the-art network that enables research across NIH and around the world; cloud-based services that give researchers a cost-effective way to access datasets and advanced computational tools and services; and the latest collaboration tools to promote flexibility and productivity. CIT collaborates with the NIH intramural community in computational bioscience, engineering, informatics and statistics to help make biomedical discoveries that protect and improve our nation’s health. Additionally, CIT provides IT infrastructure and IT services to support all of NIH.

Dr. Sean Mooney

Dr. Sean Mooney

New direct links discovered between the brain and its surrounding environment

NIH collaboration has implications for neural-immune system responses and aging

In a recent study of the brain’s waste drainage system, researchers from Washington University in St. Louis, collaborating with investigators at the National Institute of Neurological Disorders and Stroke (NINDS), a part of the National Institute of Health (NIH), discovered a direct connection between the brain and its tough protective covering, the dura mater. These links may allow waste fluid to leave the brain while also exposing the brain to immune cells and other signals coming from the dura. This challenges the conventional wisdom which has suggested that the brain is cut off from its surroundings by a series of protective barriers, keeping it safe from dangerous chemicals and toxins lurking in the environment.

“Waste fluid moves from the brain into the body much like how sewage leaves our homes,” said NINDS’s Daniel S. Reich, M.D., Ph.D. “In this study, we asked the question of what happens once the ‘drain pipes’ leave the ‘house’ — in this case, the brain — and connect up with the city sewer system within the body.” Reich’s group worked jointly with the lab of Jonathan Kipnis, Ph.D., a professor at Washington University in St. Louis.

Reich’s lab used high-resolution magnetic resonance imaging (MRI) to observe the connection between the brain and body’s lymphatic systems in humans. Meanwhile Kipnis’s group was independently using live-cell and other microscopic brain imaging techniques to study these systems in mice.

MRI images showing fluid containing light-emitting molecules slipping through the arachnoid barrier where blood vessels pass through

Fluid containing light-emitting molecules was seen to slip through the arachnoid barrier where blood vessels passed through.

Abnormal proteins found in the spinal fluid of people with ALS and frontotemporal dementia

Proteins could serve as biomarkers that improve diagnosis and guide the development of novel therapies

Researchers at the National Institutes of Health detected abnormal proteins in the spinal fluid of people with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), which could help improve diagnosis of these diseases. The findings were published in Science Translational Medicine.

The proteins in question are built from 'cryptic' exons — abnormal portions of RNA, the cell’s instructions for how to build proteins. Cryptic exons occur when TDP-43, a protein that regulates how RNA is processed, stops functioning normally. TDP-43 dysfunction is linked to ALS, FTD, Alzheimer’s disease, and Limbic Associated TDP-43 Encephalopathy (LATE).

The study showed that these mis-spliced sections of RNA can sometimes generate new proteins from the cryptic sequence. The findings advance our understanding of how cryptic exons may be involved in the dementia disease process and could help identify diseases involving TDP-43 dysfunction before symptoms appear. Currently, TDP-43 aggregates in the brain can only be detected at autopsy.

Protein containing a cryptic peptide (red) that results from a lack of functional TDP-43

Protein containing a cryptic peptide (red) that results from a lack of functional TDP-43, as in ALS and FTD.

IRP analysis reveals a significant rise in use of complementary health approaches, especially for pain management

An analysis conducted by the National Institutes of Health’s National Center for Complementary and Integrative Health (NCCIH) reveals a substantial increase in the overall use of complementary health approaches by American adults from 2002 to 2022. The study, published in the Journal of the American Medical Association, highlights a surge in the adoption of complementary health approaches for pain management over the same period.

Researchers utilized data from the 2002, 2012, and 2022 National Health Interview Survey (NHIS) to evaluate changes in the use of seven complementary health approaches, including yoga, meditation, massage therapy, chiropractic care, acupuncture, naturopathy, and guided imagery/progressive muscle relaxation.

Switching to vegan or ketogenic diet rapidly impacts immune system

Researchers at the National Institutes of Health observed rapid and distinct immune system changes in a small study of people who switched to a vegan or a ketogenic (also called keto) diet. Scientists closely monitored various biological responses of people sequentially eating vegan and keto diets for two weeks, in random order. They found that the vegan diet prompted responses linked to innate immunity — the body’s non-specific first line of defense against pathogens — while the keto diet prompted responses associated with adaptive immunity — pathogen-specific immunity built through exposures in daily life and vaccination. Metabolic changes and shifts in the participants’ microbiomes — communities of bacteria living in the gut — were also observed. More research is needed to determine if these changes are beneficial or detrimental and what effect they could have on nutritional interventions for diseases such as cancer or inflammatory conditions.

Scientific understanding of how different diets impact the human immune system and microbiome is limited. Therapeutic nutritional interventions — which involve changing the diet to improve health — are not well understood, and few studies have directly compared the effects of more than one diet. The keto diet is a low-carbohydrate diet that is generally high in fat. The vegan diet eliminates animal products and tends to be high in fiber and low in fat.

The study was conducted by researchers from the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at the Metabolic Clinical Research Unit in the NIH Clinical Center. The 20 participants were diverse with respect to ethnicity, race, gender, body mass index (BMI), and age. Each person ate as much as desired of one diet (vegan or keto) for two weeks, followed by as much as desired of the other diet for two weeks. People on the vegan diet, which contained about 10% fat and 75% carbohydrates, chose to consume fewer calories than those on the keto diet, which contained about 76% fat and 10% carbohydrates. Throughout the study period, blood, urine, and stool were collected for analysis. The effects of the diets were examined using a “multi-omics” approach that analyzed multiple data sets to assess the body’s biochemical, cellular, metabolic, and immune responses, as well as changes to the microbiome. Participants remained on site for the entire month-long study, allowing for careful control of the dietary interventions.

Researchers create safer form of Coxiella burnetii for scientific use

Scientists have unexpectedly discovered that the weakened form of the bacteria Coxiella burnetii (C. burnetii) not typically known to cause disease, naturally acquired an ability to do so. C. burnetii causes Q Fever in humans and its weakened forms are those used for scientific purposes. Subsequently, the scientists identified the genetic mutation responsible for the increased ability to cause disease (virulence) and created a form of the bacteria without the genetic flaw that could safely be used for research. The study, by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health and collaborators at Washington State University and Northern Arizona University, is published in Nature Communications.

C. burnetti naturally infects livestock, including goats, sheep and cattle. The bacterium causes Q Fever, a rare human disease with fewer than 1,000 cases annually reported in the United States. Individuals at highest risk for C. burnetii infection include farmers, veterinarians and animal researchers as infection is caused by breathing dust contaminated by infected animal products, such as feces, urine, milk, and birth products. Q Fever is characterized by mild-to-severe flu-like symptoms and can be treated with antibiotics. Those who develop severe disease may experience infection of the lungs (pneumonia) or liver (hepatitis). A small percentage of people (fewer than 5 out of 100) who are infected develop a more serious infection called chronic Q fever, which develops months or years following the initial infection. This condition requires months of antibiotic treatment and can result in death.

A dry fracture of a Vero cell exposing the contents of a vacuole where Coxiella burnetii are busy growing.

A dry fracture of a Vero cell exposing the contents of a vacuole where Coxiella burnetii are busy growing.

Continue Exploring the IRP

This page was last updated on Monday, April 22, 2024