877 resultados para Global Transcriptional Response
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Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.
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This thesis looks at how non-experts develop an opinion on climate change, and how those opinions could be changed by public discourse. I use Hubert Dreyfus’ account of skill acquisition to distinguish between experts and non-experts. I then use a combination of Walter Fisher’s narrative paradigm and the hermeneutics of Paul Ricœur to explore how non-experts form opinions, and how public narratives can provide a point of critique. In order to develop robust narratives, they must be financially realistic. I therefore consider the burgeoning field of environmental, social, and corporate governance (ESG) analysis as a way of informing realistic public narratives. I identify a potential problem with this approach: the Western assumptions of ESG analysis might make for public narratives that are not convincing to a non-Western audience. I then demonstrate how elements of the Chinese tradition, the Confucian, Neo-Confucian, and Daoist schools, as presented by David Hall and Roger Ames, can provide alternative assumptions to ESG analysis so that the public narratives will be more culturally adaptable. This research contributes to the discipline by bringing disparate traditions together in a unique way, into a practical project with a view towards applications. I conclude by considering avenues for further research.
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Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.
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It is becoming increasingly apparent that epigenetics plays a crucial role in the cellular response to hypoxia. Such epigenetic regulation may work hand in hand with the hypoxia-induced transcription factor (HIF) family or may contribute in a more substantial way to the maintenance of a hypoxia-adapted cellular phenotype long after HIF has initiated the immediate response pathways. In this article we discuss the current research implicating epigenetic mechanisms in the cellular response to hypoxic environments. This includes; the role of epigenetics in both the stabilization and binding of HIF to its transcriptional targets, the role of histone demethylase enzymes following direct HIF transactivation, and finally, the impact of hypoxic environments on global patterns of histone modifications and DNA methylation.
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In Enterobacteriaceae, the transcriptional regulator AmpR, a member of the LysR family, regulates the expression of a chromosomal β-lactamase AmpC. The regulatory repertoire of AmpR is broader in Pseudomonas aeruginosa, an opportunistic pathogen responsible for numerous acute and chronic infections including cystic fibrosis. Previous studies showed that in addition to regulating ampC, P. aeruginosa AmpR regulates the sigma factor AlgT/U and production of some quorum sensing (QS)-regulated virulence factors. In order to better understand the ampR regulon, the transcriptional profiles generated using DNA microarrays and RNA-Seq of the prototypic P. aeruginosa PAO1 strain with its isogenic ampR deletion mutant, PAO∆ampR were analyzed. Transcriptome analysis demonstrates that the AmpR regulon is much more extensive than previously thought influencing the differential expression of over 500 genes. In addition to regulating resistance to β-lactam antibiotics via AmpC, AmpR also regulates non-β-lactam antibiotic resistance by modulating the MexEF-OprN efflux pump. Virulence mechanisms including biofilm formation, QS-regulated acute virulence, and diverse physiological processes such as oxidative stress response, heat-shock response and iron uptake are AmpR-regulated. Real-time PCR and phenotypic assays confirmed the transcriptome data. Further, Caenorhabditis elegans model demonstrates that a functional AmpR is required for full pathogenicity of P. aeruginosa. AmpR, a member of the core genome, also regulates genes in the regions of genome plasticity that are acquired by horizontal gene transfer. The extensive AmpR regulon included other transcriptional regulators and sigma factors, accounting for the extensive AmpR regulon. Gene expression studies demonstrate AmpR-dependent expression of the QS master regulator LasR that controls expression of many virulence factors. Using a chromosomally tagged AmpR, ChIP-Seq studies show direct AmpR binding to the lasR promoter. The data demonstrates that AmpR functions as a global regulator in P. aeruginosa and is a positive regulator of acute virulence while negatively regulating chronic infection phenotypes. In summary, my dissertation sheds light on the complex regulatory circuit in P. aeruginosa to provide a better understanding of the bacterial response to antibiotics and how the organism coordinately regulates a myriad of virulence factors.
