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Sample records for phylogeny-guided interaction mapping

  1. Phylogeny-guided (meta)genome mining approach for the targeted discovery of new microbial natural products.

    PubMed

    Kang, Hahk-Soo

    2017-02-01

    Genomics-based methods are now commonplace in natural products research. A phylogeny-guided mining approach provides a means to quickly screen a large number of microbial genomes or metagenomes in search of new biosynthetic gene clusters of interest. In this approach, biosynthetic genes serve as molecular markers, and phylogenetic trees built with known and unknown marker gene sequences are used to quickly prioritize biosynthetic gene clusters for their metabolites characterization. An increase in the use of this approach has been observed for the last couple of years along with the emergence of low cost sequencing technologies. The aim of this review is to discuss the basic concept of a phylogeny-guided mining approach, and also to provide examples in which this approach was successfully applied to discover new natural products from microbial genomes and metagenomes. I believe that the phylogeny-guided mining approach will continue to play an important role in genomics-based natural products research.

  2. Tafuketide, a phylogeny-guided discovery of a new polyketide from Talaromyces funiculosus Salicorn 58.

    PubMed

    Guo, Jia; Ran, Huomiao; Zeng, Jie; Liu, Dong; Xin, Zhihong

    2016-06-01

    A phylogeny-guided approach was applied to screen endophytic fungi containing type I polyketide synthase (PKS I) biosynthetic gene sequences and aimed to correlate genotype to chemotype for the discovery of novel bioactive polyketides. Salicorn 58, which was identified as Talaromyces funiculosus based on its internal transcribed spacer (ITS) and ribosomal large-subunit (LSU) DNA sequences, showed significant target bands. A chemical investigation of the culture of Salicorn 58 was allowed for the isolation of a new polyketide, Talafun (1), and a new natural product, N-(2'-hydroxy-3'-octadecenoyl)-9-methyl-4,8-sphingadienin (2), together with six known compounds, including chrodrimanin A (3), chrodrimanin B (4), N-(4-hydroxy-2-methoxyphenyl) acetamide (5), butyl β-glucose (6), 3β,15β-dihydroxyl-(22E, 24R)-ergosta-5,8(14),22-trien-7-dione (7), and (3β,5a,8a,22E)-5,8-epidioxyergosta-6,22-dien-3-ol (8). Their chemical structures were elucidated by extensive spectroscopic analysis and electro circular dichroism (ECD) spectrum calculations. Antioxidant experiments revealed that compound 5 showed strong ABTS(+) radical scavenging activity with an IC50 value of 11.43 ± 1.61 μM and potent ferric reducing activity (FRAP assay) with FRAP value of 187.52 ± 2.97. Antimicrobial assays revealed that compounds 1 and 4 showed high levels of selectivity toward Escherichia coli with MIC values of 18 ± 0.40 and 43 ± 0.52 μM, respectively. Compounds 2 and 3 exhibited broad-spectrum antimicrobial activity against Staphylococcus aureus, Mycobacterium smegmatis, Micrococcus tetragenus, Mycobacterium phlei, and E. coli, respectively. The results from the current research highlight the advantage of phylogeny-guided pipeline for the screening of new polyketides from endophytic fungi containing PKS I genes.

  3. Golgi: Interactive Online Brain Mapping

    PubMed Central

    Brown, Ramsay A.; Swanson, Larry W.

    2015-01-01

    Golgi (http://www.usegolgi.com) is a prototype interactive brain map of the rat brain that helps researchers intuitively interact with neuroanatomy, connectomics, and cellular and chemical architecture. The flood of “-omic” data urges new ways to help researchers connect discrete findings to the larger context of the nervous system. Here we explore Golgi’s underlying reasoning and techniques and how our design decisions balance the constraints of building both a scientifically useful and usable tool. We demonstrate how Golgi can enhance connectomic literature searches with a case study investigating a thalamocortical circuit involving the Nucleus Accumbens and we explore Golgi’s potential and future directions for growth in systems neuroscience and connectomics. PMID:26635596

  4. Creating an Interactive Videodisc on Mapping.

    ERIC Educational Resources Information Center

    Andrews, Sona Karentz; Grozik, John

    1994-01-01

    Provides an overview of the University of Wisconsin-Milwaukee's Interactive Multimedia Cartography Project to create an interactive videodisc that would illustrate the topic of mapping and provide access to examples of cartography from the American Geographical Society Collection. (JLB)

  5. Creating an Interactive Videodisc on Mapping.

    ERIC Educational Resources Information Center

    Andrews, Sona Karentz; Grozik, John

    1994-01-01

    Provides an overview of the University of Wisconsin-Milwaukee's Interactive Multimedia Cartography Project to create an interactive videodisc that would illustrate the topic of mapping and provide access to examples of cartography from the American Geographical Society Collection. (JLB)

  6. Spatially Pressure-Mapped Thermochromic Interactive Sensor.

    PubMed

    Kim, Gwangmook; Cho, Sungjun; Chang, Kiseok; Kim, Wook Sung; Kang, Hansaem; Ryu, Sung-Pil; Myoung, Jaemin; Park, Jinwoo; Park, Cheolmin; Shim, Wooyoung

    2017-01-24

    A thermochromic-based interactive sensor that can generate local color switching and pressure mapping is developed using a 2D array of resistive pressure sensor switch. This thermochromic-based interactive sensor will enable the visualization of localized information in arbitrary shapes with dynamic responses in the context of serial/parallel pressure mapping and quantifying capability without optoelectronic arrays.

  7. Interactive Maps for Community in Online Learning

    ERIC Educational Resources Information Center

    Cavanaugh, Terence W.; Cavanaugh, Cathy

    2008-01-01

    The online courses studied here used the visual medium of the interactive geographic map as a form of dialogue to reduce students' sense of transactional distance during the course, build their skills with Web 2.0 media, and increase their motivation. Using the dynamic map and the related online spreadsheet, the course participants created digital…

  8. DIMA 3.0: Domain Interaction Map.

    PubMed

    Luo, Qibin; Pagel, Philipp; Vilne, Baiba; Frishman, Dmitrij

    2011-01-01

    Domain Interaction MAp (DIMA, available at http://webclu.bio.wzw.tum.de/dima) is a database of predicted and known interactions between protein domains. It integrates 5807 structurally known interactions imported from the iPfam and 3did databases and 46,900 domain interactions predicted by four computational methods: domain phylogenetic profiling, domain pair exclusion algorithm correlated mutations and domain interaction prediction in a discriminative way. Additionally predictions are filtered to exclude those domain pairs that are reported as non-interacting by the Negatome database. The DIMA Web site allows to calculate domain interaction networks either for a domain of interest or for entire organisms, and to explore them interactively using the Flash-based Cytoscape Web software.

  9. Interactive Geophysical Mapping on the Web

    NASA Astrophysics Data System (ADS)

    Meertens, C.; Hamburger, M.; Estey, L.; Weingroff, M.; Deardorff, R.; Holt, W.

    2002-12-01

    We have developed a set of interactive, web-based map utilities that make geophysical results accessible to a large number and variety of users. These tools provide access to pre-determined map regions via a simple Html/JavaScript interface or to user-selectable areas using a Java interface to a Generic Mapping Tools (GMT) engine. Users can access a variety of maps, satellite images, and geophysical data at a range of spatial scales for the earth and other planets of the solar system. Developed initially by UNAVCO for study of global-scale geodynamic processes, users can choose from a variety of base maps (satellite mosaics, global topography, geoid, sea-floor age, strain rate and seismic hazard maps, and others) and can then add a number of geographic and geophysical overlays for example coastlines, political boundaries, rivers and lakes, NEIC earthquake and volcano locations, stress axes, and observed and model plate motion and deformation velocity vectors representing a compilation of 2933 geodetic measurements from around the world. The software design is flexible allowing for construction of special editions for different target audiences. Custom maps been implemented for UNAVCO as the "Jules Verne Voyager" and "Voyager Junior", for the International Lithosphere Project's "Global Strain Rate Map", and for EarthScope Education and Outreach as "EarthScope Voyager Jr.". For the later, a number of EarthScope-specific features have been added, including locations of proposed USArray (seismic), Plate Boundary Observatory (geodetic), and San Andreas Fault Observatory at Depth sites plus detailed maps and geographically referenced examples of EarthScope-related scientific investigations. In addition, we are developing a website that incorporates background materials and curricular activities that encourage users to explore Earth processes. A cluster of map processing computers and nearly a terabyte of disk storage has been assembled to power the generation of

  10. Interactive map of refugee movement in Europe

    NASA Astrophysics Data System (ADS)

    Calka, Beata; Cahan, Bruce

    2016-12-01

    Considering the recent mass movement of people fleeing war and oppression, an analysis of changes in migration, in particular an analysis of the final destination refugees choose, seems to be of utmost importance. Many international organisations like UNHCR (the United Nations High Commissioner for Refugees) or EuroStat gather and provide information on the number of refugees and the routes they follow. What is also needed to study the state of affairs closely is a visual form presenting the rapidly changing situation. An analysis of the problem together with up-to-date statistical data presented in the visual form of a map is essential. This article describes methods of preparing such interactive maps displaying movement of refugees in European Union countries. Those maps would show changes taking place throughout recent years but also the dynamics of the development of the refugee crisis in Europe. The ArcGIS software was applied to make the map accessible on the Internet. Additionally, online sources and newspaper articles were used to present the movement of migrants. The interactive map makes it possible to watch spatial data with an opportunity to navigate within the map window. Because of that it is a clear and convenient tool to visualise such processes as refugee migration in Europe.

  11. Interactive mapping on 3-D terrain models

    NASA Astrophysics Data System (ADS)

    Bernardin, T.; Cowgill, E.; Gold, R.; Hamann, B.; Kreylos, O.; Schmitt, A.

    2006-10-01

    We present an interactive, real-time mapping system for use with digital elevation models and remotely sensed multispectral imagery that aids geoscientists in the creation and interpretation of geologic/neotectonic maps at length scales of 10 m to 1000 km. Our system provides a terrain visualization of the surface of the Earth or other terrestrial planets by displaying a virtual terrain model generated from a digital elevation model overlain by a color texture generated from orthophotos or satellite imagery. We use a quadtree-based, multiresolution display method to render in real time high-resolution virtual terrain models that span large spatial regions. The system allows users to measure the orientations of geologic surfaces and record their observations by drawing lines directly on the virtual terrain model. In addition, interpretive surfaces can be generated from these drawings and displayed to facilitate understanding of the three-dimensional geometry of geologic surfaces. The main strength of our system is the combination of real-time rendering and interactive mapping performed directly on the virtual terrain model with the ability to navigate the scene while changing viewpoints arbitrarily during mapping. User studies and comparisons with commercially available mapping software show that our system improves mapping accuracy and efficiency and also yields observations that cannot be made with existing systems.

  12. Dynamic Map: Representation of interactions between robots

    SciTech Connect

    Zanardi, C.

    1996-12-31

    As robotics applications become more complex, the need for tools to analyze and explain interactions between robots has become more acute. We introduce the concept of Dynamic Map (DM), which can serve as a generic tool to analyze interactions between robots or with their environment. We show that this concept can be applied to different kinds of applications, like a predator-prey situation, or collision avoidance.

  13. LANDSAT data and interactive computer mapping

    NASA Technical Reports Server (NTRS)

    Grady, R. K.

    1984-01-01

    The integration of image processing capabilities with interactive computer mapping systems is discussed. It is noted that the accomplishment of this integration will result in powerful geographic information systems which will enhance the applicatons of LANDSAT and other types of remotely sensed data in solving problems in the resource planning and management domain.

  14. Fundamentals of protein interaction network mapping.

    PubMed

    Snider, Jamie; Kotlyar, Max; Saraon, Punit; Yao, Zhong; Jurisica, Igor; Stagljar, Igor

    2015-12-17

    Studying protein interaction networks of all proteins in an organism ("interactomes") remains one of the major challenges in modern biomedicine. Such information is crucial to understanding cellular pathways and developing effective therapies for the treatment of human diseases. Over the past two decades, diverse biochemical, genetic, and cell biological methods have been developed to map interactomes. In this review, we highlight basic principles of interactome mapping. Specifically, we discuss the strengths and weaknesses of individual assays, how to select a method appropriate for the problem being studied, and provide general guidelines for carrying out the necessary follow-up analyses. In addition, we discuss computational methods to predict, map, and visualize interactomes, and provide a summary of some of the most important interactome resources. We hope that this review serves as both a useful overview of the field and a guide to help more scientists actively employ these powerful approaches in their research. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

  15. Interactive Mapping on Virtual Terrain Models Using RIMS (Real-time, Interactive Mapping System)

    NASA Astrophysics Data System (ADS)

    Bernardin, T.; Cowgill, E.; Gold, R. D.; Hamann, B.; Kreylos, O.; Schmitt, A.

    2006-12-01

    Recent and ongoing space missions are yielding new multispectral data for the surfaces of Earth and other planets at unprecedented rates and spatial resolution. With their high spatial resolution and widespread coverage, these data have opened new frontiers in observational Earth and planetary science. But they have also precipitated an acute need for new analytical techniques. To address this problem, we have developed RIMS, a Real-time, Interactive Mapping System that allows scientists to visualize, interact with, and map directly on, three-dimensional (3D) displays of georeferenced texture data, such as multispectral satellite imagery, that is draped over a surface representation derived from digital elevation data. The system uses a quadtree-based multiresolution method to render in real time high-resolution (3 to 10 m/pixel) data over large (800 km by 800 km) spatial areas. It allows users to map inside this interactive environment by generating georeferenced and attributed vector-based elements that are draped over the topography. We explain the technique using 15 m ASTER stereo-data from Iraq, P.R. China, and other remote locations because our particular motivation is to develop a technique that permits the detailed (10 m to 1000 m) neotectonic mapping over large (100 km to 1000 km long) active fault systems that is needed to better understand active continental deformation on Earth. RIMS also includes a virtual geologic compass that allows users to fit a plane to geologic surfaces and thereby measure their orientations. It also includes tools that allow 3D surface reconstruction of deformed and partially eroded surfaces such as folded bedding planes. These georeferenced map and measurement data can be exported to, or imported from, a standard GIS (geographic information systems) file format. Our interactive, 3D visualization and analysis system is designed for those who study planetary surfaces, including neotectonic geologists, geomorphologists, marine

  16. Coupled maps with local and global interactions.

    PubMed

    Ouchi, Noriyuki Bob; Kaneko, Kunihiko

    2000-06-01

    A coupled map lattice model with both local and global couplings is studied as a simple example of hierarchical pattern dynamics with different length scales of interactions. Several phases are classified according to domain structures, degree of chaotic dynamics, distribution function, and power spectra. In particular, a cascade process of formation and collapse of bubbles is found in some parameter regime. The state is characterized by spatiotemporal power-law correlation and few positive Lyapunov exponents. In a two-dimensional case, the state leads to a characteristic spatiotemporal pattern that may be regarded as a dynamic extension of a Turing pattern. The possible relevance to natural patterns is also discussed. (c) 2000 American Institute of Physics.

  17. An interactive method for digitizing zone maps

    NASA Technical Reports Server (NTRS)

    Giddings, L. E.; Thompson, E. J.

    1975-01-01

    A method is presented for digitizing maps that consist of zones, such as contour or climatic zone maps. A color-coded map is prepared by any convenient process. The map is then read into memory of an Image 100 computer by means of its table scanner, using colored filters. Zones are separated and stored in themes, using standard classification procedures. Thematic data are written on magnetic tape and these data, appropriately coded, are combined to make a digitized image on tape. Step-by-step procedures are given for digitization of crop moisture index maps with this procedure. In addition, a complete example of the digitization of a climatic zone map is given.

  18. Quantitative Genetic Interaction Mapping Using the E-MAP Approach

    PubMed Central

    Collins, Sean R.; Roguev, Assen; Krogan, Nevan J.

    2010-01-01

    Genetic interactions represent the degree to which the presence of one mutation modulates the phenotype of a second mutation. In recent years, approaches for measuring genetic interactions systematically and quantitatively have proven to be effective tools for unbiased characterization of gene function and have provided valuable data for analyses of evolution. Here, we present protocols for systematic measurement of genetic interactions with respect to organismal growth rate for two yeast species. PMID:20946812

  19. Genetic interaction mapping with microfluidic-based single cell sequencing.

    PubMed

    Haliburton, John R; Shao, Wenjun; Deutschbauer, Adam; Arkin, Adam; Abate, Adam R

    2017-01-01

    Genetic interaction mapping is useful for understanding the molecular basis of cellular decision making, but elucidating interactions genome-wide is challenging due to the massive number of gene combinations that must be tested. Here, we demonstrate a simple approach to thoroughly map genetic interactions in bacteria using microfluidic-based single cell sequencing. Using single cell PCR in droplets, we link distinct genetic information into single DNA sequences that can be decoded by next generation sequencing. Our approach is scalable and theoretically enables the pooling of entire interaction libraries to interrogate multiple pairwise genetic interactions in a single culture. The speed, ease, and low-cost of our approach makes genetic interaction mapping viable for routine characterization, allowing the interaction network to be used as a universal read out for a variety of biology experiments, and for the elucidation of interaction networks in non-model organisms.

  20. Genetic interaction mapping with microfluidic-based single cell sequencing

    PubMed Central

    Haliburton, John R.; Shao, Wenjun; Deutschbauer, Adam; Arkin, Adam; Abate, Adam R.

    2017-01-01

    Genetic interaction mapping is useful for understanding the molecular basis of cellular decision making, but elucidating interactions genome-wide is challenging due to the massive number of gene combinations that must be tested. Here, we demonstrate a simple approach to thoroughly map genetic interactions in bacteria using microfluidic-based single cell sequencing. Using single cell PCR in droplets, we link distinct genetic information into single DNA sequences that can be decoded by next generation sequencing. Our approach is scalable and theoretically enables the pooling of entire interaction libraries to interrogate multiple pairwise genetic interactions in a single culture. The speed, ease, and low-cost of our approach makes genetic interaction mapping viable for routine characterization, allowing the interaction network to be used as a universal read out for a variety of biology experiments, and for the elucidation of interaction networks in non-model organisms. PMID:28170417

  1. Protein-surface interaction maps for ion-exchange chromatography.

    PubMed

    Freed, Alexander S; Cramer, Steven M

    2011-04-05

    In this paper, protein-surface interaction maps were generated by performing coarse-grained protein-surface calculations. This approach allowed for the rapid determination of the protein-surface interaction energies at a range of orientations and distances. Interaction maps of lysozyme indicated that there was a contiguous series of orientations corresponding to several adjacent preferred binding regions on the protein surface. Examination of these orientations provided insight into the residues involved in surface interactions, which qualitatively agreed with the retention data for single-site mutants. Interaction maps of lysozyme single-site mutants were also generated and provided significant insight into why these variants exhibited significant differences in their chromatographic behavior. This approach was also employed to study the binding behavior of CspB and related mutants. The results indicated that, in addition to describing general trends in the data, these maps provided significant insight into retention data of the single-site mutants. In particular, subtle retention trends observed with the K12 and K13 mutants were well-described using this interaction map approach. Finally, the number of interaction points with energies stronger than -2 kcal/mol was shown to be able to semi-quantitatively predict the behavior of most of the mutants. This rapid approach for calculating protein-surface interaction maps is expected to facilitate future method development for separating closely related protein variants in ion-exchange systems.

  2. Visualising interactive flood risk maps in a dynamic Geobrowser

    NASA Astrophysics Data System (ADS)

    Yaw Manful, Desmond; He, Yi; Cloke, Hannah; Pappenberger, Florian; Li, Zhijia; Wetterhall, Fredrik; Huang, Yingchun; Hu, Yuzhong

    2010-05-01

    Communicating flood forecast products effectively to end-users is the final step in the flood event simulation process. A prototype of the Novel Flood Early Warning System (NEWS) based on the TIGGE (THORPEX Interactive Grand Global Ensemble) database explores new avenues to visualise flood forecast products in a dynamic and interactive manner. One of the possibilities NEWS is currently assessing is Google Maps. Google Maps is a basic web mapping service application and technology provided by Google, free (for non-commercial use). It powers many map-based services including maps embedded on third-party websites via the Google Maps API. Creating a customized map interface requires adding the Google JavaScript code to a page, and then using Javascript functions to add points to the map. Flood maps allow end-users to visualise and navigate a world that is too large and complex to be seen directly. The NEWS software will attempt to deal with the following issues: • Uncertainty visualization in hazards maps • Visualizing uncertainty for sector specific risk managers • Uncertainty representation of point and linear data The objective is improve the information content of flood risk maps making them more useful to specific end-users.

  3. Mapping interactions of Chikungunya virus nonstructural proteins.

    PubMed

    Sreejith, R; Rana, Jyoti; Dudha, Namrata; Kumar, Kapila; Gabrani, Reema; Sharma, Sanjeev K; Gupta, Amita; Vrati, Sudhanshu; Chaudhary, Vijay K; Gupta, Sanjay

    2012-10-01

    The four nonstructural proteins (nsPs1-4) of Chikungunya virus (CHIKV) play important roles involving enzymatic activities and specific interactions with both viral and host components, during different stages of viral pathogenesis. Elucidation of the presence and/or absence of interactions among nsPs in a systematic manner is thus of scientific interest. In the current study, each pair-wise combination among the four nonstructural proteins of CHIKV was systematically analyzed for possible interactions. Six novel protein interactions were identified for CHIKV, using systems such as yeast two-hybrid, GST pull down and ELISA, three of which have not been previously reported for the genus Alphavirus. These interactions form a network of organized associations that suggest the spatial arrangement of nonstructural proteins in the late replicase complex. The study identified novel interactions as well as concurred with previously described associations in related alphaviruses.

  4. Quantitative genetic-interaction mapping in mammalian cells

    PubMed Central

    Roguev, Assen; Talbot, Dale; Negri, Gian Luca; Shales, Michael; Cagney, Gerard; Bandyopadhyay, Sourav; Panning, Barbara; Krogan, Nevan J

    2013-01-01

    Mapping genetic interactions (GIs) by simultaneously perturbing pairs of genes is a powerful tool for understanding complex biological phenomena. Here we describe an experimental platform for generating quantitative GI maps in mammalian cells using a combinatorial RNA interference strategy. We performed ~11,000 pairwise knockdowns in mouse fibroblasts, focusing on 130 factors involved in chromatin regulation to create a GI map. Comparison of the GI and protein-protein interaction (PPI) data revealed that pairs of genes exhibiting positive GIs and/or similar genetic profiles were predictive of the corresponding proteins being physically associated. The mammalian GI map identified pathways and complexes but also resolved functionally distinct submodules within larger protein complexes. By integrating GI and PPI data, we created a functional map of chromatin complexes in mouse fibroblasts, revealing that the PAF complex is a central player in the mammalian chromatin landscape. PMID:23407553

  5. Quantitative genetic-interaction mapping in mammalian cells.

    PubMed

    Roguev, Assen; Talbot, Dale; Negri, Gian Luca; Shales, Michael; Cagney, Gerard; Bandyopadhyay, Sourav; Panning, Barbara; Krogan, Nevan J

    2013-05-01

    Mapping genetic interactions (GIs) by simultaneously perturbing pairs of genes is a powerful tool for understanding complex biological phenomena. Here we describe an experimental platform for generating quantitative GI maps in mammalian cells using a combinatorial RNA interference strategy. We performed ∼11,000 pairwise knockdowns in mouse fibroblasts, focusing on 130 factors involved in chromatin regulation to create a GI map. Comparison of the GI and protein-protein interaction (PPI) data revealed that pairs of genes exhibiting positive GIs and/or similar genetic profiles were predictive of the corresponding proteins being physically associated. The mammalian GI map identified pathways and complexes but also resolved functionally distinct submodules within larger protein complexes. By integrating GI and PPI data, we created a functional map of chromatin complexes in mouse fibroblasts, revealing that the PAF complex is a central player in the mammalian chromatin landscape.

  6. Building protein interaction maps for Down's syndrome.

    PubMed

    Gardiner, Katheleen; Davisson, Muriel T; Crnic, Linda S

    2004-08-01

    Now that the complete sequences for human chromosome 21 and the orthologous mouse genomic regions are known, reasonably complete, conserved, protein-coding gene catalogues are also available. The central issue now facing Down's syndrome researchers is the correlation of increased expression of specific, normal, chromosome 21 genes with the development of specific deficits in learning and memory. Because of the number of candidate genes involved, the number of alternative splice variants of individual genes and the number of pathways in which these genes function, a pathway analysis approach will be critical to success. Here, three examples, both gene specific and pathway related, that would benefit from pathway analysis are discussed: (1) the potential roles of eight chromosome 21 proteins in RNA processing pathways; (2) the chromosome 21 protein intersectin 1 and its domain composition, alternative splicing, protein interactions and functions; and (3) the interactions of ten chromosome 21 proteins with components of the mitogen-activated protein kinase and the calcineurin signalling pathways. A productive approach to developing gene-phenotype correlations in Down's syndrome will make use of known and predicted functions and interactions of chromosome 21 genes to predict pathways that may be perturbed by their increased levels of expression. Investigations may then be targeted in animal models to specific interactions, intermediate steps or end-points of such pathways and the downstream - perhaps amplified - consequences of gene dosage directly assessed. Once pathway perturbations have been identified, the potential for rational design of therapeutics becomes practical.

  7. Mapping Social Interactions: The Science of Proxemics.

    PubMed

    McCall, Cade

    Interpersonal distance and gaze provide a wealth of information during face-to-face social interactions. These "proxemic" behaviors offer a window into everyday social cognition by revealing interactants' affective states (e.g., interpersonal attitudes) and cognitive responses (e.g., social attention). Here we provide a brief overview of the social psychological literature in this domain. We focus on new techniques for experimentally manipulating and measuring proxemics, including the use of immersive virtual environments and digital motion capture. We also discuss ways in which these approaches can be integrated with psychophysiological and neuroimaging techniques. Throughout, we argue that contemporary proxemics research provides psychology and neuroscience with a means to study social cognition and behavior as they naturally emerge and unfold in vivo.

  8. Interactive computer methods for generating mineral-resource maps

    USGS Publications Warehouse

    Calkins, James Alfred; Crosby, A.S.; Huffman, T.E.; Clark, A.L.; Mason, G.T.; Bascle, R.J.

    1980-01-01

    Inasmuch as maps are a basic tool of geologists, the U.S. Geological Survey's CRIB (Computerized Resources Information Bank) was constructed so that the data it contains can be used to generate mineral-resource maps. However, by the standard methods used-batch processing and off-line plotting-the production of a finished map commonly takes 2-3 weeks. To produce computer-generated maps more rapidly, cheaply, and easily, and also to provide an effective demonstration tool, we have devised two related methods for plotting maps as alternatives to conventional batch methods. These methods are: 1. Quick-Plot, an interactive program whose output appears on a CRT (cathode-ray-tube) device, and 2. The Interactive CAM (Cartographic Automatic Mapping system), which combines batch and interactive runs. The output of the Interactive CAM system is final compilation (not camera-ready) paper copy. Both methods are designed to use data from the CRIB file in conjunction with a map-plotting program. Quick-Plot retrieves a user-selected subset of data from the CRIB file, immediately produces an image of the desired area on a CRT device, and plots data points according to a limited set of user-selected symbols. This method is useful for immediate evaluation of the map and for demonstrating how trial maps can be made quickly. The Interactive CAM system links the output of an interactive CRIB retrieval to a modified version of the CAM program, which runs in the batch mode and stores plotting instructions on a disk, rather than on a tape. The disk can be accessed by a CRT, and, thus, the user can view and evaluate the map output on a CRT immediately after a batch run, without waiting 1-3 days for an off-line plot. The user can, therefore, do most of the layout and design work in a relatively short time by use of the CRT, before generating a plot tape and having the map plotted on an off-line plotter.

  9. Galaxy Interactions with FIRE: Mapping Star Formation

    NASA Astrophysics Data System (ADS)

    Moreno, Jorge

    2016-01-01

    We utilize a suite of 75 simulations of galaxies in idealised major mergers (stellar mass ratio ~2.5:1), with a wide range of orbital parameters, to investigate the spatial extent of interaction-induced star formation. Two versions are used, one based on a Kennicult-like subgrid model (Gadget, Springel & Hernquist 2003); the other based on the new Feedback In Realistic Environments model (FIRE, Hopkins et al. 2014). Although the total star formation in galaxy encounters is generally elevated relative to isolated galaxies, we find that this elevation is a combination of intense enhancements within the central kpc and moderately suppressed activity at large galacto-centric radii. This effect appears to be stronger in the older Gadget model. Suppression is the disk is also found in the FIRE runs, but at larger scales. This is because tidal torques are weaker in the newer FIRE model, leading to a more extended nuclear starburt. Our predictions of the radial dependence of triggered star formation, and specifically the suppression of star formation beyond kpc-scales, will be testable with the next generation of integral-field spectroscopic surveys.

