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.
NIH study may inform ways to reduce male-to-female HIV transmission
Nano-sized vesicles released by certain bacteria that inhabit the vagina may protect against HIV infection, suggests a study of human cells and tissues by researchers at the National Institutes of Health and the University of Bologna, Italy. Known as extracellular vesicles, these bubble-like particles are produced by many kinds of cells and are thought to transport molecules from one cell to another. The study was led Leonid Margolis, Ph.D., of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). It appears in Nature Communications.
The researchers conducted a series of experiments showing that vesicles isolated from four strains of Lactobacillus bacteria interfere with the ability of HIV to infect cells. In one experiment, researchers added vesicles to cultures of immune cells known as T lymphocytes and infected the cultures with HIV. HIV infection in the treated cells was much lower than in the untreated cells. When the researchers increased the quantity of vesicles, a much smaller proportion of cells were infected.
Similarly, treatment with vesicles reduced HIV infection in human lymph and uterine cervix and vaginal tissues. The researchers found that bacterial vesicles suppressed the binding of viruses to the cell surface, an essential step before the virus can infect a cell. Further experiments showed that bacterial vesicles directly affect HIV rather than cells. Exposing the viruses to vesicles reduced the appearance of surface molecules on the virus’ outer covering, which it needs to attach to cells.
Diagram of a bacterial vesicle. Courtesy of the NICHD Section on Intercellular Interactions
Scientists at the National Institutes of Health found that women who use permanent hair dye and chemical hair straighteners have a higher risk of developing breast cancer than women who don’t use these products. The study published online Dec. 4 in the International Journal of Cancer and suggests that breast cancer risk increased with more frequent use of these chemical hair products.
Using data from 46,709 women in the Sister Study, researchers at the National Institute of Environmental Health Sciences (NIEHS), part of NIH, found that women who regularly used permanent hair dye in the year prior to enrolling in the study were 9% more likely than women who didn’t use hair dye to develop breast cancer. Among African American women, using permanent dyes every five to eight weeks or more was associated with a 60% increased risk of breast cancer as compared with an 8% increased risk for white women. The research team found little to no increase in breast cancer risk for semi-permanent or temporary dye use.
"Researchers have been studying the possible link between hair dye and cancer for a long time, but results have been inconsistent," said corresponding author Alexandra White, Ph.D., head of the NIEHS Environment and Cancer Epidemiology Group. "In our study, we see a higher breast cancer risk associated with hair dye use, and the effect is stronger in African American women, particularly those who are frequent users. "
The study found that women who use permanent hair dye and chemical hair straighteners have a higher risk of developing breast cancer than women who don’t use these products.
Scientists have determined that La Crosse virus, which can cause inflammation of the brain in children, affects brain cells differently depending on their developmental stage
Scientists have determined that La Crosse virus (LACV), which can cause inflammation of the brain in children, affects brain cells differently depending on their developmental stage. Neurons — the primary brain cells of the central nervous system — evolve from neural stem cells and during development “commit” to becoming neurons. A new National Institutes of Health study shows that uncommitted neural stems cells generally survive LACV infection, while LACV often kills neurons. The study also shows that neurons infected by LACV can be rescued by interferon, a powerful antiviral protein. The study results appear in the Journal of Neuroinflammation.
LACV is spread by mosquitoes and was first identified in the early 1960s. Most infections in people are mild but the virus sometimes—particularly in children—enters the brain, infects neurons and causes disease ranging from learning and memory difficulties to paralysis, seizures and death. The Centers for Disease Control and Prevention receives reports of an average of 68 LACV encephalitis cases each year in the United States, nearly all east of the Mississippi River.
The NIH scientists, from the National Institute of Allergy and Infectious Diseases Rocky Mountain Laboratories in Hamilton, Montana, used cerebral organoids to model how LACV infects the human brain. Cerebral organoids are small spheres of human brain cells ranging in size from that of a poppy seed to a small pea. Importantly, cerebral organoids contain different neuronal cell types, which allowed the investigators to assess the sensitivity of neural stem cells and neurons to LACV infection.
These images taken from LACV-infected cerebral organoids show infected cells (green) and cells that are dying from infection (magenta). The left image also shows neural stem cells (white) that have the potential to become neurons; these cells are rarely dying. In contrast, the image on the right shows committed neurons (white), many of which are shown to be dying.
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 443 scientists chosen as 2019 AAAS Fellows in recognition of their extraordinary achievements in advancing science:
John A. Beutler, Ph.D., of the National Cancer Institute (NCI) identifies and studies natural products that have the potential to be used as cancer treatments. He also builds and maintains a library of chemicals used to support high-throughput screening of compounds for molecularly-targeted cancer drug discovery.
Francesco DeMayo, Ph.D., of the National Institute of Environmental Health Sciences (NIEHS) studies the molecular mechanisms that regulate the functioning of the female reproductive system and the lungs, as well as how environmental factors contribute to diseases like endometriosis, endometrial cancer, and lung cancer.
Children of first-time mothers, those in home-based childcare log most screen time
Children’s average daily time spent watching television or using a computer or mobile device increased from 53 minutes at age 12 months to more than 150 minutes at 3 years, according to an analysis by researchers at the National Institutes of Health, the University at Albany and the New York University Langone Medical Center. By age 8, children were more likely to log the highest amount of screen time if they had been in home-based childcare or were born to first-time mothers. The study appears in JAMA Pediatrics.
