Study Challenges Evolutionary Theory That DNA Mutations Are Random; Work Suggests Vital Areas of Genome Are Protected from Mutation

A simple roadside weed may hold the key to understanding and predicting DNA mutation, according to new research from University of California (UC), Davis, and the Max Planck Institute for Developmental Biology in Germany, and collaborating institutions. The findings, published January 12 in Nature, radically change our understanding of evolution and could one day help researchers breed better crops or even help humans fight cancer. The open-access article is titled “Mutation Bias Reflects Natural Selection in Arabidopsis thaliana.”

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Researchers Reveal How Skin Cells Form a First Line of Defense Against Skin Cancer; RNA-Binding Protein (CSDE1) Is Key

A study published online on January 11, 2022 in Cell Reports reveals important insights into the molecular mechanisms that underpin the body’s natural defenses against the development of skin cancer. The findings offer new clues into the behavior of skin cancer at the cellular level, paving the way for potential new therapeutic targets to treat the disease. The open access article is titled “Coordinated Post-Transcriptional Control of Oncogene-Induced Senescence by UNR/CSDE1.” “We found that the protein CSDE1 coordinates a complex chain of events that enable senescence in skin cells, significantly slowing down their function without causing death,” says Rosario Avolio, PhD, first author of the study and postdoctoral researcher at the Centre for Genomic Regulation (CRG) at the time of submission. “The resulting cells act as a firewall against cancer, suppressing the formation of tumors.”

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Obscure Protein Is Spotlighted in Fight Against Leukemia

Acute myeloid leukemia (AML) is an aggressive cancer of white blood cells with few effective targeted therapies available to treat it. Cold Spring Harbor Laboratory (CSHL) Professor Christopher Vakoc (photo), MD, PhD, and former graduate student Sofya Polyanskaya, PhD, found that AML cells rely on a previously little-known protein called SCP4 for survival. Their discovery points to a potential new therapeutic approach for this disease. SCP4 is a phosphatase, a type of protein that regulates cell activity by removing phosphates from other proteins. Another type of protein called a kinase puts those phosphates back on. The number of phosphates added to or subtracted from a protein—its phosphorylation level—determines its activity. Polyanskaya discovered that SCP4 could pair with either one of two similar kinases called STK35 and PDIK1L. AML cells appear to need the phosphatase and kinases to work together to survive; turning off the gene that produces SCP4 kills the cancer cells.

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Vaccine-Like mRNA Injection Can Be Used to Make CAR T Cells in the Body; Penn Study Reveals an Easier, More Scalable Way to Make A Powerful Immunotherapy

An experimental immunotherapy can temporarily reprogram patients’ immune cells to attack a specific target via only a single injection of messenger RNA (mRNA), similar to the mRNA-based COVID-19 vaccines, according to a new study from researchers in the Perelman School of Medicine at the University of Pennsylvania. The researchers, whose work was published on January 6, 2022 in Science, demonstrated the new approach with an mRNA preparation that reprograms T cells—a powerful type of immune cell—to attack heart fibroblast cells. Heart failure is often driven in part by these fibroblast cells, which respond to heart injury and inflammation by chronically overproducing fibrous material that stiffens the heart muscle, impairing heart function—a condition called fibrosis. In experiments in mice that model heart failure, the reduction in cardiac fibroblasts caused by the reprogrammed T cells led to a dramatic reversal of fibrosis. The article is titled “CAR T Cells Produced in Vivo to Treat Cardiac Injury.”

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How Do We Provide Meaning to Our Environment? Trying to Crack the Neural Code of the Brain

The brain is the most complex organ in our body – constantly absorbing and interpreting our surroundings, and guiding our movement, thoughts, behaviors and emotions. Although human beings share a fundamental understanding of our surrounding environment (i.e. ice is cold, fire is hot, knives are sharp) – each of us develops a unique interpretation of the information we process. For example, two people can have very different reactions after tasting the exact same meal, hearing the same sound, or leaving a shared social interaction. Jerry Chen, PhD, a Boston University College of Arts & Sciences Assistant Professor of Biology, researches the neural code of the brain. He aims to better understand the relationship between the genetic and electrical influences that control cognitive functions like sensory processing, decision-making, and learning and memory. “In order to crack the neural code,” explains Dr. Chen, “you need to know at least two things. First, you need to be able to measure the activity of neurons in the brain as a subject is carrying out different cognitive tasks. And second, you have to know the identity of those neurons which we can learn about through the genes they express.”