  10. Interactive Web Interface to the Global Strain Rate Map Project

    NASA Astrophysics Data System (ADS)

    Meertens, C. M.; Estey, L.; Kreemer, C.; Holt, W.

    2004-05-01

    An interactive web interface allows users to explore the results of a global strain rate and velocity model and to compare them to other geophysical observations. The most recent model, an updated version of Kreemer et al., 2003, has 25 independent rigid plate-like regions separated by deformable boundaries covered by about 25,000 grid areas. A least-squares fit was made to 4900 geodetic velocities from 79 different geodetic studies. In addition, Quaternary fault slip rate data are used to infer geologic strain rate estimates (currently only for central Asia). Information about the style and direction of expected strain rate is inferred from the principal axes of the seismic strain rate field. The current model, as well as source data, references and an interactive map tool, are located at the International Lithosphere Program (ILP) "A Global Strain Rate Map (ILP II-8)" project website: http://www-world-strain-map.org. The purpose of the ILP GSRM project is to provide new information from this, and other investigations, that will contribute to a better understanding of continental dynamics and to the quantification of seismic hazards. A unique aspect of the GSRM interactive Java map tool is that the user can zoom in and make custom views of the model grid and results for any area of the globe selecting strain rate and style contour plots and principal axes, observed and model velocity fields in specified frames of reference, and geologic fault data. The results can be displayed with other data sets such Harvard CMT earthquake focal mechanisms, stress directions from the ILP World Stress Map Project, and topography. With the GSRM Java map tool, the user views custom maps generated by a Generic Mapping Tool (GMT) server. These interactive capabilities greatly extend what is possible to present in a published paper. A JavaScript version, using pre-constructed maps, as well as a related information site have also been created for broader education and outreach access

  11. Interactive Maps from the Great Basin Center for Geothermal Energy

    DOE Data Explorer

    The Great Basin Center for Geothermal Energy, part of the University of Nevada, Reno, conducts research towards the establishment of geothermal energy as an economically viable energy source within the Great Basin. The Center specializes in collecting and synthesizing geologic, geochemical, geodetic, geophysical, and tectonic data, and using Geographic Information System (GIS) technology to view and analyze this data and to produce favorability maps of geothermal potential. The interactive maps are built with layers of spatial data that are also available as direct file downloads (see DDE00299). The maps allow analysis of these many layers, with various data sets turned on or off, for determining potential areas that would be favorable for geothermal drilling or other activity. They provide information on current exploration projects and leases, Bureau of Land Management land status, and map presentation of each type of scientific spatial data: geothermal, geophysical, geologic, geodetic, groundwater, and geochemical.

  12. Tangent map analysis of the beam-beam interaction

    SciTech Connect

    Lee, S.Y.; Tepikian, S.

    1989-01-01

    We studied the tangent map of the beam-beam interaction and found no evidence of beam-beam instability for /epsilon/ = 0.04. Tracking study with tune modulation shows however large emittance growth due to the sum resonances. The emittance growth is due to the multiple crossing of the sum resonances. 12 refs., 7 figs.

  13. A Protein Interaction Map of the Kalimantacin Biosynthesis Assembly Line

    PubMed Central

    Uytterhoeven, Birgit; Lathouwers, Thomas; Voet, Marleen; Michiels, Chris W.; Lavigne, Rob

    2016-01-01

    The antimicrobial secondary metabolite kalimantacin (also called batumin) is produced by a hybrid polyketide/non-ribosomal peptide system in Pseudomonas fluorescens BCCM_ID9359. In this study, the kalimantacin biosynthesis gene cluster is analyzed by yeast two-hybrid analysis, creating a protein–protein interaction map of the entire assembly line. In total, 28 potential interactions were identified, of which 13 could be confirmed further. These interactions include the dimerization of ketosynthase domains, a link between assembly line modules 9 and 10, and a specific interaction between the trans-acting enoyl reductase BatK and the carrier proteins of modules 8 and 10. These interactions reveal fundamental insight into the biosynthesis of secondary metabolites. This study is the first to reveal interactions in a complete biosynthetic pathway. Similar future studies could build a strong basis for engineering strategies in such clusters. PMID:27853452

  14. NMR Chemical Shift Mapping of SH2 Peptide Interactions.

    PubMed

    McKercher, Marissa A; Wuttke, Deborah S

    2017-01-01

    Heteronuclear single quantum coherence (HSQC) nuclear magnetic resonance (NMR) experiments offer a rapid and high resolution approach to gaining binding and conformational insights into a protein-peptide interaction. By tracking (1)H and (15)N chemical shift changes over the course of a peptide titration into isotopically labeled protein, amide NH pairs of amino acids whose chemical environment changes upon peptide binding can be identified. When mapped onto a structure of the protein, this approach can identify the peptide-binding interface or regions undergoing conformation changes within a protein upon ligand binding. Monitoring NMR chemical shift changes can also serve as a screening technique to identify novel interaction partners for a protein or to determine the binding affinity of a weak protein-peptide interaction. Here, we describe the application of NMR chemical shift mapping to the study of peptide binding to the C-terminal SH2 domain of PLCγ1.

  15. Patterns of agent interaction scenarios as use case maps.

    PubMed

    Billard, Edward A

    2004-08-01

    A use case map (UCM) presents, in general, an abstract description of a complex system and, as such, is a good candidate for representing scenarios of autonomous agents interacting with other autonomous agents. The "gang of four" design patterns are intended for object-oriented software development but at least eight of the patterns illustrate structure, or architecture, that is appropriate for interacting agents, independent of software development. This study presents these particular patterns in the form of UCMs to describe abstract scenarios of agent interaction. Seven of the patterns attempt to balance the decentralized nature of interacting agents with an organized structure that makes for better, cleaner interactions. An example performance analysis is provided for one of the patterns, illustrating the benefit of an early abstraction of complex agent behavior. The original contribution here is a UCM presentation of the causal paths in agent behavior as suggested by software design patterns.

  16. Finding protein-protein interaction patterns by contact map matching.

    PubMed

    Melo, R C; Ribeiro, C; Murray, C S; Veloso, C J M; da Silveira, C H; Neshich, G; Meira, W; Carceroni, R L; Santoro, M M

    2007-10-05

    We propose a novel method for defining patterns of contacts present in protein-protein complexes. A new use of the traditional contact maps (more frequently used for representation of the intra-chain contacts) is presented for analysis of inter-chain contacts. Using an algorithm based on image processing techniques, we can compare protein-protein interaction maps and also obtain a dissimilarity score between them. The same algorithm used to compare the maps can align the contacts of all the complexes and be helpful in the determination of a pattern of conserved interactions at the interfaces. We present an example for the application of this method by analyzing the pattern of interaction of bovine pancreatic trypsin inhibitors and trypsins, chymotrypsins, a thrombin, a matriptase, and a kallikrein - all classified as serine proteases. We found 20 contacts conserved in trypsins and chymotrypsins and 3 specific ones are present in all the serine protease complexes studied. The method was able to identify important contacts for the protein family studied and the results are in agreement with the literature.

  17. Flow mapping and multivariate visualization of large spatial interaction data.

    PubMed

    Guo, Diansheng

    2009-01-01

    Spatial interactions (or flows), such as population migration and disease spread, naturally form a weighted location-to-location network (graph). Such geographically embedded networks (graphs) are usually very large. For example, the county-to-county migration data in the U.S. has thousands of counties and about a million migration paths. Moreover, many variables are associated with each flow, such as the number of migrants for different age groups, income levels, and occupations. It is a challenging task to visualize such data and discover network structures, multivariate relations, and their geographic patterns simultaneously. This paper addresses these challenges by developing an integrated interactive visualization framework that consists three coupled components: (1) a spatially constrained graph partitioning method that can construct a hierarchy of geographical regions (communities), where there are more flows or connections within regions than across regions; (2) a multivariate clustering and visualization method to detect and present multivariate patterns in the aggregated region-to-region flows; and (3) a highly interactive flow mapping component to map both flow and multivariate patterns in the geographic space, at different hierarchical levels. The proposed approach can process relatively large data sets and effectively discover and visualize major flow structures and multivariate relations at the same time. User interactions are supported to facilitate the understanding of both an overview and detailed patterns.

  18. Similarity interaction in information-theoretic self-organizing maps

    NASA Astrophysics Data System (ADS)

    Kamimura, Ryotaro

    2013-04-01

    In this paper, we propose a new information-theoretic computational method called 'similarity interaction' for improving visualization. Due to the fixed arrangement of neurons in the self-organizing maps, similarity between neurons is not necessarily a faithful representation of the actual similarity between neurons. To relax the fixed arrangement, we introduce a method called 'similarity interaction', because we integrate the information of connection weights into that of neurons. We applied our method to three problems, namely teaching assistant evaluation, automobile data, and dermatology data. In all three problems, we succeeded in demonstrating the better performance of our method through visual inspection and quantitative evaluation. Our method is the first step towards the interaction of multiple components in a neural network for finer representations of input patterns.

  19. Global Mapping of Human RNA-RNA Interactions.

    PubMed

    Sharma, Eesha; Sterne-Weiler, Tim; O'Hanlon, Dave; Blencowe, Benjamin J

    2016-05-19

    The majority of the human genome is transcribed into non-coding (nc)RNAs that lack known biological functions or else are only partially characterized. Numerous characterized ncRNAs function via base pairing with target RNA sequences to direct their biological activities, which include critical roles in RNA processing, modification, turnover, and translation. To define roles for ncRNAs, we have developed a method enabling the global-scale mapping of RNA-RNA duplexes crosslinked in vivo, "LIGation of interacting RNA followed by high-throughput sequencing" (LIGR-seq). Applying this method in human cells reveals a remarkable landscape of RNA-RNA interactions involving all major classes of ncRNA and mRNA. LIGR-seq data reveal unexpected interactions between small nucleolar (sno)RNAs and mRNAs, including those involving the orphan C/D box snoRNA, SNORD83B, that control steady-state levels of its target mRNAs. LIGR-seq thus represents a powerful approach for illuminating the functions of the myriad of uncharacterized RNAs that act via base-pairing interactions.

  20. A genetic interaction map of cell cycle regulators

    PubMed Central

    Billmann, Maximilian; Horn, Thomas; Fischer, Bernd; Sandmann, Thomas; Huber, Wolfgang; Boutros, Michael

    2016-01-01

    Cell-based RNA interference (RNAi) is a powerful approach to screen for modulators of many cellular processes. However, resulting candidate gene lists from cell-based assays comprise diverse effectors, both direct and indirect, and further dissecting their functions can be challenging. Here we screened a genome-wide RNAi library for modulators of mitosis and cytokinesis in Drosophila S2 cells. The screen identified many previously known genes as well as modulators that have previously not been connected to cell cycle control. We then characterized ∼300 candidate modifiers further by genetic interaction analysis using double RNAi and a multiparametric, imaging-based assay. We found that analyzing cell cycle–relevant phenotypes increased the sensitivity for associating novel gene function. Genetic interaction maps based on mitotic index and nuclear size grouped candidates into known regulatory complexes of mitosis or cytokinesis, respectively, and predicted previously uncharacterized components of known processes. For example, we confirmed a role for the Drosophila CCR4 mRNA processing complex component l(2)NC136 during the mitotic exit. Our results show that the combination of genome-scale RNAi screening and genetic interaction analysis using process-directed phenotypes provides a powerful two-step approach to assigning components to specific pathways and complexes. PMID:26912791

  1. Active Interaction Mapping Reveals the Hierarchical Organization of Autophagy.

    PubMed

    Kramer, Michael H; Farré, Jean-Claude; Mitra, Koyel; Yu, Michael Ku; Ono, Keiichiro; Demchak, Barry; Licon, Katherine; Flagg, Mitchell; Balakrishnan, Rama; Cherry, J Michael; Subramani, Suresh; Ideker, Trey

    2017-02-16

    We have developed a general progressive procedure, Active Interaction Mapping, to guide assembly of the hierarchy of functions encoding any biological system. Using this process, we assemble an ontology of functions comprising autophagy, a central recycling process implicated in numerous diseases. A first-generation model, built from existing gene networks in Saccharomyces, captures most known autophagy components in broad relation to vesicle transport, cell cycle, and stress response. Systematic analysis identifies synthetic-lethal interactions as most informative for further experiments; consequently, we saturate the model with 156,364 such measurements across autophagy-activating conditions. These targeted interactions provide more information about autophagy than all previous datasets, producing a second-generation ontology of 220 functions. Approximately half are previously unknown; we confirm roles for Gyp1 at the phagophore-assembly site, Atg24 in cargo engulfment, Atg26 in cytoplasm-to-vacuole targeting, and Ssd1, Did4, and others in selective and non-selective autophagy. The procedure and autophagy hierarchy are at http://atgo.ucsd.edu/.

  2. Systematic Mapping of Chemical-Genetic Interactions in Saccharomyces cerevisiae.

    PubMed

    Suresh, Sundari; Schlecht, Ulrich; Xu, Weihong; Bray, Walter; Miranda, Molly; Davis, Ronald W; Nislow, Corey; Giaever, Guri; Lokey, R Scott; St Onge, Robert P

    2016-09-01

    Chemical-genetic interactions (CGIs) describe a phenomenon where the effects of a chemical compound (i.e., a small molecule) on cell growth are dependent on a particular gene. CGIs can reveal important functional information about genes and can also be powerful indicators of a compound's mechanism of action. Mapping CGIs can lead to the discovery of new chemical probes, which, in contrast to genetic perturbations, operate at the level of the gene product (or pathway) and can be fast-acting, tunable, and reversible. The simple culture conditions required for yeast and its rapid growth, as well as the availability of a complete set of barcoded gene deletion strains, facilitate systematic mapping of CGIs in this organism. This process involves two basic steps: first, screening chemical libraries to identify bioactive compounds affecting growth and, second, measuring the effects of these compounds on genome-wide collections of mutant strains. Here, we introduce protocols for both steps that have great potential for the discovery and development of new small-molecule tools and medicines. © 2016 Cold Spring Harbor Laboratory Press.

  3. Distinguishing time-delayed causal interactions using convergent cross mapping

    PubMed Central

    Ye, Hao; Deyle, Ethan R.; Gilarranz, Luis J.; Sugihara, George

    2015-01-01

    An important problem across many scientific fields is the identification of causal effects from observational data alone. Recent methods (convergent cross mapping, CCM) have made substantial progress on this problem by applying the idea of nonlinear attractor reconstruction to time series data. Here, we expand upon the technique of CCM by explicitly considering time lags. Applying this extended method to representative examples (model simulations, a laboratory predator-prey experiment, temperature and greenhouse gas reconstructions from the Vostok ice core, and long-term ecological time series collected in the Southern California Bight), we demonstrate the ability to identify different time-delayed interactions, distinguish between synchrony induced by strong unidirectional-forcing and true bidirectional causality, and resolve transitive causal chains. PMID:26435402

  4. Mapping glycoconjugate-mediated interactions of marine Bacteroidetes with diatoms.

    PubMed

    Bennke, Christin M; Neu, Thomas R; Fuchs, Bernhard M; Amann, Rudolf

    2013-09-01

    The degradation of diatoms is mainly catalyzed by Bacteroidetes and this process is of global relevance for the carbon cycle. In this study, a combination of catalyzed reporter deposition-fluorescence in situ hybridization (CARD-FISH) and fluorescent lectin binding analysis (FLBA) was used to identify and map glycoconjugates involved in the specific interactions of Bacteroidetes and diatoms, as well as detritus, at the coastal marine site Helgoland Roads (German Bight, North Sea). The study probed both the presence of lectin-specific extracellular polymeric substances (EPS) of Bacteroidetes for cell attachment and that of glycoconjugates on diatoms with respect to binding sites for Bacteroidetes. Members of the clades Polaribacter and Ulvibacter were shown to form microcolonies within aggregates for which FLBA indicated the presence of galactose containing slime. Polaribacter spp. was shown to bind specifically to the setae of the abundant diatom Chaetoceros spp., and the setae were stained with fucose-specific lectins. In contrast, Ulvibacter spp. attached to diatoms of the genus Asterionella which bound, among others, the mannose-specific lectin PSA. The newly developed CARD-FISH/FLBA protocol was limited to the glycoconjugates that persisted after the initial CARD-FISH procedure. The differential attachment of bacteroidetal clades to diatoms and their discrete staining by FLBA provided evidence for the essential role that formation and recognition of glycoconjugates play in the interaction of bacteria with phytoplankton. Copyright © 2013 Elsevier GmbH. All rights reserved.

  5. A Web-Based Interactive Mapping System of State Wide School Performance: Integrating Google Maps API Technology into Educational Achievement Data

    ERIC Educational Resources Information Center

    Wang, Kening; Mulvenon, Sean W.; Stegman, Charles; Anderson, Travis

    2008-01-01

    Google Maps API (Application Programming Interface), released in late June 2005 by Google, is an amazing technology that allows users to embed Google Maps in their own Web pages with JavaScript. Google Maps API has accelerated the development of new Google Maps based applications. This article reports a Web-based interactive mapping system…

  6. A Web-Based Interactive Mapping System of State Wide School Performance: Integrating Google Maps API Technology into Educational Achievement Data

    ERIC Educational Resources Information Center

    Wang, Kening; Mulvenon, Sean W.; Stegman, Charles; Anderson, Travis

    2008-01-01

    Google Maps API (Application Programming Interface), released in late June 2005 by Google, is an amazing technology that allows users to embed Google Maps in their own Web pages with JavaScript. Google Maps API has accelerated the development of new Google Maps based applications. This article reports a Web-based interactive mapping system…

  7. Targeting chk2 kinase: molecular interaction maps and therapeutic rationale.

    PubMed

    Pommier, Yves; Sordet, Olivier; Rao, V Ashutosh; Zhang, Hongliang; Kohn, Kurt W

    2005-01-01

    Most anticancer drugs presently used clinically target genomic DNA. The selectivity of these anticancer drugs for tumor tissues is probably due to tumor-specific defects suppressing cell cycle checkpoints and DNA repair, and enhancing apoptotic response in the tumor. We will review the molecular interactions within the ATM-Chk2 pathway implicating the DNA damage sensor kinases (ATM, ATR and DNA-PK), the adaptor BRCT proteins (Nbs1, Brca1, 53BP1, MDC1) and the effector kinases (Chk2, Chk1, Plk3, JNK, p38). The molecular interaction map convention (MIM) will be used for presenting this molecular network (http://discover.nci.nih.gov/mim/). A characteristic of the ATM-Chk2 pathway is its redundancy. First, ATM and Chk2 phosphorylate common substrates including p53, E2F1, BRCA1, and Chk2 itself, which suggests that Chk2 (also known as CHECK2, Cds1 in fission yeast, and Dmchk2 or Dmnk or Loki in the fruit fly) acts as a relay for ATM and/or as a salvage pathway when ATM is inactivated. Secondly, redundancy is apparent for the substrates, which can be phosphorylated/activated at similar residues by Chk2, Chk1, and the polo kinases (Plk's). Functionally, Chk2 can activate both apoptosis (via p53, E2F1 and PML) and cell cycle checkpoint (via Cdc25A and Cdc25C, p53, and BRCA1). We will review the short list of published Chk2 inhibitors. We will also propose a novel paradigm for screening interfacial inhibitors of Chk2. Chk2 inhibitors might be used to enhance the tumor selectivity of DNA targeted agents in p53-deficient tumors, and for the treatment of tumors whose growth depends on enhanced Chk2 activity.

  8. [Studies of methods and exploitation of computer software for mapping interactive genes].

    PubMed

    Huang, Wei-Su; Zheng, Yan; Chen, Guo-Bo; Wu, Wei-Ren

    2006-10-01

    There are six possible types of gene interaction in qualitative traits, namely, complementary, duplicate, cumulative, dominant epistasis, recessive epistasis and inhibiting. In genetic studies, the problem of mapping interactive genes may be met sometimes, but no systematic researches on the methodology and computer software for the mapping of interactive genes have been reported up to date. In this paper, methods for the mapping of interactive genes based on maximum-likelihood estimation and corresponding computer software (IGMapping 1.0) are presented. Computer simulations have shown that the methods proposed can unbiasedly estimate the recombination frequency or linkage distance between a codominant marker and an interactive gene.

  9. Map model for nonlinear alpha particle interaction with toroidal Alfven waves

    SciTech Connect

    Berk, H.L.; Breizman, B.N.; Ye, H.

    1992-09-01

    A map model has been developed for studying the nonlinear interaction of alpha particles with the toroidal Alfven eigenmodes. The map is constructed by assuming a linear interaction during a single poloidal transit, which allows the study of the nonlinear interaction over many transits. By using this map, analytic expressions are obtained for the particle nonlinear bounce frequency, and the wave amplitude threshold for the onset of particle orbit stochasticity. The map model can also facilitate self-consistent simulations which incorporate the time variation of the waves.

  10. A global genetic interaction network maps a wiring diagram of cellular function.

    PubMed

    Costanzo, Michael; VanderSluis, Benjamin; Koch, Elizabeth N; Baryshnikova, Anastasia; Pons, Carles; Tan, Guihong; Wang, Wen; Usaj, Matej; Hanchard, Julia; Lee, Susan D; Pelechano, Vicent; Styles, Erin B; Billmann, Maximilian; van Leeuwen, Jolanda; van Dyk, Nydia; Lin, Zhen-Yuan; Kuzmin, Elena; Nelson, Justin; Piotrowski, Jeff S; Srikumar, Tharan; Bahr, Sondra; Chen, Yiqun; Deshpande, Raamesh; Kurat, Christoph F; Li, Sheena C; Li, Zhijian; Usaj, Mojca Mattiazzi; Okada, Hiroki; Pascoe, Natasha; San Luis, Bryan-Joseph; Sharifpoor, Sara; Shuteriqi, Emira; Simpkins, Scott W; Snider, Jamie; Suresh, Harsha Garadi; Tan, Yizhao; Zhu, Hongwei; Malod-Dognin, Noel; Janjic, Vuk; Przulj, Natasa; Troyanskaya, Olga G; Stagljar, Igor; Xia, Tian; Ohya, Yoshikazu; Gingras, Anne-Claude; Raught, Brian; Boutros, Michael; Steinmetz, Lars M; Moore, Claire L; Rosebrock, Adam P; Caudy, Amy A; Myers, Chad L; Andrews, Brenda; Boone, Charles

    2016-09-23

    We generated a global genetic interaction network for Saccharomyces cerevisiae, constructing more than 23 million double mutants, identifying about 550,000 negative and about 350,000 positive genetic interactions. This comprehensive network maps genetic interactions for essential gene pairs, highlighting essential genes as densely connected hubs. Genetic interaction profiles enabled assembly of a hierarchical model of cell function, including modules corresponding to protein complexes and pathways, biological processes, and cellular compartments. Negative interactions connected functionally related genes, mapped core bioprocesses, and identified pleiotropic genes, whereas positive interactions often mapped general regulatory connections among gene pairs, rather than shared functionality. The global network illustrates how coherent sets of genetic interactions connect protein complex and pathway modules to map a functional wiring diagram of the cell.

  11. Design Considerations for Computer-Based Interactive Map Display Systems

    DTIC Science & Technology

    1979-02-01

    REFERENCES 1. Lawrence, G.R.P. (ed.), Cartographic Methods, Methuen & Co., 1971. 2. Raisz , Erwin (ed.), Principles of Cartography, McGraw-Hill Book...classical cartography for map display designers are presented in Lawrence [lJ and Raisz [2]. A recent hook on maps which we found interesting, stimulating

  12. Web GIS in practice III: creating a simple interactive map of England's Strategic Health Authorities using Google Maps API, Google Earth KML, and MSN Virtual Earth Map Control

    PubMed Central

    Boulos, Maged N Kamel

    2005-01-01

    This eye-opener article aims at introducing the health GIS community to the emerging online consumer geoinformatics services from Google and Microsoft (MSN), and their potential utility in creating custom online interactive health maps. Using the programmable interfaces provided by Google and MSN, we created three interactive demonstrator maps of England's Strategic Health Authorities. These can be browsed online at – Google Maps API (Application Programming Interface) version, – Google Earth KML (Keyhole Markup Language) version, and – MSN Virtual Earth Map Control version. Google and MSN's worldwide distribution of "free" geospatial tools, imagery, and maps is to be commended as a significant step towards the ultimate "wikification" of maps and GIS. A discussion is provided of these emerging online mapping trends, their expected future implications and development directions, and associated individual privacy, national security and copyrights issues. Although ESRI have announced their planned response to Google (and MSN), it remains to be seen how their envisaged plans will materialize and compare to the offerings from Google and MSN, and also how Google and MSN mapping tools will further evolve in the near future. PMID:16176577

  13. Chaotic scattering in solitary wave interactions: A singular iterated-map description

    SciTech Connect

    Goodman, Roy H.

    2008-06-15

    We derive a family of singular iterated maps--closely related to Poincare maps--that describe chaotic interactions between colliding solitary waves. The chaotic behavior of such solitary-wave collisions depends on the transfer of energy to a secondary mode of oscillation, often an internal mode of the pulse. This map allows us to go beyond previous analyses and to understand the interactions in the case when this mode is excited prior to the first collision. The map is derived using Melnikov integrals and matched asymptotic expansions and generalizes a ''multipulse'' Melnikov integral. It allows one to find not only multipulse heteroclinic orbits, but exotic periodic orbits. The maps exhibit singular behavior, including regions of infinite winding. These maps are shown to be singular versions of the conservative Ikeda map from laser physics and connections are made with problems from celestial mechanics and fluid mechanics.

  14. Chaotic scattering in solitary wave interactions: a singular iterated-map description.

    PubMed

    Goodman, Roy H

    2008-06-01

    We derive a family of singular iterated maps--closely related to Poincare maps--that describe chaotic interactions between colliding solitary waves. The chaotic behavior of such solitary-wave collisions depends on the transfer of energy to a secondary mode of oscillation, often an internal mode of the pulse. This map allows us to go beyond previous analyses and to understand the interactions in the case when this mode is excited prior to the first collision. The map is derived using Melnikov integrals and matched asymptotic expansions and generalizes a "multipulse" Melnikov integral. It allows one to find not only multipulse heteroclinic orbits, but exotic periodic orbits. The maps exhibit singular behavior, including regions of infinite winding. These maps are shown to be singular versions of the conservative Ikeda map from laser physics and connections are made with problems from celestial mechanics and fluid mechanics.

  15. Evaluating web-based static, animated and interactive maps for injury prevention.

    PubMed

    Cinnamon, Jonathan; Rinner, Claus; Cusimano, Michael D; Marshall, Sean; Bakele, Tsegaye; Hernandez, Tony; Glazier, Richard H; Chipman, Mary L

    2009-11-01

    Public health planning can benefit from visual exploration and analysis of geospatial data. Maps and geovisualization tools must be developed with the user-group in mind. User-needs assessment and usability testing are crucial elements in the iterative process of map design and implementation. This study presents the results of a usability test of static, animated and interactive maps of injury rates and socio-demographic determinants of injury by a sample of potential end-users in Toronto, Canada. The results of the user-testing suggest that different map types are useful for different purposes and for satisfying the varying skill level of the individual user. The static maps were deemed to be easy to use and versatile, while the animated maps could be made more useful if animation controls were provided. The split-screen concept of the interactive maps was highlighted as particularly effective for map comparison. Overall, interactive maps were identified as the preferred map type for comparing patterns of injury and related socio-demographic risk factors. Information collected from the user-tests is being used to expand and refine the injury web maps for Toronto, and could inform other public health-related geo-visualization projects.

  16. Saharasar: An Interactive SAR Image Database for Desert Mapping

    NASA Astrophysics Data System (ADS)

    Lopez, S.; Paillou, Ph.

    2017-06-01

    We present a dedicated tool for accessing radar images acquired by the ALOS/PALSAR mission over Sahara and Arabia. We developed a dedicated web site, using the Mapserver web mapping server and the Cesium javascript library.

