In early-stage research, led by scientists from Imperial College London and The Institute of Cancer Research, London, researchers have identified a genetic “switch” in breast cancer cells that boosts the production of a type of internal scaffolding. This scaffolding is made of a protein called keratin-80 that is related to the keratin protein that helps keep hair strong. Boosting the amount of this scaffolding makes the cancer cells more rigid, which the researchers say may help the cells clump together and travel in the blood stream to other parts of the body. The researchers studied human breast cancer cells treated with a common types of breast cancer drug called aromatase inhibitors. The team found the same switch is involved in breast cancer cells becoming resistant to the medication (meaning the drugs are no longer effective if the cancer returns). Targeting this switch with a different drug could help reverse this resistance, and make the cancer less likely to spread, explained Dr. Luca Magnani, lead author of the research from the Department of Surgery and Cancer at Imperial: “Breast cancer is the most common cancer in the UK, and causes 55,200 new cases every year. Aromatase inhibitors are effective at killing cancer cells, but within a decade post-surgery around 30 per cent of patients will relapse and see their cancer return – usually because the cancer cells have adapted to the drug. Even worse, when the cancer comes back it has usually spread around the body – which is difficult to treat.” The results of this new work were published online on May 9, 2019 in Nature Communications. The open-access article is titled “SREBP1 Drives Keratin-80-Dependent Cytoskeletal Changes and Invasive Behavior in Endocrine-Resistant ERα Breast Cancer.”
A new report in th May 31, 2019 issue of Science provides the first evidence of a mammal — the highveld mole-rat, a close relative of the well-known and extraordinarily long-lived naked mole rat — being immune to pain from exposure to allyl isothiocyanate (AITC), the active ingredient of wasabi. Wasabi is a plant of the Brassicaceae family, which also includes horseradish and mustard in other genera. A paste made from wasabi’s ground rhizomes is used as a pungent condiment for sushi and other foods. The scientists who studied the highveld mole rats say that understanding how these African rodents evolved to be insensitive to this specific type of pain could point to new directions for solving pain in humans. “Mole-rats are extremely curious animals and we have been studying them at UIC for more than 20 years,” said study co-author Thomas Park, PhD, Professor of Biological Sciences at the University of Illinois at Chicago (UIC) College of Liberal Arts and Sciences. “This new discovery — that they have evolved to be insensitive to certain pain stimuli common in their environment — is another example of the cool biological lessons to be learned from studying them.” Dr. Park worked alongside scientists from the Max Delbruck Center for Molecular Medicine in Berlin and the University of Pretoria in Pretoria, South Africa, on the study. The research was conducted at UIC and in South Africa. The new Science article is titled “Rapid Molecular Evolution of Pain Insensitivity in Multiple African Rodents.” The researchers exposed the paws of eight species of mole rats to three compounds that induce a pain-like response. The three compounds were AITC, an acidic solution with a pH similar to that of lemon juice, and capsaicin, the spicy ingredient in chili peppers.
An international collaboration led by scientists at the University of Texas (UT) Southwestern Medical Center has identified a potential new therapeutic target for sepsis, a life-threatening disease that can quickly spread through the body damaging organs. UT Southwestern researchers and collaborators in China, France, and Sweden, as well as in New York and Pennsylvania in the US, made a key discovery regarding cellular processes that block pathways in immune cells that lead to sepsis. At a fundamental level, sepsis is an out-of-control inflammatory response that damages organs and critical cellular functions leading to tissue damage. “If not recognized early and managed promptly, sepsis can lead to septic shock, multiple organ failure, and even death,” said study author Rui Kang, MD, PhD, Associate Professor of Surgery at UT Southwestern who studies sepsis. “Our study provides novel insight into immune regulation related to sepsis and represents a proof of concept that immunometabolism constitutes a potential therapeutic target in sepsis.” Immunometabolism is the interaction of the body’s natural or innate immune response (how cells detect and react to threats) and metabolism (how cells convert food to energy and building blocks the body needs to function. Immunometabolism is an emerging field of study combining the two traditionally independent disciplines. Sepsis occurs when an initial infection spreads through the bloodstream to other parts of the body. Early detection and treatment of sepsis is critical, but it can be difficult to detect and to stop before damage to organs and tissue occurs. Treatments can involve antibiotics, fluids, oxygen, dialysis to ensure blood flow to affected organs, and surgery to remove damaged tissue.
