Heterosis is defined as the superiority in performance of heterozygous genotypes compared to their corresponding genetically different homozygous parents. This phenomenon is already known since the beginning of the last century and it has been widely used in plant breeding, but the underlying genetic and molecular mechanisms are not well understood. In this work, a systems biological approach based on molecular network structures is proposed to contribute to the understanding of heterosis. Hybrids are likely to contain additional regulatory possibilities compared to their homozygous parents and, therefore, they may be able to correctly respond to a higher number of environmental challenges, which leads to a higher adaptability and, thus, the heterosis phenomenon. In the network hypothesis for heterosis, presented in this work, more regulatory interactions are expected in the molecular networks of the hybrids compared to the homozygous parents. Partial correlations were used to assess this difference in the global interaction structure of regulatory networks between the hybrids and the homozygous genotypes. This network hypothesis for heterosis was tested on metabolite profiles as well as gene expression data of the two parental Arabidopsis thaliana accessions C24 and Col-0 and their reciprocal crosses. These plants are known to show a heterosis effect in their biomass phenotype. The hypothesis was confirmed for mid-parent and best-parent heterosis for either hybrid of our experimental metabolite as well as gene expression data. It was shown that this result is influenced by the used cutoffs during the analyses. Too strict filtering resulted in sets of metabolites and genes for which the network hypothesis for heterosis does not hold true for either hybrid regarding mid-parent as well as best-parent heterosis. In an over-representation analysis, the genes that show the largest heterosis effects according to our network hypothesis were compared to genes of heterotic quantitative trait loci (QTL) regions. Separately for either hybrid regarding mid-parent as well as best-parent heterosis, a significantly larger overlap between the resulting gene lists of the two different approaches towards biomass heterosis was detected than expected by chance. This suggests that each heterotic QTL region contains many genes influencing biomass heterosis in the early development of Arabidopsis thaliana. Furthermore, this integrative analysis led to a confinement and an increased confidence in the group of candidate genes for biomass heterosis in Arabidopsis thaliana identified by both approaches. / Als Heterosis-Effekt wird die Überlegenheit in einem oder mehreren Leistungsmerkmalen (z.B. Blattgröße von Pflanzen) von heterozygoten (mischerbigen) Nachkommen über deren unterschiedlich homozygoten (reinerbigen) Eltern bezeichnet. Dieses Phänomen ist schon seit Beginn des letzten Jahrhunderts bekannt und wird weit verbreitet in der Pflanzenzucht genutzt. Trotzdem sind die genetischen und molekularen Grundlagen von Heterosis noch weitestgehend unbekannt. Es wird angenommen, dass heterozygote Individuen mehr regulatorische Möglichkeiten aufweisen als ihre homozygoten Eltern und sie somit auf eine größere Anzahl an wechselnden Umweltbedingungen richtig reagieren können. Diese erhöhte Anpassungsfähigkeit führt zum Heterosis-Effekt. In dieser Arbeit wird ein systembiologischer Ansatz, basierend auf molekularen Netzwerkstrukturen verfolgt, um zu einem besseren Verständnis von Heterosis beizutragen. Dazu wird eine Netzwerkhypothese für Heterosis vorgestellt, die vorhersagt, dass die heterozygoten Individuen, die Heterosis zeigen, mehr regulatorische Interaktionen in ihren molekularen Netzwerken aufweisen als die homozygoten Eltern. Partielle Korrelationen wurden verwendet, um diesen Unterschied in den globalen Interaktionsstrukturen zwischen den Heterozygoten und ihren homozygoten Eltern zu untersuchen. Die Netzwerkhypothese wurde anhand von Metabolit- und Genexpressionsdaten der beiden homozygoten Arabidopsis thaliana Pflanzenlinien C24 und Col-0 und deren wechselseitigen Kreuzungen getestet. Arabidopsis thaliana Pflanzen sind bekannt dafür, dass sie einen Heterosis-Effekt im Bezug auf ihre Biomasse zeigen. Die heterozygoten Pflanzen weisen bei gleichem Alter eine höhere Biomasse auf als die homozygoten Pflanzen. Die Netzwerkhypothese für Heterosis konnte sowohl im Bezug auf mid-parent Heterosis (Unterschied in der Leistung des Heterozygoten im Vergleich zum Mittelwert der Eltern) als auch auf best-parent Heterosis (Unterschied in der Leistung des Heterozygoten im Vergleich zum Besseren der Eltern) für beide Kreuzungen für die Metabolit- und Genexpressionsdaten bestätigt werden. In einer Überrepräsentations-Analyse wurden die Gene, für die die größte Veränderung in der Anzahl der regulatorischen Interaktionen, an denen sie vermutlich beteiligt sind, festgestellt wurde, mit den Genen aus einer quantitativ genetischen (QTL) Analyse von Biomasse-Heterosis in Arabidopsis thaliana verglichen. Die ermittelten Gene aus beiden Studien zeigen eine größere Überschneidung als durch Zufall erwartet. Das deutet darauf hin, dass jede identifizierte QTL-Region viele Gene, die den Biomasse-Heterosis-Effekt in Arabidopsis thaliana beeinflussen, enthält. Die Gene, die in den Ergebnislisten beider Analyseverfahren überlappen, können mit größerer Zuversicht als Kandidatengene für Biomasse-Heterosis in Arabidopsis thaliana betrachtet werden als die Ergebnisse von nur einer Studie.

