904 resultados para WAY-100635


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Os transtornos de ansiedade apresentam a maior incidência na população mundial dentre os transtornos psiquiátricos, e a eficácia clínica das drogas ansiolíticas é baixa, em parte devido ao desconhecimento acerca das bases neuroquímicas desses transtornos. Para uma compreensão mais ampla e evolutivamente substanciada desses fenômenos, a utilização de espécies filogeneticamente mais antigas pode ser uma aproximação interessante no campo da modelagem comportamental; assim, sugerimos o uso do paulistinha (Danio rerio Hamilton 1822) na tentativa de compreender a modulação de comportamentos tipo-ansiedade pelo sistema serotonérgico. Demonstramos que os níveis extracelulares de serotonina no encéfalo de paulistinhas adultos expostos ao teste de preferência claro/escuro [PCE] (mas não ao teste de distribuição vertical eliciada pela novidade [DVN]) apresentam-se elevados em relação a animais manipulados mas não expostos aos aparatos. Além disso, os níveis teciduais de serotonina no rombencéfalo e no prosencéfalo são elevados pela exposição ao PCE, enquanto no mesencéfalo são elevados pela exposição ao DVN. Os níveis extracelulares de serotonina estão correlacionados negativamente com a geotaxia no DVN, e positivamente com a escototaxia, tigmotaxia e a avaliação de risco no PCE. O tratamento agudo com uma dose baixa de fluoxetina (2,5 mg/kg) aumenta a escototaxia, a tigmotaxia e a avaliação de risco no PCE, diminui a geotaxia e o congelamento e facilita a habituação no DVN. O tratamento com buspirona diminui a escototaxia, a tigmotaxia e o congelamento nas doses de 25 e 50 mg/kg no PCE, e diminui a avaliação de risco na dose de 50 mg/kg; no DVN, ambas as doses diminuem a geotaxia, enquanto somente a maior dose diminui o congelamento e facilita a habituação. O tratamento com WAY 100635 diminui a escototaxia nas doses de 0,003 e 0,03 mg/kg, enquanto somente a dose de 0,03 mg/kg diminui a tigmotaxia e a avaliação de risco no PCE. No DVN, ambas as doses diminuem a geotaxia, enquanto somente a menor dose facilita a habituação e aumenta o tempo em uma “base” (“homebase”). O tratamento com SB 224289 não produziu efeitos sobre a escototaxia, mas aumentou a avaliação de risco na dose de 2,5 mg/kg; no DVN, essa droga diminuiu a geotaxia e o nado errático nas doses de 2,5 e 5 mg/kg, enquanto a dose de 2,5 mg/kg aumentou a formação de “bases”. O tratamento com DL-para-clorofenilalanina (2 injeções de 300 mg/kg, separadas por 24 horas) diminuiu a escototaxia, a tigmotaxia e a avaliação de risco no PCE, aumentou a geotaxia e a formação de bases e diminuiu a habituação no DVN. Quando os animais são pré-expostos a uma “substância de alarme” co-específica, observa-se um aumento nos níveis extracelulares de serotonina associados a um aumento na escototaxia, congelamento e nado errático no PCE; os efeitos comportamentais e neuroquímicos foram bloqueados pelo pré tratamento com fluoxetina (2,5 mg/kg), mas não pelo pré-tratamento com WAY 100,635 (0,003 mg/kg). Animais da linhagem leopard apresentam maior escototaxia e avaliação de risco no PCE, assim como níveis teciduais elevados de serotonina no encéfalo; o fenótipo comportamental é resgatado pelo tratamento com fluoxetina (5 mg/kg). Esses dados sugerem que o sistema serotonérgico dessa espécie modula o comportamento no DVN e no PCE de forma oposta; que a resposta de medo produzida pela substância de alarme também parece aumentar a atividade do sistema serotonérgico, um efeito possivelmente mediado pelos transportadores de serotonina, e ao menos um fenótipo mutante de alta ansiedade também está associado a esses transportadores. Sugere-se que, de um ponto de vista funcional, a serotonina aumenta a ansiedade e diminui o medo em paulistinhas.

