It has been shown that the cosmic censorship conjecture holds for polarized Gowdy spacetimes. In the more general, unpolarized case, however, the question remains open. It is known that cylindrically symmetric dust can collapse to form a naked singularity. Since Gowdy universes comprise gravitational waves that are locally cylindrically symmetric, perhaps these waves can collapse onto a symmetry axis and create a naked singularity. It is known that in the case of cylindrical symmetry, event horizons will not form under gravitational collapse, so the formation of a singularity on the symmetry axis would be a violation of the cosmic censorship conjecture.To search for cosmic censorship violation in Gowdy spacetimes, we must have a better understanding of their singularities. It is known that far from the symmetry axes, the spacetimes are asymptotically velocity term dominated, but this property is not known to hold near the axes. In this thesis, we take the first steps toward understanding on and near axis behavior of Gowdy spacetimes with space-sections that have the topology of the three-sphere. Null geodesic behavior on the symmetry axes is studied, and it is found that in some cases, a photon will wrap around the universe infinitely many times on its way back toward the initial singularity.

This thesis is based in the research area of Design for Sustainable Behaviour (DfSB), a field which seeks to reduce the social and environmental impact of products in the use phase of their life cycle. There has been significant theoretical development in this area in recent years, leading to a proliferation of intervention strategies and design methodologies. However, there has been a recognised lack of a reliable means of selecting which intervention strategy to use in a given situation, and a lack of real world intervention case studies generating measurable medium-to-long term reductions in energy consumption. Addressing these gaps was a central focus of this research. This thesis documents four distinct research phases; an extensive literature review, an in-depth user study of existing energy consuming behaviours and motivations, the development and trialling of design interventions, and the evaluation of the generated theories as a tool for designers. Literature on domestic energy consumption, human behaviour, and approaches to changing behaviour was reviewed to establish the current level of thinking and to identify opportunities for further research. This guided the undertaking of the user study with a number of families in the East Midlands of the UK, which illuminated the relevant motivational goals, and highly routinized nature, displayed in many energy consuming behaviours. Over the course of this phase of the research journey a new conceptual model of behaviour in context was developed, and refined to create the Behavioural Intervention Selection Axis (BISA). These theoretical developments were then applied to the generation of DfSB intervention concepts, one of which was selected and developed to a functional prototype stage. These prototypes were trialled in situ in family homes for an extended period, and achieved a significant change in behaviour and related energy consumption. Further evaluation of the BISA as a tool to guide designers was performed through a series of workshops with design students, which ascertained its usefulness in this respect. Both the intervention development and trialling and the design workshops showed the conceptual model and BISA to be successful in providing designers with a reliable and useful means of selecting appropriate intervention strategies to change behaviour. In addition the intervention trial provided a wealth of qualitative insight into the way in which DfSB can effect behaviour, and the range of new motivational goals it can engender.

No description available.

