Translation of the F protein of hepatitis C virus is initiated at a non-AUG codon in a +1 reading frame relative to the polyprotein

The hepatitis C virus (HCV) genome contains an internal ribosome entry site (IRES) followed by a large open reading frame coding for a polyprotein that is cleaved into 10 proteins. An additional HCV protein, the F protein, was recently suggested to result from a +1 frameshift by a minority of ribosomes that initiated translation at the HCV AUG initiator codon of the polyprotein. In the present study, we reassessed the mechanism accounting for the synthesis of the F protein by measuring the expression in cultured cells of a luciferase reporter gene with an insertion encompassing the IRES plus the beginning of the HCV-coding region preceding the luciferase-coding sequence. The insertion was such that luciferase expression was either in the +1 reading frame relative to the HCV AUG initiator codon, mimicking the expression of the F protein, or in-frame with this AUG, mimicking the expression of the polyprotein. Introduction of a stop codon at various positions in-frame with the AUG initiator codon and substitution of this AUG with UAC inhibited luciferase expression in the 0 reading frame but not in the +1 reading frame, ruling out that the synthesis of the F protein results from a +1 frameshift. Introduction of a stop codon at various positions in the +1 reading frame identified the codon overlapping codon 26 of the polyprotein in the +1 reading frame as the translation start site for the F protein. This codon 26(+1) is either GUG or GCG in the viral variants. Expression of the F protein strongly increased when codon 26(+1) was replaced with AUG, or when its context was mutated into an optimal Kozak context, but was severely decreased in the presence of low concentrations of edeine. These observations are consistent with a Met-tRNA(i)-dependent initiation of translation at a non-AUG codon for the synthesis of the F protein

Transition arithmétique-algèbre : une recherche documentaire

En septembre 2000, le ministère de l’Éducation, du Loisir et du Sport amorce la réforme de l’ensemble de ses programmes de formation pour les ordres d’enseignement primaire et secondaire. Cette réforme s’articule autour du développement de compétences transversales et disciplinaires. Elle propose des programmes qui se caractérisent par des trajectoires continues entre les deux ordres d’enseignement et elle s’inscrit dans un paradigme d’apprentissage d’orientations constructiviste et socioconstructiviste. L’objectif ciblé par la réforme des programmes est la réussite pour tous les élèves. Quelques années après la mise en place de cette réforme, le rapport Savoir pour pouvoir : Entreprendre un chantier national pour la persévérance scolaire, présidé par Jacques Ménard de BMO Groupe financier, présente un sombre constat sur l’atteinte de l’objectif central de notre système d’éducation réformé. Force est de constater qu’au Québec, nous sommes encore loin du compte. Malgré tous les efforts déployés et toutes les ressources consacrées au soutien à la persévérance scolaire, notre système d’éducation échappe, bon an mal an, presque un jeune sur trois; 30 pour cent1 de nos jeunes célèbrent leur 20e anniversaire sans avoir obtenu un DES ou un DEP. (Ménard & al., 2009) Pour la mathématique, plusieurs élèves du secondaire semblent encore éprouver des difficultés en algèbre (Oliveira & Câmara, 2010). Dans un contexte de programmes réformés, ces constats sur le taux de diplomation chez les jeunes de moins de 20 ans et les difficultés en algèbre de nos élèves nous mènent à nous fixer comme objectif de construire une synthèse des écrits scientifiques portant sur les difficultés reliées au passage de la pensée arithmétique vers la pensée algébrique, sur les propositions didactiques favorisant ce passage ainsi que sur les moyens pour soutenir la mise en oeuvre des propositions didactiques. Au chapitre 1, nous débutons par la présentation de la problématique qui est à l’origine de cet essai. Il est question du contexte dans lequel se situe le problème pour la mathématique ainsi que des causes possibles qui en sont à l’origine. Le chapitre 1 se termine par la formulation des questions de recherche. Le second chapitre présente le cadre conceptuel. Nous y présentons la définition de l’algèbre que nous retenons. Nous expliquons aussi ce qui caractérise les raisonnements arithmétique et algébrique ainsi que ce qu’est la pensée algébrique et ses composantes. Nous terminons ce chapitre en expliquant ce qu’est la genèse documentaire communautaire dans un contexte de développement professionnel. Le chapitre 3 présente la méthodologie de recherche. Dans ce chapitre, nous présentons la démarche retenue pour la constitution du corpus de textes et la méthode d’analyse. Cette dernière nous permet de définir l’angle d’analyse des textes retenus. La présentation des résultats de recherche fait l’objet du quatrième chapitre. Dans ce chapitre, nous traitons successivement chaque question de recherche en dégageant des facteurs récurrents liés à la problématique et en présentant des propositions didactiques conformes à la trajectoire continue du Programme de formation de l’école québécoise. Les résultats de notre recherche sont présentés dans un contexte de développement professionnel des enseignants des ordres d’enseignement primaire et secondaire. Une conclusion termine ce travail de recherche. Nous y expliquons comment cette recherche peut contribuer à résoudre la problématique et nous présentons une réflexion métacognitive sur l’apport de cet essai à notre propre développement professionnel

