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.
Hepatic artery aneurysms are rare. It is also very uncommon to diagnose a hepatic artery aneurysm prior to rupture. We report a 53-year-old woman who presented with symptoms of gallstones, and was later diagnosed as having hepatic artery aneurysm. Abdominal ultrasound and computed tomography showed two cystic lesions located at the hepatoduodenal ligament. Color Doppler and arteriography identified two aneurysms situated at the common hepatic artery and at the bifurcation of gastroduodenal artery, respectively. A saphenous vein graft was interposed between the origin of the common hepatic artery and the bifurcation of the right and left hepatic arteries. The postoperative course was uneventful and the patient was discharged on the seventh postoperative day.
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