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.
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).
Thirteen researchers have been selected for the inaugural class of the National Institutes of Health’s Distinguished Scholars Program (DSP). The NIH-wide pilot program is designed to build diversity within the NIH Intramural Research Program, comprised of NIH scientists, by facilitating hiring and career progression of tenure-track investigators who have demonstrated a commitment to promoting diversity and inclusion in the biomedical research workforce. In addition to funding, scholars will receive mentorship from senior NIH scientific leadership, professional development, and networking opportunities.
“Nurturing diversity in the NIH Intramural Research Program is paramount to upholding our mission,” said NIH Director Francis S. Collins M.D., Ph.D. “Research has shown that a diversity of perspectives is vital to the improved quality and number of discoveries in biomedical research. We are confident the Distinguished Scholars Program will serve as a model for universities to enhance faculty diversity and eliminate the attrition of underrepresented groups, including women, in the transition from training to independent careers.”
NIH launched DSP in early 2018 to enhance the recruitment and success of scientists committed to greater inclusion of groups underrepresented in biomedical research. Underrepresented groups include but are not limited to women, Blacks, Hispanics or Latinos, American Indians and Alaska Natives, Native Hawaiians and other Pacific Islanders, individuals with disabilities, and individuals from disadvantaged backgrounds.
Microbiome-triggered Th17 cells switch from protective to destructive; may be potential treatment targets
An unhealthy population of microbes in the mouth triggers specialized immune cells that inflame and destroy tissues, leading to the type of bone loss associated with a severe form of gum disease, according to a new study in mice and humans. The research, led by scientists from the National Institute of Dental and Craniofacial Research (NIDCR) at the National Institutes of Health and the University of Pennsylvania School of Dental Medicine, Philadelphia, could have implications for new treatment approaches for the condition. The findings appear online Oct. 17, 2018, in Science Translational Medicine.
Periodontal disease is a common disorder that affects nearly half of American adults over age 30, and 70 percent of adults 65 and older. In those affected, bacteria trigger inflammation of the tissues that surround the teeth, which can lead to loss of bone and teeth in an advanced stage of the disease called periodontitis.
“We’ve known for years that microbes stimulate inflammation. Removing bacteria by tooth-brushing and dental care controls inflammation, but not permanently, suggesting there are other factors at play,” said study senior author Niki Moutsopoulos, D.D.S., Ph.D., a clinical investigator at NIDCR. “Our results suggest that immune cells known as T helper 17 cells are drivers of this process, providing the link between oral bacteria and inflammation.”
A new study suggests that periodontal disease is driven by Th17 immune cells, which are triggered by an unhealthy bacterial community.
A novel vaccine designed to protect people from both Lassa fever and rabies showed promise in preclinical testing, according to new research published in Nature Communications. The investigational vaccine, called LASSARAB, was developed and tested by scientists at Thomas Jefferson University in Philadelphia; the University of Minho in Braga, Portugal; the University of California, San Diego; and the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
The inactivated recombinant vaccine candidate uses a weakened rabies virus vector, or carrier. The research team inserted genetic material from Lassa virus into the rabies virus vector so the vaccine expresses surface proteins from both the Lassa virus and the rabies virus. These surface proteins prompt an immune response against both Lassa and rabies viruses. The recombinant vaccine was then inactivated to “kill” the live rabies virus used to make the carrier.
This transmission electron microscopic (TEM) image depicts Lassa virus virions adjacent to some cell debris.
