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.
Study findings can immediately be applied to human patients with the disease
Researchers have discovered that a hormone, fibroblast growth factor 21 (FGF21), is extremely elevated in mice with liver disease that mimics the same condition in patients with methylmalonic acidemia (MMA), a serious genomic disorder. Based on this finding, medical teams treating patients with MMA will be able to measure FGF21 levels to predict how severely patients’ livers are affected and when to refer patients for liver transplants. The findings also might shed light on more common disorders such as fatty liver disease, obesity and diabetes by uncovering similarities in how MMA and these disorders affect energy metabolism and, more specifically, the function of mitochondria, the cells’ energy powerhouses. The study, conducted by researchers at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, was published Dec. 6 in JCI Insight.
“Findings from mouse studies usually take years to translate into health care treatment, but not in this case,” said Charles P. Venditti, M.D., Ph.D., senior author and senior investigator in the NHGRI Medical Genomics and Metabolic Genetics Branch. “We can use this information today to ensure that patients with MMA are treated before they develop severe complications.”
An electron micrograph showing abnormally shaped and structured mitochondria in the liver of a mutant mouse that models methylmalonic acidemia.
The American Association for the Advancement of Science (AAAS) has elected four IRP investigators as AAAS Fellows this year. These incredibly accomplished individuals are among 416 scientists chosen as 2018 AAAS Fellows in recognition of their extraordinary achievements in advancing science:
Andy Baxevanis, Ph.D., of the National Human Genome Research Institute (NHGRI) was elected "for distinguished contributions to the field of comparative genomics, particularly for using computational approaches to study the molecular innovations driving diversity in early animal evolution."
Judith Walters, Ph.D., of the National Institute of Neurological Disorders and Stroke (NINDS) was elected "for distinguished contributions to understanding brain circuitry dysfunctions in Parkinson's disease, and for promoting outstanding mentorship of women scientists in the NIH Intramural Research Program."
The four IRP investigators elected as 2018 AAAS Fellows. Clockwise from top-left: Dr. Judith Walters, Dr. Andy Baxevanis, Dr. Mary Dasso, and Dr. Robert Angerer
Neurons in an ancient part of the brain encode decisions based on visual information
Scientists at the National Eye Institute (NEI) have found that neurons in the superior colliculus, an ancient midbrain structure found in all vertebrates, are key players in allowing us to detect visual objects and events. This structure doesn’t help us recognize what the specific object or event is; instead, it’s the part of the brain that decides something is there at all. By comparing brain activity recorded from the right and left superior colliculi at the same time, the researchers were able to predict whether an animal was seeing an event. The findings were published today in the journal Nature Neuroscience. NEI is part of the National Institutes of Health.
Perceiving objects in our environment requires not just the eyes, but also the brain’s ability to filter information, classify it, and then understand or decide that an object is actually there. Each step is handled by different parts of the brain, from the eye’s light-sensing retina to the visual cortex and the superior colliculus. For events or objects that are difficult to see (a gray chair in a dark room, for example), small changes in the amount of visual information available and recorded in the brain can be the difference between tripping over the chair or successfully avoiding it. This new study shows that this process — deciding that an object is present or that an event has occurred in the visual field — is handled by the superior colliculus.
“The superior colliculus plays a foundational role in our ability to process and detect events,” said Richard Krauzlis, Ph.D., principal investigator in the Laboratory of Sensorimotor Research at NEI and senior author of the study. “This new work not only shows that a specific population of neurons directly cause a behavior but also that a commonly used mathematical model can predict behavior based on these neurons.”
Greater activation of neurons on one side of the superior colliculus versus the other signals the detection of a relevant event.
Finding could help early diagnosis, raise concern for eye exams and transplants
National Institutes of Health scientists and their colleagues have found evidence of the infectious agent of sporadic Creutzfeldt-Jakob disease (CJD) in the eyes of deceased CJD patients. The finding suggests that the eye may be a source for early CJD diagnosis and raises questions about the safety of routine eye exams and corneal transplants. Sporadic CJD, a fatal neurodegenerative prion disease of humans, is untreatable and difficult to diagnose.
Prion diseases originate when normally harmless prion protein molecules become abnormal and gather in clusters and filaments in the body and brain. Scientists hope that early diagnosis of prion and related diseases—such as Alzheimer’s, Parkinson’s and dementia with Lewy bodies—could lead to effective treatments that slow or prevent these diseases. Scientists from NIH’s National Institute of Allergy and Infectious Diseases (NIAID) collaborated on the research with colleagues from the University of California at San Diego and UC-San Francisco.
About 40 percent of sporadic CJD patients develop eye problems that could lead to an eye exam, meaning the potential exists for the contamination of eye exam equipment designed for repeat use. Further, cadaveric corneal transplants from undiagnosed CJD patients have led to two probable and three possible cases of disease transmission, the researchers say.
Ocular tissues tested by real time quaking-induced conversion.
Exposure to uncomfortable sensations elicits a wide range of appropriate and quick reactions, from reflexive withdrawal to more complex feelings and behaviors. To better understand the body’s innate response to harmful activity, researchers at the National Center for Complementary and Integrative Health (NCCIH), part of the National Institutes of Health, have identified activity in the brain that governs these reactions. Using heat as the source of discomfort, experiments conducted by the center’s intramural program showed that bodily responses to pain are controlled by a neural pathway involving heightened activity in the spinal cord and two parts of the brainstem. Results of the study were published in the journal Neuron.
“Much is known about local spinal cord circuits for simple reflexive responses, but the mechanisms underlying more complex behaviors remain poorly understood,” said Alexander T. Chesler, Ph.D., a Stadtman Investigator at NCCIH and senior author of the study. “We set out to describe the brain pathway that controls motor responses and involuntary behaviors when the body is faced with painful experiences.”
