Dengue virus-induced regulation of the host cell translational machinery

Dengue virus (DV)-induced changes in the host cell protein synthesis machinery are not well understood. We investigated the transcriptional changes related to initiation of protein synthesis. The human hepatoma cell line, HepG2, was infected with DV serotype 2 for 1 h at a multiplicity of infection of one. RNA was extracted after 6, 24 and 48 h. Microarray results showed that 36.5% of the translation factors related to initiation of protein synthesis had significant differential expression (Z-score ≥ ±2.0). Confirmation was obtained by quantitative real-time reverse transcription-PCR. Of the genes involved in the activation of mRNA for cap-dependent translation (eIF4 factors), eIF4A, eIF4G1 and eIF4B were up-regulated while the negative regulator of translation eIF4E-BP3 was down-regulated. This activation was transient since at 24 h post-infection levels were not significantly different from control cells. However, at 48 h post-infection, eIF4A, eIF4E, eIF4G1, eIF4G3, eIF4B, and eIF4E-BP3 were down-regulated, suggesting that cap-dependent translation could be inhibited during the progression of infection. To test this hypothesis, phosphorylation of p70S6K and 4E-BP1, which induce cap-dependent protein synthesis, was assayed. Both proteins remained phosphorylated when assayed at 6 h after infection, while infection induced dephosphorylation of p70S6K and 4E-BP1 at 24 and 48 h of infection, respectively. Taken together, these results provide biological evidence suggesting that in HepG2 cells DV sustains activation of the cap-dependent machinery at early stages of infection, but progression of infection switches protein synthesis to a cap-independent process.

Hypothyroidism decreases proinsulin gene expression and the attachment of its mRNA and eEF1A protein to the actin cytoskeleton of INS-1E cells

The actions of thyroid hormone (TH) on pancreatic beta cells have not been thoroughly explored, with current knowledge being limited to the modulation of insulin secretion in response to glucose, and beta cell viability by regulation of pro-mitotic and pro-apoptotic factors. Therefore, the effects of TH on proinsulin gene expression are not known. This led us to measure: a) proinsulin mRNA expression, b) proinsulin transcripts and eEF1A protein binding to the actin cytoskeleton, c) actin cytoskeleton arrangement, and d) proinsulin mRNA poly(A) tail length modulation in INS-1E cells cultured in different media containing: i) normal fetal bovine serum - FBS (control); ii) normal FBS plus 1 µM or 10 nM T3, for 12 h, and iii) FBS depleted of TH for 24 h (Tx). A decrease in proinsulin mRNA content and attachment to the cytoskeleton were observed in hypothyroid (Tx) beta cells. The amount of eEF1A protein anchored to the cytoskeleton was also reduced in hypothyroidism, and it is worth mentioning that eEF1A is essential to attach transcripts to the cytoskeleton, which might modulate their stability and rate of translation. Proinsulin poly(A) tail length and cytoskeleton arrangement remained unchanged in hypothyroidism. T3 treatment of control cells for 12 h did not induce any changes in the parameters studied. The data indicate that TH is important for proinsulin mRNA expression and translation, since its total amount and attachment to the cytoskeleton are decreased in hypothyroid beta cells, providing evidence that effects of TH on carbohydrate metabolism also include the control of proinsulin gene expression.

Indenture between Andrew Heron and Charles Donaldson

Indenture (vellum) between Andrew Heron of Niagara Township and Charles Donaldson of Niagara Township concerning a portion of the estate of the late Colonel John Butler consisting of Three Mile Creek Farm - indenture no. 2135. This document is water damaged and wrinkled. Part of the document is missing. March 1, 1845.

