Over the last decade, the zebrafish (Danio rerio) has emerged as a model organism for cardiovascular research. Zebrafish have several advantages over mammalian models. For instance, the experimental cost of using zebrafish is comparatively low; the embryos are transparent, develop externally, and have high fecundity making them suitable for large-scale genetic screening. More recently, zebrafish embryos have been used for the screening of a variety of toxic agents, particularly for cardiotoxicity testing. Zebrafish has been shown to exhibit physiological responses that are similar to mammals after exposure to medicinal drugs including xenobiotics, hormones, cancer drugs, and also environmental pollutants, including pesticides and heavy metals. In this review, we provided a summary for recent studies that have used zebrafish to investigate the molecular mechanisms of drug-induced cardiotoxicity. More specifically, we focused on the techniques that were exploited by us and others for cardiovascular toxicity assessment and described several microscopic imaging and analysis protocols that are being used for the estimation of a variety of cardiac hemodynamic parameters.
Strategies for rolling out vaccination against Coronavirus Disease 2019 (Covid-19) varied across countries. A key question is whether delaying administration of the second vaccine dose to vaccinate the largest number of people in the shortest time, in situations of limited vaccine supplies and high incidence, could avert more disease cases, hospitalizations and deaths than the current protocol of a second dose shortly after the first dose.
SARS-CoV-2 breakthrough infections in vaccinated individuals and in those who had a prior infection have been observed globally, but the transmission potential of these infections is unknown. The RT-qPCR cycle threshold (Ct) value is inversely correlated with viral load and culturable virus. Here, we investigate differences in RT-qPCR Ct values across Qatar’s national cohorts of primary infections, reinfections, BNT162b2 (Pfizer-BioNTech) breakthrough infections, and mRNA-1273 (Moderna) breakthrough infections. Our matched-cohort analyses of the randomly diagnosed infections show higher mean Ct value in all cohorts of breakthrough infections compared to the cohort of primary infections in unvaccinated individuals. The Ct value is 1.3 (95% CI: 0.9–1.8) cycles higher for BNT162b2 breakthrough infections, 3.2 (95% CI: 1.9–4.5) cycles higher for mRNA-1273 breakthrough infections, and 4.0 (95% CI: 3.5–4.5) cycles higher for reinfections in unvaccinated individuals. Since Ct value correlates inversely with SARS-CoV-2 infectiousness, these differences imply that vaccine breakthrough infections and reinfections are less infectious than primary infections in unvaccinated individuals. Public health benefits of vaccination may have been underestimated, as COVID-19 vaccines not only protect against acquisition of infection, but also appear to protect against transmission of infection.
1 December 2018 in Arteriosclerosis, Thrombosis, and Vascular Biology
Objective—: Endothelial cells (ECs) sense and respond to flow-induced mechanical stress, in part, via microtubule-based projections called primary cilia. However, many critical steps during vascular morphogenesis occur independent of flow. The involvement of cilia in regulating these stages of cranial vascular morphogenesis is poorly understood because cilia have not been visualized in primary head vessels. The objective of this study was to investigate involvement of cilia in regulating the early stages of cranial vascular morphogenesis. Approach and Results—: Using high-resolution imaging of the Tg(kdrl:mCherry-CAAX ) y171;(bactin::Arl13b:GFP ) zebrafish line, we showed that cilia are enriched in the earliest formed cranial vessels that assemble via vasculogenesis and in angiogenic hindbrain capillaries. Cilia were more prevalent around the boundaries of putative intravascular spaces in primary and angiogenic vessels. Loss of cardiac contractility and blood flow, because of knockdown of cardiac troponin T type 2a ( tnnt2a ) expression, did not affect the distribution of cilia in primary head vasculature. In later stages of development, cilia were detected in retinal vasculature, areas of high curvature, vessel bifurcation points, and during vessel anastomosis. Loss of genes crucial for cilia biogenesis ( ift172 and ift81 ) induced intracerebral hemorrhages in an EC-autonomous manner. Exposure to high shear stress induced premature cilia disassembly in brain ECs and was associated with intracerebral hemorrhages. Conclusions—: Our study suggests a functional role for cilia in brain ECs, which is associated with the emergence and remodeling of the primary cranial vasculature. This cilia function is flow-independent, and cilia in ECs are required for cerebral-vascular stability.