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Category: biotech/medical – Page 381

When Familiar Faces Feel Better: A Framework for Social Neurocognitive Aging in a Rat Model

New in eNeuro from Dutta Gupta et al: Some older male rats prefer familiarity over new social situations, which can be reversed via transcranial magnetic stimulation without affecting hippocampus-mediated spatial memory.

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Social cognition, central to emotional and cognitive well-being, is particularly vulnerable to aging, where impairments can lead to isolation and functional decline. Despite compelling evidence that altered social behavior is associated with cognitive decline and dementia risk, experimental strategies for testing causative links remain scarce. To address this gap, we aimed to establish a rat model for research on social neurocognitive aging. We conducted a large-scale behavioral study in 169 male young (6 months) and aged (24−25 months) Long-Evans rats. In order to explore potential relationships among aging outcomes, we first documented individual differences in a widely validated water maze test of hippocampal learning and memory. Sociability and social novelty were then evaluated in the same subjects using the three-chamber social interaction test. Aging induced a selective shift in social novelty preference, marked by a striking familiarity bias in a substantial subpopulation of old rats, while sociability remained entirely normal. Changes in social novelty preference were completely independent of individual differences in spatial memory, and unrelated to anxiety or sensorimotor function. Notably, neuromodulation via TMS enhanced social novelty preference selectively in aged rats that exhibited a social introversion phenotype before treatment, consistent with the possibility that this aging condition reflects a distinct and modifiable neural network state. Together, the results establish a valuable preclinical framework for developing a comprehensive neurobiology of social cognition in aging.

Significance statement Social behavior is a critical yet underexplored component of cognitive aging. While both human and animal studies report age-related narrowing of social networks, the behavioral and neurobiological underpinnings remain unclear. Using a well-powered rat model, here we demonstrate preserved sociability in aging alongside marked individual differences in social novelty preference. A subset of aged rats preferred familiar over novel conspecifics, resembling patterns observed in older humans and non-human primates. Social phenotypes were independent of hippocampal-dependent memory, suggesting a dissociation between these aging outcomes. This dissociation was further validated using transcranial magnetic stimulation, supporting the notion of distinct underlying neurobiological mechanisms. Collectively, the findings lay a powerful foundation for advancing the translational neurobiology of social behavior in cognitive aging and reserve.

Engineering immunotherapy from within

In Science last year, researchers presented a method to safely and preferentially generate CAR T cells directly inside the body using targeted lipid nanoparticles that deliver mRNA directly to T cells.

The approach showed rapid and sustained immune reprogramming in preclinical models, highlighting its promise for treating cancer and autoimmune diseases.

Learn more on WorldCancerDay.

Lipid nanoparticles are designed to generate therapeutic T cells inside living animal models.

Vivek Peche and Stephen Gottschalk Authors Info & Affiliations

Science

Continue reading “Engineering immunotherapy from within” | >

Tethered platelets in severe infection

Platelets are cell fragments that plug leaks in blood vessels, preventing bleeding. However, they also form clots that impede blood flow (thrombosis) and increase inflammation.

Activated platelets, which can bind to each other, and hyporesponsive platelets, which do not form clots, are detected in patients with acute severe infections, such as COVID-19 and sepsis. How to uncouple the protective and harmful proinflammatory functions of platelets is a therapeutic dilemma.

In Science, researchers report the formation of platelet-derived integrin-and tetraspanin-enriched tethers (PITTs) in patients with severe infections.

PITTs, which are enriched in specific platelet proteins, remain anchored to the blood vessel wall (endothelium) and promote neutrophil recruitment, inflammation, and tissue damage, whereas the main platelet body shears off and reenters circulation in a hyporesponsive state. PITTs may contribute to blood clotting, immune dysregulation, and bleeding complications that characterize severe infections.

Learn more in a new Science Perspective.

Platelet-derived structures in blood vessel walls increase inflammation and bleeding risk.

Continue reading “Tethered platelets in severe infection” | >

Patent Foramen Ovale Closure in Stroke and PASCAL

Among patients with Stroke and PatentForamenOvale, the PASCAL classification system identified those likely to benefit from closure and those at risk of increased atrial fibrillation.

Question Among young and middle-aged individuals (ages 18–60 years) with patent foramen ovale (PFO) and otherwise cryptogenic ischemic stroke enrolled in pivotal trials, can the PASCAL classification system identify those who will experience net benefit and those who will experience net harm from PFO closure in the next 5 years?

Finding This meta-analysis showed that in the PASCAL groups probable and possible, PFO closure reduced recurrent ischemic stroke more often than it caused atrial fibrillation, but in the unlikely group, closure did not reduce stroke and caused a larger amount of atrial fibrillation.

Meaning The PASCAL classification system may identify as many as 4 of 5 patients who will experience net benefit and 1 of 5 who will experience net harm from PFO closure.