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Lactococcus garvieae is an important fish and an opportunistic human pathogen. The genomic sequences of several L. garvieae strains have been recently published, opening the possibility of global studies on the biology of this pathogen. In this study, a whole genome DNA microarray of two strains of L. garvieae was designed and validated. This DNA microarray was used to investigate the effects of growth temperature (18°C and 37°C) on the transcriptome of two clinical strains of L. garvieae that were isolated from fish (Lg8831) and from a human case of septicemia (Lg21881). The transcriptome profiles evidenced a strain-specific response to temperature, which was more evident at 18°C. Among the most significant findings, Lg8831 was found to up-regulate at 18°C several genes encoding different cold-shock and cold-induced proteins involved in an efficient adaptive response of this strain to low-temperature conditions. Another relevant result was the description, for the first time, of respiratory metabolism in L. garvieae, whose gene expression regulation was temperature-dependent in Lg21881. This study provides new insights about how environmental factors such as temperature can affect L. garvieae gene expression. These data could improve our understanding of the regulatory networks and adaptive biology of this important pathogen.
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Social and psychological theories have provided a plethora of evidence showing that the physical difficulty to express appropriate social interactions between drivers expresses itself in aggression, selfish driving and anti-social behaviour. Therefore there is a need to improve interactions between drivers and allow clearer collective decision making between them. Personal characteristics and the driving situations play strong roles in driver’s aggression. Our approach is centered around the driving situation as opposed to focusing on personality characteristics. It examines aggression and manipulates contextual variables such as driver’s eye contact exchanges. This paper presents a new unobtrusive in-vehicle system that aims at communicating drivers’ intentions, elicit social responses and increasing mutual awareness. It uses eye gaze as a social cue to affect collective decision making with the view to contribute to safe driving. The authors used a driving simulator to design a case control experiment in which eye gaze movements are conveyed with an avatar. Participants were asked to drive through different types of intersections. An avatar representing the head of the other driver was displayed and driver behaviour was analysed. Significant eye gaze pattern difference where observed when an avatar was displayed. Drivers cautiously refer to the avatar when information is required on the intention of others (e.g. when they do not have the right of way). The majority of participants reported the perception of “being looked at”. The number of glances and time spent gazing at the avatar did not indicate an unsafe distraction by standards of in-vehicle device ergonomic design. Avatars were visually consulted primarily in less demanding driving situations, which underlines their non-distractive nature.
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Through international agreement to the United Nations Framework Convention on Climate Change and the Kyoto Protocol the global community has acknowledged that climate change is a global problem and sought to achieve reductions in global emissions, within a sufficient timeframe, to avoid dangerous anthropogenic interference with the climate system. The sheer magnitude of emissions reductions required within such an urgent timeframe presents a challenge to conventional regulatory approaches both internationally and within Australia. The phenomenon of climate change is temporally and geographically challenging and it is scientifically complex and uncertain. The purpose of this paper is to analyse the current Australian legal response to climate change and to examine the legal measures which have been proposed to promote carbon trading, energy efficiency, renewable energy, and carbon sequestration initiatives across Australia. As this paper illustrates, the current Australian approach is clearly ineffective and the law as it stands overwhelmingly inadequate to address Australia’s emissions and meet the enormity of the challenges posed by climate change. Consequently, the government should look towards a more effective legal framework to achieve rapid and urgent transformations in the selection of energy sources, energy use and sequestration initiatives across the Australian community.
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The Wilms’ tumor suppressor protein WT1 is a transcriptional regulator involved in differentiation and the regulation of cell growth. WT1 is subject to alternative splicing, one isoform including a 17–amino acid region that is specific to mammals. The function of this 17–amino acid insertion is not clear, however. Here, we describe a transcriptional activation domain in WT1 that is specific to the WT1 splice isoform that contains the 17–amino acid insertion. We show that the function of this domain in transcriptional activation is dependent on a specific interaction with the prostate apoptosis response factor par4. A mutation in WT1 found in Wilms’ tumor disturbs the interaction with par4 and disrupts the function of the activation domain. Analysis of WT1 derivatives in cells treated to induce par4 expression showed a strong correlation between the transcription function of the WT1 17–amino acid insertion and the ability of WT1 to regulate cell survival and proliferation. Our results provide a molecular mechanism by which alternative splicing of WT1 can regulate cell growth in development and disease.
