Relative quantification of the proteomeic changes associated with the mycotoxin zearalenone in the H295R steroidogenesis model

Zearalenone (ZEN) is a mycotoxin with endocrine disrupting effects having vast economic implications in e.g. pig farming. Structurally, ZEN resembles 17b-estradiol, and thus is able to bind to estrogen receptors (ER) in target cells. Because of this, it is also classified as a non-steroidal estrogen, a phytoestrogen, a mycoestrogen, and a growth promoter. Quantitative proteomic analysis was undertaken using stable-isotope labeling by amino acids in cell culture (SILAC) upon exposure of the steroidogenesis cell model H295R with ZEN to elucidate its effect on protein regulation. ZEN significantly regulated 21 proteins, including proteins with known endocrine disrupting effects and several oncogenes. In addition, network analysis using Ingenuity Pathway Analysis showed that ZEN affected the oxidative phosphorylation pathway and the mitochondrial dysfunction pathway, both previously reported to be involved in endocrine dysfunction.

Cytosol protein regulation in H295R steroidogenesis model induced by the zearalenone metabolites, α- and β-zearalenol.

a- and b-zearalenol (a-ZOL and b-ZOL, respectively) are metabolites of the mycotoxin zearalenone (ZEN). All three individual mycotoxins have shown to be biological active i.e. being estrogenic and able to stimulate cellular proliferation albeit at different strengths. In this work, cytosol protein expression was determined by using stable-isotope labelling by amino acids in cell culture (SILAC) upon exposure of a-ZOL and b-ZOL to the steroidogenesis cell model H295R. A total of 14 and 5 individual proteins were found to be significantly regulated by a-ZOL and b-ZOL, respectively. Interestingly, there were no common protein regulations by the metabolites or the parent mycotoxin ZEN. Furthermore, the regulated proteins were assigned to networks and groups of actions that also differed from one another suggesting that the three individual mycotoxins may have unique biological activities.

Supernatural Beliefs, Unconscious Threat and Judgment Bias in Tibetan Buddhists

Individuals who have been subtly reminded of death display heightened in-group favouritism, or “worldview defense.” Terror management theory argues (i) that death cues engender worldview defense via psychological mechanisms specifically evolved to suppress death anxiety, and (ii) that the core function of religiosity is to suppress death anxiety. Thus, terror management theory predicts that extremely religious individuals will not evince worldview defense. Here, two studies are presented in support of an alternative perspective. According to the unconscious vigilance hypothesis, subtly processed threats (which need not pertain to death) heighten sensitivity to affectively valenced stimuli (which need not pertain to cultural attitudes). From this perspective, religiosity mitigates the influence of mortality-salience only insofar as afterlife doctrines reduce the perceived threat posed by death. Tibetan Buddhism portrays death as a perilous gateway to rebirth rather than an end to suffering; faith in this doctrine should therefore not be expected to nullify mortality-salience effects. In Study 1, devout Tibetan Buddhists who were subtly reminded of death produced exaggerated aesthetic ratings unrelated to cultural worldviews. In Study 2, devout Tibetan Buddhists produced worldview defense following subliminal exposure to non-death cues of threat. The results demonstrate both the domain-generality of the process underlying worldview defense and the importance of religious doctrinal content in moderating mortality-salience effects.

Biotransformation of zearalenone and zearalenols to their major glucuronide metabolites reduces estrogenic activity

