295 resultados para transcriptional regulation


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Much of the current academic and political discourse related the development and operations of the Waitangi Tribunal over its first twenty years portray it as a forum that provided Māori with a meaningful avenue for settling Treaty grievances compared to the formal legal systems performance in the preceding 100 years. In contrast, we argue that from its inception and throughout much of the 1980s, the Waitangi Tribunal functioned primarily as an informal justice forum that assisted the New Zealand state’s regulation of Māori Treaty activism during the transition from a Fordist to a Post-Fordist mode of capital accumulation.

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The pathological outcomes of schistosomiasis are largely dependent on the molecular and cellular mechanisms of the host immune response. In this study, we investigated the contribution of variations in host gene expression to the contrasting hepatic pathology observed between two inbred mouse strains following Schistosoma japonicum infection. Whole genome microarray analysis was employed in conjunction with histological and immunohistochemical analysis to define and compare the hepatic gene expression profiles and cellular composition associated with the hepatopathology observed in S. japonicum-infected BALB/c and CBA mice. We show that the transcriptional profiles differ significantly between the two mouse strains with high statistical confidence. We identified specific genes correlating with the more severe pathology associated with CBA mice, as well as genes which may confer the milder degree of pathology associated with BALB/c mice. In BALB/c mice, neutrophil genes exhibited striking increases in expression, which coincided with the significantly greater accumulation of neutrophils at granulomatous regions seen in histological sections of hepatic tissue. In contrast, up-regulated expression of the eosinophil chemokine CCL24 in CBA mice paralleled the cellular influx of eosinophils to the hepatic granulomas. Additionally, there was greater down-regulation of genes involved in metabolic processes in CBA mice, reflecting the more pronounced hepatic damage in these mice. Profibrotic genes showed similar levels of expression in both mouse strains, as did genes associated with Th1 and Th2 responses. However, imbalances in expression of matrix metalloproteinases (e.g. MMP12, MMP13) and tissue inhibitors of metalloproteinases (TIMP1) may contribute to the contrasting pathology observed in the two strains. Overall, these results provide a more complete picture of the molecular and cellular mechanisms which govern the pathological outcome of hepatic schistosomiasis. This improved understanding of the immunopathogenesis in the murine model schistosomiasis provides the basis for a better appreciation of the complexities associated with chronic human schistosomiasis.

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Background: Sleepiness is a direct contributor to a substantial proportion of fatal and severe road cashes. A number of technological solutions designed to detect sleepiness have been developed, but self-awareness of increasing sleepiness remains a critical component in on-road strategies for mitigating this risk. In order to take appropriate action when sleepy, drivers’ perceptions of their level of sleepiness must be accurate. Aims: This study aimed to assess capacity to accurately identify sleepiness and self-regulate driving cessation during a validated driving simulator task. Participants: Participants comprised 26 young adult drivers (20-28 years). The drivers had open licenses but no other exclusion criteria where used. Methods: Participants woke at 5am, and took part in a laboratory-based hazard perception driving simulation, either at mid-morning or mid-afternoon. Established physiological measures (including EEG) and subjective measures (sleepiness ratings) previously found sensitive to changes in sleepiness levels were utilised. Participants were instructed to ‘drive’ until they believed that sleepiness had impaired their ability to drive safely. They were then offered a nap opportunity. Results: The mean duration of the drive before cessation was 39 minutes (±18 minutes). Almost all (23/26) of the participants then achieved sleep during the nap opportunity. These data suggest that the participants’ perceptions of sleepiness were specific. However, EEG data from a number of participants suggested very high levels of sleepiness prior to driving cessation, suggesting poor sensitivity. Conclusions: Participants reported high levels of sleepiness while driving after very moderate sleep restriction. They were able to identify increasing sleepiness during the test period, could decide to cease driving and in most cases were sufficiently sleepy to achieve sleep during the daytime session. However, the levels of sleepiness achieved prior to driving cessation suggest poor accuracy in self-perception and regulation. This presents practical issues for the implementation of fatigue and sleep-related strategies to improve driver safety.

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This article examines the place of Australian and local content regulation in the new media policy framework proposed by the Convergence Review. It outlines the history of Australian content regulation and the existing policy framework, before going on to detail some of the debates around Australian content during the Review. The final section analyses the relevant recommendations in the Convergence Review Final Report, and highlights some issues and problems that may arise in the new framework.

