627 research outputs found

    Reciprocity as deliberative capacity: lessons from a citizens deliberation on carbon pricing mechanisms in Australia

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    Australia has seen a deep division in opinion in search of a carbon pricing mechanism. While concepts of carbon taxation and emission trading have comparable public support, climate scepticism is influencing the debates in political and public spheres in downplaying the need for carbon pricing. Public deliberation is a possible engagement option to address the conflict inherent in climate policy preferences. This research explores the way that a deliberative forum involving twenty-four Australians promoted effective communication between participants through which conflict between policy preferences became more tangible. While the forum did not eliminate disagreement in preferences in the choice of carbon pricing mechanisms, participants reached consensus on fundamental principles such as the need for trusted sources of information, trusted governance procedures, and transparent accountability by appropriate institutions. Shared political expectations encouraged dialogue and cooperation in discussions by enhancing reciprocal understanding. Two sceptical participants who originally had strong opinions different from the rest of the group managed to find common ground. Public deliberative forums that are conducive to reciprocal communication are able to provide a mechanism for joint problem-solving processes that are less adversarial and more responsive to the range of people\u27s preferences. Keywords: public deliberation, consensus, emission trading, carbon tax, deliberative democracy, Australi

    Patterns of Interactions in Complex Social Networks Based on Coloured Motifs Analysis

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    Coloured network motifs are small subgraphs that enable to discover and interpret the patterns of interaction within the complex networks. The analysis of three-nodes motifs where the colour of the node reflects its high – white node or low – black node centrality in the social network is presented in the paper. The importance of the vertices is assessed by utilizing two measures: degree prestige and degree centrality. The distribution of motifs in these two cases is compared to mine the interconnection patterns between nodes. The analysis is performed on the social network derived from email communication

    Requirement of Two Acyltransferases for 4-O-Acylation during Biosynthesis of Harzianum A, an Antifungal Trichothecene Produced by Trichoderma arundinaceum

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    Trichothecenes are sesquiterpenoid toxins produced by multiple fungi, including plant pathogens, entomopathogens, and saprotrophs. Most of these fungi have the acyltransferase-encoding gene tri18. Even though its function has not been determined, tri18 is predicted to be involved in trichothecene biosynthesis because of its pattern of expression and its location near other trichothecene biosynthetic genes. Here, molecular genetic, precursor feeding, and analytical chemistry experiments indicate that in the saprotroph Trichoderma arundinaceum the tri18-encoded acyltransferase (TRI18) and a previously characterized acyltransferase (TRI3) are required for conversion of the trichothecene biosynthetic intermediate trichodermol to harzianum A, an antifungal trichothecene analog with an octa-2,4,6-trienedioyl acyl group. On the basis of the results, we propose that TRI3 catalyzes trichothecene 4-O-acetylation, and subsequently, TRI18 catalyzes replacement of the resulting acetyl group with octa-2,4,6-trienedioyl to form harzianum A. Thus, the findings provide evidence for a previously unrecognized two-step acylation process during trichothecene biosynthesis in T. arundinaceum and possibly other fungiSIThe Spanish Ministry of Economy and Competitiveness supported this work (MINECO-AGL2015-70671-C2-2-R to S.G.), and the University of León granted L.L. a fellowshi

    Discrete Molecular Dynamics Distinguishes Nativelike Binding Poses from Decoys in Difficult Targets

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    Virtual screening is one of the major tools used in computer-aided drug discovery. In structure-based virtual screening, the scoring function is critical to identifying the correct docking pose and accurately predicting the binding affinities of compounds. However, the performance of existing scoring functions has been shown to be uneven for different targets, and some important drug targets have proven especially challenging. In these targets, scoring functions cannot accurately identify the native or near-native binding pose of the ligand from among decoy poses, which affects both the accuracy of the binding affinity prediction and the ability of virtual screening to identify true binders in chemical libraries. Here, we present an approach to discriminating native poses from decoys in difficult targets for which several scoring functions failed to correctly identify the native pose. Our approach employs Discrete Molecular Dynamics simulations to incorporate protein-ligand dynamics and the entropic effects of binding. We analyze a collection of poses generated by docking and find that the residence time of the ligand in the native and nativelike binding poses is distinctly longer than that in decoy poses. This finding suggests that molecular simulations offer a unique approach to distinguishing the native (or nativelike) binding pose from decoy poses that cannot be distinguished using scoring functions that evaluate static structures. The success of our method emphasizes the importance of protein-ligand dynamics in the accurate determination of the binding pose, an aspect that is not addressed in typical docking and scoring protocols

