514 resultados para bradykinin-related peptides


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This study was designed to identify the neural networks underlying automatic auditory deviance detection in 10 healthy subjects using functional magnetic resonance imaging. We measured blood oxygenation level-dependent contrasts derived from the comparison of blocks of stimuli presented as a series of standard tones (50 ms duration) alone versus blocks that contained rare duration-deviant tones (100 ms) that were interspersed among a series of frequent standard tones while subjects were watching a silent movie. Possible effects of scanner noise were assessed by a “no tone” condition. In line with previous positron emission tomography and EEG source modeling studies, we found temporal lobe and prefrontal cortical activation that was associated with auditory duration mismatch processing. Data were also analyzed employing an event-related hemodynamic response model, which confirmed activation in response to duration-deviant tones bilaterally in the superior temporal gyrus and prefrontally in the right inferior and middle frontal gyri. In line with previous electrophysiological reports, mismatch activation of these brain regions was significantly correlated with age. These findings suggest a close relationship of the event-related hemodynamic response pattern with the corresponding electrophysiological activity underlying the event-related “mismatch negativity” potential, a putative measure of auditory sensory memory.

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Insomnia is a pervasive problem involving poor sleep quality and quantity. Previous research has suggested that music listening can help alleviate insomnia, but exactly how music helps sleep problems has not been determined. A greater understanding of these processes could help practitioners to design more effective music-based insomnia treatments. This randomised controlled trial was designed to assess the influences of nightly music listening on the sleep-related thoughts and behaviours described in Harvey’s (2002) cognitive model of insomnia maintenance. University students, including a range of good and poor sleepers, were randomly assigned to a music listening group or a control group and were assessed before and after a two-week music listening intervention. Measures included a range of self-report scales, each assessing an element of Harvey’s cognitive model. During the intervention, the music listening group was asked to listen to provided music for at least 20 minutes each night. The control group was asked to maintain their regular nightly routines. Results indicated that the music listening group significantly improved on most of the factors theorised to influence sleep quality, although their actual sleep quality did not significantly improve. The control group did not change significantly on any measures. The results of this study suggest that music listening can have positive impacts on a range of factors theorised to influence sleep quality. However, as the music was not shown to actually improve sleep quality, Harvey’s cognitive model explanation of music’s effect on sleep quality may require further investigation.

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There is much for non-Indigenous researchers to consider when researching in Indigenous contexts. This paper is a story of discovery for two researchers working on a project with the Indigenous Sports Program section of the Australian Sports Commission. It documents the slow, meticulous and sometimes clumsy steps taken to gain access to communities and conduct research guided by a social justice ethic. The research was successful in that eventually it was possible to develop the trust of individuals and some of the Indigenous communities more broadly, so that information could be gathered and given within the context of shared understandings and mutual interest. However, it is the turbulent journey, filled as it is, with latent tendencies, privileged assumptions and eventually reflexive readings of the data, which remains the focus of this paper. Tentative recommendations are offered to those wishing to advance this politically and epistemologically challenging approach to culturally based research

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An effective means of facilitating DNA vaccine delivery to antigen presenting cells is through biodegradable microspheres. Microspheres offer distinct advantages over other delivery technologies by providing release of DNA vaccine in its bioactive form in a controlled fashion. In this study, biodegradable poly(D,L-lactide-coglycolide) (PLGA) microspheres containing polyethylenimine (PEI) condensed plasmid DNA (pDNA) were prepared using a 40 kHz ultrasonic atomization system. Process synthesis parameters, which are important to the scale-up of microspheres that are suitable for nasal delivery (i.e., less than 20 μm), were studied. These parameters include polymer concentration; feed flowrate; volumetric ratio of polymer and pDNA-PEI (plasmid DNA-polyethylenimine) complexes; and nitrogen to phosphorous (N/P) ratio. PDNA encapsulation efficiencies were predominantly in the range 82-96%, and the mean sizes of the particle were between 6 and 15 μm. The ultrasonic synthesis method was shown to have excellent reproducibility. PEI affected morphology of the microspheres, as it induced the formation of porous particles that accelerate the release rate of pDNA. The PLGA microspheres displayed an in vitro release of pDNA of 95-99% within 30 days and demonstrated zero order release kinetics without an initial spike of pDNA. Agarose electrophoresis confirmed conservation of the supercoiled form of pDNA throughout the synthesis and in vitro release stages. It was concluded that ultrasonic atomization is an efficient technique to overcome the key obstacles in scaling-up the manufacture of encapsulated vaccine for clinical trials and ultimately, commercial applications.

