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:
The act of cooking offers the chance to unwind and create something special, whether you’re planning to feed a crowd or just yourself. And while you may have noticed feeling good after whipping up that perfect pie or braise, there’s actually a lot of scientific data to suggest that cooking can have a positive impact on mental health.
One meta-analysis (a report of pre-existing research) from the National Institutes of Health looked at 11 studies and found that “cooking interventions” — encouraging people to follow certain recipes or giving people cooking classes — can improve a person’s mental well-being. It specifically found that people who participated in cooking interventions reported having better self-esteem and quality of life, as well as a more positive emotional state after the fact. Another study even discovered that baking can help raise a person’s confidence level.
Algorithm could revolutionize cervical cancer screening, especially in low-resource settings
A research team led by investigators from the National Institutes of Health and Global Good has developed a computer algorithm that can analyze digital images of a woman’s cervix and accurately identify precancerous changes that require medical attention. This artificial intelligence (AI) approach, called automated visual evaluation, has the potential to revolutionize cervical cancer screening, particularly in low-resource settings.
To develop the method, researchers used comprehensive datasets to "train" a deep, or machine, learning algorithm to recognize patterns in complex visual inputs, such as medical images. The approach was created collaboratively by investigators at the National Cancer Institute (NCI) and Global Good, a fund at Intellectual Ventures, and the findings were confirmed independently by experts at the National Library of Medicine (NLM). The results appeared in the Journal of the National Cancer Institute on January 10, 2019. NCI and NLM are parts of NIH.
"Our findings show that a deep learning algorithm can use images collected during routine cervical cancer screening to identify precancerous changes that, if left untreated, may develop into cancer," said Mark Schiffman, M.D., M.P.H., of NCI’s Division of Cancer Epidemiology and Genetics, and senior author of the study. "In fact, the computer analysis of the images was better at identifying precancer than a human expert reviewer of Pap tests under the microscope (cytology)."
A global resource that includes data on thousands of inherited variants in the BRCA1 and BRCA2 genes is available to the public. The BRCA Exchange was created through the BRCA Challenge, a long-term demonstration project initiated by the Global Alliance for Genomics and Health (GA4GH) to enhance sharing of BRCA1 and BRCA2 data. The resource, available through a website and a new smartphone app, allows clinicians to review expert classifications of variants in these major cancer predisposition genes as part of their individual assessment of complex questions related to cancer prevention, screening, and intervention for high-risk patients.
The five-year BRCA Challenge project was funded in part by the National Cancer Institute (NCI), part of the National Institutes of Health, and through the Cancer Moonshot. A paper detailing the development of the BRCA Exchange was published Jan. 8, 2019, in PLOS Genetics.
“This project has yielded a meta-analysis of BRCA1 and BRCA2 variants collected from multiple sources to understand how experts annotate specific mutations in the two genes,” said Stephen J. Chanock, M.D., director of NCI’s Division of Cancer Epidemiology and Genetics and lead author of the paper. “There’s an urgent need for sharing data in cancer predisposition research. The BRCA Exchange is proof of principle that large-scale collaboration and data sharing can be achieved and can provide the latest and best quality information to enable clinicians and individuals to improve care.”
Results suggest a breakdown in brain cell waste system triggers a destructive immune reaction
In a study of fruit flies, NIH scientists suggested that the body’s immune system may play a critical role in the damage caused by aging brain disorders. The results are based on experiments in which the researchers altered the activity of Cdk5, a gene that preclinical studies have suggested is important for early brain development and may be involved in neurodegenerative diseases, such as ALS, Alzheimer’s and Parkinson’s disease. Previously, they found that altering Cdk5 sped up the genetic aging process, causing the flies to die earlier than normal and have problems with walking or flying late in life and greater signs of neurodegenerative brain damage.
In this study, published in Cell Reports, they suggested that altering Cdk5 resulted in the death of dopamine releasing neurons, especially in the brains of older flies. Typically, Parkinson’s disease damages the same types of cells in humans. Further experiments in flies suggested the neuron loss happened because altering Cdk5 slowed autophagy, or a cell’s waste disposal system that rids the body of damaged cells in a contained, controlled fashion, which in turn triggered the immune system to attack the animal’s own neurons. This immune system attack is a much “messier” and more diffuse process than autophagy. Genetically restoring the waste system or blocking the immune system’s responses prevented the reduction in dopamine neurons caused by altering Cdk5. The authors concluded that this chain reaction in which a breakdown in autophagy triggers a widely destructive immune reaction may occur in human brain during several neurodegenerative disorders and that researchers may want to look to these systems for new treatment targets and strategies.
In a study of flies, NIH scientists showed how the immune system may be a culprit in the damage caused by aging brain disorders.
Proximity to nearby muscle cells may make prostate cancer cells more likely to invade nearby tissues and spread to other organs, according to an early study by researchers at the National Institutes of Health. The presence of muscle cells appears to make cancer cells more likely to fuse two or more cancer cells into a single cell, thereby increasing their invasiveness and ability to spread. The study was led by Berna Uygur, Ph.D., of NIH’s Eunice Kennedy ShriverNational Institute of Child Health and Human Development (NICHD) and includes colleagues from the National Eye Institute and the Maine Medical Center Research Institute in Scarborough. The study appears in Molecular Cancer Research.
