Search

Bats have large, thin wings that are particularly susceptible to tearing. Anatomical specializations, such as fiber reinforcement, strengthen the wing and increase its resistance to puncture, and an extensive vasculature system across the wing also promotes healing. We investigated whether tear positioning is associated with anatomy in common pipistrelles (Pipistrellus pipistrellus). Wing anatomy was described using histological techniques, imaging, and material testing. Tear information, including type, position, time in rehabilitation, and possible causes, was collected from rehabilitators of injured bats across the United Kingdom. Results suggest that the position of the plagiopatagium (the most proximal wing section to the body), rather than its anatomy, influenced the number, location, and orientation of wing tears. While material testing did not identify the plagiopatagium as being significantly weaker than the chiropatagium (the more distal sections of the wing), the plagiopatagium tended to have the most tears. The position of the tears, close to the body and toward the trailing edge, suggests that they are caused by predator attacks, such as from a cat (Felis catus), rather than collisions. Consistent with this, 38% of P. pipistrellus individuals had confirmed wing tears caused by cats, with an additional 38% identified by rehabilitators as due to suspected cat attacks. The plagiopatagium had the lowest number of blood vessels and highest amounts of elastin fibers, suggesting that healing may take longer in this section. Further investigations into the causes of tears, and their effect on flight capabilities, will help to improve bat rehabilitation.

Introduction Endothelial erosion of atherosclerotic plaques and resulting thrombosis causes approximately 30% of acute coronary syndromes (ACS). Plaque erosion is most frequently observed in smokers, which induces endothelial dysfunction, partially through elevated circulating mediators of inflammation, such as tumour necrosis factor-alpha (TNFα), as well as free radical, oxidative and chemically induced damage. We have previously demonstrated that fresh aqueous cigarette smoke extract (CSE) increases the expression of Nrf2-target genes in human coronary artery endothelial cells, which was further increased by TNFα in a shear stress-dependent manner. Methods The haemodynamic environment significantly regulates both plaque development and endothelial function, therefore we determined the haemodynamic environment permissive for plaque erosion. We reconstructed the coronary artery geometries from 17 heart attack patients with thrombi overlying intact fibrous caps (OCT-defined erosion) and performed computational fluid dynamic analysis. We created an in vitro model of erosion by culturing human coronary artery endothelial cells under elevated flow and exposing them to CSE and TNFα. Results We identified that in 14 cases of OCT-defined erosion occurred in areas of stenosis, with the preeminent flow feature being elevated flow. Exposing human coronary artery endothelial cells to elevated flow, CSE and TNFα induced significant endothelial detachment, which was enhanced by pharmacological activation of the antioxidant system controlled by transcription factor Nrf2. The Oxidative Stress Growth INhibitor genes OSGIN1 and OSGIN2 were both maximally upregulated under these conditions and also in the aortas of mice exposed to cigarette smoke. Adenoviral overexpression of OSGIN1+2 in static culture resulted in cell cycle arrest in S-phase (5.5-fold increase, p= 0.003), with a significant increase in the number of multinucleated cells (4.5-fold, p= Conclusions In summary, we have defined the haemodynamic environment in which endothelial erosion occurs and identified that smoking-induced hyperactivation of Nrf2 may promote endothelial cell detachment, contributing to plaque erosion overlying stenotic plaques, through the combined upregulation of OSGIN1 and OSGIN2. This highlights a completely novel mechanism potentially contributing to 30% of ACS and suggests possible therapeutic avenues for further investigation. Conflict of Interest none

Endothelial erosion of atherosclerotic plaques and resulting thrombosis causes approximately 30% of acute coronary syndromes (ACS). As changes in the haemodynamic environment strongly influence endothelial function and contribute to plaque development, we reconstructed the coronary artery geometries of plaques with thrombi overlying intact fibrous caps from 17 ACS patients and performed computational fluid dynamic analysis. The results demonstrated that erosions frequently occur within areas of stenosis exposed to elevated flow. We recapitulated this flow environment in vitro, exposing human coronary artery endothelial cells to elevated flow and modelled smoking (a risk factor for erosion) by exposure to a combination of aqueous cigarette smoke extract and TNFα. This treatment induced endothelial detachment, which increased with pharmacological activation of the antioxidant system controlled by transcription factor Nrf2 (encoded by NFE2L2). The expression of Oxidative Stress Growth INhibitor genes OSGIN1 and OSGIN2 increased under these conditions and also in the aortas of mice exposed to cigarette smoke. Sustained high level expression of OSGIN1+2 resulted in cell cycle arrest, induction of senescence, loss of focal adhesions and actin stress fibres, and dysregulation of autophagy. Overexpression of either Nrf2 or OSGIN1+2 induced cell detachment, which did not depend on apoptosis, and could be partially rescued by inhibition of HSP70 using VER-155008, or AMP kinase activation using metformin. These findings demonstrate that under elevated flow, smoking-induced hyperactivation of Nrf2 can trigger endothelial cell detachment, highlighting a novel mechanism that could contribute to ACS involving endothelial erosion overlying stenotic plaques.

© 2018, United States & Canadian Academy of Pathology. HIV-associated neurocognitive disorder in HIV patients substantially reduces their quality of life. We previously showed that the HIV matrix protein, p17 could stimulate lymph-angiogenesis in vitro potentially contributing to lymphoma tumour growth and in addition is associated with vascular activation in neuro-degenerating brain tissue; here, therefore, we have investigated the detailed molecular mechanisms of this action. We performed in vitro cell culture, angiogenesis experiments, phospho-protein microarrays and Western blotting to identify cellular signalling induced by p17 within human brain endothelial cells (HbMEC), and inhibitor studies to block p17-induced vascular growth. We also characterised the effects of hippocampal CA1 injection of p17 on epidermal growth factor receptor-1 (EGFR1) expression linked to our murine model of dementia. p17 strongly induced angiogenesis of HbMEC (migration, tube formation and spheroid growth). p17 concomitantly increased phosphorylation of EGFR1 as well as down-stream intermediates ERK1/2, FAK, PLC-γ and PKC-β whilst an inhibitor peptide of EGFR, blocked cell signalling and angiogenesis. Finally, Mice that showed reduced cognitive function and behavioural deficiencies after p17 injection, demonstrated that p17 localised in cortical microvessels and also neurones many of which stained positive for p-EGFR1 by histology/IHC. This work provides strong support that p17 may be involved in initiating and/or perpetuating vascular tissue pathophysiology associated with comorbidity in HIV patients.

Manual identification of capillaries in transverse muscle sections is laborious and time consuming. Although the process of classifying a structure as a capillary is facilitated by (immuno)histochemical staining methods, human judgement is still required in a significant number of cases. This is mainly due to the fact that not all capillaries stain as strongly: they may have an elongated appearance and/or there may be staining artefacts that would lead to a false identification of a capillary. Here we propose two automated methods of capillary detection: a novel image processing approach and an existing machine learning approach that has been previously used to detect nuclei-shaped objects. The robustness of the proposed methods was tested on two sets of differently stained muscle sections. On average, the image processing approach scored a True Positive Rate of 0.817 and a harmonic mean (F1 measure) of 0.804 whilst the machine learning approach scored a True Positive Rate 0.843 and F1 measure of 0.846. Both proposed methods are thus able to mimic most of the manual capillary detection, but further improvements are required for practical applications.