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:
NIH-funded research raises possibility of designer treatments for common form of pain
Ever wonder why things that normally feel gentle, like putting on soft shirts, are painful after a sunburn? In a study of four patients with a rare genetic disorder, IRP researchers found that PIEZO2, a gene previously shown to control our sense of our bodies in space and gentle touch, may also be responsible for tactile allodynia: the skin’s reaction to injury that makes normally gentle touches feel painful. This and a second NIH-funded study, both published in Science Translational Medicine, used mice to show how the gene may play an essential role in the nervous system’s reaction to injury and inflammation, making PIEZO2 a target for developing precise treatments for relieving the pain caused by cuts, burns, and other skin injuries.
“For years scientists have been trying to solve the mystery of how gentle touch becomes painful. These results suggest PIEZO2 is the gene for tactile allodynia. We hope that these results will help researchers develop better treatments for managing this form of pain,” said Alexander T. Chesler, Ph.D., a Stadtman Investigator at the National Center for Complementary and Integrative Health (NCCIH) and a senior author of one of the studies.
An IRP study found that the PIEZO2 gene may control the skin’s reaction to injuries, like sunburns, that make gentle touches feel painful.
The severity of birth defects caused by Zika virus infection may be influenced by natural variations in a pregnant woman’s genes for a key enzyme, according to a study by researchers at the National Institutes of Health, Uniformed Services University of the Health Sciences, Federal University of Rio de Janeiro, and Professor Joaquim Amorim Neto Research Institute in Campina Grande, Brazil. The enzyme, adenylate cyclase, is required to make cyclic adenosine monophosphate (cAMP), which plays a role in placental development and other cellular processes, including the immune response to infection. The findings appear in the Journal of Internal Medicine.
The study enrolled 52 women who had given birth after testing positive for Zika virus infection. Of these women, 28 gave birth to children with reduced head size and other Zika-related birth defects; infants born to the remaining 24 women did not appear to have any Zika-related effects. After sequencing genes from the women, the researchers found that mothers of severely affected infants were more likely to have variations in two genes essential for making adenylate cyclase, ADCY3 and ADCY7.
The variation in ADCY3 has previously been associated with higher levels of adenylate cyclase, leading to higher levels of cAMP. The researchers believe higher cAMP levels could stimulate reproduction of the virus. Similarly, a variation in ADCY7 has been linked to lower levels of cAMP, which could protect against the virus’ effects. The authors note that, because of the relatively small number of women studied, additional research is needed to confirm these results. However, future research on drugs that influence cAMP production might yield potential therapies that protect against Zika exposure during pregnancy.
Findings in rat cell cultures could lead to new method for tracking communications throughout the brain
Neurons absorb and release water when they relay messages throughout the brain, according to a study by researchers at the National Institutes of Health and other institutions. Tracking this water movement with imaging technology may one day provide valuable information on normal brain activity, as well as how injury or disease affect brain function. The study appears in Magnetic Resonance in Medicine.
Current functional magnetic resonance imaging (fMRI) technologies measure neuronal activity indirectly by tracking changes in blood flow and blood oxygen levels. Neurons communicate with each other by a process known as firing. In this process, they emit a slight electrical charge as an enzyme moves positively charged molecules — potassium and sodium ions — through the cell membrane. In the current study, when researchers stimulated cell cultures of rat neurons to fire, they found that the exchanges of potassium and sodium ions was accompanied by an increase in the number of water molecules moving into and out of the cell.
The researchers noted that their method works only in cultures of neurons and additional studies are necessary to advance the technology so that it can be used to monitor neuronal firing in living organisms.
Increasing time between meals made male mice healthier overall and live longer compared to mice who ate more frequently, according to a new study published in the Sept. 6, 2018 issue of Cell Metabolism. Scientists from the National Institute on Aging (NIA) at the National Institutes of Health, the University of Wisconsin-Madison, and the Pennington Biomedical Research Center, Baton Rouge, Louisiana, reported that health and longevity improved with increased fasting time, regardless of what the mice ate or how many calories they consumed.
