Pathways to Aging: The Mitochondrion at the Intersection of Biological and Psychosocial Sciences

Compelling evidence suggests that both biological and psychosocial factors impact the process of aging. However, our understanding of the dynamic interplay among biological and psychosocial factors across the life course is still fragmentary. For example, it needs to be established how the interaction of individual factors (e.g., genetic and epigenetic endowment and personality), behavioral factors (e.g., physical activity, diet, and stress management), and psychosocial experiences (e.g., social support, well-being, socioeconomic status, and marriage) in perinatal, childhood, and adulthood influence health across the aging continuum. This paper aims to outline potential intersection points serving as an interface between biological and psychosocial factors, with an emphasis on the mitochondrion. Mitochondria are cellular organelles which play a critical role in cellular senescence. Both chronic exposure to psychosocial stress and genetic-based mitochondrial dysfunction have strikingly similar biological consequences; both predispose individuals to adverse age-related health disorders and early mortality. Exploring the interactive nature of the factors resulting in pathways to normal healthy aging, as well as those leading to morbidity and early mortality, will continue to enhance our ability to translate research into effective practices that can be implemented throughout the life course to optimise the aging process

Machinima: Video Game As An Art Form?

This paper examines the new audiovisual form emerging from the video game field, Machinima. Machinima is the “art of making animated movies in a 3D virtual environment in real time” (Marino, 2004, p. 2). More simply, it means making films from video games. Studying this new hybrid form, this communication seeks to investigate the present and the future of these practices, which aspire to become a medium itself. After the exploration of the characteristics of this new technology, I will investigate its consequences on the video game industry, demonstrating how video games are used in new ways, i.e. not as a playing hobby but as a technology for producing audio-visual art, animated films to be more exact

State of Alaska Election Security Project Phase 2 Report

A laska’s election system is among the most secure in the country, and it has a number of safeguards other states are now adopting. But the technology Alaska uses to record and count votes could be improved— and the state’s huge size, limited road system, and scattered communities also create special challenges for insuring the integrity of the vote. In this second phase of an ongoing study of Alaska’s election security, we recommend ways of strengthening the system—not only the technology but also the election procedures. The lieutenant governor and the Division of Elections asked the University of Alaska Anchorage to do this evaluation, which began in September 2007.Lieutenant Governor Sean Parnell. State of Alaska Division of Elections.List of Appendices / Glossary / Study Team / Acknowledgments / Introduction / Summary of Recommendations / Part 1 Defense in Depth / Part 2 Fortification of Systems / Part 3 Confidence in Outcomes / Conclusions / Proposed Statement of Work for Phase 3: Implementation / Reference

Genetic Evidence for Elevated Pathogenicity of Mitochondrial DNA Heteroplasmy in Autism Spectrum Disorder

Increasing clinical and biochemical evidence implicate mitochondrial dysfunction in the pathophysiology of Autism Spectrum Disorder (ASD), but little is known about the biological basis for this connection. A possible cause of ASD is the genetic variation in the mitochondrial DNA (mtDNA) sequence, which has yet to be thoroughly investigated in large genomic studies of ASD. Here we evaluated mtDNA variation, including the mixture of different mtDNA molecules in the same individual (i.e., heteroplasmy), using whole-exome sequencing data from mother-proband-sibling trios from simplex families (n = 903) where only one child is affected by ASD. We found that heteroplasmic mutations in autistic probands were enriched at non-polymorphic mtDNA sites (P = 0.0015), which were more likely to confer deleterious effects than heteroplasmies at polymorphic mtDNA sites. Accordingly, we observed a ~1.5-fold enrichment of nonsynonymous mutations (P = 0.0028) as well as a ~2.2-fold enrichment of predicted pathogenic mutations (P = 0.0016) in autistic probands compared to their non-autistic siblings. Both nonsynonymous and predicted pathogenic mutations private to probands conferred increased risk of ASD (Odds Ratio, OR[95% CI] = 1.87[1.14–3.11] and 2.55[1.26–5.51], respectively), and their influence on ASD was most pronounced in families with probands showing diminished IQ and/or impaired social behavior compared to their non-autistic siblings. We also showed that the genetic transmission pattern of mtDNA heteroplasmies with high pathogenic potential differed between mother-autistic proband pairs and mother-sibling pairs, implicating developmental and possibly in utero contributions. Taken together, our genetic findings substantiate pathogenic mtDNA mutations as a potential cause for ASD and synergize with recent work calling attention to their unique metabolic phenotypes for diagnosis and treatment of children with ASD

A Mitochondrial Health Index Sensitive to Mood and Caregiving Stress.

