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.
The immune system’s attempt to eliminate Salmonella bacteria from the gastrointestinal (GI) tract instead facilitates colonization of the intestinal tract and fecal shedding, according to National Institutes of Health scientists. The study, published in Cell Host & Microbe, was conducted by National Institute of Allergy and Infectious Diseases (NIAID) scientists at Rocky Mountain Laboratories in Hamilton, Montana.
Salmonella Typhimurium bacteria (hereafter Salmonella) live in the gut and often cause gastroenteritis in people. The Centers for Disease Control and Prevention estimates Salmonella bacteria cause about 1.35 million infections, 26,500 hospitalizations and 420 deaths in the United States every year. Contaminated food is the source for most of these illnesses. Most people who get ill from Salmonella have diarrhea, fever and stomach cramps but recover without specific treatment. Antibiotics typically are used only to treat people who have severe illness or who are at risk for it.
Salmonella bacteria also can infect a wide variety of animals, including cattle, pigs and chickens. Although clinical disease usually resolves within a few days, the bacteria can persist in the GI tract for much longer. Fecal shedding of the bacteria facilitates transmission to new hosts, especially by so-called “super shedders” that release high numbers of bacteria in their feces.
National Institutes of Health Director Francis S. Collins, M.D., Ph.D., has selected Marie A. Bernard, M.D., as NIH’s next Chief Officer for Scientific Workforce Diversity (COSWD). She will lead NIH’s effort to promote diversity, inclusiveness, and equity throughout the biomedical research enterprise. Dr. Bernard has served as the acting COSWD since October 2020, after the retirement of Hannah A. Valantine, M.D., who served as NIH’s first-ever COSWD. Dr. Bernard has also served as the deputy director of the National Institute on Aging (NIA) since October 2008.
“Dr. Bernard is an accomplished physician-scientist and has championed diversity and inclusion efforts over her entire career, including serving a leadership role in NIH’s most recent efforts to end structural racism in biomedical research through the UNITE initiative,” said Dr. Collins. “Her dedication and passion in creating equity and inclusion throughout the biomedical research enterprise are profound and inspiring. I am delighted that she will now be continuing in this vital leadership role for NIH on a permanent basis.”
Dr. Bernard has played key leadership roles in a broad variety of NIH activities to further diversity, including serving as a co-chair of the UNITE initiative, and leading the development of the NIA Health Disparities Research Framework, which guides NIA research in this area. She also directed and supervised the NIA Office of Special Populations, which leads health disparities research and training for scientists from diverse backgrounds within NIA.
Marie A. Bernard, M.D., NIH Chief Officer for Scientific Workforce Diversity
Two clusters of brain cells compete to promote either the persistence or disappearance of traumatic memories, according to a new study conducted in mice. The findings could provide important insights into human conditions such as post-traumatic stress disorder (PTSD), anxiety disorders, and associated problems such as alcohol use disorder (AUD) that can arise from the persistence of traumatic memories. The new research, led by scientists at the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health, and their colleagues in Switzerland, is reported in the journal Nature.
“Over time, the distress of having experienced trauma will subside for some people, as memories of the trauma cease to provoke a fearful response,” says NIAAA Director Dr. George F. Koob. “For other people who have experienced trauma, however, the fearful memories persist, and can adversely affect their ability to engage in everyday activities. These fearful memories can continue even though a person may repeatedly encounter cues associated with a traumatic experience without a harm. The current study sheds light on the specific neural circuits that may underlie the persistence and the extinction of fearful memories associated with trauma.”
Scientists led by Andrew Holmes, Ph.D., chief of NIAAA’s Laboratory of Behavioral and Genomic Neuroscience, examined clusters of neurons, known as intercalated cells or ITCs, that are packed tightly around the mouse amygdala. Found deep within the temporal lobes of mammals’ brains, the amygdala is well-known as a hub for processing emotions. It is therefore a likely actor in the brain systems that underlie the formation of fearful memories associated with certain environmental cues and the successful extinction of those memories when the same cues later predict no harm.