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This study investigated interactions of protein-cleaving enzymes (or proteases) that promote prostate cancer progression. It provides the first evidence of a novel regulatory network of protease activity at the surface of cells. The proteases kallikrein-related peptidases 4 and 14, and matrix metalloproteinases 3 and 9 are cleaved at the cell surface by the cell surface proteases hepsin and TMPRSS2. These cleavage events potentially regulate activation of downstream targets of kallikrein 4 and 14 such as cell surface signalling via the protease-activated receptors (PARs) and cell growth-promoting factors such as hepatocyte-growth factor.

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Transfusion-related acute lung injury (TRALI) has been the leading cause of transfusion-related morbidity and mortality in the UK and the USA in recent years. A threshold mechanism of TRALI has been proposed in which both patient factors (type and/or severity of clinical insult) and blood product factors (strength and/or concentration of antibodies or biological response modifiers) interact to surpass a threshold for TRALI development (Bux et al. Br J Haematol; 2007; 136: 788-99). The risk of developing antibody-mediated TRALI has been minimised by the introduction of risk-reduction strategies such as limiting the use of plasma from female donors. In contrast, there are no strategies currently in place to mitigate the development of non-antibody mediated TRALI as the mechanisms remain largely undefined. Previous studies have implicated non-polar lipids such as arachidonic acid and various species of hydroxyeicosatetranoic acid (HETE) in the development of non-antibody mediated TRALI (Silliman et al. Transfusion; 2011; 51: 2549-54), however the contribution of these lipids to the development of an inflammatory response in TRALI is poorly understood.

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Background No tool exists to measure self-efficacy for overcoming lymphedema-related exercise barriers in individuals with cancer-related lymphedema. However, an existing scale measures confidence to overcome general exercise barriers in cancer survivors. Therefore, the purpose of this study was to develop, validate and assess the reliability of a subscale, to be used in conjunction with the general barriers scale, for determining exercise barriers self-efficacy in individuals facing lymphedema-related exercise barriers. Methods A lymphedema-specific exercise barriers self-efficacy subscale was developed and validated using a cohort of 106 cancer survivors with cancer-related lymphedema, from Brisbane, Australia. An initial ten-item lymphedema-specific barrier subscale was developed and tested, with participant feedback and principal components analysis results used to guide development of the final version. Validity and test-retest reliability analyses were conducted on the final subscale. Results The final lymphedema-specific subscale contained five items. Principal components analysis revealed these items loaded highly (> 0.75) on a separate factor when tested with a well-established nine-item general barriers scale. The final five-item subscale demonstrated good construct and criterion validity, high internal consistency (Cronbach’s alpha=0.93) and test-retest reliability (ICC=0.67, p< 0.01). Conclusions A valid and reliable lymphedema-specific subscale has been developed to assess exercise barriers self-efficacy in individuals with cancer-related lymphedema. This scale can be used in conjunction with an existing general exercise barriers scale to enhance exercise adherence in this understudied patient group.

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Carbon dioxide (CO2) is considered the most harmful of the greenhouse gases. Despite policy efforts, transport is the only sector experiencing an increase in the level of CO2 emissions and thereby possesses a major threat to sustainable development. In contrast, a reduced level of mobility has been associated with an increasing risk of being socially excluded. However, despite being the two key elements in transport policy, little effort has so far been made to investigate the links between CO2 emissions and social exclusion. This research contributes to this gap by analysing data from 157 weekly activity-travel diaries collected in rural Northern Ireland. CO2 emission levels were calculated using average speed models for different modes of transport. Regression analyses were then conducted to identify the socio-spatial patterns associated with these CO2 emissions, mode choice behaviour, and patterns of participation in activities. This research found that despite emitting a higher level of carbon dioxide, groups in rural areas possess the risk of being socially excluded due to their higher levels of mobility.

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The trans-activator of transcription (TAT) peptide is regarded as the “gold standard” for cell-penetrating peptides, capable of traversing a mammalian membrane passively into the cytosolic space. This characteristic has been exploited through conjugation of TAT for applications such as drug delivery. However, the process by which TAT achieves membrane penetration remains ambiguous and unresolved. Mechanistic details of TAT peptide action are revealed herein by using three complementary methods: quartz crystal microbalance with dissipation (QCM-D), scanning electrochemical microscopy (SECM) and atomic force microscopy (AFM). When combined, these three scales of measurement define that the membrane uptake of the TAT peptide is by trans-membrane insertion using a “worm-hole” pore that leads to ion permeability across the membrane layer. AFM data provided nanometre-scale visualisation of TAT punctuation using a mammalian-mimetic membrane bilayer. The TAT peptide does not show the same specificity towards a bacterial mimetic membrane and QCM-D and SECM showed that the TAT peptide demonstrates a disruptive action towards these membranes. This investigation supports the energy-independent uptake of the cationic TAT peptide and provides empirical data that clarify the mechanism by which the TAT peptide achieves its membrane activity. The novel use of these three biophysical techniques provides valuable insight into the mechanism for TAT peptide translocation, which is essential for improvements in the cellular delivery of TAT-conjugated cargoes including therapeutic agents required to target specific intracellular locations.

