336 research outputs found

    Information Visualisation for Project Management: Case Study of Bath Formula Student Project

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    This paper contributes to a better understanding and design of dashboards for monitoring of engineering projects based on the projects’ digital footprint and user-centered design approach. The paper presents an explicit insight-based framework for the evaluation of dashboard visualisations and compares the performance of two groups of student engineering project managers against the framework: a group with the dashboard visualisations and a group without the dashboard. The results of our exploratory study demonstrate that student project managers who used the dashboard generated more useful information and exhibited more complex reasoning on the project progress, thus informing knowledge of the provision of information to engineers in support of their project understanding

    Determination of the Molecular Basis for a Limited Dimorphism, N417K, in the Plasmodium vivax Duffy-Binding Protein

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    Invasion of human red blood cells by Plasmodium merozoites is vital for replication and survival of the parasite and, as such, is an attractive target for therapeutic intervention. Merozoite invasion is mediated by specific interactions between parasite ligands and host erythrocyte receptors. The P. vivax Duffy-binding protein (PvDBP) is heavily dependent on the interaction with the human Duffy blood group antigen/receptor for chemokines (DARC) for invasion. Region II of PvDBP contains many allelic polymorphisms likely to have arisen by host immune selection. Successful vaccine development necessitates a deeper understanding of the role of these polymorphisms in both parasite function and evasion of host immunity. A 3D structure of the homologous P. knowlesi DBP predicts that most variant residues are surface-exposed, including N417K, which is a dimorphic residue change that has previously been shown to be part of a linked haplotype that alters DBP sensitivity to inhibitory antibody. In natural isolates only two residues are found at this site, asparagine (N) and lysine (K). Site-directed mutagenesis of residue 417 was used to create a panel of 20 amino acid variants that were then examined for their binding phenotype and response to immune sera. Our results suggest that the observed dimorphism likely arose due to both structural requirements and immune selection pressure. To our knowledge, this is the first exhaustive examination of this kind of the role of a single amino acid residue in antigenic character and binding ability. Our results demonstrate that a single amino acid substitution can dramatically alter both the ability of the PvDBP to bind to human erythrocytes and its antigenic character

    Sexual selection and mating system in Zorotypus gurneyi Choe (Insecta : Zoraptera)

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    Social behavior of a species in the little-known insect order Zoraptera is described for the first time. Zorotypus gurneyi Choe (Insecta: Zoraptera) is a wing-dimorphic species that lives colonially under the bark of rotting logs in central Panama. Males are larger than females in total body size and fight each other to gain access to females. Highly linear and stable dominance hierarchies exist among males. Higher-ranking males show such agonistic behavior as jerking, chasing, head-butting, hindleg-kicking, and grappling, whereas subordinates often try to avoid contacts. Higher-ranking males, the dominant males in particular, are well recognized by others and relatively free of injuries. Although the dominant males are often the largest, the correlation between body size and dominance rank is not always significant. The mating system of Z. gurneyi is an example of female defense polygyny in which the dominant males obtain the majority of matings (75% on average). Mating success among Z. gurneyi males is much more variable than that of some lekking species.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46900/1/265_2004_Article_BF00164179.pd

    Sexual selection and mating system in Zorotypus gurneyi Choe (Insecta: Zoraptera)

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    Body size is clearly an important factor influencing the outcome of agonistic contests, but is often weakly correlated with dominance ranks in Zorotypus gurneyi Choe (Insecta: Zoraptera). The study of the development and dynamics of dominance relations using artificially constructed colonies show that age, or tenure within the colony, is the prime determinant of dominance among males. Dominance hierarchies become relatively stable within 2 or 3 days and males that emerge later normally begin at the bottom of the hierarchy regardless of size. Males interact much more frequently when they are simultaneously introduced to each other than when they are allowed to emerge at different times. In the latter case, males that emerge late appear to recognize relative dominance of older males and avoid direct contests. Considering the high correlation between dominance rank and mating success, there is a strong selective advantage to males that emerge earlier and such pressure of sexual selection may be responsible for the difference in life history strategies between Z. gurneyi and its sympatric congener, Z. barberi Gurney, in central Panama.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46901/1/265_2004_Article_BF00183473.pd

    Genetic and Cellular Characterization of Caenorhabditis elegans Mutants Abnormal in the Regulation of Many Phase II Enzymes

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    Background: The phase II detoxification enzymes execute a major protective role against xenobiotics as well as endogenous toxicants. To understand how xenobiotics regulate phase II enzyme expression, acrylamide was selected as a model xenobiotic chemical, as it induces a large number and a variety of phase II enzymes, including numerous glutathione S-transferases (GSTs) in Caenorhabditis elegans. Methodology/Principal Findings: To begin dissecting genetically xenobiotics response pathways (xrep), 24 independent mutants of C. elegans that exhibited abnormal GST expression or regulation against acrylamide were isolated by screening about 3.5610 5 genomes of gst::gfp transgenic strains mutagenized with ethyl methanesulfonate (EMS). Complementation testing assigned the mutants to four different genes, named xrep-1,-2,-3, and-4. One of the genes, xrep-1, encodes WDR-23, a nematode homologue of WD repeat-containing protein WDR23. Loss-of-function mutations in xrep-1 mutants resulted in constitutive expression of many GSTs and other phase II enzymes in the absence of acrylamide, and the wild-type xrep-1 allele carried on a DNA construct successfully cured the mutant phenotype of the constitutive enzyme expression. Conclusions/Significance: Genetic and cellular characterization of xrep-1 mutants suggest that a large number of GSTs and other phase II enzymes induced by acrylamide are under negative regulation by XREP-1 (WDR-23), which is likely to be a functional equivalent of mammalian Keap1 and a regulator of SKN-1, a C. elegans analogue of cap-n-collar Nrf2 (nuclea

