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Cooper, I.

Publications and source records attributed to Cooper, I..

2 recordsLinked to original sources

Tick hazard in the South Downs National Park (UK): species, distribution, key locations for future interventions, site density, habitats

BackgroundThe South Downs National Park (SDNP) is the UKs most visited National Park, and a foci of tick-borne Lyme disease. A range of human pathogens have been detected in UK ticks and related hosts, and the first presumed autochthonous cases of tick-borne encephalitis and babesiosis were recorded in 2019-20. SDNPs key objectives include conserving wildlife and encouraging enjoyment of the countryside, so interventions are needed that reduce hazard without negatively affecting ecosystem health. To be successful these require knowledge of site hazards, and we aimed to provide this to enable action. MethodsBritish Deer Society volunteers submitted ticks removed from deer. Key potential intervention sites were selected and ticks collected by drag-sampling six 50 m2 transects per site, in most cases twice yearly for two years. Ticks were identified in-lab (sex, life stage, species), hazard measured as tick presence, Density of Ticks (all life stages, DOT), and Density of Nymphs (DON). Sites and habitat types were analysed for association with hazard. Distribution across SDNP was mapped in a Geographic Information System (GIS), by combining and comparing our fieldwork results with records from five other data sources (recent and historic). Results87 Ixodes ricinus (all but one adults, 82%F) were removed from 14 deer (Dama dama n=10; Capreolus capreolus n=3; 1 not recorded; tick burden, 1-35) at 12 locations (commonly woodland). Five potential key intervention sites were identified and drag-sampled 2015-16, collecting 623 ticks (238 on-transects): 53.8% nymphs, 42.5% larvae, 3.7% adults (13M, 10F). Ticks were present on-transects at all sites drag-sampled (I.ricinus at three, Haemaphysalis punctata at two). The Mens (TM, the quietist site for human visitors) had the highest DOT at 30/300 m2 (DON=30/300 m2), followed by Queen Elizabeth Country Park (QECP, the busiest) at 22/300 m2 (12/300 m2), Cowdray Estate (CE) at 8/300 m2 (6/300 m2), and Seven Sisters Country Park (SSCP) at 1/300 m2 (1/300 m2). Ditchling Beacon Nature Reserve (DBNR) was sampled 2016 only (one adult H.punctata collected). Woodland had significantly higher hazard than grazed downland, but ticks were present at all downland sites drag-sampled. GIS mapping showed I.ricinus identified in 33/37 of SDNPs 10 km2 grid squares, Ixodes hexagonus 10/37, H.punctata 7/37, Dermacentor reticulatus 1/37. ConclusionsMapping shows tick hazard is broadly distributed across SDNP. Ixodes ricinuswas most common, though the seeming range expansion of H.punctata is concerning, particularly as it seems to thrive better on grazed downland than I.ricinus. Site specific recommendations include: management of small high hazard plots with heavy visitor numbers (QECP); signage on post-visit precautions (all sites); repellent impregnated clothing for deerstalkers (CE); flock trials to control H.punctata (SSCP, DBNR). Further research at TM, which has high tick density, may contribute to knowledge on ecological dynamics underlying infection density, and the potential use of predator re-introduction/protection as a public health intervention. Ecological research on H.punctata would aid control. The SDNP Authority is ideally placed to link and champion site-based and regional policies to reduce hazard, whilst avoiding or reducing conflict between public health and ecosystem health.

ecology↗

Endothelial iron homeostasis regulates BBB integrity via the HIF2α-Ve-cadherin pathway

The blood-brain barrier (BBB) serves as the guardian of the CNS, tightly regulating the movement of ions, molecules, and cells between the circulatory system and brain. This barrier is critical in maintaining brain homeostasis, allowing proper neuronal function and protecting the brain from injury and disease. Chronic and acute exposure to various chemicals lead to BBB breakdown through pathways that are also affected in neurological diseases. Therefore, we have created an in-vitro BBB injury model to gain a better understanding of the mechanisms controlling BBB integrity. This model exposes a co-culture of human stem-cell derived brain-like endothelial cells (BLEC) and brain pericytes that mimic the BBB, to the organophosphate paraoxon. This exposure results in rapid lipid peroxidation, initiating a ferroptosis-like process and leading to endothelium cell toxicity. Mitochondrial ROS formation (MRF) and increase in mitochondrial membrane permeability (MMP), which occur 8 - 10 h post paraoxon-induced injury, also trigger apoptotic cell death. Yet, these processes do not directly result in damage to barrier functionality since blocking them does not reverse the increased permeability. Looking for a crucial pathway affecting barrier functionality we analyzed the iron homeostasis in our model since the iron chelator, Desferal(C) (DFO) rescued endothelial cell viability. Upon BBB insult, the liable iron pool (LIP) is rapidly increased, preventing the increased expression of the stress related hypoxia-induced factor 2 (HIF2) transcription factor. This results in a decrease in surface expression of the adherens junction and permeability master regulator protein, Ve-cadherin, ultimately damaging BBB integrity. Unlike the apoptosis inhibitor ZVAD that rescues BLEC from cell toxicity, yet exacerbates damage to the barrier functionality, DFO significantly decreases MRF and apoptosis subsequent to PX exposure, while also rescuing barrier integrity by inhibiting the liable iron pool increase, inducing HIF2 expression and preventing the degradation of Ve-cadherin on the cell surface. Moreover, the novel nitroxide JP4-039 significantly rescues both injury-induced endothelium cell toxicity and barrier functionality. Collectively, we have elucidated the cellular processes initiated by chemical injury to the endothelium barrier that result in cell toxicity; yet, inhibiting these processes does not necessarily protect BBB integrity which is regulated by the iron mediated HIF2 - Ve-Cadherin axis. DFO protects BBB integrity by inhibiting the injury-induced deregulation of this axis. Additionally, we have discovered a novel compound, JP4-039, that inhibits both damage to endothelium functionality and cell toxicity. Elucidating a regulatory pathway that maintains BBB integrity and discovering both a novel and an FDA approved compound that interfere with this pathway elucidates a potential therapeutic approach to protect the BBB degradation that is evident in many neurological diseases.

neuroscience↗