  17. Matrix model maps and reconstruction of AdS supergravity interactions

    SciTech Connect

    Cremonini, Sera; Mello Koch, Robert de; Jevicki, Antal

    2008-05-15

    We consider the question of reconstructing (cubic) SUGRA interactions in AdS/CFT. The method we introduce is based on the matrix model maps (MMP) which were previously successfully employed at the linearized level. The strategy is to start with the map for 1/2 BPS configurations, which is exactly known (to all orders) in the Hamiltonian framework. We then use the extension of the matrix model map with the corresponding Ward identities to completely specify the interaction. A central point in this construction is the nonvanishing of off-shell interactions (even for highest-weight states)

  18. Mapping Control and Affiliation in Teacher-Student Interaction with State Space Grids

    ERIC Educational Resources Information Center

    Mainhard, M. Tim; Pennings, Helena J. M.; Wubbels, Theo; Brekelmans, Mieke

    2012-01-01

    This paper explores how State Space Grids (SSG), a dynamic systems research method, can be used to map teacher-student interactions from moment-to-moment and thereby to incorporate temporal aspects of interaction. Interactions in two secondary school classrooms are described in terms of level of interpersonal control and affiliation, and of…

  19. Mapping Control and Affiliation in Teacher-Student Interaction with State Space Grids

    ERIC Educational Resources Information Center

    Mainhard, M. Tim; Pennings, Helena J. M.; Wubbels, Theo; Brekelmans, Mieke

    2012-01-01

    This paper explores how State Space Grids (SSG), a dynamic systems research method, can be used to map teacher-student interactions from moment-to-moment and thereby to incorporate temporal aspects of interaction. Interactions in two secondary school classrooms are described in terms of level of interpersonal control and affiliation, and of…

  20. CapsidMaps: Protein-protein interaction pattern discovery platform for the structural analysis of virus capsids using Google Maps

    PubMed Central

    Carrillo-Tripp, Mauricio; Montiel-García, Daniel Jorge; Brooks, Charles L.; Reddy, Vijay

    2016-01-01

    Structural analysis and visualization of protein-protein interactions is a challenging task since it is difficult to appreciate easily the extent of all contacts made by the residues forming the interfaces. In the case of viruses, structural analysis becomes even more demanding because several interfaces coexist and, in most cases, these are formed by hundreds of contacting residues that belong to multiple interacting coat proteins. CapsidMaps is an interactive analysis and visualization tool that is designed to benefit the structural virology community. Developed as an improved extension of the φ-ψ Explorer, here we describe the details of its design and implementation. We present results of analysis of a spherical virus to showcase the features and utility of the new tool. CapsidMaps also facilitates the comparison of quaternary interactions between two spherical virus particles by computing a similarity (S)-score. The tool can also be used to identify residues that are solvent exposed and in the process of locating antigenic epitope regions as well as residues forming the inside surface of the capsid that interact with the nucleic acid genome. CapsidMaps is part of the VIPERdb Science Gateway, and is freely available as a web-based and cross-browser compliant application at http://viperdb.scripps.edu. PMID:25697908

  1. CapsidMaps: protein-protein interaction pattern discovery platform for the structural analysis of virus capsids using Google Maps.

    PubMed

    Carrillo-Tripp, Mauricio; Montiel-García, Daniel Jorge; Brooks, Charles L; Reddy, Vijay S

    2015-04-01

    Structural analysis and visualization of protein-protein interactions is a challenging task since it is difficult to appreciate easily the extent of all contacts made by the residues forming the interfaces. In the case of viruses, structural analysis becomes even more demanding because several interfaces coexist and, in most cases, these are formed by hundreds of contacting residues that belong to multiple interacting coat proteins. CapsidMaps is an interactive analysis and visualization tool that is designed to benefit the structural virology community. Developed as an improved extension of the φ-ψ Explorer, here we describe the details of its design and implementation. We present results of analysis of a spherical virus to showcase the features and utility of the new tool. CapsidMaps also facilitates the comparison of quaternary interactions between two spherical virus particles by computing a similarity (S)-score. The tool can also be used to identify residues that are solvent exposed and in the process of locating antigenic epitope regions as well as residues forming the inside surface of the capsid that interact with the nucleic acid genome. CapsidMaps is part of the VIPERdb Science Gateway, and is freely available as a web-based and cross-browser compliant application at http://viperdb.scripps.edu. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Shared-Screen Interaction: Engaging Groups in Map-Mediated Nonverbal Communication

    NASA Astrophysics Data System (ADS)

    Chorianopoulos, Konstantinos; Rieniets, Tim

    This chapter describes the design and development of an interactive video installation that allows participants to explore a map narrative, and engage in group interactions through a shared screen. For this purpose, several layers of cartographic information were employed in a computer application, which was programmed with motion-tracking libraries in the open source tool processing. The interactive video installation has been chosen as a medium to achieve the following aims: (1) The visualization of urban-conflict as an interactive map narrative, and (2) the encouragement of social encounters through a shared screen. The development process begins with the design of interaction between the system and the participants, as well as between the participants themselves. Then we map the interaction design concepts into multimedia and architectural design. Finally, we provide a discussion on the creative process and the collaboration between different disciplines, such as architecture, urban planning, cartography, computer engineering, and media studies.

  3. Interactive NCORP Map Details Community Research Sites | Division of Cancer Prevention

    Cancer.gov

    An interactive map of the NCI Community Oncology Research Program (NCORP) with detailed information on hundreds of community sites that take part in clinical trials is available on the NCORP website. NCORP Map NCORP Community Sites, Minority/Underserved Community Sites, and Research Bases |

  4. A double-mutant collection targeting MAP kinase related genes in Arabidopsis for studying genetic interactions.

    PubMed

    Su, Shih-Heng; Krysan, Patrick J

    2016-12-01

    Mitogen-activated protein kinase cascades are conserved in all eukaryotes. In Arabidopsis thaliana there are approximately 80 genes encoding MAP kinase kinase kinases (MAP3K), 10 genes encoding MAP kinase kinases (MAP2K), and 20 genes encoding MAP kinases (MAPK). Reverse genetic analysis has failed to reveal abnormal phenotypes for a majority of these genes. One strategy for uncovering gene function when single-mutant lines do not produce an informative phenotype is to perform a systematic genetic interaction screen whereby double-mutants are created from a large library of single-mutant lines. Here we describe a new collection of 275 double-mutant lines derived from a library of single-mutants targeting genes related to MAP kinase signaling. To facilitate this study, we developed a high-throughput double-mutant generating pipeline using a system for growing Arabidopsis seedlings in 96-well plates. A quantitative root growth assay was used to screen for evidence of genetic interactions in this double-mutant collection. Our screen revealed four genetic interactions, all of which caused synthetic enhancement of the root growth defects observed in a MAP kinase 4 (MPK4) single-mutant line. Seeds for this double-mutant collection are publicly available through the Arabidopsis Biological Resource Center. Scientists interested in diverse biological processes can now screen this double-mutant collection under a wide range of growth conditions in order to search for additional genetic interactions that may provide new insights into MAP kinase signaling.

  5. EPA Updates Flint Response Website with Interactive Map, Chlorine Sampling Results

    EPA Pesticide Factsheets

    FLINT, MICH. -- The U.S. Environmental Protection Agency is releasing preliminary water quality data about chlorine levels in Flint's drinking water, as well as an interactive map of sampling results in Flint. The map includes data from initial chlorine te

  6. Methods for Mapping of Interaction Networks Involving Membrane Proteins

    SciTech Connect

    Hooker, Brian S.; Bigelow, Diana J.; Lin, Chiann Tso

    2007-11-23

    Numerous approaches have been taken to study protein interactions, such as tagged protein complex isolation followed by mass spectrometry, yeast two-hybrid methods, fluorescence resonance energy transfer, surface plasmon resonance, site-directed mutagenesis, and crystallography. Membrane protein interactions pose significant challenges due to the need to solubilize membranes without disrupting protein-protein interactions. Traditionally, analysis of isolated protein complexes by high-resolution 2D gel electrophoresis has been the main method used to obtain an overall picture of proteome constituents and interactions. However, this method is time consuming, labor intensive, detects only abundant proteins and is not suitable for the coverage required to elucidate large interaction networks. In this review, we discuss the application of various methods to elucidate interactions involving membrane proteins. These techniques include methods for the direct isolation of single complexes or interactors as well as methods for characterization of entire subcellular and cellular interactomes.

  7. NATCARB Interactive Maps and the National Carbon Explorer: a National Look at Carbon Sequestration

    DOE Data Explorer

    NATCARB is a national look at carbon sequestration. The NATCARB home page, National Carbon Explorer (http://www.natcarb.org/) provides access to information and interactive maps on a national scale about climate change, DOE's carbon sequestration program and its partnerships, CO2 emissions, and sinks. This portal provides access to interactive maps based on the Carbon Sequestration Atlas of the United States and Canada.

  8. Mapping out atom-wall interaction with atomic clocks.

    PubMed

    Derevianko, A; Obreshkov, B; Dzuba, V A

    2009-09-25

    We explore the feasibility of probing atom-wall interaction with atomic clocks based on atoms trapped in engineered optical lattices. Optical lattice is normal to the wall. By monitoring the wall-induced clock shift at individual wells of the lattice, one would measure the dependence of the atom-wall interaction on the atom-wall separation. We find that the induced clock shifts are large and observable at already experimentally demonstrated levels of accuracy. We show that this scheme may uniquely probe the long-range atom-wall interaction in all three qualitatively distinct regimes of the interaction: van der Waals (image-charge interaction), Casimir-Polder (QED vacuum fluctuations), and Lifshitz (thermal-bath fluctuations) regimes.

  9. Mapping Out Atom-Wall Interaction with Atomic Clocks

    SciTech Connect

    Derevianko, A.; Obreshkov, B.; Dzuba, V. A.

    2009-09-25

    We explore the feasibility of probing atom-wall interaction with atomic clocks based on atoms trapped in engineered optical lattices. Optical lattice is normal to the wall. By monitoring the wall-induced clock shift at individual wells of the lattice, one would measure the dependence of the atom-wall interaction on the atom-wall separation. We find that the induced clock shifts are large and observable at already experimentally demonstrated levels of accuracy. We show that this scheme may uniquely probe the long-range atom-wall interaction in all three qualitatively distinct regimes of the interaction: van der Waals (image-charge interaction), Casimir-Polder (QED vacuum fluctuations), and Lifshitz (thermal-bath fluctuations) regimes.

  10. Interactive applications for sketch-based editable polycube map.

    PubMed

    Garcia, Ismael; Xia, Jiazhi; He, Ying; Xin, Shi-Qing; Patow, Gustavo

    2013-07-01

    In this paper, we propose a sketch-based editable polycube mapping method that, given a general mesh and a simple polycube that coarsely resembles the shape of the object, plus sketched features indicating relevant correspondences between the two, provides a uniform, regular, and user-controllable quads-only mesh that can be used as a basis structure for subdivision. Large scale models with complex geometry and topology can be processed efficiently with simple, intuitive operations. We show that the simple, intuitive nature of the polycube map is a substantial advantage from the point of view of the interface by demonstrating a series of applications, including kit-basing, shape morphing, painting over the parameterization domain, and GPU-friendly tessellated subdivision displacement, where the user is also able to control the number of patches in the base mesh by the construction of the base polycube.

  11. Mapping Haplotype-haplotype Interactions with Adaptive LASSO

    PubMed Central

    2010-01-01

    Background The genetic etiology of complex diseases in human has been commonly viewed as a complex process involving both genetic and environmental factors functioning in a complicated manner. Quite often the interactions among genetic variants play major roles in determining the susceptibility of an individual to a particular disease. Statistical methods for modeling interactions underlying complex diseases between single genetic variants (e.g. single nucleotide polymorphisms or SNPs) have been extensively studied. Recently, haplotype-based analysis has gained its popularity among genetic association studies. When multiple sequence or haplotype interactions are involved in determining an individual's susceptibility to a disease, it presents daunting challenges in statistical modeling and testing of the interaction effects, largely due to the complicated higher order epistatic complexity. Results In this article, we propose a new strategy in modeling haplotype-haplotype interactions under the penalized logistic regression framework with adaptive L1-penalty. We consider interactions of sequence variants between haplotype blocks. The adaptive L1-penalty allows simultaneous effect estimation and variable selection in a single model. We propose a new parameter estimation method which estimates and selects parameters by the modified Gauss-Seidel method nested within the EM algorithm. Simulation studies show that it has low false positive rate and reasonable power in detecting haplotype interactions. The method is applied to test haplotype interactions involved in mother and offspring genome in a small for gestational age (SGA) neonates data set, and significant interactions between different genomes are detected. Conclusions As demonstrated by the simulation studies and real data analysis, the approach developed provides an efficient tool for the modeling and testing of haplotype interactions. The implementation of the method in R codes can be freely downloaded from

  12. Mapping haplotype-haplotype interactions with adaptive LASSO.

    PubMed

    Li, Ming; Romero, Roberto; Fu, Wenjiang J; Cui, Yuehua

    2010-08-27

    The genetic etiology of complex diseases in human has been commonly viewed as a complex process involving both genetic and environmental factors functioning in a complicated manner. Quite often the interactions among genetic variants play major roles in determining the susceptibility of an individual to a particular disease. Statistical methods for modeling interactions underlying complex diseases between single genetic variants (e.g. single nucleotide polymorphisms or SNPs) have been extensively studied. Recently, haplotype-based analysis has gained its popularity among genetic association studies. When multiple sequence or haplotype interactions are involved in determining an individual's susceptibility to a disease, it presents daunting challenges in statistical modeling and testing of the interaction effects, largely due to the complicated higher order epistatic complexity. In this article, we propose a new strategy in modeling haplotype-haplotype interactions under the penalized logistic regression framework with adaptive L1-penalty. We consider interactions of sequence variants between haplotype blocks. The adaptive L1-penalty allows simultaneous effect estimation and variable selection in a single model. We propose a new parameter estimation method which estimates and selects parameters by the modified Gauss-Seidel method nested within the EM algorithm. Simulation studies show that it has low false positive rate and reasonable power in detecting haplotype interactions. The method is applied to test haplotype interactions involved in mother and offspring genome in a small for gestational age (SGA) neonates data set, and significant interactions between different genomes are detected. As demonstrated by the simulation studies and real data analysis, the approach developed provides an efficient tool for the modeling and testing of haplotype interactions. The implementation of the method in R codes can be freely downloaded from http://www.stt.msu.edu/~cui/software.html.

  13. Toward accelerating landslide mapping with interactive machine learning techniques

    NASA Astrophysics Data System (ADS)

    Stumpf, André; Lachiche, Nicolas; Malet, Jean-Philippe; Kerle, Norman; Puissant, Anne

    2013-04-01

    Despite important advances in the development of more automated methods for landslide mapping from optical remote sensing images, the elaboration of inventory maps after major triggering events still remains a tedious task. Image classification with expert defined rules typically still requires significant manual labour for the elaboration and adaption of rule sets for each particular case. Machine learning algorithm, on the contrary, have the ability to learn and identify complex image patterns from labelled examples but may require relatively large amounts of training data. In order to reduce the amount of required training data active learning has evolved as key concept to guide the sampling for applications such as document classification, genetics and remote sensing. The general underlying idea of most active learning approaches is to initialize a machine learning model with a small training set, and to subsequently exploit the model state and/or the data structure to iteratively select the most valuable samples that should be labelled by the user and added in the training set. With relatively few queries and labelled samples, an active learning strategy should ideally yield at least the same accuracy than an equivalent classifier trained with many randomly selected samples. Our study was dedicated to the development of an active learning approach for landslide mapping from VHR remote sensing images with special consideration of the spatial distribution of the samples. The developed approach is a region-based query heuristic that enables to guide the user attention towards few compact spatial batches rather than distributed points resulting in time savings of 50% and more compared to standard active learning techniques. The approach was tested with multi-temporal and multi-sensor satellite images capturing recent large scale triggering events in Brazil and China and demonstrated balanced user's and producer's accuracies between 74% and 80%. The assessment also

  14. Self-organizing maps of document collections: A new approach to interactive exploration

    SciTech Connect

    Lagus, K.; Honkela, T.; Kaski, S.; Kohonen, T.

    1996-12-31

    Powerful methods for interactive exploration and search from collections of free-form textual documents axe needed to manage the ever-increasing flood of digital information. In this article we present a method, WEBSOM, for automatic organization of full-text document collections using the self-organizing map (SOM) algorithm. The document collection is ordered onto a map in an unsupervised manner utilizing statistical information of short word contexts. The resulting ordered map where similar documents lie near each other thus presents a general view of the document space. With the aid of a suitable (WWW-based) interface, documents in interesting areas of the map can be browsed. The browsing can also be interactively extended to related topics, which appear in nearby areas on the map. Along with the method we present a case study of its use.

  15. Facilitating participatory multilevel decision-making by using interactive mental maps.

    PubMed

    Pfeiffer, Constanze; Glaser, Stephanie; Vencatesan, Jayshree; Schliermann-Kraus, Elke; Drescher, Axel; Glaser, Rüdiger

    2008-11-01

    Participation of citizens in political, economic or social decisions is increasingly recognized as a precondition to foster sustainable development processes. Since spatial information is often important during planning and decision making, participatory mapping gains in popularity. However, little attention has been paid to the fact that information must be presented in a useful way to reach city planners and policy makers. Above all, the importance of visualisation tools to support collaboration, analytical reasoning, problem solving and decision-making in analysing and planning processes has been underestimated. In this paper, we describe how an interactive mental map tool has been developed in a highly interdisciplinary disaster management project in Chennai, India. We moved from a hand drawn mental maps approach to an interactive mental map tool. This was achieved by merging socio-economic and geospatial data on infrastructure, local perceptions, coping and adaptation strategies with remote sensing data and modern technology of map making. This newly developed interactive mapping tool allowed for insights into different locally-constructed realities and facilitated the communication of results to the wider public and respective policy makers. It proved to be useful in visualising information and promoting participatory decision-making processes. We argue that the tool bears potential also for health research projects. The interactive mental map can be used to spatially and temporally assess key health themes such as availability of, and accessibility to, existing health care services, breeding sites of disease vectors, collection and storage of water, waste disposal, location of public toilets or defecation sites.

  16. Reference Map Technique for Incompressible Fluid-Structure Interaction Problems

    NASA Astrophysics Data System (ADS)

    Rycroft, Chris; Wu, Chen-Hung; Yu, Yue; Kamrin, Ken

    2016-11-01

    We present a fully Eulerian approach to simulate soft structures immersed in an incompressible fluid. The flow is simulated on a fixed grid using a second order projection method to solve the incompressible Navier-Stokes equations, and the fluid-structure interfaces are modeled using the level set method. By introducing a reference map variable to model finite-deformation constitutive relations in the structure on the same grid as the fluid, the interfacial coupling is highly simplified. This fully Eulerian approach provides a computationally efficient alternative to moving mesh approaches. Example simulations featuring many-body contacts and flexible swimmers will be presented.

  17. Comparative mapping of host–pathogen protein–protein interactions

    PubMed Central

    Shah, Priya S.; Wojcechowskyj, Jason A.; Eckhardt, Manon; Krogan, Nevan J.

    2015-01-01

    Pathogens usurp a variety of host pathways via protein–protein interactions to ensure efficient pathogen replication. Despite the existence of an impressive toolkit of systematic and unbiased approaches, we still lack a comprehensive list of these PPIs and an understanding of their functional implications. Here, we highlight the importance of harnessing genetic diversity of hosts and pathogens for uncovering the biochemical basis of pathogen restriction, virulence, fitness, and pathogenesis. We further suggest that integrating physical interaction data with orthogonal types of data will allow researchers to draw meaningful conclusions both for basic and translational science. PMID:26275922

  18. Network Physiology: Mapping Interactions Between Networks of Physiologic Networks

    NASA Astrophysics Data System (ADS)

    Ivanov, Plamen Ch.; Bartsch, Ronny P.

    The human organism is an integrated network of interconnected and interacting organ systems, each representing a separate regulatory network. The behavior of one physiological system (network) may affect the dynamics of all other systems in the network of physiologic networks. Due to these interactions, failure of one system can trigger a cascade of failures throughout the entire network. We introduce a systematic method to identify a network of interactions between diverse physiologic organ systems, to quantify the hierarchical structure and dynamics of this network, and to track its evolution under different physiologic states. We find a robust relation between network structure and physiologic states: every state is characterized by specific network topology, node connectivity and links strength. Further, we find that transitions from one physiologic state to another trigger a markedly fast reorganization in the network of physiologic interactions on time scales of just a few minutes, indicating high network flexibility in response to perturbations. This reorganization in network topology occurs simultaneously and globally in the entire network as well as at the level of individual physiological systems, while preserving a hierarchical order in the strength of network links. Our findings highlight the need of an integrated network approach to understand physiologic function, since the framework we develop provides new information which can not be obtained by studying individual systems. The proposed system-wide integrative approach may facilitate the development of a new field, Network Physiology.

  19. Understanding Urban Watersheds through Digital Interactive Maps, San Francisco Bay Area, California

    NASA Astrophysics Data System (ADS)

    Sowers, J. M.; Ticci, M. G.; Mulvey, P.

    2014-12-01

    Dense urbanization has resulted in the "disappearance" of many local creeks in urbanized areas surrounding the San Francisco Bay. Long reaches of creeks now flow in underground pipes. Municipalities and water agencies trying to reduce non-point-source pollution are faced with a public that cannot see and therefore does not understand the interconnected nature of the drainage system or its ultimate discharge to the bay. Since 1993, we have collaborated with the Oakland Museum, the San Francisco Estuary Institute, public agencies, and municipalities to create creek and watershed maps to address the need for public understanding of watershed concepts. Fifteen paper maps are now published (www.museumca.org/creeks), which have become a standard reference for educators and anyone working on local creek-related issues. We now present digital interactive creek and watershed maps in Google Earth. Four maps are completed covering urbanized areas of Santa Clara and Alameda Counties. The maps provide a 3D visualization of the watersheds, with cartography draped over the landscape in transparent colors. Each mapped area includes both Present and Past (circa 1800s) layers which can be clicked on or off by the user. The Present layers include the modern drainage network, watershed boundaries, and reservoirs. The Past layers include the 1800s-era creek systems, tidal marshes, lagoons, and other habitats. All data are developed in ArcGIS software and converted to Google Earth format. To ensure the maps are interesting and engaging, clickable icons pop-up provide information on places to visit, restoration projects, history, plants, and animals. Maps of Santa Clara Valley are available at http://www.valleywater.org/WOW.aspx. Maps of western Alameda County will soon be available at http://acfloodcontrol.org/. Digital interactive maps provide several advantages over paper maps. They are seamless within each map area, and the user can zoom in or out, and tilt, and fly over to explore

  20. Stochastic interaction between neural activity and molecular cues in the formation of topographic maps

    PubMed Central

    Owens, Melinda T.; Feldheim, David A.; Stryker, Michael P.; Triplett, Jason W.

    2015-01-01

    SUMMARY Topographic maps in visual processing areas maintain the spatial order of the visual world. Molecular cues and neuronal activity both play critical roles in map formation, but their interaction remains unclear. Here, we demonstrate that when molecular- and activity-dependent cues are rendered nearly equal in force, they drive topographic mapping stochastically. The functional and anatomical representation of azimuth in the superior colliculus of heterozygous Islet2-EphA3 knock-in (Isl2EphA3/+) mice is variable: maps may be single, duplicated, or a combination of the two. This heterogeneity is not due to genetic differences, since map organizations in individual mutant animals often differ between colliculi. Disruption of spontaneous waves of retinal activity resulted in uniform map organization in Isl2EphA3/+ mice, demonstrating that correlated spontaneous activity is required for map heterogeneity. Computational modeling replicates this heterogeneity, revealing that molecular- and activity-dependent forces interact simultaneously and stochastically during topographic map formation. PMID:26402608

  1. Whole-proteome prediction of protein function via graph-theoretic analysis of interaction maps.

    PubMed

    Nabieva, Elena; Jim, Kam; Agarwal, Amit; Chazelle, Bernard; Singh, Mona

    2005-06-01

    Determining protein function is one of the most important problems in the post-genomic era. For the typical proteome, there are no functional annotations for one-third or more of its proteins. Recent high-throughput experiments have determined proteome-scale protein physical interaction maps for several organisms. These physical interactions are complemented by an abundance of data about other types of functional relationships between proteins, including genetic interactions, knowledge about co-expression and shared evolutionary history. Taken together, these pairwise linkages can be used to build whole-proteome protein interaction maps. We develop a network-flow based algorithm, FunctionalFlow, that exploits the underlying structure of protein interaction maps in order to predict protein function. In cross-validation testing on the yeast proteome, we show that FunctionalFlow has improved performance over previous methods in predicting the function of proteins with few (or no) annotated protein neighbors. By comparing several methods that use protein interaction maps to predict protein function, we demonstrate that FunctionalFlow performs well because it takes advantage of both network topology and some measure of locality. Finally, we show that performance can be improved substantially as we consider multiple data sources and use them to create weighted interaction networks. http://compbio.cs.princeton.edu/function

  2. Interacting damage models mapped onto ising and percolation models

    SciTech Connect

    Toussaint, Renaud; Pride, Steven R.

    2004-03-23

    The authors introduce a class of damage models on regular lattices with isotropic interactions between the broken cells of the lattice. Quasistatic fiber bundles are an example. The interactions are assumed to be weak, in the sense that the stress perturbation from a broken cell is much smaller than the mean stress in the system. The system starts intact with a surface-energy threshold required to break any cell sampled from an uncorrelated quenched-disorder distribution. The evolution of this heterogeneous system is ruled by Griffith's principle which states that a cell breaks when the release in potential (elastic) energy in the system exceeds the surface-energy barrier necessary to break the cell. By direct integration over all possible realizations of the quenched disorder, they obtain the probability distribution of each damage configuration at any level of the imposed external deformation. They demonstrate an isomorphism between the distributions so obtained and standard generalized Ising models, in which the coupling constants and effective temperature in the Ising model are functions of the nature of the quenched-disorder distribution and the extent of accumulated damage. In particular, they show that damage models with global load sharing are isomorphic to standard percolation theory, that damage models with local load sharing rule are isomorphic to the standard ising model, and draw consequences thereof for the universality class and behavior of the autocorrelation length of the breakdown transitions corresponding to these models. they also treat damage models having more general power-law interactions, and classify the breakdown process as a function of the power-law interaction exponent. Last, they also show that the probability distribution over configurations is a maximum of Shannon's entropy under some specific constraints related to the energetic balance of the fracture process, which firmly relates this type of quenched-disorder based damage model

  3. Interactive Web-based Access and Analysis Tools for the Western Climate Mapping Initiative (WestMap)

    NASA Astrophysics Data System (ADS)

    Comrie, A. C.; Redmond, K.; Glueck, M. F.; Reinbold, H.

    2006-12-01

    The Western Climate Mapping Consortium (WestMap) has developed a prototype web-based interactive access and resource interface to optimize public dissemination and usage of fine-scale spatial climate time series for the western United States. The western U.S. focus reflects the complex climate interactions and diverse geography that make resource management, policy considerations, and climate research challenging in this region. WestMap was conceived by a consortium comprised of the University of Arizona/CLIMAS, the Western Regional Climate Center (WRCC)/Desert Research Institute, and the PRISM group at Oregon State University, along with collaborators at Scripps Institute of Oceanography/California Applications Project, NOAA Climate Diagnostics Center, and the USDA Natural Resource Conservation Service. WestMap evolved in direct response to a multitude of requests to the WRCC and the RISAs from public and private stakeholder communities for lengthy time series of fine-scale spatial climate aggregated to user-specified domains, and related user-friendly web-based access and analysis tools. The WestMap interface is designed to link three stakeholder-driven components, 1) climate data development and operations (access, maintenance); 2) error assessment, data analysis, diagnostics, and related tools; and (3) data access, visualization, and educational resources. The 100-year PRISM 4km monthly temperature and precipitation series serve as the initial data archive, updating automatically once in operational mode. Operational user components are being designed to allow direct stakeholder access to user-specified data and resources most relevant to current needs in a timely manner. Requested resources currently in development and limited testing stages include clickable maps, regional aggregate capabilities, basic statistical analysis, time series visualization, error assessment, and download/print capability. Phased prototype testing, currently underway internally, will

  4. Mapping protein-DNA interactions using ChIP-sequencing.

    PubMed

    Massie, Charles E; Mills, Ian G

    2012-01-01

    Chromatin immunoprecipitation (ChIP) allows enrichment of genomic regions which are associated with specific transcription factors, histone modifications, and indeed any other epitopes which are present on chromatin. The original ChIP methods used site-specific PCR and Southern blotting to confirm which regions of the genome were enriched, on a candidate basis. The combination of ChIP with genomic tiling arrays (ChIP-chip) allowed a more unbiased approach to map ChIP-enriched sites. However, limitations of microarray probe design and probe number have a detrimental impact on the coverage, resolution, sensitivity, and cost of whole-genome tiling microarray sets for higher eukaryotes with large genomes. The combination of ChIP with high-throughput sequencing technology has allowed more comprehensive surveys of genome occupancy, greater resolution, and lower cost for whole genome coverage. Herein, we provide a comparison of high-throughput sequencing platforms and a survey of ChIP-seq analysis tools, discuss experimental design, and describe a detailed ChIP-seq method.Chromatin immunoprecipitation (ChIP) allows enrichment of genomic regions which are associated with specific transcription factors, histone modifications, and indeed any other epitopes which are present on chromatin. The original ChIP methods used site-specific PCR and Southern blotting to confirm which regions of the genome were enriched, on a candidate basis. The combination of ChIP with genomic tiling arrays (ChIP-chip) allowed a more unbiased approach to map ChIP-enriched sites. However, limitations of microarray probe design and probe number have a detrimental impact on the coverage, resolution, sensitivity, and cost of whole-genome tiling microarray sets for higher eukaryotes with large genomes. The combination of ChIP with high-throughput sequencing technology has allowed more comprehensive surveys of genome occupancy, greater resolution, and lower cost for whole genome coverage. Herein, we

  5. Extracting Between-Pathway Models from E-MAP Interactions Using Expected Graph Compression

    NASA Astrophysics Data System (ADS)

    Kelley, David R.; Kingsford, Carl

    Genetic interactions (such as synthetic lethal interactions) have become quantifiable on a large-scale using the epistatic miniarray profile (E-MAP) method. An E-MAP allows the construction of a large, weighted network of both aggravating and alleviating genetic interactions between genes. By clustering genes into modules and establishing relationships between those modules, we can discover compensatory pathways. We introduce a general framework for applying greedy clustering heuristics to probabilistic graphs. We use this framework to apply a graph clustering method called graph summarization to an E-MAP that targets yeast chromosome biology. This results in a new method for clustering E-MAP data that we call Expected Graph Compression (EGC). We validate modules and compensatory pathways using enriched Gene Ontology annotations and a novel method based on correlated gene expression. EGC finds a number of modules that are not found by any previous methods to cluster E-MAP data. EGC also uncovers core submodules contained within several previously found modules, suggesting that EGC can reveal the finer structure of E-MAP networks.

