Multimodal principal component analysis to identify major features of white matter structure and links to reading

The role of white matter in reading has been established by diffusion tensor imaging (DTI), but DTI cannot identify specific microstructural features driving these relationships. Neurite orientation dispersion and density imaging (NODDI), inhomogeneous magnetization transfer (ihMT) and multicomponent driven equilibrium single-pulse observation of T1/T2 (mcDESPOT) can be used to link more specific aspects of white matter microstructure and reading due to their sensitivity to axonal packing and fiber coherence (NODDI) and myelin (ihMT and mcDESPOT). We applied principal component analysis (PCA) to combine DTI, NODDI, ihMT and mcDESPOT measures (10 in total), identify major features of white matter structure, and link these features to both reading and age. Analysis was performed for nine reading-related tracts in 46 neurotypical 6–16 year olds. We identified three principal components (PCs) which explained 79.5% of variance in our dataset. PC1 probed tissue complexity, PC2 described myelin and axonal packing, while PC3 was related to axonal diameter. Mixed effects regression models did not identify any significant relationships between principal components and reading skill. Bayes factor analysis revealed that the absence of relationships was not due to low power. Increasing PC1 in the left arcuate fasciculus with age suggest increases in tissue complexity, while increases of PC2 in the bilateral arcuate, inferior longitudinal, inferior fronto-occipital fasciculi, and splenium suggest increases in myelin and axonal packing with age. Multimodal white matter imaging and PCA provide microstructurally informative, powerful principal components which can be used by future studies of development and cognition. Our findings suggest major features of white matter undergo development during childhood and adolescence, but changes are not linked to reading during this period in our typically-developing sample

Interactions et actions de hnRNP A1/UP1 et caractérisation des extensions télomériques simple-brin chez la levure et chez l'humain

Les protéines hnRNP A1/UP1 et hnRNP A2 sont des protéines nucléaires abondantes qui possèdent plusieurs rôles dans la cellule, en particulier dans l'épissage alternatif et la biogénèse des télomères. L'action de ces protéines dans l'épissage alternatif semble directe, tandis que leur action au niveau des télomères pourrait être indirecte. Pour mieux caractériser le rôle de hnRNP A1/UP1 aux télomères, nous avons utilisé une approche de criblage double-hybride dans la levure afin d'identifier leurs partenaires cellulaires. Avec ce criblage, nous avons récupéré plusieurs protéines différentes, mais aucune protéine ayant une implication ou une localisation aux télomères n'a été récupérée. Cependant, une forte interaction entre des molécules hnRNP A1 elles-mêmes a été montrée avec ce criblage. Une telle interaction entre des protéines hnRNP A1 est à la base d'un modèle qui a été proposé pour expliquer le rôle de hnRNP A1 dans la modulation de l'épissage alternatif. En utilisant diverses approches de mutagénèse, nous avons tenté de déterminer les domaines de hnRNP A1 requis pour cette modulation. Les résultats obtenus suggèrent que le modèle élaboré pour l'explication du mécanisme d'action de hnRNP A1 dans l'épissage est valide, c'est-à-dire qu'un mécanisme comme celui qui est proposé, pourrait servir à moduler l'épissage alternatif de hnRNP A1. De plus, nous avons montré que la protéine hnRNP A2, qui fait partie de la même famille de protéines que hnRNP A1, possède des fonctions similaires à celles de hnRNP A1 dans la modulation de l'épissage alternatif. En utilisant deux différents groupes de transcrits modèles, nous avons montré que hnRNP A2 peut se substituer à hnRNP A1 dans certaines conditions d'épissage, mais ce processus est dépendant de la présence des sites de liaison optimaux dans l'ARN. Les télomères sont les extrémités des chromosomes eucaryotes. Ils sont constitués de répétitions de courtes séquences, dont un des brins est riche en guanines (G). Chez toutes les espèces étudiées, ce brin se retrouve à l'extrémité des chromosomes sous forme d'une extension 3' simple-brin. Lors de la réplication des télomères chez la levure Saccharomyces cerevisiae, les extrémités des chromosomes acquièrent de longues extensions 3' simple-brin riches en G (plus de 30 bases). La présence de ces extensions en dehors de la phase S (phase où a lieu la réplication de l'ADN) est inconnue chez la levure. Également, les protéines impliquées dans la génération et le maintien de ces extensions sont peu connues

Capacité de mentalisation parentale et représentations d'attachement d'enfants d'âge préscolaire ayant vécu de la maltraitance

