On the Brink of the Waters of Life and Truth, We are Miserably Dying: Ralph Waldo Emerson as a Predecessor to Deconstruction and Postmodernism

Between his pivotal essays Nature in 1836 and The Poet in 1844, Ralph Waldo Emerson\u27s increasingly negative and distrustful view of language can best be described as a precursor to deconstruction and postmodernism. Contemporary critics are too quick to dismiss a deconstructionist Emerson. There is evidence within his major essays that Emerson\u27s understanding of language not only leads him to public and private displays of pessimism, but also to feelings of internal solipsism, agnosticism, and epistemological anxiety. Emerson demanded that mankind should utilize nature and aesthetics to experience the sublime and an immediate and original relationship with God. Yet, Emerson\u27s essays evidence the idea that art and language itself futilely failed in bringing about an original relationship with God. By the time he wrote The Poet, Emerson officially succumbed to the belief that truth and God were ultimately unattainable, a belief that 20th century literary criticism defines as deconstructionist and postmoder

On the Brink of the Waters of Life and Truth, We are Miserably Dying: Ralph Waldo Emerson as a Predecessor to Deconstruction and Postmodernism

Between his pivotal essays Nature in 1836 and The Poet in 1844, Ralph Waldo Emerson\u27s increasingly negative and distrustful view of language can best be described as a precursor to deconstruction and postmodernism. Contemporary critics are too quick to dismiss a deconstructionist Emerson. There is evidence within his major essays that Emerson\u27s understanding of language not only leads him to public and private displays of pessimism, but also to feelings of internal solipsism, agnosticism, and epistemological anxiety. Emerson demanded that mankind should utilize nature and aesthetics to experience the sublime and an immediate and original relationship with God. Yet, Emerson\u27s essays evidence the idea that art and language itself futilely failed in bringing about an original relationship with God. By the time he wrote The Poet, Emerson officially succumbed to the belief that truth and God were ultimately unattainable, a belief that 20th century literary criticism defines as deconstructionist and postmoder

High-Resolution Mass Spectrometry Based Proteomic Analysis of the Response to Vancomycin-Induced Cell Wall Stress in Streptomyces coelicolor A3(2).

Understanding how bacteria survive periods of cell wall stress is of fundamental interest and can help generate ideas for improved antibacterial treatments. In this study we use tandem mass tagging to characterize the proteomic response of vancomycin resistant Streptomyces coelicolor to the exposure to sublethal levels of the antibiotic. A common set of 804 proteins were identified in triplicate experiments. Contrasting changes in the abundance of proteins closely associated with the cytoplasmic membrane with those taking place in the cytosol identified aspects of protein spatial localization that are associated with the response to vancomycin. Enzymes for peptidoglycan precursor, mycothiol, ectoine and menaquinone biosynthesis together with a multisubunit nitrate reductase were recruited to the membrane following vancomycin treatment. Many proteins with regulatory functions (including sensor protein kinases) also exhibited significant changes in abundance exclusively in the membrane-associated protein fraction. Several enzymes predicted to be involved in extracellular peptidoglycan crossbridge formation became significantly depleted from the membrane. A comparison with data previously acquired on the changes in gene transcription following vancomycin treatment identified a common high-confidence set of changes in gene expression. Generalized changes in protein abundance indicate roles for proteolysis, the pentose phosphate pathway and a reorganization of amino acid biosynthesis in the stress response.HJH was supported by the Royal Society (516002.K5877/ROG) and by grant number GO700141 from the Medical Research Council.This is the final version of the article. It first appeared from ACS Publications via http://dx.doi.org/10.1021/acs.jproteome.5b0024

ATP-dependent substrate transport by the ABC transporter MsbA is proton-coupled.