Doctor of Philosophy / Department of Biology / Susan J. Brown / How animals polarize and establish the main axis during embryogenesis has been one of the most attractive questions in Biology. Increasing body of work in various model organisms implicates that most metazoans utilize the canonical Wnt signaling pathway to pattern the anterior-posterior (AP) axis, despite the limited evidence from arthropods. In Drosophila, a highly derived insect, canonical Wnt activity is not required for global AP patterning, but in typical insects including Tribolium castaneum, loss of canonical Wnt activity results in posterior truncation. To determine the eff ects of increased canonical Wnt levels, I analyzed the function of axin, encoding a highly conserved negative regulator of the pathway. Tc-axin transcripts are maternally localized to the anterior pole in freshly laid eggs. Parental RNAi for Tc-axin produced progeny phenotypes that ranged from mildly a ffected embryos with cuticles displaying a graded loss of anterior structures, to severely a ffected embryos lacking cuticles and condensing to the posterior pole of the egg without any de finable structures. Altered expression patterns of several blastodermal markers indicated anterior expansion of posterior fates. Epistasis analysis of other canonical Wnt pathway components and the expansion of Tc-caudal expression, a Wnt target, suggest that the eff ects of Tc-axin depletion are mediated through this pathway and that canonical Wnt activity must be repressed for proper anterior development in Tribolium. These studies provide unique evidence that canonical Wnt activity must be carefully regulated along the AP axis in an arthropod, and support an ancestral role for Wnt signaling in de fining AP polarity and patterning in metazoan development. Additionally, as an anterior structure, the extraembryonic serosa is reduced in Tc-axin RNAi progeny. However, in Tc-pangolin (Tc-pan, a homolog of Wnt downstream component) RNAi progeny, an interesting phenotype was produced that serosa was not only reduced but also separated into distinct anterior and dorsal domains. I carefully recorded this phenomenon with live imaging using a Tribolium transgenic line that expresses GFP in each nucleus. Through careful examination with embryonic fate-map markers, I found that the tissue between separated serosa domains is dorsally extended head lobe. And I also found that in severe phenotype, dorsal serosa was completely gone while anterior serosa not, suggesting independent regulation mechanisms for anterior and dorsal serosa formation. This descriptive data will complement future study in the genetic mechanism underlying serosa formation by providing more details in morphogenesis.

Simultaneously achieving high-sensitivity and a large resonance frequency of micromachined accelerometers is difficult because of the inherent trade-off between the two. In this thesis, we present a mechanical displacement-amplifying technique that is amenable to micromachining to enhance sensitivity without compromising on the resonance frequency and cross-axis sensitivity. Depending on the requirements of sensitivity alone or sensitivity and resonance frequency, Displacement-amplifying Compliant Mechanisms (DaCMs) are designed using the selection map-based technique, which indicates the limits of what is possible for given specifications on size and microfabrication. In order to prove the benefits of a DaCM, we modified the designs of two very sensitive capacitive micromachined accelerometers from the literature by incorporating DaCMs and showed that, within the same footprint on the chip, the displacement sensitivity could be enhanced by more than 60% while the resonance frequency was also improved by more than 30%. As the focus of the thesis is to explore the integration of DaCMs into accelerometers, the analytical, computational, and practical aspects are discussed in detail. Both single and dual axis in-plane accelerometers are considered. The fabrication processes used are Silicon-on-Insulator Multi-user MEMS Processes (SOIMUMPs) and a customized Silicon-on-Insulator (SOI) based process. The fabricated accelerometers are packaged and brought to the product form. They were tested at the die level as well as in the packaged form. Under dynamic conditions, the measured amplification factor of the fabricated single-axis in-plane accelerometer was observed to be 11. The overall dimension of the accelerometer was 4.25 mm × 1.25 mm. The first in-plane natural