Étude des mécanismes non-conventionnels de traduction chez le virus de l'immunodéficience humaine de type 1 et le virus de l'hépatite C

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal

Hepatitis C Virus NS3/4A Protease Inhibitors: A Light at the End of the Tunnel

Hepatitis C virus (HCV) infection is a serious and growing threat to human health. The current treatment provides limited efficacy and is poorly tolerated, highlighting the urgent medical need for novel therapeutics. The membrane-targeted NS3 protein in complex with the NS4A comprises a serine protease domain (NS3/4A protease) that is essential for viral polyprotein maturation and contributes to the evasion of the host innate antiviral immunity by HCV. Therefore, the NS3/4A protease represents an attractive target for drug discovery, which is tied in with the challenge to develop selective small-molecule inhibitors. A rational drug design approach, based on the discovery of N-terminus product inhibition, led to the identification of potent and orally bioavailable NS3 inhibitors that target the highly conserved protease active site. This review summarizes the NS3 protease inhibitors currently challenged in clinical trials as one of the most promising antiviral drug class, and possibly among the first anti-HCV agents to be approved for the treatment of HCV infection

Influence of normal and radial contributions of local current density on local electrochemical impedance spectroscopy.

A new tri-electrode probe is presented and applied to local electrochemical impedance spectroscopy (LEIS) measurements. As opposed to two-probe systems, the three-probe one allows measurement not only of normal, but also of radial contributions of local current densities to the local impedance values. The results concerning the cases of the blocking electrode and the electrode with faradaic reaction are discussed from the theoretical point of view for a disk electrode. Numerical simulations and experimental results are compared for the case of the ferri/ferrocyanide electrode reaction at the Pt working electrode disk. At the centre of the disk, the impedance taking into account both normal and radial contributions was in good agreement with the local impedance measured in terms of only the normal contribution. At the periphery of the electrode, the impedance taking into account both normal and radial contributions differed significantly from the local impedance measured in terms of only the normal contribution. The radial impedance results at the periphery of the electrode are in good agreement with the usual explanation that the associated larger current density is attributed to the geometry of the electrode, which exhibits a greater accessibility at the electrode edge

Comparative Assessment of Soil Contamination by Lead and Heavy Metals in Riparian and Agricultural Areas (Southern Québec, Canada)

Soils contaminated with hydrocarbons (C10–C50), PAHS, lead and other heavy metals were recently found in the banks of two major rivers in southern Québec. Alluvial soils are contaminated over a distance of 100 kilometers. Eight sampling sites, including some located in agriculture areas (farm woodlots) have been selected to compare air pollution (aerosol fallout and rainout) and river pollution values. The concentrations detected in soil profiles for As, Cd and Pb vary between 3.01 to 37.88 mg kg−1 (As), 0.11 to 0.81 mg kg−1 (Cd) 12.32 to 149.13 mg kg−1 (Pb). These metallic elements are considered highly toxic and can harm wildlife and human health at high levels. The maximum concentration of Pb (149.13 mg kg−1) in soils of the riparian zone is twelve times higher than the average Pb concentration found in a natural state evaluated at 15.3 mg kg−1 (SD 17.5). Pb concentrations in soils of agricultural areas (woodland control sites) range between 12 and 22 mg kg−1, and given that these values are recorded in surrounding cultivated land, the issue of the quality of agricultural products (crops and forage) to feed livestock or destined for human consumption must be further addressed in detail

Application of AC-SECM in Corrosion Science - Local visualisation of inhibitor films on active metals for corrosion protection

The suitability of frequency-dependent alternating-current scanning electrochemical microscopy (4D AC-SECM) for the investigation of the thin passivating layers covering the surface of corrosion-inhibited metals has been demonstrated. The inhibition of copper corrosion by benzotriazole (BTAH) and methyl-benzotriazole (MBTAH), which are effective inhibitors for this metal in many environmental conditions, was investigated. Strong dependencies were found for the AC z-approach curves with both the duration of the inhibitor treatment and the frequency of the AC excitation signal applied in AC-SECM. Both negative and positive feedback behaviours were observed in the AC approach curves for untreated copper and for Cu-BTAH and Cu-MBTAH samples. Negative feedback behaviour occurred in the low frequency range, whereas the positive feedback effect was observed at higher frequencies. A threshold frequency related to the passage from negative to positive regimes could be determined in each case. The value of the threshold frequency for inhibitor-modified samples was found always to be significantly higher than for the untreated metal, because the inhibitor film provides electrical insulation for the surface. Moreover, the threshold frequency increased with greater surface coverage by the inhibitor. 3D AC-SECM was successfully applied to visualizing spatially-resolved differences in the local electrochemical activity between inhibitor-free and inhibitor-covered areas of the sampl