New Blood Biomarker (Abnormal Astrocyte Reactivity) Can Predict If Cognitively Healthy Elderly Will Develop Alzheimer’s Disease
Why do some people develop Alzheimer’s disease while others do not? And, even more puzzlingly, why do many individuals whose brains are chock-full of toxic amyloid aggregates—a telltale sign of Alzheimer’s brain pathology—never go on to develop Alzheimer’s-associated dementias? University of Pittsburgh School of Medicine researchers appear to have found the answer. Star-shaped brain cells called astrocytes are key to swaying the pendulum in Alzheimer’s disease progression, shows new game-changing research published on May29, 2023 in Nature Medicine. The open-access article is titled “Astrocyte Reactivity Influences Amyloid-Βeta Effects on Tau Pathology in Preclinical Alzheimer’s Disease.” By testing the blood of more than 1,000 cognitively unimpaired elderly people with and without amyloid pathology, the Pitt-led research team found that only those who had a combination of amyloid burden and blood markers of abnormal astrocyte activation, or reactivity, would progress to symptomatic Alzheimer’s in the future, a critical discovery for drug development aimed at halting disease progression.
Scientists Develop New Assay That Can Identify Specific Neurodegenerative Diseases by Detecting Abnormal Alpha-Synuclein in Patient Sera
Synucleinopathies are a group of neurodegenerative diseases caused by the abnormal accumulation of α-synuclein, a protein normally found in the brain and neurons. Incorrect folding of α-synuclein leads to formation of “seeds,” which attract more α-synuclein proteins to form larger clumps. Although α-synuclein seeds have been found in various tissues and blood of patients with synucleinopathies, its potential as a biomarker is ambiguous. Recently, in a study published May 29, 2023 in Nature Medicine, Associate Professor Ayami Okuzumi, along with Senior Associate Professor Taku Hatano, both from the Juntendo University School of Medicine; Senior Assistant Professor Gen Matsumoto at the Nagasaki University School of Medicine; and Professor Nobutaka Hattori from Juntendo University Faculty of Medicine /RIKEN Center for Brain Science, presented a novel assay that can efficiently detect α-synuclein seeds from a patient’s serum. The open-access article is titled “Propagative α-Synuclein Seeds As Serum Biomarkers for Synucleinopathies.”
“Breakthrough Article” in Nucleic Acids Research Reports Enhanced Nonenzymatic RNA Copying with In-Situ Activation of Short Oligonucleotides; Process Believed Crucial to Origin of Life; Senior Author Is Nobel Prize Winner (2009)
A team of investigators led by Nobel Prize winner (2009) Jack Szostak, PhD, (University of Chicago and the Howard Hughes Medical Institute)has described a significant step forward in understanding the nonenzymatic copying of RNA (a process believed to be crucial for the origins of life) by demonstrating the activation of short oligonucleotides and the subsequent formation of monomer-bridged-oligonucleotides, leading to efficient nonenzymatic template copying in the same reaction mixture. The work has been selected as a “Breakthrough Article” by Nucleic Acids Research, whichis a publication of Oxford University Press and is fully open access. The journal’s mission is to provide outstanding, scientist-led evaluation and dissemination of the highest-caliber research across a wide range of disciplines focused on the role of nucleic acids and nucleic acid-interacting molecules in cellular and molecular biology. Breakthrough Articles at NAR describe studies that solve a long-standing problem in their field or provide exceptional new insight and understanding into an area of research that will clearly motivate and guide new research opportunities and directions. They represent the top papers that NAR receives for publication, and are selected by the Editors based on nominations by authors and/or reviewers, and on the subsequent recommendation of the reviewers and Editorial Board members.
ASCO Honors Dr. Monica Bertagnolli for Leadership and Innovations in Cancer Care
Monica M. Bertagnolli, MD, FACS, FASCO, Director of the U.S. National Cancer Institute (NCI) and newly nominated Director of the NIH, will receive the 2023 Allen Lichter Visionary Leader Award in recognition of her work to improve the understanding of cancer and develop innovations that promote high-quality care. Dr. Bertagnolli will receive the award at the 2023 ASCO (American Society of Clinical Oncology) Annual Meeting (June 2-6) in Chicago. “Allen has been an inspiring mentor and role model for me, and it is an honor to receive this award,” Dr. Bertagnolli said. “He is a great example of someone who is able to take great ideas and turn them into realities on a national scale.”
4,000-Year-Old Plague DNA Found–Oldest Cases to Date in Britain
Researchers at the Francis Crick Institute in the UK have identified three 4,000-year-old British cases of Yersinia pestis, the bacteria causing the plague–the oldest evidence of the plague in Britain to date. The work is reported in a paper published May 30, 2023 in Nature Communications. The open-access article is titled “Yersinia pestis Genomes Reveal Plague in Britain 4000 Years Ago.” Working with the University of Oxford, the Levens Local History Group, and the Wells and Mendip Museum, the team identified two cases of Yersinia pestis in human remains found in a mass burial in Charterhouse Warren in Somerset and one in a ring cairn monument in Levens in Cumbria.