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Public health experts have developed education campaigns based on nutritional messaging to alleviate illnesses related to unhealthy food consumption. This thesis examines cultural factors affecting the accessibility of such messaging, such as economic status, ethnicity, role in the family, access to transportation and markets, and familiarity with the topics of messaging. I explore how these variables affect learning and applying new nutrition knowledge in an individual's daily life. The methods used were semi-structured interviews (n=10) and participant observations conducted in an Integrative Medicine clinic at an urban hospital.

Previous psychological research has demonstrated the benefits of visiting natural environments, especially coastal areas. However, research within Marine Biology has shown that such visits can harm natural habitats. Consequently, this thesis uses an integrative approach to examine both the risks to the environment and benefits to the human visitors in the context of rocky shores (intertidal areas where solid rock predominates). This was investigated using seven studies that involved a range of methods. Perception-based surveys (Studies 1 & 2) explored the perceived impacts on the visitor, and the potential impacts these visits can have on the rocky shore. Study 3 then examined the impacts on visitors’ well-being & marine awareness directly using a before-after survey on current visitors to two rocky shores. The most prominent habitat threat (leaving rubbish) was then examined in greater detail. Studies 4 and 5 examined the effects of marine litter on individuals’ well-being using two laboratory experimental designs; comparing individuals’ quantitative (Study 4) and qualitative (Study 5) responses to natural and littered shores. The final two studies then focused on an activity that reduces marine litter: Study 6 adopted a pre-post design to examine the benefits of engaging in beach cleans for current volunteers, whilst Study 7 used an experimental design comparing beach cleans with two other coastal activities on a more naïve sample. Overall, these studies provide evidence that experiencing rocky shores are beneficial for well-being and marine awareness. Counteracting such benefits, litter left behind after recreational visits were found to be detrimental to individuals’ well-being. As one potential solution to this issue, beach cleans were found to have the same, and additional beneficial effects on the individual as other coastal activities. Thus, activities which have a relatively positive impact on the environment can also have similar if not additional benefits to the visitor. This programme of research shows the importance of taking a holistic, integrative approach that takes into account both the risks to the environment and benefits to the individual resulting from recreational visits to natural environments.

To address the need to improve student achievement in STEM disciplines, effort has been made to develop a new of tools for STEM education (Bybee, 2013). The Robotics and Engineering Design Curriculum (REDC) provides students an opportunity to develop systems thinking abilities while integrating science and mathematics concepts. Using an exploratory case study approach within a situated cognition framework, this study examines the effects of using REDC on 54 eighth grade students’ performance and engagement during 5-week integrative STEM instruction in the mathematics and science class. Situational factors that contribute to students’ success in learning STEM concepts are also examined. This study employed mixed-methods techniques. The quantitative data collected included pre/post achievement tests and pre/post motivation and engagement scale (MES) surveys. Quantitative data analysis included reliability analyses and paired sample t-tests. The results of the reliability analyses for the achievement test and MES survey report acceptable Cronbach’s alpha (.843 and .787, respectively). Qualitative data collected included semi-structured interviews, field notes and student artifacts (engineering notebook and printed prototypes). Qualitative data analysis used coding procedures suggested by Saldana (2012) where patterns were identified and grouped to allow the emergence of themes. Collectively, the data was triangulated to support six emerging themes. The emerging themes regarding the effect of using the curriculum are as follows: (1) the developing anthropomorphic relationship with the robot enhances engagement, (2) engagement is impacted by purposeful and intentional physical action, and (3) purposeful collaboration promotes engagement through the construction of meaning and interaction. Three themes emerged identifying factors that contribute to success: (1) learning environment must have transformative learning potential, (2) learning experiences underpinned by design thinking contribute to success and (3) contextual relevance is enhanced when students have the freedom to their design learning journey. This study addresses the need for research into the implementation of 3-D design and manufacturing in the middle school classroom. Bybee, R. W. (2013). The case for STEM education: Challenges and opportunities. National Science Teachers Association. Saldaña, J. (2012). The coding manual for qualitative researchers (No. 14). Los Angeles, Ca: Sage.

