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:
BETHESDA, Md. (AP) — Sam Srisatta, a 20-year-old Florida college student, spent a month living inside a government hospital here last fall, playing video games and allowing scientists to document every morsel of food that went into his mouth.
From big bowls of salad to platters of meatballs and spaghetti sauce, Srisatta noshed his way through a nutrition study aimed at understanding the health effects of ultraprocessed foods, the controversial fare that now accounts for more than 70% of the U.S. food supply. He allowed The Associated Press to tag along for a day.
“Today my lunch was chicken nuggets, some chips, some ketchup,” said Srisatta, one of three dozen participants paid $5,000 each to devote 28 days of their lives to science. “It was pretty fulfilling.”
Examining exactly what made those nuggets so satisfying is the goal of the widely anticipated research led by National Institutes of Health nutrition researcher Kevin Hall.
“What we hope to do is figure out what those mechanisms are so that we can better understand that process,” Hall said.
Gene expression data suggest potential role of sex chromosomes
A scientific analysis of more than 2,000 brain scans found evidence for highly reproducible sex differences in the volume of certain regions in the human brain. This pattern of sex-based differences in brain volume corresponds with patterns of sex-chromosome gene expression observed in postmortem samples from the brain’s cortex, suggesting that sex chromosomes may play a role in the development or maintenance of sex differences in brain anatomy. The study, led by researchers at the National Institute of Mental Health (NIMH), part of the National Institutes of Health, is published in Proceedings of the National Academy of Sciences.
“Developing a clearer understanding of sex differences in human brain organization has great importance for how we think about well-established sex differences in cognition, behavior, and risk for psychiatric illness. We were inspired by new findings on sex differences in animal models and wanted to try to close the gap between these animal data and our models of sex differences in the human brain,” said Armin Raznahan, M.D., Ph.D., study co-author and chief of the NIMH Section on Developmental Neurogenomics.
Researchers have long observed consistent sex-based differences in subcortical brain structures in mice. Some studies have suggested these anatomical differences are largely due to the effects of sex hormones, lending weight to a “gonad-centric” explanation for sex-based differences in brain development. However, more recent mouse studies have revealed consistent sex differences in cortical structures, as well, and gene-expression data suggest that sex chromosomes may play a role in shaping these anatomical sex differences. Although the mouse brain shares many similarities with the human brain, it is not clear whether these key findings in mice also apply to humans.
The accomplishment opens a new era in genomics research
Researchers at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, have produced the first end-to-end DNA sequence of a human chromosome. The results, published today in Nature, show that generating a precise, base-by-base sequence of a human chromosome is now possible, and will enable researchers to produce a complete sequence of the human genome.
Humans have two sets of chromosomes, one set from each parent. For example, biologically female humans inherit two X chromosomes, one from their mother and one from their father. However, those two X chromosomes are not identical and will contain many differences in their DNA sequences.
In this study, researchers did not sequence the X chromosome from a normal human cell. Instead, they used a special cell type – one that has two identical X chromosomes. Such a cell provides more DNA for sequencing than a male cell, which has only a single copy of an X chromosome. It also avoids sequence differences encountered when analyzing two X chromosomes of a typical female cell.
NIH study may help explain why the virus has rarely been found in fetuses or newborns of women with COVID-19
The placental membranes that contain the fetus and amniotic fluid lack the messenger RNA (mRNA) molecule required to manufacture the ACE2 receptor, the main cell surface receptor used by the SARS-CoV-2 virus to cause infection, according to a study by researchers at the National Institutes of Health. Their findings appear in the journal eLife.
These placental tissues also lack mRNA needed to make an enzyme, called TMPRSS2, that SARS-CoV-2 uses to enter a cell. Both the receptor and enzyme are present in only miniscule amounts in the placenta, suggesting a possible explanation for why SARS-CoV-2 has only rarely been found in fetuses or newborns of women infected with the virus, according to the study authors.
The researchers, led by Roberto Romero, M.D., chief of the Perinatology Research Branch at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), found that the placenta contains molecules that previous studies have suggested as potential routes for SARS-CoV-2 infection, including the CD147 receptor and the enzymes cathepsin L and Furin. They also detected in placental and membrane tissue a type of macrophage (immune cell) that has the ACE2 receptor. However, they noted that there is little evidence showing that infected macrophages could spread the SARS-CoV-2 virus to the placenta, membranes and fetus in normal pregnancy.