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The idea that microbes induce disease has steered medical research toward the discovery of antibacterial products for the prevention and treatment of microbial infections. The twentieth century saw increasing dependency on antimicrobials as mainline therapy accentuating the notion that bacterial interactions with humans were to be avoided or desirably controlled. The last two decades, though, have seen a refocusing of thinking and research effort directed towards elucidating the critical inter-relationships between the gut microbiome and its host that control health/wellness or disease. This research has redefined the interactions between gut microbes and vertebrates, now recognizing that the microbial active cohort and its mammalian host have shared co-evolutionary metabolic interactions that span millennia. Microbial interactions in the gastrointestinal tract provide the necessary cues for the development of regulated pro- and anti-inflammatory signals that promotes immunological tolerance, metabolic regulation and other factors which may then control local and extra-intestinal inflammation. Pharmacobiotics, using nutritional and functional food additives to regulate the gut microbiome, will be an exciting growth area of therapeutics, developing alongside an increased scientific understanding of gut-microbiome symbiosis in health and disease.

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Introduction: Sleepiness contributes to a substantial proportion of fatal and severe road crashes. Efforts to reduce the incidence of sleep-related crashes have largely focussed on driver education to promote self-regulation of driving behaviour. However, effective self-regulation requires accurate self-perception of sleepiness. The aim of this study was to assess capacity to accurately identify sleepiness, and self-regulate driving cessation, during a validated driving simulator task. Methods: Participants comprised 26 young adult drivers (20-28 years) who had open licenses. No other exclusion criteria where used. Participants were partially sleep deprived (05:00 wake up) and completed a laboratory-based hazard perception driving simulation, counterbalanced to either at mid-morning or mid-afternoon. Established physiological measures (i.e., EEG, EOG) and subjective measures (Karolinska Sleepiness Scale), previously found sensitive to changes in sleepiness levels, were utilised. Participants were instructed to ‘drive’ on the simulator until they believed that sleepiness had impaired their ability to drive safely. They were then offered a nap opportunity. Results: The mean duration of the drive before cessation was 36.1 minutes (±17.7 minutes). Subjective sleepiness increased significantly from the beginning (KSS=6.6±0.7) to the end (KSS=8.2±0.5) of the driving period. No significant differences were found for EEG spectral power measures of sleepiness (i.e., theta or alpha spectral power) from the start of the driving task to the point of cessation of driving. During the nap opportunity, 88% of the participants (23/26) were able to reach sleep onset with an average latency of 9.9 minutes (±7.5 minutes). The average nap duration was 15.1 minutes (±8.1 minutes). Sleep architecture during the nap was predominately comprised of Stages I and II (combined 92%). Discussion: Participants reported high levels of sleepiness during daytime driving after very moderate sleep restriction. They were able to report increasing sleepiness during the test period despite no observed change in standard physiological indices of sleepiness. This increased subjective sleepiness had behavioural validity as the participants had high ‘napability’ at the point of driving cessation, with most achieving some degree of subsequent sleep. This study suggests that the nature of a safety instruction (i.e. how to view sleepiness) can be a determinant of driver behaviour.

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This article outlines the key recommendations of the Australian Law Reform Commission’s review of the National Classification Scheme, as outlined in its report Classification – Content Regulation and Convergent Media (ALRC, 2012). It identifies key contextual factors that underpin the need for reform of media classification laws and policies, including the fragmentation of regulatory responsibilities and the convergence of media platforms, content and services, as well as discussing the ALRC’s approach to law reform.

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Purpose To study the protective effects and underlying molecular mechanisms of SAMC on carbon tetrachloride (CCl4)-induced acute hepatotoxicity in the mouse model. Methods Mice were intraperitoneally injected with CCl4 (50 μl/kg; single dose) to induce acute hepatotoxicity with or without a 2-h pre-treatment of SAMC intraperitoneal injection (200 mg/kg; single dose). After 8 h, the blood serum and liver samples of mice were collected and subjected to measurements of histological and molecular parameters of hepatotoxicity. Results SAMC reduced CCl4-triggered cellular necrosis and inflammation in the liver under histological analysis. Since co-treatment of SAMC and CCl4 enhanced the expressions of antioxidant enzymes, reduced the nitric oxide (NO)-dependent oxidative stress, and inhibited lipid peroxidation induced by CCl4. SAMC played an essential antioxidative role during CCl4-induced hepatotoxicity. Administration of SAMC also ameliorated hepatic inflammation induced by CCl4 via inhibiting the activity of NF-κB subunits p50 and p65, thus reducing the expressions of pro-inflammatory cytokines, mediators, and chemokines, as well as promoting pro-regenerative factors at both transcriptional and translational levels. Conclusions Our results indicate that SAMC mitigates cellular damage, oxidative stress, and inflammation in CCl4-induced acute hepatotoxicity mouse model through regulation of NF-κB. Garlic or garlic derivatives may therefore be a potential food supplement in the prevention of liver damage.