    Effect of High-Fat and Low-Fat Dairy Products on Cardiometabolic Risk Factors and Immune Function in a Low Birthweight Swine Model of Diet-Induced Insulin Resistance

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    Although dairy intake has been shown to have a neutral or some beneficial effect on major cardiometabolic risk factors, the impact of dairy, and especially dairy fat, on immune function remains to be investigated. To understand the effect of consuming dairy fat on cardiometabolic risk factors and immune function, we used an established low birthweight (LBW) swine model of diet-induced insulin resistance to compare high-fat and low-fat dairy products to a control high-fat diet (CHF). LBW piglets were randomized to consume one of the 3 experimental HF diets: (1) CHF, (2) CHF diet supplemented with 3 servings/day of high-fat dairy (HFDairy) and (3) CHF diet supplemented with 3 servings/day of low-fat dairy (LFDairy). As comparison groups, normal birthweight (NBW) piglets were fed a CHF (NBW-CHF) or standard pig grower diet (NBW-Chow). A total of 35 pigs completed the study and were fed for a total of 7 weeks, including 1 week of CHF transition diet. At 12 weeks of age, piglets were euthanized. Fasting blood and tissue samples were collected. Ex vivo cytokine production by peripheral blood mononuclear cells (PBMCs) stimulated with pokeweed (PWM), phytohemagglutinin (PHA) and phorbol myristate acetate-ionomycin (PMA-I) were assessed. As expected, LBW-CHF piglets showed early signs of insulin resistance (HOMA-IR, P model = 0.08). Feeding high-fat dairy products improved fasting plasma glucose concentrations more than low-fat dairy compared to LBW-CHF (P < 0.05). Irrespective of fat content, dairy consumption had neutral effect on fasting lipid profile. We have also observed lower production of IL-2 after PWM and PHA stimulation as well as lower production of TNF-α and IFN-γ after PWM stimulation in LBW-CHF than in NBW-Chow (all, P < 0.05), suggesting impaired T cell and antigen presenting cell function. While feeding high-fat dairy had minimal effect on immune function, feeding low-fat dairy significantly improved the production of IL-2, TNF-α and IFN-γ after PWM stimulation, IL-2 and IFN-γ after PHA stimulation as well as TNF-α after PMA-I stimulation compared to LBW-CHF (all, P < 0.05). These data provide novel insights into the role of dairy consumption in counteracting some obesity-related cardiometabolic and immune perturbations

    Daptomycin resistance mechanisms in clinically derived Staphylococcus aureus strains assessed by a combined transcriptomics and proteomics approach

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    Objectives The development of daptomycin resistance in Staphylococcus aureus is associated with clinical treatment failures. The mechanism(s) of such resistance have not been clearly defined. Methods We studied an isogenic daptomycin-susceptible (DAPS) and daptomycin-resistant (DAPR) S. aureus strain pair (616; 701) from a patient with relapsing endocarditis during daptomycin treatment, using comparative transcriptomic and proteomic techniques. Results Minor differences in the genome content were found between strains by DNA hybridization. Transcriptomic analyses identified a number of genes differentially expressed in important functional categories: cell division; metabolism of bacterial envelopes; and global regulation. Of note, the DAPR isolate exhibited reduced expression of the major cell wall autolysis gene coincident with the up-regulation of genes involved in cell wall teichoic acid production. Using quantitative (q)RT-PCR on the gene cadre putatively involved in cationic peptide resistance, we formulated a putative regulatory network compatible with microarray data sets, mainly implicating bacterial envelopes. Of interest, qRT-PCR of this same gene cadre from two distinct isogenic DAPS/DAPR clinical strain pairs revealed evidence of other strain-dependent networks operative in the DAPR phenotype. Comparative proteomics of 616 versus 701 revealed a differential abundance of proteins in various functional categories, including cell wall-associated targets and biofilm formation proteins. Phenotypically, strains 616 and 701 showed major differences in their ability to develop bacterial biofilms in the presence of the antibacterial lipid, oleic acid. Conclusions Compatible with previous in vitro observations, in vivo-acquired DAPR in S. aureus is a complex, multistep phenomenon involving: (i) strain-dependent phenotypes; (ii) transcriptome adaptation; and (iii) modification of the lipid and protein contents of cellular envelope