BACKGROUND:Chronic life stress, such as the stress of caregiving, can promote pathophysiology, but the underlying cellular mechanisms are not well understood. Chronic stress may induce recalibrations in mitochondria leading to changes either in mitochondrial content per cell, or in mitochondrial functional capacity (i.e., quality). METHODS:Here we present a functional index of mitochondrial health (MHI) for human leukocytes that can distinguish between these two possibilities. The MHI integrates nuclear and mitochondrial DNA-encoded respiratory chain enzymatic activities and mitochondrial DNA copy number. We then use the MHI to test the hypothesis that daily emotional states and caregiving stress influence mitochondrial function by comparing healthy mothers of a child with an autism spectrum disorder (high-stress caregivers, n = 46) with mothers of a neurotypical child (control group, n = 45). RESULTS:The MHI outperformed individual mitochondrial function measures. Elevated positive mood at night was associated with higher MHI, and nightly positive mood was also a mediator of the association between caregiving and MHI. Moreover, MHI was correlated to positive mood on the days preceding, but not following the blood draw, suggesting for the first time in humans that mitochondria may respond to proximate emotional states within days. Correspondingly, the caregiver group, which had higher perceived stress and lower positive and greater negative daily affect, exhibited lower MHI. This effect was not explained by a mismatch between nuclear and mitochondrial genomes. CONCLUSIONS:Daily mood and chronic caregiving stress are associated with mitochondrial functional capacity. Mitochondrial health may represent a nexus between psychological stress and health

Les enjeux esthétiques du jeu vidéo : entre art, stylistique et interactivité

Dans cet article, l’auteur questionne le lien complexe entre le jeu vidéo et l’art en tentant de réfléchir à l’esthétique du jeu vidéo. Selon lui, le questionnement sur la qualité artistique du jeu vidéo repose principalement sur une confusion dans la définition de la notion d’art. Trois conceptions différentes semblent être en cause dans le discours général : le jeu vidéo comme production ou technique artistique, le jeu vidéo comme média audiovisuel, et le jeu vidéo comme pratique interactive. En distinguant à tour de rôle ces trois acceptions, l’auteur se penche également sur la question des styles visuels de jeu vidéo, alors que ces derniers contribuent de manière primordiale à la perception du jeu vidéo en tant qu’objet esthétique et culturel.In this article, the author questions the complex relationship between video game and art in trying to think about the aesthetics of video games. According to him, the questioning of the artistic quality of the medium is mainly based on a confusion in the definition of the concept of art. Three different significations seem to be involved in the general discourse: video game as an artistic production or technique, video game as an audiovisual medium, and video game as an interactive practice. While distinguishing between the three meanings, the author also addresses the issue of video game visual styles, since they contribute significantly to the perception of video game as an aesthetic and cultural object

Pour une esthétique du cinéma transludique : figures du jeu vidéo et de l'animation dans le cinéma d'effets visuels du tournant du XXIe siècle

