Sample records for identify active grazers

  1. Grazer Impacts on Synechococcus Populations in the Coastal Gulf of Maine; Identifying Specific Microbial Interactions to Understand Bloom Dynamics

    NASA Astrophysics Data System (ADS)

    Countway, P. D.; Poulton, N.; Sieracki, M.; Hoeglund, A.; Anderson, S.; Burns, W. G.

    2016-02-01

    Protistan grazers help to shape the diversity, abundance, and composition of bacterial and phytoplankton communities, yet very little is known about the specific interactions between grazers and their prey. Grazers play key roles in the demise of phytoplankton blooms, with the abundance of grazers often increasing dramatically as prey-species decline. The timing and fate of Synechococcus blooms was investigated over a two-year period in Booth Bay, Maine (USA). The Synechococcus bloom in this region is characterized by several peaks in cell abundance, followed by periods of rapid decline. Two clades of Synechococcus (rpoC1 gene clades I and IV) were detected at our study site, with clade I typically present at higher abundance than clade IV. Modified grazing experiments were conducted at different stages of the Synechococcus bloom in which the natural plankton community was diluted with either 0.45 µm (grazer-free) or 30 kDa (grazer- and virus-free) filtered seawater. In general, the impact of grazers on Synechococcus populations was greater than the impact due to encounters with viruses during 24-hour in situ incubations. Interactions between grazers and Synechococcus were investigated using Fluorescence Activated Cell Sorting (FACS) combined with single-cell genomics to identify specific associations between sorted-grazers and their prey. Single-cell sequencing revealed a diverse array of heterotrophic protists on sampling dates that occurred after periods of rapid decrease in the abundance of Synechococcus. Cultures of Synechococcus were added to natural plankton communities to stimulate grazers, which were subsequently cell-sorted in bulk mode and sequenced. These experiments revealed similar taxonomic affiliations of putative grazer types (e.g., Cercozoa) that responded to the presence of Synechococcus prey. Protistan grazers appear to exert a strong degree of control on the abundance and duration of the annual Synechococcus bloom in the coastal Gulf of Maine.

  2. Reconstructing Grazer Assemblages for Protected Area Restoration

    PubMed Central

    Venter, Jan A.; Prins, Herbert H. T.; Balfour, David A.; Slotow, Rob

    2014-01-01

    Protected area management agencies often struggle to reliably reconstruct grazer assemblages due to a lack of historical distribution data for their regions. Wrong predictions of grazing assemblages could potentially affect biodiversity negatively. The objective of the study was to determine how well grazing herbivores have become established since introduction to the Mkambati Nature Reserve, South Africa, how this was influenced by facilitation and competition, and how indigenous grazer assemblages can best be predicted for effective ecological restoration. Population trends of several grazing species were investigated in in order to determine how well they have become established since introduction. Five different conceivable grazing assemblages reflecting a range of approaches that are commonly encountered during conservation planning and management decision making were assessed. Species packing was used to predict whether facilitation, competition or co-existence were more likely to occur, and the species packing of the different assemblages were assessed using ANCOVA. Reconstructing a species assemblage using biogeographic and biological information provides the opportunity for a grazer assemblage that allows for facilitatory effects, which in turn leads to an ecosystem that is able to maintain its grazer assemblage structure. The strength of this approach lies in the ability to overcome the problem of depauperate grazer assemblages, resulting from a lack of historical data, by using biogeographical and biological processes, to assist in more effectively reconstructing grazer assemblages. Adaptive management of grazer assemblage restoration through reintroduction, using this approach would further mitigate management risks. PMID:24603663

  3. The role of grazer predation strategies in the dynamics of consumer-resource based ecological models

    NASA Astrophysics Data System (ADS)

    Cropp, Roger; Moroz, Irene; Norbury, John

    2017-07-01

    We analyse a simple plankton system to provide a heuristic for more complex models such as Dynamic Green Ocean Models (DGOMs). Zooplankton foraging is either by generalist grazers that consume whatever they bump into or specialist grazers that actively seek particular prey. The zooplankton may further be classified as either facultative grazers that can survive on any of their prey or obligate grazers that depend on the presence of specific prey. A key result is that different prey dependencies can result in dramatically different impacts of grazing strategies on system outcomes. The grazing strategy can determine whether a system with obligate grazers will be stable, have regular, predictable cycles or be chaotic. Conversely, whether facultative zooplankton functioned as specialist or generalist grazers makes no qualitative difference to the dynamics of the system. These results demonstrate that the effect of different grazing strategies can be critically dependent on the grazer's dependency on specific prey. Great care must be taken when choosing functional forms for population interactions in DGOMs, particularly in scenarios such as climate change where parameters such as mortality and growth coefficients may change. A robust theoretical framework supporting model development and analysis is key to understanding how such choices can affect model properties and hence predictions.

  4. Early detection of protozoan grazers in algal biofuel cultures.

    PubMed

    Day, John G; Thomas, Naomi J; Achilles-Day, Undine E M; Leakey, Raymond J G

    2012-06-01

    Future micro-algal biofuels will most likely be derived from open-pond production systems. These are by definition open to "invasion" by grazers, which could devastate micro-algal mass-cultures. There is an urgent requirement for methodologies capable of early detection and control of grazers in dense algal cultures. In this study a model system employing the marine alga Nannochloropsis oculata was challenged by grazers including ciliates, amoebae and a heterotrophic dinoflagellate. A FlowCAM flow-cytometer was used to detect all grazers investigated (size range <20->80 μm in length) in the presence of algae. Detection limits were <10 cells ml(-1) for both "large" and "small" model grazers, Euplotes vannus (80 × 45 μm) and an unidentified holotrichous ciliate (~18 × 8 μm) respectively. Furthermore, the system can distinguish the presence of ciliates in N. oculata cultures with biotechnologically relevant cell densities; i.e. >1.4 × 10(8) cells ml(-1) (>0.5 g l(-1) dry wt.). Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Monitoring and Modeling the Impact of Grazers Using Visual, Remote and Traditional Field Techniques

    NASA Astrophysics Data System (ADS)

    Roadknight, C. M.; Marshall, I. W.; Rose, R. J.

    2009-04-01

    The relationship between wild and domestic animals and the landscape they graze upon is important to soil erosion studies because they are a strong influence on vegetation cover (a key control on the rate of overland flow runoff), and also because the grazers contribute directly to sediment transport via carriage and indirectly by exposing fresh soil by trampling and burrowing/excavating. Quantifying the impacts of these effects on soil erosion and their dependence on grazing intensity, in complex semi-natural habitats has proved difficult. This is due to lack of manpower to collect sufficient data and weak standardization of data collection between observers. The advent of cheaper and more sophisticated digital camera technology and GPS tracking devices has lead to an increase in the amount of habitat monitoring information that is being collected. We report on the use of automated trail cameras to continuously capture images of grazer (sheep, rabbits, deer) activity in a variety of habitats at the Moor House nature reserve in northern England. As well as grazer activity these cameras also give valuable information on key climatic soil erosion factors such as snow, rain and wind and plant growth and thus allow the importance of a range of grazer activities and the grazing intensity to be estimated. GPS collars and more well established survey methods (erosion monitoring, dung counting and vegetation surveys) are being used to generate a detailed representation of land usage and plan camera siting. This paper describes the data collection techniques, outlines the quantitative and qualitative data collected and proposes online and offline systems that can reduce the data processing time and increase focus on important subsets in the collected data. We also present a land usage model that estimates grazing intensity, grazer behaviours and their impact on soil coverage at sites where cameras have not been deployed, based on generalising from camera sites to other

  6. Trophic cascades result in large-scale coralline algae loss through differential grazer effects.

    PubMed

    O'Leary, Jennifer K; McClanahan, Timothy R

    2010-12-01

    Removal of predators can have strong indirect effects on primary producers through trophic cascades. Crustose coralline algae (CCA) are major primary producers worldwide that may be influenced by predator removal through changes in grazer composition and biomass. CCA have been most widely studied in Caribbean and temperate reefs, where cover increases with increasing grazer biomass due to removal of competitive fleshy algae. However, each of these systems has one dominant grazer type, herbivorous fishes or sea urchins, which may not be functionally equivalent. Where fishes and sea urchins co-occur, fishing can result in a phase shift in the grazing community with subsequent effects on CCA and other substrata. Kenyan reefs have herbivorous fishes and sea urchins, providing an opportunity to determine the relative impacts of each grazer type and evaluate potential human-induced trophic cascades. We hypothesized that fish benefit CCA, abundant sea urchins erode CCA, and that fishing indirectly reduces CCA cover by removing sea urchin predators. We used closures and fished reefs as a large-scale, long-term natural experiment to assess how fishing and resultant changes in communities affect CCA abundance. We used a short-term caging experiment to directly test the effects of grazing on CCA. CCA cover declined with increasing fish and sea urchin abundance, but the negative impact of sea urchin grazing was much stronger than that of fishes. Abundant sea urchins reduced the CCA growth rate to almost zero and prevented CCA accumulation. A warming event (El Niño Southern Oscillation, ENSO) occurred during the 18-year study and had a strong but short-term positive effect on CCA cover. However, the effect of the ENSO on CCA was lower in magnitude than the effect of sea urchin grazing. We compare our results with worldwide literature on bioerosion by fishes and sea urchins. Grazer influence depends on whether benefits of fleshy algae removal outweigh costs of grazer

  7. Grazer-induced transcriptomic and metabolomic response of the chain-forming diatom Skeletonema marinoi.

    PubMed

    Amato, Alberto; Sabatino, Valeria; Nylund, Göran M; Bergkvist, Johanna; Basu, Swaraj; Andersson, Mats X; Sanges, Remo; Godhe, Anna; Kiørboe, Thomas; Selander, Erik; Ferrante, Maria I

    2018-06-01

    Diatoms and copepods are main actors in marine food webs. The prey-predator interactions between them affect bloom dynamics, shape marine ecosystems and impact the energy transfer to higher trophic levels. Recently it has been demonstrated that the presence of grazers may affect the diatom prey beyond the direct effect of grazing. Here, we investigated the response of the chain-forming centric diatom Skeletonema marinoi to grazer cues, including changes in morphology, gene expression and metabolic profile. S. marinoi cells were incubated with Calanus finmarchicus or with Centropages typicus and in both cases responded by reducing the chain length, whereas changes in gene expression indicated an activation of stress response, changes in the lipid and nitrogen metabolism, in cell cycle regulation and in frustule formation. Transcripts linked to G protein-coupled receptors and to nitric oxide synthesis were differentially expressed suggesting involvement of these signalling transduction pathways in the response. Downregulation of a lipoxygenase in the transcriptomic data and of its products in the metabolomic data also indicate an involvement of oxylipins. Our data contribute to a better understanding of the gene function in diatoms, providing information on the nature of genes implicated in the interaction with grazers, a crucial process in marine ecosystems.

  8. Body size and the division of niche space: food and predation differentially shape the distribution of Serengeti grazers.

    PubMed

    Hopcraft, J Grant C; Anderson, T Michael; Pérez-Vila, Saleta; Mayemba, Emilian; Olff, Han

    2012-01-01

    1. Theory predicts that small grazers are regulated by the digestive quality of grass, while large grazers extract sufficient nutrients from low-quality forage and are regulated by its abundance instead. In addition, predation potentially affects populations of small grazers more than large grazers, because predators have difficulty capturing and handling large prey. 2. We analyse the spatial distribution of five grazer species of different body size in relation to gradients of food availability and predation risk. Specifically, we investigate how the quality of grass, the abundance of grass biomass and the associated risks of predation affect the habitat use of small, intermediate and large savanna grazers at a landscape level. 3. Resource selection functions of five mammalian grazer species surveyed over a 21-year period in Serengeti are calculated using logistic regressions. Variables included in the analyses are grass nitrogen, rainfall, topographic wetness index, woody cover, drainage lines, landscape curvature, water and human habitation. Structural equation modelling (SEM) is used to aggregate predictor variables into 'composites' representing food quality, food abundance and predation risk. Subsequently, SEM is used to investigate species' habitat use, defined as their recurrence in 5 × 5 km cells across repeated censuses. 4. The distribution of small grazers is constrained by predation and food quality, whereas the distribution of large grazers is relatively unconstrained. The distribution of the largest grazer (African buffalo) is primarily associated with forage abundance but not predation risk, while the distributions of the smallest grazers (Thomson's gazelle and Grant's gazelle) are associated with high grass quality and negatively with the risk of predation. The distributions of intermediate sized grazers (Coke's hartebeest and topi) suggest they optimize access to grass biomass of sufficient quality in relatively predator-safe areas. 5. The results

  9. The newly described heterotrophic dinoflagellate Gyrodinium moestrupii, an effective protistan grazer of toxic dinoflagellates.

    PubMed

    Yoo, Yeong Du; Yoon, Eun Young; Jeong, Hae Jin; Lee, Kyung Ha; Hwang, Yeong Jong; Seong, Kyeong Ah; Kim, Jae Seong; Park, Jae Yeon

    2013-01-01

    Few protistan grazers feed on toxic dinoflagellates, and low grazing pressure on toxic dinoflagellates allows these dinoflagellates to form red-tide patches. We explored the feeding ecology of the newly described heterotrophic dinoflagellate Gyrodinium moestrupii when it fed on toxic strains of Alexandrium minutum, Alexandrium tamarense, and Karenia brevis and on nontoxic strains of A. tamarense, Prorocentrum minimum, and Scrippsiella trochoidea. Specific growth rates of G. moestrupii feeding on each of these dinoflagellates either increased continuously or became saturated with increasing mean prey concentration. The maximum specific growth rate of G. moestrupii feeding on toxic A. minutum (1.60/d) was higher than that when feeding on nontoxic S. trochoidea (1.50/d) or P. minimum (1.07/d). In addition, the maximum growth rate of G. moestrupii feeding on the toxic strain of A. tamarense (0.68/d) was similar to that when feeding on the nontoxic strain of A. tamarense (0.71/d). Furthermore, the maximum ingestion rate of G. moestrupii on A. minutum (2.6 ng C/grazer/d) was comparable to that of S. trochoidea (3.0 ng C/grazer/d). Additionally, the maximum ingestion rate of G. moestrupii on the toxic strain of A. tamarense (2.1 ng C/grazer/d) was higher than that when feeding on the nontoxic strain of A. tamarense (1.3 ng C/grazer/d). Thus, feeding by G. moestrupii is not suppressed by toxic dinoflagellate prey, suggesting that it is an effective protistan grazer of toxic dinoflagellates. © 2012 The Author(s) Journal of Eukaryotic Microbiology © 2012 International Society of Protistologists.

  10. Grazer responses to variable macroalgal resource conditions facilitate habitat structuring

    PubMed Central

    Perissinotto, Renzo; Bird, Matthew S.; Pelletier, Noémie

    2018-01-01

    Consumer responses to altered resource conditions can vary depending on dietary preference, resource characteristics and secondary resource features such as shelter. These can have cascading effects, especially if the consumed resource impacts on overall ecological functioning. In this study, we assessed the dietary composition of grazer communities following seasonal changes in the characteristics of their staple food-source (macroalgae). This was conducted in the living stromatolite pools growing along the coast of South Africa. Stable isotope mixing models suggested that following macroalgal bleaching in summer, metazoan consumers shifted their diet from predominantly macroalgae to a generalist composition. This has important implications for the integrity of the stromatolite matrix and its layered deposition. Where previously in winter stromatolite microalgae comprised a minor component of metazoan consumer diets, in summer, following a change in the resource conditions of macroalgae, microalgae featured more prominently in grazer diets. This seasonal grazing pressure on stromatolite-related resources probably promotes the pattern of annual layering observed in the stromatolite accretion. It also demonstrates a mechanism whereby grazer dietary shifts following a change in their preferred food resource can affect the ecosystem structure of their environment, specifically the stromatolite layering process which responds to microalgal growth or grazing conditions. PMID:29410845

  11. Interaction strength between different grazers and macroalgae mediated by ocean acidification over warming gradients.

    PubMed

    Sampaio, E; Rodil, I F; Vaz-Pinto, F; Fernández, A; Arenas, F

    2017-04-01

    Since the past century, rising CO 2 levels have led to global changes (ocean warming and acidification) with subsequent effects on marine ecosystems and organisms. Macroalgae-herbivore interactions have a main role in the regulation of marine community structure (top-down control). Gradients of warming prompt complex non-linear effects on organism metabolism, cascading into altered trophic interactions and community dynamics. However, not much is known on how will acidification and grazer assemblage composition shape these effects. Within this context, we aimed to assess the combined effects of warming gradients and acidification on macroalgae-herbivore interactions, using three cosmopolitan species, abundant in the Iberian Peninsula and closely associated in nature: the amphipod Melita palmata, the gastropod Gibbula umbilicalis, and the green macroalga Ulva rigida. Under two CO 2 treatments (ΔCO 2 ≃ 450 μatm) across a temperature gradient (13.5, 16.6, 19.9 and 22.1 °C), two mesocosm experiments were performed to assess grazer consumption rates and macroalgae-herbivore interaction, respectively. Warming (Experiment I and II) and acidification (Experiment II) prompted negative effects in grazer's survival and species-specific differences in consumption rates. M. palmata was shown to be the stronger grazer per biomass (but not per capita), and also the most affected by climate stressors. Macroalgae-herbivore interaction strength was markedly shaped by the temperature gradient, while simultaneous acidification lowered thermal optimal threshold. In the near future, warming and acidification are likely to strengthen top-down control, but further increases in disturbances may lead to bottom-up regulated communities. Finally, our results suggest that grazer assemblage composition may modulate future macroalgae-herbivore interactions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Mammoth grazers on the ocean's minuteness: a review of selective feeding using mucous meshes

    PubMed Central

    2018-01-01

    Mucous-mesh grazers (pelagic tunicates and thecosome pteropods) are common in oceanic waters and efficiently capture, consume and repackage particles many orders of magnitude smaller than themselves. They feed using an adhesive mucous mesh to capture prey particles from ambient seawater. Historically, their grazing process has been characterized as non-selective, depending only on the size of the prey particle and the pore dimensions of the mesh. The purpose of this review is to reverse this assumption by reviewing recent evidence that shows mucous-mesh feeding can be selective. We focus on large planktonic microphages as a model of selective mucus feeding because of their important roles in the ocean food web: as bacterivores, prey for higher trophic levels, and exporters of carbon via mucous aggregates, faecal pellets and jelly-falls. We identify important functional variations in the filter mechanics and hydrodynamics of different taxa. We review evidence that shows this feeding strategy depends not only on the particle size and dimensions of the mesh pores, but also on particle shape and surface properties, filter mechanics, hydrodynamics and grazer behaviour. As many of these organisms remain critically understudied, we conclude by suggesting priorities for future research. PMID:29720410

  13. Diverse protist grazers select for virulence-related traits in Legionella

    PubMed Central

    Amaro, Francisco; Wang, Wen; Gilbert, Jack A; Roger Anderson, O; Shuman, Howard A

    2015-01-01

    It is generally accepted that selection for resistance to grazing by protists has contributed to the evolution of Legionella pneumophila as a pathogen. Grazing resistance is becoming more generally recognized as having an important role in the ecology and evolution of bacterial pathogenesis. However, selection for grazing resistance presupposes the existence of protist grazers that provide the selective pressure. To determine whether there are protists that graze on pathogenic Legionella species, we investigated the existence of such organisms in a variety of environmental samples. We isolated and characterized diverse protists that graze on L. pneumophila and determined the effects of adding L. pneumophila on the protist community structures in microcosms made from these environmental samples. Several unrelated organisms were able to graze efficiently on L. pneumophila. The community structures of all samples were markedly altered by the addition of L. pneumophila. Surprisingly, some of the Legionella grazers were closely related to species that are known hosts for L. pneumophila, indicating the presence of unknown specificity determinants for this interaction. These results provide the first direct support for the hypothesis that protist grazers exert selective pressure on Legionella to acquire and retain adaptations that contribute to survival, and that these properties are relevant to the ability of the bacteria to cause disease in people. We also report a novel mechanism of killing of amoebae by one Legionella species that requires an intact Type IV secretion system but does not involve intracellular replication. We refer to this phenomenon as ‘food poisoning'. PMID:25575308

  14. The impact of exploiting grazers (Scaridae) on the dynamics of Caribbean coral reefs.

    PubMed

    Mumby, Peter J

    2006-04-01

    Coral reefs provide a number of ecosystem services including coastal defense from storms, the generation of building materials, and fisheries. It is increasingly clear that the management of reef resources requires an ecosystem approach in which extractive activities are weighed against the needs of the ecosystem and its functions rather than solely those of the fishery. Here, I use a spatially explicit simulation model of a Caribbean coral reef to examine the ecosystem requirements for grazing which is primarily conducted by parrotfishes (Scaridae). The model allows the impact of fishing grazers to be assessed in the wider context of other ecosystem processes including coral-algal competition, hurricanes, and mass extinction of the herbivorous urchin Diadema antillarum. Using a new analytical model of scarid grazing, it is estimated that parrotfishes can only maintain between 10% and 30% of a structurally complex forereef in a grazed state. Predictions from this grazing model were then incorporated into a broader simulation model of the ecosystem. Simulations predict that scarid grazing is unable to maintain high levels of coral cover (> or = 30%) when severe hurricanes occur on a decadal basis, such as occurs in parts of the northern Caribbean. However, reefs can withstand such intense disturbance when grazing is undertaken by both scarids and the urchin Diadema. Scarid grazing is predicted to allow recovery from hurricanes when their incidence falls to 20 years or less (e.g., most of Central and South America). Sensitivity analyses revealed that scarid grazing had the most acute impact on model behavior, and depletion led to the emergence of a stable, algal-dominated community state. Under conditions of heavy grazer depletion, coral cover was predicted to decline rapidly from an initial level of 30% to less than 1% within 40 years, even when hurricane frequency was low at 60 years. Depleted grazers caused a population bottleneck in juvenile corals in which algal

  15. Loss of a large grazer impacts savanna grassland plant communities similarly in North America and South Africa.

    PubMed

    Eby, Stephanie; Burkepile, Deron E; Fynn, Richard W S; Burns, Catherine E; Govender, Navashni; Hagenah, Nicole; Koerner, Sally E; Matchett, Katherine J; Thompson, Dave I; Wilcox, Kevin R; Collins, Scott L; Kirkman, Kevin P; Knapp, Alan K; Smith, Melinda D

    2014-05-01

    Large herbivore grazing is a widespread disturbance in mesic savanna grasslands which increases herbaceous plant community richness and diversity. However, humans are modifying the impacts of grazing on these ecosystems by removing grazers. A more general understanding of how grazer loss will impact these ecosystems is hampered by differences in the diversity of large herbivore assemblages among savanna grasslands, which can affect the way that grazing influences plant communities. To avoid this we used two unique enclosures each containing a single, functionally similar large herbivore species. Specifically, we studied a bison (Bos bison) enclosure at Konza Prairie Biological Station, USA and an African buffalo (Syncerus caffer) enclosure in Kruger National Park, South Africa. Within these enclosures we erected exclosures in annually burned and unburned sites to determine how grazer loss would impact herbaceous plant communities, while controlling for potential fire-grazing interactions. At both sites, removal of the only grazer decreased grass and forb richness, evenness and diversity, over time. However, in Kruger these changes only occurred with burning. At both sites, changes in plant communities were driven by increased dominance with herbivore exclusion. At Konza, this was caused by increased abundance of one grass species, Andropogon gerardii, while at Kruger, three grasses, Themeda triandra, Panicum coloratum, and Digitaria eriantha increased in abundance.

  16. Grazers and phytoplankton growth in the oceans: an experimental and evolutionary perspective.

    PubMed

    Ratti, Simona; Knoll, Andrew H; Giordano, Mario

    2013-01-01

    The taxonomic composition of phytoplankton responsible for primary production on continental shelves has changed episodically through Earth history. Geological correlations suggest that major changes in phytoplankton composition correspond in time to changes in grazing and seawater chemistry. Testing hypotheses that arise from these correlations requires experimentation, and so we carried out a series of experiments in which selected phytoplankton species were grown in treatments that differed with respect to the presence or absence of grazers as well as seawater chemistry. Both protistan (Euplotes sp.) and microarthropod (Acartia tonsa) grazers changed the growth dynamics and biochemical composition of the green alga Tetraselmis suecica, the diatom Thalassiosira weissflogii, and the cyanobacterium Synechococcus sp., increasing the specific growth rate and palatability of the eukaryotic algae, while decreasing or leaving unchanged both parameters in the cyanobacteria. Synechococcus (especially) and Thalassiosira produced toxins effective against the copepod, but ciliate growth was unaffected. Acartia induced a 4-6 fold increase of Si cell quota in the diatom, but Euplotes had no similar effect. The differential growth responses of the eukaryotic algae and cyanobacteria to ciliate grazing may help to explain the apparently coeval radiation of eukaryophagic protists and rise of eukaryotes to ecological prominence as primary producers in Neoproterozoic oceans. The experimental results suggest that phytoplankton responses to the later radiation of microarthropod grazers were clade-specific, and included changes in growth dynamics, toxin synthesis, encystment, and (in diatoms) enhanced Si uptake.

  17. Use of stable isotope-labelled cells to identify active grazers of picocyanobacteria in ocean surface waters.

    PubMed

    Frias-Lopez, Jorge; Thompson, Anne; Waldbauer, Jacob; Chisholm, Sallie W

    2009-02-01

    Prochlorococcus and Synechococcus are the two most abundant marine cyanobacteria. They represent a significant fraction of the total primary production of the world oceans and comprise a major fraction of the prey biomass available to phagotrophic protists. Despite relatively rapid growth rates, picocyanobacterial cell densities in open-ocean surface waters remain fairly constant, implying steady mortality due to viral infection and consumption by predators. There have been several studies on grazing by specific protists on Prochlorococcus and Synechococcus in culture, and of cell loss rates due to overall grazing in the field. However, the specific sources of mortality of these primary producers in the wild remain unknown. Here, we use a modification of the RNA stable isotope probing technique (RNA-SIP), which involves adding labelled cells to natural seawater, to identify active predators that are specifically consuming Prochlorococcus and Synechococcus in the surface waters of the Pacific Ocean. Four major groups were identified as having their 18S rRNA highly labelled: Prymnesiophyceae (Haptophyta), Dictyochophyceae (Stramenopiles), Bolidomonas (Stramenopiles) and Dinoflagellata (Alveolata). For the first three of these, the closest relative of the sequences identified was a photosynthetic organism, indicating the presence of mixotrophs among picocyanobacterial predators. We conclude that the use of RNA-SIP is a useful method to identity specific predators for picocyanobacteria in situ, and that the method could possibly be used to identify other bacterial predators important in the microbial food-web.

  18. Hydrologic drivers and controls of stream biofilm-grazer interactions

    NASA Astrophysics Data System (ADS)

    Ceola, S.; Bertuzzo, E.; Mari, L.; Botter, G.; Hödl, I.; Battin, T.; Rinaldo, A.

    2012-04-01

    Understanding the dynamics of fluvial ecosystems linked to hydrology is one of the most important challenges of ecohydrology. In fact, streamflow, which chiefly relies on rainfall, climate, land use and geomorphologic properties, plays a fundamental role in sustaining and regulating fluvial ecosystem integrity. To analyze possible implications of hydrological fluctuations on the biofilm-grazer interaction, an experimental campaign has been conducted between June and September 2011 at the Wasser Cluster Lunz, in Lunz am See (AU). 36 flumes have been used to perform biofilm growth and grazing activity under two distinct discharge conditions (i.e., constant and stochastic discharge regimes) and four different light regimes (from natural light conditions to nearly 70% attenuation). Experimental results concerning (i) dynamics of biofilm growth, (ii) grazing effect, and (iii) grazing rate will be presented. Results of performed statistical analysis for testing the effects of discharge treatment and light regime on the grazing rate will be also discussed.

  19. Endemic grazers control benthic microalgal growth in a eutrophic tropical brackish ecosystem

    Treesearch

    T.S. Sakihara; B.D. Dudley; R.A. MacKenzie; J.P. Beets

    2015-01-01

    Anthropogenic changes to nutrient supply, numbers and behavior of grazers and interactions of these factors are known to change epilithon composition and biomass. In brackish waters, these changes occur across wide-ranging abiotic conditions (e.g. nutrient concentrations and salinity), which may alter their relative impacts on microphytobenthic communities. Such...

  20. NUTRIENTS, CANOPY COVER, AND GRAZERS: THEIR EFFECTS ON SUMMER PERIPHYTON IN SMALL MIDWESTERN STREAMS

    EPA Science Inventory

    Numerous studies in artificial streams suggest the relationship between nurients and periphyton biomass (AFDM) and chlorophyll a in streams is affected by ambient light, which is influenced by canopy cover, and by grazer densities. To assess the relationships between nutrients a...

  1. Short-term effects of increased temperature and lowered pH on a temperate grazer-seaweed interaction (Littorina obtusata/Ascophyllum nodosum)

    NASA Astrophysics Data System (ADS)

    Cardoso, Patricia G.; Grilo, Tiago F.; Dionísio, Gisela; Aurélio, Maria; Lopes, Ana R.; Pereira, Ricardo; Pacheco, Mário; Rosa, Rui

    2017-10-01

    There has been a significant increase in the literature regarding the effects of warming and acidification on the marine ecosystem. To our knowledge, there is very little information on the potential effects of both combined stressors on marine grazer-seaweed interactions. Here, we evaluated, for the first time several phenotypic responses (e.g periwinkle survival, condition index, consumption rates, seaweed photosynthetic activity and oxidative stress) of the temperate periwinkle Littorina obtusata (grazer) and the brown seaweed Ascophyllum nodosum (prey) to such climate change-related variables, for 15 days. Increased temperature (22 °C, pH 8.0) elicited a significant lethal effect on the periwinkle within a short-term period (mortality rate > 90%). Acidification condition (18 °C, pH 7.6) was the one that showed lower mortality rates (≈20%), reflected by lower impact on periwinkle fitness and consumption rates. Under a scenario of increased temperature and lowered pH the antioxidant defences of L. obtusata seemed to be supressed increasing the risk of peroxidative damage. The seaweed evidenced signs of cellular damage under such conditions. These results suggest that: i) lower pH per se seems to benefit the interaction between grazer and seaweed while, ii) a combined scenario of increased temperature and lowered pH may be negative for the interaction, due to the unbalance between periwinkle mortality rates and consumption rates. But most importantly, since grazing often plays an important role on structuring natural communities, such predator-prey disturbances can elicit cascading effects on the remaining community structure and functioning of the temperate rocky-shore ecosystems.

  2. Interspecific Competition for Shelters in Territorial and Gregarious Intertidal Grazers: Consequences for Individual Behaviour

    PubMed Central

    Aguilera, Moisés A.; Navarrete, Sergio A.

    2012-01-01

    Experiments have shown that interspecific interactions within consumer guilds can alter patterns of distribution, abundance and size of species. Plastic behavioural responses can be modulated by agonistic interactions. In many cases, consumers compete for space and shelters, and these interactions change the manner in which they exploit food. This study investigates the consequences of competition in the spatial and temporal organization of behaviour of intertidal grazers, which share algal resources and the use of rock crevices while resting, but exhibit different body sizes, spatial behaviour and foraging modes. We evaluate interaction strength between small gregarious Siphonaria lessoni and the larger territorial keyhole limpet Fissurella crassa and between S. lessoni and the medium-size gregarious chiton Chiton granosus. Using field manipulations and artificial arenas in the laboratory, we tested whether the use of crevices, micro-spatial distribution and activity are modified by the density of conspecifics and the presence of heterospecifics. Our results show that small-scale spatial segregation observed in the field between S. lessoni and C. granosus result from species-specific differences in habitat use. In turn, we found evidence that spatial segregation between F. crassa and S. lessoni results from highly asymmetric interference competition in the use of shelters. The presence of F. crassa reduced the use of crevices and growth rates of S. lessoni. Effects on growth rates are assumed to result from exposure to harsh environmental conditions rather than food limitation. Thus, neither gregarious behaviour nor differences in activity were sufficient to prevent competition with the larger grazer. Our study illustrates the importance of competition for shelters, which results in behavioural changes of the smaller-sized species, and how these plastic responses can translate into differences in growth rates. Use of shelters can thus be modulated by environmental

  3. Effects of co-existing microalgae and grazers on the production of hemolytic toxins in Karenia mikimotoi

    NASA Astrophysics Data System (ADS)

    Yang, Weidong; Zhang, Naisheng; Cui, Weimin; Xu, Yanyan; Li, Hongye; Liu, Jiesheng

    2011-11-01

    Karenia mikimotoi (Miyake & Kominami ex Oda) Hansen & Moestrup is associated with harmful algal blooms in temperate and subtropical zones of the world. The hemolytic substances produced by K. mikimotoi are thought to cause mortality in fishes and invertebrates. We evaluated the composition of the hemolytic toxin produced by K. mikimotoi cultured in the laboratory using thin-layer chromatography. In addition, we evaluated the effect of co-occuring algae ( Prorocentrum donghaiense and Alexandrium tamarense) and the cladoceran grazer Moina mongolica on hemolytic toxin production in K. mikimotoi. The hemolytic toxins from K. mikimotoi were a mixture of 2 liposaccharides and 1 lipid. Waterborne clues from P. donghaiense and A. tamarense inhibited the growth of K. mikimotoi but increased the production of hemolytic toxins. Conversely, K. mikimotoi strongly inhibited the growth of caged P. donghaiense and A. tamarense. In addition, the ingestion of K. mikimotoi by M. mongolica induced the production of hemolytic toxins in K. mikimotoi. Taken together, our results suggest that the presence of other microalgae and grazers may be as important as environmental factors for controlling the production of hemolytic substances. K. mikimotoi secreted allelochemicals other than unstable fatty acids with hemolytic activity. The production of hemolytic toxins in dinoflagellates was not only dependent on resource availability, but also on the risk of predation. Hemolytic toxins likely play an important role as chemical deterrents secreted by K. mikimotoi.

  4. Do pelagic grazers benefit from sea ice? Insights from the Antarctic sea ice proxy IPSO25

    NASA Astrophysics Data System (ADS)

    Schmidt, Katrin; Brown, Thomas A.; Belt, Simon T.; Ireland, Louise C.; Taylor, Kyle W. R.; Thorpe, Sally E.; Ward, Peter; Atkinson, Angus

    2018-04-01

    Sea ice affects primary production in polar regions in multiple ways. It can dampen water column productivity by reducing light or nutrient supply, provide a habitat for ice algae and condition the marginal ice zone (MIZ) for phytoplankton blooms on its seasonal retreat. The relative importance of three different carbon sources (sea ice derived, sea ice conditioned, non-sea-ice associated) for the polar food web is not well understood, partly due to the lack of methods that enable their unambiguous distinction. Here we analysed two highly branched isoprenoid (HBI) biomarkers to trace sea-ice-derived and sea-ice-conditioned carbon in Antarctic krill (Euphausia superba) and relate their concentrations to the grazers' body reserves, growth and recruitment. During our sampling in January-February 2003, the proxy for sea ice diatoms (a di-unsaturated HBI termed IPSO25, δ13C = -12.5 ± 3.3 ‰) occurred in open waters of the western Scotia Sea, where seasonal ice retreat was slow. In suspended matter from surface waters, IPSO25 was present at a few stations close to the ice edge, but in krill the marker was widespread. Even at stations that had been ice-free for several weeks, IPSO25 was found in krill stomachs, suggesting that they gathered the ice-derived algae from below the upper mixed layer. Peak abundances of the proxy for MIZ diatoms (a tri-unsaturated HBI termed HBI III, δ13C = -42.2 ± 2.4 ‰) occurred in regions of fast sea ice retreat and persistent salinity-driven stratification in the eastern Scotia Sea. Krill sampled in the area defined by the ice edge bloom likewise contained high amounts of HBI III. As indicators for the grazer's performance we used the mass-length ratio, size of digestive gland and growth rate for krill, and recruitment for the biomass-dominant calanoid copepods Calanoides acutus and Calanus propinquus. These indices consistently point to blooms in the MIZ as an important feeding ground for pelagic grazers. Even though ice

  5. Macro-grazer herbivory regulates seagrass response to pulse and press nutrient loading.

    PubMed

    Ravaglioli, Chiara; Capocchi, Antonella; Fontanini, Debora; Mori, Giovanna; Nuccio, Caterina; Bulleri, Fabio

    2018-05-01

    Coastal ecosystems are exposed to multiple stressors. Predicting their outcomes is complicated by variations in their temporal regimes. Here, by means of a 16-month experiment, we investigated tolerance and resistance traits of Posidonia oceanica to herbivore damage under different regimes of nutrient loading. Chronic and pulse nutrient supply were combined with simulated fish herbivory, treated as a pulse stressor. At ambient nutrient levels, P. oceanica could cope with severe herbivory, likely through an increase in photosynthetic activity. Elevated nutrient levels, regardless of the temporal regime, negatively affected plant growth and increased leaf nutritional quality. This ultimately resulted in a reduction of plant biomass that was particularly severe under chronic fertilization. Our results suggest that both chronic and pulse nutrient loadings increase plant palatability to macro-grazers. Strategies for seagrass management should not be exclusively applied in areas exposed to chronic fertilization since even short-term nutrient pulses could alter seagrass meadows. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Acidification increases abundances of Vibrionales and Planctomycetia associated to a seaweed-grazer system: potential consequences for disease and prey digestion efficiency.

    PubMed

    Aires, Tania; Serebryakova, Alexandra; Viard, Frédérique; Serrão, Ester A; Engelen, Aschwin H

    2018-01-01

    Ocean acidification significantly affects marine organisms in several ways, with complex interactions. Seaweeds might benefit from rising CO 2 through increased photosynthesis and carbon acquisition, with subsequent higher growth rates. However, changes in seaweed chemistry due to increased CO 2 may change the nutritional quality of tissue for grazers. In addition, organisms live in close association with a diverse microbiota, which can also be influenced by environmental changes, with feedback effects. As gut microbiomes are often linked to diet, changes in seaweed characteristics and associated microbiome can affect the gut microbiome of the grazer, with possible fitness consequences. In this study, we experimentally investigated the effects of acidification on the microbiome of the invasive brown seaweed Sargassum muticum and a native isopod consumer Synisoma nadejda . Both were exposed to ambient CO 2 conditions (380 ppm, pH 8.16) and an acidification treatment (1,000 ppm, pH 7.86) for three weeks. Microbiome diversity and composition were determined using high-throughput sequencing of the variable regions V5-7 of 16S rRNA. We anticipated that as a result of acidification, the seaweed-associated bacterial community would change, leading to further changes in the gut microbiome of grazers. However, no significant effects of elevated CO 2 on the overall bacterial community structure and composition were revealed in the seaweed. In contrast, significant changes were observed in the bacterial community of the grazer gut. Although the bacterial community of S. muticum as whole did not change, Oceanospirillales and Vibrionales (mainly Pseudoalteromonas ) significantly increased their abundance in acidified conditions. The former, which uses organic matter compounds as its main source, may have opportunistically taken advantage of the possible increase of the C/N ratio in the seaweed under acidified conditions. Pseudoalteromonas, commonly associated to diseased

  7. Acidification increases abundances of Vibrionales and Planctomycetia associated to a seaweed-grazer system: potential consequences for disease and prey digestion efficiency

    PubMed Central

    Viard, Frédérique; Serrão, Ester A.

    2018-01-01

    Ocean acidification significantly affects marine organisms in several ways, with complex interactions. Seaweeds might benefit from rising CO2 through increased photosynthesis and carbon acquisition, with subsequent higher growth rates. However, changes in seaweed chemistry due to increased CO2 may change the nutritional quality of tissue for grazers. In addition, organisms live in close association with a diverse microbiota, which can also be influenced by environmental changes, with feedback effects. As gut microbiomes are often linked to diet, changes in seaweed characteristics and associated microbiome can affect the gut microbiome of the grazer, with possible fitness consequences. In this study, we experimentally investigated the effects of acidification on the microbiome of the invasive brown seaweed Sargassum muticum and a native isopod consumer Synisoma nadejda. Both were exposed to ambient CO2 conditions (380 ppm, pH 8.16) and an acidification treatment (1,000 ppm, pH 7.86) for three weeks. Microbiome diversity and composition were determined using high-throughput sequencing of the variable regions V5-7 of 16S rRNA. We anticipated that as a result of acidification, the seaweed-associated bacterial community would change, leading to further changes in the gut microbiome of grazers. However, no significant effects of elevated CO2 on the overall bacterial community structure and composition were revealed in the seaweed. In contrast, significant changes were observed in the bacterial community of the grazer gut. Although the bacterial community of S. muticum as whole did not change, Oceanospirillales and Vibrionales (mainly Pseudoalteromonas) significantly increased their abundance in acidified conditions. The former, which uses organic matter compounds as its main source, may have opportunistically taken advantage of the possible increase of the C/N ratio in the seaweed under acidified conditions. Pseudoalteromonas, commonly associated to diseased seaweeds

  8. Grazers structure the bacterial and algal diversity of aquatic metacommunities.

    PubMed

    Birtel, Julia; Matthews, Blake

    2016-12-01

    Consumers can have strong effects on the biotic and abiotic dynamics of spatially-structured ecosystems. In metacommunities, dispersing consumers can alter local assembly dynamics either directly through trophic interactions or indirectly by modifying local environmental conditions. In aquatic systems, very little is known about how key grazers, such as Daphnia, structure the microbial diversity of metacommunities and influence bacterial-mediated ecosystem functions. In an outdoor mesocosm experiment with replicate metacommunities (two 300 L mesocosms), we tested how the presence and absence of Daphnia and the initial density of the microbial community (manipulated via dilution) influenced the diversity and community structure of algae and bacteria, and several ecosystem properties (e.g., pH, dissolved substances) and functions (e.g., enzyme activity, respiration). We found that Daphnia strongly affected the local and regional diversity of both phytoplankton and bacteria, the taxonomic composition of bacterial communities, the biomass of algae, and ecosystem metabolism (i.e., respiration). Diluting the microbial inoculum (0.2-5 μm size fraction) to the metacommunities increased local phytoplankton diversity, decreased bacteria beta-diversity, and changed the relative abundance of bacterial classes. Changes in the rank abundance of different bacterial groups exhibited phylogenetic signal, implying that closely related bacteria species might share similar responses to the presence of Daphnia. © 2016 by the Ecological Society of America.

  9. Climatic warming and the future of bison as grazers

    NASA Astrophysics Data System (ADS)

    Craine, Joseph M.; Towne, E. Gene; Miller, Mary; Fierer, Noah

    2015-11-01

    Climatic warming is likely to exacerbate nutritional stress and reduce weight gain in large mammalian herbivores by reducing plant nutritional quality. Yet accurate predictions of the effects of climatic warming on herbivores are limited by a poor understanding of how herbivore diet varies along climate gradients. We utilized DNA metabarcoding to reconstruct seasonal variation in the diet of North American bison (Bison bison) in two grasslands that differ in mean annual temperature by 6 °C. Here, we show that associated with greater nutritional stress in warmer climates, bison consistently consumed fewer graminoids and more shrubs and forbs, i.e. eudicots. Bison in the warmer grassland consumed a lower proportion of C3 grass, but not a greater proportion of C4 grass. Instead, bison diet in the warmer grassland had a greater proportion of N2-fixing eudicots, regularly comprising >60% of their protein intake in spring and fall. Although bison have been considered strict grazers, as climatic warming reduces grass protein concentrations, bison may have to attempt to compensate by grazing less and browsing more. Promotion of high-protein, palatable eudicots or increasing the protein concentrations of grasses will be critical to minimizing warming-imposed nutritional stress for bison and perhaps other large mammalian herbivores.

  10. Ocean acidification and rising temperatures may increase biofilm primary productivity but decrease grazer consumption

    PubMed Central

    Russell, Bayden D.; Connell, Sean D.; Findlay, Helen S.; Tait, Karen; Widdicombe, Stephen; Mieszkowska, Nova

    2013-01-01

    Climate change may cause ecosystems to become trophically restructured as a result of primary producers and consumers responding differently to increasing CO2 and temperature. This study used an integrative approach using a controlled microcosm experiment to investigate the combined effects of CO2 and temperature on key components of the intertidal system in the UK, biofilms and their consumers (Littorina littorea). In addition, to identify whether pre-exposure to experimental conditions can alter experimental outcomes we explicitly tested for differential effects on L. littorea pre-exposed to experimental conditions for two weeks and five months. In contrast to predictions based on metabolic theory, the combination of elevated temperature and CO2 over a five-week period caused a decrease in the amount of primary productivity consumed by grazers, while the abundance of biofilms increased. However, long-term pre-exposure to experimental conditions (five months) altered this effect, with grazing rates in these animals being greater than in animals exposed only for two weeks. We suggest that the structure of future ecosystems may not be predictable using short-term laboratory experiments alone owing to potentially confounding effects of exposure time and effects of being held in an artificial environment over prolonged time periods. A combination of laboratory (physiology responses) and large, long-term experiments (ecosystem responses) may therefore be necessary to adequately predict the complex and interactive effects of climate change as organisms may acclimate to conditions over the longer term. PMID:23980241

  11. Ocean acidification and rising temperatures may increase biofilm primary productivity but decrease grazer consumption.

    PubMed

    Russell, Bayden D; Connell, Sean D; Findlay, Helen S; Tait, Karen; Widdicombe, Stephen; Mieszkowska, Nova

    2013-01-01

    Climate change may cause ecosystems to become trophically restructured as a result of primary producers and consumers responding differently to increasing CO2 and temperature. This study used an integrative approach using a controlled microcosm experiment to investigate the combined effects of CO2 and temperature on key components of the intertidal system in the UK, biofilms and their consumers (Littorina littorea). In addition, to identify whether pre-exposure to experimental conditions can alter experimental outcomes we explicitly tested for differential effects on L. littorea pre-exposed to experimental conditions for two weeks and five months. In contrast to predictions based on metabolic theory, the combination of elevated temperature and CO2 over a five-week period caused a decrease in the amount of primary productivity consumed by grazers, while the abundance of biofilms increased. However, long-term pre-exposure to experimental conditions (five months) altered this effect, with grazing rates in these animals being greater than in animals exposed only for two weeks. We suggest that the structure of future ecosystems may not be predictable using short-term laboratory experiments alone owing to potentially confounding effects of exposure time and effects of being held in an artificial environment over prolonged time periods. A combination of laboratory (physiology responses) and large, long-term experiments (ecosystem responses) may therefore be necessary to adequately predict the complex and interactive effects of climate change as organisms may acclimate to conditions over the longer term.

  12. Stochastic spatio-temporal model of coral cover as a function of herbivorous grazers, water quality, and coral demographics

    NASA Astrophysics Data System (ADS)

    Neuhausler, R.; Robinson, M.; Bruna, M.

    2017-12-01

    Over the last 60 years we have seen an increased amount of ecological regime shifts in tropical coastal zones, from coral reefs to macroalgae dominated states, as a result of natural and anthropogenic stresses. However, these shifts are not always immediate- macroalgae are generally present in coral reefs, with their distribution regulated by herbivorous fish. This is especially true in Moorea, French Polynesia, where macroalgae are shown to flourish in spaces that provide refuge from roaming herbivores. While there are currently modeling efforts in projecting ecological regime shifts in Moorea, temporal deterministic models have been utilized, which fail to capture metastability between multiple steady states and can have issues when dealing with very small populations. To address these concerns, we build on these models to account for spatial variations and individual organisms, as well as stochasticity. Our model can project the percent cover of coral, macroalgae, and algae turf as a function of herbivorous grazers, water quality, and coral demographics. Grazers, included as individual fish (particles), evolve according to a kinetic model and interact with neighbouring benthic assemblages, represented as nodes. Water quality and coral demographics are input parameters that can vary over time, allowing our model to be run for temporally changing scenarios and to be adjusted for different reefs. We plan to engage with previous Moorea Reef Resilience Models through a comparative analysis of our models' outcomes and existing Moorea data. Coupling projective models with available data is useful for informing environmental policy and advancing the modeling field.

  13. Thick-shelled, grazer-protected diatoms decouple ocean carbon and silicon cycles in the iron-limited Antarctic Circumpolar Current

    PubMed Central

    Assmy, Philipp; Smetacek, Victor; Montresor, Marina; Klaas, Christine; Henjes, Joachim; Strass, Volker H.; Arrieta, Jesús M.; Bathmann, Ulrich; Berg, Gry M.; Breitbarth, Eike; Cisewski, Boris; Friedrichs, Lars; Fuchs, Nike; Herndl, Gerhard J.; Jansen, Sandra; Krägefsky, Sören; Latasa, Mikel; Peeken, Ilka; Röttgers, Rüdiger; Scharek, Renate; Schüller, Susanne E.; Steigenberger, Sebastian; Webb, Adrian; Wolf-Gladrow, Dieter

    2013-01-01

    Diatoms of the iron-replete continental margins and North Atlantic are key exporters of organic carbon. In contrast, diatoms of the iron-limited Antarctic Circumpolar Current sequester silicon, but comparatively little carbon, in the underlying deep ocean and sediments. Because the Southern Ocean is the major hub of oceanic nutrient distribution, selective silicon sequestration there limits diatom blooms elsewhere and consequently the biotic carbon sequestration potential of the entire ocean. We investigated this paradox in an in situ iron fertilization experiment by comparing accumulation and sinking of diatom populations inside and outside the iron-fertilized patch over 5 wk. A bloom comprising various thin- and thick-shelled diatom species developed inside the patch despite the presence of large grazer populations. After the third week, most of the thinner-shelled diatom species underwent mass mortality, formed large, mucous aggregates, and sank out en masse (carbon sinkers). In contrast, thicker-shelled species, in particular Fragilariopsis kerguelensis, persisted in the surface layers, sank mainly empty shells continuously, and reduced silicate concentrations to similar levels both inside and outside the patch (silica sinkers). These patterns imply that thick-shelled, hence grazer-protected, diatom species evolved in response to heavy copepod grazing pressure in the presence of an abundant silicate supply. The ecology of these silica-sinking species decouples silicon and carbon cycles in the iron-limited Southern Ocean, whereas carbon-sinking species, when stimulated by iron fertilization, export more carbon per silicon. Our results suggest that large-scale iron fertilization of the silicate-rich Southern Ocean will not change silicon sequestration but will add carbon to the sinking silica flux. PMID:24248337

  14. Effects of road deicer (NaCl) and amphibian grazers on detritus processing in pond mesocosms.

    PubMed

    Van Meter, Robin J; Swan, Christopher M; Trossen, Carrie A

    2012-10-01

    Road deicers have been identified as potential stressors in aquatic habitats throughout the United States, but we know little regarding associated impacts to ecosystem function. A critical component of ecosystem function that has not previously been evaluated with respect to freshwater salinization is the impact on organic matter breakdown. The purpose of this study was to evaluate cumulative effects of road deicers and tadpole grazers on leaf litter breakdown rate (g d(-1) ) and microbial respiration (mg O(2)  g leaf(-1) h(-1) ). To test this interaction, in May 2008 the authors added dry leaf litter (Quercus spp.) to forty 600-L pond mesocosms and inoculated each with algae and zooplankton. In a full-factorial design, they manipulated a realistic level of road salt (ambient or elevated at 645 mg L(-1) Cl(-) ) and tadpole (Hyla versicolor) presence or absence. The elevated chloride treatment reduced microbial respiration by 24% in the presence of tadpoles. The breakdown of leaf litter by tadpoles occurred 9.7% faster under ambient chloride conditions relative to the elevated chloride treatment. Results of the present study suggest that the microbial community is directly impacted by road deicers and heavy tadpole grazing under ambient conditions limits microbial capacity to process detritus. Road salts and tadpoles interact to limit microbial respiration, but to a lesser extent leaf mass loss rate, thereby potentially restricting energy flow from detrital sources in pond ecosystems. Copyright © 2012 SETAC.

  15. Morphological and physiological responses of seagrasses (Alismatales) to grazers (Testudines: Cheloniidae) and the role of these responses as grazing patch abandonment cues.

    PubMed

    Lacey, Elizabeth A; Collado-Vides, Ligia; Fourqurean, James W

    2014-12-01

    Green sea turtles, Chelonia mydas, are grazers influencing the distribution of seagrass within shallow coastal ecosystems, yet the drivers behind C. mydas patch use within seagrass beds are largely unknown. Current theories center on food quality (nutrient content) as the plant responds to grazing disturbances; however, no study has monitored these parameters in a natural setting without grazer manipulation. To determine the morphological and physiological responses potentially influencing seagrass recovery from grazing disturbances, seagrasses were monitored for one year under three different grazing scenarios (turtle grazed, fish grazed and ungrazed) in a tropical ecosystem in Akumal Bay, Quintana Roo, Mexico. Significantly less soluble carbohydrates and increased nitrogen and phosphorus content in Thalassia testudinum were indicative of the stresses placed on seagrasses during herbivory. To determine if these physiological responses were the drivers of the heterogeneous grazing behavior by C. mydas recorded in Akumal Bay, patches were mapped and monitored over a six-month interval. The abandoned patches had the lowest standing crop rather than leaf nutrient or rhi- zome soluble carbohydrate content. This suggests a modified Giving Up Density (GUD) behavior: the critical threshold where cost of continued grazing does not provide minimum nutrients, therefore, new patches must be utilized, explains resource abandonment and mechanism behind C. mydas grazing. This study is the first to apply GUD theory, often applied in terrestrial literature, to explain marine herbivore grazing behavior.

  16. Multivariate statistical analysis of stream-sediment geochemistry in the Grazer Paläozoikum, Austria

    USGS Publications Warehouse

    Weber, L.; Davis, J.C.

    1990-01-01

    The Austrian reconnaissance study of stream-sediment composition — more than 30000 clay-fraction samples collected over an area of 40000 km2 — is summarized in an atlas of regional maps that show the distributions of 35 elements. These maps, rich in information, reveal complicated patterns of element abundance that are difficult to compare on more than a small number of maps at one time. In such a study, multivariate procedures such as simultaneous R-Q mode components analysis may be helpful. They can compress a large number of variables into a much smaller number of independent linear combinations. These composite variables may be mapped and relationships sought between them and geological properties. As an example, R-Q mode components analysis is applied here to the Grazer Paläozoikum, a tectonic unit northeast of the city of Graz, which is composed of diverse lithologies and contains many mineral deposits.

  17. The importance of an underestimated grazer under climate change: how crab density, consumer competition, and physical stress affect salt marsh resilience.

    PubMed

    Angelini, Christine; van Montfrans, Schuyler G; Hensel, Marc J S; He, Qiang; Silliman, Brian R

    2018-05-01

    Climate change and consumer outbreaks are driving ecosystem collapse worldwide. Although much research has demonstrated that these factors can interact, how heterogeneity in top-down control intensity and physical forcing modulates ecosystem resilience to climate stress remains poorly understood. Here, we explore whether the nocturnal herbivorous crab Sesarma reticulatum can control spatially dominant cordgrass (Spartina alterniflora) growth and how its top-down effects vary with crab density, drought stress, and large-scale disturbance in southeastern US salt marshes. In multiple field experiments and surveys, we show that Sesarma depresses cordgrass growth and that its effects increase in a saturating manner with increasing crab density, such that the highest naturally occurring densities of this consumer can trigger local cordgrass die-off. This top-down effect of Sesarma is similar in magnitude to what is thought to be the dominant grazer in the system, the marsh periwinkle snail Littoraria irrorata. In a drought stress by Sesarma density experiment, we further show that salinity stress and intensive crab herbivory additively suppress cordgrass drought resistance. After drought subsides, surveys and experiments reveal that Sesarma also stifles cordgrass re-growth into existing die-off areas. Together, these results show that multiple grazers powerfully regulate the productivity and drought resilience of these intertidal grasslands and that heterogeneity in physical stress and consumer density can dictate when and where top-down forcing is important. More generally, this work provides a rare, experimental demonstration of the critical role top-down control can play across the initiation and recovery stages of ecosystem die-off.

  18. Multiscale responses of soil stability and invasive plants to removal of non-native grazers from an arid conservation reserve

    USGS Publications Warehouse

    Beever, E.A.; Huso, M.; Pyke, D.A.

    2006-01-01

    Disturbances and ecosystem recovery from disturbance both involve numerous processes that operate on multiple spatial and temporal scales. Few studies have investigated how gradients of disturbance intensity and ecosystem responses are distributed across multiple spatial resolutions and also how this relationship changes through time during recovery. We investigated how cover of non-native species and soil-aggregate stability (a measure of vulnerability to erosion by water) in surface and subsurface soils varied spatially during grazing by burros and cattle and whether patterns in these variables changed after grazer removal from Mojave National Preserve, California, USA. We compared distance from water and number of ungulate defecations - metrics of longer-term and recent grazing intensity, respectively, - as predictors of our response variables. We used information-theoretic analyses to compare hierarchical linear models that accounted for important covariates and allowed for interannual variation in the disturbance-response relationship at local and landscape scales. Soil stability was greater under perennial vegetation than in bare interspaces, and surface soil stability decreased with increasing numbers of ungulate defecations. Stability of surface samples was more affected by time since removal of grazers than was stability of subsurface samples, and subsurface soil stability in bare spaces was not related to grazing intensity, time since removal, or any of our other predictors. In the high rainfall year (2003) after cattle had been removed for 1-2 years, cover of all non-native plants averaged nine times higher than in the low-rainfall year (2002). Given the heterogeneity in distribution of large-herbivore impacts that we observed at several resolutions, hierarchical analyses provided a more complete understanding of the spatial and temporal complexities of disturbance and recovery processes in arid ecosystems. ?? 2006 Blackwell Publishing Ltd.

  19. Multi-scale responses of soil stability and invasive plants to removal of non-native grazers from an arid conservation reserve

    USGS Publications Warehouse

    Beever, Erik A.; Huso, Manuela M. P.; Pyke, David A.

    2006-01-01

    Disturbances and ecosystem recovery from disturbance both involve numerous processes that operate on multiple spatial and temporal scales. Few studies have investigated how gradients of disturbance intensity and ecosystem responses are distributed across multiple spatial resolutions and also how this relationship changes through time during recovery. We investigated how cover of non-native species and soil-aggregate stability (a measure of vulnerability to erosion by water) in surface and subsurface soils varied spatially during grazing by burros and cattle and whether patterns in these variables changed after grazer removal from Mojave National Preserve, California, USA. We compared distance from water and number of ungulate defecations — metrics of longer-term and recent grazing intensity, respectively, — as predictors of our response variables. We used information-theoretic analyses to compare hierarchical linear models that accounted for important covariates and allowed for interannual variation in the disturbance–response relationship at local and landscape scales. Soil stability was greater under perennial vegetation than in bare interspaces, and surface soil stability decreased with increasing numbers of ungulate defecations. Stability of surface samples was more affected by time since removal of grazers than was stability of subsurface samples, and subsurface soil stability in bare spaces was not related to grazing intensity, time since removal, or any of our other predictors. In the high rainfall year (2003) after cattle had been removed for 1–2 years, cover of all non-native plants averaged nine times higher than in the low-rainfall year (2002). Given the heterogeneity in distribution of large-herbivore impacts that we observed at several resolutions, hierarchical analyses provided a more complete understanding of the spatial and temporal complexities of disturbance and recovery processes in arid ecosystems.

  20. Grazer-induced morphological defense in Scenedesmus obliquus is affected by competition against Microcystis aeruginosa

    PubMed Central

    Zhu, Xuexia; Wang, Jun; Lu, Yichun; Chen, Qinwen; Yang, Zhou

    2015-01-01

    The green alga Scenedesmus is known for its phenotypic plasticity in response to grazing risk. However, the benefits of colony formation induced by infochemicals from zooplankton should come with costs. That is, a tradeoff in benefit-to-cost ratios is likely under complex environmental conditions. In this study, we hypothesized that the coexistence of Scenedesmus and its competitors decreases the formation of anti-grazer colonies in Scenedesmus. Results demonstrated that the presence of a competitor Microcystis aeruginosa inhibited inducible defensive colony formation of Scenedesmus obliquus, and the established defensive colonies negatively affected the competitive ability of S. obliquus. The proportion of induced defensive colonies in cultures was dependent on the relative abundance of competitors. Under low competition intensity, large amount of eight-celled colonies were formed but at the cost of decreased competitive inhibition on M. aeruginosa. By contrast, defensive colony formation of S. obliquus slacked in the presence of high competition intensity to maintain a high displacement rate (competitive ability). In conclusion, S. obliquus exhibited different responses to potential grazing pressure under different intensities of competition, i.e., Scenedesmus morphological response to grazing infochemicals was affected by competition against Microcystis. PMID:26224387

  1. Grazer-induced morphological defense in Scenedesmus obliquus is affected by competition against Microcystis aeruginosa.

    PubMed

    Zhu, Xuexia; Wang, Jun; Lu, Yichun; Chen, Qinwen; Yang, Zhou

    2015-07-30

    The green alga Scenedesmus is known for its phenotypic plasticity in response to grazing risk. However, the benefits of colony formation induced by infochemicals from zooplankton should come with costs. That is, a tradeoff in benefit-to-cost ratios is likely under complex environmental conditions. In this study, we hypothesized that the coexistence of Scenedesmus and its competitors decreases the formation of anti-grazer colonies in Scenedesmus. Results demonstrated that the presence of a competitor Microcystis aeruginosa inhibited inducible defensive colony formation of Scenedesmus obliquus, and the established defensive colonies negatively affected the competitive ability of S. obliquus. The proportion of induced defensive colonies in cultures was dependent on the relative abundance of competitors. Under low competition intensity, large amount of eight-celled colonies were formed but at the cost of decreased competitive inhibition on M. aeruginosa. By contrast, defensive colony formation of S. obliquus slacked in the presence of high competition intensity to maintain a high displacement rate (competitive ability). In conclusion, S. obliquus exhibited different responses to potential grazing pressure under different intensities of competition, i.e., Scenedesmus morphological response to grazing infochemicals was affected by competition against Microcystis.

  2. Viral and grazer regulation of prokaryotic growth efficiency in temperate freshwater pelagic environments.

    PubMed

    Pradeep Ram, A S; Colombet, Jonathan; Perriere, Fanny; Thouvenot, Antoine; Sime-Ngando, Telesphore

    2015-02-01

    In aquatic systems, limited data exists on the impact of mortality forces such as viral lysis and flagellate grazing when seeking to explain factors regulating prokaryotic metabolism. We explored the relative influence of top-down factors (viral lysis and heterotrophic nanoflagellate grazing) on prokaryotic mortality and their subsequent impact on their community metabolism in the euphotic zone of 21 temperate freshwater lakes located in the French Massif Central. Prokaryotic growth efficiency (PGE, index of prokaryotic community metabolism) determined from prokaryotic production and respiration measurements varied from 5 to 74% across the lakes. Viral and potential grazer-induced mortality of prokaryotes had contrasting impact on PGE. Potential flagellate grazing was found to enhance PGE whereas viral lysis had antagonistic impacts on PGE. The average PGE value in the grazing and viral lysis dominated lake water samples was 35.4% (±15.2%) and 17.2% (±8.1%), respectively. Selective viral lysis or flagellate grazing on prokaryotes together with the nature of contrasted substrates released through mortality processes can perhaps explain for the observed variation and differences in PGE among the studied lakes. The influences of such specific top-down processes on PGE can have strong implications on the carbon and nutrient fluxes in freshwater pelagic environments. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Large-scale associations between macroalgal cover and grazer biomass on mid-depth reefs in the Caribbean

    NASA Astrophysics Data System (ADS)

    Williams, I.; Polunin, N.

    2001-05-01

    Since the 1970s, macroalgae have become considerably more abundant on many Caribbean reefs and overfishing of grazing fishes has been implicated as a contributory factor. We explored relationships between algal cover and grazers (biomass of herbivorous fishes and abundance of the sea-urchin Diadema antillarum) on mid-depth reefs (12-15 m) in 19 areas at seven locations in Jamaica, Barbados, Belize, Grand Cayman and Cuba, between April 1997 and April 1998. Diadema antillarum density was never >0.01 m-2, while herbivorous fish biomass (acanthurids and scarids ≥12 cm total length) varied from 2-5 g m-2 in Jamaica to 17.1 g m-2 in Barbados, and was strongly correlated, negatively with macroalgal cover and positively with 'cropped' substratum (sum of 'bare', turf and crustose-coralline substrata) cover. However, overfishing of herbivorous fishes alone cannot explain the widespread abundance of macroalgae, as even on lightly fished reefs, macroalgal cover was mostly >20%. Herbivorous fish populations on those reefs were apparently only able to maintain approximately 40-60% of reef substratum in cropped states, but due to low space-occupation by coral and other invertebrates, 70-90% of substratum was available to algae. The abundance of macroalgae on lightly fished reefs may therefore be a symptom of low coral cover in combination with the continuing absence of Diadema antillarum.

  4. MEASURING INVERTEBRATE GRAZING ON SEAGRASSES AND EPIPHYTES

    EPA Science Inventory

    The chapter describes methods to assess grazing rates, grazer preferences, and grazer impacts, by mobile organisms living in the canopy or in the rhizome layer in any seagrass system. One set of methods quantifies grazing activity in small to medium sized, mobile organisms livin...

  5. Sub-arctic Wetland Greenhouse Gases (CO2, CH4 & N2O) Emissions are Driven by Interactions of Environmental Controls and Herbivore Grazers

    NASA Astrophysics Data System (ADS)

    Kelsey, K.; Leffler, A. J.; Beard, K. H.; Choi, R. T.; Welker, J. M.

    2015-12-01

    Climate change is increasing temperatures, altering precipitation regimes and causing earlier growing seasons, particularly at northern latitudes. Such changes in local environmental conditions have the potential to affect biogeochemical cycling including the exchange of greenhouses gases between the atmosphere and the terrestrial biosphere. In addition to the effects of these environmental controls, animals such as migratory geese also influence biogeochemical cycles through grazing, trampling and delivering nutrient-rich fecal matter. In this work we aimed to quantify how local environmental conditions and the presence of grazing interact as drivers of emissions of three key greenhouse gases, CO2, CH4 and N2O, in coastal wetlands of the Yukon Kuskokwim Delta. We explored the magnitude of emissions across gradients of soil temperature and water table depth, and across vegetation types related to the presence of grazing, ranging from no vegetation through grazed and ungrazed vegetation. We also investigated emissions from grazed areas using experimental manipulations of the timing of grazing and advancement of the growing season. We found that local environmental conditions and use by grazers exert interacting controls on emissions of CO2, CH4 and N2O. Emissions of CO2 and CH4 were positively related to soil temperature and CH4 emissions were inversely related to water table depth, but the relationship varied by vegetation type. Net emissions of CO2 were greatest in ungrazed vegetation types (6.62 umols CO2 m-2 sec-1; p=0.0007) whereas CH4 emissions were greatest in the grazed vegetation (122.56 nmols CH4 m-2 sec-1; p=0.037). Flux of N2O was less than 1 nmol N2O m-2 sec-1 across all landscape positions under typical grazing and temperature conditions, but emissions were stimulated to over 10 nmols m-2 sec-1 when grazing occurred early relative to a typical season. Our results indicate that environmental conditions and the presence of migratory herbivores are both

  6. Identifying Emotions on the Basis of Neural Activation

    PubMed Central

    Kassam, Karim S.; Markey, Amanda R.; Cherkassky, Vladimir L.; Loewenstein, George; Just, Marcel Adam

    2013-01-01

    We attempt to determine the discriminability and organization of neural activation corresponding to the experience of specific emotions. Method actors were asked to self-induce nine emotional states (anger, disgust, envy, fear, happiness, lust, pride, sadness, and shame) while in an fMRI scanner. Using a Gaussian Naïve Bayes pooled variance classifier, we demonstrate the ability to identify specific emotions experienced by an individual at well over chance accuracy on the basis of: 1) neural activation of the same individual in other trials, 2) neural activation of other individuals who experienced similar trials, and 3) neural activation of the same individual to a qualitatively different type of emotion induction. Factor analysis identified valence, arousal, sociality, and lust as dimensions underlying the activation patterns. These results suggest a structure for neural representations of emotion and inform theories of emotional processing. PMID:23840392

  7. Identifying Emotions on the Basis of Neural Activation.

    PubMed

    Kassam, Karim S; Markey, Amanda R; Cherkassky, Vladimir L; Loewenstein, George; Just, Marcel Adam

    2013-01-01

    We attempt to determine the discriminability and organization of neural activation corresponding to the experience of specific emotions. Method actors were asked to self-induce nine emotional states (anger, disgust, envy, fear, happiness, lust, pride, sadness, and shame) while in an fMRI scanner. Using a Gaussian Naïve Bayes pooled variance classifier, we demonstrate the ability to identify specific emotions experienced by an individual at well over chance accuracy on the basis of: 1) neural activation of the same individual in other trials, 2) neural activation of other individuals who experienced similar trials, and 3) neural activation of the same individual to a qualitatively different type of emotion induction. Factor analysis identified valence, arousal, sociality, and lust as dimensions underlying the activation patterns. These results suggest a structure for neural representations of emotion and inform theories of emotional processing.

  8. Amino Acid Isotopic Trophic Enrichment in Mesozooplankton: Is Alanine a Better Predictor of Protistan Grazer Steps?

    NASA Astrophysics Data System (ADS)

    Decima, M.; Landry, M. R.; Bradley, C. J.; Fogel, M. L.

    2016-02-01

    Food-web studies within marine environments are increasingly reliant upon results from compound-specific isotope analysis of amino acids (CSIA-AA). The approach is advantageous because it allows consumer trophic positions to be estimated without sampling the dynamic primary producers. The baseline signal in the source AA phenylalanine is preserved, and a constant enrichment in glutamic acid at each trophic step is assumed, regardless of consumer type or diet. However, a number of recent studies challenge the assumption of universal and invariant isotopic fractionation of glutamic acid for all trophic levels, as well as its specific applicability to the main grazers in the ocean: the protistan microzooplankton. We present results from both laboratory and field studies that further explore this issue. Experiments include six 2-stage chemostats, using two different microzooplankton-phytoplankton pairs and one copepod-phytoplankton pair, and one 3-stage experiment using a copepod-microzooplankton-phytoplankton chain. We confirm previous observations of negligible fractionation of glutamic acid in protistan consumers when nutrients are limiting. In contrast, a consistent trophic enrichment effect was observed for alanine, with increasing δ15N values by trophic level for both metazoan and protistan consumers. A re-analysis of published CSIA-AA data of zooplankton species show that an index using alanine and phenylalanine gives trophic level estimates closer to expected given current understanding of the linkages within microbial food webs. Our results examine the details of isotopic fractionation of alanine within defined food chains and generally support its potential use as a trophic level indicator that includes the protistan contribution to mesozooplankton diet.

  9. Identifying clusters of active transportation using spatial scan statistics.

    PubMed

    Huang, Lan; Stinchcomb, David G; Pickle, Linda W; Dill, Jennifer; Berrigan, David

    2009-08-01

    There is an intense interest in the possibility that neighborhood characteristics influence active transportation such as walking or biking. The purpose of this paper is to illustrate how a spatial cluster identification method can evaluate the geographic variation of active transportation and identify neighborhoods with unusually high/low levels of active transportation. Self-reported walking/biking prevalence, demographic characteristics, street connectivity variables, and neighborhood socioeconomic data were collected from respondents to the 2001 California Health Interview Survey (CHIS; N=10,688) in Los Angeles County (LAC) and San Diego County (SDC). Spatial scan statistics were used to identify clusters of high or low prevalence (with and without age-adjustment) and the quantity of time spent walking and biking. The data, a subset from the 2001 CHIS, were analyzed in 2007-2008. Geographic clusters of significantly high or low prevalence of walking and biking were detected in LAC and SDC. Structural variables such as street connectivity and shorter block lengths are consistently associated with higher levels of active transportation, but associations between active transportation and socioeconomic variables at the individual and neighborhood levels are mixed. Only one cluster with less time spent walking and biking among walkers/bikers was detected in LAC, and this was of borderline significance. Age-adjustment affects the clustering pattern of walking/biking prevalence in LAC, but not in SDC. The use of spatial scan statistics to identify significant clustering of health behaviors such as active transportation adds to the more traditional regression analysis that examines associations between behavior and environmental factors by identifying specific geographic areas with unusual levels of the behavior independent of predefined administrative units.

  10. Identifying Clusters of Active Transportation Using Spatial Scan Statistics

    PubMed Central

    Huang, Lan; Stinchcomb, David G.; Pickle, Linda W.; Dill, Jennifer; Berrigan, David

    2009-01-01

    Background There is an intense interest in the possibility that neighborhood characteristics influence active transportation such as walking or biking. The purpose of this paper is to illustrate how a spatial cluster identification method can evaluate the geographic variation of active transportation and identify neighborhoods with unusually high/low levels of active transportation. Methods Self-reported walking/biking prevalence, demographic characteristics, street connectivity variables, and neighborhood socioeconomic data were collected from respondents to the 2001 California Health Interview Survey (CHIS; N=10,688) in Los Angeles County (LAC) and San Diego County (SDC). Spatial scan statistics were used to identify clusters of high or low prevalence (with and without age-adjustment) and the quantity of time spent walking and biking. The data, a subset from the 2001 CHIS, were analyzed in 2007–2008. Results Geographic clusters of significantly high or low prevalence of walking and biking were detected in LAC and SDC. Structural variables such as street connectivity and shorter block lengths are consistently associated with higher levels of active transportation, but associations between active transportation and socioeconomic variables at the individual and neighborhood levels are mixed. Only one cluster with less time spent walking and biking among walkers/bikers was detected in LAC, and this was of borderline significance. Age-adjustment affects the clustering pattern of walking/biking prevalence in LAC, but not in SDC. Conclusions The use of spatial scan statistics to identify significant clustering of health behaviors such as active transportation adds to the more traditional regression analysis that examines associations between behavior and environmental factors by identifying specific geographic areas with unusual levels of the behavior independent of predefined administrative units. PMID:19589451

  11. Identifying Crucial Parameter Correlations Maintaining Bursting Activity

    PubMed Central

    Doloc-Mihu, Anca; Calabrese, Ronald L.

    2014-01-01

    Recent experimental and computational studies suggest that linearly correlated sets of parameters (intrinsic and synaptic properties of neurons) allow central pattern-generating networks to produce and maintain their rhythmic activity regardless of changing internal and external conditions. To determine the role of correlated conductances in the robust maintenance of functional bursting activity, we used our existing database of half-center oscillator (HCO) model instances of the leech heartbeat CPG. From the database, we identified functional activity groups of burster (isolated neuron) and half-center oscillator model instances and realistic subgroups of each that showed burst characteristics (principally period and spike frequency) similar to the animal. To find linear correlations among the conductance parameters maintaining functional leech bursting activity, we applied Principal Component Analysis (PCA) to each of these four groups. PCA identified a set of three maximal conductances (leak current, Leak; a persistent K current, K2; and of a persistent Na+ current, P) that correlate linearly for the two groups of burster instances but not for the HCO groups. Visualizations of HCO instances in a reduced space suggested that there might be non-linear relationships between these parameters for these instances. Experimental studies have shown that period is a key attribute influenced by modulatory inputs and temperature variations in heart interneurons. Thus, we explored the sensitivity of period to changes in maximal conductances of Leak, K2, and P, and we found that for our realistic bursters the effect of these parameters on period could not be assessed because when varied individually bursting activity was not maintained. PMID:24945358

  12. Dietary uptake of Cu sorbed to hydrous iron oxide is linked to cellular toxicity and feeding inhibition in a benthic grazer

    USGS Publications Warehouse

    Cain, Daniel J.; Croteau, Marie-Noele; Fuller, Christopher C.; Ringwood, Amy H.

    2016-01-01

    Whereas feeding inhibition caused by exposure to contaminants has been extensively documented, the underlying mechanism(s) are less well understood. For this study, the behavior of several key feeding processes, including ingestion rate and assimilation efficiency, that affect the dietary uptake of Cu were evaluated in the benthic grazer Lymnaea stagnalis following 4–5 h exposures to Cu adsorbed to synthetic hydrous ferric oxide (Cu–HFO). The particles were mixed with a cultured alga to create algal mats with Cu exposures spanning nearly 3 orders of magnitude at variable or constant Fe concentrations, thereby allowing first order and interactive effects of Cu and Fe to be evaluated. Results showed that Cu influx rates and ingestion rates decreased as Cu exposures of the algal mat mixture exceeded 104 nmol/g. Ingestion rate appeared to exert primary control on the Cu influx rate. Lysosomal destabilization rates increased directly with Cu influx rates. At the highest Cu exposure where the incidence of lysosomal membrane damage was greatest (51%), the ingestion rate was suppressed 80%. The findings suggested that feeding inhibition was a stress response emanating from excessive uptake of dietary Cu and cellular toxicity.

  13. Identifying transcription factor functions and targets by phenotypic activation

    PubMed Central

    Chua, Gordon; Morris, Quaid D.; Sopko, Richelle; Robinson, Mark D.; Ryan, Owen; Chan, Esther T.; Frey, Brendan J.; Andrews, Brenda J.; Boone, Charles; Hughes, Timothy R.

    2006-01-01

    Mapping transcriptional regulatory networks is difficult because many transcription factors (TFs) are activated only under specific conditions. We describe a generic strategy for identifying genes and pathways induced by individual TFs that does not require knowledge of their normal activation cues. Microarray analysis of 55 yeast TFs that caused a growth phenotype when overexpressed showed that the majority caused increased transcript levels of genes in specific physiological categories, suggesting a mechanism for growth inhibition. Induced genes typically included established targets and genes with consensus promoter motifs, if known, indicating that these data are useful for identifying potential new target genes and binding sites. We identified the sequence 5′-TCACGCAA as a binding sequence for Hms1p, a TF that positively regulates pseudohyphal growth and previously had no known motif. The general strategy outlined here presents a straightforward approach to discovery of TF activities and mapping targets that could be adapted to any organism with transgenic technology. PMID:16880382

  14. Carbon budget of sea-ice algae in spring: Evidence of a significant transfer to zooplankton grazers

    NASA Astrophysics Data System (ADS)

    Michel, C.; Legendre, L.; Ingram, R. G.; Gosselin, M.; Levasseur, M.

    1996-08-01

    The fate of ice-bottom algae, before and after release from the first-year sea ice into the water column, was assessed during the period of ice-algal growth and decline in Resolute Passage (Canadian Arctic). During spring 1992 (from April to June), algae in the bottom ice layer and those suspended and sinking in the upper water column (top 15 m) were sampled approximately every 4 days. Ice-bottom chlorophyll a reached a maximum concentration of 160 mg m-2 in mid-May, after which it decreased to lower values. In the water column, chlorophyll a concentrations were low until the period of ice-algal decline (˜0.1 mg m-3), with most biomass in the <5-μm fraction. In both the suspended and sinking material, large increases of algal biomass occurred at the beginning of June, following the release of ice-algae into the water column. The input of ice-algal derived carbon to the upper water column and the proportions exported through sinking or remaining in suspension were assessed using a carbon budget for the two periods of ice-algal growth and decline. For each period the output terms closely balanced the input. The carbon budget showed that most of the biomass introduced into the upper water column remained suspended (>65% of total export) and that ice-algae were ingested by under-ice grazers after release from the ice. These results stress the importance of ice algae for pelagic consumers during the early stages of ice melt and show that the transfer of ice algae to higher trophic levels extends beyond the period of maximum algal production in the ice bottom.

  15. Identifying Metabolically Active Chemicals Using a Consensus ...

    EPA Pesticide Factsheets

    Endocrine disrupting chemicals (EDCs) are abundant throughout the environment and can alter neurodevelopment, behavior, and reproductive success of humans and other species by perturbing signaling pathways related to the estrogen receptor (ER). A recent study compared results across 18 ER-related assays in the ToxCast™ in vitro screening program to predict the likelihood of a chemical exhibiting in vivo estrogenic activity, with the purpose of eliminating chemicals that may produce a false signal by interfering with the technological attributes of an individual assay. However, flaws in in vitro assay design can also prevent induction of signal activity by EDCs. Another reason for not observing activity for some EDCs in in vitro assays is that metabolic activation is required to perturb ER-related pathways. In the current study, 1,024 chemicals were identified as lacking ER activity after establishing a consensus across each of the 18 ER-related in vitro assays, and nearly 2,000 primary and 3,700 secondary unique metabolites were predicted for these chemicals. The ER binding activity for each metabolite was then predicted using an existing ER activity quantitative structure activity relationship (QSAR) consensus model. Binding activity was predicted for 2-3% of the metabolites within each generation. Of the inactive parent compounds generating at least one metabolite predicted to have ER-binding activity, nearly 30% were found to have metabolites from both gene

  16. Variable viral and grazer control of prokaryotic growth efficiency in temperate freshwater lakes (French Massif Central).

    PubMed

    Ram, A S Pradeep; Palesse, S; Colombet, J; Sabart, M; Perriere, F; Sime-Ngando, T

    2013-11-01

    The effects of viral lysis and heterotrophic nanoflagellate grazing (top down forces) on prokaryotic mortality and their subsequent impact on their metabolism were estimated in the upper euphotic and deeper aphotic depth of 11 freshwater lakes located in the French Massif Central. The standing stocks of viruses (VA) and heterotrophic nanoflagellate (HNF) varied significantly (p < 0.05) with sampled depth. VA was substantially (twofold on an average) and significantly higher (p < 0.03) at the aphotic compared to euphotic depth, whereas the reverse was true (p < 0.02) for HNF. Among the prokaryote subgroup, high nucleic acid content prokaryotes explained for significant variability in the total VA and served as principle host target for viral proliferation. Like standing stocks, flagellate grazing and viral infection rates also followed similar patterns. In the investigated lakes, the mechanism for regulating prokaryotic production varied with sampled depth from grazing control in the euphotic to control due to viral lysis in the aphotic. We also tested the hypothesis of top down control on prokaryotic growth efficiency (PGE, which we used as an index of prokaryotic physiological and energetic status at the community level) at both depths. Overall, among the studied lakes, PGE varied widely (4-51 %) with significantly (p < 0.05) lower values in the aphotic (mean = 18 ± 4 %) than euphotic depth (mean = 32 ± 9 %). Contrasting observations on the top down control of PGE between sampled depths were observed. The presence of grazers was found to stimulate PGE at the euphotic, whereas viruses through their lytic infection had a strong negative impact on PGE at the aphotic depth. Such observed differences in PGE and the mechanism controlling prokaryotic production with depth could eventually have strong implication on carbon and nutrient flux patterns in the studied lakes.

  17. Tooth wear in captive giraffes (Giraffa camelopardalis): mesowear analysis classifies free-ranging specimens as browsers but captive ones as grazers.

    PubMed

    Clauss, Marcus; Franz-Odendaal, Tamara A; Brasch, Juliane; Castell, Johanna C; Kaiser, Thomas

    2007-09-01

    Captive giraffe (Giraffa camelopardalis) mostly do not attain the longevity possible for this species and frequently have problems associated with low energy intake and fat storage mobilization. Abnormal tooth wear has been among the causes suggested as an underlying problem. This study utilizes a tooth wear scoring method ("mesowear") primarily used in paleobiology. This scoring method was applied to museum specimens of free-ranging (n=20) and captive (n=41) giraffes. The scoring system allows for the differentiation between attrition--(typical for browsers, as browse contains little abrasive silica) and abrasion--(typical for grazers, as grass contains abrasive silica) dominated tooth wear. The dental wear pattern of the free-ranging population is dominated by attrition, resembles that previously published for free-ranging giraffe, and clusters within browsing herbivores in comparative analysis. In contrast, the wear pattern of the captive population is dominated by abrasion and clusters among grazing herbivores in comparative analyses. A potential explanation for this difference in tooth wear is likely related to the content of abrasive elements in zoo diets. Silica content (measured as acid insoluble ash) is low in browse and alfalfa. However, grass hay and the majority of pelleted compound feeds contain higher amounts of silica. It can be speculated that the abnormal wear pattern in captivity compromises tooth function in captive giraffe, with deleterious long-term consequences.

  18. SABER: A computational method for identifying active sites for new reactions

    PubMed Central

    Nosrati, Geoffrey R; Houk, K N

    2012-01-01

    A software suite, SABER (Selection of Active/Binding sites for Enzyme Redesign), has been developed for the analysis of atomic geometries in protein structures, using a geometric hashing algorithm (Barker and Thornton, Bioinformatics 2003;19:1644–1649). SABER is used to explore the Protein Data Bank (PDB) to locate proteins with a specific 3D arrangement of catalytic groups to identify active sites that might be redesigned to catalyze new reactions. As a proof-of-principle test, SABER was used to identify enzymes that have the same catalytic group arrangement present in o-succinyl benzoate synthase (OSBS). Among the highest-scoring scaffolds identified by the SABER search for enzymes with the same catalytic group arrangement as OSBS were l-Ala d/l-Glu epimerase (AEE) and muconate lactonizing enzyme II (MLE), both of which have been redesigned to become effective OSBS catalysts, demonstrated by experiments. Next, we used SABER to search for naturally existing active sites in the PDB with catalytic groups similar to those present in the designed Kemp elimination enzyme KE07. From over 2000 geometric matches to the KE07 active site, SABER identified 23 matches that corresponded to residues from known active sites. The best of these matches, with a 0.28 Å catalytic atom RMSD to KE07, was then redesigned to be compatible with the Kemp elimination using RosettaDesign. We also used SABER to search for potential Kemp eliminases using a theozyme predicted to provide a greater rate acceleration than the active site of KE07, and used Rosetta to create a design based on the proteins identified. PMID:22492397

  19. SABER: a computational method for identifying active sites for new reactions.

    PubMed

    Nosrati, Geoffrey R; Houk, K N

    2012-05-01

    A software suite, SABER (Selection of Active/Binding sites for Enzyme Redesign), has been developed for the analysis of atomic geometries in protein structures, using a geometric hashing algorithm (Barker and Thornton, Bioinformatics 2003;19:1644-1649). SABER is used to explore the Protein Data Bank (PDB) to locate proteins with a specific 3D arrangement of catalytic groups to identify active sites that might be redesigned to catalyze new reactions. As a proof-of-principle test, SABER was used to identify enzymes that have the same catalytic group arrangement present in o-succinyl benzoate synthase (OSBS). Among the highest-scoring scaffolds identified by the SABER search for enzymes with the same catalytic group arrangement as OSBS were L-Ala D/L-Glu epimerase (AEE) and muconate lactonizing enzyme II (MLE), both of which have been redesigned to become effective OSBS catalysts, demonstrated by experiments. Next, we used SABER to search for naturally existing active sites in the PDB with catalytic groups similar to those present in the designed Kemp elimination enzyme KE07. From over 2000 geometric matches to the KE07 active site, SABER identified 23 matches that corresponded to residues from known active sites. The best of these matches, with a 0.28 Å catalytic atom RMSD to KE07, was then redesigned to be compatible with the Kemp elimination using RosettaDesign. We also used SABER to search for potential Kemp eliminases using a theozyme predicted to provide a greater rate acceleration than the active site of KE07, and used Rosetta to create a design based on the proteins identified. Copyright © 2012 The Protein Society.

