Charting water quality improvements and practice reversion with pesticide interventions at catchment scale.

Freshwater quality, and the impacts of farming practice on drinking water supplies, are of concern in many countries and time-limited catchment management interventions are commonly used to improve water quality. However, ending such schemes may result in practice reversion. This study adopts an interdisciplinary approach combining evidence from water quality monitoring data with a behavioural study of farmers to explore changes in land use practice with reference to the pesticide MCPA (2-methyl-4-chlorophenoxyacetic acid) following a catchment-based management scheme delivered in the cross-border Derg catchment in Northern Ireland/Ireland between 2018 and 2021.

Immunoproteasome inhibition reduces donor specific antibody production and cardiac allograft vasculopathy in a mouse heart transplantation model.

Objective: Cardiac Allograft Vasculopathy (CAV), a process of vascular damage accelerated by antibody-mediated rejection (AMR), is one of the leading causes of cardiac transplant failure. Proteasome inhibitors (PIs) are utilized to treat AMR, however PI-associated toxicity limits their therapeutic utility. Novel immunoproteasome inhibitors (IPIs) have higher specificity for immune cells and have not been investigated for AMR in cardiac transplant patients.

Mechanisms driving epigenetic and transcriptional responses of microglia in a neurodegenerative lysosomal storage disorder model.

Lysosomal dysfunction is causally linked to neurodegeneration in many lysosomal storage disorders (LSDs) and is associated with various age-related neurodegenerative diseases , but there is limited understanding of the mechanisms by which altered lysosomal function leads to changes in gene expression that drive pathogenic cellular phenotypes. To investigate this question, we performed systematic imaging, transcriptomic, and epigenetic studies of major brain cell types in null (KO) mice, a preclinical mouse model for Sanfilippo syndrome (Mucopolysaccharidosis Type IIIA, MPS-IIIA) . MPS-IIIA is a neurodegenerative LSD caused by homozygous loss-of-function (LoF) mutations in which results in severe early-onset developmental, behavioral, and neurocognitive impairment .