For every cell in the body there comes a time when it must decide what it wants to do for the rest of its life. In an article published in the journal PNAS, National Institutes of Health researchers report for the first time that ancient viral genes that were once considered “junk DNA” may play a role in this process. The article describes a series of preclinical experiments that showed how some human endogenous retrovirus (HERV-K) genes inscribed into chromosomes 12 and 19 may help control the differentiation, or maturation, of human stem cells into the trillions of neurons that are wired into our nervous systems. The experiments were performed by researchers in a lab led by Avindra Nath, M.D., clinical director, at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS).
Over the course of evolution, the human genome has absorbed thousands of human endogenous retrovirus genes. As a result, nearly eight percent of the DNA that lines our chromosomes includes remnants of these genes. Although once thought to be inactive, or “junk”, recent studies have shown that these genes may be involved in human embryonic development, the growth of some tumors, and nerve damage during multiple sclerosis. Previously, researchers in Dr. Nath’s lab showed that amyotrophic lateral sclerosis (ALS) may be linked to activation of the HERV-K gene. In this study, led by Tongguang (David) Wang, M.D., Ph.D., staff scientist at NINDS, the team showed that deactivation of the gene may free stem cells to become neurons.
Comparing epigenetic differences between humans and domestic dogs provides an emerging model of aging
One of the most common misconceptions is that one human year equals seven dog years in terms of aging. However, this equivalency is misleading and has been consistently dismissed by veterinarians. A recent study, published in the journal Cell Systems, lays out a new framework for comparing dog-to-human aging. In one such comparison, the researchers found the first eight weeks of a dog’s life is comparable to the first nine months of human infancy, but the ratio changes over time. The research used epigenetics, a process by which modifications occur in the genome, as a biological marker to study the aging process. By comparing when and what epigenetic changes mark certain developmental periods in humans and dogs, researchers hope to gain specific insight into human aging as well.
Researchers performed a comprehensive analysis and quantitatively compared the progression of aging between two mammals, dogs and humans. Scientists at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, and collaborators at the University of California (UC) San Diego, UC Davis and the University of Pittsburgh School of Medicine carried out the research.
All mammals experience the same overarching developmental timeline: birth, infancy, youth, puberty, adulthood and death. But researchers have long sought specific biological events that govern when such life stages take place. One means to study such a progression involves epigenetics — gene expression changes caused by factors other than the DNA sequence itself. Recent findings have shown that epigenetic changes are linked to specific stages of aging and that these are shared among species.
A study from the National Institutes of Health confirms that neurofilament light chain as a blood biomarker can detect brain injury and predict recovery in multiple groups, including professional hockey players with acute or chronic concussions and clinic-based patients with mild, moderate, or severe traumatic brain injury. The research was conducted by scientists at the NIH Clinical Center, Bethesda, Maryland, and published in the July 8, 2020, online issue of Neurology.
After a traumatic brain injury, neurofilament light chain breaks away from neurons in the brain and collects in the cerebrospinal fluid (CSF). The scientists confirmed that neurofilament light chain also collects in the blood in levels that correlate closely with the levels in the CSF. They demonstrated that neurofilament light chain in the blood can detect brain injury and predict recovery across all stages of traumatic brain injury.
“Currently, there are no validated blood-based biomarkers to provide an objective diagnosis of mild traumatic brain injury or to predict recovery,” said Leighton Chan, M.D., M.P.H., chief of the Rehabilitation Medicine Department at the NIH Clinical Center. “Our study reinforces the need and a way forward for a non-invasive test of neurofilament light chain to aid in the diagnosis of patients and athletes whose brain injuries are often unrecognized, undiagnosed or underreported."
Neurofilament light chain on a neuron. Image credit: Pashtun Shahim, M.D., Ph.D.
Large-scale study of U.S. teens shows associations between outdoor, artificial light at night and health outcomes
Research shows that adolescents who live in areas that have high levels of artificial light at night tend to get less sleep and are more likely to have a mood disorder relative to teens who live in areas with low levels of night-time light. The research was funded by the National Institute of Mental Health (NIMH), part of the National Institutes of Health, and is published in JAMA Psychiatry.
“These findings illustrate the importance of joint consideration of both broader environmental-level and individual-level exposures in mental health and sleep research,” says study author Diana Paksarian, Ph.D., a postdoctoral research fellow at NIMH.
