Examines the application of discourse analysis in the empirical context of learning technology innovation, describing an action program involving 22 trans-European projects. Various theoretical & ...methodological principles are outlined, along with technical procedures related to the operationalization of an evaluation design using discourse analysis. Focusing on stakeholders' subjective & experiential knowledge structures that underlie a culture of technology innovation, it is shown how technology innovation is discursively constituted through the creation of shared meanings & images. 12 References. Adapted from the source document.
Prostate cancer is characterized by a dependence upon androgen receptor (AR) signaling, and androgen deprivation therapy (ADT) is the accepted treatment for progressive prostate cancer. Although ADT ...is usually initially effective, acquired resistance termed castrate-resistant prostate cancer (CRPC) develops. PTEN and TP53 are two of the most commonly deleted or mutated genes in prostate cancer, the compound loss of which is enriched in CRPC. To interrogate the metabolic alterations associated with survival following ADT, we used an orthotopic model of Pten/Tp53 null prostate cancer. Metabolite profiles and associated regulators were compared in tumors from androgen-intact mice and in tumors surviving castration. AR inhibition led to changes in the levels of glycolysis and tricarboxylic acid (TCA) cycle pathway intermediates. As anticipated for inhibitory reciprocal feedback between AR and PI3K/AKT signaling pathways, pAKT levels were increased in androgen-deprived tumors. Elevated mitochondrial hexokinase 2 (HK2) levels and enzyme activities also were observed in androgen-deprived tumors, consistent with pAKT-dependent HK2 protein induction and mitochondrial association. Competitive inhibition of HK2-mitochondrial binding in prostate cancer cells led to decreased viability. These data argue for AKT-associated HK2-mediated metabolic reprogramming and mitochondrial association in PI3K-driven prostate cancer as one survival mechanism downstream of AR inhibition.
It is well established that the glutamate decarboxylase (GAD) system is central to the survival of Listeria monocytogenes at low pH, both in acidic foods and within the mammalian stomach. The ...accepted model proposes that under acidic conditions extracellular glutamate is transported into the cell in exchange for an intracellular γ-aminobutyrate (GABAi). The glutamate is then decarboxylated to GABAi, a reaction that consumes a proton, thereby helping to prevent acidification of the cytoplasm. In this study, we show that glutamate supplementation had no influence on either growth rate at pH 5.0 or survival at pH 2.5 when L. monocytogenes 10403S was grown in a chemically defined medium (DM). In response to acidification, cells grown in DM failed to efflux GABA, even when glutamate was added to the medium. In contrast, in brain heart infusion (BHI), the same strain produced significant extracellular GABA (GABAe) in response to acidification. In addition, high levels of GABAi (>80 mM) were found in the cytoplasm in response to low pH in both growth media. Medium-swap and medium-mixing experiments revealed that the GABA efflux apparatus was nonfunctional in DM, even when glutamate was present. It was also found that the GadT2D2 antiporter/decarboxylase system was transcribed poorly in DM-grown cultures while overexpression of gadD1T1 and gadD3 occurred in response to pH 3.5. Interestingly, BHI-grown cells did not respond with upregulation of any of the GAD system genes when challenged at pH 3.5. The accumulation of GABAi in cells grown in DM in the absence of extracellular glutamate indicates that intracellular glutamate is the source of the GABAi. These results demonstrate that GABA production can be uncoupled from GABA efflux, a finding that alters the way we should view the operation of bacterial GAD systems.
White-clawed crayfish (
Austropotamobius pallipes
) is a keystone species found in western European freshwater bodies, where it has suffered drastic declines due to pathogens, competition with ...non-indigenous crayfish species (NICS) and habitat deterioration. In Ireland, populations of (naturalised)
A. pallipes
have been considered healthy and abundant mainly because no diseases or NICS have been reported in the past decades. The present study investigated a sudden mass mortality event that occurred in the Erne catchment in 2015. Molecular analysis confirmed that the cause of the event was infection by the oomycete
Aphanomyces astaci
(the causative agent of the crayfish plague). While in 2015 the spread of the pathogen appeared to remain confined to the outbreak’s epicentre and nearby upstream waters, follow up surveys using conventional methods and environmental DNA (eDNA) approaches indicated that by a year later (2016), the pathogen was still present and had spread downstream beyond Lough Gowna. No NICS were detected during the surveys conducted. This crayfish plague outbreak is of grave concern to Irish white-clawed crayfish and associated ecosystems.