Marriage Bond between Harrison Narrel of Gainsborough and Anna Simmermon of Clinton

Marriage Bond between Harrison Narrel of Gainsborough and Anna Simmermon of Clinton signed by Andrew Snyder of Gainsborough and William Jacobs of Grimsby, Sept. 1, 1834

The Broken "I" : fragmentation of self and otherness in modern urban narratives

Ce mémoire mélange théorie et fiction pour explorer la technique narrative du “nous” performatif. Le premier chapitre démontre le role du discours dans le processus de formation d’identité, pour éventuellement démontrer que la nature performative du langage est responsable de la creation des constructions sociales du soi et de l’autre. En étudiant les failles de ce système, cet essai tentera de créer une entité narrative libre de ces contraintes. Un second chapitre théorique, après des exemples de fiction, se penchera sur l’entité narrative du flâneur, qui à travers sa relation intime avec la cité, souligne une dichotomie présente dans la relation entre le soi et l’autre. Le flâneur emergera comme un site de traduction dans lequel le “nous” performatif peut prendre action. Toutefois, les limites du flâneur en tant qu’outil narratif l’empêchera d’être la representation ultime de cette dichotomie. Après d’autres exemples de fiction, un troisième chapitre combinera ce qui aura été apprit dans les chapitres précédents pour démontrer que le “nous” performatif et sa dissolution du “je” et du “tu” mène à une narration qui est responsable, consciente d’elle-même et représentative de la réalité urbaine moderne et ses effets sur la création de l’identité.

Health promotion program implementation, a socio-technical networking process : a case study of a school-based nutrition intervention

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal.

Frequent translation strategies used by Iranian translators in subtitles to translate metaphors

En tant que moyen de communication qui détermine les structures de base des langues, la métaphore se classe parmi les enjeux les plus importants du domaine de la traductologie, d’où la complexité de la rendre traduisible. La nature indirecte de la métaphore étant problématique, celle-ci exige une étude approfondie, surtout vis-à-vis le transfert de la culture d’une langue à une autre. Un survol de la littérature académique traitant des théories et des approches différentes en traductologie révèle une façon de rendre possible la traduction de la métaphore. Cette étude traite de la traduction des métaphores du perse aux sous-titres anglais. Elle indique également les approches et les stratégies appliquées à la traduction des expressions linguistiques métaphoriques telles que proposées par Newmark (1988). En se fondant sur des exemples authentiques tirés des textes sources (deux films perses bien connus) et leurs traductions anglaises, cette étude démontre la façon dont certains traducteurs iraniens traduisent des expressions métaphoriques en se servant d’une des sept stratégies proposées par Newmark. Elle explique également comment certains éléments (par ex. les difficultés de la traduction) ont été influents sur leurs conclusions, tout en soutenant l’hypothèse que la reproduction d’une même image d’une langue source dans une langue cible ainsi que l’effacement sont respectivement la plus fréquente et la moins fréquente des stratégies employées par les sous-titreurs iraniens.

Translation Invariance in Object Recognition, and Its Relation to Other Visual Transformations

Human object recognition is generally considered to tolerate changes of the stimulus position in the visual field. A number of recent studies, however, have cast doubt on the completeness of translation invariance. In a new series of experiments we tried to investigate whether positional specificity of short-term memory is a general property of visual perception. We tested same/different discrimination of computer graphics models that were displayed at the same or at different locations of the visual field, and found complete translation invariance, regardless of the similarity of the animals and irrespective of direction and size of the displacement (Exp. 1 and 2). Decisions were strongly biased towards same decisions if stimuli appeared at a constant location, while after translation subjects displayed a tendency towards different decisions. Even if the spatial order of animal limbs was randomized ("scrambled animals"), no deteriorating effect of shifts in the field of view could be detected (Exp. 3). However, if the influence of single features was reduced (Exp. 4 and 5) small but significant effects of translation could be obtained. Under conditions that do not reveal an influence of translation, rotation in depth strongly interferes with recognition (Exp. 6). Changes of stimulus size did not reduce performance (Exp. 7). Tolerance to these object transformations seems to rely on different brain mechanisms, with translation and scale invariance being achieved in principle, while rotation invariance is not.

