282 research outputs found

    Marketing Cooperatives' Re-engineering: Influences among Organizational Attributes, Strategic Attributes & Performance

    Get PDF
    ABSTRACT In this paper we expand the agribusiness co-op literature by studying the re-engineering process of marketing cooperatives (co-ops). More specifically we discuss and empirically examine organizational innovations adopted by marketing co-ops in Greece. We hypothesize three types of relationships: a) the influence of organizational (i.e., collective ownership, control and cost/benefit allocation) and strategic (i.e., market and brand orientation) attributes on organizational performance; b) the influence of organizational attributes on market orientation; and c) influences among strategic attributes. Data for this study were collected from a largescale survey with CEOs of marketing co-op in Greece. The results show that strategic attributes have a much greater influence on organizational performance than organizational attributes have, as only a few among the examined elements of re-engineered attributes have a (marginal) positive influence on performance. This result raises the question whether the influence of the re-engineered structures on performance has been over-emphasized in the co-op literature. Moreover, the results demonstrate positive influences among the strategic attributes of co-ops, contrary to the non-significant results of organizational attributes on market orientation. This may imply that organizational attributes do not seem to act as drivers or barriers to the adoption of strategic attributes, and, hence, reinforces the conclusion that emphasis in co-op theory and practice should also be also placed on the strategies and tactics that co-ops should adopt and implement in order to capture market benefits. Keywords: marketing cooperatives, attributes, organizational, strategic, performance, Greec

    Diagnosing member-customer ostracism in co-operatives and counterpoising its relationship-poisoning effects

    Get PDF
    Purpose: This paper aims to examine a core member-customer threat in co-operatives (co-ops) by drawing from ostracism research, assessing co-op ostracismā€™s impact on critical membership and relational exchange outcomes and discussing why relationship marketing research needs to pay more attention to the overlooked role of implicit mistreatment forms in customer harm-doing. Design/methodology/approach: Three studies were conducted. In Study 1, ostracism in co-ops was explored, and a measurement scale for co-op ostracism was developed. In Study 2, the core conceptual model was empirically tested with data from members of three different co-ops. In Study 3, a coping strategy was integrated into an extended model and empirically tested with a new sample of co-op members. Findings: Ostracism is present in co-ops and ā€œpoisonsā€ crucial relational (and membership) outcomes, despite the presence of other relationship-building or relationship-destroying accounts. Coupling entitativity with cognitive capital attenuates ostracismā€™s impact. Research limitations/implications: Inspired by co-opsā€™ membership model and inherent relational advantage, this research is the first to adopt a co-op member-customer perspective and shed light on an implicit relationship-destroying factor. Practical implications: Co-op decision makers might use the diagnostic tool developed in the paper to detect ostracism and fight it. Moreover, a novel coping strategy for how co-ops (or other firms) might fend off ostracism threats is offered in the article. Originality/value: The present study illuminates a dark side of a relationally profuse customer context, painting a more complete picture of relationship marketing determinants. Little attention has been given to ostracism as a distinct and important social behaviour in marketing research and to co-ops as a research context

    Localisation of Putative Mechanoelectrical Transducer Channels in Cochlear Hair Cells by Immunoelectron Microscopy

    Get PDF
    Displacement of the apical stereociliary bundle of cochlear hair cells mechanically gates transducer channels. Knowing the position of the channels with regard to the apical structures of the hair cell could indicate how this mechanism operates. At present, there is conflicting evidence regarding their precise location; the channels have been suggested to be located either towards the base of the stereocilia or at the tips where they could be operated by extracellular links running from the top of shorter stereocilia to the sides of adjacent taller ones. The channels have been shown to be reversibly blocked by amiloride. This has prompted us to use a polyclonal antibody raised against another amiloride-sensitive channel to search for them using immunolabelling. The location of the primary antibody has been revealed using pre-embedding labelling with a colloidal gold-conjugated secondary antibody followed by scanning transmission electron microscopy of semi-thin sections. In this way, more complete information on the relationship of the labelling to the three-dimensional organisation of the stereociliary bundle has been obtained in comparison with previous immunofluorescence and transmission electron microscopic results. Labelling occurs in discrete areas towards the tips of the stereocilia, one of the possible sites for the transducer channels, predominantly between the membranes of shorter and taller stereocilia

