The age at which women go through menopause is critical for fertility and impacts healthy aging in women, but reproductive ageing has been difficult for scientists to study and insights into the underlying biology are limited. Now, scientists have identified nearly 300 gene variations that influence reproductive lifespan in women. Additionally, in mice, they have successfully manipulated several key genes associated with these variants to extend their reproductive lifespan. The scientists’ findings, published online on August 4, 2021 in Nature, substantially increase our knowledge of the reproductive aging process, as well as providing ways to improve the prediction of which women might reach menopause earlier than others. The article is titled “Genetic Insights into Biological Mechanisms Governing Human Ovarian Ageing.”
From the time of Aristotle, it has been known that the human liver has the greatest regenerative capacity of any organ in the body, being able to regrow even from a 70% amputation, which has enabled live-donor transplants. Although the liver regenerates fully upon injury, the mechanisms that regulate how to activate or stop the process and when regeneration is terminated, are still unknown. Researchers at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden (Germany), at the Gurdon Institute (Cambridge, UK) and at the University of Cambridge (Biochemistry Department) have now found that a regulatory cell type–mesenchymal cell–can activate or stop liver regeneration. The mesenchymal cells do so by the number of contacts they establish with the regenerating cells (epithelial cells). This study suggests that mistakes in the regeneration process, which can give rise to cancer or chronic liver diseases, are caused by the wrong number of contacts between both populations. The work is described in a paper published online in Cell Stem Cell on August 2, 2021. The open-access article is titled “Dynamic Cell Contacts Between Periportal Mesenchyme and Ductal Epithelium Act As a Rheostat for Liver Cell Proliferation.”
Removing a protein that is often overexpressed in a rare and aggressive subtype of leukemia can help to slow the cancer’s development and significantly increase the likelihood of survival, according to a study in mice led by scientists at the UCLA Jonsson Comprehensive Cancer Center. The research, published online on June 29, 2021 in Leukemia, could aid in the development of targeted therapies for cancers that have high levels of the RNA-binding protein IGF2BP3 (insulin-like growth factor 2 mRNA-binding protein 3)–especially acute lymphoblastic and myeloid leukemias that are characterized by chromosomal rearrangements in the mixed lineage leukemia (MLL) gene. The open-access article is titled “The RNA-Binding Protein IGF2BP3 Is Critical for MLL-AF4-Mediated Leukemogenesis.” In these MLL-rearranged leukemias, IGF2BP3 attaches to certain RNA molecules that carry genetic instructions for cancer-related proteins, markedly amplifying cancer development. Children and adults diagnosed with this subtype have a poor prognosis and a high risk of relapse after treatment.
The mutations that give rise to melanoma result mainly from a chemical conversion in DNA fueled by sunlight–not just a DNA copying error as previously believed, reports a study by Van Andel Institute scientists published in the July 30, 2021 issue of Science Advances. The open-access article is titled “The Major Mechanism of Melanoma Mutations Is Based on Deamination of Cytosine in Pyrimidine Dimers As Determined by Circle Damage Sequencing.” The findings upend long-held beliefs about the mechanisms underlying the disease, reinforce the importance of prevention efforts, and offer a path forward for investigating the origins of other cancer types. “Cancers result from DNA mutations that allow defective cells to survive and invade other tissues. However, in most cases, the source of these mutations is not clear, which complicates development of therapies and prevention methods,” said Gerd Pfeifer, PhD, a VAI professor and the study’s corresponding author. “In melanoma, we’ve now shown that damage from sunlight primes the DNA by creating ‘premutations’ that then give way to full mutations during DNA replication.”
Amyotrophic lateral sclerosis (ALS) (Lou Gehrig’s disease) is a rapidly progressive and fatal degenerative disease affecting the nerve cells in the brain and spinal cord responsible for controlling voluntary muscle movement. “Sporadic” or non-inherited ALS, accounts for roughly 90% percent of cases, and 10% of cases are due to known genetic mutations. By studying lab-grown neurons derived from skin or blood cells from 10 normal controls, from 8 individuals with an ALS-causing mutation, and from 17 people with non-inherited ALS, researchers have found a possible starting point for the dysfunction that causes the disease. The study, which was published online on July 28, 2021 in Science Translational Medicine, was funded in part by the National Institute for Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health. The article is titled “Nuclear Accumulation of CHMP7 Initiates Nuclear Pore Complex Injury and Subsequent TDP-43 Dysfunction in Sporadic and Familial ALS.”