Pregnant women made only modest dietary changes after being diagnosed with gestational diabetes, according to a study by researchers at the National Institutes of Health. Women with gestational diabetes are generally advised to reduce their carbohydrate intake, and the women in the study did cut their daily intake of juice and added sugars. They also increased their intake of cheese and artificially sweetened beverages. However, certain groups of women did not reduce their carbohydrate intake, including women with obesity, had more than one child, were Hispanic, had a high school degree or less, or were between the ages of 35-41 years.
Patients with gestational (or pregnancy-related) diabetes have a higher risk of maternal high blood pressure, larger babies, cesarean delivery, low blood sugar in newborns, and development of chronic diabetes later in life.
“The improvements in diet that we observed were not equitable across all groups of women,” said Dr. Hinkle. “This research highlights the importance of creating individualized programs to ensure that all women with gestational diabetes are successful at modifying their diet and optimizing their health.”
Scientists at the National Institutes of Health determined that stomach inflammation is regulated differently in male and female mice after finding that androgens, or male sex hormones, play a critical role in preventing inflammation in the stomach. The finding suggests that physicians could consider treating male patients with stomach inflammation differently than female patients with the same condition. The study was published in Gastroenterology.
Researchers at NIH’s National Institute of Environmental Health Sciences (NIEHS) made the discovery after removing adrenal glands from mice of both sexes. Adrenal glands produce glucocorticoids, hormones that have several functions, one of them being suppressing inflammation. With no glucocorticoids, the female mice soon developed stomach inflammation. The males did not. However, after removing androgens from the males, they exhibited the same stomach inflammation seen in the females.
"The fact that androgens are regulating inflammation is a novel idea," said co-corresponding author John Cidlowski, Ph.D., deputy chief of the NIEHS Laboratory of Signal Transduction and head of the Molecular Endocrinology Group. "Along with glucocorticoids, androgens offer a new way to control immune function in humans."
Glucocorticoids and androgens promote a healthy stomach pit by inhibiting inflammation, left, while their absence promotes inflammation and SPEM seen in a diseased pit, right. SPEM glands are also much larger than healthy stomach glands.
Researchers at the National Institutes of Health have devised a four-part small-molecule cocktail that can protect stem cells called induced pluripotent stem cells (iPSCs) from stress and maintain normal stem cell structure and function. The researchers suggest that the cocktail could enhance the potential therapeutic uses of stem cells, ranging from treating diseases and conditions — such as diabetes, Parkinson’s disease and spinal cord injury — to genome editing.
Human pluripotent stem cells are cells that, in theory, can grow forever and serve as an inexhaustible source for specialized cells, such as brain, kidney and heart cells. But stem cells are sensitive, and their potential uses in medicine are hampered by the stress of growing in a cell culture dish, which can damage their DNA and lead to cell death.
In a series of experiments, scientists led by Ilyas Singeç, M.D., Ph.D., director of the Stem Cell Translation Laboratory at NIH’s National Center for Advancing Translational Sciences (NCATS), used high-throughput screening to systematically test thousands of compounds and drugs to identify a unique combination that greatly improved stem cell survival and reduced cell culture stress. Singeç and his co-investigators described how they developed the cocktail, called CEPT, and its potential applications May 3 in Nature Methods.
“The small-molecule cocktail is safeguarding cells and making stem cell use more predictable and efficient. In preventing cellular stress and DNA damage that typically occur, we’re avoiding cell death and improving the quality of surviving cells,” said Singeç. “The cocktail will become a broadly used staple of the stem cell field and boost stem cell applications in both research and the clinic.”
In two landmark studies, researchers have used cutting-edge genomic tools to investigate the potential health effects of exposure to ionizing radiation, a known carcinogen, from the 1986 accident at the Chernobyl nuclear power plant in northern Ukraine. One study found no evidence that radiation exposure to parents resulted in new genetic changes being passed from parent to child. The second study documented the genetic changes in the tumors of people who developed thyroid cancer after being exposed as children or fetuses to the radiation released by the accident.
