2,014 research outputs found
Antioxidant responses and NRF2 in synergistic developmental toxicity of PAHs in zebrafish
Author Posting. © The Authors, 2009. This is the author's version of the work. It is posted here by permission of Oxford University Press for personal use, not for redistribution. The definitive version was published in Toxicological Sciences 109 (2009): 217-227, doi:10.1093/toxsci/kfp038.Early piscine life-stages are sensitive to polycyclic aromatic hydrocarbon (PAH) exposure,
which can cause pericardial effusion and craniofacial malformations. We previously reported that
certain combinations of PAHs cause synergistic developmental toxicity, as observed with co-exposure
to the aryl hydrocarbon receptor (AHR) agonist ÎČ-naphthoflavone (BNF) and cytochrome P4501A
inhibitor α-naphthoflavone (ANF). Herein, we hypothesized that oxidative stress is a component of
this toxicity. We examined induction of antioxidant genes in zebrafish embryos (Danio rerio)
exposed to BNF or ANF individually, a BNF+ANF combination, and a pro-oxidant positive control,
tert-butylhydroperoxide (tBOOH). We measured total glutathione, and attempted to modulate
deformities using the glutathione synthesis inhibitor buthionine sulfoxamine (BSO) and increase
glutathione pools with N-acetyl cysteine (NAC). In addition, we used a morpholino to knockdown
expression of the antioxidant response element transcription factor NRF2 to determine if this would
alter gene expression or increase deformity severity. BNF+ANF co-exposure significantly increased
expressions of superoxide dismutase1 and2, glutathione peroxidase 1, pi class glutathione-s-transferase,
and glutamate cysteine-ligase to a greater extent than tBOOH, BNF, or ANF alone. BSO
pretreatment decreased some glutathione levels, but did not worsen deformities, nor did NAC
diminish toxicity. Knockdown of NRF2 increased mortality following tBOOH challenge, prevented
significant upregulation of antioxidant genes following both tBOOH and BNF+ANF exposures, and
exacerbated BNF+ANFârelated deformities. Collectively, these findings demonstrate that antioxidant
responses are a component of PAH synergistic developmental toxicity, and that NRF2 is protective
against prooxidant and PAH challenges during development.This work was supported by the National Institute for Environmental Health Sciencessupported
Duke University Superfund Basic Research Program (P42 ES10356), National Institute for
Environmental Health Sciencesâsupported Duke University Integrated Toxicology & Environmental
Health Program (TS ES07031), United States Environmental Protection Agency STAR fellowship (to
A.T.âL.), Duke University RJRâLeon Golberg Memorial Postdoctoral Training Program in Toxicology
(to A.T.âL.), and the Postdoctoral Scholar Program at the Woods Hole Oceanographic Institution,
with funding provided by the J. Seward Johnson Fund and The Walter A. and Hope Noyes Smith
Chair (to A.TâL)
Development of the morpholino gene knockdown technique in Fundulus heteroclitus : a tool for studying molecular mechanisms in an established environmental model
Author Posting. © Elsevier B.V., 2008. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Aquatic Toxicology 87 (2008): 289-295, doi:10.1016/j.aquatox.2008.02.010.A significant challenge in environmental toxicology is that many genetic and genomic tools available in laboratory models are not developed for commonly used environmental models. The Atlantic killifish (Fundulus heteroclitus) is one of the most studied teleost environmental models, yet few genetic or genomic tools have been developed for use in this species. The advancement of genetic and evolutionary toxicology will require that many of the tools developed in laboratory models be transferred into species more applicable to environmental toxicology. Antisense morpholino oligonucleotide (MO) gene knockdown technology has been widely utilized to study development in zebrafish and has been proven to be a powerful tool in toxicological investigations through direct manipulation of molecular pathways. To expand the utility of killifish as an environmental model, MO gene knockdown technology was adapted for use in Fundulus. Morpholino microinjection methods were altered to overcome the significant differences between these two species. Morpholino efficacy and functional duration were evaluated with molecular and phenotypic methods. A cytochrome P450-1A (CYP1A) MO was used to confirm effectiveness of the methodology. For CYP1A MO-injected embryos, a 70% reduction in CYP1A activity, a 86% reduction in total CYP1A protein, a significant increase in ÎČ-naphthoflavone-induced teratogenicity, and estimates of functional duration (50% reduction in activity 10 dpf, and 86% reduction in total protein 12 dpf) conclusively demonstrated that MO technologies can be used effectively in killifish and will likely be just as informative as they have been in zebrafish.This work was funded in part by the National Institute of Environmental Health Sciences through the Duke Superfund Basic Research Center (P42ES010356), the Boston University Superfund Basic Research Program (P42ES007381), and the Duke Integrated Toxicology and Environmental Health Program (ES-T32-0007031). Additional support was provided by a U.S. Environmental Protection Agency STAR fellowship awarded to C.R.F
INFN Camera demonstrator for the Cherenkov Telescope Array
The Cherenkov Telescope Array is a world-wide project for a new generation of
ground-based Cherenkov telescopes of the Imaging class with the aim of