    Organizational Readiness in Specialty Mental Health Care

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    Implementing quality improvement efforts in clinics is challenging. Assessment of organizational “readiness” for change can set the stage for implementation by providing information regarding existing strengths and deficiencies, thereby increasing the chance of a successful improvement effort. This paper discusses organizational assessment in specialty mental health, in preparation for improving care for individuals with schizophrenia. To assess organizational readiness for change in specialty mental health in order to facilitate locally tailored implementation strategies. EQUIP-2 is a site-level controlled trial at nine VA medical centers (four intervention, five control). Providers at all sites completed an organizational readiness for change (ORC) measure, and key stakeholders at the intervention sites completed a semi-structured interview at baseline. At the four intervention sites, 16 administrators and 43 clinical staff completed the ORC, and 38 key stakeholders were interviewed. The readiness domains of training needs, communication, and change were the domains with lower mean scores (i.e., potential deficiencies) ranging from a low of 23.8 to a high of 36.2 on a scale of 10–50, while staff attributes of growth and adaptability had higher mean scores (i.e., potential strengths) ranging from a low of 35.4 to a high of 41.1. Semi-structured interviews revealed that staff perceptions and experiences of change and decision-making are affected by larger structural factors such as change mandates from VA headquarters. Motivation for change, organizational climate, staff perceptions and beliefs, and prior experience with change efforts contribute to readiness for change in specialty mental health. Sites with less readiness for change may require more flexibility in the implementation of a quality improvement intervention. We suggest that uptake of evidence-based practices can be enhanced by tailoring implementation efforts to the strengths and deficiencies of the organizations that are implementing quality improvement changes

    Botrydial and botcinins produced by Botrytis cinerea regulate the expression of Trichoderma arundinaceum genes involved in trichothecene biosynthesis

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    Trichoderma arundinaceum IBT 40837 (Ta37) and Botrytis cinerea produce the sesquiterpenes harzianum A (HA) and botrydial (BOT), respectively, and also the polyketides aspinolides and botcinins (Botcs), respectively. We analysed the role of BOT and Botcs in the Ta37-B. cinerea interaction, including the transcriptomic changes in the genes involved in HA (tri) and ergosterol biosynthesis, as well as changes in the level of HA and squalene-ergosterol. We found that, when confronted with B. cinerea, the tri biosynthetic genes were up-regulated in all dual cultures analysed, but at higher levels when Ta37 was confronted with the BOT non-producer mutant bcbot2Δ. The production of HA was also higher in the interaction area with this mutant. In Ta37-bcbot2Δ confrontation experiments, the expression of the hmgR gene, encoding the 3-hydroxy-3-methylglutaryl coenzyme A reductase, which is the first enzyme of the terpene biosynthetic pathway, was also up-regulated, resulting in an increase in squalene production compared with the confrontation with B. cinerea B05.10. Botcs had an up-regulatory effect on the tri biosynthetic genes, with BotcA having a stronger effect than BotcB. The results indicate that the interaction between Ta37 and B. cinerea exerts a stimulatory effect on the expression of the tri biosynthetic genes, which, in the interaction zone, can be attenuated by BOT produced by B. cinerea B05.10. The present work provides evidence for a metabolic dialogue between T. arundinaceum and B. cinerea that is mediated by sesquiterpenes and polyketides, and that affects the outcome of the interaction of these fungi with each other and their environmentSIFunding was obtained from the Junta de Castilla y Leon (SA260A11-2,LE125A12-2 and LE228U14) and Spanish Government grants MICINN-AGL2009-13431-C02-02, MINECO-AGL2012-40041-C02-01, AGL2012-40041-C02-02 and AGL2012-39798-C02-01. MGM and II-B were granted fellowships from the Spanish Ministry of Science and Innovation(AP2007-02835, BES-2013-063411
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