Zearalenone (ZEN) is a mycotoxin produced by Fusarium fungi. Once ingested, ZEN may be absorbed andmetabolised to a- and b-zearalenol (a-ZOL, b-ZOL), and to a lesser extent a- and b-zearalanol (a-ZAL,b-ZAL). Further biotransformation to glucuronide conjugates also occurs to facilitate the elimination ofthese toxins from the body. Unlike ZEN and its metabolites, information regarding the estrogenic activityof these glucuronide conjugates in various tissues is lacking. ZEN-14-O-glucuronide, a-ZOL-14-O-glucuronide,a-ZOL-7-O-glucuronide, b-ZOL-14-O-glucuronide and b-ZOL-16-O-glucuronide, previouslyobtained as the major products from preparative enzymatic synthesis, were investigated for their potentialto cause endocrine disruption through interference with estrogen receptor transcriptional activity.All five glucuronide conjugates showed a very weak agonist response in an estrogen responsive reportergene assay (RGA), with activity ranging from 0.0001% to 0.01% of that of 17b-estradiol, and also lessthan that of ZEN, a-ZOL and b-ZOL which have previously shown estrogenic potencies of the order 17bestradiol> a-ZOL > ZEN > b-ZOL. Confirmatory mass spectrometry revealed that any activity observedwas likely a result of minor deconjugation of the glucuronide moiety. This study confirms that formationof ZEN and ZOL glucuronides is a detoxification reaction with regard to estrogenicity, serving as a potentialhost defence mechanism against ZEN-induced estrogenic activity.

Poeta, ou aquele que faz: a poética como inovação em design

Com o objectivo de cumprir com as normas legais em vigor na Universidade de Aveiro conducentes ao reconhecimento do grau de Doutor em Design por avaliação da obra realizada, o presente relatório descreve os objectivos e procedimentos metodológicos, demonstrando o argumento da inovação no conjunto compilado das 100 obras seleccionadas entre os projectos de design realizados no período dos últimos dez anos de actividade profissional do candidato. Para além do enunciado em conformidade com os pressupostos legais, e porque a obra desenvolvida decorre de um contínuo processo de reflexão sobre a própria prática, entende o candidato oportuna a apresentação de um conjunto de textos realizados no mesmo período e que conformarão assim, uma cosmologia teórica própria, sobre a história e teoria do design que contribuirá para o melhor esclarecimento em contexto, das intenções éticas e estéticas dessa obra. O conjunto de contributos de reflexão teórica, que aqui se encontram revelam uma continuidade (maculada pela experiência existencial), que atribui à prática um desempenho quase sempre contaminado pelo corpo de afectos do seu agente, que assim dá origem ao género criativo (poietico) autobiográfico, fundado na metodologia fenomenológica (revelando a ciência do design nos seus próprios procedimentos, “voltando às próprias coisas”). Ao reflectir sobre a prática de projecto enquanto definição disciplinar de Design, verificou-se urgente o esclarecimento ontológico da disciplina, assim procurando perscrutar a definição do que seja, para compreender melhor de que forma lhe pudesse servir os seus interesses bioculturais, numa perspectiva metaprojectual, social, política e estética. O Design, enquanto disciplina da con-formação (da atribuição de forma às coisas), é também o lugar da atribuição de sentido, elevando-as à condição de seres idealizados _ formas são ideias, ainda que imperfeitamente desenhadas (Platão). Neste pressuposto parece inevitável a aproximação da prática projectual do design ao exercício da filosofia, já que a filosofia serve, sobretudo, para inventar conceitos operativos, funcionalizando a mudança (Deleuze). No entanto, o que se encontra neste registo não é uma produção prática que ilustra a jusante uma intencionalidade teórica motivadora mas, bem pelo contrário, uma teorização que anda a zorro da prática da vida, procurando perceber o que parecia inconscientemente suspeitar, confirmando-o. O conjunto de temas teoricamente tratados, constituem aproximações naturalistas por tentativa e erro, que se repetem no tempo em torno de palavras chave como poética, criação, criatividade, tecnologia, artesanato, ontologia, disciplina, desenho, desejo-desenho-desígnio, engenharia-arte-gestão, design, projecto, humano, humanização, diferença, dispositivo, ética, estética, domínio, submissão, zen. Muitos destes temas foram apropriados recorrendo a um conjunto muito diverso e heterogéneo de autores. Aqui misturam-se os filósofos universalmente consagrados, com outros pensadores do Design (Adorno, Aristóteles, Badiou, Di Bártolo, Branco, Brusatin, Calvera, Deleuze, Descartes, Doberti, Espinosa, Flusser, Heidegger, Leiro, Maldonado, Munari, Platão, Pombo, Séneca, Simon, Zizek, e Zumthor), aos quais se associa uma terceira vaga de colegas menos conhecidos, estudantes e investigadores, respigados no grande acaso da web. Na sua assistemática forma de abordagem teórica (Flusser), a teoria não é aqui convocada como janela modernista, abrindo-se sem limites sobre a paisagem organizada, mas como múltiplas aberturas determinadas pela urgência da necessidade, conformando uma arquitectura orgânica e espontânea, do vernacular dirigido por pontos de vista pertinentes e dispersos, produzindo uma visão caleidoscópica, múltipla, cubista, mas sincronicamente orientada sobre o objecto que, tendo vida própria, não pára para posar.