Congenital heart disease occurs in up to 1% of live births, and the infants who are affected may require multiple surgeries, life-long medication, or heart transplants. In many patients, the exact cause of congenital heart disease is unknown. While it is becoming increasingly clear that these heart defects can be caused by genetic mutations, it is not well understood which genes are involved and how they interact. Genetic mutations, also called genetic variants, can also cause poor heart function, but the type and severity of dysfunction varies widely even among those with the same mutation. The Human Genome project allowed scientists to identify some rare cases of disease caused by severe mutations of a single gene, but scientists believe that more common forms of disease may be the result of a combination of subtler genetic mutations that act together. Yet, experimental proof for this concept of human disease has remained elusive – until now. In a paper published online in Science on May 30, 2019 and scheduled for publication in the May 31 issue of that journal, scientists from the Gladstone Institutes in San Francisco and the University of California, San Francisco (UCSF) used technological advances to prove that three subtle genetic variants inherited within a family worked together to cause heart disease in multiple siblings at a very young age. The article is titled “Oligogenic Inheritance of a Human Heart Disease Involving a Genetic Modifier.” “The idea that several genetic variants are necessary to cause most complex diseases has been around for a long time, but proving it has been difficult,” said Casey Gifford, PhD, a staff scientist at Gladstone who is the first author on the paper.
In a discovery that might be likened to finding medicine’s version of the Loch Ness monster, a research team from Johns Hopkins Medicine, IBM Research, and four additional collaborating institutions is the first to document the existence of a long-doubted “X cell,” a “rogue hybrid” immune system cell that may play a key role in the development of type 1 diabetes. The researchers report the unusual lymphocyte (a type of white blood cell) — formally known as a dual expressor (DE) cell — in a new paper published as a featured article in the May 30, 2019 issue of Cell (www.cell.com/cell/fulltext/S0092-8674(19)30505-7). The open-access article is titled “A Public BCR Present in a Unique Dual-Receptor-Expression Lymphocyte from Type 1 Diabetes Patients Encodes a Potent T Cell Autoantigen.” “The cell we have identified is a hybrid between the two primary workhorses of the adaptive immune system, B lymphocytes and T lymphocytes,” says Abdel-Rahim A. Hamad, MVSc, PhD., Associate Professor of Pathology at the Johns Hopkins University School of Medicine and one of the authors of the paper. “Our findings not only show that the X cell exists, but that there is strong evidence for it being a major driver of the autoimmune response believed to cause type 1 diabetes.” Type 1 diabetes, formerly known as juvenile diabetes or insulin-dependent diabetes, is a chronic condition in which there is destruction of the beta cells in the pancreas that produce insulin (image), the hormone that regulates a person’s blood sugar level. Diagnosed mostly in childhood, but presenting at all ages, the disease accounts for between 5% and 10 % of all diabetes cases in the United States or about 1.3 million people.
People with autism often suffer from gut problems, but nobody has known why. Researchers have now discovered the same gene mutations – found both in the brain and the gut – could be the cause. The discovery confirms a gut-brain nervous system link in autism, opening a new direction in the search for potential treatments that could ease behavioral issues associated with autism by targeting the gut. Chief Investigator Associate Professor Elisa Hill-Yardin (photo), PhD, RMIT University in Melbourne, Australia, said scientists trying to understand autism have long been looking in the brain, but the links with the gut nervous system have only been recently explored. “We know the brain and gut share many of the same neurons and now, for the first time, we’ve confirmed that they also share autism-related gene mutations,” Dr. Hill-Yardin said. “Up to 90% of people with autism suffer from gut issues, which can have a significant impact on daily life for them and their families. “Our findings suggest these gastrointestinal problems may stem from the same mutations in genes that are responsible for brain and behavioral issues in autism. It’s a whole new way of thinking about it – for clinicians, families, and researchers – and it broadens our horizons in the search for treatments to improve the quality of life for people with autism.” The study reveals a gene mutation that affects neuron communication in the brain, and was the first identified as a cause of autism, also causes dysfunction in the gut. The research brings together new results from pre-clinical animal studies with previously unpublished clinical work from a landmark 2003 study led by Swedish researchers and a French geneticist.