  20. Ecology of grazing lawns in Africa.

    PubMed

    Hempson, Gareth P; Archibald, Sally; Bond, William J; Ellis, Roger P; Grant, Cornelia C; Kruger, Fred J; Kruger, Laurence M; Moxley, Courtney; Owen-Smith, Norman; Peel, Mike J S; Smit, Izak P J; Vickers, Karen J

    2015-08-01

    Grazing lawns are a distinct grassland community type, characterised by short-stature and with their persistence and spread promoted by grazing. In Africa, they reveal a long co-evolutionary history of grasses and large mammal grazers. The attractiveness to grazers of a low-biomass sward lies in the relatively high quality of forage, largely due to the low proportion of stem material in the sward; this encourages repeat grazing that concomitantly suppresses tall-grass growth forms that would otherwise outcompete lawn species for light. Regular grazing that prevents shading and maintains sward quality is thus the cornerstone of grazing lawn dynamics. The strong interplay between abiotic conditions and disturbance factors, which are central to grazing lawn existence, can also cause these systems to be highly dynamic. Here we identify differences in growth form among grazing lawn grass species, and assess how compositional differences among lawn types, as well as environmental variables, influence their maintenance requirements (i.e. grazing frequency) and vulnerability to degradation. We also make a clear distinction between the processes of lawn establishment and lawn maintenance. Rainfall, soil nutrient status, grazer community composition and fire regime have strong and interactive influences on both processes. However, factors that concentrate grazing pressure (e.g. nutrient hotspots and sodic sites) have more bearing on where lawns establish. Similarly, we discuss the relevance of enhanced rates of nitrogen cycling and of sodium levels to lawn maintenance. Grazer community composition and density has considerable significance to grazing lawn dynamics; not all grazers are adapted to foraging on short-grass swards, and differences in body size and relative mouth dimensions determine which species are able to convert tall-grass swards into grazing lawns under different conditions. Hence, we evaluate the roles of different grazers in lawn dynamics, as well as the

  1. Active faults newly identified in Pacific Northwest

    NASA Astrophysics Data System (ADS)

    Balcerak, Ernie

    2012-05-01

    The Bellingham Basin, which lies north of Seattle and south of Vancouver around the border between the United States and Canada in the northern part of the Cascadia subduction zone, is important for understanding the regional tectonic setting and current high rates of crustal deformation in the Pacific Northwest. Using a variety of new data, Kelsey et al. identified several active faults in the Bellingham Basin that had not been previously known. These faults lie more than 60 kilometers farther north of the previously recognized northern limit of active faulting in the area. The authors note that the newly recognized faults could produce earthquakes with magnitudes between 6 and 6.5 and thus should be considered in hazard assessments for the region. (Journal of Geophysical Reserch-Solid Earth, doi:10.1029/2011JB008816, 2012)

  2. Whole-organism screening for gluconeogenesis identifies activators of fasting metabolism

    PubMed Central

    Gut, Philipp; Baeza-Raja, Bernat; Andersson, Olov; Hasenkamp, Laura; Hsiao, Joseph; Hesselson, Daniel; Akassoglou, Katerina; Verdin, Eric; Hirschey, Matthew D.; Stainier, Didier Y.R.

    2012-01-01

    Improving the control of energy homeostasis can lower cardiovascular risk in metabolically compromised individuals. To identify new regulators of whole-body energy control, we conducted a high-throughput screen in transgenic reporter zebrafish for small molecules that modulate the expression of the fasting-inducible gluconeogenic gene pck1. We show that this in vivo strategy identified several drugs that impact gluconeogenesis in humans, as well as metabolically uncharacterized compounds. Most notably, we find that the Translocator Protein (TSPO) ligands PK 11195 and Ro5-4864 are glucose lowering agents despite a strong inductive effect on pck1 expression. We show that these drugs are activators of a fasting-like energy state, and importantly that they protect high-fat diet induced obese mice from hepatosteatosis and glucose intolerance, two pathological manifestations of metabolic dysregulation. Thus, using a whole-organism screening strategy, this study has identified new small molecule activators of fasting metabolism. PMID:23201900

  3. The convenience food market in Great Britain: convenience food lifestyle (CFL) segments.

    PubMed

    Buckley, Marie; Cowan, Cathal; McCarthy, Mary

    2007-11-01

    Convenience foods enable the consumer to save time and effort in food activities, related to shopping, meal preparation and cooking, consumption and post-meal activities. The objective of this paper is to report on the attitudes and reported behaviour of food consumers in Great Britain based on a review of their convenience food lifestyle (CFLs). The paper also reports the development and application of a segmentation technique that can supply information on consumer attitudes towards convenience foods. The convenience food market in Great Britain is examined and the key drivers of growth in this market are highlighted. A survey was applied to a nationally representative sample of 1000 consumers (defined as the persons primarily responsible for food shopping and cooking in the household) in Great Britain in 2002. Segmentation analysis, based on the identification of 20 convenience lifestyle factors, identified four CFL segments of consumers: the 'food connoisseurs' (26%), the 'home meal preparers' (25%), the 'kitchen evaders' (16%) and the 'convenience-seeking grazers' (33%). In particular, the 'kitchen evaders' and the 'convenience-seeking grazers' are identified as convenience-seeking segments. Implications for food producers, in particular, convenience food manufacturers are discussed. The study provides an understanding of the lifestyles of food consumers in Great Britain, and provides food manufacturers with an insight into what motivates individuals to purchase convenience foods.

  4. Using Indices of Fidelity to Intervention Core Components to Identify Program Active Ingredients

    ERIC Educational Resources Information Center

    Abry, Tashia; Hulleman, Chris S.; Rimm-Kaufman, Sara E.

    2015-01-01

    Identifying the active ingredients of an intervention--intervention-specific components serving as key levers of change--is crucial for unpacking the intervention black box. Measures of intervention fidelity can be used to identify specific active ingredients, yet such applications are rare. We illustrate how fidelity measures can be used to…

  5. Identifying facilitators and barriers to physical activity for adults with Down syndrome.

    PubMed

    Mahy, J; Shields, N; Taylor, N F; Dodd, K J

    2010-09-01

    Adults with Down syndrome are typically sedentary, and many do not participate in the recommended levels of physical activity per week. The aim of this study was to identify the facilitators and barriers to physical activity for this group. Semi-structured interviews were conducted to elicit the views of adults with Down syndrome and their support people about what factors facilitate physical activity and what factors are barriers to activity. A sample of 18 participants (3 men, 15 women) was recruited through two agencies providing services for adults with disabilities; six participants were adults with Down syndrome and 12 participants were support people (four were parents of adults with Down syndrome and eight participants were employed by day programmes attended by the adults with Down syndrome). The interviews were recorded, transcribed verbatim and independently coded by two researchers. Three themes around facilitators to physical activity were identified: (1) support from others; (2) that the physical activity was fun or had an interesting purpose; and (3) routine and familiarity. Three themes around barriers were also identified: (1) lack of support; (2) not wanting to engage in physical activity; and (3) medical and physiological factors. The results suggest that support people play a key role, both as facilitators and barriers, in the participation by adults with Down syndrome in physical activity. Many of the barriers and facilitators of activity for adults with Down syndrome indentified are similar to those reported for adults without impairment. Our findings are also consistent with established theories in the field of health behaviour change.

  6. Identifying protist consumers of photosynthetic picoeukaryotes in the surface ocean using stable isotope probing.

    PubMed

    Orsi, William D; Wilken, Susanne; Del Campo, Javier; Heger, Thierry; James, Erick; Richards, Thomas A; Keeling, Patrick J; Worden, Alexandra Z; Santoro, Alyson E

    2018-02-01

    Photosynthetic picoeukaryotes contribute a significant fraction of primary production in the upper ocean. Micromonas pusilla is an ecologically relevant photosynthetic picoeukaryote, abundantly and widely distributed in marine waters. Grazing by protists may control the abundance of picoeukaryotes such as M. pusilla, but the diversity of the responsible grazers is poorly understood. To identify protists consuming photosynthetic picoeukaryotes in a productive North Pacific Ocean region, we amended seawater with living 15 N, 13 C-labelled M. pusilla cells in a 24-h replicated bottle experiment. DNA stable isotope probing, combined with high-throughput sequencing of V4 hypervariable regions from 18S rRNA gene amplicons (Tag-SIP), identified 19 operational taxonomic units (OTUs) of microbial eukaryotes that consumed M. pusilla. These OTUs were distantly related to cultured taxa within the dinoflagellates, ciliates, stramenopiles (MAST-1C and MAST-3 clades) and Telonema flagellates, thus, far known only from their environmental 18S rRNA gene sequences. Our discovery of eukaryotic prey consumption by MAST cells confirms that their trophic role in marine microbial food webs includes grazing upon picoeukaryotes. Our study provides new experimental evidence directly linking the genetic identity of diverse uncultivated microbial eukaryotes to the consumption of picoeukaryotic phytoplankton in the upper ocean. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  7. A modified reverse one-hybrid screen identifies transcriptional activation in Phyochrome-Interacting Factor 3

    USDA-ARS?s Scientific Manuscript database

    Transcriptional activation domains (TAD) are difficult to predict and identify, since they are not conserved and have little consensus. Here, we describe a yeast-based screening method that is able to identify individual amino acid residues involved in transcriptional activation in a high throughput...

  8. Using Deep UV Raman Spectroscopy to Identify In Situ Microbial Activity

    NASA Astrophysics Data System (ADS)

    Sapers, H. M.; Wanger, G.; Amend, J.; Orphan, V. J.; Bhartia, R.

    2017-12-01

    Microbial communities living in close association with lithic substrates play a critical role in biogeochemical cycles. Understanding the interactions between microorganisms and their abiotic substrates requires knowledge of microbial activity. Identifying active cells adhered to complex environmental substrates, especially in low biomass systems, remains a challenge. Stable isotope probing (SIP) provides a means to trace microbial activity in environmental systems. Active members of the community take up labeled substrates and incorporate the labels into biomolecules that can be detected through downstream analyses. Here we show for the first time that Deep UV (248 nm) Raman spectroscopy can differentiate microbial cells labeled with stable isotopes. Previous studies have used Raman spectroscopy with a 532 nm source to identify active bacterial cells by measuring a Raman shift between peaks corresponding to amino acids incorporating 13C compared to controls. However, excitation at 532 nm precludes detection on complex substrates due to high autofluorescence of native minerals. Excitation in the DUV range offers non-destructive imaging on mineral surfaces - retaining critical contextual information. We prepared cultures of E. coli grown in 50 atom% 13C glucose spotted onto Al wafers to test the ability of DUV Raman spectroscopy to differentiate labeled and unlabeled cells. For the first time, we are able to demonstrate a distinct and repeatable shift between cells grown in labeled media and unlabeled media when imaged on Al wafers with DUV Raman spectroscopy. The Raman spectra are dominated by the characteristic Raman bands of guanine. The dominant marker peak for guanine attributed to N7-C8 and C8-N9 ring stretching and C8-H in-plane bending, is visible at 1480 cm-1 in the unlabeled cells and is blue-shifted by 20 wavenumbers to 1461 cm-1 in the labeled cells. The ability of DUV Raman to effectively identify regions containing cells that have incorporated isotopic

  9. A stoichiometric organic matter decomposition model in a chemostat culture.

    PubMed

    Kong, Jude D; Salceanu, Paul; Wang, Hao

    2018-02-01

    Biodegradation, the disintegration of organic matter by microorganism, is essential for the cycling of environmental organic matter. Understanding and predicting the dynamics of this biodegradation have increasingly gained attention from the industries and government regulators. Since changes in environmental organic matter are strenuous to measure, mathematical models are essential in understanding and predicting the dynamics of organic matters. Empirical evidence suggests that grazers' preying activity on microorganism helps to facilitate biodegradation. In this paper, we formulate and investigate a stoichiometry-based organic matter decomposition model in a chemostat culture that incorporates the dynamics of grazers. We determine the criteria for the uniform persistence and extinction of the species and chemicals. Our results show that (1) if at the unique internal steady state, the per capita growth rate of bacteria is greater than the sum of the bacteria's death and dilution rates, then the bacteria will persist uniformly; (2) if in addition to this, (a) the grazers' per capita growth rate is greater than the sum of the dilution rate and grazers' death rate, and (b) the death rate of bacteria is less than some threshold, then the grazers will persist uniformly. These conditions can be achieved simultaneously if there are sufficient resources in the feed bottle. As opposed to the microcosm decomposition models' results, in a chemostat culture, chemicals always persist. Besides the transcritical bifurcation observed in microcosm models, our chemostat model exhibits Hopf bifurcation and Rosenzweig's paradox of enrichment phenomenon. Our sensitivity analysis suggests that the most effective way to facilitate degradation is to decrease the dilution rate.

  10. Using Active Learning to Identify Health Information Technology Related Patient Safety Events.

    PubMed

    Fong, Allan; Howe, Jessica L; Adams, Katharine T; Ratwani, Raj M

    2017-01-18

    The widespread adoption of health information technology (HIT) has led to new patient safety hazards that are often difficult to identify. Patient safety event reports, which are self-reported descriptions of safety hazards, provide one view of potential HIT-related safety events. However, identifying HIT-related reports can be challenging as they are often categorized under other more predominate clinical categories. This challenge of identifying HIT-related reports is exacerbated by the increasing number and complexity of reports which pose challenges to human annotators that must manually review reports. In this paper, we apply active learning techniques to support classification of patient safety event reports as HIT-related. We evaluated different strategies and demonstrated a 30% increase in average precision of a confirmatory sampling strategy over a baseline no active learning approach after 10 learning iterations.

  11. Canopy-Forming Seaweeds in Urchin-Dominated Systems in Eastern Canada: Structuring Forces or Simple Prey for Keystone Grazers?

    PubMed Central

    Blain, Caitlin; Gagnon, Patrick

    2014-01-01

    Models of benthic community dynamics for the extensively studied, shallow rocky ecosystems in eastern Canada emphasize kelp-urchin interactions. These models may bias the perception of factors and processes that structure communities, for they largely overlook the possible contribution of other seaweeds to ecosystem resilience. We examined the persistence of the annual, acidic (H2SO4), brown seaweed Desmarestia viridis in urchin barrens at two sites in Newfoundland (Canada) throughout an entire growth season (February to October). We also compared changes in epifaunal assemblages in D. viridis and other conspicuous canopy-forming seaweeds, the non-acidic conspecific Desmarestia aculeata and kelp Agarum clathratum. We show that D. viridis can form large canopies within the 2-to-8 m depth range that represent a transient community state termed “Desmarestia bed”. The annual resurgence of Desmarestia beds and continuous occurrence of D. aculeata and A. clathratum, create biological structure for major recruitment pulses in invertebrate and fish assemblages (e.g. from quasi-absent gastropods to >150 000 recruits kg−1 D. viridis). Many of these pulses phase with temperature-driven mass release of acid to the environment and die-off in D. viridis. We demonstrate experimentally that the chemical makeup of D. viridis and A. clathratum helps retard urchin grazing compared to D. aculeata and the highly consumed kelp Alaria esculenta. In light of our findings and related studies, we propose fundamental changes to the study of community shifts in shallow, rocky ecosystems in eastern Canada. In particular, we advocate the need to regard certain canopy-forming seaweeds as structuring forces interfering with top-down processes, rather than simple prey for keystone grazers. We also propose a novel, empirical model of ecological interactions for D. viridis. Overall, our study underscores the importance of studying organisms together with cross-scale environmental variability

  12. Using FMRI brain activation to identify cognitive states associated with perception of tools and dwellings.

    PubMed

    Shinkareva, Svetlana V; Mason, Robert A; Malave, Vicente L; Wang, Wei; Mitchell, Tom M; Just, Marcel Adam

    2008-01-02

    Previous studies have succeeded in identifying the cognitive state corresponding to the perception of a set of depicted categories, such as tools, by analyzing the accompanying pattern of brain activity, measured with fMRI. The current research focused on identifying the cognitive state associated with a 4s viewing of an individual line drawing (1 of 10 familiar objects, 5 tools and 5 dwellings, such as a hammer or a castle). Here we demonstrate the ability to reliably (1) identify which of the 10 drawings a participant was viewing, based on that participant's characteristic whole-brain neural activation patterns, excluding visual areas; (2) identify the category of the object with even higher accuracy, based on that participant's activation; and (3) identify, for the first time, both individual objects and the category of the object the participant was viewing, based only on other participants' activation patterns. The voxels important for category identification were located similarly across participants, and distributed throughout the cortex, focused in ventral temporal perceptual areas but also including more frontal association areas (and somewhat left-lateralized). These findings indicate the presence of stable, distributed, communal, and identifiable neural states corresponding to object concepts.

  13. Identifying active methane-oxidizers in thawed Arctic permafrost by proteomics

    NASA Astrophysics Data System (ADS)

    Lau, C. M.; Stackhouse, B. T.; Chourey, K.; Hettich, R. L.; Vishnivetskaya, T. A.; Pfiffner, S. M.; Layton, A. C.; Mykytczuk, N. C.; Whyte, L.; Onstott, T. C.

    2012-12-01

    The rate of CH4 release from thawing permafrost in the Arctic has been regarded as one of the determining factors on future global climate. It is uncertain how indigenous microorganisms would interact with such changing environmental conditions and hence their impact on the fate of carbon compounds that are sequestered in the cryosol. Multitudinous studies of pristine surface cryosol (top 5 cm) and microcosm experiments have provided growing evidence of effective methanotrophy. Cryosol samples corresponding to active layer were sampled from a sparsely vegetated, ice-wedge polygon at the McGill Arctic Research Station at Axel Heiberg Island, Nunavut, Canada (N79°24, W90°45) before the onset of annual thaw. Pyrosequencing of 16S rRNA gene indicated the occurrence of methanotroph-containing bacterial families as minor components (~5%) in pristine cryosol including Bradyrhizobiaceae, Methylobacteriaceae and Methylocystaceae within alpha-Proteobacteria, and Methylacidiphilaceae within Verrucomicrobia. The potential of methanotrophy is supported by preliminary analysis of metagenome data, which indicated putative methane monooxygenase gene sequences relating to Bradyrhizobium sp. and Pseudonocardia sp. are present. Proteome profiling in general yielded minute traces of proteins, which likely hints at dormant nature of the soil microbial consortia. The lack of specific protein database for permafrost posted additional challenge to protein identification. Only 35 proteins could be identified in the pristine cryosol and of which 60% belonged to Shewanella sp. Most of the identified proteins are known to be involved in energy metabolism or post-translational modification of proteins. Microcosms amended with sodium acetate exhibited a net methane consumption of ~65 ngC-CH4 per gram (fresh weight) of soil over 16 days of aerobic incubation at room temperature. The pH in microcosm materials remained acidic (decreased from initial 4.7 to 4.5). Protein extraction and

  14. Response to dietary tannin challenges in view of the browser/grazer dichotomy in an Ethiopian setting: Bonga sheep versus Kaffa goats.

    PubMed

    Yisehak, Kechero; Kibreab, Yoseph; Taye, Tolemariam; Lourenço, Marta Ribeiro Alves; Janssens, Geert Paul Jules

    2016-01-01

    It has been suggested that goats (typical browser) are better adapted to digest tannin-rich diets than sheep (typical grazer). To evaluate this, Bonga sheep and Kaffa goats were used in a 2 × 3 randomized crossover design with two species, three diets, and three periods (15-day adaptation + 7-day collection). The dietary treatments consisted of grass-based hay only (tannin-free diet = FT), a high-tannin diet (36% Albizia schimperiana (AS) + 9% Ficus elastica (FE) + 55% FT (HT)), and HT + polyethylene glycol 6000 (PEG). Animals were individually fed at 50 g dry matter (DM)/kg body weight (BW) and had free access to clean drinking water and mineralized salt licks. Nutrient intake, apparent nutrient digestibility, nutrient conversion ratios, and live weight changes were determined. Condensed tannin concentrations in AS and FE were 110 and 191 g/kg DM, respectively. Both sheep and goats ate 47% more of HT than FT, and dry matter intake further increased by 9% when PEG was added, with clear difference in effect size between goats and sheep (P < 0.001). The effects of the tannin-rich diet and PEG addition were similarly positive for DM digestibility between sheep and goats, but crude protein (CP) digestibility was higher in HT + PEG-fed goats than in sheep fed the same diet. However, PEG addition induced a larger improvement in growth performance and feed efficiency ratio in sheep than in goat (P < 0.001). The addition of PEG as a tannin binder improved digestion and performance in both species, but with the highest effect size in sheep.

  15. The OPTX Project. V. Identifying Distant Active Galactic Nuclei

    NASA Astrophysics Data System (ADS)

    Trouille, L.; Barger, A. J.; Tremonti, C.

    2011-11-01

    The Baldwin, Phillips, and Terlevich emission-line ratio diagnostic ([O III]/Hβ versus [N II]/Hα, hereafter BPT diagram) efficiently separates galaxies whose signal is dominated by star formation (BPT-SF) from those dominated by active galactic nucleus (AGN) activity (BPT-AGN). Yet this BPT diagram is limited to z < 0.5, the redshift at which [N II]λ6584 leaves the optical spectral window. Using the Sloan Digital Sky Survey (SDSS), we construct a new diagnostic, or TBT diagram, that is based on rest-frame g - z color, [Ne III]λ3869, and [O II]λλ3726 + 3729 and can be used for galaxies out to z < 1.4. The TBT diagram identifies 98.7% of the SDSS BPT-AGN as TBT-AGN and 97% of the SDSS BPT-SF as TBT-SF. Furthermore, it identifies 97% of the OPTX Chandra X-ray-selected AGNs as TBT-AGN. This is in contrast to the BPT diagram, which misidentifies 20% of X-ray-selected AGNs as BPT-SF. We use the Great Observatories Origins Deep Survey North and Lockman Hole galaxy samples, with their accompanying deep Chandra imaging, to perform X-ray and infrared stacking analyses to further validate our TBT-AGN and TBT-SF selections; that is, we verify the dominance of AGN activity in the former and star formation activity in the latter. Finally, we address the inclusion of the majority of the BPT-comp (sources lying between the BPT-SF and BPT-AGN regimes) in our TBT-AGN regime. We find that the stacked BPT-comp source is X-ray hard (langΓeffrang = 1.0+0.4 -0.4) and has a high X-ray luminosity to total infrared luminosity ratio. This suggests that, on average, the X-ray signal in BPT-comp is dominated by obscured or low accretion rate AGN activity rather than by star formation, supporting their inclusion in the TBT-AGN regime. Some of the data presented herein were obtained at the W. M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and the National Aeronautics and Space Administration

  16. Identifying Facilitators and Barriers to Physical Activity for Adults with Down Syndrome

    ERIC Educational Resources Information Center

    Mahy, J.; Shields, N.; Taylor, N. F.; Dodd, K. J.

    2010-01-01

    Background: Adults with Down syndrome are typically sedentary, and many do not participate in the recommended levels of physical activity per week. The aim of this study was to identify the facilitators and barriers to physical activity for this group. Method: Semi-structured interviews were conducted to elicit the views of adults with Down…

  17. Emodin is identified as the active component of ether extracts from Rhizoma Polygoni Cuspidati, for anti-MRSA activity.

    PubMed

    Cao, Feng; Peng, Wei; Li, Xiaoli; Liu, Ming; Li, Bin; Qin, Rongxin; Jiang, Weiwei; Cen, Yanyan; Pan, Xichun; Yan, Zifei; Xiao, Kangkang; Zhou, Hong

    2015-06-01

    This study investigated the anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activity and chemical compositions of ether extracts from Rhizoma Polygoni Cuspidati (ET-RPC). Significant anti-MRSA activities of ET-RPC against MRSA252 and MRSA clinical strains were tested in in vitro antibacterial experiments, such as inhibition zone diameter test, minimal inhibitory concentration test, and dynamic bacterial growth assay. Subsequently, 7 major compounds of ET-RPC were purified and identified as polydatin, resveratrol-4-O-d-(6'-galloyl)-glucopyranoside, resveratrol, torachryson-8-O-glucoside, emodin-8-O-glucoside, 6-hydroxy-emodin, and emodin using liquid chromatography - electrospray ionization - tandem mass spectrometry. After investigation of anti-MRSA activities of the 7 major compounds, only emodin had significant anti-MRSA activity. Further, transmission electron microscopy was used to observe morphological changes in the cell wall of MRSA252, and the result revealed that emodin could damage the integrity of cell wall, leading to loss of intracellular components. In summary, our results showed ET-RPC could significantly inhibit bacterial growth of MRSA strains. Emodin was identified as the major compound with anti-MRSA activity; this activity was related to destruction of the integrity of the cell wall and cell membrane.

  18. Planktonic food web structure at a coastal time-series site: II. Spatiotemporal variability of microbial trophic activities

    NASA Astrophysics Data System (ADS)

    Connell, Paige E.; Campbell, Victoria; Gellene, Alyssa G.; Hu, Sarah K.; Caron, David A.

    2017-03-01

    The grazing activities of phagotrophic protists on various microbial assemblages play key roles in determining the amount of carbon available for higher trophic levels and for export out of the photic zone. However, comparisons of the proportion of carbon consumed from the phytoplankton (cyanobacteria+photosynthetic eukaryotes) and heterotrophic bacteria (bacteria+archaea, excluding cyanobacteria) are rare. In this study, microbial community composition, phytoplankton growth and mortality rates (total chlorophyll a, Synechococcus, Prochlorococcus, and photosynthetic picoeukaryotes), and bacterial mortality rates were measured seasonally from 2012 to 2014 in the surface waters of three environmentally distinct sites in the San Pedro Channel, off the coast of southern CA, USA. Higher nutrient concentrations at the nearshore site supported community standing stocks that were 1.3-4.5x those found offshore, yet average growth and grazing rates of the phytoplankton and bacterial assemblages were generally similar between sites and across seasons. Thus, the amount of carbon consumed by the grazer assemblage was largely dictated by prey standing stocks. Heterotrophic bacteria constituted an important source of carbon for microbial consumers, particularly at the two offshore sites where bacterial carbon consumed was roughly equivalent to the amount of phytoplankton carbon consumed. Carbon removal by grazers at the nearshore station was predominantly from the diatoms, which were the primary component of the photosynthetic community at that site. This study highlights the significant contribution of protistan-bacterial trophic interactions to planktonic food webs and provides unique community composition and turnover data to inform biogeochemical models.

  19. Water-Borne Cues of a Non-Indigenous Seaweed Mediate Grazer-Deterrent Responses in Native Seaweeds, but Not Vice Versa

    PubMed Central

    Yun, Hee Young; Engelen, Aschwin H.; Santos, Rui O.; Molis, Markus

    2012-01-01

    Plants optimise their resistance to herbivores by regulating deterrent responses on demand. Induction of anti-herbivory defences can occur directly in grazed plants or from emission of risk cues to the environment, which modifies interactions of adjacent plants with, for instance, their consumers. This study confirmed the induction of anti-herbivory responses by water-borne risk cues between adjoining con-specific seaweeds and firstly examined whether plant-plant signalling also exists among adjacent hetero-specific seaweeds. Furthermore, differential abilities and geographic variation in plant-plant signalling by a non-indigenous seaweed as well as native seaweeds were assessed. Twelve-day induction experiments using the non-indigenous seaweed Sargassum muticum were conducted in the laboratory in Portugal and Germany with one local con-familiar (Portugal: Cystoseira humilis, Germany: Halidrys siliquosa) and hetero-familiar native species (Portugal: Fucus spiralis, Germany: F. vesiculosus). All seaweeds were grazed by a local isopod species (Portugal: Stenosoma nadejda, Germany: Idotea baltica) and were positioned upstream of con- and hetero-specific seaweeds. Grazing-induced modification in seaweed traits were tested in three-day feeding assays between cue-exposed and cue-free ( = control) pieces of both fresh and reconstituted seaweeds. Both Fucus species reduced their palatability when positioned downstream of isopod-grazed con-specifics. Yet, the palatability of non-indigenous S. muticum remained constant in the presence of upstream grazed con-specifics and native hetero-specifics. In contrast, both con-familiar (but neither hetero-familiar) native species reduced palatability when located downstream of grazed S. muticum. Similar patterns of grazer-deterrent responses to water-borne cues were observed on both European shores, and were almost identical between assays using fresh and reconstituted seaweeds. Hence, seaweeds may use plant-plant signalling to

  20. Water-borne cues of a non-indigenous seaweed mediate grazer-deterrent responses in native seaweeds, but not vice versa.

    PubMed

    Yun, Hee Young; Engelen, Aschwin H; Santos, Rui O; Molis, Markus

    2012-01-01

    Plants optimise their resistance to herbivores by regulating deterrent responses on demand. Induction of anti-herbivory defences can occur directly in grazed plants or from emission of risk cues to the environment, which modifies interactions of adjacent plants with, for instance, their consumers. This study confirmed the induction of anti-herbivory responses by water-borne risk cues between adjoining con-specific seaweeds and firstly examined whether plant-plant signalling also exists among adjacent hetero-specific seaweeds. Furthermore, differential abilities and geographic variation in plant-plant signalling by a non-indigenous seaweed as well as native seaweeds were assessed. Twelve-day induction experiments using the non-indigenous seaweed Sargassum muticum were conducted in the laboratory in Portugal and Germany with one local con-familiar (Portugal: Cystoseira humilis, Germany: Halidrys siliquosa) and hetero-familiar native species (Portugal: Fucus spiralis, Germany: F. vesiculosus). All seaweeds were grazed by a local isopod species (Portugal: Stenosoma nadejda, Germany: Idotea baltica) and were positioned upstream of con- and hetero-specific seaweeds. Grazing-induced modification in seaweed traits were tested in three-day feeding assays between cue-exposed and cue-free ( = control) pieces of both fresh and reconstituted seaweeds. Both Fucus species reduced their palatability when positioned downstream of isopod-grazed con-specifics. Yet, the palatability of non-indigenous S. muticum remained constant in the presence of upstream grazed con-specifics and native hetero-specifics. In contrast, both con-familiar (but neither hetero-familiar) native species reduced palatability when located downstream of grazed S. muticum. Similar patterns of grazer-deterrent responses to water-borne cues were observed on both European shores, and were almost identical between assays using fresh and reconstituted seaweeds. Hence, seaweeds may use plant-plant signalling to

  1. Functional Brain Activation Differences in Stuttering Identified with a Rapid fMRI Sequence

    ERIC Educational Resources Information Center

    Loucks, Torrey; Kraft, Shelly Jo; Choo, Ai Leen; Sharma, Harish; Ambrose, Nicoline G.

    2011-01-01

    The purpose of this study was to investigate whether brain activity related to the presence of stuttering can be identified with rapid functional MRI (fMRI) sequences that involved overt and covert speech processing tasks. The long-term goal is to develop sensitive fMRI approaches with developmentally appropriate tasks to identify deviant speech…

  2. Validation of mercury tip-switch and accelerometer activity sensors for identifying resting and active behavior in bears

    USGS Publications Warehouse

    Jasmine Ware,; Rode, Karyn D.; Pagano, Anthony M.; Bromaghin, Jeffrey F.; Robbins, Charles T.; Joy Erlenbach,; Shannon Jensen,; Amy Cutting,; Nicole Nicassio-Hiskey,; Amy Hash,; Owen, Megan A.; Heiko Jansen,

    2015-01-01

    Activity sensors are often included in wildlife transmitters and can provide information on the behavior and activity patterns of animals remotely. However, interpreting activity-sensor data relative to animal behavior can be difficult if animals cannot be continuously observed. In this study, we examined the performance of a mercury tip-switch and a tri-axial accelerometer housed in collars to determine whether sensor data can be accurately classified as resting and active behaviors and whether data are comparable for the 2 sensor types. Five captive bears (3 polar [Ursus maritimus] and 2 brown [U. arctos horribilis]) were fitted with a collar specially designed to internally house the sensors. The bears’ behaviors were recorded, classified, and then compared with sensor readings. A separate tri-axial accelerometer that sampled continuously at a higher frequency and provided raw acceleration values from 3 axes was also mounted on the collar to compare with the lower resolution sensors. Both accelerometers more accurately identified resting and active behaviors at time intervals ranging from 1 minute to 1 hour (≥91.1% accuracy) compared with the mercury tip-switch (range = 75.5–86.3%). However, mercury tip-switch accuracy improved when sampled at longer intervals (e.g., 30–60 min). Data from the lower resolution accelerometer, but not the mercury tip-switch, accurately predicted the percentage of time spent resting during an hour. Although the number of bears available for this study was small, our results suggest that these activity sensors can remotely identify resting versus active behaviors across most time intervals. We recommend that investigators consider both study objectives and the variation in accuracy of classifying resting and active behaviors reported here when determining sampling interval.

  3. Functional brain activation differences in stuttering identified with a rapid fMRI sequence

    PubMed Central

    Kraft, Shelly Jo; Choo, Ai Leen; Sharma, Harish; Ambrose, Nicoline G.

    2011-01-01

    The purpose of this study was to investigate whether brain activity related to the presence of stuttering can be identified with rapid functional MRI (fMRI) sequences that involved overt and covert speech processing tasks. The long-term goal is to develop sensitive fMRI approaches with developmentally appropriate tasks to identify deviant speech motor and auditory brain activity in children who stutter closer to the age at which recovery from stuttering is documented. Rapid sequences may be preferred for individuals or populations who do not tolerate long scanning sessions. In this report, we document the application of a picture naming and phoneme monitoring task in three minute fMRI sequences with adults who stutter (AWS). If relevant brain differences are found in AWS with these approaches that conform to previous reports, then these approaches can be extended to younger populations. Pairwise contrasts of brain BOLD activity between AWS and normally fluent adults indicated the AWS showed higher BOLD activity in the right inferior frontal gyrus (IFG), right temporal lobe and sensorimotor cortices during picture naming and and higher activity in the right IFG during phoneme monitoring. The right lateralized pattern of BOLD activity together with higher activity in sensorimotor cortices is consistent with previous reports, which indicates rapid fMRI sequences can be considered for investigating stuttering in younger participants. PMID:22133409

  4. Dietary bioavailability of Cu adsorbed to colloidal hydrous ferric oxide

    USGS Publications Warehouse

    Cain, Daniel J.; Croteau, Marie-Noële; Fuller, Christopher C.

    2013-01-01

    The dietary bioavailability of copper (Cu) adsorbed to synthetic colloidal hydrous ferric oxide (HFO) was evaluated from the assimilation of 65Cu by two benthic grazers, a gastropod and a larval mayfly. HFO was synthesized, labeled with 65Cu to achieve a Cu/Fe ratio comparable to that determined in naturally formed HFO, and then aged. The labeled colloids were mixed with a food source (the diatom Nitzschia palea) to yield dietary 65Cu concentrations ranging from 211 to 2204 nmol/g (dry weight). Animals were pulse fed the contaminated diet and assimilation of 65Cu from HFO was determined following 1–3 days of depuration. Mass transfer of 65Cu from HFO to the diatom was less than 1%, indicating that HFO was the source of 65Cu to the grazers. Estimates of assimilation efficiency indicated that the majority of Cu ingested as HFO was assimilated (values >70%), implying that colloidal HFO potentially represents a source of dietary Cu to benthic grazers, especially where there is active formation and infiltration of these particles into benthic substrates.

  5. Re-constructing nutritional history of Serengeti wildebeest from stable isotopes in tail hair: seasonal starvation patterns in an obligate grazer.

    PubMed

    Rysava, K; McGill, R A R; Matthiopoulos, J; Hopcraft, J G C

    2016-07-15

    Nutritional bottlenecks often limit the abundance of animal populations and alter individual behaviours; however, establishing animal condition over extended periods of time using non-invasive techniques has been a major limitation in population ecology. We test if the sequential measurement of δ(15) N values in a continually growing tissue, such as hair, can be used as a natural bio-logger akin to tree rings or ice cores to provide insights into nutritional stress. Nitrogen stable isotope ratios were measured by continuous-flow isotope-ratio mass spectrometry (IRMS) from 20 sequential segments along the tail hairs of 15 migratory wildebeest. Generalized Linear Models were used to test for variation between concurrent segments of hair from the same individual, and to compare the δ(15) N values of starved and non-starved animals. Correlations between δ(15) N values in the hair and periods of above-average energy demand during the annual cycle were tested using Generalized Additive Mixed Models. The time series of nitrogen isotope ratios in the tail hair are comparable between strands from the same individual. The most likely explanation for the pattern of (15) N enrichment between individuals is determined by life phase, and especially the energetic demands associated with reproduction. The mean δ(15) N value of starved animals was greater than that of non-starved animals, suggesting that higher δ(15) N values correlate with periods of nutritional stress. High δ(15) N values in the tail hair of wildebeest are correlated with periods of negative energy balance, suggesting they may be used as a reliable indicator of the animal's nutritional history. This technique might be applicable to other obligate grazers. Most importantly, the sequential isotopic analysis of hair offers a continuous record of the chronic condition of wildebeest (effectively converting point data into time series) and allows researchers to establish the animal's nutritional diary. © 2016

  6. Removal of novel antiandrogens identified in biological effluents of domestic wastewater by activated carbon.

    PubMed

    Ma, Dehua; Chen, Lujun; Liu, Rui

    2017-10-01

    Environmental antiandrogenic (AA) contaminants in effluents from wastewater treatment plants have the potential for negative impacts on wildlife and human health. The aim of our study was to identify chemical contaminants with likely AA activity in the biological effluents and evaluate the removal of these antiandrogens (AAs) during advanced treatment comprising adsorption onto granular activated carbon (GAC). In this study, profiling of AA contaminants in biological effluents and tertiary effluents was conducted using effect-directed analysis (EDA) including high performance liquid chromatography (HPLC) fractionation, a recombinant yeast screen containing androgen receptor (YAS), in combination with mass spectrometry analyses. Analysis of a wastewater secondary effluent from a membrane bioreactor revealed complex profiles of AA activity comprising 14 HPLC fractions and simpler profiles of GAC effluents with only 2 to 4 moderately polar HPLC fractions depending on GAC treatment conditions. Gas chromatography-mass spectrometry and ultra-high performance liquid chromatography-nanospray mass spectrometry analyses of AA fractions in the secondary effluent resulted in detection of over 10 chemical contaminants, which showed inhibition of YAS activity and were potential AAs. The putative AAs included biocides, food additives, flame retardants, pharmaceuticals and industrial contaminants. To our knowledge, it is the first time that the AA properties of N-ethyl-2-isopropyl-5-methylcyclohexanecarboxamide (WS3), cetirizine, and oxcarbazepine are reported. The EDA used in this study was proven to be a powerful tool to identify novel chemical structures with AA activity in the complex aquatic environment. The adsorption process to GAC of all the identified antiandrogens, except WS3 and triclosan, fit well with the pseudo-second order kinetics models. Adsorption to GAC could further remove most of the AAs identified in the biological effluents with high efficiencies. Copyright

  7. [Preventive activities in primary health care: identifying the agreement among evidence-based guidelines].

    PubMed

    Gosalbes Soler, V; Márquez Calderón, S; Maiques Galán, A; Latour Pérez, J; Bernal Delgado, E; Puig Barberá, J; Arranz Lázaro, M

    2000-01-01

    The purpose of this article is to identify the agreement among evidence-based guidelines about recommendations on preventive activities in low risk adults. For which we identified, from the 1996 US Task Force on Preventive Services Guide those preventives activities classified like A or B (recommendation in favour of provision) and like D or E (recommendation against provision), excepting those D and E recommendations based on descriptives studies or expert opinions. Both preventive activities aimed at pregnant women and children and those which are not applicable to our context were excluded. Selected preventive services were compared with the range of age, sex and periodicity in which agreement with the recommendations of American College of Physicians and Canadian Task Force on Preventive Services existed. We found the following agreements. Screening activities. In favour: screening for hypercholesterolemia, hypertension, breast cancer, colorectal cancer, uterine cervix cancer, rubella, visual and hearing impairment and problem drinking. Against: cancer of prostate, lung, bladder and thyroid, and asymptomatic bacteriuria. Counseling activities. In favour: smoking, motor-vehicles injuries, alcohol consumption, unintended pregnancy. Immunizations and quimioprophylaxis. In favour: Vaccines for influenza, tetanus-diphtheria, hepatitis B and measles-mumps-rubella. Postexposure prophylaxis to hepatitis A, hepatitis B, meningococcal, rabies and tetanus. We see then, that a high degree in agreement among the main guidelines exists; about the preventive activities to perform in Primary Health Services, nevertheless we observed low fulfillment of certain preventive activities in Primary Health Services, different barriers for the accomplishment from these activities were described.

  8. Global Proteome Analysis Identifies Active Immunoproteasome Subunits in Human Platelets*

    PubMed Central

    Klockenbusch, Cordula; Walsh, Geraldine M.; Brown, Lyda M.; Hoffman, Michael D.; Ignatchenko, Vladimir; Kislinger, Thomas; Kast, Juergen

    2014-01-01

    The discovery of new functions for platelets, particularly in inflammation and immunity, has expanded the role of these anucleate cell fragments beyond their primary hemostatic function. Here, four in-depth human platelet proteomic data sets were generated to explore potential new functions for platelets based on their protein content and this led to the identification of 2559 high confidence proteins. During a more detailed analysis, consistently high expression of the proteasome was discovered, and the composition and function of this complex, whose role in platelets has not been thoroughly investigated, was examined. Data set mining resulted in identification of nearly all members of the 26S proteasome in one or more data sets, except the β5 subunit. However, β5i, a component of the immunoproteasome, was identified. Biochemical analyses confirmed the presence of all catalytically active subunits of the standard 20S proteasome and immunoproteasome in human platelets, including β5, which was predominantly found in its precursor form. It was demonstrated that these components were assembled into the proteasome complex and that standard proteasome as well as immunoproteasome subunits were constitutively active in platelets. These findings suggest potential new roles for platelets in the immune system. For example, the immunoproteasome may be involved in major histocompatibility complex I (MHC I) peptide generation, as the MHC I machinery was also identified in our data sets. PMID:25146974

  9. Pesticide-exposure Matrix helps identify active ingredients in pesticides used in past years

    Cancer.gov

    Pesticide-exposure Matrix was developed to help epidemiologists and other researchers identify the active ingredients to which people were likely exposed when their homes and gardens were treated for pests in past years

  10. Global proteome analysis identifies active immunoproteasome subunits in human platelets.

    PubMed

    Klockenbusch, Cordula; Walsh, Geraldine M; Brown, Lyda M; Hoffman, Michael D; Ignatchenko, Vladimir; Kislinger, Thomas; Kast, Juergen

    2014-12-01

    The discovery of new functions for platelets, particularly in inflammation and immunity, has expanded the role of these anucleate cell fragments beyond their primary hemostatic function. Here, four in-depth human platelet proteomic data sets were generated to explore potential new functions for platelets based on their protein content and this led to the identification of 2559 high confidence proteins. During a more detailed analysis, consistently high expression of the proteasome was discovered, and the composition and function of this complex, whose role in platelets has not been thoroughly investigated, was examined. Data set mining resulted in identification of nearly all members of the 26S proteasome in one or more data sets, except the β5 subunit. However, β5i, a component of the immunoproteasome, was identified. Biochemical analyses confirmed the presence of all catalytically active subunits of the standard 20S proteasome and immunoproteasome in human platelets, including β5, which was predominantly found in its precursor form. It was demonstrated that these components were assembled into the proteasome complex and that standard proteasome as well as immunoproteasome subunits were constitutively active in platelets. These findings suggest potential new roles for platelets in the immune system. For example, the immunoproteasome may be involved in major histocompatibility complex I (MHC I) peptide generation, as the MHC I machinery was also identified in our data sets. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Identifying knowledge activism in worker health and safety representation: A cluster analysis.

    PubMed

    Hall, Alan; Oudyk, John; King, Andrew; Naqvi, Syed; Lewchuk, Wayne

    2016-01-01

    Although worker representation in OHS has been widely recognized as contributing to health and safety improvements at work, few studies have examined the role that worker representatives play in this process. Using a large quantitative sample, this paper seeks to confirm findings from an earlier exploratory qualitative study that worker representatives can be differentiated by the knowledge intensive tactics and strategies that they use to achieve changes in their workplace. Just under 900 worker health and safety representatives in Ontario completed surveys which asked them to report on the amount of time they devoted to different types of representation activities (i.e., technical activities such as inspections and report writing vs. political activities such as mobilizing workers to build support), the kinds of conditions or hazards they tried to address through their representation (e.g., housekeeping vs. modifications in ventilation systems), and their reported success in making positive improvements. A cluster analysis was used to determine whether the worker representatives could be distinguished in terms of the relative time devoted to different activities and the clusters were then compared with reference to types of intervention efforts and outcomes. The cluster analysis identified three distinct groupings of representatives with significant differences in reported types of interventions and in their level of reported impact. Two of the clusters were consistent with the findings in the exploratory study, identified as knowledge activism for greater emphasis on knowledge based political activity and technical-legal representation for greater emphasis on formalized technical oriented procedures and legal regulations. Knowledge activists were more likely to take on challenging interventions and they reported more impact across the full range of interventions. This paper provides further support for the concepts of knowledge activism and technical

  12. Tracking heavy water (D2O) incorporation for identifying and sorting active microbial cells

    PubMed Central

    Berry, David; Mader, Esther; Lee, Tae Kwon; Woebken, Dagmar; Wang, Yun; Zhu, Di; Palatinszky, Marton; Schintlmeister, Arno; Schmid, Markus C.; Hanson, Buck T.; Shterzer, Naama; Mizrahi, Itzhak; Rauch, Isabella; Decker, Thomas; Bocklitz, Thomas; Popp, Jürgen; Gibson, Christopher M.; Fowler, Patrick W.; Huang, Wei E.; Wagner, Michael

    2015-01-01

    Microbial communities are essential to the function of virtually all ecosystems and eukaryotes, including humans. However, it is still a major challenge to identify microbial cells active under natural conditions in complex systems. In this study, we developed a new method to identify and sort active microbes on the single-cell level in complex samples using stable isotope probing with heavy water (D2O) combined with Raman microspectroscopy. Incorporation of D2O-derived D into the biomass of autotrophic and heterotrophic bacteria and archaea could be unambiguously detected via C-D signature peaks in single-cell Raman spectra, and the obtained labeling pattern was confirmed by nanoscale-resolution secondary ion MS. In fast-growing Escherichia coli cells, label detection was already possible after 20 min. For functional analyses of microbial communities, the detection of D incorporation from D2O in individual microbial cells via Raman microspectroscopy can be directly combined with FISH for the identification of active microbes. Applying this approach to mouse cecal microbiota revealed that the host-compound foragers Akkermansia muciniphila and Bacteroides acidifaciens exhibited distinctive response patterns to amendments of mucin and sugars. By Raman-based cell sorting of active (deuterated) cells with optical tweezers and subsequent multiple displacement amplification and DNA sequencing, novel cecal microbes stimulated by mucin and/or glucosamine were identified, demonstrating the potential of the nondestructive D2O-Raman approach for targeted sorting of microbial cells with defined functional properties for single-cell genomics. PMID:25550518

  13. Benthic food web structure in the Comau fjord, Chile (∼42°S): Preliminary assessment including a site with chemosynthetic activity

    NASA Astrophysics Data System (ADS)

    Zapata-Hernández, Germán; Sellanes, Javier; Mayr, Christoph; Muñoz, Práxedes

    2014-12-01

    Using C and N stable isotopes we analyzed different trophic aspects of the benthic fauna at two sites in the Comau fjord: one with presence of venting of chemically reducing fluids and extensive patches of bacterial mats (XH: X-Huinay), and one control site (PG: Punta Gruesa) with a typical fjord benthic habitat. Due to the widespread presence of such microbial patches in the fjord and their recognized trophic role in reducing environments, we hypothesize that these microbial communities could be contributing to the assimilated food of consumers and transferring carbon into high trophic levels in the food web. Food sources in the area included macroalgae with a wide range of δ13C values (-34.7 to -11.9‰), particulate organic matter (POM, δ13C = -20.1‰), terrestrial organic matter (TOM, δ13C = -32.3‰ to -27.9‰) and chemosynthetic filamentous bacteria (δ13C = ∼-33‰). At both sites, fauna depicted typical values indicating photosynthetic production as a main food source (>-20‰). However, at XH selected taxa reported lower δ13C values (e.g. -26.5‰ in Nacella deaurata), suggesting a partial use of chemosynthetic production. Furthermore, enhanced variability at this site in δ13C values of the polyplacophoran Chiton magnificus, the limpet Fissurella picta and the tanaid Zeuxoides sp. may also be responding to the use of a wider scope of primary food sources. Trophic position estimates suggest three trophic levels of consumers at both sites. However, low δ15N values in some grazer and suspension-feeder species suggest that these taxa could be using other sources still to be identified (e.g. bacterial films, microalgae and organic particles of small size-fractions). Furthermore, between-site comparisons of isotopic niche width measurements in some trophic guilds indicate that grazers from XH have more heterogenic trophic niches than at PG (measured as mean distance to centroid and standard deviation of nearest neighbor distance). This last could be

  14. Tracking heavy water (D 2O) incorporation for identifying and sorting active microbial cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Berry, David; Mader, Esther; Lee, Tae Kwon

    Here, microbial communities are essential to the function of virtually all ecosystems and eukaryotes, including humans. However, it is still a major challenge to identify microbial cells active under natural conditions in complex systems. Here in this study, we developed a new method to identify and sort active microbes on the single-cell level in complex samples using stable isotope probing with heavy water (D 2O) combined with Raman microspectroscopy. Incorporation of D 2O-derived D into the biomass of autotrophic and heterotrophic bacteria and archaea could be unambiguously detected via C-D signature peaks in single-cell Raman spectra, and the obtained labelingmore » pattern was confirmed by nanoscale-resolution secondary ion MS. In fast-growing Escherichia coli cells, label detection was already possible after 20 min. For functional analyses of microbial communities, the detection of D incorporation from D 2O in individual microbial cells via Raman microspectroscopy can be directly combined with FISH for the identification of active microbes. Applying this approach to mouse cecal microbiota revealed that the host-compound foragers Akkermansia muciniphila and Bacteroides acidifaciens exhibited distinctive response patterns to amendments of mucin and sugars. By Raman-based cell sorting of active (deuterated) cells with optical tweezers and subsequent multiple displacement amplification and DNA sequencing, novel cecal microbes stimulated by mucin and/or glucosamine were identified, demonstrating the potential of the nondestructive D 2O-Raman approach for targeted sorting of microbial cells with defined functional properties for single-cell genomics.« less

  15. Tracking heavy water (D 2O) incorporation for identifying and sorting active microbial cells

    DOE PAGES

    Berry, David; Mader, Esther; Lee, Tae Kwon; ...

    2014-12-30

    Here, microbial communities are essential to the function of virtually all ecosystems and eukaryotes, including humans. However, it is still a major challenge to identify microbial cells active under natural conditions in complex systems. Here in this study, we developed a new method to identify and sort active microbes on the single-cell level in complex samples using stable isotope probing with heavy water (D 2O) combined with Raman microspectroscopy. Incorporation of D 2O-derived D into the biomass of autotrophic and heterotrophic bacteria and archaea could be unambiguously detected via C-D signature peaks in single-cell Raman spectra, and the obtained labelingmore » pattern was confirmed by nanoscale-resolution secondary ion MS. In fast-growing Escherichia coli cells, label detection was already possible after 20 min. For functional analyses of microbial communities, the detection of D incorporation from D 2O in individual microbial cells via Raman microspectroscopy can be directly combined with FISH for the identification of active microbes. Applying this approach to mouse cecal microbiota revealed that the host-compound foragers Akkermansia muciniphila and Bacteroides acidifaciens exhibited distinctive response patterns to amendments of mucin and sugars. By Raman-based cell sorting of active (deuterated) cells with optical tweezers and subsequent multiple displacement amplification and DNA sequencing, novel cecal microbes stimulated by mucin and/or glucosamine were identified, demonstrating the potential of the nondestructive D 2O-Raman approach for targeted sorting of microbial cells with defined functional properties for single-cell genomics.« less

  16. Identifying the Active Microbiome Associated with Roots and Rhizosphere Soil of Oilseed Rape

    PubMed Central

    Mahmood, Shahid; Ekblad, Alf; Alström, Sadhna; Högberg, Nils; Finlay, Roger

    2017-01-01

    ABSTRACT RNA stable isotope probing and high-throughput sequencing were used to characterize the active microbiomes of bacteria and fungi colonizing the roots and rhizosphere soil of oilseed rape to identify taxa assimilating plant-derived carbon following 13CO2 labeling. Root- and rhizosphere soil-associated communities of both bacteria and fungi differed from each other, and there were highly significant differences between their DNA- and RNA-based community profiles. Verrucomicrobia, Proteobacteria, Planctomycetes, Acidobacteria, Gemmatimonadetes, Actinobacteria, and Chloroflexi were the most active bacterial phyla in the rhizosphere soil. Bacteroidetes were more active in roots. The most abundant bacterial genera were well represented in both the 13C- and 12C-RNA fractions, while the fungal taxa were more differentiated. Streptomyces, Rhizobium, and Flavobacterium were dominant in roots, whereas Rhodoplanes and Sphingomonas (Kaistobacter) were dominant in rhizosphere soil. “Candidatus Nitrososphaera” was enriched in 13C in rhizosphere soil. Olpidium and Dendryphion were abundant in the 12C-RNA fraction of roots; Clonostachys was abundant in both roots and rhizosphere soil and heavily 13C enriched. Cryptococcus was dominant in rhizosphere soil and less abundant, but was 13C enriched in roots. The patterns of colonization and C acquisition revealed in this study assist in identifying microbial taxa that may be superior competitors for plant-derived carbon in the rhizosphere of Brassica napus. IMPORTANCE This microbiome study characterizes the active bacteria and fungi colonizing the roots and rhizosphere soil of Brassica napus using high-throughput sequencing and RNA-stable isotope probing. It identifies taxa assimilating plant-derived carbon following 13CO2 labeling and compares these with other less active groups not incorporating a plant assimilate. Brassica napus is an economically and globally important oilseed crop, cultivated for edible oil, biofuel

  17. Identifying the Active Microbiome Associated with Roots and Rhizosphere Soil of Oilseed Rape.

    PubMed

    Gkarmiri, Konstantia; Mahmood, Shahid; Ekblad, Alf; Alström, Sadhna; Högberg, Nils; Finlay, Roger

    2017-11-15

    RNA stable isotope probing and high-throughput sequencing were used to characterize the active microbiomes of bacteria and fungi colonizing the roots and rhizosphere soil of oilseed rape to identify taxa assimilating plant-derived carbon following 13 CO 2 labeling. Root- and rhizosphere soil-associated communities of both bacteria and fungi differed from each other, and there were highly significant differences between their DNA- and RNA-based community profiles. Verrucomicrobia , Proteobacteria , Planctomycetes , Acidobacteria , Gemmatimonadetes , Actinobacteria , and Chloroflexi were the most active bacterial phyla in the rhizosphere soil. Bacteroidetes were more active in roots. The most abundant bacterial genera were well represented in both the 13 C- and 12 C-RNA fractions, while the fungal taxa were more differentiated. Streptomyces , Rhizobium , and Flavobacterium were dominant in roots, whereas Rhodoplanes and Sphingomonas ( Kaistobacter ) were dominant in rhizosphere soil. " Candidatus Nitrososphaera" was enriched in 13 C in rhizosphere soil. Olpidium and Dendryphion were abundant in the 12 C-RNA fraction of roots; Clonostachys was abundant in both roots and rhizosphere soil and heavily 13 C enriched. Cryptococcus was dominant in rhizosphere soil and less abundant, but was 13 C enriched in roots. The patterns of colonization and C acquisition revealed in this study assist in identifying microbial taxa that may be superior competitors for plant-derived carbon in the rhizosphere of Brassica napus IMPORTANCE This microbiome study characterizes the active bacteria and fungi colonizing the roots and rhizosphere soil of Brassica napus using high-throughput sequencing and RNA-stable isotope probing. It identifies taxa assimilating plant-derived carbon following 13 CO 2 labeling and compares these with other less active groups not incorporating a plant assimilate. Brassica napus is an economically and globally important oilseed crop, cultivated for edible oil

  18. High Throughput Screening Identifies Novel Lead Compounds with Activity against Larval, Juvenile and Adult Schistosoma mansoni

    PubMed Central

    Gardner, J. Mark F.; Bell, Andrew S.; Parkinson, Tanya; Bickle, Quentin

    2016-01-01

    An estimated 600 million people are affected by the helminth disease schistosomiasis caused by parasites of the genus Schistosoma. There is currently only one drug recommended for treating schistosomiasis, praziquantel (PZQ), which is effective against adult worms but not against the juvenile stage. In an attempt to identify improved drugs for treating the disease, we have carried out high throughput screening of a number of small molecule libraries with the aim of identifying lead compounds with balanced activity against all life stages of Schistosoma. A total of almost 300,000 compounds were screened using a high throughput assay based on motility of worm larvae and image analysis of assay plates. Hits were screened against juvenile and adult worms to identify broadly active compounds and against a mammalian cell line to assess cytotoxicity. A number of compounds were identified as promising leads for further chemical optimization. PMID:27128493

  19. A Virtual Screening Approach For Identifying Plants with Anti H5N1 Neuraminidase Activity

    PubMed Central

    2016-01-01

    Recent outbreaks of highly pathogenic and occasional drug-resistant influenza strains have highlighted the need to develop novel anti-influenza therapeutics. Here, we report computational and experimental efforts to identify influenza neuraminidase inhibitors from among the 3000 natural compounds in the Malaysian-Plants Natural-Product (NADI) database. These 3000 compounds were first docked into the neuraminidase active site. The five plants with the largest number of top predicted ligands were selected for experimental evaluation. Twelve specific compounds isolated from these five plants were shown to inhibit neuraminidase, including two compounds with IC50 values less than 92 μM. Furthermore, four of the 12 isolated compounds had also been identified in the top 100 compounds from the virtual screen. Together, these results suggest an effective new approach for identifying bioactive plant species that will further the identification of new pharmacologically active compounds from diverse natural-product resources. PMID:25555059

  20. A Path Analysis to Identify the Psychosocial Factors Influencing Physical Activity and Bone Health in Middle-School Girls

    PubMed Central

    Sharma, Shreela V.; Hoelscher, Deanna M.; Kelder, Steven H.; Diamond, Pamela M.; Day, R. Sue; Hergenroeder, Albert C.

    2011-01-01

    Background The purpose of this study was to identify pathways used by psychosocial factors to influence physical activity and bone health in middle-school girls. Methods Baseline data from the Incorporating More Physical Activity and Calcium in Teens (IMPACT) study collected in 2001 to 2003 were used. IMPACT was a 1 1/2 years nutrition and physical activity intervention study designed to improve bone density in 717 middle-school girls in Texas. Structural Equations Modeling was used to examine the interrelationships and identify the direct and indirect pathways used by various psychosocial and environmental factors to influence physical activity and bone health. Results Results show that physical activity self-efficacy and social support (friend, family engagement, and encouragement in physical activity) had a significant direct and indirect influence on physical activity with participation in sports teams as the mediator. Participation in sports teams had a direct effect on both physical activity (β= 0.20, P < .05) and bone health and (β=0.13, P < .05). Conclusion The current study identified several direct and indirect pathways that psychosocial factors use to influence physical activity and bone health among adolescent girls. These findings are critical for the development of effective interventions for promoting bone health in this population. PMID:19953837

  1. A path analysis to identify the psychosocial factors influencing physical activity and bone health in middle-school girls.

    PubMed

    Sharma, Shreela V; Hoelscher, Deanna M; Kelder, Steven H; Diamond, Pamela M; Day, R Sue; Hergenroeder, Albert C

    2009-09-01

    The purpose of this study was to identify pathways used by psychosocial factors to influence physical activity and bone health in middle-school girls. Baseline data from the Incorporating More Physical Activity and Calcium in Teens (IMPACT) study collected in 2001 to 2003 were used. IMPACT was a 1 1/2 years nutrition and physical activity intervention study designed to improve bone density in 717 middle-school girls in Texas. Structural Equations Modeling was used to examine the interrelationships and identify the direct and indirect pathways used by various psychosocial and environmental factors to influence physical activity and bone health. Results show that physical activity self-efficacy and social support (friend, family engagement, and encouragement in physical activity) had a significant direct and indirect influence on physical activity with participation in sports teams as the mediator. Participation in sports teams had a direct effect on both physical activity (beta = 0.20, P < .05) and bone health and (beta = 0.13, P < .05). The current study identified several direct and indirect pathways that psychosocial factors use to influence physical activity and bone health among adolescent girls. These findings are critical for the development of effective interventions for promoting bone health in this population.

  2. Health e-mavens: identifying active online health information users.

    PubMed

    Sun, Ye; Liu, Miao; Krakow, Melinda

    2016-10-01

    Given the rapid increase of Internet use for effective health communication, it is important for health practitioners to be able to identify and mobilize active users of online health information across various web-based health intervention programmes. We propose the concept 'health e-mavens' to characterize individuals actively engaged in online health information seeking and sharing activities. This study aimed to address three goals: (i) to test the factor structure of health e-mavenism, (ii) to assess the reliability and validity of this construct and (iii) to determine what predictors are associated with health e-mavenism. This study was a secondary analysis of nationally representative data from the 2010 Health Tracking Survey. We assessed the factor structure of health e-mavenism using confirmatory factor analysis and examined socio-demographic variables, health-related factors and use of technology as potential predictors of health e-mavenism through ordered regression analysis. Confirmatory factor analyses showed that a second-order two-factor structure best captured the health e-maven construct. Health e-mavenism comprised two second-order factors, each encompassing two first-order dimensions: information acquisition (consisting of information tracking and consulting) and information transmission (consisting of information posting and sharing). Both first-order and second-order factors exhibited good reliabilities. Several factors were found to be significant predictors of health e-mavenism. This study offers a starting point for further inquiries about health e-mavens. It is a fruitful construct for health promotion research in the age of new media technologies. We conclude with specific recommendations to further develop the health e-maven concept through continued empirical research. © 2015 The Authors. Health Expectations. Published by John Wiley & Sons Ltd.

  3. Evaluating digestion efficiency in full-scale anaerobic digesters by identifying active microbial populations through the lens of microbial activity

    NASA Astrophysics Data System (ADS)

    Mei, Ran; Narihiro, Takashi; Nobu, Masaru K.; Kuroda, Kyohei; Liu, Wen-Tso

    2016-09-01

    Anaerobic digestion is a common technology to biologically stabilize wasted solids produced in municipal wastewater treatment. Its efficiency is usually evaluated by calculating the reduction in volatile solids, which assumes no biomass growth associated with digestion. To determine whether this assumption is valid and further evaluate digestion efficiency, this study sampled 35 digester sludge from different reactors at multiple time points together with the feed biomass in a full-scale water reclamation plant at Chicago, Illinois. The microbial communities were characterized using Illumina sequencing technology based on 16S rRNA and 16S rRNA gene (rDNA). 74 core microbial populations were identified and represented 58.7% of the entire digester community. Among them, active populations were first identified using the ratio of 16S rRNA and 16S rDNA (rRNA/rDNA) for individual populations, but this approach failed to generate consistent results. Subsequently, a recently proposed mass balance model was applied to calculate the specific growth rate (μ), and this approach successfully identified active microbial populations in digester (positive μ) that could play important roles than those with negative μ. It was further estimated that 82% of microbial populations in the feed sludge were digested in comparison with less than 50% calculated using current equations.

  4. Grazing-Activated Production of Dimethyl Sulfide (DMS) by two clones of Emiliania huxleyi

    NASA Technical Reports Server (NTRS)

    Wolfe, Gordon V.; Steinke, Michael

    1996-01-01

    Emiliania huxleyi clones CCMP 370 and CCMP 373 produced similar amounts of dimethylsulfoniopropionate (DMSP) during axenic exponential growth, averaging 109 mM internal DMSP. Both clones had detectable DMSP lyase activity, as measured by production of dimethyl sulfide (DMS) during in vitro assays of crude cell preparations, but activities and conditions differed considerably between clones. Clone 373 had high activity; clone 370 had low activity and required chloride. For both strains, enzyme activity per cell was constant during exponential growth, but little DMS was produced by healthy cells. Rather, DMS production was activated when cells were subjected to physical or chemical stresses that caused cell lysis. We propose that DMSP lyase and DMSP are segregated within these cells and re-action only under conditions that result in cell stress or damage. Such activation occurs during microzooplankton grazing. When these clones were grazed by the dinoflagellate Oxyrrhis marina, DMS was produced; ungrazed cells, as well as those exposed to grazer exudates and associated bacteria, generated no DMS. Grazing of clone 373 produced much more DMS than grazing of clone 370, consistent with their relative in vitro DMSP lyase activities. DMS was only generated when cells were actually being grazed, indicating that ingested cells were responsible for the DMS formation. We suggest that even low levels of grazing can greatly accelerate DMS production.

  5. A rapid review to identify physical activity accrued while playing golf

    PubMed Central

    Luscombe, Jack; Murray, Andrew D; Jenkins, Evan; Archibald, Daryll

    2017-01-01

    Objective To identify physical activity (PA) accrued while playing golf and modifiers of PA accrued. Design A rapid review of primary research studies. Quality was assessed using the National Heart, Lung, and Blood Institute quality assessment tool for cohort and cross-sectional studies. Methods and outcomes The following databases were searched from 1900 to March 2017: SPORTDiscus, Web of Science, PsycINFO, MEDLINE, Google Scholar, Google Advanced Search, ProQuest, WHO International Clinical Trials Registry Platform. All primary research investigating golf or golfers with any of the following outcomes was included: metabolic equivalent of task, oxygen uptake, energy expenditure, heart rate, step count, distance covered, strength, flexibility, balance, sedentary behaviour. Results Phase one searching identified 4944 citations and phase two searching identified 170 citations. In total, 19 articles met inclusion criteria. Golf is primarily a moderate intensity PA, but may be low intensity depending on the playing population and various modifiers. Less PA is accrued by those who ride a golf cart compared with those walking the course. Conclusions Golf can be encouraged in order to attain PA recommendations. Further research is required into the relationship between golf and strength and flexibility PA recommendations and how modifiers affect PA accrued. PROSPERO registration number CRD42017058237. PMID:29187418

  6. Identifying the barriers and facilitators to participation in physical activity for children with Down syndrome.

    PubMed

    Barr, M; Shields, N

    2011-11-01

    Many children with Down syndrome do not undertake the recommended amount of daily physical activity. The aim of this study was to explore the barriers and facilitators to physical activity for this group. Eighteen in-depth interviews were conducted with 20 parents (16 mothers, 4 fathers) of children with Down syndrome aged between 2 and 17 years to examine what factors facilitate physical activity and what factors are barriers to activity for their children. The participants were recruited through a community disability organisation that advocates for people with Down syndrome and their families. Interviews were recorded, transcribed and independently coded and analysed by two researchers using thematic analysis. Four themes on facilitators of physical activity were identified: (1) the positive role of the family; (2) opportunity for social interaction with peers; (3) structured accessible programmes that make adaptations for children with Down syndrome; and (4) children who were determined to succeed and physically skilled. Four themes on the barriers to physical activity were also identified: (1) characteristics commonly associated with Down syndrome; (2) competing family responsibilities; (3) reduced physical or behavioural skills; and (4) a lack of accessible programmes. The results highlight the important role of families in determining how much physical activity children with Down syndrome undertake and the effect that common characteristics associated with Down syndrome can have on maintaining an active lifestyle. Future research needs to concentrate on successful methods of encouraging physical activity, such as ensuring social interaction is part of the activity, and eliminating barriers to physical activity such as the a lack of appropriate programmes for children with Down syndrome. Implementing these strategies may encourage children with Down syndrome to participate more frequently in a physically active lifestyle. © 2011 The Authors. Journal of

  7. How to Identify Success Among Networks That Promote Active Living.

    PubMed

    Litt, Jill; Varda, Danielle; Reed, Hannah; Retrum, Jessica; Tabak, Rachel; Gustat, Jeanette; O'Hara Tompkins, Nancy

    2015-11-01

    We evaluated organization- and network-level factors that influence organizations' perceived success. This is important for managing interorganizational networks, which can mobilize communities to address complex health issues such as physical activity, and for achieving change. In 2011, we used structured interview and network survey data from 22 states in the United States to estimate multilevel random-intercept models to understand organization- and network-level factors that explain perceived network success. A total of 53 of 59 "whole networks" met the criteria for inclusion in the analysis (89.8%). Coordinators identified 559 organizations, with 3 to 12 organizations from each network taking the online survey (response rate = 69.7%; range = 33%-100%). Occupying a leadership position (P < .01), the amount of time with the network (P < .05), and support from community leaders (P < .05) emerged as correlates of perceived success. Organizations' perceptions of success can influence decisions about continuing involvement and investment in networks designed to promote environment and policy change for active living. Understanding these factors can help leaders manage complex networks that involve diverse memberships, varied interests, and competing community-level priorities.

  8. How to Identify Success Among Networks That Promote Active Living

    PubMed Central

    Varda, Danielle; Reed, Hannah; Retrum, Jessica; Tabak, Rachel; Gustat, Jeanette; O'Hara Tompkins, Nancy

    2015-01-01

    Objectives. We evaluated organization- and network-level factors that influence organizations’ perceived success. This is important for managing interorganizational networks, which can mobilize communities to address complex health issues such as physical activity, and for achieving change. Methods. In 2011, we used structured interview and network survey data from 22 states in the United States to estimate multilevel random-intercept models to understand organization- and network-level factors that explain perceived network success. Results. A total of 53 of 59 “whole networks” met the criteria for inclusion in the analysis (89.8%). Coordinators identified 559 organizations, with 3 to 12 organizations from each network taking the online survey (response rate = 69.7%; range = 33%–100%). Occupying a leadership position (P < .01), the amount of time with the network (P < .05), and support from community leaders (P < .05) emerged as correlates of perceived success. Conclusions. Organizations’ perceptions of success can influence decisions about continuing involvement and investment in networks designed to promote environment and policy change for active living. Understanding these factors can help leaders manage complex networks that involve diverse memberships, varied interests, and competing community-level priorities. PMID:26378863

  9. The large mean body size of mammalian herbivores explains the productivity paradox during the Last Glacial Maximum.

    PubMed

    Zhu, Dan; Ciais, Philippe; Chang, Jinfeng; Krinner, Gerhard; Peng, Shushi; Viovy, Nicolas; Peñuelas, Josep; Zimov, Sergey

    2018-04-01

    Large herbivores are a major agent in ecosystems, influencing vegetation structure, and carbon and nutrient flows. During the last glacial period, a mammoth steppe ecosystem prevailed in the unglaciated northern lands, supporting a high diversity and density of megafaunal herbivores. The apparent discrepancy between abundant megafauna and the expected low vegetation productivity under a generally harsher climate with a lower CO 2 concentration, termed the productivity paradox, requires large-scale quantitative analysis using process-based ecosystem models. However, most of the current global dynamic vegetation models (DGVMs) lack explicit representation of large herbivores. Here we incorporated a grazing module in a DGVM based on physiological and demographic equations for wild large grazers, taking into account feedbacks of large grazers on vegetation. The model was applied globally for present-day and the Last Glacial Maximum (LGM). The present-day results of potential grazer biomass, combined with an empirical land-use map, infer a reduction in wild grazer biomass by 79-93% owing to anthropogenic land replacement of natural grasslands. For the LGM, we find that the larger mean body size of mammalian herbivores than today is the crucial clue to explain the productivity paradox, due to a more efficient exploitation of grass production by grazers with a large body size.

  10. Identifying Novel Phenotypes of Vulnerability and Resistance to Activity-Based Anorexia in Adolescent Female Rats

    PubMed Central

    Barbarich-Marsteller, Nicole C.; Underwood, Mark D.; Foltin, Richard W.; Myers, Michael M.; Walsh, B. Timothy; Barrett, Jeffrey S.; Marsteller, Douglas A.

    2018-01-01

    Objective Activity-based anorexia is a translational rodent model that results in severe weight loss, hyperactivity, and voluntary self-starvation. The goal of our investigation was to identify vulnerable and resistant phenotypes of activity-based anorexia in adolescent female rats. Method Sprague-Dawley rats were maintained under conditions of restricted access to food (N = 64; or unlimited access, N = 16) until experimental exit, predefined as a target weight loss of 30–35% or meeting predefined criteria for animal health. Nonlinear mixed effects statistical modeling was used to describe wheel running behavior, time to event analysis was used to assess experimental exit, and a regressive partitioning algorithm was used to classify phenotypes. Results Objective criteria were identified for distinguishing novel phenotypes of activity-based anorexia, including a vulnerable phenotype that conferred maximal hyperactivity, minimal food intake, and the shortest time to experimental exit, and a resistant phenotype that conferred minimal activity and the longest time to experimental exit. Discussion The identification of objective criteria for defining vulnerable and resistant phenotypes of activity-based anorexia in adolescent female rats provides an important framework for studying the neural mechanisms that promote vulnerability to or protection against the development of self-starvation and hyperactivity during adolescence. Ultimately, future studies using these novel phenotypes may provide important translational insights into the mechanisms that promote these maladaptive behaviors characteristic of anorexia nervosa. PMID:23853140

  11. Identifying novel phenotypes of vulnerability and resistance to activity-based anorexia in adolescent female rats.

    PubMed

    Barbarich-Marsteller, Nicole C; Underwood, Mark D; Foltin, Richard W; Myers, Michael M; Walsh, B Timothy; Barrett, Jeffrey S; Marsteller, Douglas A

    2013-11-01

    Activity-based anorexia is a translational rodent model that results in severe weight loss, hyperactivity, and voluntary self-starvation. The goal of our investigation was to identify vulnerable and resistant phenotypes of activity-based anorexia in adolescent female rats. Sprague-Dawley rats were maintained under conditions of restricted access to food (N = 64; or unlimited access, N = 16) until experimental exit, predefined as a target weight loss of 30-35% or meeting predefined criteria for animal health. Nonlinear mixed effects statistical modeling was used to describe wheel running behavior, time to event analysis was used to assess experimental exit, and a regressive partitioning algorithm was used to classify phenotypes. Objective criteria were identified for distinguishing novel phenotypes of activity-based anorexia, including a vulnerable phenotype that conferred maximal hyperactivity, minimal food intake, and the shortest time to experimental exit, and a resistant phenotype that conferred minimal activity and the longest time to experimental exit. The identification of objective criteria for defining vulnerable and resistant phenotypes of activity-based anorexia in adolescent female rats provides an important framework for studying the neural mechanisms that promote vulnerability to or protection against the development of self-starvation and hyperactivity during adolescence. Ultimately, future studies using these novel phenotypes may provide important translational insights into the mechanisms that promote these maladaptive behaviors characteristic of anorexia nervosa. Copyright © 2013 Wiley Periodicals, Inc.

  12. Significant Centers of Tectonic Activity as Identified by Wrinkle Ridges for the Western Hemisphere of Mars

    NASA Technical Reports Server (NTRS)

    Anderson, R.C.; Haldemann, A. F. C.; Golombek, M. P.; Franklin, B. J.; Dohm, J. M.; Lias, J.

    2000-01-01

    The western hemisphere region of Mars has been the site of numerous scientific investigations regarding its tectonic evolution. For this region of Mars, the dominant tectonic region is the Tharsis province. Tharsis is characterized by an enormous system of radiating grabens and a circumferential system of wrinkle ridges. Past investigations of grabens associated with Tharsis have identified specific centers of tectonic activity. A recent structural analysis of the western hemisphere region of Mars which includes the Tharsis region, utilized 25,000 structures to determine the history of local and regional centers of tectonic activity based primarily on the spatial and temporal relationships of extensional features. This investigation revealed that Tharsis is more structurally complex (heterogeneous) than has been previously identified: it consists of numerous regional and local centers of tectonic activity (some are more dominant and/or more long lived than others). Here we use the same approach as Anderson et al. to determine whether the centers of tectonic activity that formed the extensional features also contributed to wrinkle ridge (compressional) formation.

  13. Synthesis and Structure activity relationships of EGCG Analogues, A Recently Identified Hsp90 Inhibitor

    PubMed Central

    Khandelwal, Anuj; Hall, Jessica

    2014-01-01

    Epigallocatechin-3-gallate (EGCG), the principal polyphenol isolated from green tea, was recently shown to inhibit Hsp90, however structure-activity relationships for this natural product have not yet been produced. Herein, we report the synthesis and biological evaluation of EGCG analogues to establish structure-activity relationships between EGCG and Hsp90. All four rings as well as the linker connecting the C- and the D-rings were systematically investigated, which led to the discovery of compounds that inhibit Hs90 and display improvement in efficacy over EGCG. Anti-proliferative activity of all the analogues was determined against MCF-7 and SKBr3 cell lines and Hsp90 inhibitory activity of four most potent analogues was further evaluated by western blot analyses and degradation of Hsp90-dependent client proteins. Prenyl substituted aryl ester of 3,5-dihydroxychroman-3-ol ring system was identified as novel scaffold that exhibit Hsp90 inhibitory activity. PMID:23834230

  14. Relationships between oral morphology and feeding style in the Ungulata: a phylogenetically controlled evaluation.

    PubMed

    Pérez-Barbería, F J; Gordon, I J

    2001-05-22

    In ungulates it is argued that specialization in the consumption of a particular type of food (feeding style) is reflected in morphological adaptations of the organs involved in the selection, processing and digestion of food. We analysed the differences in size and morphology of some oral traits that have been functionally related to food-selection ability (muzzle width, incisor-arcade shape, incisor shape), prehension of food (incisor protrusion), food comminution (molar occlusal surface area, hypsodonty (high-crowned molars)) and intake rate (incisor breadth) between ungulate species with different feeding styles (browser, mixed feeder, grazer). Grazers were characterized by large-body-size species. After controlling only for body mass, we found that grazers had wider muzzles and incisors, more-protruding incisors and more-bulky and higher-crowned molars than did mixed feeders and browsers. When the analyses took into account both body mass and phylogeny, only body mass and two out of the three hypsodonty indexes used remained significantly different between feeding styles. Browsers were smaller, on average, than mixed feeders and grazers, whilst grazers and mixed feeders did not differ in size. Also, browsers had shorter and less-bulky molars than did mixed feeders and grazers; the latter two feeding styles did not differ from each other in any of the hypsodonty indexes. We conclude that the adaptation to different dietary types in most of the oral traits studied is subsumed by the effects of body mass and the sharing of common ancestors. We hypothesize that differences in the ability to exploit different food resources primarily result from differences in body mass between species, and also discuss why hypsodonty characterizes feeding styles.

  15. Relationships between oral morphology and feeding style in the Ungulata: a phylogenetically controlled evaluation.

    PubMed Central

    Pérez-Barbería, F. J.; Gordon, I. J.

    2001-01-01

    In ungulates it is argued that specialization in the consumption of a particular type of food (feeding style) is reflected in morphological adaptations of the organs involved in the selection, processing and digestion of food. We analysed the differences in size and morphology of some oral traits that have been functionally related to food-selection ability (muzzle width, incisor-arcade shape, incisor shape), prehension of food (incisor protrusion), food comminution (molar occlusal surface area, hypsodonty (high-crowned molars)) and intake rate (incisor breadth) between ungulate species with different feeding styles (browser, mixed feeder, grazer). Grazers were characterized by large-body-size species. After controlling only for body mass, we found that grazers had wider muzzles and incisors, more-protruding incisors and more-bulky and higher-crowned molars than did mixed feeders and browsers. When the analyses took into account both body mass and phylogeny, only body mass and two out of the three hypsodonty indexes used remained significantly different between feeding styles. Browsers were smaller, on average, than mixed feeders and grazers, whilst grazers and mixed feeders did not differ in size. Also, browsers had shorter and less-bulky molars than did mixed feeders and grazers; the latter two feeding styles did not differ from each other in any of the hypsodonty indexes. We conclude that the adaptation to different dietary types in most of the oral traits studied is subsumed by the effects of body mass and the sharing of common ancestors. We hypothesize that differences in the ability to exploit different food resources primarily result from differences in body mass between species, and also discuss why hypsodonty characterizes feeding styles. PMID:11375086

  16. Cross-shelf differences in the pattern and pace of bioerosion of experimental carbonate substrates exposed for 3 years on the northern Great Barrier Reef, Australia

    NASA Astrophysics Data System (ADS)

    Tribollet, A.; Golubic, S.

    2005-11-01

    Patterns of bioerosion of dead corals and rubbles on the northern Great Barrier Reef were studied by using blocks of the massive coral Porites experimentally exposed at six sites, located on an inshore-offshore profile, for 1 year and 3 years. Rates of microbioerosion by microborers, grazing by fish, and macrobioerosion by filter-feeding organisms were simultaneously evaluated using image analysis. Microbioerosion, grazing, and total bioerosion were lower at reefs near the Queensland coast than at the edge of the continental shelf (1.81 kg m-2 and 6.07 kg m-2 after 3 years of exposure respectively, for total bioerosion). The opposite pattern was observed for macrobioerosion. Bioaccretion was negligible. These patterns were evident after 1 year of exposure, and became enhanced after 3 years. Microborers were established and were the main agent of bioerosion after 1 year of exposure, and as the principal support for grazing, continued to be the main cause of carbonate loss after 3 years. Full grazing activity and establishment of a mature community of macroborers required more than 1 year of exposure. After 1 year, macroborers and grazers were the second most important agents of bioerosion on both inshore and offshore reefs. However, after 3 years, grazers became the main agents at all sites except at the inshore sites, where macroborers were the principal agents. Because the contribution of microborers, grazers, and macroborers to bioerosion varies in space and time, we suggest that the estimation of reef carbonate budgets need to take in account the activities of all bioerosion agents.

  17. Network-Based Methods for Identifying Key Active Proteins in the Extracellular Electron Transfer Process in Shewanella oneidensis MR-1.

    PubMed

    Ding, Dewu; Sun, Xiao

    2018-01-16

    Shewanella oneidensis MR-1 can transfer electrons from the intracellular environment to the extracellular space of the cells to reduce the extracellular insoluble electron acceptors (Extracellular Electron Transfer, EET). Benefiting from this EET capability, Shewanella has been widely used in different areas, such as energy production, wastewater treatment, and bioremediation. Genome-wide proteomics data was used to determine the active proteins involved in activating the EET process. We identified 1012 proteins with decreased expression and 811 proteins with increased expression when the EET process changed from inactivation to activation. We then networked these proteins to construct the active protein networks, and identified the top 20 key active proteins by network centralization analysis, including metabolism- and energy-related proteins, signal and transcriptional regulatory proteins, translation-related proteins, and the EET-related proteins. We also constructed the integrated protein interaction and transcriptional regulatory networks for the active proteins, then found three exclusive active network motifs involved in activating the EET process-Bi-feedforward Loop, Regulatory Cascade with a Feedback, and Feedback with a Protein-Protein Interaction (PPI)-and identified the active proteins involved in these motifs. Both enrichment analysis and comparative analysis to the whole-genome data implicated the multiheme c -type cytochromes and multiple signal processing proteins involved in the process. Furthermore, the interactions of these motif-guided active proteins and the involved functional modules were discussed. Collectively, by using network-based methods, this work reported a proteome-wide search for the key active proteins that potentially activate the EET process.

  18. Grazer removal and nutrient enrichment as recovery enhancers for overexploited rocky subtidal habitats.

    PubMed

    Guarnieri, Giuseppe; Bevilacqua, Stanislao; Vignes, Fabio; Fraschetti, Simonetta

    2014-07-01

    Increasing anthropogenic pressures are causing long-lasting regime shifts from high-diversity ecosystems to low-diversity degraded ones. Understanding the effects of multiple threats on ecosystems, and identifying processes allowing for the recovery of biodiversity, are the current major challenges in ecology. In several temperate marine areas, large parts of rocky subtidal habitats characterised by high diversity have been completely degraded to barren grounds by overfishing, including illegal date mussel fishing. Bare areas are characterized by the dominance of sea urchins whose grazing perpetuates the impact of overfishing. We investigated experimentally the separate and combined effects of nutrient enrichment and sea urchin exclusion on the recovery of barren grounds. Our results indicate that the two factors have a synergistic effect leading to the re-establishment of erect macroalgal canopies, enhancing the structural complexity of subtidal assemblages. In particular, in the overfished system considered here, the recovery of disturbed assemblages could occur only if sea urchins are removed. However, the recolonization of barren grounds by erect macroalgae is further enhanced under enriched conditions. This study demonstrates that the recovery of dramatically depleted marine habitats is possible, and provides useful indications for specific management actions, which at present are totally lacking, to achieve the restoration of barren grounds caused by human activity.

  19. Activity of posaconazole and other antifungal agents against Mucorales strains identified by sequencing of internal transcribed spacers.

    PubMed

    Alastruey-Izquierdo, Ana; Castelli, Maria Victoria; Cuesta, Isabel; Monzon, Araceli; Cuenca-Estrella, Manuel; Rodriguez-Tudela, Juan Luis

    2009-04-01

    The antifungal susceptibility profiles of 77 clinical strains of Mucorales species, identified by internal transcribed spacer sequencing, were analyzed. MICs obtained at 24 and 48 h were compared. Amphotericin B was the most active agent against all isolates, except for Cunninghamella and Apophysomyces isolates. Posaconazole also showed good activity for all species but Cunninghamella bertholletiae. Voriconazole had no activity against any of the fungi tested. Terbinafine showed good activity, except for Rhizopus oryzae, Mucor circinelloides, and Rhizomucor variabilis isolates.