“This study showed that mice who ate one meal per day, and thus had the longest fasting period, seemed to have a longer lifespan and better outcomes for common age-related liver disease and metabolic disorders,” said NIA Director Richard J. Hodes, M.D. “These intriguing results in an animal model show that the interplay of total caloric intake and the length of feeding and fasting periods deserves a closer look.”
The scientists randomly divided 292 male mice into two diet groups. One group received a naturally sourced diet that was lower in purified sugars and fat, and higher in protein and fiber than the other diet. The mice in each diet group were then divided into three sub-groups based on how often they had access to food. The first group of mice had access to food around the clock. A second group of mice was fed 30 percent less calories per day than the first group. The third group was meal fed, getting a single meal that added up to the exact number of calories as the round-the-clock group. Both the meal-fed and calorie-restricted mice learned to eat quickly when food was available, resulting in longer daily fasting periods for both groups.
Asthma patients, with a specific genetic profile, exhibit more intense symptoms following exposure to traffic pollution, according to researchers at the National Institutes of Health and collaborators. The study appeared online in Scientific Reports.
The research team, made up of scientists from the National Institute of Environmental Health Sciences (NIEHS), part of NIH, and Rice University, Houston, also found that asthma patients that lack this genetic profile do not have the same sensitivity to traffic pollution and do not experience worse asthma symptoms. The work brings scientists closer to being able to use precision medicine, an emerging field that intends to prevent and treat disease based on factors specific to an individual.
Co-lead author Shepherd Schurman, M.D., associate medical director of the NIEHS Clinical Research Unit, stated the results are based on genetic variation, the subtle differences in DNA that make each person unique. He further added that to understand the concept, one should think of human genes, which are made up of DNA base pairs A, C, G, and T, as written instructions for making proteins.
The research suggests when individuals with specific variations in certain genes are exposed to traffic pollution, they display more intense asthma symptoms than people that lack those same gene variations.
IRP study identifies potential new target for malaria drug development
Researchers from the National Institutes of Health and other institutions have deciphered the role of a key protein that the malaria parasite Plasmodium falciparum uses to obtain nutrients while infecting red blood cells. Their study appears in Nature Microbiology.
According to the World Health Organization, in 2016 there were an estimated 216 million malaria cases and 445,000 malaria deaths. P. falciparum is responsible for most malaria-related deaths globally.
The parasite remodels the red blood cell it infects to obtain nutrients. During this process, the parasite secretes hundreds of proteins that need to be transported from the vacuole, the compartment in which the parasite resides, to the interior of the cell. A group of proteins, called the Plasmodium translocon of exported proteins (PTEX), has been shown to be essential for transporting materials to and from the vacuole. Previous studies have uncovered the function of one of the proteins in the PTEX group to reshape proteins for transport, but the function of other proteins in the group have not been well understood.
In the current study, researchers analyzing blood cell cultures from healthy people determined that the PTEX protein EXP2 forms a channel in the vacuole membrane, which allows for passage of proteins and cellular nutrients to supply the parasite. The researchers hope that their discovery will lead to the development of new drugs to prevent formation of the channel and block the transport of nutrients and proteins to the parasite.
Researchers at NIH have determined that the protein EXP2 forms a channel in the vacuole membrane, which allows for passage of proteins and cellular nutrients to supply the parasite.
In a new study, researchers developed a gene expression predictor that can indicate whether melanoma in a specific patient is likely to respond to treatment with immune checkpoint inhibitors, a novel type of immunotherapy. The predictor was developed by Noam Auslander, Ph.D., with other researchers in the Center for Cancer Research (CCR) at the National Cancer Institute (NCI), part of the National Institutes of Health, and colleagues at Harvard University, Cambridge, Massachusetts; the University of Pennsylvania, Philadelphia; and the University of Maryland, College Park. The study was published Aug. 20, 2018 in Nature Medicine.
“There is a critical need to be able to predict how cancer patients will respond to this type of immunotherapy,” said Eytan Ruppin, M.D., Ph.D., of NCI’s newly established Cancer Data Science Laboratory, who led the study. “Being able to predict who is highly likely to respond and who isn’t will enable us to more accurately and precisely guide patients’ treatment.”