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The medial amygdaloid nucleus (MeA) is a sub-region of the amygdaloid complex that has been described as participating in food intake regulation. Serotonin has been known to play an important role in appetite and food intake regulation. Moreover, serotonin 5-HT2C and 5-HT1A receptors appear to be critical in food intake regulation. We investigated the role of the serotoninergic system in the MeA on feeding behavior regulation in rats. The current study examined the effects on feeding behavior regulation of the serotonin reuptake inhibitor, zimelidine, administered directly into the MeA or given systemically, and the serotoninergic receptors mediating its effect. Our results showed that microinjection of zimelidine (0.2, 2 and 20 nmol/100 nL) into the MeA evoked dose dependent hypophagic effects in fasted rats. The selective 5-HT1A receptor antagonist WAY-100635 (18.5 nmol/100 nL) or the 5-HT1B receptor antagonist SB-216641 microinjected bilaterally into the MeA did not change the hypophagic effect evoked by local MeA zimelidine treatment. However, microinjection of the selective 5-HT2C receptor antagonist SB-242084 (10 nmol/100 nL) was able to block the hypophagic effect of zimelidine. Moreover, microinjection of the 5-HT2C receptor antagonist SB-242084 into the MeA also blocked the hypophagic effect caused by zimelidine administered systemically. These results suggest that MeA 5-HT2C receptors modulate the hypophagic effect caused by local MeA administration as well as by systemic zimelidine administration. Furthermore, 5-HT2C into the MeA could be a potential target for systemic administration of zimelidine. (C) 2012 Elsevier Ltd. All rights reserved.

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Changes in brain-derived neurotrophic factor (BDNF)mediated signaling in the hippocampus have been implicated in the etiology of depression and in the mode of action of antidepressant drugs. There is also evidence from animal studies to suggest that BDNF-induced changes in the hippocampus may play a role in another stress-related pathology: anxiety. However, it is still unknown whether this neurotrophin plays a differential role in defensive responses associated with distinguished subtypes of anxiety disorders found in the clinic, such as generalized anxiety and panic disorder. In the present study, we investigated the effect of an acute BDNF injection into the rat dorsal hippocampus (DH) on inhibitory avoidance acquisition and escape expression measured in the elevated T-maze (ETM). We also assessed whether serotonergic neurotransmission may account for such effects. Intra-DH BDNF injection (200 pg) facilitated inhibitory avoidance in ETM. BDNF was equally anxiogenic in the light/dark transition test. Preadministration of the 5-HT1A receptor antagonist WAY-100635 fully counteracted the anxiogenic effect of BDNF in both tests. Intra-DH midazolam administration (10 nmol) impaired avoidance acquisition in ETM, suggesting an anxiolytic effect. Therefore, in the DH, facilitation of BDNF signaling seems to enhance 5-HT1A receptor-mediated neurotransmission to exert an anxiogenic effect associated with generalized anxiety. Behavioural Pharmacology 23:80-88 (C) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

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Tic-like movements in rodents bear close similarities to those observed in humans both pharmacologically and morphologically. Pharmacologically, tics are modulated by serotonergic and dopaminergic systems and abnormalities of these systems have been reported in Tourette's Syndrome (TS). Therefore, serotonergic and dopaminergic modulation of tics induced by a thyrotrophin-releasing hormone (TRH) analogue were studied as possible models for TS. The TRH analogue MK771 induced a variety of tic like movements in mice; blinking fore-paw-licking and fore-paw-tremor were quantified and serotonergic and dopaminergic modulation was investigated. The selective dopamine D1 receptor antagonists SCH23390 and SCH39166 and dopamine D2 antagonists raclopride and sulpiride had no effect on MK771 induced blinking. The D1 antagonists attenuated fore-paw-tremor and -licking while the D2 antagonists were generally without effect on these behaviours. Ketanserin (5-HT2A/ alpha-1 antagonist) and ritanserin (5-HT2A/2C antagonist) were able to attenuate MK771-induced blinking and ketanserin, mianserin (5-HT2A/2C antagonist) and prazosin (alpha-1 adrenoceptor antagonist) were able to attenuate MK771-induced fore-paw-tremor and -licking. The 5-HT2C/2B antagonist SB200646A was without effect on blinking and fore-paw-licking but dose-dependently potentiated fore-paw-tremor. The 5-HT1A agonists 8-OH DPAT and buspirone attenuated blinking at the lower doses tested but were ineffective at the higher doses; the converse was found for fore-paw-licking and -tremor behaviours.The effects of these ligands appeared to be at a postsynaptic 5-HTlA site since para-chlorophenylalanine was without effect on the manipulation of these behaviours. (S)-W A Y100135 was without effect on MK771-induced behaviours, spontaneous and DOl-induced head shakes. Because kynurenine potentiates head shakes and plasma concentrations are raised in TS patients the effects of kynurenine on the 5-HT2A/2C agonist DOl mediated head shake were established. Kynurenine potentiated the DOl head shake. Attempts were made to correlate serotonergic unit activity with tic like behaviour in cats but this proved unsuccessful. However, the pharmacological understanding of 5-HTlA receptor function has been hampered because of the lack of selective antagonists for this site. For this reason the effects of the novel 5-HTlA antagonists (S)-WA Y- 100135 and WAY -100635 were tested on 5-HT single-unit activity recorded from the dorsal-raphe-nucleus in the behaving cat. Both drugs antagonised the suppression of unit activity caused by 8-0H DPAT. (S)-WA Y-100135 reduced unit activity whereas WAY-100635 increased it. This suggests that WAY-100635 is acting as an antagonist at the 5-HTlA somatodendritic autoreceptor and that (S)W A Y -100135 acts as a partial agonist at this site. Aspects of tic like behaviour and serotonergic control are discussed.