frequency of the fabricated accelerometer was found to be 6.25 kHz. The voltage sensitivity of the packaged accelerometer with the DaCM measured 26.7 mV/g at 40 Hz with differential capacitance sensitivity of 3926 ppm/g around the base capacitance of 0.75 pF. The fabricated dual-axis accelerometer has a special configuration of twelve folded-beam suspension blocks that de-couple any displacements along the two in-plane orthogonal axes. The decoupling feature is retained even after adding the DaCMs along both the axes. The total device size was 8.6 mm × 8.6 mm. The device was also fabricated and packaged inside a ceramic flat-pin package using hybrid die-to-die wire-bonding. Die-level dynamic characterization showed that the average geometric advantage achieved using the DaCMs is 6.2 along both the in-plane axes. The measured axial voltage sensitivity of about 580 mV/g for both the axes was achieved with a cross-axial sensitivity of less than 2% and a natural frequency of 920 Hz. The static capacitance sensitivity was found to be 0.296 × 106 ppm/g with a base capacitance of 0.977 pF. Also presented in this work is a wide-band dual-axis accelerometer without an amplifying mechanism. Its first two in-plane modal frequencies measured 14.2 kHz. The measured sensitivity of the packaged accelerometer along both the axes of the device was found to be 62 mV/g at 200 Hz. Aiming at towards cost-effective accelerometers for small-volume markets, we also developed a single-axis and two dual-axis meso-scale spring-steel in-plane accelerometers equipped with Allegro A1395 linear Hall-effect sensors for sensing the displacement of the proof-mass. The single-axis in-plane meso-scale accelerometer also contains a DaCM. It is observed through simulation that the single-axis design with a DaCM is 39% more sensitive and has 41% more bandwidth compared to a single-axis design without a DaCM. The measured sensitivity of the fabricated single-axis spring-steel accelerometer with a DaCM was found to be 71.4 mV/g with a minimum resolvable acceleration of 14 milli-g. The unique features of the first generation of dual-axis accelerometers are that a rechargeable Li-ion battery adds to the proof-mass. It also contains a de-coupling mechanism that can decompose any planar acceleration into its axial components. The second generation of dual-axis accelerometers is more compact in size. All the mechanical elements of the accelerometers are made of EN J42/AISI 1080 spring steel foil machined using Wire-cut Electro-Discharge- Machining. The measured sensitivity of the first generation of dual-axis meso-scale accelerometers is 78 and 108 mV/g along the X and Y axes whereas the second generation device exhibits a sensitivity of 40 mV/g for both the axes. The thesis concludes that the sensitivity of a displacement-based sensor can be improved using a suitably designed DaCM without compromising the resonance frequency and hence the bandwidth. Furthermore, the work describing the development of meso-scale accelerometers also establishes spring steel as a viable material for meso-scale applications.

[pt] O eixo medial é uma descrição compacta de um objeto que preserva sua topologia e induz naturalmente uma discretização da sua forma como união de bolas. O estudo de união de bolas possui aplicações em diversas áreas da Matemática, em particular na Geometria Computacional onde se usa, por exemplo, para reconstrução de curvas e superfícies. Este trabalho pretende utilizar união de bolas para simular deformações a partir do eixo medial, apresentando conceitos e teoremas a fim de construir algoritmos para a extração do eixo medial em R3. A deformação será, então, definida por movimentos locais das bolas ao longo das direções do eixo medial. Este trabalho contém resultados com movimentos simples, em um programa que utiliza a biblioteca CGAL / [en] The medial axis is a compact description of an object that preserves its topology and naturally induces a discretisation of its forma in terms of union of balls. The study of union of balls has applications in various areas of Mathematics, in particular in Computational Geometry where it is used for curve and surface reconstruction. This work pretends to use union of balls in order to simulate deformations described on the medial axis. It introduces concepts and theorems in order to setup algorithms for medial axis extraction in R3. The deformation will thus be defined by local ball moves along the medial axis directions. This work contains results with simple movements, in a program that uses the CGAL library