The findings, published around the 35th anniversary of the disaster, are from international teams of investigators led by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health. The studies were published online in Science on April 22.
“Scientific questions about the effects of radiation on human health have been investigated since the atomic bombings of Hiroshima and Nagasaki and have been raised again by Chernobyl and by the nuclear accident that followed the tsunami in Fukushima, Japan,” said Stephen J. Chanock, M.D., director of NCI’s Division of Cancer Epidemiology and Genetics (DCEG). “In recent years, advances in DNA sequencing technology have enabled us to begin to address some of the important questions, in part through comprehensive genomic analyses carried out in well-designed epidemiological studies.”
MK-4482 shows potential to prevent and treat SARS-CoV-2 infection
The experimental antiviral drug MK-4482 significantly decreased levels of virus and disease damage in the lungs of hamsters treated for SARS-CoV-2 infection, according to a new study from National Institutes of Health scientists. SARS-CoV-2 is the virus that causes COVID-19. MK-4482, delivered orally, is now in human clinical trials. Remdesivir, an antiviral drug already approved by the U.S. Food and Drug Administration for use against COVID-19, must be provided intravenously, making its use primarily limited to clinical settings.
In their study, published in the journal Nature Communications, the scientists found MK-4482 treatment effective when provided up to 12 hours before or 12 hours after infecting the hamsters with SARS-CoV-2. These data suggest that MK-4482 treatment potentially could mitigate high-risk exposures to SARS-CoV-2, and might be used to treat established SARS-CoV-2 infection alone or possibly in combination with other agents.
The same research group, located at Rocky Mountain Laboratories, part of NIH’s National Institute of Allergy and Infectious Diseases in Hamilton, Montana, developed the hamster model last year to mimic SARS-CoV-2 infection and mild disease in people. The University of Plymouth in the United Kingdom collaborated on these most recent studies.
This scanning electron microscope image shows SARS-CoV-2 (orange)—also known as 2019-nCoV, the virus that causes COVID-19—isolated from a patient in the U.S., emerging from the surface of cells (gray) cultured in the lab.
NIH study results bolster previous studies finding no growth, development differences with IVF
Compared to newborns conceived traditionally, newborns conceived through in vitro fertilization (IVF) are more likely to have certain chemical modifications to their DNA, according to a study by researchers at the National Institutes of Health. The changes involve DNA methylation — the binding of compounds known as methyl groups to DNA — which can alter gene activity. Only one of the modifications was seen by the time the children were 9 years old.
“Our study found only small differences in DNA methylation at birth and these were not seen in early childhood,” Dr. Yeung said. “When considered along with our previous studies finding no differences in children’s growth and development, our current study should be reassuring to couples who have conceived with fertility treatments and to those considering these methods.”
Researchers from the National Institutes of Health have identified and tested a drug combination that exploits a weakness in small cell lung cancer (SCLC), an aggressive, dangerous cancer. The scientists targeted a vulnerability in how the cancer cells reproduce, increasing already high levels of replication stress — a hallmark of out-of-control cell growth in many cancers that can damage DNA and force cancer cells to constantly work to repair themselves. In a small clinical trial, the drug duo shrank the tumors of SCLC patients. The team reported its findings April 12 in Cancer Cell.
While many patients with small cell lung cancer initially respond to chemotherapy, they lack an effective follow-up treatment. These patients usually live a matter of weeks after their first treatment stops working and their disease returns. Scientists at NIH’s National Cancer Institute (NCI) and National Center for Advancing Translational Sciences (NCATS) teamed up to find another option to treat these cancers, which are part of a larger group of similar diseases called small cell neuroendocrine cancers.
“We wanted to identify novel drugs and combinations to leverage this vulnerability therapeutically,” said NCI’s Anish Thomas, M.D., who led the study. “We saw potential opportunities because the armamentarium of new chemicals and drugs was rapidly expanding.”
