In vitro and in vivo antiviral activity of a fluoronucleoside analog, NCC, against Coxsackie virus B3.

Coxsackie virus B3 (CVB3) is believed to be a major cause of viral myocarditis, with virus-induced apoptosis playing an important role in pathogenesis. The purpose of this study was to characterize the antiviral activity of a novel fluoronucleoside analogue, N-cyclopropyl-4'-azido-2'-deoxy-2'-fluoro-ß-D-cytidine (NCC), against CVB3 in vitro and in vivo, and to establish whether NCC inhibits apoptosis in infected cells. In this study, HeLa cells infected with CVB3 were treated with NCC. Cell viability and apoptosis were examined. Caspase-3 and Bcl-2 levels were monitored by real-time RT PCR and Western blot analysis. For in vivo studies, BALB/c mice infected with CVB3 were treated with NCC daily. Serum markers of myocardial injury and histological studies were measured to examine myocardial injury on day 8 post-infection. To measure apoptosis, levels of Bcl-2 and caspase-3 were examined by immunohistochemistry and real-time RT-PCR. We found that NCC inhibited virus-mediated cytopathic effects in HeLa cells with an EC50 of 116.60 ± 0.32 µM. In infected mice, administration of NCC (2 mg/kg) decreased the activities of serum creatine kinase and lactic dehydrogenase, inhibited the replication of CVB3 and alleviated damage to the heart. Importantly, NCC suppressed CVB3-induced apoptosis in HeLa cells and affected the expression of apoptosis-related factors in infected mice. Together, our results demonstrate that NCC exerts significant antiviral activities against CVB3. We conclude that NCC is a potential therapeutic agent for the treatment of viral myocarditis. Keywords: coxsackie virus B3; viral myocarditis; N-cyclopropyl-4'-azido-2'-deoxy-2'-fluoro-ß-D-cytidine; apoptosis.

3D reconstruction and analysis of wing deformation in free-flying dragonflies.

Insect wings demonstrate elaborate three-dimensional deformations and kinematics. These deformations are key to understanding many aspects of insect flight including aerodynamics, structural dynamics and control. In this paper, we propose a template-based subdivision surface reconstruction method that is capable of reconstructing the wing deformations and kinematics of free-flying insects based on the output of a high-speed camera system. The reconstruction method makes no rigid wing assumptions and allows for an arbitrary arrangement of marker points on the interior and edges of each wing. The resulting wing surfaces are projected back into image space and compared with expert segmentations to validate reconstruction accuracy. A least squares plane is then proposed as a universal reference to aid in making repeatable measurements of the reconstructed wing deformations. Using an Eastern pondhawk (Erythimus simplicicollis) dragonfly for demonstration, we quantify and visualize the wing twist and camber in both the chord-wise and span-wise directions, and discuss the implications of the results. In particular, a detailed analysis of the subtle deformation in the dragonfly's right hindwing suggests that the muscles near the wing root could be used to induce chord-wise camber in the portion of the wing nearest the specimen's body. We conclude by proposing a novel technique for modeling wing corrugation in the reconstructed flapping wings. In this method, displacement mapping is used to combine wing surface details measured from static wings with the reconstructed flapping wings, while not requiring any additional information be tracked in the high speed camera output.