Theo Murphy meeting organised by Professor Robert Barton, Professor Zanna Clay and Professor Nicky Clayton FRS

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The brain's extracellular matrix (ECM) is highly specialized and unique. Unlike the collagen-rich matrices found in other tissues, it consists of complex proteoglycans and glycosaminoglycans that play critical roles in neuroplasticity including the integration and storage of new memories. Cystatin-related epididymal spermatogenic (CRES) is a member of a reproductive subgroup of family 2 cystatins and part of a specialized functional amyloid-containing ECM with host defense functions in the epididymal lumen. CRES and the endogenous epididymal amyloid matrix exhibit high plasticity, forming distinct amyloid structures, with antimicrobial functions tailored to specific bacterial strains. Recent studies show that CRES/CRES amyloid is also present in the mammalian brain ECM and suggest its inherent shape-shifting properties might contribute to neuroplasticity. In this study, we utilized a CRES knock-out (KO) mouse model to determine if the loss of CRES altered the structure of the hippocampal and cortical ECM and impacted brain function. We report that CRES KO male and female mice exhibited sex-specific structural changes in both the loose/interstitial and perineuronal net (PNN) ECM. Additionally, young CRES KO males—but not females—displayed deficits in learning, memory, and executive functioning when compared with WT controls. In contrast, older CRES KO males did not exhibit behavioral deficits, a finding that correlated with the observation of a similar PNN ECM structure when compared with WT mice. Our data suggest that CRES functions as a regulatory or structural component of the brain ECM, contributing to its sex-specific structural organization and plasticity, affecting sex-specific behaviors of learning and memory.

Abstract page for arXiv paper 2610.41482: KEEPER: Learning Control-Sufficient Textual Memory for Long-Horizon LLM Agents

Maastricht study of 31 adults aged 60-75 finds 60g daily unsalted skin-roasted peanuts for 16 weeks improves insulin responsiveness in memory-related brain regions.

Previously, we showed that bumblebees encode reward value relative to local alternatives and, when comparing options learned in separate contexts, retrieve only their ordinal rank rather than absolute reward magnitude (Solvi et al., 2022). However, that study, like related work across species, varied reward along a single dimension. Natural rewards such as nectar are multidimensional, yet how such rewards are represented in relative memory remains unknown. We tested this by training bumblebees in separate contexts with rewards varying in two intrinsic dimensions, sucrose concentration and NaCl content, and then comparing options never encountered together. When only sucrose concentration varied, bees showed no preference between options that had each been locally better, despite differing in absolute concentration. With multidimensional rewards, however, this equivalence no longer held: bees preferred an option that had been locally better on both sucrose and NaCl over one better on only sucrose or only NaCl. A two-dimensional advantage also produced a stronger preference than a one-dimensional advantage 48 h after training. Thus, the ordinal rank we previously identified captures only part of the relative reward representation: with multidimensional rewards, bumblebees also retain information about the dimensions on which an option had been locally better.

Sparse Mixture-of-Experts (MoE) models offer scalable capacity for Web applications, but uneven routing creates computation and communication bottlenecks. Existing placement and replication methods redistribute this workload, yet additional expert copies compete with token-related buffers for limit…

Radioactive waste repositories are designed to isolate waste from the living environment without human intervention over extended periods of time. Nevertheless, the intention is not to abandon the rep...

Previously, we showed that bumblebees encode reward value relative to local alternatives and, when comparing options learned in separate contexts, retrieve only their ordinal rank rather than absolute reward magnitude (Solvi et al., 2022). However, that study, like related work across species, varied reward along a single dimension. Natural rewards such as nectar are multidimensional, yet how such rewards are represented in relative memory remains unknown. We tested this by training bumblebees in separate contexts with rewards varying in two intrinsic dimensions, sucrose concentration and NaCl content, and then comparing options never encountered together. When only sucrose concentration varied, bees showed no preference between options that had each been locally better, despite differing in absolute concentration. With multidimensional rewards, however, this equivalence no longer held: bees preferred an option that had been locally better on both sucrose and NaCl over one better on only sucrose or only NaCl. A two-dimensional advantage also produced a stronger preference than a one-dimensional advantage 48 h after training. Thus, the ordinal rank we previously identified captures only part of the relative reward representation: with multidimensional rewards, bumblebees also retain information about the dimensions on which an option had been locally better.