Ubiquitination Regulates ER-Phagy and Remodeling of Endoplasmic Reticulum; Researchers Find Mechanisms Involved in Regulation of Structure and Function of ER; Defects in System Can Cause Neurodenerative Disease
A tangle of pockets, tubes, and sac-like membrane structures runs through the cells of humans, animals, plants, and fungi: the endoplasmic reticulum (ER). In the ER, proteins are manufactured, folded into their three-dimensional structure and modified, lipids and hormones are produced, and calcium concentrations in the cell are controlled. In addition, the ER forms the basis for the cellular transport system, feeds misfolded proteins to intracellular disposal and renders toxins that have entered the cell harmless. In view of its multiple tasks, the ER is constantly being remodeled. A process called ER-phagy (roughly “self-digestion of the ER”) is responsible for ER degradation. Involved is a group of signal-receiving proteins—receptors–that are responsible for the membrane curvatures of the ER and thus for its multiple forms in the cell. In ER-phagy, the receptors accumulate at specific sites on the ER and increase membrane curvature to such an extent that, as a consequence, part of the ER is strangulated and broken down into its component parts by cellular recycling structures (autophagosomes).
Clearest Snapshot Yet of Human Genomic Diversity Is Revealed in New Nature Article
For more than 20 years, scientists have relied on the human reference genome, a consensus genetic sequence, as a standard against which to compare other genetic data. Used in countless studies, the reference genome has made it possible to identify genes implicated in specific diseases and trace the evolution of human traits, among other things. But it has always been a flawed tool. One of its biggest problems is that about 70 percent of its data came from a single man of predominantly African-European background whose DNA was sequenced during the Human Genome Project, the first effort to capture all of a person’s DNA. As a result, it can tell us little about the 0.2 to 1 percent of genetic sequence that makes each of the seven billion people on this planet different from each other, creating an inherent bias in biomedical data believed to be responsible for some of the health disparities affecting patients today. Many genetic variants found in non-European populations, for instance, aren’t represented in the reference genome at all. For years, researchers have called for a resource more inclusive of human diversity with which to diagnose diseases and guide medical treatments. Now scientists with the Human Pangenome Reference Consortium have made ground-breaking progress in characterizing the fraction of human DNA that varies between individuals. As they published on May 10, 2023 in Nature, they’ve assembled genomic sequences of 47 people from around the world into a so-called “pangenome” in which more than 99 percent of each sequence is rendered with high accuracy. The open-access article is titled “A Draft Human Pangenome Reference.”
Exploring the Links Between Diet and Cancer; MIT Scientist’s Work on How Diet Influences Intestinal Stem Cells Could Lead to New Ways to Treat or Prevent Gastrointestinal Cancers
Every three to five days, all of the cells lining the human intestine are replaced. That constant replenishment of cells helps the intestinal lining withstand the damage caused by food passing through the digestive tract. This rapid turnover of cells relies on intestinal stem cells, which give rise to all of the other types of cells found in the intestine. Recent research has shown that those stem cells are heavily influenced by diet, which can help keep them healthy or stimulate them to become cancerous. “Low-calorie diets such as fasting and caloric restriction can have anti-aging effects and anti-tumor effects, and we want to understand why that is. On the other hand, diets that lead to obesity can promote diseases of aging, such as cancer,” says Omer Yilmaz, PhD, the Eisen and Chang Career Development Associate Professor of Biology at MIT. For the past decade, Dr. Yilmaz has been studying how different diets and environmental conditions affect intestinal stem cells, and how those factors can increase the risk of cancer and other diseases. This work could help researchers develop new ways to improve gastrointestinal health, either through dietary interventions or drugs that mimic the beneficial effects of certain diets, he says. “Our findings have raised the possibility that fasting interventions, or small molecules that mimic the effects of fasting, might have a role in improving intestinal regeneration,” says Dr. Yilmaz, who is also a member of MIT’s Koch Institute for Integrative Cancer Research.
New Assay Can Identify Specific Neurodegenerative Diseases by Detecting Abnormal Alpha-Synuclein in Patient Serum
Synucleinopathies are a group of neurodegenerative diseases caused by the abnormal accumulation α-synuclein, a protein normally found in the brain and neurons. Incorrect folding of α-synuclein leads to formation of “seeds,” which attract more α-synuclein proteins to form larger clumps. Although, α-synuclein seeds have been found in various tissues and blood of patients with synucleinopathies, its potential as a biomarker is ambiguous. Recently, in a study published in Nature Medicine, Associate Professor Ayami Okuzumi along with Senior Associate Professor Taku Hatano, both from the Juntendo University School of Medicine, Senior Assistant Professor Gen Matsumoto at the Nagasaki University School of Medicine, and Professor Nobutaka Hattori from Juntendo University Faculty of Medicine /RIKEN Center for Brain Science, present a novel assay that can efficiently detect α-synuclein seeds from a patient’s serum.