Zebrafish, a novel model system to study uremic toxins: The case for the sulfur amino acid lanthionine

The non-proteinogenic amino acid lanthionine is a byproduct of hydrogen sulfide biosynthesis: the third endogenous vasodilator gas, after nitric oxide and carbon monoxide. While hydrogen sulfide is decreased in uremic patients on hemodialysis, lanthionine is increased and has been proposed as a new uremic toxin, since it is able to impair hydrogen sulfide production in hepatoma cells. To characterize lanthionine as a uremic toxin, we explored its effects during the early development of the zebrafish (Danio rerio), a widely used model to study the organ and tissue alterations induced by xenobiotics. Lanthionine was employed at concentrations reproducing those previously detected in uremia. Light-induced visual motor response was also studied by means of the DanioVision system. Treatment of zebrafish embryos with lanthionine determined acute phenotypical alterations, on heart organogenesis (disproportion in cardiac chambers), increased heart beating, and arrhythmia. Lanthionine also induced locomotor alterations in zebrafish embryos. Some of these effects could be counteracted by glutathione. Lanthionine exerted acute effects on transsulfuration enzymes and the expression of genes involved in inflammation and metabolic regulation, and modified microRNA expression in a way comparable with some alterations detected in uremia. Lanthionine meets the criteria for classification as a uremic toxin. Zebrafish can be successfully used to explore uremic toxin effects

Prospects for detecting Gamma-Ray Bursts with the Cherenkov Telescope Array

The Large Area Telescope (LAT) on the Fermi gamma-ray satellite telescope observes Gamma-Ray Bursts (GRBs) at energies above 100 MeV. Thanks to a new detection algorithm and a new event reconstruction, it is expected to publish a catalogue with more than 100 GRBs. This work aims at revising the prospects for GRB alerts with the Cherenkov Telescope Array (CTA) based on the new LAT results. We start by considering the simulation of the observations with the full CTA of two extremely bright events, the long GRB 130427A and the short GRB 090510; then we investigate how these GRBs would be observed by different subsamples of the array pointing to different directions, adopting the \u201ccoupled divergent\u201d mode

Measurements and tests on FBK silicon sensors with an optimized electronic design for a CTA camera

In October 2013, the Italian Ministry approved the funding of a Research & Development (R&D) study, within the "Progetto Premiale TElescopi CHErenkov made in Italy (TECHE)", devoted to the development of a demonstrator for a camera for the Cherenkov Telescope Array (CTA) consortium. The demonstrator consists of a sensor plane based on the Silicon Photomultiplier (SiPM) technology and on an electronics designed for signal sampling. Preliminary tests on a matrix of sensors produced by the Fondazione Bruno Kessler (FBK-Trento, Italy) and on electronic prototypes produced by SITAEL S.p.A. will be presented. In particular, we used different designs of the electronics in order to optimize the output signals in terms of tail cancellation. This is crucial for applications where a high background is expected, as for the CTA experiment.Comment: 5 pages, 6 figures; Proceedings of the 10th Workshop on Science with the New Generation of High-Energy Gamma-ray experiments (SciNeGHE) - PoS(Scineghe2014)00

Divergent behavior of hydrogen sulfide pools and of the sulfur metabolite lanthionine, a novel uremic toxin, in dialysis patients.

Dialysis patients display a high cardiovascular mortality, the causes of which are still not completely explained, but are related to uremic toxicity. Among uremic toxins, homocysteine and cysteine are both substrates of cystathionine β-synthase and cystathionine γ-lyase in hydrogen sulfide biosynthesis, leading to the formation of two sulfur metabolites, lanthionine and homolanthionine, considered stable indirect biomarkers of its production. Hydrogen sulfide is involved in the modulation of multiple pathophysiological responses. In uremia, we have demonstrated low plasma total hydrogen sulfide levels, due to reduced cystathionine γ-lyase expression. Plasma hydrogen sulfide levels were measured in hemodialysis patients and healthy controls with three different techniques in comparison, allowing to discern the different pools of this gas. The protein-bound (the one thought to be the most active) and acid-labile forms are significantly decreased, while homolanthionine, but especially lanthionine, accumulate in the blood of uremic patients. The hemodialysis regimen plays a role in determining sulfur compounds levels, and lanthionine is partially removed by a single dialysis session. Lanthionine inhibits hydrogen sulfide production in cell cultures under conditions comparable to in vivo ones. We therefore propose that lanthionine is a novel uremic toxin. The possible role of high lanthionine as a contributor to the genesis of hyperhomocysteinemia in uremia is discusse