Caractérisation d'un produit d'excision hybride nommé Rm II obtenu dans un clone (S48) de cellules permissives transformées par le virus du polyome

Nous avons caractérisé une molécule d'ADN hybride virale-cellulaire, nommée Rm II, produite par un clone de cellules permissives transformées par le virus du polyome tsP155 (la lignée cellulaire Cyp). Rm II doit son intérêt au fait qu'elle est un autre produit d'excision obtenu dans les cellules Cyp lors d'un simple tranfert de 39°C à 33°C (induction) et qu'elle contient une portion cellulaire emportée lors de l'excision du génome viral intégré plus importante que celle de Rm I, molécule à laquelle s'apparente Rm II et très extensivement étudiée dans notre laboratoire. L'obtention facile de Rm II (par simple induction) et la nature des séquences qu'elle contient en ont fait un sujet de choix pour éclaircir le mécanisme d'excision du génome viral dans les cellules Cyp

Empirical studies on the computational and cognitive mechanisms of human learning and movement

The topic of human movement, and the question of how humans learn new behaviors, has puzzled philosophers and scientists since classical times. A commonly held assumption is that there are two qualitatively distinct learning systems, one responsible for remembering knowledge of facts and events, and the other responsible for forming associations and learning new skills, including motor learning. The evidence in support of this dissociation has been independently reproduced through many different experiments and methods of analysis. One line of evidence that has recently been investigated is the dual-component nature of adaptation learning. When humans and animals are challenged with a change in their environment or the physiology of their bodies, such as what might happen through growth and development or because of injury, the nervous system adjusts its control mechanisms to maintain accurate movements. Learning of this form is known as adaptation, and had originally been theorized to be achieved through an implicit learning mechanism. Furthermore, it was often thought that this same learning mechanism was responsible for more general forms of learning, such as learning the use of new tools. This model has recently come under scrutiny as evidence has emerged demonstrating a role for memory of facts in adaptation. If there are at least two mechanisms responsible for adaptation learning, which one of them, if either, is actually responsible for more general skill learning? If one, but not the other, of these mechanisms is responsible for skill learning, what is adaptation really a model of? And how might the conclusions of other studies that used adaptation as a general model for learning need to be reconsidered? For instance, the results from neurophysiological studies of adaptation may find neural correlates that are uniquely related to adaptation but not to other types of motor learning. Having a better behavioral- and computational-level understanding of the mechanisms involved in adaptation learning is necessary to address these and potentially many other questions. Given the challenges present in the study of adaptation, there is a need for other models of learning and movement that give different perspectives and emphasize other aspects of learning that might be missing from adaptation. For instance, adaptation involves correction of movements around an existing ability, such as reaching. How is reaching itself learned? Acquiring or building new behavioral abilities might involve qualitatively different mechanisms compared to adaptation. Furthermore, new methods for analyzing the kinematics of movements are necessary, as adaptation paradigms typically limit their analysis to the choice of reaching direction only. In this dissertation, I will present several original, empirical studies on the role of cognition and explicit knowledge in motor learning. I will investigate the computational mechanisms that underlie learning new behaviors. I will introduce a new model for human motor skills and skill learning, and show how this model fills gaps that exist in the repertoire of models, methods, and concepts currently popular in the science of learning. I will show evidence that adaptation learning is made up of at least two qualitatively distinct learning components. One component appears to be deliberate, driven by explicit knowledge, and is computationally expensive. The other is implicit, driven by sensory-prediction errors, and is automatic and readily expressed. I will demonstrate that the deliberate component becomes automatic following practice, and will argue that this process is a plausible mechanism for how more general motor skills are learned. Implicit recalibration does not change with practice and therefore appears unlikely to be responsible for skill learning. I will show that learning a new continuous-movement behavior, like skiing or riding a bike, is done through the creation of a flexible feedback control policy. I will discuss the inconsistency of sequence learning and chunking hypotheses, and contrast them with the control policy theory. The studies, results, and conclusions presented here demonstrate that motor learning intrinsically involves cognition and explicit representations of knowledge. The classical concept of motor learning being a subset of implicit memory is inconsistent with the present findings and other recent work. Instead, a view of motor learning as being a phenomenon emergent from the interaction of multiple forms of memory and algorithms of learning is emerging