Researchers grew human prostate cancer cells in laboratory dishes along with human muscle cells — stand-ins for the smooth muscle surrounding the prostate gland and the striated muscle of the urethral sphincter at the base of the prostate. The muscle cells secreted interleukins 4 and 13, cellular proteins that stimulated the cancer cells to produce two additional proteins, annexin A5 and syncytin 1, which triggered the cancer cells to fuse together. Testing revealed that the fused cells developed characteristics of more malignant cells, which are more likely to invade surrounding tissues and spread to other parts of the body. The researchers note that drugs to inhibit annexin A5 and syncytin 1 could be studied for their potential to treat prostate cancer. According to the National Cancer Institute, approximately 11.2 percent of men in the United States will be diagnosed with prostate cancer at some point during their lifetime.
From left to right: prostate cancer cells (square) near skeletal (oblong) and smooth (oval) muscle cells respond to Interleukins 4 and 13 (IL4/13) by producing annexin A5 and syncytin 1 (Syn1 & AnxA5) and fusing. Fused cells (starburst) develop increased capacity to invade tissue and spread.
Findings could lead to early diagnosis, better treatment studies
An ultrasensitive test has been developed that detects a corrupted protein associated with Alzheimer’s disease and chronic traumatic encephalopathy (CTE), a condition found in athletes, military veterans, and others with a history of repetitive brain trauma. This advance could lead to early diagnosis of these conditions and open new research into how they originate, according to National Institutes of Health scientists and their colleagues. In their new study, published in Acta Neuropathologica, the researchers explain how they adapted a diagnostic test originally developed for prion diseases to detect abnormal clusters of tau protein. Like other proteins involved in neurological diseases, tau protein clusters can seed themselves and contribute substantially to the disease processes of Alzheimer’s and CTE. The study involved brain samples from 16 Alzheimer’s patients, two boxers with CTE, and numerous control cases involving other brain diseases.
The test is extremely sensitive. For example, if a pinhead-sized sample of brain tissue from an Alzheimer’s patient were pulverized and diluted into a thousand gallons of liquid, the test still could detect tau seeds in a pinhead-sized volume of that dilution. The test is called AD RT-QuIC: Alzheimer’s disease real-time quaking induced conversion.
Scientists at NIH’s National Institute of Allergy and Infectious Diseases developed RT-QuIC about a decade ago to detect Creutzfeldt-Jakob (CJD) and other prion diseases. Since then, they have repeatedly improved and adapted it to detect other neurological diseases, such as Parkinson’s and dementia with Lewy bodies. The test, which already is used in clinical settings to diagnose sporadic CJD, is noted for its rapid and accurate results.
Findings from a new study by researchers at the National Cancer Institute (NCI) show that patients treated with chemotherapy for most solid tumors during 2000–2014 experienced an increased risk of therapy-related myelodysplastic syndrome/acute myeloid leukemia (tMDS/AML). The study, which used U.S. population-based cancer registry data from NCI’s Surveillance, Epidemiology, and End Results (SEER) program and treatment information from the SEER–Medicare database, was published December 20, 2018, in JAMA Oncology. NCI is part of the National Institutes of Health.
Advances in treatment over the last several decades have resulted in improved survival for patients with many types of cancer. However, survivors may be at increased risk of developing a subsequent treatment-related cancer. In this study, researchers aimed to quantify the risk of developing tMDS/AML, a rare but often fatal blood cancer, in patients treated with chemotherapy.
“We’ve known for a long time that the development of myeloid leukemia is a very rare adverse effect of some types of cancer treatments that damage cells,” said Lindsay Morton, Ph.D., lead author of the study and a senior investigator in NCI’s Division of Cancer Epidemiology and Genetics. “There have been many changes in cancer treatment over time, including the introduction of new chemotherapy drugs and drug combinations, but we didn’t know what the risk of therapy-related leukemia looked like for patients since these changes were made.”
Breast cancer risk remains elevated 20-30 years after childbirth
In general, women who have had children have a lower risk of breast cancer compared to women who have never given birth. However, new research has found that moms don’t experience this breast cancer protection until many years later and may face elevated risk for more than 20 years after their last pregnancy.
Scientists at the National Institutes of Health, along with members of the international Premenopausal Breast Cancer Collaborative Group, found breast cancer risk increases in the years after a birth, with the highest risk of developing the disease about five years later. The findings, which appeared online in the Annals of Internal Medicine, suggest breast cancer protection from pregnancy may not begin until as many as 30 years after the birth of the last child.
According to senior author Dale Sandler, Ph.D., head of the Epidemiology Branch at the National Institute of Environmental Health Sciences (NIEHS), part of NIH, a few prior studies reported an increase in breast cancer risk after childbirth. However, most of what researchers knew about breast cancer risk factors came from studies of women who have gone through menopause. Since breast cancer is relatively uncommon in younger women, it is more difficult to study.
The study suggests breast cancer protection from pregnancy may not begin until as many as 30 years after the last pregnancy.
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.