  20. Postural transitions during activities of daily living could identify frailty status – Application of wearable technology to identify frailty during unsupervised condition

    PubMed Central

    Parvaneh, Saman; Mohler, Jane; Toosizadeh, Nima; Grewal, Gurtej Singh; Najafi, Bijan

    2017-01-01

    Background Impairment of physical function is a major indicator of frailty. Functional performance tests have been shown to be useful for identification of frailty in older adults. However, these tests are often not translatable into unsupervised and remote monitoring of frailty status at home and/or community settings. Objective In this study, we explored daily postural transition quantified using a chest-worn wearable technology to identify frailty in community-dwelling older adults. Methods Spontaneous daily physical activity was monitored over 24 hours in 120 community dwelling (age: 78±8 years) using an unobtrusive wearable sensor (PAMSys™, Biosensics LLC). Participants were classified as non-frail and pre-frail/frail using Fried’s criteria. A validated software was used to identify body postures and postural transition between each independent postural activities such as sit-to-stand, stand-to-sit, stand-to-walk, and walk-to-stand. Transition from walking to sitting was further classified as quick-sitting and cautious-sitting based on presence/absence of a standing-posture pause between sitting and walking. General linear model univariate test was used for between groups comparison. Pearson’s correlation was used to determine the association between sensor-derived parameters with age. Logistic regression model was used to identify independent predictors of frailty. Results According to Fried’s criteria, 63% of participants were pre-frail/frail. The total number of postural transitions, stand-to-walk, and walk-to-stand were, respectively, 25.2%, 30.2%, and 30.6% lower in the pre-frail/frail group when compared to non-frails (p<0.05, Cohen’s d=0.73–0.79). Furthermore, ratio of cautious-sitting was significantly higher by 6.2% in pre-frail/frail compared to non-frail (p=0.025, Cohen’s d=0.22). Total number of postural transitions and ratio of cautious-sitting also showed significant negative and positive correlations with age, respectively (r=-0

  1. Biased and unbiased strategies to identify biologically active small molecules.

    PubMed

    Abet, Valentina; Mariani, Angelica; Truscott, Fiona R; Britton, Sébastien; Rodriguez, Raphaël

    2014-08-15

    Small molecules are central players in chemical biology studies. They promote the perturbation of cellular processes underlying diseases and enable the identification of biological targets that can be validated for therapeutic intervention. Small molecules have been shown to accurately tune a single function of pluripotent proteins in a reversible manner with exceptional temporal resolution. The identification of molecular probes and drugs remains a worthy challenge that can be addressed by the use of biased and unbiased strategies. Hypothesis-driven methodologies employs a known biological target to synthesize complementary hits while discovery-driven strategies offer the additional means of identifying previously unanticipated biological targets. This review article provides a general overview of recent synthetic frameworks that gave rise to an impressive arsenal of biologically active small molecules with unprecedented cellular mechanisms. Copyright © 2014. Published by Elsevier Ltd.

  2. Ecological Congruence Assessment for Classroom Activities and Routines: Identifying Goals and Intervention Practices in Childcare.

    ERIC Educational Resources Information Center

    Wolery, Mark; Brashers, Margaret Sigalove; Neitzel, Jennifer C.

    2002-01-01

    This article explains how educators can use the ecological congruence assessment process for identifying functional goals for young children with disabilities. Process steps include: teacher collects information about functioning in usual classroom activities, routines, and transitions; summarizes the collected information; and shares the…

  3. Potent Plasmodium falciparum gametocytocidal activity of diaminonaphthoquinones, lead antimalarial chemotypes identified in an antimalarial compound screen.

    PubMed

    Tanaka, Takeshi Q; Guiguemde, W Armand; Barnett, David S; Maron, Maxim I; Min, Jaeki; Connelly, Michele C; Suryadevara, Praveen Kumar; Guy, R Kiplin; Williamson, Kim C

    2015-03-01

    Forty percent of the world's population is threatened by malaria, which is caused by Plasmodium parasites and results in an estimated 200 million clinical cases and 650,000 deaths each year. Drug resistance has been reported for all commonly used antimalarials and has prompted screens to identify new drug candidates. However, many of these new candidates have not been evaluated against the parasite stage responsible for transmission, gametocytes. If Plasmodium falciparum gametocytes are not eliminated, patients continue to spread malaria for weeks after asexual parasite clearance. Asymptomatic individuals can also harbor gametocyte burdens sufficient for transmission, and a safe, effective gametocytocidal agent could also be used in community-wide malaria control programs. Here, we identify 15 small molecules with nanomolar activity against late-stage gametocytes. Fourteen are diaminonaphthoquinones (DANQs), and one is a 2-imino-benzo[d]imidazole (IBI). One of the DANQs identified, SJ000030570, is a lead antimalarial candidate. In contrast, 94% of the 650 compounds tested are inactive against late-stage gametocytes. Consistent with the ineffectiveness of most approved antimalarials against gametocytes, of the 19 novel compounds with activity against known anti-asexual-stage targets, only 3 had any strong effect on gametocyte viability. These data demonstrate the distinct biology of the transmission stages and emphasize the importance of screening for gametocytocidal activity. The potent gametocytocidal activity of DANQ and IBI coupled with their efficacy against asexual parasites provides leads for the development of antimalarials with the potential to prevent both the symptoms and the spread of malaria. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  4. Expression of GARP selectively identifies activated human FOXP3+ regulatory T cells.

    PubMed

    Wang, Rui; Kozhaya, Lina; Mercer, Frances; Khaitan, Alka; Fujii, Hodaka; Unutmaz, Derya

    2009-08-11

    The molecules that define human regulatory T cells (Tregs) phenotypically and functionally remain to be fully characterized. We recently showed that activated human Tregs express mRNA for a transmembrane protein called glycoprotein A repetitions predominant (GARP, or LRRC32). Here, using a GARP-specific mAb, we demonstrate that expression of GARP on activated Tregs correlates with their suppressive capacity. However, GARP was not induced on T cells activated in the presence of TGFbeta, which expressed high levels of FOXP3 and lacked suppressive function. Ectopic expression of FOXP3 in conventional T cells was also insufficient for induction of GARP expression in most donors. Functionally, silencing GARP in Tregs only moderately attenuated their suppressive activity. CD25+ T cells sorted for high GARP expression displayed more potent suppressive activity compared with CD25+GARP- cells. Remarkably, CD25+GARP- T cells expanded in culture contained 3-5 fold higher IL-17-secreting cells compared with either CD25+GARP+ or CD25-GARP- cells, suggesting that high GARP expression can potentially discriminate Tregs from those that have switched to Th17 lineage. We also determined whether GARP expression correlates with FOXP3-expressing T cells in human immunodeficiency virus (HIV) -infected subjects. A subset of HIV+ individuals with high percentages of FOXP3+ T cells did not show proportionate increase in GARP+ T cells. This finding suggests that higher FOXP3 levels observed in these HIV+ individuals is possibly due to immune activation rather than to an increase in Tregs. Our findings highlight the significance of GARP both in dissecting duality of Treg/Th17 cell differentiation and as a marker to identify bona fide Tregs during diseases with chronic immune activation.

  5. Expression of GARP selectively identifies activated human FOXP3+ regulatory T cells

    PubMed Central

    Wang, Rui; Kozhaya, Lina; Mercer, Frances; Khaitan, Alka; Fujii, Hodaka; Unutmaz, Derya

    2009-01-01

    The molecules that define human regulatory T cells (Tregs) phenotypically and functionally remain to be fully characterized. We recently showed that activated human Tregs express mRNA for a transmembrane protein called glycoprotein A repetitions predominant (GARP, or LRRC32). Here, using a GARP-specific mAb, we demonstrate that expression of GARP on activated Tregs correlates with their suppressive capacity. However, GARP was not induced on T cells activated in the presence of TGFβ, which expressed high levels of FOXP3 and lacked suppressive function. Ectopic expression of FOXP3 in conventional T cells was also insufficient for induction of GARP expression in most donors. Functionally, silencing GARP in Tregs only moderately attenuated their suppressive activity. CD25+ T cells sorted for high GARP expression displayed more potent suppressive activity compared with CD25+GARP− cells. Remarkably, CD25+GARP− T cells expanded in culture contained 3–5 fold higher IL-17-secreting cells compared with either CD25+GARP+ or CD25−GARP− cells, suggesting that high GARP expression can potentially discriminate Tregs from those that have switched to Th17 lineage. We also determined whether GARP expression correlates with FOXP3-expressing T cells in human immunodeficiency virus (HIV) −infected subjects. A subset of HIV+ individuals with high percentages of FOXP3+ T cells did not show proportionate increase in GARP+ T cells. This finding suggests that higher FOXP3 levels observed in these HIV+ individuals is possibly due to immune activation rather than to an increase in Tregs. Our findings highlight the significance of GARP both in dissecting duality of Treg/Th17 cell differentiation and as a marker to identify bona fide Tregs during diseases with chronic immune activation. PMID:19666573

  6. Activity of Posaconazole and Other Antifungal Agents against Mucorales Strains Identified by Sequencing of Internal Transcribed Spacers▿

    PubMed Central

    Alastruey-Izquierdo, Ana; Castelli, Maria Victoria; Cuesta, Isabel; Monzon, Araceli; Cuenca-Estrella, Manuel; Rodriguez-Tudela, Juan Luis

    2009-01-01

    The antifungal susceptibility profiles of 77 clinical strains of Mucorales species, identified by internal transcribed spacer sequencing, were analyzed. MICs obtained at 24 and 48 h were compared. Amphotericin B was the most active agent against all isolates, except for Cunninghamella and Apophysomyces isolates. Posaconazole also showed good activity for all species but Cunninghamella bertholletiae. Voriconazole had no activity against any of the fungi tested. Terbinafine showed good activity, except for Rhizopus oryzae, Mucor circinelloides, and Rhizomucor variabilis isolates. PMID:19171801

  7. 30 CFR 285.803 - How must I conduct my approved activities to protect essential fish habitats identified and...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... protect essential fish habitats identified and described under the Magnuson-Stevens Fishery Conservation... fish habitats identified and described under the Magnuson-Stevens Fishery Conservation and Management Act? (a) If, during the conduct of your approved activities, MMS finds that essential fish habitat or...

  8. Identifying barriers to remaining physically active after rehabilitation: differences in perception between physical therapists and older adult patients.

    PubMed

    Zalewski, Kathryn; Alt, Carlynn; Arvinen-Barrow, Monna

    2014-06-01

    Cross-sectional study. To describe readiness for change and barriers to physical activity in older adults and to contrast perceptions of physical therapists and patients using the Barriers to Being Active Quiz. Regular physical activity is vital to recovery after discharge from physical therapy. Physical therapists are positioned to support change in physical activity habits for those transitioning to home care. Understanding of readiness for change and barriers to physical activity could optimize recovery. Thirteen physical therapists enrolled in the study and invited patients who met the inclusion criteria to enroll (79 patients enrolled). The physical therapists provided the ICD-9 code, the physical therapist diagnosis, and completed the Barriers to Being Active Quiz as they perceived their patients would. The enrolled patients provided demographics and filled out the Satisfaction With Life Scale, the stages-of-change scale for physical activity, and the Barriers to Being Active Quiz. Patients were predominantly in the early stages of readiness for change. Both patients and physical therapists identified lack of willpower as the primary barrier to physical activity. Patients identified lack of willpower and social influence as critical barriers more often than physical therapists, whereas physical therapists identified fear of injury and lack of time more often than their patients did. Differences between physical therapists and their patients were noted for fear of injury (z = 2.66, P = .008) and lack of time (z = 3.46, P = .001). The stage of change for physical activity impacted perception of social influence (χ2 = 9.64, P<.05), lack of willpower (χ2 = 21.91, P<.01), and lack of skill (χ2 = 12.46, P<.05). Women ranked fear of injury higher than men did (χ2 = 6.76, P<.01). Understanding readiness for change in and barriers to physical activity may allow physical therapists to better tailor intervention strategies to impact physical activity behavior change.

  9. Epigenetic priors for identifying active transcription factor binding sites.

    PubMed

    Cuellar-Partida, Gabriel; Buske, Fabian A; McLeay, Robert C; Whitington, Tom; Noble, William Stafford; Bailey, Timothy L

    2012-01-01

    Accurate knowledge of the genome-wide binding of transcription factors in a particular cell type or under a particular condition is necessary for understanding transcriptional regulation. Using epigenetic data such as histone modification and DNase I, accessibility data has been shown to improve motif-based in silico methods for predicting such binding, but this approach has not yet been fully explored. We describe a probabilistic method for combining one or more tracks of epigenetic data with a standard DNA sequence motif model to improve our ability to identify active transcription factor binding sites (TFBSs). We convert each data type into a position-specific probabilistic prior and combine these priors with a traditional probabilistic motif model to compute a log-posterior odds score. Our experiments, using histone modifications H3K4me1, H3K4me3, H3K9ac and H3K27ac, as well as DNase I sensitivity, show conclusively that the log-posterior odds score consistently outperforms a simple binary filter based on the same data. We also show that our approach performs competitively with a more complex method, CENTIPEDE, and suggest that the relative simplicity of the log-posterior odds scoring method makes it an appealing and very general method for identifying functional TFBSs on the basis of DNA and epigenetic evidence. FIMO, part of the MEME Suite software toolkit, now supports log-posterior odds scoring using position-specific priors for motif search. A web server and source code are available at http://meme.nbcr.net. Utilities for creating priors are at http://research.imb.uq.edu.au/t.bailey/SD/Cuellar2011. t.bailey@uq.edu.au Supplementary data are available at Bioinformatics online.

  10. Physical activity and exercise training in multiple sclerosis: a review and content analysis of qualitative research identifying perceived determinants and consequences.

    PubMed

    Learmonth, Yvonne C; Motl, Robert W

    2016-01-01

    This systematic review was conducted to provide rich and deep evidence of the perceived determinants and consequences of physical activity and exercise based on qualitative research in multiple sclerosis (MS). Electronic databases and article reference lists were searched to identify qualitative studies of physical activity and exercise in MS. Studies were included if they were written in English and examined consequences/determinants of physical activity in persons with MS. Content analysis of perceived determinants and consequences of physical activity and exercise was undertaken using an inductive analysis guided by the Physical Activity for people with Disabilities framework and Social Cognitive Theory, respectively. Nineteen articles were reviewed. The most commonly identified perceived barriers of physical activity and exercise were related to the environmental (i.e. minimal or no disabled facilities, and minimal or conflicting advice from healthcare professionals) and related to personal barriers (i.e. fatigue, and fear and apprehension). The most commonly identified perceived facilitators of physical activity were related to the environment (i.e. the type of exercise modality and peer support) and related to personal facilitators (i.e. appropriate exercise and feelings of accomplishment). The most commonly identified perceived beneficial consequences of physical activity and exercise were maintaining physical functions, increased social participation and feelings of self-management and control. The most commonly identified perceived adverse consequences were increased fatigue and feelings of frustration and lost control. Results will inform future research on the perceived determinants and consequences of physical activity and exercise in those with MS and can be adopted for developing professional education and interventions for physical activity and exercise in MS. Physical activity and exercise behaviour in people with multiple sclerosis (MS) is subject

  11. Reactive Oxygen Species (ROS)-Activated ATM-Dependent Phosphorylation of Cytoplasmic Substrates Identified by Large-Scale Phosphoproteomics Screen*

    PubMed Central

    Kozlov, Sergei V.; Waardenberg, Ashley J.; Engholm-Keller, Kasper; Arthur, Jonathan W.; Graham, Mark E.; Lavin, Martin

    2016-01-01

    Ataxia-telangiectasia, mutated (ATM) protein plays a central role in phosphorylating a network of proteins in response to DNA damage. These proteins function in signaling pathways designed to maintain the stability of the genome and minimize the risk of disease by controlling cell cycle checkpoints, initiating DNA repair, and regulating gene expression. ATM kinase can be activated by a variety of stimuli, including oxidative stress. Here, we confirmed activation of cytoplasmic ATM by autophosphorylation at multiple sites. Then we employed a global quantitative phosphoproteomics approach to identify cytoplasmic proteins altered in their phosphorylation state in control and ataxia-telangiectasia (A-T) cells in response to oxidative damage. We demonstrated that ATM was activated by oxidative damage in the cytoplasm as well as in the nucleus and identified a total of 9,833 phosphorylation sites, including 6,686 high-confidence sites mapping to 2,536 unique proteins. A total of 62 differentially phosphorylated peptides were identified; of these, 43 were phosphorylated in control but not in A-T cells, and 19 varied in their level of phosphorylation. Motif enrichment analysis of phosphopeptides revealed that consensus ATM serine glutamine sites were overrepresented. When considering phosphorylation events, only observed in control cells (not observed in A-T cells), with predicted ATM sites phosphoSerine/phosphoThreonine glutamine, we narrowed this list to 11 candidate ATM-dependent cytoplasmic proteins. Two of these 11 were previously described as ATM substrates (HMGA1 and UIMCI/RAP80), another five were identified in a whole cell extract phosphoproteomic screens, and the remaining four proteins had not been identified previously in DNA damage response screens. We validated the phosphorylation of three of these proteins (oxidative stress responsive 1 (OSR1), HDGF, and ccdc82) as ATM dependent after H2O2 exposure, and another protein (S100A11) demonstrated ATM

  12. Benthic grazing in a eutrophic river: cascading effects of zoobenthivorous fish mask direct effects of herbivorous fish

    PubMed Central

    Cob Chaves, Daniel; Richter, Marc; Mewes, Daniela; Schneider, Jörg; Hübner, Dirk; Winkelmann, Carola

    2018-01-01

    Benthic grazing strongly controls periphyton biomass. The question therefore arises whether benthic grazing could be used as a tool to reduce excessive growth of periphyton in nutrient-enriched rivers. Although benthic invertebrate grazers reduce the growth of periphyton, this is highly context dependent. Here we assessed whether the only obligate herbivorous fish in European rivers, the common nase (Chondrostoma nasus L.), is able to reduce periphyton biomass in a eutrophic river. We conducted three consecutive in situ experiments at low, intermediate and high densities of nase in the river using standard tiles on the river bottom naturally covered with periphyton that were accessible to fish and tiles that excluded fish foraging with electric exclosures. The biomass of benthic invertebrate grazers was very low relative to nase. We hypothesised that nase would reduce periphyton biomass on accessible tiles and therefore expected higher periphyton biomass on the exclosure tiles, at least at intermediate and high densities of nase in the river. Contrary to our expectation, the impact of fish grazing was low even at high fish density, as judged by the significantly lower chlorophyll a concentration on exclosure tiles even though the ash-free dry mass on accessible and exclosure tiles did not differ. The lower chlorophyll a concentrations on exclosure tiles might be explained by a higher biomass of invertebrate grazers on the exclosure tiles, which would indicate that the effect of invertebrate grazers was stronger than that of herbivorous fish grazers. The high biomass of invertebrate grazers on exclosure tiles likely arose from the exclusion of zoobenthivorous fish, which occur in the river at high densities. The results of our small-scale experiments suggested that cascading top-down effects of zoobenthivorous fish have a higher impact on periphyton biomass than direct effects of herbivorous nase. PMID:29473006

  13. Nitrogen processing by grazers in a headwater stream: riparian connections

    DOE PAGES

    Hill, Walter R.; Griffiths, Natalie A.

    2016-10-19

    Primary consumers play important roles in the cycling of nutrients in headwater streams, storing assimilated nutrients in growing tissue and recycling them through excretion. Though environmental conditions in most headwater streams and their surrounding terrestrial ecosystems vary considerably over the course of a year, relatively little is known about the effects of seasonality on consumer nutrient recycling these streams. Here, we measured nitrogen accumulated through growth and excreted by the grazing snail Elimia clavaeformis (Pleuroceridae) over the course of 12 months in Walker Branch, identifying close connections between in-stream nitrogen processing and seasonal changes in the surrounding forest.

  14. Identifying relationships between unrelated pharmaceutical target proteins on the basis of shared active compounds.

    PubMed

    Miljković, Filip; Kunimoto, Ryo; Bajorath, Jürgen

    2017-08-01

    Computational exploration of small-molecule-based relationships between target proteins from different families. Target annotations of drugs and other bioactive compounds were systematically analyzed on the basis of high-confidence activity data. A total of 286 novel chemical links were established between distantly related or unrelated target proteins. These relationships involved a total of 1859 bioactive compounds including 147 drugs and 141 targets. Computational analysis of large amounts of compounds and activity data has revealed unexpected relationships between diverse target proteins on the basis of compounds they share. These relationships are relevant for drug discovery efforts. Target pairs that we have identified and associated compound information are made freely available.

  15. Serum interleukin measurement may help identify thyroid cancer patients with active disease.

    PubMed

    Martins, Mariana Bonjiorno; Marcello, Marjory Alana; Batista, Fernando de Assis; Peres, Karina Colombera; Meneghetti, Murilo; Ward, Mirela Andrea Latham; Etchebehere, Elba Cristina Sá de Camargo; da Assumpção, Ligia Vera Montali; Ward, Laura Sterian

    2018-02-01

    Investigate the clinical utility of serum interleukin dosages of IL-2, IL-2R, IL-4, IL-6, IL-6R, IL-8, IL-10 and IL-12 in the diagnosis and characterization of patients with DTC. In particular, verify ILs utility in the identification of individuals who are evolving disease-free or with the active disease. We evaluated 200 patients with malignant nodules (100 patients disease-free and 100 patients with recurrence/active disease); 60 benign nodules and 100 healthy controls, serum levels were assessed by ELISA. All ILs, but not IL-4, differentiated these three groups. We observed that IL-2, 2R and 10 serum concentrations were associated with thyroglobulin levels. Serum IL-2 was able to differentiate patients with active disease from the disease-free with a sensitivity of 98%, specificity of 58%, positive predictive value (PPV) of 70% and negative predictive value (NPV) of 97% (p=0.0007). IL-6R levels differentiated patients with active disease from the disease-free patients with 56% sensitivity, 63% specificity, PPV of 60% and NPV of 59% (p<0.0001). IL-8 values also distinguished patients with active disease from the disease-free ones with sensitivity of 50%, specificity of 76%, PPV of 68% and NPV of 60% (p=0.0025); using IL-12, we obtained a sensitivity value of 73%, specificity of 66%, PPV of 68% and NPV of 71% (p<0.0001). Furthermore, interleukin levels showed association with some tumor characteristics of aggressiveness. We suggest that the serum concentration of ILs may assist in the diagnosis and characterization of tumor malignancy helping identify patients with active disease who deserve closer medical attention. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  16. Identifying Strategies Programs Adopt to Meet Healthy Eating and Physical Activity Standards in Afterschool Programs

    ERIC Educational Resources Information Center

    Weaver, Robert G.; Moore, Justin B.; Turner-McGrievy, Brie; Saunders, Ruth; Beighle, Aaron; Khan, M. Mahmud; Chandler, Jessica; Brazendale, Keith; Randell, Allison; Webster, Collin; Beets, Michael W.

    2017-01-01

    Background: The YMCA of USA has adopted Healthy Eating and Physical Activity (HEPA) Standards for its afterschool programs (ASPs). Little is known about strategies YMCA ASPs are implementing to achieve Standards and these strategies' effectiveness. Aims: (1) Identify strategies implemented in YMCA ASPs and (2) evaluate the relationship between…

  17. GASS-WEB: a web server for identifying enzyme active sites based on genetic algorithms.

    PubMed

    Moraes, João P A; Pappa, Gisele L; Pires, Douglas E V; Izidoro, Sandro C

    2017-07-03

    Enzyme active sites are important and conserved functional regions of proteins whose identification can be an invaluable step toward protein function prediction. Most of the existing methods for this task are based on active site similarity and present limitations including performing only exact matches on template residues, template size restraints, despite not being capable of finding inter-domain active sites. To fill this gap, we proposed GASS-WEB, a user-friendly web server that uses GASS (Genetic Active Site Search), a method based on an evolutionary algorithm to search for similar active sites in proteins. GASS-WEB can be used under two different scenarios: (i) given a protein of interest, to match a set of specific active site templates; or (ii) given an active site template, looking for it in a database of protein structures. The method has shown to be very effective on a range of experiments and was able to correctly identify >90% of the catalogued active sites from the Catalytic Site Atlas. It also managed to achieve a Matthew correlation coefficient of 0.63 using the Critical Assessment of protein Structure Prediction (CASP 10) dataset. In our analysis, GASS was ranking fourth among 18 methods. GASS-WEB is freely available at http://gass.unifei.edu.br/. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  18. Identifying group-sensitive physical activities: a differential item functioning analysis of NHANES data.

    PubMed

    Gao, Yong; Zhu, Weimo

    2011-05-01

    The purpose of this study was to identify subgroup-sensitive physical activities (PA) using differential item functioning (DIF) analysis. A sub-unweighted sample of 1857 (men=923 and women=934) from the 2003-2004 National Health and Nutrition Examination Survey PA questionnaire data was used for the analyses. Using the Mantel-Haenszel, the simultaneous item bias test, and the ANOVA DIF methods, 33 specific leisure-time moderate and/or vigorous PA (MVPA) items were analyzed for DIF across race/ethnicity, gender, education, income, and age groups. Many leisure-time MVPA items were identified as large DIF items. When participating in the same amount of leisure-time MVPA, non-Hispanic blacks were more likely to participate in basketball and dance activities than non-Hispanic whites (NHW); NHW were more likely to participated in golf and hiking than non-Hispanic blacks; Hispanics were more likely to participate in dancing, hiking, and soccer than NHW, whereas NHW were more likely to engage in bicycling, golf, swimming, and walking than Hispanics; women were more likely to participate in aerobics, dancing, stretching, and walking than men, whereas men were more likely to engage in basketball, fishing, golf, running, soccer, weightlifting, and hunting than women; educated persons were more likely to participate in jogging and treadmill exercise than less educated persons; persons with higher incomes were more likely to engage in golf than those with lower incomes; and adults (20-59 yr) were more likely to participate in basketball, dancing, jogging, running, and weightlifting than older adults (60+ yr), whereas older adults were more likely to participate in walking and golf than younger adults. DIF methods are able to identify subgroup-sensitive PA and thus provide useful information to help design group-sensitive, targeted interventions for disadvantaged PA subgroups. © 2011 by the American College of Sports Medicine

  19. Heart rate biofeedback fails to enhance children's ability to identify time spent in moderate to vigorous physical activity.

    PubMed

    Conley, Marguerite M; Gastin, Paul B; Brown, Helen; Shaw, Christine

    2011-03-01

    Physical activity recommendations for children in several countries advise that all young people should accumulate at least 60 min of moderate to vigorous physical activity every day. Perceiving physical activity intensity, however, can be a difficult task for children and it is not clear whether children can identify their levels of moderate to vigorous physical activity in accordance with the recommended guidelines. This study aimed to (1) explore whether children can identify time spent in moderate to vigorous physical activity; and (2) investigate whether heart rate biofeedback would improve children's ability to estimate time spent in moderate to vigorous physical activity. Thirty seven children (15 boys and 22 girls, mean age 12.6 years) wore data recording Polar E600 heart rate monitors during eight physical education lessons. At the end of each lesson children's estimated time in zone was compared to their actual time in zone. During a six lesson Intervention phase, one class was assigned to a biofeedback group whilst the other class acted as the control group and received no heart rate biofeedback. Post-Intervention, students in the biofeedback group were no better than the control group at estimating time spent in zone (mean relative error of estimation biofeedback group: Pre-Intervention 41±32% to Post-Intervention 28±26%; control group: Pre-Intervention 40±39% to Post-Intervention 31±37%). Thus it seems that identifying time spent in moderate to vigorous physical activity remains a complex task for children aged 11-13 even with the help of heart rate biofeedback. Copyright © 2010 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  20. Phytotoxicity of vulpia residues: III. Biological activity of identified allelochemicals from Vulpia myuros.

    PubMed

    An, M; Pratley, J E; Haig, T

    2001-02-01

    Twenty compounds identified in vulpia (Vulpia myuros) residues as allelochemicals were individually and collectively tested for biological activity. Each exhibited characteristic allelochemical behavior toward the test plant, i.e., inhibition at high concentrations and stimulation or no effect at low concentrations, but individual activities varied. Allelopathins present in large quantities, such as syringic, vanillic, and succinic acids, possessed low activity, while those present in small quantities, such as catechol and hydrocinnamic acid, possessed strong inhibitory activity. The concept of a phytotoxic strength index was developed for quantifying the biological properties of each individual allelopathin in a concise, comprehensive, and meaningful format. The individual contribution of each allelopathin, assessed by comparing the phytotoxic strength index to the overall toxicity of vulpia residues, was variable according to structure and was influenced by its relative proportion in the residue. The majority of compounds possessed low or medium biological activity and contributed most of the vulpia phytotoxicity, while compounds with high biological activity were in the minority and only present at low concentration. Artificial mixtures of these pure allelochemicals also produced phytotoxicity. There were additive/synergistic effects evident in the properties of these mixtures. One such mixture, formulated from allelochemicals found in the same proportions as occur in vulpia extract, produced stronger activity than another formulated from the same set of compounds but in equal proportions. These results suggest that the exploration of the relative composition of a cluster of allelopathins may be more important than simply focusing on the identification of one or two compounds with strong biological activity and that synergism is fundamental to the understanding of allelopathy.

  1. Identifying physical activity gender differences among youth

    USDA-ARS?s Scientific Manuscript database

    Physical activity (PA) is an important part of a healthy lifestyle and reduces risk of certain chronic diseases. Many youth do not currently meet PA guidelines; evidence suggests that girls are less active than boys are at all ages. PA differences need to be understood, so that gender-specific inter...

  2. Do classic blood biomarkers of JSLE identify active lupus nephritis? Evidence from the UK JSLE Cohort Study.

    PubMed

    Smith, E M D; Jorgensen, A L; Beresford, M W

    2017-10-01

    Background Lupus nephritis (LN) affects up to 80% of juvenile-onset systemic lupus erythematosus (JSLE) patients. The value of commonly available biomarkers, such as anti-dsDNA antibodies, complement (C3/C4), ESR and full blood count parameters in the identification of active LN remains uncertain. Methods Participants from the UK JSLE Cohort Study, aged <16 years at diagnosis, were categorized as having active or inactive LN according to the renal domain of the British Isles Lupus Assessment Group score. Classic biomarkers: anti-dsDNA, C3, C4, ESR, CRP, haemoglobin, total white cells, neutrophils, lymphocytes, platelets and immunoglobulins were assessed for their ability to identify active LN using binary logistic regression modeling, with stepAIC function applied to select a final model. Receiver-operating curve analysis was used to assess diagnostic accuracy. Results A total of 370 patients were recruited; 191 (52%) had active LN and 179 (48%) had inactive LN. Binary logistic regression modeling demonstrated a combination of ESR, C3, white cell count, neutrophils, lymphocytes and IgG to be best for the identification of active LN (area under the curve 0.724). Conclusions At best, combining common classic blood biomarkers of lupus activity using multivariate analysis provides a 'fair' ability to identify active LN. Urine biomarkers were not included in these analyses. These results add to the concern that classic blood biomarkers are limited in monitoring discrete JSLE manifestations such as LN.

  3. Identifying Strategies Programs Adopt to Meet Healthy Eating and Physical Activity Standards in Afterschool Programs.

    PubMed

    Weaver, Robert G; Moore, Justin B; Turner-McGrievy, Brie; Saunders, Ruth; Beighle, Aaron; Khan, M Mahmud; Chandler, Jessica; Brazendale, Keith; Randell, Allison; Webster, Collin; Beets, Michael W

    2017-08-01

    The YMCA of USA has adopted Healthy Eating and Physical Activity (HEPA) Standards for its afterschool programs (ASPs). Little is known about strategies YMCA ASPs are implementing to achieve Standards and these strategies' effectiveness. (1) Identify strategies implemented in YMCA ASPs and (2) evaluate the relationship between strategy implementation and meeting Standards. HEPA was measured via accelerometer (moderate-to-vigorous-physical-activity [MVPA]) and direct observation (snacks served) in 20 ASPs. Strategies were identified and mapped onto a capacity building framework ( Strategies To Enhance Practice [STEPs]). Mixed-effects regression estimated increases in HEPA outcomes as implementation increased. Model-implied estimates were calculated for high (i.e., highest implementation score achieved), moderate (median implementation score across programs), and low (lowest implementation score achieved) implementation for both HEPA separately. Programs implemented a variety of strategies identified in STEPs. For every 1-point increase in implementation score 1.45% (95% confidence interval = 0.33% to 2.55%, p ≤ .001) more girls accumulated 30 min/day of MVPA and fruits and/or vegetables were served on 0.11 more days (95% confidence interval = 0.11-0.45, p ≤ .01). Relationships between implementation and other HEPA outcomes did not reach statistical significance. Still regression estimates indicated that desserts are served on 1.94 fewer days (i.e., 0.40 vs. 2.34) in the highest implementing program than the lowest implementing program and water is served 0.73 more days (i.e., 2.37 vs. 1.64). Adopting HEPA Standards at the national level does not lead to changes in routine practice in all programs. Practical strategies that programs could adopt to more fully comply with the HEPA Standards are identified.

  4. Notch pathway activity identifies cells with cancer stem cell-like properties and correlates with worse survival in lung adenocarcinoma

    PubMed Central

    Hassan, Khaled A.; Wang, Luo; Korkaya, Hasan; Chen, Guoan; Maillard, Ivan; Beer, David G.; Kalemkerian, Gregory P.; Wicha, Max S.

    2013-01-01

    Purpose The cancer stem cell theory postulates that tumors contain a subset of cells with stem cell properties of self-renewal, differentiation and tumor-initiation. The purpose of this study is to determine the role of Notch activity in identifying lung cancer stem cells. Experimental Design We investigated the role of Notch activity in lung adenocarcinoma utilizing a Notch GFP-reporter construct and a gamma-secretase inhibitor (GSI), which inhibits Notch pathway activity. Results Transduction of lung cancer cells with Notch GFP-reporter construct identified a subset of cells with high Notch activity (GFP-bright). GFP-bright cells had the ability to form more tumor spheres in serum-free media, and were able to generate both GFP-bright and GFP-dim (lower Notch activity) cell populations. GFP-bright cells were resistant to chemotherapy and were tumorigenic in serial xenotransplantation assays. Tumor xenografts of mice treated with GSI had decreased expression of downstream effectors of Notch pathway and failed to regenerate tumors upon reimplantation in NOD/SCID mice. Using multivariate analysis, we detected a statistically significant correlation between poor clinical outcome and Notch activity (reflected in increased Notch ligand expression or decreased expression of the negative modulators), in a group of 441 lung adenocarcinoma patients. This correlation was further confirmed in an independent group of 89 adenocarcinoma patients where Hes-1 overexpression correlated with poor overall survival. Conclusions Notch activity can identify lung cancer stem cell-like population and its inhibition may be an appropriate target for treating lung adenocarcinoma. PMID:23444212

  5. Difficulty identifying feelings and automatic activation in the fusiform gyrus in response to facial emotion.

    PubMed

    Eichmann, Mischa; Kugel, Harald; Suslow, Thomas

    2008-12-01

    Difficulties in identifying and differentiating one's emotions are a central characteristic of alexithymia. In the present study, automatic activation of the fusiform gyrus to facial emotion was investigated as a function of alexithymia as assessed by the 20-item Toronto Alexithymia Scale. During 3 Tesla fMRI scanning, pictures of faces bearing sad, happy, and neutral expressions masked by neutral faces were presented to 22 healthy adults who also responded to the Toronto Alexithymia Scale. The fusiform gyrus was selected as the region of interest, and voxel values of this region were extracted, summarized as means, and tested among the different conditions (sad, happy, and neutral faces). Masked sad facial emotions were associated with greater bilateral activation of the fusiform gyrus than masked neutral faces. The subscale, Difficulty Identifying Feelings, was negatively correlated with the neural response of the fusiform gyrus to masked sad faces. The correlation results suggest that automatic hyporesponsiveness of the fusiform gyrus to negative emotion stimuli may reflect problems in recognizing one's emotions in everyday life.

  6. Identifying minimal hepatic encephalopathy in cirrhotic patients by measuring spontaneous brain activity.

    PubMed

    Chen, Hua-Jun; Zhang, Ling; Jiang, Long-Feng; Chen, Qiu-Feng; Li, Jun; Shi, Hai-Bin

    2016-08-01

    It has been demonstrated that minimal hepatic encephalopathy (MHE) is associated with aberrant regional intrinsic brain activity in cirrhotic patients. However, few studies have investigated whether altered intrinsic brain activity can be used as a biomarker of MHE among cirrhotic patients. In this study, 36 cirrhotic patients (with MHE, n = 16; without MHE [NHE], n = 20) underwent resting-state functional magnetic resonance imaging (fMRI). Spontaneous brain activity was measured by examining the amplitude of low-frequency fluctuations (ALFF) in the fMRI signal. MHE was diagnosed based on the Psychometric Hepatic Encephalopathy Score (PHES). A two-sample t-test was used to determine the regions of interest (ROIs) in which ALFF differed significantly between the two groups; then, ALFF values within ROIs were selected as classification features. A linear discriminative analysis was used to differentiate MHE patients from NHE patients. The leave-one-out cross-validation method was used to estimate the performance of the classifier. The classification analysis was 80.6 % accurate (81.3 % sensitivity and 80.0 % specificity) in terms of distinguishing between the two groups. Six ROIs were identified as the most discriminative features, including the bilateral medial frontal cortex/anterior cingulate cortex, posterior cingulate cortex/precuneus, left precentral and postcentral gyrus, right lingual gyrus, middle frontal gyrus, and inferior/superior parietal lobule. The ALFF values within ROIs were correlated with PHES in cirrhotic patients. Our findings suggest that altered regional brain spontaneous activity is a useful biomarker for MHE detection among cirrhotic patients.

  7. Air-cathode microbial fuel cell array: a device for identifying and characterizing electrochemically active microbes.

    PubMed

    Hou, Huijie; Li, Lei; de Figueiredo, Paul; Han, Arum

    2011-01-15

    Microbial fuel cells (MFCs) have generated excitement in environmental and bioenergy communities due to their potential for coupling wastewater treatment with energy generation and powering diverse devices. The pursuit of strategies such as improving microbial cultivation practices and optimizing MFC devices has increased power generating capacities of MFCs. However, surprisingly few microbial species with electrochemical activity in MFCs have been identified because current devices do not support parallel analyses or high throughput screening. We have recently demonstrated the feasibility of using advanced microfabrication methods to fabricate an MFC microarray. Here, we extend these studies by demonstrating a microfabricated air-cathode MFC array system. The system contains 24 individual air-cathode MFCs integrated onto a single chip. The device enables the direct and parallel comparison of different microbes loaded onto the array. Environmental samples were used to validate the utility of the air-cathode MFC array system and two previously identified isolates, 7Ca (Shewanella sp.) and 3C (Arthrobacter sp.), were shown to display enhanced electrochemical activities of 2.69 mW/m(2) and 1.86 mW/m(2), respectively. Experiments using a large scale conventional air-cathode MFC validated these findings. The parallel air-cathode MFC array system demonstrated here is expected to promote and accelerate the discovery and characterization of electrochemically active microbes. Copyright © 2010 Elsevier B.V. All rights reserved.

  8. Release and Consumption of DMSP from Emiliania Huxleyi during grazing by Oxyrrhis Marina

    NASA Technical Reports Server (NTRS)

    Wolfe, Gordon V.; Sherr, Evelyn B.; Sherr, Barry F.

    1994-01-01

    Degradation and release to solution of intracellular dimethylsulfoniopropionate (DMSP) from Emiliania huxleyi 370 was observed during grazing by the heterotrophic dinoflagellate Oxyrrhis marina in 24 h bottle incubations. Between 30 and 70% of the lost algal DMSP was metabolized by the grazers without production of dimethylsulfide (DMS) when grazer densities were 150 to 450/ml. The rest was released to solution and about 30% was converted to DMS by bacteria associated with the grazer culture. These experiments demonstrate that grazing by herbivorous protists may be an important sink for DMSP in marine waters, removing a potential source of DMS. Microzooplankton grazing may also indirectly increase the production of DMS by transferring algal DMSP to the dissolved pool, making it available for bacterial metabolism.

  9. Identifying Creative Activities in Preschool Children.

    ERIC Educational Resources Information Center

    Keily, Margaret Mary

    This study compared the creative self-direction, creative behavior, and creative activities of preschool children to determine if students and teachers trained in the creative process and in observation techniques can, with reliability, observe the creative potential of young children. Creative abilities of 155 children from four preschool centers…

  10. Substitution scanning identifies a novel, catalytically active ibrutinib-resistant BTK cysteine 481 to threonine (C481T) variant

    PubMed Central

    Hamasy, A; Wang, Q; Blomberg, K E M; Mohammad, D K; Yu, L; Vihinen, M; Berglöf, A; Smith, C I E

    2017-01-01

    Irreversible Bruton tyrosine kinase (BTK) inhibitors, ibrutinib and acalabrutinib have demonstrated remarkable clinical responses in multiple B-cell malignancies. Acquired resistance has been identified in a sub-population of patients in which mutations affecting BTK predominantly substitute cysteine 481 in the kinase domain for catalytically active serine, thereby ablating covalent binding of inhibitors. Activating substitutions in the BTK substrate phospholipase Cγ2 (PLCγ2) instead confers resistance independent of BTK. Herein, we generated all six possible amino acid substitutions due to single nucleotide alterations for the cysteine 481 codon, in addition to threonine, requiring two nucleotide substitutions, and performed functional analysis. Replacement by arginine, phenylalanine, tryptophan or tyrosine completely inactivated the catalytic activity, whereas substitution with glycine caused severe impairment. BTK with threonine replacement was catalytically active, similar to substitution with serine. We identify three potential ibrutinib resistance scenarios for cysteine 481 replacement: (1) Serine, being catalytically active and therefore predominating among patients. (2) Threonine, also being catalytically active, but predicted to be scarce, because two nucleotide changes are needed. (3) As BTK variants replaced with other residues are catalytically inactive, they presumably need compensatory mutations, therefore being very scarce. Glycine and tryptophan variants were not yet reported but likely also provide resistance. PMID:27282255

  11. Diagnostic Utility of the Posttraumatic Stress Disorder (PTSD) Checklist for Identifying Full and Partial PTSD in Active-Duty Military.

    PubMed

    Dickstein, Benjamin D; Weathers, Frank W; Angkaw, Abigail C; Nievergelt, Caroline M; Yurgil, Kate; Nash, William P; Baker, Dewleen G; Litz, Brett T

    2015-06-01

    The aim of this study was to determine optimally efficient cutoff scores on the Posttraumatic Stress Disorder Checklist (PCL) for identifying full posttraumatic stress disorder (PTSD) and partial PTSD (P-PTSD) in active-duty Marines and Sailors. Participants were 1,016 Marines and Sailors who were administered the PCL and Clinician-Administered PTSD Scale (CAPS) 3 months after returning from Operations Iraqi and Enduring Freedom. PCL cutoffs were tested against three CAPS-based classifications: full PTSD, stringent P-PTSD, and lenient P-PTSD. A PCL score of 39 was found to be optimally efficient for identifying full PTSD. Scores of 38 and 33 were found to be optimally efficient for identifying stringent and lenient P-PTSD, respectively. Findings suggest that the PCL cutoff that is optimally efficient for detecting PTSD in active-duty Marines and Sailors is substantially lower than the score of 50 commonly used by researchers. In addition, findings provide scores useful for identifying P-PTSD in returning service members. © The Author(s) 2014.

  12. Newly identified essential amino acid residues affecting ^8-sphingolipid desaturase activity revealed by site-directed mutagenesis

    USDA-ARS?s Scientific Manuscript database

    In order to identify amino acid residues crucial for the enzymatic activity of ^8-sphingolipid desaturases, a sequence comparison was performed among ^8-sphingolipid desaturases and ^6-fatty acid desaturase from various plants. In addition to the known conserved cytb5 (cytochrome b5) HPGG motif and...

  13. Interannual and seasonal variability in short-term grazing impact of Euphausia superba in nearshore and offshore waters west of the Antarctic Peninsula

    NASA Astrophysics Data System (ADS)

    Ross, R. M.; Quetin, L. B.; Haberman, K. L.

    1998-11-01

    Our focus in this paper is the interaction between macrozooplanktonic grazers and primary producers, and the interannual and seasonal variability in the Palmer Long-Term Ecological Research (Palmer LTER) study region from Anvers Island to Adelaide Island. Short-term grazing estimates are calculated by integrating (1) theoretical and experimental estimates of ingestion rates in response to the standing stock of phytoplankton, and (2) field measurements of phytoplankton standing stock and grazer biomass. Field data come from three austral summer cruises (January/February of 1993, 1994, and 1995) and one sequence of seasonal cruises (summer, fall and winter 1993). The relative and absolute abundance of the dominant macrozooplankton grazers, Euphausia superba and Salpa thompsoni, varied by at least an order of magnitude on the spatial and temporal scales observed. Mean grazing rates ranged from 0.4 to 9.0 μg chlorophyll m -2 h -1 for the Antarctic krill and salp populations over the three summer cruises. This leads to variability in the flow of carbon from the primary producers through the grazers on the same scales. Temporal and spatial variability in grazing impact and faecal pellet production are high.

  14. A leukocyte activation test identifies food items which induce release of DNA by innate immune peripheral blood leucocytes.

    PubMed

    Garcia-Martinez, Irma; Weiss, Theresa R; Yousaf, Muhammad N; Ali, Ather; Mehal, Wajahat Z

    2018-01-01

    Leukocyte activation (LA) testing identifies food items that induce a patient specific cellular response in the immune system, and has recently been shown in a randomized double blinded prospective study to reduce symptoms in patients with irritable bowel syndrome (IBS). We hypothesized that test reactivity to particular food items, and the systemic immune response initiated by these food items, is due to the release of cellular DNA from blood immune cells. We tested this by quantifying total DNA concentration in the cellular supernatant of immune cells exposed to positive and negative foods from 20 healthy volunteers. To establish if the DNA release by positive samples is a specific phenomenon, we quantified myeloperoxidase (MPO) in cellular supernatants. We further assessed if a particular immune cell population (neutrophils, eosinophils, and basophils) was activated by the positive food items by flow cytometry analysis. To identify the signaling pathways that are required for DNA release we tested if specific inhibitors of key signaling pathways could block DNA release. Foods with a positive LA test result gave a higher supernatant DNA content when compared to foods with a negative result. This was specific as MPO levels were not increased by foods with a positive LA test. Protein kinase C (PKC) inhibitors resulted in inhibition of positive food stimulated DNA release. Positive foods resulted in CD63 levels greater than negative foods in eosinophils in 76.5% of tests. LA test identifies food items that result in release of DNA and activation of peripheral blood innate immune cells in a PKC dependent manner, suggesting that this LA test identifies food items that result in release of inflammatory markers and activation of innate immune cells. This may be the basis for the improvement in symptoms in IBS patients who followed an LA test guided diet.

  15. Herbivory enhances the diversity of primary producers in pond ecosystems.

    PubMed

    Leibold, Mathew A; Hall, Spencer R; Smith, Val H; Lytle, David A

    2017-01-01

    Diversity of primary producer is often surprisingly high, despite few limiting factors such as nutrients and light to facilitate species coexistence. In theory, the presence of herbivores could increase the diversity of primary producers, resolving this "paradox of the plankton." Little experimental evidence supports this natural enemies hypothesis, but previous tests suffer from several deficiencies. Previous experiments often did not allow for multigeneration effects; utilized low diversity assemblages of herbivores; and limited opportunities for new primary producer and herbivore species to colonize and undergo species sorting that favors some species over others. Using pond plankton, we designed a mesocosm experiment that overcame these problems by allowing more time for interactions over multiple generations, openness to allow new colonists, and manipulated higher diversity of primary producers and grazers than have previous studies. With this design, the presence of zooplankton grazers doubled phytoplankton richness. The additional phytoplankton species in grazed mesocosms were larger, and therefore likely more grazer resistant. Furthermore, phytoplankton richness in grazed mesocosms was similar to that observed in natural ponds whereas it was much lower in mesocosms without grazers. However, stoichiometric imbalance caused by variation in nitrogen : phosphorus ratios and light supply did not alter phytoplankton richness. Therefore, grazers enhanced primary producer richness more strongly than ratios of nutrient supply (even though both grazing and ratios of resource supply altered composition of primary producer assemblages). Taken together, these experimental and field data show that grazing from a diverse assemblage of herbivores greatly elevated richness of phytoplankton producers in pond ecosystems. © 2016 by the Ecological Society of America.

  16. Consumers mediate the effects of experimental ocean acidification and warming on primary producers.

    PubMed

    Alsterberg, Christian; Eklöf, Johan S; Gamfeldt, Lars; Havenhand, Jonathan N; Sundbäck, Kristina

    2013-05-21

    It is well known that ocean acidification can have profound impacts on marine organisms. However, we know little about the direct and indirect effects of ocean acidification and also how these effects interact with other features of environmental change such as warming and declining consumer pressure. In this study, we tested whether the presence of consumers (invertebrate mesograzers) influenced the interactive effects of ocean acidification and warming on benthic microalgae in a seagrass community mesocosm experiment. Net effects of acidification and warming on benthic microalgal biomass and production, as assessed by analysis of variance, were relatively weak regardless of grazer presence. However, partitioning these net effects into direct and indirect effects using structural equation modeling revealed several strong relationships. In the absence of grazers, benthic microalgae were negatively and indirectly affected by sediment-associated microalgal grazers and macroalgal shading, but directly and positively affected by acidification and warming. Combining indirect and direct effects yielded no or weak net effects. In the presence of grazers, almost all direct and indirect climate effects were nonsignificant. Our analyses highlight that (i) indirect effects of climate change may be at least as strong as direct effects, (ii) grazers are crucial in mediating these effects, and (iii) effects of ocean acidification may be apparent only through indirect effects and in combination with other variables (e.g., warming). These findings highlight the importance of experimental designs and statistical analyses that allow us to separate and quantify the direct and indirect effects of multiple climate variables on natural communities.

  17. Individual Human Brain Areas Can Be Identified from Their Characteristic Spectral Activation Fingerprints

    PubMed Central

    Keitel, Anne; Gross, Joachim

    2016-01-01

    The human brain can be parcellated into diverse anatomical areas. We investigated whether rhythmic brain activity in these areas is characteristic and can be used for automatic classification. To this end, resting-state MEG data of 22 healthy adults was analysed. Power spectra of 1-s long data segments for atlas-defined brain areas were clustered into spectral profiles (“fingerprints”), using k-means and Gaussian mixture (GM) modelling. We demonstrate that individual areas can be identified from these spectral profiles with high accuracy. Our results suggest that each brain area engages in different spectral modes that are characteristic for individual areas. Clustering of brain areas according to similarity of spectral profiles reveals well-known brain networks. Furthermore, we demonstrate task-specific modulations of auditory spectral profiles during auditory processing. These findings have important implications for the classification of regional spectral activity and allow for novel approaches in neuroimaging and neurostimulation in health and disease. PMID:27355236

  18. Individual Human Brain Areas Can Be Identified from Their Characteristic Spectral Activation Fingerprints.

    PubMed

    Keitel, Anne; Gross, Joachim

    2016-06-01

    The human brain can be parcellated into diverse anatomical areas. We investigated whether rhythmic brain activity in these areas is characteristic and can be used for automatic classification. To this end, resting-state MEG data of 22 healthy adults was analysed. Power spectra of 1-s long data segments for atlas-defined brain areas were clustered into spectral profiles ("fingerprints"), using k-means and Gaussian mixture (GM) modelling. We demonstrate that individual areas can be identified from these spectral profiles with high accuracy. Our results suggest that each brain area engages in different spectral modes that are characteristic for individual areas. Clustering of brain areas according to similarity of spectral profiles reveals well-known brain networks. Furthermore, we demonstrate task-specific modulations of auditory spectral profiles during auditory processing. These findings have important implications for the classification of regional spectral activity and allow for novel approaches in neuroimaging and neurostimulation in health and disease.

  19. Intrinsic ruminal innervation in ruminants of different feeding types

    PubMed Central

    Münnich, Juliane; Gäbel, Gotthold; Pfannkuche, Helga

    2008-01-01

    According to their feeding habits, ruminants can be classified as grazers, concentrate selectors and those of intermediate type. The different feeding types are reflected in distinct anatomical properties of the forestomachs. The present study was designed to investigate whether the intrinsic innervation patterns of the rumen (the main part of the forestomach) differ between intermediate types and grazers. Myenteric plexus preparations from the rumen of goats (intermediate type), fallow deer (intermediate type), cattle (grazer) and sheep (grazer) were analysed by immunohistochemical detection of the following antigens: Hu-protein (HuC/D), choline acetyltransferase (ChAT), nitric oxide synthase (NOS), vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), substance P (SP), calbindin (CALB) and somatostatin (SOM). Myenteric ganglia of cattle contained 73 ± 6 neurons per ganglion, whereas the ganglia of sheep were significantly smaller (45 ± 18 neurons per ganglion). The ganglion density of the myenteric plexus was highest in fallow deer (15 ± 3 ganglia per cm2) and lowest in cattle (6 ± 1 ganglia per cm2). All myenteric neurons were either ChAT or NOS positive. The proportion of NOS-positive neurons was significantly lower in sheep (29.5 ± 8.2% of all neurons) than in goats (44.2 ± 9.8%). In all species, additional analysis of the different neuropeptides revealed the following subpopulations in descending order of percentile appearance: ChAT/SP > NOS/VIP/NPY > ChAT/– > NOS/NPY. Expression of CALB was detected in a minority of the ChAT-positive neurons in all species. Somatostatin immunoreactive somata were found only in preparations obtained from fallow deer and sheep. These data suggest that the rumen of grazers is under stronger cholinergic control than the rumen of species belonging to the intermediate type, although most subpopulations of neurons are present in all species. However, whether the strong mixing patterns of low quality roughage during

  20. A bioassay-guided fractionation system to identify endogenous small molecules that activate plasma membrane H+-ATPase activity in Arabidopsis.

    PubMed

    Han, Xiuli; Yang, Yongqing; Wu, Yujiao; Liu, Xiaohui; Lei, Xiaoguang; Guo, Yan

    2017-05-17

    Plasma membrane (PM) H+-ATPase is essential for plant growth and development. Various environmental stimuli regulate its activity, a process that involves many protein cofactors. However, whether endogenous small molecules play a role in this regulation remains unknown. Here, we describe a bio-guided isolation method to identify endogenous small molecules that regulate PM H+-ATPase activity. We obtained crude extracts from Arabidopsis seedlings with or without salt treatment and then purified them into fractions based on polarity and molecular mass by repeated column chromatography. By evaluating the effect of each fraction on PM H+-ATPase activity, we found that fractions containing the endogenous, free unsaturated fatty acids oleic acid (C18:1), linoleic acid (C18:2), and linolenic acid (C18:3) extracted from salt-treated seedlings stimulate PM H+-ATPase activity. These results were further confirmed by the addition of exogenous C18:1, C18:2, or C18:3 in the activity assay. The ssi2 mutant, with reduced levels of C18:1, C18:2, and C18:3, displayed reduced PM H+-ATPase activity. Furthermore, C18:1, C18:2, and C18:3 directly bound to the C-terminus of the PM H+-ATPase AHA2. Collectively, our results demonstrate that the binding of free unsaturated fatty acids to the C-terminus of PM H+-ATPase is required for its activation under salt stress. The bio-guided isolation model described in this study could enable the identification of new endogenous small molecules that modulate essential protein functions, as well as signal transduction, in plants. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  1. Identifying and Enhancing the Strengths of Gifted Learners, K-8: Easy-to-Use Activities and Lessons

    ERIC Educational Resources Information Center

    Maccagnano, Ann Marie

    2007-01-01

    Educators can identify children's strengths early on and gain insight into each student's unique abilities by using the numerous ideas and informal assessments in this exciting guide. Gifted and talented specialist Ann Maccagnano offers K-8 teachers challenging activities and engaging lessons to develop and nurture gifted learners' talents.…

  2. Time-driven activity-based costing to identify opportunities for cost reduction in pediatric appendectomy.

    PubMed

    Yu, Yangyang R; Abbas, Paulette I; Smith, Carolyn M; Carberry, Kathleen E; Ren, Hui; Patel, Binita; Nuchtern, Jed G; Lopez, Monica E

    2016-12-01

    As reimbursement programs shift to value-based payment models emphasizing quality and efficient healthcare delivery, there exists a need to better understand process management to unearth true costs of patient care. We sought to identify cost-reduction opportunities in simple appendicitis management by applying a time-driven activity-based costing (TDABC) methodology to this high-volume surgical condition. Process maps were created using medical record time stamps. Labor capacity cost rates were calculated using national median physician salaries, weighted nurse-patient ratios, and hospital cost data. Consumable costs for supplies, pharmacy, laboratory, and food were derived from the hospital general ledger. Time-driven activity-based costing resulted in precise per-minute calculation of personnel costs. Highest costs were in the operating room ($747.07), hospital floor ($388.20), and emergency department ($296.21). Major contributors to length of stay were emergency department evaluation (270min), operating room availability (395min), and post-operative monitoring (1128min). The TDABC model led to $1712.16 in personnel costs and $1041.23 in consumable costs for a total appendicitis cost of $2753.39. Inefficiencies in healthcare delivery can be identified through TDABC. Triage-based standing delegation orders, advanced practice providers, and same day discharge protocols are proposed cost-reducing interventions to optimize value-based care for simple appendicitis. II. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Identifying barriers to patient acceptance of active surveillance: content analysis of online patient communications.

    PubMed

    Mishra, Mark V; Bennett, Michele; Vincent, Armon; Lee, Olivia T; Lallas, Costas D; Trabulsi, Edouard J; Gomella, Leonard G; Dicker, Adam P; Showalter, Timothy N

    2013-01-01

    Qualitative research aimed at identifying patient acceptance of active surveillance (AS) has been identified as a public health research priority. The primary objective of this study was to determine if analysis of a large-sample of anonymous internet conversations (ICs) could be utilized to identify unmet public needs regarding AS. English-language ICs regarding prostate cancer (PC) treatment with AS from 2002-12 were identified using a novel internet search methodology. Web spiders were developed to mine, aggregate, and analyze content from the world-wide-web for ICs centered on AS. Collection of ICs was not restricted to any specific geographic region of origin. NLP was used to evaluate content and perform a sentiment analysis. Conversations were scored as positive, negative, or neutral. A sentiment index (SI) was subsequently calculated according to the following formula to compare temporal trends in public sentiment towards AS: [(# Positive IC/#Total IC)-(#Negative IC/#Total IC) x 100]. A total of 464 ICs were identified. Sentiment increased from -13 to +2 over the study period. The increase sentiment has been driven by increased patient emphasis on quality-of-life factors and endorsement of AS by national medical organizations. Unmet needs identified in these ICs include: a gap between quantitative data regarding long-term outcomes with AS vs. conventional treatments, desire for treatment information from an unbiased specialist, and absence of public role models managed with AS. This study demonstrates the potential utility of online patient communications to provide insight into patient preferences and decision-making. Based on our findings, we recommend that multidisciplinary clinics consider including an unbiased specialist to present treatment options and that future decision tools for AS include quantitative data regarding outcomes after AS.

  4. Ghostly grazers and Sky Islands

    Treesearch

    Paul S. Martin

    2005-01-01

    The evolution of the western range involves millions of years of coexistence of herbaceous plants with a great many kinds of large herbivores, most of the latter suddenly removed around 13,000 years ago. The fossil record indicates more diversity of large herbivores before this time, not less, and with more taxa of large herbivores consuming more forage than livestock...

  5. Active Learning with Rationales for Identifying Operationally Significant Anomalies in Aviation

    NASA Technical Reports Server (NTRS)

    Sharma, Manali; Das, Kamalika; Bilgic, Mustafa; Matthews, Bryan; Nielsen, David Lynn; Oza, Nikunj C.

    2016-01-01

    A major focus of the commercial aviation community is discovery of unknown safety events in flight operations data. Data-driven unsupervised anomaly detection methods are better at capturing unknown safety events compared to rule-based methods which only look for known violations. However, not all statistical anomalies that are discovered by these unsupervised anomaly detection methods are operationally significant (e.g., represent a safety concern). Subject Matter Experts (SMEs) have to spend significant time reviewing these statistical anomalies individually to identify a few operationally significant ones. In this paper we propose an active learning algorithm that incorporates SME feedback in the form of rationales to build a classifier that can distinguish between uninteresting and operationally significant anomalies. Experimental evaluation on real aviation data shows that our approach improves detection of operationally significant events by as much as 75% compared to the state-of-the-art. The learnt classifier also generalizes well to additional validation data sets.

  6. Identifying parents' perceptions about physical activity: a qualitative exploration of salient behavioural, normative and control beliefs among mothers and fathers of young children.

    PubMed

    Hamilton, Kyra; White, Katherine M

    2010-11-01

    Drawing on the belief-based framework of the Theory of Planned Behaviour, this study employs qualitative methodology involving individual and group interviews to examine the beliefs associated with regular physical activity performance among parents of young children (N = 40). The data were analysed using thematic content analysis. A range of advantages (e.g. improves parenting practices), disadvantages (e.g. interferes with commitments), barriers (e.g. time), and facilitators (e.g. social support) to performing physical activity are identified. Normative pressures are also identified as affecting parents' activity behaviour. These identified beliefs can be used to inform interventions to challenge inactivity among this at-risk group.

  7. Antibiotic discovery throughout the Small World Initiative: A molecular strategy to identify biosynthetic gene clusters involved in antagonistic activity.

    PubMed

    Davis, Elizabeth; Sloan, Tyler; Aurelius, Krista; Barbour, Angela; Bodey, Elijah; Clark, Brigette; Dennis, Celeste; Drown, Rachel; Fleming, Megan; Humbert, Allison; Glasgo, Elizabeth; Kerns, Trent; Lingro, Kelly; McMillin, MacKenzie; Meyer, Aaron; Pope, Breanna; Stalevicz, April; Steffen, Brittney; Steindl, Austin; Williams, Carolyn; Wimberley, Carmen; Zenas, Robert; Butela, Kristen; Wildschutte, Hans

    2017-06-01

    The emergence of bacterial pathogens resistant to all known antibiotics is a global health crisis. Adding to this problem is that major pharmaceutical companies have shifted away from antibiotic discovery due to low profitability. As a result, the pipeline of new antibiotics is essentially dry and many bacteria now resist the effects of most commonly used drugs. To address this global health concern, citizen science through the Small World Initiative (SWI) was formed in 2012. As part of SWI, students isolate bacteria from their local environments, characterize the strains, and assay for antibiotic production. During the 2015 fall semester at Bowling Green State University, students isolated 77 soil-derived bacteria and genetically characterized strains using the 16S rRNA gene, identified strains exhibiting antagonistic activity, and performed an expanded SWI workflow using transposon mutagenesis to identify a biosynthetic gene cluster involved in toxigenic compound production. We identified one mutant with loss of antagonistic activity and through subsequent whole-genome sequencing and linker-mediated PCR identified a 24.9 kb biosynthetic gene locus likely involved in inhibitory activity in that mutant. Further assessment against human pathogens demonstrated the inhibition of Bacillus cereus, Listeria monocytogenes, and methicillin-resistant Staphylococcus aureus in the presence of this compound, thus supporting our molecular strategy as an effective research pipeline for SWI antibiotic discovery and genetic characterization. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  8. In vitro and in vivo structure and activity relationship analysis of polymethoxylated flavonoids: identifying sinensetin as a novel antiangiogenesis agent.

    PubMed

    Lam, In Kei; Alex, Deepa; Wang, You-Hua; Liu, Ping; Liu, Ai-Lin; Du, Guan-Hua; Lee, Simon Ming Yuen

    2012-06-01

    Polymethoxylated flavonoids are present in citrus fruit in a range of chemical structures and abundance. These compounds have potential for anticarcinogenesis, antitumor, and cardiovascular protective activity, but the effect on angiogenesis has not been well studied. Human umbilical vein endothelial cells (HUVECs) in vitro and zebrafish (Danio rerio) in vivo models were used to screen and identify the antiangiogenesis activity of seven polymethoxylated flavonoids; namely, hesperetin, naringin, neohesperidin, nobiletin, scutellarein, scutellarein tetramethylether, and sinensetin. Five, excluding naringin and neohesperidin, showed different degrees of potency of antiangiogenesis activity. Sinensetin, which had the most potent antiangiogenesis activity and the lowest toxicity, inhibited angiogenesis by inducing cell cycle arrest in the G0/G1 phase in HUVEC culture and downregulating the mRNA expressions of angiogenesis genes flt1, kdrl, and hras in zebrafish. The in vivo structure-activity relationship (SAR) analysis indicated that a flavonoid with a methoxylated group at the C3' position offers a stronger antiangiogenesis activity, whereas the absence of a methoxylated group at the C8 position offers lower lethal toxicity in addition to enhancing the antiangiogenesis activity. This study provides new insight into how modification of the chemical structure of polymethoxylated flavonoids affects this newly identified antiangiogenesis activity. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Memory-Augmented Active Deep Learning for Identifying Relations Between Distant Medical Concepts in Electroencephalography Reports.

    PubMed

    Maldonado, Ramon; Goodwin, Travis R; Harabagiu, Sanda M

    2018-01-01

    The automatic identification of relations between medical concepts in a large corpus of Electroencephalography (EEG) reports is an important step in the development of an EEG-specific patient cohort retrieval system as well as in the acquisition of EEG-specific knowledge from this corpus. EEG-specific relations involve medical concepts that are not typically mentioned in the same sentence or even the same section of a report, thus requiring extraction techniques that can handle such long-distance dependencies. To address this challenge, we present a novel frame work which combines the advantages of a deep learning framework employing Dynamic Relational Memory (DRM) with active learning. While DRM enables the prediction of long-distance relations, active learning provides a mechanism for accurately identifying relations with minimal training data, obtaining an 5-fold cross validationF1 score of 0.7475 on a set of 140 EEG reports selected with active learning. The results obtained with our novel framework show great promise.

  10. Identifying Metabolically Active Chemicals Using a Consensus ...

    EPA Pesticide Factsheets

    Traditional toxicity testing provides insight into the mechanisms underlying toxicological responses but requires a high investment in a large number of resources. The new paradigm of testing approaches involves rapid screening studies able to evaluate thousands of chemicals across hundreds of biological targets through use of in vitro assays. Endocrine disrupting chemicals (EDCs) are of concern due to their ability to alter neurodevelopment, behavior, and reproductive success of humans and other species. A recent integrated computational model examined results across 18 ER-related assays in the ToxCast in vitro screening program to eliminate chemicals that produce a false signal by possibly interfering with the technological attributes of an individual assay. However, in vitro assays can also lead to false negatives when the complex metabolic processes that render a chemical bioactive in a living system might be unable to be replicated in an in vitro environment. In the current study, the influence of metabolism was examined for over 1,400 chemicals considered inactive using the integrated computational model. Over 2,000 first-generation and over 4,000 second-generation metabolites were generated for the inactive chemicals using in silico techniques. Next, a consensus model comprised of individual structure activity relationship (SAR) models was used to predict ER-binding activity for each of the metabolites. Binding activity was predicted for 8-10% of the meta

  11. Identifying factors associated with regular physical activity in leisure time among Canadian adolescents.

    PubMed

    Godin, Gaston; Anderson, Donna; Lambert, Léo-Daniel; Desharnais, Raymond

    2005-01-01

    The purpose of this study was to identify the factors explaining regular physical activity among Canadian adolescents. A cohort study conducted over a period of 2 years. A French-language high school located near Québec City. A cohort of 740 students (352 girls; 388 boys) aged 13.3 +/- 1.0 years at baseline. Psychosocial, life context, profile, and sociodemographic variables were assessed at baseline and 1 and 2 years after baseline. Exercising almost every day during leisure time at each measurement time was the dependent variable. The Generalized Estimating Equations (GEE) analysis indicated that exercising almost every day was significantly associated with a high intention to exercise (odds ratio [OR]: 8.33, confidence interval [CI] 95%: 5.26, 13.18), being satisfied with the activity practiced (OR: 2.07, CI 95%: 1.27, 3.38), perceived descriptive norm (OR: 1.82, CI 95%: 1.41, 2.35), being a boy (OR: 1.83, CI 95%: 1.37, 2.46), practicing "competitive" activities (OR: 1.80, CI 95%: 1.37, 2.36), eating a healthy breakfast (OR: 1.68, CI 95%: 1.09, 2.60), and normative beliefs (OR: 1.48, CI 95%: 1.14, 1.90). Specific GEE analysis for gender indicated slight but significant differences. This study provides evidence for the need to design interventions that are gender specific and that focus on increasing intention to exercise regularly.

  12. Identifying common pressure pathways from a complex network of human activities to support ecosystem-based management.

    PubMed

    Knights, Antony M; Koss, Rebecca S; Robinson, Leonie A

    2013-06-01

    The marine environment is heavily exploited, but unintentional consequences cause wide-ranging negative effects to its characteristics. Linkage frameworks (e.g., DPSIR [driver-pressure-state-impact-response]) are commonly used to describe an interaction between human activities and ecological characteristics of the ecosystem, but as each linkage is viewed independently, the diversity of pressures that affect those characteristics may not be identified or managed effectively. Here we demonstrate an approach for using linkages to build a simple network to capture the complex relationships arising from multiple sectors and their activities. Using data-analysis tools common to ecology, we show how linkages can be placed into mechanistically similar groups. Management measures can be combined into fewer and more simplified measures that target groups of pressures rather than individual pressures, which is likely to increase compliance and the success of the measure while reducing the cost of enforcement. Given that conservation objectives (regional priorities) can vary, we also demonstrate by way of a case study example from the Marine Strategy Framework Directive, how management priorities might change, and illustrate how the approach can be used to identify sectors for control that best support the conservation objectives.

  13. Development of a QPatch automated electrophysiology assay for identifying KCa3.1 inhibitors and activators.

    PubMed

    Jenkins, David Paul; Yu, Weifeng; Brown, Brandon M; Løjkner, Lars Damgaard; Wulff, Heike

    2013-01-01

    The intermediate-conductance Ca(2+)-activated K(+) channel KCa3.1 (also known as KCNN4, IK1, or the Gárdos channel) plays an important role in the activation of T and B cells, mast cells, macrophages, and microglia by regulating membrane potential, cellular volume, and calcium signaling. KCa3.1 is further involved in the proliferation of dedifferentiated vascular smooth muscle cells and fibroblast and endothelium-derived hyperpolarization responses in the vascular endothelium. Accordingly, KCa3.1 inhibitors are therapeutically interesting as immunosuppressants and for the treatment of a wide range of fibroproliferative disorders, whereas KCa3.1 activators constitute a potential new class of endothelial function preserving antihypertensives. Here, we report the development of QPatch assays for both KCa3.1 inhibitors and activators. During assay optimization, the Ca(2+) sensitivity of KCa3.1 was studied using varying intracellular Ca(2+) concentrations. A free Ca(2+) concentration of 1 μM was chosen to optimally test inhibitors. To identify activators, which generally act as positive gating modulators, a lower Ca(2+) concentration (∼200 nM) was used. The QPatch results were benchmarked against manual patch-clamp electrophysiology by determining the potency of several commonly used KCa3.1 inhibitors (TRAM-34, NS6180, ChTX) and activators (EBIO, riluzole, SKA-31). Collectively, our results demonstrate that the QPatch provides a comparable but much faster approach to study compound interactions with KCa3.1 channels in a robust and reliable assay.

  14. Identifying physical activity type in manual wheelchair users with spinal cord injury by means of accelerometers.

    PubMed

    García-Massó, X; Serra-Añó, P; Gonzalez, L M; Ye-Lin, Y; Prats-Boluda, G; Garcia-Casado, J

    2015-10-01

    This was a cross-sectional study. The main objective of this study was to develop and test classification algorithms based on machine learning using accelerometers to identify the activity type performed by manual wheelchair users with spinal cord injury (SCI). The study was conducted in the Physical Therapy department and the Physical Education and Sports department of the University of Valencia. A total of 20 volunteers were asked to perform 10 physical activities, lying down, body transfers, moving items, mopping, working on a computer, watching TV, arm-ergometer exercises, passive propulsion, slow propulsion and fast propulsion, while fitted with four accelerometers placed on both wrists, chest and waist. The activities were grouped into five categories: sedentary, locomotion, housework, body transfers and moderate physical activity. Different machine learning algorithms were used to develop individual and group activity classifiers from the acceleration data for different combinations of number and position of the accelerometers. We found that although the accuracy of the classifiers for individual activities was moderate (55-72%), with higher values for a greater number of accelerometers, grouped activities were correctly classified in a high percentage of cases (83.2-93.6%). With only two accelerometers and the quadratic discriminant analysis algorithm we achieved a reasonably accurate group activity recognition system (>90%). Such a system with the minimum of intervention would be a valuable tool for studying physical activity in individuals with SCI.

  15. Development and application of a sensitive, phenotypic, high-throughput image-based assay to identify compound activity against Trypanosoma cruzi amastigotes

    PubMed Central

    Sykes, Melissa L.; Avery, Vicky M.

    2015-01-01

    We have developed a high content 384-well, image-based assay to estimate the effect of compound treatment on Trypanosoma cruzi amastigotes in 3T3 fibroblasts. In the same well, the effect of compound activity on host cells can also be determined, as an initial indicator of cytotoxicity. This assay has been used to identify active compounds from an in-house library of compounds with either known biological activity or that are FDA approved, and separately, from the Medicines for Malaria Venture Malaria Box collection. Active compounds were screened against T. cruzi trypomastigotes, utilising an assay developed with the viability dye resazurin. Twelve compounds with reconfirmed solid sample activity, with IC50 values of less than 10 μM and selectivity indices to T. cruzi amastigotes over 3T3 host cells of between >22 and 319 times were identified from these libraries. As 3T3 cells are contact inhibited, with limited proliferation in the assay, selective compounds of interest were profiled in a separate assay to estimate the viability of compound treated, replicating HEK293 cells. Selective compounds that were not previously reported in the literature were further profiled by extending the incubation time against amastigote infected 3T3 cells to determine if there were residual amastigotes post-treatment, important for the consideration of the exposure time required for further biological characterisation. The assay development process and the suitability of identified compounds as hit molecules for Chagas disease research are discussed. PMID:27120069

  16. Development and application of a sensitive, phenotypic, high-throughput image-based assay to identify compound activity against Trypanosoma cruzi amastigotes.

    PubMed

    Sykes, Melissa L; Avery, Vicky M

    2015-12-01

    We have developed a high content 384-well, image-based assay to estimate the effect of compound treatment on Trypanosoma cruzi amastigotes in 3T3 fibroblasts. In the same well, the effect of compound activity on host cells can also be determined, as an initial indicator of cytotoxicity. This assay has been used to identify active compounds from an in-house library of compounds with either known biological activity or that are FDA approved, and separately, from the Medicines for Malaria Venture Malaria Box collection. Active compounds were screened against T. cruzi trypomastigotes, utilising an assay developed with the viability dye resazurin. Twelve compounds with reconfirmed solid sample activity, with IC50 values of less than 10 μM and selectivity indices to T. cruzi amastigotes over 3T3 host cells of between >22 and 319 times were identified from these libraries. As 3T3 cells are contact inhibited, with limited proliferation in the assay, selective compounds of interest were profiled in a separate assay to estimate the viability of compound treated, replicating HEK293 cells. Selective compounds that were not previously reported in the literature were further profiled by extending the incubation time against amastigote infected 3T3 cells to determine if there were residual amastigotes post-treatment, important for the consideration of the exposure time required for further biological characterisation. The assay development process and the suitability of identified compounds as hit molecules for Chagas disease research are discussed. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Is scaffold hopping a reliable indicator for the ability of computational methods to identify structurally diverse active compounds?

    NASA Astrophysics Data System (ADS)

    Dimova, Dilyana; Bajorath, Jürgen

    2017-07-01

    Computational scaffold hopping aims to identify core structure replacements in active compounds. To evaluate scaffold hopping potential from a principal point of view, regardless of the computational methods that are applied, a global analysis of conventional scaffolds in analog series from compound activity classes was carried out. The majority of analog series was found to contain multiple scaffolds, thus enabling the detection of intra-series scaffold hops among closely related compounds. More than 1000 activity classes were found to contain increasing proportions of multi-scaffold analog series. Thus, using such activity classes for scaffold hopping analysis is likely to overestimate the scaffold hopping (core structure replacement) potential of computational methods, due to an abundance of artificial scaffold hops that are possible within analog series.

  18. CETSA screening identifies known and novel thymidylate synthase inhibitors and slow intracellular activation of 5-fluorouracil

    PubMed Central

    Almqvist, Helena; Axelsson, Hanna; Jafari, Rozbeh; Dan, Chen; Mateus, André; Haraldsson, Martin; Larsson, Andreas; Molina, Daniel Martinez; Artursson, Per; Lundbäck, Thomas; Nordlund, Pär

    2016-01-01

    Target engagement is a critical factor for therapeutic efficacy. Assessment of compound binding to native target proteins in live cells is therefore highly desirable in all stages of drug discovery. We report here the first compound library screen based on biophysical measurements of intracellular target binding, exemplified by human thymidylate synthase (TS). The screen selected accurately for all the tested known drugs acting on TS. We also identified TS inhibitors with novel chemistry and marketed drugs that were not previously known to target TS, including the DNA methyltransferase inhibitor decitabine. By following the cellular uptake and enzymatic conversion of known drugs we correlated the appearance of active metabolites over time with intracellular target engagement. These data distinguished a much slower activation of 5-fluorouracil when compared with nucleoside-based drugs. The approach establishes efficient means to associate drug uptake and activation with target binding during drug discovery. PMID:27010513

  19. Food Web Architecture and Basal Resources Interact to Determine Biomass and Stoichiometric Cascades along a Benthic Food Web

    PubMed Central

    Guariento, Rafael D.; Carneiro, Luciana S.; Caliman, Adriano; Leal, João J. F.; Bozelli, Reinaldo L.; Esteves, Francisco A.

    2011-01-01

    Understanding the effects of predators and resources on primary producers has been a major focus of interest in ecology. Within this context, the trophic cascade concept especially concerning the pelagic zone of lakes has been the focus of the majority of these studies. However, littoral food webs could be especially interesting because base trophic levels may be strongly regulated by consumers and prone to be light limited. In this study, the availability of nutrients and light and the presence of an omnivorous fish (Hyphessobrycon bifasciatus) were manipulated in enclosures placed in a humic coastal lagoon (Cabiúnas Lagoon, Macaé – RJ) to evaluate the individual and interactive effects of resource availability (nutrients and light) and food web configuration on the biomass and stoichiometry of periphyton and benthic grazers. Our findings suggest that light and nutrients interact to determine periphyton biomass and stoichiometry, which propagates to the consumer level. We observed a positive effect of the availability of nutrients on periphytic biomass and grazers' biomass, as well as a reduction of periphytic C∶N∶P ratios and an increase of grazers' N and P content. Low light availability constrained the propagation of nutrient effects on periphyton biomass and induced higher periphytic C∶N∶P ratios. The effects of fish presence strongly interacted with resource availability. In general, a positive effect of fish presence was observed for the total biomass of periphyton and grazer's biomass, especially with high resource availability, but the opposite was found for periphytic autotrophic biomass. Fish also had a significant effect on periphyton stoichiometry, but no effect was observed on grazers' stoichiometric ratios. In summary, we observed that the indirect effect of fish predation on periphyton biomass might be dependent on multiple resources and periphyton nutrient stoichiometric variation can affect consumers' stoichiometry. PMID:21789234

  20. The Animadora Project: Identifying factors related to the promotion of physical activity among Mexican Americans with diabetes

    PubMed Central

    Ingram, Maia; Ruis, Maricruz; Mayorga, Maria Theresa; Rosales, Cecilia

    2015-01-01

    Purpose There is a dearth of information about factors related to physical activity among Mexican Americans with diabetes. Self efficacy and social support are associated with physical activity, however little is known about their role within different cultural groups. Design Focus groups were used to identify factors that motivate walking. Setting Two Mexican American communities located in Tucson, Arizona. Subjects Individuals who attended diabetes education. Intervention A community-based provider organized walking groups with people who previously attended diabetes classes. Walkers participated in focus groups exploring themes related to their experience. Measures Self efficacy, social support, and collective efficacy. Grounded theory was used to analyze focus group results using two rounds of analysis; the first identifying references to self efficacy and social support and the second adding collective efficacy as a theoretical basis for walking. Results Among 43 eligible participants, 20 participated in focus groups. Social support was expressed as commitment and companionship. Walkers demonstrated a high level of self efficacy for walking. Development of group identity/social cohesion was also a motivator to walk. Collective efficacy emerged as an applicable theoretical model encompassing these themes and their interrelationship. Conclusion Collective efficacy, or the belief that the group can improve their lives through collective effort, is a viable theoretical construct in the development of physical activity interventions targeting Mexican Americans with diabetes. PMID:19601479

  1. Gene Expression Profiling of Multiple Sclerosis Pathology Identifies Early Patterns of Demyelination Surrounding Chronic Active Lesions

    PubMed Central

    Hendrickx, Debbie A. E.; van Scheppingen, Jackelien; van der Poel, Marlijn; Bossers, Koen; Schuurman, Karianne G.; van Eden, Corbert G.; Hol, Elly M.; Hamann, Jörg; Huitinga, Inge

    2017-01-01

    In multiple sclerosis (MS), activated microglia and infiltrating macrophages phagocytose myelin focally in (chronic) active lesions. These demyelinating sites expand in time, but at some point turn inactive into a sclerotic scar. To identify molecular mechanisms underlying lesion activity and halt, we analyzed genome-wide gene expression in rim and peri-lesional regions of chronic active and inactive MS lesions, as well as in control tissue. Gene clustering revealed patterns of gene expression specifically associated with MS and with the presumed, subsequent stages of lesion development. Next to genes involved in immune functions, we found regulation of novel genes in and around the rim of chronic active lesions, such as NPY, KANK4, NCAN, TKTL1, and ANO4. Of note, the presence of many foamy macrophages in active rims was accompanied by a congruent upregulation of genes related to lipid binding, such as MSR1, CD68, CXCL16, and OLR1, and lipid uptake, such as CHIT1, GPNMB, and CCL18. Except CCL18, these genes were already upregulated in regions around active MS lesions, showing that such lesions are indeed expanding. In vitro downregulation of the scavenger receptors MSR1 and CXCL16 reduced myelin uptake. In conclusion, this study provides the gene expression profile of different aspects of MS pathology and indicates that early demyelination, mediated by scavenger receptors, is already present in regions around active MS lesions. Genes involved in early demyelination events in regions surrounding chronic active MS lesions might be promising therapeutic targets to stop lesion expansion. PMID:29312322

  2. Gene Expression Profiling of Multiple Sclerosis Pathology Identifies Early Patterns of Demyelination Surrounding Chronic Active Lesions.

    PubMed

    Hendrickx, Debbie A E; van Scheppingen, Jackelien; van der Poel, Marlijn; Bossers, Koen; Schuurman, Karianne G; van Eden, Corbert G; Hol, Elly M; Hamann, Jörg; Huitinga, Inge

    2017-01-01

    In multiple sclerosis (MS), activated microglia and infiltrating macrophages phagocytose myelin focally in (chronic) active lesions. These demyelinating sites expand in time, but at some point turn inactive into a sclerotic scar. To identify molecular mechanisms underlying lesion activity and halt, we analyzed genome-wide gene expression in rim and peri-lesional regions of chronic active and inactive MS lesions, as well as in control tissue. Gene clustering revealed patterns of gene expression specifically associated with MS and with the presumed, subsequent stages of lesion development. Next to genes involved in immune functions, we found regulation of novel genes in and around the rim of chronic active lesions, such as NPY, KANK4, NCAN, TKTL1 , and ANO4 . Of note, the presence of many foamy macrophages in active rims was accompanied by a congruent upregulation of genes related to lipid binding, such as MSR1, CD68, CXCL16 , and OLR1 , and lipid uptake, such as CHIT1, GPNMB , and CCL18 . Except CCL18 , these genes were already upregulated in regions around active MS lesions, showing that such lesions are indeed expanding. In vitro downregulation of the scavenger receptors MSR1 and CXCL16 reduced myelin uptake. In conclusion, this study provides the gene expression profile of different aspects of MS pathology and indicates that early demyelination, mediated by scavenger receptors, is already present in regions around active MS lesions. Genes involved in early demyelination events in regions surrounding chronic active MS lesions might be promising therapeutic targets to stop lesion expansion.

  3. Identifying Diverse Means for Assessing Physical Activity

    ERIC Educational Resources Information Center

    Perlman, Dana J.; Pearson, Phil

    2012-01-01

    Physical inactivity is of concern for the majority of age groups within the United States. Limited engagement in physical activity (PA) has been linked with an increased risk for a host of health problems, including but not limited to heart disease, diabetes and cancer. Benefits of PA are widely documented and accepted yet many people, especially…

  4. In vitro and in silico studies on the anticancer and apoptosis-inducing activities of the sterols identified from the soft coral, subergorgia reticulata

    PubMed Central

    Byju, Kuniyil; Anuradha, Vattoni; Vasundhara, Gopalakrishnapai; Nair, S. Muraleedharan; Kumar, N. Chandramohana

    2014-01-01

    Background: Gorgonians and other octocorals are known to possess a huge array of secondary metabolites in which sterols are the major group of secondary metabolites apart from sesquiterpenes and diterpenes, and the bioactive metabolites could show marked biomedical potential for future drug discovery. Objective: This study was intended for the isolation and identification of sterols from the octocoral Subergorgia reticulata and to evaluate the anticancer and apoptosis-inducing activities of the identified sterols through in vitro and in silico approach. Materials and Methods: The organism was collected from Lakshadweep Island. The isolated sterols were identified using Gas chromatography-mass spectrometry (GC-MS). The structure was confirmed by using comparison of their spectra those in National Institute of Standard Technology (NIST) library. The apoptosis inducing effect of identified sterols were determined by PASS online prediction. In vitro cytotoxity studies were carried out using Dalton's lymphoma ascites cells (DLA) and the cell viability was determined by trypan blue exclusion method. Results: Six sterols were identified from the soft coral S. reticulata. They are Cholesta-5,22-diene-3ol (3β), Ergosta-5-22-dien-3ol (3β,22E 24S), Cholesterol, 26,26-Dimethyl-5,24(28)-ergostadien-3β-ol. β-sitosterol, and Fucosterol. In silico predictions showed that the identified sterols exhibited remarkable apoptosis agonist activity. The probability of apoptosis agonist activity were found maximum for 26,26-Dimethyl-5,24 (28)-S. reticulata sterol fractions isolated were found to be having anticancer activity. Conclusions: These findings suggest that S. reticulata contained biologically active sterol compounds that may be useful in the treatment of cancer. PMID:24914311

  5. Preventing, Identifying, and Treating Prescription Drug Misuse Among Active-Duty Service Members

    PubMed Central

    Pacula, Rosalie Liccardo; Hunter, Sarah B.; Ober, Allison J.; Osilla, Karen Chan; Vardavas, Raffaele; Blanchard, Janice C.; DeVries, David; Drabo, Emmanuel F.; Leuschner, Kristin J.; Stewart, Warren; Walters, Jennifer

    2017-01-01

    Abstract Prescription drug misuse (PDM) is of critical concern for the military because of its potential impact on military readiness, the health and well-being of military personnel, and associated health care costs. The purpose of this study is to summarize insights gleaned from a series of activities that the RAND Corporation undertook for the Deputy Assistant Secretary of Defense for Readiness to address this important health and military readiness issue. The authors completed a review of U.S. Department of Defense policies and a comprehensive literature review of clinical guidelines and the empirical literature on the prevention and treatment of PDM and conducted individual face-to-face interviews with 66 health and behavioral health care providers at nine medical treatment facilities across three regions within the contiguous United States to identify best practices in the prevention, identification, and treatment of PDM and the extent to which those practices are known and followed. The study also presents the framework of an analytic tool that, once informed by data available to the military but not available to the authors, can assist the military in predicting future trends in PDM based on current demographics of active-duty service members and rates of injury and prescribing of prescription drugs. The findings from this work led the authors to formulate a set of key insights that they believe might improve the rapid identification and treatment of service members dealing with PDM, thereby improving future force readiness. PMID:29057158

  6. Differential activation of an identified motor neuron and neuromodulation provide Aplysia's retractor muscle an additional function.