  6. An Interactive Cluster Heat Map to Visualize and Explore Multidimensional Metabolomic Data

    PubMed Central

    Rinehart, Duane; Epstein, Adrian; Kurczy, Michael E.; Boska, Michael D.; Gendelman, Howard E.

    2014-01-01

    Heat maps are a commonly used visualization tool for metabolomic data where the relative abundance of ions detected in each sample is represented with color intensity. A limitation of applying heat maps to global metabolomic data, however, is the large number of ions that have to be displayed and the lack of information provided about important metabolomic parameters such as m/z and retention time. Here we address these challenges by introducing the interactive cluster heat map in the data-processing software XCMS Online. XCMS Online (xcmsonline.scripps.edu) is a cloud-based informatic platform designed to process, statistically evaluate, and visualize mass-spectrometry based metabolomic data. An interactive heat map is provided for all data processed by XCMS Online. The heat map is clickable, allowing users to zoom and explore specific metabolite metadata (EICs, Box-and-whisker plots, mass spectra) that are linked to the METLIN metabolite database. The utility of the XCMS interactive heat map is demonstrated on metabolomic data set generated from different anatomical regions of the mouse brain. PMID:26195918

  7. Optimal design method to minimize users' thinking mapping load in human-machine interactions.

    PubMed

    Huang, Yanqun; Li, Xu; Zhang, Jie

    2015-01-01

    The discrepancy between human cognition and machine requirements/behaviors usually results in serious mental thinking mapping loads or even disasters in product operating. It is important to help people avoid human-machine interaction confusions and difficulties in today's mental work mastered society. Improving the usability of a product and minimizing user's thinking mapping and interpreting load in human-machine interactions. An optimal human-machine interface design method is introduced, which is based on the purpose of minimizing the mental load in thinking mapping process between users' intentions and affordance of product interface states. By analyzing the users' thinking mapping problem, an operating action model is constructed. According to human natural instincts and acquired knowledge, an expected ideal design with minimized thinking loads is uniquely determined at first. Then, creative alternatives, in terms of the way human obtains operational information, are provided as digital interface states datasets. In the last, using the cluster analysis method, an optimum solution is picked out from alternatives, by calculating the distances between two datasets. Considering multiple factors to minimize users' thinking mapping loads, a solution nearest to the ideal value is found in the human-car interaction design case. The clustering results show its effectiveness in finding an optimum solution to the mental load minimizing problems in human-machine interaction design.

  8. The FIRST experiment: interaction region and MAPS vertex detector

    NASA Astrophysics Data System (ADS)

    Spiriti, E.; de Napoli, M.; Romano, F.; FIRST Collaboration

    2011-06-01

    The improvement of the precision of the measurement of the nuclear cross-section, in order to fulfill the requirements of the actual Monte Carlo simulations for hadrontherapy and space radioprotection, is the main goal of the FIRST experiment. After a brief introduction on the treatment planning in hadrontherapy, this paper describes main characteristics and components of the experiment. The features of the interaction region detectors and their main needs (low material budget, high angular coverage, two tracks resolution and large trigger rate) are discussed. Special emphasis is devoted in discussing the new silicon pixel vertex detector, in particular its new developed data acquisition and its characterization with the first test results obtained with a prototype of the detector.

  9. Mapping RNA-protein interactions using hydroxyl-radical footprinting.

    PubMed

    Nilsen, Timothy W

    2014-12-01

    The binding of a protein to an RNA sequence protects the region of the RNA from cleavage by chemicals or RNases; this protected region is known as the protein's "footprint." In the footprinting protocol presented here, end-labeled RNAs with and without bound protein are cleaved using chemical methods. Fe(II)-EDTA is used to generate hydroxyl radicals in the presence of a reducing agent. These hydroxyl radicals indiscriminately cleave ribose groups in regions of the ribose-phosphate backbone that are exposed to solvent. After termination of cleavage, the resulting RNA fragments are analyzed by gel electrophoresis on denaturing polyacrylamide gels. Because hydroxyl radicals are smaller and cleave less specifically than RNases, this approach, if feasible, is often the method of choice for monitoring sites of RNA-protein interactions. © 2014 Cold Spring Harbor Laboratory Press.

  10. Invariants, Attractors and Bifurcation in Two Dimensional Maps with Polynomial Interaction

    NASA Astrophysics Data System (ADS)

    Hacinliyan, Avadis Simon; Aybar, Orhan Ozgur; Aybar, Ilknur Kusbeyzi

    This work will present an extended discrete-time analysis on maps and their generalizations including iteration in order to better understand the resulting enrichment of the bifurcation properties. The standard concepts of stability analysis and bifurcation theory for maps will be used. Both iterated maps and flows are used as models for chaotic behavior. It is well known that when flows are converted to maps by discretization, the equilibrium points remain the same but a richer bifurcation scheme is observed. For example, the logistic map has a very simple behavior as a differential equation but as a map fold and period doubling bifurcations are observed. A way to gain information about the global structure of the state space of a dynamical system is investigating invariant manifolds of saddle equilibrium points. Studying the intersections of the stable and unstable manifolds are essential for understanding the structure of a dynamical system. It has been known that the Lotka-Volterra map and systems that can be reduced to it or its generalizations in special cases involving local and polynomial interactions admit invariant manifolds. Bifurcation analysis of this map and its higher iterates can be done to understand the global structure of the system and the artifacts of the discretization by comparing with the corresponding results from the differential equation on which they are based.

  11. Jules Verne Voyager, Jr: An Interactive Map Tool for Teaching Plate Tectonics

    NASA Astrophysics Data System (ADS)

    Hamburger, M. W.; Meertens, C. M.

    2010-12-01

    We present an interactive, web-based map utility that can make new geological and geophysical results accessible to a large number and variety of users. The tool provides a user-friendly interface that allows users to access a variety of maps, satellite images, and geophysical data at a range of spatial scales. The map tool, dubbed 'Jules Verne Voyager, Jr.', allows users to interactively create maps of a variety of study areas around the world. The utility was developed in collaboration with the UNAVCO Consortium for study of global-scale tectonic processes. Users can choose from a variety of base maps (including "Face of the Earth" and "Earth at Night" satellite imagery mosaics, global topography, geoid, sea-floor age, strain rate and seismic hazard maps, and others), add a number of geographic and geophysical overlays (coastlines, political boundaries, rivers and lakes, earthquake and volcano locations, stress axes, etc.), and then superimpose both observed and model velocity vectors representing a compilation of 2933 GPS geodetic measurements from around the world. A remarkable characteristic of the geodetic compilation is that users can select from some 21 plates' frames of reference, allowing a visual representation of both 'absolute' plate motion (in a no-net rotation reference frame) and relative motion along all of the world's plate boundaries. The tool allows users to zoom among at least three map scales. The map tool can be viewed at http://jules.unavco.org/VoyagerJr/Earth. A more detailed version of the map utility, developed in conjunction with the EarthScope initiative, focuses on North America geodynamics, and provides more detailed geophysical and geographic information for the United States, Canada, and Mexico. The ‘EarthScope Voyager’ can be accessed at http://jules.unavco.org/VoyagerJr/EarthScope. Because the system uses pre-constructed gif images and overlays, the system can rapidly create and display maps to a large number of users

  12. Interactome mapping for analysis of complex phenotypes: insights from benchmarking binary interaction assays.

    PubMed

    Braun, Pascal

    2012-05-01

    Protein interactions mediate essentially all biological processes and analysis of protein-protein interactions using both large-scale and small-scale approaches has contributed fundamental insights to the understanding of biological systems. In recent years, interactome network maps have emerged as an important tool for analyzing and interpreting genetic data of complex phenotypes. Complementary experimental approaches to test for binary, direct interactions, and for membership in protein complexes are used to explore the interactome. The two approaches are not redundant but yield orthogonal perspectives onto the complex network of physical interactions by which proteins mediate biological processes. In recent years, several publications have demonstrated that interactions from high-throughput experiments can be equally reliable as the high quality subset of interactions identified in small-scale studies. Critical for this insight was the introduction of standardized experimental benchmarking of interaction and validation assays using reference sets. The data obtained in these benchmarking experiments have resulted in greater appreciation of the limitations and the complementary strengths of different assays. Moreover, benchmarking is a central element of a conceptual framework to estimate interactome sizes and thereby measure progress toward near complete network maps. These estimates have revealed that current large-scale data sets, although often of high quality, cover only a small fraction of a given interactome. Here, I review the findings of assay benchmarking and discuss implications for quality control, and for strategies toward obtaining a near-complete map of the interactome of an organism.

  13. Perceived usefulness, perceived ease of use, and perceived enjoyment as drivers for the user acceptance of interactive mobile maps

    NASA Astrophysics Data System (ADS)

    Hussain, Azham; Mkpojiogu, Emmanuel O. C.; Yusof, Muhammad Mat

    2016-08-01

    This study examines the user perception of usefulness, ease of use and enjoyment as drivers for the users' complex interaction with map on mobile devices. TAM model was used to evaluate users' intention to use and their acceptance of interactive mobile map using the above three beliefs as antecedents. Quantitative research (survey) methodology was employed and the analysis and findings showed that all the three explanatory variables used in this study, explain the variability in the user acceptance of interactive mobile map technology. Perceived usefulness, perceived ease of use, and perceived enjoyment each have significant positive influence on user acceptance of interactive mobile maps. This study further validates the TAM model.

  14. An Interactive Immersive Serious Game Application for Kunyu Quantu World Map

    NASA Astrophysics Data System (ADS)

    Peng, S.-T.; Hsu, S.-Y.; Hsieh, K.-C.

    2015-08-01

    In recent years, more and more digital technologies and innovative concepts are applied on museum education. One of the concepts applied is "Serious game." Serious game is not designed for entertainment purpose but allows users to learn real world's cultural and educational knowledge in the virtual world through game-experiencing. Technologies applied on serious game are identical to those applied on entertainment game. Nowadays, the interactive technology applications considering users' movement and gestures in physical spaces are developing rapidly, which are extensively used in entertainment games, such as Kinect-based games. The ability to explore space via Kinect-based games can be incorporated into the design of serious game. The ancient world map, Kunyu Quantu, from the collection of the National Palace Museum is therefore applied in serious game development. In general, the ancient world map does not only provide geological information, but also contains museum knowledge. This particular ancient world map is an excellent content applied in games as teaching material. In the 17th century, it was first used by a missionary as a medium to teach the Kangxi Emperor of the latest geologic and scientific spirits from the West. On this map, it also includes written biological knowledge and climate knowledge. Therefore, this research aims to present the design of the interactive and immersive serious game based installation that developed from the rich content of the Kunyu Quantu World Map, and to analyse visitor's experience in terms of real world's cultural knowledge learning and interactive responses.

  15. Large-scale mapping of human protein-protein interactions by mass spectrometry.

    PubMed

    Ewing, Rob M; Chu, Peter; Elisma, Fred; Li, Hongyan; Taylor, Paul; Climie, Shane; McBroom-Cerajewski, Linda; Robinson, Mark D; O'Connor, Liam; Li, Michael; Taylor, Rod; Dharsee, Moyez; Ho, Yuen; Heilbut, Adrian; Moore, Lynda; Zhang, Shudong; Ornatsky, Olga; Bukhman, Yury V; Ethier, Martin; Sheng, Yinglun; Vasilescu, Julian; Abu-Farha, Mohamed; Lambert, Jean-Philippe; Duewel, Henry S; Stewart, Ian I; Kuehl, Bonnie; Hogue, Kelly; Colwill, Karen; Gladwish, Katharine; Muskat, Brenda; Kinach, Robert; Adams, Sally-Lin; Moran, Michael F; Morin, Gregg B; Topaloglou, Thodoros; Figeys, Daniel

    2007-01-01

    Mapping protein-protein interactions is an invaluable tool for understanding protein function. Here, we report the first large-scale study of protein-protein interactions in human cells using a mass spectrometry-based approach. The study maps protein interactions for 338 bait proteins that were selected based on known or suspected disease and functional associations. Large-scale immunoprecipitation of Flag-tagged versions of these proteins followed by LC-ESI-MS/MS analysis resulted in the identification of 24,540 potential protein interactions. False positives and redundant hits were filtered out using empirical criteria and a calculated interaction confidence score, producing a data set of 6463 interactions between 2235 distinct proteins. This data set was further cross-validated using previously published and predicted human protein interactions. In-depth mining of the data set shows that it represents a valuable source of novel protein-protein interactions with relevance to human diseases. In addition, via our preliminary analysis, we report many novel protein interactions and pathway associations.

  16. Mapping.

    ERIC Educational Resources Information Center

    Kinney, Douglas M.; McIntosh, Willard L.

    1979-01-01

    The area of geological mapping in the United States in 1978 increased greatly over that reported in 1977; state geological maps were added for California, Idaho, Nevada, and Alaska last year. (Author/BB)

  17. Complete switchgrass genetic maps reveal subgenome collinearity, preferential pairing and multilocus interactions.

    PubMed

    Okada, Miki; Lanzatella, Christina; Saha, Malay C; Bouton, Joe; Wu, Rongling; Tobias, Christian M

    2010-07-01

    Polyploidy is an important aspect of the evolution of flowering plants. The potential of gene copies to diverge and evolve new functions is influenced by meiotic behavior of chromosomes leading to segregation as a single locus or duplicated loci. Switchgrass (Panicum virgatum) linkage maps were constructed using a full-sib population of 238 plants and SSR and STS markers to access the degree of preferential pairing and the structure of the tetraploid genome and as a step toward identification of loci underlying biomass feedstock quality and yield. The male and female framework map lengths were 1645 and 1376 cM with 97% of the genome estimated to be within 10 cM of a mapped marker in both maps. Each map coalesced into 18 linkage groups arranged into nine homeologous pairs. Comparative analysis of each homology group to the diploid sorghum genome identified clear syntenic relationships and collinear tracts. The number of markers with PCR amplicons that mapped across subgenomes was significantly fewer than expected, suggesting substantial subgenome divergence, while both the ratio of coupling to repulsion phase linkages and pattern of marker segregation indicated complete or near complete disomic inheritance. The proportion of transmission ratio distorted markers was relatively low, but the male map was more extensively affected by distorted transmission ratios and multilocus interactions, associated with spurious linkages.

  18. Inclusive Composite Interval Mapping of QTL by Environment Interactions in Biparental Populations.

    PubMed

    Li, Shanshan; Wang, Jiankang; Zhang, Luyan

    2015-01-01

    Identification of environment-specific QTL and stable QTL having consistent genetic effects across a wide range of environments is of great importance in plant breeding. Inclusive Composite Interval Mapping (ICIM) has been proposed for additive, dominant and epistatic QTL mapping in biparental populations for single environment. In this study, ICIM was extended to QTL by environment interaction (QEI) mapping for multi-environmental trials, where the QTL average effect and QEI effects could be properly estimated. Stepwise regression was firstly applied in each environment to identify the most significant marker variables which were then used to adjust the phenotypic values. One-dimensional scanning was then conducted on the adjusted phenotypic values across the environments in order to detect QTL with either average effect or QEI effects, or both average effect and QEI effects. In this way, the genetic background could be well controlled while the conventional interval mapping was applied. An empirical method to determine the threshold of logarithm of odds was developed, and the efficiency of the ICIM QEI mapping was demonstrated in simulated populations under different genetic models. One actual recombinant inbred line population was used to compare mapping results between QEI mapping and single-environment analysis.

  19. Inclusive Composite Interval Mapping of QTL by Environment Interactions in Biparental Populations

    PubMed Central

    Li, Shanshan; Wang, Jiankang; Zhang, Luyan

    2015-01-01

    Identification of environment-specific QTL and stable QTL having consistent genetic effects across a wide range of environments is of great importance in plant breeding. Inclusive Composite Interval Mapping (ICIM) has been proposed for additive, dominant and epistatic QTL mapping in biparental populations for single environment. In this study, ICIM was extended to QTL by environment interaction (QEI) mapping for multi-environmental trials, where the QTL average effect and QEI effects could be properly estimated. Stepwise regression was firstly applied in each environment to identify the most significant marker variables which were then used to adjust the phenotypic values. One-dimensional scanning was then conducted on the adjusted phenotypic values across the environments in order to detect QTL with either average effect or QEI effects, or both average effect and QEI effects. In this way, the genetic background could be well controlled while the conventional interval mapping was applied. An empirical method to determine the threshold of logarithm of odds was developed, and the efficiency of the ICIM QEI mapping was demonstrated in simulated populations under different genetic models. One actual recombinant inbred line population was used to compare mapping results between QEI mapping and single-environment analysis. PMID:26161656

  20. Teacher Use of the Interactive Whiteboards in Flemish Secondary Education--Mapping against a Transition Framework

    ERIC Educational Resources Information Center

    Van Laer, Stijn; Beauchamp, Gary; Colpaert, Jozef

    2014-01-01

    Interactive Whiteboards (IWBs) are a relatively new, but increasingly more common, tool in the classrooms of Flemish Secondary schools. This paper reports on research which attempted to map not only the amount of IWB use in Flemish secondary schools but, perhaps more importantly, to assess how they are used and the progress of teachers in…

  1. High Quality Binary Protein Interaction Map of the Yeast Interactome Network

    PubMed Central

    Yu, Haiyuan; Braun, Pascal; Yildirim, Muhammed A.; Lemmens, Irma; Venkatesan, Kavitha; Sahalie, Julie; Hirozane-Kishikawa, Tomoko; Gebreab, Fana; Li, Na; Simonis, Nicolas; Hao, Tong; Rual, Jean-Franćois; Dricot, Amélie; Vazquez, Alexei; Murray, Ryan R.; Simon, Christophe; Tardivo, Leah; Tam, Stanley; Svrzikapa, Nenad; Fan, Changyu; de Smet, Anne-Sophie; Motyl, Adriana; Hudson, Michael E.; Park, Juyong; Xin, Xiaofeng; Cusick, Michael E.; Moore, Troy; Boone, Charlie; Snyder, Michael; Roth, Frederick P.; Barabási, Albert-László; Tavernier, Jan; Hill, David E.; Vidal, Marc

    2009-01-01

    Current yeast interactome network maps contain several hundred molecular complexes with limited and somewhat controversial representation of direct binary interactions. We carried out a comparative quality assessment of current yeast interactome datasets, demonstrating that high-throughput yeast two-hybrid (Y2H) provides high-quality binary interaction information. As a large fraction of the yeast binary interactome remains to be mapped, we developed an empirically-controlled mapping framework to produce a “second-generation” high-quality high-throughput Y2H dataset covering ~20% of all yeast binary interactions. Both Y2H and affinity-purification followed by mass spectrometry (AP/MS) data are of equally high quality but of a fundamentally different and complementary nature resulting in networks with different topological and biological properties. Compared to co-complex interactome models, this binary map is enriched for transient signaling interactions and inter-complex connections with a highly significant clustering between essential proteins. Rather than correlating with essentiality, protein connectivity correlates with genetic pleiotropy. PMID:18719252

  2. Mapping the interaction sites of Mucin 1 and DNA aptamer by atomic force microscopy.

    PubMed

    Wang, Nan; Zhang, Miaomiao; Chen, Xuejuan; Ma, Xingxing; Li, Chen; Zhang, Zhe; Tang, Jilin

    2017-10-09

    Mucin 1 (MUC1) is an attractive tumor marker for cancer diagnosis. An advanced atomic force microscopy (AFM) mode, peak-force tapping AFM with an aptamer functionalized tip, was introduced to map the specific interaction sites of an aptamer and MUC1. Single molecular force spectroscopy (SMFS) was used to investigate dynamic parameters of the aptamer-MUC1.

  3. RE Atlas: The U.S. Atlas of Renewable Resources (Interactive Map, GIS Data)

    DOE Data Explorer

    This interactive data map allows a user to explore the locations across the U.S. of many different basic, renewable energy resources. The many layers can be activated one at a time or in multiple combinations and the GIS display draws from a rich combination of data collections.

  4. NaviCell: a web-based environment for navigation, curation and maintenance of large molecular interaction maps.

    PubMed

    Kuperstein, Inna; Cohen, David P A; Pook, Stuart; Viara, Eric; Calzone, Laurence; Barillot, Emmanuel; Zinovyev, Andrei

    2013-10-07

    Molecular biology knowledge can be formalized and systematically represented in a computer-readable form as a comprehensive map of molecular interactions. There exist an increasing number of maps of molecular interactions containing detailed and step-wise description of various cell mechanisms. It is difficult to explore these large maps, to organize discussion of their content and to maintain them. Several efforts were recently made to combine these capabilities together in one environment, and NaviCell is one of them. NaviCell is a web-based environment for exploiting large maps of molecular interactions, created in CellDesigner, allowing their easy exploration, curation and maintenance. It is characterized by a combination of three essential features: (1) efficient map browsing based on Google Maps; (2) semantic zooming for viewing different levels of details or of abstraction of the map and (3) integrated web-based blog for collecting community feedback. NaviCell can be easily used by experts in the field of molecular biology for studying molecular entities of interest in the context of signaling pathways and crosstalk between pathways within a global signaling network. NaviCell allows both exploration of detailed molecular mechanisms represented on the map and a more abstract view of the map up to a top-level modular representation. NaviCell greatly facilitates curation, maintenance and updating the comprehensive maps of molecular interactions in an interactive and user-friendly fashion due to an imbedded blogging system. NaviCell provides user-friendly exploration of large-scale maps of molecular interactions, thanks to Google Maps and WordPress interfaces, with which many users are already familiar. Semantic zooming which is used for navigating geographical maps is adopted for molecular maps in NaviCell, making any level of visualization readable. In addition, NaviCell provides a framework for community-based curation of maps.

  5. NaviCell: a web-based environment for navigation, curation and maintenance of large molecular interaction maps

    PubMed Central

    2013-01-01

    Background Molecular biology knowledge can be formalized and systematically represented in a computer-readable form as a comprehensive map of molecular interactions. There exist an increasing number of maps of molecular interactions containing detailed and step-wise description of various cell mechanisms. It is difficult to explore these large maps, to organize discussion of their content and to maintain them. Several efforts were recently made to combine these capabilities together in one environment, and NaviCell is one of them. Results NaviCell is a web-based environment for exploiting large maps of molecular interactions, created in CellDesigner, allowing their easy exploration, curation and maintenance. It is characterized by a combination of three essential features: (1) efficient map browsing based on Google Maps; (2) semantic zooming for viewing different levels of details or of abstraction of the map and (3) integrated web-based blog for collecting community feedback. NaviCell can be easily used by experts in the field of molecular biology for studying molecular entities of interest in the context of signaling pathways and crosstalk between pathways within a global signaling network. NaviCell allows both exploration of detailed molecular mechanisms represented on the map and a more abstract view of the map up to a top-level modular representation. NaviCell greatly facilitates curation, maintenance and updating the comprehensive maps of molecular interactions in an interactive and user-friendly fashion due to an imbedded blogging system. Conclusions NaviCell provides user-friendly exploration of large-scale maps of molecular interactions, thanks to Google Maps and WordPress interfaces, with which many users are already familiar. Semantic zooming which is used for navigating geographical maps is adopted for molecular maps in NaviCell, making any level of visualization readable. In addition, NaviCell provides a framework for community-based curation of maps

  6. On the Mapping of Epistatic Genetic Interactions in Natural Isolates: Combining Classical Genetics and Genomics.

    PubMed

    Hou, Jing; Schacherer, Joseph

    2016-01-01

    Genetic variation within species is the substrate of evolution. Epistasis, which designates the non-additive interaction between loci affecting a specific phenotype, could be one of the possible outcomes of genetic diversity. Dissecting the basis of such interactions is of current interest in different fields of biology, from exploring the gene regulatory network, to complex disease genetics, to the onset of reproductive isolation and speciation. We present here a general workflow to identify epistatic interactions between independently evolving loci in natural populations of the yeast Saccharomyces cerevisiae. The idea is to exploit the genetic diversity present in the species by evaluating a large number of crosses and analyzing the phenotypic distribution in the offspring. For a cross of interest, both parental strains would have a similar phenotypic value, whereas the resulting offspring would have a bimodal distribution of the phenotype, possibly indicating the presence of epistasis. Classical segregation analysis of the tetrads uncovers the penetrance and complexity of the interaction. In addition, this segregation could serve as the guidelines for choosing appropriate mapping strategies to narrow down the genomic regions involved. Depending on the segregation patterns observed, we propose different mapping strategies based on bulk segregant analysis or consecutive backcrosses followed by high-throughput genome sequencing. Our method is generally applicable to all systems with a haplodiplobiontic life cycle and allows high resolution mapping of interacting loci that govern various DNA polymorphisms from single nucleotide mutations to large-scale structural variations.

  7. Web Mapping for Promoting Interaction and Collaboration in Community Land Planning

    NASA Astrophysics Data System (ADS)

    Veenendaal, B.; Dhliwayo, M.

    2013-10-01

    There is an inherent advantage of geographic information Systems (GIS) and mapping in facilitating dialogue between experts and non-experts during land use plan development. Combining visual mapping information and effective user interaction can result in considerable benefits for developing countries like Botswana. Although the adoption of information and communication technologies has lagged behind that for developed countries, initiatives by the Botswana government in providing suitable information infrastructures, including internet and web based communications, are enabling multiple users to interact and collaborate in community land planning. A web mapping application was developed for the Maun Development Plan (MDP) in the Okavango Delta region in Botswana. It was designed according to requirements of land planners and managers and implemented using ArcGIS Viewer for Flex. Land planners and managers from two organisations in Maun involved in the development of the MDP were asked to evaluate the web mapping tools. This paper describes the results of implementation and some preliminary results of the web mapping evaluation.

  8. A Prototype Interactive Mapping Tool to Target Low Health Literacy in Missouri.

    PubMed

    Martin, Laurie T; Fremont, Allen; Felton, Alexandria; Ruder, Teague; Bird, Chloe E; Miyashiro, Lisa; Hanson, Mark; Lurie, Nicole

    2011-01-01

    An estimated 36 percent of American adults have health literacy levels rated at "basic or below," indicating that they have difficulty obtaining, processing, and understanding basic health information and services. To help healthcare decisionmakers in Missouri identify neighborhood-level "hotspots" of suboptimal health or healthcare that may be due to low health literacy, RAND developed a prototype interactive web-based mapping tool. This builds on earlier RAND work to develop a predictive model of health literacy and estimate levels of health literacy in small geographic areas (e.g., census tracts). The interactive mapping tool allows stakeholders to select the level of geography (e.g., census tract, county), obtain information for and map specific regions of interest, select the characteristics to be mapped (i.e., estimates of community-level health literacy, health outcomes and care quality, neighborhood sociodemographic characteristics, and neighborhood health services data), and generate tables and reports on the regions and characteristics of interest. Housed on a dedicated RAND website (http://www.rand.org/health/projects/missouri-health-literacy.html), the mapping tool makes it possible for a range of stakeholders, from health plans to community organizations, to access and use the tool to help address healthcare disparities in their communities.