Circadian rhythms are ubiquitous among organisms, influencing a wide array of physiological processes and behaviors including aggression. While many neurophysiological mechanisms are involved in the regulation of aggressive behaviors, relatively few studies have investigated the underlying components involved in the interplay between circadian rhythms and aggression. Spiders are an ideal model system for studying circadian regulation of aggression as they are ecologically both predators and prey. Recent studies have revealed a nocturnal orb- weaving spider Larinioides cornutus exhibits a diel and circadian rhythm in anti-predator behavior (i.e. boldness) that can be manipulated by administration of octopamine (OA) and serotonin (5- HT). Dosing of OA increases boldness of an individual while 5-HT decreases boldness levels. Thus, it appears the serotonergic and octopaminergic system are playing a key role in the daily fluctuations of boldness. This study took a holistic approach to investigate OA and 5-HT levels of head tissue and hemolymph (i.e. blood) as well as the genes involved in synthesis, signaling, and degradation of these monoamines throughout the day (0100, 0700, 1300, and 1900 hours) using HPLC-ED and RNA-sequencing. Although endogenous and circulating levels of OA did not significantly fluctuate, putative transcripts involved in synthesis and signaling did increase in relative expression levels at dusk when L. cornutus begins to actively forage for prey. Endogenous and circulating levels of 5-HT also did not significantly change at the four different time points, but clear patterns of upregulation of 5-HT synthesis enzymes as well as some receptor transcripts were upregulated during the day when L. cornutus would be mostly inactive in its retreat. Lastly, monoamine oxidase, a major catabolic enzyme of monoamines in vertebrates and some invertebrates, was identified in L. cornutus and exhibited substrate specificity for OA compared to 5-HT. Together with the higher enzymatic activity at mid-day compared to dusk, MAO appears to be playing a significant role in regulating the OA and 5-HT signaling in L. cornutus. In conclusion, these results allow a unique preliminary perspective on how OA and 5-HT are influencing the diel shifts in aggression-related behaviors in an ecologically dynamic arthropod.

O desenvolvimento de metodologias sobre integração de dados na área de biologia de sistemas é de grande importância devido ao aumento contínuo de dados resultantes de análises globais que são depositados em bancos de dados públicos. Poucas metodologias e ferramentas de bioinformática levam em consideração a diferenciação entre drivers e passengers, fundamental para a identificação de genes importantes para o desenvolvimento e progressão tumoral. Os perfis de expressão gênica têm possibilitado a identificação de assinaturas genéticas em uma grande variedade de tumores humanos. Além disso, as alterações epigenéticas, como a expressão de microRNAs (miRNA) e a metilação do DNA, também contribuem para o desenvolvimento de diversos tipos de doenças. Entretanto, a grande maioria destes estudos não mostra integração dos resultados obtidos pelas diferentes estratégias utilizadas, o que teria maior impacto na identificação de drivers moleculares. Neste estudo foi realizada a integração de quatro níveis de alterações em 31 amostras de câncer de pênis (CaPe): alteração do número de cópias do DNA, metilação de ilhas CpGs, expressão de miRNAs e expressão de transcritos codificadores. O conhecimento das alterações genéticas e epigenéticas relacionadas ao desenvolvimento de câncer de pênis é bastante limitado, devido principalmente a sua rara incidência. Uma parcela significativa dos casos de CaPe tem sido associada com a infecção pelo Papilomavírus Humano (HPV). A metodologia para integração de dados foi aplicada utilizando duas abordagens: (1) estudo das alterações em câncer de pênis (tumor e normal) independente da infecção pelo HPV e (2) estudo das alterações relacionadas à infecção pelo HPV. A análise foi dividida em duas etapas, com a seleção de genes alvos específicos da doença e inferência de módulos a partir desses alvos. Destacam-se na metodologia a seleção de genes candidatos a driver utilizando a atribuição de pesos para cada alteração seguindo critérios pré-determinados, e.g. se o gene estava presente em uma região rara, após classificação pelo DGV (Database of Genomic Variants) e a utilização desses genes como alvos para identificação das possíveis relações entre eles e os módulos. Também foi realizada a adaptação da metodologia de redes em módulos, com a inclusão de genes passengers e interação proteína-proteína (PPI) como um critério para seleção dos módulos. Essa análise se mostrou eficaz na identificação de módulos gênicos bem relacionados com os drivers, resultando na escolha de vias biológicas potencialmente responsáveis pelo desenvolvimento do