Tenecteplase in Prosthetic Valve Thrombosis

RCT: Among patients with obstructive prosthetic heart valve thrombosis, tenecteplase achieved higher complete thrombolytic success (97.5%) than alteplase (81.5%) and a shorter hospital stay.

Question What is the safety and efficacy of a single bolus of intravenous tenecteplase as compared with a low-dose slow-infusion protocol of alteplase in patients with obstructive mechanical prosthetic heart valve thrombosis?

Findings In this randomized clinical trial including 83 patients, tenecteplase was found to have noninferior rates of complete thrombolytic therapy success compared with alteplase. There was no difference in adverse events between the 2 groups.

Meaning Study results show that a regimen of bolus-dose tenecteplase may be a safe and efficacious alternative to current therapy for patients with prosthetic heart valve thrombosis.

Abstract: Over 100 years ago, platelets were observed to interact with neutrophils in a blood clot

Eric Boilard & team now detail platelet-neutrophil interactions as being more abundant in arthritic mice than in healthy mice, reporting neutrophils migrate in tissue to play a pathogenic role in autoimmune arthritis and noting that they fail to migrate in the absence of platelets:

Image credit: Emma Bourgeault (emmabourgeault).

1Faculté de Médecine de l’Université Laval, Université Laval, Québec City, Québec, Canada.

2Centre de Recherche ARThrite – Arthrite, Recherche, Traitements, Université Laval, Québec City, Québec, Canada.

3Axe maladies infectieuses et immunitaires du Centre de recherche du Centre hospitalier universitaire de Québec-Université Laval, Québec City, Québec, Canada.

Hypoxia tolerance of intertidal triplefin fish is associated with low critical oxygen tension and high phosphorylating capacity in brain mitochondria

At the terminus of the O2 cascade, mitochondria play an important role in O2 utilisation and energy conservation, with adaptive modifications occasionally shared among hypoxia-tolerant species. Here, we sought to determine whether mitochondrial adaptations in brain tissue explain the hypoxia tolerance of New Zealand triplefin fishes (Tripterygiidae). We compared two intertidal species (Bellapiscis medius and Forsterygion lapillum), both likely adapted to hypoxia-reoxygenation exposures, and two subtidal species (F. varium and F. malcomi), which inhabit normoxic waters. To assess hypoxia tolerance, we determined loss of equilibrium (LOE) during hypoxia exposure and measured the critical O2 tension (Pcrit). Intertidal species displayed superior hypoxia tolerance as assessed by LOE and also had lower Pcrit (LOE versus Pcrit R2 = 0.99).

Neuroimmune axis in gastrointestinal cancers: From mechanisms to therapeutic breakthrough

Targeting the neuro-immuno-tumor axis in GI cancer👇

✅Recent advances in cancer biology highlight the neuro-immuno-tumor axis as a critical regulatory network within the gastrointestinal (GI) tumor microenvironment (TME). Tumors are closely innervated, and neural signals actively shape immune cell behavior, influencing disease progression and therapeutic response.

✅A key first step toward translational impact is the identification of dominant neuroimmune pathways operating in GI cancers. Understanding how neural inputs interact with tumor cells and infiltrating immune populations provides a mechanistic framework for disrupting pro-tumor signaling circuits.

✅Pharmacological strategies offer promising opportunities for therapeutic repurposing. β-blockers such as propranolol can attenuate stress-related adrenergic signaling, while CGRP antagonists like rimegepant target nociceptor-derived immunosuppressive cues. In parallel, serotonin inhibitors, including selective serotonin reuptake inhibitors (SSRIs), may modulate enteric and immune signaling to rebalance anti-tumor immunity.

✅Beyond drug-based approaches, surgical interventions such as vagotomy illustrate how physical disruption of neural inputs can reshape the tumor ecosystem. These strategies underscore the concept that nerves are not passive bystanders, but active drivers of tumor–immune interactions.

✅Together, these insights position the neuro-immuno-tumor axis as a powerful and underexplored therapeutic target. By integrating neurobiology with cancer immunology, future treatments may unlock more effective and durable anti-tumor responses in GI cancers.

Continue reading “Neuroimmune axis in gastrointestinal cancers: From mechanisms to therapeutic breakthrough” | >

Mathematical Innovation Advances Complex Simulations for Science’s Toughest Problems

Berkeley researchers have developed a proven mathematical framework for the compression of large reversible Markov chains—probabilistic models used to describe how systems change over time, such as proteins folding for drug discovery, molecular reactions for materials science, or AI algorithms making decisions—while preserving their output probabilities (likelihoods of events) and spectral properties (key dynamical patterns that govern the system’s long-term behavior).

While describing the dynamics of ubiquitous physical systems, Markov chains also allow for rich theoretical and computational investigation. By exploiting the special mathematical structure behind these dynamics, the researchers’ new theory delivers models that are quicker to compute, equally accurate, and easier to interpret, enabling scientists to efficiently explore and understand complex systems. This advance sets a new benchmark for efficient simulation, opening the door to scientific explorations once thought computationally out of reach.

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