Il a été documenté que la vaste majorité des enfants hébergés sous la protection de la jeunesse ont subi des traumas au sein de la relation avec leurs parents. Le contexte de négligence, de maltraitance ou d’abus dans lequel ces enfants ont vécu compromet grandement leur développement psychoaffectif ainsi que la qualité de leur lien d’attachement. Les recherches en psychologie au cours des dernières années mettent en lumière le rôle essentiel de la capacité de mentalisation parentale (CMP), d’une part, pour prévenir les conduites de maltraitance et, d’autre part, pour prédire la sécurité de l’attachement de l’enfant. Toutefois, peu de recherches ont exploré ces variables dans le contexte de la protection de l’enfance et encore moins d’études se sont intéressées plus particulièrement aux pères. Les deux études de cas présentées dans ce mémoire doctoral visent d’abord à explorer la CMP des pères signalés pour maltraitance et les représentations d’attachement de leurs enfants afin de mieux saisir le portrait clinique de cette population à risque. Pour ce faire, les pères ont pris part à un entretien semi-structuré visant à explorer leur CMP. De leur côté, les enfants ont participé à un jeu structuré permettant d’évaluer leurs représentations d’attachement. Ensuite, la CMP des pères a été mise en relation avec les représentations d’attachement de leurs enfants. Les résultats ont soulevé la présence de difficultés de mentalisation importantes chez les pères. Du côté des enfants, il est possible de constater des difficultés au niveau de la régulation émotionnelle et comportementale ainsi que des représentations d’attachement de type insécurisé. Les résultats de cette étude de cas, bien que non généralisable statistiquement étant donné le nombre restreint de participants, donne accès à une analyse approfondie de deux dyades père-enfant dans un contexte de placement. Ces résultats sont particulièrement intéressants non seulement puisqu’il existe peu d’études concernant la CMP des pères, mais également compte-tenu des difficultés de recrutement de cette population et des exigences éthiques associées. Enfin, les résultats soulignent l’importance de tenir compte de la CMP et des représentations d’attachement de l’enfant dans les interventions offertes à cette population

Mesial temporal sclerosis is linked with more widespread white matter changes in temporal lobe epilepsy

AbstractTemporal lobe epilepsy patients with unilateral mesial temporal sclerosis (TLE+uMTS) have been demonstrated to have extensive white matter abnormalities both ipsilateral and contralateral to the seizure onset zone. However, comparatively less is known about the white matter integrity of TLE patients without MTS (non-lesional TLE, nl-TLE). The purpose of the study was to investigate the diffusion properties of thirteen major white matter tracts in patients with TLE+uMTS and nl-TLE. Diffusion tensor imaging (DTI) was performed on 23 TLE+uMTS (15 left MTS and 8 right MTS), 15nl-TLE and 21 controls. Thirteen tracts were delineated by tractography and their diffusion parameters compared for the two TLE groups relative to controls, with left and right hemispheres combined per tract. A subgroup analysis investigated left and right MTS separately. Compared to controls, reduced anisotropy was detected in ten tracts for TLE+uMTS, but only the parahippocampal cingulum and tapetum for nl-TLE. Right MTS subgroup showed reduced anisotropy in 7 tracts bilaterally (3 limbic, 3 association, 1 projection) and 2 tracts ipsilaterally (1 association, 1 projection) and the body of the corpus callosum whereas the left MTS subgroup showed reduced anisotropy in 4 tracts bilaterally (2 limbic, 1 association, 1 projection) and 2 tracts ipsilaterally (1 limbic, 1 association). Diffusion abnormalities in tracts were observed within and beyond the temporal lobe in TLE+uMTS and were more widespread than in nl-TLE. Patients with right MTS had more extensive, bilateral abnormalities in comparison to left MTS. These findings suggest different dysfunctional networks in TLE patients with and without MTS

The TPR-containing domain within Est1 homologs exhibits species-specific roles in telomerase interaction and telomere length homeostasis

<p>Abstract</p> <p>Background</p> <p>The first telomerase-associated protein (Est1) was isolated in yeast due to its essential role in telomere maintenance. The human counterparts EST1A, EST1B, and EST1C perform diverse functions in nonsense-mediated mRNA decay (NMD), telomere length homeostasis, and telomere transcription. Although Est1 and EST1A/B interact with the catalytic subunit of yeast and human telomerase (Est2 and TERT, respectively), the molecular determinants of these interactions have not been elaborated fully.</p> <p>Results</p> <p>To investigate the functional conservation of the EST1 protein family, we performed protein-protein interaction mapping and structure-function analysis. The domain in hEST1A most conserved between species, containing a TPR (tricotetrapeptide repeat), was sufficient for interaction of hEST1A with multiple fragments of hTERT including the N-terminus. Two mutations within the hTERT N-terminus that perturb <it>in vivo </it>function (NAAIRS₉₂, NAAIRS₁₂₂) did not affect this protein interaction. ScEst1 hybrids containing the TPR of hEST1A, hEST1B, or hEST1C were expressed in yeast strains lacking <it>EST1</it>, yet they failed to complement senescence. Point mutations within and outside the cognate ScEst1 TPR, chosen to disrupt a putative protein interaction surface, resulted in telomere lengthening or shortening without affecting recruitment to telomeres.</p> <p>Conclusions</p> <p>These results identify a domain encompassing the TPR of hEST1A as an hTERT interaction module. The TPR of <it>S. cerevisiae </it>Est1 is required for telomerase-mediated telomere length maintenance in a manner that appears separable from telomere recruitment. Discrete residues in or adjacent to the TPR of Est1 also regulate telomere length homeostasis.</p

