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Rapamycin’s Anti-Aging Promise Gains Further Support

Brief exposure to rapamycin in early adulthood has the same anti-ageing effects as lifelong treatment, scientists claim. Life-long or long-term rapamycin dosing can have negative side effects, earlier studies had reported. These can be overcome through short-term treatments at the lowest effective dose in early adulthood, retaining the positive effects of the drug: increased lifespan, decreased age-related intestinal decline, and long-term increase in the degradation of damaged intestinal cells, the current study shows.

Mucus Reveals New Evolutionary Mechanism

Scientists from the University at Buffalo compared genomic differences in a class of sugary proteins found in mucus called mucins and discovered 15 instances in 49 species where mucins evolved by incorporating repeats in the protein-coding regions of their genes (exons) that induce the protein product to acquire a dense brush of projecting sugar molecules upon synthesis, through a process called O-glycosylation. The researchers used a combination of bioinformatics, phylogenetics, proteomics and histology, in their work.

Gene Activity Enlists Navigation Cells to Lend a Sense of Space

A study on mice uncovers molecular mechanisms that underlie spatial mapping in the brain. Researchers have found a gene called Fos plays a key role in helping the brain use specialized navigation cells to form and stabilize spatial maps. The findings help better understand the process of spatial mapping in the brain and informs our capacity for navigation. The mechanistic insights may help understand the disruption of spatial memory mechanisms in patients suffering from injuries to the brain, or neurodegeneration.

Fear and Unpleasant Memories Depend on Integrated Parallel Pathways

Neurons expressing calcitonin gene-related peptide (CGRP) in the thalamus and the brainstem respond to multi-sensory threat cues from various sensory modalities and relay negatively tagged signals to the lateral and central amygdala, respectively. Both CGRP neural populations and their projections to the amygdala are required for the perception of threat that generally involves cues from multiple sense organs, and the formation of unpleasant memories. The integrated threat pathway may lead to therapies for fear-related disorders.

Single-Cell Functional Proteome Profiling Uncovers Novel Targets for Alzheimer’s Disease

A new cyclic microchip assay analyzes hundreds of proteins in individual neurons to identify new drug targets for Alzheimer’s disease in mice and increases throughput and sensitivity of single-cell protein detection using affinity reagents. The assay achieves high throughput by repeated labeling of cellular proteins with affinity reagents and decoding biotin labelled unique DNA tags. Individual cells in a microchip well are stained for four rounds by a cocktail of DNA barcoded antibodies.

Obesity-Induced Liver Cancer Triggered by Leaky Membranes

Leaky membranes in aging liver cells release cancer-promoting factors that activate regulatory T cells, a new study demonstrates. High-fat diet weakens gut barrier function, resulting in the migration and accumulation of lipoteichoic acid in the liver, that is secreted by gut bacteria. Lipoteichoic acid stimulates the cleavage of gasdermin D protein that forms pores in the cell membrane through which cancer promoting IL-1β and IL-33 are released from liver fibroblasts.

Hair Regeneration Requires Regulatory T Cells Signal Skin Stem Cells

The crosstalk between regulatory T cells and stem cells in hair follicles is mediated by glucocorticoid hormones, their receptor and transforming growth factor-beta3, Salk scientists claim in a new study. This study demonstrates that regulatory T cells and glucocorticoid hormones are not just immunosuppressants but also have a regenerative function. The new findings highlight a possible strategy of manipulating regulatory T cells to support tissue regeneration.

All-in-One AAV Delivery Realized by a Compact Base Editor

A compact new adenine base editor, Nme2-ABE, that includes a Cas9 isolated from Neisseria meningitidis, targets a distinct range and editing window, generates fewer off-target edits, and can efficiently correct mutations in both mouse and human genomes, compared to ABEs that include the commonly used Cas9 from Streptococcus pyogenes. The advantage of the new ABE is that it allows the packaging of the entire editing machinery in a single AAV instead of two. This will improve safety and efficacy of a range of therapeutic applications.

Physical Performance Boosted by Ion Channel Gene Variant in Mice

A variant of a gene that encodes a mechanosensitive ion channel in tendons can make mice run faster and jump further. The variant widens tendons, enlarges collagen fibril diameter, increases compliance and elastic energy and is common in individuals of African descent. It has no effect on muscles or nerves, but only alters cells in tendons. The finding opens doors for new treatments for tendon injuries and age-related decline in mobility.

Drug Resistant Tuberculosis Could be Treated with Derivative of Tropical Plant

South Korean scientists have isolated and purified an active ingredient from Cynanchum atratum, a flowering plant used in traditional Chinese medicine, called deoxypergularinine (DPG) and developed and tested multiple analogues of the compound for their ability to inhibit M. tuberculosis without harming infected cells. PP derivates of DPG specifically inhibited normal and drug-resistant strains of Mycobacterium tuberculosis without significantly changing the intestinal microbiome in mice.