A inflamação é um processo fisiológico que promove o reconhecimento e retirada de um agente agressor e restauração de tecidos lesados. Em casos onde a resposta imune é mal regulada, como no caso do choque séptico, ela própria torna-se lesiva, comprometendo diversos órgãos e sistemas e podendo levar ao óbito. Estes quadros podem ser mimetizados experimentalmente com a utilização de lipopolissacarídeos (LPS) induzindo o chamado choque endotoxêmico. Dentre os eixos de regulação da resposta imune, temos a ativação do Eixo Imune-Pineal que atuando desde a montagem do processo inflamatório até sua resolução, vem sendo atualmente considerado como uma peça chave na regulação entre os sistemas neuroendócrino e imunológico. Processos inflamatórios mal regulados podem estar associados com uma disfunção na ativação do sistema melatonérgico, mas pouco se sabe sobre as diferenças no seu padrão de ativação durante quadros endotóxicos letais e não letais. O presente trabalho avalia a ativação do Eixo Imune-Pineal frente desafios endotóxicos letal e não letal induzido por LPS. Além disso, os efeitos do tratamento com eletroacupuntura e os efeitos da utilização de fármaco que atua diretamente sobre os receptores de melatonina também foram avaliados. Foi possível observar que o sistema melatonérgico está alterado em um quadro de choque endotoxêmico em relação a uma situação em que o sistema imune está bem regulado. Esta alteração se reflete na produção tanto da melatonina central como na produzida por células imunocompetentes periféricas e em diferentes padrões de expressão dos receptores de melatonina MT1 e MT2. O estímulo neuroimune causado pela eletroacupuntura em ratos que receberam dose letal de LPS alterou os níveis de melatonina, corticosterona e citocinas circulantes sem, no entanto, alterar a letalidade do choque endotóxico. Por fim, a injeção de 5-HEAT, um agonista MT1 e antagonista MT2 alterou a concentração de citocinas em ratos que receberam dose letal LPS e reduziu a mortalidade dos animais. Demonstramos assim que a ativação doe Eixo Imune Pineal está alterada em situação de choque endotóxico e que a modulação adequada dos receptores de melatonina pode ser considerada no tratamento de quadros similares / Inflammation is a physiological process that promotes the recognition and removal of an aggressive agent and restoration of injured tissues. In cases that the immune response is poorly regulated, as in the case of septic shock it becomes harmful itself increasing lethality. This framework can be experimentally mimicked with lipopolysaccharides (LPS) inducing an endotoxemic shock. Among the axes of regulation of the immune response, we have the activation of the Pineal Immune Axis, which has been acting since the assembly of the inflammatory process until its resolution, and is currently considered a key part in the regulation between the neuroendocrine and immunological systems. Poorly regulated inflammatory processes may be associated with a dysfunction in the activation of the melatonergic system, but little is known about the differences in their pattern of activation during lethal and non-lethal endotoxic conditions. The present work evaluates the activation of the Pineal-Immune Axis against lethal and non-lethal endotoxic challenges induced by LPS. In addition, the effects of treatment with electroacupuncture and the effects of the use of drug that acts directly on the melatonin receptors were also evaluated. It has been observed that the melatonergic system is altered in an endotoxemic shock in relation to a situation in which the immune system is well regulated. This change is reflected in the production of both central melatonin and that produced by peripheral immunocompetent cells and in different patterns of MT1 and MT2 melatonin receptor expression. The neuroimmune stimulus caused by electroacupuncture in rats given lethal dose of LPS altered levels of melatonin, corticosterone and circulating cytokines without altering the lethality of the endotoxic shock. Finally, the injection of 5-HEAT, an MT1 agonist and MT2 antagonist altered the concentration of cytokines in rats receiving lethal dose LPS and reduced mortality of the animals. We thus demonstrated that the activation of the Pineal Immune Axis is altered in a situation of endotoxic shock and that the appropriate modulation of the melatonin receptors can be considered in the treatment of similar conditions