ATP-binding cassette transporters mediate the transbilayer movement of a vast number of substrates in or out of cells in organisms ranging from bacteria to humans. Current alternating access models for ABC exporters including the multidrug and Lipid A transporter MsbA from Escherichia coli suggest a role for nucleotide as the fundamental source of free energy. These models involve cycling between conformations with inward- and outward-facing substrate-binding sites in response to engagement and hydrolysis of ATP at the nucleotide-binding domains. Here we report that MsbA also utilizes another major energy currency in the cell by coupling substrate transport to a transmembrane electrochemical proton gradient. The dependence of ATP-dependent transport on proton coupling, and the stimulation of MsbA-ATPase by the chemical proton gradient highlight the functional integration of both forms of metabolic energy. These findings introduce ion coupling as a new parameter in the mechanism of this homodimeric ABC transporter.Himansha Singh is supported by the Cambridge Commonwealth, European and International Trust. Saroj Velamakanni was a recipient of a Cambridge Nehru Scholarship. Shen L. Wei was funded by the Cambridge Overseas Trust. This research in the Van Veen group was supported by Biotechnology and Biological Sciences Research Council (BBSRC) grant BB/I002383/1 and BB/C004663/1, Medical Research Council (MRC) grant G0401165 and by further support from the Human Frontier Science Program (HFSP) and the British Society for Antimicrobial Chemotherapy (BSAC).This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms1238

Tourism destination modelling: building a sustainable planning tool for Australian tourism destinations

The Ningaloo Destination Model is a tourism planning tool for the Ningaloo Coast region of Western Australia that assesses the economic, social and environmental impacts of different planning decisions and events. This report describes the features of the tourism destination model, and analyses its application in the region and to other parts of Australia. Destination modelling integrates a number of research methodologies developed through past STCRC projects (on visitor spending and characteristics, social impacts and economic impacts), secondary data and ecological research. The key to this process is a model development technique that uses scenario planning methodologies to facilitate stakeholder engagement and conceptual modelling techniques to facilitate research integration. The report describes the methodologies used for model development and for data collection, provides two case studies demonstrating outputs, and explores applications of the Ningaloo Destination Model to the region, to other locations and to other sectors. The Ningaloo Destination Model provides estimates of the impacts of plans and events related to tourism in four dimensions: tourism specific; economy; social; and environmental (both resource use and ecological). These outputs are explored through two case studies: a nodal coastal development; and a large resort development. The model can be used for four broad (oftentimes overlapping) categories of assessment: operational planning and decision making for specific organisations and groups (such as local government or agencies that manage land or sea use), regional planning, participatory planning and collaborations and to assist monitoring and evaluation.The Ningaloo Destination Model will be available to the general public (in a limited format) through websites; to agencies through a desktop version; and through integration into a larger model of the region being developed by the CSIRO. Destination modelling is relevant for other tourism destinations and a process for the rapid and cost-effective application of destination modelling is feasible. While much of the data is available, a broader roll-out would require benchmarking of water, electricity and waste data, and developing a wireframe for all tourism destinations. Making destination modelling tools broadly available would significantly broaden the impacts considered in tourism planning and lead to enhancement of desirable effects of tourism development, and early mitigation of negative impacts across Australia. The techniques developed for destination modelling were also found to be applicable to other sectors

Analysis of Drosophila melanogaster proteome dynamics during embryonic development by a combination of label-free proteomics approaches.

During embryogenesis, organisms undergo considerable cellular remodelling requiring the combined action of thousands of proteins. In case of the well-studied model Drosophila melanogaster, transcriptomic studies, most notably from the modENCODE project, have described in detail changes in gene expression at the mRNA level across development. Although such data are clearly very useful to understand how the genome is regulated during embryogenesis, it is important to understand how changes in gene expression are reflected at the level of the proteome. In this study, we describe a combination of two quantitative label-free approaches, SWATH and data-dependent acquisition, to monitor changes in protein expression across a timecourse of D. melanogaster embryonic development. We demonstrate that both approaches provide robust and reproducible methods for the analysis of proteome changes. In a preliminary analysis of Drosophila embryogenesis, we identified several pathways, including the heat-shock response, nuclear protein import and energy production that are regulated during embryo development. In some cases changes in protein expression mirrored transcript levels across development, whereas other proteins showed signatures of post-transcriptional regulation. Taken together, our pilot study provides a solid platform for a more detailed exploration of the embryonic proteome.Funding: B.F, D.K and L.G are funded by BBSRC (Ref: BB/L002817/1). MR and JV acknowledge funding by the Wellcome Trust (RG 093735/Z/10/Z) the ERC (Starting grant 260809), M.R. is a Wellcome Trust Research Career Development and Wellcome-Beit Prize fellow.  This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/pmic.20150048