Two different groups of parabrachial neurons, one expressing calcitonin gene-related peptide (green) and the other expressing substance P (red).
Technique enables direct imaging of neural tissue; could lead to earlier detection of diseases affecting eye tissue
By combining two imaging modalities — adaptive optics and angiography — investigators at the National Eye Institute (NEI) can see live neurons, epithelial cells, and blood vessels deep in the eye’s light-sensing retina. Resolving these tissues and cells in the outermost region of the retina in such unprecedented detail promises to transform the detection and treatment of diseases such as age-related macular degeneration (AMD), a leading cause of blindness among the elderly. NEI is part of the National Institutes of Health, and the paper was published online in Communications Biology.
“For studying diseases, there’s no substitute for watching live cells interact. However, conventional technologies are limited in their ability to show such detail,” said the paper’s lead author, Johnny Tam, Ph.D., Stadtman Investigator in the Clinical and Translational Imaging Unit at NEI.
Biopsied and postmortem tissues are commonly used to study disease at the cellular level, but they are less than ideal for watching subtle changes that occur as a disease progresses over time. Technologies for noninvasively imaging retinal tissues are hampered by distortions to light as it passes through the cornea, lens, and the gel-like vitreous in the center of the eye.
Images show multimodal technique using adaptive optics and angiography to simultaneously see photoreceptors (top), retinal pigment epithelial cells (center), and choriocapillaris in the living human eye.
National Institutes of Health scientists and their collaborators found that hepatitis B virus (HBV)-associated acute liver failure (ALF) — a rare condition that can turn fatal within days without liver transplantation — results from an uncommon encounter between a highly mutated HBV variant and an unusual immune response in the patient’s liver that is mainly sustained by antibody-producing B cells.
By applying state-of-the-art technologies, the researchers discovered important new mechanisms about the disease by examining liver samples taken from four patients who developed HBV-ALF. HBV-ALF is one of the most dramatic clinical syndromes in medicine, according to the research team, but so rare that samples of this type are seldom available for study.
This transmission electron microscopic (TEM) image revealed the presence of hepatitis B virus (HBV) particles (orange). The round virions, which measure 42nm in diameter, are known as Dane particles.
New research suggests that infant girls fed soy formula are more likely to develop severe menstrual pain as young adults. The finding adds to the growing body of literature that suggests exposure to soy formula during early life may have detrimental effects on the reproductive system. The study appears online in the journal Human Reproduction.
Scientists at the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health, along with collaborators from Vanderbilt University Medical Center in Nashville, Tennessee, and the Henry Ford Health System in Detroit, examined data from 1,553 African-American women, aged 23-35, participating in the NIEHS Study of Environment, Lifestyle, and Fibroids (SELF).
The researchers found that women who had ever been fed soy formula as babies were 50 percent more likely to have experienced moderate or severe menstrual discomfort between the ages of 18 and 22, and 40 percent more likely to have used hormonal contraception to help alleviate menstrual pain.
NTP releases final reports on rat and mouse studies of radio frequency radiation like that used in 2G and 3G cell phone technologies.
The National Toxicology Program (NTP) concluded there is clear evidence that male rats exposed to high levels of radio frequency radiation (RFR) like that used in 2G and 3G cell phones developed cancerous heart tumors, according to final reports released today. There was also some evidence of tumors in the brain and adrenal gland of exposed male rats. For female rats, and male and female mice, the evidence was equivocal as to whether cancers observed were associated with exposure to RFR. The final reports represent the consensus of NTP and a panel of external scientific experts who reviewed the studies in March after draft reports were issued in February.
“The exposures used in the studies cannot be compared directly to the exposure that humans experience when using a cell phone,” said John Bucher, Ph.D., NTP senior scientist. “In our studies, rats and mice received radio frequency radiation across their whole bodies. By contrast, people are mostly exposed in specific local tissues close to where they hold the phone. In addition, the exposure levels and durations in our studies were greater than what people experience.”
The lowest exposure level used in the studies was equal to the maximum local tissue exposure currently allowed for cell phone users. This power level rarely occurs with typical cell phone use. The highest exposure level in the studies was four times higher than the maximum power level permitted.
“We believe that the link between radio frequency radiation and tumors in male rats is real, and the external experts agreed,” said Bucher.
NIH findings in rodents suggest astrocytes play important role in how the brain processes information.
The transmission speed of neurons fluctuates in the brain to achieve an optimal flow of information required for day-to-day activities, according to a National Institutes of Health study. The results, appearing in PNAS, suggest that brain cells called astrocytes alter the transmission speed of neurons by changing the thickness of myelin, an insulation material, and the width of gaps in myelin called nodes of Ranvier, which amplify signals.
“Scientists used to think that myelin could not be thinned except when destroyed in demyelinating diseases, such as multiple sclerosis,” said R. Douglas Fields, Ph.D., senior author and chief of the Section on Nervous System Development and Plasticity at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). “Our study suggests that under normal conditions, the myelin sheath and structure of the nodes of Ranvier are dynamic, even in adults.”
The brain is composed of neurons, which have extensions called axons that can stretch for long distances. Axons are wrapped by layers of myelin, which serve as insulation to increase the speed of signals relayed by neurons. Gaps between segments of myelin are called nodes of Ranvier, and the number and width of these gaps can also regulate transmission speed.
3D reconstruction of electron microscopy images of a perinodal astrocyte (blue), node of Ranvier (gray), compact myelin (purple), and layers of myelin detaching from the axon (tan).