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The concept of a substantive integrator is introduced as a method for integrated resource and environmental management as a means to assimilate different resource values at the operational or field level. A substantive integrator is a strategic management tool for integrating multiple uses into coprorate management regimes that traditionally manage for single values. Wildlife habitat management is presented as a substantive integrator for managing vegetation on electric utility power line corridors. A case study from northern British Columbia provides an example of wildlife habitat management as a means to integrate other resource values such as aesthetics, access and subsistence along British Columbia Hydro and Power Authority's transmission rights-of-way.

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This is an initial report of the PolyU SD part of the team to study Pre-fabricated Building Design and Construction Methodology and marks the completion of Phase 1. It follows our first notes prepared for the meeting on 2 February that identified some critical issues including future lifestyles, life expectancy of buildings, sustainability, size, flexibility and planning considerations. It is also an expansion of our presentation in Dongguan on 23 February. It is not a comprehensive survey of existing approaches or possible ways forward, but it has homed in on certain specific issues and does give specific examples to make the suggestions concrete. It is recommended that more comprehensive research be done to establish previous work and experience internationally. It is also recommended that more research be done on lifestyles as a preliminary to developing at least three concepts for evaluation before proceeding to the detailed design of one concept for full prototyping and market testing. The goal at this point is not to define a single direction but to suggest several future trajectories for further consideration. By the same token, this report is not intended as an exhaustive description of the considerable base of knowledge and ideas brought by the PolyU team to this exciting task. Before taking on an issue of this magnitude and importance in the definition of Hong Kong's future, one must carry out a thoughtful analysis of the issues at hand and an informed definition of paradigms, directions, goals and methods whereby our energies can be best used in the next steps. This report is the result of this analysis

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Literature addressing methodological issues in organisational research is extensive and multidisciplinary, encompassing debates about methodological choices, data-collection techniques, epistemological approaches and statistical procedures. However, little scholarship has tackled an important aspect of organisational research that precedes decisions about data collection and analysis – access to the organisations themselves, including the people, processes and documents within them. This chapter looks at organisational access through the experiences of three research fellows in the course of their work with their respective industry partners. In doing so, it reveals many of the challenges and changing opportunities associated with access to organisations, which are rarely explicitly addressed, but often assumed, in traditional methods texts and journal publications. Although the level of access granted varied somewhat across the projects at different points in time and according to different organisational contexts, we shared a number of core and consistent experiences in attempting to collect data and implement strategies.

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The Way-fi nding in the Built Environment project is a worldwide review identifying those way-fi nding systems and technologies that could be used to make it easier and safer for people with a sensory impairment (and in particular a vision impairment) to fi nd their way around buildings and large public spaces. The project makes recommendations on how these technologies and systems may be incorporated, by law or otherwise, into Australia’s building and construction practice. Way-fi nding aims to ensure that people with a sensory impairment know where they are in a building or an environment, where their desired location is, and how to get there from their present location. It is unlawful to discriminate against people with a disability under the Disability Discrimination Act 1992.