INTRODUÇÃO: A exposição ao estresse precoce (EP) pode estar associada à depressão na vida adulta. Evidencias demonstram que alterações na capacidade regulatória do eixo hipotálamo-pituitária-adrenal (HPA) sejam subjacentes a essa associação. Pacientes depressivos com EP tendem a apresentar quadros clinicamente mais graves, com pior prognóstico e resposta limitada aos tratamentos usuais. Não se sabe ainda como é o perfil cognitivo desses pacientes e como as alterações na atividade do eixo HPA impactam no desempenho neuropsicológico. OBJETIVO: O objetivo deste trabalho foi investigar a atividade do eixo HPA, através dos níveis de cortisol basal, e as funções cognitivas em pacientes depressivos com história de estresse precoce. METODO: Integrou a amostra total do estudo 107 sujeitos, sendo 77 pacientes depressivos e 30 sujeitos saudáveis com idade entre 21 e 60 anos de ambos os sexos. Foram incluídos pacientes com diagnóstico confirmado de episódio depressivo maior e gravidade de sintomas pelo menos moderada no momento das avaliações. O Questionário de Traumas na Infância (CTQ) avaliou a história de EP dividindo a amostra de pacientes em dois grupos, um com estresse precoce (EP+) e outro sem estresse precoce (EP-). Os participantes foram avaliados quanto a gravidade de sintomas psiquiátricos relacionados ao quadro depressivo, quanto à impulsividade e ao temperamento afetivo. A avaliação neuropsicológica incluiu testes de memória verbal, memória visuoespacial, memória de trabalho, atenção sustentada e dividida, além de medidas de controle inibitório, flexibilidade cognitiva, fluência verbal e QI. Na avaliação endócrina cinco amostras de cortisol salivar e de uma amostra de cortisol plasmático foram analisadas para a avaliação da atividade do eixo HPA. RESULTADOS: Setenta e dois por cento dos pacientes depressivos apresentaram EP. A história de EP influenciou o início mais precoce dos quadros depressivos (p=0,03). Não foram encontradas diferenças entre os grupos de pacientes na gravidade de sintomas psiquiátricos, comorbidades clínicas. Não encontramos diferenças entre os pacientes EP+ e EP- comparados a controles no temperamento hipertímico. Na avaliação da atividade do eixo HPA, o grupo EP+ apresentou perda do ritmo circadiano (RC) de cortisol em relação ao grupo controle, além de aumento dos níveis de cortisol salivar às 22h em comparação ao grupo EP- (p=0,04) e uma tendência comparado ao grupo controle (p=0,06). No desempenho neuropsicológico, os pacientes EP+ apresentaram prejuízos em relação aos controles em todos os subdomínios cognitivos avaliados (p<0,05 para todos os escores), exceto memória visuoespacial (p=0,13). Em contraste, os pacientes EP- mostraram déficits apenas em memória de trabalho (p=0,006), alternância atencional (p=0,01) e controle inibitório (p=0,004) comparados aos controles. Na comparação entre os grupos de pacientes, os EP+ apresentaram déficit na nomeação de cores (p=0,01) e uma tendência de prejuízo na memória verbal tardia (p=0,07). Entre os pacientes EP+ encontramos correlações moderadas entre a diminuição da variabilidade nos níveis de cortisol salivar no RC com os prejuízos na flexibilidade cognitiva (?=0,61; p=0,002) e com o controle inibitório (?=0,42; p=0,048). CONCLUSÃO: Nossos achados apontam para um perfil endócrino e neuropsicológico distinto nos pacientes EP+ em comparação com pacientes com depressão EP- e controles. A combinação da história de EP à depressão resultou em inicio mais precoce da doença, prejuízos cognitivos abrangentes e perda na manutenção do ritmo circadiano de cortisol. / BACKGROUND: Exposure to early-life stress (ELS) may be associated with depression in adulthood. Evidence shows that changes in the regulatory capacity of the hypothalamicpituitary-adrenal axis (HPA) underlie association. Patients with ELS usually are more clinically ill, showing poorer prognosis and limited response to usual treatments. It is not known yet what the cognitive profile of those patients is and how changes in the HPA axis activity would impact on cognitive functioning. AIM: The aim of this study was to investigate the HPA axis activity through basal cortisol levels and cognitive functions mediated by the hippocampus and the prefrontal cortex in depressed patients with early stress history. METHOD: Study total study sample was 107 subjects, 77 depressed patients and 30 healthy subjects aged between 21 and 60 years of both sexes. Patients had diagnosis confirmed for major depressive episode with symptom severity at least moderate by the time of the