On July 28, 2021, EV Biologics Corp. (OTC PINK:YECO) announced that it has signed an agreement with Lonza Cell Bio Services to implement a custom cell isolation in preparation for a novel, clonal, master cell bank. These cells will also be used in optimization of the process for production of therapeutically active, native, extracellular vesicles (EVs) and extracellular particles (EVPs). Lonza Cell Bio Services is a leading provider of cell banks and custom cell isolation services. EV Biologics CEO, Daniel Mckinney said “Leveraging Lonza’s infrastructure for this important step in our first novel cell line generation will establish a solid foundation for further development of cutting-edge native and engineered EVP therapeutics. Our innovative technological approach will be implemented for the first time within the rigorous framework of Lonza’s cell isolation and tissue-processing facilities to accelerate our cGMP process development for novel cell line generation and standardization of EVP-based therapeutics production.”
On July 27, 2021, it was announced that Rice University (Houston, Texas) bioengineers are using 3D printing and smart biomaterials to create an insulin-producing implant for Type 1 diabetics. The three-year project is a partnership between the laboratories of Omid Veiseh, PhD, and Jordan Miller, PhD, that’s supported by a grant from the Juvenile Diabetes Research Foundation (JDRF), the leading global funder of diabetes research. Dr. Veiseh and Dr. Miller will use insulin-producing beta cells made from human stem cells to create an implant that senses and regulates blood glucose levels by responding with the correct amount of insulin at a given time.
Blood group analyses for three Neandertals and one Denisovan by a team from the Anthropologie Bio-Culturelle, Droit, Éthique et Santé research unit (CNRS / Aix-Marseille University / EFS) in France confirm hypotheses concerning their African origin, Eurasian dispersal, and interbreeding with early Homo sapiens. The researchers also found further evidence of low genetic diversity and possible demographic fragility. Their findings were published online on July 28, 2021 in PLOS ONE. The open-access article is titled “Blood Groups of Neandertals and Denisova Decrypted.” The extinct hominin lineages of the Neandertals and Denisovans were present throughout Eurasia from 300,000 to 40,000 years ago. Despite prior sequencing of about 15 Neandertal and Denisovan individuals, the study of the genes underlying blood groups had hitherto been neglected. Yet blood group systems were the first markers used by anthropologists to reconstruct the origins of hominin populations, their migrations, and their interbreeding.
Building on recent research confirming how ketamine induces rapid antidepressant action, Professor of Pharmacology Lisa Monteggia, PhD, at Vanderbilt University, and her collaborators, have now shown how the molecular mechanism of the gene MeCP2 (coding for methyl CpG binding protein 2) and associated synaptic adaptability are critical to the long-term antidepressant effects of ketamine. While MeCP2 has been shown to be important for typical antidepressants, this new research indicates that, in cooperation with ketamine’s initial target, the gene is important for long-term antidepressant action, Dr. Monteggia said. The researchers discovered that MeCP2 influences ketamine’s behavioral effect as well as potentiation—the strengthening of synapses—improving its antidepressant effects over time. The new work also shows that the long-term effects of ketamine involve synaptic adaptability, or plasticity—not simply structural changes. Dr. Monteggia and her team went on to show that repeated exposure to ketamine further strengthened synaptic plasticity—eliciting more plasticity of plasticity—which the team termed “metaplasticity.” This may explain why repeated doses of ketamine produce a cumulative and prolonged effect.
On July 28, 2021, The University of Texas MD Anderson Cancer Center and Blueprint Medicines Corporation announced a three-year strategic research collaboration focused on accelerating development of BLU-222, an investigational precision cancer therapy designed to target cyclin-dependent kinase 2 (CDK2) (image), a critical cell-cycle regulator. The collaboration brings together MD Anderson translational research scientists, the drug development capabilities of MD Anderson’s Therapeutics Discovery division, and Blueprint Medicines’ precision therapy pipeline and expertise. The teams seek to characterize the range of cancer types susceptible to treatment with a selective CDK2 inhibitor, advance BLU-222 mono- and combination-therapy strategies with the potential to maximize patient benefit, and identify novel biomarkers that may better predict treatment response and optimize patient selection.