    PubMed

    McManus, Jeffrey M; Lu, Hui; Cullins, Miranda J; Chiel, Hillel J

    2014-08-15

    To survive, animals must use the same peripheral structures to perform a variety of tasks. How does a nervous system employ one muscle to perform multiple functions? We addressed this question through work on the I3 jaw muscle of the marine mollusk Aplysia californica's feeding system. This muscle mediates retraction of Aplysia's food grasper in multiple feeding responses and is innervated by a pool of identified neurons that activate different muscle regions. One I3 motor neuron, B38, is active in the protraction phase, rather than the retraction phase, suggesting the muscle has an additional function. We used intracellular, extracellular, and muscle force recordings in several in vitro preparations as well as recordings of nerve and muscle activity from intact, behaving animals to characterize B38's activation of the muscle and its activity in different behavior types. We show that B38 specifically activates the anterior region of I3 and is specifically recruited during one behavior, swallowing. The function of this protraction-phase jaw muscle contraction is to hold food; thus the I3 muscle has an additional function beyond mediating retraction. We additionally show that B38's typical activity during in vivo swallowing is insufficient to generate force in an unmodulated muscle and that intrinsic and extrinsic modulation shift the force-frequency relationship to allow contraction. Using methods that traverse levels from individual neuron to muscle to intact animal, we show how regional muscle activation, differential motor neuron recruitment, and neuromodulation are key components in Aplysia's generation of multifunctionality. Copyright © 2014 the American Physiological Society.

  7. CD147 (Basigin/Emmprin) identifies FoxP3+CD45RO+CTLA4+-activated human regulatory T cells.

    PubMed

    Solstad, Therese; Bains, Simer Jit; Landskron, Johannes; Aandahl, Einar Martin; Thiede, Bernd; Taskén, Kjetil; Torgersen, Knut Martin

    2011-11-10

    Human CD4(+)FoxP3(+) T cells are functionally and phenotypically heterogeneous providing plasticity to immune activation and regulation. To better understand the functional dynamics within this subset, we first used a combined strategy of subcellular fractionation and proteomics to describe differences at the protein level between highly purified human CD4(+)CD25(+) and CD4(+)CD25(-) T-cell populations. This identified a set of membrane proteins highly expressed on the cell surface of human regulatory T cells (Tregs), including CD71, CD95, CD147, and CD148. CD147 (Basigin or Emmprin) divided CD4(+)CD25(+) cells into distinct subsets. Furthermore, CD147, CD25, FoxP3, and in particular CTLA-4 expression correlated. Phenotypical and functional analyses suggested that CD147 marks the switch between resting (CD45RA(+)) and activated (CD45RO(+)) subsets within the FoxP3(+) T-cell population. Sorting of regulatory T cells into CD147(-) and CD147(+) populations demonstrated that CD147 identifies an activated and highly suppressive CD45RO(+) Treg subset. When analyzing CD4(+) T cells for their cytokine producing potential, CD147 levels grouped the FoxP3(+) subset into 3 categories with different ability to produce IL-2, TNF-α, IFN-γ, and IL-17. Together, this suggests that CD147 is a direct marker for activated Tregs within the CD4(+)FoxP3(+) subset and may provide means to manipulate cells important for immune homeostasis.

  8. Extreme Outlier Analysis Identifies Occult Mitogen-Activated Protein Kinase Pathway Mutations in Patients With Low-Grade Serous Ovarian Cancer

    PubMed Central

    Grisham, Rachel N.; Sylvester, Brooke E.; Won, Helen; McDermott, Gregory; DeLair, Deborah; Ramirez, Ricardo; Yao, Zhan; Shen, Ronglai; Dao, Fanny; Bogomolniy, Faina; Makker, Vicky; Sala, Evis; Soumerai, Tara E.; Hyman, David M.; Socci, Nicholas D.; Viale, Agnes; Gershenson, David M.; Farley, John; Levine, Douglas A.; Rosen, Neal; Berger, Michael F.; Spriggs, David R.; Aghajanian, Carol A.; Solit, David B.; Iyer, Gopa

    2015-01-01

    Purpose No effective systemic therapy exists for patients with metastatic low-grade serous (LGS) ovarian cancers. BRAF and KRAS mutations are common in serous borderline (SB) and LGS ovarian cancers, and MEK inhibition has been shown to induce tumor regression in a minority of patients; however, no correlation has been observed between mutation status and clinical response. With the goal of identifying biomarkers of sensitivity to MEK inhibitor treatment, we performed an outlier analysis of a patient who experienced a complete, durable, and ongoing (> 5 years) response to selumetinib, a non-ATP competitive MEK inhibitor. Patients and Methods Next-generation sequencing was used to analyze this patient's tumor as well as an additional 28 SB/LGS tumors. Functional characterization of an identified novel alteration of interest was performed. Results Analysis of the extraordinary responder's tumor identified a 15-nucleotide deletion in the negative regulatory helix of the MAP2K1 gene encoding for MEK1. Functional characterization demonstrated that this mutant induced extracellular signal-regulated kinase pathway activation, promoted anchorage-independent growth and tumor formation in mice, and retained sensitivity to selumetinib. Analysis of additional LGS/SB tumors identified mutations predicted to induce extracellular signal-regulated kinase pathway activation in 82% (23 of 28), including two patients with BRAF fusions, one of whom achieved an ongoing complete response to MEK inhibitor–based combination therapy. Conclusion Alterations affecting the mitogen-activated protein kinase pathway are present in the majority of patients with LGS ovarian cancer. Next-generation sequencing analysis revealed deletions and fusions that are not detected by older sequencing approaches. These findings, coupled with the observation that a subset of patients with recurrent LGS ovarian cancer experienced dramatic and durable responses to MEK inhibitor therapy, support additional

  9. Past Strategies and Future Directions for Identifying AMP-Activated Protein Kinase (AMPK) Modulators

    PubMed Central

    Sinnett, Sarah E.; Brenman, Jay E.

    2014-01-01

    AMP-activated protein kinase (AMPK) is a promising therapeutic target for cancer, type II diabetes, and other illnesses characterized by abnormal energy utilization. During the last decade, numerous labs have published a range of methods for identifying novel AMPK modulators. The current understanding of AMPK structure and regulation, however, has propelled a paradigm shift in which many researchers now consider ADP to be an additional regulatory nucleotide of AMPK. How can the AMPK community apply this new understanding of AMPK signaling to translational research? Recent insights into AMPK structure, regulation, and holoenzyme-sensitive signaling may provide the hindsight needed to clearly evaluate the strengths and weaknesses of past AMPK drug discovery efforts. Improving future strategies for AMPK drug discovery will require pairing the current understanding of AMPK signaling with improved experimental designs. PMID:24583089

  10. Biodegradation of composite resin with ester linkages: identifying human salivary enzyme activity with a potential role in the esterolytic process.

    PubMed

    Cai, Kuihua; Delaviz, Yasaman; Banh, Michael; Guo, Yi; Santerre, J Paul

    2014-08-01

    The ester linkages contained within dental resin monomers (such as Bisphenol A-glycidylmethacrylate (BisGMA) and triethylene glycol dimethacrylate (TEGDMA)) are susceptible to hydrolytic degradation by salivary esterases, however very little is known about the specific esterase activities implicated in this process. The objective of this work was to isolate and identify the dominant proteins from saliva that are associated with the esterase activities shown to be involved in the degradation of BisGMA. Human whole saliva was collected and processed prior to separation in a HiPrep 16/60 Sephacryl S-200 HR column. The fraction with the highest esterase activity was further separated by an anion exchange column (Mono-Q (10/100G)). Isolated fractions were then separated by gel electrophoresis, and compared to a common bench marker esterase, cholesterol esterase (CE), and commercial albumin which has been reported to express esterase activity. Proteins suspected of containing esterase activity were analyzed by Mass Spectroscopy (MS). Commercially available proteins, similar to the salivary esterase proteins identified by MS, were used to replicate the enzymatic complexes and confirm their degradation activity with respect to BisGMA. MS data suggested that the enzyme fraction with the highest esterase activity was contained among a group of proteins consisting of albumin, Zn-α2-glycoprotein, α-amylase, TALDO1 protein, transferrin, lipocalin2, and prolactin-induced protein. Studies concluded that the main esterase bands on the gels in each fraction did not overlap with CE activity, and that albumin activity emerged as a lead candidate with significant esterase activity relative to BisGMA degradation, particularly when it formed a complex with Zn-α2-glycoprotein, under slightly basic conditions. These enzyme complexes can be used as a physiologically relevant formulation to test the biostability of composite resins. Copyright © 2014 Academy of Dental Materials

  11. Identifying profiles of actual and perceived motor competence among adolescents: associations with motivation, physical activity, and sports participation.

    PubMed

    De Meester, An; Maes, Jolien; Stodden, David; Cardon, Greet; Goodway, Jacqueline; Lenoir, Matthieu; Haerens, Leen

    2016-11-01

    The present study identified adolescents' motor competence (MC)-based profiles (e.g., high actual and low perceived MC), and accordingly investigated differences in motivation for physical education (PE), physical activity (PA) levels, and sports participation between profiles by using regression analyses. Actual MC was measured with the Körperkoordinationstest für Kinder. Adolescents (n = 215; 66.0% boys; mean age = 13.64 ± .58 years) completed validated questionnaires to assess perceived MC, motivation for PE, PA-levels, and sports participation. Actual and perceived MC were only moderately correlated and cluster analyses identified four groups. Two groups of overestimators (low - overestimation, average - overestimation) were identified (51%), who particularly displayed better motivation for PE when compared to their peers who accurately estimated themselves (low - accurate, average - accurate). Moreover, adolescents with low actual MC, but high perceived MC were significantly more active than adolescents with low actual MC who accurately estimated themselves. Results pointed in the same direction for organised sports participation. Underestimators were not found in the current sample, which is positive as underestimation might negatively influence adolescents' motivation to achieve and persist in PA and sports. In conclusion, results emphasise that developing perceived MC, especially among adolescents with low levels of actual MC, seems crucial to stimulate motivation for PE, and engagement in PA and sports.

  12. Functional measures developed for clinical populations identified impairment among active workers with upper extremity disorders

    PubMed Central

    Gardner, Bethany T.; Dale, Ann Marie; Buckner-Petty, Skye; Rachford, Robert; Strickland, Jaime; Kaskutas, Vicki; Evanoff, Bradley

    2017-01-01

    Purpose Few studies have explored measures of function across a range of health outcomes in a general working population. Using four upper extremity (UE) case definitions from the scientific literature, we described the performance of functional measures of work, activities of daily living, and overall health. Methods A sample of 573 workers completed several functional measures: modified recall versions of the QuickDASH, Levine Functional Status Scale (FSS), DASH Work module (DASH-W), and standard SF-8 physical component score. We determined case status based on four UE case definitions: 1) UE symptoms, 2) UE musculoskeletal disorders (MSD), 3) carpal tunnel syndrome (CTS), and 4) work limitations due to UE symptoms. We calculated effect sizes for each case definition to show the magnitude of the differences that were detected between cases and non-cases for each case definition on each functional measure. Sensitivity and specificity analyses showed how well each measure identified functional impairments across the UE case definitions. Results All measures discriminated between cases and non-cases for each case definition with the largest effect sizes for CTS and work limitations, particularly for the modified FSS and DASH-W measures. Specificity was high and sensitivity was low for outcomes of UE symptoms and UE MSD in all measures. Sensitivity was high for CTS and work limitations. Conclusions Functional measures developed specifically for use in clinical, treatment-seeking populations may identify mild levels of impairment in relatively healthy, active working populations, but measures performed better among workers with CTS or those reporting limitations at work. PMID:26091980

  13. Comparative evaluation of features and techniques for identifying activity type and estimating energy cost from accelerometer data

    PubMed Central

    Kate, Rohit J.; Swartz, Ann M.; Welch, Whitney A.; Strath, Scott J.

    2016-01-01

    Wearable accelerometers can be used to objectively assess physical activity. However, the accuracy of this assessment depends on the underlying method used to process the time series data obtained from accelerometers. Several methods have been proposed that use this data to identify the type of physical activity and estimate its energy cost. Most of the newer methods employ some machine learning technique along with suitable features to represent the time series data. This paper experimentally compares several of these techniques and features on a large dataset of 146 subjects doing eight different physical activities wearing an accelerometer on the hip. Besides features based on statistics, distance based features and simple discrete features straight from the time series were also evaluated. On the physical activity type identification task, the results show that using more features significantly improve results. Choice of machine learning technique was also found to be important. However, on the energy cost estimation task, choice of features and machine learning technique were found to be less influential. On that task, separate energy cost estimation models trained specifically for each type of physical activity were found to be more accurate than a single model trained for all types of physical activities. PMID:26862679

  14. An Action Research Inquiry into the Relationship Among Aerobic Activities, Memory, and Stress with Students Identified as Gifted

    NASA Astrophysics Data System (ADS)

    Ford, Denise Marie

    Students identified as gifted come from varying socio-economic strata and nationalities with a range of talents and temperaments comprising a diverse community. They may experience stress for a variety of reasons. Although a certain amount of stress can enhance the learning process, too much stress can impede learning, especially memory. Strategies have been offered for relieving stress, yet the benefits of physical activities as stress reducers for the gifted have frequently been overlooked. The purpose of this study was to investigate the relationship among aerobic activity, stress, and memory ability in students in an elementary school gifted program. An exceptional aspect of this research was that the students were an integral part of their own study. As co-researchers they had a vested interest in what they were doing, enhancing the significance of the experience and heightening learning. This action research project conducted in a mid-western school district with fourth and fifth grade students examined the impact of aerobic movement on physical indicators of stress and memory. The study lasted twelve weeks with data collected on physical indicators of stress, memory test scores, parent observations, interviews with students, a parent focus group session, observational data, student comments, and investigator/teacher journal. By infusing regular exercise into curricula, stress levels in students identified as gifted were examined. Students' scores on declarative memory tasks conducted with and without an accompanying aerobic activity were documented. Students learned of the delicate relationship between stress and memory as they studied the physiology of the brain. Twenty-four hour retention rates of declarative memory items were higher when a 20-minute aerobic activity intervention preceded the memory activity. Perceived stress levels were lowered for 14 of the 16 co-researchers. Students indicated a positive attitude toward physical activity and its

  15. Target-similarity search using Plasmodium falciparum proteome identifies approved drugs with anti-malarial activity and their possible targets

    PubMed Central

    Akala, Hoseah M.; Macharia, Rosaline W.; Juma, Dennis W.; Cheruiyot, Agnes C.; Andagalu, Ben; Brown, Mathew L.; El-Shemy, Hany A.; Nyanjom, Steven G.

    2017-01-01

    Malaria causes about half a million deaths annually, with Plasmodium falciparum being responsible for 90% of all the cases. Recent reports on artemisinin resistance in Southeast Asia warrant urgent discovery of novel drugs for the treatment of malaria. However, most bioactive compounds fail to progress to treatments due to safety concerns. Drug repositioning offers an alternative strategy where drugs that have already been approved as safe for other diseases could be used to treat malaria. This study screened approved drugs for antimalarial activity using an in silico chemogenomics approach prior to in vitro verification. All the P. falciparum proteins sequences available in NCBI RefSeq were mined and used to perform a similarity search against DrugBank, TTD and STITCH databases to identify similar putative drug targets. Druggability indices of the potential P. falciparum drug targets were obtained from TDR targets database. Functional amino acid residues of the drug targets were determined using ConSurf server which was used to fine tune the similarity search. This study predicted 133 approved drugs that could target 34 P. falciparum proteins. A literature search done at PubMed and Google Scholar showed 105 out of the 133 drugs to have been previously tested against malaria, with most showing activity. For further validation, drug susceptibility assays using SYBR Green I method were done on a representative group of 10 predicted drugs, eight of which did show activity against P. falciparum 3D7 clone. Seven had IC50 values ranging from 1 μM to 50 μM. This study also suggests drug-target association and hence possible mechanisms of action of drugs that did show antiplasmodial activity. The study results validate the use of proteome-wide target similarity approach in identifying approved drugs with activity against P. falciparum and could be adapted for other pathogens. PMID:29088219

  16. Silicon, endophytes and secondary metabolites as grass defenses against mammalian herbivores

    PubMed Central

    Huitu, Otso; Forbes, Kristian M.; Helander, Marjo; Julkunen-Tiitto, Riitta; Lambin, Xavier; Saikkonen, Kari; Stuart, Peter; Sulkama, Sini; Hartley, Sue

    2014-01-01

    Grasses have been considered to primarily employ tolerance in lieu of defense in mitigating damage caused by herbivory. Yet a number of mechanisms have been identified in grasses, which may deter feeding by grazers. These include enhanced silicon uptake, hosting of toxin-producing endophytic fungi and induction of secondary metabolites. While these mechanisms have been individually studied, their synergistic responses to grazing, as well as their effects on grazers, are poorly known. A field experiment was carried out in 5 × 5 m outdoor enclosures to quantify phytochemical changes of either endophyte-infected (E+) or endophyte-free (E-) meadow fescue (Schedonorus pratensis) in response to medium intensity (corresponding with densities of ca. 1200 voles/ha for 5 weeks during 3 months) or heavy intensity (ca. 1200 voles/ha for 8 weeks during 3 months) grazing by a mammalian herbivore, the field vole (Microtus agrestis). A laboratory experiment was then conducted to evaluate the effects of endophyte infection status and grazing history of the grass diet on vole performance. As predicted, grazing increased foliar silicon content, by up to 13%. Grazing also increased foliar levels of phosphorous and several phenolic compounds, most notably those of the flavonols isorhamnetin-diglycoside and rhamnetin derivative. Silicon concentrations were consistently circa 16% higher in E+ grasses than in E-grasses, at all levels of grazing. Similarly, concentrations of chlorogenic acid derivative were found to be consistently higher in E+ than in E- grasses. Female voles maintained on heavily grazed grasses suffered higher mortality rates in the laboratory than female voles fed ungrazed grass, regardless of endophyte infection status. Our results conclusively demonstrate that, in addition to tolerance, grasses employ multi-tiered, effective defenses against mammalian grazers. PMID:25278951

  17. Identifying Feasible Physical Activity Programs for Long-Term Care Homes in the Ontario Context

    PubMed Central

    Shakeel, Saad; Newhouse, Ian; Malik, Ali; Heckman, George

    2015-01-01

    Background Structured exercise programs for frail institutionalized seniors have shown improvement in physical, functional, and psychological health of this population. However, the ‘feasibility’ of implementation of such programs in real settings is seldom discussed. The purpose of this systematic review was to gauge feasibility of exercise and falls prevention programs from the perspective of long-term care homes in Ontario, given the recent changes in funding for publically funded physiotherapy services. Method Six electronic databases were searched by two independent researchers for randomized controlled trials that targeted long-term care residents and included exercise as an independent component of the intervention. Results A total of 39 studies were included in this review. A majority of these interventions were led by physiotherapist(s), carried out three times per week for 30–45 minutes per session. However, a few group-based interventions that were led by long-term care staff, volunteers, or trained non-exercise specialists were identified that also required minimal equipment. Conclusion This systematic review has identified ‘feasible’ physical activity and falls prevention programs that required minimal investment in staff and equipment, and demonstrated positive outcomes. Implementation of such programs represents cost-effective means of providing long-term care residents with meaningful gains in physical, psychological, and social health. PMID:26180563

  18. Quantitative Protein Sulfenic Acid Analysis Identifies Platelet Releasate-Induced Activation of Integrin β2 on Monocytes via NADPH Oxidase.

    PubMed

    Li, Ru; Klockenbusch, Cordula; Lin, Liwen; Jiang, Honghui; Lin, Shujun; Kast, Juergen

    2016-12-02

    Physiological stimuli such as thrombin, or pathological stimuli such as lysophosphatidic acid (LPA), activate platelets. The activated platelets bind to monocytes through P-selectin-PSGL-1 interactions but also release the contents of their granules, commonly called "platelet releasate". It is known that monocytes in contact with platelet releasate produce reactive oxygen species (ROS). Reversible cysteine oxidation by ROS is considered to be a potential regulator of protein function. In a previous study, we used THP-1 monocytic cells exposed to LPA- or thrombin-induced platelet releasate and a modified biotin switch assay to unravel the biological processes that are influenced by reversible cysteine oxidation. To gain a better understanding of the redox regulation of monocytes in atherosclerosis, we have now altered the modified biotin switch to selectively quantify protein sulfenic acid, a subpopulation of reversible cysteine oxidation. Using arsenite as reducing agent in the modified biotin switch assay, we were able to quantify 1161 proteins, in which more than 100 sulfenic acid sites were identified. Bioinformatics analysis of the quantified sulfenic acid sites highlighted the relevant, previously missed biological process of monocyte transendothelial migration, which included integrin β 2 . Flow cytometry validated the activation of LFA-1 (α L β 2 ) and Mac-1 (α M β 2 ), two subfamilies of integrin β 2 complexes, on human primary monocytes following platelet releasate treatment. The activation of LFA-1 was mediated by ROS from NADPH oxidase (NOX) activation. Production of ROS and activation of LFA-1 in human primary monocytes were independent of P-selectin-PSGL-1 interaction. Our results proved the modified biotin switch assay to be a powerful tool with the ability to reveal new regulatory mechanisms and identify new therapeutic targets.

  19. Grazers: biocatalysts of terrestrial silica cycling

    PubMed Central

    Vandevenne, Floor Ina; Barão, Ana Lúcia; Schoelynck, Jonas; Smis, Adriaan; Ryken, Nick; Van Damme, Stefan; Meire, Patrick; Struyf, Eric

    2013-01-01

    Silica is well known for its role as inducible defence mechanism countering herbivore attack, mainly through precipitation of opaline, biogenic silica (BSi) bodies (phytoliths) in plant epidermal tissues. Even though grazing strongly interacts with other element cycles, its impact on terrestrial silica cycling has never been thoroughly considered. Here, BSi content of ingested grass, hay and faeces of large herbivores was quantified by performing multiple chemical extraction procedures for BSi, allowing the assessment of chemical reactivity. Dissolution experiments with grass and faeces were carried out to measure direct availability of BSi for dissolution. Average BSi and readily soluble silica numbers were higher in faeces as compared with grass or hay, and differences between herbivores could be related to distinct digestive strategies. Reactivity and dissolvability of BSi increases after digestion, mainly due to degradation of organic matrices, resulting in higher silica turnover rates and mobilization potential from terrestrial to aquatic ecosystems in non-grazed versus grazed pasture systems (2 versus 20 kg Si ha−1 y−1). Our results suggest a crucial yet currently unexplored role of herbivores in determining silica export from land to ocean, where its availability is linked to eutrophication events and carbon sequestration through C–Si diatom interactions. PMID:24107532

  20. Increasing fish taxonomic and functional richness affects ecosystem properties of small headwater prairie streams

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Martin, Erika C.; Gido, Keith B.; Bello, Nora

    Stream fish can regulate their environment through direct and indirect pathways, and the relative influence of communities with different taxonomic and functional richness on ecosystem properties likely depends on habitat structure. Given this complexity, it is not surprising that observational studies of how stream fish communities influence ecosystems have shown mixed results. In this study, we evaluated the effect of an observed gradient of taxonomic (zero, one, two or three species) and functional (zero, one or two groups) richness of fishes on several key ecosystem properties in experimental stream mesocosms. Our study simulated small (less than two metres wide) headwatermore » prairie streams with a succession of three pool-riffle structures (upstream, middle and downstream) per mesocosm. Additionally, ecosystem responses included chlorophyll a from floating algal mats and benthic algae, benthic organic matter, macroinvertebrates (all as mass per unit area), algal filament length and stream metabolism (photosynthesis and respiration rate). Ecosystem responses were analysed individually using general linear mixed models. Significant treatment (taxonomic and functional richness) by habitat (pools and riffles) interactions were found for all but one ecosystem response variable. After accounting for location (upstream, middle and downstream) effects, the presence of one or two grazers resulted in shorter mean algal filament lengths in pools compared to no-fish controls. These observations suggest grazers can maintain short algal filaments in pools, which may inhibit long filaments from reaching the surface. Accordingly, floating algal mats decreased in mid- and downstream locations in grazer treatment relative to no-fish controls. At the scale of the entire reach, gross primary productivity and respiration were greater in treatments with two grazer species compared to mixed grazer/insectivore or control treatments. Lastly, the distribution of stream resources

  1. Increasing fish taxonomic and functional richness affects ecosystem properties of small headwater prairie streams

    DOE PAGES

    Martin, Erika C.; Gido, Keith B.; Bello, Nora; ...

    2016-04-06

    Stream fish can regulate their environment through direct and indirect pathways, and the relative influence of communities with different taxonomic and functional richness on ecosystem properties likely depends on habitat structure. Given this complexity, it is not surprising that observational studies of how stream fish communities influence ecosystems have shown mixed results. In this study, we evaluated the effect of an observed gradient of taxonomic (zero, one, two or three species) and functional (zero, one or two groups) richness of fishes on several key ecosystem properties in experimental stream mesocosms. Our study simulated small (less than two metres wide) headwatermore » prairie streams with a succession of three pool-riffle structures (upstream, middle and downstream) per mesocosm. Additionally, ecosystem responses included chlorophyll a from floating algal mats and benthic algae, benthic organic matter, macroinvertebrates (all as mass per unit area), algal filament length and stream metabolism (photosynthesis and respiration rate). Ecosystem responses were analysed individually using general linear mixed models. Significant treatment (taxonomic and functional richness) by habitat (pools and riffles) interactions were found for all but one ecosystem response variable. After accounting for location (upstream, middle and downstream) effects, the presence of one or two grazers resulted in shorter mean algal filament lengths in pools compared to no-fish controls. These observations suggest grazers can maintain short algal filaments in pools, which may inhibit long filaments from reaching the surface. Accordingly, floating algal mats decreased in mid- and downstream locations in grazer treatment relative to no-fish controls. At the scale of the entire reach, gross primary productivity and respiration were greater in treatments with two grazer species compared to mixed grazer/insectivore or control treatments. Lastly, the distribution of stream resources

  2. Transactivation Assays that Identify Indirect and Direct Activators of Human Pregnane X Receptor (PXR, NR1I2) and Constitutive Androstane Receptor (CAR, NR1I3).

    PubMed

    Pinne, Marija; Ponce, Elsa; Raucy, Judy L

    2017-01-01

    Nuclear Receptors (NRs), including PXR and CAR, are presumed to be ligand-dependent transcription factors, but ligand binding is not an absolute requirement for activation. Indeed, many compounds activate PXR and CAR by indirect mechanisms. Detecting these indirect activators of specific nuclear receptors in vitro has been difficult. As NR activation of either or both PXR and CAR can lead to drug-drug interactions and adverse drug effects, false negatives obtained with screening tools incapable of detecting indirect activators could present liabilities. The aim of this study was to establish assays that identify indirect activators of human PXR and CAR. Commercially available human PXR and CAR transactivation assays were used for analyses. We show that transactivation assays containing full-length nuclear receptors with native promoters can identify indirect activators of human CAR and PXRwhen compared to those of commercially available assays containing only the LBD of PXR and CAR. Of these two assay systems, only human PXR and CAR1 assays with full-length receptors and native promoters are capable of detecting indirect and ligand activators. With this capability, several kinase inhibitors were identified that activate PXR and CAR by indirect mechanisms. Furthermore by using both the LBD and full-length receptors, phenobarbital and midostaurin were found to be direct and indirect activators of PXR while human CAR activation by phenobarbital occurs by indirect mechanisms only. Cell based transactivation assays employing the full-length receptors and native promoters identify both direct and indirect activators of either or both human PXR and CAR. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Novel Active Learning Experiences for Students to Identify Barriers to Independent Living for People with Disabilities.

    PubMed

    McArthur, Polly; Burch, Lillian; Moore, Katherine; Hodges, Mary Sue

    2016-07-01

    This article describes interactive learning about independent living for people with disabilities and features the partnership of the College of Nursing and a Center for Independent Living (CIL). Using qualitative descriptive approach, students' written reflections were analyzed. Through "Xtreme Challenge," 82 undergraduate nursing students participated in aspects of independent living as well as identifying barriers. Students were engaged and learned to consider the person before the disability. Moreover, students valued the activity leaders' openness, which facilitated understanding the point of view of a person with disability. The value of partnership was evident as it allowed students to participate in active learning, which led to growth in the affective domain. Students became aware of potential education resources through the CIL. This article will guide educators in designing experiences that teach nursing care at the individual, family, and community level for people living with disabilities. © 2015 Association of Rehabilitation Nurses.

  4. Urban school leadership for elementary science instruction: Identifying and activating resources in an undervalued school subject

    NASA Astrophysics Data System (ADS)

    Spillane, James P.; Diamond, John B.; Walker, Lisa J.; Halverson, Rich; Jita, Loyiso

    2001-10-01

    This article explores school leadership for elementary school science teaching in an urban setting. We examine how school leaders bring resources together to enhance science instruction when there appear to be relatively few resources available for it. From our study of 13 Chicago elementary (K-8) schools' efforts to lead instructional change in mathematics, language arts, and science education, we show how resources for leading instruction are unequally distributed across subject areas. We also explore how over time leaders in one school successfully identified and activated resources for leading change in science education. The result has been a steady, although not always certain, development of science as an instructional area in the school. We argue that leading change in science education involves the identification and activation of material resources, the development of teachers' and school leaders' human capital, and the development and use of social capital.

  5. Identifying the Nonradical Mechanism in the Peroxymonosulfate Activation Process: Singlet Oxygenation Versus Mediated Electron Transfer.

    PubMed

    Yun, Eun-Tae; Lee, Jeong Hoon; Kim, Jaesung; Park, Hee-Deung; Lee, Jaesang

    2018-06-01

    Select persulfate activation processes were demonstrated to initiate oxidation not reliant on sulfate radicals, although the underlying mechanism has yet to be identified. This study explored singlet oxygenation and mediated electron transfer as plausible nonradical mechanisms for organic degradation by carbon nanotube (CNT)-activated peroxymonosulfate (PMS). The degradation of furfuryl alcohol (FFA) as a singlet oxygen ( 1 O 2 ) indicator and the kinetic retardation of FFA oxidation in the presence of l-histidine and azide as 1 O 2 quenchers apparently supported a role of 1 O 2 in the CNT/PMS system. However, the 1 O 2 scavenging effect was ascribed to a rapid PMS depletion by l-histidine and azide. A comparison of CNT/PMS and photoexcited Rose Bengal (RB) excluded the possibility of singlet oxygenation during heterogeneous persulfate activation. In contrast to the case of excited RB, solvent exchange (H 2 O to D 2 O) did not enhance FFA degradation by CNT/PMS and the pH- and substrate-dependent reactivity of CNT/PMS did not reflect the selective nature of 1 O 2 . Alternatively, concomitant PMS reduction and trichlorophenol oxidation were achieved when PMS and trichlorophenol were physically separated in two chambers using a conductive vertically aligned CNT membrane. This result suggested that CNT-mediated electron transfer from organics to persulfate was primarily responsible for the nonradical degradative route.

  6. Outdoor cultures of Chlorella pyrenoidosa in the effluent of anaerobically digested activated sludge: The effects of pH and free ammonia.

    PubMed

    Tan, Xiao-Bo; Zhang, Ya-Lei; Yang, Li-Bin; Chu, Hua-Qiang; Guo, Jun

    2016-01-01

    A freshwater algae Chlorella pyrenoidosa was cultured outdoors using anaerobically digested activated sludge effluent. The effects of pH variations were evaluated. The coupled pH variations and free ammonia toxicity significantly affected the algal growth, lipids accumulation and contamination control during every season. The free ammonia toxicity at high pH levels actually inhibited the algal growth. Compared to an optimal algal growth at a pH of 5.7-6.5, biomass productivity at a high pH of 8.3-8.8 was reduced by 67.15±6.98%, 54.39±6.42% and 83.63±5.71% in the spring, fall and summer, respectively. When the pH rose above 9.1-9.6, algae were unable to grow in the wastewater. However, high pH levels reduced contamination (e.g., bacteria and microalgae grazers) and triggered lipids accumulation in algal cells. These findings suggest that pH control strategies are essential for this type of algal wastewater system, where ammonia is the dominant nitrogen source. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Why are adult women physically active? A systematic review of prospective cohort studies to identify intrapersonal, social environmental and physical environmental determinants.

    PubMed

    Prince, S A; Reed, J L; Martinello, N; Adamo, K B; Fodor, J G; Hiremath, S; Kristjansson, E A; Mullen, K A; Nerenberg, K A; Tulloch, H E; Reid, R D

    2016-10-01

    This study aims to systematically review available evidence from prospective cohort studies to identify intrapersonal, social environmental and physical environmental determinants of moderate-to-vigorous intensity physical activity (MVPA) among working-age women. Six databases were searched to identify all prospective cohort studies that reported on intrapersonal (e.g. self-efficacy and socioeconomic status [SES]), social (e.g. crime, area SES and social support) and/or physical (e.g. weather, work and recreation) environmental determinants of MVPA in working-age (mean 18-65 years) women. A qualitative synthesis including harvest plots was completed. CRD42014009750 RESULTS: Searching identified 17,387 potential articles; 97 were used in the analysis. The majority (n = 87 studies) reported on ≥1 intrapersonal determinant. Very few (n = 34) examined factors in the social or physical environments, and none looked at social policy. Positive and consistent influencers included higher self-efficacy (n = 18/23), self-rated health (n = 8/13) and intentions (n = 10/11) and perceived behavioural control (n = 5/7) to be physically active. Having children in the household was negatively related to MVPA (n = 9/15). Physical activity intervention studies should consider a woman's level of self-efficacy and perceived behavioural control to be physically active. Additional studies are needed on the impact of children in the household, having a spouse/partner and using group goal setting. More evidence is needed to evaluate the impact of environmental factors. © 2016 World Obesity.

  8. Reduction of herbivorous fish pressure can facilitate focal algal species forestation on artificial structures.

    PubMed

    Gianni, Fabrizio; Bartolini, Fabrizio; Airoldi, Laura; Mangialajo, Luisa

    2018-07-01

    Coastal areas have been transformed worldwide by urbanization, so that artificial structures are now widespread. Current coastal development locally depletes many native marine species, while offering limited possibilities for their expansion. Eco-engineering interventions intend to identify ways to facilitate the presence of focal species and their associated functions on artificial habitats. An important but overlooked factor controlling restoration operations is overgrazing by herbivores. The aim of this study was to quantify the effects of different potential feeders on Cystoseira amentacea, a native canopy-forming alga of the Mediterranean infralittoral fringe, and test whether manipulation of grazing pressure can facilitate the human-guided installation of this focal species on coastal structures. Results of laboratory tests and field experiments revealed that Sarpa salpa, the only strictly native herbivorous fish in the Western Mediterranean Sea, can be a very effective grazer of C. amentacea in artificial habitats, up to as far as the infralittoral fringe, which is generally considered less accessible to fishes. S. salpa can limit the success of forestation operations in artificial novel habitats, causing up to 90% of Cystoseira loss after a few days. Other grazers, such as limpets and crabs, had only a moderate impact. Future engineering operations,intended to perform forestation of canopy-forming algae on artificial structures, should consider relevant biotic factors, such as fish overgrazing, identifying cost-effective techniques to limit their impact, as is the usual practice in restoration programmes on land. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. A high throughput Cre–lox activated viral membrane fusion assay identifies pharmacological inhibitors of HIV entry

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Esposito, Anthony M.; Cheung, Pamela; Swartz, Talia H.

    Enveloped virus entry occurs when viral and cellular membranes fuse releasing particle contents into the target cell. Human immunodeficiency virus (HIV) entry occurs by cell-free virus or virus transferred between infected and uninfected cells through structures called virological synapses. We developed a high-throughput cell-based assay to identify small molecule inhibitors of cell-free or virological synapse-mediated entry. An HIV clone carrying Cre recombinase as a Gag-internal gene fusion releases active Cre into cells upon viral entry activating a recombinatorial gene switch changing dsRed to GFP-expression. A screen of a 1998 known-biological profile small molecule library identified pharmacological HIV entry inhibitors thatmore » block both cell-free and cell-to-cell infection. Many top hits were noted as HIV inhibitors in prior studies, but not previously recognized as entry antagonists. Modest therapeutic indices for simvastatin and nigericin were observed in confirmatory HIV infection assays. This robust assay is adaptable to study HIV and heterologous viral pseudotypes. - Highlights: • Cre recombinase viral fusion assay screens cell-free or cell–cell entry inhibitors. • This Gag-iCre based assay is specific for the entry step of HIV replication. • Screened a library of known pharmacologic compounds for HIV fusion antagonists. • Many top hits were previously noted as HIV inhibitors, but here are classified as entry antagonists. Many top hits were previously noted as HIV inhibitors, but not as entry antagonists. • The assay is compatible with pseudotyping with HIV and heterologous viruses.« less

  10. Identifying the interacting roles of stressors in driving the global loss of canopy-forming to mat-forming algae in marine ecosystems.

    PubMed

    Strain, Elisabeth M A; Thomson, Russell J; Micheli, Fiorenza; Mancuso, Francesco P; Airoldi, Laura

    2014-11-01

    Identifying the type and strength of interactions between local anthropogenic and other stressors can help to set achievable management targets for degraded marine ecosystems and support their resilience by identifying local actions. We undertook a meta-analysis, using data from 118 studies to test the hypothesis that ongoing global declines in the dominant habitat along temperate rocky coastlines, forests of canopy-forming algae and/or their replacement by mat-forming algae are driven by the nonadditive interactions between local anthropogenic stressors that can be addressed through management actions (fishing, heavy metal pollution, nutrient enrichment and high sediment loads) and other stressors (presence of competitors or grazers, removal of canopy algae, limiting or excessive light, low or high salinity, increasing temperature, high wave exposure and high UV or CO2 ), not as easily amenable to management actions. In general, the cumulative effects of local anthropogenic and other stressors had negative effects on the growth and survival of canopy-forming algae. Conversely, the growth or survival of mat-forming algae was either unaffected or significantly enhanced by the same pairs of stressors. Contrary to our predictions, the majority of interactions between stressors were additive. There were however synergistic interactions between nutrient enrichment and heavy metals, the presence of competitors, low light and increasing temperature, leading to amplified negative effects on canopy-forming algae. There were also synergistic interactions between nutrient enrichment and increasing CO2 and temperature leading to amplified positive effects on mat-forming algae. Our review of the current literature shows that management of nutrient levels, rather than fishing, heavy metal pollution or high sediment loads, would provide the greatest opportunity for preventing the shift from canopy to mat-forming algae, particularly in enclosed bays or estuaries because of the

  11. A Drug Combination Screen Identifies Drugs Active against Amoxicillin-Induced Round Bodies of In Vitro Borrelia burgdorferi Persisters from an FDA Drug Library

    PubMed Central

    Feng, Jie; Shi, Wanliang; Zhang, Shuo; Sullivan, David; Auwaerter, Paul G.; Zhang, Ying

    2016-01-01

    Although currently recommended antibiotics for Lyme disease such as doxycycline or amoxicillin cure the majority of the patients, about 10–20% of patients treated for Lyme disease may experience lingering symptoms including fatigue, pain, or joint and muscle aches. Under experimental stress conditions such as starvation or antibiotic exposure, Borrelia burgdorferi can develop round body forms, which are a type of persister bacteria that appear resistant in vitro to customary first-line antibiotics for Lyme disease. To identify more effective drugs with activity against the round body form of B. burgdorferi, we established a round body persister model induced by exposure to amoxicillin (50 μg/ml) and then screened the Food and Drug Administration drug library consisting of 1581 drug compounds and also 22 drug combinations using the SYBR Green I/propidium iodide viability assay. We identified 23 drug candidates that have higher activity against the round bodies of B. burgdorferi than either amoxicillin or doxycycline. Eleven individual drugs scored better than metronidazole and tinidazole which have been previously described to be active against round bodies. In this amoxicillin-induced round body model, some drug candidates such as daptomycin and clofazimine also displayed enhanced activity which was similar to a previous screen against stationary phase B. burgdorferi persisters not exposure to amoxicillin. Additional candidate drugs active against round bodies identified include artemisinin, ciprofloxacin, nifuroxime, fosfomycin, chlortetracycline, sulfacetamide, sulfamethoxypyridazine and sulfathiozole. Two triple drug combinations had the highest activity against amoxicillin-induced round bodies and stationary phase B. burgdorferi persisters: artemisinin/cefoperazone/doxycycline and sulfachlorpyridazine/daptomycin/doxycycline. These findings confirm and extend previous findings that certain drug combinations have superior activity against B. burgdorferi

  12. A Drug Combination Screen Identifies Drugs Active against Amoxicillin-Induced Round Bodies of In Vitro Borrelia burgdorferi Persisters from an FDA Drug Library.

    PubMed

    Feng, Jie; Shi, Wanliang; Zhang, Shuo; Sullivan, David; Auwaerter, Paul G; Zhang, Ying

    2016-01-01

    Although currently recommended antibiotics for Lyme disease such as doxycycline or amoxicillin cure the majority of the patients, about 10-20% of patients treated for Lyme disease may experience lingering symptoms including fatigue, pain, or joint and muscle aches. Under experimental stress conditions such as starvation or antibiotic exposure, Borrelia burgdorferi can develop round body forms, which are a type of persister bacteria that appear resistant in vitro to customary first-line antibiotics for Lyme disease. To identify more effective drugs with activity against the round body form of B. burgdorferi, we established a round body persister model induced by exposure to amoxicillin (50 μg/ml) and then screened the Food and Drug Administration drug library consisting of 1581 drug compounds and also 22 drug combinations using the SYBR Green I/propidium iodide viability assay. We identified 23 drug candidates that have higher activity against the round bodies of B. burgdorferi than either amoxicillin or doxycycline. Eleven individual drugs scored better than metronidazole and tinidazole which have been previously described to be active against round bodies. In this amoxicillin-induced round body model, some drug candidates such as daptomycin and clofazimine also displayed enhanced activity which was similar to a previous screen against stationary phase B. burgdorferi persisters not exposure to amoxicillin. Additional candidate drugs active against round bodies identified include artemisinin, ciprofloxacin, nifuroxime, fosfomycin, chlortetracycline, sulfacetamide, sulfamethoxypyridazine and sulfathiozole. Two triple drug combinations had the highest activity against amoxicillin-induced round bodies and stationary phase B. burgdorferi persisters: artemisinin/cefoperazone/doxycycline and sulfachlorpyridazine/daptomycin/doxycycline. These findings confirm and extend previous findings that certain drug combinations have superior activity against B. burgdorferi

  13. A 12,000 year record of changes in herbivore niche separation and palaeoclimate (Wonderwerk Cave, South Africa)

    NASA Astrophysics Data System (ADS)

    Ecker, Michaela; Brink, James; Horwitz, Liora Kolska; Scott, Louis; Lee-Thorp, Julia A.

    2018-01-01

    The large mammalian fauna of southern Africa is characterised by strong niche separation into grazer and browser species, with few falling into the intermediate mixed-feeder niche. Moreover, the modern fauna is reduced in species diversity compared to the Pleistocene, following the extinction of several specialized grazers in the late Pleistocene and early Holocene. How did this state develop, and how might it be connected to climatic change during the Holocene? To better understand this development, we obtained extensive carbon and oxygen stable light isotope data from herbivore tooth enamel samples from Wonderwerk Cave, South Africa, spanning about 12,000-500 cal. BP. This is a unique dataset since it is the only site in the southern Kalahari with a robust chronometric record and well-preserved faunal remains for the last 12,000 years without significant gaps. Combining the stable isotopes with pollen and micromammal data from Wonderwerk Cave, we have explored shifts in the proportions of C3 and C4 plants and moisture availability. Although climate remained generally semi-arid for much of this period, the results show significant hydrological and vegetation shifts in the sequence, particularly with the strengthening of summer rainfall in the mid-Holocene. The results for the sixteen herbivore species reveal a reinforcement of the grazer-browser niche partitioning through the Holocene and shows how niche specialization follows changes in local vegetation composition. In the light of this reconstruction of the local ecology we discuss grazer extinctions, human adaptations, and the drivers behind climatic changes in the summer rainfall zone of southern Africa.

  14. PSP toxin levels and plankton community composition and abundance in size-fractionated vertical profiles during spring/summer blooms of the toxic dinoflagellate Alexandrium fundyense in the Gulf of Maine and on Georges Bank, 2007, 2008, and 2010: 2. Plankton community composition and abundance.

    PubMed

    Petitpas, Christian M; Turner, Jefferson T; Deeds, Jonathan R; Keafer, Bruce A; McGillicuddy, Dennis J; Milligan, Peter J; Shue, Vangie; White, Kevin D; Anderson, Donald M

    2014-05-01

    As part of the Gulf of Maine Toxicity (GOMTOX) project, we determined Alexandrium fundyense abundance, paralytic shellfish poisoning (PSP) toxin levels in various plankton size fractions, and the community composition of potential grazers of A. fundyense in plankton size fractions during blooms of this toxic dinoflagellate in the coastal Gulf of Maine and on Georges Bank in spring and summer of 2007, 2008, and 2010. PSP toxins and A. fundyense cells were found throughout the sampled water column (down to 50 m) in the 20-64 μm size fractions. While PSP toxins were widespread throughout all size classes of the zooplankton grazing community, the majority of the toxin was measured in the 20-64 μm size fraction. A. fundyense cellular toxin content estimated from field samples was significantly higher in the coastal Gulf of Maine than on Georges Bank. Most samples containing PSP toxins in the present study had diverse assemblages of grazers. However, some samples clearly suggested PSP toxin accumulation in several different grazer taxa including tintinnids, heterotrophic dinoflagellates of the genus Protoperidinium , barnacle nauplii, the harpacticoid copepod Microsetella norvegica , the calanoid copepods Calanus finmarchicus and Pseudocalanus spp., the marine cladoceran Evadne nordmanni , and hydroids of the genus Clytia . Thus, a diverse assemblage of zooplankton grazers accumulated PSP toxins through food-web interactions. This raises the question of whether PSP toxins pose a potential human health risk not only from nearshore bivalve shellfish, but also potentially from fish and other upper-level consumers in zooplankton-based pelagic food webs.

  15. Identifying bilingual semantic neural representations across languages

    PubMed Central

    Buchweitz, Augusto; Shinkareva, Svetlana V.; Mason, Robert A.; Mitchell, Tom M.; Just, Marcel Adam

    2015-01-01

    The goal of the study was to identify the neural representation of a noun's meaning in one language based on the neural representation of that same noun in another language. Machine learning methods were used to train classifiers to identify which individual noun bilingual participants were thinking about in one language based solely on their brain activation in the other language. The study shows reliable (p < .05) pattern-based classification accuracies for the classification of brain activity for nouns across languages. It also shows that the stable voxels used to classify the brain activation were located in areas associated with encoding information about semantic dimensions of the words in the study. The identification of the semantic trace of individual nouns from the pattern of cortical activity demonstrates the existence of a multi-voxel pattern of activation across the cortex for a single noun common to both languages in bilinguals. PMID:21978845

  16. Natural bounds on herbivorous coral reef fishes

    PubMed Central

    Hoey, Andrew S.; Williams, Gareth J.; Williams, Ivor D.

    2016-01-01

    Humans are an increasingly dominant driver of Earth's biological communities, but differentiating human impacts from natural drivers of ecosystem state is crucial. Herbivorous fish play a key role in maintaining coral dominance on coral reefs, and are widely affected by human activities, principally fishing. We assess the relative importance of human and biophysical (habitat and oceanographic) drivers on the biomass of five herbivorous functional groups among 33 islands in the central and western Pacific Ocean. Human impacts were clear for some, but not all, herbivore groups. Biomass of browsers, large excavators, and of all herbivores combined declined rapidly with increasing human population density, whereas grazers, scrapers, and detritivores displayed no relationship. Sea-surface temperature had significant but opposing effects on the biomass of detritivores (positive) and browsers (negative). Similarly, the biomass of scrapers, grazers, and detritivores correlated with habitat structural complexity; however, relationships were group specific. Finally, the biomass of browsers and large excavators was related to island geomorphology, both peaking on low-lying islands and atolls. The substantial variability in herbivore populations explained by natural biophysical drivers highlights the need for locally appropriate management targets on coral reefs. PMID:27881745

  17. Natural bounds on herbivorous coral reef fishes.

    PubMed

    Heenan, Adel; Hoey, Andrew S; Williams, Gareth J; Williams, Ivor D

    2016-11-30

    Humans are an increasingly dominant driver of Earth's biological communities, but differentiating human impacts from natural drivers of ecosystem state is crucial. Herbivorous fish play a key role in maintaining coral dominance on coral reefs, and are widely affected by human activities, principally fishing. We assess the relative importance of human and biophysical (habitat and oceanographic) drivers on the biomass of five herbivorous functional groups among 33 islands in the central and western Pacific Ocean. Human impacts were clear for some, but not all, herbivore groups. Biomass of browsers, large excavators, and of all herbivores combined declined rapidly with increasing human population density, whereas grazers, scrapers, and detritivores displayed no relationship. Sea-surface temperature had significant but opposing effects on the biomass of detritivores (positive) and browsers (negative). Similarly, the biomass of scrapers, grazers, and detritivores correlated with habitat structural complexity; however, relationships were group specific. Finally, the biomass of browsers and large excavators was related to island geomorphology, both peaking on low-lying islands and atolls. The substantial variability in herbivore populations explained by natural biophysical drivers highlights the need for locally appropriate management targets on coral reefs. © 2016 The Authors.

  18. Functional Semi-Blind Source Separation Identifies Primary Motor Area Without Active Motor Execution.

    PubMed

    Porcaro, Camillo; Cottone, Carlo; Cancelli, Andrea; Salustri, Carlo; Tecchio, Franca

    2018-04-01

    High time resolution techniques are crucial for investigating the brain in action. Here, we propose a method to identify a section of the upper-limb motor area representation (FS_M1) by means of electroencephalographic (EEG) signals recorded during a completely passive condition (FS_M1bySS). We delivered a galvanic stimulation to the median nerve and we applied to EEG the semi-Blind Source Separation (s-BSS) algorithm named Functional Source Separation (FSS). In order to prove that FS_M1bySS is part of FS_M1, we also collected EEG in a motor condition, i.e. during a voluntary movement task (isometric handgrip) and in a rest condition, i.e. at rest with eyes open and closed. In motor condition, we show that the cortico-muscular coherence (CMC) of FS_M1bySS does not differ from FS_ M1 CMC (0.04 for both sources). Moreover, we show that the FS_M1bySS's ongoing whole band activity during Motor and both rest conditions displays high mutual information and time correlation with FS_M1 (above 0.900 and 0.800, respectively) whereas much smaller ones with the primary somatosensory cortex [Formula: see text] (about 0.300 and 0.500, [Formula: see text]). FS_M1bySS as a marker of the upper-limb FS_M1 representation obtainable without the execution of an active motor task is a great achievement of the FSS algorithm, relevant in most experimental, neurological and psychiatric protocols.

  19. Heterogeneous activation of the TGFβ pathway in glioblastomas identified by gene expression-based classification using TGFβ-responsive genes

    PubMed Central

    Xu, Xie L; Kapoun, Ann M

    2009-01-01

    Background TGFβ has emerged as an attractive target for the therapeutic intervention of glioblastomas. Aberrant TGFβ overproduction in glioblastoma and other high-grade gliomas has been reported, however, to date, none of these reports has systematically examined the components of TGFβ signaling to gain a comprehensive view of TGFβ activation in large cohorts of human glioma patients. Methods TGFβ activation in mammalian cells leads to a transcriptional program that typically affects 5–10% of the genes in the genome. To systematically examine the status of TGFβ activation in high-grade glial tumors, we compiled a gene set of transcriptional response to TGFβ stimulation from tissue culture and in vivo animal studies. These genes were used to examine the status of TGFβ activation in high-grade gliomas including a large cohort of glioblastomas. Unsupervised and supervised classification analysis was performed in two independent, publicly available glioma microarray datasets. Results Unsupervised and supervised classification using the TGFβ-responsive gene list in two independent glial tumor gene expression data sets revealed various levels of TGFβ activation in these tumors. Among glioblastomas, one of the most devastating human cancers, two subgroups were identified that showed distinct TGFβ activation patterns as measured from transcriptional responses. Approximately 62% of glioblastoma samples analyzed showed strong TGFβ activation, while the rest showed a weak TGFβ transcriptional response. Conclusion Our findings suggest heterogeneous TGFβ activation in glioblastomas, which may cause potential differences in responses to anti-TGFβ therapies in these two distinct subgroups of glioblastomas patients. PMID:19192267

  20. Polycyclic aromatic hydrocarbons alter the structure of oceanic and oligotrophic microbial food webs.

    PubMed

    Cerezo, Maria Isabel; Agusti, Susana

    2015-12-30

    One way organic pollutants reach remote oceanic regions is by atmospheric transport. During the Malaspina-2010 expedition, across the Atlantic, Indian, and Pacific Oceans, we analyzed the polycyclic aromatic hydrocarbon (PAH) effects on oceanic microbial food webs. We performed perturbation experiments adding PAHs to classic dilution experiments. The phytoplankton growth rates were reduced by more than 5 times, being Prochlorococcus spp. the most affected. 62% of the experiments showed a reduction in the grazing rates due to the presence of PAHs. For the remaining experiments, grazing usually increased likely due to cascading effects. We identified changes in the slope of the relation between the growth rate and the dilution fraction induced by the pollutants, moving from no grazing to V-shape, or to negative slope, indicative of grazing increase by cascade effects and alterations of the grazers' activity structure. Our perturbation experiments indicate that PAHs could influence the structure oceanic food-webs structure. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Atomic-scale distortion of optically activated Sm dopants identified with site-selective X-ray absorption spectroscopy

    NASA Astrophysics Data System (ADS)

    Ishii, Masashi; Crowe, Iain F.; Halsall, Matthew P.; Hamilton, Bruce; Hu, Yongfeng; Sham, Tsun-Kong; Harako, Susumu; Zhao, Xin-Wei; Komuro, Shuji

    2013-10-01

    The local structure of luminescent Sm dopants was investigated using an X-ray absorption fine-structure technique with X-ray-excited optical luminescence. Because this technique evaluates X-ray absorption from luminescence, only optically active sites are analyzed. The Sm L3 near-edge spectrum contains split 5d states and a shake-up transition that are specific to luminescent Sm. Theoretical calculations using cluster models identified an atomic-scale distortion that can reproduce the split 5d states. The model with C4v local symmetry and compressive bond length of Sm-O of a six-fold oxygen (SmO6) cluster is most consistent with the experimental results.

  2. Mechanomyogram for identifying muscle activity and fatigue.

    PubMed

    Yang, Zhao Feng; Kumar, Dinesh Kant; Arjunan, Sridhar Poosapadi

    2009-01-01

    Mechanomyogram is the recording of the acoustic activity associated with the muscle contraction. While discovered nearly a decade ago with the intention of providing an alternate to the surface electromyogram, it has not yet been investigated thoroughly and there are no current applications associated with MMG. This paper reports an experimental study of MMG against force of contraction and muscle fatigue during cyclic contraction. The results indicate that there is a relationship between the intensity of the MMG recording and force of contraction. A change in the intensity of MMG is also observed with the onset of muscle fatigue. However, the inter-subject variation is very large. The results also indicate that the spectrum of the MMG is very inconsistent and not a useful feature of the signal.

  3. Involvement in Extracurricular Activities: Identifying Differences in Perceptions of School Climate

    ERIC Educational Resources Information Center

    Martinez, Andrew; Coker, Crystal; McMahon, Susan D.; Cohen, Jonathan; Thapa, Amrit

    2016-01-01

    Many youth participate in extracurricular activities, and research has linked activity participation with school engagement and academic success. Social-ecological theory suggests that the social contexts of different types of extracurricular activities may differentially affect student outcomes. Yet, there is scant research examining the relation…

  4. Lack of in vitro constitutive activity for four previously reported TSH receptor mutations identified in patients with nonautoimmune hyperthyroidism and hot thyroid carcinomas.

    PubMed

    Jaeschke, Holger; Mueller, Sandra; Eszlinger, Markus; Paschke, Ralf

    2010-12-01

    Constitutively activating mutations (CAMs) of the TSHR are the major cause for nonautoimmune hyperthyroidism. Re-examination of constitutive activity previously determined in CHO cell lines recently demonstrated the caveats for the in vitro determination of constitutive TSHR activity, which leads to false positive conclusions regarding the molecular origin of hyperthyroidism or hot thyroid carcinomas. Mutations L677V and T620I identified in hot thyroid carcinomas were previously characterized in CHO and in 3T3-Vill cell lines, respectively, stably expressing the mutant without determination of TSHR expression. F666L identified in a patient with hot thyroid nodules, I691F in a family with nonautoimmune hyperthyroidism and F631I identified in a hot thyroid carcinoma were not characterized for their in vitro function. Therefore, we decided to (re)evaluate the in vitro function of these five TSHR variants by determination of cell surface expression, and intracellular cAMP and inositol phosphate levels and performed additionally linear regression analyses to determine basal activity independently from the mutant's cell surface expression in COS-7 and HEK(GT) cells. Only one (F631I) of the five investigated TSHR variants displayed constitutive activity for G(α) s signalling and showed correlation with the clinical phenotype. The previous false classification of T620I and L677V as CAMs is most likely related to the fact that both mutations were characterized in cell lines stably expressing the mutated receptor construct without assessing the respective receptor number per cell. Other molecular aetiologies for the nonautoimmune hyperthyroidism and/or hot thyroid carcinomas in these three patients and one family should be elucidated. © 2010 Blackwell Publishing Ltd.

  5. Validity of consumer-grade activity monitor to identify manual wheelchair propulsion in standardized activities of daily living.

    PubMed

    Leving, Marika T; Horemans, Henricus L D; Vegter, Riemer J K; de Groot, Sonja; Bussmann, Johannes B J; van der Woude, Lucas H V

    2018-01-01

    Hypoactive lifestyle contributes to the development of secondary complications and lower quality of life in wheelchair users. There is a need for objective and user-friendly physical activity monitors for wheelchair-dependent individuals in order to increase physical activity through self-monitoring, goal setting, and feedback provision. To determine the validity of Activ8 Activity Monitors to 1) distinguish two classes of activities: independent wheelchair propulsion from other non-propulsive wheelchair-related activities 2) distinguish five wheelchair-related classes of activities differing by the movement intensity level: sitting in a wheelchair (hands may be moving but wheelchair remains stationary), maneuvering, and normal, high speed or assisted wheelchair propulsion. Sixteen able-bodied individuals performed sixteen various standardized 60s-activities of daily living. Each participant was equipped with a set of two Activ8 Professional Activity Monitors, one at the right forearm and one at the right wheel. Task classification by the Active8 Monitors was validated using video recordings. For the overall agreement, sensitivity and positive predictive value, outcomes above 90% are considered excellent, between 70 and 90% good, and below 70% unsatisfactory. Division in two classes resulted in overall agreement of 82.1%, sensitivity of 77.7% and positive predictive value of 78.2%. 84.5% of total duration of all tasks was classified identically by Activ8 and based on the video material. Division in five classes resulted in overall agreement of 56.6%, sensitivity of 52.8% and positive predictive value of 51.9%. 59.8% of total duration of all tasks was classified identically by Activ8 and based on the video material. Activ8 system proved to be suitable for distinguishing between active wheelchair propulsion and other non-propulsive wheelchair-related activities. The ability of the current system and algorithms to distinguish five various wheelchair-related activities

  6. Validity of consumer-grade activity monitor to identify manual wheelchair propulsion in standardized activities of daily living

    PubMed Central

    Horemans, Henricus L. D.; Vegter, Riemer J. K.; de Groot, Sonja; Bussmann, Johannes B. J.; van der Woude, Lucas H. V.

    2018-01-01

    Background Hypoactive lifestyle contributes to the development of secondary complications and lower quality of life in wheelchair users. There is a need for objective and user-friendly physical activity monitors for wheelchair-dependent individuals in order to increase physical activity through self-monitoring, goal setting, and feedback provision. Objective To determine the validity of Activ8 Activity Monitors to 1) distinguish two classes of activities: independent wheelchair propulsion from other non-propulsive wheelchair-related activities 2) distinguish five wheelchair-related classes of activities differing by the movement intensity level: sitting in a wheelchair (hands may be moving but wheelchair remains stationary), maneuvering, and normal, high speed or assisted wheelchair propulsion. Methods Sixteen able-bodied individuals performed sixteen various standardized 60s-activities of daily living. Each participant was equipped with a set of two Activ8 Professional Activity Monitors, one at the right forearm and one at the right wheel. Task classification by the Active8 Monitors was validated using video recordings. For the overall agreement, sensitivity and positive predictive value, outcomes above 90% are considered excellent, between 70 and 90% good, and below 70% unsatisfactory. Results Division in two classes resulted in overall agreement of 82.1%, sensitivity of 77.7% and positive predictive value of 78.2%. 84.5% of total duration of all tasks was classified identically by Activ8 and based on the video material. Division in five classes resulted in overall agreement of 56.6%, sensitivity of 52.8% and positive predictive value of 51.9%. 59.8% of total duration of all tasks was classified identically by Activ8 and based on the video material. Conclusions Activ8 system proved to be suitable for distinguishing between active wheelchair propulsion and other non-propulsive wheelchair-related activities. The ability of the current system and algorithms to

  7. Identifying activating mutations in the EGFR gene: prognostic and therapeutic implications in non-small cell lung cancer *

    PubMed Central

    Lopes, Gabriel Lima; Vattimo, Edoardo Filippo de Queiroz; de Castro, Gilberto

    2015-01-01

    Abstract Lung cancer is the leading cause of cancer-related deaths worldwide. Promising new therapies have recently emerged from the development of molecular targeted drugs; particularly promising are those blocking the signal transduction machinery of cancer cells. One of the most widely studied cell signaling pathways is that of EGFR, which leads to uncontrolled cell proliferation, increased cell angiogenesis, and greater cell invasiveness. Activating mutations in the EGFR gene (deletions in exon 19 and mutation L858R in exon 21), first described in 2004, have been detected in approximately 10% of all non-squamous non-small cell lung cancer (NSCLC) patients in Western countries and are the most important predictors of a response to EGFR tyrosine-kinase inhibitors (EGFR-TKIs). Studies of the EGFR-TKIs gefitinib, erlotinib, and afatinib, in comparison with platinum-based regimens, as first-line treatments in chemotherapy-naïve patients have shown that the EGFR-TKIs produce gains in progression-free survival and overall response rates, although only in patients whose tumors harbor activating mutations in the EGFR gene. Clinical trials have also shown EGFR-TKIs to be effective as second- and third-line therapies in advanced NSCLC. Here, we review the main aspects of EGFR pathway activation in NSCLC, underscore the importance of correctly identifying activating mutations in the EGFR gene, and discuss the main outcomes of EGFR-TKI treatment in NSCLC. PMID:26398757

  8. Identifying activating mutations in the EGFR gene: prognostic and therapeutic implications in non-small cell lung cancer.

    PubMed

    Lopes, Gabriel Lima; Vattimo, Edoardo Filippo de Queiroz; Castro Junior, Gilberto de

    2015-01-01

    Lung cancer is the leading cause of cancer-related deaths worldwide. Promising new therapies have recently emerged from the development of molecular targeted drugs; particularly promising are those blocking the signal transduction machinery of cancer cells. One of the most widely studied cell signaling pathways is that of EGFR, which leads to uncontrolled cell proliferation, increased cell angiogenesis, and greater cell invasiveness. Activating mutations in the EGFR gene (deletions in exon 19 and mutation L858R in exon 21), first described in 2004, have been detected in approximately 10% of all non-squamous non-small cell lung cancer (NSCLC) patients in Western countries and are the most important predictors of a response to EGFR tyrosine-kinase inhibitors (EGFR-TKIs). Studies of the EGFR-TKIs gefitinib, erlotinib, and afatinib, in comparison with platinum-based regimens, as first-line treatments in chemotherapy-naïve patients have shown that the EGFR-TKIs produce gains in progression-free survival and overall response rates, although only in patients whose tumors harbor activating mutations in the EGFR gene. Clinical trials have also shown EGFR-TKIs to be effective as second- and third-line therapies in advanced NSCLC. Here, we review the main aspects of EGFR pathway activation in NSCLC, underscore the importance of correctly identifying activating mutations in the EGFR gene, and discuss the main outcomes of EGFR-TKI treatment in NSCLC.

  9. Antioxidant Peptides Identified from Ovotransferrin by the ORAC Method Did Not Show Anti-Inflammatory and Antioxidant Activities in Endothelial Cells.

    PubMed

    Jahandideh, Forough; Chakrabarti, Subhadeep; Davidge, Sandra T; Wu, Jianping

    2016-01-13

    Oxygen radical absorbance capacity (ORAC) is a widely used method of measuring antioxidant capacities of various antioxidant components. Surprisingly, 16 antioxidant peptides previously identified from egg protein ovotransferrin using the ORAC method did not show any anti-inflammatory and antioxidant activities in cells. After simulated gastro-intestinal digestion (GID), several peptide digests significantly reduced the expression of tumor necrosis factor-α (TNF-α)-induced pro-inflammatory intercellular cell adhesion molecule-1 (ICAM-1) by 65.7 ± 10.4% and vascular cell adhesion molecule-1 (VCAM-1) by 53.5 ± 9.6% to 61.0 ± 14.5%, but only GWNI reduced TNF-α-activated superoxide generation by 71.0 ± 12.9% when tested with dihydroethidium (DHE) assay. Mass spectrometer analysis identified two new peptides, GWN and GW, in the GWNI digest; however, only GW reduced TNF-α-induced VCAM-1 expression (64.3 ± 20.6%) significantly compared to the TNF-α treated cells. Our study suggested that ORAC lacked biological relevance in assessing bioactive peptides.

  10. Identifying typical physical activity on smartphone with varying positions and orientations.

    PubMed

    Miao, Fen; He, Yi; Liu, Jinlei; Li, Ye; Ayoola, Idowu

    2015-04-13

    Traditional activity recognition solutions are not widely applicable due to a high cost and inconvenience to use with numerous sensors. This paper aims to automatically recognize physical activity with the help of the built-in sensors of the widespread smartphone without any limitation of firm attachment to the human body. By introducing a method to judge whether the phone is in a pocket, we investigated the data collected from six positions of seven subjects, chose five signals that are insensitive to orientation for activity classification. Decision trees (J48), Naive Bayes and Sequential minimal optimization (SMO) were employed to recognize five activities: static, walking, running, walking upstairs and walking downstairs. The experimental results based on 8,097 activity data demonstrated that the J48 classifier produced the best performance with an average recognition accuracy of 89.6% during the three classifiers, and thus would serve as the optimal online classifier. The utilization of the built-in sensors of the smartphone to recognize typical physical activities without any limitation of firm attachment is feasible.

  11. In Silico Repositioning-Chemogenomics Strategy Identifies New Drugs with Potential Activity against Multiple Life Stages of Schistosoma mansoni

    PubMed Central

    Neves, Bruno J.; Braga, Rodolpho C.; Bezerra, José C. B.; Cravo, Pedro V. L.; Andrade, Carolina H.

    2015-01-01

    Morbidity and mortality caused by schistosomiasis are serious public health problems in developing countries. Because praziquantel is the only drug in therapeutic use, the risk of drug resistance is a concern. In the search for new schistosomicidal drugs, we performed a target-based chemogenomics screen of a dataset of 2,114 proteins to identify drugs that are approved for clinical use in humans that may be active against multiple life stages of Schistosoma mansoni. Each of these proteins was treated as a potential drug target, and its amino acid sequence was used to interrogate three databases: Therapeutic Target Database (TTD), DrugBank and STITCH. Predicted drug-target interactions were refined using a combination of approaches, including pairwise alignment, conservation state of functional regions and chemical space analysis. To validate our strategy, several drugs previously shown to be active against Schistosoma species were correctly predicted, such as clonazepam, auranofin, nifedipine, and artesunate. We were also able to identify 115 drugs that have not yet been experimentally tested against schistosomes and that require further assessment. Some examples are aprindine, gentamicin, clotrimazole, tetrabenazine, griseofulvin, and cinnarizine. In conclusion, we have developed a systematic and focused computer-aided approach to propose approved drugs that may warrant testing and/or serve as lead compounds for the design of new drugs against schistosomes. PMID:25569258

  12. A hybrid spectral representation of phytoplankton growth and zooplankton response: The ''control rod'' model of plankton interaction

    NASA Astrophysics Data System (ADS)

    Armstrong, Robert A.

    2003-11-01

    Phytoplankton species interact through competition for light and nutrients; they also interact through grazers they hold in common. Both interactions are expected to be size-dependent: smaller phytoplankton species will be at an advantage when nutrients are scarce due to surface/volume considerations, while species that are similar in size are more likely to be consumed by grazers held in common than are species that differ greatly in size. While phytoplankton competition for nutrients and light has been extensively characterized, size-based interaction through shared grazers has not been represented systematically. The latter situation is particularly unfortunate because small changes in community structure can give rise to large changes in ecosystem dynamics and, in inverse modeling, to large changes in estimated parameter values. A simple, systematic way to represent phytoplankton interaction through shared grazers, one resistant to unintended idiosyncrasy of model construction yet capable of representing scientifically justifiable idiosyncrasy, would aid greatly in the modeling process. Here I develop a model structure that allows systematic representation of plankton interaction. In this model, the zooplankton community is represented as a continuous size spectrum, while phytoplankton species can be represented individually. The mechanistic basis of the model is a shift in the zooplankton community from carnivory to omnivory to herbivory as phytoplankton density increases. I discuss two limiting approximations in some detail, and fit both to data from the IronEx II experiment. The first limiting case represents a community with no grazer-based interaction among phytoplankton species; this approximation illuminates the general structure of the model. In particular, the zooplankton spectrum can be viewed as the analog of a control rod in a nuclear reactor, which prevents (or fails to prevent) an exponential bloom of phytoplankton. A second, more complex limiting

  13. The nematode Caenorhabditis elegans as a tool to predict chemical activity on mammalian development and identify mechanisms influencing toxicological outcome.

    PubMed

    Harlow, Philippa H; Perry, Simon J; Widdison, Stephanie; Daniels, Shannon; Bondo, Eddie; Lamberth, Clemens; Currie, Richard A; Flemming, Anthony J

    2016-03-18

    To determine whether a C. elegans bioassay could predict mammalian developmental activity, we selected diverse compounds known and known not to elicit such activity and measured their effect on C. elegans egg viability. 89% of compounds that reduced C. elegans egg viability also had mammalian developmental activity. Conversely only 25% of compounds found not to reduce egg viability in C. elegans were also inactive in mammals. We conclude that the C. elegans egg viability assay is an accurate positive predictor, but an inaccurate negative predictor, of mammalian developmental activity. We then evaluated C. elegans as a tool to identify mechanisms affecting toxicological outcomes among related compounds. The difference in developmental activity of structurally related fungicides in C. elegans correlated with their rate of metabolism. Knockdown of the cytochrome P450s cyp-35A3 and cyp-35A4 increased the toxicity to C. elegans of the least developmentally active compounds to the level of the most developmentally active. This indicated that these P450s were involved in the greater rate of metabolism of the less toxic of these compounds. We conclude that C. elegans based approaches can predict mammalian developmental activity and can yield plausible hypotheses for factors affecting the biological potency of compounds in mammals.

  14. An open simulation approach to identify chances and limitations for vulnerable road user (VRU) active safety.

    PubMed

    Seiniger, Patrick; Bartels, Oliver; Pastor, Claus; Wisch, Marcus

    2013-01-01

    It is commonly agreed that active safety will have a significant impact on reducing accident figures for pedestrians and probably also bicyclists. However, chances and limitations for active safety systems have only been derived based on accident data and the current state of the art, based on proprietary simulation models. The objective of this article is to investigate these chances and limitations by developing an open simulation model. This article introduces a simulation model, incorporating accident kinematics, driving dynamics, driver reaction times, pedestrian dynamics, performance parameters of different autonomous emergency braking (AEB) generations, as well as legal and logical limitations. The level of detail for available pedestrian accident data is limited. Relevant variables, especially timing of the pedestrian appearance and the pedestrian's moving speed, are estimated using assumptions. The model in this article uses the fact that a pedestrian and a vehicle in an accident must have been in the same spot at the same time and defines the impact position as a relevant accident parameter, which is usually available from accident data. The calculations done within the model identify the possible timing available for braking by an AEB system as well as the possible speed reduction for different accident scenarios as well as for different system configurations. The simulation model identifies the lateral impact position of the pedestrian as a significant parameter for system performance, and the system layout is designed to brake when the accident becomes unavoidable by the vehicle driver. Scenarios with a pedestrian running from behind an obstruction are the most demanding scenarios and will very likely never be avoidable for all vehicle speeds due to physical limits. Scenarios with an unobstructed person walking will very likely be treatable for a wide speed range for next generation AEB systems.

  15. Mechanism-based screen for G1/S checkpoint activators identifies a selective activator of EIF2AK3/PERK signalling.

    PubMed

    Stockwell, Simon R; Platt, Georgina; Barrie, S Elaine; Zoumpoulidou, Georgia; Te Poele, Robert H; Aherne, G Wynne; Wilson, Stuart C; Sheldrake, Peter; McDonald, Edward; Venet, Mathilde; Soudy, Christelle; Elustondo, Frédéric; Rigoreau, Laurent; Blagg, Julian; Workman, Paul; Garrett, Michelle D; Mittnacht, Sibylle

    2012-01-01

    Human cancers often contain genetic alterations that disable G1/S checkpoint control and loss of this checkpoint is thought to critically contribute to cancer generation by permitting inappropriate proliferation and distorting fate-driven cell cycle exit. The identification of cell permeable small molecules that activate the G1/S checkpoint may therefore represent a broadly applicable and clinically effective strategy for the treatment of cancer. Here we describe the identification of several novel small molecules that trigger G1/S checkpoint activation and characterise the mechanism of action for one, CCT020312, in detail. Transcriptional profiling by cDNA microarray combined with reverse genetics revealed phosphorylation of the eukaryotic initiation factor 2-alpha (EIF2A) through the eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3/PERK) as the mechanism of action of this compound. While EIF2AK3/PERK activation classically follows endoplasmic reticulum (ER) stress signalling that sets off a range of different cellular responses, CCT020312 does not trigger these other cellular responses but instead selectively elicits EIF2AK3/PERK signalling. Phosphorylation of EIF2A by EIF2A kinases is a known means to block protein translation and hence restriction point transit in G1, but further supports apoptosis in specific contexts. Significantly, EIF2AK3/PERK signalling has previously been linked to the resistance of cancer cells to multiple anticancer chemotherapeutic agents, including drugs that target the ubiquitin/proteasome pathway and taxanes. Consistent with such findings CCT020312 sensitizes cancer cells with defective taxane-induced EIF2A phosphorylation to paclitaxel treatment. Our work therefore identifies CCT020312 as a novel small molecule chemical tool for the selective activation of EIF2A-mediated translation control with utility for proof-of-concept applications in EIF2A-centered therapeutic approaches, and as a chemical starting point for

  16. Bacterial Abundance and Activity across Sites within Two Northern Wisconsin Sphagnum Bogs.

    PubMed

    Fisher; Graham; Graham

    1998-11-01

    Abstract Bacterial abundance, temperature, pH, and dissolved organic carbon (DOC) concentration were compared across surface sites within and between two northern Wisconsin Sphagnum peatlands over the summer seasons in 1995 and 1996. Sites of interest were the Sphagnum mat surface, the water-filled moat (lagg) at the bog margin, and the bog lake littoral zone. Significant differences in both bacterial populations and water chemistry were observed between sites. pH was highest in the lake and lowest in the mat at both bogs; the opposite was true for DOC. Large populations of bacteria were present in surface interstitial water from the mat; abundance in this site was consistently higher than in the moat or lake. Bacterial abundance also increased across sites of increasing DOC concentration and declining pH. Bacterial activities (rates of [3H]leucine incorporation) and growth in dilution cultures (with grazers removed) were also assessed in lake, moat, and mat sites. Results using these measures generally supported the trends observed in abundance, although high rates of [3H]leucine incorporation were recorded in the moat at one of the bogs. Our results indicate that bacterial populations in Sphagnum peatlands are not adversely affected by acidity, and that DOC may be more important than pH in determining bacterial abundance in these environments.

  17. Identifying buried segments of active faults in the northern Rio Grande Rift using aeromagnetic, LiDAR,and gravity data, south-central Colorado, USA

    USGS Publications Warehouse

    Grauch, V.J.S.; Ruleman, Chester A.

    2013-01-01

    Combined interpretation of aeromagnetic and LiDAR data builds on the strength of the aeromagnetic method to locate normal faults with significant offset under cover and the strength of LiDAR interpretation to identify the age and sense of motion of faults. Each data set helps resolve ambiguities in interpreting the other. In addition, gravity data can be used to infer the sense of motion for totally buried faults inferred solely from aeromagnetic data. Combined interpretation to identify active faults at the northern end of the San Luis Basin of the northern Rio Grande rift has confirmed general aspects of previous geologic mapping but has also provided significant improvements. The interpretation revises and extends mapped fault traces, confirms tectonic versus fluvial origins of steep stream banks, and gains additional information on the nature of active and potentially active partially and totally buried faults. Detailed morphology of surfaces mapped from the LiDAR data helps constrain ages of the faults that displace the deposits. The aeromagnetic data provide additional information about their extents in between discontinuous scarps and suggest that several totally buried, potentially active faults are present on both sides of the valley.

  18. A High-Throughput Cell-Based Screen Identified a 2-[(E)-2-Phenylvinyl]-8-Quinolinol Core Structure That Activates p53

    PubMed Central

    Bechill, John; Zhong, Rong; Zhang, Chen; Solomaha, Elena

    2016-01-01

    p53 function is frequently inhibited in cancer either through mutations or by increased degradation via MDM2 and/or E6AP E3-ubiquitin ligases. Most agents that restore p53 expression act by binding MDM2 or E6AP to prevent p53 degradation. However, fewer compounds directly bind to and activate p53. Here, we identified compounds that shared a core structure that bound p53, caused nuclear localization of p53 and caused cell death. To identify these compounds, we developed a novel cell-based screen to redirect p53 degradation to the Skip-Cullin-F-box (SCF) ubiquitin ligase complex in cells expressing high levels of p53. In a multiplexed assay, we coupled p53 targeted degradation with Rb1 targeted degradation in order to identify compounds that prevented p53 degradation while not inhibiting degradation through the SCF complex or other proteolytic machinery. High-throughput screening identified several leads that shared a common 2-[(E)-2-phenylvinyl]-8-quinolinol core structure that stabilized p53. Surface plasmon resonance analysis indicated that these compounds bound p53 with a KD of 200 ± 52 nM. Furthermore, these compounds increased p53 nuclear localization and transcription of the p53 target genes PUMA, BAX, p21 and FAS in cancer cells. Although p53-null cells had a 2.5±0.5-fold greater viability compared to p53 wild type cells after treatment with core compounds, loss of p53 did not completely rescue cell viability suggesting that compounds may target both p53-dependent and p53-independent pathways to inhibit cell proliferation. Thus, we present a novel, cell-based high-throughput screen to identify a 2-[(E)-2-phenylvinyl]-8-quinolinol core structure that bound to p53 and increased p53 activity in cancer cells. These compounds may serve as anti-neoplastic agents in part by targeting p53 as well as other potential pathways. PMID:27124407

  19. Anti-inflammatory activity of aqueous extract and bioactive compounds identified from the fruits of Hancornia speciosa Gomes (Apocynaceae).

    PubMed

    Torres-Rêgo, Manoela; Furtado, Allanny Alves; Bitencourt, Mariana Angélica Oliveira; Lima, Maira Conceição Jerônimo de Souza; Andrade, Rafael Caetano Lisbôa Castro de; Azevedo, Eduardo Pereira de; Soares, Thaciane da Cunha; Tomaz, José Carlos; Lopes, Norberto Peporine; da Silva-Júnior, Arnóbio Antônio; Zucolotto, Silvana Maria; Fernandes-Pedrosa, Matheus de Freitas

    2016-08-05

    Hancornia speciosa Gomes (Apocynaceae), popularly known as "mangabeira," has been used in folk medicine to treat inflammatory disorders, hypertension, dermatitis, diabetes, liver diseases and gastric disorders. Although the ethnobotany indicates that its fruits can be used for the treatment of ulcers and inflammatory disorders, only few studies have been conducted to prove such biological activities. This study investigated the anti-inflammatory properties of the aqueous extract of the fruits of H. speciosa Gomes as well as its bioactive compounds using in vivo experimental models. The bioactive compounds were identified by High Performance Liquid Chromatography coupled with diode array detector (HPLC-DAD) and Liquid Chromatography coupled with Mass Spectrometry (LC-MS). The anti-inflammatory properties were investigated through in vivo tests, which comprised xylene-induced ear edema, carrageenan-induced peritonitis and zymosan-induced air pouch. The levels of IL-1β, IL-6, IL-12 and TNF-α were determined using ELISA. Rutin and chlorogenic acid were identified in the extract as the main secondary metabolites. In addition, the extract as well as rutin and chlorogenic acid significantly inhibited the xilol-induced ear edema and also reduced the cell migration in both carrageenan-induced peritonitis and zymosan-induced air pouch models. Reduced levels of cytokines were also observed. This is the first study that demonstrated the anti-inflammatory activity of the extract of H. speciosa fruits against different inflammatory agents in animal models, suggesting that its bioactive molecules, especially rutin and chlorogenic acid are, at least in part, responsible for such activity. These findings support the widespread use of Hancornia speciosa in popular medicine and demonstrate that its aqueous extract has therapeutical potential for the development of herbal drugs with anti-inflammatory properties.

  20. Tiered High-Throughput Screening Approach to Identify ...

    EPA Pesticide Factsheets

    High-throughput screening (HTS) for potential thyroid–disrupting chemicals requires a system of assays to capture multiple molecular-initiating events (MIEs) that converge on perturbed thyroid hormone (TH) homeostasis. Screening for MIEs specific to TH-disrupting pathways is limited in the US EPA ToxCast screening assay portfolio. To fill one critical screening gap, the Amplex UltraRed-thyroperoxidase (AUR-TPO) assay was developed to identify chemicals that inhibit TPO, as decreased TPO activity reduces TH synthesis. The ToxCast Phase I and II chemical libraries, comprised of 1,074 unique chemicals, were initially screened using a single, high concentration to identify potential TPO inhibitors. Chemicals positive in the single concentration screen were retested in concentration-response. Due to high false positive rates typically observed with loss-of-signal assays such as AUR-TPO, we also employed two additional assays in parallel to identify possible sources of nonspecific assay signal loss, enabling stratification of roughly 300 putative TPO inhibitors based upon selective AUR-TPO activity. A cell-free luciferase inhibition assay was used to identify nonspecific enzyme inhibition among the putative TPO inhibitors, and a cytotoxicity assay using a human cell line was used to estimate the cellular tolerance limit. Additionally, the TPO inhibition activities of 150 chemicals were compared between the AUR-TPO and an orthogonal peroxidase oxidation assay using

  1. Using c-Jun to identify fear extinction learning-specific patterns of neural activity that are affected by single prolonged stress.

    PubMed

    Knox, Dayan; Stanfield, Briana R; Staib, Jennifer M; David, Nina P; DePietro, Thomas; Chamness, Marisa; Schneider, Elizabeth K; Keller, Samantha M; Lawless, Caroline

    2018-04-02

    Neural circuits via which stress leads to disruptions in fear extinction is often explored in animal stress models. Using the single prolonged stress (SPS) model of post traumatic stress disorder and the immediate early gene (IEG) c-Fos as a measure of neural activity, we previously identified patterns of neural activity through which SPS disrupts extinction retention. However, none of these stress effects were specific to fear or extinction learning and memory. C-Jun is another IEG that is sometimes regulated in a different manner to c-Fos and could be used to identify emotional learning/memory specific patterns of neural activity that are sensitive to SPS. Animals were either fear conditioned (CS-fear) or presented with CSs only (CS-only) then subjected to extinction training and testing. C-Jun was then assayed within neural substrates critical for extinction memory. Inhibited c-Jun levels in the hippocampus (Hipp) and enhanced functional connectivity between the ventromedial prefrontal cortex (vmPFC) and basolateral amygdala (BLA) during extinction training was disrupted by SPS in the CS-fear group only. As a result, these effects were specific to emotional learning/memory. SPS also disrupted inhibited Hipp c-Jun levels, enhanced BLA c-Jun levels, and altered functional connectivity among the vmPFC, BLA, and Hipp during extinction testing in SPS rats in the CS-fear and CS-only groups. As a result, these effects were not specific to emotional learning/memory. Our findings suggest that SPS disrupts neural activity specific to extinction memory, but may also disrupt the retention of fear extinction by mechanisms that do not involve emotional learning/memory. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Phylogenetic and Chemical Diversity of Three Chemotypes of Bloom-Forming Lyngbya Species (Cyanobacteria: Oscillatoriales) from Reefs of Southeastern Florida▿

    PubMed Central

    Sharp, Koty; Arthur, Karen E.; Gu, Liangcai; Ross, Cliff; Harrison, Genelle; Gunasekera, Sarath P.; Meickle, Theresa; Matthew, Susan; Luesch, Hendrik; Thacker, Robert W.; Sherman, David H.; Paul, Valerie J.