evaluations. We used the Childhood Trauma Questionnaire (CTQ) to assess the ELS history splitting the patient sample into two groups, one with early life stress (ELS+) and the other without early stress (ELS-). Participants were assessed for severity of psychiatric symptoms related to depression, such as impulsivity and affective temperament. The neuropsychological evaluation included tests for verbal memory, visuospatial memory, working memory, sustained and divided attention, inhibitory control measures, cognitive flexibility, verbal fluency, and IQ. For the endocrine assessment five samples of salivary cortisol and plasma cortisol were analyzed to evaluate HPA axis functioning. RESULTS Seventy-two percent of depressive patients had ELS. ELS itself influenced earlier onset of depressive disorders in patients (p = 0.03). Most of the affective temperaments are more prominent in patients with mood disorders than health controls. Regarding the assessment of the HPA axis activity, ELS + group showed lack of cortisol circadian rhythm (CR) compared to the control group. We also found increased salivary cortisol levels at 22 pm compared to the EP- group (p = 0.04) and a trend toward the control group (p = 0.06). In neuropsychological performance, patients EP + showed deficits compared to controls in all of the cognitive subdomains evaluated (p <0.05 for all test scores) except visuospatial memory (p = 0.13). In contrast, ELS-patients showed worse performance only in working memory (p = 0.006), attentional switching (p = 0.01) and inhibitory control (p = 0.004) compared to controls. Comparisons between patient groups showed that EP + patients had a deficit in color naming (p = 0.01) and a trend toward delayed verbal memory (p = 0.07). We found moderate positive correlations for EP+ patients between decreased variation in salivary cortisol levels in the CR and impairments in cognitive flexibility (? = 0.61; p = 0.002) and also to inhibitory control ( ? = 0.42, p = 0.048). CONCLUSION: Our findings indicate a distinct endocrine and neuropsychological profile in patients ELS + compared to depressed EP-. The combination of ELS history and depression resulted in early onset of the depression symptoms, comprehensive cognitive impairment in tasks related to the CPF and hippocampus, and failure in maintaining the circadian rhythm of cortisol.

A produção noturna de melatonina pela glândula pineal é fundamental no controle do sistema oscilatório endógeno de mamíferos. Sua síntese é iniciada pela ativação de receptores adrenérgicos em resposta à liberação noturna de noradrenalina (NA) por terminais simpáticos. A ativação adrenérgica induz, em roedores, a transcrição do gene e a ativação da enzima arilalquil-N-acetiltransferase (AA-NAT) que converte a serotonina em N-acetilserotonina (NAS). A NAS é então convertida em melatonina pela ação da enzima hidroxiindol-O-metiltransferase (HIOMT). Além das funções cronobiológicas, a pineal apresenta comunicação bidirecional com o sistema imunológico, descrita pelo conceito do eixo imune-pineal. Nosso grupo de pesquisa tem demonstrado que mediadores imunológicos, como o lipopolissacarídeo (LPS) de bactérias gram-negativas e o fator de necrose tumoral (TNF), inibem a síntese de melatonina pela pineal por um mecanismo dependente da ativação do fator nuclear de transcrição kappa B (NF-&kappa;B). Por outro lado, fatores que inibem esta via (glicocorticoides) aumentam a produção de melatonina pela glândula pineal. Outros mediadores imunológicos que sinalizam por vias distintas à do NF-&kappa;B também são capazes de atingir e modular a produção de melatonina. A citocina inteferon-gama (IFN-&gamma;) classicamente sinaliza pela via do STAT1 (do inglês Signal Transducer and Activator of Transcription) e é capaz de aumentar a produção de melatonina em pineais. Contudo, não existem relatos do papel desta via de sinalização sobre a síntese hormonal da glândula pineal. Sabendo-se que o IFN-&gamma; também é capaz de sinalizar pela ativação do NF-&kappa;B, o objetivo do presente trabalho foi caracterizar e avaliar o papel destas duas vias de sinalização ativadas pelo IFN-&gamma; sobre as produções de NAS e melatonina, induzidas por NA, em pineais em cultura. Nossos dados mostram que o aumento da síntese de NAS e melatonina induzida pelo IFN-&gamma; está associado ao aumento da expressão dos genes Aanat e Hiomt. A incubação das glândulas com IFN-&gamma; aumenta a translocação nuclear de STAT1 e de dímeros de NF-&kappa;B ativadores da transcrição gênica. Além