  9. GIS-based interactive tool to map the advent of world conquerors

    NASA Astrophysics Data System (ADS)

    Lakkaraju, Mahesh

    The objective of this thesis is to show the scale and extent of some of the greatest empires the world has ever seen. This is a hybrid project between the GIS based interactive tool and the web-based JavaScript tool. This approach lets the students learn effectively about the emperors themselves while understanding how long and far their empires spread. In the GIS based tool, a map is displayed with various points on it, and when a user clicks on one point, the relevant information of what happened at that particular place is displayed. Apart from this information, users can also select the interactive animation button and can walk through a set of battles in chronological order. As mentioned, this uses Java as the main programming language, and MOJO (Map Objects Java Objects) provided by ESRI. MOJO is very effective as its GIS related features can be included in the application itself. This app. is a simple tool and has been developed for university or high school level students. D3.js is an interactive animation and visualization platform built on the Javascript framework. Though HTML5, CSS3, Javascript and SVG animations can be used to derive custom animations, this tool can help bring out results with less effort and more ease of use. Hence, it has become the most sought after visualization tool for multiple applications. D3.js has provided a map-based visualization feature so that we can easily display text-based data in a map-based interface. To draw the map and the points on it, D3.js uses data rendered in TOPO JSON format. The latitudes and longitudes can be provided, which are interpolated into the Map svg. One of the main advantages of doing it this way is that more information is retained when we use a visual medium.

  10. A comprehensive modular map of molecular interactions in RB/E2F pathway.

    PubMed

    Calzone, Laurence; Gelay, Amélie; Zinovyev, Andrei; Radvanyi, François; Barillot, Emmanuel

    2008-01-01

    We present, here, a detailed and curated map of molecular interactions taking place in the regulation of the cell cycle by the retinoblastoma protein (RB/RB1). Deregulations and/or mutations in this pathway are observed in most human cancers. The map was created using Systems Biology Graphical Notation language with the help of CellDesigner 3.5 software and converted into BioPAX 2.0 pathway description format. In the current state the map contains 78 proteins, 176 genes, 99 protein complexes, 208 distinct chemical species and 165 chemical reactions. Overall, the map recapitulates biological facts from approximately 350 publications annotated in the diagram. The network contains more details about RB/E2F interaction network than existing large-scale pathway databases. Structural analysis of the interaction network revealed a modular organization of the network, which was used to elaborate a more summarized, higher-level representation of RB/E2F network. The simplification of complex networks opens the road for creating realistic computational models of this regulatory pathway.

  11. Capturing nonlocal interaction effects in the Hubbard model: Optimal mappings and limits of applicability

    NASA Astrophysics Data System (ADS)

    van Loon, E. G. C. P.; Schüler, M.; Katsnelson, M. I.; Wehling, T. O.

    2016-10-01

    We investigate the Peierls-Feynman-Bogoliubov variational principle to map Hubbard models with nonlocal interactions to effective models with only local interactions. We study the renormalization of the local interaction induced by nearest-neighbor interaction and assess the quality of the effective Hubbard models in reproducing observables of the corresponding extended Hubbard models. We compare the renormalization of the local interactions as obtained from numerically exact determinant quantum Monte Carlo to approximate but more generally applicable calculations using dual boson, dynamical mean field theory, and the random phase approximation. These more approximate approaches are crucial for any application with real materials in mind. Furthermore, we use the dual boson method to calculate observables of the extended Hubbard models directly and benchmark these against determinant quantum Monte Carlo simulations of the effective Hubbard model.

  12. Mapping of the regions involved in self-interaction of rice stripe virus P3 protein.

    PubMed

    Zhao, S L; Hao, J H; Xue, Y N; Liang, C Y

    2016-03-01

    Rice stripe virus (RSV) protein P3 is a suppressor of RNA silencing in plants. P3 has been shown by biomolecular fluorescence complementation assay to self-interact in planta but the regions responsible for homotypic interaction have not been determined. Here we analyzed the domains for the self-interaction of P3 by using yeast two-hybrid, co-immunoprecipitation and fluorescence experiments. The results showed that P3 was also able to interact with itself in yeast and insect cells. The domain responsible for P3-P3 interaction was mapped to amino acids 15-30 at the N-terminal region of P3. Furthermore, subcellular localization suggested that the homo-oligomerization was the prerequisite for P3 to form larger protein aggregates in the nucleus of insect cell.

  13. Genome-wide maps of nuclear lamina interactions in single human cells

    PubMed Central

    Kind, Jop; Pagie, Ludo; de Vries, Sandra S.; Nahidiazar, Leila; Dey, Siddharth S.; Bienko, Magda; Zhan, Ye; Lajoie, Bryan; de Graaf, Carolyn A.; Amendola, Mario; Fudenberg, Geoffrey; Imakaev, Maxim; Mirny, Leonid A.; Jalink, Kees; Dekker, Job; van Oudenaarden, Alexander; van Steensel, Bas

    2015-01-01

    Summary Mammalian interphase chromosomes interact with the nuclear lamina (NL) through hundreds of large Lamina Associated Domains (LADs). We report a method to map NL contacts genome-wide in single human cells. Analysis of nearly 400 maps reveals a core architecture of gene-poor LADs that contact the NL with high cell-to-cell consistency, interspersed by LADs with more variable NL interactions. The variable contacts tend to be cell-type specific and are more sensitive to changes in genome ploidy than the consistent contacts. Single-cell maps indicate that NL contacts involve multivalent interactions over hundreds of kilobases. Moreover, we observe extensive intra-chromosomal coordination of NL contacts, even over tens of megabases. Such coordinated loci exhibit preferential interactions as detected by Hi-C. Finally, consistency of NL contacts is inversely linked to gene activity in single cells, and correlates positively with the heterochromatic histone modification H3K9me3. These results highlight fundamental principles of single cell chromatin organization. PMID:26365489

  14. Genome-wide map of regulatory interactions in the human genome

    PubMed Central

    Heidari, Nastaran; Phanstiel, Douglas H.; He, Chao; Grubert, Fabian; Jahanbani, Fereshteh; Kasowski, Maya; Zhang, Michael Q.

    2014-01-01

    Increasing evidence suggests that interactions between regulatory genomic elements play an important role in regulating gene expression. We generated a genome-wide interaction map of regulatory elements in human cells (ENCODE tier 1 cells, K562, GM12878) using Chromatin Interaction Analysis by Paired-End Tag sequencing (ChIA-PET) experiments targeting six broadly distributed factors. Bound regions covered 80% of DNase I hypersensitive sites including 99.7% of TSS and 98% of enhancers. Correlating this map with ChIP-seq and RNA-seq data sets revealed cohesin, CTCF, and ZNF143 as key components of three-dimensional chromatin structure and revealed how the distal chromatin state affects gene transcription. Comparison of interactions between cell types revealed that enhancer–promoter interactions were highly cell-type-specific. Construction and comparison of distal and proximal regulatory networks revealed stark differences in structure and biological function. Proximal binding events are enriched at genes with housekeeping functions, while distal binding events interact with genes involved in dynamic biological processes including response to stimulus. This study reveals new mechanistic and functional insights into regulatory region organization in the nucleus. PMID:25228660

  15. Mapping the Complex Morphology of Cell Interactions with Nanowire Substrates Using FIB-SEM

    PubMed Central

    Jensen, Mikkel R. B.; Łopacińska, Joanna; Schmidt, Michael S.; Skolimowski, Maciej; Abeille, Fabien; Qvortrup, Klaus; Mølhave, Kristian

    2013-01-01

    Using high resolution focused ion beam scanning electron microscopy (FIB-SEM) we study the details of cell-nanostructure interactions using serial block face imaging. 3T3 Fibroblast cellular monolayers are cultured on flat glass as a control surface and on two types of nanostructured scaffold substrates made from silicon black (Nanograss) with low- and high nanowire density. After culturing for 72 hours the cells were fixed, heavy metal stained, embedded in resin, and processed with FIB-SEM block face imaging without removing the substrate. The sample preparation procedure, image acquisition and image post-processing were specifically optimised for cellular monolayers cultured on nanostructured substrates. Cells display a wide range of interactions with the nanostructures depending on the surface morphology, but also greatly varying from one cell to another on the same substrate, illustrating a wide phenotypic variability. Depending on the substrate and cell, we observe that cells could for instance: break the nanowires and engulf them, flatten the nanowires or simply reside on top of them. Given the complexity of interactions, we have categorised our observations and created an overview map. The results demonstrate that detailed nanoscale resolution images are required to begin understanding the wide variety of individual cells’ interactions with a structured substrate. The map will provide a framework for light microscopy studies of such interactions indicating what modes of interactions must be considered. PMID:23326412

  16. Mapping the complex morphology of cell interactions with nanowire substrates using FIB-SEM.

    PubMed

    Wierzbicki, Rafał; Købler, Carsten; Jensen, Mikkel R B; Lopacińska, Joanna; Schmidt, Michael S; Skolimowski, Maciej; Abeille, Fabien; Qvortrup, Klaus; Mølhave, Kristian

    2013-01-01

    Using high resolution focused ion beam scanning electron microscopy (FIB-SEM) we study the details of cell-nanostructure interactions using serial block face imaging. 3T3 Fibroblast cellular monolayers are cultured on flat glass as a control surface and on two types of nanostructured scaffold substrates made from silicon black (Nanograss) with low- and high nanowire density. After culturing for 72 hours the cells were fixed, heavy metal stained, embedded in resin, and processed with FIB-SEM block face imaging without removing the substrate. The sample preparation procedure, image acquisition and image post-processing were specifically optimised for cellular monolayers cultured on nanostructured substrates. Cells display a wide range of interactions with the nanostructures depending on the surface morphology, but also greatly varying from one cell to another on the same substrate, illustrating a wide phenotypic variability. Depending on the substrate and cell, we observe that cells could for instance: break the nanowires and engulf them, flatten the nanowires or simply reside on top of them. Given the complexity of interactions, we have categorised our observations and created an overview map. The results demonstrate that detailed nanoscale resolution images are required to begin understanding the wide variety of individual cells' interactions with a structured substrate. The map will provide a framework for light microscopy studies of such interactions indicating what modes of interactions must be considered.

  17. Genome-wide map of regulatory interactions in the human genome.

    PubMed

    Heidari, Nastaran; Phanstiel, Douglas H; He, Chao; Grubert, Fabian; Jahanbani, Fereshteh; Kasowski, Maya; Zhang, Michael Q; Snyder, Michael P

    2014-12-01

    Increasing evidence suggests that interactions between regulatory genomic elements play an important role in regulating gene expression. We generated a genome-wide interaction map of regulatory elements in human cells (ENCODE tier 1 cells, K562, GM12878) using Chromatin Interaction Analysis by Paired-End Tag sequencing (ChIA-PET) experiments targeting six broadly distributed factors. Bound regions covered 80% of DNase I hypersensitive sites including 99.7% of TSS and 98% of enhancers. Correlating this map with ChIP-seq and RNA-seq data sets revealed cohesin, CTCF, and ZNF143 as key components of three-dimensional chromatin structure and revealed how the distal chromatin state affects gene transcription. Comparison of interactions between cell types revealed that enhancer-promoter interactions were highly cell-type-specific. Construction and comparison of distal and proximal regulatory networks revealed stark differences in structure and biological function. Proximal binding events are enriched at genes with housekeeping functions, while distal binding events interact with genes involved in dynamic biological processes including response to stimulus. This study reveals new mechanistic and functional insights into regulatory region organization in the nucleus. © 2014 Heidari et al.; Published by Cold Spring Harbor Laboratory Press.

  18. Functional dissection of protein complexes involved in yeast chromosome biology using a genetic interaction map.

    PubMed

    Collins, Sean R; Miller, Kyle M; Maas, Nancy L; Roguev, Assen; Fillingham, Jeffrey; Chu, Clement S; Schuldiner, Maya; Gebbia, Marinella; Recht, Judith; Shales, Michael; Ding, Huiming; Xu, Hong; Han, Junhong; Ingvarsdottir, Kristin; Cheng, Benjamin; Andrews, Brenda; Boone, Charles; Berger, Shelley L; Hieter, Phil; Zhang, Zhiguo; Brown, Grant W; Ingles, C James; Emili, Andrew; Allis, C David; Toczyski, David P; Weissman, Jonathan S; Greenblatt, Jack F; Krogan, Nevan J

    2007-04-12

    Defining the functional relationships between proteins is critical for understanding virtually all aspects of cell biology. Large-scale identification of protein complexes has provided one important step towards this goal; however, even knowledge of the stoichiometry, affinity and lifetime of every protein-protein interaction would not reveal the functional relationships between and within such complexes. Genetic interactions can provide functional information that is largely invisible to protein-protein interaction data sets. Here we present an epistatic miniarray profile (E-MAP) consisting of quantitative pairwise measurements of the genetic interactions between 743 Saccharomyces cerevisiae genes involved in various aspects of chromosome biology (including DNA replication/repair, chromatid segregation and transcriptional regulation). This E-MAP reveals that physical interactions fall into two well-represented classes distinguished by whether or not the individual proteins act coherently to carry out a common function. Thus, genetic interaction data make it possible to dissect functionally multi-protein complexes, including Mediator, and to organize distinct protein complexes into pathways. In one pathway defined here, we show that Rtt109 is the founding member of a novel class of histone acetyltransferases responsible for Asf1-dependent acetylation of histone H3 on lysine 56. This modification, in turn, enables a ubiquitin ligase complex containing the cullin Rtt101 to ensure genomic integrity during DNA replication.

  19. Web GIS in practice VIII: HTML5 and the canvas element for interactive online mapping.

    PubMed

    Boulos, Maged N Kamel; Warren, Jeffrey; Gong, Jianya; Yue, Peng

    2010-03-03

    HTML5 is being developed as the next major revision of HTML (Hypertext Markup Language), the core markup language of the World Wide Web. It aims at reducing the need for proprietary, plug-in-based rich Internet application (RIA) technologies such as Adobe Flash. The canvas element is part of HTML5 and is used to draw graphics using scripting (e.g., JavaScript). This paper introduces Cartagen, an open-source, vector-based, client-side framework for rendering plug-in-free, offline-capable, interactive maps in native HTML5 on a wide range of Web browsers and mobile phones. Cartagen was developed at MIT Media Lab's Design Ecology group. Potential applications of the technology as an enabler for participatory online mapping include mapping real-time air pollution, citizen reporting, and disaster response, among many other possibilities.

  20. Web GIS in practice VIII: HTML5 and the canvas element for interactive online mapping

    PubMed Central

    2010-01-01

    HTML5 is being developed as the next major revision of HTML (Hypertext Markup Language), the core markup language of the World Wide Web. It aims at reducing the need for proprietary, plug-in-based rich Internet application (RIA) technologies such as Adobe Flash. The canvas element is part of HTML5 and is used to draw graphics using scripting (e.g., JavaScript). This paper introduces Cartagen, an open-source, vector-based, client-side framework for rendering plug-in-free, offline-capable, interactive maps in native HTML5 on a wide range of Web browsers and mobile phones. Cartagen was developed at MIT Media Lab's Design Ecology group. Potential applications of the technology as an enabler for participatory online mapping include mapping real-time air pollution, citizen reporting, and disaster response, among many other possibilities. PMID:20199681

  1. Carbene footprinting accurately maps binding sites in protein-ligand and protein-protein interactions

    NASA Astrophysics Data System (ADS)

    Manzi, Lucio; Barrow, Andrew S.; Scott, Daniel; Layfield, Robert; Wright, Timothy G.; Moses, John E.; Oldham, Neil J.

    2016-11-01

    Specific interactions between proteins and their binding partners are fundamental to life processes. The ability to detect protein complexes, and map their sites of binding, is crucial to understanding basic biology at the molecular level. Methods that employ sensitive analytical techniques such as mass spectrometry have the potential to provide valuable insights with very little material and on short time scales. Here we present a differential protein footprinting technique employing an efficient photo-activated probe for use with mass spectrometry. Using this methodology the location of a carbohydrate substrate was accurately mapped to the binding cleft of lysozyme, and in a more complex example, the interactions between a 100 kDa, multi-domain deubiquitinating enzyme, USP5 and a diubiquitin substrate were located to different functional domains. The much improved properties of this probe make carbene footprinting a viable method for rapid and accurate identification of protein binding sites utilizing benign, near-UV photoactivation.

  2. Development of a novel 2D color map for interactive segmentation of histological images

    PubMed Central

    Chaudry, Qaiser; Sharma, Yachna; Raza, Syed H.; Wang, May D.

    2016-01-01

    We present a color segmentation approach based on a two-dimensional color map derived from the input image. Pathologists stain tissue biopsies with various colored dyes to see the expression of biomarkers. In these images, because of color variation due to inconsistencies in experimental procedures and lighting conditions, the segmentation used to analyze biological features is usually ad-hoc. Many algorithms like K-means use a single metric to segment the image into different color classes and rarely provide users with powerful color control. Our 2D color map interactive segmentation technique based on human color perception information and the color distribution of the input image, enables user control without noticeable delay. Our methodology works for different staining types and different types of cancer tissue images. Our proposed method’s results show good accuracy with low response and computational time making it a feasible method for user interactive applications involving segmentation of histological images.

  3. Carbene footprinting accurately maps binding sites in protein–ligand and protein–protein interactions

    PubMed Central

    Manzi, Lucio; Barrow, Andrew S.; Scott, Daniel; Layfield, Robert; Wright, Timothy G.; Moses, John E.; Oldham, Neil J.

    2016-01-01

    Specific interactions between proteins and their binding partners are fundamental to life processes. The ability to detect protein complexes, and map their sites of binding, is crucial to understanding basic biology at the molecular level. Methods that employ sensitive analytical techniques such as mass spectrometry have the potential to provide valuable insights with very little material and on short time scales. Here we present a differential protein footprinting technique employing an efficient photo-activated probe for use with mass spectrometry. Using this methodology the location of a carbohydrate substrate was accurately mapped to the binding cleft of lysozyme, and in a more complex example, the interactions between a 100 kDa, multi-domain deubiquitinating enzyme, USP5 and a diubiquitin substrate were located to different functional domains. The much improved properties of this probe make carbene footprinting a viable method for rapid and accurate identification of protein binding sites utilizing benign, near-UV photoactivation. PMID:27848959

  4. Carbene footprinting accurately maps binding sites in protein-ligand and protein-protein interactions.

    PubMed

    Manzi, Lucio; Barrow, Andrew S; Scott, Daniel; Layfield, Robert; Wright, Timothy G; Moses, John E; Oldham, Neil J

    2016-11-16

    Specific interactions between proteins and their binding partners are fundamental to life processes. The ability to detect protein complexes, and map their sites of binding, is crucial to understanding basic biology at the molecular level. Methods that employ sensitive analytical techniques such as mass spectrometry have the potential to provide valuable insights with very little material and on short time scales. Here we present a differential protein footprinting technique employing an efficient photo-activated probe for use with mass spectrometry. Using this methodology the location of a carbohydrate substrate was accurately mapped to the binding cleft of lysozyme, and in a more complex example, the interactions between a 100 kDa, multi-domain deubiquitinating enzyme, USP5 and a diubiquitin substrate were located to different functional domains. The much improved properties of this probe make carbene footprinting a viable method for rapid and accurate identification of protein binding sites utilizing benign, near-UV photoactivation.

  5. Quantitative Chemical-Genetic Interaction Map Connects Gene Alterations to Drug Responses | Office of Cancer Genomics

    Cancer.gov

    In a recent Cancer Discovery report, CTD2 researchers at the University of California in San Francisco developed a new quantitative chemical-genetic interaction mapping approach to evaluate drug sensitivity or resistance in isogenic cell lines. Performing a high-throughput screen with isogenic cell lines allowed the researchers to explore the impact of a panel of emerging and established drugs on cells overexpressing a single cancer-associated gene in isolation.

  6. Automatic Generation of Issue Maps: Structured, Interactive Outputs for Complex Information Needs

    DTIC Science & Technology

    2012-09-01

    keys fell into the river during rafting), and for being a great friend (with a perfect sense of timing); Ali Kemal Sinop, for spring carnivals...ship president , Clinton, water portauprince, building, body Silsby, abduct, jail Figure 4.4: Map about the earthquake in Haiti, before interaction...structure. Instead, articles are sorted chronologically and displayed in a fashion similar to Google News. We recruited participants in the study via Amazon

  7. Proteome-wide Mapping of Cholesterol-Interacting Proteins in Mammalian Cells

    PubMed Central

    Hulce, Jonathan J.; Cognetta, Armand B.; Niphakis, Micah J.; Tully, Sarah E.; Cravatt, Benjamin F.

    2013-01-01

    Cholesterol is an essential structural component of cellular membranes and serves as a precursor for several classes of signaling molecules. Cholesterol exerts its effects and is, itself, regulated in large part by engaging in specific interactions with proteins. The full complement of sterol-binding proteins that exist in mammalian cells, however, remains unknown. Here, we describe a chemoproteomic strategy that uses clickable, photoreactive sterol probes in combination with quantitative mass spectrometry to globally map cholesterol-protein interactions directly in living cells. We identified over 250 cholesterol-binding proteins, including many established and previously unreported interactions with receptors, channels, and enzymes. Prominent among the newly identified interactions were enzymes that regulate sugars, glycerolipids, and cholesterol itself, as well as those involved in vesicular transport and protein glycosylation and degradation, pointing to key nodes in biochemical pathways that may couple sterol concentrations to the control of other metabolites and protein localization and modification. PMID:23396283

  8. A Rice Kinase-Protein Interaction Map1[W][OA

    PubMed Central

    Ding, Xiaodong; Richter, Todd; Chen, Mei; Fujii, Hiroaki; Seo, Young Su; Xie, Mingtang; Zheng, Xianwu; Kanrar, Siddhartha; Stevenson, Rebecca A.; Dardick, Christopher; Li, Ying; Jiang, Hao; Zhang, Yan; Yu, Fahong; Bartley, Laura E.; Chern, Mawsheng; Bart, Rebecca; Chen, Xiuhua; Zhu, Lihuang; Farmerie, William G.; Gribskov, Michael; Zhu, Jian-Kang; Fromm, Michael E.; Ronald, Pamela C.; Song, Wen-Yuan

    2009-01-01

    Plants uniquely contain large numbers of protein kinases, and for the vast majority of the 1,429 kinases predicted in the rice (Oryza sativa) genome, little is known of their functions. Genetic approaches often fail to produce observable phenotypes; thus, new strategies are needed to delineate kinase function. We previously developed a cost-effective high-throughput yeast two-hybrid system. Using this system, we have generated a protein interaction map of 116 representative rice kinases and 254 of their interacting proteins. Overall, the resulting interaction map supports a large number of known or predicted kinase-protein interactions from both plants and animals and reveals many new functional insights. Notably, we found a potential widespread role for E3 ubiquitin ligases in pathogen defense signaling mediated by receptor-like kinases, particularly by the kinases that may have evolved from recently expanded kinase subfamilies in rice. We anticipate that the data provided here will serve as a foundation for targeted functional studies in rice and other plants. The application of yeast two-hybrid and TAPtag analyses for large-scale plant protein interaction studies is also discussed. PMID:19109415

  9. Functional genomics platform for pooled screening and mammalian genetic interaction maps

    PubMed Central

    Kampmann, Martin; Bassik, Michael C.; Weissman, Jonathan S.

    2014-01-01

    Systematic genetic interaction maps in microorganisms are powerful tools for identifying functional relationships between genes and defining the function of uncharacterized genes. We have recently implemented this strategy in mammalian cells as a two-stage approach. First, genes of interest are robustly identified in a pooled genome-wide screen using complex shRNA libraries. Second, phenotypes for all pairwise combinations of hit genes are measured in a double-shRNA screen and used to construct a genetic interaction map. Our protocol allows for rapid pooled screening under various conditions without a requirement for robotics, in contrast to arrayed approaches. Each stage of the protocol can be implemented in ~2 weeks, with additional time for analysis and generation of reagents. We discuss considerations for screen design, and present complete experimental procedures as well as a full computational analysis suite for identification of hits in pooled screens and generation of genetic interaction maps. While the protocols outlined here were developed for our original shRNA-based approach, they can be applied more generally, including to CRISPR-based approaches. PMID:24992097

  10. Mapping of Protein–Protein Interaction Sites by the ‘Absence of Interference’ Approach

    PubMed Central

    Dhayalan, Arunkumar; Jurkowski, Tomasz P.; Laser, Heike; Reinhardt, Richard; Jia, Da; Cheng, Xiaodong; Jeltsch, Albert

    2008-01-01

    Protein–protein interactions are critical to most biological processes, and locating protein–protein interfaces on protein structures is an important task in molecular biology. We developed a new experimental strategy called the ‘absence of interference’ approach to determine surface residues involved in protein–protein interaction of established yeast two-hybrid pairs of interacting proteins. One of the proteins is subjected to high-level randomization by error-prone PCR. The resulting library is selected by yeast two-hybrid system for interacting clones that are isolated and sequenced. The interaction region can be identified by an absence or depletion of mutations. For data analysis and presentation, we developed a Web interface that analyzes the mutational spectrum and displays the mutational frequency on the surface of the structure (or a structural model) of the randomized protein†. Additionally, this interface might be of use for the display of mutational distributions determined by other types of random mutagenesis experiments. We applied the approach to map the interface of the catalytic domain of the DNA methyltransferase Dnmt3a with its regulatory factor Dnmt3L. Dnmt3a was randomized with high mutational load. A total of 76 interacting clones were isolated and sequenced, and 648 mutations were identified. The mutational pattern allowed to identify a unique interaction region on the surface of Dnmt3a, which comprises about 500−600 Å2. The results were confirmed by site-directed mutagenesis and structural analysis. The absence-of-interference approach will allow high-throughput mapping of protein interaction sites suitable for functional studies and protein docking. PMID:18191145

  11. MAPS

    Atmospheric Science Data Center

    2014-07-03

    ... Measurement of Air Pollution from Satellites (MAPS) data were collected during Space Shuttle flights in 1981, ... Facts Correlative Data  - CDIAC - Spring & Fall 1994 - Field and Aircraft Campaigns SCAR-B Block:  ...

  12. Systematic Mapping of RNA-Chromatin Interactions In Vivo.

    PubMed

    Sridhar, Bharat; Rivas-Astroza, Marcelo; Nguyen, Tri C; Chen, Weizhong; Yan, Zhangming; Cao, Xiaoyi; Hebert, Lucie; Zhong, Sheng

    2017-02-20

    RNA molecules can attach to chromatin. It remains difficult to know what RNAs are associated with chromatin and where the genomic target loci of these RNAs are. Here, we present MARGI (mapping RNA-genome interactions), a technology to massively reveal native RNA-chromatin interactions from unperturbed cells. The gist of this technology is to ligate chromatin-associated RNAs (caRNAs) with their target genomic sequences by proximity ligation, forming RNA-DNA chimeric sequences, which are converted to a sequencing library for paired-end sequencing. Using MARGI, we produced RNA-genome interaction maps for human embryonic stem cells (ESCs) and human embryonic kidney (HEK) cells. MARGI revealed hundreds of caRNAs, including previously known XIST, SNHG1, NEAT1, and MALAT1, as well as each caRNA's genomic interaction loci. Using a cross-species experiment, we estimated that approximately 2.2% of MARGI-identified interactions were false positives. In ESCs and HEK cells, the RNA ends of more than 5% of MARGI read pairs were mapped to distal or inter-chromosomal locations as compared to the locations of their corresponding DNA ends. The majority of transcription start sites are associated with distal or inter-chromosomal caRNAs. Chromatin-immunoprecipitation-sequencing (ChIP-seq)-reported H3K27ac and H3K4me3 levels are positively correlated, while H3K9me3 is negatively correlated, with MARGI-reported RNA attachment levels. The MARGI technology should facilitate revealing novel RNA functions and their genomic target regions.

  13. Mapping, genetic effects, and epistatic interaction of two bacterial canker resistance QTLs from Lycopersicon hirsutum.

    PubMed

    Coaker, G L; Francis, D M

    2004-04-01

    Two quantitative trait loci (QTL) from Lycopersicon hirsutum, Rcm 2.0 and Rcm 5.1, control resistance to Clavibacter michiganensis subsp. michiganensis ( Cmm). To precisely map both loci, we applied interval mapping techniques to 1,056 individuals in three populations exhibiting F(2) segregation. Based on a 1-LOD confidence interval, Rcm 2.0 mapped to a 14.9-cM interval on chromosome 2 and accounted for 25.7-34.0% of the phenotypic variation in disease severity. Rcm 5.1 mapped to a 4.3-cM interval on chromosome 5 and accounted for 25.8-27.9% of the phenotypic variation. Progeny testing of recombinant plants narrowed the QTL location for Rcm 2.0 to a 4.4-cM interval between TG537-TG091 and to a 2.2-cM interval between CT202-TG358 for Rcm 5.1. A population of 750 individuals exhibiting F(2) segregation was used to detect epistasis between both loci using ANOVA and orthogonal contrasts ( P=0.027), suggesting that resistance was determined by additive gene action and an additive-by-additive epistatic interaction. A partial diallel mating design was used to confirm epistasis, advance superior genotypes, randomize genetic backgrounds, and create recombination opportunities. This crossing scheme created a more balanced population ( n=112) containing the nine F(2) genotypic classes. Parents in the diallel were selected from the previous population based on resistance, genotype at the Rcm 2.0 and Rcm 5.1 loci, and horticultural traits. A replicated trial using the diallel population confirmed additive-by-additive epistasis ( P<0.0001). These results validate the gene action, intra -locus interaction, and map position of two loci controlling resistance to Cmm.