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1. The vasodilator effects of adenosine receptor agonists, isoprenaline and histamine were examined in perfused heart preparations from young (4–6 weeks) and mature (12–20 weeks) rats. 2. Adenosine induced a biphasic concentration-dependent decrease in KCl (35 mM) raised coronary perfusion pressure in hearts from young and mature rats, suggesting the presence of both high- and low-affinity sites for adenosine receptors in the two age groups tested. In heart preparations from mature rats, vasodilator responses to adenosine were significantly reduced compared with responses observed in young rats. 3. Responses to 5′-N-ethylcarboxamidoadenosine (NECA) and 2-p-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxamidoadenosine hydrochloride (CGS-21680) were reduced in preparations from mature rats, whereas the vasodilator actions of N6-cyclopentyladenosine (CPA) and N6-2-(4-aminophenyl)ethyladenosine (APNEA) did not change with age. 4. The results presented in this study suggest that several adenosine receptor subtypes mediate vasodilator responses in the coronary circulation of the rat and that a reduction in response to adenosine with age may be due to changes in the high-affinity receptor site.

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Global climate change will affect all domains of person-environment relations. Tackling climate change will require social change that can be motivated by people’s imaginings of the future of their society where such social change has occurred. We use the “collective futures” framework to examine whether beliefs about the future of society are related to present-day intentions to take climate change action. Participants from two Brazilian samples imagined their society in 2050 where climate change was mitigated and then rated how this future society would differ from Brazilian society today in terms of societal-level dysfunction and development and personal-level traits and values. To the extent that participants believed preventing climate change would result in societal development and more competence traits, they were more willing to engage in environmental citizenship activities. Individual differences in future time perspective also impacted environmental citizenship intention. Societal development and consideration of future consequences seem to be distinct routes by which future thinking influence climate change action.

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Background Climate change may affect mortality associated with air pollutants, especially for fine particulate matter (PM2.5) and ozone (O3). Projection studies of such kind involve complicated modelling approaches with uncertainties. Objectives We conducted a systematic review of researches and methods for projecting future PM2.5-/O3-related mortality to identify the uncertainties and optimal approaches for handling uncertainty. Methods A literature search was conducted in October 2013, using the electronic databases: PubMed, Scopus, ScienceDirect, ProQuest, and Web of Science. The search was limited to peer-reviewed journal articles published in English from January 1980 to September 2013. Discussion Fifteen studies fulfilled the inclusion criteria. Most studies reported that an increase of climate change-induced PM2.5 and O3 may result in an increase in mortality. However, little research has been conducted in developing countries with high emissions and dense populations. Additionally, health effects induced by PM2.5 may dominate compared to those caused by O3, but projection studies of PM2.5-related mortality are fewer than those of O3-related mortality. There is a considerable variation in approaches of scenario-based projection researches, which makes it difficult to compare results. Multiple scenarios, models and downscaling methods have been used to reduce uncertainties. However, few studies have discussed what the main source of uncertainties is and which uncertainty could be most effectively reduced. Conclusions Projecting air pollution-related mortality requires a systematic consideration of assumptions and uncertainties, which will significantly aid policymakers in efforts to manage potential impacts of PM2.5 and O3 on mortality in the context of climate change.

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We identified the active ingredients in people’s visions of society’s future (“collective futures”) that could drive political behavior in the present. In eight studies (N = 595), people imagined society in 2050 where climate change was mitigated (Study 1), abortion laws relaxed (Study 2), marijuana legalized (Study 3), or the power of different religious groups had increased (Studies 4-8). Participants rated how this future society would differ from today in terms of societal-level dysfunction and development (e.g., crime, inequality, education, technology), people’s character (warmth, competence, morality), and their values (e.g., conservation, self-transcendence). These measures were related to present-day attitudes/intentions that would promote/prevent this future (e.g., act on climate change, vote for a Muslim politician). A projection about benevolence in society (i.e., warmth/morality of people’s character) was the only dimension consistently and uniquely associated with present-day attitudes and intentions across contexts. Implications for social change theories, political communication, and policy design are discussed.

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The rise of social media as communication channels has enabled customers to provide feedback or to ask for assistance quickly and easily. In the context of brand crises, the microblogging platform Twitter is highly relevant because of its ability to support information sharing. By investigating communication on Twitter, the authors examine Twitter activity patterns based on a dataset of some 240,000 tweets during two major brand crises affecting the Australian airline Qantas – the volcanic ash cloud caused by the eruption of Chilean volcano Puyehue in June 2011, and the global grounding of Qantas flights by management in the course of an industrial dispute in October/November 2011. Through this case study we find that characteristics of communication change significantly during different stages of the crisis. Further, we demonstrate that different kinds of crisis result in different communication patterns on Twitter.