Treatment with checkpoint inhibitors is effective for some patients with late-stage melanoma and certain other types of cancer. However, not all patients with melanoma respond to this treatment, and it can have considerable side effects. But developing a predictor of response has been challenging, partly because of the limited number of patients who have received this relatively new form of treatment.
IRP analysis suggests early screening could allow for lifestyle changes before condition develops
A blood test conducted as early as the 10th week of pregnancy may help identify women at risk for gestational diabetes, a pregnancy-related condition that poses potentially serious health risks for mothers and infants, according to researchers at the National Institutes of Health and other institutions. The study appears in Scientific Reports.
Gestational diabetes occurs only in pregnancy and results when the level of blood sugar, or glucose, rises too high. Gestational diabetes increases the mother’s chances for high blood pressure disorders of pregnancy and the need for cesarean delivery, and the risk for cardiovascular disease and type 2 diabetes later in life. For infants, gestational diabetes increases the risk for large birth size. Unless they have a known risk factor, such as obesity, women typically are screened for gestational diabetes between 24 and 28 weeks of pregnancy.
In the current study, researchers evaluated whether the HbA1c test (also called the A1C test), commonly used to diagnose type 2 diabetes, could identify signs of gestational diabetes in the first trimester of pregnancy. The test approximates the average blood glucose levels over the previous 2 or 3 months, based on the amount of glucose that has accumulated on the surface of red blood cells. According to the authors, comparatively few studies have examined whether the HbA1c test could help identify the risk for gestational diabetes, and these studies have been limited to women already at high risk for the condition. The test is not currently recommended to diagnose gestational diabetes at any point in pregnancy.
IRP study reveals prevalence of and risk factors for phantom odor perception
Imagine the foul smell of an ash tray or burning hair. Now imagine if these kinds of smells were present in your life, but without a source. A new study finds that 1 in 15 Americans (or 6.5 percent) over the age of 40 experiences phantom odors. The study, published in JAMA Otolaryngology-Head and Neck Surgery, is the first in the U.S. to use nationally representative data to examine the prevalence of and risk factors for phantom odor perception. The study could inform future research aiming to unlock the mysteries of phantom odors.
The study was led by Kathleen Bainbridge, Ph.D., of the Epidemiology and Biostatistics Program at the National Institute on Deafness and Other Communication Disorders (NIDCD), part of the National Institutes of Health. Bainbridge and her team used data from 7,417 participants over 40 years of age from the 2011-2014 National Health and Nutrition Examination Survey (NHANES). The NHANES data were collected by the National Center for Health Statistics, which is part of the Centers for Disease Control and Prevention; data collection was partly funded by the NIDCD.
"Problems with the sense of smell are often overlooked, despite their importance. They can have a big impact on appetite, food preferences, and the ability to smell danger signals such as fire, gas leaks, and spoiled food,” said Judith A. Cooper, Ph.D., acting director of the NIDCD.
In the past 15 years, two outbreaks of severe respiratory disease were caused by coronaviruses transmitted from animals to humans. In 2003, SARS-CoV (severe acute respiratory syndrome coronavirus) spread from civets to infect more than 8,000 people, leading to a year-long global public health emergency. MERS-CoV (Middle East respiratory syndrome coronavirus), first identified in 2012, consistently jumps from dromedary camels to people, resulting in periodic outbreaks with a roughly 35 percent fatality rate. Evidence suggests that both viruses originated in bats before transmitting to civets and camels, respectively. While many other coronaviruses in nature are not known to infect people, MERS-CoV and SARS-CoV are notable for their ability to infect a variety of different species, including humans.
New research published in Cell Reports from scientists at the National Institute of Allergy and Infectious Diseases (NIAID) shows how MERS-CoV can adapt to infect cells of a new species, which suggests that other coronaviruses might be able to do the same.
This illustration shows the bat species used in the study, Desmodus rotundus, or vampire bat, and representations of MERS-CoV (purple) interacting with host receptor DPP4 (gold).