Writing : a concrete strategy to facilitate the integration of conflicting identities into the self

Je reconnais l’aide financière du Centre d’études ethniques des Universités montréalaises (CEETUM), du Ministère de l’Éducation – Aide Financières au Études (AFE), et ainsi que de l’Université de Montréal (Département de psychologie et Faculté des études supérieures) dans la réalisation de ce mémoire.De plus en plus, les gens doivent apprendre à intégrer de nouvelles identités dans leur concept de soi, ce qui est souvent la source de conflits identitaires. Afin de réduire ces conflits identitaires, plusieurs chercheurs proposent que d’avoir des identités bien intégrées augmente le bien-être psychologique (Amiot, de la Sablonnière, Terry & Smith, 2007; Benet-Martinez & Haritatos, 2005; de la Sablonnière, Amiot, Sadykova, Cardenas, & Gorborukova, 2010). Jusqu’à ce jour, aucune stratégie favorisant cette intégration identitaire à été suggérée. Parallèlement, diverses études sur l’écriture démontrent qu’écrire aide à organiser et structurer les idées tout en augmentant le bien-être psychologique (Lyubomirsky, Sousa & Dickerhoof, 2006; Pennebaker & Graybeal,2001; Pennebaker & Seagal, 1999; Smyth, 1998). Notre hypothèse est que l'écriture faciliterait le processus d’intégration identitaire des identités conflictuelles dans le soi. Nos études 1 et 2 démontrent qu’écrire sur les conflits identitaires, comparativement à écrire sur un sujet neutre ou ne pas écrire, est associé à une augmentation de bien-être seulement chez les gens qui rapportent un haut niveau d’intégration identitaire. Nos études 3 et 4 confirment qu’en offrant plusieurs sessions d’écriture tout en adaptant les directives de rédaction, les participants augmentent leur niveau d’intégration identitaire et de bien-être indépendamment de leur niveau initial d’intégration identitaire. Des analyses de contenu sur les textes d’écriture des participants ont été étudiées afin d’approfondir notre compréhension.More and more, people must learn to integrate new identities in their self-concept, which is often the source of identity conflicts. To reduce these identity conflicts, previous research suggests that high levels of identity integration increases psychological wellbeing (Amiot, de la Sablonnière, Terry & Smith, 2007; Benet-Martinez & Haritatos,2005; de la Sablonnière, Amiot, Sadykova, Cardenas, & Gorborukova, 2010). So far, no strategy to promote identity integration was suggested. In parallel, the action of writing about a negative experience demonstrates that writing helps organize and structure ideas while enhancing psychological well-being (Lyubomirsky, Sousa & Dickerhoof, 2006; Pennebaker & Graybeal, 2001; Pennebaker & Seagal, 1999; Smyth, 1998). Thus, we hypothesize that writing will facilitate the integration of conflicting identities into the self. Studies 1 and 2 reveal that writing about identity conflicts, as compared to writing about a neutral topic or no writing, is associated with superior levels of psychological well-being only for participants scoring high on identity integration. Studies 3 and 4 confirm that several writing sessions using clearer writing instructions helped participants to increase both levels of identity integration and psychological well-being regardless of the initial level of identity integration. Analyses of participants’ written content were performed to deepen our understanding

Foucault's Archaeological Method: Dispersing the Temporal Unity of Phenomenological Experience