Time-based combinatorial auction for timber allocation and delivery coordination

The timber auction system currently used in the province of Québec, Canada, is a single unit auction, in which timber users bid on the entire forest stands located within a specific area. In this procurement system, timber users (i.e., winners) are responsible for harvesting the entire stands and for reselling undesirable timber species to others. In order to improve the limits of this system, this paper proposes a sustainable auction system, referred to as time-based timber combinatorial auction. In this approach, time is not part of the definition of the goods for sale. It is used to valuate the good for sale with respect to their expected delivery period. Therefore, this system aims to simultaneously allocate multiple goods, or products in mixed forest stand, to multiple winners, and address the coordination of timber deliveries to their winners. The proposed timber combinatorial auction provides an open access allocation of timber, based on its intrinsic economic value, while allowing the Ministry of natural resources to exercise high standard for environmentally friendly forest operations. From a logistic point of view, a sensitive analysis is conducted in order to compare the proposed time-based combinatorial auction with a combinatorial auction with no delivery coordination. Both models are compared according to bidders' and seller's time flexibility. Experimental results illustrate the impact (i.e., cost) of delivery coordination on total revenue due to loss of value when time preference is not fully satisfied. This cost evaluation can then be used as an upper bound of the cost of coordination, when delivery coordination must be manually negotiated among multi-stakeholders

Multiple-round timber auction design and simulation

This paper presents a multiple-round timber auction simulation, developed in order to study various configurations of auction design. In this study, simultaneous sequential timber auctions are modelled and analysed using agent-based simulation technology. As there are many individual items in the auction to be sold, the auction designer defines several rounds that are sequential at pre-defined intervals. At each round, the auction designer announces several simultaneous auctions. Since bidders are offered different items at each round, a mathematical linear programing model for selecting the best set of items to bid for is presented. Different bidding patterns are simulated and compared in various setup configurations. The most advanced of these strategies are adaptive and use agent-learning capability. The comparisons include the success rate of winning the auction and the winning price per m3. This study suggests an efficient bidding pattern for bidders to bid in order to achieve to their goal and increase their profit. Similarly, in order to increase profit, the auctioneer (i.e. the government) needs to control several auction parameters including the number of auctions per year, the lot size, the auction periodicity, and the number of bidders. This study also suggests parameters configurations that to maximise revenue for the auctioneer

Arcuate fasciculus and pre-reading language development in children with prenatal alcohol exposure

IntroductionPrenatal alcohol exposure (PAE) contributes to widespread neurodevelopmental challenges, including reading, and has been associated with altered white matter. Here, we aimed to investigate whether arcuate fasciculus (AF) development is associated with pre-reading language skills in young children with PAE.MethodsA total of 51 children with confirmed PAE (25 males; 5.6 ± 1.1 years) and 116 unexposed controls (57 males; 4.6 ± 1.2 years) underwent longitudinal diffusion tensor imaging (DTI), for a total of 111 scans from participants with PAE and 381 scans in the unexposed control group. We delineated the left and right AF and extracted mean fractional anisotropy (FA) and mean diffusivity (MD). Pre-reading language ability was assessed using age-standardized phonological processing (PP) and speeded naming (SN) scores of the NEPSY-II. Linear mixed effects models were run to determine the relationship between diffusion metrics and age, group, sex, and age-by-group interactions, with subject modeled as a random factor. A secondary mixed effect model analysis assessed the influence of white matter microstructure and PAE on pre-reading language ability using diffusion metric-by-age-by-group interactions, with 51 age- and sex-matched unexposed controls.ResultsPhonological processing (PP) and SN scores were significantly lower in the PAE group (p &lt; 0.001). In the right AF, there were significant age-by-group interactions for FA (p &lt; 0.001) and MD (p = 0.0173). In the left AF, there was a nominally significant age-by-group interaction for MD that failed to survive correction (p = 0.0418). For the pre-reading analysis, a significant diffusion-by-age-by-group interaction was found for left FA (p = 0.0029) in predicting SN scores, and for the right FA (p = 0.00691) in predicting PP scores.DiscussionChildren with PAE showed altered developmental trajectories for the AF, compared with unexposed controls. Children with PAE, regardless of age, showed altered brain-language relationships that resembled those seen in younger typically developing children. Our findings support the contention that altered developmental trajectories in the AF may be associated with functional outcomes in young children with PAE

Monetary Policy and Large Crises in a Financial Accelerator Agent-Based Model

An accommodating monetary policy followed by a sudden increase of the short term interest rate often leads to a bubble burst and to an economic slowdown. Two examples are the Great Depression of 1929 and the Great Recession of 2008. Through the implementation of an Agent Based Model with a financial accelerator mechanism we are able to study the relationship between monetary policy and large scale crisis events. The main results can be summarized as follow: a) sudden and sharp increases of the policy rate can generate recessions; b) after a crisis, returning too soon and too quickly to a normal monetary policy regime can generate a "double dip" recession, while c) keeping the short term interest rate anchored to the zero lower bound in the short run can successfully avoid a further slowdown