PubMed · 11190413
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C D Burns. 2000. Sentinel event.. https://pubmed.ncbi.nlm.nih.gov/11190413/
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Claudin-14 (CLDN14) is a key component of tight junctions (TJs) critical for maintaining paracellular barrier function. Variants of CLDN14 have been linked to Vein of Galen malformations (VOGMs), a rare cerebrovascular disorder; however, the molecular mechanisms underlying their pathogenicity remain unknown. Here, we investigate the mechanistic effects of two VOGM-associated mutations, A113P and V143M, using reinforcement-learning driven enhanced sampling molecular dynamics simulations combined with DiffNets-based deep learning and independent trajectory-wide structural analyses. Our analysis reveals that A113P induces broader structural disruption of CLDN14, perturbing paracellular sealing, pore symmetry, and inter-protomer communication, whereas V143M induces structural rearrangements centred around TM3 and the TM3-ECL2 region. In both cases, mutation-specific alterations are observed in structural stability and interfacial organization across oligomeric assemblies. Notably, these effects are qualitatively consistent across different modelled architectures, despite variability in local responses. In the absence of experimentally resolved structures, the structural perturbations reported here provide a mechanistic understanding of how VOGM-associated variants may influence CLDN14 structure and dynamics.
This is a case of a 51-year-old female with difficult-to-control hypertension and a 3-cm renal artery aneurysm. Successful exclusion of this was performed using a prefabricated stent graft. To our knowledge, this is the first report on the use of a prefabricated covered stent for this indication.
We present a case with asymptomatic mediastinal bronchial artery aneurysm at the origin of the left bronchial artery. This bronchial artery aneurysm was successfully treated with percutaneous transluminal coil embolization. Complete embolization of the feeding artery and tributaries from the aneurysm is the key to successful isolation of a large bronchial artery aneurysm from the circulation. Percutaneous transluminal embolization is one of the treatment options for a patient with asymptomatic, incidentally-identified bronchial artery aneurysm.