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Why You Drink Black Coffee: It’s in Your Genes; Black Coffee Drinkers Also Prefer Dark Chocolate Due to Genes

People who like to drink their coffee black also prefer dark chocolate, a new Northwestern Medicine study found. The reason is in their genes. Northwestern scientists have found coffee drinkers who have a genetic variant that reflects a faster metabolism of caffeine prefer bitter, black coffee. And the same genetic variant is found in people who prefer the more bitter dark chocolate over the more mellow milk chocolate. The reason is not because they love the taste, but rather because they associate the bitter flavor with the boost in mental alertness they expect from caffeine.

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Microglial Methylation “Landscape” in Human Brain; Profiles Differ Across Age, Disease State, Brain Region, and Individual; Early Data Point to Pathology of Microglia, Key Immune Cells of Brain, in Biology of Depression

In the central nervous system, microglial cells play critical roles in development, aging, brain homeostasis, and pathology. Recent studies have shown variation in the gene-expression profile and phenotype of microglia across brain regions and between different age and disease states. But the molecular mechanisms that contribute to these transcriptomic changes in the human brain are not well understood. Now, a new study targets the methylation profile of microglia from human brain. The study was published online on October 30, 2021 in Biological Psychiatry, published by Elsevier. The open-access article is titled “Contribution of Age, Brain Region, Mood Disorder Pathology, and Interindividual Factors on Methylome of Human Microglia.”

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Ketamine Therapy Has Swift Short-Term Effect on Reducing Symptoms of Depression and Suicidal Thoughts, According to Comprehensive Review of All Available Evidence

Ketamine therapy has a swift short-term effect on reducing symptoms of depression and suicidal thoughts, according to a recent systematic review of all the available evidence. The review was led by the University of Exeter and funded by the Medical Research Council and it analyzed evidence from 83 published research papers. The strongest evidence emerged around the use of ketamine to treat both major depression and bipolar depression. Symptoms were reduced as swiftly as one to four hours after a single treatment, and lasted up to two weeks. Some evidence suggested that repeated treatment may prolong the effects, however more high-quality research is needed to determine by how long. Similarly, single or multiple doses of ketamine resulted in moderate to large reductions in suicidal thoughts. This improvement was seen as early as four hours following ketamine treatment and lasted on average three days, and up to a week.

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Cracking Code for Newly Recognized System of Cell-to-Cell Signaling–Joslin Researchers Discover How Cells Select MicroRNAs Secreted in Exosomes and Regulate Metabolism in Other Cells at a Distance; Ability to Manipulate MicroRNA Codes in Exosomes Could Improve Gene Therapies for Diabetes and Other Metabolic Diseases

Control of most bodily functions depends on the ability of cells to talk to each other. We have long known about two routes for cell-to-cell communication: the nervous system and the secretion of hormones. Over the past five years, scientists have recognized an important third route of communication based on exosomes—tiny sacs or vesicles containing protein and RNA molecules that cells secrete into circulation where they can be taken up by other cells to regulate metabolism. Many labs are now focusing on exosomes carrying microRNAs. These are very short RNAs that can regulate the ability of other longer RNAs that make different cellular proteins and control cell function. Thus, microRNAs affect many aspects of cellular behavior in health and disease. Scientists at Joslin Diabetes Center, and collaborators, have now discovered how cells pick a collection of microRNAs for their exosomes, said C. Ronald Kahn, MD, a Joslin Senior Investigator and Professor of Medicine at Harvard Medical School.

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Anthrax Toxins Reduce Pain by Altering Signaling in Pain-Sensing Neurons and Can Deliver Molecular Cargo

Anthrax has a scary reputation. Widely known to cause serious lung infections in humans and unsightly, albeit painless, skin lesions in livestock and people, the anthrax bacterium has even been used as a weapon of terror. Now, the findings of a new study suggest the dreaded microbe also has unexpected beneficial potential—one of its toxins can silence multiple types of pain in animals. The research reveals that this specific anthrax toxin works to alter signaling in pain-sensing neurons and, when delivered in a targeted manner into neurons of the central and peripheral nervous system, can offer relief to animals in distress. The work, led by investigators at Harvard Medical School (HMS) in collaboration with industry scientists and researchers from other institutions, was published online on December 20, 2021 in Nature Neuroscience. The article is titled “Anthrax Toxins Regulate Pain Signaling and Can Deliver Molecular Cargoes into ANTXR2+ DRG Sensory Neurons.”

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