1,646 research outputs found

    PoSSuM: a database of similar protein–ligand binding and putative pockets

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    Numerous potential ligand-binding sites are available today, along with hundreds of thousands of known binding sites observed in the PDB. Exhaustive similarity search for such vastly numerous binding site pairs is useful to predict protein functions and to enable rapid screening of target proteins for drug design. Existing databases of ligand-binding sites offer databases of limited scale. For example, SitesBase covers only ∼33 000 known binding sites. Inferring protein function and drug discovery purposes, however, demands a much more comprehensive database including known and putative-binding sites. Using a novel algorithm, we conducted a large-scale all-pairs similarity search for 1.8 million known and potential binding sites in the PDB, and discovered over 14 million similar pairs of binding sites. Here, we present the results as a relational database Pocket Similarity Search using Multiple-sketches (PoSSuM) including all the discovered pairs with annotations of various types. PoSSuM enables rapid exploration of similar binding sites among structures with different global folds as well as similar ones. Moreover, PoSSuM is useful for predicting the binding ligand for unbound structures, which provides important clues for characterizing protein structures with unclear functions. The PoSSuM database is freely available at http://possum.cbrc.jp/PoSSuM/

    Evidence of Introgression of the ace-1R Mutation and of the ace-1 Duplication in West African Anopheles gambiae s. s

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    Background: The role of inter-specific hybridisation is of particular importance in mosquito disease vectors for predicting the evolution of insecticide resistance. Two molecular forms of Anopheles gambiae s.s., currently recognized as S and M taxa, are considered to be incipient sibling species. Hybrid scarcity in the field was suggested that differentiation of M and S taxa is maintained by limited or absent gene flow. However, recent studies have revealed shared polymorphisms within the M and S forms, and a better understanding of the occurrence of gene flow is needed. One such shared polymorphism is the G119S mutation in the ace-1 gene (which is responsible for insecticide resistance); this mutation has been described in both the M and S forms of A. gambiae s.s. Methods and Results: To establish whether the G119S mutation has arisen independently in each form or by genetic introgression, we analysed coding and non-coding sequences of ace-1 alleles in M and S mosquitoes from representative field populations. Our data revealed many polymorphic sites shared by S and M forms, but no diversity was associated with the G119S mutation. These results indicate that the G119S mutation was a unique event and that genetic introgression explains the observed distribution of the G119S mutation within the two forms. However, it was impossible to determine from our data whether the mutation occurred first in the S form or in the M form. Unexpectedly, sequence analysis of some resistant individuals revealed a duplication of the ace-1 gene that was observed in both A. gambiae s.s. M and S forms. Again, the distribution of this duplication in the two forms most likely occurred through introgression. Conclusions: These results highlight the need for more research to understand the forces driving the evolution of insecticide resistance in malaria vectors and to regularly monitor resistance in mosquito populations of Africa

    Electronic transport in EuB6_6

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    EuB6_6 is a magnetic semiconductor in which defects introduce charge carriers into the conduction band with the Fermi energy varying with temperature and magnetic field. We present experimental and theoretical work on the electronic magnetotransport in single-crystalline EuB6_6. Magnetization, magnetoresistance and Hall effect data were recorded at temperatures between 2 and 300 K and in magnetic fields up to 5.5 T. The negative magnetoresistance is well reproduced by a model in which the spin disorder scattering is reduced by the applied magnetic field. The Hall effect can be separated into an ordinary and an anomalous part. At 20 K the latter accounts for half of the observed Hall voltage, and its importance decreases rapidly with increasing temperature. As for Gd and its compounds, where the rare-earth ion adopts the same Hund's rule ground state as Eu2+^{2+} in EuB6_{6}, the standard antisymmetric scattering mechanisms underestimate the sizesize of this contribution by several orders of magnitude, while reproducing its shapeshape almost perfectly. Well below the bulk ferromagnetic ordering at TCT_C = 12.5 K, a two-band model successfully describes the magnetotransport. Our description is consistent with published de Haas van Alphen, optical reflectivity, angular-resolved photoemission, and soft X-ray emission as well as absorption data, but requires a new interpretation for the gap feature deduced from the latter two experiments.Comment: 35 pages, 12 figures, submitted to PR

    Diversity of Zoanthids (Anthozoa: Hexacorallia) on Hawaiian Seamounts: Description of the Hawaiian Gold Coral and Additional Zoanthids

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    The Hawaiian gold coral has a history of exploitation from the deep slopes and seamounts of the Hawaiian Islands as one of the precious corals commercialised in the jewellery industry. Due to its peculiar characteristic of building a scleroproteic skeleton, this zoanthid has been referred as Gerardia sp. (a junior synonym of Savalia Nardo, 1844) but never formally described or examined by taxonomists despite its commercial interest. While collection of Hawaiian gold coral is now regulated, globally seamounts habitats are increasingly threatened by a variety of anthropogenic impacts. However, impact assessment studies and conservation measures cannot be taken without consistent knowledge of the biodiversity of such environments. Recently, multiple samples of octocoral-associated zoanthids were collected from the deep slopes of the islands and seamounts of the Hawaiian Archipelago. The molecular and morphological examination of these zoanthids revealed the presence of at least five different species including the gold coral. Among these only the gold coral appeared to create its own skeleton, two other species are simply using the octocoral as substrate, and the situation is not clear for the final two species. Phylogenetically, all these species appear related to zoanthids of the genus Savalia as well as to the octocoral-associated zoanthid Corallizoanthus tsukaharai, suggesting a common ancestor to all octocoral-associated zoanthids. The diversity of zoanthids described or observed during this study is comparable to levels of diversity found in shallow water tropical coral reefs. Such unexpected species diversity is symptomatic of the lack of biological exploration and taxonomic studies of the diversity of seamount hexacorals