Mind in Dispute: The Section on Mind in Harivarman’s *Tattvasiddhi

Thesis (Ph.D.)--University of Washington, 2015

Perspectives of Identity in Julio Cortázar’s Rayuela

My aim was to produce a dissertation, based on Rayuela, which focuses on Cortázar’s questioning of identity. With this objective in mind, I have studied some of the salient elements in the novel that relate to this topic and the subsequent, interrelated, areas of study that arose in doing so. The cities of Paris and Buenos Aires are placed in contrast within the novel and reflect a dichotomy that reflects Oliveira’s condition as a “foreigner,” (more specifically as a South American in Europe). This duality is further reflected in Cortázar’s use of gender, and the development of the notions of active and passive, and an investigation into the traditional modes of thought, symbols, and stereotypes, and an open-ended questioning of their validity. These topics are framed by a notion of Judeo-Christian History that is in many ways flawed and, as such, contrasts with a more intuitive (or “oriental”) perception of reality, which is centred in figures such as la Maga. I found many explicit references to Zen philosophy, and related oriental references, that led me to believe that this area was worthy of further investigation. Rayuela is considered a classic novel within the canon of Spanish language literature. It’s famous “tabla,” like the rules for a game between the writer and the receptor that produce alternative readings, has led to many discussions regarding the novel’s structure and form, and also created a certain amount of polemic with the use of concepts such as the “lector hembra.” Many consider Cortázar a greater short story writer than a novelist, but nevertheless this novel had a profound effect on young readers upon its publication, much to Cortázar’s surprise, and continues to attract readers, dealing as it does with issues that continue to be relevant to many people.

Method and truth in MÄ dhyamika

Abstract The study was undertaken to identify what motivates registered nurses to participate in continuing education activities. The primary questions were whether basic nursing education, employment status, clinical area, and position, as well as readiness for selfdirected learning influenced Canadian nurses' motivational orientations when deciding to participate in continuing education activities. Other individual differences (e.g., age) were also examined. The sample included 142 registered nurses employed at an urban community hospital. Three instruments were used for data collection: the Education Participation Scale, the Self-Directed Learning Readiness Scale, and a nursing survey consisting of demographic questions. Basic nursing education and employment status did not effect motivational orientation or self-directed learning readiness. Clinical area and level of position significantly influenced nurses' decisions to participate in continuing education activities. Motivational orientation had a significant relationship with selfdirected learning readiness. Implications for practice as a result of this study involves program planning and delivery. The identification of the motivational orientations of participants may assist in the development and delivery of continuing education programs that are beneficial, relevant, and address the identified learning needs of participants. Implications for future research also exist in relation to studying different groups of nurses, for example, registered nursing assistants, and investigating related issues, for example, what are the deterrents to participation in continuing education?