    Markov Chain-based Promoter Structure Modeling for Tissue-specific Expression Pattern Prediction

    Get PDF
    Transcriptional regulation is the first level of regulation of gene expression and is therefore a major topic in computational biology. Genes with similar expression patterns can be assumed to be co-regulated at the transcriptional level by promoter sequences with a similar structure. Current approaches for modeling shared regulatory features tend to focus mainly on clustering of cis-regulatory sites. Here we introduce a Markov chain-based promoter structure model that uses both shared motifs and shared features from an input set of promoter sequences to predict candidate genes with similar expression. The model uses positional preference, order, and orientation of motifs. The trained model is used to score a genomic set of promoter sequences: high-scoring promoters are assumed to have a structure similar to the input sequences and are thus expected to drive similar expression patterns. We applied our model on two datasets in Caenorhabditis elegans and in Ciona intestinalis. Both computational and experimental verifications indicate that this model is capable of predicting candidate promoters driving similar expression patterns as the input-regulatory sequences. This model can be useful for finding promising candidate genes for wet-lab experiments and for increasing our understanding of transcriptional regulation

    An intuitionistic approach to scoring DNA sequences against transcription factor binding site motifs

    Get PDF
    Background: Transcription factors (TFs) control transcription by binding to specific regions of DNA called transcription factor binding sites (TFBSs). The identification of TFBSs is a crucial problem in computational biology and includes the subtask of predicting the location of known TFBS motifs in a given DNA sequence. It has previously been shown that, when scoring matches to known TFBS motifs, interdependencies between positions within a motif should be taken into account. However, this remains a challenging task owing to the fact that sequences similar to those of known TFBSs can occur by chance with a relatively high frequency. Here we present a new method for matching sequences to TFBS motifs based on intuitionistic fuzzy sets (IFS) theory, an approach that has been shown to be particularly appropriate for tackling problems that embody a high degree of uncertainty. Results: We propose SCintuit, a new scoring method for measuring sequence-motif affinity based on IFS theory. Unlike existing methods that consider dependencies between positions, SCintuit is designed to prevent overestimation of less conserved positions of TFBSs. For a given pair of bases, SCintuit is computed not only as a function of their combined probability of occurrence, but also taking into account the individual importance of each single base at its corresponding position. We used SCintuit to identify known TFBSs in DNA sequences. Our method provides excellent results when dealing with both synthetic and real data, outperforming the sensitivity and the specificity of two existing methods in all the experiments we performed. Conclusions: The results show that SCintuit improves the prediction quality for TFs of the existing approaches without compromising sensitivity. In addition, we show how SCintuit can be successfully applied to real research problems. In this study the reliability of the IFS theory for motif discovery tasks is proven

    Molecular Modeling of Mechanosensory Ion Channel Structural and Functional Features

    Get PDF
    The DEG/ENaC (Degenerin/Epithelial Sodium Channel) protein family comprises related ion channel subunits from all metazoans, including humans. Members of this protein family play roles in several important biological processes such as transduction of mechanical stimuli, sodium re-absorption and blood pressure regulation. Several blocks of amino acid sequence are conserved in DEG/ENaC proteins, but structure/function relations in this channel class are poorly understood. Given the considerable experimental limitations associated with the crystallization of integral membrane proteins, knowledge-based modeling is often the only route towards obtaining reliable structural information. To gain insight into the structural characteristics of DEG/ENaC ion channels, we derived three-dimensional models of MEC-4 and UNC-8, based on the available crystal structures of ASIC1 (Acid Sensing Ion Channel 1). MEC-4 and UNC-8 are two DEG/ENaC family members involved in mechanosensation and proprioception respectively, in the nematode Caenorhabditis elegans. We used these models to examine the structural effects of specific mutations that alter channel function in vivo. The trimeric MEC-4 model provides insight into the mechanism by which gain-of-function mutations cause structural alterations that result in increased channel permeability, which trigger cell degeneration. Our analysis provides an introductory framework to further investigate the multimeric organization of the DEG/ENaC ion channel complex

    Features of mammalian microRNA promoters emerge from polymerase II chromatin immunoprecipitation data