    Data for Millennia of genomic stability within the invasive Para C Lineage of Salmonella enterica: date estimation 1

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    Salmonella enterica serovar Paratyphi C is the causative agent of enteric (paratyphoid) fever. While today a potentially lethal infection of humans that occurs in Africa and Asia, early 20th century observations in Eastern Europe suggest it may once have had a wider-ranging impact on human societies. We recovered a draft Paratyphi C genome from the 800-year-old skeleton of a young woman in Trondheim, Norway, who likely died of enteric fever. Analysis of this genome against a new, significantly expanded database of related modern genomes demonstrated that Paratyphi C is descended from the ancestors of swine pathogens, serovars Choleraesuis and Typhisuis, together forming the Para C Lineage. Our results indicate that Paratyphi C has been a pathogen of humans for at least 1,000 years, and may have evolved after zoonotic transfer from swine during the Neolithic period

    A Modified View on Octocorals: Heteroxenia fuscescens Nematocysts Are Diverse, Featuring Both an Ancestral and a Novel Type

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    Cnidarians are characterized by the presence of stinging cells containing nematocysts, a sophisticated injection system targeted mainly at prey-capture and defense. In the anthozoan subclass Octocorallia nematocytes have been considered to exist only in low numbers, to be small, and all of the ancestral atrichous-isorhiza type. This study, in contrast, revealed numerous nematocytes in the octocoral Heteroxenia fuscescens. The study demonstrates the applicability of cresyl-violet dye for differential staining and stimulating discharge of the nematocysts. In addition to the atrichous isorhiza-type of nematocysts, a novel type of macrobasic-mastigophore nematocysts was found, featuring a shaft, uniquely comprised of three loops and densely packed arrow-like spines. In contrast to the view that octocorals possess a single type of nematocyst, Heteroxenia fuscescens features two distinct types, indicating for the first time the diversification and complexity of nematocysts for Octocorallia

    Comparative Genomics of Recent Shiga Toxin-Producing Escherichia coli O104:H4: Short-Term Evolution of an Emerging Pathogen

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    The large outbreak of diarrhea and hemolytic uremic syndrome (HUS) caused by Shiga toxin-producing Escherichia coli O104:H4 in Europe from May to July 2011 highlighted the potential of a rarely identified E. coli serogroup to cause severe disease. Prior to the outbreak, there were very few reports of disease caused by this pathogen and thus little known of its diversity and evolution. The identification of cases of HUS caused by E. coli O104:H4 in France and Turkey after the outbreak and with no clear epidemiological links raises questions about whether these sporadic cases are derived from the outbreak. Here, we report genome sequences of five independent isolates from these cases and results of a comparative analysis with historical and 2011 outbreak isolates. These analyses revealed that the five isolates are not derived from the outbreak strain; however, they are more closely related to the outbreak strain and each other than to isolates identified prior to the 2011 outbreak. Over the short time scale represented by these closely related organisms, the majority of genome variation is found within their mobile genetic elements: none of the nine O104:H4 isolates compared here contain the same set of plasmids, and their prophages and genomic islands also differ. Moreover, the presence of closely related HUS-associated E. coli O104:H4 isolates supports the contention that fully virulent O104:H4 isolates are widespread and emphasizes the possibility of future food-borne E. coli O104:H4 outbreaks

    Blockchain and Organizational Characteristics : Towards Business Model Innovation

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    Blockchain seems to challenge the current business models by providing opportunities for new value creation. However, several research gaps remain in literature in evaluating how firms can leverage new approaches to innovation management and opportunities created by blockchain. Supporting organizational characteristics affecting digital innovation management process also need attention in order to challenge the traditional theories while developing unique fundamental assumptions between innovation processes and outcomes. Thus, blockchain and organizational characteristics need to be understood as an encompassing, overarching and interrelated ecosystem in digital innovation management. Grounding on digitalization and innovation management, this research conceptualizes how blockchain technology and supporting organizational characteristics (i.e., R&D investment, strategic alignment, cultural support, top management knowledge and involvement, insights from customers and end-users) can be integrated for business model innovation. This research develops a conceptual framework involving multi-disciplinary collaborative actions that strengthen and empower business model innovation.©2020 Springer. This is a post-peer-review, pre-copyedit version of an article published in Advances in Creativity, Innovation, Entrepreneurship and Communication of Design: Proceedings of the AHFE 2020 Virtual Conferences on Creativity, Innovation and Entrepreneurship, and Human Factors in Communication of Design, July 16-20, 2020, USA. The final authenticated version is available online at: http://dx.doi.org/10.1007/978-3-030-51626-0_9.fi=vertaisarvioitu|en=peerReviewed
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