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November 20th, 2018

DNA Vaccine Reduces Both Toxic Proteins (Beta-Amyloid & Tau) Linked to Alzheimer’s in Mouse Model

A DNA vaccine tested in mice reduces accumulation of both types of toxic proteins associated with Alzheimer’s disease, according to research that scientists say may pave the way to a clinical trial. A new study by the University of Texas (UT) Southwestern’s Peter O’Donnell Jr. Brain Institute shows that a vaccine delivered to the skin prompts an immune response that reduces buildup of harmful tau and beta-amyloid – without triggering severe brain swelling that earlier antibody treatments caused in some patients. “This study is the culmination of a decade of research that has repeatedly demonstrated that this vaccine can effectively and safely target in animal models what we think may cause Alzheimer’s disease,” said Dr. Roger Rosenberg, founding Director of the Alzheimer’s Disease Center at UT Southwestern. “I believe we’re getting close to testing this therapy in people.” The research, published online on October 20, 2018 in Alzheimer’s Research and Therapy, demonstrates how a vaccine containing DNA coding for a segment of beta-amyloid also reduces tau in mice modeled to have Alzheimer’s disease. In addition, the vaccine elicits a different immune response that may be safe for humans. The open-accessa article is titled “Active Full-Length DNA Aβ42 Immunization in 3xTg-AD Mice Reduces Not Only Amyloid Deposition But Also Tau Pathology.” Two previous studies from Dr. Rosenberg’s lab showed similar immune responses in rabbits and monkeys. The vaccine is on a shortlist of promising antibody treatments aimed at protecting against both types of proteins that kill brain cells as they spread in deadly plaques and tangles on the brains of Alzheimer’s disease patients. Although earlier research established that antibodies significantly reduce amyloid buildup in the brain, Dr. Rosenberg’s team needed to find a safe way to introduce them into the body.

November 19th

Activation of Inhibitory Neurons Prior to Epileptic Seizures Observed for First Time in Humans

(BY RACHEL DERITA, PhD Candidate,Thomas Jefferson University, Department of Cancer Biology) Epileptic seizures are established to neuroscience as global excitation of neurons in the brain. However, new research from Jefferson (Philadelphia University & Jefferson University) in Philadelphia and collaborating institutions has uncovered a previously unknown period of time before an epileptic seizure in which there is an activation of inhibitory neurons. “This is the first time, to our knowledge, that this phenomenon of inhibition at the start of a seizure has been observed in humans,” states senior author of the study Shennan Weiss, MD, PhD, Assistant Professor of Neurology and Head of the Thomas Jefferson Computational Epilepsy Laboratory at the Vickie & Jack Farber Institute for Neuroscience at Jefferson. Before now, this was a phenomenon only observed in chemically-induced seizures in research animals, and was therefore considered an artifact of the experimental models. In the current study, published online on September 4, 2018, in the Annals of Neurology, surgeons collaborating between Jefferson and the University of California at Los Angeles (UCLA), used electrodes to determine the exact location of the seizures occurring in an epilepsy patient. They then were able to track action potentials from single neurons, classified as either excitatory or inhibitory. It was observed that there was a burst of activity from the inhibitory neurons prior to activity of the excitatory neurons. Epileptic patients often experience a period of time prior to a seizure characterized by auras, confusion, and an inability to speak clearly or form coherent sentences.

New Work Suggests That Non-Homologous End-Joining (NHEJ) & Retrotransposons Led to Evolution of Spliceosome and Advance of Eukaryotic Life