    2009-01-01

    The cyanobacterial genus Lyngbya includes free-living, benthic, filamentous cyanobacteria that form periodic nuisance blooms in lagoons, reefs, and estuaries. Lyngbya spp. are prolific producers of biologically active compounds that deter grazers and help blooms persist in the marine environment. Here, our investigations reveal the presence of three distinct Lyngbya species on nearshore reefs in Broward County, FL, sampled in 2006 and 2007. With a combination of morphological measurements, molecular biology techniques, and natural products chemistry, we associated these three Lyngbya species with three distinct Lyngbya chemotypes. One species, identified as Lyngbya cf. confervoides via morphological measurements and 16S rRNA gene sequencing, produces a diverse array of bioactive peptides and depsipeptides. Our results indicate that the other two Lyngbya species produce either microcolins A and B or curacin D and dragonamides C and D. Results from screening for the biosynthetic capacity for curacin production among the three Lyngbya chemotypes in this study correlated that capacity with the presence of curacin D. Our work on these bloom-forming Lyngbya species emphasizes the significant phylogenetic and chemical diversity of the marine cyanobacteria on southern Florida reefs and identifies some of the genetic components of those differences. PMID:19270119

  3. Higher trophic level affects nutrient, silicon, metal(loid), and radionuclide mobilization from freshwater sediments

    NASA Astrophysics Data System (ADS)

    Schaller, Jörg; Planer-Friedrich, Britta

    2017-04-01

    Organic sediments in aquatic ecosystems are well known sinks for nutrients, silicon, and metal(loid)s. Organic matter-decomposing organisms like invertebrate shredders, grazers, bioturbators, and filter feeder are key-species for the carbon and energy turnover within the decomposer community. We could show that invertebrate shredders and grazer affect element fixation or remobilization by changing binding properties of organic sediments and the attached biofilm. Bioturbators affect element fixation or remobilization by changing redox conditions within the uppermost sediment layer. Last but not least filter feeders, like the zebra mussel Dreissena polymorpha, an invasive organism in North American and European freshwater ecosystems significantly contributed to element mobilization of silicon, iron, phosphorus, arsenic, and copper and to immobilization of uranium (p<0.001), probably driven by redox conditions, microbial activity within the gut system, or active control of element homeostasis. Except of the filter feeder D. polymorpha, the invertebrates are able to minimize the accumulation of non-nutrient elements due to specific strategies, which is an important strategy for species living in systems tending to element accumulation. However, D. polymorpha revealed a significant uptake and accumulation of arsenic, copper, iron, and especially uranium both into the soft body tissues and the seashell. This accumulation by D. polymorpha is in line with previous observations of metal(loid) accumulation from biomonitoring studies. In summary, higher trophic level strongly contributes to element fixation or remobilization in aquatic systems.

  4. QM/MM simulations identify the determinants of catalytic activity differences between type II dehydroquinase enzymes.

    PubMed

    Lence, Emilio; van der Kamp, Marc W; González-Bello, Concepción; Mulholland, Adrian J

    2018-05-16

    Type II dehydroquinase enzymes (DHQ2), recognized targets for antibiotic drug discovery, show significantly different activities dependent on the species: DHQ2 from Mycobacterium tuberculosis (MtDHQ2) and Helicobacter pylori (HpDHQ2) show a 50-fold difference in catalytic efficiency. Revealing the determinants of this activity difference is important for our understanding of biological catalysis and further offers the potential to contribute to tailoring specificity in drug design. Molecular dynamics simulations using a quantum mechanics/molecular mechanics potential, with correlated ab initio single point corrections, identify and quantify the subtle determinants of the experimentally observed difference in efficiency. The rate-determining step involves the formation of an enolate intermediate: more efficient stabilization of the enolate and transition state of the key step in MtDHQ2, mainly by the essential residues Tyr24 and Arg19, makes it more efficient than HpDHQ2. Further, a water molecule, which is absent in MtDHQ2 but involved in generation of the catalytic Tyr22 tyrosinate in HpDHQ2, was found to destabilize both the transition state and the enolate intermediate. The quantification of the contribution of key residues and water molecules in the rate-determining step of the mechanism also leads to improved understanding of higher potencies and specificity of known inhibitors, which should aid ongoing inhibitor design.

  5. Preclinical Antileukemia Activity of Tramesan: A Newly Identified Bioactive Fungal Metabolite.

    PubMed

    Ricciardi, M R; Licchetta, R; Mirabilii, S; Scarpari, M; Parroni, A; Fabbri, A A; Cescutti, P; Reverberi, M; Fanelli, C; Tafuri, A

    2017-01-01

    Despite improvements that occurred in the last decades in the acute myeloid leukemia (AML) treatment, clinical results are still unsatisfactory. More effective therapies are required, and innovative approaches are ongoing, including the discovery of novel antileukemia natural compounds. Several studies have described the activity of extracts from mushrooms which produce compounds that exhibited immunological and antitumor activities. The latter has been demonstrated to be promoted in vitro by mushroom polysaccharides via induction of apoptosis. However, the antileukemia activity of these compounds on primary cells is still not reported. In the present study, we examined the in vitro effects of Tramesan (TR), a bioactive compound extracted from Trametes versicolor , on leukemic cell lines and primary cells. Our results demonstrated that TR induced a marked growth inhibition of leukemic cell lines and primary cells from AML patients. The antiproliferative effects of TR were associated in primary AML cells with a significant increase of apoptosis. No significant cytotoxic effects were observed in normal peripheral blood mononuclear cells (MNC) from healthy donors. Our data demonstrated a cytotoxic activity of TR on leukemia cells prompting further translational applications. Ongoing studies are elucidating the molecular mechanisms underlying its antileukemic activity.

  6. Preclinical Antileukemia Activity of Tramesan: A Newly Identified Bioactive Fungal Metabolite

    PubMed Central

    Scarpari, M.; Parroni, A.; Fabbri, A. A.; Cescutti, P.; Reverberi, M.; Fanelli, C.

    2017-01-01

    Despite improvements that occurred in the last decades in the acute myeloid leukemia (AML) treatment, clinical results are still unsatisfactory. More effective therapies are required, and innovative approaches are ongoing, including the discovery of novel antileukemia natural compounds. Several studies have described the activity of extracts from mushrooms which produce compounds that exhibited immunological and antitumor activities. The latter has been demonstrated to be promoted in vitro by mushroom polysaccharides via induction of apoptosis. However, the antileukemia activity of these compounds on primary cells is still not reported. In the present study, we examined the in vitro effects of Tramesan (TR), a bioactive compound extracted from Trametes versicolor, on leukemic cell lines and primary cells. Our results demonstrated that TR induced a marked growth inhibition of leukemic cell lines and primary cells from AML patients. The antiproliferative effects of TR were associated in primary AML cells with a significant increase of apoptosis. No significant cytotoxic effects were observed in normal peripheral blood mononuclear cells (MNC) from healthy donors. Our data demonstrated a cytotoxic activity of TR on leukemia cells prompting further translational applications. Ongoing studies are elucidating the molecular mechanisms underlying its antileukemic activity. PMID:29270245

  7. Identifying Distant AGNs

    NASA Astrophysics Data System (ADS)

    Trouille, Laura; Barger, Amy; Tremonti, Christy

    2014-07-01

    The Baldwin, Phillips, and Terlevich emission-line ratio diagnostic ([OIII]/Hβ versus [NII]/Hα, hereafter BPT diagram) efficiently separates galaxies whose signal is dominated by star formation (BPT-SF) from those dominated by AGN activity (BPT-AGN). Yet the BPT diagram is limited to z<0.5, the redshift at which [NII]λ6584 leaves the optical spectral window. Using the Sloan Digital Sky Survey (SDSS), we construct a new diagnostic, or TBT diagram, that is based on rest-frame g-z color, [NeIII]λ3869, and [OII]λλ3726+3729 and can be used for galaxies out to z<1.4. The TBT diagram identifies 98.7% of the SDSS BPT-AGN as TBT-AGN and 97% of the SDSS BPT-SF as TBT-SF. Furthermore, it identifies 97% of the OPTX Chandra X-ray selected AGNs as TBT-AGN. This is in contrast to the BPT diagram, which misidentifies 20% of X-ray selected AGNs as BPT-SF.

  8. NG2 expression in glioblastoma identifies an actively proliferating population with an aggressive molecular signature

    PubMed Central

    Al-Mayhani, M. Talal F.; Grenfell, Richard; Narita, Masashi; Piccirillo, Sara; Kenney-Herbert, Emma; Fawcett, James W.; Collins, V. Peter; Ichimura, Koichi; Watts, Colin

    2011-01-01

    Glioblastoma multiforme (GBM) is the most common type of primary brain tumor and a highly malignant and heterogeneous cancer. Current conventional therapies fail to eradicate or curb GBM cell growth. Hence, exploring the cellular and molecular basis of GBM cell growth is vital to develop novel therapeutic approaches. Neuroglia (NG)-2 is a transmembrane proteoglycan expressed by NG2+ progenitors and is strongly linked to cell proliferation in the normal brain. By using NG2 as a biomarker we identify a GBM cell population (GBM NG2+ cells) with robust proliferative, clonogenic, and tumorigenic capacity. We show that a significant proportion (mean 83%) of cells proliferating in the tumor mass express NG2 and that over 50% of GBM NG2+ cells are proliferating. Compared with the GBM NG2− cells from the same tumor, the GBM of NG2+ cells overexpress genes associated with aggressive tumorigenicity, including overexpression of Mitosis and Cell Cycling Module genes (e.g., MELK, CDC, MCM, E2F), which have been previously shown to correlate with poor survival in GBM. We also show that the coexpression pattern of NG2 with other glial progenitor markers in GBM does not recapitulate that described in the normal brain. The expression of NG2 by such an aggressive and actively cycling GBM population combined with its location on the cell surface identifies this cell population as a potential therapeutic target in a subset of patients with GBM. PMID:21798846

  9. Identifying non-point sources of endocrine active compounds and their biological impacts in freshwater lakes

    USGS Publications Warehouse

    Baker, Beth H.; Martinovic-Weigelt, Dalma; Ferrey, Mark L.; Barber, Larry B.; Writer, Jeffrey H.; Rosenberry, Donald O.; Kiesling, Richard L.; Lundy, James R.; Schoenfuss, Heiko L.

    2014-01-01

    Contaminants of emerging concern, particularly endocrine active compounds (EACs), have been identified as a threat to aquatic wildlife. However, little is known about the impact of EACs on lakes through groundwater from onsite wastewater treatment systems (OWTS). This study aims to identify specific contributions of OWTS to Sullivan Lake, Minnesota, USA. Lake hydrology, water chemistry, caged bluegill sunfish (Lepomis macrochirus), and larval fathead minnow (Pimephales promelas) exposures were used to assess whether EACs entered the lake through OWTS inflow and the resultant biological impact on fish. Study areas included two OWTS-influenced near-shore sites with native bluegill spawning habitats and two in-lake control sites without nearby EAC sources. Caged bluegill sunfish were analyzed for plasma vitellogenin concentrations, organosomatic indices, and histological pathologies. Surface and porewater was collected from each site and analyzed for EACs. Porewater was also collected for laboratory exposure of larval fathead minnow, before analysis of predator escape performance and gene expression profiles. Chemical analysis showed EACs present at low concentrations at each study site, whereas discrete variations were reported between sites and between summer and fall samplings. Body condition index and liver vacuolization of sunfish were found to differ among study sites as did gene expression in exposed larval fathead minnows. Interestingly, biological exposure data and water chemistry did not match. Therefore, although results highlight the potential impacts of seepage from OWTS, further investigation of mixture effects and life history factor as well as chemical fate is warranted.

  10. Multidimensional Single Cell Based STAT Phosphorylation Profiling Identifies a Novel Biosignature for Evaluation of Systemic Lupus Erythematosus Activity

    PubMed Central

    Huang, Xinfang; Guo, Yanzhi; Bao, Chunde; Shen, Nan

    2011-01-01

    Introduction Dysregulated cytokine action on immune cells plays an important role in the initiation and progress of systemic lupus erythematosus (SLE), a complex autoimmune disease. Comprehensively quantifying basal STATs phosphorylation and their signaling response to cytokines should help us to better understand the etiology of SLE. Methods Phospho-specific flow cytometry was used to measure the basal STAT signaling activation in three immune cell types of peripheral-blood mononuclear cells from 20 lupus patients, 9 rheumatoid arthritis (RA) patients and 13 healthy donors (HDs). A panel of 27 cytokines, including inflammatory cytokines, was measured with Bio-Plex™ Human Cytokine Assays. Serum Prolactin levels were measured with an immunoradiometric assay. STAT signaling responses to inflammatory cytokines (interferon α [IFNα], IFNγ, interleukin 2 [IL2], IL6, and IL10) were also monitored. Results We observed the basal activation of STAT3 in SLE T cells and monocytes, and the basal activation of STAT5 in SLE T cells and B cells. The SLE samples clustered into two main groups, which were associated with the SLE Disease Activity Index 2000, their erythrocyte sedimentation rate, and their hydroxychloroquine use. The phosphorylation of STAT5 in B cells was associated with cytokines IL2, granulocyte colony-stimulating factor (G-CSF), and IFNγ, whereas serum prolactin affected STAT5 activation in T cells. The responses of STAT1, STAT3, and STAT5 to IFNα were greatly reduced in SLE T cells, B cells, and monocytes, except for the STAT1 response to IFNα in monocytes. The response of STAT3 to IL6 was reduced in SLE T cells. Conclusions The basal activation of STATs signaling and reduced response to cytokines may be helpful us to identify the activity and severity of SLE. PMID:21799742

  11. Identifying the controls of wildfire activity in Namibia using multivariate statistics

    NASA Astrophysics Data System (ADS)

    Mayr, Manuel; Le Roux, Johan; Samimi, Cyrus

    2015-04-01

    Despite large areas of Namibia being unaffected by fires due to aridity, substantial burning in the northern and north-eastern parts of the country is observed every year. Within the fire-affected regions, a strong spatial and inter-annual variability characterizes the dry-season fire situation. In order to understand these patterns, it appears critical to identify the causative factors behind fire occurrence and to examine their interactions in detail. Furthermore, most studies dealing with causative factor examination focus either on the local or the regional scale. However, these scales seem to be inappropriate from a management perspective, as fire-related strategic action plans are most often set up nationwide. Here, we will present an examination of the fire regimes of Namibia based on a dataset conducted by Le Roux (2011). A decade-spanning fire record (1994-2003) derived from NOAA's Advanced Very High Resolution Radiometer (AVHRR) imagery was used to generate four fire regime metrics (Burned Area, Fire Season Length, Month of Peak Fire Season, and Fire Return Period) and quantitative information on vegetation and phenology derived from Normalized Difference Vegetation Index (NDVI) time series. Further variables contained by this dataset are related to climate, biodiversity, and human activities. Le Roux (2011) analyzed the correlations between the fire metrics mentioned above and the predictor variables. We hypothesize that linear correlations (as estimated by correlation coefficients) simplify the interactions between response and predictor variables. For instance, moderate population densities could induce the highest number of fires, whereas the complete absence of humans lacks one major source of ignition. Around highly populated areas, in contrary, fuels are usually reduced and space is more fragmented - thus, the initiation and spread of a potential fire could as well be inhibited. From a total of over 40 explanatory variables, we will initially use

  12. Novel Inducers of Fetal Globin Identified through High Throughput Screening (HTS) Are Active In Vivo in Anemic Baboons and Transgenic Mice.

    PubMed

    Boosalis, Michael S; Sangerman, Jose I; White, Gary L; Wolf, Roman F; Shen, Ling; Dai, Yan; White, Emily; Makala, Levi H; Li, Biaoru; Pace, Betty S; Nouraie, Mehdi; Faller, Douglas V; Perrine, Susan P

    2015-01-01

    High-level fetal (γ) globin expression ameliorates clinical severity of the beta (β) hemoglobinopathies, and safe, orally-bioavailable γ-globin inducing agents would benefit many patients. We adapted a LCR-γ-globin promoter-GFP reporter assay to a high-throughput robotic system to evaluate five diverse chemical libraries for this activity. Multiple structurally- and functionally-diverse compounds were identified which activate the γ-globin gene promoter at nanomolar concentrations, including some therapeutics approved for other conditions. Three candidates with established safety profiles were further evaluated in erythroid progenitors, anemic baboons and transgenic mice, with significant induction of γ-globin expression observed in vivo. A lead candidate, Benserazide, emerged which demonstrated > 20-fold induction of γ-globin mRNA expression in anemic baboons and increased F-cell proportions by 3.5-fold in transgenic mice. Benserazide has been used chronically to inhibit amino acid decarboxylase to enhance plasma levels of L-dopa. These studies confirm the utility of high-throughput screening and identify previously unrecognized fetal globin inducing candidates which can be developed expediently for treatment of hemoglobinopathies.

  13. Novel Inducers of Fetal Globin Identified through High Throughput Screening (HTS) Are Active In Vivo in Anemic Baboons and Transgenic Mice

    PubMed Central

    Boosalis, Michael S.; Sangerman, Jose I.; White, Gary L.; Wolf, Roman F.; Shen, Ling; Dai, Yan; White, Emily; Makala, Levi H.; Li, Biaoru; Pace, Betty S.; Nouraie, Mehdi; Faller, Douglas V.; Perrine, Susan P.

    2015-01-01

    High-level fetal (γ) globin expression ameliorates clinical severity of the beta (β) hemoglobinopathies, and safe, orally-bioavailable γ-globin inducing agents would benefit many patients. We adapted a LCR-γ-globin promoter-GFP reporter assay to a high-throughput robotic system to evaluate five diverse chemical libraries for this activity. Multiple structurally- and functionally-diverse compounds were identified which activate the γ-globin gene promoter at nanomolar concentrations, including some therapeutics approved for other conditions. Three candidates with established safety profiles were further evaluated in erythroid progenitors, anemic baboons and transgenic mice, with significant induction of γ-globin expression observed in vivo. A lead candidate, Benserazide, emerged which demonstrated > 20-fold induction of γ-globin mRNA expression in anemic baboons and increased F-cell proportions by 3.5-fold in transgenic mice. Benserazide has been used chronically to inhibit amino acid decarboxylase to enhance plasma levels of L-dopa. These studies confirm the utility of high-throughput screening and identify previously unrecognized fetal globin inducing candidates which can be developed expediently for treatment of hemoglobinopathies. PMID:26713848

  14. Molecular and functional analyses of a maize autoactive NB-LRR protein identify precise structural requirements for activity.

    PubMed

    Wang, Guan-Feng; Ji, Jiabing; El-Kasmi, Farid; Dangl, Jeffery L; Johal, Guri; Balint-Kurti, Peter J

    2015-02-01

    Plant disease resistance is often mediated by nucleotide binding-leucine rich repeat (NLR) proteins which remain auto-inhibited until recognition of specific pathogen-derived molecules causes their activation, triggering a rapid, localized cell death called a hypersensitive response (HR). Three domains are recognized in one of the major classes of NLR proteins: a coiled-coil (CC), a nucleotide binding (NB-ARC) and a leucine rich repeat (LRR) domains. The maize NLR gene Rp1-D21 derives from an intergenic recombination event between two NLR genes, Rp1-D and Rp1-dp2 and confers an autoactive HR. We report systematic structural and functional analyses of Rp1 proteins in maize and N. benthamiana to characterize the molecular mechanism of NLR activation/auto-inhibition. We derive a model comprising the following three main features: Rp1 proteins appear to self-associate to become competent for activity. The CC domain is signaling-competent and is sufficient to induce HR. This can be suppressed by the NB-ARC domain through direct interaction. In autoactive proteins, the interaction of the LRR domain with the NB-ARC domain causes de-repression and thus disrupts the inhibition of HR. Further, we identify specific amino acids and combinations thereof that are important for the auto-inhibition/activity of Rp1 proteins. We also provide evidence for the function of MHD2, a previously uncharacterized, though widely conserved NLR motif. This work reports several novel insights into the precise structural requirement for NLR function and informs efforts towards utilizing these proteins for engineering disease resistance.

  15. Tetrandrine identified in a small molecule screen to activate mesenchymal stem cells for enhanced immunomodulation.

    PubMed

    Yang, Zijiang; Concannon, John; Ng, Kelvin S; Seyb, Kathleen; Mortensen, Luke J; Ranganath, Sudhir; Gu, Fangqi; Levy, Oren; Tong, Zhixiang; Martyn, Keir; Zhao, Weian; Lin, Charles P; Glicksman, Marcie A; Karp, Jeffrey M

    2016-07-26

    Pre-treatment or priming of mesenchymal stem cells (MSC) prior to transplantation can significantly augment the immunosuppressive effect of MSC-based therapies. In this study, we screened a library of 1402 FDA-approved bioactive compounds to prime MSC. We identified tetrandrine as a potential hit that activates the secretion of prostaglandin E2 (PGE2), a potent immunosuppressive agent, by MSC. Tetrandrine increased MSC PGE2 secretion through the NF-κB/COX-2 signaling pathway. When co-cultured with mouse macrophages (RAW264.7), tetrandrine-primed MSC attenuated the level of TNF-α secreted by RAW264.7. Furthermore, systemic transplantation of primed MSC into a mouse ear skin inflammation model significantly reduced the level of TNF-α in the inflamed ear, compared to unprimed cells. Screening of small molecules to pre-condition cells prior to transplantation represents a promising strategy to boost the therapeutic potential of cell therapy.

  16. Tracking the autochthonous carbon transfer in stream biofilm food webs.

    PubMed

    Risse-Buhl, Ute; Trefzger, Nicolai; Seifert, Anne-Gret; Schönborn, Wilfried; Gleixner, Gerd; Küsel, Kirsten

    2012-01-01

    Food webs in the rhithral zone rely mainly on allochthonous carbon from the riparian vegetation. However, autochthonous carbon might be more important in open canopy streams. In streams, most of the microbial activity occurs in biofilms, associated with the streambed. We followed the autochthonous carbon transfer toward bacteria and grazing protozoa within a stream biofilm food web. Biofilms that developed in a second-order stream (Thuringia, Germany) were incubated in flow channels under climate-controlled conditions. Six-week-old biofilms received either ¹³C- or ¹²C-labeled CO₂, and uptake into phospholipid fatty acids was followed. The dissolved inorganic carbon of the flow channel water became immediately labeled. In biofilms grown under 8-h light/16-h dark conditions, more than 50% of the labeled carbon was incorporated in biofilm algae, mainly filamentous cyanobacteria, pennate diatoms, and nonfilamentous green algae. A mean of 29% of the labeled carbon reached protozoan grazer. The testate amoeba Pseudodifflugia horrida was highly abundant in biofilms and seemed to be the most important grazer on biofilm bacteria and algae. Hence, stream biofilms dominated by cyanobacteria and algae seem to play an important role in the uptake of CO₂ and transfer of autochthonous carbon through the microbial food web.

  17. Focusing on Teacher Learning Opportunities to Identify Potentially Productive Coaching Activities

    ERIC Educational Resources Information Center

    Gibbons, Lynsey K.; Cobb, Paul

    2017-01-01

    Instructional improvement initiatives in many districts include instructional coaching as a primary form of job-embedded support for teachers. However, the coaching literature provides little guidance about what activities coaches should engage in with teachers to improve instruction. When researchers do propose activities, they rarely justify why…

  18. Transcriptome Profiling Identifies Multiplexin as a Target of SAGA Deubiquitinase Activity in Glia Required for Precise Axon Guidance During Drosophila Visual Development.

    PubMed

    Ma, Jingqun; Brennan, Kaelan J; D'Aloia, Mitch R; Pascuzzi, Pete E; Weake, Vikki M

    2016-08-09

    The Spt-Ada-Gcn5 Acetyltransferase (SAGA) complex is a transcriptional coactivator with histone acetylase and deubiquitinase activities that plays an important role in visual development and function. In Drosophila melanogaster, four SAGA subunits are required for the deubiquitination of monoubiquitinated histone H2B (ubH2B): Nonstop, Sgf11, E(y)2, and Ataxin 7. Mutations that disrupt SAGA deubiquitinase activity cause defects in neuronal connectivity in the developing Drosophila visual system. In addition, mutations in SAGA result in the human progressive visual disorder spinocerebellar ataxia type 7 (SCA7). Glial cells play a crucial role in both the neuronal connectivity defect in nonstop and sgf11 flies, and in the retinal degeneration observed in SCA7 patients. Thus, we sought to identify the gene targets of SAGA deubiquitinase activity in glia in the Drosophila larval central nervous system. To do this, we enriched glia from wild-type, nonstop, and sgf11 larval optic lobes using affinity-purification of KASH-GFP tagged nuclei, and then examined each transcriptome using RNA-seq. Our analysis showed that SAGA deubiquitinase activity is required for proper expression of 16% of actively transcribed genes in glia, especially genes involved in proteasome function, protein folding and axon guidance. We further show that the SAGA deubiquitinase-activated gene Multiplexin (Mp) is required in glia for proper photoreceptor axon targeting. Mutations in the human ortholog of Mp, COL18A1, have been identified in a family with a SCA7-like progressive visual disorder, suggesting that defects in the expression of this gene in SCA7 patients could play a role in the retinal degeneration that is unique to this ataxia. Copyright © 2016 Ma et al.

  19. Patterns of top-down control in a seagrass ecosystem: could a roving apex predator induce a behaviour-mediated trophic cascade?

    PubMed

    Burkholder, Derek A; Heithaus, Michael R; Fourqurean, James W; Wirsing, Aaron; Dill, Lawrence M

    2013-11-01

    1. The loss of large-bodied herbivores and/or top predators has been associated with large-scale changes in ecosystems around the world, but there remain important questions regarding the contexts in which such changes are most likely and the mechanisms through which they occur, particularly in marine ecosystems. 2. We used long-term exclusion cages to examine the effects of large grazers (sea cows, Dugong dugon; sea turtles Chelonia mydas) on seagrass community structure, biomass and nutrient dynamics. Experiments were conducted in habitats with high risk of predation (interior of shallow banks) and lower risk (edges of banks) to elucidate whether nonconsumptive (risk) effects of tiger sharks (Galeocerdo cuvier), a roving predator, structure herbivore impacts on seagrasses. 3. In lower-risk habitats, excluding large herbivores resulted in increased leaf length for Cymodocea angustata and Halodule uninervis. C. angustata shoot densities nearly tripled when released from herbivory, while H. uninervis nearly disappeared from exclusion cages over the course of the study. 4. We found no support for the hypothesis that grazing increases seagrass nutrient content. Instead, phosphorus content was higher in seagrasses within exclosures. This pattern is consistent with decreased light availability in the denser C. angustata canopies that formed in exclosures, and may indicate that competition for light led to the decrease in H. uninervis. 5. Impacts of large grazers were consistent with a behaviour-mediated trophic cascade (BMTC) initiated by tiger sharks and mediated by risk-sensitive foraging by large grazers. 6, Our results suggest that large-bodied grazers likely played important roles in seagrass ecosystem dynamics historically and that roving predators are capable of initiating a BMTC. Conservation efforts in coastal ecosystems must account for such interactions or risk unintended consequences. © 2013 The Authors. Journal of Animal Ecology © 2013 British Ecological

  20. Declines in predatory fish promote bloom-forming macroalgae.

    PubMed

    Eriksson, Britas Klemens; Ljunggren, Lars; Sandström, Alfred; Johansson, Gustav; Mattila, Johanna; Rubach, Anja; Råberg, Sonja; Snickars, Martin

    2009-12-01

    In the Baltic Sea, increased dominance of ephemeral and bloom-forming algae is presently attributed to increased nutrient loads. Simultaneously, coastal predatory fish are in strong decline. Using field data from nine areas covering a 700-km coastline, we examined whether formation of macroalgal blooms could be linked to the composition of the fish community. We then tested whether predator or nutrient availability could explain the field patterns in two small-scale field experiments, by comparing joint effects on algal net production from nutrient enrichment with agricultural fertilizer and exclusion of larger predatory fish with cages. We also manipulated the presence of invertebrate grazers. The abundance of piscivorous fish had a strong negative correlation with the large-scale distribution of bloom-forming macroalgae. Areas with depleted top-predator communities displayed massive increases in their prey, small-bodied fish, and high covers of ephemeral algae. Combining the results from the two experiments showed that excluding larger piscivorous fish: (1) increased the abundance of small-bodied predatory fish; (2) changed the size distribution of the dominating grazers, decreasing the smaller gastropod scrapers; and (3) increased the net production of ephemeral macroalgae. Effects of removing top predators and nutrient enrichment were similar and additive, together increasing the abundance of ephemeral algae many times. Predator effects depended on invertebrate grazers; in the absence of invertebrates there were no significant effects of predator exclusion on algal production. Our results provide strong support for regional declines of larger predatory fish in the Baltic Sea promoting algal production by decreasing invertebrate grazer control. This highlights the importance of trophic interactions for ecosystem responses to eutrophication. The view emerges that to achieve management goals for water quality we need to consider the interplay between top-down and

  1. Transcriptome Analysis of Mycobacteria-Specific CD4+ T Cells Identified by Activation-Induced Expression of CD154.

    PubMed

    Kunnath-Velayudhan, Shajo; Goldberg, Michael F; Saini, Neeraj K; Johndrow, Christopher T; Ng, Tony W; Johnson, Alison J; Xu, Jiayong; Chan, John; Jacobs, William R; Porcelli, Steven A

    2017-10-01

    Analysis of Ag-specific CD4 + T cells in mycobacterial infections at the transcriptome level is informative but technically challenging. Although several methods exist for identifying Ag-specific T cells, including intracellular cytokine staining, cell surface cytokine-capture assays, and staining with peptide:MHC class II multimers, all of these have significant technical constraints that limit their usefulness. Measurement of activation-induced expression of CD154 has been reported to detect live Ag-specific CD4 + T cells, but this approach remains underexplored and, to our knowledge, has not previously been applied in mycobacteria-infected animals. In this article, we show that CD154 expression identifies adoptively transferred or endogenous Ag-specific CD4 + T cells induced by Mycobacterium bovis bacillus Calmette-Guérin vaccination. We confirmed that Ag-specific cytokine production was positively correlated with CD154 expression by CD4 + T cells from bacillus Calmette-Guérin-vaccinated mice and show that high-quality microarrays can be performed from RNA isolated from CD154 + cells purified by cell sorting. Analysis of microarray data demonstrated that the transcriptome of CD4 + CD154 + cells was distinct from that of CD154 - cells and showed major enrichment of transcripts encoding multiple cytokines and pathways of cellular activation. One notable finding was the identification of a previously unrecognized subset of mycobacteria-specific CD4 + T cells that is characterized by the production of IL-3. Our results support the use of CD154 expression as a practical and reliable method to isolate live Ag-specific CD4 + T cells for transcriptomic analysis and potentially for a range of other studies in infected or previously immunized hosts. Copyright © 2017 by The American Association of Immunologists, Inc.

  2. Faunal isotope records reveal trophic and nutrient dynamics in twentieth century Yellowstone grasslands.

    PubMed

    Fox-Dobbs, Kena; Nelson, Abigail A; Koch, Paul L; Leonard, Jennifer A

    2012-10-23

    Population sizes and movement patterns of ungulate grazers and their predators have fluctuated dramatically over the past few centuries, largely owing to overharvesting, land-use change and historic management. We used δ(13)C and δ(15)N values measured from bone collagen of historic and recent gray wolves and their potential primary prey from Yellowstone National Park to gain insight into the trophic dynamics and nutrient conditions of historic and modern grasslands. The diet of reintroduced wolves closely parallels that of the historic population. We suggest that a significant shift in faunal δ(15)N values over the past century reflects impacts of anthropogenic environmental changes on grassland ecosystems, including grazer-mediated shifts in grassland nitrogen cycle processes.

  3. Identifying state-level policy and provision domains for physical education and physical activity in high school

    PubMed Central

    2013-01-01

    Background It is important to quickly and efficiently identify policies that are effective at changing behavior; therefore, we must be able to quantify and evaluate the effect of those policies and of changes to those policies. The purpose of this study was to develop state-level physical education (PE) and physical activity (PA) policy domain scores at the high-school level. Policy domain scores were developed with a focus on measuring policy change. Methods Exploratory factor analysis was used to group items from the state-level School Health Policies and Programs Study (SHPPS) into policy domains. Items that related to PA or PE at the High School level were identified from the 7 SHPPS health program surveys. Data from 2000 and 2006 were used in the factor analysis. RESULTS: From the 98 items identified, 17 policy domains were extracted. Average policy domain change scores were positive for 12 policy domains, with the largest increases for “Discouraging PA as Punishment”, “Collaboration”, and “Staff Development Opportunities”. On average, states increased scores in 4.94 ± 2.76 policy domains, decreased in 3.53 ± 2.03, and had no change in 7.69 ± 2.09 policy domains. Significant correlations were found between several policy domain scores. Conclusions Quantifying policy change and its impact is integral to the policy making and revision process. Our results build on previous research offering a way to examine changes in state-level policies related to PE and PA of high-school students and the faculty and staff who serve them. This work provides methods for combining state-level policies relevant to PE or PA in youth for studies of their impact. PMID:23815860

  4. SPARQL-enabled identifier conversion with Identifiers.org

    PubMed Central

    Wimalaratne, Sarala M.; Bolleman, Jerven; Juty, Nick; Katayama, Toshiaki; Dumontier, Michel; Redaschi, Nicole; Le Novère, Nicolas; Hermjakob, Henning; Laibe, Camille

    2015-01-01

    Motivation: On the semantic web, in life sciences in particular, data is often distributed via multiple resources. Each of these sources is likely to use their own International Resource Identifier for conceptually the same resource or database record. The lack of correspondence between identifiers introduces a barrier when executing federated SPARQL queries across life science data. Results: We introduce a novel SPARQL-based service to enable on-the-fly integration of life science data. This service uses the identifier patterns defined in the Identifiers.org Registry to generate a plurality of identifier variants, which can then be used to match source identifiers with target identifiers. We demonstrate the utility of this identifier integration approach by answering queries across major producers of life science Linked Data. Availability and implementation: The SPARQL-based identifier conversion service is available without restriction at http://identifiers.org/services/sparql. Contact: sarala@ebi.ac.uk PMID:25638809

  5. SPARQL-enabled identifier conversion with Identifiers.org.

    PubMed

    Wimalaratne, Sarala M; Bolleman, Jerven; Juty, Nick; Katayama, Toshiaki; Dumontier, Michel; Redaschi, Nicole; Le Novère, Nicolas; Hermjakob, Henning; Laibe, Camille

    2015-06-01

    On the semantic web, in life sciences in particular, data is often distributed via multiple resources. Each of these sources is likely to use their own International Resource Identifier for conceptually the same resource or database record. The lack of correspondence between identifiers introduces a barrier when executing federated SPARQL queries across life science data. We introduce a novel SPARQL-based service to enable on-the-fly integration of life science data. This service uses the identifier patterns defined in the Identifiers.org Registry to generate a plurality of identifier variants, which can then be used to match source identifiers with target identifiers. We demonstrate the utility of this identifier integration approach by answering queries across major producers of life science Linked Data. The SPARQL-based identifier conversion service is available without restriction at http://identifiers.org/services/sparql. © The Author 2015. Published by Oxford University Press.

  6. Transposon mutagenesis of probiotic Lactobacillus casei identifies asnH, an asparagine synthetase gene involved in its immune-activating capacity.

    PubMed

    Ito, Masahiro; Kim, Yun-Gi; Tsuji, Hirokazu; Takahashi, Takuya; Kiwaki, Mayumi; Nomoto, Koji; Danbara, Hirofumi; Okada, Nobuhiko

    2014-01-01

    Lactobacillus casei ATCC 27139 enhances host innate immunity, and the J1 phage-resistant mutants of this strain lose the activity. A transposon insertion mutant library of L. casei ATCC 27139 was constructed, and nine J1 phage-resistant mutants out of them were obtained. Cloning and sequencing analyses identified three independent genes that were disrupted by insertion of the transposon element: asnH, encoding asparagine synthetase, and dnaJ and dnaK, encoding the molecular chaperones DnaJ and DnaK, respectively. Using an in vivo mouse model of Listeria infection, only asnH mutant showed deficiency in their ability to enhance host innate immunity, and complementation of the mutation by introduction of the wild-type asnH in the mutant strain recovered the immuno-augmenting activity. AsnH protein exhibited asparagine synthetase activity when the lysozyme-treated cell wall extracts of L. casei ATCC 27139 was added as substrate. The asnH mutants lost the thick and rigid peptidoglycan features that are characteristic to the wild-type cells, indicating that AsnH of L. casei is involved in peptidoglycan biosynthesis. These results indicate that asnH is required for the construction of the peptidoglycan composition involved in the immune-activating capacity of L. casei ATCC 27139.

  7. Anomalous rise in algal production linked to lakewater calcium decline through food web interactions

    PubMed Central

    Korosi, Jennifer B.; Burke, Samantha M.; Thienpont, Joshua R.; Smol, John P.

    2012-01-01

    Increased algal blooms are a threat to aquatic ecosystems worldwide, although the combined effects of multiple stressors make it difficult to determine the underlying causes. We explore whether changes in trophic interactions in response to declining calcium (Ca) concentrations, a water quality issue only recently recognized in Europe and North America, can be linked with unexplained bloom production. Using a palaeolimnological approach analysing the remains of Cladocera (herbivorous grazers) and visual reflectance spectroscopically inferred chlorophyll a from the sediments of a Nova Scotia (Canada) lake, we show that a keystone grazer, Daphnia, declined in the early 1990s and was replaced by a less effective grazer, Bosmina, while inferred chlorophyll a levels tripled at constant total phosphorus (TP) concentrations. The decline in Daphnia cannot be attributed to changes in pH, thermal stratification or predation, but instead is linked to declining lakewater [Ca]. The consistency in the timing of changes in Daphnia and inferred chlorophyll a suggests top-down control on algal production, providing, to our knowledge, the first evidence of a link between lakewater [Ca] decline and elevated algal production mediated through the effects of [Ca] decline on Daphnia. [Ca] decline has severe implications for whole-lake food webs, and presents yet another mechanism for potential increases in algal blooms. PMID:21957138

  8. The duality of ocean acidification as a resource and a stressor.

    PubMed

    Connell, Sean D; Doubleday, Zoë A; Foster, Nicole R; Hamlyn, Sarah B; Harley, Christopher D G; Helmuth, Brian; Kelaher, Brendan P; Nagelkerken, Ivan; Rodgers, Kirsten L; Sarà, Gianluca; Russell, Bayden D

    2018-05-01

    Ecologically dominant species often define ecosystem states, but as human disturbances intensify, their subordinate counterparts increasingly displace them. We consider the duality of disturbance by examining how environmental drivers can simultaneously act as a stressor to dominant species and as a resource to subordinates. Using a model ecosystem, we demonstrate that CO 2 -driven interactions between species can account for such reversals in dominance; i.e., the displacement of dominants (kelp forests) by subordinates (turf algae). We established that CO 2 enrichment had a direct positive effect on productivity of turfs, but a negligible effect on kelp. CO 2 enrichment further suppressed the abundance and feeding rate of the primary grazer of turfs (sea urchins), but had an opposite effect on the minor grazer (gastropods). Thus, boosted production of subordinate producers, exacerbated by a net reduction in its consumption by primary grazers, accounts for community change (i.e., turf displacing kelp). Ecosystem collapse, therefore, is more likely when resource enrichment alters competitive dominance of producers, and consumers fail to compensate. By recognizing such duality in the responses of interacting species to disturbance, which may stabilize or exacerbate change, we can begin to understand how intensifying human disturbances determine whether or not ecosystems undergo phase shifts. © 2018 by the Ecological Society of America.

  9. Ecological and physiological controls of species composition in green macroalgal blooms.

    PubMed

    Nelson, Timothy A; Haberlin, Karalon; Nelson, Amorah V; Ribarich, Heather; Hotchkiss, Ruth; Van Alstyne, Kathryn L; Buckingham, Lee; Simunds, Dejah J; Fredrickson, Kerri

    2008-05-01

    Green macroalgal blooms have substantially altered marine community structure and function, specifically by smothering seagrasses and other primary producers that are critical to commercial fisheries and by creating anoxic conditions in enclosed embayments. Bottom-up factors are viewed as the primary drivers of these blooms, but increasing attention has been paid to biotic controls of species composition. In Washington State, USA, blooms are often dominated by Ulva spp. intertidally and Ulvaria obscura subtidally. Factors that could cause this spatial difference were examined, including competition, grazer preferences, salinity, photoacclimation, nutrient requirements, and responses to nutrient enrichment. Ulva specimens grew faster than Ulvaria in intertidal chambers but not significantly faster in subtidal chambers. Ulva was better able to acclimate to a high-light environment and was more tolerant of low salinity than Ulvaria. Ulvaria had higher tissue N content, chlorophyll, chlorophyll b: chlorophyll a, and protein content than Ulva. These differences suggest that nitrogen availability could affect species composition. A suite of five grazers preferred Ulva to Ulvaria in choice experiments. Thus, bottom-up factors allow Ulva to dominate the intertidal zone while resistance to grazers appears to allow Ulvaria to dominate the subtidal zone. While ulvoid algae are in the same functional-form group, they are not functionally redundant.

  10. Grazing preferences of marine isopods and amphipods on three prominent algal species of the Baltic Sea [rapid communication

    NASA Astrophysics Data System (ADS)

    Goecker, Margene E.; Kåll, Sara E.

    2003-12-01

    Preference tests were performed over a two-week period in September 2001 in which isopods ( Idotea baltica) and amphipods ( Gammarus oceanicus) were offered choices of three common species of algae from the Baltic Sea: Enteromorpha intestinalis, Cladophora spp., and Fucus vesiculosus. After a 48-hour starvation period, 20 individuals of each grazer species were placed in aquaria containing approximately 1.0 g of each algal species. Fifteen trials for each grazer species were run for 20 hours. We found that G. oceanicus ate significantly more Cladophora spp. and E. intestinalis than F. vesiculosus (p<0.001), with a preference order of: Cladophora spp.> E. intestinalis> F. vesiculosus. Similarly, I. baltica ate significantly more of both the filamentous green algae than F. vesiculosus (p<0.001), with a preference order of: E. intestinalis> Cladophora spp.> F. vesiculosus. Given the preference of isopods and amphipods for filamentous green algae, we might expect these algae to be maintained at low biomass levels. However, this is clearly not the case in the Baltic Sea. Nutrient enrichment (bottom-up effects) is the accepted dominant reason for the non-controlling impact of algal grazers, but other reasons may include cascading trophic effects resulting from the removal of large piscivorous fish (top-down effects).

  11. Oil Spills and Dispersants Can Cause the Initiation of Potentially Harmful Dinoflagellate Blooms ("Red Tides").

    PubMed

    Almeda, Rodrigo; Cosgrove, Sarah; Buskey, Edward J

    2018-05-15

    After oil spills and dispersant applications the formation of red tides or harmful algal blooms (HABs) has been observed, which can cause additional negative impacts in areas affected by oil spills. However, the link between oil spills and HABs is still unknown. Here, we present experimental evidence that demonstrates a connection between oil spills and HABs. We determined the effects of oil, dispersant-treated oil, and dispersant alone on the structure of natural plankton assemblages in the Northern Gulf of Mexico. In coastal waters, large tintinnids and oligotrich ciliates, major grazers of phytoplankton, were negatively affected by the exposure to oil and dispersant, whereas bloom-forming dinoflagellates ( Prorocentrum texanum, P. triestinum, and Scrippsiella trochoidea) notably increased their concentration. The removal of key grazers due to oil and dispersant disrupts the predator-prey controls ("top-down controls") that normally function in plankton food webs. This disruption of grazing pressure opens a "loophole" that allows certain dinoflagellates with higher tolerance to oil and dispersants than their grazers to grow and form blooms when there are no growth limiting factors (e.g., nutrients). Therefore, oil spills and dispersants can act as disrupters of predator-prey controls in plankton food webs and as indirect inducers of potentially harmful dinoflagellate blooms.

  12. Twitter as a Potential Disaster Risk Reduction Tool. Part II: Descriptive Analysis of Identified Twitter Activity during the 2013 Hattiesburg F4 Tornado.

    PubMed

    Cooper, Guy Paul; Yeager, Violet; Burkle, Frederick M; Subbarao, Italo

    2015-06-29

    This article describes a novel triangulation methodological approach for identifying twitter activity of regional active twitter users during the 2013 Hattiesburg EF-4 Tornado. A data extraction and geographically centered filtration approach was utilized to generate Twitter data for 48 hrs pre- and post-Tornado. The data was further validated using six sigma approach utilizing GPS data. The regional analysis revealed a total of 81,441 tweets, 10,646 Twitter users, 27,309 retweets and 2637 tweets with GPS coordinates. Twitter tweet activity increased 5 fold during the response to the Hattiesburg Tornado.  Retweeting activity increased 2.2 fold. Tweets with a hashtag increased 1.4 fold. Twitter was an effective disaster risk reduction tool for the Hattiesburg EF-4 Tornado 2013.

  13. Persistent Identifiers Implementation in EOSDIS

    NASA Technical Reports Server (NTRS)

    Ramapriyan, H. K. " Rama"

    2016-01-01

    This presentation provides the motivation for and status of implementation of persistent identifiers in NASA's Earth Observation System Data and Information System (EOSDIS). The motivation is provided from the point of view of long-term preservation of datasets such that a number of questions raised by current and future users can be answered easily and precisely. A number of artifacts need to be preserved along with datasets to make this possible, especially when the authors of datasets are no longer available to address users questions. The artifacts and datasets need to be uniquely and persistently identified and linked with each other for full traceability, understandability and scientific reproducibility. Current work in the Earth Science Data and Information System (ESDIS) Project and the Distributed Active Archive Centers (DAACs) in assigning Digital Object Identifiers (DOI) is discussed as well as challenges that remain to be addressed in the future.

  14. De Novo Sequencing of Hypericum perforatum Transcriptome to Identify Potential Genes Involved in the Biosynthesis of Active Metabolites

    PubMed Central

    He, Miao; Wang, Ying; Hua, Wenping; Zhang, Yuan; Wang, Zhezhi

    2012-01-01

    Background Hypericum perforatum L. (St. John’s wort) is a medicinal plant with pharmacological properties that are antidepressant, anti-inflammatory, antiviral, anti-cancer, and antibacterial. Its major active metabolites are hypericins, hyperforins, and melatonin. However, little genetic information is available for this species, especially that concerning the biosynthetic pathways for active ingredients. Methodology/Principal Findings Using de novo transcriptome analysis, we obtained 59,184 unigenes covering the entire life cycle of these plants. In all, 40,813 unigenes (68.86%) were annotated and 2,359 were assigned to secondary metabolic pathways. Among them, 260 unigenes are involved in the production of hypericin, hyperforin, and melatonin. Another 2,291 unigenes are classified as potential Type III polyketide synthase. Our BlastX search against the AGRIS database reveals 1,772 unigenes that are homologous to 47 known Arabidopsis transcription factor families. Further analysis shows that 10.61% (6,277) of these unigenes contain 7,643 SSRs. Conclusion We have identified a set of putative genes involved in several secondary metabolism pathways, especially those related to the synthesis of its active ingredients. Our results will serve as an important platform for public information about gene expression, genomics, and functional genomics in H. perforatum. PMID:22860059

  15. Retroviral insertional mutagenesis identifies Zeb2 activation as a novel leukemogenic collaborating event in CALM-AF10 transgenic mice.

    PubMed

    Caudell, David; Harper, David P; Novak, Rachel L; Pierce, Rachel M; Slape, Christopher; Wolff, Linda; Aplan, Peter D

    2010-02-11

    The t(10;11) translocation results in a CALM-AF10 fusion gene in a subset of leukemia patients. Expression of a CALM-AF10 transgene results in leukemia, with prolonged latency and incomplete penetrance, suggesting that additional events are necessary for leukemic transformation. CALM-AF10 mice infected with the MOL4070LTR retrovirus developed acute leukemia, and ligation-mediated polymerase chain reaction was used to identify retroviral insertions at 19 common insertion sites, including Zeb2, Nf1, Mn1, Evi1, Ift57, Mpl, Plag1, Kras, Erg, Vav1, and Gata1. A total of 26% (11 of 42) of the mice had retroviral integrations near Zeb2, a transcriptional corepressor leading to overexpression of the Zeb2-transcript. A total of 91% (10 of 11) of mice with Zeb2 insertions developed B-lineage acute lymphoblastic leukemia, suggesting that Zeb2 activation promotes the transformation of CALM-AF10 hematopoietic precursors toward B-lineage leukemias. More than half of the mice with Zeb2 integrations also had Nf1 integrations, suggesting cooperativity among CALM-AF10, Zeb2, and Ras pathway mutations. We searched for Nras, Kras, and Ptpn11 point mutations in the CALM-AF10 leukemic mice. Three mutations were identified, all of which occurred in mice with Zeb2 integrations, consistent with the hypothesis that Zeb2 and Ras pathway activation promotes B-lineage leukemic transformation in concert with CALM-AF10.

  16. Retroviral insertional mutagenesis identifies Zeb2 activation as a novel leukemogenic collaborating event in CALM-AF10 transgenic mice

    PubMed Central

    Caudell, David; Harper, David P.; Novak, Rachel L.; Pierce, Rachel M.; Slape, Christopher; Wolff, Linda

    2010-01-01

    The t(10;11) translocation results in a CALM-AF10 fusion gene in a subset of leukemia patients. Expression of a CALM-AF10 transgene results in leukemia, with prolonged latency and incomplete penetrance, suggesting that additional events are necessary for leukemic transformation. CALM-AF10 mice infected with the MOL4070LTR retrovirus developed acute leukemia, and ligation-mediated polymerase chain reaction was used to identify retroviral insertions at 19 common insertion sites, including Zeb2, Nf1, Mn1, Evi1, Ift57, Mpl, Plag1, Kras, Erg, Vav1, and Gata1. A total of 26% (11 of 42) of the mice had retroviral integrations near Zeb2, a transcriptional corepressor leading to overexpression of the Zeb2-transcript. A total of 91% (10 of 11) of mice with Zeb2 insertions developed B-lineage acute lymphoblastic leukemia, suggesting that Zeb2 activation promotes the transformation of CALM-AF10 hematopoietic precursors toward B-lineage leukemias. More than half of the mice with Zeb2 integrations also had Nf1 integrations, suggesting cooperativity among CALM-AF10, Zeb2, and Ras pathway mutations. We searched for Nras, Kras, and Ptpn11 point mutations in the CALM-AF10 leukemic mice. Three mutations were identified, all of which occurred in mice with Zeb2 integrations, consistent with the hypothesis that Zeb2 and Ras pathway activation promotes B-lineage leukemic transformation in concert with CALM-AF10. PMID:20007546

  17. Generalized query-based active learning to identify differentially methylated regions in DNA.

    PubMed

    Haque, Md Muksitul; Holder, Lawrence B; Skinner, Michael K; Cook, Diane J

    2013-01-01

    Active learning is a supervised learning technique that reduces the number of examples required for building a successful classifier, because it can choose the data it learns from. This technique holds promise for many biological domains in which classified examples are expensive and time-consuming to obtain. Most traditional active learning methods ask very specific queries to the Oracle (e.g., a human expert) to label an unlabeled example. The example may consist of numerous features, many of which are irrelevant. Removing such features will create a shorter query with only relevant features, and it will be easier for the Oracle to answer. We propose a generalized query-based active learning (GQAL) approach that constructs generalized queries based on multiple instances. By constructing appropriately generalized queries, we can achieve higher accuracy compared to traditional active learning methods. We apply our active learning method to find differentially DNA methylated regions (DMRs). DMRs are DNA locations in the genome that are known to be involved in tissue differentiation, epigenetic regulation, and disease. We also apply our method on 13 other data sets and show that our method is better than another popular active learning technique.

  18. An Investigation of Adolescent Girls' Global Self-Concept, Physical Self-Concept, Identified Regulation, and Leisure-Time Physical Activity in Physical Education

    ERIC Educational Resources Information Center

    Beasley, Emily Kristin; Garn, Alex C.

    2013-01-01

    This study examined the relationships among identified regulation, physical self-concept, global self-concept, and leisure-time physical activity with a sample of middle and high school girls (N = 319) enrolled in physical education. Based on Marsh's theory of self-concept, it was hypothesized that a) physical self-concept would mediate the…

  19. A Presenilin-1 Mutation Identified in Familial Alzheimer Disease with Cotton Wool Plaques Causes a Nearly Complete Loss of γ-Secretase Activity*

    PubMed Central

    Heilig, Elizabeth A.; Xia, Weiming; Shen, Jie; Kelleher, Raymond J.

    2010-01-01

    Mutations in presenilin-1 and presenilin-2 (PS1 and PS2) are the most common cause of familial Alzheimer disease. PS1 and PS2 are the presumptive catalytic components of the multisubunit γ-secretase complex, which proteolyzes a number of type I transmembrane proteins, including the amyloid precursor protein (APP) and Notch. APP processing by γ-secretase produces β-amyloid peptides (Aβ40 and Aβ42) that accumulate in the Alzheimer disease brain. Here we identify a pathogenic L435F mutation in PS1 in two affected siblings with early-onset familial Alzheimer disease characterized by deposition of cerebral cotton wool plaques. The L435F mutation resides in a conserved C-terminal PAL sequence implicated in active site conformation and catalytic activity. The impact of PS1 mutations in and around the PAL motif on γ-secretase activity was assessed by expression of mutant PS1 in mouse embryo fibroblasts lacking endogenous PS1 and PS2. Surprisingly, the L435F mutation caused a nearly complete loss of γ-secretase activity, including >90% reductions in the generation of Aβ40, Aβ42, and the APP and Notch intracellular domains. Two nonpathogenic PS1 mutations, P433L and L435R, caused essentially complete loss of γ-secretase activity, whereas two previously identified pathogenic PS1 mutations, P436Q and P436S, caused partial loss of function with substantial reductions in production of Aβ40, Aβ42, and the APP and Notch intracellular domains. These results argue against overproduction of Aβ42 as an essential property of presenilin proteins bearing pathogenic mutations. Rather, our findings provide support for the hypothesis that pathogenic mutations cause a general loss of presenilin function. PMID:20460383

  20. Identifying active foraminifera in the Sea of Japan using metatranscriptomic approach

    NASA Astrophysics Data System (ADS)

    Lejzerowicz, Franck; Voltsky, Ivan; Pawlowski, Jan

    2013-02-01

    Metagenetics represents an efficient and rapid tool to describe environmental diversity patterns of microbial eukaryotes based on ribosomal DNA sequences. However, the results of metagenetic studies are often biased by the presence of extracellular DNA molecules that are persistent in the environment, especially in deep-sea sediment. As an alternative, short-lived RNA molecules constitute a good proxy for the detection of active species. Here, we used a metatranscriptomic approach based on RNA-derived (cDNA) sequences to study the diversity of the deep-sea benthic foraminifera and compared it to the metagenetic approach. We analyzed 257 ribosomal DNA and cDNA sequences obtained from seven sediments samples collected in the Sea of Japan at depths ranging from 486 to 3665 m. The DNA and RNA-based approaches gave a similar view of the taxonomic composition of foraminiferal assemblage, but differed in some important points. First, the cDNA dataset was dominated by sequences of rotaliids and robertiniids, suggesting that these calcareous species, some of which have been observed in Rose Bengal stained samples, are the most active component of foraminiferal community. Second, the richness of monothalamous (single-chambered) foraminifera was particularly high in DNA extracts from the deepest samples, confirming that this group of foraminifera is abundant but not necessarily very active in the deep-sea sediments. Finally, the high divergence of undetermined sequences in cDNA dataset indicate the limits of our database and lack of knowledge about some active but possibly rare species. Our study demonstrates the capability of the metatranscriptomic approach to detect active foraminiferal species and prompt its use in future high-throughput sequencing-based environmental surveys.

  1. Using a behaviour change techniques taxonomy to identify active ingredients within trials of implementation interventions for diabetes care.

    PubMed

    Presseau, Justin; Ivers, Noah M; Newham, James J; Knittle, Keegan; Danko, Kristin J; Grimshaw, Jeremy M

    2015-04-23

    Methodological guidelines for intervention reporting emphasise describing intervention content in detail. Despite this, systematic reviews of quality improvement (QI) implementation interventions continue to be limited by a lack of clarity and detail regarding the intervention content being evaluated. We aimed to apply the recently developed Behaviour Change Techniques Taxonomy version 1 (BCTTv1) to trials of implementation interventions for managing diabetes to assess the capacity and utility of this taxonomy for characterising active ingredients. Three psychologists independently coded a random sample of 23 trials of healthcare system, provider- and/or patient-focused implementation interventions from a systematic review that included 142 such studies. Intervention content was coded using the BCTTv1, which describes 93 behaviour change techniques (BCTs) grouped within 16 categories. We supplemented the generic coding instructions within the BCTTv1 with decision rules and examples from this literature. Less than a quarter of possible BCTs within the BCTTv1 were identified. For implementation interventions targeting providers, the most commonly identified BCTs included the following: adding objects to the environment, prompts/cues, instruction on how to perform the behaviour, credible source, goal setting (outcome), feedback on outcome of behaviour, and social support (practical). For implementation interventions also targeting patients, the most commonly identified BCTs included the following: prompts/cues, instruction on how to perform the behaviour, information about health consequences, restructuring the social environment, adding objects to the environment, social support (practical), and goal setting (behaviour). The BCTTv1 mapped well onto implementation interventions directly targeting clinicians and patients and could also be used to examine the impact of system-level interventions on clinician and patient behaviour. The BCTTv1 can be used to characterise

  2. Twitter as a Potential Disaster Risk Reduction Tool. Part II: Descriptive Analysis of Identified Twitter Activity during the 2013 Hattiesburg F4 Tornado

    PubMed Central

    Cooper, Guy Paul; Yeager, Violet; Burkle, Frederick M.; Subbarao, Italo

    2015-01-01

    Background: This article describes a novel triangulation methodological approach for identifying twitter activity of regional active twitter users during the 2013 Hattiesburg EF-4 Tornado. Methodology: A data extraction and geographically centered filtration approach was utilized to generate Twitter data for 48 hrs pre- and post-Tornado. The data was further validated using six sigma approach utilizing GPS data. Results: The regional analysis revealed a total of 81,441 tweets, 10,646 Twitter users, 27,309 retweets and 2637 tweets with GPS coordinates. Conclusions: Twitter tweet activity increased 5 fold during the response to the Hattiesburg Tornado.  Retweeting activity increased 2.2 fold. Tweets with a hashtag increased 1.4 fold. Twitter was an effective disaster risk reduction tool for the Hattiesburg EF-4 Tornado 2013.  PMID:26203396

  3. Estrogen Degraders and Estrogen Degradation Pathway Identified in an Activated Sludge.

    PubMed

    Chen, Yi-Lung; Fu, Han-Yi; Lee, Tzong-Huei; Shih, Chao-Jen; Huang, Lina; Wang, Yu-Sheng; Ismail, Wael; Chiang, Yin-Ru

    2018-05-15

    The environmental release and fate of estrogens are becoming an increasing public concern. Bacterial degradation has been considered the main process for eliminating estrogens from wastewater treatment plants. Various bacterial isolates are reportedly capable of aerobic estrogen degradation, and several estrogen degradation pathways have been proposed in proteobacteria and actinobacteria. However, the ecophysiological relevance of estrogen-degrading bacteria in the environment is unclear. In this study, we investigated the estrogen degradation pathway and corresponding degraders in activated sludge collected from the Dihua Sewage Treatment Plant, Taipei, Taiwan. Cultivation-dependent and cultivation-independent methods were used to assess estrogen biodegradation in the collected activated sludge. Estrogen metabolite profile analysis revealed the production of pyridinestrone acid and two A/B-ring cleavage products in activated sludge incubated with estrone (1 mM), which are characteristic of the 4,5- seco pathway. PCR-based functional assays detected sequences closely related to alphaproteobacterial oecC , a key gene of the 4,5- seco pathway. Metagenomic analysis suggested that Novosphingobium spp. are major estrogen degraders in estrone-amended activated sludge. Novosphingobium sp. strain SLCC, an estrone-degrading alphaproteobacterium, was isolated from the examined activated sludge. The general physiology and metabolism of this strain were characterized. Pyridinestrone acid and the A/B-ring cleavage products were detected in estrone-grown strain SLCC cultures. The production of pyridinestrone acid was also observed during the aerobic incubation of strain SLCC with 3.7 nM (1 μg/liter) estrone. This concentration is close to that detected in many natural and engineered aquatic ecosystems. The presented data suggest the ecophysiological relevance of Novosphingobium spp. in activated sludge. IMPORTANCE Estrogens, which persistently contaminate surface water

  4. Multiplex image-based autophagy RNAi screening identifies SMCR8 as ULK1 kinase activity and gene expression regulator

    PubMed Central

    Jung, Jennifer; Nayak, Arnab; Schaeffer, Véronique; Starzetz, Tatjana; Kirsch, Achim K; Müller, Stefan; Dikic, Ivan; Mittelbronn, Michel; Behrends, Christian

    2017-01-01

    Autophagy is an intracellular recycling and degradation pathway that depends on membrane trafficking. Rab GTPases are central for autophagy but their regulation especially through the activity of Rab GEFs remains largely elusive. We employed a RNAi screen simultaneously monitoring different populations of autophagosomes and identified 34 out of 186 Rab GTPase, GAP and GEF family members as potential autophagy regulators, amongst them SMCR8. SMCR8 uses overlapping binding regions to associate with C9ORF72 or with a C9ORF72-ULK1 kinase complex holo-assembly, which function in maturation and formation of autophagosomes, respectively. While focusing on the role of SMCR8 during autophagy initiation, we found that kinase activity and gene expression of ULK1 are increased upon SMCR8 depletion. The latter phenotype involved association of SMCR8 with the ULK1 gene locus. Global mRNA expression analysis revealed that SMCR8 regulates transcription of several other autophagy genes including WIPI2. Collectively, we established SMCR8 as multifaceted negative autophagy regulator. DOI: http://dx.doi.org/10.7554/eLife.23063.001 PMID:28195531

  5. Genes Activated by Vibrio cholerae upon Exposure to Caenorhabditis elegans Reveal the Mannose-Sensitive Hemagglutinin To Be Essential for Colonization.

    PubMed

    List, Cornelia; Grutsch, Andreas; Radler, Claudia; Cakar, Fatih; Zingl, Franz G; Schild-Prüfert, Kristina; Schild, Stefan

    2018-01-01

    During its life cycle, the facultative human pathogen Vibrio cholerae , which is the causative agent of the diarrheal disease cholera, needs to adapt to a variety of different conditions, such as the human host or the aquatic environment. Importantly, cholera infections originate from the aquatic reservoir where V. cholerae persists between the outbreaks. In the aquatic environment, bacteria are constantly threatened by predatory protozoa and nematodes, but our knowledge of the response pathways and adaptation strategies of V. cholerae to such stressors is limited. Using a temporally controlled reporter system of transcription, we identified more than 100 genes of V. cholerae induced upon exposure to the nematode Caenorhabditis elegans , which emerged recently as a valuable model for environmental predation during the aquatic lifestyle of V. cholerae Besides others, we identified and validated the genes encoding the mannose-sensitive hemagglutinin (MSHA) type IV pilus to be significantly induced upon exposure to the nematode. Subsequent analyses demonstrated that the mannose-sensitive hemagglutinin is crucial for attachment of V. cholerae in the pharynx of the worm and initiation of colonization, which results in growth retardation and developmental delay of C. elegans Thus, the surface adhesion factor MSHA could be linked to a fitness advantage of V. cholerae upon contact with bacterium-grazing nematodes. IMPORTANCE The waterborne diarrheal disease cholera is caused by the bacterium Vibrio cholerae The facultative human pathogen persists as a natural inhabitant in the aquatic ecosystem between outbreaks. In contrast to the human host, V. cholerae requires a different set of genes to survive in this hostile environment. For example, predatory micrograzers are commonly found in the aquatic environment and use bacteria as a nutrient source, but knowledge of the interaction between bacterivorous grazers and V. cholerae is limited. In this study, we

  6. Gap-junctional channel and hemichannel activity of two recently identified connexin 26 mutants associated with deafness.

    PubMed

    Dalamon, Viviana; Fiori, Mariana C; Figueroa, Vania A; Oliva, Carolina A; Del Rio, Rodrigo; Gonzalez, Wendy; Canan, Jonathan; Elgoyhen, Ana B; Altenberg, Guillermo A; Retamal, Mauricio A

    2016-05-01

    Gap-junction channels (GJCs) are formed by head-to-head association of two hemichannels (HCs, connexin hexamers). HCs and GJCs are permeable to ions and hydrophilic molecules of up to Mr ~1 kDa. Hearing impairment of genetic origin is common, and mutations of connexin 26 (Cx26) are its major cause. We recently identified two novel Cx26 mutations in hearing-impaired subjects, L10P and G109V. L10P forms functional GJCs with slightly altered voltage dependence and HCs with decrease ATP/cationic dye selectivity. G109V does not form functional GJCs, but forms functional HCs with enhanced extracellular Ca(2+) sensitivity and subtle alterations in voltage dependence and ATP/cationic dye selectivity. Deafness associated with G109V could result from decreased GJCs activity, whereas deafness associated to L10P may have a more complex mechanism that involves changes in HC permeability.

  7. NRIP is newly identified as a Z-disc protein, activating calmodulin signaling for skeletal muscle contraction and regeneration.

    PubMed

    Chen, Hsin-Hsiung; Chen, Wen-Pin; Yan, Wan-Lun; Huang, Yuan-Chun; Chang, Szu-Wei; Fu, Wen-Mei; Su, Ming-Jai; Yu, I-Shing; Tsai, Tzung-Chieh; Yan, Yu-Ting; Tsao, Yeou-Ping; Chen, Show-Li

    2015-11-15

    Nuclear receptor interaction protein (NRIP, also known as DCAF6 and IQWD1) is a Ca(2+)-dependent calmodulin-binding protein. In this study, we newly identify NRIP as a Z-disc protein in skeletal muscle. NRIP-knockout mice were generated and found to have reduced muscle strength, susceptibility to fatigue and impaired adaptive exercise performance. The mechanisms of NRIP-regulated muscle contraction depend on NRIP being downstream of Ca(2+) signaling, where it stimulates activation of both 'calcineurin-nuclear factor of activated T-cells, cytoplasmic 1' (CaN-NFATc1; also known as NFATC1) and calmodulin-dependent protein kinase II (CaMKII) through interaction with calmodulin (CaM), resulting in the induction of mitochondrial activity and the expression of genes encoding the slow class of myosin, and in the regulation of Ca(2+) homeostasis through the internal Ca(2+) stores of the sarcoplasmic reticulum. Moreover, NRIP-knockout mice have a delayed regenerative capacity. The amount of NRIP can be enhanced after muscle injury and is responsible for muscle regeneration, which is associated with the increased expression of myogenin, desmin and embryonic myosin heavy chain during myogenesis, as well as for myotube formation. In conclusion, NRIP is a novel Z-disc protein that is important for skeletal muscle strength and regenerative capacity. © 2015. Published by The Company of Biologists Ltd.

  8. Faunal isotope records reveal trophic and nutrient dynamics in twentieth century Yellowstone grasslands

    PubMed Central

    Fox-Dobbs, Kena; Nelson, Abigail A.; Koch, Paul L.; Leonard, Jennifer A.

    2012-01-01

    Population sizes and movement patterns of ungulate grazers and their predators have fluctuated dramatically over the past few centuries, largely owing to overharvesting, land-use change and historic management. We used δ13C and δ15N values measured from bone collagen of historic and recent gray wolves and their potential primary prey from Yellowstone National Park to gain insight into the trophic dynamics and nutrient conditions of historic and modern grasslands. The diet of reintroduced wolves closely parallels that of the historic population. We suggest that a significant shift in faunal δ15N values over the past century reflects impacts of anthropogenic environmental changes on grassland ecosystems, including grazer-mediated shifts in grassland nitrogen cycle processes. PMID:22675135

  9. Ruminant diets and the Miocene extinction of European great apes

    PubMed Central

    Merceron, Gildas; Kaiser, Thomas M.; Kostopoulos, Dimitris S.; Schulz, Ellen

    2010-01-01

    The successful evolutionary radiations of European hominoids and pliopithecoids came to an end during the Late Miocene. Using ruminant diets as environmental proxies, it becomes possible to detect variations in vegetation over time with the potential to explain fluctuations in primate diversity along a NW–SE European transect. Analysis shows that ruminants had diverse diets when primate diversity reached its peak, with more grazers in eastern Europe and more browsers farther west. After the drop in primate diversity, grazers accounted for a greater part of western and central European communities. Eastwards, the converse trend was evident with more browsing ruminants. These opposite trends indicate habitat loss and an increase in environmental uniformity that may have severely favoured the decline of primate diversity. PMID:20519220

  10. Ruminant diets and the Miocene extinction of European great apes.

    PubMed

    Merceron, Gildas; Kaiser, Thomas M; Kostopoulos, Dimitris S; Schulz, Ellen

    2010-10-22

    The successful evolutionary radiations of European hominoids and pliopithecoids came to an end during the Late Miocene. Using ruminant diets as environmental proxies, it becomes possible to detect variations in vegetation over time with the potential to explain fluctuations in primate diversity along a NW-SE European transect. Analysis shows that ruminants had diverse diets when primate diversity reached its peak, with more grazers in eastern Europe and more browsers farther west. After the drop in primate diversity, grazers accounted for a greater part of western and central European communities. Eastwards, the converse trend was evident with more browsing ruminants. These opposite trends indicate habitat loss and an increase in environmental uniformity that may have severely favoured the decline of primate diversity.

  11. Quantitative High-Throughput Luciferase Screening in Identifying CAR Modulators.

    PubMed

    Lynch, Caitlin; Zhao, Jinghua; Wang, Hongbing; Xia, Menghang

    2016-01-01

    The constitutive androstane receptor (CAR, NR1I3) is responsible for the transcription of multiple drug metabolizing enzymes and transporters. There are two possible methods of activation for CAR, direct ligand binding and a ligand-independent method, which makes this a unique nuclear receptor. Both of these mechanisms require translocation of CAR from the cytoplasm into the nucleus. Interestingly, CAR is constitutively active in immortalized cell lines due to the basal nuclear location of this receptor. This creates an important challenge in most in vitro assay models because immortalized cells cannot be used without inhibiting the high basal activity. In this book chapter, we go into detail of how to perform quantitative high-throughput screens to identify hCAR1 modulators through the employment of a double stable cell line. Using this line, we are able to identify activators, as well as deactivators, of the challenging nuclear receptor, CAR.

  12. Application of Quantitative Structure–Activity Relationship Models of 5-HT1A Receptor Binding to Virtual Screening Identifies Novel and Potent 5-HT1A Ligands

    PubMed Central

    2015-01-01

    The 5-hydroxytryptamine 1A (5-HT1A) serotonin receptor has been an attractive target for treating mood and anxiety disorders such as schizophrenia. We have developed binary classification quantitative structure–activity relationship (QSAR) models of 5-HT1A receptor binding activity using data retrieved from the PDSP Ki database. The prediction accuracy of these models was estimated by external 5-fold cross-validation as well as using an additional validation set comprising 66 structurally distinct compounds from the World of Molecular Bioactivity database. These validated models were then used to mine three major types of chemical screening libraries, i.e., drug-like libraries, GPCR targeted libraries, and diversity libraries, to identify novel computational hits. The five best hits from each class of libraries were chosen for further experimental testing in radioligand binding assays, and nine of the 15 hits were confirmed to be active experimentally with binding affinity better than 10 μM. The most active compound, Lysergol, from the diversity library showed very high binding affinity (Ki) of 2.3 nM against 5-HT1A receptor. The novel 5-HT1A actives identified with the QSAR-based virtual screening approach could be potentially developed as novel anxiolytics or potential antischizophrenic drugs. PMID:24410373

  13. Use of an activated beta-catenin to identify Wnt pathway target genes in caenorhabditis elegans, including a subset of collagen genes expressed in late larval development.

    PubMed

    Jackson, Belinda M; Abete-Luzi, Patricia; Krause, Michael W; Eisenmann, David M

    2014-04-16

    The Wnt signaling pathway plays a fundamental role during metazoan development, where it regulates diverse processes, including cell fate specification, cell migration, and stem cell renewal. Activation of the beta-catenin-dependent/canonical Wnt pathway up-regulates expression of Wnt target genes to mediate a cellular response. In the nematode Caenorhabditis elegans, a canonical Wnt signaling pathway regulates several processes during larval development; however, few target genes of this pathway have been identified. To address this deficit, we used a novel approach of conditionally activated Wnt signaling during a defined stage of larval life by overexpressing an activated beta-catenin protein, then used microarray analysis to identify genes showing altered expression compared with control animals. We identified 166 differentially expressed genes, of which 104 were up-regulated. A subset of the up-regulated genes was shown to have altered expression in mutants with decreased or increased Wnt signaling; we consider these genes to be bona fide C. elegans Wnt pathway targets. Among these was a group of six genes, including the cuticular collagen genes, bli-1 col-38, col-49, and col-71. These genes show a peak of expression in the mid L4 stage during normal development, suggesting a role in adult cuticle formation. Consistent with this finding, reduction of function for several of the genes causes phenotypes suggestive of defects in cuticle function or integrity. Therefore, this work has identified a large number of putative Wnt pathway target genes during larval life, including a small subset of Wnt-regulated collagen genes that may function in synthesis of the adult cuticle.

  14. Rhodium(II) proximity-labeling identifies a novel target site on STAT3 for inhibitors with potent anti-leukemia activity

    PubMed Central

    Minus, Matthew B.; Liu, Wei; Vohidov, Farrukh; Kasembeli, Moses M.; Long, Xin; Krueger, Michael; Stevens, Alexandra; Kolosov, Mikhail I.; Sison, Edward Allen R.; Ball, Zachary T.

    2015-01-01

    Nearly 40% of children with acute myeloid leukemia (AML) suffer relapse due to chemoresistance, often involving upregulation of the oncoprotein STAT3 (signal transducer and activator of transcription 3). In this paper, rhodium(II)-catalyzed, proximity-driven modification identifies the STAT3 coiled-coil domain (CCD) as a novel ligand-binding site, and we describe a new naphthalene sulfonamide inhibitor that targets the CCD, blocks STAT3 function, and halts its disease-promoting effects in vitro, in tumor growth models, and in a leukemia mouse model, validating this new therapeutic target for resistant AML. PMID:26480340

  15. Emerging Fabric of Science: Persistent Identifiers and Knowledge Networks

    NASA Astrophysics Data System (ADS)

    Hugo, W.

    2017-12-01

    There is an increasing emphasis on the use of persistent identifiers in the description of scientific activity, whether this is done to cite scholarly publications and research output, reliably identify role players such as funders and researchers, or to provide long-lasting references to controlled vocabulary. The ICSU World Data System has been promoting the establishment of a "Knowledge Network" to describe research activity, realising that parts of the network will be established as a federated `system', based on linkages between registries of persistent identifiers. In addition, there is a growing focus on not only the relationship between these major role players and associated digital objects, but also on the processes of science: provenance, reproducibility, and re-usability being significant topics of discussion. The paper will focus on description of the `Fabric of Science' from the perspectives of both structure and processes, review the state of implementation of real services and infrastructure in support of it. A case is made for inclusion of persistent identifiers into the mainstream activities of scientists and data infrastructure managers, and for the development of services, such as Scholix, to make better use of the relationships between digital objects and major role players. A proposal is made for the adoption of a federated system of services that are based on a hybrid graph-object framework similar to Scholix for recording the activity of scientific research. Finally, links to related ideas are explored: novel ways of representing of knowledge (such as Nanopublications) and the possibility that the publication paradigm currently in use may have to be amended.

  16. Temporal Coupling with Cortex Distinguishes Spontaneous Neuronal Activities in Identified Basal Ganglia-Recipient and Cerebellar-Recipient Zones of the Motor Thalamus

    PubMed Central

    Nakamura, Kouichi C.; Sharott, Andrew; Magill, Peter J.

    2014-01-01

    Neurons of the motor thalamus mediate basal ganglia and cerebellar influences on cortical activity. To elucidate the net result of γ-aminobutyric acid-releasing or glutamatergic bombardment of the motor thalamus by basal ganglia or cerebellar afferents, respectively, we recorded the spontaneous activities of thalamocortical neurons in distinct identified “input zones” in anesthetized rats during defined cortical activity states. Unexpectedly, the mean rates and brain state dependencies of the firing of neurons in basal ganglia-recipient zone (BZ) and cerebellar-recipient zone (CZ) were matched during slow-wave activity (SWA) and cortical activation. However, neurons were distinguished during SWA by their firing regularities, low-threshold spike bursts and, more strikingly, by the temporal coupling of their activities to ongoing cortical oscillations. The firing of neurons across the BZ was stronger and more precisely phase-locked to cortical slow (∼1 Hz) oscillations, although both neuron groups preferentially fired at the same phase. In contrast, neurons in BZ and CZ fired at different phases of cortical spindles (7–12 Hz), but with similar strengths of coupled firing. Thus, firing rates do not reflect the predicted inhibitory–excitatory imbalance across the motor thalamus, and input zone-specific temporal coding through oscillatory synchronization with the cortex could partly mediate the different roles of basal ganglia and cerebellum in behavior. PMID:23042738

  17. Anomaly detection driven active learning for identifying suspicious tracks and events in WAMI video

    NASA Astrophysics Data System (ADS)

    Miller, David J.; Natraj, Aditya; Hockenbury, Ryler; Dunn, Katherine; Sheffler, Michael; Sullivan, Kevin

    2012-06-01

    We describe a comprehensive system for learning to identify suspicious vehicle tracks from wide-area motion (WAMI) video. First, since the road network for the scene of interest is assumed unknown, agglomerative hierarchical clustering is applied to all spatial vehicle measurements, resulting in spatial cells that largely capture individual road segments. Next, for each track, both at the cell (speed, acceleration, azimuth) and track (range, total distance, duration) levels, extreme value feature statistics are both computed and aggregated, to form summary (p-value based) anomaly statistics for each track. Here, to fairly evaluate tracks that travel across different numbers of spatial cells, for each cell-level feature type, a single (most extreme) statistic is chosen, over all cells traveled. Finally, a novel active learning paradigm, applied to a (logistic regression) track classifier, is invoked to learn to distinguish suspicious from merely anomalous tracks, starting from anomaly-ranked track prioritization, with ground-truth labeling by a human operator. This system has been applied to WAMI video data (ARGUS), with the tracks automatically extracted by a system developed in-house at Toyon Research Corporation. Our system gives promising preliminary results in highly ranking as suspicious aerial vehicles, dismounts, and traffic violators, and in learning which features are most indicative of suspicious tracks.

  18. Quantitative High-throughput Luciferase Screening in Identifying CAR Modulators

    PubMed Central

    Lynch, Caitlin; Zhao, Jinghua; Wang, Hongbing; Xia, Menghang

    2017-01-01

    Summary The constitutive androstane receptor (CAR, NR1I3) is responsible for the transcription of multiple drug metabolizing enzymes and transporters. There are two possible methods of activation for CAR, direct ligand binding and a ligand-independent method, which makes this a unique nuclear receptor. Both of these mechanisms require translocation of CAR from the cytoplasm into the nucleus. Interestingly, CAR is constitutively active in immortalized cell lines due to the basal nuclear location of this receptor. This creates an important challenge in most in vitro assay models because immortalized cells cannot be used without inhibiting the basal activity. In this book chapter, we go into detail of how to perform quantitative high-throughput screens to identify hCAR1 modulators through the employment of a double stable cell line. Using this line, we are able to identify activators, as well as deactivators, of the challenging nuclear receptor, CAR. PMID:27518621

  19. A high-throughput screen against pantothenate synthetase (PanC) identifies 3-biphenyl-4-cyanopyrrole-2-carboxylic acids as a new class of inhibitor with activity against Mycobacterium tuberculosis.

    PubMed

    Kumar, Anuradha; Casey, Allen; Odingo, Joshua; Kesicki, Edward A; Abrahams, Garth; Vieth, Michal; Masquelin, Thierry; Mizrahi, Valerie; Hipskind, Philip A; Sherman, David R; Parish, Tanya

    2013-01-01

    The enzyme pantothenate synthetase, PanC, is an attractive drug target in Mycobacterium tuberculosis. It is essential for the in vitro growth of M. tuberculosis and for survival of the bacteria in the mouse model of infection. PanC is absent from mammals. We developed an enzyme-based assay to identify inhibitors of PanC, optimized it for high-throughput screening, and tested a large and diverse library of compounds for activity. Two compounds belonging to the same chemical class of 3-biphenyl-4- cyanopyrrole-2-carboxylic acids had activity against the purified recombinant protein, and also inhibited growth of live M. tuberculosis in manner consistent with PanC inhibition. Thus we have identified a new class of PanC inhibitors with whole cell activity that can be further developed.

  20. SOCIODEMOGRAPHIC DATA USED FOR IDENTIFYING ...

    EPA Pesticide Factsheets

    Due to unique social and demographic characteristics, various segments of the population may experience exposures different from those of the general population, which, in many cases, may be greater. When risk assessments do not characterize subsets of the general population, the populations that may experience the greatest risk remain unidentified. When such populations are not identified, the social and demographic data relevant to these populations is not considered when preparing exposure estimates, which can underestimate exposure and risk estimates for at-risk populations. Thus, it is necessary for risk or exposure assessors characterizing a diverse population, to first identify and then enumerate certain groups within the general population who are at risk for greater contaminant exposures. The document entitled Sociodemographic Data Used for Identifying Potentially Highly Exposed Populations (also referred to as the Highly Exposed Populations document), assists assessors in identifying and enumerating potentially highly exposed populations. This document presents data relating to factors which potentially impact an individual or group's exposure to environmental contaminants based on activity patterns (how time is spent), microenvironments (locations where time is spent), and other socio-demographic data such as age, gender, race and economic status. Populations potentially more exposed to various chemicals of concern, relative to the general population

  1. Activated iron-containing microglia in the human hippocampus identified by magnetic resonance imaging in Alzheimer disease

    PubMed Central

    Zeineh, Michael M.; Chen, Yuanxin; Kitzler, Hagen H.; Hammond, Robert; Vogel, Hannes; Rutt, Brian K.

    2016-01-01

    Although amyloid plaques and neurofibrillary pathology play important roles in Alzheimer disease (AD), our understanding of AD is incomplete, and the contribution of microglia and iron to neurodegeneration is unknown. High-field magnetic resonance imaging (MRI) is exquisitely sensitive to microscopic iron. To explore iron-associated neuroinflammatory AD pathology, we studied AD and control human brain specimens by (1) performing ultra-high resolution ex vivo 7 Tesla MRI, (2) coregistering the MRI with successive histologic staining for iron, microglia, amyloid beta, and tau, and (3) quantifying the relationship between magnetic resonance signal intensity and histological staining. In AD, we identified numerous small MR hypointensities primarily within the subiculum that were best explained by the combination of microscopic iron and activated microglia (p = 0.025), in contradistinction to the relatively lesser contribution of tau or amyloid. Neuropathologically, this suggests that microglial-mediated neurodegeneration may occur in the hippocampal formation in AD and is detectable by ultra-high resolution MRI. PMID:26190634

  2. Activated iron-containing microglia in the human hippocampus identified by magnetic resonance imaging in Alzheimer disease.

    PubMed

    Zeineh, Michael M; Chen, Yuanxin; Kitzler, Hagen H; Hammond, Robert; Vogel, Hannes; Rutt, Brian K

    2015-09-01

    Although amyloid plaques and neurofibrillary pathology play important roles in Alzheimer disease (AD), our understanding of AD is incomplete, and the contribution of microglia and iron to neurodegeneration is unknown. High-field magnetic resonance imaging (MRI) is exquisitely sensitive to microscopic iron. To explore iron-associated neuroinflammatory AD pathology, we studied AD and control human brain specimens by (1) performing ultra-high resolution ex vivo 7 Tesla MRI, (2) coregistering the MRI with successive histologic staining for iron, microglia, amyloid beta, and tau, and (3) quantifying the relationship between magnetic resonance signal intensity and histological staining. In AD, we identified numerous small MR hypointensities primarily within the subiculum that were best explained by the combination of microscopic iron and activated microglia (p = 0.025), in contradistinction to the relatively lesser contribution of tau or amyloid. Neuropathologically, this suggests that microglial-mediated neurodegeneration may occur in the hippocampal formation in AD and is detectable by ultra-high resolution MRI. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Maximal Predictability Approach for Identifying the Right Descriptors for Electrocatalytic Reactions.

    PubMed

    Krishnamurthy, Dilip; Sumaria, Vaidish; Viswanathan, Venkatasubramanian

    2018-02-01

    Density functional theory (DFT) calculations are being routinely used to identify new material candidates that approach activity near fundamental limits imposed by thermodynamics or scaling relations. DFT calculations are associated with inherent uncertainty, which limits the ability to delineate materials (distinguishability) that possess high activity. Development of error-estimation capabilities in DFT has enabled uncertainty propagation through activity-prediction models. In this work, we demonstrate an approach to propagating uncertainty through thermodynamic activity models leading to a probability distribution of the computed activity and thereby its expectation value. A new metric, prediction efficiency, is defined, which provides a quantitative measure of the ability to distinguish activity of materials and can be used to identify the optimal descriptor(s) ΔG opt . We demonstrate the framework for four important electrochemical reactions: hydrogen evolution, chlorine evolution, oxygen reduction and oxygen evolution. Future studies could utilize expected activity and prediction efficiency to significantly improve the prediction accuracy of highly active material candidates.

  4. Context-dependency in the effects of nutrient loading and consumers on the availability of space in marine rocky environments.

    PubMed

    Bulleri, Fabio; Russell, Bayden D; Connell, Sean D

    2012-01-01

    Enhanced nutrient loading and depletion of consumer populations interact to alter the structure of aquatic plant communities. Nonetheless, variation between adjacent habitats in the relative strength of bottom-up (i.e. nutrients) versus top-down (i.e. grazing) forces as determinants of community structure across broad spatial scales remains unexplored. We experimentally assessed the importance of grazing pressure and nutrient availability on the development of macroalgal assemblages and the maintenance of unoccupied space in habitats differing in physical conditions (i.e. intertidal versus subtidal), across regions of contrasting productivity (oligotrophic coasts of South Australia versus the more productive coasts of Eastern Australia). In Eastern Australia, grazers were effective in maintaining space free of macroalgae in both intertidal and subtidal habitats, irrespective of nutrient levels. Conversely, in South Australia, grazers could not prevent colonization of space by turf-forming macroalgae in subtidal habitats regardless of nutrients levels, yet in intertidal habitats removal of grazers reduced unoccupied space when nutrients were elevated. Assessing the effects of eutrophication in coastal waters requires balancing our understanding between local consumer pressure and background oceanographic conditions that affect productivity. This broader-based understanding may assist in reconciling disproportionately large local-scale variation, a characteristic of ecology, with regional scale processes that are often of greater relevance to policy making and tractability to management.

