Panton–Valentine Leukocidin Colocalizes with Retinal Ganglion and Amacrine Cells and Activates Glial Reactions and Microglial Apoptosis

International audienceExperimental models have established Panton-Valentine leukocidin (PVL) as a potential critical virulence factor during Staphylococcus aureus endophthalmitis. In the present study, we aimed to identify retinal cell targets for PVL and to analyze early retinal changes during infection. After the intravitreous injection of PVL, adult rabbits were euthanized at different time points (30 min, 1, 2, 4 and 8 h). PVL location in the retina, expression of its binding receptor C5a receptor (C5aR), and changes in Müller and microglial cells were analyzed using immunohistochemistry, Western blotting and RT-qPCR. In this model of PVL eye intoxication, only retinal ganglion cells (RGCs) expressed C5aR, and PVL was identified on the surface of two kinds of retinal neural cells. PVL-linked fluorescence increased in RGCs over time, reaching 98% of all RGCs 2 h after PVL injection. However, displaced amacrine cells (DACs) transiently colocalized with PVL. Müller and microglial cells were increasingly activated after injection over time. IL-6 expression in retina increased and some microglial cells underwent apoptosis 4 h and 8 h after PVL infection, probably because of abnormal nitrotyrosine production in the retina

Hepatitis C virus and the risk to the healthcare worker

The risk of hepatitis C virus (HCV) transmission is six times higher per needle-stick exposure than is the risk of HIV infection (1.8% vs 0.3%). The prevalence of HCV in South Africa is not known but estimated to be between 0.1 and 0.7%. Genotype 5 is predominantly found in South Africa. Currently there is no protocol in place for HCV exposure. The treatment cost of HCV is expensive. Currently none of the insurance companies covers post-HCV exposure.http://www.saoa.org.zaam201

The real Nemo movie: Description of embryonic development in Amphiprion ocellaris from first division to hatching

BACKGROUNDAmphiprion ocellaris is one of the rare reef fish species that can be reared in aquaria. It is increasingly used as a model species for Eco-Evo-Devo. Therefore, it is important to have an embryonic development table based on high quality images that will allow for standardized sampling by the scientific community. RESULTSHere we provide high-resolution time-lapse videos to accompany a detailed description of embryonic development in A ocellaris. We describe a series of developmental stages and we define six broad periods of embryogenesis: zygote, cleavage, blastula, gastrula, segmentation, and organogenesis that we further subdivide into 32 stages. These periods highlight the changing spectrum of major developmental processes that occur during embryonic development. CONCLUSIONSWe provide an easy system for the determination of embryonic stages, enabling the development of A ocellaris as a coral reef fish model species. This work will facilitate evolutionary development studies, in particular studies of the relationship between climate change and developmental trajectories in the context of coral reefs. Thanks to its lifestyle, complex behavior, and ecology, A ocellaris will undoubtedly become a very attractive model in a wide range of biological fields

Unraveling persistent dyspnea after mild COVID: insights from a case series on hyperventilation provocation tests

Dyspnea is a common yet poorly understood symptom of long COVID, affecting many patients. This brief report examines the role of dysfunctional breathing in persistent dyspnea among patients with mild post-COVID-19 using hyperventilation provocation tests (HVPT). In this case series, six patients with unexplained dyspnea and normal cardiopulmonary function underwent HVPT. Despite normal exercise testing results, all patients exhibited delayed PETCO2 recovery, indicative of a hyperventilation pattern consistent with chronic hyperventilation syndrome, without typical symptomatic manifestations. These findings suggest underlying post-COVID respiratory dysregulation, emphasizing the importance of targeted diagnostic and therapeutic approaches for persistent respiratory symptoms in long COVID patients

A star is born again: Methods for larval rearing of an emerging model organism, the False clownfish Amphiprion ocellaris