disso, a incubação de pineais com IFN-&gamma; aumenta a transcrição de 27 genes relacionados com a via das STATs. IFN-&gamma; tende a aumentar a ligação da STAT1 com uma região do promotor do gene Aanat e a utilização de uma droga que potencia a ativação da STAT1 também aumenta a produção de NAS e melatonina. Por fim, o bloqueio da via do NF-&kappa;B inibe o aumento na produção de NAS e melatonina e da expressão de Aanat e Hiomt induzido pelo IFN-&gamma;. Nossos dados demonstram, pela primeira vez, a importância da via da STAT1 em associação com a via NF-&kappa;B sobre a produção hormonal da glândula pineal / The nocturnal production of melatonin by the pineal gland is crucial in the control of the mammalian endogenous oscillatory system. Melatonin synthesis is initiated by the activation of adrenergic receptors in response to nocturnal release of noradrenaline (NA) by sympathetic terminals. The adrenergic activation induces, in rodents, gene transcription and activation of the arylalkyl-N-acetyltransferase enzyme (AA-NAT) that converts serotonin into N-acetilserotonin (NAS). NAS is then converted to melatonin by the action of the enzyme hydroxyindole-O-methyltransferase (HIOMT). In addition to the chronobiological functions, the pineal has a bidirectional communication with the immune system as described by the concept of the immune-pineal axis. Our research group has demonstrated that immunological mediators as the lipopolysaccharide (LPS) of gram-negative bacteria and the tumor necrosis factor (TNF) inhibit the synthesis of melatonin by the pineal in a mechanism dependent on the activation of the nuclear transcription factor kappa B (NF-&kappa;B). Moreover, factors that inhibit NF-&kappa;B pathway (glucocorticoids) increase the production of melatonin by the pineal gland. Other immunological mediators that signalize by distinct signaling pathways are also able to target and modulate the melatonin production. The cytokine interferon-gamma (IFN-&gamma;) classically signals trough STAT1 (Signal transducer and Activator of Transcription) and is able to increase the production of melatonin by the pineal. However, there are no reports of the role of STAT1 pathway on the hormonal synthesis of the pineal gland. Considering that IFN-&gamma; is also able to signalize through NF-&kappa;B, the aim of this study was to characterize and evaluate the role of these two signaling pathways activated by IFN-&gamma; on the production of NAS and melatonin induced by NA in cultured pineals. Our data show that the increase in NAS and melatonin synthesis induced by IFN-&gamma; is associated with increased expression of the genes Aanat and Hiomt. Incubation of the glands with IFN-&gamma; increases the nuclear translocation of STAT1 and of p50:RelA NF-&kappa;B dimers. In addition, pineal incubation with IFN-&gamma; increases the transcription of 27 related to STAT pathway. IFN-&gamma; tends to increase the binding of STAT1 to a promoter region and the Aanat gene and the use of a STAT1-enhancer also increased the production of NAS and melatonin. Finally, the blockade of NF-&kappa;B pathway inhibits the increase in melatonin and NAS productions and also of Aanat and Hiomt genes expression induced by IFN-&gamma;. Our data demonstrate, for the first time, the importance of the STAT1 pathway in association with NF-&kappa;B pathway on the hormonal production of the pineal gland

O exercício físico é mediado por mecanismos neuroendócrinos altamente específicos, que apresenta uma aparente relação dose-resposta com o aumento da concentração de GH, o qual, em conjunto com o IGF-1, compõe o eixo GH-IGF, determinante para o processo de crescimento muscular. A resposta do hormônio GH induzida pelo exercício está associada à intensidade, duração, frequência e método de treinamento utilizado. Desta forma, a prática de exercícios, principalmente contra uma resistência, está intimamente ligada à função anabólica, envolvendo processos de síntese proteica e ressíntese de glicogênio. Diante de relatos na literatura, o treinamento físico é capaz de promover um aumento dos níveis de IGFBP-3, proteína ligadora responsável por ampliar a atividade secretória do eixo GH-IGF. Em preparações de modalidades como o fisiculturismo, em que os atletas são julgados pela simetria muscular e definição corporal, é comum a adoção de estratégias dietéticas, bem como, desidratação, períodos de jejum prolongado, restrição calórica severa, uso de diuréticos e utilização de esteroides anabolizantes. Nesse sentido, o