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Archive - Apr 15, 2015

Paternal Sperm and Altered DNA Methylation Patterns May Hold Clues to Autism Risk, Hopkins Study Suggests

In a small study, Johns Hopkins researchers found that DNA from the sperm of men whose children had early signs of autism shows distinct patterns of regulatory tags that could contribute to the condition. A detailed report of these new findings was published online on April 14, 2015 in an open-access article in the International Journal of Epidemiology. The article is titled “Paternal Sperm DNA Methylation Associated with Early Signs of Autism Risk in an Autism-Enriched Cohort.” Autism spectrum disorder (ASD) affects one in 68 children in the U.S. Although studies have identified some culprit genes, most cases remain unexplained. But most experts agree that autism is usually inherited, because the condition tends to run in families. In this study, investigators looked for possible causes for the condition not in genes themselves, but in the "epigenetic tags" that help regulate genes' activity. "We wondered if we could learn what happens before someone gets autism," says Andrew Feinberg, M.D., M.P.H., the King Fahd Professor of Molecular Medicine and Director of the Center for Epigenetics at the Johns Hopkins University School of Medicine. "If epigenetic changes are being passed from fathers to their children, we should be able to detect them in sperm," adds co-lead investigator Daniele Fallin, Ph.D., Professor and Chair of the Department of Mental Health in the Bloomberg School of Public Health and director of the Wendy Klag Center for Autism and Developmental Disabilities. In addition to being easier to sample than egg cells from women, sperm are more susceptible to environmental influences that could alter the epigenetic tags on their DNA. Dr. Feinberg, Dr. Fallin, and their team assessed the epigenetic tags on DNA from sperm from 44 dads.

Controlled Activation of ERBB2 for Short Time After Heart Attack Almost Completely Regenerates Damaged Heart Tissue in Mouse Model; Senior Author Terms Results “Amazing”

When a heart attack strikes, heart muscle cells die and scar tissue forms, paving the way for heart failure. Cardiovascular diseases are a major cause of death worldwide, in part, because the cells in our most vital organ do not get renewed. As opposed to blood, hair, or skin cells that can renew themselves throughout life, our heart cells cease to divide shortly after birth, and there is very little renewal in adulthood. New research at the Weizmann Institute of Science provides insight into the question of why the mammalian heart fails to regenerate, on one hand, and demonstrated, in adult mice, the possibility of turning back this fate. This research was published online on April 6, 2015 in Nature Cell Biology. The article is titled “ERBB2 Triggers Mammalian Heart Regeneration by Promoting Cardiomyocyte Dedifferentiation and Proliferation.” Professor Eldad Tzahor, of the Institute’s Biological Regulation Department and senior author of the article, thought that part of the answer to the regeneration puzzle might lie in his area of expertise: embryonic development, especially of the heart. Indeed, it was known that a protein called ERBB2 – which is well studied because it can pass along growth signals promoting certain kinds of cancer – plays a role in heart development. ERBB2 is a specialized receptor – a protein that transmits external messages into the cell. ERBB2 generally works together with a second, related, receptor by binding a growth factor called Neuregulin 1 (NRG1) to transmit its message. NGR1 is already being tested in clinical studies for treating heart failure. Dr. Gabriele D’Uva, a postdoctoral fellow in the research group of Professor Eldad Tzahor, wanted to know exactly how NRG1 and ERBB2 are involved in heart regeneration.

Arginine Deprivation May Play Key Role in Causing Alzheimer’s, Duke Study Indicates; Senior Researcher Says Such a Different Perspective on Long-Perplexing Disease Is Highly Desirable

Increasingly, evidence supports the idea that the immune system, which protects our bodies from foreign invaders, plays a part in Alzheimer's disease. But the exact role of immunity in the disease is still a mystery. A new Duke University study in mice suggests that in Alzheimer's disease, certain immune cells that normally protect the brain begin to abnormally consume an important nutrient: arginine (image). Blocking this process with a small-molecule drug prevented the characteristic brain plaques and memory loss in a mouse model of the disease. Published in the April 15, 2015 issue of the Journal of Neuroscience, the new research not only points to a new potential cause of Alzheimer's, but also may eventually lead to a new treatment strategy. The article is titled “"Arginine Deprivation and Immune Suppression in a Mouse Model of Alzheimer's Disease." "If indeed arginine consumption is so important to the disease process, maybe we could block it and reverse the disease," said senior author Dr. Carol Colton, Professor of Neurology at the Duke University School of Medicine, and a member of the Duke Institute for Brain Sciences. The brains of people with Alzheimer's disease show two hallmarks, “plaques” and “tangles,” that researchers have puzzled over for some time. Plaques are the build-up of sticky proteins called beta amyloid, and tangles are twisted strands of a protein called tau. In the current study, the scientists used a type of mouse, called CVN-AD, that they had created several years ago by swapping out a handful of important genes to make the animal's immune system more similar to a human's. Compared with other mice used in Alzheimer's research, the CVN-AD mouse has it all: plaques and tangles, behavior changes, and neuron loss.

Antibody-Bound IL-2 Stimulates T-Cell Killing of Cancer Cells; This New Version of IL-2 Use Halts Aggressive Melanoma in Mice

The human immune system is poised to spring into action at the first sign of a foreign invader, but it often fails to eliminate tumors that arise from the body’s own cells. Cancer biologists hope to harness that untapped power using an approach known as cancer immunotherapy. Orchestrating a successful immune attack against tumors has proven difficult so far, but a new study from MIT suggests that such therapies could be improved by simultaneously activating both arms of the immune system. Until now, most researchers have focused on one of two strategies: attacking tumors with antibodies, which activate the innate immune system, or stimulating T cells, which form the backbone of the adaptive immune system. By combining these approaches, the MIT team was able to halt the growth of a very aggressive form of melanoma in mice. “An anti-tumor antibody can improve adoptive T-cell therapy to a surprising extent,” says Dr. Dane Wittrup, the Carbon P. Dubbs Professor in Chemical Engineering at MIT. “These two different parts of the immune therapy are interdependent and synergistic.” Dr. Wittrup, an associate director of MIT’s Koch Institute for Integrative Cancer Research and also a faculty member in the Department of Biological Engineering, is the senior author of a paper describing the work in the April 13, 2015 issue of the journal Cancer Cell. The article is titled “Synergistic Innate and Adaptive Immune Response to Combination Immunotherapy with Anti-Tumor Antigen Antibodies and Extended Serum Half-Life IL-2.” Lead authors are graduate students Eric Zhu and Cary Opel and recent Ph.D. recipient Dr. Shuning Gai.