NICHD researchers and their colleagues analyzed data from the Upstate KIDS Study, originally undertaken to follow the development of children conceived after infertility treatments and born in New York State from 2008 to 2010. Mothers of nearly 4,000 children who took part in the study responded to questions on their kids’ media habits when they were 12, 18, 24, 30, and 36 months of age. They also responded to similar questions when the children were 7 and 8 years old. The study compiled additional demographic information on the mothers and children from birth records and other surveys.
Among Asian/Pacific Islander women living in the United States, those who reside in ethnic enclaves — areas with a high concentration of residents of a similar ancestry — are less likely to have pregnancy or birth complications than those living in other areas, suggests a study by researchers at the National Institutes of Health and other institutions. The findings appear in the Journal of Racial and Ethnic Health Disparities.
Women in enclaves were less likely to have gestational diabetes, to deliver preterm, or to have an infant who was small for gestational age (a possible indicator of failure to grow adequately in the uterus). The researchers theorize that living in ethnic enclaves may improve health by offering easier access to health professionals of similar ancestry, access to traditional diets that are healthier than typical U.S. diets, and less incentive to engage in unhealthy habits like smoking and alcohol abuse.
Studies in cell and animal models reveal insights into cancer cells’ vulnerability that could lead to new strategies against brain cancers
Researchers have devised a new plan of attack against a group of deadly childhood brain cancers collectively called diffuse midline gliomas (DMG), including diffuse intrinsic pontine glioma (DIPG), thalamic glioma and spinal cord glioma. Scientists at the National Institutes of Health, Stanford University, California, and Dana-Farber Cancer Institute, Boston, identified a drug pair that worked together to both kill cancer cells and counter the effects of a genetic mutation that causes the diseases.
The researchers showed that combining the two drugs – panobinostat and marizomib – was more effective than either drug by itself in killing DMG patient cells grown in the laboratory and in animal models. Their studies also uncovered a previously unrecognized vulnerability in the cancer cells that scientists may be able to exploit to develop new strategies against the cancer and related diseases. The results were published Nov. 20 in Science Translational Medicine.
DIPG is a rare, deadly childhood brain cancer. Here, a confocal micrograph shows DIPG cells, grown from patient cells, in culture.
Safety data analyzed from five NIH inpatient clinical trials
National Institutes of Health researchers found that a single, low-dose ketamine infusion was relatively free of side effects for patients with treatment-resistant depression. Elia Acevedo-Diaz, M.D., Carlos Zarate, M.D., and colleagues at the NIH’s National Institute of Mental Health (NIMH) report their findings in the Journal of Affective Disorders.
Studies have shown that a single, subanesthetic-dose (a lower dose than would cause anesthesia) ketamine infusion can often rapidly relieve depressive symptoms within hours in people who have not responded to conventional antidepressants, which typically take weeks or months to work. However, widespread off-label use of intravenous subanesthetic-dose ketamine for treatment-resistant depression has raised concerns about side effects, especially given its history as a drug of abuse.
“The most common short-term side effect was feeling strange or loopy,” said Acevedo-Diaz, of the Section on the Neurobiology and Treatment of Mood Disorders, part of the NIMH Intramural Research Program (IRP) in Bethesda, Maryland. “Most side effects peaked within an hour of ketamine administration and were gone within two hours. We did not see any serious, drug-related adverse events or increased ketamine cravings with a single-administration.”
Technique key to scale up manufacturing of therapies from induced pluripotent stem cells
Researchers used artificial intelligence (AI) to evaluate stem cell-derived “patches” of retinal pigment epithelium (RPE) tissue for implanting into the eyes of patients with age-related macular degeneration (AMD), a leading cause of blindness.
The proof-of-principle study helps pave the way for AI-based quality control of therapeutic cells and tissues. The method was developed by researchers at the National Eye Institute (NEI) and the National Institute of Standards and Technology (NIST) and is described in a report appearing online today in the Journal of Clinical Investigation. NEI is part of the National Institutes of Health.
“This AI-based method of validating stem cell-derived tissues is a significant improvement over conventional assays, which are low-yield, expensive, and require a trained user,” said Kapil Bharti, Ph.D., a senior investigator in the NEI Ocular and Stem Cell Translational Research Section.
“Our approach will help scale up manufacturing and will speed delivery of tissues to the clinic,” added Bharti, who led the research along with Carl Simon Jr., Ph.D., and Peter Bajcsy, Ph.D., of NIST.
Scanning electron micrograph showing iPS cell-derived RPE tissue (gray) cultured on a fiber-based scaffold (blue).
Exceptional early stage scientists mark NIH’s commitment to build the next generation of biomedical researchers
The National Institutes of Health has selected five scientists as Lasker Clinical Research Scholars, part of a joint initiative with the Albert and Mary Lasker Foundation, to continue building a pipeline of exemplary clinical scientists. This highly competitive program provides talented, early stage researchers the opportunity to carry out independent clinical and translational research for five to seven years at NIH. The researchers also have the possibility of additional years of financial support, at NIH or an NIH-funded research institution, upon project review. The new researchers join 23 Lasker Scholars hired since 2012.
“The addition of these five creative minds to the Lasker Clinical Research Scholars program builds upon a remarkable foundation of clinician-scientists who will lead the NIH in producing innovative biomedical discoveries,” said NIH Director Francis S. Collins, M.D., Ph.D.
Lasker Scholars have access to the NIH Clinical Center, the largest hospital in the world devoted to clinical research. The Lasker Foundation will provide additional developmental support to the scholars while they are working at NIH by funding travel to scientific meetings and providing the opportunity to participate in selected foundation activities, including the Lasker Award ceremonies.
