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Magnesium Enables Immune Cells to Tackle Infections and Cancer

A new study has identified extracellular magnesium as a critical immune modulator of CD8+ T cells. The paper provides evidence that magnesium is sensed via a protein called LFA-1 on CD8+ T cells and that LFA-1 mediated activation of CD8+ T cells depends on extracellular magnesium. Through retrospective analysis of clinical trial data, the researchers showed low serum magnesium levels are associated with worse outcomes in cancer immunotherapy. The study opens new avenues for exploring magnesium modulation in cancer immunotherapies.

Gene Therapy for a Rare Muscular Dystrophy Overcomes Earlier Roadblocks

A preclinical study provides proof-of-concept evidence for a new gene therapy approach that offers a potential long-term treatment for limb-girdle muscular dystrophy 2B. Researchers at Children’s National have developed the first non-muscle targeted gene therapy that enhances diseased muscle fiber repair and improves muscle function through a single low dose of an AAV vector that produces human acid sphingomyelinase, released by muscle cells immediately following muscle injury.

How to Make an Ear

A new study from researchers at Harvard Medical School shows that the extracellular matrix can provide the driving force needed for tissue morphogenesis, challenging earlier studies that proposed motor proteins within cells drive tissue-structuring processes. The authors showed that hyaluronate pressure in combination with proteins that connect cells and direct the pressure generated through the swelling of hyaluronate in water, powers morphological change. The findings provide new insights for bioengineering, regenerative medicine, and basic biology.

Modifying Memories Depends on Initial Learning, Hippocampal Stars Indicate

Scientists have identified a molecular mechanism that renders memories flexible. Cognitive flexibility is very important in adapting to a changing environment. The findings lay the foundation for research on how to restore cognitive flexibility with age or in diseases such as autism and schizophrenia. The authors showed that cognitive flexibility is determined at the time of initial learning which refutes previous theories that proposed synaptic plasticity only occurs after memory formation.

Softening a Hardened Heart Counts on Cardiac Splicing Regulators

Scientists have developed a therapeutic agent to treat heart failure caused by the stiffening of the walls of the chambers of the heart that prevents adequate filling of the chambers even when the pumping activity of the heart is normal. This form of heart failure has no available treatment at present. The authors have targeted a splicing factor that regulates the splicing of titin, a protein that regulates the elasticity of the heart walls.

Psoriasis Therapeutic Could Tweak an Alternate Target in a Trio

Mice having a keratinocyte-specific deletion of the receptor for the cytokine TWEAK, Fn14, display reduced skin inflammation upon chemical induction, including decreased epidermal hyperplasia and less expression of psoriasis signature genes. Based on this finding and transcriptomic analysis of human keratinocytes, Michael Croft, PhD, and his team have shown TWEAK works together with the known cytokines TNF or IL-17 in provoking inflammation in psoriasis. The study shows targeting TWEAK could offer an alternative approach to treating the disease.

Time of Day Determines Immune Response to Infections

New research provides evidence that the migration of immune cells called dendritic cells into skin lymphatic vessels is a rhythmic process. The study showed circadian molecular clock systems in the dendritic cells and in the cells lining the lymphatic vessels are an essential and broad regulator of dendritic cell migration. This process is fundamental for the generation of adaptive immunity, the authors noted, and should prove useful to exploit in vaccination and immunotherapeutic regimens.

Immunotherapy Increasing Dead Cell Clean Up Limits Post-Stroke Neurological Deficits

New research from the University of Tsukuba, Japan, shows that mice that have either low levels of a phosphatidylserine receptor called CD300a, or where CD300a is pharmacologically blocked, suffer limited neurological deficits after middle cerebral artery occlusion (MCAO)—a condition that recapitulates an ischemic stroke. These results open doors for potential new immunotherapies that can suppress stroke-related inflammation at its earliest stages, which often results in brain damage and permanent impairment.

Cartilage Matrix Integrity Rests on Respiring Mitochondria

Genetically turning off mitochondrial respiration in mice results in an abnormal expansion of cartilage at the head of the femur, disorganized cartilage cells, and excessive extracellular matrix, a new study led by scientists at the University of Cologne shows. Osteoporosis, arthrosis, and other musculoskeletal diseases can be caused by changes in the extracellular matrix, significantly affecting quality of life. The findings demonstrated that mitochondrial respiratory chain dysfunction is a key factor promoting extracellular matrix integrity and mechanical stability in cartilage, and may contribute to the development of new diagnostic and therapeutic approaches for musculoskeletal diseases.

Pediatric Leukemia Drug Candidate Benefits from Structure-Based Design

Researchers at Mount Sinai, New York, have used a structure-based designing approach to develop a small-molecule chimera called MS67 that targets protein degradation mechanisms and selectively breaks down WDR5, a chromatin binding protein that contributes to tumorigenesis of a wide range of human cancers including both solid tumors and blood cancers.