tumor. Os genes identificados após a comparação entre amostras tumorais e normais (SOX17, TWIST1, CAV1, PPARG, FLI1 e TNFSF10) e no estudo entre amostras positivas e negativas para infecção pelo HPV (PCNA, SOX14 e RFC4) foram validados in situ por técnicas independentes. Para validação in silico das alterações encontradas na metodologia de integração de dados e para validação da metodologia de redes em módulos foram utilizadas 255 amostras de glioblastoma multiforme obtidas no banco de dados TCGA (The Cancer Genome Atlas). Foram identificadas vias biológicas importantes relacionadas ao processo tumoral, como regulação do crescimento celular (GO:0001558, p=0,0062), homeostase (GO:0048872, $p=0,0082) e regulação da transcrição (GO:0003700, p=0,00089). Também foi realizada uma meta-análise utilizando amostras do TCGA, que encontrou um perfil similar de expressão para os genes CAV1, DLC1,FLI1, MSX1, NRN1, PML, PPARG e SOX17 (T vs N) e PCNA e RFC4 (HPV+ vs HPV-). Para o nosso conhecimento, esse é o primeiro estudo em CaPe utilizando análise integrada de quatro níveis de alteração. Além disso, foram encontradas alterações não randômicas capazes de modificar transcritos específicos e contribuir para o conhecimento da patobiologia dos tumores de pênis. / Methodologies for data integration in systems biology area have great importance due to continuous increase of public data resulting from large-scale analysis, which are deposited in public databases. Few methodologies and bioinformatics tools take into consideration the differentiation between drivers and passengers, fundamental for the identification of important genes for tumor development and progression. The gene expression profiles have allowed the identification of genetic signatures in a wide variety of human tumors. In addition, epigenetic changes, such as the expression of microRNA (miRNA) and DNA methylation, also contribute to the development of a veriety of diseases. However, most of these studies did not show integration of results obtained by different strategies used, which would have increased impact to identify molecular drivers. This study provides a methodology for integration of four levels of changes in 31 samples of penile cancer (PeCa): copy number alterations, DNA methylation of CpG islands, miRNA expression and gene expression of coding transcripts. Knowledge about genetic and epigenetic changes related to the development of penile cancer is very limited, mainly due to its rare incidence. A significant portion of PeCa samples has been associated with infection by Human papillomavirus (HPV). The methodology for integrative data was applied using two approaches: (1) the study considering alterations in penile carcinoma (tumor and normal), independent of HPV infection and (2) the study considering alteration related to HPV infection in PeCa. In each study, the methodology was divided into two stages, with the selection of target genes and the inference of disease specific modules from these targets. It is highlighted in the methodology the selection of candidate genes using the driver assigning weights to each change following predetermined criteria, e.g if the gene was present in a rare region after classification using the DGV database (Database of Genomic Variants) and the use of these genes as seeds for identification of possible relationships between them and the modules. For this, another contribution of this study was the adaptation of module network methodology, with the inclusion of passengers genes and protein-protein interaction (PPI) as a criteria to select the modules. This analysis was effective in identifying gene modules and related drivers, resulting in the choice of biological pathway potentially responsible for the tumor development. The genes identified after comparing tumor and normal samples (SOX17, TWIST1, CAV1, PPARG, FLI1 and TNFSF10) and the genes identified in the study of positive and negative samples for HPV infection (PCNA, SOX14 and RFC4) were validated in situ by independent techniques. For in silico validation of the changes found in the integrative methodology and the modules network were used 255 samples of glioblastoma multiforme obtained at TCGA database (The Cancer Genome Atlas). Biological pathways have been identified related to the tumoral process, such as cell growth regulation (GO:0001558, p=0,0062), homeostasis (GO:0048872, p=0,0082) and transcription regulation (GO:0003700, p=0,00089). Also, a meta-analysis was performed using samples from TCGA, who found a similar expression profile for CAV1, DLC1, FLI1, MSX1, NRN1, PML, PPARG and SOX17 (T vs N) and PCNA and RFC4 genes (HPV + vs HPV-). To our knowledge, this is the first integrative analysis in PeCa using a four-level of gene alterations. In addition, it was found non-random alterations capable to modifying specific transcripts and contribute to the knowledge about the pathobiology of penile tumors.