A previously unappreciated interaction in the genome turns out to have possibly been one of the driving forces in the emergence of advanced life, billions of years ago. This discovery began with a curiosity for retrotransposons, known as "jumping genes," which are DNA sequences that copy and paste themselves within the genome, multiplying rapidly. Nearly half of the human genome is made up of retrotransposons, but bacteria hardly have them at all. Nigel Goldenfeld, PhD, Swanlund Endowed Chair of Physics at the University of Illinois at Urbana-Champaigne (UIUC), and Director of NASA Astrobiology Institute for Universal Biology at UIUC; and Thomas Kuhlman, PhD, a former Physics Professor at UIUC who is now at the University of California, Riverside, wondered why this is. "We thought a really simple thing to try was to just take one (retrotransposon) out of my genome and put it into the bacteria just to see what would happen," Dr. Kuhlman said. "And it turned out to be really quite interesting." Their results, published online on November 19, 2018 in PNAS, give more depth to the history of how advanced life may have emerged billions of years ago -- and could also help determine the possibility and nature of life on other planets. The title of the open-access PNAS article is “Testing the Retroelement Invasion Hypothesis for the Emergence of the Ancestral Eukaryotic Cell.”Along the way to explaining life, the researchers first encountered death -- bacterial death, that is. When they put retrotransposons in bacteria, the outcome was fatal. "As they jump around and make copies of themselves, they jump into genes that the bacteria need to survive," Dr. Kuhlman said. "It's incredibly lethal to them."

Good Nutrition Could Protect Children from Cognitive Difficulties Caused by Early-Life Stress

Good nutrition in early life may protect against stress-induced changes in brain development in young mice, according to data presented at the Society for Endocrinology 2018 Annual Conference in Glasgow (November 19-21). The study findings suggests that a nutrient-rich diet may have protective effects on brain development in young mice exposed to early-life stress, which reduces their risk of learning and memory issues in later life. It has been reported, in humans and animals, that exposure to adversities, such as stress, in early life can have long-lasting effects on brain function, and may lead to cognitive problems in later life. The period just after birth is critical for brain development and demand for nutrients is high, both for energy and as essential building blocks for the developing brain. Therefore any deficit in essential nutrients during this time could result in long-lasting abnormalities in brain function, including learning processes. The stress and metabolic processes of the body are closely interlinked, and whether stress-related cognitive problems in early life can be prevented or even reversed by ensuring good nutrition has not been fully investigated. In this study, Dr. Aniko Korosi and colleagues from the University of Amsterdam, investigated the effects of essential nutrients on brain function using a mouse model of early-life stress. Early-life stress was mimicked by reducing the amount of maternal care and attention given to pups within the first 2 weeks of birth. By the age of 4 months, these neglected mice show several impairments, including increased body fat levels, high stress hormone levels, and poor performance in learning and memory tasks.

Michael Bloomberg Gives Record $1.8 Billion to Johns Hopkins for Financial Aid--Historic Gift Is Largest Ever to a US College or University

Philanthropist, business leader, and three-term New York City Mayor Michael R. Bloomberg will commit a record-breaking $1.8 billion to support undergraduate financial aid at Johns Hopkins, the university announced on October 18, 2018, the largest-ever single contribution to a US college or university. "This historic gift reflects Mike Bloomberg's deep belief in the transformative power of higher education and his insistence that it be accessible to all qualified students, regardless of financial means," Johns Hopkins University President Ronald J. Daniels wrote in a message to the university community today (see text below). "It also affirms Mike's profound devotion to this university for the role that it played in enriching his life." Bloomberg, a 1964 Johns Hopkins graduate, announced his historic gift in a New York Times op-ed (https://www.nytimes.com/2018/11/18/opinion/bloomberg-college-donation-fi...) in which he identified college affordability as a national challenge. "America is at its best when we reward people based on the quality of their work, not the size of their pocketbook," Bloomberg said. "Denying students entry to a college based on their ability to pay undermines equal opportunity. It perpetuates inter-generational poverty. And it strikes at the heart of the American dream: the idea that every person, from every community, has the chance to rise based on merit." For more on Bloomberg's gift, read the full text of President Daniels' message to the community below. "Dear Members of the Johns Hopkins Community:

November 16th

Exosomes “Swarm” to Protect Against Bacteria Inhaled Through Nose; “Armed” Exosomes Contain Increased Nitric Oxide Synthase to Make Potent Anti-Bacterial Compound (Nitric Oxide); Finding May Also Lead to Improved Airway Drug Delivery