[À l'origine dans / Was originally part of : Thèses et mémoires - FAS - Département de littérature comparée]Cette thèse propose une analyse croisée du cinéma et du jeu vidéo sous un angle interdisciplinaire afin de montrer la réappropriation et le remédiatisation des structures narratives et formelles du jeu vidéo dans le cinéma d’effets visuels du tournant du XXIe siècle. Plus spécifiquement, la thèse porte sur l’analyse de trois figures majeures du jeu vidéo et de l’animation dans la trilogie Matrix (Larry et Andy Wachowski, 1999-2003), dans Avalon (Mamoru Oshii, 2001) et dans Kung-Fu Hustle (Stephen Chow, 2004). La première section de la thèse consiste en une mise en place théorique par la présentation de certains paramètres esthétiques du cinéma d’effets visuels et du jeu vidéo. Quelques réflexions préliminaires sur l’esthétique du cinéma d’effets visuels sont d’abord esquissées avant de présenter les principales relations transmédiales entre le cinéma et le jeu vidéo. Ensuite, c’est le cinéma transludique qui est défini alors que le terme découle de la synergie singulière entre le cinéma et le jeu vidéo. Puisque le cinéma transludique concerne spécifiquement la récupération de l’esthétique du jeu vidéo dans le cinéma contemporain, les prémisses d’une esthétique du jeu vidéo sont alors établies. Dans la deuxième section, ce sont les figures et sous-figures au cœur de cette réflexion qui sont développées, pour ensuite les appliquer aux films du corpus. La première figure à l’étude est celle de l’exploration, alors que l’analyse de la signification de cette figure dans la conception de jeu vidéo et dans les récits cinématographiques de science-fiction montre l’importance de la navigation comme expérience spatio-temporelle dans les univers virtuels. Ensuite, c’est l’utilisation récurrente de la figure vidéoludique du niveau (level) dans le cinéma hybride contemporain qui est soulignée, figure qui structure autant le récit que la forme représentationnelle des films transludiques. Enfin, la figure de la métamorphose, indissociable du cinéma d’animation, est étudiée afin de souligner l’importance de cette figure dans la création numérique et d’expliquer la transformation de l’image qui affecte le cinéma transludique, image qualifiée d’image-frontière.This thesis proposes an analysis between cinema and video games from an interdisciplinary standpoint to demonstrate the remediation of video games’ narrative structures and forms in visual effects-driven films of the early twenty-first century. More specifically, the thesis focuses on the analysis of three major figures of video games and animation films in The Matrix trilogy (Larry and Andy Wachowski, 1999-2003), Avalon (Mamoru Oshii, 2001) and Kung Fu Hustle (Stephen Chow, 2004). The first section of the thesis is a theoretical framework in which the aesthetic parameters of visual effects-driven films and video games are introduced. Some preliminary thoughts on the aesthetics of visual effects-driven films are first outlined before presenting the main transmedial relationships between cinema and video game. Then, it is the transludic cinema which is defined as the term derives from the unique synergy between cinema and video game. Since transludic cinema specifically concerns the remediation of the aesthetics of video games in contemporary cinema, the grounds of an aesthetics of video game are established. In the second section, the figures and subfigures at the heart of this thesis are developed, and then applied to an analysis of the films. The first figure to be discussed is the motif of exploration, where I analyze the significance of this figure in the video game design and science-fiction films narratives, and the meaning of navigation as a spatio-temporal experience in virtual worlds. Then, I demonstrate the use of the recurring figure of the game level in the contemporary hybrid cinema, which structures the narrative as much as the representational image. Finally, the figure of metamorphosis, an essential characteristic of animation, is being studied to highlight the importance of this figure in digital films. I also explain the transformation of the image that affects the transludic film, an image qualified as an “image-frontière”

Multifaceted mitochondria: moving mitochondrial science beyond function and dysfunction.

Mitochondria have cell-type specific phenotypes, perform dozens of interconnected functions and undergo dynamic and often reversible physiological recalibrations. Given their multifunctional and malleable nature, the frequently used terms 'mitochondrial function' and 'mitochondrial dysfunction' are misleading misnomers that fail to capture the complexity of mitochondrial biology. To increase the conceptual and experimental specificity in mitochondrial science, we propose a terminology system that distinguishes between (1) cell-dependent properties, (2) molecular features, (3) activities, (4) functions and (5) behaviours. A hierarchical terminology system that accurately captures the multifaceted nature of mitochondria will achieve three important outcomes. It will convey a more holistic picture of mitochondria as we teach the next generations of mitochondrial biologists, maximize progress in the rapidly expanding field of mitochondrial science, and also facilitate synergy with other disciplines. Improving specificity in the language around mitochondrial science is a step towards refining our understanding of the mechanisms by which this unique family of organelles contributes to cellular and organismal health.S

Développement d’un modèle dual au modèle t-J pour l’étude de l’intrication interparticule par réseaux de tenseurs

Dans un système à plusieurs corps, l’entropie d’intrication nous permet d’évaluer la magnitude de l’intrication entre deux parties du système. Nous pouvons imaginer deux types de partitions. Dans un premier temps, nous pouvons partitionner entre les sites du réseau. Dans un second temps, nous pouvons partitionner entre les particules dans le système. Dans un hamiltonien fermionique régulier, la position des sites est très bien définie et il sera aisé de partitionner entre les sites. Cependant, la position des particules n’est pas bien définie et il va être difficile d’identifier le nombre de particules de chaque côté d’une partition. Dans ce mémoire, nous présentons une représentation duale pour le modèle t-J où les particules sont fixées à un site spécifique, ce qui permet l’étude de l’intrication entre particules dans des systèmes de grande taille. Nous comparons cette représentation au modèle t-J régulier en utilisant diverses métriques. Plus spécifiquement, nous étudions : l’énergie de l’état fondamental, le diagramme de phase ainsi que le coefficient d’entropie des deux modèles. Nos simulations ont montré que l’entropie d’intrication agit différemment dans une partition entre les sites par rapport à une partition entre les particules. Dans la représentation originale, le coefficient d’entropie avec la taille du réseau est constant sans transition de phase. Cependant, elle varie dans la représentation duale. La difficulté de représenter un état avec des réseaux de tenseurs est principalement due à l’intrication dans le système. Dès lors, le modèle dual peut potentiellement représenter des états qui sont intraitables dans la représentation originale