As interest increases in ecological, evolutionary, and developmental biology (Eco-Evo-Devo), wild species are increasingly used as experimental models. However, we are still lacking a suitable model for marine fish species, as well as coral reef fishes that can be reared at laboratory scales. Extensive knowledge of the life cycle of anemonefishes, and the peculiarities of their biology, make them relevant marine fish models for developmental biology, ecology, and evolutionary sciences. Here, we present standard methods to maintain breeding pairs of the anemonefish Amphiprion ocellaris in captivity, obtain regular good quality spawning, and protocols to ensure larval survival throughout rearing. We provide a detailed description of the anemonefish husbandry system and life prey culturing protocols. Finally, a “low-volume” rearing protocol useful for the pharmacological treatment of larvae is presented. Such methods are important as strict requirements for large volumes in rearing tanks often inhibit continuous treatments with expensive or rare compounds

Absence of triadin, a protein of the calcium release complex, is responsible for cardiac arrhythmia with sudden death in human

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease so far related to mutations in the cardiac ryanodine receptor (RYR2) or the cardiac calsequestrin (CASQ2) genes. Because mutations in RYR2 or in CASQ2 are not retrieved in all CPVT cases, we searched for mutations in the physiological protein partners of RyR2 and CSQ2 in a large cohort of CPVT patients with no detected mutation in these two genes. Based on a candidate gene approach, we focused our investigations on triadin and junctin, two proteins that link RyR2 and CSQ2. Mutations in the triadin (TRDN) and in the junctin (ASPH) genes were searched in a cohort of 97 CPVT patients. We identified three mutations in triadin which cosegregated with the disease on a recessive mode of transmission in two families, but no mutation was found in junctin. Two TRDN mutations, a 4 bp deletion and a nonsense mutation, resulted in premature stop codons; the third mutation, a p.T59R missense mutation, was further studied. Expression of the p.T59R mutant in COS-7 cells resulted in intracellular retention and degradation of the mutant protein. This was confirmed after in vivo expression of the mutant triadin in triadin knock-out mice by viral transduction. In this work, we identified TRDN as a new gene responsible for an autosomal recessive form of CPVT. The mutations identified in the two families lead to the absence of the protein, thereby demonstrating the importance of triadin for the normal function of the cardiac calcium release complex in humans

Politics and Community-Based Research

Politics and Community-Based Research: Perspectives from Yeoville Studio, Johannesburg offers a substantive and compelling analysis for a diverse readership interested in urban politics, community mapping and the built environment. The book draws on a critical reflection of Yeoville Studio, a research project conducted by Wits University academics from a diversity of disciplinary backgrounds, together with community partners and postgraduate students. A collection of vignettes portraying people and places in Yeoville interwoven with theoretically analytical chapters, it explores the politics of community research at a neighbourhood scale in its multiple facets, and will resonate with similar contested and complex neighbourhoods across the world. The mix of analysis, vignettes, photographs, architectural design and graphics builds the discussion in engaging, rich and integrated ways, to capture the many participatory approaches taken to this city-community studio

Toll-Like Receptor 3 (TLR3) Plays a Major Role in the Formation of Rabies Virus Negri Bodies

Human neurons express the innate immune response receptor, Toll-like receptor 3 (TLR3). TLR3 levels are increased in pathological conditions such as brain virus infection. Here, we further investigated the production, cellular localisation, and function of neuronal TLR3 during neuronotropic rabies virus (RABV) infection in human neuronal cells. Following RABV infection, TLR3 is not only present in endosomes, as observed in the absence of infection, but also in detergent-resistant perinuclear inclusion bodies. As well as TLR3, these inclusion bodies contain the viral genome and viral proteins (N and P, but not G). The size and composition of inclusion bodies and the absence of a surrounding membrane, as shown by electron microscopy, suggest they correspond to the previously described Negri Bodies (NBs). NBs are not formed in the absence of TLR3, and TLR3−/− mice—in which brain tissue was less severely infected—had a better survival rate than WT mice. These observations demonstrate that TLR3 is a major molecule involved in the spatial arrangement of RABV–induced NBs and viral replication. This study shows how viruses can exploit cellular proteins and compartmentalisation for their own benefit