    Nestedness of Ectoparasite-Vertebrate Host Networks

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    Determining the structure of ectoparasite-host networks will enable disease ecologists to better understand and predict the spread of vector-borne diseases. If these networks have consistent properties, then studying the structure of well-understood networks could lead to extrapolation of these properties to others, including those that support emerging pathogens. Borrowing a quantitative measure of network structure from studies of mutualistic relationships between plants and their pollinators, we analyzed 29 ectoparasite-vertebrate host networksβ€”including three derived from molecular bloodmeal analysis of mosquito feeding patternsβ€”using measures of nestedness to identify non-random interactions among species. We found significant nestedness in ectoparasite-vertebrate host lists for habitats ranging from tropical rainforests to polar environments. These networks showed non-random patterns of nesting, and did not differ significantly from published estimates of nestedness from mutualistic networks. Mutualistic and antagonistic networks appear to be organized similarly, with generalized ectoparasites interacting with hosts that attract many ectoparasites and more specialized ectoparasites usually interacting with these same β€œgeneralized” hosts. This finding has implications for understanding the network dynamics of vector-born pathogens. We suggest that nestedness (rather than random ectoparasite-host associations) can allow rapid transfer of pathogens throughout a network, and expand upon such concepts as the dilution effect, bridge vectors, and host switching in the context of nested ectoparasite-vertebrate host networks

    Human PAPS Synthase Isoforms Are Dynamically Regulated Enzymes with Access to Nucleus and Cytoplasm

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    In higher eukaryotes, PAPS synthases are the only enzymes producing the essential sulphate-donor 3β€²-phospho-adenosine-5β€²-phosphosulphate (PAPS). Recently, PAPS synthases have been associated with several genetic diseases and retroviral infection. To improve our understanding of their pathobiological functions, we analysed the intracellular localisation of the two human PAPS synthases, PAPSS1 and PAPSS2. For both enzymes, we observed pronounced heterogeneity in their subcellular localisation. PAPSS1 was predominantly nuclear, whereas PAPSS2 localised mainly within the cytoplasm. Treatment with the nuclear export inhibitor leptomycin B had little effect on their localisation. However, a mutagenesis screen revealed an Arg-Arg motif at the kinase interface exhibiting export activity. Notably, both isoforms contain a conserved N-terminal basic Lys-Lys-Xaa-Lys motif indispensable for their nuclear localisation. This nuclear localisation signal was more efficient in PAPSS1 than in PAPSS2. The activities of the identified localisation signals were confirmed by microinjection studies. Collectively, we describe unusual localisation signals of both PAPS synthase isoforms, mobile enzymes capable of executing their function in the cytoplasm as well as in the nucleus

    The Caenorhabditis elegans Mucin-Like Protein OSM-8 Negatively Regulates Osmosensitive Physiology Via the Transmembrane Protein PTR-23

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    The molecular mechanisms of animal cell osmoregulation are poorly understood. Genetic studies of osmoregulation in yeast have identified mucin-like proteins as critical regulators of osmosensitive signaling and gene expression. Whether mucins play similar roles in higher organisms is not known. Here, we show that mutations in the Caenorhabditis elegans mucin-like gene osm-8 specifically disrupt osmoregulatory physiological processes. In osm-8 mutants, normal physiological responses to hypertonic stress, such as the accumulation of organic osmolytes and activation of osmoresponsive gene expression, are constitutively activated. As a result, osm-8 mutants exhibit resistance to normally lethal levels of hypertonic stress and have an osmotic stress resistance (Osr) phenotype. To identify genes required for Osm-8 phenotypes, we performed a genome-wide RNAi osm-8 suppressor screen. After screening ∼18,000 gene knockdowns, we identified 27 suppressors that specifically affect the constitutive osmosensitive gene expression and Osr phenotypes of osm-8 mutants. We found that one suppressor, the transmembrane protein PTR-23, is co-expressed with osm-8 in the hypodermis and strongly suppresses several Osm-8 phenotypes, including the transcriptional activation of many osmosensitive mRNAs, constitutive glycerol accumulation, and osmotic stress resistance. Our studies are the first to show that an extracellular mucin-like protein plays an important role in animal osmoregulation in a manner that requires the activity of a novel transmembrane protein. Given that mucins and transmembrane proteins play similar roles in yeast osmoregulation, our findings suggest a possible evolutionarily conserved role for the mucin-plasma membrane interface in eukaryotic osmoregulation

    VHA-19 Is Essential in Caenorhabditis elegans Oocytes for Embryogenesis and Is Involved in Trafficking in Oocytes

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    There is an urgent need to develop new drugs against parasitic nematodes, which are a significant burden on human health and agriculture. Information about the function of essential nematode-specific genes provides insight to key nematode-specific processes that could be targeted with drugs. We have characterized the function of a novel, nematode-specific Caenorhabditis elegans protein, VHA-19, and show that VHA-19 is essential in the germline and, specifically, the oocytes, for the completion of embryogenesis. VHA-19 is also involved in trafficking the oocyte receptor RME-2 to the oocyte plasma membrane and is essential for osmoregulation in the embryo, probably because VHA-19 is required for proper eggshell formation via exocytosis of cortical granules or other essential components of the eggshell. VHA-19 may also have a role in cytokinesis, either directly or as an indirect effect of its role in osmoregulation. Critically, VHA-19 is expressed in the excretory cell in both larvae and adults, suggesting that it may have a role in osmoregulation in C. elegans more generally, probably in trafficking or secretion pathways. This is the first time a role for VHA-19 has been described
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