exploring the highest energy region of the electromagnetic spectrum. With two
planned arrays, one for each hemisphere, it will guarantee a good sky coverage
in the energy range from a few tens of GeV to hundreds of TeV, with improved
angular resolution and a sensitivity in the TeV energy region better by one
order of magnitude than the currently operating arrays. In order to cover this
wide energy range, three different telescope types are envisaged, with
different mirror sizes and focal plane features. In particular, for the highest
energies a possible design is a dual-mirror Schwarzschild-Couder optical
scheme, with a compact focal plane. A silicon photomultiplier (SiPM) based
camera is being proposed as a solution to match the dimensions of the pixel
(angular size of ~ 0.17 degrees). INFN is developing a camera demonstrator made
by 9 Photo Sensor Modules (PSMs, 64 pixels each, with total coverage 1/4 of the
focal plane) equipped with FBK (Fondazione Bruno Kessler, Italy) Near
UltraViolet High Fill factor SiPMs and Front-End Electronics (FEE) based on a
Target 7 ASIC, a 16 channels fast sampler (up to 2GS/s) with deep buffer,
self-trigger and on-demand digitization capabilities specifically developed for
this purpose. The pixel dimensions of mm lead to a very compact
design with challenging problems of thermal dissipation. A modular structure,
made by copper frames hosting one PSM and the corresponding FEE, has been
conceived, with a water cooling system to keep the required working
temperature. The actual design, the adopted technical solutions and the
achieved results for this demonstrator are presented and discussed.Comment: In Proceedings of the 34th International Cosmic Ray Conference
(ICRC2015), The Hague, The Netherlands. All CTA contributions at
arXiv:1508.0589
Treatment decision-making of secondary prevention after venous thromboembolism. data from the real-life START2-POST-VTE register
Patients with venous thromboembolism (VTE) should receive a decision on the duration of anticoagulant treatment (AT) that is often not easy to make. Sixteen Italian clinical centers included patients with recent VTE in the START2-POST-VTE register and reported the decisions taken on duration of AT in each patient and the reasons for them. At the moment of this report, 472 (66.9%) of the 705 patients included in the registry were told to stop AT in 59.3% and to extend it in 40.7% of patients. Anticoagulant treatment lasted â„3 months in >90% of patients and was extended in patients with proximal deep vein thrombosis because considered at high risk of recurrence or had thrombophilic abnormalities. d-dimer testing, assessment of residual thrombus, and patient preference were also indicated among the criteria influencing the decision. In conclusion, Italian doctors stuck to the minimum 3 months AT after VTE, while the secondary or unprovoked nature of the event was not seen as the prevalent factor influencing AT duration which instead was the result of a complex and multifactorial evaluation of each patient
!CHAOS: A cloud of controls
The paper is aimed to present the !CHAOS open source project
aimed to develop a prototype of a national private Cloud Computing infrastructure, devoted to accelerator control systems and large experiments of High Energy Physics (HEP). The !CHAOS project has been financed by MIUR (Italian Ministry of Research and Education) and aims to develop a new concept of control system and data acquisition framework by providing, with a high level of abstraction, all the services needed for controlling and managing a large scientific, or non-scientific, infrastructure. A beta version of the !CHAOS infrastructure will be released at the end of December 2015 and will run on private Cloud infrastructures based on OpenStack
Intermittent control models of human standing: similarities and differences
Two architectures of intermittent control are compared and contrasted in the context of the single inverted pendulum model often used for describing standing in humans. The architectures are similar insofar as they use periods of open-loop control punctuated by switching events when crossing a switching surface to keep the system state trajectories close to trajectories leading to equilibrium. The architectures differ in two significant ways. Firstly, in one case, the open-loop control trajectory is generated by a system-matched hold, and in the other case, the open-loop control signal is zero. Secondly, prediction is used in one case but not the other. The former difference is examined in this paper. The zero control alternative leads to periodic oscillations associated with limit cycles; whereas the system-matched control alternative gives trajectories (including homoclinic orbits) which contain the equilibrium point and do not have oscillatory behaviour. Despite this difference in behaviour, it is further shown that behaviour can appear similar when either the system is perturbed by additive noise or the system-matched trajectory generation is perturbed. The purpose of the research is to come to a common approach for understanding the theoretical properties of the two alternatives with the twin aims of choosing which provides the best explanation of current experimental data (which may not, by itself, distinguish beween the two alternatives) and suggesting future experiments to distinguish between the two alternatives
Use of barbed suture without fashioning the "classical" Wirsung-jejunostomy in a modified end-to-side robotic pancreatojejunostomy
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