Manual versus powered toothbrushes for oral health; an update

Background: Plaque removal is a cornerstone in the prevention and treatment of periodontal diseases. Powered toothbrushes have been devised to assist in plaque removal. An earlier Cochrane systematic review found that only powered toothbrushes with a rotation-oscillation action were more effective at removing plaque and reducing gingivitis. That review requires updating to include recent trials. Objective: To compare the effects of manual and powered toothbrushes on plaque removal and gingival health. Method: We searched the Cochrane Oral Health Group Trials Register, CENTRAL; MEDLINE, EMBASE and CINAHL to 9 March 2011. Manufacturers and authors were contacted for additional data. Trials were selected for random allocation of participants to use a manual or powered toothbrush. Participants were members of the public with uncompromised manual dexterity who brushed unsupervised for at least 4 weeks. There was no language restriction. Primary outcomes were plaque and gingivitis scores at the end of the trial. Assessment of methodological quality and data extraction were conducted in duplicate. Potential sources of heterogeneity were examined, along with sensitivity analyses for quality and publication bias. Results: Fifty trials, involving 4326 participants, provided data. Effect sizes, calculated as standardized mean difference (95% confidence intervals) for brushes with a rotation oscillation action were: 1 to 3 months >3 months Plaque -0.53 (-0.74 to -0.31) -0.66 (-1.28 to -0.03) Gingivitis -0.49 (-0.73 to -0.26) -0.34 (-0.56 to -0.11) This represents approximately 27% fewer sites with bleeding on probing in the long term. No other powered designs were consistently superior to manual toothbrushes. There was considerable heterogeneity between trials. Sensitivity analyses revealed the results to be robust when selecting trials of high quality. Conclusion: Rotation-oscillation powered toothbrushes remove plaque and reduce gingivitis more than manual brushes in the short and long term

Stat3-mediated alterations in lysosomal membrane protein composition.

Lysosome function is essential in cellular homeostasis. In addition to its recycling role, the lysosome has recently been recognized as a cellular signaling hub. We have shown in mammary epithelial cells, both in vivo and in vitro, that signal transducer and activator of transcription 3 (Stat3) modulates lysosome biogenesis and can promote the release of lysosomal proteases that culminates in cell death. To further investigate the impact of Stat3 on lysosomal function, we conducted a proteomic screen of changes in lysosomal membrane protein components induced by Stat3 using an iron nanoparticle enrichment strategy. Our results show that Stat3 activation not only elevates the levels of known membrane proteins but results in the appearance of unexpected factors, including cell surface proteins such as annexins and flotillins. These data suggest that Stat3 may coordinately regulate endocytosis, intracellular trafficking, and lysosome biogenesis to drive lysosome-mediated cell death in mammary epithelial cells. The methodologies described in this study also provide significant improvements to current techniques used for the purification and analysis of the lysosomal proteome

Functional reconstruction of a eukaryotic-like E1/E2/(RING) E3 ubiquitylation cascade from an uncultured archaeon.

The covalent modification of protein substrates by ubiquitin regulates a diverse range of critical biological functions. Although it has been established that ubiquitin-like modifiers evolved from prokaryotic sulphur transfer proteins it is less clear how complex eukaryotic ubiquitylation system arose and diversified from these prokaryotic antecedents. The discovery of ubiquitin, E1-like, E2-like and small-RING finger (srfp) protein components in the Aigarchaeota and the Asgard archaea superphyla has provided a substantive step toward addressing this evolutionary question. Encoded in operons, these components are likely representative of the progenitor apparatus that founded the modern eukaryotic ubiquitin modification systems. Here we report that these proteins from the archaeon Candidatus 'Caldiarchaeum subterraneum' operate together as a bona fide ubiquitin modification system, mediating a sequential ubiquitylation cascade reminiscent of the eukaryotic process. Our observations support the hypothesis that complex eukaryotic ubiquitylation signalling pathways have developed from compact systems originally inherited from an archaeal ancestor