  5. Peer Promotions as a Method to Identify Quality Content

    ERIC Educational Resources Information Center

    Gunnarsson, Bjorn Levi; Alterman, Richard

    2014-01-01

    Promoting blog content is a social activity--a means of communicating one student's appreciation of another student's work. This article explores the feasibility of using student promotions of content, in a blogosphere, to identify quality content, and implications for students and instructors. We show that students actively and voluntarily…

  6. Raman spectroscopy applied to identify metabolites in urine of physically active subjects.

    PubMed

    Moreira, Letícia Parada; Silveira, Landulfo; da Silva, Alexandre Galvão; Fernandes, Adriana Barrinha; Pacheco, Marcos Tadeu Tavares; Rocco, Débora Dias Ferraretto Moura

    2017-11-01

    Raman spectroscopy is a rapid and non-destructive technique suitable for biological fluids analysis. In this work, dispersive Raman spectroscopy has been employed as a rapid and nondestructive technique to detect the metabolites in urine of physically active subjects before and after vigorous 30min pedaling or running compared to sedentary subjects. For so, urine samples from 9 subjects were obtained before and immediately after physical activities and submitted to Raman spectroscopy (830nm excitation, 250mW laser power, 20s integration time) and compared to urine from 5 sedentary subjects. The Raman spectra of urine from sedentary showed peaks related to urea, creatinine, ketone bodies, phosphate and other nitrogenous compounds. These metabolic biomarkers presented peaks with different intensities in the urine of physically active individuals after exercises compared to before, measured by the intensity of selected peaks the Raman spectra, which means different concentrations after training. These peaks presented different intensity values for each subject before physical activity, also behaving differently compared to the post-training: some subjects presented increase while others decrease the intensity. Raman spectroscopy may allow the development of a rapid and non-destructive test for metabolic evaluation of the physical training in active and trained subjects using urine samples, allowing nutrition adjustment with the sport's performance. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Identifying key areas for active interprofessional learning partnerships: A facilitated dialogue.

    PubMed

    Steven, Kathryn; Angus, Allyson; Breckenridge, Jenna; Davey, Peter; Tully, Vicki; Muir, Fiona

    2016-11-01

    Student and service user involvement is recognised as an important factor in creating interprofessional education (IPE) opportunities. We used a team-based learning approach to bring together undergraduate health professional students, early career professionals (ECPs), public partners, volunteers, and carers to explore learning partnerships. Influenced by evaluative inquiry, this qualitative study used a free text response to allow participants to give their own opinion. A total of 153 participants (50 public partners and 103 students and professionals representing 11 healthcare professions) took part. Participants were divided into mixed groups of six (n = 25) and asked to identify areas where students, professionals, and public could work together to improve health professional education. Each group documented their discussions by summarising agreed areas and next steps. Responses were collected and transcribed for inductive content analysis. Seven key themes (areas for joint working) were identified: communication, public as partners, standards of conduct, IPE, quality improvement, education, and learning environments. The team-based learning format enabled undergraduate and postgraduate health professionals to achieve consensus with public partners on areas for IPE and collaboration. Some of our results may be context-specific but the approach is generalisable to other areas.

  8. Nonnutrient Anthropogenic Chemicals in Seagrass Ecosystems: Fate and Effects

    EPA Science Inventory

    Literature reviews have been published for seagrass taxonomy, geographical distribution, species diversity, grazer-epiphyte interactions, morphology, physiology, salinity requirements, and nutrient impacts (Schaffer 1995; Jernakoff et al. 1996; Touchette and Burholder 2000; Borto...

  9. Exercise and physical activity in asylum seekers in Northern England; using the theoretical domains framework to identify barriers and facilitators.

    PubMed

    Haith-Cooper, Melanie; Waskett, Catherine; Montague, Jane; Horne, Maria

    2018-06-19

    Many asylum seekers have complex mental health needs which can be exacerbated by the challenging circumstances in which they live and difficulties accessing health services. Regular moderate physical activity can improve mental health and would be a useful strategy to achieve this. Evidence suggests there are barriers to engaging black and minority ethnic groups in physical activity, but there is little research around asylum seekers to address the key barriers and facilitators in this group. A two stage qualitative study used semi-structured interviews underpinned by the Theoretical Domains Framework. The interviews were conducted in voluntary sector groups in four towns/ cities in Northern England. Purposive sampling recruited 36 asylum seekers from 18 different countries. Interviews were audio recorded, transcribed verbatim and subject to framework analysis. Stage two involved a nominal group technique with five key stakeholders including asylum seekers and those that work with them. They followed a four stage process to rank and reach consensus on the key barrier to undertaking physical activity/ exercise that could be addressed locally through a future intervention. A number of barriers and facilitators were identified including a lack of understanding of the term physical activity and recommended levels but knowledge of the health benefits of physical activity/ exercise and the motivation to increase levels having engaged with activities back home. Living as an asylum seeker was considered a barrier due to the stress, poverty and temporary nature of living in an unfamiliar place. The outcome of the nominal group technique was that a lack of knowledge of facilities in the local area was the prevailing barrier that could be addressed. Public health practitioners could develop interventions which capitalise on the motivation and knowledge of asylum seekers to encourage an increase in physical activity which may in turn reduce the breadth and depth of mental

  10. Periodic colonic motor activity identified by 24-h pancolonic ambulatory manometry in humans.

    PubMed

    Hagger, R; Kumar, Devinder; Benson, M; Grundy, A

    2002-06-01

    The pattern of colonic motor activity in healthy humans has not been fully elucidated to date. The aim of this study was to evaluate colorectal motor activity employing 24-h ambulant pancolonic manometry. Ten healthy volunteers (6F, 4M), aged 19-31 years were studied. Motor activity was measured using two custom-made silicone coated catheters, each with five solid-state pressure transducers. No bowel preparation or sedation was used. The study period was 24 h. A total of 232 h of recording was obtained. Sixty-three high amplitude propagated contractions were observed, median six per 24-h period. Low-amplitude colonic contractile activity showed regional and diurnal variations. Frequency of contraction was highest in the right colon [median 5.26 cpm (cycles per minute)], and transverse colon and splenic flexure (median 5.15 cpm). The interval between colonic motor complexes was shortest in the transverse colon and splenic flexure. This study introduces a new technique for the evaluation of colorectal motor activity. Subjects were studied in an ambulant setting in their own environment ensuring that this method of study is as physiological as possible. This study demonstrates that colonic motor activity has two main components: high amplitude propagated contractions and low amplitude colonic contractile activity.

  11. Summertime grazing impact of the dominant macrozooplankton off the Western Antarctic Peninsula

    NASA Astrophysics Data System (ADS)

    Bernard, Kim S.; Steinberg, Deborah K.; Schofield, Oscar M. E.

    2012-04-01

    The Western Antarctic Peninsula (WAP) is a region of rapid climate change that is altering plankton community structure. To investigate how these changes may impact carbon and energy transfer in the pelagic food web, grazing rates of the five dominant macrozooplankton species (euphausiids Euphausia superba, Euphausia crystallorophias, and Thysanöessa macrura; the pteropod Limacina helicina, and the salp Salpa thompsoni) in the WAP were measured in January 2009 and 2010 as part of the Palmer Antarctica Long-Term Ecological Research (LTER) study. Measurements were made across the coastal-shelf-offshore and north-south gradients of the LTER survey grid. Highest grazing rates occurred offshore in both years, and in the south during 2009 and north during 2010, all associated with the presence of large localized salp blooms. During both years, E. superba was the major grazer at the coast, while S. thompsoni dominated grazing offshore. L. helicina was an important grazer throughout the study area during both years, but especially so over the shelf during 2009. During 2009, there was little difference in the relative importance of the macrozooplankton grazers along the north-south gradient. The presence of a salp bloom in the north during 2010, though, resulted in a distinct shift in the relative importance of major grazers from the euphausiids and L. helicina in the south to salps in the north. Grazing impact was low in coastal waters (≤0.3% of phytoplankton standing stock and ≤0.6% of primary productivity). In contrast, in the offshore waters, where salp blooms were observed, grazing impacts of up to 30% of standing stock and 169% of primary productivity were recorded. If S. thompsoni and L. helicina continue to expand their ranges and increase in abundance, the associated shift in the food web dynamics of the WAP will alter the regional flow of carbon through the WAP food webs and the export of carbon to depth.

  12. Organ-specific carboxylesterase profiling identifies the small intestine and kidney as major contributors of activation of the anticancer prodrug CPT-11

    PubMed Central

    Hatfield, M. Jason; Tsurkan, Lyudmila; Garrett, Michael; Shaver, Timothy M.; Hyatt, Janice L.; Edwards, Carol C.; Hicks, Latorya D.; Potter, Philip M.

    2010-01-01

    The activation of the anticancer prodrug CPT-11, to its active metabolite SN-38, is primarily mediated by carboxylesterases (CE). In humans, three CEs have been identified, of which human liver CE (hCE1; CES1) and human intestinal CE (hiCE; CES2) demonstrate significant ability to hydrolyze the drug. However, while the kinetic parameters of CPT-11 hydrolysis have been measured, the actual contribution of each enzyme to activate the drug in biological samples has not been addressed. Hence, we have used a combination of specific CE inhibition and conventional chromatographic techniques to determine the amounts, and hydrolytic activity, of CEs present within human liver, kidney, intestinal and lung specimens. These studies confirm that hiCE demonstrates the most efficient kinetic parameters for CPT-11 activation, however, due to the high levels of hCE1 that are expressed in liver, the latter enzyme can contribute up to 50% of the total of drug hydrolysis in this tissue. Conversely, in human duodenum, jejunum, ileum and kidney, where hCE1 expression is very low, greater than 99% of the conversion of CPT-11 to SN-38 was mediated by hiCE. Furthermore, analysis of lung microsomal extracts indicated that CPT-11 activation was more proficient in samples obtained from smokers. Overall, our studies demonstrate that hCE1 plays a significant role in CPT-11 hydrolysis even though it is up to 100-fold less efficient at drug activation than hiCE, and that drug activation in the intestine and kidney are likely major contributors to SN-38 production in vivo. PMID:20833148

  13. Rhodium(II) Proximity-Labeling Identifies a Novel Target Site on STAT3 for Inhibitors with Potent Anti-Leukemia Activity.

    PubMed

    Minus, Matthew B; Liu, Wei; Vohidov, Farrukh; Kasembeli, Moses M; Long, Xin; Krueger, Michael J; Stevens, Alexandra; Kolosov, Mikhail I; Tweardy, David J; Sison, Edward Allan R; Redell, Michele S; Ball, Zachary T

    2015-10-26

    Nearly 40 % of children with acute myeloid leukemia (AML) suffer relapse arising from chemoresistance, often involving upregulation of the oncoprotein STAT3 (signal transducer and activator of transcription 3). Herein, rhodium(II)-catalyzed, proximity-driven modification identifies the STAT3 coiled-coil domain (CCD) as a novel ligand-binding site, and we describe a new naphthalene sulfonamide inhibitor that targets the CCD, blocks STAT3 function, and halts its disease-promoting effects in vitro, in tumor growth models, and in a leukemia mouse model, validating this new therapeutic target for resistant AML. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Scientometric methods for identifying emerging technologies

    DOEpatents

    Abercrombie, Robert K; Schlicher, Bob G; Sheldon, Frederick T

    2015-11-03

    Provided is a method of generating a scientometric model that tracks the emergence of an identified technology from initial discovery (via original scientific and conference literature), through critical discoveries (via original scientific, conference literature and patents), transitioning through Technology Readiness Levels (TRLs) and ultimately on to commercial application. During the period of innovation and technology transfer, the impact of scholarly works, patents and on-line web news sources are identified. As trends develop, currency of citations, collaboration indicators, and on-line news patterns are identified. The combinations of four distinct and separate searchable on-line networked sources (i.e., scholarly publications and citation, worldwide patents, news archives, and on-line mapping networks) are assembled to become one collective network (a dataset for analysis of relations). This established network becomes the basis from which to quickly analyze the temporal flow of activity (searchable events) for the example subject domain.

  15. The Protein Identifier Cross-Referencing (PICR) service: reconciling protein identifiers across multiple source databases.

    PubMed

    Côté, Richard G; Jones, Philip; Martens, Lennart; Kerrien, Samuel; Reisinger, Florian; Lin, Quan; Leinonen, Rasko; Apweiler, Rolf; Hermjakob, Henning

    2007-10-18

    Each major protein database uses its own conventions when assigning protein identifiers. Resolving the various, potentially unstable, identifiers that refer to identical proteins is a major challenge. This is a common problem when attempting to unify datasets that have been annotated with proteins from multiple data sources or querying data providers with one flavour of protein identifiers when the source database uses another. Partial solutions for protein identifier mapping exist but they are limited to specific species or techniques and to a very small number of databases. As a result, we have not found a solution that is generic enough and broad enough in mapping scope to suit our needs. We have created the Protein Identifier Cross-Reference (PICR) service, a web application that provides interactive and programmatic (SOAP and REST) access to a mapping algorithm that uses the UniProt Archive (UniParc) as a data warehouse to offer protein cross-references based on 100% sequence identity to proteins from over 70 distinct source databases loaded into UniParc. Mappings can be limited by source database, taxonomic ID and activity status in the source database. Users can copy/paste or upload files containing protein identifiers or sequences in FASTA format to obtain mappings using the interactive interface. Search results can be viewed in simple or detailed HTML tables or downloaded as comma-separated values (CSV) or Microsoft Excel (XLS) files suitable for use in a local database or a spreadsheet. Alternatively, a SOAP interface is available to integrate PICR functionality in other applications, as is a lightweight REST interface. We offer a publicly available service that can interactively map protein identifiers and protein sequences to the majority of commonly used protein databases. Programmatic access is available through a standards-compliant SOAP interface or a lightweight REST interface. The PICR interface, documentation and code examples are available at

  16. The Protein Identifier Cross-Referencing (PICR) service: reconciling protein identifiers across multiple source databases

    PubMed Central

    Côté, Richard G; Jones, Philip; Martens, Lennart; Kerrien, Samuel; Reisinger, Florian; Lin, Quan; Leinonen, Rasko; Apweiler, Rolf; Hermjakob, Henning

    2007-01-01

    Background Each major protein database uses its own conventions when assigning protein identifiers. Resolving the various, potentially unstable, identifiers that refer to identical proteins is a major challenge. This is a common problem when attempting to unify datasets that have been annotated with proteins from multiple data sources or querying data providers with one flavour of protein identifiers when the source database uses another. Partial solutions for protein identifier mapping exist but they are limited to specific species or techniques and to a very small number of databases. As a result, we have not found a solution that is generic enough and broad enough in mapping scope to suit our needs. Results We have created the Protein Identifier Cross-Reference (PICR) service, a web application that provides interactive and programmatic (SOAP and REST) access to a mapping algorithm that uses the UniProt Archive (UniParc) as a data warehouse to offer protein cross-references based on 100% sequence identity to proteins from over 70 distinct source databases loaded into UniParc. Mappings can be limited by source database, taxonomic ID and activity status in the source database. Users can copy/paste or upload files containing protein identifiers or sequences in FASTA format to obtain mappings using the interactive interface. Search results can be viewed in simple or detailed HTML tables or downloaded as comma-separated values (CSV) or Microsoft Excel (XLS) files suitable for use in a local database or a spreadsheet. Alternatively, a SOAP interface is available to integrate PICR functionality in other applications, as is a lightweight REST interface. Conclusion We offer a publicly available service that can interactively map protein identifiers and protein sequences to the majority of commonly used protein databases. Programmatic access is available through a standards-compliant SOAP interface or a lightweight REST interface. The PICR interface, documentation and

  17. DNA metabarcoding illuminates dietary niche partitioning by African large herbivores.

    PubMed

    Kartzinel, Tyler R; Chen, Patricia A; Coverdale, Tyler C; Erickson, David L; Kress, W John; Kuzmina, Maria L; Rubenstein, Daniel I; Wang, Wei; Pringle, Robert M

    2015-06-30

    Niche partitioning facilitates species coexistence in a world of limited resources, thereby enriching biodiversity. For decades, biologists have sought to understand how diverse assemblages of large mammalian herbivores (LMH) partition food resources. Several complementary mechanisms have been identified, including differential consumption of grasses versus nongrasses and spatiotemporal stratification in use of different parts of the same plant. However, the extent to which LMH partition food-plant species is largely unknown because comprehensive species-level identification is prohibitively difficult with traditional methods. We used DNA metabarcoding to quantify diet breadth, composition, and overlap for seven abundant LMH species (six wild, one domestic) in semiarid African savanna. These species ranged from almost-exclusive grazers to almost-exclusive browsers: Grass consumption inferred from mean sequence relative read abundance (RRA) ranged from >99% (plains zebra) to <1% (dik-dik). Grass RRA was highly correlated with isotopic estimates of % grass consumption, indicating that RRA conveys reliable quantitative information about consumption. Dietary overlap was greatest between species that were similar in body size and proportional grass consumption. Nonetheless, diet composition differed between all species-even pairs of grazers matched in size, digestive physiology, and location-and dietary similarity was sometimes greater across grazing and browsing guilds than within them. Such taxonomically fine-grained diet partitioning suggests that coarse trophic categorizations may generate misleading conclusions about competition and coexistence in LMH assemblages, and that LMH diversity may be more tightly linked to plant diversity than is currently recognized.

  18. DNA metabarcoding illuminates dietary niche partitioning by African large herbivores

    PubMed Central

    Kartzinel, Tyler R.; Chen, Patricia A.; Coverdale, Tyler C.; Erickson, David L.; Kress, W. John; Kuzmina, Maria L.; Rubenstein, Daniel I.; Wang, Wei; Pringle, Robert M.

    2015-01-01

    Niche partitioning facilitates species coexistence in a world of limited resources, thereby enriching biodiversity. For decades, biologists have sought to understand how diverse assemblages of large mammalian herbivores (LMH) partition food resources. Several complementary mechanisms have been identified, including differential consumption of grasses versus nongrasses and spatiotemporal stratification in use of different parts of the same plant. However, the extent to which LMH partition food-plant species is largely unknown because comprehensive species-level identification is prohibitively difficult with traditional methods. We used DNA metabarcoding to quantify diet breadth, composition, and overlap for seven abundant LMH species (six wild, one domestic) in semiarid African savanna. These species ranged from almost-exclusive grazers to almost-exclusive browsers: Grass consumption inferred from mean sequence relative read abundance (RRA) ranged from >99% (plains zebra) to <1% (dik-dik). Grass RRA was highly correlated with isotopic estimates of % grass consumption, indicating that RRA conveys reliable quantitative information about consumption. Dietary overlap was greatest between species that were similar in body size and proportional grass consumption. Nonetheless, diet composition differed between all species—even pairs of grazers matched in size, digestive physiology, and location—and dietary similarity was sometimes greater across grazing and browsing guilds than within them. Such taxonomically fine-grained diet partitioning suggests that coarse trophic categorizations may generate misleading conclusions about competition and coexistence in LMH assemblages, and that LMH diversity may be more tightly linked to plant diversity than is currently recognized. PMID:26034267

  19. Recurrent TERT promoter mutations identified in a large-scale study of multiple tumor types are associated with increased TERT expression and telomerase activation

    PubMed Central

    Huang, Dong-Sheng; Wang, Zhaohui; He, Xu-Jun; Diplas, Bill H.; Yang, Rui; Killela, Patrick J.; Liang, Junbo; Meng, Qun; Ye, Zai-Yuan; Wang, Wei; Jiang, Xiao-Ting; Xu, Li; He, Xiang-Lei; Zhao, Zhong-Sheng; Xu, Wen-Juan; Wang, Hui-Ju; Ma, Ying-Yu; Xia, Ying-Jie; Li, Li; Zhang, Ru-Xuan; Jin, Tao; Zhao, Zhong-Kuo; Xu, Ji; Yu, Sheng; Wu, Fang; Wang, Si-Zhen; Jiao, Yu-Chen; Yan, Hai; Tao, Hou-Quan

    2015-01-01

    Background Several somatic mutation hotspots were recently identified in the TERT promoter region in human cancers. Large scale studies of these mutations in multiple tumor types are limited, in particular in Asian populations. This study aimed to: analyze TERT promoter mutations in multiple tumor types in a large Chinese patient cohort, investigate novel tumor types and assess the functional significance of the mutations. Methods TERT promoter mutation status was assessed by Sanger sequencing for 13 different tumor types and 799 tumor tissues from Chinese cancer patients. Thymic epithelial tumors, gastrointestinal leiomyoma, and gastric schwannoma were included, for which the TERT promoter has not been previously sequenced. Functional studies included TERT expression by RT-qPCR, telomerase activity by the TRAP assay, and promoter activity by the luciferase reporter assay. Results TERT promoter mutations were highly frequent in glioblastoma (83.9%), urothelial carcinoma (64.5%), oligodendroglioma (70.0%), medulloblastoma (33.3%), and hepatocellular carcinoma (31.4%). C228T and C250T were the most common mutations. In urothelial carcinoma, several novel rare mutations were identified. TERT promoter mutations were absent in GIST, thymic epithelial tumors, gastrointestinal leiomyoma, gastric schwannoma, cholangiocarcinoma, gastric and pancreatic cancer. TERT promoter mutations highly correlated with upregulated TERT mRNA expression and telomerase activity in adult gliomas. These mutations differentially enhanced the transcriptional activity of the TERT core promoter. Conclusions TERT promoter mutations are frequent in multiple tumor types and have similar distributions in Chinese cancer patients. The functional significance of these mutations reflect the importance to telomere maintenance and hence tumorigenesis, making them potential therapeutic targets. PMID:25843513

  20. Identifying risk event in Indonesian fresh meat supply chain

    NASA Astrophysics Data System (ADS)

    Wahyuni, H. C.; Vanany, I.; Ciptomulyono, U.

    2018-04-01

    The aim of this paper is to identify risk issues in Indonesian fresh meat supply chain from the farm until to the “plate”. The critical points for food safety in physical fresh meat product flow are also identified. The paper employed one case study in the Indonesian fresh meat company by conducting observations and in-depth three stages of interviews. At the first interview, the players, process, and activities in the fresh meat industry were identified. In the second interview, critical points for food safety were recognized. The risk events in each player and process were identified in the last interview. The research will be conducted in three stages, but this article focuses on risk identification process (first stage) only. The second stage is measuring risk and the third stage focuses on determining the value of risk priority. The results showed that there were four players in the fresh meat supply chain: livestock (source), slaughter (make), distributor and retail (deliver). Each player has different activities and identified 16 risk events in the fresh meat supply chain. Some of the strategies that can be used to reduce the occurrence of such risks include improving the ability of laborers on food safety systems, improving cutting equipment and distribution processes

  1. A data-driven approach to identify controls on global fire activity from satellite and climate observations (SOFIA V1)

    NASA Astrophysics Data System (ADS)

    Forkel, Matthias; Dorigo, Wouter; Lasslop, Gitta; Teubner, Irene; Chuvieco, Emilio; Thonicke, Kirsten

    2017-12-01

    Vegetation fires affect human infrastructures, ecosystems, global vegetation distribution, and atmospheric composition. However, the climatic, environmental, and socioeconomic factors that control global fire activity in vegetation are only poorly understood, and in various complexities and formulations are represented in global process-oriented vegetation-fire models. Data-driven model approaches such as machine learning algorithms have successfully been used to identify and better understand controlling factors for fire activity. However, such machine learning models cannot be easily adapted or even implemented within process-oriented global vegetation-fire models. To overcome this gap between machine learning-based approaches and process-oriented global fire models, we introduce a new flexible data-driven fire modelling approach here (Satellite Observations to predict FIre Activity, SOFIA approach version 1). SOFIA models can use several predictor variables and functional relationships to estimate burned area that can be easily adapted with more complex process-oriented vegetation-fire models. We created an ensemble of SOFIA models to test the importance of several predictor variables. SOFIA models result in the highest performance in predicting burned area if they account for a direct restriction of fire activity under wet conditions and if they include a land cover-dependent restriction or allowance of fire activity by vegetation density and biomass. The use of vegetation optical depth data from microwave satellite observations, a proxy for vegetation biomass and water content, reaches higher model performance than commonly used vegetation variables from optical sensors. We further analyse spatial patterns of the sensitivity between anthropogenic, climate, and vegetation predictor variables and burned area. We finally discuss how multiple observational datasets on climate, hydrological, vegetation, and socioeconomic variables together with data

  2. Can the vector space model be used to identify biological entity activities?

    PubMed Central

    2011-01-01

    Background Biological systems are commonly described as networks of entity interactions. Some interactions are already known and integrate the current knowledge in life sciences. Others remain unknown for long periods of time and are frequently discovered by chance. In this work we present a model to predict these unknown interactions from a textual collection using the vector space model (VSM), a well known and established information retrieval model. We have extended the VSM ability to retrieve information using a transitive closure approach. Our objective is to use the VSM to identify the known interactions from the literature and construct a network. Based on interactions established in the network our model applies the transitive closure in order to predict and rank new interactions. Results We have tested and validated our model using a collection of patent claims issued from 1976 to 2005. From 266,528 possible interactions in our network, the model identified 1,027 known interactions and predicted 3,195 new interactions. Iterating the model according to patent issue dates, interactions found in a given past year were often confirmed by patent claims not in the collection and issued in more recent years. Most confirmation patent claims were found at the top 100 new interactions obtained from each subnetwork. We have also found papers on the Web which confirm new inferred interactions. For instance, the best new interaction inferred by our model relates the interaction between the adrenaline neurotransmitter and the androgen receptor gene. We have found a paper that reports the partial dependence of the antiapoptotic effect of adrenaline on androgen receptor. Conclusions The VSM extended with a transitive closure approach provides a good way to identify biological interactions from textual collections. Specifically for the context of literature-based discovery, the extended VSM contributes to identify and rank relevant new interactions even if these

  3. Identifying protein β-turns with vibrational Raman optical activity.

    PubMed

    Weymuth, Thomas; Jacob, Christoph R; Reiher, Markus

    2011-04-18

    β-turns belong to the most important secondary structure elements in proteins. On the basis of density functional calculations, vibrational Raman optical activity signatures of different types of β-turns are established and compared as well as related to other signatures proposed in the literature earlier. Our findings indicate that there are much more characteristic ROA signals of β-turns than have been hitherto suggested. These suggested signatures are, however, found to be valid for the most important type of β-turns. Moreover, we compare the influence of different amino acid side chains on these signatures and investigate the discrimination of β-turns from other secondary structure elements, namely α- and 3(10)-helices. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Transcript and protein profiling identifies signaling, growth arrest, apoptosis, and NF-κB survival signatures following GNRH receptor activation

    PubMed Central

    Meyer, Colette; Sims, Andrew H; Morgan, Kevin; Harrison, Beth; Muir, Morwenna; Bai, Jianing; Faratian, Dana; Millar, Robert P; Langdon, Simon P

    2013-01-01

    GNRH significantly inhibits proliferation of a proportion of cancer cell lines by activating GNRH receptor (GNRHR)-G protein signaling. Therefore, manipulation of GNRHR signaling may have an under-utilized role in treating certain breast and ovarian cancers. However, the precise signaling pathways necessary for the effect and the features of cellular responses remain poorly defined. We used transcriptomic and proteomic profiling approaches to characterize the effects of GNRHR activation in sensitive cells (HEK293-GNRHR, SCL60) in vitro and in vivo, compared to unresponsive HEK293. Analyses of gene expression demonstrated a dynamic response to the GNRH superagonist Triptorelin. Early and mid-phase changes (0.5–1.0 h) comprised mainly transcription factors. Later changes (8–24 h) included a GNRH target gene, CGA, and up- or downregulation of transcripts encoding signaling and cell division machinery. Pathway analysis identified altered MAPK and cell cycle pathways, consistent with occurrence of G2/M arrest and apoptosis. Nuclear factor kappa B (NF-κB) pathway gene transcripts were differentially expressed between control and Triptorelin-treated SCL60 cultures. Reverse-phase protein and phospho-proteomic array analyses profiled responses in cultured cells and SCL60 xenografts in vivo during Triptorelin anti-proliferation. Increased phosphorylated NF-κB (p65) occurred in SCL60 in vitro, and p-NF-κB and IκBϵ were higher in treated xenografts than controls after 4 days Triptorelin. NF-κB inhibition enhanced the anti-proliferative effect of Triptorelin in SCL60 cultures. This study reveals details of pathways interacting with intense GNRHR signaling, identifies potential anti-proliferative target genes, and implicates the NF-κB survival pathway as a node for enhancing GNRH agonist-induced anti-proliferation. PMID:23202794

  5. Identifying and assessing human activity impacts on groundwater quality through hydrogeochemical anomalies and NO3-, NH4+, and COD contamination: a case study of the Liujiang River Basin, Hebei Province, P.R. China.

    PubMed

    Peng, Cong; He, Jiang-Tao; Wang, Man-Li; Zhang, Zhen-Guo; Wang, Lei

    2018-02-01

    In the face of rapid economic development and increasing human activity, the deterioration of groundwater quality has seriously affected the safety of the groundwater supply in eastern China. Identifying and assessing the impact of human activities is key to finding solutions to this problem. This study is an effort to scientifically and systematically identify and assess the influence of human activities on groundwater based on irregularities in hydrochemical properties and water contamination, which are considered to directly result from anthropogenic activity. The combination of the hydrochemical anomaly identification (HAI) and the contaminant identification (CI) was proposed to identify the influence of human activities on groundwater quality. And the degree of abnormality was quantified by the background threshold value. The principal component analysis (PCA) and land use map were used to verify the reliability of the identification result. The final result show that the strong influence areas mainly distributed in the south of the basin and the affected indicators contained the major elements and NO 3 - , NH 4 + , COD. Impacts from anthropogenic activities can be divided into two types: mine drainage that disrupts natural water-rock interaction processes, agricultural cultivation, and sewage emissions that contribute to nitrate pollution.

  6. Oxygen transfer rate identifies priming compounds in parsley cells.

    PubMed

    Schilling, Jana Viola; Schillheim, Britta; Mahr, Stefan; Reufer, Yannik; Sanjoyo, Sandi; Conrath, Uwe; Büchs, Jochen

    2015-11-25

    In modern agriculture, the call for an alternative crop protection strategy increases because of the desired reduction of fungicide and pesticide use and the continuously evolving resistance of pathogens and pests to agrochemicals. The direct activation of the plant immune system does not provide a promising plant protection measure because of high fitness costs. However, upon treatment with certain natural or synthetic compounds, plant cells can promote to a fitness cost-saving, primed state of enhanced defense. In the primed state, plants respond to biotic and abiotic stress with faster and stronger activation of defense, and this is often associated with immunity and abiotic stress tolerance. Until now, the identification of chemical compounds with priming-inducing activity (so-called plant activators) relied on tedious and invasive approaches, or required the late detection of secreted furanocoumarin phytoalexins in parsley cell cultures. Thus, simple, fast, straightforward, and noninvasive techniques for identifying priming-inducing compounds for plant protection are very welcome. This report demonstrates that a respiration activity-monitoring system (RAMOS) can identify compounds with defense priming-inducing activity in parsley cell suspension in culture. RAMOS relies on the quasi-continuous, noninvasive online determination of the oxygen transfer rate (OTR). Treatment of parsley culture cells with the known plant activator salicylic acid (SA), a natural plant defense signal, resulted in an OTR increase. Addition of the defense elicitor Pep13, a cell wall peptide of Phythophthora sojae, induced two distinctive OTR peaks that were higher in SA-primed cells than in unprimed cells upon Pep13 challenge. Both, the OTR increase after priming with SA and the Pep13 challenge were dose-dependent. Furthermore, there was a close correlation of a compound's activity to enhance the oxygen consumption in parsley cells and its capacity to prime Pep13-induced furanocoumarin

  7. Recurrent TERT promoter mutations identified in a large-scale study of multiple tumour types are associated with increased TERT expression and telomerase activation.

    PubMed

    Huang, Dong-Sheng; Wang, Zhaohui; He, Xu-Jun; Diplas, Bill H; Yang, Rui; Killela, Patrick J; Meng, Qun; Ye, Zai-Yuan; Wang, Wei; Jiang, Xiao-Ting; Xu, Li; He, Xiang-Lei; Zhao, Zhong-Sheng; Xu, Wen-Juan; Wang, Hui-Ju; Ma, Ying-Yu; Xia, Ying-Jie; Li, Li; Zhang, Ru-Xuan; Jin, Tao; Zhao, Zhong-Kuo; Xu, Ji; Yu, Sheng; Wu, Fang; Liang, Junbo; Wang, Sizhen; Jiao, Yuchen; Yan, Hai; Tao, Hou-Quan

    2015-05-01

    Several somatic mutation hotspots were recently identified in the telomerase reverse transcriptase (TERT) promoter region in human cancers. Large scale studies of these mutations in multiple tumour types are limited, in particular in Asian populations. This study aimed to: analyse TERT promoter mutations in multiple tumour types in a large Chinese patient cohort, investigate novel tumour types and assess the functional significance of the mutations. TERT promoter mutation status was assessed by Sanger sequencing for 13 different tumour types and 799 tumour tissues from Chinese cancer patients. Thymic epithelial tumours, gastrointestinal leiomyoma, and gastric schwannoma were included, for which the TERT promoter has not been previously sequenced. Functional studies included TERT expression by reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR), telomerase activity by the telomeric repeat amplification protocol (TRAP) assay and promoter activity by the luciferase reporter assay. TERT promoter mutations were highly frequent in glioblastoma (83.9%), urothelial carcinoma (64.5%), oligodendroglioma (70.0%), medulloblastoma (33.3%) and hepatocellular carcinoma (31.4%). C228T and C250T were the most common mutations. In urothelial carcinoma, several novel rare mutations were identified. TERT promoter mutations were absent in gastrointestinal stromal tumour (GIST), thymic epithelial tumours, gastrointestinal leiomyoma, gastric schwannoma, cholangiocarcinoma, gastric and pancreatic cancer. TERT promoter mutations highly correlated with upregulated TERT mRNA expression and telomerase activity in adult gliomas. These mutations differentially enhanced the transcriptional activity of the TERT core promoter. TERT promoter mutations are frequent in multiple tumour types and have similar distributions in Chinese cancer patients. The functional significance of these mutations reflect the importance to telomere maintenance and hence tumourigenesis, making them

  8. Identifying a Small Molecule Blocking Antigen Presentation in Autoimmune Thyroiditis.

    PubMed

    Li, Cheuk Wun; Menconi, Francesca; Osman, Roman; Mezei, Mihaly; Jacobson, Eric M; Concepcion, Erlinda; David, Chella S; Kastrinsky, David B; Ohlmeyer, Michael; Tomer, Yaron

    2016-02-19

    We previously showed that an HLA-DR variant containing arginine at position 74 of the DRβ1 chain (DRβ1-Arg74) is the specific HLA class II variant conferring risk for autoimmune thyroid diseases (AITD). We also identified 5 thyroglobulin (Tg) peptides that bound to DRβ1-Arg74. We hypothesized that blocking the binding of these peptides to DRβ1-Arg74 could block the continuous T-cell activation in thyroiditis needed to maintain the autoimmune response to the thyroid. The aim of the current study was to identify small molecules that can block T-cell activation by Tg peptides presented within DRβ1-Arg74 pockets. We screened a large and diverse library of compounds and identified one compound, cepharanthine that was able to block peptide binding to DRβ1-Arg74. We then showed that Tg.2098 is the dominant peptide when inducing experimental autoimmune thyroiditis (EAT) in NOD mice expressing human DRβ1-Arg74. Furthermore, cepharanthine blocked T-cell activation by thyroglobulin peptides, in particular Tg.2098 in mice that were induced with EAT. For the first time we identified a small molecule that can block Tg peptide binding and presentation to T-cells in autoimmune thyroiditis. If confirmed cepharanthine could potentially have a role in treating human AITD. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Bacterivory by a Summer Assemblage of Nanoplankton in the Ross Sea, Antarctica: Mixotrophic Versus Heterotrophic Protists

    NASA Astrophysics Data System (ADS)

    Sanders, R. W.; Gast, R. J.

    2016-02-01

    Many protists traditionally described as phototrophic have recently been shown to have retained the primitive trait of phagotrophy, and thus function as mixotrophs. Mixotrophic nanoflagellates were identified in every sample examined from a summer cruise in the Ross Sea, Antarctica, where they often were more abundant than heterotrophic nanoflagellates that have previously been considered the major bacterivores in marine waters. Mixotrophs, identified by uptake of fluorescent tracers, comprised similar proportions (9-75%) of the total bacterivorous flagellates in summer as were previously determined for an earlier spring cruise in the Ross Sea. Protist diversity also was linked to functional bacterivores using a culture-independent method in which BrdU-labeled DNA of bacterial prey was incorporated into the DNA of eukaryotic grazers. Immunoprecipitation of the BrdU-labeld DNA was followed by high-throughput sequencing to identify a diverse group of bacterivores, including numerous uncultured eukaryotes. However, its utility for identification of mixotrophs was limited by the availability of sequences from known mixotrophs.

  10. Artemisinin activity-based probes identify multiple molecular targets within the asexual stage of the malaria parasites Plasmodium falciparum 3D7

    PubMed Central

    Ismail, Hanafy M.; Barton, Victoria; Phanchana, Matthew; Charoensutthivarakul, Sitthivut; Wong, Michael H. L.; Hemingway, Janet; Biagini, Giancarlo A.; O’Neill, Paul M.; Ward, Stephen A.

    2016-01-01

    The artemisinin (ART)-based antimalarials have contributed significantly to reducing global malaria deaths over the past decade, but we still do not know how they kill parasites. To gain greater insight into the potential mechanisms of ART drug action, we developed a suite of ART activity-based protein profiling probes to identify parasite protein drug targets in situ. Probes were designed to retain biological activity and alkylate the molecular target(s) of Plasmodium falciparum 3D7 parasites in situ. Proteins tagged with the ART probe can then be isolated using click chemistry before identification by liquid chromatography–MS/MS. Using these probes, we define an ART proteome that shows alkylated targets in the glycolytic, hemoglobin degradation, antioxidant defense, and protein synthesis pathways, processes essential for parasite survival. This work reveals the pleiotropic nature of the biological functions targeted by this important class of antimalarial drugs. PMID:26858419

  11. Dietary traits of the late Early Pleistocene Bison menneri (Bovidae, Mammalia) from its type site Untermassfeld (Central Germany) and the problem of Pleistocene 'wood bison'

    NASA Astrophysics Data System (ADS)

    van Asperen, Eline N.; Kahlke, Ralf-Dietrich

    2017-12-01

    Over the course of the Early and early Middle Pleistocene, a climatic cooling trend led to the partial opening up of landscapes in the western Palaearctic. This led to a gradual replacement of browsers by grazers, whilst some herbivore species shifted their diet towards including more grass. Wear patterns of herbivore cheek teeth can inform our understanding of the timing and extent of this change and indicate levels of dietary plasticity. One of the indicator species of the faunal turnover is the first large-sized form of bison in the Palaearctic, Bison menneri. The dental mesowear of the palaeopopulation from the species' late Early Pleistocene type site of Untermassfeld in Central Germany and the Late Pleistocene B. priscus from Taubach, both from habitat mosaics of forested habitats and more open landscapes, have a mixed feeder profile similar to that of North American wood bison, which has a distinct preference for open habitats but occasionally consumes a high amount of browse as a fall-back food. In contrast, the grazer mesowear signature of early Middle Pleistocene B. schoetensacki voigtstedtensis from Voigtstedt indicates these animals likely did not regularly feed in the densely forested area around the site. The mesowear of B. schoetensacki from Süssenborn, in a more open environment, is similar to that of extant European bison. Both Pleistocene and extant bison are grazers to mixed feeders with relatively high tolerance of a suboptimal browsing diet. None of these species can be regarded as true 'wood bison'.

  12. Alpha-Fetoprotein, Identified as a Novel Marker for the Antioxidant Effect of Placental Extract, Exhibits Synergistic Antioxidant Activity in the Presence of Estradiol

    PubMed Central

    Choi, Hye Yeon; Kim, Seung Woo; Kim, BongWoo; Lee, Hae Na; Kim, Su-Jeong; Song, Minjung; Kim, Sol; Kim, Jungho; Kim, Young Bong; Kim, Jin-Hoi; Cho, Ssang-Goo

    2014-01-01

    Placenta, as a reservoir of nutrients, has been widely used in medical and cosmetic materials. Here, we focused on the antioxidant properties of placental extract and attempted to isolate and identify the main antioxidant factors. Porcine placental extracts were prepared through homogenization or acid hydrolysis, and their antioxidant activity was investigated in the human keratinocyte HaCaT cell line. Treatment with homogenized placental extract (H-PE) increased the cell viability of H2O2-treated HaCaT cells more than two-fold. H-PE treatment suppressed H2O2-induced apoptotic and necrotic cell death and decreased intracellular ROS levels in H2O2-treated HaCaT cells. The antioxidant factors in H-PE were found to be thermo-unstable and were thus expected to include proteins. The candidate antioxidant proteins were fractionated with cation-exchange, anion-exchange, and size-exclusion chromatography, and the antioxidant properties of the chromatographic fractions were investigated. We obtained specific antioxidant fractions that suppressed ROS generation and ROS-induced DNA strand breaks. From silver staining and MALDI-TOF analyses, alpha-fetoprotein (AFP) precursor was identified as a main marker for the antioxidant effect of H-PE. Purified AFP or ectopically expressed AFP exhibited synergistic antioxidant activity in the presence of estradiol. Taken together, our data suggest that AFP, a serum glycoprotein produced at high levels during fetal development, is a novel marker protein for the antioxidant effect of the placenta that exhibits synergistic antioxidant activity in the presence of estradiol. PMID:24922551

  13. Distinct Activities of Glycolytic Enzymes Identify Chronic Lymphocytic Leukemia Patients with a more Aggressive Course and Resistance to Chemo-Immunotherapy.

    PubMed

    Gdynia, Georg; Robak, Tadeusz; Kopitz, Jürgen; Heller, Anette; Grekova, Svetlana; Duglova, Katarina; Laukemper, Gloria; Heinzel-Gutenbrunner, Monika; Gutenbrunner, Cornelius; Roth, Wilfried; Ho, Anthony D; Schirmacher, Peter; Schmitt, Michael; Dreger, Peter; Sellner, Leopold

    2018-06-05

    A higher capacity to grow under hypoxic conditions can lead to a more aggressive behavior of tumor cells. Determining tumor activity under hypoxia may identify chronic lymphocytic leukemia (CLL) with aggressive clinical course and predict response to chemo-immunotherapy (CIT). A metabolic score was generated by determining pyruvate kinase and lactate dehydrogenase, key enzymes of glycolysis, ex vivo in primary CLL samples under normoxic and hypoxic conditions. This score was further correlated with clinical endpoints and response to CIT in 96 CLL patients. 45 patients were classified as metabolic high risk (HR), 51 as low risk (LR). Treatment-free survival (TFS) was significantly shorter in HR patients (median 394 vs 723 days, p = .021). 15 HR patients and 14 LR patients received CIT after sample acquisition. HR patients had a significantly shorter progression-free survival after treatment compared to LR patients (median 216 days vs not reached, p = .008). Multivariate analysis evaluating age, IGHV, TP53 deletion or mutation and 11q22-23 deletion besides the capacity of tumor cells to grow under severe hypoxic conditions identified the metabolic profile as the strongest independent risk factor for shorter TFS (hazard ratio 2.37, p = .011). The metabolic risk can provide prognostic and predictive information complementary to genetic biomarkers and identify patients who might benefit from alternative treatment approaches. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Quantitative Analysis of Flow through Free-swimming Appendicularians

    NASA Astrophysics Data System (ADS)

    Sutherland, K.; Conley, K. R.; Gemmell, B. J.; Thompson, E.; Bouquet, J. M.

    2016-02-01

    Appendicularians are pelagic tunicates (Phylum: Chordata, Subphylum: Tunicata) that frequently dominate the mesozooplankton community and are key grazers in both coastal shallow seas and oligotrophic environments. Understanding of their feeding mechanisms, specifically selective feeding, has important ramifications for predicting their impact on particle distributions in the upper ocean. The goal of the current study was to determine the role of flow morphology in regulating particle capture within the houses of free-swimming appendicularians (Oikopleura dioica). We used two methods— standard Particle Image Velocimetry (PIV) with laser sheet illumination and bright field micro-PIV— to gain unprecedented spatial and temporal resolution of body kinematics and fluid motion through the mucous-mesh house. Analysis of small-scale fluid interactions at various parts of the house provided insight into factors that influence particle capture and selection in these important grazers.

  15. The use of natural infochemicals for sustainable and efficient harvesting of the microalgae Scenedesmus spp. for biotechnology: insights from a meta-analysis.

    PubMed

    Roccuzzo, Sebastiana; Beckerman, Andrew P; Pandhal, Jagroop

    2016-12-01

    Open raceway ponds are regarded as the most economically viable option for large-scale cultivation of microalgae for low to mid-value bio-products, such as biodiesel. However, improvements are required including reducing the costs associated with harvesting biomass. There is now a growing interest in exploiting natural ecological processes within biotechnology. We review how chemical cues produced by algal grazers induce colony formation in algal cells, which subsequently leads to their sedimentation. A statistical meta-analysis of more than 80 studies reveals that Daphnia grazers can induce high levels of colony formation and sedimentation in Scenedesmus obliquus and that these natural, infochemical induced sedimentation rates are comparable to using commercial chemical equivalents. These data suggest that natural ecological interactions can be co-opted in biotechnology as part of a promising, low energy and clean harvesting method for use in large raceway systems.

  16. Interrogator system for identifying electrical circuits

    DOEpatents

    Jatko, W.B.; McNeilly, D.R.

    1988-04-12

    A system for interrogating electrical leads to correctly ascertain the identity of equipment attached to remote ends of the leads is disclosed. The system includes a source of a carrier signal generated in a controller/receiver to be sent over the leads and an identifier unit at the equipment. The identifier is activated by command of the carrier and uses a portion of the carrier to produce a supply voltage. Each identifier is uniquely programmed for a specific piece of equipment, and causes the impedance of the circuit to be modified whereby the carrier signal is modulated according to that program. The modulation can be amplitude, frequency or phase modulation. A demodulator in the controller/receiver analyzes the modulated carrier signal, and if a verified signal is recognized displays and/or records the information. This information can be utilized in a computer system to prepare a wiring diagram of the electrical equipment attached to specific leads. Specific circuit values are given for amplitude modulation, and the system is particularly described for use with thermocouples. 6 figs.

  17. Interrogator system for identifying electrical circuits

    DOEpatents

    Jatko, William B.; McNeilly, David R.

    1988-01-01

    A system for interrogating electrical leads to correctly ascertain the identity of equipment attached to remote ends of the leads. The system includes a source of a carrier signal generated in a controller/receiver to be sent over the leads and an identifier unit at the equipment. The identifier is activated by command of the carrier and uses a portion of the carrier to produce a supply voltage. Each identifier is uniquely programmed for a specific piece of equipment, and causes the impedance of the circuit to be modified whereby the carrier signal is modulated according to that program. The modulation can be amplitude, frequency or phase modulation. A demodulator in the controller/receiver analyzes the modulated carrier signal, and if a verified signal is recognized displays and/or records the information. This information can be utilized in a computer system to prepare a wiring diagram of the electrical equipment attached to specific leads. Specific circuit values are given for amplitude modulation, and the system is particularly described for use with thermocouples.

  18. A high throughput screen identifies benzoquinoline compounds as inhibitors of Ebola virus replication.

    PubMed

    Luthra, Priya; Liang, Jue; Pietzsch, Colette A; Khadka, Sudip; Edwards, Megan R; Wei, Shuguang; De, Sampriti; Posner, Bruce; Bukreyev, Alexander; Ready, Joseph M; Basler, Christopher F

    2018-02-01

    Ebola virus (EBOV) is an enveloped negative-sense, single-stranded RNA virus of the filovirus family that causes severe disease in humans. Approved therapies for EBOV disease are lacking. EBOV RNA synthesis is carried out by a virus-encoded complex with RNA-dependent RNA polymerase activity that is required for viral propagation. This complex and its activities are therefore potential antiviral targets. To identify potential lead inhibitors of EBOV RNA synthesis, a library of small molecule compounds was screened against a previously established assay of EBOV RNA synthesis, the EBOV minigenome assay (MGA), in 384 well microplate format. The screen identified 56 hits that inhibited EBOV MGA activity by more than 70% while exhibiting less than 20% cell cytotoxicity. Inhibitory chemical scaffolds included angelicin derivatives, derivatives of the antiviral compound GSK983 and benzoquinolines. Structure-activity relationship (SAR) studies of the benzoquinoline scaffold produced ∼50 analogs and led to identification of an optimized compound, SW456, with a submicromolar IC 50 in the EBOV MGA and antiviral activity against infectious EBOV in cell culture. The compound was also active against a MGA for another deadly filovirus, Marburg virus. It also exhibited antiviral activity towards a negative-sense RNA virus from the rhabdovirus family, vesicular stomatitis virus, and a positive-sense RNA virus, Zika virus. Overall, these data demonstrate the potential of the EBOV MGA to identify anti-EBOV compounds and identifies the benzoquinoline series as a broad-spectrum antiviral lead. Copyright © 2017. Published by Elsevier B.V.

  19. Environmental pollutants, diet, physical activity, body size, and breast cancer: where do we stand in research to identify opportunities for prevention?

    PubMed

    Brody, Julia Green; Rudel, Ruthann A; Michels, Karin B; Moysich, Kirsten B; Bernstein, Leslie; Attfield, Kathleen R; Gray, Sharon

    2007-06-15

    Breast cancer is the most common invasive cancer in women worldwide and the leading cause of death in US women in mid-life. Treatment has adverse effects, adding to the importance of finding modifiable risk factors. At the invitation of Susan G. Komen for the Cure, we reviewed studies of breast cancer and environmental pollutants, diet (assessed prospectively), body size, and physical activity, and animal studies that identify chemicals as potential mammary carcinogens. Databases developed in the review include information on 216 chemicals that increased mammary gland tumors in animal studies and 450 epidemiologic studies (accessible at www.silentspring.org/sciencereview and www.komen.org/environment). Exposure to potential mammary carcinogens is widespread from chemicals found in consumer products, air and drinking water pollution, food, and women's workplaces. Epidemiologic studies have included only a small number of chemicals identified as mammary carcinogens or as hormone disruptors, which may have implications for breast cancer; however, evidence is emerging for associations between breast cancer and polychlorinated biphenyls, polycyclic aromatic hydrocarbons, and organic solvents. Prospective diet studies have not revealed consistent associations with breast cancer. Improved exposure assessment methods will help advance future human studies of both diet and environmental pollutants. Studies of physical activity show that it is protective. In the same vein as evidence-based medicine, messages for patients, policymakers, and the public should support decision-making based on the strength of current evidence; such messages might address exposure reduction for some pollutants. Investments in research on environmental factors in breast cancer have potentially large public health benefits.

  20. Methods and compositions for identifying cellular genes exploited by viral pathogens.

    USDA-ARS?s Scientific Manuscript database

    Methods and compositions for rapidly identifying CGEPs required for viral infection of mammalian cells are provided. Also provided are methods of inhibiting viral infection of mammalian cells by inhibiting the activity of one or more CGEPs (e.g., as identified in accordance with methods of the inve...

  1. Identifying Beneficial Physical Activity during School Recess: Utility and Feasibility of the Fitbit

    ERIC Educational Resources Information Center

    Van Camp, Carole M.; Hayes, Lynda B.

    2017-01-01

    The purpose of the current study was to assess the utility, feasibility, and reliability of Fitbit accelerometers to measure physical activity (via steps) of 15 young children simultaneously during recess. Fitbit-recorded steps per minute (SPM) were used as the primary measure to assess levels of activity in children playing in various structured…

  2. Identifying Key Features of Effective Active Learning: The Effects of Writing and Peer Discussion

    PubMed Central

    Pangle, Wiline M.; Wyatt, Kevin H.; Powell, Karli N.; Sherwood, Rachel E.

    2014-01-01

    We investigated some of the key features of effective active learning by comparing the outcomes of three different methods of implementing active-learning exercises in a majors introductory biology course. Students completed activities in one of three treatments: discussion, writing, and discussion + writing. Treatments were rotated weekly between three sections taught by three different instructors in a full factorial design. The data set was analyzed by generalized linear mixed-effect models with three independent variables: student aptitude, treatment, and instructor, and three dependent (assessment) variables: change in score on pre- and postactivity clicker questions, and coding scores on in-class writing and exam essays. All independent variables had significant effects on student performance for at least one of the dependent variables. Students with higher aptitude scored higher on all assessments. Student scores were higher on exam essay questions when the activity was implemented with a writing component compared with peer discussion only. There was a significant effect of instructor, with instructors showing different degrees of effectiveness with active-learning techniques. We suggest that individual writing should be implemented as part of active learning whenever possible and that instructors may need training and practice to become effective with active learning. PMID:25185230

  3. Teacher's Role: IDentifying and Overcoming Sex Bias in Classroom Management. Trainer Manual.

    ERIC Educational Resources Information Center

    Fair, Martha H.; And Others

    Outlines are presented for teacher workshops on identifying and overcoming biased attitudes reflected in current literature and classroom instructional materials. Each session includes: (1) a needs assessment activity or exercise to express initial concerns; (2) a lecture introducing new concepts and activities; (3) activities providing an…

  4. High aldehyde dehydrogenase activity identifies cancer stem cells in human cervical cancer

    PubMed Central

    Liu, Shu-Yan; Zheng, Peng-Sheng

    2013-01-01

    High aldehyde dehydrogenase (ALDH) activity characterizes a subpopulation of cells with cancer stem cell (CSC) properties in several malignancies. To clarify whether ALDH can be used as a marker of cervical cancer stem cells (CCSCs), ALDHhigh and ALDHlow cells were sorted from 4 cervical cancer cell lines and 5 primary tumor xenografts and examined for CSC characteristics. Here, we demonstrate that cervical cancer cells with high ALDH activity fulfill the functional criteria for CSCs: (1) ALDHhigh cells, unlike ALDHlow cells, are highly tumorigenic in vivo; (2) ALDHhigh cells can give rise to both ALDHhigh and ALDHlow cells in vitro and in vivo, thereby establishing a cellular hierarchy; and (3) ALDHhigh cells have enhanced self-renewal and differentiation potentials. Additionally, ALDHhigh cervical cancer cells are more resistant to cisplatin treatment than ALDHlow cells. Finally, expression of the stem cell self-renewal-associated transcription factors OCT4, NANOG, KLF4 and BMI1 is elevated in ALDHhigh cervical cancer cells. Taken together, our data indicated that high ALDH activity may represent both a functional marker for CCSCs and a target for novel cervical cancer therapies. PMID:24318570

  5. Neural underpinnings of the identifiable victim effect: affect shifts preferences for giving.

    PubMed

    Genevsky, Alexander; Västfjäll, Daniel; Slovic, Paul; Knutson, Brian

    2013-10-23

    The "identifiable victim effect" refers to peoples' tendency to preferentially give to identified versus anonymous victims of misfortune, and has been proposed to partly depend on affect. By soliciting charitable donations from human subjects during behavioral and neural (i.e., functional magnetic resonance imaging) experiments, we sought to determine whether and how affect might promote the identifiable victim effect. Behaviorally, subjects gave more to orphans depicted by photographs versus silhouettes, and their shift in preferences was mediated by photograph-induced feelings of positive arousal, but not negative arousal. Neurally, while photographs versus silhouettes elicited activity in widespread circuits associated with facial and affective processing, only nucleus accumbens activity predicted and could statistically account for increased donations. Together, these findings suggest that presenting evaluable identifiable information can recruit positive arousal, which then promotes giving. We propose that affect elicited by identifiable stimuli can compel people to give more to strangers, even despite costs to the self.

  6. Neural Underpinnings of the Identifiable Victim Effect: Affect Shifts Preferences for Giving

    PubMed Central

    Västfjäll, Daniel; Slovic, Paul; Knutson, Brian

    2013-01-01

    The “identifiable victim effect” refers to peoples' tendency to preferentially give to identified versus anonymous victims of misfortune, and has been proposed to partly depend on affect. By soliciting charitable donations from human subjects during behavioral and neural (i.e., functional magnetic resonance imaging) experiments, we sought to determine whether and how affect might promote the identifiable victim effect. Behaviorally, subjects gave more to orphans depicted by photographs versus silhouettes, and their shift in preferences was mediated by photograph-induced feelings of positive arousal, but not negative arousal. Neurally, while photographs versus silhouettes elicited activity in widespread circuits associated with facial and affective processing, only nucleus accumbens activity predicted and could statistically account for increased donations. Together, these findings suggest that presenting evaluable identifiable information can recruit positive arousal, which then promotes giving. We propose that affect elicited by identifiable stimuli can compel people to give more to strangers, even despite costs to the self. PMID:24155323

  7. NITRATE AND FECAL COLIFORM CONCENTRATIONS IN SILVOPASTURE AND PASTURE LEACHATES

    USDA-ARS?s Scientific Manuscript database

    A major limitation to efficient forage-based livestock production in Appalachia is asynchrony of forage availability and quality with nutritional requirements of the grazer. Silvopasture is being studied to improve the seasonal distribution and persistence of high quality herbage, sustainability an...

  8. Nbs1 ChIP-Seq Identifies Off-Target DNA Double-Strand Breaks Induced by AID in Activated Splenic B Cells

    PubMed Central

    Linehan, Erin K.; Schrader, Carol E.; Stavnezer, Janet

    2015-01-01

    Activation-induced cytidine deaminase (AID) is required for initiation of Ig class switch recombination (CSR) and somatic hypermutation (SHM) of antibody genes during immune responses. AID has also been shown to induce chromosomal translocations, mutations, and DNA double-strand breaks (DSBs) involving non-Ig genes in activated B cells. To determine what makes a DNA site a target for AID-induced DSBs, we identify off-target DSBs induced by AID by performing chromatin immunoprecipitation (ChIP) for Nbs1, a protein that binds DSBs, followed by deep sequencing (ChIP-Seq). We detect and characterize hundreds of off-target AID-dependent DSBs. Two types of tandem repeats are highly enriched within the Nbs1-binding sites: long CA repeats, which can form Z-DNA, and tandem pentamers containing the AID target hotspot WGCW. These tandem repeats are not nearly as enriched at AID-independent DSBs, which we also identified. Msh2, a component of the mismatch repair pathway and important for genome stability, increases off-target DSBs, similar to its effect on Ig switch region DSBs, which are required intermediates during CSR. Most of the off-target DSBs are two-ended, consistent with generation during G1 phase, similar to DSBs in Ig switch regions. However, a minority are one-ended, presumably due to conversion of single-strand breaks to DSBs during replication. One-ended DSBs are repaired by processes involving homologous recombination, including break-induced replication repair, which can lead to genome instability. Off-target DSBs, especially those present during S phase, can lead to chromosomal translocations, deletions and gene amplifications, resulting in the high frequency of B cell lymphomas derived from cells that express or have expressed AID. PMID:26263206

  9. The effects of grazing by gastropods and physical factors on the upper limits of distribution of intertidal macroalgae.

    PubMed

    Underwood, A J

    1980-01-01

    The cover of foliose algae is sparse to non-existent above a low-level algal zone on many shores in N.S.W., except in rock-pools. Above this algal zone, encrusting algae, mostly Hildenbrandia prototypus, occupy most of the primary substratum on sheltered shores. Experimental manipulations at midtidal levels were used to test hypotheses about the effects of grazing by molluses and of physical factors during low tide on this pattern of algal community structure.Fences and cages were used to exclude grazers: molluscs grazed under roofs and in open areas. Cages and roofs provided shade, and decreased the harshness of the environment during low tide: fences and open areas had the normal environmental regime.In the absence of grazers, rapid colonization of Ulva and slower colonization by other foliose algae occurred in all experimental areas. The rate of colonization by Ulva sporelings was initially retarded on existing encrusting algae, but after a few months, cover of Ulva equalled that on cleared rock.Most species of algae only grew to maturity inside cages, and remained as a turf of sporelings inside fences. No foliose algae grew to a visible size in open, grazed areas. Grazing thus prevents the establishment of foliose algae above their normal upper limit on the shore, but the effects of physical factors during low tide prevent the growth of algae which become established when grazers are removed. Physical factors thus limit the abundance of foliose algae at mid-tidal levels.The recolonization of cleared areas by Hildenbrandia was not affected by the presence of a turf of sporelings, nor by the shade cast by roofs, but was retarded in cages where mature algae formed a canopy. Even under such a canopy, Hildenbrandia eventually covered as much primary substratum as in open, grazed areas. This encrusting alga is able to escape from the effects of grazing by having a tough thallus, and by its vegetative growth which allows individual plants to cover a lot of substratum

  10. Identifying Balance Measures Most Likely to Identify Recent Falls.

    PubMed

    Criter, Robin E; Honaker, Julie A

    2016-01-01

    Falls sustained by older adults are an increasing health care issue. Early identification of those at risk for falling can lead to successful prevention of falls. Balance complaints are common among individuals who fall or are at risk for falling. The purpose of this study was to evaluate the clinical utility of a multifaceted balance protocol used for fall risk screening, with the hypothesis that this protocol would successfully identify individuals who had a recent fall (within the previous 12 months). This is a retrospective review of 30 individuals who self-referred for a free fall risk screening. Measures included case history, Activities-Specific Balance Confidence Scale, modified Clinical Test of Sensory Interaction on Balance, Timed Up and Go test, and Dynamic Visual Acuity. Statistical analyses were focused on the ability of the test protocol to identify a fall within the past 12 months and included descriptive statistics, clinical utility indices, logistic regression, receiver operating characteristic curve, area under the curve analysis, effect size (Cohen d), and Spearman correlation coefficients. All individuals who self-referred for this free screening had current imbalance complaints, and were typically women (70%), had a mean age of 77.2 years, and had a fear of falling (70%). Almost half (46.7%) reported at least 1 lifetime fall and 40.0% within the past 12 months. Regression analysis suggested that the Timed Up and Go test was the most important indicator of a recent fall. A cutoff score of 12 or more seconds was optimal (sensitivity: 83.3%; specificity: 61.1%). Older adults with current complaints of imbalance have a higher rate of falls, fall-related injury, and fear of falling than the general community-dwelling public. The Timed Up and Go test is useful for determining recent fall history in individuals with imbalance.

  11. Development of gastric cancer in nonatrophic stomach with highly active inflammation identified by serum levels of pepsinogen and Helicobacter pylori antibody together with endoscopic rugal hyperplastic gastritis.

    PubMed

    Watanabe, Mika; Kato, Jun; Inoue, Izumi; Yoshimura, Noriko; Yoshida, Takeichi; Mukoubayashi, Chizu; Deguchi, Hisanobu; Enomoto, Shotaro; Ueda, Kazuki; Maekita, Takao; Iguchi, Mikitaka; Tamai, Hideyuki; Utsunomiya, Hirotoshi; Yamamichi, Nobutake; Fujishiro, Mitsuhiro; Iwane, Masataka; Tekeshita, Tatsuya; Mohara, Osamu; Ushijima, Toshikazu; Ichinose, Masao

    2012-12-01

    This study aimed to elucidate groups at high risk of developing cancer among patients with serologically identified Helicobacter pylori infection and nonatrophic stomach. Annual endoscopy was performed for a mean of 5.4 years in 496 asymptomatic middle-aged men who were H. pylori antibody-positive and pepsinogen (PG) test-negative. Subjects were stratified according to the activity of H. pylori-associated gastritis measured by serum levels of PG and H. pylori antibody, and/or by endoscopic findings of rugal hyperplastic gastritis (RHG), and cancer development was investigated. During the study period, seven cases of cancer developed in the cohort (incidence rate, 261/100,000 person-years), with 85.7% developing in the group showing a PGI/II ratio ≤ 3.0, reflecting active inflammation-based high PGII levels. Cancer incidence was significantly higher in this group (750/100,000 person-years) than in groups with less active gastritis. Furthermore, cancer incidence for this group was significantly higher in the subgroup with high H. pylori antibody titers than in the low-titer subgroup. Meanwhile, endoscopic findings revealed that 11.7% of subjects showed RHG reflecting localized highly active inflammation, and cancer risk was significantly higher in patients with RHG than in patients without. Combining the two serum tests and endoscopic examination for RHG allowed identification of subjects with more active gastritis and higher cancer risk. No cancer development was observed in these high-risk subjects after H. pylori eradication. Subjects with highly active gastritis identified by the two serological tests and endoscopic RHG constitute a group at high risk of cancer development with H. pylori-infected nonatrophic stomach. Copyright © 2012 UICC.

  12. Identifying Active Travel Behaviors in Challenging Environments Using GPS, Accelerometers, and Machine Learning Algorithms.

    PubMed

    Ellis, Katherine; Godbole, Suneeta; Marshall, Simon; Lanckriet, Gert; Staudenmayer, John; Kerr, Jacqueline

    2014-01-01

    Active travel is an important area in physical activity research, but objective measurement of active travel is still difficult. Automated methods to measure travel behaviors will improve research in this area. In this paper, we present a supervised machine learning method for transportation mode prediction from global positioning system (GPS) and accelerometer data. We collected a dataset of about 150 h of GPS and accelerometer data from two research assistants following a protocol of prescribed trips consisting of five activities: bicycling, riding in a vehicle, walking, sitting, and standing. We extracted 49 features from 1-min windows of this data. We compared the performance of several machine learning algorithms and chose a random forest algorithm to classify the transportation mode. We used a moving average output filter to smooth the output predictions over time. The random forest algorithm achieved 89.8% cross-validated accuracy on this dataset. Adding the moving average filter to smooth output predictions increased the cross-validated accuracy to 91.9%. Machine learning methods are a viable approach for automating measurement of active travel, particularly for measuring travel activities that traditional accelerometer data processing methods misclassify, such as bicycling and vehicle travel.

  13. Identifying the perceptive users for online social systems

    PubMed Central

    Liu, Xiao-Lu; Guo, Qiang; Han, Jing-Ti

    2017-01-01

    In this paper, the perceptive user, who could identify the high-quality objects in their initial lifespan, is presented. By tracking the ratings given to the rewarded objects, we present a method to identify the user perceptibility, which is defined as the capability that a user can identify these objects at their early lifespan. Moreover, we investigate the behavior patterns of the perceptive users from three dimensions: User activity, correlation characteristics of user rating series and user reputation. The experimental results for the empirical networks indicate that high perceptibility users show significantly different behavior patterns with the others: Having larger degree, stronger correlation of rating series and higher reputation. Furthermore, in view of the hysteresis in finding the rewarded objects, we present a general framework for identifying the high perceptibility users based on user behavior patterns. The experimental results show that this work is helpful for deeply understanding the collective behavior patterns for online users. PMID:28704382

  14. Identifying the perceptive users for online social systems.

    PubMed

    Liu, Jian-Guo; Liu, Xiao-Lu; Guo, Qiang; Han, Jing-Ti

    2017-01-01

    In this paper, the perceptive user, who could identify the high-quality objects in their initial lifespan, is presented. By tracking the ratings given to the rewarded objects, we present a method to identify the user perceptibility, which is defined as the capability that a user can identify these objects at their early lifespan. Moreover, we investigate the behavior patterns of the perceptive users from three dimensions: User activity, correlation characteristics of user rating series and user reputation. The experimental results for the empirical networks indicate that high perceptibility users show significantly different behavior patterns with the others: Having larger degree, stronger correlation of rating series and higher reputation. Furthermore, in view of the hysteresis in finding the rewarded objects, we present a general framework for identifying the high perceptibility users based on user behavior patterns. The experimental results show that this work is helpful for deeply understanding the collective behavior patterns for online users.

  15. Semiochemicals released from five bacteria identified from animal wounds infested by primary screwworms and their effects on fly behavioral activity.

    PubMed

    Zhu, Junwei J; Chaudhury, Muhammad F; Durso, Lisa M; Sagel, Agustin; Skoda, Steven R; Jelvez-Serra, Nadia S; Santanab, Euzebio Goulart

    2017-01-01

    The Primary screwworm, Cochliomyia hominivorax (Coquerel), is a serious pest feeding on living flesh of any warm-blooded animal, including humans. It was eradicated from the United States in the early 1980s using the sterile male technique. However, it was recently detected in populations of wild deer and pets in the Florida Keys of the US. For monitoring purposes, screwworm flies are normally trapped using attractant bait with liver. However, there has been little effort to develop an efficient monitoring system for detection of screwworm flies using a specific synthetic attractant blend. Several studies have shown that odors from animal wound fluids attract screwworm adults, particularly gravid females. Bacteria associated with animal wounds have been identified that act as a major source for this attraction. To understand what volatiles attract screwworms we inoculated bovine blood with previously identified bacteria. We identified volatile chemicals released from the inoculated blood and other selected media over time and assessed the effect of those chemicals on behavioral activity of adult screwworm flies. A total of 7 volatile compounds were collected from bacteria incubated in either broth or blood using solid-phase microextraction, and their chemical structures were identified by their characteristic mass spectrum fragments and confirmed by retention times in comparison to those of synthetic standards via gas chromatograph combined mass spectrometry analyses. Five major volatiles including dimethyl disulfide, dimethyl trisulfide, phenol, p-cresol and indole were detected from a mixture of 5 bacteria incubated in blood. The ratios of volatiles released differed among different incubation media, time and individual bacteria. A synthetic mixture containing the five compounds was demonstrated to be attractive to adult screwworm flies both in laboratory assays and field trapping trials. The results obtained from this study may assist in developing an efficient

  16. Effects of the oxylipin-producing diatom Skeletonema marinoi on gene expression levels of the calanoid copepod Calanus sinicus.

    PubMed

    Lauritano, Chiara; Carotenuto, Ylenia; Vitiello, Valentina; Buttino, Isabella; Romano, Giovanna; Hwang, Jiang-Shiou; Ianora, Adrianna

    2015-12-01

    Diatoms are eukaryotic unicellular plants that constitute one of the major components of marine phytoplankton, comprising up to 40% of annual productivity at sea and representing 25% of global carbon-fixation. Diatoms have traditionally been considered a preferential food for zooplankton grazers such as copepods, but, in the last two decades, this beneficial role has been challenged after the discovery that many species of diatoms produce toxic metabolites, collectively termed oxylipins, that induce reproductive failure in zooplankton grazers. Diatoms are the dominant natural diet of Calanus sinicus, a cold-temperate calanoid copepod that supports secondary production of important fisheries in the shelf ecosystems of the Northwest Pacific Ocean, Yellow Sea, Sea of Japan and South China Sea. In this study, the effect of the oxylipin-producing diatom Skeletonema marinoi on C. sinicus has been evaluated by analyzing expression level changes of genes involved in defense and detoxification systems. Results show that C. sinicus is more resistant to a diet of this diatom species in terms of gene expression patterns, compared to the congeneric species Calanus helgolandicus which is an important constituent of the temperate waters of the Atlantic Ocean and northern Mediterranean Sea. These findings contribute to the better understanding of genetic and/or phenotypic flexibility of copepod species and their capabilities to cope with stress by identifying molecular markers (such as stress and detoxification genes) as biosensors for environmental perturbations (e.g. toxins and contaminants) affecting marine copepods. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Electroencephalographic identifiers of motor adaptation learning

    NASA Astrophysics Data System (ADS)

    Özdenizci, Ozan; Yalçın, Mustafa; Erdoğan, Ahmetcan; Patoğlu, Volkan; Grosse-Wentrup, Moritz; Çetin, Müjdat

    2017-08-01

    Objective. Recent brain-computer interface (BCI) assisted stroke rehabilitation protocols tend to focus on sensorimotor activity of the brain. Relying on evidence claiming that a variety of brain rhythms beyond sensorimotor areas are related to the extent of motor deficits, we propose to identify neural correlates of motor learning beyond sensorimotor areas spatially and spectrally for further use in novel BCI-assisted neurorehabilitation settings. Approach. Electroencephalographic (EEG) data were recorded from healthy subjects participating in a physical force-field adaptation task involving reaching movements through a robotic handle. EEG activity recorded during rest prior to the experiment and during pre-trial movement preparation was used as features to predict motor adaptation learning performance across subjects. Main results. Subjects learned to perform straight movements under the force-field at different adaptation rates. Both resting-state and pre-trial EEG features were predictive of individual adaptation rates with relevance of a broad network of beta activity. Beyond sensorimotor regions, a parieto-occipital cortical component observed across subjects was involved strongly in predictions and a fronto-parietal cortical component showed significant decrease in pre-trial beta-powers for users with higher adaptation rates and increase in pre-trial beta-powers for users with lower adaptation rates. Significance. Including sensorimotor areas, a large-scale network of beta activity is presented as predictive of motor learning. Strength of resting-state parieto-occipital beta activity or pre-trial fronto-parietal beta activity can be considered in BCI-assisted stroke rehabilitation protocols with neurofeedback training or volitional control of neural activity for brain-robot interfaces to induce plasticity.

  18. Mostly Plants. Individualized Biology Activities on: I. Investigating Bread Mold; II. Transpiration; III. Botany Project; IV. Collecting/Preserving/Identifying Leaves; [and] V. Student Science Laboratory Write-Ups.

    ERIC Educational Resources Information Center

    Gibson, Paul R.

    Individualized biology activities for secondary students are presented in this teaching guide. The guide is divided into five sections: (1) investigating bread mold; (2) investigating transpiration; (3) completing a botany project; (4) collecting, preserving, and identifying leaves; and (5) writing up science laboratory investigations. The…

  19. Development of a cell-based high throughput luciferase enzyme fragment complementation assay to identify nuclear-factor-e2-related transcription factor 2 activators.

    PubMed

    Xie, Wensheng; Pao, Christina; Graham, Taylor; Dul, Ed; Lu, Quinn; Sweitzer, Thomas D; Ames, Robert S; Li, Hu

    2012-12-01

    Nuclear-factor-E2-related transcription factor 2 (Nrf2) regulates a large panel of Phase II genes and plays an important role in cell survival. Nrf2 activation has been shown as preventing cigarette smoke-induced alveolar enlargement in mice. Therefore, activation of the Nrf2 protein by small-molecule activators represents an attractive therapeutic strategy that is used for chronic obstructive pulmonary disease. In this article, we describe a cell-based luciferase enzyme fragment complementation assay that identifies Nrf2 activators. This assay is based on the interaction of Nrf2 with its nuclear partner MafK or runt-related transcription factor 2 (RunX2) and is dependent on the reconstitution of a "split" luciferase. Firefly luciferase is split into two fragments, which are genetically fused to Nrf2 and MafK or RunX2, respectively. BacMam technology was used to deliver the fusion constructs into cells for expression of the tagged proteins. When the BacMam-transduced cells were treated with Nrf2 activators, the Nrf2 protein was stabilized and translocated into the nucleus where it interacted with MafK or RunX2. The interaction of Nrf2 and MafK or RunX2 brought together the two luciferase fragments that form an active luciferase. The assay was developed in a 384-well format and was optimized by titrating the BacMam concentration, transduction time, cell density, and fetal bovine serum concentration. It was further validated with known Nrf2 activators. Our data show that this assay is robust, sensitive, and amenable to high throughput screening of a large compound collection for the identification of novel Nrf2 activators.

  20. Identifying Active Travel Behaviors in Challenging Environments Using GPS, Accelerometers, and Machine Learning Algorithms

    PubMed Central

    Ellis, Katherine; Godbole, Suneeta; Marshall, Simon; Lanckriet, Gert; Staudenmayer, John; Kerr, Jacqueline

    2014-01-01

    Background: Active travel is an important area in physical activity research, but objective measurement of active travel is still difficult. Automated methods to measure travel behaviors will improve research in this area. In this paper, we present a supervised machine learning method for transportation mode prediction from global positioning system (GPS) and accelerometer data. Methods: We collected a dataset of about 150 h of GPS and accelerometer data from two research assistants following a protocol of prescribed trips consisting of five activities: bicycling, riding in a vehicle, walking, sitting, and standing. We extracted 49 features from 1-min windows of this data. We compared the performance of several machine learning algorithms and chose a random forest algorithm to classify the transportation mode. We used a moving average output filter to smooth the output predictions over time. Results: The random forest algorithm achieved 89.8% cross-validated accuracy on this dataset. Adding the moving average filter to smooth output predictions increased the cross-validated accuracy to 91.9%. Conclusion: Machine learning methods are a viable approach for automating measurement of active travel, particularly for measuring travel activities that traditional accelerometer data processing methods misclassify, such as bicycling and vehicle travel. PMID:24795875

  1. EFFECTS OF NUTRIENT AND PESTICIDE LOADING ON AQUATIC ECOSYSTEMS AS PERTAINING TO THE EMERGENCE AND TRANSMISSION OF HUMAN DISEASE: THE CASE OF “SWIMMERS’ ITCH”

    EPA Science Inventory

    It is expected that nutrient additions (nitrogen and phosphorus in the form of fertilizers, sewage effluent, etc.) boost both food quantity and food quality for aquatic snails (the intermediate hosts for cercarial dermatitis). As a result, these grazers will be more competent ...

  2. ANNUAL CYCLE OF PERIPHYTON, ZOOPLANKTON, AND WATER QUALITY PARAMETERS ALONG A 5 STATION TRANSECT OF ESCAMBIA BAY, FL

    EPA Science Inventory

    Phytoplankton, zooplankton and water quality parameters were monitored monthly along a 5-station transect in Escambia Bay (Pensacola, FL) from fall 1999 to fall 2000. To provide insight into nutrient processing in Escambia Bay and effects of grazers on phytoplankton community st...

  3. Identifying key features of effective active learning: the effects of writing and peer discussion.

    PubMed

    Linton, Debra L; Pangle, Wiline M; Wyatt, Kevin H; Powell, Karli N; Sherwood, Rachel E

    2014-01-01

    We investigated some of the key features of effective active learning by comparing the outcomes of three different methods of implementing active-learning exercises in a majors introductory biology course. Students completed activities in one of three treatments: discussion, writing, and discussion + writing. Treatments were rotated weekly between three sections taught by three different instructors in a full factorial design. The data set was analyzed by generalized linear mixed-effect models with three independent variables: student aptitude, treatment, and instructor, and three dependent (assessment) variables: change in score on pre- and postactivity clicker questions, and coding scores on in-class writing and exam essays. All independent variables had significant effects on student performance for at least one of the dependent variables. Students with higher aptitude scored higher on all assessments. Student scores were higher on exam essay questions when the activity was implemented with a writing component compared with peer discussion only. There was a significant effect of instructor, with instructors showing different degrees of effectiveness with active-learning techniques. We suggest that individual writing should be implemented as part of active learning whenever possible and that instructors may need training and practice to become effective with active learning. © 2014 D. L. Linton et al. CBE—Life Sciences Education © 2014 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  4. Identifying environmental factors harmful to reproduction.

    PubMed Central

    Palmer, A K

    1993-01-01

    Reproduction is essential for the continuation of the species and for life itself. In biological terms, living and reproducing are essentially one and the same. There is, therefore, no sharp division between identifying factors harmful to reproduction and identifying factors harmful to life or vice versa. Detection of harmful factors requires balanced use of a variety of methodologies from databases on structure-activity relationships through in vitro and in vivo test systems of varying complexity to surveys of wildlife and human populations. Human surveys provide the only assured means of discriminating between real and imagined harmful factors, but they are time consuming and provide information after the harm has been done. Test systems with whole animals provide the best prospects for identifying harmful factors quickly, but currently available methods used for testing agrochemicals and drugs need a thorough overhaul before they can provide a role model. Whether there is a need for new methodology is doubtful. More certain is the need to use existing methodology more wisely. We need a better understanding of the environment--whatever it is--and a more thoughtful approach to investigation of multifactorial situations. PMID:8243390

  5. Activation tagging in indica rice identifies ribosomal proteins as potential targets for manipulation of water-use efficiency and abiotic stress tolerance in plants.

    PubMed

    Moin, Mazahar; Bakshi, Achala; Saha, Anusree; Udaya Kumar, M; Reddy, Attipalli R; Rao, K V; Siddiq, E A; Kirti, P B

    2016-11-01

    We have generated 3900 enhancer-based activation-tagged plants, in addition to 1030 stable Dissociator-enhancer plants in a widely cultivated indica rice variety, BPT-5204. Of them, 3000 were screened for water-use efficiency (WUE) by analysing photosynthetic quantum efficiency and yield-related attributes under water-limiting conditions that identified 200 activation-tagged mutants, which were analysed for flanking sequences at the site of enhancer integration in the genome. We have further selected five plants with low Δ 13 C, high quantum efficiency and increased plant yield compared with wild type for a detailed investigation. Expression studies of 18 genes in these mutants revealed that in four plants one of the three to four tagged genes became activated, while two genes were concurrently up-regulated in the fifth plant. Two genes coding for proteins involved in 60S ribosomal assembly, RPL6 and RPL23A, were among those that became activated by enhancers. Quantitative expression analysis of these two genes also corroborated the results on activating-tagging. The high up-regulation of RPL6 and RPL23A in various stress treatments and the presence of significant cis-regulatory elements in their promoter regions along with the high up-regulation of several of RPL genes in various stress treatments indicate that they are potential targets for manipulating WUE/abiotic stress tolerance. © 2016 John Wiley & Sons Ltd.

  6. Identifying solutions to increase participation in physical activity interventions within a socio-economically disadvantaged community: a qualitative study.

    PubMed

    Cleland, Claire L; Hunter, Ruth F; Tully, Mark A; Scott, David; Kee, Frank; Donnelly, Michael; Prior, Lindsay; Cupples, Margaret E

    2014-05-23

    There is an urgent need to increase population levels of physical activity, particularly amongst those who are socio-economically disadvantaged. Multiple factors influence physical activity behaviour but the generalisability of current evidence to such 'hard-to-reach' population subgroups is limited by difficulties in recruiting them into studies. Also, rigorous qualitative studies of lay perceptions and perceptions of community leaders about public health efforts to increase physical activity are sparse. We sought to explore, within a socio-economically disadvantaged community, residents' and community leaders' perceptions of physical activity (PA) interventions and issues regarding their implementation, in order to improve understanding of needs, expectations, and social/environmental factors relevant to future interventions. Within an ongoing regeneration project (Connswater Community Greenway), in a socio-economically disadvantaged community in Belfast, we collaborated with a Community Development Agency to purposively sample leaders from public- and voluntary-sector community groups and residents. Individual semi-structured interviews were conducted with 12 leaders. Residents (n = 113), of both genders and a range of ages (14 to 86 years) participated in focus groups (n = 14) in local facilities. Interviews and focus groups were recorded, transcribed verbatim and analysed using a thematic framework. Three main themes were identified: awareness of PA interventions; factors contributing to intervention effectiveness; and barriers to participation in PA interventions. Participants reported awareness only of interventions in which they were involved directly, highlighting a need for better communications, both inter- and intra-sectoral, and with residents. Meaningful engagement of residents in planning/organisation, tailoring to local context, supporting volunteers, providing relevant resources and an 'exit strategy' were perceived as important factors

  7. Resolving Microzooplankton Functional Groups In A Size-Structured Planktonic Model

    NASA Astrophysics Data System (ADS)

    Taniguchi, D.; Dutkiewicz, S.; Follows, M. J.; Jahn, O.; Menden-Deuer, S.

    2016-02-01

    Microzooplankton are important marine grazers, often consuming a large fraction of primary productivity. They consist of a great diversity of organisms with different behaviors, characteristics, and rates. This functional diversity, and its consequences, are not currently reflected in large-scale ocean ecological simulations. How should these organisms be represented, and what are the implications for their biogeography? We develop a size-structured, trait-based model to characterize a diversity of microzooplankton functional groups. We compile and examine size-based laboratory data on the traits, revealing some patterns with size and functional group that we interpret with mechanistic theory. Fitting the model to the data provides parameterizations of key rates and properties, which we employ in a numerical ocean model. The diversity of grazing preference, rates, and trophic strategies enables the coexistence of different functional groups of micro-grazers under various environmental conditions, and the model produces testable predictions of the biogeography.

  8. Intoxicated copepods: ingesting toxic phytoplankton leads to risky behaviour

    PubMed Central

    Lasley-Rasher, Rachel S.; Nagel, Kathryn; Angra, Aakanksha; Yen, Jeannette

    2016-01-01

    Understanding interactions between harmful algal bloom (HAB) species and their grazers is essential for determining mechanisms of bloom proliferation and termination. We exposed the common calanoid copepod, Temora longicornis to the HAB species Alexandrium fundyense and examined effects on copepod survival, ingestion, egg production and swimming behaviour. A. fundyense was readily ingested by T. longicornis and significantly altered copepod swimming behaviour without affecting copepod survival or fitness. A. fundyense caused T. longicornis to increase their swimming speed, and the straightness of their path long after the copepods had been removed from the A. fundyense treatment. Models suggest that these changes could lead to a 25–56% increase in encounter frequency between copepods and their predators. This work highlights the need to determine how ingesting HAB species alters grazer behaviour as this can have significant impacts on the fate of HAB toxins in marine systems. PMID:27122557

  9. On the Utility of ToxCast™ and ToxPi as Methods for Identifying New Obesogens

    PubMed Central

    Janesick, Amanda Shaine; Dimastrogiovanni, Giorgio; Vanek, Lenka; Boulos, Christy; Chamorro-García, Raquel; Tang, Weiyi; Blumberg, Bruce

    2016-01-01

    Background: In ToxCast™ Phase I, the U.S. EPA commissioned screening of 320 pesticides, herbicides, fungicides, and other chemicals in a series of high-throughput assays. The agency also developed a toxicological prioritization tool, ToxPi, to facilitate using ToxCast™ assays to predict biological function. Objectives: We asked whether top-scoring PPARγ activators identified in ToxCast™ Phase I were genuine PPARγ activators and inducers of adipogenesis. Next, we identified ToxCast™ assays that should predict adipogenesis, developed an adipogenesis ToxPi, and asked how well the ToxPi predicted adipogenic activity. Methods: We used transient transfection to test the ability of ToxCast™ chemicals to modulate PPARγ and RXRα, and differentiation assays employing 3T3-L1 preadipocytes and mouse bone marrow-derived mesenchymal stem cells (mBMSCs) to evaluate the adipogenic capacity of ToxCast™ chemicals. Results: Only 5/21 of the top scoring ToxCast™ PPARγ activators were activators in our assays, 3 were PPARγ antagonists, the remainder were inactive. The bona fide PPARγ activators we identified induced adipogenesis in 3T3-L1 cells and mBMSCs. Only 7 of the 17 chemicals predicted to be active by the ToxPi promoted adipogenesis, 1 inhibited adipogenesis, and 2 of the 7 predicted negatives were also adipogenic. Of these 9 adipogenic chemicals, 3 activated PPARγ, and 1 activated RXRα. Conclusions: ToxCast™ PPARγ and RXRα assays do not correlate well with laboratory measurements of PPARγ and RXRα activity. The adipogenesis ToxPi performed poorly, perhaps due to the performance of ToxCast™ assays. We observed a modest predictive value of ToxCast™ for PPARγ and RXRα activation and adipogenesis and it is likely that many obesogenic chemicals remain to be identified. Citation: Janesick AS, Dimastrogiovanni G, Vanek L, Boulos C, Chamorro-García R, Tang W, Blumberg B. 2016. On the utility of ToxCast™ and ToxPi as methods for identifying new

  10. Identifying functional reorganization of spelling networks: an individual peak probability comparison approach

    PubMed Central

    Purcell, Jeremy J.; Rapp, Brenda

    2013-01-01

    Previous research has shown that damage to the neural substrates of orthographic processing can lead to functional reorganization during reading (Tsapkini et al., 2011); in this research we ask if the same is true for spelling. To examine the functional reorganization of spelling networks we present a novel three-stage Individual Peak Probability Comparison (IPPC) analysis approach for comparing the activation patterns obtained during fMRI of spelling in a single brain-damaged individual with dysgraphia to those obtained in a set of non-impaired control participants. The first analysis stage characterizes the convergence in activations across non-impaired control participants by applying a technique typically used for characterizing activations across studies: Activation Likelihood Estimate (ALE) (Turkeltaub et al., 2002). This method was used to identify locations that have a high likelihood of yielding activation peaks in the non-impaired participants. The second stage provides a characterization of the degree to which the brain-damaged individual's activations correspond to the group pattern identified in Stage 1. This involves performing a Mahalanobis distance statistics analysis (Tsapkini et al., 2011) that compares each of a control group's peak activation locations to the nearest peak generated by the brain-damaged individual. The third stage evaluates the extent to which the brain-damaged individual's peaks are atypical relative to the range of individual variation among the control participants. This IPPC analysis allows for a quantifiable, statistically sound method for comparing an individual's activation pattern to the patterns observed in a control group and, thus, provides a valuable tool for identifying functional reorganization in a brain-damaged individual with impaired spelling. Furthermore, this approach can be applied more generally to compare any individual's activation pattern with that of a set of other individuals. PMID:24399981

  11. Visualizing in situ translational activity for identifying and sorting slow-growing archaeal−bacterial consortia

    PubMed Central

    Hatzenpichler, Roland; Connon, Stephanie A.; Goudeau, Danielle; Malmstrom, Rex R.; Woyke, Tanja; Orphan, Victoria J.