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Industrial employment growth has been one of the most dynamic areas of expansion in Asia; however, current trends in industrialised working environments have resulted in greater employee stress. Despite research showing that cultural values affect the way people cope with stress, there is a dearth of psychometrically established tools for use in non-Western countries to measure these constructs. Studies of the "Way of Coping Checklist-Revised" (WCCL-R) in the West suggest that the WCCL-R has good psychometric properties, but its applicability in the East is still understudied. A confirmatory factor analysis (CFA) is used to validate the WCCL-R constructs in an Asian population. This study used 1,314 participants from Indonesia, Sri Lanka, Singapore, and Thailand. An initial exploratory factor analysis revealed that original structures were not confirmed; however, a subsequent EFA and CFA showed that a 38-item, five-factor structure model was confirmed. The revised WCCL-R in the Asian sample was also found to have good reliability and sound construct and concurrent validity. The 38-item structure of the WCCL-R has considerable potential in future occupational stress-related research in Asian countries.

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Over the last decade in Australia, the role of the teacher has changed. Teachers are now expected to model and foster in their students a wide range of skills such as critical thinking, self-regulated learning, knowledge of self and others and lifelong learning. These changes are having a significant impact on the design of pre-service teacher education programmes, with university educators re-evaluating the teacher training curriculum and embedded pedagogical processes in order to consider how they might develop these skills in pre-service teachers. One approach is to consider the processes and practices inherent in philosophical inquiry. This paper reports on three participants’ reflections of a 12-week philosophy programme that was conducted for teacher educators at Queensland’s University of Technology (QUT) in 2008. The programme was facilitated by teachers from Buranda State School who have been teaching philosophy in their P-7 school for more than ten years. This paper provides insight into teacher educators’ reflections on the philosophy programme and the associated changes and challenges of implementing such a programme in pre-service teacher education degrees.

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Actions Towards Sustainable Outcomes Environmental Issues/Principal Impacts The increasing urbanisation of cities brings with it several detrimental consequences, such as: • Significant energy use for heating and cooling many more buildings has led to urban heat islands and increased greenhouse gas emissions. • Increased amount of hard surfaces, which not only contributes to higher temperatures in cities, but also to increased stormwater runoff. • Degraded air quality and noise. • Health and general well-being of people is frequently compromised, by inadequate indoor air quality. • Reduced urban biodiversity. Basic Strategies In many design situations, boundaries and constraints limit the application of cutting EDGe actions. In these circumstances, designers should at least consider the following: • Living walls are an emerging technology, and many Australian examples function more as internal feature walls. However,as understanding of the benefits and construction of living walls develops this technology could be part of an exterior facade that enhances a building’s thermal performance. • Living walls should be designed to function with an irrigation system using non-potable water. Cutting EDGe Strategies • Living walls can be part of a design strategy that effectively improves the thermal performance of a building, thereby contributing to lower energy use and greenhouse gas emissions. • Including living walls in the initial stages of design would provide greater flexibility to the design, especially of the facade, structural supports, mechanical ventilation and watering systems, thus lowering costs. • Designing a building with an early understanding of living walls can greatly reduce maintenance costs. • Including plant species and planting media that would be able to remove air impurities could contribute to improved indoor air quality, workplace productivity and well-being. Synergies and References • Living walls are a key research topic at the Centre for Subtropical Design, Queensland University of Technology: http://www.subtropicaldesign.bee.qut.edu.au • BEDP Environment Design Guide: DES 53: Roof and Facade Gardens • BEDP Environment Design Guide: GEN 4: Positive Development – Designing for Net Positive Impacts (see green scaffolding and green space frame walls). • Green Roofs Australia: www.greenroofs.wordpress.com • Green Roofs for Healthy Cities USA: www.greenroofs.org