Background: Cardiovascular disease (CVD) is the number one cause of death globally. Whilst initiatives such as Ireland’s ‘Chronic Disease Management Programme’ have helped in the fight against CVD, a ...more intensive approach may be required to meet high risk patients’ needs. The High-Risk Prevention Programme (HRPP), led by the Irish Heart Foundation, University College Dublin (UCD), and Ireland’s Health Service Executive (HSE) aims to design, deliver, and evaluate an intensive, six-week behaviour change programme among people at high risk of CVD living in Irish communities. In this paper, we aim to describe the HRPP intervention and the approach that will be used to evaluate it. Methods: The HRPP has been informed by an inclusive co-design process involving health provider and patient input, has been operating since February 2021 and will run until February 2023. Six general practices have agreed to take part in the project, and it is planned that 400 patients at high risk of CVD will participate. Participating patients attend either a practice nurse or health promotion coordinator-led six-week one-to-one consultation programme focusing on self-management of health issues. Feasibility, acceptability, and likely effectiveness will be assessed by means of a process evaluation involving quantitative survey (patient health and health behaviours assessments) at baseline and 12 months, and in-depth qualitative interviews with patients, practice nurses and general practitioners. Conclusions: Project findings will inform whether a general practice-based intervention to prevent CVD among at-risk patients is feasible, acceptable in practice, has a positive impact, and what outcome measures might form the focus of future research.
It is well established that the glutamate decarboxylase (GAD) system is central to the survival of Listeria monocytogenes at low pH, both in acidic foods and within the mammalian stomach. The ...accepted model proposes that under acidic conditions extracellular glutamate is transported into the cell in exchange for an intracellular ...-aminobutyrate (GABA...). The glutamate is then decarboxylated to GABA..., a reaction that consumes a proton, thereby helping to prevent acidification of the cytoplasm. In this study, we show that glutamate supplementation had no influence on either growth rate at pH 5.0 or survival at pH 2.5 when L. monocytogenes 10403S was grown in a chemically defined medium (DM). In response to acidification, cells grown in DM failed to efflux GABA, even when glutamate was added to the medium. In contrast, in brain heart infusion (BHI), the same strain produced significant extracellular GABA (GABA...) in response to acidification. In addition, high levels of GABA... (>80 mM) were found in the cytoplasm in response to low pH in both growth media. Medium-swap and medium-mixing experiments revealed that the GABA efflux apparatus was nonfunctional in DM, even when glutamate was present. It was also found that the GadT2D2 antiporter/decarboxylase system was transcribed poorly in DM-grown cultures while overexpression of gadD1T1 and gadD3 occurred in response to pH 3.5. Interestingly, BHI-grown cells did not respond with upregulation of any of the GAD system genes when challenged at pH 3.5. The accumulation of GABA... in cells grown in DM in the absence of extracellular glutamate indicates that intracellular glutamate is the source of the GABA... These results demonstrate that GABA production can be uncoupled from GABA efflux, a finding that alters the way we should view the operation of bacterial GAD systems. (ProQuest: ... denotes formulae/symbols omitted.)
Department of Agriculture, Fisheries and Food (grant no. 06/RD/C/459)
It is well established that the glutamate decarboxylase (GAD) system is central to the survival of Listeria monocytogenes at low ...pH, both in acidic foods and within the mammalian stomach. The accepted model proposes that under acidic conditions extracellular glutamate is transported into the cell in exchange for an intracellular gamma-aminobutyrate (GABA(i)). The glutamate is then decarboxylated to GABA(i), a reaction that consumes a proton, thereby helping to prevent acidification of the cytoplasm. In this study, we show that glutamate supplementation had no influence on either growth rate at pH 5.0 or survival at pH 2.5 when L. monocytogenes 10403S was grown in a chemically defined medium (DM). In response to acidification, cells grown in DM failed to efflux GABA, even when glutamate was added to the medium. In contrast, in brain heart infusion (BHI), the same strain produced significant extracellular GABA (GABA(e)) in response to acidification. In addition, high levels of GABA(i) (>80 mM) were found in the cytoplasm in response to low pH in both growth media. Medium-swap and medium-mixing experiments revealed that the GABA efflux apparatus was nonfunctional in DM, even when glutamate was present. It was also found that the GadT2D2 antiporter/decarboxylase system was transcribed poorly in DM-grown cultures while overexpression of gadD1T1 and gadD3 occurred in response to pH 3.5. Interestingly, BHI-grown cells did not respond with upregulation of any of the GAD system genes when challenged at pH 3.5. The accumulation of GABA(i) in cells grown in DM in the absence of extracellular glutamate indicates that intracellular glutamate is the source of the GABA(i). These results demonstrate that GABA production can be uncoupled from GABA efflux, a finding that alters the way we should view the operation of bacterial GAD systems.
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