  14. iMAR: An Interactive Web-Based Application for Mapping Herbicide Resistant Weeds.

    PubMed

    Panozzo, Silvia; Colauzzi, Michele; Scarabel, Laura; Collavo, Alberto; Rosan, Valentina; Sattin, Maurizio

    2015-01-01

    Herbicides are the major weed control tool in most cropping systems worldwide. However, the high reliance on herbicides has led to environmental issues as well as to the evolution of herbicide-resistant biotypes. Resistance is a major concern in modern agriculture and early detection of resistant biotypes is therefore crucial for its management and prevention. In this context, a timely update of resistance biotypes distribution is fundamental to devise and implement efficient resistance management strategies. Here we present an innovative web-based application called iMAR (interactive MApping of Resistance) for the mapping of herbicide resistant biotypes. It is based on open source software tools and translates into maps the data reported in the GIRE (Italian herbicide resistance working group) database of herbicide resistance at national level. iMAR allows an automatic, easy and cost-effective updating of the maps a nd provides two different systems, "static" and "dynamic". In the first one, the user choices are guided by a hierarchical tree menu, whereas the latter is more flexible and includes a multiple choice criteria (type of resistance, weed species, region, cropping systems) that permits customized maps to be created. The generated information can be useful to various stakeholders who are involved in weed resistance management: farmers, advisors, national and local decision makers as well as the agrochemical industry. iMAR is freely available, and the system has the potential to handle large datasets and to be used for other purposes with geographical implications, such as the mapping of invasive plants or pests.

  15. iMAR: An Interactive Web-Based Application for Mapping Herbicide Resistant Weeds

    PubMed Central

    Panozzo, Silvia; Colauzzi, Michele; Scarabel, Laura; Collavo, Alberto; Rosan, Valentina; Sattin, Maurizio

    2015-01-01

    Herbicides are the major weed control tool in most cropping systems worldwide. However, the high reliance on herbicides has led to environmental issues as well as to the evolution of herbicide-resistant biotypes. Resistance is a major concern in modern agriculture and early detection of resistant biotypes is therefore crucial for its management and prevention. In this context, a timely update of resistance biotypes distribution is fundamental to devise and implement efficient resistance management strategies. Here we present an innovative web-based application called iMAR (interactive MApping of Resistance) for the mapping of herbicide resistant biotypes. It is based on open source software tools and translates into maps the data reported in the GIRE (Italian herbicide resistance working group) database of herbicide resistance at national level. iMAR allows an automatic, easy and cost-effective updating of the maps a nd provides two different systems, “static” and “dynamic”. In the first one, the user choices are guided by a hierarchical tree menu, whereas the latter is more flexible and includes a multiple choice criteria (type of resistance, weed species, region, cropping systems) that permits customized maps to be created. The generated information can be useful to various stakeholders who are involved in weed resistance management: farmers, advisors, national and local decision makers as well as the agrochemical industry. iMAR is freely available, and the system has the potential to handle large datasets and to be used for other purposes with geographical implications, such as the mapping of invasive plants or pests. PMID:26266545

  16. Mapping the genetic basis of symbiotic variation in legume-rhizobium interactions in Medicago truncatula.

    PubMed

    Gorton, Amanda J; Heath, Katy D; Pilet-Nayel, Marie-Laure; Baranger, Alain; Stinchcombe, John R

    2012-11-01

    Mutualisms are known to be genetically variable, where the genotypes differ in the fitness benefits they gain from the interaction. To date, little is known about the loci that underlie such genetic variation in fitness or whether the loci influencing fitness are partner specific, and depend on the genotype of the interaction partner. In the legume-rhizobium mutualism, one set of potential candidate genes that may influence the fitness benefits of the symbiosis are the plant genes involved in the initiation of the signaling pathway between the two partners. Here we performed quantitative trait loci (QTL) mapping in Medicago truncatula in two different rhizobium strain treatments to locate regions of the genome influencing plant traits, assess whether such regions are dependent on the genotype of the rhizobial mutualist (QTL × rhizobium strain), and evaluate the contribution of sequence variation at known symbiosis signaling genes. Two of the symbiotic signaling genes, NFP and DMI3, colocalized with two QTL affecting average fruit weight and leaf number, suggesting that natural variation in nodulation genes may potentially influence plant fitness. In both rhizobium strain treatments, there were QTL that influenced multiple traits, indicative of either tight linkage between loci or pleiotropy, including one QTL with opposing effects on growth and reproduction. There was no evidence for QTL × rhizobium strain or genotype × genotype interactions, suggesting either that such interactions are due to small-effect loci or that more genotype-genotype combinations need to be tested in future mapping studies.

  17. Mapping the Genetic Basis of Symbiotic Variation in Legume-Rhizobium Interactions in Medicago truncatula

    PubMed Central

    Gorton, Amanda J.; Heath, Katy D.; Pilet-Nayel, Marie-Laure; Baranger, Alain

    2012-01-01

    Mutualisms are known to be genetically variable, where the genotypes differ in the fitness benefits they gain from the interaction. To date, little is known about the loci that underlie such genetic variation in fitness or whether the loci influencing fitness are partner specific, and depend on the genotype of the interaction partner. In the legume-rhizobium mutualism, one set of potential candidate genes that may influence the fitness benefits of the symbiosis are the plant genes involved in the initiation of the signaling pathway between the two partners. Here we performed quantitative trait loci (QTL) mapping in Medicago truncatula in two different rhizobium strain treatments to locate regions of the genome influencing plant traits, assess whether such regions are dependent on the genotype of the rhizobial mutualist (QTL × rhizobium strain), and evaluate the contribution of sequence variation at known symbiosis signaling genes. Two of the symbiotic signaling genes, NFP and DMI3, colocalized with two QTL affecting average fruit weight and leaf number, suggesting that natural variation in nodulation genes may potentially influence plant fitness. In both rhizobium strain treatments, there were QTL that influenced multiple traits, indicative of either tight linkage between loci or pleiotropy, including one QTL with opposing effects on growth and reproduction. There was no evidence for QTL × rhizobium strain or genotype × genotype interactions, suggesting either that such interactions are due to small-effect loci or that more genotype-genotype combinations need to be tested in future mapping studies. PMID:23173081

  18. Construction and application of a protein interaction map for white spot syndrome virus (WSSV).

    PubMed

    Sangsuriya, Pakkakul; Huang, Jiun-Yan; Chu, Yu-Fei; Phiwsaiya, Kornsunee; Leekitcharoenphon, Pimlapas; Meemetta, Watcharachai; Senapin, Saengchan; Huang, Wei-Pang; Withyachumnarnkul, Boonsirm; Flegel, Timothy W; Lo, Chu-Fang

    2014-01-01

    White spot syndrome virus (WSSV) is currently the most serious global threat for cultured shrimp production. Although its large, double-stranded DNA genome has been completely characterized, most putative protein functions remain obscure. To provide more informative knowledge about this virus, a proteomic-scale network of WSSV-WSSV protein interactions was carried out using a comprehensive yeast two-hybrid analysis. An array of yeast transformants containing each WSSV open reading frame fused with GAL4 DNA binding domain and GAL4 activation domain was constructed yielding 187 bait and 182 prey constructs, respectively. On screening of ∼28,000 pairwise combinations, 710 interactions were obtained from 143 baits. An independent coimmunoprecipitation assay (co-IP) was performed to validate the selected protein interaction pairs identified from the yeast two-hybrid approach. The program Cytoscape was employed to create a WSSV protein-protein interaction (PPI) network. The topology of the WSSV PPI network was based on the Barabási-Albert model and consisted of a scale-free network that resembled other established viral protein interaction networks. Using the RNA interference approach, knocking down either of two candidate hub proteins gave shrimp more protection against WSSV than knocking down a nonhub gene. The WSSV protein interaction map established in this study provides novel guidance for further studies on shrimp viral pathogenesis, host-viral protein interaction and potential targets for therapeutic and preventative antiviral strategies in shrimp aquaculture.

  19. Interactive Maps on War and Peace: A WebGIS Application for Civic Education

    NASA Astrophysics Data System (ADS)

    Wirkus, Lars; Strunck, Alexander

    2013-04-01

    War and violent conflict are omnipresent-be it war in the Middle East, violent conflicts in failed states or increasing military expenditures and exports/ imports of military goods. To understand certain conflicts or peace processes and their possible interrelation, to conduct a well-founded political discussion and to support or influence decision-making, one matter is of special importance: easily accessible and, in particular, reliable data and information. Against this background, the Bonn International Center for Conversion (BICC) in close cooperation with the German Federal Agency for Civic Education (bpb) has been developing a map-based information portal on war and peace with various thematic modules for the latter's online service (http://sicherheitspolitik.bpb.de). The portal will eventually offer nine of such modules that are intended to give various target groups, such as interested members of the public, teachers and learners, policymakers and representatives of the media access to the required information in form of an interactive and country-based global overview or a comparison of different issues. Five thematic modules have been completed so far: War and conflict, peace and demobilization, military capacities, resources and conflict, conventional weapons. The portal offers a broad spectrum of different data processing and visualization tools. Its central feature is an interactive mapping component based on WebGIS and a relational database. Content and data provided through thematic maps in the form of WebGIS layers are generally supplemented by info graphics, data tables and short articles providing deeper knowledge on the respective issue. All modules and their sub-chapters are introduced by background texts. They put all interactive maps of a module into an appropriate context and help the users to also understand the interrelation between various layers. If a layer is selected, all corresponding texts and graphics are shown automatically below

  20. An Interactive Map Viewer for the Urban Geology of Ottawa (Canada): an Example of Web Publishing

    NASA Astrophysics Data System (ADS)

    Giroux, D.; Bélanger, R.

    2003-04-01

    Developed by the Terrain Sciences Division (TSD) of the Geological Survey of Canada (GSC), an interactive map viewer, called GEOSERV (www.geoserv.org), is now available on the Internet. The purpose of this viewer is to provide engineers, planners, decision makers, and the general public with the geoscience information required for sound regional planning in densely populated areas, such as Canada's national capital, Ottawa (Ontario). Urban geology studies rely on diverse branches of earth sciences such as hydrology, engineering geology, geochemistry, stratigraphy, and geomorphology in order to build a three-dimensional model of the character of the land and to explain the geological processes involved in the dynamic equilibrium of the local environment. Over the past few years, TSD has compiled geoscientific information derived from various sources such as borehole logs, geological maps, hydrological reports and digital elevation models, compiled it in digital format and stored it in georeferenced databases in the form of point, linear, and polygonal data. This information constitutes the geoscience knowledge base which is then processed by Geographic Information Systems (GIS) to integrate the various sources of information and produce derived graphics, maps and models describing the geological infrastructure and response of the geological environment to human activities. Urban Geology of Canada's National Capital Area is a pilot project aiming at developing approaches, methodologies and standards that can be applied to other major urban centres of the country, while providing the geoscience knowledge required for sound regional planning and environmental protection of the National Capital Area. Based on an application developed by ESRI (Environmental System Research Institute), namely ArcIMS, the TSD has customized this web application to give free access to geoscience information of the Ottawa/Outaouais (Ontario/Québec) area including geological history

  1. Delineating the functional map of the interaction between nimotuzumab and the epidermal growth factor receptor

    PubMed Central

    Tundidor, Yaima; García-Hernández, Claudia Patricia; Pupo, Amaury; Infante, Yanelys Cabrera; Rojas, Gertrudis

    2014-01-01

    Molecular details of epidermal growth factor receptor (EGFR) targeting by nimotuzumab, a therapeutic anti-cancer antibody, have been largely unknown. The current study delineated a functional map of their interface, based on phage display and extensive mutagenesis of both the target antigen and the Fv antibody fragment. Five residues in EGFR domain III (R353, S356, F357, T358, and H359T) and the third hypervariable region of nimotuzumab heavy chain were shown to be major functional contributors to the interaction. Fine specificity differences between nimotuzumab and other anti-EGFR antibodies were revealed. Mapping information guided the generation of a plausible in silico binding model. Knowledge about the epitope/paratope interface opens new avenues for the study of tumor sensitivity/resistance to nimotuzumab and for further engineering of its binding site. The developed mapping platform, also validated with the well-known cetuximab epitope, allows a comprehensive exploration of antigenic regions and could be expanded to map other anti-EGFR antibodies. PMID:24759767

  2. Delineating the functional map of the interaction between nimotuzumab and the epidermal growth factor receptor.

    PubMed

    Tundidor, Yaima; García-Hernández, Claudia Patricia; Pupo, Amaury; Cabrera Infante, Yanelys; Rojas, Gertrudis

    2014-01-01

    Molecular details of epidermal growth factor receptor (EGFR) targeting by nimotuzumab, a therapeutic anti-cancer antibody, have been largely unknown. The current study delineated a functional map of their interface, based on phage display and extensive mutagenesis of both the target antigen and the Fv antibody fragment. Five residues in EGFR domain III (R353, S356, F357, T358, and H359T) and the third hypervariable region of nimotuzumab heavy chain were shown to be major functional contributors to the interaction. Fine specificity differences between nimotuzumab and other anti-EGFR antibodies were revealed. Mapping information guided the generation of a plausible in silico binding model. Knowledge about the epitope/paratope interface opens new avenues for the study of tumor sensitivity/resistance to nimotuzumab and for further engineering of its binding site. The developed mapping platform, also validated with the well-known cetuximab epitope, allows a comprehensive exploration of antigenic regions and could be expanded to map other anti-EGFR antibodies.

  3. Mapping texts through dimensionality reduction and visualization techniques for interactive exploration of document collections

    NASA Astrophysics Data System (ADS)

    de Andrade Lopes, Alneu; Minghim, Rosane; Melo, Vinícius; Paulovich, Fernando V.

    2006-01-01

    The current availability of information many times impair the tasks of searching, browsing and analyzing information pertinent to a topic of interest. This paper presents a methodology to create a meaningful graphical representation of documents corpora targeted at supporting exploration of correlated documents. The purpose of such an approach is to produce a map from a document body on a research topic or field based on the analysis of their contents, and similarities amongst articles. The document map is generated, after text pre-processing, by projecting the data in two dimensions using Latent Semantic Indexing. The projection is followed by hierarchical clustering to support sub-area identification. The map can be interactively explored, helping to narrow down the search for relevant articles. Tests were performed using a collection of documents pre-classified into three research subject classes: Case-Based Reasoning, Information Retrieval, and Inductive Logic Programming. The map produced was capable of separating the main areas and approaching documents by their similarity, revealing possible topics, and identifying boundaries between them. The tool can deal with the exploration of inter-topics and intra-topic relationship and is useful in many contexts that need deciding on relevant articles to read, such as scientific research, education, and training.

  4. Maps of context-dependent putative regulatory regions and genomic signal interactions.

    PubMed

    Diamanti, Klev; Umer, Husen M; Kruczyk, Marcin; Dąbrowski, Michał J; Cavalli, Marco; Wadelius, Claes; Komorowski, Jan

    2016-11-02

    Gene transcription is regulated mainly by transcription factors (TFs). ENCODE and Roadmap Epigenomics provide global binding profiles of TFs, which can be used to identify regulatory regions. To this end we implemented a method to systematically construct cell-type and species-specific maps of regulatory regions and TF-TF interactions. We illustrated the approach by developing maps for five human cell-lines and two other species. We detected ∼144k putative regulatory regions among the human cell-lines, with the majority of them being ∼300 bp. We found ∼20k putative regulatory elements in the ENCODE heterochromatic domains suggesting a large regulatory potential in the regions presumed transcriptionally silent. Among the most significant TF interactions identified in the heterochromatic regions were CTCF and the cohesin complex, which is in agreement with previous reports. Finally, we investigated the enrichment of the obtained putative regulatory regions in the 3D chromatin domains. More than 90% of the regions were discovered in the 3D contacting domains. We found a significant enrichment of GWAS SNPs in the putative regulatory regions. These significant enrichments provide evidence that the regulatory regions play a crucial role in the genomic structural stability. Additionally, we generated maps of putative regulatory regions for prostate and colorectal cancer human cell-lines.

  5. A triangular prism solid and shell interactive mapping element for electromagnetic sheet metal forming process

    NASA Astrophysics Data System (ADS)

    Cui, Xiangyang; Li, She; Feng, Hui; Li, Guangyao

    2017-05-01

    In this paper, a novel triangular prism solid and shell interactive mapping element is proposed to solve the coupled magnetic-mechanical formulation in electromagnetic sheet metal forming process. A linear six-node ;Triprism; element is firstly proposed for transient eddy current analysis in electromagnetic field. In present ;Triprism; element, shape functions are given explicitly, and a cell-wise gradient smoothing operation is used to obtain the gradient matrices without evaluating derivatives of shape functions. In mechanical field analysis, a shear locking free triangular shell element is employed in internal force computation, and a data mapping method is developed to transfer the Lorentz force on solid into the external forces suffered by shell structure for dynamic elasto-plasticity deformation analysis. Based on the deformed triangular shell structure, a ;Triprism; element generation rule is established for updated electromagnetic analysis, which means inter-transformation of meshes between the coupled fields can be performed automatically. In addition, the dynamic moving mesh is adopted for air mesh updating based on the deformation of sheet metal. A benchmark problem is carried out for confirming the accuracy of the proposed ;Triprism; element in predicting flux density in electromagnetic field. Solutions of several EMF problems obtained by present work are compared with experiment results and those of traditional method, which are showing excellent performances of present interactive mapping element.

  6. Maps of context-dependent putative regulatory regions and genomic signal interactions

    PubMed Central

    Diamanti, Klev; Umer, Husen M.; Kruczyk, Marcin; Dąbrowski, Michał J.; Cavalli, Marco; Wadelius, Claes; Komorowski, Jan

    2016-01-01

    Gene transcription is regulated mainly by transcription factors (TFs). ENCODE and Roadmap Epigenomics provide global binding profiles of TFs, which can be used to identify regulatory regions. To this end we implemented a method to systematically construct cell-type and species-specific maps of regulatory regions and TF–TF interactions. We illustrated the approach by developing maps for five human cell-lines and two other species. We detected ∼144k putative regulatory regions among the human cell-lines, with the majority of them being ∼300 bp. We found ∼20k putative regulatory elements in the ENCODE heterochromatic domains suggesting a large regulatory potential in the regions presumed transcriptionally silent. Among the most significant TF interactions identified in the heterochromatic regions were CTCF and the cohesin complex, which is in agreement with previous reports. Finally, we investigated the enrichment of the obtained putative regulatory regions in the 3D chromatin domains. More than 90% of the regions were discovered in the 3D contacting domains. We found a significant enrichment of GWAS SNPs in the putative regulatory regions. These significant enrichments provide evidence that the regulatory regions play a crucial role in the genomic structural stability. Additionally, we generated maps of putative regulatory regions for prostate and colorectal cancer human cell-lines. PMID:27625394

  7. Interactive web-based mapping: bridging technology and data for health

    PubMed Central

    2011-01-01

    Background The Community Health Information System (CHIS) online mapping system was first launched in 1998. Its overarching goal was to provide researchers, residents and organizations access to health related data reflecting the overall health and well-being of their communities within the Greater Houston area. In September 2009, initial planning and development began for the next generation of CHIS. The overarching goal for the new version remained to make health data easily accessible for a wide variety of research audiences. However, in the new version we specifically sought to make the CHIS truly interactive and give the user more control over data selection and reporting. Results In July 2011, a beta version of the next-generation of the application was launched. This next-generation is also a web based interactive mapping tool comprised of two distinct portals: the Breast Health Portal and Project Safety Net. Both are accessed via a Google mapping interface. Geographic coverage for the portals is currently an 8 county region centered on Harris County, Texas. Data accessed by the application include Census 2000, Census 2010 (underway), cancer incidence from the Texas Cancer Registry (TX Dept. of State Health Services), death data from Texas Vital Statistics, clinic locations for free and low-cost health services, along with service lists, hours of operation, payment options and languages spoken, uninsured and poverty data. Conclusions The system features query on the fly technology, which means the data is not generated until the query is provided to the system. This allows users to interact in real-time with the databases and generate customized reports and maps. To the author's knowledge, the Breast Health Portal and Project Safety Net are the first local-scale interactive online mapping interfaces for public health data which allow users to control the data generated. For example, users may generate breast cancer incidence rates by Census tract, in real

  8. Tentative Mapping of Transcription-Induced Interchromosomal Interaction using Chimeric EST and mRNA Data

    PubMed Central

    Unneberg, Per; Claverie, Jean-Michel

    2007-01-01

    Recent studies on chromosome conformation show that chromosomes colocalize in the nucleus, bringing together active genes in transcription factories. This spatial proximity of actively transcribing genes could provide a means for RNA interaction at the transcript level. We have screened public databases for chimeric EST and mRNA sequences with the intent of mapping transcription-induced interchromosomal interactions. We suggest that chimeric transcripts may be the result of close encounters of active genes, either as functional products or “noise” in the transcription process, and that they could be used as probes for chromosome interactions. We have found a total of 5,614 chimeric ESTs and 587 chimeric mRNAs that meet our selection criteria. Due to their higher quality, the mRNA findings are of particular interest and we hope that they may serve as food for thought for specialists in diverse areas of molecular biology. PMID:17330142

  9. Electrostatic interaction map reveals a new binding position for tropomyosin on F-actin

    PubMed Central

    Rynkiewicz, Michael J.; Schott, Veronika; Orzechowski, Marek

    2015-01-01

    Azimuthal movement of tropomyosin around the F-actin thin filament is responsible for muscle activation and relaxation. Recently a model of αα-tropomyosin, derived from molecular-mechanics and electron microscopy of different contractile states, showed that tropomyosin is rather stiff and pre-bent to present one specific face to F-actin during azimuthal transitions. However, a new model based on cryo-EM of troponin- and myosin-free filaments proposes that the interacting-face of tropomyosin can differ significantly from that in the original model. Because resolution was insufficient to assign tropomyosin side-chains, the interacting-face could not be unambiguously determined. Here, we use structural analysis and energy landscapes to further examine the proposed models. The observed bend in seven crystal structures of tropomyosin is much closer in direction and extent to the original model than to the new model. Additionally, we computed the interaction map for repositioning tropomyosin over the F-actin surface, but now extended over a much larger surface than previously (using the original interacting-face). This map shows two energy minima— one corresponding to the “blocked-state” as in the original model, and the other related by a simple 24 Å translation of tropomyosin parallel to the F-actin axis. The tropomyosinactin complex defined by the second minimum fits perfectly into the recent cryo-EM density, without requiring any change in the interacting-face. Together, these data suggest that movement of tropomyosin between regulatory states does not require interacting-face rotation. Further, they imply that thin filament assembly may involve an interplay between initially seeded tropomyosin molecules growing from distinct binding-site regions on actin. PMID:26286845

  10. Mapping the Interactions between the NS4B and NS3 Proteins of Dengue Virus

    PubMed Central

    Zou, Jing; Lee, Le Tian; Wang, Qing Yin; Xie, Xuping; Lu, Siyan; Yau, Yin Hoe; Yuan, Zhiming; Geifman Shochat, Susana; Kang, Congbao

    2015-01-01

    ABSTRACT Flavivirus RNA synthesis is mediated by a multiprotein complex associated with the endoplasmic reticulum membrane, named the replication complex (RC). Within the flavivirus RC, NS4B, an integral membrane protein with a role in virulence and regulation of the innate immune response, binds to the NS3 protease-helicase. NS4B modulates the RNA helicase activity of NS3, but the molecular details of their interaction remain elusive. Here, we used dengue virus (DENV) to map the determinants for the NS3-NS4B interaction. Coimmunoprecipitation and an in situ proximity ligation assay confirmed that NS3 colocalizes with NS4B in both DENV-infected cells and cells coexpressing both proteins. Surface plasmon resonance demonstrated that subdomains 2 and 3 of the NS3 helicase region and the cytoplasmic loop of NS4B are required for binding. Using nuclear magnetic resonance (NMR), we found that the isolated cytoplasmic loop of NS4B is flexible, with a tendency to form a three-turn α-helix and two short β-strands. Upon binding to the NS3 helicase, 12 amino acids within the cytoplasmic loop of NS4B exhibited line broadening, suggesting a participation in the interaction. Sequence alignment showed that 4 of these 12 residues are strictly conserved across different flaviviruses. Mutagenesis analysis showed that three (Q134, G140, and N144) of the four evolutionarily conserved NS4B residues are essential for DENV replication. The mapping of the NS3/NS4B-interacting regions described here can assist the design of inhibitors that disrupt their interface for antiviral therapy. IMPORTANCE NS3 and NS4B are essential components of the flavivirus RC. Using DENV as a model, we mapped the interaction between the viral NS3 and NS4B proteins. The subdomains 2 and 3 of NS3 helicase as well as the cytoplasmic loop of NS4B are critical for the interaction. Functional analysis delineated residues within the NS4B cytoplasmic loop that are crucial for DENV replication. Our findings reveal

  11. Analyzing Interactions by an IIS-Map-Based Method in Face-to-Face Collaborative Learning: An Empirical Study

    ERIC Educational Resources Information Center

    Zheng, Lanqin; Yang, Kaicheng; Huang, Ronghuai

    2012-01-01

    This study proposes a new method named the IIS-map-based method for analyzing interactions in face-to-face collaborative learning settings. This analysis method is conducted in three steps: firstly, drawing an initial IIS-map according to collaborative tasks; secondly, coding and segmenting information flows into information items of IIS; thirdly,…

  12. Analyzing Interactions by an IIS-Map-Based Method in Face-to-Face Collaborative Learning: An Empirical Study

    ERIC Educational Resources Information Center

    Zheng, Lanqin; Yang, Kaicheng; Huang, Ronghuai

    2012-01-01

    This study proposes a new method named the IIS-map-based method for analyzing interactions in face-to-face collaborative learning settings. This analysis method is conducted in three steps: firstly, drawing an initial IIS-map according to collaborative tasks; secondly, coding and segmenting information flows into information items of IIS; thirdly,…

  13. Genome-wide mapping of in vivo protein-DNA interactions.

    PubMed

    Johnson, David S; Mortazavi, Ali; Myers, Richard M; Wold, Barbara

    2007-06-08

    In vivo protein-DNA interactions connect each transcription factor with its direct targets to form a gene network scaffold. To map these protein-DNA interactions comprehensively across entire mammalian genomes, we developed a large-scale chromatin immunoprecipitation assay (ChIPSeq) based on direct ultrahigh-throughput DNA sequencing. This sequence census method was then used to map in vivo binding of the neuron-restrictive silencer factor (NRSF; also known as REST, for repressor element-1 silencing transcription factor) to 1946 locations in the human genome. The data display sharp resolution of binding position [+/-50 base pairs (bp)], which facilitated our finding motifs and allowed us to identify noncanonical NRSF-binding motifs. These ChIPSeq data also have high sensitivity and specificity [ROC (receiver operator characteristic) area >/= 0.96] and statistical confidence (P <10(-4)), properties that were important for inferring new candidate interactions. These include key transcription factors in the gene network that regulates pancreatic islet cell development.

  14. Membrane Yeast Two-Hybrid (MYTH) Mapping of Full-Length Membrane Protein Interactions.

    PubMed

    Snider, Jamie; Stagljar, Igor

    2016-01-04

    Mapping of protein interaction networks is a major strategy for obtaining a global understanding of protein function in cells and represents one of the primary goals of proteomics research. Membrane proteins, which play key roles in human disease and as drug targets, are of considerable interest; however, because of their hydrophobic nature, mapping their interactions presents significant technical challenges and requires the use of special methodological approaches. One powerful approach is the membrane yeast two-hybrid (MYTH) assay, a split-ubiquitin-based system specifically suited to the study of full-length membrane protein interactions in vivo using the yeast Saccharomyces cerevisiae as a host. The system can be used in both low- and high-throughput formats to study proteins from a wide range of different organisms. There are two primary variants of MYTH: integrated (iMYTH), which involves endogenous expression and tagging of baits and is suitable for studying native yeast membrane proteins, and traditional (tMYTH), which involves ectopic plasmid-based expression of tagged baits and is suitable for studying membrane proteins from other organisms. Here we provide an introduction to the MYTH assay, including both the iMYTH and tMYTH variants. MYTH can be set up in almost any laboratory environment, with results typically obtainable within 4 to 6 wk. © 2016 Cold Spring Harbor Laboratory Press.

  15. Bayesian Mapping of Genomewide Interacting Quantitative Trait Loci for Ordinal Traits

    PubMed Central

    Yi, Nengjun; Banerjee, Samprit; Pomp, Daniel; Yandell, Brian S.