Acupuncture has been used for thousands of years to treat a wide range of diseases, but the mechanisms involved in the process have remained a mystery. The present study measures EEG responses to stimulation of a specific acupuncture point, GB37 (Guang Ming), with two different types of manual needle stimulation. Previous studies stimulated for a maximum of 2 minutes. The present study reflects the normal acupuncture treatment time of 20 minutes, with EEG recordings during and for 10 minutes prior to and after stimulation. Our results show no changes in the global spatial and temporal properties of EEG during and shortly after acupuncture treatment of acupoint GB37. The second part of this study examines the global protein expression of glutamic acid decarboxylase (GAD) knockout mice. GAD is the rate-limiting enzyme in the synthesis of GABA, the major inhibitory neurotransmitter in the brain. The protein content of wild type, hetero-, and homozygous GAD knockout mice brains were determined using a LC-MS-based gel-free shotgun profiling of complex protein mixtures. The data was analyzed using the Raculovic algorithm to determine the proteins differences. A short list of 32 proteins was determined with four that have been shown to be significant proteins that influence cell survival and excitotoxicity in the brain and have potential relationships with GABA. These proteins include VATPase, Glutamine synthetase, Beta-synuclein, and Micortuble associated protein (MAP). The proteomics results provide a preliminary best guess list of proteins influencing GAD and GABA production. / by Michael L. Marshall. / Thesis (Ph.D.)--Florida Atlantic University, 2011. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2011. Mode of access: World Wide Web.

Atendendo à premissa de expor a vivência do pesquisador em inovação e empreendedorismo, esse trabalho trata-se de um estudo de caso adaptado que teve como objetivo, propor um quadro de modelo de negócios para uma organização de Medicina Integrativa. A proposta do modelo de negócios atendeu um processo proposto por Kolb, onde através da experiência concreta, observação reflexiva e experimentação ativa, conseguiu-se realizar a conceptualização abstrata para um modelo de negócios inovador. Engajando-se na racionalidade médica contemporânea, que busca encontrar um mecanismo de cuidado com o indivíduo por práticas e protocolos que possam ser eficientes e de menor custo, e impulsionado pela experiência profissional e interesse de um investidor, realizou-se uma sequência de ações que pudessem formar um modelo de negócios estruturado e que atendesse um negócio inovador. Foi possível observar que: A) O modelo de negócios mostra-se bastante eficaz para compreender um negócio inovador; B) A Medicina Integrativa é um conjunto de práticas que envolve o cuidado global do indivíduo; C) APor meio do modelo de negócios, é possível proporcionar subsídios para alcançar investidores e, por fim, D) Por meio do modelo de negócios foi possível que o principal stakeholder, o médico proprietário, pôde obter, após a aplicação da ferramenta, novas ideias e insights a respeito de ações imediatas e futuras. Para os outros, a compreensão estabeleceu clareza e direcionamento maior dos objetivos, assim como, possibilitou a definição das responsabilidades e prioridades de cada um. / Given the premise of exposing the experience of research in innovation and entrepreneurship, this work is an appropriate case study that aimed to propose a business model framework for an organization of Integrative Medicine. The proposed business model attended a process proposed by Kolb, which through concrete experience, reflective observation and active experimentation, was managed to achieve the abstract conceptualization to an innovative business model. Engaging in contemporary medical rationality, which seeks to find a care facility with the individual for practices and protocols that may be efficient and lower-cost, driven by experience and interest of an investor, was held a sequence of actions that could form a structured business model and that meets an innovative business. It was observed that: A) The business model is the most effective way to understand an innovative business; B) The Integrative Medicine is undoubtedly the most effective and involves less cost in the overall individual care; C) Through the business model, it is possible to provide subsidies to reach investors and, finally, D) Through the business model it was possible that the main stakeholder, the physician owner could get, after application of the tool, new ideas and insights regarding immediate and future actions. For others, understanding clearly established and greater targeting of objectives, as well as made possible the definition of responsibilities and priorities of each.