Daily rhythms, including the circadian rhythms that drive our sleep-wake cycles, are thought to be important factors that contribute to physical and mental health. The presence of artificial light at night can disrupt these rhythms, altering the light-dark cycle that influences hormonal, cellular, and other biological processes. Researchers have investigated associations among indoor artificial light, daily rhythms, and mental health, but the impact of outdoor artificial light has received relatively little attention, especially in teens.
In this study, Paksarian, Kathleen Merikangas, Ph.D., senior investigator and chief of the Genetic Epidemiology Research Branch at NIMH, and coauthors examined data from a nationally representative sample of adolescents in the United States, which was collected from 2001 to 2004 as part of the National Comorbidity Survey Adolescent Supplement (NCS-A). The dataset included information about individual-level and neighborhood-level characteristics, mental health outcomes, and sleep patterns for a total of 10,123 teens, ages 13 to 18 years old.
Iodine solutions are commonly used as disinfectants to prepare the skin for surgical or other procedures
Exposure to iodine used for medical procedures in a neonatal intensive care unit (NICU) may increase an infant’s risk for congenital hypothyroidism (loss of thyroid function), suggests a study by researchers at the National Institutes of Health and other institutions. The authors found that infants diagnosed with congenital hypothyroidism following a NICU stay had higher blood iodine levels on average than infants who had a NICU stay but had normal thyroid function. Their study appears in The Journal of Nutrition.
“Limiting iodine exposure among this group of infants whenever possible may help lower the risk of losing thyroid function,” said the study’s first author, James L. Mills, M.D., of the Epidemiology Branch at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).
Congenital hypothyroidism is a partial or complete loss of thyroid function. The thyroid, located in the throat, makes iodine-containing hormones that regulate growth, brain development and the rate of chemical reactions in the body. Treatment consists of thyroid hormone therapy and must begin within four weeks after birth or permanent intellectual disability may result.
National Institutes of Health Director Francis S. Collins, M.D., Ph.D., has selected Shannon N. Zenk, Ph.D., M.P.H., R.N., F.A.A.N., as director of NIH’s National Institute of Nursing Research (NINR). A registered nurse and leading nurse researcher, Dr. Zenk is currently Nursing Collegiate Professor in the Department of Population Health Nursing Science at the University of Illinois at Chicago (UIC) College of Nursing, and a fellow at the UIC Institute for Health Research and Policy. She is expected to begin her new role as the NINR director in early fall. NINR supports and conducts basic and clinical research that spans and integrates the behavioral and biological sciences and develops the scientific basis for clinical practice.
“Dr. Zenk’s diverse and original research experience paired with her expertise as a nurse educator make her an ideal choice to lead NIH’s efforts in nursing science,” said Dr. Collins. “I am delighted to have her join the NIH leadership team in the fall. I also want to recognize Tara A. Schwetz, Ph.D., for her exemplary leadership in serving as the NINR acting director since January 2020, in addition to her role as NIH associate deputy director in the NIH Office of the Director.”
As NINR director, Dr. Zenk will oversee NINR’s annual budget of nearly $170 million, the large majority of which supports extramural research at institutions across the Nation. NINR science seeks to improve the lives of individuals and families living with illness and to develop personalized strategies to maximize health and well-being at all stages of life, and across diverse populations and settings. NINR’s intramural program on the NIH campus conducts research to better understand and manage symptoms. Within both of those programs, NINR devotes significant resources to training and career development to foster the next generation of nurse scientists.
NIH researchers put complex, high-resolution data within reach for many more scientists
Scientists have developed new image processing techniques for microscopes that can reduce post-processing time up to several thousand-fold. The researchers are from the National Institutes of Health with collaborators at the University of Chicago and Zhejiang University, China.
In a paper published in Nature Biotechnology, Hari Shroff, Ph.D., chief of laboratory on High Resolution Optical Imaging at the National Institute of Biomedical Imaging and Bioengineering (NIBIB), describes new techniques that can significantly reduce the time needed to process the highly complex images that are created by the most cutting-edge microscopes. Such microscopes are often used to capture blood and brain cells moving through fish, visualize the neural development of worm embryos, and pinpoint individual organelles within entire organs.
As microscopes continue to get better, creating higher resolution images faster, researchers are finding they have more data than time to process it. While the videos themselves can be captured in minutes, the images could be terabytes in size and require weeks or, in some cases, months of processing time to be useable.
3D image of a mouse intestine with different antibodies in green, red, yellow, and purple.