    2007-01-01

    Development of statistical methods and software for mapping interacting QTL has been the focus of much recent research. We previously developed a Bayesian model selection framework, based on the composite model space approach, for mapping multiple epistatic QTL affecting continuous traits. In this study we extend the composite model space approach to complex ordinal traits in experimental crosses. We jointly model main and epistatic effects of QTL and environmental factors on the basis of the ordinal probit model (also called threshold model) that assumes a latent continuous trait underlies the generation of the ordinal phenotypes through a set of unknown thresholds. A data augmentation approach is developed to jointly generate the latent data and the thresholds. The proposed ordinal probit model, combined with the composite model space framework for continuous traits, offers a convenient way for genomewide interacting QTL analysis of ordinal traits. We illustrate the proposed method by detecting new QTL and epistatic effects for an ordinal trait, dead fetuses, in a F2 intercross of mice. Utility and flexibility of the method are also demonstrated using a simulated data set. Our method has been implemented in the freely available package R/qtlbim, which greatly facilitates the general usage of the Bayesian methodology for genomewide interacting QTL analysis for continuous, binary, and ordinal traits in experimental crosses. PMID:17507680

  16. Interactions between cochlear implant electrode insertion depth and frequency-place mapping

    NASA Astrophysics Data System (ADS)

    Başkent, Deniz; Shannon, Robert V.

    2005-03-01

    While new electrode designs allow deeper insertion and wider coverage in the cochlea, there is still considerable variation in the insertion depth of the electrode array among cochlear implant users. The present study measures speech recognition as a function of insertion depth, varying from a deep insertion of 10 electrodes at 28.8 mm to a shallow insertion of a single electrode at 7.2 mm, in four Med-El Combi 40+ users. Short insertion depths were simulated by inactivating apical electrodes. Speech recognition increased with deeper insertion, reaching an asymptotic level at 21.6 or 26.4 mm depending on the frequency-place map used. Başkent and Shannon [J. Acoust. Soc. Am. 116, 3130-3140 (2004)] showed that speech recognition by implant users was best when the acoustic input frequency was matched onto the cochlear location that normally processes that frequency range, minimizing the spectral distortions in the map. However, if an electrode array is not fully inserted into the cochlea, a matched map will result in the loss of considerable low-frequency information. The results show a strong interaction between the optimal frequency-place mapping and electrode insertion depth. Consistent with previous studies, frequency-place matching produced better speech recognition than compressing the full speech range onto the electrode array for full insertion ranges (20 to 25 mm from the round window). For shallower insertions (16.8 and 19.2 mm) a mild amount of frequency-place compression was better than truncating the frequency range to match the basal cochlear location. These results show that patients with shallow electrode insertions might benefit from a map that assigns a narrower frequency range than patients with full insertions. .

  17. Genomes as geography: using GIS technology to build interactive genome feature maps

    PubMed Central

    Dolan, Mary E; Holden, Constance C; Beard, M Kate; Bult, Carol J

    2006-01-01

    Background Many commonly used genome browsers display sequence annotations and related attributes as horizontal data tracks that can be toggled on and off according to user preferences. Most genome browsers use only simple keyword searches and limit the display of detailed annotations to one chromosomal region of the genome at a time. We have employed concepts, methodologies, and tools that were developed for the display of geographic data to develop a Genome Spatial Information System (GenoSIS) for displaying genomes spatially, and interacting with genome annotations and related attribute data. In contrast to the paradigm of horizontally stacked data tracks used by most genome browsers, GenoSIS uses the concept of registered spatial layers composed of spatial objects for integrated display of diverse data. In addition to basic keyword searches, GenoSIS supports complex queries, including spatial queries, and dynamically generates genome maps. Our adaptation of the geographic information system (GIS) model in a genome context supports spatial representation of genome features at multiple scales with a versatile and expressive query capability beyond that supported by existing genome browsers. Results We implemented an interactive genome sequence feature map for the mouse genome in GenoSIS, an application that uses ArcGIS, a commercially available GIS software system. The genome features and their attributes are represented as spatial objects and data layers that can be toggled on and off according to user preferences or displayed selectively in response to user queries. GenoSIS supports the generation of custom genome maps in response to complex queries about genome features based on both their attributes and locations. Our example application of GenoSIS to the mouse genome demonstrates the powerful visualization and query capability of mature GIS technology applied in a novel domain. Conclusion Mapping tools developed specifically for geographic data can be

  18. Multi-Modal, Multi-Touch Interaction with Maps in Disaster Management Applications

    NASA Astrophysics Data System (ADS)

    Paelke, V.; Nebe, K.; Geiger, C.; Klompmaker, F.; Fischer, H.

    2012-07-01

    Multi-touch interaction has become popular in recent years and impressive advances in technology have been demonstrated, with the presentation of digital maps as a common presentation scenario. However, most existing systems are really technology demonstrators and have not been designed with real applications in mind. A critical factor in the management of disaster situations is the access to current and reliable data. New sensors and data acquisition platforms (e.g. satellites, UAVs, mobile sensor networks) have improved the supply of spatial data tremendously. However, in many cases this data is not well integrated into current crisis management systems and the capabilities to analyze and use it lag behind sensor capabilities. Therefore, it is essential to develop techniques that allow the effective organization, use and management of heterogeneous data from a wide variety of data sources. Standard user interfaces are not well suited to provide this information to crisis managers. Especially in dynamic situations conventional cartographic displays and mouse based interaction techniques fail to address the need to review a situation rapidly and act on it as a team. The development of novel interaction techniques like multi-touch and tangible interaction in combination with large displays provides a promising base technology to provide crisis managers with an adequate overview of the situation and to share relevant information with other stakeholders in a collaborative setting. However, design expertise on the use of such techniques in interfaces for real-world applications is still very sparse. In this paper we report on interdisciplinary research with a user and application centric focus to establish real-world requirements, to design new multi-modal mapping interfaces, and to validate them in disaster management applications. Initial results show that tangible and pen-based interaction are well suited to provide an intuitive and visible way to control who is

  19. The interaction of high-resolution electrophoresis and computational analysis in genome mapping

    SciTech Connect

    Carrano, A.V.; Branscomb, E.W.; de Jong, P.J.; Mohrenweiser, H.; Olsen, A.; Slezak, T.

    1990-07-26

    The construction of physical maps and the determination of the DNA sequence of chromosome-size segments of the human genome is a complex, multidisciplinary undertaking. The approach we have taken to construct a physical map and sequence of human chromosome 19 typifies these interactions. We exploit the power of both acrylamide and agarose gel electrophoresis to provide a simple and versatile method for DNA fingerprinting and the creation of contigs or sets of overlapping genomic clones. Cosmid libraries are constructed from Yeast Artificial Chromosomes (YAC) clones or from flow-sorted chromosomes. Cosmid DNA isolated from the screened library array is cut with a combination of five restriction enzymes and the fragment ends labeled with one of four different fluorochromes. Our approach to contig construction uses a robotic system to label restriction fragments from cosmids with fluorochromes, use of an automated DNA sequencer to capture fragment mobility data in a high resolution multiplex mode processes the mobility data to determine fragment length and provide a statistical measure of overlap among cosmids; and display the contigs and underlying cosmids for operator interaction and access to a database. Data analyses and interactions are conducted over a network of SUN workstations using a set of software tools that we developed and coupled to a commercially available database. Applying these methods, we have analyzed 5154 cosmid clones and assembled 515 contigs for chromosome 19. Some of these contigs have been identified with known genes and many have been mapped to the chromosome by fluorescence in situ hybridization. Existing contigs are being extended by a combination of walking and fingerprinting. 21 refs., 2 figs.

  20. Mapping the bound conformation and protein interactions of microtubule destabilizing peptides by STD-NMR spectroscopy.

    PubMed

    Milton, Mark J; Thomas Williamson, R; Koehn, Frank E

    2006-08-15

    Using the hemiasterlin analogs taltobulin (I, HTI-286), II, and III as model compounds, we demonstrate that relaxation-compensated STD-NMR can be used as an effective tool to efficiently provide a qualitative epitope map for microtubule destabilizing peptides. Due to the disparate relaxation behavior of the protons in these model compounds, it was essential to collect STD with very short saturation times to render an accurate picture of the binding interaction. The conformation of HTI-286 (I) in complex with the protein was determined from TRNOESY/ROESY experiments and is similar to the X-ray crystal structure conformation observed for hemiasterlin methyl ester in the absence of protein.

  1. Mapping the distribution of specific antibody interaction forces on individual red blood cells

    NASA Astrophysics Data System (ADS)

    Yeow, Natasha; Tabor, Rico F.; Garnier, Gil

    2017-02-01

    Current blood typing methods rely on the agglutination of red blood cells (RBCs) to macroscopically indicate a positive result. An indirect agglutination mechanism is required when blood typing with IgG forms of antibodies. To date, the interaction forces between anti-IgG and IgG antibodies have been poorly quantified, and blood group related antigens have never been quantified with the atomic force microscope (AFM). Instead, the total intensity resulting from fluorescent-tagged antibodies adsorbed on RBC has been measured to calculate an average antigen density on a series of RBCs. In this study we mapped specific antibody interaction forces on the RBC surface. AFM cantilever tips functionalized with anti-IgG were used to probe RBCs incubated with specific IgG antibodies. This work provides unique insight into antibody-antigen interactions in their native cell-bound location, and crucially, on a per-cell basis rather than an ensemble average set of properties. Force profiles obtained from the AFM directly provide not only the anti-IgG - IgG antibody interaction force, but also the spatial distribution and density of antigens over a single cell. This new understanding might be translated into the development of very selective and quantitative interactions that underpin the action of drugs in the treatment of frontier illnesses.

  2. RefSOFI for Mapping Nanoscale Organization of Protein-protein Interactions in Living cells

    PubMed Central

    Hertel, Fabian; Mo, Gary C. H.; Duwé, Sam; Dedecker, Peter; Zhang, Jin

    2015-01-01

    Summary It has become increasingly clear that protein-protein interactions (PPIs) are compartmentalized in nanoscale domains that define the biochemical architecture of the cell. Despite tremendous advances in super-resolution imaging, strategies to observe PPIs at sufficient resolution to discern their organization are just emerging. Here we describe a strategy in which PPIs induce reconstitution of fluorescent proteins (FPs) that are capable of exhibiting single-molecule fluctuations suitable for Stochastic Optical Fluctuation Imaging (SOFI). Subsequently, spatial maps of these interactions can be resolved in super-resolution in living cells. Using this strategy, termed reconstituted fluorescence-based SOFI (refSOFI), we investigated the interaction between the endoplasmic reticulum Ca2+ sensor STIM1 and the pore-forming channel subunit ORAI1, a crucial process in store-operated Ca2+ entry (SOCE). Stimulating SOCE does not appear to change the size of existing STIM1/ORAI1 interaction puncta at the ER-plasma membrane junctions, but results in an apparent increase in the number of interaction puncta. PMID:26748717

  3. Mapping Protein-Ligand Interactions with Proteolytic Fragmentation, Hydrogen/Deuterium Exchange-Mass Spectrometry.

    PubMed

    Gallagher, Elyssia S; Hudgens, Jeffrey W

    2016-01-01

    Biological processes are the result of noncovalent, protein-ligand interactions, where the ligands range from small organic and inorganic molecules to lipids, nucleic acids, peptides, and proteins. Amide groups within proteins constantly exchange protons with water. When immersed in heavy water (D2O), mass spectrometry (MS) can measure the change of mass associated with the hydrogen to deuterium exchange (HDX). Protein-ligand interactions modify the hydrogen exchange rates of amide protons, and the measurement of the amide exchange rates can provide rich information regarding the dynamical structure of the protein-ligand complex. This chapter describes a protocol for conducting bottom-up, continuous uptake, proteolytic fragmentation HDX-MS experiments that can help identify and map the interacting peptides of a protein-ligand interface. This tutorial outlines the fundamental theory governing hydrogen exchange; provides practical information regarding the preparation of protein samples and solutions; and describes the exchange reaction, reaction quenching, enzymatic digestion, chromatographic separation, and peptide analysis by MS. Tables list representative combinations of fluidic components used by HDX-MS researchers and summarize the available HDX-MS analysis software packages. Additionally, two HDX-MS case studies are used to illustrate protein-ligand interactions involving: (1) a continuous sequence of interacting residues and (2) a set of discontinuously numbered residues, residing spatially near each other. © 2016 Elsevier Inc. All rights reserved.

  4. Mapping the distribution of specific antibody interaction forces on individual red blood cells

    PubMed Central

    Yeow, Natasha; Tabor, Rico F.; Garnier, Gil

    2017-01-01

    Current blood typing methods rely on the agglutination of red blood cells (RBCs) to macroscopically indicate a positive result. An indirect agglutination mechanism is required when blood typing with IgG forms of antibodies. To date, the interaction forces between anti-IgG and IgG antibodies have been poorly quantified, and blood group related antigens have never been quantified with the atomic force microscope (AFM). Instead, the total intensity resulting from fluorescent-tagged antibodies adsorbed on RBC has been measured to calculate an average antigen density on a series of RBCs. In this study we mapped specific antibody interaction forces on the RBC surface. AFM cantilever tips functionalized with anti-IgG were used to probe RBCs incubated with specific IgG antibodies. This work provides unique insight into antibody-antigen interactions in their native cell-bound location, and crucially, on a per-cell basis rather than an ensemble average set of properties. Force profiles obtained from the AFM directly provide not only the anti-IgG – IgG antibody interaction force, but also the spatial distribution and density of antigens over a single cell. This new understanding might be translated into the development of very selective and quantitative interactions that underpin the action of drugs in the treatment of frontier illnesses. PMID:28157207

  5. A comprehensive Plasmodium falciparum protein interaction map reveals a distinct architecture of a core interactome

    PubMed Central

    Wuchty, Stefan; Adams, John H.; Ferdig, Michael T.

    2011-01-01

    We derive a map of protein interactions in the parasite P. falciparum from conserved interactions in S. cerevisiae, C. elegans, D. melanogaster and E. coli and pool them with experimental interaction data. The application of a clique-percolation algorithm allows us to find overlapping clusters, strongly correlated with yeast specific conserved protein complexes. Such clusters contain core activities that govern gene expression, largely dominated by components of protein production and degradation processes as well as RNA metabolism. A critical role of protein hubs in the interactome of P. falciparum is supported by their appearance in multiple clusters and the tendencies of their interactions to reach into many distinct protein clusters. Parasite proteins with a human ortholog tend to appear in single complexes. Annotating each protein with the stage where it is maximally expressed we observe a high level of cluster integrity in the ring stage. While we find no signal in the trophozoite phase, expression patterns are reversed in the schizont phase, implying a preponderance of parasite specific functions in this late, invasive schizont stage. As such, the inference of potential protein interactions and their analysis contributes to our understanding of the parasite, indicating basic pathways and processes as unique targets for therapeutic intervention. PMID:19333996

  6. Software Mapping Assessment Tool Documenting Behavioral Content in Computer Interaction: Examples of Mapped Problems with "Kid Pix" Program

    ERIC Educational Resources Information Center

    Bayram, Servet

    2005-01-01

    The purpose of software mapping is to delineate a method for software menu, tool, and palette use in the construction of elementary school science and mathematics curriculum activities. With this method, software "maps" were created for traversing science and math curriculum problems and activities using software. The other purpose of…

  7. Gene-gene interaction and RNA splicing profiles of MAP2K4 gene in rheumatoid arthritis.

    PubMed

    Shchetynsky, Klementy; Protsyuk, Darya; Ronninger, Marcus; Diaz-Gallo, Lina-Marcela; Klareskog, Lars; Padyukov, Leonid

    2015-05-01

    We performed gene-gene interaction analysis, with HLA-DRB1 shared epitope (SE) alleles for 195 SNPs within immunologically important MAP2K, MAP3K and MAP4K gene families, in 2010 rheumatoid arthritis (RA) patients and 2280 healthy controls. We found a significant statistical interaction for rs10468473 with SE alleles in autoantibody-positive RA. Individuals heterozygous for rs10468473 demonstrated higher expression of total MAP2K4 mRNA in blood, compared to A-allele homozygous. We discovered a novel, putatively translated, "cassette exon" RNA splice form of MAP2K4, differentially expressed in peripheral blood mononuclear cells from 88 RA cases and controls. Within the group of RA patients, we observed a correlation of MAP2K4 isoform expression with carried SE alleles, autoantibody, and rheumatoid factor profiles. TNF-dependent modulation of isoform expression pattern was detected in the Jurkat cell line. Our data suggest a genetic interaction between MAP2K4 and HLA-DRB1, and the importance of rs10468473 and MAP2K4 splice variants in the development of autoantibody-positive RA. Copyright © 2015. Published by Elsevier Inc.

  8. Topological and functional analysis of nonalcoholic steatohepatitis through protein interaction mapping

    PubMed Central

    Asadzadeh-Aghdaee, Hamid; Mansouri, Vahid; Peyvandi, Ali Asghar; Moztarzadeh, Fathollah; Okhovatian, Farshad; Lahmi, Farhad; Vafaee, Reza; Zali, Mohammad Reza

    2016-01-01

    Aim: The corresponding proteins are important for network mapping since the interaction analysis can provide a new interpretation about disease underlying mechanisms as the aim of this study. Backgroud: Nonalcoholic steatohepatitis (NASH) is one of the main causes of liver disease in the world. It has been known with many susceptible proteins that play essential role in its pathogenesis. Methods: In this paper, protein-protein interaction (PPI) network analysis of fatty liver disease retrieved from STRING db by the application of Cytoscape Software. ClueGO analyzed the associated pathways for the selected top proteins. Results: INS, PPARA, LEP, SREBF1, and ALB are the introduced biomarker panel for fatty liver disease. Conclusion: It seems that pathways related to insulin have a prominent role in fatty liver disease. Therefore, investigation in this case is required to confirm the possible linkage of introduced panel and involvement of insulin pathway in the disease. PMID:28224024

  9. Web GIS in practice V: 3-D interactive and real-time mapping in Second Life

    PubMed Central

    Boulos, Maged N Kamel; Burden, David

    2007-01-01

    This paper describes technologies from Daden Limited for geographically mapping and accessing live news stories/feeds, as well as other real-time, real-world data feeds (e.g., Google Earth KML feeds and GeoRSS feeds) in the 3-D virtual world of Second Life, by plotting and updating the corresponding Earth location points on a globe or some other suitable form (in-world), and further linking those points to relevant information and resources. This approach enables users to visualise, interact with, and even walk or fly through, the plotted data in 3-D. Users can also do the reverse: put pins on a map in the virtual world, and then view the data points on the Web in Google Maps or Google Earth. The technologies presented thus serve as a bridge between mirror worlds like Google Earth and virtual worlds like Second Life. We explore the geo-data display potential of virtual worlds and their likely convergence with mirror worlds in the context of the future 3-D Internet or Metaverse, and reflect on the potential of such technologies and their future possibilities, e.g. their use to develop emergency/public health virtual situation rooms to effectively manage emergencies and disasters in real time. The paper also covers some of the issues associated with these technologies, namely user interface accessibility and individual privacy. PMID:18042275

  10. The Potential for Signal Integration and Processing in Interacting Map Kinase Cascades

    PubMed Central

    Schwacke, John H.; Voit, Eberhard O.

    2009-01-01

    The cellular response to environmental stimuli requires biochemical information processing through which sensory inputs and cellular status are integrated and translated into appropriate responses by way of interacting networks of enzymes. One such network, the Mitogen Activated Protein (MAP) kinase cascade is a highly conserved signal transduction module that propagates signals from cell surface receptors to various cytosolic and nuclear targets by way of a phosphorylation cascade. We have investigated the potential for signal processing within a network of interacting feed-forward kinase cascades typified by the MAP kinase cascade. A genetic algorithm was used to search for sets of kinetic parameters demonstrating representative key input-output patterns of interest. We discuss two of the networks identified in our study, one implementing the exclusive-or function (XOR) and another implementing what we refer to as an in-band detector (IBD) or two-sided threshold. These examples confirm the potential for logic and amplitude-dependent signal processing in interacting MAP kinase cascades demonstrating limited cross-talk. Specifically, the XOR function allows the network to respond to either one, but not both signals simultaneously, while the IBD permits the network to respond exclusively to signals within a given range of strength, and to suppress signals below as well as above this range. The solution to the XOR problem is interesting in that it requires only two interacting pathways, crosstalk at only one layer, and no feedback or explicit inhibition. These types of responses are not only biologically relevant but constitute signal processing modules that can be combined to create other logical functions and that, in contrast to amplification, cannot be achieved with a single cascade or with two non-interacting cascades. Our computational results revealed surprising similarities between experimental data describing the JNK/MKK4/MKK7 pathway and the solution for

  11. Mapping burn severity, pine beetle infestation, and their interaction at the High Park Fire

    NASA Astrophysics Data System (ADS)

    Stone, Brandon

    North America's western forests are experiencing wildfire and mountain pine beetle (MPB) disturbances that are unprecedented in the historic record, but it remains unclear whether and how MPB infestation influences post-infestation fire behavior. The 2012 High Park Fire burned in an area that's estimated to have begun a MPB outbreak cycle within five years before the wildfire, resulting in a landscape in which disturbance interactions can be studied. A first step in studying these interactions is mapping regions of beetle infestation and post-fire disturbance. We implemented an approach for mapping beetle infestation and burn severity using as source data three 5 m resolution RapidEye satellite images (two pre-fire, one post-fire). A two-tiered methodology was developed to overcome the spatial limitations of many classification approaches through explicit analyses at both pixel and plot level. Major land cover classes were photo-interpreted at the plot-level and their spectral signature used to classify 5 m images. A new image was generated at 25 m resolution by tabulating the fraction of coincident 5 m pixels in each cover class. The original photo interpretation was then used to train a second classification using as its source image the new 25 m image. Maps were validated using k-fold analysis of the original photo interpretation, field data collected immediately post-fire, and publicly available classifications. To investigate the influence of pre-fire beetle infestation on burn severity within the High Park Fire, we fit a log-linear model of conditional independence to our thematic maps after controlling for forest cover class and slope aspect. Our analysis revealed a high co-occurrence of severe burning and beetle infestation within high elevation lodgepole pine stands, but did not find statistically significant evidence that infected stands were more likely to burn severely than similar uninfected stands. Through an inspection of the year-to-year changes in

  12. Mapping QTL main and interaction influences on milling quality in elite US rice germplasm.

    PubMed

    Nelson, J C; McClung, A M; Fjellstrom, R G; Moldenhauer, K A K; Boza, E; Jodari, F; Oard, J H; Linscombe, S; Scheffler, B E; Yeater, K M

    2011-02-01

    Rice (Oryza sativa L.) head-rice yield (HR) is a key export and domestic quality trait whose genetic control is poorly understood. With the goal of identifying genomic regions influencing HR, quantitative-trait-locus (QTL) mapping was carried out for quality-related traits in recombinant inbred lines (RILs) derived from crosses of common parent Cypress, a high-HR US japonica cultivar, with RT0034, a low-HR indica line (129 RILs) and LaGrue, a low-HR japonica cultivar (298 RILs), grown in two US locations in 2005-2007. Early heading increased HR in the Louisiana (LA) but not the Arkansas (AR) location. Fitting QTL-mapping models to separate QTL main and QTL × environment interaction (QEI) effects and identify epistatic interactions revealed six main-effect HR QTLs in the two crosses, at four of which Cypress contributed the increasing allele. Multi-QTL models accounted for 0.36 of genetic and 0.21 of genetic × environment interaction of HR in MY1, and corresponding proportions of 0.25 and 0.37 in MY2. The greater HR advantage of Cypress in LA than in AR corresponded to a genomewide pattern of opposition of HR-increasing QTL effects by AR-specific effects, suggesting a selection strategy for improving this cultivar for AR. Treating year-location combinations as independent environments resulted in underestimation of QEI effects, evidently owing to lower variation among years within location than between location. Identification of robust HR QTLs in elite long-grain germplasm is suggested to require more detailed attention to the interaction of plant and grain development parameters with environmental conditions than has been given to date.

  13. Genotype by watering regime interaction in cultivated tomato: lessons from linkage mapping and gene expression.

    PubMed

    Albert, Elise; Gricourt, Justine; Bertin, Nadia; Bonnefoi, Julien; Pateyron, Stéphanie; Tamby, Jean-Philippe; Bitton, Frédérique; Causse, Mathilde

    2016-02-01

    In tomato, genotype by watering interaction resulted from genotype re-ranking more than scale changes. Interactive QTLs according to watering regime were detected. Differentially expressed genes were identified in some intervals. As a result of climate change, drought will increasingly limit crop production in the future. Studying genotype by watering regime interactions is necessary to improve plant adaptation to low water availability. In cultivated tomato (Solanum lycopersicum L.), extensively grown in dry areas, well-mastered water deficits can stimulate metabolite production, increasing plant defenses and concentration of compounds involved in fruit quality, at the same time. However, few tomato Quantitative Trait Loci (QTLs) and genes involved in response to drought are identified or only in wild species. In this study, we phenotyped a population of 119 recombinant inbred lines derived from a cross between a cherry tomato and a large fruit tomato, grown in greenhouse under two watering regimes, in two locations. A large genetic variability was measured for 19 plant and fruit traits, under the two watering treatments. Highly significant genotype by watering regime interactions were detected and resulted from re-ranking more than scale changes. The population was genotyped for 679 SNP markers to develop a genetic map. In total, 56 QTLs were identified among which 11 were interactive between watering regimes. These later mainly exhibited antagonist effects according to watering treatment. Variation in gene expression in leaves of parental accessions revealed 2259 differentially expressed genes, among which candidate genes presenting sequence polymorphisms were identified under two main interactive QTLs. Our results provide knowledge about the genetic control of genotype by watering regime interactions in cultivated tomato and the possible use of deficit irrigation to improve tomato quality.

  14. The Westfield River Watershed Interactive Atlas: mapping recreation data on the web

    Treesearch

    Robert S. Bristow; Steven Riberdy

    2002-01-01

    Imagine searching the web to create a map to your house. You could use one of the many Internet mapping sites like MapBlast™ or MapQuest™ to create such a map. But maybe you wish to get a map of trails for the Grand Canyon. The National Park Service web site could serve that need. Or you may wish to get a map to show you the way from the Orlando...

  15. Neurophysiological and simulation studies of striate cortex receptive field maps: the role of intracortical interneuronal interactions.

    PubMed

    Lazareva, N A; Saltykov, K A; Shevelev, I A; Tikhomirov, A S; Novikova, R V; Tsutskiridze, D Yu

    2007-07-01

    Acute experiments on 27 adult anesthetized and immobilized cats investigated 101 on and off receptive fields in 67 neurons in visual cortex field 17 by mapping using single local stimuli presented sequentially at different parts of the visual field, as well as in combination with additional stimulation of the center of the receptive field. Both classical and combined mapping identified receptive fields with single receptive zones (63.4% and 29.3% respectively), along with fields consisting of several (2-5) excitatory and/or inhibitory zones (36.6% and 70.7%). We provide the first report of receptive fields with horseshoe, cross, and T shapes. Simulations of horizontal interneuronal interactions in the visual cortex responsible for the multiplicity of excitatory and inhibitory zones of receptive fields were performed. A role for cooperative interactions of neurons in this effect was demonstrated. The possible functional role of receptive fields of different types in extracting the features of visual images is discussed.

  16. An Interactive Macrophage Signal Transduction Map Facilitates Comparative Analyses of High-Throughput Data.

    PubMed

    Wentker, Pia; Eberhardt, Martin; Dreyer, Florian S; Bertrams, Wilhelm; Cantone, Martina; Griss, Kathrin; Schmeck, Bernd; Vera, Julio

    2017-03-01

    Macrophages (Mϕs) are key players in the coordination of the lifesaving or detrimental immune response against infections. The mechanistic understanding of the functional modulation of Mϕs by pathogens and pharmaceutical interventions at the signal transduction level is still far from complete. The complexity of pathways and their cross-talk benefits from holistic computational approaches. In the present study, we reconstructed a comprehensive, validated, and annotated map of signal transduction pathways in inflammatory Mϕs based on the current literature. In a second step, we selectively expanded this curated map with database knowledge. We provide both versions to the scientific community via a Web platform that is designed to facilitate exploration and analysis of high-throughput data. The platform comes preloaded with logarithmic fold changes from 44 data sets on Mϕ stimulation. We exploited three of these data sets-human primary Mϕs infected with the common lung pathogens Streptococcus pneumoniae, Legionella pneumophila, or Mycobacterium tuberculosis-in a case study to show how our map can be customized with expression data to pinpoint regulated subnetworks and druggable molecules. From the three infection scenarios, we extracted a regulatory core of 41 factors, including TNF, CCL5, CXCL10, IL-18, and IL-12 p40, and identified 140 drugs targeting 16 of them. Our approach promotes a comprehensive systems biology strategy for the exploitation of high-throughput data in the context of Mϕ signal transduction. In conclusion, we provide a set of tools to help scientists unravel details of Mϕ signaling. The interactive version of our Mϕ signal transduction map is accessible online at https://vcells.net/macrophage. Copyright © 2017 by The American Association of Immunologists, Inc.