Bacteria are present in just about every breath of air we take in. How the airway protects itself from infection from these bacteria has largely remained a mystery — until now. When bacteria are inhaled, exosomes, or tiny fluid-filled vesicles, are immediately secreted from cells that directly attack the bacteria and also shuttle protective antimicrobial proteins from the front of the nose to the back along the airway, protecting other cells against the bacteria before they get too far into the body. A research team from Massachusetts Eye and Ear describes this newly discovered mechanism in a report publishd online on November 12, 2018 in the Journal of Allergy and Clinical Immunology (JACI). The findings shed new light on our immune systems — and also pave the way for drug delivery techniques to be developed that harness this natural transportation process from one group of cells to another. The article is titled “Exosome Swarms Eliminate Airway Pathogens and Provide Passive Epithelial Immunoprotection Through Nitric Oxide.” “Similar to kicking a hornets’ nest, the nose releases billions of exosomes into the mucus at the first sign bacteria, killing the bacteria and arming cells throughout the airway with a natural, potent defense,” said senior author Benjamin S. Bleier, MD, a sinus surgeon at Massachusetts Eye and Ear and Associate Professor of Otolaryngology at Harvard Medical School. “It’s almost like this swarm of exosomes vaccinates cells farther down the airway against a microbe before they even have a chance to see it.” The JACI study was motivated by a perplexing previous finding from Dr. Bleier’s lab a few years ago. In studies of sinus inflammation, researchers found that proteins in the cells of the nasal cavity were also present in patients’ nasal mucus.

November 15th

Non-Coding Rare Genetic Variant (rs17114036) Could Improve Key Vascular Functions and May Reduce Risk of Risk of Coronary Artery Disease (CAD)

Atherosclerotic disease, the slow and silent hardening and narrowing of the arteries, is a leading cause of mortality worldwide. It is responsible for more than 15 million deaths each year, including an estimated 610,000 people in the United States. In an pen-access article published online on November 14, 2018 in PNAS, a team of physicians, geneticists, and biologists describes a previously unknown genetic factor that can either raise or reduce the risk of coronary artery disease or ischemic stroke. The article is titled “Genetic Variant at Coronary Artery Disease & Ischemic Stroke Locus 1p32.2 Regulates Endothelial Responses to Hemodynamics.” The researchers found that a common non-coding sequence of DNA -- known as rs17114036 and located on chromosome 1p32.2 -- helps regulate gene expression in the cells that line the interior surface of blood vessels, the vascular endothelium. This sequence of DNA contains a single nucleotide polymorphism (SNP). SNPs are common. There is, on average, 1 SNP for every 300 nucleotides scattered throughout a person's DNA. SNPs tend to reside between genes. Most have no known effect, but some play a distinct role. The research team found that rs17114036 plays a significant role in endothelial function and is relevant to human disease incidence. "This particular polymorphism is a previously unappreciated layer of regulatory control," said Yun Fang, PhD, an Assistant Professor of Medicine at the University of Chicago and senior author of the study. The endothelium helps smooth and speed the flow of blood through complex vascular intersections, places where branches or bifurcations disrupt the flow from an artery to two smaller vessels. When the flow is smooth and in one direction, the endothelium is quiescent.

Charles Halasz, MD, Yale College 1973, Wins Award for 20 Years of Distinguished Community Service