Calicivirus translation initiation requires an interaction between VPg and eIF4E

Unlike other positive-stranded RNA viruses that use either a 5'-cap structure or an internal ribosome entry site to direct translation of their messenger RNA, calicivirus translation is dependent on the presence of a protein covalently linked to the 50 end of the viral genome (VPg). We have shown a direct interaction of the calicivirus VPg with the cap-binding protein eIF4E. This interaction is required for calicivirus mRNA translation, as sequestration of eIF4E by 4E-BP1 inhibits translation. Functional analysis has shown that VPg does not interfere with the interaction between eIF4E and the cap structure or 4E-BP1, suggesting that VPg binds to eIF4E at a different site from both cap and 4E-BP1. This work lends support to the idea that calicivirus VPg acts as a novel 'cap substitute' during initiation of translation on virus mRNA.

Reduced incorporation of the influenza B virus BM2 protein in virus particles decreases infectivity

BM2 is the fourth integral membrane protein encoded by the influenza B virus genome. It is synthesized late in infection and transported to the plasma membrane from where it is subsequently incorporated into progeny virus particles. It has recently been reported that BM2 has ion channel activity and may be the functional homologue of the influenza A virus M2 protein acting as an ion channel involved in viral entry. Using a reverse genetic approach it was not possible to recover virus which lacked BM2. A recombinant influenza B virus was generated in which the BM2 AUG initiation codon was mutated to GUG. This decreased the efficiency of translation of BM2 protein such that progeny virions contained only 1/8 the amount of BM2 seen in wild-type virus. The reduction in BM2 incorporation resulted in a reduction in infectivity although there was no concomitant decrease in the numbers of virions released from the infected cells. These data imply that the incorporation of sufficient BM2 protein into influenza B virions is required for infectivity of the virus particles. (C) 2004 Elsevier Inc. All rights reserved.

Assessing the process of knowledge transfer – An empirical study

This paper investigates and evaluates the process of knowledge transfer in construction projects. Due to the highly competitive nature of business environments, knowledge transfer between organisations has become increasingly popular in recent years. However, although organisations can realise remarkable benefits by transferring knowledge from one unit to another, successful knowledge transfer can be difficult to achieve. The discussions presented in the paper are mainly based on findings of two case studies. The two cases were selected from Private Finance Initiative (PFI) projects in the UK. According to the case study findings, different stages of a knowledge transfer process can be overlapped, omitted, repeated as well as intermitted and then restarted. One of the significant findings of the case studies was the role of the "knowledge mediator". In selected case studies, there were external consultants and expert staff in the form of knowledge mediators. The importance of their roles was frequently highlighted by the interview participants. They were not only facilitating the close liaison between the knowledge source and the receiver, but also their role was strongly associated with practices of translation and interpretation. This combined role of mediator/translator, therefore, appears to be particularly significant for inter-organisational knowledge transfer in PFI projects.

Eye-movements aid the control of locomotion

Eye-movements have long been considered a problem when trying to understand the visual control of locomotion. They transform the retinal image from a simple expanding pattern of moving texture elements (pure optic flow), into a complex combination of translation and rotation components (retinal flow). In this article we investigate whether there are measurable advantages to having an active free gaze, over a static gaze or tracking gaze, when steering along a winding path. We also examine patterns of free gaze behavior to determine preferred gaze strategies during active locomotion. Participants were asked to steer along a computer-simulated textured roadway with free gaze, fixed gaze, or gaze tracking the center of the roadway. Deviation of position from the center of the road was recorded along with their point of gaze. It was found that visually tracking the middle of the road produced smaller steering errors than for fixed gaze. Participants performed best at the steering task when allowed to sample naturally from the road ahead with free gaze. There was some variation in the gaze strategies used, but sampling was predominantly of areas proximal to the center of the road. These results diverge from traditional models of flow analysis.

Sources of alpha and beta in property funds

This paper examines issues related to potential analytical performance systems for global property funds. These will include traditional attribution methods but will also cover the performance concepts of alpha and beta widely used in other asset classes. We look at issues including...what creates beta, and what drives alpha in real estate investment? How can it be measured and isolated? How do these concepts relate to traditional attribution systems? Can performance records and performance fees adequately distinguish between these drivers? In this paper we illustrate these issues by reference to a case study addressing the complete performance record of a single unlisted fund.