36 research outputs found

    Relational norms in customer–company relationships: Net and configurational effects

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    publisher: Elsevier articletitle: Relational norms in customer–company relationships: Net and configurational effects journaltitle: Journal of Business Research articlelink: http://dx.doi.org/10.1016/j.jbusres.2016.04.101 content_type: article copyright: © 2016 Published by Elsevier Inc.publisher: Elsevier articletitle: Relational norms in customer–company relationships: Net and configurational effects journaltitle: Journal of Business Research articlelink: http://dx.doi.org/10.1016/j.jbusres.2016.04.101 content_type: article copyright: © 2016 Published by Elsevier Inc.publisher: Elsevier articletitle: Relational norms in customer–company relationships: Net and configurational effects journaltitle: Journal of Business Research articlelink: http://dx.doi.org/10.1016/j.jbusres.2016.04.101 content_type: article copyright: © 2016 Published by Elsevier Inc

    Distribution and Phylogeny of EFL and EF-1α in Euglenozoa Suggest Ancestral Co-Occurrence Followed by Differential Loss

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    BACKGROUND: The eukaryotic elongation factor EF-1alpha (also known as EF1A) catalyzes aminoacyl-tRNA binding by the ribosome during translation. Homologs of this essential protein occur in all domains of life, and it was previously thought to be ubiquitous in eukaryotes. Recently, however, a number of eukaryotes were found to lack EF-1alpha and instead encode a related protein called EFL (for EF-Like). EFL-encoding organisms are scattered widely across the tree of eukaryotes, and all have close relatives that encode EF-1alpha. This intriguingly complex distribution has been attributed to multiple lateral transfers because EFL's near mutual exclusivity with EF-1alpha makes an extended period of co-occurrence seem unlikely. However, differential loss may play a role in EFL evolution, and this possibility has been less widely discussed. METHODOLOGY/PRINCIPAL FINDINGS: We have undertaken an EST- and PCR-based survey to determine the distribution of these two proteins in a previously under-sampled group, the Euglenozoa. EF-1alpha was found to be widespread and monophyletic, suggesting it is ancestral in this group. EFL was found in some species belonging to each of the three euglenozoan lineages, diplonemids, kinetoplastids, and euglenids. CONCLUSIONS/SIGNIFICANCE: Interestingly, the kinetoplastid EFL sequences are specifically related despite the fact that the lineages in which they are found are not sisters to one another, suggesting that EFL and EF-1alpha co-occurred in an early ancestor of kinetoplastids. This represents the strongest phylogenetic evidence to date that differential loss has contributed to the complex distribution of EFL and EF-1alpha

    Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness

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    Chagas disease, leishmaniasis and sleeping sickness affect 20 million people worldwide and lead to more than 50,000 deaths annually. The diseases are caused by infection with the kinetoplastid parasites Trypanosoma cruzi, Leishmania spp. and Trypanosoma brucei spp., respectively. These parasites have similar biology and genomic sequence, suggesting that all three diseases could be cured with drugs that modulate the activity of a conserved parasite target. However, no such molecular targets or broad spectrum drugs have been identified to date. Here we describe a selective inhibitor of the kinetoplastid proteasome (GNF6702) with unprecedented in vivo efficacy, which cleared parasites from mice in all three models of infection. GNF6702 inhibits the kinetoplastid proteasome through a non-competitive mechanism, does not inhibit the mammalian proteasome or growth of mammalian cells, and is well-tolerated in mice. Our data provide genetic and chemical validation of the parasite proteasome as a promising therapeutic target for treatment of kinetoplastid infections, and underscore the possibility of developing a single class of drugs for these neglected diseases

    Differential Trypanosome Surface Coat Regulation by a CCCH Protein That Co-Associates with procyclin mRNA cis-Elements

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    The genome of Trypanosoma brucei is unusual in being regulated almost entirely at the post-transcriptional level. In terms of regulation, the best-studied genes are procyclins, which encode a family of major surface GPI-anchored glycoproteins (EP1, EP2, EP3, GPEET) that show differential expression in the parasite's tsetse-fly vector. Although procyclin mRNA cis-regulatory sequences have provided the paradigm for post-transcriptional control in kinetoplastid parasites, trans-acting regulators of procyclin mRNAs are unidentified, despite intensive effort over 15 years. Here we identify the developmental regulator, TbZFP3, a CCCH-class predicted RNA binding protein, as an isoform-specific regulator of Procyclin surface coat expression in trypanosomes. We demonstrate (i) that endogenous TbZFP3 shows sequence-specific co-precipitation of EP1 and GPEET, but not EP2 and EP3, procyclin mRNA isoforms, (ii) that ectopic overexpression of TbZFP3 does not perturb the mRNA abundance of procyclin transcripts, but rather that (iii) their protein expression is regulated in an isoform-specific manner, as evidenced by mass spectrometric analysis of the Procyclin expression signature in the transgenic cell lines. The TbZFP3 mRNA-protein complex (TbZFP3mRNP) is identified as a trans-regulator of differential surface protein expression in trypanosomes. Moreover, its sequence-specific interactions with procyclin mRNAs are compatible with long-established predictions for Procyclin regulation. Combined with the known association of TbZFP3 with the translational apparatus, this study provides a long-sought missing link between surface protein cis-regulatory signals and the gene expression machinery in trypanosomes. © 2009 Walrad et al

    Open sustainability: Conceptualization and considerations

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    Sustainability represents a ‘grand challenge’, which can often not be addressed by actions of individuals or single organizations alone. To understand collaborative sustainability activities, in this article we propose the concept of open sustainability. We derive open sustainability from literature in the areas of sustainability, open approaches, and open innovation, and define the concept based on key tenets as follow: open sustainability refers to an orchestrated distributed process in which a focal company interacts with partners across organizational boundaries in order to better achieve its own (micro-level) sustainability objectives, its direct nets' (meso-level) sustainability objectives, and the broader networks' (macro-level) sustainability objectives, both short and long term. Based on this definition, we introduce the articles of our special section on open sustainability

    Touch-flavor transference: Assessing the effect of packaging weight on gustatory evaluations, desire for food and beverages, and willingness to pay

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    Product packaging serves a number of distinct functions and influences the way in which consumers respond to various product offerings. The research reported here examines whether the haptic characteristics of a non-diagnostic product packaging cue, namely its weight, affects the response of consumers. This article reviews existing research on haptic transference and proposes a conceptual framework to explore how the weight of product packaging affects the flavor of the food or beverages, and, in turn, consumers' desire for consumption and willingness to pay. Two studies demonstrate that an increase in packaging weight affects both desire and willingness to pay for the product. These effects are serially mediated by perceived flavor intensity and overall flavor evaluation. Based on these insights, implications for the design of food and beverages packaging are discussed
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