    2016-01-01

    To understand the biogeochemical roles of microorganisms in the environment, it is important to determine when and under which conditions they are metabolically active. Bioorthogonal noncanonical amino acid tagging (BONCAT) can reveal active cells by tracking the incorporation of synthetic amino acids into newly synthesized proteins. The phylogenetic identity of translationally active cells can be determined by combining BONCAT with rRNA-targeted fluorescence in situ hybridization (BONCAT-FISH). In theory, BONCAT-labeled cells could be isolated with fluorescence-activated cell sorting (BONCAT-FACS) for subsequent genetic analyses. Here, in the first application, to our knowledge, of BONCAT-FISH and BONCAT-FACS within an environmental context, we probe the translational activity of microbial consortia catalyzing the anaerobic oxidation of methane (AOM), a dominant sink of methane in the ocean. These consortia, which typically are composed of anaerobic methane-oxidizing archaea (ANME) and sulfate-reducing bacteria, have been difficult to study due to their slow in situ growth rates, and fundamental questions remain about their ecology and diversity of interactions occurring between ANME and associated partners. Our activity-correlated analyses of >16,400 microbial aggregates provide the first evidence, to our knowledge, that AOM consortia affiliated with all five major ANME clades are concurrently active under controlled conditions. Surprisingly, sorting of individual BONCAT-labeled consortia followed by whole-genome amplification and 16S rRNA gene sequencing revealed previously unrecognized interactions of ANME with members of the poorly understood phylum Verrucomicrobia. This finding, together with our observation that ANME-associated Verrucomicrobia are found in a variety of geographically distinct methane seep environments, suggests a broader range of symbiotic relationships within AOM consortia than previously thought. PMID:27357680

  12. Visualizing in situ translational activity for identifying and sorting slow-growing archaeal-bacterial consortia

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hatzenpichler, Roland; Connon, Stephanie A.; Goudeau, Danielle

    To understand the biogeochemical roles of microorganisms in the environment, it is important to determine when and under which conditions they are metabolically active. Bioorthogonal noncanonical amino acid tagging (BONCAT) can reveal active cells by tracking the incorporation of synthetic amino acids into newly synthesized proteins. The phylogenetic identity of translationally active cells can be determined by combining BONCAT with rRNA-targeted fluorescence in situ hybridization (BONCAT-FISH). In theory, BONCAT-labeled cells could be isolated with fluorescence-activated cell sorting (BONCAT-FACS) for subsequent genetic analyses. Here, in the first application, to our knowledge, of BONCAT-FISH and BONCAT-FACS within an environmental context, we probemore » the translational activity of microbial consortia catalyzing the anaerobic oxidation of methane (AOM), a dominant sink of methane in the ocean. These consortia, which typically are composed of anaerobic methane-oxidizing archaea (ANME) and sulfate-reducing bacteria, have been difficult to study due to their slow in situ growth rates, and fundamental questions remain about their ecology and diversity of interactions occurring between ANME and associated partners. Our activity-correlated analyses of > 16,400 microbial aggregates provide the first evidence, to our knowledge, that AOM consortia affiliated with all five major ANME clades are concurrently active under controlled conditions. Surprisingly, sorting of individual BONCAT-labeled consortia followed by whole-genome amplification and 16S rRNA gene sequencing revealed previously unrecognized interactions of ANME with members of the poorly understood phylum Verrucomicrobia. This finding, together with our observation that ANME-associated Verrucomicrobia are found in a variety of geographically distinct methane seep environments, suggests a broader range of symbiotic relationships within AOM consortia than previously thought.« less

  13. Visualizing in situ translational activity for identifying and sorting slow-growing archaeal-bacterial consortia

    DOE PAGES

    Hatzenpichler, Roland; Connon, Stephanie A.; Goudeau, Danielle; ...

    2016-06-28

    To understand the biogeochemical roles of microorganisms in the environment, it is important to determine when and under which conditions they are metabolically active. Bioorthogonal noncanonical amino acid tagging (BONCAT) can reveal active cells by tracking the incorporation of synthetic amino acids into newly synthesized proteins. The phylogenetic identity of translationally active cells can be determined by combining BONCAT with rRNA-targeted fluorescence in situ hybridization (BONCAT-FISH). In theory, BONCAT-labeled cells could be isolated with fluorescence-activated cell sorting (BONCAT-FACS) for subsequent genetic analyses. Here, in the first application, to our knowledge, of BONCAT-FISH and BONCAT-FACS within an environmental context, we probemore » the translational activity of microbial consortia catalyzing the anaerobic oxidation of methane (AOM), a dominant sink of methane in the ocean. These consortia, which typically are composed of anaerobic methane-oxidizing archaea (ANME) and sulfate-reducing bacteria, have been difficult to study due to their slow in situ growth rates, and fundamental questions remain about their ecology and diversity of interactions occurring between ANME and associated partners. Our activity-correlated analyses of > 16,400 microbial aggregates provide the first evidence, to our knowledge, that AOM consortia affiliated with all five major ANME clades are concurrently active under controlled conditions. Surprisingly, sorting of individual BONCAT-labeled consortia followed by whole-genome amplification and 16S rRNA gene sequencing revealed previously unrecognized interactions of ANME with members of the poorly understood phylum Verrucomicrobia. This finding, together with our observation that ANME-associated Verrucomicrobia are found in a variety of geographically distinct methane seep environments, suggests a broader range of symbiotic relationships within AOM consortia than previously thought.« less

  14. Mutualists and antagonists drive among-population variation in selection and evolution of floral display in a perennial herb

    PubMed Central

    Ågren, Jon; Hellström, Frida; Toräng, Per; Ehrlén, Johan

    2013-01-01

    Spatial variation in the direction of selection drives the evolution of adaptive differentiation. However, few experimental studies have examined the relative importance of different environmental factors for variation in selection and evolutionary trajectories in natural populations. Here, we combine 8 y of observational data and field experiments to assess the relative importance of mutualistic and antagonistic interactions for spatial variation in selection and short-term evolution of a genetically based floral display dimorphism in the short-lived perennial herb Primula farinosa. Natural populations of this species include two floral morphs: long-scaped plants that present their flowers well above the ground and short-scaped plants with flowers positioned close to the ground. The direction and magnitude of selection on scape morph varied among populations, and so did the frequency of the short morph (median 19%, range 0–100%; n = 69 populations). A field experiment replicated at four sites demonstrated that variation in the strength of interactions with grazers and pollinators were responsible for among-population differences in relative fitness of the two morphs. Selection exerted by grazers favored the short-scaped morph, whereas pollinator-mediated selection favored the long-scaped morph. Moreover, variation in selection among natural populations was associated with differences in morph frequency change, and the experimental removal of grazers at nine sites significantly reduced the frequency of the short-scaped morph over 8 y. The results demonstrate that spatial variation in intensity of grazing and pollination produces a selection mosaic, and that changes in biotic interactions can trigger rapid genetic changes in natural plant populations. PMID:24145439

  15. Mutualists and antagonists drive among-population variation in selection and evolution of floral display in a perennial herb.

    PubMed

    Agren, Jon; Hellström, Frida; Toräng, Per; Ehrlén, Johan

    2013-11-05

    Spatial variation in the direction of selection drives the evolution of adaptive differentiation. However, few experimental studies have examined the relative importance of different environmental factors for variation in selection and evolutionary trajectories in natural populations. Here, we combine 8 y of observational data and field experiments to assess the relative importance of mutualistic and antagonistic interactions for spatial variation in selection and short-term evolution of a genetically based floral display dimorphism in the short-lived perennial herb Primula farinosa. Natural populations of this species include two floral morphs: long-scaped plants that present their flowers well above the ground and short-scaped plants with flowers positioned close to the ground. The direction and magnitude of selection on scape morph varied among populations, and so did the frequency of the short morph (median 19%, range 0-100%; n = 69 populations). A field experiment replicated at four sites demonstrated that variation in the strength of interactions with grazers and pollinators were responsible for among-population differences in relative fitness of the two morphs. Selection exerted by grazers favored the short-scaped morph, whereas pollinator-mediated selection favored the long-scaped morph. Moreover, variation in selection among natural populations was associated with differences in morph frequency change, and the experimental removal of grazers at nine sites significantly reduced the frequency of the short-scaped morph over 8 y. The results demonstrate that spatial variation in intensity of grazing and pollination produces a selection mosaic, and that changes in biotic interactions can trigger rapid genetic changes in natural plant populations.

  16. Non-Linear Interactions between Consumers and Flow Determine the Probability of Plant Community Dominance on Maine Rocky Shores

    PubMed Central

    Silliman, Brian R.; McCoy, Michael W.; Trussell, Geoffrey C.; Crain, Caitlin M.; Ewanchuk, Patrick J.; Bertness, Mark D.

    2013-01-01

    Although consumers can strongly influence community recovery from disturbance, few studies have explored the effects of consumer identity and density and how they may vary across abiotic gradients. On rocky shores in Maine, recent experiments suggest that recovery of plant- or animal- dominated community states is governed by rates of water movement and consumer pressure. To further elucidate the mechanisms of consumer control, we examined the species-specific and density-dependent effects of rocky shore consumers (crabs and snails) on community recovery under both high (mussel dominated) and low flow (plant dominated) conditions. By partitioning the direct impacts of predators (crabs) and grazers (snails) on community recovery across a flow gradient, we found that grazers, but not predators, are likely the primary agent of consumer control and that their impact is highly non-linear. Manipulating snail densities revealed that herbivorous and bull-dozing snails (Littorina littorea) alone can control recovery of high and low flow communities. After ∼1.5 years of recovery, snail density explained a significant amount of the variation in macroalgal coverage at low flow sites and also mussel recovery at high flow sites. These density-dependent grazer effects were were both non-linear and flow-dependent, with low abundance thresholds needed to suppress plant community recovery, and much higher levels needed to control mussel bed development. Our study suggests that consumer density and identity are key in regulating both plant and animal community recovery and that physical conditions can determine the functional forms of these consumer effects. PMID:23940510

  17. Ocean plankton. Determinants of community structure in the global plankton interactome.

    PubMed

    Lima-Mendez, Gipsi; Faust, Karoline; Henry, Nicolas; Decelle, Johan; Colin, Sébastien; Carcillo, Fabrizio; Chaffron, Samuel; Ignacio-Espinosa, J Cesar; Roux, Simon; Vincent, Flora; Bittner, Lucie; Darzi, Youssef; Wang, Jun; Audic, Stéphane; Berline, Léo; Bontempi, Gianluca; Cabello, Ana M; Coppola, Laurent; Cornejo-Castillo, Francisco M; d'Ovidio, Francesco; De Meester, Luc; Ferrera, Isabel; Garet-Delmas, Marie-José; Guidi, Lionel; Lara, Elena; Pesant, Stéphane; Royo-Llonch, Marta; Salazar, Guillem; Sánchez, Pablo; Sebastian, Marta; Souffreau, Caroline; Dimier, Céline; Picheral, Marc; Searson, Sarah; Kandels-Lewis, Stefanie; Gorsky, Gabriel; Not, Fabrice; Ogata, Hiroyuki; Speich, Sabrina; Stemmann, Lars; Weissenbach, Jean; Wincker, Patrick; Acinas, Silvia G; Sunagawa, Shinichi; Bork, Peer; Sullivan, Matthew B; Karsenti, Eric; Bowler, Chris; de Vargas, Colomban; Raes, Jeroen

    2015-05-22

    Species interaction networks are shaped by abiotic and biotic factors. Here, as part of the Tara Oceans project, we studied the photic zone interactome using environmental factors and organismal abundance profiles and found that environmental factors are incomplete predictors of community structure. We found associations across plankton functional types and phylogenetic groups to be nonrandomly distributed on the network and driven by both local and global patterns. We identified interactions among grazers, primary producers, viruses, and (mainly parasitic) symbionts and validated network-generated hypotheses using microscopy to confirm symbiotic relationships. We have thus provided a resource to support further research on ocean food webs and integrating biological components into ocean models. Copyright © 2015, American Association for the Advancement of Science.

  18. Identifying different learning styles to enhance the learning experience.

    PubMed

    Anderson, Irene

    2016-10-12

    Identifying your preferred learning style can be a useful way to optimise learning opportunities, and can help learners to recognise their strengths and areas for development in the way that learning takes place. It can also help teachers (educators) to recognise where additional activities are required to ensure the learning experience is robust and effective. There are several models available that may be used to identify learning styles. This article discusses these models and considers their usefulness in healthcare education. Models of teaching styles are also considered.

  19. Simulating Food Web Dynamics along a Gradient: Quantifying Human Influence

    PubMed Central

    Jordán, Ferenc; Gjata, Nerta; Mei, Shu; Yule, Catherine M.

    2012-01-01

    Realistically parameterized and dynamically simulated food-webs are useful tool to explore the importance of the functional diversity of ecosystems, and in particular relations between the dynamics of species and the whole community. We present a stochastic dynamical food web simulation for the Kelian River (Borneo). The food web was constructed for six different locations, arrayed along a gradient of increasing human perturbation (mostly resulting from gold mining activities) along the river. Along the river, the relative importance of grazers, filterers and shredders decreases with increasing disturbance downstream, while predators become more dominant in governing eco-dynamics. Human activity led to increased turbidity and sedimentation which adversely impacts primary productivity. Since the main difference between the study sites was not the composition of the food webs (structure is quite similar) but the strengths of interactions and the abundance of the trophic groups, a dynamical simulation approach seemed to be useful to better explain human influence. In the pristine river (study site 1), when comparing a structural version of our model with the dynamical model we found that structurally central groups such as omnivores and carnivores were not the most important ones dynamically. Instead, primary consumers such as invertebrate grazers and shredders generated a greater dynamical response. Based on the dynamically most important groups, bottom-up control is replaced by the predominant top-down control regime as distance downstream and human disturbance increased. An important finding, potentially explaining the poor structure to dynamics relationship, is that indirect effects are at least as important as direct ones during the simulations. We suggest that our approach and this simulation framework could serve systems-based conservation efforts. Quantitative indicators on the relative importance of trophic groups and the mechanistic modeling of eco

  20. Mass Spectrometry to Identify New Biomarkers of Nerve Agent Exposure

    DTIC Science & Technology

    2010-04-01

    target for oganophosphorus agent (OP) binding to enzymes is the active site serine in the consensus sequence GlyXSerXGly of acetylcholinesterase. By...human plasma. Task 6. Use a second method, for example enzyme activity assays or immunoprecipitation, to confirm the identity of soman-labeled proteins...spectrometry identifies covalent binding of soman, sarin, chlorpyrifos oxon, diisopropyl fluorophosphate, and FP-biotin to tyrosines on tubulin: a potential

  1. Evolving a NASA Digital Object Identifiers System with Community Engagement

    NASA Technical Reports Server (NTRS)

    Wanchoo, Lalit; James, Nathan

    2016-01-01

    To demonstrate how the ESDIS (Earth Science Data and Information System) DOI (Digital Object Identifier) system and its processes have evolved over these years based on the recommendations provided by the user community (whether the community members create and manage DOI information or use DOIs in the data citations). The user community is comprised of people with common interests and needs for data identifiers who are actively involved in the creation and usage process. Engagement describes the interactive context wherein the community provides information, evaluates the proposed processes, and provides guidance in the area of identifiers.

  2. Congruence between gender stereotypes and activity preference in self-identified tomboys and non-tomboys.

    PubMed

    Martin, Carol Lynn; Dinella, Lisa M

    2012-06-01

    The major goal was to examine a central tenet of cognitive approaches to gender development, namely, that congruence exists between personal gender stereotypes and behaviors. Item-by-item comparisons of girls' stereotypes about activities and their preferences for activities were conducted, for both girls who claimed to be tomboys and those who did not. Congruence was expected for all girls, but because of their gender non-normative interests, tomboys may exhibit less congruence. A secondary goal was to examine factors that might influence congruence, specifically, whether tomboys develop more inclusive stereotypes and develop greater understanding of stereotype variability. Participants included 112 girls (7-12 years old, M age=9). Girls were interviewed about their activity preferences, beliefs about girls' and boys' activity preferences, understanding variability of stereotypes, and identification as tomboys. Tomboys (30% of the sample) and non-tomboys did not differ in their liking of or in the number of liked feminine activities. However, tomboys showed more interest in masculine activities than non-tomboys. Tomboys and non-tomboys did not differ in stereotype inclusiveness, although tomboys showed a trend toward more inclusive stereotypes. Both groups showed high levels of congruence between stereotypes and preferences. Congruence was stronger for nontomboys (14 times more likely to exhibit responses congruent with stereotypes vs. incongruent ones), as compared to tomboys who were four times more likely to exhibit responses congruent with stereotypes versus incongruent ones. Implications of these findings for cognitive approaches to gender development are discussed.

  3. Sensitive kinase assay linked with phosphoproteomics for identifying direct kinase substrates

    PubMed Central

    Xue, Liang; Wang, Wen-Horng; Iliuk, Anton; Hu, Lianghai; Galan, Jacob A.; Yu, Shuai; Hans, Michael; Geahlen, Robert L.; Tao, W. Andy

    2012-01-01

    Our understanding of the molecular control of many disease pathologies requires the identification of direct substrates targeted by specific protein kinases. Here we describe an integrated proteomic strategy, termed kinase assay linked with phosphoproteomics, which combines a sensitive kinase reaction with endogenous kinase-dependent phosphoproteomics to identify direct substrates of protein kinases. The unique in vitro kinase reaction is carried out in a highly efficient manner using a pool of peptides derived directly from cellular kinase substrates and then dephosphorylated as substrate candidates. The resulting newly phosphorylated peptides are then isolated and identified by mass spectrometry. A further comparison of these in vitro phosphorylated peptides with phosphopeptides derived from endogenous proteins isolated from cells in which the kinase is either active or inhibited reveals new candidate protein substrates. The kinase assay linked with phosphoproteomics strategy was applied to identify unique substrates of spleen tyrosine kinase (Syk), a protein-tyrosine kinase with duel properties of an oncogene and a tumor suppressor in distinctive cell types. We identified 64 and 23 direct substrates of Syk specific to B cells and breast cancer cells, respectively. Both known and unique substrates, including multiple centrosomal substrates for Syk, were identified, supporting a unique mechanism that Syk negatively affects cell division through its centrosomal kinase activity. PMID:22451900

  4. Grazing history effects on rangeland biomass, cover and diversity responses to fire and grazing utilization

    USDA-ARS?s Scientific Manuscript database

    Exclusion of large grazers from rangelands that evolved with significant grazing pressure can alter natural processes and may have legacy effects by changing magnitude or direction of community responses to subsequent disturbance. Three moderately grazed pastures were paired with 12-ha areas that h...

  5. Use of DEAD-box polypeptide-4 (Ddx4) gene promoter-driven fluorescent reporter mice to identify mitotically active germ cells in post-natal mouse ovaries

    PubMed Central

    Park, Eun-Sil; Tilly, Jonathan L.

    2015-01-01

    Several laboratories have independently isolated mitotically active germ cells, termed female germline stem cells or oogonial stem cells (OSCs), from adult mouse ovaries. However, a recent study using Ddx4-Cre;Rosa26 reporter mice concluded that such germ cells do not exist. Given the disparity in conclusions drawn in this study compared with others, we felt it was important to re-assess the utility of Ddx4-Cre;Rosa26 reporter mice for identification of OSCs in adult mouse ovaries. Transgenic Ddx4-Cre mice were crossed with Rosa26tdTm/tdTm mice to drive restricted tomato red (tdTm) gene expression in cells in which the Ddx4 gene promoter has been activated. Crude dispersion of ovaries from recombined offspring generated cell fractions containing tdTm-positive immature oocytes, which are incapable of proliferation and thus probably represent the uncharacterized reporter-positive ovarian cells identified in the paper Zhang et al. (2012) as being mitotically inactive. Dispersed ovaries further subjected to fluorescence-activated cell sorting yielded a large population of non-germline tdTm-positive cells, indicative of promoter ‘leakiness’ in the Ddx4-Cre mouse line. Nonetheless, a small percentage of these tdTm-positive cells exhibited externalized (extracellular, ec) expression of Ddx4 protein (ecDdx4-positive), expressed markers of primitive germ cells but not of oocytes, and actively proliferated in culture, all of which are characteristic features of OSCs. Thus, crude dispersion of ovaries collected from Ddx4 gene promoter-driven reporter mice is not, by itself, a reliable approach to identify OSCs, whereas the same ovarian dispersates further subjected to cell sorting strategies yield purified OSCs that can be expanded in culture. PMID:25147160

  6. The Microbial Food Web in the Recently Flooded Sep Reservoir: Diel Fluctuations in Bacterial Biomass and Metabolic Activity in Relation to Phytoplankton and Flagellate Grazers.

    PubMed

    Jugnia, L.-B.; Tadonléké, R.D.; Sime-Ngando, T.; Devaux, J.

    2000-12-01

    The spatial distribution of the bacterial biomass and production and of potential heterotrophic activity (PHA) were measured every 4 h between 23 July (10:00 h) and 25 July (10:00 h) 1997 in a recently flooded oligo-mesotrophic reservoir (the Sep Reservoir, Puy-de-Dôme, France), in relation to temperature, the phytoplankton biomass and production, and the abundance of heterotrophic flagellates. The temperature varied slightly with time during the study, but the well-established thermal stratification agreed well with vertical distribution of the biological variables that were measured. Only the bacterial production and the PHA showed significant diel changes (t-test, p <0.05), with maxima at 18:00 h and minima at 02:00 h. A significant positive relation was found between bacterial abundance and that of heterotrophic flagellates, which, rather than being an association related to the thermal stratification of the water column, was considered to reflect a trophic relation between these two communities. A carbon balance analysis suggested that at least 30% of the C from primary production measured during the sampling period was used by bacteria, and that 42% of this secondary production, or 6% of the primary production, would be used for the development of the heterotrophic flagellates present. We conclude that the bacterioplankton forms, at least occasionally, an important source of carbon for higher trophic levels, and reject the hypothesis that bacterial production in the Sep Reservoir depends exclusively on organic matter of allochthonous origin.

  7. Identifying apicoplast-targeting antimalarials using high-throughput compatible approaches

    PubMed Central

    Ekland, Eric H.; Schneider, Jessica; Fidock, David A.

    2011-01-01

    Malarial parasites have evolved resistance to all previously used therapies, and recent evidence suggests emerging resistance to the first-line artemisinins. To identify antimalarials with novel mechanisms of action, we have developed a high-throughput screen targeting the apicoplast organelle of Plasmodium falciparum. Antibiotics known to interfere with this organelle, such as azithromycin, exhibit an unusual phenotype whereby the progeny of drug-treated parasites die. Our screen exploits this phenomenon by assaying for “delayed death” compounds that exhibit a higher potency after two cycles of intraerythrocytic development compared to one. We report a primary assay employing parasites with an integrated copy of a firefly luciferase reporter gene and a secondary flow cytometry-based assay using a nucleic acid stain paired with a mitochondrial vital dye. Screening of the U.S. National Institutes of Health Clinical Collection identified known and novel antimalarials including kitasamycin. This inexpensive macrolide, used for agricultural applications, exhibited an in vitro IC50 in the 50 nM range, comparable to the 30 nM activity of our control drug, azithromycin. Imaging and pharmacologic studies confirmed kitasamycin action against the apicoplast, and in vivo activity was observed in a murine malaria model. These assays provide the foundation for high-throughput campaigns to identify novel chemotypes for combination therapies to treat multidrug-resistant malaria.—Ekland, E. H., Schneider, J., Fidock, D. A. Identifying apicoplast-targeting antimalarials using high-throughput compatible approaches. PMID:21746861

  8. Reduction in hepatic drug metabolizing CYP3A4 activities caused by P450 oxidoreductase mutations identified in patients with disordered steroid metabolism

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Flueck, Christa E.; Mullis, Primus E.; Pandey, Amit V., E-mail: amit@pandeylab.org

    2010-10-08

    Research highlights: {yields} Cytochrome P450 3A4 (CYP3A4), metabolizes 50% of drugs in clinical use and requires NADPH-P450 reductase (POR). {yields} Mutations in human POR cause congenital adrenal hyperplasia from diminished activities of steroid metabolizing P450s. {yields} We are reporting that mutations in POR may reduce CYP3A4 activity. {yields} POR mutants Y181D, A457H, Y459H, V492E and R616X lost 99%, while A287P, C569Y and V608F lost 60-85% CYP3A4 activity. {yields} Reduction of CYP3A4 activity may cause increased risk of drug toxicities/adverse drug reactions in patients with POR mutations. -- Abstract: Cytochrome P450 3A4 (CYP3A4), the major P450 present in human liver metabolizesmore » approximately half the drugs in clinical use and requires electrons supplied from NADPH through NADPH-P450 reductase (POR, CPR). Mutations in human POR cause a rare form of congenital adrenal hyperplasia from diminished activities of steroid metabolizing P450s. In this study we examined the effect of mutations in POR on CYP3A4 activity. We used purified preparations of wild type and mutant human POR and in vitro reconstitution with purified CYP3A4 to perform kinetic studies. We are reporting that mutations in POR identified in patients with disordered steroidogenesis/Antley-Bixler syndrome (ABS) may reduce CYP3A4 activity, potentially affecting drug metabolism in individuals carrying mutant POR alleles. POR mutants Y181D, A457H, Y459H, V492E and R616X had more than 99% loss of CYP3A4 activity, while POR mutations A287P, C569Y and V608F lost 60-85% activity. Loss of CYP3A4 activity may result in increased risk of drug toxicities and adverse drug reactions in patients with POR mutations.« less

  9. OXIDATION OF ANTIBIOTICS IN WASTEWATER: IDENTIFYING PRODUCTS AND IMPACTS ON ANTIBACTERIAL ACTIVITY

    EPA Science Inventory

    It is hypothesized that advanced oxidation can be applied effectively and in an economically responsible manner for the removal of the antibacterial activity of antibiotics. Ultimately, this study will develop a set of recommendations for the application of advanced oxidation ...

  10. Crizotinib-Resistant Mutants of EML4-ALK Identified Through an Accelerated Mutagenesis Screen

    PubMed Central

    Zhang, Sen; Wang, Frank; Keats, Jeffrey; Zhu, Xiaotian; Ning, Yaoyu; Wardwell, Scott D; Moran, Lauren; Mohemmad, Qurish K; Anjum, Rana; Wang, Yihan; Narasimhan, Narayana I; Dalgarno, David; Shakespeare, William C; Miret, Juan J; Clackson, Tim; Rivera, Victor M

    2011-01-01

    Activating gene rearrangements of anaplastic lymphoma kinase (ALK) have been identified as driver mutations in non-small-cell lung cancer, inflammatory myofibroblastic tumors, and other cancers. Crizotinib, a dual MET/ALK inhibitor, has demonstrated promising clinical activity in patients with non-small-cell lung cancer and inflammatory myofibroblastic tumors harboring ALK translocations. Inhibitors of driver kinases often elicit kinase domain mutations that confer resistance, and such mutations have been successfully predicted using in vitro mutagenesis screens. Here, this approach was used to discover an extensive set of ALK mutations that can confer resistance to crizotinib. Mutations at 16 residues were identified, structurally clustered into five regions around the kinase active site, which conferred varying degrees of resistance. The screen successfully predicted the L1196M, C1156Y, and F1174L mutations, recently identified in crizotinib-resistant patients. In separate studies, we demonstrated that crizotinib has relatively modest potency in ALK-positive non-small-cell lung cancer cell lines. A more potent ALK inhibitor, TAE684, maintained substantial activity against mutations that conferred resistance to crizotinib. Our study identifies multiple novel mutations in ALK that may confer clinical resistance to crizotinib, suggests that crizotinib's narrow selectivity window may underlie its susceptibility to such resistance and demonstrates that a more potent ALK inhibitor may be effective at overcoming resistance. PMID:22034911

  11. Small-molecule studies identify CDK8 as a regulator of IL-10 in myeloid cells.

    PubMed

    Johannessen, Liv; Sundberg, Thomas B; O'Connell, Daniel J; Kolde, Raivo; Berstler, James; Billings, Katelyn J; Khor, Bernard; Seashore-Ludlow, Brinton; Fassl, Anne; Russell, Caitlin N; Latorre, Isabel J; Jiang, Baishan; Graham, Daniel B; Perez, Jose R; Sicinski, Piotr; Phillips, Andrew J; Schreiber, Stuart L; Gray, Nathanael S; Shamji, Alykhan F; Xavier, Ramnik J

    2017-10-01

    Enhancing production of the anti-inflammatory cytokine interleukin-10 (IL-10) is a promising strategy to suppress pathogenic inflammation. To identify new mechanisms regulating IL-10 production, we conducted a phenotypic screen for small molecules that enhance IL-10 secretion from activated dendritic cells. Mechanism-of-action studies using a prioritized hit from the screen, BRD6989, identified the Mediator-associated kinase CDK8, and its paralog CDK19, as negative regulators of IL-10 production during innate immune activation. The ability of BRD6989 to upregulate IL-10 is recapitulated by multiple, structurally differentiated CDK8 and CDK19 inhibitors and requires an intact cyclin C-CDK8 complex. Using a highly parallel pathway reporter assay, we identified a role for enhanced AP-1 activity in IL-10 potentiation following CDK8 and CDK19 inhibition, an effect associated with reduced phosphorylation of a negative regulatory site on c-Jun. These findings identify a function for CDK8 and CDK19 in regulating innate immune activation and suggest that these kinases may warrant consideration as therapeutic targets for inflammatory disorders.

  12. Can We Identify the Active Ingredients of Behaviour Change Interventions for Coronary Heart Disease Patients? A Systematic Review and Meta-Analysis.

    PubMed

    Goodwin, Laura; Ostuzzi, Giovanni; Khan, Nadia; Hotopf, Matthew H; Moss-Morris, Rona

    2016-01-01

    The main behaviour change intervention available for coronary heart disease (CHD) patients is cardiac rehabilitation. There is little recognition of what the active ingredients of behavioural interventions for CHD might be. Using a behaviour change technique (BCT) framework to code existing interventions may help to identify this. The objectives of this systematic review are to determine the effectiveness of CHD behaviour change interventions and how this may be explained by BCT content and structure. A systematic search of Medline, EMBASE and PsycInfo electronic databases was conducted over a twelve year period (2003-2015) to identify studies which reported on behaviour change interventions for CHD patients. The content of the behaviour change interventions was coded using the Coventry Aberdeen and London-Refined (CALO-RE) taxonomy. Meta-regression analyses examined the BCT content as a predictor of mortality. Twenty two papers met the criteria for this review, reporting data on 16,766 participants. The most commonly included BCTs were providing information, and goal setting. There was a small but significant effect of the interventions on smoking (risk ratio (RR) = 0.89, 95% CI 0.81-0.97). The interventions did not reduce the risk of CHD events (RR = 0.86, 95% CI 0.68, 1.09), but significantly reduced the risk of mortality (RR = 0.82, 95% CI 0.69, 0.97). Sensitivity analyses did not find that any of the BCT variables predicted mortality and the number of BCTs included in an intervention was not associated with mortality (β = -0.02, 95% CI -0.06-0.03). Behaviour change interventions for CHD patients appear to have a positive impact on a number of outcomes. Using an existing BCT taxonomy to code the interventions helped us to understand which were the most commonly used techniques, providing information and goal setting, but not the active components of these complex interventions.

  13. Towards a Methodology for Identifying Program Constraints During Requirements Analysis

    NASA Technical Reports Server (NTRS)

    Romo, Lilly; Gates, Ann Q.; Della-Piana, Connie Kubo

    1997-01-01

    Requirements analysis is the activity that involves determining the needs of the customer, identifying the services that the software system should provide and understanding the constraints on the solution. The result of this activity is a natural language document, typically referred to as the requirements definition document. Some of the problems that exist in defining requirements in large scale software projects includes synthesizing knowledge from various domain experts and communicating this information across multiple levels of personnel. One approach that addresses part of this problem is called context monitoring and involves identifying the properties of and relationships between objects that the system will manipulate. This paper examines several software development methodologies, discusses the support that each provide for eliciting such information from experts and specifying the information, and suggests refinements to these methodologies.

  14. Geothermal Target Areas in Colorado as Identified by Remote Sensing Techniques

    DOE Data Explorer

    Khalid Hussein

    2012-02-01

    This layer contains the areas identified as targets of potential geothermal activity. The Criteria used to identify the target areas include: hot/warm surface exposures modeled from ASTER/Landsat satellite imagery and geological characteristics, alteration mineral commonly associated with hot springs (clays, Si, and FeOx) modeled from ASTER and Landsat data, Colorado Geological Survey (CGS) known thermal hot springs/wells and heat-flow data points, Colorado deep-seated fault zones, weakened basement identified from isostatic gravity data, and Colorado sedimentary and topographic characteristics.

  15. A Genomics-Based Approach Identifies a Thioviridamide-Like Compound with Selective Anticancer Activity.

    PubMed

    Frattaruolo, Luca; Lacret, Rodney; Cappello, Anna Rita; Truman, Andrew W

    2017-11-17

    Thioviridamide is a structurally novel ribosomally synthesized and post-translational modified peptide (RiPP) produced by Streptomyces olivoviridis NA005001. It is characterized by a structure that features a series of thioamide groups and possesses potent antiproliferative activity in cancer cell lines. Its unusual structure allied to its promise as an anticancer compound led us to investigate the diversity of thioviridamide-like pathways across sequenced bacterial genomes. We have isolated and characterized three diverse members of this family of natural products. This characterization is supported by transformation-associated recombination cloning and heterologous expression of one of these compounds, thiostreptamide S4. Our work provides an insight into the diversity of this rare class of compound and indicates that the unusual N-terminus of thioviridamide is not introduced biosynthetically but is instead introduced during acetone extraction. A detailed analysis of the biological activity of one of the newly discovered compounds, thioalbamide, indicates that it is highly cytotoxic to cancer cells, while exhibiting significantly less activity toward a noncancerous epithelial cell line.

  16. Identifying Differentially Abundant Metabolic Pathways in Metagenomic Datasets

    NASA Astrophysics Data System (ADS)

    Liu, Bo; Pop, Mihai

    Enabled by rapid advances in sequencing technology, metagenomic studies aim to characterize entire communities of microbes bypassing the need for culturing individual bacterial members. One major goal of such studies is to identify specific functional adaptations of microbial communities to their habitats. Here we describe a powerful analytical method (MetaPath) that can identify differentially abundant pathways in metagenomic data-sets, relying on a combination of metagenomic sequence data and prior metabolic pathway knowledge. We show that MetaPath outperforms other common approaches when evaluated on simulated datasets. We also demonstrate the power of our methods in analyzing two, publicly available, metagenomic datasets: a comparison of the gut microbiome of obese and lean twins; and a comparison of the gut microbiome of infant and adult subjects. We demonstrate that the subpathways identified by our method provide valuable insights into the biological activities of the microbiome.

  17. Identifying the Active Surfaces of Electrochemically Tuned LiCoO 2 for Oxygen Evolution Reaction

    DOE PAGES

    Lu, Zhiyi; Chen, Guangxu; Li, Yanbin; ...

    2017-04-18

    Identification of active sites for catalytic processes has both fundamental and technological implications for rational design of future catalysts. Herein, we study the active surfaces of layered lithium cobalt oxide (LCO) for the oxygen evolution reaction (OER) using the enhancement effect of electrochemical delithiation (De-LCO). Our theoretical results indicate that the most stable (0001) surface has a very large overpotential for OER independent of lithium content. In contrast, edge sites such as the nonpolar (1120) and polar (0112) surfaces are predicted to be highly active and dependent on (de)lithiation. The effect of lithium extraction from LCO on the surfaces andmore » their OER activities can be understood by the increase of Co 4+ sites relative to Co 3+ and by the shift of active oxygen 2p states. Experimentally, it is demonstrated that LCO nanosheets, which dominantly expose the (0001) surface show negligible OER enhancement upon delithiation. However, a noticeable increase in OER activity (~0.1 V in overpotential shift at 10 mA cm –2) is observed for the LCO nanoparticles, where the basal plane is greatly diminished to expose the edge sites, consistent with the theoretical simulations. In addition, we find that the OER activity of De-LCO nanosheets can be improved if we adopt an acid etching method on LCO to create more active edge sites, which in turn provides a strong evidence for the theoretical indication.« less

  18. High-throughput screen of drug repurposing library identifies inhibitors of Sarcocystis neurona growth.

    PubMed

    Bowden, Gregory D; Land, Kirkwood M; O'Connor, Roberta M; Fritz, Heather M

    2018-04-01

    The apicomplexan parasite Sarcocystis neurona is the primary etiologic agent of equine protozoal myeloencephalitis (EPM), a serious neurologic disease of horses. Many horses in the U.S. are at risk of developing EPM; approximately 50% of all horses in the U.S. have been exposed to S. neurona and treatments for EPM are 60-70% effective. Advancement of treatment requires new technology to identify new drugs for EPM. To address this critical need, we developed, validated, and implemented a high-throughput screen to test 725 FDA-approved compounds from the NIH clinical collections library for anti-S. neurona activity. Our screen identified 18 compounds with confirmed inhibitory activity against S. neurona growth, including compounds active in the nM concentration range. Many identified inhibitory compounds have well-defined mechanisms of action, making them useful tools to study parasite biology in addition to being potential therapeutic agents. In comparing the activity of inhibitory compounds identified by our screen to that of other screens against other apicomplexan parasites, we found that most compounds (15/18; 83%) have activity against one or more related apicomplexans. Interestingly, nearly half (44%; 8/18) of the inhibitory compounds have reported activity against dopamine receptors. We also found that dantrolene, a compound already formulated for horses with a peak plasma concentration of 37.8 ± 12.8 ng/ml after 500 mg dose, inhibits S. neurona parasites at low concentrations (0.065 μM [0.036-0.12; 95% CI] or 21.9 ng/ml [12.1-40.3; 95% CI]). These studies demonstrate the use of a new tool for discovering new chemotherapeutic agents for EPM and potentially providing new reagents to elucidate biologic pathways required for successful S. neurona infection. Copyright © 2018. Published by Elsevier Ltd.

  19. Using factor analysis to identify neuromuscular synergies during treadmill walking

    NASA Technical Reports Server (NTRS)

    Merkle, L. A.; Layne, C. S.; Bloomberg, J. J.; Zhang, J. J.

    1998-01-01

    Neuroscientists are often interested in grouping variables to facilitate understanding of a particular phenomenon. Factor analysis is a powerful statistical technique that groups variables into conceptually meaningful clusters, but remains underutilized by neuroscience researchers presumably due to its complicated concepts and procedures. This paper illustrates an application of factor analysis to identify coordinated patterns of whole-body muscle activation during treadmill walking. Ten male subjects walked on a treadmill (6.4 km/h) for 20 s during which surface electromyographic (EMG) activity was obtained from the left side sternocleidomastoid, neck extensors, erector spinae, and right side biceps femoris, rectus femoris, tibialis anterior, and medial gastrocnemius. Factor analysis revealed 65% of the variance of seven muscles sampled aligned with two orthogonal factors, labeled 'transition control' and 'loading'. These two factors describe coordinated patterns of muscular activity across body segments that would not be evident by evaluating individual muscle patterns. The results show that factor analysis can be effectively used to explore relationships among muscle patterns across all body segments to increase understanding of the complex coordination necessary for smooth and efficient locomotion. We encourage neuroscientists to consider using factor analysis to identify coordinated patterns of neuromuscular activation that would be obscured using more traditional EMG analyses.

  20. Molecular markers for addressing the genetic consequences of fragmentation on black grama (Bouteloua eriopoda) grasslands

    USDA-ARS?s Scientific Manuscript database

    Grasses and grasslands are among the most important biological systems on the planet, providing habitat for wildlife, forage for grazers, and grain for animal and human consumption. Bouteloua eriopoda (black grama) is a key species of the grasslands that once covered large parts of the Northern Chi...

  1. Effects of feral free-roaming horses on semi-arid rangeland ecosystems: an example from the sagebrush steppe

    USDA-ARS?s Scientific Manuscript database

    Feral horses (Equus caballus) are viewed as a symbol of freedom and power; however, they are also a largely unmanaged, non-native grazer in North America, South America, and Australia. Information on their influence on vegetation and soil characteristics in semi-arid rangelands has been limited by ...

  2. In silico screening of small molecule libraries using the dengue virus envelope E protein has identified compounds with antiviral activity against multiple flaviviruses.

    PubMed

    Kampmann, Thorsten; Yennamalli, Ragothaman; Campbell, Phillipa; Stoermer, Martin J; Fairlie, David P; Kobe, Bostjan; Young, Paul R

    2009-12-01

    The flaviviruses comprise a large group of related viruses, many of which pose a significant global human health threat, most notably the dengue viruses (DENV), West Nile virus (WNV) and yellow fever virus (YFV). Flaviviruses enter host cells via fusion of the viral and cellular membranes, a process mediated by the major viral envelope protein E as it undergoes a low pH induced conformational change in the endosomal compartment of the host cell. This essential entry stage in the flavivirus life cycle provides an attractive target for the development of antiviral agents. We performed an in silico docking screen of the Maybridge chemical database within a previously described ligand binding pocket in the dengue E protein structure that is thought to play a key role in the conformational transitions that lead to membrane fusion. The biological activity of selected compounds identified from this screen revealed low micromolar antiviral potency against dengue virus for two of the compounds. Our results also provide the first evidence that compounds selected to bind to this ligand binding site on the flavivirus E protein abrogate fusion activity. Interestingly, one of these compounds also has antiviral activity against both WNV (kunjin strain) and YFV.

  3. Identifying and assessing views among physically-active adult gym members in Israel on dietary supplements.

    PubMed

    Druker, Inbal; Gesser-Edelsburg, Anat

    2017-01-01

    Sports dietary supplements are available for sale in public places including sports clubs. Although there is uncertainty regarding their safety, many gym members who regularly work out consume them. The present study aimed to identify the approaches and perspectives of the public who work out in gyms and take dietary supplements. It examined how professionals view sports dietary supplement consumption, and how they communicate this issue to gym members. The literature discusses the prevalence of SDS use among athletes, but rarely discusses or compares between the risk perceptions of gym members, trainers, and dietitians, who represent the physically-active general public, regarding SDS. We conducted constructivist qualitative research in semi-structured one-on-one interviews ( n  = 34). We held in-depth interviews ( n  = 20) with a heterogeneous population of adult gym members who take dietary supplements, and ( n  = 14) with dietitians and fitness trainers. The main finding was a gap in risk perception of dietary supplement use between dietitians, gym members and fitness trainers. There was low risk perception among dietary supplements consumers. Trainers believed that benefits of supplement consumption exceeded risk, and therefore they did not convey a message to their clients about risk. In contrast, dietitians interviewed for this study renounced general use of sports dietary supplements and doubted whether trainers had proper nutritional knowledge to support it. Lack of awareness of risks suggests that there is a need for communication on this issue. We recommend that professionals (physicians and dietitians) be present in sports clubs that sell such products in an uncontrolled way.

  4. Using C. elegans Forward and Reverse Genetics to Identify New Compounds with Anthelmintic Activity

    PubMed Central

    Mathew, Mark D.; Mathew, Neal D.; Miller, Angela; Simpson, Mike; Au, Vinci; Garland, Stephanie; Gestin, Marie; Edgley, Mark L.; Flibotte, Stephane; Balgi, Aruna; Chiang, Jennifer; Giaever, Guri; Dean, Pamela; Tung, Audrey; Roberge, Michel; Roskelley, Calvin; Forge, Tom; Nislow, Corey; Moerman, Donald

    2016-01-01

    Background The lack of new anthelmintic agents is of growing concern because it affects human health and our food supply, as both livestock and plants are affected. Two principal factors contribute to this problem. First, nematode resistance to anthelmintic drugs is increasing worldwide and second, many effective nematicides pose environmental hazards. In this paper we address this problem by deploying a high throughput screening platform for anthelmintic drug discovery using the nematode Caenorhabditis elegans as a surrogate for infectious nematodes. This method offers the possibility of identifying new anthelmintics in a cost-effective and timely manner. Methods/Principal findings Using our high throughput screening platform we have identified 14 new potential anthelmintics by screening more than 26,000 compounds from the Chembridge and Maybridge chemical libraries. Using phylogenetic profiling we identified a subset of the 14 compounds as potential anthelmintics based on the relative sensitivity of C. elegans when compared to yeast and mammalian cells in culture. We showed that a subset of these compounds might employ mechanisms distinct from currently used anthelmintics by testing diverse drug resistant strains of C. elegans. One of these newly identified compounds targets mitochondrial complex II, and we used structural analysis of the target to suggest how differential binding of this compound may account for its different effects in nematodes versus mammalian cells. Conclusions/Significance The challenge of anthelmintic drug discovery is exacerbated by several factors; including, 1) the biochemical similarity between host and parasite genomes, 2) the geographic location of parasitic nematodes and 3) the rapid development of resistance. Accordingly, an approach that can screen large compound collections rapidly is required. C. elegans as a surrogate parasite offers the ability to screen compounds rapidly and, equally importantly, with specificity, thus

  5. A mixed-methods study identifying key intervention targets to improve participation in daily living activities in primary Sjögren's syndrome patients.

    PubMed

    Hackett, Katie L; Deane, Katherine H O; Newton, Julia L; Deary, Vincent; Bowman, Simon; Rapley, Tim; Ng, Wan-Fai

    2018-02-06

    Functional ability and participation in life situations are compromised in many primary Sjögren's syndrome (PSS) patients. This study aims to identify the key barriers and priorities to participation in daily living activities, in order to develop potential future interventions. Group concept mapping (GCM), a semi-quantitative, mixed-methods, approach was used to identify and structure ideas from UK PSS patients, adults living with a PSS patient (AHMs) and health care professionals (HCPs). Brainstorming generated ideas, which were summarised into a final set of statements. Participants individually arranged these statements into themes and rated each statement for importance. Multidimensional scaling and hierarchical cluster analysis were applied to sorted and rated data to produce visual representations of the ideas (concept maps), enabling identification of agreed priority areas for interventions. 121 patients, 43 AHMs and 67 HCPs took part. 463 ideas were distilled down to 94 statements. These statements were grouped into seven clusters; 'Patient empowerment', 'Symptoms', 'Wellbeing', 'Access and coordination of healthcare', 'Knowledge and support', 'Public awareness and support' and 'Family and friends'. Patient empowerment and Symptoms were rated as priority conceptual themes. Important statements within priority clusters indicate patients should be taken seriously and supported to self-manage symptoms of oral and ocular dryness, fatigue, pain and poor sleep. Our data highlighted that in addition to managing PSS symptoms; interventions aiming to improve patient empowerment, general wellbeing, access to healthcare, patient education and social support are important to facilitate improved participation in daily living activities. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  6. Using Long-Term Satellite Observations to Identify Sensitive Regimes and Active Regions of Aerosol Indirect Effects for Liquid Clouds Over Global Oceans

    NASA Astrophysics Data System (ADS)

    Zhao, Xuepeng; Liu, Yangang; Yu, Fangquan; Heidinger, Andrew K.

    2018-01-01

    Long-term (1981-2011) satellite climate data records of clouds and aerosols are used to investigate the aerosol-cloud interaction of marine water cloud from a climatology perspective. Our focus is on identifying the regimes and regions where the aerosol indirect effects (AIEs) are evident in long-term averages over the global oceans through analyzing the correlation features between aerosol loading and the key cloud variables including cloud droplet effective radius (CDER), cloud optical depth (COD), cloud water path (CWP), cloud top height (CTH), and cloud top temperature (CTT). An aerosol optical thickness (AOT) range of 0.13 < AOT < 0.3 is identified as the sensitive regime of the conventional first AIE where CDER is more susceptible to AOT than the other cloud variables. The first AIE that manifests as the change of long-term averaged CDER appears only in limited oceanic regions. The signature of aerosol invigoration of water clouds as revealed by the increase of cloud cover fraction (CCF) and CTH with increasing AOT at the middle/high latitudes of both hemispheres is identified for a pristine atmosphere (AOT < 0.08). Aerosol invigoration signature is also revealed by the concurrent increase of CDER, COD, and CWP with increasing AOT for a polluted marine atmosphere (AOT > 0.3) in the tropical convergence zones. The regions where the second AIE is likely to manifest in the CCF change are limited to several oceanic areas with high CCF of the warm water clouds near the western coasts of continents. The second AIE signature as represented by the reduction of the precipitation efficiency with increasing AOT is more likely to be observed in the AOT regime of 0.08 < AOT < 0.4. The corresponding AIE active regions manifested themselves as the decline of the precipitation efficiency are mainly limited to the oceanic areas downwind of continental aerosols. The sensitive regime of the conventional AIE identified in this observational study is likely associated with the

  7. Significance of Plankton Community Structure and Nutrient Availability for the Control of Dinoflagellate Blooms by Parasites: A Modeling Approach

    PubMed Central

    Alves-de-Souza, Catharina; Pecqueur, David; Le Floc’h, Emilie; Mas, Sébastien; Roques, Cécile; Mostajir, Behzad; Vidussi, Franscesca; Velo-Suárez, Lourdes; Sourisseau, Marc; Fouilland, Eric; Guillou, Laure

    2015-01-01

    Dinoflagellate blooms are frequently observed under temporary eutrophication of coastal waters after heavy rains. Growth of these opportunistic microalgae is believed to be promoted by sudden input of nutrients and the absence or inefficiency of their natural enemies, such as grazers and parasites. Here, numerical simulations indicate that increasing nutrient availability not only promotes the formation of dinoflagellate blooms but can also stimulate their control by protozoan parasites. Moreover, high abundance of phytoplankton other than dinoflagellate hosts might have a significant dilution effect on the control of dinoflagellate blooms by parasites, either by resource competition with dinoflagellates (thus limiting the number of hosts available for infection) or by affecting numerical-functional responses of grazers that consume free-living parasite stages. These outcomes indicate that although both dinoflagellates and their protozoan parasites are directly affected by nutrient availability, the efficacy of the parasitic control of dinoflagellate blooms under temporary eutrophication depends strongly on the structure of the plankton community as a whole. PMID:26030411

  8. Spatial variability in community composition on a granite breakwater versus natural rocky shores: lack of microhabitats suppresses intertidal biodiversity.

    PubMed

    Aguilera, Moisés A; Broitman, Bernardo R; Thiel, Martin

    2014-10-15

    Strong differences have been observed between the assemblages on artificial reefs and on natural hard-bottom habitats worldwide, but little is known about the mechanisms that cause contrasting biodiversity patterns. We examined the influence of spatial attributes in relation to both biogenic and topographic microhabitats, in the distribution and composition of intertidal species on both artificial and natural reefs. We found higher small-scale spatial heterogeneity on the natural reef compared with the study breakwater. Species richness and diversity were associated with a higher availability of crevices, rock pools and mussels in natural habitats. Spatial distribution of certain grazers corresponded well with the spatial structure of microhabitats. In contrast, the lack of microhabitats on the breakwater resulted in the absence of several grazers reflected in lower species richness. Biogenic and topographic microhabitats can have interactive effects providing niche opportunities for multiple species, explaining differences in species diversity between artificial versus natural reefs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Biodiversity mediates top-down control in eelgrass ecosystems: a global comparative-experimental approach.

    PubMed

    Duffy, J Emmett; Reynolds, Pamela L; Boström, Christoffer; Coyer, James A; Cusson, Mathieu; Donadi, Serena; Douglass, James G; Eklöf, Johan S; Engelen, Aschwin H; Eriksson, Britas Klemens; Fredriksen, Stein; Gamfeldt, Lars; Gustafsson, Camilla; Hoarau, Galice; Hori, Masakazu; Hovel, Kevin; Iken, Katrin; Lefcheck, Jonathan S; Moksnes, Per-Olav; Nakaoka, Masahiro; O'Connor, Mary I; Olsen, Jeanine L; Richardson, J Paul; Ruesink, Jennifer L; Sotka, Erik E; Thormar, Jonas; Whalen, Matthew A; Stachowicz, John J

    2015-07-01

    Nutrient pollution and reduced grazing each can stimulate algal blooms as shown by numerous experiments. But because experiments rarely incorporate natural variation in environmental factors and biodiversity, conditions determining the relative strength of bottom-up and top-down forcing remain unresolved. We factorially added nutrients and reduced grazing at 15 sites across the range of the marine foundation species eelgrass (Zostera marina) to quantify how top-down and bottom-up control interact with natural gradients in biodiversity and environmental forcing. Experiments confirmed modest top-down control of algae, whereas fertilisation had no general effect. Unexpectedly, grazer and algal biomass were better predicted by cross-site variation in grazer and eelgrass diversity than by global environmental gradients. Moreover, these large-scale patterns corresponded strikingly with prior small-scale experiments. Our results link global and local evidence that biodiversity and top-down control strongly influence functioning of threatened seagrass ecosystems, and suggest that biodiversity is comparably important to global change stressors. © 2015 John Wiley & Sons Ltd/CNRS.

  10. List identifies threatened ecosystems

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2012-09-01

    The International Union for Conservation of Nature (IUCN) announced on 9 September that it will develop a new Red List of Ecosystems that will identify which ecosystems are vulnerable or endangered. The list, which is modeled on the group's Red List of Threatened Species™, could help to guide conservation activities and influence policy processes such as the Convention on Biological Diversity, according to the group. “We will assess the status of marine, terrestrial, freshwater, and subterranean ecosystems at local, regional, and global levels,” stated Jon Paul Rodriguez, leader of IUCN's Ecosystems Red List Thematic Group. “The assessment can then form the basis for concerted implementation action so that we can manage them sustainably if their risk of collapse is low or restore them if they are threatened and then monitor their recovery.”

  11. 3D Printing in Instructional Settings: Identifying a Curricular Hierarchy of Activities

    ERIC Educational Resources Information Center

    Brown, Abbie

    2015-01-01

    A report of a year-long study in which the author engaged in 3D printing activity in order to determine how to facilitate and support skill building, concept attainment, and increased confidence with its use among teachers. Use of 3D printing tools and their applications in instructional settings are discussed. A hierarchy of 3D printing…

  12. Intracellular screen to identify metagenomic clones that induce or inhibit a quorum-sensing biosensor.

    PubMed

    Williamson, Lynn L; Borlee, Bradley R; Schloss, Patrick D; Guan, Changhui; Allen, Heather K; Handelsman, Jo

    2005-10-01

    The goal of this study was to design and evaluate a rapid screen to identify metagenomic clones that produce biologically active small molecules. We built metagenomic libraries with DNA from soil on the floodplain of the Tanana River in Alaska. We extracted DNA directly from the soil and cloned it into fosmid and bacterial artificial chromosome vectors, constructing eight metagenomic libraries that contain 53,000 clones with inserts ranging from 1 to 190 kb. To identify clones of interest, we designed a high throughput "intracellular" screen, designated METREX, in which metagenomic DNA is in a host cell containing a biosensor for compounds that induce bacterial quorum sensing. If the metagenomic clone produces a quorum-sensing inducer, the cell produces green fluorescent protein (GFP) and can be identified by fluorescence microscopy or captured by fluorescence-activated cell sorting. Our initial screen identified 11 clones that induce and two that inhibit expression of GFP. The intracellular screen detected quorum-sensing inducers among metagenomic clones that a traditional overlay screen would not. One inducing clone carries a LuxI homologue that directs the synthesis of an N-acyl homoserine lactone quorum-sensing signal molecule. The LuxI homologue has 62% amino acid sequence identity to its closest match in GenBank, AmfI from Pseudomonas fluorescens, and is on a 78-kb insert that contains 67 open reading frames. Another inducing clone carries a gene with homology to homocitrate synthase. Our results demonstrate the power of an intracellular screen to identify functionally active clones and biologically active small molecules in metagenomic libraries.

  13. Identifying Cancer Driver Genes Using Replication-Incompetent Retroviral Vectors

    PubMed Central

    Bii, Victor M.; Trobridge, Grant D.

    2016-01-01

    Identifying novel genes that drive tumor metastasis and drug resistance has significant potential to improve patient outcomes. High-throughput sequencing approaches have identified cancer genes, but distinguishing driver genes from passengers remains challenging. Insertional mutagenesis screens using replication-incompetent retroviral vectors have emerged as a powerful tool to identify cancer genes. Unlike replicating retroviruses and transposons, replication-incompetent retroviral vectors lack additional mutagenesis events that can complicate the identification of driver mutations from passenger mutations. They can also be used for almost any human cancer due to the broad tropism of the vectors. Replication-incompetent retroviral vectors have the ability to dysregulate nearby cancer genes via several mechanisms including enhancer-mediated activation of gene promoters. The integrated provirus acts as a unique molecular tag for nearby candidate driver genes which can be rapidly identified using well established methods that utilize next generation sequencing and bioinformatics programs. Recently, retroviral vector screens have been used to efficiently identify candidate driver genes in prostate, breast, liver and pancreatic cancers. Validated driver genes can be potential therapeutic targets and biomarkers. In this review, we describe the emergence of retroviral insertional mutagenesis screens using replication-incompetent retroviral vectors as a novel tool to identify cancer driver genes in different cancer types. PMID:27792127

  14. Structural and mechanistic analysis of a β-glycoside phosphorylase identified by screening a metagenomic library.

    PubMed

    Macdonald, Spencer S; Patel, Ankoor; Larmour, Veronica L C; Morgan-Lang, Connor; Hallam, Steven J; Mark, Brian L; Withers, Stephen G

    2018-03-02

    Glycoside phosphorylases have considerable potential as catalysts for the assembly of useful glycans for products ranging from functional foods and prebiotics to novel materials. However, the substrate diversity of currently identified phosphorylases is relatively small, limiting their practical applications. To address this limitation, we developed a high-throughput screening approach using the activated substrate 2,4-dinitrophenyl β-d-glucoside (DNPGlc) and inorganic phosphate for identifying glycoside phosphorylase activity and used it to screen a large insert metagenomic library. The initial screen, based on release of 2,4-dinitrophenyl from DNPGlc in the presence of phosphate, identified the gene bglP, encoding a retaining β-glycoside phosphorylase from the CAZy GH3 family. Kinetic and mechanistic analysis of the gene product, BglP, confirmed a double displacement ping-pong mechanism involving a covalent glycosyl-enzyme intermediate. X-ray crystallographic analysis provided insights into the phosphate-binding mode and identified a key glutamine residue in the active site important for substrate recognition. Substituting this glutamine for a serine swapped the substrate specificity from glucoside to N -acetylglucosaminide. In summary, we present a high-throughput screening approach for identifying β-glycoside phosphorylases, which was robust, simple to implement, and useful in identifying active clones within a metagenomics library. Implementation of this screen enabled discovery of a new glycoside phosphorylase class and has paved the way to devising simple ways in which enzyme specificity can be encoded and swapped, which has implications for biotechnological applications. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Riluzole activates TRPC5 channels independently of PLC activity

    PubMed Central

    Richter, Julia M; Schaefer, Michael; Hill, Kerstin

    2014-01-01

    BACKGROUND AND PURPOSE The transient receptor potential channel C5 (TRPC5) is a Ca2+-permeable cation channel, which is predominantly expressed in the brain. TRPC5 is activated in a PLC-dependent manner by, as yet, unidentified endogenous messengers. Recently, modulators of TRPC5, like Ca2+, pH and phospholipids, have been identified. However, the role of TRPC5 in vivo is only poorly understood. Novel specific modulators of TRPC5 might help to elucidate its function. EXPERIMENTAL APPROACH Novel modulators of TRPC5 were identified in a compound screening of approved drugs and natural compounds. The potency and selectivity of TRPC5-activating compounds were determined by fluorometric calcium imaging. The biophysical properties of channel activation by these compounds were analysed using electrophysiological measurements. KEY RESULTS Riluzole was identified as a novel activator of TRPC5 (EC50 9.2 ± 0.5 μM) and its mechanism of action was shown to be independent of G protein signalling and PLC activity. Riluzole-induced TRPC5 currents were potentiated by La3+ and, utilizing TRPC5 mutants that lack La3+ binding sites, it was confirmed that riluzole and La3+ activate TRPC5 by different mechanisms. Recordings of excised inside-out patches revealed a relatively direct effect of riluzole on TRPC5. CONCLUSIONS AND IMPLICATIONS Riluzole can activate TRPC5 heterologously expressed in HEK293 cells as well as those endogenously expressed in the U-87 glioblastoma cell line. Riluzole does not activate any other member of the TRPC family and could, therefore, despite its action on other ion channels, be a useful pharmacological tool for identifying TRPC5-specific currents in immortalized cell lines or in acutely isolated primary cells. PMID:24117252

  16. Microzooplankton herbivory and community structure in the Amundsen Sea, Antarctica

    NASA Astrophysics Data System (ADS)

    Yang, Eun Jin; Jiang, Yong; Lee, SangHoon

    2016-01-01

    We examined microzooplankton abundance, community structure, and grazing impact on phytoplankton in the Amundsen Sea, Western Antarctica, during the early austral summer from December 2010 to January 2011. Our study area was divided into three regions based on topography, hydrographic properties, and trophic conditions: (1) the Oceanic Zone (OZ), with free sea ice and low phytoplankton biomass dominated by diatoms; (2) the Sea Ice Zone (SIZ), covered by heavy sea ice with colder water, lower salinity, and dominated by diatoms; and (3) the Amundsen Sea Polynya (ASP), with high phytoplankton biomass dominated by Phaeocystis antarctica. Microzooplankton biomass and communities associated with phytoplankton biomass and composition varied among regions. Heterotrophic dinoflagellates (HDF) were the most significant grazers in the ASP and OZ, whereas ciliates co-dominated with HDF in the SIZ. Microzooplankton grazing impact is significant in our study area, particularly in the ASP, and consumed 55.4-107.6% of phytoplankton production (average 77.3%), with grazing impact increasing with prey and grazer biomass. This result implies that a significant proportion of the phytoplankton production is not removed by sinking or other grazers but grazed by microzooplankton. Compared with diatom-based systems, Phaeocystis-based production would be largely remineralized and/or channeled through the microbial food web through microzooplankton grazing. In these waters the major herbivorous fate of phytoplankton is likely mediated by the microzooplankton population. Our study confirms the importance of herbivorous protists in the planktonic ecosystems of high latitudes. In conclusion, microzooplankton herbivory may be a driving force controlling phytoplankton growth in early summer in the Amundsen Sea, particularly in the ASP.

  17. Feast or flee: bioelectrical regulation of feeding and predator evasion behaviors in the planktonic alveolate Favella sp. (Spirotrichia).

    PubMed

    Echevarria, Michael L; Wolfe, Gordon V; Taylor, Alison R

    2016-02-01

    Alveolate (ciliates and dinoflagellates) grazers are integral components of the marine food web and must therefore be able to sense a range of mechanical and chemical signals produced by prey and predators, integrating them via signal transduction mechanisms to respond with effective prey capture and predator evasion behaviors. However, the sensory biology of alveolate grazers is poorly understood. Using novel techniques that combine electrophysiological measurements and high-speed videomicroscopy, we investigated the sensory biology of Favella sp., a model alveolate grazer, in the context of its trophic ecology. Favella sp. produced frequent rhythmic depolarizations (∼500 ms long) that caused backward swimming and are responsible for endogenous swimming patterns relevant to foraging. Contact of both prey cells and non-prey polystyrene microspheres at the cilia produced immediate mechanostimulated depolarizations (∼500 ms long) that caused backward swimming, and likely underlie aggregative swimming patterns of Favella sp. in response to patches of prey. Contact of particles at the peristomal cavity that were not suitable for ingestion resulted in depolarizations after a lag of ∼600 ms, allowing time for particles to be processed before rejection. Ingestion of preferred prey particles was accompanied by transient hyperpolarizations (∼1 s) that likely regulate this step of the feeding process. Predation attempts by the copepod Acartia tonsa elicited fast (∼20 ms) animal-like action potentials accompanied by rapid contraction of the cell to avoid predation. We have shown that the sensory mechanisms of Favella sp. are finely tuned to the type, location, and intensity of stimuli from prey and predators. © 2016. Published by The Company of Biologists Ltd.

  18. Controls on microalgal community structures in cryoconite holes upon high Arctic glaciers, Svalbard

    NASA Astrophysics Data System (ADS)

    Vonnahme, T. R.; Devetter, M.; Žárský, J. D.; Šabacká, M.; Elster, J.

    2015-07-01

    Glaciers are known to harbor surprisingly complex ecosystems. On their surface, distinct cylindrical holes filled with meltwater and sediments are considered as hot spots for microbial life. The present paper addresses possible biological interactions within the community of prokaryotic cyanobacteria and eukaryotic microalgae (microalgae) and relations to their potential grazers, additional to their environmental controls. Svalbard glaciers with substantial allochthonous input of material from local sources reveal high microalgal densities. Small valley glaciers with high sediment coverages and high impact of birds show high biomasses and support a high biological diversity. Invertebrate grazer densities do not show any significant negative correlation with microalgal abundances, but a positive correlation with eukaryotic microalgae. Most microalgae found in this study form large colonies (< 10 cells, or > 25 μm), which may protect them against invertebrate grazing. This finding rather indicates grazing as a positive control on eukaryotic microalgae by nutrient recycling. Density differences between the eukaryotic microalgae and prokaryotic cyanobacteria and their high distinction in RDA and PCA analyses indicate that these two groups are in strong contrast. Eukaryotic microalgae occurred mainly in unstable cryoconite holes with high sediment loads, high N : P ratios, and a high impact of bird guano, as a proxy for nutrients. In these environments autochthonous nitrogen fixation appears to be negligible. Selective wind transport of Oscillatoriales via soil and dust particles is proposed to explain their dominance in cryoconites further away from the glacier margins. We propose that, for the studied glaciers, nutrient levels related to recycling of limiting nutrients is the main factor driving variation in the community structure of microalgae and grazers.

  19. Habitat Preference of German Mantis religiosa Populations (Mantodea: Mantidae) and Implications for Conservation.

    PubMed

    Linn, Catherine Anne; Griebeler, Eva Maria

    2016-08-01

    In Germany, the thermophilic European mantid (Mantis religiosa L.) is endangered. Here, we study habitat requirements during its life, and discuss the applicability of the two conservation measures grazing and mowing to this insect species. At two study sites in south-western Germany, which were each subject to one of these measures, we recorded structural and climatic conditions within different microhabitats. We also conducted capture-mark-recapture studies for adult M. religiosa, and mapped adult roosting, oothecae deposition, egg hatching, and imaginal molting in microhabitats over two vegetation periods. In order to assess microhabitat preference of M. religiosa during its life, and identify climatic conditions driving preferences, we applied the Lille habitat preference index and conducted logistic regression analysis for life phases. Our results suggest that temperature is important for egg and nymph development. For egg deposition, females preferred solid substrates with high heat-storing capacities, as those attenuate the negative influence of cold weather periods on egg development. Being ambush predators, males and females preferred roosting sites with sufficient shelter and high prey abundance. Contrary to our expectation, the conservation measures reduced adult population sizes, and presumably reproduction rates. We thus suggest that mowing during the adult phase should reduce vegetation height to a moderate level to keep prey abundance high. Mowing with a clearing saw or grazing over a short period in small fenced areas should be preferred over prolonged grazing, as grazers collaterally stamp down the vegetation. Grazers indirectly reduce prey availability by deteriorating prevailing microclimatic conditions. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Use of DEAD-box polypeptide-4 (Ddx4) gene promoter-driven fluorescent reporter mice to identify mitotically active germ cells in post-natal mouse ovaries.

    PubMed

    Park, Eun-Sil; Tilly, Jonathan L

    2015-01-01

    Several laboratories have independently isolated mitotically active germ cells, termed female germline stem cells or oogonial stem cells (OSCs), from adult mouse ovaries. However, a recent study using Ddx4-Cre;Rosa26 reporter mice concluded that such germ cells do not exist. Given the disparity in conclusions drawn in this study compared with others, we felt it was important to re-assess the utility of Ddx4-Cre;Rosa26 reporter mice for identification of OSCs in adult mouse ovaries. Transgenic Ddx4-Cre mice were crossed with Rosa26(tdTm/tdTm) mice to drive restricted tomato red (tdTm) gene expression in cells in which the Ddx4 gene promoter has been activated. Crude dispersion of ovaries from recombined offspring generated cell fractions containing tdTm-positive immature oocytes, which are incapable of proliferation and thus probably represent the uncharacterized reporter-positive ovarian cells identified in the paper Zhang et al. (2012) as being mitotically inactive. Dispersed ovaries further subjected to fluorescence-activated cell sorting yielded a large population of non-germline tdTm-positive cells, indicative of promoter 'leakiness' in the Ddx4-Cre mouse line. Nonetheless, a small percentage of these tdTm-positive cells exhibited externalized (extracellular, ec) expression of Ddx4 protein (ecDdx4-positive), expressed markers of primitive germ cells but not of oocytes, and actively proliferated in culture, all of which are characteristic features of OSCs. Thus, crude dispersion of ovaries collected from Ddx4 gene promoter-driven reporter mice is not, by itself, a reliable approach to identify OSCs, whereas the same ovarian dispersates further subjected to cell sorting strategies yield purified OSCs that can be expanded in culture. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Identifying and Responding to Personal Stressors: Utilizing Photo Elicitation in Health Education Courses

    ERIC Educational Resources Information Center

    Hunter, Theresa

    2014-01-01

    The "Photo Elicitation Project" teaching idea applies the techniques of photo elicitation to stress prevention and management. This activity is designed to help students identify their personal stressors and to determine which stress prevention strategies are most useful for them. Objectives: students will be able to (a) identify current…

  2. An RNAi Screen To Identify Protein Phosphatases That Function Within the Drosophila Circadian Clock.

    PubMed

    Agrawal, Parul; Hardin, Paul E

    2016-12-07

    Circadian clocks in eukaryotes keep time via cell-autonomous transcriptional feedback loops. A well-characterized example of such a transcriptional feedback loop is in Drosophila, where CLOCK-CYCLE (CLK-CYC) complexes activate transcription of period (per) and timeless (tim) genes, rising levels of PER-TIM complexes feed-back to repress CLK-CYC activity, and degradation of PER and TIM permits the next cycle of CLK-CYC transcription. The timing of CLK-CYC activation and PER-TIM repression is regulated posttranslationally, in part through rhythmic phosphorylation of CLK, PER, and TIM. Previous behavioral screens identified several kinases that control CLK, PER, and TIM levels, subcellular localization, and/or activity, but two phosphatases that function within the clock were identified through the analysis of candidate genes from other pathways or model systems. To identify phosphatases that play a role in the clock, we screened clock cell-specific RNA interference (RNAi) knockdowns of all annotated protein phosphatases and protein phosphatase regulators in Drosophila for altered activity rhythms. This screen identified 19 protein phosphatases that lengthened or shortened the circadian period by ≥1 hr (p ≤ 0.05 compared to controls) or were arrhythmic. Additional RNAi lines, transposon inserts, overexpression, and loss-of-function mutants were tested to independently confirm these RNAi phenotypes. Based on genetic validation and molecular analysis, 15 viable protein phosphatases remain for future studies. These candidates are expected to reveal novel features of the circadian timekeeping mechanism in Drosophila that are likely to be conserved in all animals including humans. Copyright © 2016 Agrawal and Hardin.

  3. Physiological responses to variations in grazing and light conditions in native and invasive fucoids.

    PubMed

    Olabarria, Celia; Arenas, Francisco; Fernández, Ángela; Troncoso, Jesús S; Martínez, Brezo

    2018-08-01

    Poor physiological acclimatization to climate change has led to shifts in the distributional ranges of various species and to biodiversity loss. However, evidence also suggests the relevance of non-climatic physical factors, such as light, and biotic factors, which may act in interactive or additive way. We used a mechanistic approach to evaluate the ecophysiological responses of four seaweed species (three dominant intertidal fucoids, Fucus serratus, Ascophyllum nodosum, Bifurcaria bifurcata, and the invasive Sargassum muticum) to different conditions of grazing, light irradiance and ultraviolet (UV) radiation. We performed a large-scale mesocosm experiment with a total of 800 individual thalli of macroalgae. The factorial experimental design included major algal traits, photoacclimation, nutrient stoichiometry and chemical defence as response variables. Few significant effects of the factors acting alone or in combination were observed, suggesting a good capacity for acclimatization in all four species. The significant effects were generally additive and there were no potentially deleterious synergistic effects between factors. Fucus serratus, a species currently undergoing a drastic contraction of its southern distribution limit in Europe, was the most strongly affected species, showing overall lower photosynthetic efficiency than the other species. The growth rate of F. serratus decreased when UV radiation was filtered out, but only in the presence of grazers. Moreover, more individuals of this species tended to reach maturity in the absence of grazers, and the nitrogen content of tissues decreased under full-spectrum light. Only the phlorotannin content of tissues of B. bifurcata and of exudates of A. nodosum, both slow-growing species, were positively affected by respectively removal of UVB radiation and the presence of grazers. The findings for S. muticum, a well-established invasive seaweed across European coasts, suggested similar physiological response of

  4. Data Identifiers, Versioning, and Micro-citation

    NASA Astrophysics Data System (ADS)

    Parsons, M. A.; Duerr, R. E.

    2012-12-01

    Data citation, especially using Digital Object Identifiers (DOIs), is an increasingly accepted scientific practice. For example, the AGU Council asserts that data "publications" should "be credited and cited like the products of any other scientific activity," and Thomson Reuters has recently announced a data citation index built from DOIs assigned to data sets. Correspondingly, formal guidelines for how to cite a data set (using DOIs or similar identifiers/locators) have recently emerged, notably those from the international DataCite consortium, the UK Digital Curation Centre, and the US Federation of Earth Science Information Partners. These different data citation guidelines are largely congruent. They agree on the basic practice and elements of data citation, especially for relatively static, whole data collections. There is less agreement on some of the more subtle nuances of data citation. They define different methods for handling different data set versions, especially for the very dynamic, growing data sets that are common in Earth Sciences. They also differ in how people should cite specific, arbitrarily large elements, "passages," or subsets of a larger data collection, i.e., the precise data records actually used in a study. This detailed "micro-citation", and careful reference to exact versions of data are essential to ensure scientific reproducibility. Identifiers such as DOIs are necessary but not sufficient for the precise, detailed, references necessary. Careful practice must be coupled with the use of curated identifiers. In this paper we review the pros and cons of different approaches to versioning and micro-citation. We suggest a workable solution for most existing Earth science data and suggest a more rigorous path forward for the future.

  5. 24 CFR 1000.508 - If the recipient monitoring identifies programmatic concerns, what happens?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... concerns, what happens? If the recipient's monitoring activities identify areas of concerns, the recipient... 24 Housing and Urban Development 4 2014-04-01 2014-04-01 false If the recipient monitoring... INDIAN HOUSING, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT NATIVE AMERICAN HOUSING ACTIVITIES Recipient...

  6. 24 CFR 1000.508 - If the recipient monitoring identifies programmatic concerns, what happens?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... concerns, what happens? If the recipient's monitoring activities identify areas of concerns, the recipient... 24 Housing and Urban Development 4 2013-04-01 2013-04-01 false If the recipient monitoring... INDIAN HOUSING, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT NATIVE AMERICAN HOUSING ACTIVITIES Recipient...

  7. 24 CFR 1000.508 - If the recipient monitoring identifies programmatic concerns, what happens?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... concerns, what happens? If the recipient's monitoring activities identify areas of concerns, the recipient... 24 Housing and Urban Development 4 2012-04-01 2012-04-01 false If the recipient monitoring... INDIAN HOUSING, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT NATIVE AMERICAN HOUSING ACTIVITIES Recipient...

  8. 24 CFR 1000.508 - If the recipient monitoring identifies programmatic concerns, what happens?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... concerns, what happens? If the recipient's monitoring activities identify areas of concerns, the recipient... 24 Housing and Urban Development 4 2011-04-01 2011-04-01 false If the recipient monitoring... INDIAN HOUSING, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT NATIVE AMERICAN HOUSING ACTIVITIES Recipient...

  9. 24 CFR 1000.508 - If the recipient monitoring identifies programmatic concerns, what happens?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... concerns, what happens? If the recipient's monitoring activities identify areas of concerns, the recipient... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false If the recipient monitoring... INDIAN HOUSING, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT NATIVE AMERICAN HOUSING ACTIVITIES Recipient...

  10. Identifying factors of activities of daily living important for cost and caregiver outcomes in Alzheimer's disease.

    PubMed

    Reed, Catherine; Belger, Mark; Vellas, Bruno; Andrews, Jeffrey Scott; Argimon, Josep M; Bruno, Giuseppe; Dodel, Richard; Jones, Roy W; Wimo, Anders; Haro, Josep Maria

    2016-02-01

    We aimed to obtain a better understanding of how different aspects of patient functioning affect key cost and caregiver outcomes in Alzheimer's disease (AD). Baseline data from a prospective observational study of community-living AD patients (GERAS) were used. Functioning was assessed using the Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale. Generalized linear models were conducted to analyze the relationship between scores for total activities of daily living (ADL), basic ADL (BADL), instrumental ADL (IADL), ADL subdomains (confirmed through factor analysis) and individual ADL questions, and total societal costs, patient healthcare and social care costs, total and supervision caregiver time, and caregiver burden. Four distinct ADL subdomains were confirmed: basic activities, domestic/household activities, communication, and outside activities. Higher total societal costs were associated with impairments in all aspects of ADL, including all subdomains; patient costs were associated with total ADL and BADL, and basic activities subdomain scores. Both total and supervision caregiver hours were associated with total ADL and IADL scores, and domestic/household and outside activities subdomain scores (greater hours associated with greater functional impairments). There was no association between caregiver burden and BADL or basic activities subdomain scores. The relationship between total ADL, IADL, and the outside activities subdomain and outcomes differed between patients with mild and moderate-to-severe AD. Identification of ADL subdomains may lead to a better understanding of the association between patient function and costs and caregiver outcomes at different stages of AD, in particular the outside activities subdomain within mild AD.

  11. A proposed approach to systematically identify and monitor the corporate political activity of the food industry with respect to public health using publicly available information.

    PubMed

    Mialon, M; Swinburn, B; Sacks, G

    2015-07-01

    Unhealthy diets represent one of the major risk factors for non-communicable diseases. There is currently a risk that the political influence of the food industry results in public health policies that do not adequately balance public and commercial interests. This paper aims to develop a framework for categorizing the corporate political activity of the food industry with respect to public health and proposes an approach to systematically identify and monitor it. The proposed framework includes six strategies used by the food industry to influence public health policies and outcomes: information and messaging; financial incentive; constituency building; legal; policy substitution; opposition fragmentation and destabilization. The corporate political activity of the food industry could be identified and monitored through publicly available data sourced from the industry itself, governments, the media and other sources. Steps for country-level monitoring include identification of key food industry actors and related sources of information, followed by systematic data collection and analysis of relevant documents, using the proposed framework as a basis for classification of results. The proposed monitoring approach should be pilot tested in different countries as part of efforts to increase the transparency and accountability of the food industry. This approach has the potential to help redress any imbalance of interests and thereby contribute to the prevention and control of non-communicable diseases. © 2015 World Obesity.

  12. A Genome-wide CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) Screen Identifies NEK7 as an Essential Component of NLRP3 Inflammasome Activation.

    PubMed

    Schmid-Burgk, Jonathan L; Chauhan, Dhruv; Schmidt, Tobias; Ebert, Thomas S; Reinhardt, Julia; Endl, Elmar; Hornung, Veit

    2016-01-01

    Inflammasomes are high molecular weight protein complexes that assemble in the cytosol upon pathogen encounter. This results in caspase-1-dependent pro-inflammatory cytokine maturation, as well as a special type of cell death, known as pyroptosis. The Nlrp3 inflammasome plays a pivotal role in pathogen defense, but at the same time, its activity has also been implicated in many common sterile inflammatory conditions. To this effect, several studies have identified Nlrp3 inflammasome engagement in a number of common human diseases such as atherosclerosis, type 2 diabetes, Alzheimer disease, or gout. Although it has been shown that known Nlrp3 stimuli converge on potassium ion efflux upstream of Nlrp3 activation, the exact molecular mechanism of Nlrp3 activation remains elusive. Here, we describe a genome-wide CRISPR/Cas9 screen in immortalized mouse macrophages aiming at the unbiased identification of gene products involved in Nlrp3 inflammasome activation. We employed a FACS-based screen for Nlrp3-dependent cell death, using the ionophoric compound nigericin as a potassium efflux-inducing stimulus. Using a genome-wide guide RNA (gRNA) library, we found that targeting Nek7 rescued macrophages from nigericin-induced lethality. Subsequent studies revealed that murine macrophages deficient in Nek7 displayed a largely blunted Nlrp3 inflammasome response, whereas Aim2-mediated inflammasome activation proved to be fully intact. Although the mechanism of Nek7 functioning upstream of Nlrp3 yet remains elusive, these studies provide a first genetic handle of a component that specifically functions upstream of Nlrp3. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Identifying 21st Century STEM Competencies Using Workplace Data

    NASA Astrophysics Data System (ADS)

    Jang, Hyewon

    2016-04-01

    Gaps between science, technology, engineering, and mathematics (STEM) education and required workplace skills have been identified in industry, academia, and government. Educators acknowledge the need to reform STEM education to better prepare students for their future careers. We pursue this growing interest in the skills needed for STEM disciplines and ask whether frameworks for 21st century skills and engineering education cover all of important STEM competencies. In this study, we identify important STEM competencies and evaluate the relevance of current frameworks applied in education using the standardized job-specific database operated and maintained by the US Department of Labor. Our analysis of the importance of 109 skills, types of knowledge and work activities, revealed 18 skills, seven categories of knowledge, and 27 work activities important for STEM workers. We investigate the perspectives of STEM and non-STEM job incumbents, comparing the importance of each skill, knowledge, and work activity for the two groups. We aimed to condense dimensions of the 52 key areas by categorizing them according to the Katz and Kahn (1978) framework and testing for inter-rater reliability. Our findings show frameworks for 21st century skills and engineering education do not encompass all important STEM competencies. Implications for STEM education programs are discussed, including how they can bridge gaps between education and important workplace competencies.

  14. Effects of feral horse herds on plant communities across a precipitation gradient

    Treesearch

    Laura Baur

    2016-01-01

    Feral horse herds in the western United States are managed with the goal of maintaining "a thriving natural ecological balance" with their environment. Because rangeland ecology is complex and grazers such as horses can have different effects under different environmental conditions, more data are needed to better inform Appropriate Management Levels...

  15. Using Long‐Term Satellite Observations to Identify Sensitive Regimes and Active Regions of Aerosol Indirect Effects for Liquid Clouds Over Global Oceans

    PubMed Central

    Liu, Yangang; Yu, Fangquan; Heidinger, Andrew K.

    2018-01-01

    Abstract Long‐term (1981–2011) satellite climate data records of clouds and aerosols are used to investigate the aerosol‐cloud interaction of marine water cloud from a climatology perspective. Our focus is on identifying the regimes and regions where the aerosol indirect effects (AIEs) are evident in long‐term averages over the global oceans through analyzing the correlation features between aerosol loading and the key cloud variables including cloud droplet effective radius (CDER), cloud optical depth (COD), cloud water path (CWP), cloud top height (CTH), and cloud top temperature (CTT). An aerosol optical thickness (AOT) range of 0.13 < AOT < 0.3 is identified as the sensitive regime of the conventional first AIE where CDER is more susceptible to AOT than the other cloud variables. The first AIE that manifests as the change of long‐term averaged CDER appears only in limited oceanic regions. The signature of aerosol invigoration of water clouds as revealed by the increase of cloud cover fraction (CCF) and CTH with increasing AOT at the middle/high latitudes of both hemispheres is identified for a pristine atmosphere (AOT < 0.08). Aerosol invigoration signature is also revealed by the concurrent increase of CDER, COD, and CWP with increasing AOT for a polluted marine atmosphere (AOT > 0.3) in the tropical convergence zones. The regions where the second AIE is likely to manifest in the CCF change are limited to several oceanic areas with high CCF of the warm water clouds near the western coasts of continents. The second AIE signature as represented by the reduction of the precipitation efficiency with increasing AOT is more likely to be observed in the AOT regime of 0.08 < AOT < 0.4. The corresponding AIE active regions manifested themselves as the decline of the precipitation efficiency are mainly limited to the oceanic areas downwind of continental aerosols. The sensitive regime of the conventional AIE identified in this observational study

  16. Using Long-Term Satellite Observations to Identify Sensitive Regimes and Active Regions of Aerosol Indirect Effects for Liquid Clouds Over Global Oceans.