This paper reads Foucault’s empirico-transcendental doublet from The Order of Things as his contribution to the tradition of transcendental critique. The motivations are twofold: (1) intervening in the scholarship on Foucault’s method that has largely dismissed archaeology in favour of genealogy; (2) revealing his unique account of temporality. The result is an elevation of archaeology over genealogy due to the former’s infamous yet often forgotten critique of phenomenology, out of which Foucault’s view of temporality emerges. Establishing Foucault’s philosophical lineage and his contemporaneous interlocutors is therefore of crucial importance, for it elucidates the conceptual armature that animates his methodology, helping us understand how it works and how it ought to work. Foucault’s archaeological method is productive of the concept of temporality which manifests in the discontinuity of history and the dispersion of subjects of experience. Moreover, discontinuous temporality is Foucault’s ontological answer to the transcendental question of how conditions and the conditioned relate. Foucault’s innovative reply is that their relation lacks unity but is tenuously held together by the strained efforts of ‘historical man’. The substance of this account is what distinguishes archaeology from phenomenology, despite their shared modality as transcendental critique. But, most importantly, Foucault thoroughly historicizes the transcendental, and he does not stop there: Foucault further argues for the immanence of the transcendental to the empirical in discontinuous temporality’s disintegration of experience. It is only through archaeology that this form of experience can be grasped, for it requires suspending the projective-retroactive synthesis of experience with the concepts of unity and continuity enacted by the constitutive subject of phenomenology

GW182-Free microRNA Silencing Complex Controls Post-transcriptional Gene Expression during Caenorhabditis elegans Embryogenesis

MicroRNAs and Argonaute form the microRNA induced silencing complex or miRISC that recruits GW182, causing mRNA degradation and/or translational repression. Despite the clear conservation and molecular significance, it is unknown if miRISC-GW182 interaction is essential for gene silencing during animal development. Using Caenorhabditis elegans to explore this question, we examined the relationship and effect on gene silencing between the GW182 orthologs, AIN-1 and AIN-2, and the microRNA-specific Argonaute, ALG-1. Homology modeling based on human Argonaute structures indicated that ALG-1 possesses conserved Tryptophan-binding Pockets required for GW182 binding. We show in vitro and in vivo that their mutations severely altered the association with AIN-1 and AIN-2. ALG-1 tryptophan-binding pockets mutant animals retained microRNA-binding and processing ability, but were deficient in reporter silencing activity. Interestingly, the ALG-1 tryptophan-binding pockets mutant phenocopied the loss of alg-1 in worms during larval stages, yet was sufficient to rescue embryonic lethality, indicating the dispensability of AINs association with the miRISC at this developmental stage. The dispensability of AINs in miRNA regulation is further demonstrated by the capacity of ALG-1 tryptophan-binding pockets mutant to regulate a target of the embryonic mir-35 microRNA family. Thus, our results demonstrate that the microRNA pathway can act independently of GW182 proteins during C. elegans embryogenesis

Proprioceptive loss and the perception, control and learning of arm movements in humans: evidence from sensory neuronopathy

© 2018 The Author(s) It is uncertain how vision and proprioception contribute to adaptation of voluntary arm movements. In normal participants, adaptation to imposed forces is possible with or without vision, suggesting that proprioception is sufficient; in participants with proprioceptive loss (PL), adaptation is possible with visual feedback, suggesting that proprioception is unnecessary. In experiment 1 adaptation to, and retention of, perturbing forces were evaluated in three chronically deafferented participants. They made rapid reaching movements to move a cursor toward a visual target, and a planar robot arm applied orthogonal velocity-dependent forces. Trial-by-trial error correction was observed in all participants. Such adaptation has been characterized with a dual-rate model: a fast process that learns quickly, but retains poorly and a slow process that learns slowly and retains well. Experiment 2 showed that the PL participants had large individual differences in learning and retention rates compared to normal controls. Experiment 3 tested participants’ perception of applied forces. With visual feedback, the PL participants could report the perturbation’s direction as well as controls; without visual feedback, thresholds were elevated. Experiment 4 showed, in healthy participants, that force direction could be estimated from head motion, at levels close to the no-vision threshold for the PL participants. Our results show that proprioceptive loss influences perception, motor control and adaptation but that proprioception from the moving limb is not essential for adaptation to, or detection of, force fields. The differences in learning and retention seen between the three deafferented participants suggest that they achieve these tasks in idiosyncratic ways after proprioceptive loss, possibly integrating visual and vestibular information with individual cognitive strategies