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Nuclear Factor Y (NF-Y) is a trimeric complex that binds to the CCAAT box, a ubiquitous eukaryotic promoter element. The three subunits NF-YA, NF-YB and NF-YC are represented by single genes in yeast and mammals. However, in model plant species (Arabidopsis and rice) multiple genes encode each subunit providing the impetus for the investigation of the NF-Y transcription factor family in wheat. A total of 37 NF-Y and Dr1 genes (10 NF-YA, 11 NF-YB, 14 NF-YC and 2 Dr1) in Triticum aestivum were identified in the global DNA databases by computational analysis in this study. Each of the wheat NF-Y subunit families could be further divided into 4-5 clades based on their conserved core region sequences. Several conserved motifs outside of the NF-Y core regions were also identified by comparison of NF-Y members from wheat, rice and Arabidopsis. Quantitative RT-PCR analysis revealed that some of the wheat NF-Y genes were expressed ubiquitously, while others were expressed in an organ-specific manner. In particular, each TaNF-Y subunit family had members that were expressed predominantly in the endosperm. The expression of nine NF-Y and two Dr1 genes in wheat leaves appeared to be responsive to drought stress. Three of these genes were up-regulated under drought conditions, indicating that these members of the NF-Y and Dr1 families are potentially involved in plant drought adaptation. The combined expression and phylogenetic analyses revealed that members within the same phylogenetic clade generally shared a similar expression profile. Organ-specific expression and differential response to drought indicate a plant-specific biological role for various members of this transcription factor family.
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Tony Fitzgerald’s visionary leap was to see beyond localised, individual wrongdoing. He suggested remedies that were systemic, institutionalised, and directed at underlying structural problems that led to corruption. His report said ‘the problems with which this Inquiry is concerned are not merely associated with individuals, but are institutionalized and related to attitudes which have become entrenched’ (Fitzgerald Report 1989, 13). His response was to suggest an enmeshed system of measures to not only respond reactively to future corruption, but also to prevent its recurrence through improved integrity systems. In the two decades since that report the primary focus of corruption studies and anti-corruption activism has remained on corruption at the local level or within sovereign states. International activism was largely directed at co-ordinating national campaigns and to use international instruments to make these campaigns more effective domestically. This reflects the broader fact that, since the rise of the nation state, states have comprised the majority of the largest institutional actors and have been the most significant institution in the lives of most individuals. This made states the ‘main game in town’ for the ‘governance disciplines’ of ethics, law, political science and economics.
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Agricultural soils emit about 50% of the global flux of N2O attributable to human influence, mostly in response to nitrogen fertilizer use. Recent evidence that the relationship between N2O fluxes and N-fertilizer additions to cereal maize are non-linear provides an opportunity to estimate regional N2O fluxes based on estimates of N application rates rather than as a simple percentage of N inputs as used by the Intergovernmental Panel on Climate Change (IPCC). We combined a simple empirical model of N2O production with the SOCRATES soil carbon dynamics model to estimate N2O and other sources of Global Warming Potential (GWP) from cereal maize across 19,000 cropland polygons in the North Central Region (NCR) of the US over the period 1964–2005. Results indicate that the loading of greenhouse gases to the atmosphere from cereal maize production in the NCR was 1.7 Gt CO2e, with an average 268 t CO2e produced per tonne of grain. From 1970 until 2005, GHG emissions per unit product declined on average by 2.8 t CO2e ha−1 annum−1, coinciding with a stabilisation in N application rate and consistent increases in grain yield from the mid-1970’s. Nitrous oxide production from N fertilizer inputs represented 59% of these emissions, soil C decline (0–30 cm) represented 11% of total emissions, with the remaining 30% (517 Mt) from the combustion of fuel associated with farm operations. Of the 126 Mt of N fertilizer applied to cereal maize from 1964 to 2005, we estimate that 2.2 Mt N was emitted as N2O when using a non-linear response model, equivalent to 1.75% of the applied N.