    Get PDF
    Background: MicroRNAs (miRNAs) are short, non-coding RNA regulators of protein coding genes. miRNAs play a very important role in diverse biological processes and various diseases. Many algorithms are able to predict miRNA genes and their targets, but their transcription regulation is still under investigation. It is generally believed that intragenic miRNAs (located in introns or exons of protein coding genes) are co-transcribed with their host genes and most intergenic miRNAs transcribed from their own RNA polymerase II (Pol II) promoter. However, the length of the primary transcripts and promoter organization is currently unknown. Methodology: We performed Pol II chromatin immunoprecipitation (ChIP)-chip using a custom array surrounding regions of known miRNA genes. To identify the true core transcription start sites of the miRNA genes we developed a new tool (CPPP). We showed that miRNA genes can be transcribed from promoters located several kilobases away and that their promoters share the same general features as those of protein coding genes. Finally, we found evidence that as many as 26% of the intragenic miRNAs may be transcribed from their own unique promoters. Conclusion: miRNA promoters have similar features to those of protein coding genes, but miRNA transcript organization is more complex. Ā© 2009 Corcoran et al

    Expression of Regulatory Platelet MicroRNAs in Patients with Sickle Cell Disease

    Get PDF
    Background: Increased platelet activation in sickle cell disease (SCD) contributes to a state of hypercoagulability and confers a risk of thromboembolic complications. The role for post-transcriptional regulation of the platelet transcriptome by microRNAs (miRNAs) in SCD has not been previously explored. This is the first study to determine whether platelets from SCD exhibit an altered miRNA expression profile. Methods and Findings: We analyzed the expression of miRNAs isolated from platelets from a primary cohort (SCD = 19, controls = 10) and a validation cohort (SCD = 7, controls = 7) by hybridizing to the Agilent miRNA microarrays. A dramatic difference in miRNA expression profiles between patients and controls was noted in both cohorts separately. A total of 40 differentially expressed platelet miRNAs were identified as common in both cohorts (p-value 0.05, fold change>2) with 24 miRNAs downregulated. Interestingly, 14 of the 24 downregulated miRNAs were members of three families - miR-329, miR-376 and miR-154 - which localized to the epigenetically regulated, maternally imprinted chromosome 14q32 region. We validated the downregulated miRNAs, miR-376a and miR-409-3p, and an upregulated miR-1225-3p using qRT-PCR. Over-expression of the miR-1225-3p in the Meg01 cells was followed by mRNA expression profiling to identify mRNA targets. This resulted in significant transcriptional repression of 1605 transcripts. A combinatorial approach using Meg01 mRNA expression profiles following miR-1225-3p overexpression, a computational prediction analysis of miRNA target sequences and a previously published set of differentially expressed platelet transcripts from SCD patients, identified three novel platelet mRNA targets: PBXIP1, PLAGL2 and PHF20L1. Conclusions: We have identified significant differences in functionally active platelet miRNAs in patients with SCD as compared to controls. These data provide an important inventory of differentially expressed miRNAs in SCD patients and an experimental framework for future studies of miRNAs as regulators of biological pathways in platelets. Ā© 2013 Jain et al

    Experimentally based contact energies decode interactions responsible for proteinā€“DNA affinity and the role of molecular waters at the binding interface

    Get PDF
    A major obstacle towards understanding the molecular basis of transcriptional regulation is the lack of a recognition code for proteinā€“DNA interactions. Using high-quality crystal structures and binding data on the promiscuous family of C2H2 zinc fingers (ZF), we decode 10 fundamental specific interactions responsible for proteinā€“DNA recognition. The interactions include five hydrogen bond types, three atomic desolvation penalties, a favorable non-polar energy, and a novel water accessibility factor. We apply this code to three large datasets containing a total of 89 C2H2 transcription factor (TF) mutants on the three ZFs of EGR. Guided by molecular dynamics simulations of individual ZFs, we map the interactions into homology models that embody all feasible intra- and intermolecular bonds, selecting for each sequence the structure with the lowest free energy. These interactions reproduce the change in affinity of 35 mutants of finger I (R2 = 0.998), 23 mutants of finger II (R2 = 0.96) and 31 finger III human domains (R2 = 0.94). Our findings reveal recognition rules that depend on DNA sequence/structure, molecular water at the interface and induced fit of the C2H2 TFs. Collectively, our method provides the first robust framework to decode the molecular basis of TFs binding to DNA
    • ā€¦
    corecore