Caractérisation d'un produit d'excision hybride nommé Rm II obtenu dans un clone (S48) de cellules permissives transformées par le virus du polyome

Nous avons caractérisé une molécule d'ADN hybride virale-cellulaire, nommée Rm II, produite par un clone de cellules permissives transformées par le virus du polyome tsP155 (la lignée cellulaire Cyp). Rm II doit son intérêt au fait qu'elle est un autre produit d'excision obtenu dans les cellules Cyp lors d'un simple tranfert de 39°C à 33°C (induction) et qu'elle contient une portion cellulaire emportée lors de l'excision du génome viral intégré plus importante que celle de Rm I, molécule à laquelle s'apparente Rm II et très extensivement étudiée dans notre laboratoire. L'obtention facile de Rm II (par simple induction) et la nature des séquences qu'elle contient en ont fait un sujet de choix pour éclaircir le mécanisme d'excision du génome viral dans les cellules Cyp

Participation du système kallikreine-kinine au développement de l'hypertension artérielle expérimentale chez le rat

Nous avons voulu étudier la participation du système kallikréine-kinine (SKK) au développement de l'hypertension expérimentale chez le rat. Pour ce faire, nous avons mesuré, par essai radioimmunologique, l'excrétion urinaire, les quantités rénales et pulmonaires de bradykinine (BK) et de deux métabolites, la des-Arg9-BK et la des-Phe8, des-Arg9-BK (1-7 BK). Nous avons mesuré l'activité des kininase I et II (Kl et KII) plasmatiques et, dans quelques échantillons, les concentrations de BK circulante. Chez les rats hypertendus spontanés (SHR) et chez les rats hypertendus au DOCA-sel, les quantités de BK urinaire, exprimées en ng/mg créatinine/100 g PC, sont plus élevées que chez les rats normotendus témoins. Ces quantités ne sont pas modifiées chez les rats hypertendus rénovasculaires de type Goldblatt à un ou deux reins. De façon générale, les quantités de 1-7 BK urinaire suivent celles de BK alors que nous n'avons pu mesurer la des-Arg9-BK qui se retrouve en quantité trop faible. Chez les rats hypertendus au DOCA-sel, la proportion de 1-7 BK est plus faible que chez les autres groupes expérimentaux; cela est probablement dû à une inhibition des kininases urinaires apportée par le faible pH des urines. Les actions natriurétique et diurétique de la BK sont confirmées par nos résultats: en effet, nous avons calculé une forte corrélation entre l'excrétion de BK et la diurèse et la natriurèse. Les quantités rénales de BK et de ses métabolites ne sont pas corrélées avec les quantités urinaires; cela nous laisse suggérer que l'excrétion de BK ne reflète pas l'activité du SKK rénal. Les quantités de peptides pulmonaires ne sont pas différentes entre les animaux hypertendus et leurs témoins, à l'exception des rats de type Goldblatt à un rein où une augmentation des quantités de BK pulmonaire a été observée. Les activités des Kl et KII plasmatiques sont diminuées autant chez les rats SHR que chez les rats WKY, lorsque comparés aux rats Wistar. L'activité de la KII n'est pas modifiée chez les autres groupes d'animaux hypertendus alors que celle de la Kl est augmentée par l'uninéphrectomie, une diète riche en sel et un traitement au DOCA. Les quantités de BK circulante sont remarquablement constantes chez les groupes où celles-ci ont été étudiées. Alors que nous ne pouvons pas démontrer clairement que le SKK puisse être impliqué dans le développement de l'hypertension artérielle, nous croyons que, chez certains animaux, l'hypertension a contribué à la synthèse de BK à des vitesses qui assurent une diurèse et une natriurèse adéquates