objetivo do estudo foi investigar o comportamento do eixo GH-IGF, sob suplementação de nutrientes, como carboidrato (maltodextrina) e proteína (whey protein), comumente utilizados por fisiculturistas, pela técnica de imuno-ensaios realizados em amostras de sangue obtidas em uma sessão de treinamento padronizada. A amostra foi composta por 10 atletas fisiculturistas da categoria Men\'s Physique que foram analisados em fase off season , ou seja, fora da fase preparatória para a competição, no momento que antecede a sessão de treinamento (PRÉ TREINO), 30 minutos após (PÓS TREINO 30\') e 60 minutos após o término da sessão (PÓS TREINO 60\'). Foram analisados dados antropométricos, composição nutricional da dieta e concentrações de IGF-1. Para as análises estatísticas foram utilizadas ANOVA two way de medidas repetidas, Magnitude de Efeito (ES) e Probabilidade Quantitativa de Chances (QC). Os resultados mostram uma tendência de aumento nas concentrações de IGF-1 para os estados alimentado e suplementado nos momentos de pré treino e pós treino 30 e 60 minutos. Além disso, de uma maneira geral, observou-se um aumento nas concentrações de IGF-1 no estado suplementado , em comparação ao estado de jejum e alimentado, independente do momento do treino. Ademais, observa-se uma restrição na ingestão de carboidratos em contrapartida de um maior consumo de proteínas, ou seja, estratégias necessárias para corroborar com as exigências do Esporte. Desta forma, diante do importante papel do IGF-1 sob o processo de hipertrofia muscular e dos achados no seu comportamento submetido ao uso de um suplemento alimentar contendo carboidrato + whey protein, torna-se interessante uso desta solução em prol do desempenho e sucesso dos atletas fisiculturistas / The physical exercise is mediated by highly specific neuroendocrine mechanisms, which presents an apparent dose-response relationship with the increase in GH concentration, which, together with IGF-1, makes up the GH-IGF axis, which is determinant for the muscle growth. Exercise-induced GH hormone response is associated with the intensity, duration, frequency, and training method used. In this way, the practice of exercises, mainly against a resistance, is closely linked to the anabolic function, involving processes of protein synthesis and glycogen resynthesis. According to reports in the literature, physical training is capable of promoting an increase in levels of IGFBP-3, a binding protein responsible for enhancing the secretory activity of the GH-IGF axis. In preparation for modalities such as bodybuilding, where athletes are judged by muscular symmetry and body definition, dietary strategies, as well as dehydration, periods of prolonged fasting, severe caloric restriction, use of diuretics, and steroid use are common anabolic. In this sense, the objective of the study was to investigate the behavior of the GH-IGF axis, under nutrient supplementation, such as carbohydrate (maltodextrin) and protein (whey protein), commonly used by bodybuilders, by the immunoassay technique performed in blood samples obtained in a standardized training session. The sample consisted of 10 bodybuilders from the Men\'s Physique category who were analyzed in the off-season phase, that is, outside the preparatory phase for the competition, at the moment before the training session (PRE-TRAINING), 30 minutes after (POST-TRAINING 30 \') and 60 minutes after the end of the session (POST TRAIN 60\'). Anthropometric data, nutritional composition of the diet and concentrations of IGF-1 were analyzed. Two-way ANOVA of repeated measures, Magnitude of Effect (ES) and Quantitative Chance of Chance (QC) were used for statistical analysis. The results show a trend of increase in IGF-1 concentrations for the fed and supplemented states at pre-workout and post-workout 30 and 60 minutes. In addition, in general, an increase in IGF-1 concentrations in the supplemented state, as compared to the fed and fed state, was observed irrespective of the training time. In addition, a restriction in the carbohydrate intake is observed in counterpart of a greater consumption of proteins, that is, strategies necessary to corroborate with the requirements of the Sport. Thus, in view of the important role of IGF-1 under the process of muscular hypertrophy and the findings in the in its behavior submitted to the use of a food supplement containing carbohydrate + whey protein, it becomes interesting to use this solution for the performance and success of the athletes bodybuilders