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I would argue that the problems that contemporary capitalism gives rise to are not the result of the classic exercise of power and hegemony characteristic of the monopoly phase of capitalism but of the “creative destruction” of such a phase. Schumpeter’s famous phrase is reflective of Lash and Urry’s (1987) notion of “disorganised capitalism” or of Robert Reich’s (2007) claim that large corporations have significantly less power now than three decades ago. The consequence is that there is a need to explore an economic “middle way” in debates about the narrative of the relationship between culture and economy, between the Scylla of total explanatory political economy and the Charybdis of tedium-by-case-study. This involves a Schumpeterian emphasis on entrepreneurial or enterprise economics (Cunningham, Banks, and Potts 2008). Schumpeter, in 1962, in Capitalism, Socialism and Democracy, argued that Marx had “no adequate theory of enterprise” and failed to “distinguish the entrepreneur from the capitalist” (quoted in McCraw 2007: 349). Schumpeter, his most recent biographer, Thomas McCraw, “told of capitalism in the way most people experience it: as consumer desires aroused by endless advertising; as forcible jolts up and down the social pecking order; as goals reached, shattered, altered, then reached once more as people try, try again.” He knew that “creative destruction fosters economic growth but also that it undercuts cherished human values” (p. 6). Schumpeter’s most recent biographer, Thomas McCraw, says that he elucidated what capitalism “really feels like” (as quoted in McCraw 2007: 349, 6).

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Anecdotal evidence highlights issues of alcohol and other drugs (AODs) and its association with safety risk on construction sites. Information is limited however regarding the prevalence of AODs in the workplace and there is limited evidential guidance regarding how to effectively address it. This research aimed to scientifically evaluate the use of AODs within the Australian construction industry in order to reduce the potential resulting safety and performance impacts and engender a cultural change in the workforce. A national qualitative and quantitative evaluation of the use of AODs was conducted with approximately 500 employees. Results indicate that as in the general population, a proportion of those sampled in the construction sector may be at risk of hazardous alcohol consumption and support the need for evidence-based, tailored responses. This is the first known study to scientifically evaluate the use of AODs and potential workplace safety impacts in the construction sector.

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Traffic law enforcement is based on deterrence principles, whereby drivers control their behaviour in order to avoid an undesirable sanction. For “hooning”-related driving behaviours in Queensland, the driver’s vehicle can be impounded for 48 hours, 3 months, or permanently depending on the number of previous hooning offences. It is assumed that the threat of losing something of value, their vehicle, will discourage drivers from hooning. While official data shows that the rate of repeat offending is low, an in-depth understanding of the deterrent effects of these laws should involve qualitative research with targeted drivers. A sample of 22 drivers who reported engaging in hooning behaviours participated in focus group discussions about the vehicle impoundment laws as applied to hooning offences in Queensland. The findings suggested that deterrence theory alone cannot fully explain hooning behaviour, as participants reported hooning frequently, and intended to continue doing so, despite reporting that it is likely that they will be caught, and perceiving the vehicle impoundment laws to be extremely severe. The punishment avoidance aspect of deterrence theory appears important, as well as factors over and above legal issues, particularly social influences. A concerning finding was drivers’ willingness to flee from police in order to avoid losing their vehicle permanently for a third offence, despite acknowledging risks to their own safety and that of others. This paper discusses the study findings in terms of the implications for future research directions, enforcement practices and policy development for hooning and other traffic offences for which vehicle impoundment is applied.

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Mapping the physical world, the arrangement of continents and oceans, cities and villages, mountains and deserts, while not without its own contentious aspects, can at least draw upon centuries of previous work in cartography and discovery. To map virtual spaces is another challenge altogether. Are cartographic conventions applicable to depictions of the blogosphere, or the internet in general? Is a more mathematical approach required to even start to make sense of the shape of the blogosphere, to understand the network created by and between blogs? With my research comparing information flows in the Australian and French political blogs, visualising the data obtained is important as it can demonstrate the spread of ideas and topics across blogs. However, how best to depict the flows, links, and the spaces between is still unclear. Is network theory and systems of hubs and nodes more relevant than mass communication theories to the research at hand, influencing the nature of any map produced? Is it even a good idea to try and apply boundaries like ‘Australian’ and ‘French’ to parts of a map that does not reflect international borders or the Mercator projection? While drawing upon some of my work-in-progress, this paper will also evaluate previous maps of the blogosphere and approaches to depicting networks of blogs. As such, the paper will provide a greater awareness of the tools available and the strengths and limitations of mapping methodologies, helping to shape the direction of my research in a field still very much under development.