The neurobiology of meditation for the control of pain

La douleur est une expérience multidimensionnelle comportant des aspects sensoriels, émotionnels et cognitifs. Il a été montré que cette expérience peut être modulée par des facteurs psychologiques ou des interventions cognitives comme l’attention, la distraction, l’hypnose ou les attentes. La tradition orientale suggère également que la pratique de la méditation pourrait avoir des effets analgésiques. D’un point de vue théorique, plusieurs mécanismes pourraient expliquer ces effets. Cependant, très peu d’études ont testé ces hypothèses. Les études présentées dans cette thèse avaient donc pour objectif d’examiner les mécanismes analgésiques de la méditation. Dans un premier temps, une étude psychophysique a été réalisée afin de comparer les réponses à la douleur entre des adeptes de la méditation Zen et des sujets contrôles, dans différentes conditions attentionnelles. Durant la condition attentionnelle de type « mindful », les adeptes de la méditation ont présenté une plus faible sensibilité à la douleur, des réponses attentionnelles à la douleur atypiques et une diminution de la perception de la douleur associée à l’entraînement à la méditation. Une deuxième étude a été réalisée en imagerie par résonance magnétique fonctionnelle (IRMf) avec des groupes de participants similaires. Dans une condition sans méditation, les adeptes de la méditation ont présenté de plus fortes réponses nociceptives dans les régions primaires de la douleur. Les régions cérébrales associées aux processus d’évaluation, à la mémoire et aux émotions ont quant à elles montré une diminution d’activité. De plus, cette diminution était plus importante chez les adeptes de la méditation les plus expérimentés et elle était associée à des évaluations de douleur plus faibles. Par ailleurs, des changements de connectivité fonctionnelle entre le cortex préfrontal et une région primaires de la douleur étaient associés à la sensibilité à la douleur chez les adeptes de la méditation. Finalement, une étude d’imagerie cérébrale structurale (publiée comme deux études séparées) a été réalisée pour examiner les différences d’épaisseur corticale entre les groupes, pour des régions associées à la douleur. Les adeptes de la méditation ont présenté une épaisseur plus importante de matière grise dans plusieurs régions associées à la douleur et l’attention. De plus, ces différences étaient associées à une mesure expérientielle de l’attention, à la sensibilité à la douleur et à l’expérience de méditation. Dans l’ensemble, ces résultats suggèrent que la méditation pourrait influencer la perception de la douleur par des changements fonctionnels et physiques dans le cerveau. De plus, le patron d’activation et la modulation de l’expérience paraissent uniques en comparaison à ceux d’autres interventions, ce qui suggère qu’un état de détachement et un focus mental favorisent la dissociation entre les aspects désagréables et sensoriels d’un stimulus nociceptif.

L'éveil dans le « Sûtra de Vimalakîrti »

Notre analyse porte sur la notion d’éveil au sein du Sûtra de Vimalakîrti. Premièrement, nous présentons et comparons les modèles d’éveil exposés dans ce texte, soit la figure du bouddha et – surtout – celle du bodhisattva; nous analysons leurs deux grands traits caractéristiques, c’est-à-dire la connaissance transcendante et les méthodes habiles, puis élaborons leur rôle par rapport à l’éveil. Il apparaît d’emblée que la connaissance transcendante est une connaissance non discursive de la réelle nature de toute chose et qu’elle est une condition nécessaire à l’éveil, alors que les méthodes habiles – aussi appelées expédients salvifiques – constituent la myriade de moyens rusés et provisoires conçus et employés par les bouddhas et bodhisattva dans le but d’amener les êtres ignorants à l’éveil et d’ainsi les libérer de l’attachement et de la souffrance. Dans le second chapitre, nous caractérisons l’état de conscience de l’éveillé à l’aide de notions telles la non-dualité, la non-discrimination et la non-pensée, puis présentons la conception de la pratique méditationnelle soutenue dans notre sûtra. Nous montrons que l’état d’éveil est un état de conscience non discriminateur au sein duquel l’identité personnelle et les phénomènes – ou la dualité sujet-objet – sont reconnus comme étant des illusions ou, plus précisément, des constructions mentales et langagières. Ainsi, la méditation apparaît comme étant une méthode habile provisoire dont les buts sont essentiellement la déconstruction du paradigme dualiste de la pensée discursive et la réalisation qu’il n’existe, ultimement et paradoxalement, aucune réelle entrave à l’éveil et aucune pratique méditationnelle nécessaire à l’expérience de l’éveil.

Médecine et santé à Angkor : pouvoir royal, compassion et offre médicale sous le règne de Jayavarman VII (1181-1220)

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