    PubMed

    Zhao, Xuepeng; Liu, Yangang; Yu, Fangquan; Heidinger, Andrew K

    2018-01-16

    Long-term (1981-2011) satellite climate data records of clouds and aerosols are used to investigate the aerosol-cloud interaction of marine water cloud from a climatology perspective. Our focus is on identifying the regimes and regions where the aerosol indirect effects (AIEs) are evident in long-term averages over the global oceans through analyzing the correlation features between aerosol loading and the key cloud variables including cloud droplet effective radius (CDER), cloud optical depth (COD), cloud water path (CWP), cloud top height (CTH), and cloud top temperature (CTT). An aerosol optical thickness (AOT) range of 0.13 < AOT < 0.3 is identified as the sensitive regime of the conventional first AIE where CDER is more susceptible to AOT than the other cloud variables. The first AIE that manifests as the change of long-term averaged CDER appears only in limited oceanic regions. The signature of aerosol invigoration of water clouds as revealed by the increase of cloud cover fraction (CCF) and CTH with increasing AOT at the middle/high latitudes of both hemispheres is identified for a pristine atmosphere (AOT < 0.08). Aerosol invigoration signature is also revealed by the concurrent increase of CDER, COD, and CWP with increasing AOT for a polluted marine atmosphere (AOT > 0.3) in the tropical convergence zones. The regions where the second AIE is likely to manifest in the CCF change are limited to several oceanic areas with high CCF of the warm water clouds near the western coasts of continents. The second AIE signature as represented by the reduction of the precipitation efficiency with increasing AOT is more likely to be observed in the AOT regime of 0.08 < AOT < 0.4. The corresponding AIE active regions manifested themselves as the decline of the precipitation efficiency are mainly limited to the oceanic areas downwind of continental aerosols. The sensitive regime of the conventional AIE identified in this observational study is likely associated

  17. The Transposon impala Is Activated by Low Temperatures: Use of a Controlled Transposition System To Identify Genes Critical for Viability of Aspergillus fumigatus ▿ †

    PubMed Central

    Carr, Paul D.; Tuckwell, Danny; Hey, Peter M.; Simon, Laurence; d'Enfert, Christophe; Birch, Mike; Oliver, Jason D.; Bromley, Michael J.

    2010-01-01

    Genes that are essential for viability represent potential targets for the development of anti-infective agents. However, relatively few have been determined in the filamentous fungal pathogen Aspergillus fumigatus. A novel solution employing parasexual genetics coupled with transposon mutagenesis using the Fusarium oxysporum transposon impala had previously enabled the identification of 20 essential genes from A. fumigatus; however, further use of this system required a better understanding of the mode of action of the transposon itself. Examination of a range of conditions indicated that impala is activated by prolonged exposure to low temperatures. This newly identified property was then harnessed to identify 96 loci that are critical for viability in A. fumigatus, including genes required for RNA metabolism, organelle organization, protein transport, ribosome biogenesis, and transcription, as well as a number of noncoding RNAs. A number of these genes represent potential targets for much-needed novel antifungal drugs. PMID:20097738

  18. A small molecule screen identifies a novel compound that induces a homeotic transformation in Hydra

    PubMed Central

    Glauber, Kristine M.; Dana, Catherine E.; Park, Steve S.; Colby, David A.; Noro, Yukihiko; Fujisawa, Toshitaka; Chamberlin, A. Richard; Steele, Robert E.

    2013-01-01

    Developmental processes such as morphogenesis, patterning and differentiation are continuously active in the adult Hydra polyp. We carried out a small molecule screen to identify compounds that affect patterning in Hydra. We identified a novel molecule, DAC-2-25, that causes a homeotic transformation of body column into tentacle zone. This transformation occurs in a progressive and polar fashion, beginning at the oral end of the animal. We have identified several strains that respond to DAC-2-25 and one that does not, and we used chimeras from these strains to identify the ectoderm as the target tissue for DAC-2-25. Using transgenic Hydra that express green fluorescent protein under the control of relevant promoters, we examined how DAC-2-25 affects tentacle patterning. Genes whose expression is associated with the tentacle zone are ectopically expressed upon exposure to DAC-2-25, whereas those associated with body column tissue are turned off as the tentacle zone expands. The expression patterns of the organizer-associated gene HyWnt3 and the hypostome-specific gene HyBra2 are unchanged. Structure-activity relationship studies have identified features of DAC-2-25 that are required for activity and potency. This study shows that small molecule screens in Hydra can be used to dissect patterning processes. PMID:24255098

  19. A small molecule screen identifies a novel compound that induces a homeotic transformation in Hydra.

    PubMed

    Glauber, Kristine M; Dana, Catherine E; Park, Steve S; Colby, David A; Noro, Yukihiko; Fujisawa, Toshitaka; Chamberlin, A Richard; Steele, Robert E

    2013-12-01

    Developmental processes such as morphogenesis, patterning and differentiation are continuously active in the adult Hydra polyp. We carried out a small molecule screen to identify compounds that affect patterning in Hydra. We identified a novel molecule, DAC-2-25, that causes a homeotic transformation of body column into tentacle zone. This transformation occurs in a progressive and polar fashion, beginning at the oral end of the animal. We have identified several strains that respond to DAC-2-25 and one that does not, and we used chimeras from these strains to identify the ectoderm as the target tissue for DAC-2-25. Using transgenic Hydra that express green fluorescent protein under the control of relevant promoters, we examined how DAC-2-25 affects tentacle patterning. Genes whose expression is associated with the tentacle zone are ectopically expressed upon exposure to DAC-2-25, whereas those associated with body column tissue are turned off as the tentacle zone expands. The expression patterns of the organizer-associated gene HyWnt3 and the hypostome-specific gene HyBra2 are unchanged. Structure-activity relationship studies have identified features of DAC-2-25 that are required for activity and potency. This study shows that small molecule screens in Hydra can be used to dissect patterning processes.

  20. High-throughput combinatorial screening identifies drugs that cooperate with ibrutinib to kill activated B-cell–like diffuse large B-cell lymphoma cells

    PubMed Central

    Mathews Griner, Lesley A.; Guha, Rajarshi; Shinn, Paul; Young, Ryan M.; Keller, Jonathan M.; Liu, Dongbo; Goldlust, Ian S.; Yasgar, Adam; McKnight, Crystal; Boxer, Matthew B.; Duveau, Damien Y.; Jiang, Jian-Kang; Michael, Sam; Mierzwa, Tim; Huang, Wenwei; Walsh, Martin J.; Mott, Bryan T.; Patel, Paresma; Leister, William; Maloney, David J.; Leclair, Christopher A.; Rai, Ganesha; Jadhav, Ajit; Peyser, Brian D.; Austin, Christopher P.; Martin, Scott E.; Simeonov, Anton; Ferrer, Marc; Staudt, Louis M.; Thomas, Craig J.

    2014-01-01

    The clinical development of drug combinations is typically achieved through trial-and-error or via insight gained through a detailed molecular understanding of dysregulated signaling pathways in a specific cancer type. Unbiased small-molecule combination (matrix) screening represents a high-throughput means to explore hundreds and even thousands of drug–drug pairs for potential investigation and translation. Here, we describe a high-throughput screening platform capable of testing compounds in pairwise matrix blocks for the rapid and systematic identification of synergistic, additive, and antagonistic drug combinations. We use this platform to define potential therapeutic combinations for the activated B-cell–like subtype (ABC) of diffuse large B-cell lymphoma (DLBCL). We identify drugs with synergy, additivity, and antagonism with the Bruton’s tyrosine kinase inhibitor ibrutinib, which targets the chronic active B-cell receptor signaling that characterizes ABC DLBCL. Ibrutinib interacted favorably with a wide range of compounds, including inhibitors of the PI3K-AKT-mammalian target of rapamycin signaling cascade, other B-cell receptor pathway inhibitors, Bcl-2 family inhibitors, and several components of chemotherapy that is the standard of care for DLBCL. PMID:24469833

  1. RNA-seq analysis identifies potential modulators of gravity response in spores of Ceratopteris (Parkeriaceae): evidence for modulation by calcium pumps and apyrase activity.

    PubMed

    Bushart, Thomas J; Cannon, Ashley E; Ul Haque, Aeraj; San Miguel, Phillip; Mostajeran, Kathy; Clark, Gregory B; Porterfield, D Marshall; Roux, Stanley J

    2013-01-01

    Gravity regulates the magnitude and direction of a trans-cell calcium current in germinating spores of Ceratopteris richardii. Blocking this current with nifedipine blocks the spore's downward polarity alignment, a polarization that is fixed by gravity ∼10 h after light induces the spores to germinate. RNA-seq analysis at 10 h was used to identify genes potentially important for the gravity response. The data set will be valuable for other developmental and phylogenetic studies. De novo Newbler assembly of 958 527 reads from Roche 454 sequencing was executed. The sequences were identified and analyzed using in silico methods. The roles of endomembrane Ca(2+)-ATPase pumps and apyrases in the gravity response were further tested using pharmacological agents. Transcripts related to calcium signaling and ethylene biosynthesis were identified as notable constituents of the transcriptome. Inhibiting the activity of endomembrane Ca(2+)-ATPase pumps with 2,5-di-(t-butyl)-1,4-hydroquinone diminished the trans-cell current, but increased the orientation of the polar axis to gravity. The effects of applied nucleotides and purinoceptor antagonists gave novel evidence implicating extracellular nucleotides as regulators of the gravity response in these fern spores. In addition to revealing general features of the transcriptome of germinating spores, the results highlight a number of calcium-responsive and light-receptive transcripts. Pharmacologic assays indicate endomembrane Ca(2+)-ATPases and extracellular nucleotides may play regulatory roles in the gravity response of Ceratopteris spores.

  2. Retro-binding thrombin active site inhibitors: identification of an orally active inhibitor of thrombin catalytic activity.

    PubMed

    Iwanowicz, Edwin J; Kimball, S David; Lin, James; Lau, Wan; Han, W-C; Wang, Tammy C; Roberts, Daniel G M; Schumacher, W A; Ogletree, Martin L; Seiler, Steven M

    2002-11-04

    A series of retro-binding inhibitors of human alpha-thrombin was prepared to elucidate structure-activity relationships (SAR) and optimize in vivo performance. Compounds 9 and 11, orally active inhibitors of thrombin catalytic activity, were identified to be efficacious in a thrombin-induced lethality model in mice.

  3. 30 CFR 206.113 - How will MMS identify market centers?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Section 206.113 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR MINERALS REVENUE MANAGEMENT PRODUCT VALUATION Federal Oil § 206.113 How will MMS identify market centers? MMS periodically will publish in the Federal Register a list of market centers. MMS will monitor market activity and, if...

  4. DEVELOPMENT OF A MOLECULAR METHOD TO IDENTIFY ...

    EPA Pesticide Factsheets

    Hepatitis E virus (HEV) is an emerging pathogen that causes significant illness in the developing world. Like the hepatitis A virus, it is transmitted via the fecal-oral route and can cause short-term, acute hepatitis. In addition, hepatitis E has been found to cause a significant rate of mortality in pregnant women. Thus far, a hepatitis E outbreak has not been reported in the U. S. although a swine variant of the virus is common in Midwestern hogs. Since it will be important to identify the presence of this virus in the water supply, we have developed and are testing a reverse transcription-polymerase chain reaction (RT-PCR) method that should be able to identify all of the known HEV strains. Develop sensitive techniques to detect and identify emerging human waterborne pathogenic viruses and viruses on the CCL.Determine effectiveness of viral indicators to measure microbial quality in water matrices.Support activities: (a) culture and distribution of mammalian cells for Agency and scientific community research needs, (b) provide operator expertise for research requiring confocal and electron microscopy, (c) glassware cleaning, sterilization and biological waste disposal for the Cincinnati EPA facility, (d) operation of infectious pathogenic suite, (e) maintenance of walk-in constant temperature rooms and (f) provide Giardia cysts.

  5. Epirubicin, Identified Using a Novel Luciferase Reporter Assay for Foxp3 Inhibitors, Inhibits Regulatory T Cell Activity.

    PubMed

    Kashima, Hajime; Momose, Fumiyasu; Umehara, Hiroshi; Miyoshi, Nao; Ogo, Naohisa; Muraoka, Daisuke; Shiku, Hiroshi; Harada, Naozumi; Asai, Akira

    2016-01-01

    Forkhead box protein p3 (Foxp3) is crucial to the development and suppressor function of regulatory T cells (Tregs) that have a significant role in tumor-associated immune suppression. Development of small molecule inhibitors of Foxp3 function is therefore considered a promising strategy to enhance anti-tumor immunity. In this study, we developed a novel cell-based assay system in which the NF-κB luciferase reporter signal is suppressed by the co-expressed Foxp3 protein. Using this system, we screened our chemical library consisting of approximately 2,100 compounds and discovered that a cancer chemotherapeutic drug epirubicin restored the Foxp3-inhibited NF-κB activity in a concentration-dependent manner without influencing cell viability. Using immunoprecipitation assay in a Treg-like cell line Karpas-299, we found that epirubicin inhibited the interaction between Foxp3 and p65. In addition, epirubicin inhibited the suppressor function of murine Tregs and thereby improved effector T cell stimulation in vitro. Administration of low dose epirubicin into tumor-bearing mice modulated the function of immune cells at the tumor site and promoted their IFN-γ production without direct cytotoxicity. In summary, we identified the novel action of epirubicin as a Foxp3 inhibitor using a newly established luciferase-based cellular screen. Our work also demonstrated our screen system is useful in accelerating discovery of Foxp3 inhibitors.

  6. High-throughput screening (HTS) and hit validation to identify small molecule inhibitors with activity against NS3/4A proteases from multiple hepatitis C virus genotypes.

    PubMed

    Lee, Hyun; Zhu, Tian; Patel, Kavankumar; Zhang, Yan-Yan; Truong, Lena; Hevener, Kirk E; Gatuz, Joseph L; Subramanya, Gitanjali; Jeong, Hyun-Young; Uprichard, Susan L; Johnson, Michael E

    2013-01-01

    Development of drug-resistant mutations has been a major problem with all currently developed Hepatitis C Virus (HCV) NS3/4A inhibitors, including the two FDA approved drugs, significantly reducing the efficacy of these inhibitors. The high incidence of drug-resistance mutations and the limited utility of these inhibitors against only genotype 1 highlight the need for novel, broad-spectrum HCV therapies. Here we used high-throughput screening (HTS) to identify low molecular weight inhibitors against NS3/4A from multiple genotypes. A total of 40,967 compounds from four structurally diverse molecular libraries were screened by HTS using fluorescence-based enzymatic assays, followed by an orthogonal binding analysis using surface plasmon resonance (SPR) to eliminate false positives. A novel small molecule compound was identified with an IC50 value of 2.2 µM against the NS3/4A from genotype 1b. Mode of inhibition analysis subsequently confirmed this compound to be a competitive inhibitor with respect to the substrate, indicating direct binding to the protease active site, rather than to the allosteric binding pocket that was discovered to be the binding site of a few recently discovered small molecule inhibitors. This newly discovered inhibitor also showed promising inhibitory activity against the NS3/4As from three other HCV genotypes, as well as five common drug-resistant mutants of genotype 1b NS3/4A. The inhibitor was selective for NS3 from multiple HCV genotypes over two human serine proteases, and a whole cell lysate assay confirmed inhibitory activity in the cellular environment. This compound provides a lead for further development of potentially broader spectrum inhibitors.

  7. Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Krauthammer, Michael; Kong, Yong; Ha, Byung Hak

    We characterized the mutational landscape of melanoma, the form of skin cancer with the highest mortality rate, by sequencing the exomes of 147 melanomas. Sun-exposed melanomas had markedly more ultraviolet (UV)-like C>T somatic mutations compared to sun-shielded acral, mucosal and uveal melanomas. Among the newly identified cancer genes was PPP6C, encoding a serine/threonine phosphatase, which harbored mutations that clustered in the active site in 12% of sun-exposed melanomas, exclusively in tumors with mutations in BRAF or NRAS. Notably, we identified a recurrent UV-signature, an activating mutation in RAC1 in 9.2% of sun-exposed melanomas. This activating mutation, the third most frequentmore » in our cohort of sun-exposed melanoma after those of BRAF and NRAS, changes Pro29 to serine (RAC1{sup P29S}) in the highly conserved switch I domain. Crystal structures, and biochemical and functional studies of RAC1{sup P29S} showed that the alteration releases the conformational restraint conferred by the conserved proline, causes an increased binding of the protein to downstream effectors, and promotes melanocyte proliferation and migration. These findings raise the possibility that pharmacological inhibition of downstream effectors of RAC1 signaling could be of therapeutic benefit.« less

  8. Impairment of O-antigen production confers resistance to grazing in a model amoeba-cyanobacterium predator-prey system.

    PubMed

    Simkovsky, Ryan; Daniels, Emy F; Tang, Karen; Huynh, Stacey C; Golden, Susan S; Brahamsha, Bianca

    2012-10-09

    The grazing activity of predators on photosynthetic organisms is a major mechanism of mortality and population restructuring in natural environments. Grazing is also one of the primary difficulties in growing cyanobacteria and other microalgae in large, open ponds for the production of biofuels, as contaminants destroy valuable biomass and prevent stable, continuous production of biofuel crops. To address this problem, we have isolated a heterolobosean amoeba, HGG1, that grazes upon unicellular and filamentous freshwater cyanobacterial species. We have established a model predator-prey system using this amoeba and Synechococcus elongatus PCC 7942. Application of amoebae to a library of mutants of S. elongatus led to the identification of a grazer-resistant knockout mutant of the wzm ABC O-antigen transporter gene, SynPCC7942_1126. Mutations in three other genes involved in O-antigen synthesis and transport also prevented the expression of O-antigen and conferred resistance to HGG1. Complementation of these rough mutants returned O-antigen expression and susceptibility to amoebae. Rough mutants are easily identifiable by appearance, are capable of autoflocculation, and do not display growth defects under standard laboratory growth conditions, all of which are desired traits for a biofuel production strain. Thus, preventing the production of O-antigen is a pathway for producing resistance to grazing by certain amoebae.

  9. A Quantitative RNAi Screen for JNK Modifiers Identifies Pvr as a Novel Regulator of Drosophila Immune Signaling

    PubMed Central

    Bond, David; Foley, Edan

    2009-01-01

    Drosophila melanogaster responds to gram-negative bacterial challenges through the IMD pathway, a signal transduction cassette that is driven by the coordinated activities of JNK, NF-κB and caspase modules. While many modifiers of NF-κB activity were identified in cell culture and in vivo assays, the regulatory apparatus that determines JNK inputs into the IMD pathway is relatively unexplored. In this manuscript, we present the first quantitative screen of the entire genome of Drosophila for novel regulators of JNK activity in the IMD pathway. We identified a large number of gene products that negatively or positively impact on JNK activation in the IMD pathway. In particular, we identified the Pvr receptor tyrosine kinase as a potent inhibitor of JNK activation. In a series of in vivo and cell culture assays, we demonstrated that activation of the IMD pathway drives JNK-dependent expression of the Pvr ligands, Pvf2 and Pvf3, which in turn act through the Pvr/ERK MAP kinase pathway to attenuate the JNK and NF-κB arms of the IMD pathway. Our data illuminate a poorly understood arm of a critical and evolutionarily conserved innate immune response. Furthermore, given the pleiotropic involvement of JNK in eukaryotic cell biology, we believe that many of the novel regulators identified in this screen are of interest beyond immune signaling. PMID:19893628

  10. Fine Time Course Expression Analysis Identifies Cascades of Activation and Repression and Maps a Putative Regulator of Mammalian Sex Determination

    PubMed Central

    Looger, Loren L.; Ohler, Uwe; Capel, Blanche

    2013-01-01

    In vertebrates, primary sex determination refers to the decision within a bipotential organ precursor to differentiate as a testis or ovary. Bifurcation of organ fate begins between embryonic day (E) 11.0–E12.0 in mice and likely involves a dynamic transcription network that is poorly understood. To elucidate the first steps of sexual fate specification, we profiled the XX and XY gonad transcriptomes at fine granularity during this period and resolved cascades of gene activation and repression. C57BL/6J (B6) XY gonads showed a consistent ∼5-hour delay in the activation of most male pathway genes and repression of female pathway genes relative to 129S1/SvImJ, which likely explains the sensitivity of the B6 strain to male-to-female sex reversal. Using this fine time course data, we predicted novel regulatory genes underlying expression QTLs (eQTLs) mapped in a previous study. To test predictions, we developed an in vitro gonad primary cell assay and optimized a lentivirus-based shRNA delivery method to silence candidate genes and quantify effects on putative targets. We provide strong evidence that Lmo4 (Lim-domain only 4) is a novel regulator of sex determination upstream of SF1 (Nr5a1), Sox9, Fgf9, and Col9a3. This approach can be readily applied to identify regulatory interactions in other systems. PMID:23874228

  11. Identifying the computational requirements of an integrated top-down-bottom-up model for overt visual attention within an active vision system.

    PubMed

    McBride, Sebastian; Huelse, Martin; Lee, Mark

    2013-01-01

    Computational visual attention systems have been constructed in order for robots and other devices to detect and locate regions of interest in their visual world. Such systems often attempt to take account of what is known of the human visual system and employ concepts, such as 'active vision', to gain various perceived advantages. However, despite the potential for gaining insights from such experiments, the computational requirements for visual attention processing are often not clearly presented from a biological perspective. This was the primary objective of this study, attained through two specific phases of investigation: 1) conceptual modeling of a top-down-bottom-up framework through critical analysis of the psychophysical and neurophysiological literature, 2) implementation and validation of the model into robotic hardware (as a representative of an active vision system). Seven computational requirements were identified: 1) transformation of retinotopic to egocentric mappings, 2) spatial memory for the purposes of medium-term inhibition of return, 3) synchronization of 'where' and 'what' information from the two visual streams, 4) convergence of top-down and bottom-up information to a centralized point of information processing, 5) a threshold function to elicit saccade action, 6) a function to represent task relevance as a ratio of excitation and inhibition, and 7) derivation of excitation and inhibition values from object-associated feature classes. The model provides further insight into the nature of data representation and transfer between brain regions associated with the vertebrate 'active' visual attention system. In particular, the model lends strong support to the functional role of the lateral intraparietal region of the brain as a primary area of information consolidation that directs putative action through the use of a 'priority map'.

  12. Transcriptome analysis of Pseudomonas syringae identifies new genes, ncRNAs, and antisense activity

    USDA-ARS?s Scientific Manuscript database

    To fully understand how bacteria respond to their environment, it is essential to assess genome-wide transcriptional activity. New high throughput sequencing technologies make it possible to query the transcriptome of an organism in an efficient unbiased manner. We applied a strand-specific method t...

  13. Can Australians identify snakes?

    PubMed

    Morrison, J J; Pearn, J H; Covacevich, J; Nixon, J

    1983-07-23

    A study of the ability of Australians to identify snakes was undertaken, in which 558 volunteers (primary and secondary schoolchildren, doctors and university science and medical students) took part. Over all, subjects correctly identified an average of 19% of snakes; 28% of subjects could identify a taipan, 59% could identify a death adder, 18% a tiger snake, 23% an eastern (or common) brown snake, and 0.5% a rough-scaled snake. Eighty-six per cent of subjects who grew up in rural areas could identify a death adder; only 4% of those who grew up in an Australian capital city could identify a nonvenomous python. Male subjects identified snakes more accurately than did female subjects. Doctors and medical students correctly identified an average of 25% of snakes. The ability to identify medically significant Australian snakes was classified according to the observer's background, education, sex, and according to the individual snake species. Australians need to be better educated about snakes indigenous to this country.

  14. Quantitative Proteomics Identifies Activation of Hallmark Pathways of Cancer in Patient Melanoma.

    PubMed

    Byrum, Stephanie D; Larson, Signe K; Avaritt, Nathan L; Moreland, Linley E; Mackintosh, Samuel G; Cheung, Wang L; Tackett, Alan J

    2013-03-01

    Molecular pathways regulating melanoma initiation and progression are potential targets of therapeutic development for this aggressive cancer. Identification and molecular analysis of these pathways in patients has been primarily restricted to targeted studies on individual proteins. Here, we report the most comprehensive analysis of formalin-fixed paraffin-embedded human melanoma tissues using quantitative proteomics. From 61 patient samples, we identified 171 proteins varying in abundance among benign nevi, primary melanoma, and metastatic melanoma. Seventy-three percent of these proteins were validated by immunohistochemistry staining of malignant melanoma tissues from the Human Protein Atlas database. Our results reveal that molecular pathways involved with tumor cell proliferation, motility, and apoptosis are mis-regulated in melanoma. These data provide the most comprehensive proteome resource on patient melanoma and reveal insight into the molecular mechanisms driving melanoma progression.

  15. Identifying Novel Molecular Structures for Advanced Melanoma by Ligand-Based Virtual Screening

    PubMed Central

    Wang, Zhao; Lu, Yan; Seibel, William; Miller, Duane D.; Li, Wei

    2009-01-01

    We recently discovered a new class of thiazole analogs that are highly potent against melanoma cells. To expand the structure-activity relationship study and to explore potential new molecular scaffolds, we performed extensive ligand-based virtual screening against a compound library containing 342,910 small molecules. Two different approaches of virtual screening were carried out using the structure of our lead molecule: 1) connectivity-based search using Scitegic Pipeline Pilot from Accelerys and 2) molecular shape similarity search using Schrodinger software. Using a testing compound library, both approaches can rank similar compounds very high and rank dissimilar compounds very low, thus validating our screening methods. Structures identified from these searches were analyzed, and selected compounds were tested in vitro to assess their activity against melanoma cancer cell lines. Several molecules showed good anticancer activity. While none of the identified compounds showed better activity than our lead compound, they provided important insight into structural modifications for our lead compound and also provided novel platforms on which we can optimize new classes of anticancer compounds. One of the newly synthesized analogs based on this virtual screening has improved potency and selectivity against melanoma. PMID:19445498

  16. Identifying the Barriers and Facilitators to Participation in Physical Activity for Children with Down Syndrome

    ERIC Educational Resources Information Center

    Barr, M.; Shields, N.

    2011-01-01

    Background: Many children with Down syndrome do not undertake the recommended amount of daily physical activity. The aim of this study was to explore the barriers and facilitators to physical activity for this group. Methods: Eighteen in-depth interviews were conducted with 20 parents (16 mothers, 4 fathers) of children with Down syndrome aged…

  17. CONCEPTUAL APPROACHES TO IDENTIFY AND ASSESS MULTPLE STRESSORS, SECTION 1.1

    EPA Science Inventory

    Every ecosystem is subject to multiple stressors arising from the interactions of biological, physical, and socioeconomic processes (e.g. exploitation and development). These stressors and their interactions need to be identified if risks associated with a planned activity are to...

  18. Ancestry-based stratified analysis of Immunochip data identifies novel associations with celiac disease.

    PubMed

    Garcia-Etxebarria, Koldo; Jauregi-Miguel, Amaia; Romero-Garmendia, Irati; Plaza-Izurieta, Leticia; Legarda, Maria; Irastorza, Iñaki; Bilbao, Jose Ramon

    2016-12-01

    To identify candidate genes in celiac disease (CD), we reanalyzed the whole Immunochip CD cohort using a different approach that clusters individuals based on immunoancestry prior to disease association analysis, rather than by geographical origin. We detected 636 new associated SNPs (P<7.02 × 10 -07 ) and identified 5 novel genomic regions, extended 8 others previously identified and also detected 18 isolated signals defined by one or very few significant SNPs. To test whether we could identify putative candidate genes, we performed expression analyses of several genes from the top novel region (chr2:134533564-136169524), from a previously identified locus that is now extended, and a gene marked by an isolated SNP, in duodenum biopsies of active and treated CD patients, and non-celiac controls. In the largest novel region, CCNT2 and R3HDM1 were constitutively underexpressed in disease, even after gluten removal. Moreover, several genes within this region were coexpressed in patients, but not in controls. Other novel genes like KIF21B, REL and SORD also showed altered expression in active disease. Apart from the identification of novel CD loci, these results suggest that ancestry-based stratified analysis is an efficient strategy for association studies in complex diseases.

  19. Relationships between public health nurse-delivered physical activity interventions and client physical activity behavior.

    PubMed

    Olsen, Jeanette M; Horning, Melissa L; Thorson, Diane; Monsen, Karen A

    2018-04-01

    The purpose of this study was to identify physical activity interventions delivered by public health nurses (PHNs) and examine their association with physical activity behavior change among adult clients. Physical activity is a public health priority, yet little is known about nurse-delivered physical activity interventions in day-to-day practice or their outcomes. This quantitative retrospective evaluation examined de-identified electronic-health-record data. Adult clients with at least two Omaha System Physical activity Knowledge, Behavior, and Status (KBS) ratings documented by PHNs between October 2010-June 2016 (N=419) were included. Omaha System baseline and follow-up Physical activity KBS ratings, interventions, and demographics were examined. Younger clients typically receiving maternal-child/family services were more likely to receive interventions than older clients (p<0.001). A total of 2869 Physical activity interventions were documented among 197 clients. Most were from categories of Teaching, Guidance, Counseling (n=1639) or Surveillance (n=1183). Few were Case Management (n=46). Hierarchical regression modeling explained 15.4% of the variance for change in Physical activity Behavior rating with significant influence from intervention dose (p=0.03) and change in Physical activity Knowledge (p<0.001). This study identified and described physical activity interventions delivered by PHNs. Implementation of department-wide policy requiring documentation of Physical activity assessment for all clients enabled the evaluation. A higher dose of physical activity interventions and increased Physical activity knowledge were associated with increased Physical activity Behavior. More research is needed to identify factors influencing who receives interventions and how interventions are selected. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Psychosocial counselling of identifiable sperm donors.

    PubMed

    Visser, M; Mochtar, M H; de Melker, A A; van der Veen, F; Repping, S; Gerrits, T

    2016-05-01

    What do identifiable sperm donors feel about psychosocial counselling? Identifiable sperm donors found it important that psychosocial counselling focused on emotional consequences and on rules and regulations and they expected to have access to psychosocial counselling at the time that donor-offspring actually sought contact. Most studies on sperm donors are on anonymous donors and focus on recruitment, financial compensation, anonymity and motivations. There is limited knowledge on the value that identifiable sperm donors place on psychosocial counselling and what their needs are in this respect. We performed a qualitative study from March until June 2014 with 25 identifiable sperm donors, who were or had been a donor at the Centre for Reproductive Medicine of the Academic Medical Centre in Amsterdam any time between 1989 and 2014. We held semi-structured in-depth interviews with identifiable sperm donors with an average age of 44 years. The interviews were fully transcribed and analysed using the constant comparative method of grounded theory. Twelve out of 15 donors (former donors ITALIC! n = 8, active donors ITALIC! n = 7) who had received a counselling session during their intake procedure found it important that they had been able to talk about issues such as the emotional consequences of donation, disclosure to their own children, family and friends, future contact with donor-offspring and rules and regulations. Of the 10 former donors who had received no counselling session, 8 had regretted the lack of intensive counselling. In the years following their donation, most donors simply wanted to know how many offspring had been born using their sperm and had no need for further counselling. Nevertheless, they frequently mentioned that they were concerned about the well-being of 'their' offspring. In addition, they would value the availability of psychosocial counselling in the event that donor-offspring actually sought contact. A limitation of our study is its

  1. Bioassay-guided isolation of active principles from Nigerian medicinal plants identifies new trypanocides with low toxicity and no cross-resistance to diamidines and arsenicals.

    PubMed

    Ebiloma, Godwin Unekwuojo; Igoli, John Ogbaji; Katsoulis, Evangelos; Donachie, Anne-Marie; Eze, Anthonius; Gray, Alexander Ian; de Koning, Harry P

    2017-04-18

    Leaves from the plant species studied herein are traditionally used in northern Nigeria against various protozoan infections. However, none of these herbal preparations have been standardized, nor have their toxicity to mammalian cells been investigated. In search of improved and non-toxic active antiprotozoal principles that are not cross-resistant with current anti-parasitics, we here report the results of the in vitro screening of extracts from seven selected medicinal plant species (Centrosema pubescens, Moringa oleifera, Tridax procumbens, Polyalthia longifolia, Newbouldia laevis, Eucalyptus maculate, Jathropha tanjorensis), used traditionally to treat kinetoplastid infections in Nigeria, and the isolation of their bioactive principles. To investigate the efficacies of medicinal plant extracts, and of compounds isolated therefrom, against kinetoplastid parasites, assess cross-resistance to existing chemotherapy, and assay their toxicity against mammalian cells in vitro. Plants were extracted with hexane, ethyl acetate and methanol. Active principles were isolated by bioassay-led fractionation, testing for trypanocidal activity, and identified using NMR and mass spectrometry. EC 50 values for their activity against wild-type and multi-drug resistant Trypanosoma brucei were obtained using the viability indicator dye resazurin. Seven medicinal plants were evaluated for activity against selected kinetoplastid parasites. The result shows that crude extracts and isolated active compounds from Polyalthia longifolia and Eucalyptus maculata, in particular, display promising activity against drug-sensitive and multi-drug resistant Trypanosoma brucei. The EC 50 value of a clerodane (16α-hydroxy-cleroda-3,13(14)-Z-dien-15,16-olide) isolated from Polyalthia longifolia was as low as 0.38µg/mL, while a triterpenoid (3β,13β-dihydroxy-urs-11-en-28-oic acid) isolated from Eucalyptus maculata displayed an EC 50 of 1.58µg/mL. None of the isolated compounds displayed toxicity

  2. Identifying Dynamic Protein Complexes Based on Gene Expression Profiles and PPI Networks

    PubMed Central

    Li, Min; Chen, Weijie; Wang, Jianxin; Pan, Yi

    2014-01-01

    Identification of protein complexes from protein-protein interaction networks has become a key problem for understanding cellular life in postgenomic era. Many computational methods have been proposed for identifying protein complexes. Up to now, the existing computational methods are mostly applied on static PPI networks. However, proteins and their interactions are dynamic in reality. Identifying dynamic protein complexes is more meaningful and challenging. In this paper, a novel algorithm, named DPC, is proposed to identify dynamic protein complexes by integrating PPI data and gene expression profiles. According to Core-Attachment assumption, these proteins which are always active in the molecular cycle are regarded as core proteins. The protein-complex cores are identified from these always active proteins by detecting dense subgraphs. Final protein complexes are extended from the protein-complex cores by adding attachments based on a topological character of “closeness” and dynamic meaning. The protein complexes produced by our algorithm DPC contain two parts: static core expressed in all the molecular cycle and dynamic attachments short-lived. The proposed algorithm DPC was applied on the data of Saccharomyces cerevisiae and the experimental results show that DPC outperforms CMC, MCL, SPICi, HC-PIN, COACH, and Core-Attachment based on the validation of matching with known complexes and hF-measures. PMID:24963481

  3. Methanotrophic bacteria in warm geothermal spring sediments identified using stable-isotope probing.

    PubMed

    Sharp, Christine E; Martínez-Lorenzo, Azucena; Brady, Allyson L; Grasby, Stephen E; Dunfield, Peter F

    2014-10-01

    We investigated methanotrophic bacteria in sediments of several warm geothermal springs ranging in temperature from 22 to 45 °C. Methane oxidation was measured at potential rates up to 141 μmol CH4 d(-1) g(-1) sediment. Active methanotrophs were identified using (13) CH4 stable-isotope probing (SIP) incubations performed at close to in situ temperatures for each site. Quantitative (q) PCR of pmoA genes identified the position of the heavy ((13) C-labelled) DNA fractions in density gradients, and 16S rRNA gene pyrotag sequencing of the heavy fractions was performed to identify the active methanotrophs. Methanotroph communities identified in heavy fractions of all samples were predominated by species similar (≥ 95% 16S rRNA gene identities) to previously characterized Gammaproteobacteria and Alphaproteobacteria methanotrophs. Among the five hottest samples (45 °C), members of the Gammaproteobacteria genus Methylocaldum dominated in two cases, while three others were dominated by an OTU closely related (96.8% similarity) to the Alphaproteobacteria genus Methylocapsa. These results suggest that diverse methanotroph groups are adapted to warm environments, including the Methylocapsa-Methylocella-Methyloferula group, which has previously only been detected in cooler sites. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  4. Identifying and Researching Market Opportunities for New High Technology Products.

    ERIC Educational Resources Information Center

    Dunstan, Peter

    Using a product called the synchro-pulse welder as a case study example, this paper discusses the activities of CSIRO (Commonwealth Scientific and Industrial Research Organisation) in identifying and marketing new high-technology products. A general discussion of CSIRO's market research plans includes two goals to be attained within the next 5…

  5. Grazing alters net ecosystem C fluxes and the global warming potential of a subtropical pasture.

    PubMed

    Gomez-Casanovas, Nuria; DeLucia, Nicholas J; Bernacchi, Carl J; Boughton, Elizabeth H; Sparks, Jed P; Chamberlain, Samuel D; DeLucia, Evan H

    2018-03-01

    The impact of grazing on C fluxes from pastures in subtropical and tropical regions and on the environment is uncertain, although these systems account for a substantial portion of global C storage. We investigated how cattle grazing influences net ecosystem CO 2 and CH 4 exchange in subtropical pastures using the eddy covariance technique. Measurements were made over several wet-dry seasonal cycles in a grazed pasture, and in an adjacent pasture during the first three years of grazer exclusion. Grazing increased soil wetness but did not affect soil temperature. By removing aboveground biomass, grazing decreased ecosystem respiration (R eco ) and gross primary productivity (GPP). As the decrease in R eco was larger than the reduction in GPP, grazing consistently increased the net CO 2 sink strength of subtropical pastures (55, 219 and 187 more C/m 2 in 2013, 2014, and 2015). Enteric ruminant fermentation and increased soil wetness due to grazers, increased total net ecosystem CH 4 emissions in grazed relative to ungrazed pasture (27-80%). Unlike temperate, arid, and semiarid pastures, where differences in CH 4 emissions between grazed and ungrazed pastures are mainly driven by enteric ruminant fermentation, our results showed that the effect of grazing on soil CH 4 emissions can be greater than CH 4 produced by cattle. Thus, our results suggest that the interactions between grazers and soil hydrology affecting soil CH 4 emissions play an important role in determining the environmental impacts of this management practice in a subtropical pasture. Although grazing increased total net ecosystem CH 4 emissions and removed aboveground biomass, it increased the net storage of C and decreased the global warming potential associated with C fluxes of pasture by increasing its net CO 2 sink strength. © 2017 by the Ecological Society of America.

  6. Controls on microalgal community structures in cryoconite holes upon high-Arctic glaciers, Svalbard

    NASA Astrophysics Data System (ADS)

    Vonnahme, T. R.; Devetter, M.; Žárský, J. D.; Šabacká, M.; Elster, J.

    2016-02-01

    Glaciers are known to harbor surprisingly complex ecosystems. On their surface, distinct cylindrical holes filled with meltwater and sediments are considered hot spots for microbial life. The present paper addresses possible biological interactions within the community of prokaryotic cyanobacteria and eukaryotic microalgae (microalgae) and relations to their potential grazers, such as tardigrades and rotifers, additional to their environmental controls. Svalbard glaciers with substantial allochthonous input of material from local sources reveal high microalgal densities. Small valley glaciers with high sediment coverages and high impact of birds show high biomasses and support a high biological diversity. Invertebrate grazer densities do not show any significant negative correlation with microalgal abundances but rather a positive correlation with eukaryotic microalgae. Shared environmental preferences and a positive effect of grazing are the proposed mechanisms to explain these correlations. Most microalgae found in this study form colonies (< 10 cells, or > 25 µm), which may protect them against invertebrate grazing. This finding rather indicates grazing as a positive control on eukaryotic microalgae by nutrient recycling. Density differences between the eukaryotic microalgae and prokaryotic cyanobacteria and their high distinction in redundancy (RDA) and principal component (PCA) analyses indicate that these two groups are in strong contrast. Eukaryotic microalgae occurred mainly in unstable cryoconite holes with high sediment loads, high N : P ratios, and a high impact of nutrient input by bird guano, as a proxy for nutrients. In these environments autochthonous nitrogen fixation appears to be negligible. Selective wind transport of Oscillatoriales via soil and dust particles is proposed to explain their dominance in cryoconites further away from the glacier margins. We propose that, for the studied glaciers, nutrient levels related to recycling of limiting

  7. Interactive effects of large herbivores and plant diversity on insect abundance in a meadow steppe in China

    Treesearch

    Hui Zhu; Deli Wang; Qinfeng Guo; Jun Liu; Ling Wang

    2015-01-01

    The structure and dynamics of insect community in grasslands can be influenced by grazing management via altered characteristics of plant community. However, attempts to better understand the complex relationships among plants, insects, and large herbivores is still hampered largely by the interactive effects of plants, insects, and large grazers on each other. In this...

  8. Identified Serotonin-Releasing Neurons Induce Behavioral Quiescence and Suppress Mating in Drosophila.

    PubMed

    Pooryasin, Atefeh; Fiala, André

    2015-09-16

    Animals show different levels of activity that are reflected in sensory responsiveness and endogenously generated behaviors. Biogenic amines have been determined to be causal factors for these states of arousal. It is well established that, in Drosophila, dopamine and octopamine promote increased arousal. However, little is known about factors that regulate arousal negatively and induce states of quiescence. Moreover, it remains unclear whether global, diffuse modulatory systems comprehensively affecting brain activity determine general states of arousal. Alternatively, individual aminergic neurons might selectively modulate the animals' activity in a distinct behavioral context. Here, we show that artificially activating large populations of serotonin-releasing neurons induces behavioral quiescence and inhibits feeding and mating. We systematically narrowed down a role of serotonin in inhibiting endogenously generated locomotor activity to neurons located in the posterior medial protocerebrum. We identified neurons of this cell cluster that suppress mating, but not feeding behavior. These results suggest that serotonin does not uniformly act as global, negative modulator of general arousal. Rather, distinct serotoninergic neurons can act as inhibitory modulators of specific behaviors. An animal's responsiveness to external stimuli and its various types of endogenously generated, motivated behavior are highly dynamic and change between states of high activity and states of low activity. It remains unclear whether these states are mediated by unitary modulatory systems globally affecting brain activity, or whether distinct neurons modulate specific neuronal circuits underlying particular types of behavior. Using the model organism Drosophila melanogaster, we find that activating large proportions of serotonin-releasing neurons induces behavioral quiescence. Moreover, distinct serotonin-releasing neurons that we genetically isolated and identified negatively affect

  9. Ichnology of deglaciation deposits from the Upper Carboniferous Rio do Sul Formation (Itararé Group, Paraná Basin) at central-east Santa Catarina State (southern Brazil)

    NASA Astrophysics Data System (ADS)

    Lima, João Henrique Dobler; Netto, Renata Guimarães; Corrêa, Camila Graziele; Lavina, Ernesto Luiz Corrêa

    2015-11-01

    Trace fossil assemblages dominated by arthropod trackways are common in sediments deposited during the Late Paleozoic Ice Age. Ichnofaunas preserved in glacially-influenced sedimentary successions were previously reported from Paraná Basin in southern Brazil. The ichnofauna of the Rio do Sul Formation preserved in the rhythmites exposed in Trombudo Central quarries (Santa Catarina State, southern Brazil) is revised in this paper. Cruziana problematica, Diplichnites gouldi, Diplopodichnus biformis, Glaciichnium liebegastensis, Gluckstadtella elongata isp. nov., Helminthoidichnites tenuis, Mermia carickensis, Protovirgularia dichotoma, Treptichnus pollardi and Umfolozia sinuosa were recorded. Two trace fossil suites were recognized. The undermat miners suite is dominated by H. tenuis, indicating the presence of surface grazers (insect larvae, isopods and amphipods). C. problematica, D. gouldi and U. sinuosa dominate the overmat grazers suite, as result of displacement of terrestrial and aquatic arthropods. The integrated sedimentological and ichnological data from Trombudo Central region suggests colonization of ephemeral, shallow water bodies filled by freshwater from glacier melting. The deposition of the rhythmites took place in a glaciolacustrine context represented by shallow ponds in marginal marine settings.

  10. Assessing the herbivore role of the sea-urchin Echinometra viridis: Keys to determine the structure of communities in disturbed coral reefs.

    PubMed

    Sangil, Carlos; Guzman, Hector M

    2016-09-01

    Echinometra viridis previously was considered a cryptic species unable to control the development and growth of macroalgae on coral reefs. Its role as a herbivore was seen as minor compared to other grazers present on the reef. However, the present disturbed state of some reefs has highlighted the role played by this sea-urchin. Combining field data with experiments on the Caribbean coast of Panama, we demonstrate that the current community organization on disturbed coral reefs in the Mesoamerican Caribbean is largely due to the action of E. viridis. It is the most abundant sea-urchin species, together with two others (Diadema antillarum and Echinometra lucunter). Field data also indicate that the relationship between its density and the abundance of macroalgae is stronger and it is more negative in impact than those of the other two. However, the niche this urchin exploits most efficiently is confined to leeward reefs with low levels of sedimentation. Outside these habitats, their populations are not decisive in controlling macroalgal growth. Grazing experiments showed that E. viridis consumes more fresh macroalgae per day and per weight of sea-urchin, and is a more effective grazer than D. antillarum or E. lucunter. E. viridis showed food preferences for early-successional turf macroalgae (Acanthophora spicifera), avoiding the less palatable late-successional and fleshy macroalgae (Lobophora variegata, Halimeda opuntia). However, it becomes a generalist herbivore feeding on all varieties of macroalgae when resources are scarce. H. opuntia is the macroalga that most resists E. viridis activity, which may explain its wide distribution. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Fumigant activity of (E)-anethole identified in Illicium verum fruit against Blattella germanica.

    PubMed

    Chang, Kyu-Sik; Ahn, Young-Joon

    2002-02-01

    The insecticidal activities of materials derived from the fruit of star anise, Illicium verum, against adults of Blattella germanica were examined by direct contact application and fumigation methods, and compared with those of DDVP, deltamethrin and hydramethylnon. The biologically active constituent of the Illicium fruit was characterized as the phenylpropene, (E)-anethole, by spectroscopic analysis. In a filter paper diffusion test with females, (E)-anethole caused 80.3% mortality at 0.159 mg cm-2 at 1 and 3 days after treatment (DAT), whereas 16.7% mortality at 3 DAT was achieved at 0.079 mg cm-2. DDVP and deltamethrin gave > 90% mortality at 0.019 mg cm-2 at 1 DAT. At 0.009 mg cm-2, DDVP and deltamethrin showed 73.3 and 60% mortality at 1 DAT, respectively, but 93.3 and 76.7% mortality at 3 DAT. Hydramethylnon exhibited 0 and 93.3% mortality at 0.159 mg cm-2 at 1 and 3 DAT, respectively, whereas 6.7% mortality at 3 DAT was observed at 0.079 mg cm-2. In a fumigation test with females, (E)-anethole was much more effective in closed cups than in open ones, indicating that the insecticidal activity of the compound was largely attributable to fumigant action. (E)-Anethole and DDVP caused 100% mortality at 0.398 and 0.051 mg cm-2 4 and 1 h after treatment, respectively. (E)-Anethole showed 46.7% mortality at 0.199 mg cm-2 at 3 DAT, whereas deltamethrin and hydramethylnon at 0.796 mg cm-2 was ineffective for 3-day period. As naturally occurring insect-control agents, the I verum fruit-derived materials described could be useful for managing populations of B germanica.

  12. Enzyme-Sensitive MR Imaging Targeting Myeloperoxidase Identifies Active Inflammation in Experimental Rabbit Atherosclerotic Plaques

    PubMed Central

    Ronald, John A.; Chen, John W.; Chen, Yuanxin; Hamilton, Amanda M.; Rodriguez, Elisenda; Reynolds, Fred; Hegele, Robert A.; Rogers, Kem A.; Querol, Manel; Bogdanov, Alexei; Weissleder, Ralph; Rutt, Brian K.

    2009-01-01

    Background Inflammation undermines the stability of atherosclerotic plaques, rendering them susceptible to acute rupture, the cataclysmic event that underlies clinical expression of this disease. Myeloperoxidase (MPO) is a central inflammatory enzyme secreted by activated macrophages, and is involved in multiple stages of plaque destabilization and patient outcome. We report here that a unique functional in vivo magnetic resonance (MR) agent can visualize MPO activity in atherosclerotic plaques in a rabbit model. Methods and Results We performed MR imaging of the thoracic aorta of New Zealand white (NZW) rabbits fed a cholesterol (n=11) or normal (n=4) diet up to 2 hours after injection of the MPO sensor bis-5HT-DTPA(Gd) (MPO(Gd)), the conventional agent, DTPA(Gd), or an MPO (Gd) analog, bis-tyr-DTPA(Gd), as controls. Delayed MPO(Gd) images (2 hour post injection) showed focal areas of increased contrast (>2-fold) in diseased wall, but not in normal wall (p=0.84), compared to both DTPA(Gd) (n=11; p<0.001) and bis-tyr-DTPA(Gd) (n=3; p<0.05). Biochemical assays confirmed that diseased wall possessed three-fold elevated MPO activity compared to normal wall (p<0.01). Areas detected by MPO(Gd) imaging co-localized and correlated with MPO-rich areas infiltrated by macrophages on histopathological evaluations (r=0.91, p<0.0001). While macrophages were the main source of MPO, not all macrophages secreted MPO, suggesting that distinct subpopulations contribute differently to atherogenesis and supporting our functional approach. Conclusions Our study represents a unique approach in the detection of inflammation in atherosclerotic plaques by examining macrophage function and the activity of an effector enzyme, to noninvasively provide both anatomic and functional information in vivo. PMID:19652086

  13. Computationally identified novel agonists for GPRC6A

    PubMed Central

    Ye, Ruisong; Hwang, Dong-Jin; Miller, Duane D.; Smith, Jeremy C.; Baudry, Jerome; Quarles, L. Darryl

    2018-01-01

    New insights into G protein coupled receptor regulation of glucose metabolism by β-cells, skeletal muscle and liver hepatocytes identify GPRC6A as a potential therapeutic target for treating type 2 diabetes mellitus (T2D). Activating GPRC6A with a small molecule drug represents a potential paradigm-shifting opportunity to make significant strides in regulating glucose homeostasis by simultaneously correcting multiple metabolic derangements that underlie T2D, including abnormalities in β-cell proliferation and insulin secretion and peripheral insulin resistance. Using a computational, structure-based high-throughput screening approach, we identified novel tri-phenyl compounds predicted to bind to the venus fly trap (VFT) and 7-transmembrane (7-TM) domains of GPRC6A. Experimental testing found that these compounds dose-dependently stimulated GPRC6A signaling in a heterologous cell expression system. Additional chemical modifications and functional analysis identified one tri-phenyl lead compound, DJ-V-159 that demonstrated the greatest potency in stimulating insulin secretion in β-cells and lowering serum glucose in wild-type mice. Collectively, these studies show that GPRC6A is a “druggable” target for developing chemical probes to treat T2DM. PMID:29684031

  14. Identifying and Aligning Expectations in a Mentoring Relationship

    PubMed Central

    Huskins, W. Charles; Silet, Karin; Weber‐Main, Anne Marie; Begg, Melissa D.; Fowler, Jr, Vance G.; Hamilton, John; Fleming, Michael

    2011-01-01

    Abstract The mentoring relationship between a scholar and their primary mentor is a core feature of research training. Anecdotal evidence suggests this relationship is adversely affected when scholar and mentor expectations are not aligned. We examined three questions: (1) What is the value in assuring that the expectations of scholars and mentors are mutually identified and aligned? (2) What types of programmatic interventions facilitate this process? (3) What types of expectations are important to identify and align? We addressed these questions through a systematic literature review, focus group interviews of mentors and scholars, a survey of Clinical and Translational Science Award (CTSA) KL2 program directors, and review of formal programmatic mechanisms used by KL2 programs. We found broad support for the importance of identifying and aligning the expectations of scholars and mentors and evidence that mentoring contracts, agreements, and training programs facilitate this process. These tools focus on aligning expectations with respect to the scholar’s research, education, professional development and career advancement as well as support, communication, and personal conduct and interpersonal relations. Research is needed to assess test the efficacy of formal alignment activities. Clin Trans Sci 2011; Volume 4: 439–447 PMID:22212226

  15. Identifying cooperative transcriptional regulations using protein–protein interactions

    PubMed Central

    Nagamine, Nobuyoshi; Kawada, Yuji; Sakakibara, Yasubumi

    2005-01-01

    Cooperative transcriptional activations among multiple transcription factors (TFs) are important to understand the mechanisms of complex transcriptional regulations in eukaryotes. Previous studies have attempted to find cooperative TFs based on gene expression data with gene expression profiles as a measure of similarity of gene regulations. In this paper, we use protein–protein interaction data to infer synergistic binding of cooperative TFs. Our fundamental idea is based on the assumption that genes contributing to a similar biological process are regulated under the same control mechanism. First, the protein–protein interaction networks are used to calculate the similarity of biological processes among genes. Second, we integrate this similarity and the chromatin immuno-precipitation data to identify cooperative TFs. Our computational experiments in yeast show that predictions made by our method have successfully identified eight pairs of cooperative TFs that have literature evidences but could not be identified by the previous method. Further, 12 new possible pairs have been inferred and we have examined the biological relevances for them. However, since a typical problem using protein–protein interaction data is that many false-positive data are contained, we propose a method combining various biological data to increase the prediction accuracy. PMID:16126847

  16. Two types of putative preneoplastic lesions identified by hexosaminidase activity in whole-mounts of colons from F344 rats treated with carcinogen.

    PubMed

    Pretlow, T P; O'Riordan, M A; Spancake, K M; Pretlow, T G

    1993-06-01

    Previous studies identified as putative preneoplastic lesions 1) enzyme-altered foci in sections of methacrylate-embedded colon and 2) aberrant crypts in methylene blue-stained unembedded (whole-mount) colon and established that aberrant crypts embedded in methacrylate had enzyme alterations. We have now studied histochemically demonstrable hexosaminidase activity in unembedded or whole-mount preparations of colons from carcinogen-treated rats. These preparations have revealed two populations of crypts that are enzyme-altered: those that are morphologically altered or aberrant and those that are morphologically normal. Both populations can be quantified rigorously in less than an hour with whole-mount preparations reacted for hexosaminidase. The demonstration of phenotypic characteristics with histochemical techniques in whole-mount preparations should have wide applicability to functional studies in many normal and diseased tissues.

  17. Two types of putative preneoplastic lesions identified by hexosaminidase activity in whole-mounts of colons from F344 rats treated with carcinogen.

    PubMed Central

    Pretlow, T. P.; O'Riordan, M. A.; Spancake, K. M.; Pretlow, T. G.

    1993-01-01

    Previous studies identified as putative preneoplastic lesions 1) enzyme-altered foci in sections of methacrylate-embedded colon and 2) aberrant crypts in methylene blue-stained unembedded (whole-mount) colon and established that aberrant crypts embedded in methacrylate had enzyme alterations. We have now studied histochemically demonstrable hexosaminidase activity in unembedded or whole-mount preparations of colons from carcinogen-treated rats. These preparations have revealed two populations of crypts that are enzyme-altered: those that are morphologically altered or aberrant and those that are morphologically normal. Both populations can be quantified rigorously in less than an hour with whole-mount preparations reacted for hexosaminidase. The demonstration of phenotypic characteristics with histochemical techniques in whole-mount preparations should have wide applicability to functional studies in many normal and diseased tissues. Images Figure 1 PMID:8506941

  18. IDENTIFYING PERFORMANCE ASSURANCE CHALLENGES FOR SMART MANUFACTURING.

    PubMed

    Helu, Moneer; Morris, Katherine; Jung, Kiwook; Lyons, Kevin; Leong, Swee

    2015-10-01

    Smart manufacturing has the potential to address many of the challenges faced by industry. However, the manufacturing community often needs assistance to leverage available technologies to improve their systems. To assure the performance of these technologies, this paper proposes a shared knowledge base that collects problem areas, solutions, and best practices for manufacturing technology. An Implementation Risk Assessment Framework (IRAF) is also described to identify the primary weaknesses of technologies in specific manufacturing contexts. Such approaches have the potential to stimulate new ideas and drive standardization activities critical to scale up and deploy smart manufacturing technologies successfully and quickly.

  19. IDENTIFYING PERFORMANCE ASSURANCE CHALLENGES FOR SMART MANUFACTURING

    PubMed Central

    Helu, Moneer; Morris, Katherine; Jung, Kiwook; Lyons, Kevin; Leong, Swee

    2015-01-01

    Smart manufacturing has the potential to address many of the challenges faced by industry. However, the manufacturing community often needs assistance to leverage available technologies to improve their systems. To assure the performance of these technologies, this paper proposes a shared knowledge base that collects problem areas, solutions, and best practices for manufacturing technology. An Implementation Risk Assessment Framework (IRAF) is also described to identify the primary weaknesses of technologies in specific manufacturing contexts. Such approaches have the potential to stimulate new ideas and drive standardization activities critical to scale up and deploy smart manufacturing technologies successfully and quickly. PMID:26783512

  20. An RNA Interference Screen Identifies the Deubiquitinase STAMBPL1 as a Critical Regulator of Human T-Cell Leukemia Virus Type 1 Tax Nuclear Export and NF-κB Activation

    PubMed Central

    Lavorgna, Alfonso

    2012-01-01

    The human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein actively shuttles between the nucleus, where it interacts with transcriptional and splicing regulatory proteins, and the cytoplasm, where it activates NF-κB. Posttranslational modifications of Tax such as ubiquitination regulate its subcellular localization and hence its function; however, the regulation of Tax trafficking and NF-κB activation by host factors is poorly understood. By screening a deubiquitinating (DUB) enzyme small interfering RNA (siRNA) library, we identified the metalloprotease STAM-binding protein-like 1 (STAMBPL1) as a positive regulator of Tax-mediated NF-κB activation. Overexpression of wild-type STAMBPL1, but not a catalytically inactive mutant, enhanced Tax-mediated NF-κB activation, whereas silencing of STAMBPL1 with siRNA impaired Tax activation of both the canonical and noncanonical NF-κB signaling pathways. STAMBPL1 regulated Tax-induced NF-κB signaling indirectly by controlling Tax nuclear/cytoplasmic transport and was required for DNA damage-induced Tax nuclear export. Together, these results reveal that the deubiquitinase STAMBPL1 is a key regulator of Tax trafficking and function. PMID:22258247

  1. Somatic mutations in histiocytic sarcoma identified by next generation sequencing.

    PubMed

    Liu, Qingqing; Tomaszewicz, Keith; Hutchinson, Lloyd; Hornick, Jason L; Woda, Bruce; Yu, Hongbo

    2016-08-01

    Histiocytic sarcoma is a rare malignant neoplasm of presumed hematopoietic origin showing morphologic and immunophenotypic evidence of histiocytic differentiation. Somatic mutation importance in the pathogenesis or disease progression of histiocytic sarcoma was largely unknown. To identify somatic mutations in histiocytic sarcoma, we studied 5 histiocytic sarcomas [3 female and 2 male patients; mean age 54.8 (20-72), anatomic sites include lymph node, uterus, and pleura] and matched normal tissues from each patient as germ line controls. Somatic mutations in 50 "Hotspot" oncogenes and tumor suppressor genes were examined using next generation sequencing. Three (out of five) histiocytic sarcoma cases carried somatic mutations in BRAF. Among them, G464V [variant frequency (VF) of 43.6 %] and G466R (VF of 29.6 %) located at the P loop potentially interfere with the hydrophobic interaction between P and activating loops and ultimately activation of BRAF. Also detected was BRAF somatic mutation N581S (VF of 7.4 %), which was located at the catalytic loop of BRAF kinase domain: its role in modifying kinase activity was unclear. A similar mutational analysis was also performed on nine acute monocytic/monoblastic leukemia cases, which did not identify any BRAF somatic mutations. Our study detected several BRAF mutations in histiocytic sarcomas, which may be important in understanding the tumorigenesis of this rare neoplasm and providing mechanisms for potential therapeutical opportunities.

  2. Recommended Mass Spectrometry-Based Strategies to Identify Ricin-Containing Samples.

    PubMed

    Kalb, Suzanne R; Schieltz, David M; Becher, François; Astot, Crister; Fredriksson, Sten-Åke; Barr, John R

    2015-11-25

    Ricin is a protein toxin produced by the castor bean plant (Ricinus communis) together with a related protein known as R. communis agglutinin (RCA120). Mass spectrometric (MS) assays have the capacity to unambiguously identify ricin and to detect ricin's activity in samples with complex matrices. These qualitative and quantitative assays enable detection and differentiation of ricin from the less toxic RCA120 through determination of the amino acid sequence of the protein in question, and active ricin can be monitored by MS as the release of adenine from the depurination of a nucleic acid substrate. In this work, we describe the application of MS-based methods to detect, differentiate and quantify ricin and RCA120 in nine blinded samples supplied as part of the EQuATox proficiency test. Overall, MS-based assays successfully identified all samples containing ricin or RCA120 with the exception of the sample spiked with the lowest concentration (0.414 ng/mL). In fact, mass spectrometry was the most successful method for differentiation of ricin and RCA120 based on amino acid determination. Mass spectrometric methods were also successful at ranking the functional activities of the samples, successfully yielding semi-quantitative results. These results indicate that MS-based assays are excellent techniques to detect, differentiate, and quantify ricin and RCA120 in complex matrices.

  3. Recommended Mass Spectrometry-Based Strategies to Identify Ricin-Containing Samples

    PubMed Central

    Kalb, Suzanne R.; Schieltz, David M.; Becher, François; Astot, Crister; Fredriksson, Sten-Åke; Barr, John R.

    2015-01-01

    Ricin is a protein toxin produced by the castor bean plant (Ricinus communis) together with a related protein known as R. communis agglutinin (RCA120). Mass spectrometric (MS) assays have the capacity to unambiguously identify ricin and to detect ricin’s activity in samples with complex matrices. These qualitative and quantitative assays enable detection and differentiation of ricin from the less toxic RCA120 through determination of the amino acid sequence of the protein in question, and active ricin can be monitored by MS as the release of adenine from the depurination of a nucleic acid substrate. In this work, we describe the application of MS-based methods to detect, differentiate and quantify ricin and RCA120 in nine blinded samples supplied as part of the EQuATox proficiency test. Overall, MS-based assays successfully identified all samples containing ricin or RCA120 with the exception of the sample spiked with the lowest concentration (0.414 ng/mL). In fact, mass spectrometry was the most successful method for differentiation of ricin and RCA120 based on amino acid determination. Mass spectrometric methods were also successful at ranking the functional activities of the samples, successfully yielding semi-quantitative results. These results indicate that MS-based assays are excellent techniques to detect, differentiate, and quantify ricin and RCA120 in complex matrices. PMID:26610568

  4. Discovering Anti-platelet Drug Combinations with an Integrated Model of Activator-Inhibitor Relationships, Activator-Activator Synergies and Inhibitor-Inhibitor Synergies

    PubMed Central

    Lombardi, Federica; Golla, Kalyan; Fitzpatrick, Darren J.; Casey, Fergal P.; Moran, Niamh; Shields, Denis C.

    2015-01-01

    Identifying effective therapeutic drug combinations that modulate complex signaling pathways in platelets is central to the advancement of effective anti-thrombotic therapies. However, there is no systems model of the platelet that predicts responses to different inhibitor combinations. We developed an approach which goes beyond current inhibitor-inhibitor combination screening to efficiently consider other signaling aspects that may give insights into the behaviour of the platelet as a system. We investigated combinations of platelet inhibitors and activators. We evaluated three distinct strands of information, namely: activator-inhibitor combination screens (testing a panel of inhibitors against a panel of activators); inhibitor-inhibitor synergy screens; and activator-activator synergy screens. We demonstrated how these analyses may be efficiently performed, both experimentally and computationally, to identify particular combinations of most interest. Robust tests of activator-activator synergy and of inhibitor-inhibitor synergy required combinations to show significant excesses over the double doses of each component. Modeling identified multiple effects of an inhibitor of the P2Y12 ADP receptor, and complementarity between inhibitor-inhibitor synergy effects and activator-inhibitor combination effects. This approach accelerates the mapping of combination effects of compounds to develop combinations that may be therapeutically beneficial. We integrated the three information sources into a unified model that predicted the benefits of a triple drug combination targeting ADP, thromboxane and thrombin signaling. PMID:25875950

  5. Culling a clinical terminology: a systematic approach to identifying problematic content.

    PubMed Central

    Sable, J. H.; Nash, S. K.; Wang, A. Y.

    2001-01-01

    The College of American Pathologists and the National Health Service (NHS) in the United Kingdom are merging their respective clinical terminologies, SNOMED RT and Clinical Terms Version 3, into a new terminology, SNOMED CT. This requires mapping concept descriptions between the two existing terminologies. During the mapping process, many descriptions were identified as being potentially problematic. They require further review by the SNOMED editorial process before either (1) being incorporated into SNOMED CT, or (2) retired from active use. This article presents data on the concept descriptions that were identified as needing further review during the early phases of SNOMED CT development. Based on this work, we describe fourteen types of problematic terminology content. Identifying problematic terminology content can be approached in a systematic manner. PMID:11825253

  6. Assay development and case history of a 32K-biased library high-content MK2-EGFP translocation screen to identify p38 mitogen-activated protein kinase inhibitors on the ArrayScan 3.1 imaging platform.

    PubMed

    Trask, Oscar J; Baker, Audrey; Williams, Rhonda Gates; Nickischer, Debra; Kandasamy, Ramani; Laethem, Carmen; Johnston, Patricia A; Johnston, Paul A

    2006-01-01

    This chapter describes the conversion and assay development of a 96-well MK2-EGFP translocation assay into a higher density 384-well format high-content assay to be screened on the ArrayScan 3.1 imaging platform. The assay takes advantage of the well-substantiated hypothesis that mitogen-activated protein kinase-activating protein kinase-2 (MK2) is a substrate of p38 MAPK kinase and that p38-induced phosphorylation of MK-2 induces a nucleus-to-cytoplasm translocation. This chapter also presents a case history of the performance of the MK2-EGFP translocation assay, run as a "high-content" screen of a 32K kinase-biased library to identify p38 inhibitors. The assay performed very well and a number of putative p38 inhibitor hits were identified. Through the use of multiparameter data provided by the nuclear translocation algorithm and by checking images, a number of compounds were identified that were potential artifacts due to interference with the imaging format. These included fluorescent compounds, or compounds that dramatically reduced cell numbers due to cytotoxicity or by disrupting cell adherence. A total of 145 compounds produced IC(50) values <50.0 muM in the MK2-EGFP translocation assay, and a cross target query of the Lilly-RTP HTS database confirmed their inhibitory activity against in vitro kinase targets, including p38a. Compounds were confirmed structurally by LCMS analysis and profiled in cell-based imaging assays for MAPK signaling pathway selectivity. Three of the hit scaffolds identified in the MK2-EGFP translocation HCS run on the ArrayScan were selected for a p38a inhibitor hit-to-lead structure activity relationship (SAR) chemistry effort.

  7. High-content screening identifies kinase inhibitors that overcome venetoclax resistance in activated CLL cells.

    PubMed

    Oppermann, Sina; Ylanko, Jarkko; Shi, Yonghong; Hariharan, Santosh; Oakes, Christopher C; Brauer, Patrick M; Zúñiga-Pflücker, Juan C; Leber, Brian; Spaner, David E; Andrews, David W

    2016-08-18

    Novel agents such as the Bcl-2 inhibitor venetoclax (ABT-199) are changing treatment paradigms for chronic lymphocytic leukemia (CLL) but important problems remain. Although some patients exhibit deep and durable responses to venetoclax as a single agent, other patients harbor subpopulations of resistant leukemia cells that mediate disease recurrence. One hypothesis for the origin of resistance to venetoclax is by kinase-mediated survival signals encountered in proliferation centers that may be unique for individual patients. An in vitro microenvironment model was developed with primary CLL cells that could be incorporated into an automated high-content microscopy-based screen of kinase inhibitors (KIs) to identify agents that may improve venetoclax therapy in a personalized manner. Marked interpatient variability was noted for which KIs were effective; nevertheless, sunitinib was identified as the most common clinically available KI effective in overcoming venetoclax resistance. Examination of the underlying mechanisms indicated that venetoclax resistance may be induced by microenvironmental signals that upregulate antiapoptotic Bcl-xl, Mcl-1, and A1, which can be counteracted more efficiently by sunitinib than by ibrutinib or idelalisib. Although patient-specific drug responses are common, for many patients, combination therapy with sunitinib may significantly improve the therapeutic efficacy of venetoclax. © 2016 by The American Society of Hematology.

  8. High-content screening identifies kinase inhibitors that overcome venetoclax resistance in activated CLL cells

    PubMed Central

    Oppermann, Sina; Ylanko, Jarkko; Shi, Yonghong; Hariharan, Santosh; Oakes, Christopher C.; Brauer, Patrick M.; Zúñiga-Pflücker, Juan C.; Leber, Brian; Spaner, David E.

    2016-01-01

    Novel agents such as the Bcl-2 inhibitor venetoclax (ABT-199) are changing treatment paradigms for chronic lymphocytic leukemia (CLL) but important problems remain. Although some patients exhibit deep and durable responses to venetoclax as a single agent, other patients harbor subpopulations of resistant leukemia cells that mediate disease recurrence. One hypothesis for the origin of resistance to venetoclax is by kinase-mediated survival signals encountered in proliferation centers that may be unique for individual patients. An in vitro microenvironment model was developed with primary CLL cells that could be incorporated into an automated high-content microscopy-based screen of kinase inhibitors (KIs) to identify agents that may improve venetoclax therapy in a personalized manner. Marked interpatient variability was noted for which KIs were effective; nevertheless, sunitinib was identified as the most common clinically available KI effective in overcoming venetoclax resistance. Examination of the underlying mechanisms indicated that venetoclax resistance may be induced by microenvironmental signals that upregulate antiapoptotic Bcl-xl, Mcl-1, and A1, which can be counteracted more efficiently by sunitinib than by ibrutinib or idelalisib. Although patient-specific drug responses are common, for many patients, combination therapy with sunitinib may significantly improve the therapeutic efficacy of venetoclax. PMID:27297795

  9. Computational modeling identifies key gene regulatory interactions underlying phenobarbital-mediated tumor promotion

    PubMed Central

    Luisier, Raphaëlle; Unterberger, Elif B.; Goodman, Jay I.; Schwarz, Michael; Moggs, Jonathan; Terranova, Rémi; van Nimwegen, Erik

    2014-01-01

    Gene regulatory interactions underlying the early stages of non-genotoxic carcinogenesis are poorly understood. Here, we have identified key candidate regulators of phenobarbital (PB)-mediated mouse liver tumorigenesis, a well-characterized model of non-genotoxic carcinogenesis, by applying a new computational modeling approach to a comprehensive collection of in vivo gene expression studies. We have combined our previously developed motif activity response analysis (MARA), which models gene expression patterns in terms of computationally predicted transcription factor binding sites with singular value decomposition (SVD) of the inferred motif activities, to disentangle the roles that different transcriptional regulators play in specific biological pathways of tumor promotion. Furthermore, transgenic mouse models enabled us to identify which of these regulatory activities was downstream of constitutive androstane receptor and β-catenin signaling, both crucial components of PB-mediated liver tumorigenesis. We propose novel roles for E2F and ZFP161 in PB-mediated hepatocyte proliferation and suggest that PB-mediated suppression of ESR1 activity contributes to the development of a tumor-prone environment. Our study shows that combining MARA with SVD allows for automated identification of independent transcription regulatory programs within a complex in vivo tissue environment and provides novel mechanistic insights into PB-mediated hepatocarcinogenesis. PMID:24464994

  10. Anaerobic carboxydotrophic bacteria in geothermal springs identified using stable isotope probing.

    PubMed

    Brady, Allyson L; Sharp, Christine E; Grasby, Stephen E; Dunfield, Peter F

    2015-01-01

    Carbon monoxide (CO) is a potential energy and carbon source for thermophilic bacteria in geothermal environments. Geothermal sites ranging in temperature from 45 to 65°C were investigated for the presence and activity of anaerobic CO-oxidizing bacteria. Anaerobic CO oxidation potentials were measured at up to 48.9 μmoles CO g(-1) (wet weight) day(-1) within five selected sites. Active anaerobic carboxydotrophic bacteria were identified using (13)CO DNA stable isotope probing (SIP) combined with pyrosequencing of 16S rRNA genes amplified from labeled DNA. Bacterial communities identified in heavy DNA fractions were predominated by Firmicutes, which comprised up to 95% of all sequences in (13)CO incubations. The predominant bacteria that assimilated (13)C derived from CO were closely related (>98% 16S rRNA gene sequence identity) to genera of known carboxydotrophs including Thermincola, Desulfotomaculum, Thermolithobacter, and Carboxydocella, although a few species with lower similarity to known bacteria were also found that may represent previously unconfirmed CO-oxidizers. While the distribution was variable, many of the same OTUs were identified across sample sites from different temperature regimes. These results show that bacteria capable of using CO as a carbon source are common in geothermal springs, and that thermophilic carboxydotrophs are probably already quite well known from cultivation studies.

  11. Soil conditions moderate the effects of herbivores, but not mycorrhizae, on a native bunchgrass

    NASA Astrophysics Data System (ADS)

    Connolly, Brian M.; Orrock, John L.; Witter, Martha S.

    2016-11-01

    Herbivores, microbial mutualists, and soil nutrients can affect plant survival, growth, and reproduction, demographic parameters that are essential to plant restoration. In this study we ask: 1) whether native plants that form early associations with mycorrhizal fungi are more tolerant of mammalian grazers, and 2) how early plant associations with mycorrhizal fungi influence mammalian grazing across gradients in soil nutrients. In eight grassland sites in California (USA), we transplanted seedlings of a native bunchgrass, Stipa pulchra, that were or were not pretreated with mycorrhizal fungi in exclosures designed to exclude different guilds of vertebrate grazers. Pretreated plants had greater establishment eight months after transplantation than untreated plants. Mycorrhizal inoculation resulted in twofold greater biomass and fourfold greater seed production when plants were protected from herbivores; inoculation with mycorrhizae resulted in twofold greater biomass and seed production when plants were accessible by all herbivores. Soil phosphate and potassium concentrations influenced herbivory: vertebrate grazing had less effect on transplant biomass and seed production at sites with high phosphate - low potassium soils, but the effects of grazing were more severe in low phosphate - high potassium soils. Pretreatment with mycorrhizal fungi can result in greater survival, growth, and reproduction of transplanted seedlings of native bunchgrass S. pulchra. Our results also illustrate that soil conditions may influence the extent to which the vertebrate herbivore community limits restoration of S. pulchra: the effects of some small mammalian herbivores (e.g., voles) was little affected by soil conditions, but grazing by larger herbivores had a greater effect on S. pulchra performance at sites with low phosphate - high potassium soils. In helping identify the contribution of soil nutrients, herbivores, and mycorrhizae to establishment and performance, our work has

  12. Identifiability, reducibility, and adaptability in allosteric macromolecules.

    PubMed

    Bohner, Gergő; Venkataraman, Gaurav

    2017-05-01

    The ability of macromolecules to transduce stimulus information at one site into conformational changes at a distant site, termed "allostery," is vital for cellular signaling. Here, we propose a link between the sensitivity of allosteric macromolecules to their underlying biophysical parameters, the interrelationships between these parameters, and macromolecular adaptability. We demonstrate that the parameters of a canonical model of the mSlo large-conductance Ca 2+ -activated K + (BK) ion channel are non-identifiable with respect to the equilibrium open probability-voltage relationship, a common functional assay. We construct a reduced model with emergent parameters that are identifiable and expressed as combinations of the original mechanistic parameters. These emergent parameters indicate which coordinated changes in mechanistic parameters can leave assay output unchanged. We predict that these coordinated changes are used by allosteric macromolecules to adapt, and we demonstrate how this prediction can be tested experimentally. We show that these predicted parameter compensations are used in the first reported allosteric phenomena: the Bohr effect, by which hemoglobin adapts to varying pH. © 2017 Bohner and Venkataraman.

  13. Identifiability, reducibility, and adaptability in allosteric macromolecules

    PubMed Central

    Bohner, Gergő

    2017-01-01

    The ability of macromolecules to transduce stimulus information at one site into conformational changes at a distant site, termed “allostery,” is vital for cellular signaling. Here, we propose a link between the sensitivity of allosteric macromolecules to their underlying biophysical parameters, the interrelationships between these parameters, and macromolecular adaptability. We demonstrate that the parameters of a canonical model of the mSlo large-conductance Ca2+-activated K+ (BK) ion channel are non-identifiable with respect to the equilibrium open probability-voltage relationship, a common functional assay. We construct a reduced model with emergent parameters that are identifiable and expressed as combinations of the original mechanistic parameters. These emergent parameters indicate which coordinated changes in mechanistic parameters can leave assay output unchanged. We predict that these coordinated changes are used by allosteric macromolecules to adapt, and we demonstrate how this prediction can be tested experimentally. We show that these predicted parameter compensations are used in the first reported allosteric phenomena: the Bohr effect, by which hemoglobin adapts to varying pH. PMID:28416647

  14. An evolutionary analysis identifies a conserved pentapeptide stretch containing the two essential lysine residues for rice L-myo-inositol 1-phosphate synthase catalytic activity

    PubMed Central

    Basak, Papri; Maitra-Majee, Susmita; Das, Jayanta Kumar; Mukherjee, Abhishek; Ghosh Dastidar, Shubhra; Pal Choudhury, Pabitra

    2017-01-01

    A molecular evolutionary analysis of a well conserved protein helps to determine the essential amino acids in the core catalytic region. Based on the chemical properties of amino acid residues, phylogenetic analysis of a total of 172 homologous sequences of a highly conserved enzyme, L-myo-inositol 1-phosphate synthase or MIPS from evolutionarily diverse organisms was performed. This study revealed the presence of six phylogenetically conserved blocks, out of which four embrace the catalytic core of the functional protein. Further, specific amino acid modifications targeting the lysine residues, known to be important for MIPS catalysis, were performed at the catalytic site of a MIPS from monocotyledonous model plant, Oryza sativa (OsMIPS1). Following this study, OsMIPS mutants with deletion or replacement of lysine residues in the conserved blocks were made. Based on the enzyme kinetics performed on the deletion/replacement mutants, phylogenetic and structural comparison with the already established crystal structures from non-plant sources, an evolutionarily conserved peptide stretch was identified at the active pocket which contains the two most important lysine residues essential for catalytic activity. PMID:28950028

  15. A lanthipeptide library used to identify a protein-protein interaction inhibitor.

    PubMed

    Yang, Xiao; Lennard, Katherine R; He, Chang; Walker, Mark C; Ball, Andrew T; Doigneaux, Cyrielle; Tavassoli, Ali; van der Donk, Wilfred A

    2018-04-01

    In this article we describe the production and screening of a genetically encoded library of 10 6 lanthipeptides in Escherichia coli using the substrate-tolerant lanthipeptide synthetase ProcM. This plasmid-encoded library was combined with a bacterial reverse two-hybrid system for the interaction of the HIV p6 protein with the UEV domain of the human TSG101 protein, which is a critical protein-protein interaction for HIV budding from infected cells. Using this approach, we identified an inhibitor of this interaction from the lanthipeptide library, whose activity was verified in vitro and in cell-based virus-like particle-budding assays. Given the variety of lanthipeptide backbone scaffolds that may be produced with ProcM, this method may be used for the generation of genetically encoded libraries of natural product-like lanthipeptides containing substantial structural diversity. Such libraries may be combined with any cell-based assay to identify lanthipeptides with new biological activities.

  16. Profiling of engineering hotspots identifies an allosteric CRISPR-Cas9 switch.

    PubMed

    Oakes, Benjamin L; Nadler, Dana C; Flamholz, Avi; Fellmann, Christof; Staahl, Brett T; Doudna, Jennifer A; Savage, David F

    2016-06-01

    The clustered, regularly interspaced, short palindromic repeats (CRISPR)-associated protein Cas9 from Streptococcus pyogenes is an RNA-guided DNA endonuclease with widespread utility for genome modification. However, the structural constraints limiting the engineering of Cas9 have not been determined. Here we experimentally profile Cas9 using randomized insertional mutagenesis and delineate hotspots in the structure capable of tolerating insertions of a PDZ domain without disruption of the enzyme's binding and cleavage functions. Orthogonal domains or combinations of domains can be inserted into the identified sites with minimal functional consequence. To illustrate the utility of the identified sites, we construct an allosterically regulated Cas9 by insertion of the estrogen receptor-α ligand-binding domain. This protein showed robust, ligand-dependent activation in prokaryotic and eukaryotic cells, establishing a versatile one-component system for inducible and reversible Cas9 activation. Thus, domain insertion profiling facilitates the rapid generation of new Cas9 functionalities and provides useful data for future engineering of Cas9.

  17. Active Volcanism on Io: Global Distribution and Variations in Activity

    USGS Publications Warehouse

    Lopes-Gautier, R.; McEwen, A.S.; Smythe, W.B.; Geissler, P.E.; Kamp, L.; Davies, A.G.; Spencer, J.R.; Keszthelyi, L.; Carlson, R.; Leader, F.E.; Mehlman, R.; Soderblom, L.

    1999-01-01

    Io's volcanic activity has been monitored by instruments aboard the Galileo spacecraft since June 28, 1996. We present results from observations by the near-infrared mapping spectrometer (NIMS) for the first 10 orbits of Galileo, correlate them with results from the Solid State Imaging System (SSI) and from groundbased observations, and compare them to what was known about Io's volcanic activity from observations made during the two Voyager flybys in 1979. A total of 61 active volcanic centers have been identified from Voyager, groundbased, and Galileo observations. Of these, 41 are hot spots detected by NIMS and/or SSI. Another 25 locations were identified as possible active volcanic centers, mostly on the basis of observed surface changes. Hot spots are correlated with surface colors, particularly dark and red deposits, and generally anti-correlated with white, SO2-rich areas. Surface features corresponding to the hot spots, mostly calderas or flows, were identified from Galileo and Voyager images. Hot spot temperatures obtained from both NIMS and SSI are consistent with silicate volcanism, which appears to be widespread on Io. Two types of hot spot activity are present: persistent-type activity, lasting from months to years, and sporadic events, which may represent either short-lived activity or low-level activity that occasionally flares up. Sporadic events are not often detected, but may make an important contribution to Io's heat flow and resurfacing. The distribution of active volcanic centers on the surface does not show any clear correlation with latitude, longitude, Voyager-derived global topography, or heat flow patterns predicted by the asthenosphere and deep mantle tidal dissipation models. However, persistent hot spots and active plumes are concentrated toward lower latitudes, and this distribution favors the asthenosphere rather than the deep mantle tidal dissipation model. ?? 1999 Academic Press.

  18. Newly identified invertebrate-type lysozyme (Splys-i) in mud crab (Scylla paramamosain) exhibiting muramidase-deficient antimicrobial activity.

    PubMed

    Zhou, Jian; Zhao, Shu; Fang, Wen-Hong; Zhou, Jun-Fang; Zhang, Jing-Xiao; Ma, Hongyu; Lan, Jiang-Feng; Li, Xin-Cang

    2017-09-01

    Lysozymes are widely distributed immune effectors exerting muramidase activity against the peptidoglycan of the bacterial cell wall to trigger cell lysis. However, some invertebrate-type (i-type) lysozymes deficient of muramidase activity still exhibit antimicrobial activity. To date, the mechanism underlying the antimicrobial effect of muramidase-deficient i-type lysozymes remains unclear. Accordingly, this study characterized a novel i-type lysozyme, Splys-i, in the mud crab Scylla paramamosain. Splys-i shared the highest identity with the Litopenaeus vannamei i-type lysozyme (Lvlys-i2, 54% identity) at the amino acid level. Alignment analysis and 3D structure comparison show that Splys-i may be a muramidase-deficient i-type lysozyme because it lacks the two conserved catalytic residues (Glu and Asp) that are necessary for muramidase activity. Splys-i is mainly distributed in the intestine, stomach, gills, hepatopancreas, and hemocytes, and it is upregulated by Vibrio harveyi or Staphylococcus aureus challenge. Recombinant Splys-i protein (rSplys-i) can inhibit the growth of Gram-negative bacteria (V. harveyi, Vibrio alginolyticus, Vibrio parahemolyticus, and Escherichia coli), Gram-positive bacteria (S. aureus, Bacillus subtilis, and Bacillus megaterium), and the fungus Candida albicans to varying degrees. In this study, two binding assays and a bacterial agglutination assay were conducted to elucidate the potential antimicrobial mechanisms of Splys-i. Results demonstrated that rSplys-i could bind to all nine aforementioned microorganisms. It also exhibited a strong binding activity to lipopolysaccharide from E. coli and lipoteichoic acid and peptidoglycan (PGN) from S. aureus but a weak binding activity to PGN from B. subtilis and β-glucan from fungi. Moreover, rSplys-i could agglutinate these nine types of microorganisms in the presence of Ca 2+ at different protein concentrations. These results suggest that the binding activity and its triggered

  19. Identifying Information Behavior in Information Search and Retrieval through Learning Activities Using an E-learning Platform Case: Interamerican School of Library and Information Science at the University of Antioquia (Medellin-Colombia)

    ERIC Educational Resources Information Center

    Tirado, Alejandro Uribe; Munoz, Wilson Castano

    2011-01-01

    This text presents the future of librarian education as exemplified by the Interamerican School of Library and Information Science at the University of Antioquia (Medellin-Colombia), using an online learning platform-LMS (Moodle) and through different personalized and collaborative learning activities and tools that help students identify their…

  20. Using Long-term Satellite Observations to Identify Sensitive Regimes and Active Regions of Aerosol Indirect Effects for Liquid Clouds over Global Oceans

    DOE PAGES

    Zhao, Xuepeng; Liu, Yangang; Yu, Fangquan; ...

    2017-11-16

    Long-term (1981-2011) satellite climate data records (CDRs) of clouds and aerosols are used to investigate the aerosol-cloud interaction of marine water cloud from a climatology perspective. Our focus is on identifying the regimes and regions where the aerosol indirect effect (AIE) are evident in long-term averages over the global oceans through analyzing the correlation features between aerosol loading and the key cloud variables including cloud droplet effective radius (CDER), cloud optical depth (COD), cloud water path (CWP), cloud top height (CTH), and cloud top temperature (CTT). An aerosol optical thickness (AOT) range of 0.13 < AOT < 0.3 is identifiedmore » as the sensitive regime of the conventional first AIE where CDER is more susceptible to AOT than the other cloud variables. The first AIE that manifests as the change of long-term averaged CDER appears only in limited oceanic regions. The signature of aerosol invigoration of water clouds as revealed by the increase of cloud cover fraction (CCF) and CTH with increasing AOT at the middle/high latitudes of both hemispheres is identified for a pristine atmosphere (AOT < 0.08). Aerosol invigoration signature is also revealed by the concurrent increase of CDER, COD, and CWP with increasing AOT for a polluted marine atmosphere (AOT > 0.3) in the tropical convergence zones. The regions where the second AIE is likely to manifest in the CCF change are limited to several oceanic areas with high CCF of the warm water clouds near the western coasts of continents. The second AIE signature as represented by the reduction of the precipitation efficiency with increasing AOT is more likely to be observed in the AOT regime of 0.08 < AOT < 0.4. The corresponding AIE active regions manifested themselves as the decline of the precipitation efficiency are mainly limited to the oceanic areas downwind of continental aerosols. Furthermore, the sensitive regime of the conventional AIE identified in this observational study is