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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.

Z-DNA Triggering Drug Kills Immunotherapy Resistant Melanoma by Mimicking Flu

A candidate drug triggers Z-DNA conformations in cells that in turn activates a highly immunogenic programmed pathway of inflammatory cell death in cancer-associated fibroblasts. In mouse studies, researchers showed that the compound (CBL0137), a member of the curaxin family, rekindles immune responses against melanoma resistant to immune checkpoint blockade immunotherapy by mimicking influenza infections. Combining a "virus mimetic" immune adjuvant with immunotherapy may rekindle an immune response in otherwise unresponsive patients.

Antibiotics Induce Invasive Candidiasis in Mice and Humans, Immunotherapy Could Help

Pre-exposure to broad-spectrum antibiotics increases susceptibility to Candida albicans infections in mice and affects ensuing immune responses, a new study claims. Antifungal immunity in the gut specifically depletes in antibiotic administered mice, and is compounded by bacterial escape and systemic bacterial co-infections. Mice treated with a cocktail of broad-spectrum antibiotics show reductions in T helper cells that express IL-17 and impaired lymphocyte-dependent IL-17A- and GM-CSF-mediated antifungal immunity in the gut. Hospitalized patients pre-exposed to broad-spectrum antibiotics also showed increased risk of invasive candidiasis and decreased survival post-infection.

Brain Rejuvenating Factor Triggers Myelin to Restore Recall in Aged Mice

A new study on mice identifies a potential systemic therapeutic target in the cerebrospinal fluid (CSF) that promotes myelin formation in hippocampal oligodendrocytes, stimulates proliferation of oligodendrocyte progenitor cells, improves neuronal functions, and increases memory recall. The authors investigate the rejuvenating properties of 10-week-old CSF when injected into 18-month-old mice. The study also suggests that routes of drug administration that allow therapeutics to directly access the CSF could be beneficial in treating dementia.

How Mice Brains Compute Social Rank

Salk scientists discover a neural circuit involving the mPFC and the hypothalamus by which the brain exerts a top-down effect on social rank in mice. The study suggests all animals who live in social hierarchies experience different brain states and use different neurons when in the company of others compared to when alone. Understanding how the brain computes social rank may help understand animal and human behaviors and the interplay between social rank, isolation, and psychiatric diseases.

Mitochondria Function as Micro-Lenses in Retinal Cone Receptors

A new study shows mitochondria in cone shaped photoreceptors in ground squirrels act as micro-lenses that redirect light to the tapering outer segments where light is converted into electrical signals. This new finding may explain the Stiles Crawford effect, that describes a basic phenomenon where light entering the eye through the periphery of the pupil does not appear as bright as light passing through its center. Insights from the study could also help in the early detection of eye diseases such as retinitis pigmentosa.