In this grim honorless age of evil greedy Trump, there is yet some great good in the world. Yale College (1973) and University of Connecticut School of Medicine (1977) graduate Charles Halasz, MD, has just been awarded Americares Free Clinics' prestigious 2018 Dr. Patch Adams Award for over 20 years of distinguished community service to low-income patients with no insurance or not eligible for government support. Dr. Halasz is a Norwalk, Connecticut dermatologist, who is also board-certified in internal medicine. Dr. Halasz is also Assistant Clinical Professor of Dermatology at Columbia Univristy’s College of Physicians & Surgeons in New York City. The Dr. Patch Adams award was presented as part of the Fairfield County Medical Association (FCMA) Physician Extraordinaire Award Ceremony October 25. Dr. Halasz’s low-income patients, over 200 each year for over 20 years, are typically refugees from foreign countries and continents such as Nepal, the former Yugoslavia, Central America, and South America. When Americares opened its first free clinic, in Norwalk, CT, two decades ago, Dr. Halasz was one of the clinic's first volunteers. He provided his expert medical services for no charge in order to help people in need. And he has done so now for over 20 years. Below are comments given at the ceremony by the award presenters and by Charley himself. Suffice it to say that this is a great and well-deserved award that recognizes Dr. Halasz’s extraordinary compassion and nobility of soul. One of the presenters said the following: “Patch Adams said, ‘The unencumbered practice of care is an ecstatic experience worth paying to do.’ Dr. Patch Adams is a real physician. When most people hear the name Patch Adams, they think of Robin Williams (star of the Patch Adams movie).

November 14th

Number of EVs from RBCs and Expression of Eight Different Proteins in Those EVs May Be Biomarker for Progression of Parkinson’s Disease

A new blood-based analysis that evaluates the levels and content of tiny vesicles released by red blood cells may help diagnose patients with Parkinson’s disease according to disease stage, researchers suggest. The new method was described in the study, “Portrait of Blood-Derived Extracellular Vesicles in Patients with Parkinson’s Disease,” published online on November 5, 2018 in Neurobiology of Disease. Parkinson’s disease is linked to a broad spectrum of clinical manifestations and several molecular mechanisms. This represents a challenge for the development and identification of useful biomarkers for diagnosis and disease progression, as well as to track the effectiveness of new treatments. All human cells produce tiny vesicles that can contain fatty molecules, proteins, and genetic information, which they release to the surrounding environment. These so-called extracellular vesicles (EVs) are produced both in healthy states and disease conditions, and are used by cells to communicate among themselves. Given the major role these EVs may have, researchers hypothesized that their cargo could hold useful information on the biological state of the body, representing a possible new diagnostic tool. To this end, Canadian researchers developed a new method of isolating EVs from blood samples that would preserve the EVs’ integrity, while still removing any potential contaminants. Using flow cytometry, a technique that allows the visualization and sorting of cells and small particles according to their size and shape, the team could identify not only EVs, but also which cells they originatd from. After the EVs were isolated, the team could analyze their content. Following the assay’s optimization, the team analyzed blood samples collected from 60 Parkinson’s patients and 37 age- and sex-matched healthy volunteers.

2018 Lasker-Koshland Special Achievement Award in Medical Science Goes to Yale’s Pioneering Woman Biochemist Joan Steitz for Leadership in RNA Biology & Scientific Mentorship, Especially for Women

The 2018 Lasker-Koshland Award for Special Achievement in Medical Science honors an individual whose lifetime contributions have engendered among her colleagues the deepest feelings of awe and respect. For four decades, Joan Argetsinger Steitz (Yale University) has provided leadership in biomedical science. She has made pioneering discoveries about RNA biology, generously mentored budding scientists, and vigorously and passionately supported women in science. She has generated a cascade of discoveries that have illuminated wide-ranging and unanticipated functions for RNA molecules within our cells, and has served as a role model in multiple ways, especially for rising female investigators. Dr. Steitz has campaigned for full inclusion of all members of the scientific community, fueled by the conviction that reaching this goal is necessary to ensure a robust and innovative scientific enterprise. When Steitz encountered the molecular basis of genetics in the early 1960s as an undergraduate lab technician, she was enchanted, but despite her passion and curiosity, she could not envision a future for herself as an academic researcher. The absence of female biology professors shrouded that potential career path. She did know that women could be physicians, so she decided to become a doctor. The summer before medical school, Steitz joined the lab of Joseph Gall (Albert Lasker Special Achievement Award in Medical Science, 2006), where she undertook her first independent project. Thrilled by the joy of discovery and the challenges of steering her own experiments, she could no longer resist the draw of research.