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Neurons use physical signals, not electricity, to stabilize communication

Every movement you make and every memory you form depends on precise communication between neurons. When that communication is disrupted, the brain must rapidly rebalance its internal signaling to keep circuits functioning properly. New research from the USC Dornsife College of Letters, Arts and Sciences shows that neurons can stabilize their signaling using a fast, physical mechanism—not the electrical activity scientists long assumed was required.

The discovery, published recently in Proceedings of the National Academy of Sciences, reveals a system that doesn’t depend on the flow of charged particles to maintain signaling when part of a synapse—the junction between neurons—suddenly stops working.

Maintaining this balance between neurons is essential for muscle control, learning and overall brain health. Failure to maintain this “homeostasis” has been linked to neurological conditions such as epilepsy and autism.

Real-time tracking of mRNP complex assembly reveals various mechanisms that synergistically enhance translation repression

Using single-molecule fluorescence microscopy, Payr et al. reveal how multiple RNA-binding proteins synergize to repress translation. One RNA-binding protein binds via facilitated diffusion, recruits other proteins with highly accelerated on rate, and gets stabilized by several co-factors. The findings highlight various mRNP assembly mechanism as key to efficient translational control.

‘Zombie’ cells spark inflammation in severe fatty liver disease, researchers find

Mayo Clinic researchers have uncovered how aging “zombie cells” trigger harmful inflammation that accelerates a severe and increasingly common form of fatty liver disease called metabolic dysfunction-associated steatohepatitis (MASH). As obesity rates rise worldwide, MASH is projected to increase and is already one of the leading causes of liver transplantation.

“Liver scarring and inflammation are hallmarks of MASH. If left untreated, it can progress to liver cancer. This is why it’s so important to understand the mechanisms driving the disease so that we can prevent it or develop more effective treatments,” says Stella Victorelli, Ph.D., who is the lead author of the study published in Nature Communications.

Dr. Victorelli and colleagues, who study aged or senescent “zombie” cells, identified a mechanism by which these cells drive liver scarring and inflammation. They found that small molecules called mitochondrial RNA, typically found within the cell’s energy-producing mitochondria, can leak into the main part of the cell, where they mistakenly activate antiviral sensors called RIG-I and MDA5—normally triggered when a virus infects a cell. In this case, the danger signal comes from the cell’s own mitochondria, prompting a wave of inflammation that can damage nearby healthy tissue.

Fertility gene helps glioblastoma tumors survive chemotherapy and return after treatment, researchers discover

Research by University of Sydney scientists has uncovered a mechanism that may explain why glioblastoma returns after treatment, offering new clues for future therapies which they will now investigate as part of an Australian industry collaboration.

Glioblastoma is one of the deadliest brain cancers, with a median survival rate of just 15 months. Despite surgery and chemotherapy, more than 1,250 clinical trials over the past 20 years have struggled to improve survival rates.

Published in Nature Communications, the study shows that a small population of drug-tolerant cells known as “persister cells” rewires its metabolism to survive chemotherapy, using an unexpected ally as an invisibility cloak: a fertility gene called PRDM9.

How 3 imaginary physics demons tore up the laws of nature

Science has a rich tradition of physics by imagination. From the 16th century, scientists and philosophers have conjured ‘demons’ that test the limits of our strongest theories of reality.

Three stand out today: Laplace’s demon, capable of perfectly predicting the future; Loschmidt’s demon, which could reverse time and violate the second law of thermodynamics; and Maxwell’s demon, which create a working heat engine at no cost.

Though imaginary, these paradoxical beings have pushed physicists towards sharper theories. From quantum theory to thermodynamics, these demons have legacies that we still feel today.

Image: Antonio Sortino

Three thought experiments involving “demons” have haunted physics for centuries. What should we make of them today?

Circadian clock control of ribosome composition promotes rhythmic translation and termination fidelity

Lamb et al. show that the circadian clock rhythmically remodels ribosome composition in Neurospora crassa. Clock-regulated incorporation of the ribosomal protein eL31 is required for rhythmic translation and translation fidelity, linking temporal ribosome remodeling to daily changes in proteome diversity.

Abstract: From synaptogenic to synaptotoxic

This issue’s cover features work by Alberto Siddu & team on the promotion of synapse formation in human neurons by free amyloid-beta peptides, in contrast to aggregated forms that are synaptotoxic:

The image shows a human induced neuron exposed to a nontoxic concentration of amyloid-beta42 peptide, revealing enhanced synaptogenesis, visible as synaptic puncta along the dendritic arbor.

Address correspondence to: Alberto Siddu, Lorry Lokey Stem Cell Building, 265 Campus Dr., Room G1015, Stanford, California 94,305, USA. Phone: 650.721.1418; Email: [email protected]. Or to: Thomas C. Südhof, Lorry Lokey Stem Cell Building, 265 Campus Dr., Room G1021, Stanford, California 94,305, USA. Phone: 650.721.1418; Email: [email protected].

A power move in the study of sepsis-associated acute kidney injury

Using a new strategy for quantifying mitochondrial DNA, Mark L. Hepokoski & team show the release of mtDNA from the kidney directly contributes to interleukin-6 release during sepsis associated AKI.

1VA San Diego Healthcare System, San Diego, California, USA.

2Division of Pulmonary and Critical Care and Sleep Medicine, UCSD, La Jolla, California, USA.

3Department of Critical Care Medicine, Yantai Yuhuangding Hospital, Affiliated with Medical College of Qingdao University, Yantai, Shandong, China.

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