Discovery of an unrecognized nidovirus associated with granulomatous hepatitis in rainbow trout

Rainbow trout (Oncorhynchus mykiss) is the principal species of inland-farmed fish in the Western hemisphere. Recently, we diagnosed in farmed rainbow trout a disease in which the hallmark is granulomatous-like hepatitis. No biotic agents could be isolated from lesions. Still, unbiased high-throughput sequencing and bioinformatics analyses revealed the presence of a novel piscine nidovirus that we named “Trout Granulomatous Virus” (TGV). TGV genome (28,767 nucleotides long) is predicted to encode non-structural (1a and 1 ab) and structural (S, M, and N) proteins that resemble proteins of other known piscine nidoviruses. High loads of TGV transcripts were detected by quantitative RT-PCR in diseased fish and visualized in hepatic granulomatous sites by fluorescence in situ hybridization. Transmission electron microscopy (TEM) revealed coronavirus-like particles in these lesions. Together, these analyses corroborated the association of TGV with the lesions. The identification and detection of TGV provide means to control TGV spread in trout populations

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

STUDIES OF INNATE IMMUNITY PARAMETERS (TLR2, TLR4 AND HBD1) OF URETHERAL MUCOUS EPITHELIUM IN CHRONIC BACTERIAL CYSTITIS

The study for quantitation of TLR2, TLR4 and HBD-1 gene expression in urethral mucosal epithelium from women with chronic bacterial cystitis and healthy females. Materials and methods: RNA was extracted from the samples of urethral mucosa followed by RT-PCR. Results: increased expression of TLR2, TLR4 (respectively, 6.9-, 2.6-fold), along with 13.6-fold decrease in HBD-1 was revealed in women with chronic bacterial cystitis, as compared with appropriate parameters in normal women. Six months later, after combined therapy with autologous immunopeptide complex, TLR2, TLR4 и HBD1 expression levels proved to be near-normal in the patients, being similar to those in healthy females. Conclusion: Imbalanced expression of genes controlling innate immunity was revealed in urethral mucosa of the patients with chronic cystitis, thus increasing risk for urinary tract infections

Evidence for a consistent use of external cues by marine fish larvae for orientation

The larval stage is the main dispersive process of most marine teleost species. The degree to which larval behavior controls dispersal has been a subject of debate. Here, we apply a cross-species meta-analysis, focusing on the fundamental question of whether larval fish use external cues for directional movement (i.e., directed movement). Under the assumption that directed movement results in straighter paths (i.e., higher mean vector lengths) compared to undirected, we compare observed patterns to those expected under undirected pattern of Correlated Random Walk (CRW). We find that the bulk of larvae exhibit higher mean vector lengths than those expected under CRW, suggesting the use of external cues for directional movement. We discuss special cases which diverge from our assumptions. Our results highlight the potential contribution of orientation to larval dispersal outcomes. This finding can improve the accuracy of larval dispersal models, and promote a sustainable management of marine resources

Cardiac Protection by Preconditioning Is Generated via an Iron-Signal Created by Proteasomal Degradation of Iron Proteins

<div><p>Ischemia associated injury of the myocardium is caused by oxidative damage during reperfusion. Myocardial protection by ischemic preconditioning (IPC) was shown to be mediated by a transient ‘iron-signal’ that leads to the accumulation of apoferritin and sequestration of reactive iron released during the ischemia. Here we identified the source of this ‘iron signal’ and evaluated its role in the mechanisms of cardiac protection by hypoxic preconditioning. Rat hearts were retrogradely perfused and the effect of proteasomal and lysosomal protease inhibitors on ferritin levels were measured. The iron-signal was abolished, ferritin levels were not increased and cardiac protection was diminished by inhibition of the proteasome prior to IPC. Similarly, double amounts of ferritin and better recovery after <em>ex vivo</em> ischemia-and-reperfusion (I/R) were found in hearts from <em>in vivo</em> hypoxia pre-conditioned animals. IPC followed by normoxic perfusion for 30 min (‘delay’) prior to I/R caused a reduced ferritin accumulation at the end of the ischemia phase and reduced protection. Full restoration of the IPC-mediated cardiac protection was achieved by employing lysosomal inhibitors during the ‘delay’. In conclusion, proteasomal protein degradation of iron-proteins causes the generation of the ‘iron-signal’ by IPC, ensuing <em>de-novo</em> apoferritin synthesis and thus, sequestering reactive iron. Lysosomal proteases are involved in subsequent ferritin breakdown as revealed by the use of specific pathway inhibitors during the ‘delay’. We suggest that proteasomal iron-protein degradation is a stress response causing an expeditious cytosolic iron release thus, altering iron homeostasis to protect the myocardium during I/R, while lysosomal ferritin degradation is part of housekeeping iron homeostasis.</p> </div

Ferritin and ferritin-bound iron levels in hearts subjected to I/R.

<p>Ferritin and ferritin-bound iron levels with or without prior IPC and a ‘delay’ period. a. Relative ferritin protein levels (% of the post stabilization period). b. Ferritin-bound iron (number of iron atoms per molecule of ferritin). c. Relative ferritin protein levels (% of the post stabilization period) in hearts infused with a cocktail of protease inhibitors (MG132-3 µmol/L, leupeptin-11.7 µmol/L, pepstatin-A-4.4 µmol/L): perfusion -black diamond, IPC+‘delay’ +I/R - black circle, ‘delay’+I/R- white square. Results are means±SE of 6 experiments. SE for perfusion and ‘delay’+I/R groups are too small to be seen.</p