105 research outputs found

    Proteins with Complex Architecture as Potential Targets for Drug Design: A Case Study of Mycobacterium tuberculosis

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    Lengthy co-evolution of Homo sapiens and Mycobacterium tuberculosis, the main causative agent of tuberculosis, resulted in a dramatically successful pathogen species that presents considerable challenge for modern medicine. The continuous and ever increasing appearance of multi-drug resistant mycobacteria necessitates the identification of novel drug targets and drugs with new mechanisms of action. However, further insights are needed to establish automated protocols for target selection based on the available complete genome sequences. In the present study, we perform complete proteome level comparisons between M. tuberculosis, mycobacteria, other prokaryotes and available eukaryotes based on protein domains, local sequence similarities and protein disorder. We show that the enrichment of certain domains in the genome can indicate an important function specific to M. tuberculosis. We identified two families, termed pkn and PE/PPE that stand out in this respect. The common property of these two protein families is a complex domain organization that combines species-specific regions, commonly occurring domains and disordered segments. Besides highlighting promising novel drug target candidates in M. tuberculosis, the presented analysis can also be viewed as a general protocol to identify proteins involved in species-specific functions in a given organism. We conclude that target selection protocols should be extended to include proteins with complex domain architectures instead of focusing on sequentially unique and essential proteins only

    Untapped Riches of Meso-Level Applications in Multilevel Entrepreneurship Mechanisms

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    A dynamic theory of network failure

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    Organizational and sociological research dealing with network governance has mainly focused on network advantages rather than on their problems or dysfunctionalities. This left partially unexplored the field of network failure. Even if some early attempts at explicitly theorizing network failures have been made, we argue that explanations based mainly on social conditions (ignorance and opportunism) offered by this emerging theory (e.g. Schrank and Whitford, 2011), are not exhaustive. In this article we report the results of our empirical investigation on the underperforming network between the worldwide famous Venice Film Festival and its local hospitality system (in Venice, Italy). In the case study we are presenting, we will show how institutions have not been able to inhibit opportunism and sustain trust among network members because of mobilizing practices developed across formal lines of communication. With this work we propose a dynamic theory of network failure, answering to the more general call for network theories to focus the attention on agency and micro-processes

    Which Problems to Solve? Online Knowledge Sharing and Attention Allocation in Organizations

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