  17. Compositional mapping of bitumen using local electrostatic force interactions in atomic force microscopy.

    PubMed

    Magonov, Sergei; Alexander, John; Surtchev, Marko; Hung, Albert M; Fini, Elham H

    2017-02-01

    In recent years, many researchers have investigated bitumen surface morphology, especially the so-called bee-like structures, in an attempt to relate the chemical composition and molecular conformation to bitumen micromechanics and ultimately performance properties. Even though recent studies related surface morphology and its evolution to stiffness and stress localization, the complex chemical nature of bitumen and its time- and temperature-dependent properties still engender significant questions about the nature and origin of the observed morphological features and how they evolve due to exposure to various environmental and loading conditions. One such question is whether the observed surface features are formed from wax or from the coprecipitation of wax and asphaltene. Our prior work was mainly theoretical; it used density functional theory and showed that the coprecipitation theory may not stand, mainly because wax-asphaltene interactions are not thermodynamically favourable compared to wax-wax interactions. This paper presents a comprehensive approach based on experiments to study surface morphology of bitumen and conduct compositional mapping to shed light on the origin of the bee-like surface morphological features. We used Atomic Force Microscopy (AFM), with the main focus being on single-pass detection and mapping of local electric properties, as a novel approach to enhance existing compositional mapping techniques. This method was found to be highly effective in differentiating various domains with respect to their polarity. The results of our study favour the hypothesis that the bee-like features are mainly composed of wax, including a variety of alkanes. © 2016 The Authors Journal of Microscopy © 2016 Royal Microscopical Society.

  18. Molstack - interactive visualization tool for presentation, interpretation, and validation of macromolecules and electron density maps.

    PubMed

    Porebski, Przemyslaw J; Sroka, Piotr; Zheng, Heping; Cooper, David R; Minor, Wladek

    2017-08-17

    Our understanding of the world of biomolecular structures is based upon the interpretation of macromolecular models, of which ∼ 90% are themselves the interpretation of electron density maps. This structural information guides scientific progress and exploration in many biomedical disciplines. The Protein Data Bank's web portals have made these structures available for mass scientific consumption and greatly broaden the scope of information presented in scientific publications. The portals provide numerous quality metrics; however, the portion of the structure that is most vital for interpretation of the function may have the most difficult to interpret electron density and this ambiguity is not reflected by any single metric. The possible consequences of basing research on suboptimal models makes it imperative to inspect the agreement of a model with its experimental evidence. Molstack, a web based interactive publishing platform for structural data, allows users to present density maps and structural models by displaying a collection of maps and models, including different interpretation of one's own data, re-refinements and corrections of existing structures. Molstack organizes the sharing and dissemination of these structural models along with their experimental evidence as an interactive session. Molstack was designed with three groups of users in mind; researchers can present the evidence of their interpretation, reviewers and readers can independently judge the experimental evidence of the authors' conclusions, and other researchers can present or even publish their new hypotheses in the context of prior results. The server is available at http://molstack.bioreproducibility.org. This article is protected by copyright. All rights reserved. © 2017 The Protein Society.

  19. A protein-protein interaction map of yeast RNA polymerase III.

    PubMed

    Flores, A; Briand, J F; Gadal, O; Andrau, J C; Rubbi, L; Van Mullem, V; Boschiero, C; Goussot, M; Marck, C; Carles, C; Thuriaux, P; Sentenac, A; Werner, M

    1999-07-06

    The structure of the yeast RNA polymerase (pol) III was investigated by exhaustive two-hybrid screening using a library of random genomic fragments fused to the Gal4 activation domain. This procedure allowed us to identify contacts between individual polypeptides, localize the contact domains, and deduce a protein-protein interaction map of the multisubunit enzyme. In all but one case, pol III subunits were able to interact in vivo with one or sometimes two partner subunits of the enzyme or with subunits of TFIIIC. Four subunits that are common to pol I, II, and III (ABC27, ABC14.5, ABC10alpha, and ABC10beta), two that are common to pol I and III (AC40 and AC19), and one pol III-specific subunit (C11) can associate with defined regions of the two large subunits. These regions overlapped with highly conserved domains. C53, a pol III-specific subunit, interacted with a 37-kDa polypeptide that copurifies with the enzyme and therefore appears to be a unique pol III subunit (C37). Together with parallel interaction studies based on dosage-dependent suppression of conditional mutants, our data suggest a model of the pol III preinitiation complex.

  20. Features of the Chaperone Cellular Network Revealed through Systematic Interaction Mapping.

    PubMed

    Rizzolo, Kamran; Huen, Jennifer; Kumar, Ashwani; Phanse, Sadhna; Vlasblom, James; Kakihara, Yoshito; Zeineddine, Hussein A; Minic, Zoran; Snider, Jamie; Wang, Wen; Pons, Carles; Seraphim, Thiago V; Boczek, Edgar Erik; Alberti, Simon; Costanzo, Michael; Myers, Chad L; Stagljar, Igor; Boone, Charles; Babu, Mohan; Houry, Walid A

    2017-09-12

    A comprehensive view of molecular chaperone function in the cell was obtained through a systematic global integrative network approach based on physical (protein-protein) and genetic (gene-gene or epistatic) interaction mapping. This allowed us to decipher interactions involving all core chaperones (67) and cochaperones (15) of Saccharomyces cerevisiae. Our analysis revealed the presence of a large chaperone functional supercomplex, which we named the naturally joined (NAJ) chaperone complex, encompassing Hsp40, Hsp70, Hsp90, AAA+, CCT, and small Hsps. We further found that many chaperones interact with proteins that form foci or condensates under stress conditions. Using an in vitro reconstitution approach, we demonstrate condensate formation for the highly conserved AAA+ ATPases Rvb1 and Rvb2, which are part of the R2TP complex that interacts with Hsp90. This expanded view of the chaperone network in the cell clearly demonstrates the distinction between chaperones having broad versus narrow substrate specificities in protein homeostasis. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  1. AxiSketcher: Interactive Nonlinear Axis Mapping of Visualizations through User Drawings.

    PubMed

    Kwon, Bum Chul; Kim, Hannah; Wall, Emily; Choo, Jaegul; Park, Haesun; Endert, Alex

    2017-01-01

    Visual analytics techniques help users explore high-dimensional data. However, it is often challenging for users to express their domain knowledge in order to steer the underlying data model, especially when they have little attribute-level knowledge. Furthermore, users' complex, high-level domain knowledge, compared to low-level attributes, posits even greater challenges. To overcome these challenges, we introduce a technique to interpret a user's drawings with an interactive, nonlinear axis mapping approach called AxiSketcher. This technique enables users to impose their domain knowledge on a visualization by allowing interaction with data entries rather than with data attributes. The proposed interaction is performed through directly sketching lines over the visualization. Using this technique, users can draw lines over selected data points, and the system forms the axes that represent a nonlinear, weighted combination of multidimensional attributes. In this paper, we describe our techniques in three areas: 1) the design space of sketching methods for eliciting users' nonlinear domain knowledge; 2) the underlying model that translates users' input, extracts patterns behind the selected data points, and results in nonlinear axes reflecting users' complex intent; and 3) the interactive visualization for viewing, assessing, and reconstructing the newly formed, nonlinear axes.

  2. An Overview of Plume Tracker: Mapping Volcanic Emissions with Interactive Radiative Transfer Modeling

    NASA Astrophysics Data System (ADS)

    Realmuto, V. J.; Berk, A.; Guiang, C.

    2014-12-01

    Infrared remote sensing is a vital tool for the study of volcanic plumes, and radiative transfer (RT) modeling is required to derive quantitative estimation of the sulfur dioxide (SO2), sulfate aerosol (SO4), and silicate ash (pulverized rock) content of these plumes. In the thermal infrared, we must account for the temperature, emissivity, and elevation of the surface beneath the plume, plume altitude and thickness, and local atmospheric temperature and humidity. Our knowledge of these parameters is never perfect, and interactive mapping allows us to evaluate the impact of these uncertainties on our estimates of plume composition. To enable interactive mapping, the Jet Propulsion Laboratory is collaborating with Spectral Sciences, Inc., (SSI) to develop the Plume Tracker toolkit. This project is funded by a NASA AIST Program Grant (AIST-11-0053) to SSI. Plume Tracker integrates (1) retrieval procedures for surface temperature and emissivity, SO2, NH3, or CH4 column abundance, and scaling factors for H2O vapor and O3 profiles, (2) a RT modeling engine based on MODTRAN, and (3) interactive visualization and analysis utilities under a single graphics user interface. The principal obstacle to interactive mapping is the computational overhead of the RT modeling engine. Under AIST-11-0053 we have achieved a 300-fold increase in the performance of the retrieval procedures through the use of indexed caches of model spectra, optimization of the minimization procedures, and scaling of the effects of surface temperature and emissivity on model radiance spectra. In the final year of AIST-11-0053 we will implement parallel processing to exploit multi-core CPUs and cluster computing, and optimize the RT engine to eliminate redundant calculations when iterating over a range of gas concentrations. These enhancements will result in an additional 8 - 12X increase in performance. In addition to the improvements in performance, we have improved the accuracy of the Plume Tracker

  3. WHERE MULTIFUNCTIONAL DNA REPAIR PROTEINS MEET: MAPPING THE INTERACTION DOMAINS BETWEEN XPG AND WRN

    SciTech Connect

    Rangaraj, K.; Cooper, P.K.; Trego, K.S.

    2009-01-01

    The rapid recognition and repair of DNA damage is essential for the maintenance of genomic integrity and cellular survival. Multiple complex and interconnected DNA damage responses exist within cells to preserve the human genome, and these repair pathways are carried out by a specifi c interplay of protein-protein interactions. Thus a failure in the coordination of these processes, perhaps brought about by a breakdown in any one multifunctional repair protein, can lead to genomic instability, developmental and immunological abnormalities, cancer and premature aging. This study demonstrates a novel interaction between two such repair proteins, Xeroderma pigmentosum group G protein (XPG) and Werner syndrome helicase (WRN), that are both highly pleiotropic and associated with inherited genetic disorders when mutated. XPG is a structure-specifi c endonuclease required for the repair of UV-damaged DNA by nucleotide excision repair (NER), and mutations in XPG result in the diseases Xeroderma pigmentosum (XP) and Cockayne syndrome (CS). A loss of XPG incision activity results in XP, whereas a loss of non-enzymatic function(s) of XPG causes CS. WRN is a multifunctional protein involved in double-strand break repair (DSBR), and consists of 3’–5’ DNA-dependent helicase, 3’–5’ exonuclease, and single-strand DNA annealing activities. Nonfunctional WRN protein leads to Werner syndrome, a premature aging disorder with increased cancer incidence. Far Western analysis was used to map the interacting domains between XPG and WRN by denaturing gel electrophoresis, which separated purifi ed full length and recombinant XPG and WRN deletion constructs, based primarily upon the length of each polypeptide. Specifi c interacting domains were visualized when probed with the secondary protein of interest which was then detected by traditional Western analysis using the antibody of the secondary protein. The interaction between XPG and WRN was mapped to the C-terminal region of

  4. TheCellMap.org: A Web-Accessible Database for Visualizing and Mining the Global Yeast Genetic Interaction Network.

    PubMed

    Usaj, Matej; Tan, Yizhao; Wang, Wen; VanderSluis, Benjamin; Zou, Albert; Myers, Chad L; Costanzo, Michael; Andrews, Brenda; Boone, Charles

    2017-03-21

    Providing access to quantitative genomic data is key to ensure large-scale data validation and promote new discoveries. TheCellMap.org serves as a central repository for storing and analyzing quantitative genetic interaction data produced by genome-scale Synthetic Genetic Array (SGA) experiments with the budding yeast Saccharomyces cerevisiae In particular, TheCellMap.org allows users to easily access, visualize, explore and functionally annotate genetic interactions, or to extract and reorganize sub-networks, using data-driven network layouts in an intuitive and interactive manner.

  5. Genome contact map explorer: a platform for the comparison, interactive visualization and analysis of genome contact maps.

    PubMed

    Kumar, Rajendra; Sobhy, Haitham; Stenberg, Per; Lizana, Ludvig

    2017-09-29

    Hi-C experiments generate data in form of large genome contact maps (Hi-C maps). These show that chromosomes are arranged in a hierarchy of three-dimensional compartments. But to understand how these compartments form and by how much they affect genetic processes such as gene regulation, biologists and bioinformaticians need efficient tools to visualize and analyze Hi-C data. However, this is technically challenging because these maps are big. In this paper, we remedied this problem, partly by implementing an efficient file format and developed the genome contact map explorer platform. Apart from tools to process Hi-C data, such as normalization methods and a programmable interface, we made a graphical interface that let users browse, scroll and zoom Hi-C maps to visually search for patterns in the Hi-C data. In the software, it is also possible to browse several maps simultaneously and plot related genomic data. The software is openly accessible to the scientific community. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  6. GPU-Based Interactive Exploration and Online Probability Maps Calculation for Visualizing Assimilated Ocean Ensembles Data

    NASA Astrophysics Data System (ADS)

    Hoteit, I.; Hollt, T.; Hadwiger, M.; Knio, O. M.; Gopalakrishnan, G.; Zhan, P.

    2016-02-01

    Ocean reanalyses and forecasts are nowadays generated by combining ensemble simulations with data assimilation techniques. Most of these techniques resample the ensemble members after each assimilation cycle. Tracking behavior over time, such as all possible paths of a particle in an ensemble vector field, becomes very difficult, as the number of combinations rises exponentially with the number of assimilation cycles. In general a single possible path is not of interest but only the probabilities that any point in space might be reached by a particle at some point in time. We present an approach using probability-weighted piecewise particle trajectories to allow for interactive probability mapping. This is achieved by binning the domain and splitting up the tracing process into the individual assimilation cycles, so that particles that fall into the same bin after a cycle can be treated as a single particle with a larger probability as input for the next cycle. As a result we loose the possibility to track individual particles, but can create probability maps for any desired seed at interactive rates. The technique is integrated in an interactive visualization system that enables the visual analysis of the particle traces side by side with other forecast variables, such as the sea surface height, and their corresponding behavior over time. By harnessing the power of modern graphics processing units (GPUs) for visualization as well as computation, our system allows the user to browse through the simulation ensembles in real-time, view specific parameter settings or simulation models and move between different spatial or temporal regions without delay. In addition our system provides advanced visualizations to highlight the uncertainty, or show the complete distribution of the simulations at user-defined positions over the complete time series of the domain.

  7. A simple thermal mapping method for seasonal spatial patterns of groundwater-surface water interaction

    NASA Astrophysics Data System (ADS)

    Anibas, Christian; Buis, Kerst; Verhoeven, Ronny; Meire, Patrick; Batelaan, Okke

    2011-01-01

    SummaryA simple thermal mapping method for simulating seasonal and spatial patterns of groundwater-surface water interaction is developed and tested for a segment of the Aa River, Belgium. Spatially distributed temperature profiles in the hyporheic zone of the river are measured in winter and summer seasons of three consecutive years. Inverse modeling of the one-dimensional heat transport equation is applied to estimate vertical advective fluxes using the numerical STRIVE model and an analytical model. Results of the study show that seasonal flux estimates for summer and winter can be derived with a minimum data input and simulation effort. The estimated fluxes are analyzed via non-parametric statistical tests, while spatial interpolation techniques are used to generate maps of distributed flux exchange. The estimated seepage is compared with volumetric flux obtained from piezometer measurements and output of a groundwater model. The thermal method shows higher discharge rates in winter and that the relative contribution of exfiltration to the river discharge is higher in summer. A higher flux and a more heterogeneous flow pattern are observed in the upper reach of the river compared to the lower reach. This spatial difference shows the importance of the local geomorphology and to a lesser extent the hydrogeologic setting on hyporheic flux exchange in the river. A significantly higher flux is noted on the banks than in the center of the river, which is driven by the relatively high hydraulic conductivity of the river banks. It is concluded that bank flow in groundwater-surface water interaction deserves more attention. The main channel of the Aa River alone accounts for about 15% of the total river discharge at its outlet. As the developed thermal method is cost-effective, simple and fast, it is recommended for use in identifying zones of interest in initial stages of field investigations of groundwater-surface water interaction.

  8. MAP4 Mechanism that Stabilizes Mitochondrial Permeability Transition in Hypoxia: Microtubule Enhancement and DYNLT1 Interaction with VDAC1

    PubMed Central

    Zhang, Yi-ming; Zhang, Jia-ping; Hu, Jiong-yu; Zhang, Qiong; Dai, Xia; Teng, Miao; Zhang, Dong-xia; Huang, Yue-sheng

    2011-01-01

    Mitochondrial membrane permeability has received considerable attention recently because of its key role in apoptosis and necrosis induced by physiological events such as hypoxia. The manner in which mitochondria interact with other molecules to regulate mitochondrial permeability and cell destiny remains elusive. Previously we verified that hypoxia-induced phosphorylation of microtubule-associated protein 4 (MAP4) could lead to microtubules (MTs) disruption. In this study, we established the hypoxic (1% O2) cell models of rat cardiomyocytes, H9c2 and HeLa cells to further test MAP4 function. We demonstrated that increase in the pool of MAP4 could promote the stabilization of MT networks by increasing the synthesis and polymerization of tubulin in hypoxia. Results showed MAP4 overexpression could enhance cell viability and ATP content under hypoxic conditions. Subsequently we employed a yeast two-hybrid system to tag a protein interacting with mitochondria, dynein light chain Tctex-type 1 (DYNLT1), by hVDAC1 bait. We confirmed that DYNLT1 had protein-protein interactions with voltage-dependent anion channel 1 (VDAC1) using co-immunoprecipitation; and immunofluorescence technique showed that DYNLT1 was closely associated with MTs and VDAC1. Furthermore, DYNLT1 interactions with MAP4 were explored using a knockdown technique. We thus propose two possible mechanisms triggered by MAP4: (1) stabilization of MT networks, (2) DYNLT1 modulation, which is connected with VDAC1, and inhibition of hypoxia-induced mitochondrial permeabilization. PMID:22164227

  9. Two domains of interaction with calcium binding proteins can be mapped using fragments of calponin.

    PubMed Central

    Wills, F. L.; McCubbin, W. D.; Gimona, M.; Strasser, P.; Kay, C. M.

    1994-01-01

    Native calponin is able to bind 2 mol of calcium binding protein (CaBP) per mole calponin. This study extends this observation to define the 2 domains of interaction, one of which is near the actin binding site, and the other in the amino-terminal region of calponin. Also, the first evidence for a differentiation in the response of calponin to interaction with caltropin versus calmodulin is demonstrated. The binding of caltropin to cleavage and recombinant fragments of calponin was determined by 3 techniques: tryptophan fluorescence of the fragments, CD measurements to determine secondary structure changes, and analytical ultracentrifugation. In order to delineate the sites of interaction, 3 fragments of calponin have been studied. From a cyanogen bromide cleavage of calponin, residues 2-51 were isolated. This fragment is shown to bind to CaBPs and the affinity for caltropin is slightly higher than that for calmodulin. A carboxyl-terminal truncated mutant of calponin comprising residues 1-228 (CP 1-228) has been produced by recombinant techniques. Analytical ultracentrifugation has shown that CP 1-228, like the parent calponin, is able to bind 2 mol of caltropin per mol of 1-228 in a Ca(2+)-dependent fashion, indicating that there is a second site of interaction between residues 52-228. Temperature denaturation of the carboxyl-terminal truncated fragment compared with whole calponin show that the carboxyl-terminal region does not change the temperature at which calponin melts; however, there is greater residual secondary structure with whole calponin versus the fragment. A second mutant produced through recombinant techniques comprises residues 45-228 and is also able to bind caltropin, thus mapping the location of the second site of interaction to near the actin binding site. PMID:7756987

  10. Association mapping and gene-gene interaction for stem rust resistance in CIMMYT spring wheat germplasm.

    PubMed

    Yu, Long-Xi; Lorenz, Aaron; Rutkoski, Jessica; Singh, Ravi P; Bhavani, Sridhar; Huerta-Espino, Julio; Sorrells, Mark E

    2011-12-01

    The recent emergence of wheat stem rust Ug99 and evolution of new races within the lineage threatens global wheat production because they overcome widely deployed stem rust resistance (Sr) genes that had been effective for many years. To identify loci conferring adult plant resistance to races of Ug99 in wheat, we employed an association mapping approach for 276 current spring wheat breeding lines from the International Maize and Wheat Improvement Center (CIMMYT). Breeding lines were genotyped with Diversity Array Technology (DArT) and microsatellite markers. Phenotypic data was collected on these lines for stem rust race Ug99 resistance at the adult plant stage in the stem rust resistance screening nursery in Njoro, Kenya in seasons 2008, 2009 and 2010. Fifteen marker loci were found to be significantly associated with stem rust resistance. Several markers appeared to be linked to known Sr genes, while other significant markers were located in chromosome regions where no Sr genes have been previously reported. Most of these new loci colocalized with QTLs identified recently in different biparental populations. Using the same data and Q + K covariate matrices, we investigated the interactions among marker loci using linear regression models to calculate P values for pairwise marker interactions. Resistance marker loci including the Sr2 locus on 3BS and the wPt1859 locus on 7DL had significant interaction effects with other loci in the same chromosome arm and with markers on chromosome 6B. Other resistance marker loci had significant pairwise interactions with markers on different chromosomes. Based on these results, we propose that a complex network of gene-gene interactions is, in part, responsible for resistance to Ug99. Further investigation may provide insight for understanding mechanisms that contribute to this resistance gene network.

  11. Interaction maps of the Saccharomyces cerevisiae ESCRT-III protein Snf7.

    PubMed

    Sciskala, Barbara; Kölling, Ralf

    2013-11-01

    The Saccharomyces cerevisiae ESCRT-III protein Snf7 is part of an intricate interaction network at the endosomal membrane. Interaction maps of Snf7 were established by measuring the degree of binding of individual binding partners to putative binding motifs along the Snf7 sequence by glutathione S-transferase (GST) pulldown. For each interaction partner, distinct binding profiles were obtained. The following observations were made. The ESCRT-III subunits Vps20 and Vps24 showed a complementary binding pattern, suggesting a model for the series of events in the ESCRT-III functional cycle. Vps4 bound to individual Snf7 motifs but not to full-length Snf7. This suggests that Vps4 does not bind to the closed conformation of Snf7. We also demonstrate for the first time that the ALIX/Bro1 homologue Rim20 binds to the α6 helix of Snf7. Analysis of a Snf7 α6 deletion mutant showed that the α6 helix is crucial for binding of Bro1 and Rim20 in vivo and is indispensable for the multivesicular body (MVB)-sorting and Rim-signaling functions of Snf7. The Snf7Δα6 protein still appeared to be incorporated into ESCRT-III complexes at the endosomal membrane, but disassembly of the complex seemed to be defective. In summary, our study argues against the view that the ESCRT cycle is governed by single one-to-one interactions between individual components and emphasizes the network character of the ESCRT interactions.

  12. Systematic protein-protein interaction mapping for clinically relevant human GPCRs.

    PubMed

    Sokolina, Kate; Kittanakom, Saranya; Snider, Jamie; Kotlyar, Max; Maurice, Pascal; Gandía, Jorge; Benleulmi-Chaachoua, Abla; Tadagaki, Kenjiro; Oishi, Atsuro; Wong, Victoria; Malty, Ramy H; Deineko, Viktor; Aoki, Hiroyuki; Amin, Shahreen; Yao, Zhong; Morató, Xavier; Otasek, David; Kobayashi, Hiroyuki; Menendez, Javier; Auerbach, Daniel; Angers, Stephane; Pržulj, Natasa; Bouvier, Michel; Babu, Mohan; Ciruela, Francisco; Jockers, Ralf; Jurisica, Igor; Stagljar, Igor

    2017-03-15

    G-protein-coupled receptors (GPCRs) are the largest family of integral membrane receptors with key roles in regulating signaling pathways targeted by therapeutics, but are difficult to study using existing proteomics technologies due to their complex biochemical features. To obtain a global view of GPCR-mediated signaling and to identify novel components of their pathways, we used a modified membrane yeast two-hybrid (MYTH) approach and identified interacting partners for 48 selected full-length human ligand-unoccupied GPCRs in their native membrane environment. The resulting GPCR interactome connects 686 proteins by 987 unique interactions, including 299 membrane proteins involved in a diverse range of cellular functions. To demonstrate the biological relevance of the GPCR interactome, we validated novel interactions of the GPR37, serotonin 5-HT4d, and adenosine ADORA2A receptors. Our data represent the first large-scale interactome mapping for human GPCRs and provide a valuable resource for the analysis of signaling pathways involving this druggable family of integral membrane proteins. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  13. Bayesian mapping of genotype x expression interactions in quantitative and qualitative traits.

    PubMed

    Hoti, F; Sillanpää, M J

    2006-07-01

    A novel Bayesian gene mapping method, which can simultaneously utilize both molecular marker and gene expression data, is introduced. The approach enables a quantitative or qualitative phenotype to be expressed as a linear combination of the marker genotypes, gene expression levels, and possible genotype x gene expression interactions. The interaction data, given as marker-gene pairs, contains possible in cis and in trans effects obtained from earlier allelic expression studies, genetical genomics studies, biological hypotheses, or known pathways. The method is presented for an inbred line cross design and can be easily generalized to handle other types of populations and designs. The model selection is based on the use of effect-specific variance components combined with Jeffreys' non-informative prior--the method operates by adaptively shrinking marker, expression, and interaction effects toward zero so that non-negligible effects are expected to occur only at very few positions. The estimation of the model parameters and the handling of missing genotype or expression data is performed via Markov chain Monte Carlo sampling. The potential of the method including heritability estimation is presented using simulated examples and novel summary statistics. The method is also applied to a real yeast data set with known pathways.

  14. Interactive segmentation of tongue contours in ultrasound video sequences using quality maps

    NASA Astrophysics Data System (ADS)

    Ghrenassia, Sarah; Ménard, Lucie; Laporte, Catherine

    2014-03-01

    Ultrasound (US) imaging is an effective and non invasive way of studying the tongue motions involved in normal and pathological speech, and the results of US studies are of interest for the development of new strategies in speech therapy. State-of-the-art tongue shape analysis techniques based on US images depend on semi-automated tongue segmentation and tracking techniques. Recent work has mostly focused on improving the accuracy of the tracking techniques themselves. However, occasional errors remain inevitable, regardless of the technique used, and the tongue tracking process must thus be supervised by a speech scientist who will correct these errors manually or semi-automatically. This paper proposes an interactive framework to facilitate this process. In this framework, the user is guided towards potentially problematic portions of the US image sequence by a segmentation quality map that is based on the normalized energy of an active contour model and automatically produced during tracking. When a problematic segmentation is identified, corrections to the segmented contour can be made on one image and propagated both forward and backward in the problematic subsequence, thereby improving the user experience. The interactive tools were tested in combination with two different tracking algorithms. Preliminary results illustrate the potential of the proposed framework, suggesting that the proposed framework generally improves user interaction time, with little change in segmentation repeatability.

  15. Mapping Interaction Energies in Chorismate Mutase with the Fragment Molecular Orbital Method.

    PubMed

    Pruitt, Spencer R; Steinmann, Casper

    2017-03-02

    The Claisen rearrangement of chorismate to prephenate is mapped across the entire reaction pathway using the fragment molecular orbital (FMO) method. Three basis sets (6-31G(d), cc-pVDZ, and pcseg-1) are studied to provide guidance toward obtaining high accuracy with the FMO method on such systems. Using a fragmentation scheme of one residue per fragment, the FMO method using the 6-31G(d) basis set and second-order Møller-Plesset perturbation theory (MP2) with the hybrid orbital projection fragmentation scheme provides the most reliable results across the entire reaction pathway. Calculations using the multilayer FMO method are performed and shown to be in agreement with single-layer calculations in all cases with differences of less than one kilocalorie per mole for all tested basis set combinations along the entire reaction path. The use of restricted Hartree-Fock for the lower-level layer and MP2 for the higher-level layer gives the most consistent results when using the same basis set for both layers. Pair interaction energy decomposition analysis calculations confirm that electrostatic interactions are the predominant force between three key arginine residues and chorismate and that dispersion and charge transfer interactions in the binding pocket also play a role in the local chemistry of the reaction.

  16. Quantitative interaction mapping reveals an extended UBX domain in ASPL that disrupts functional p97 hexamers

    PubMed Central

    Arumughan, Anup; Roske, Yvette; Barth, Carolin; Forero, Laura Lleras; Bravo-Rodriguez, Kenny; Redel, Alexandra; Kostova, Simona; McShane, Erik; Opitz, Robert; Faelber, Katja; Rau, Kirstin; Mielke, Thorsten; Daumke, Oliver; Selbach, Matthias; Sanchez-Garcia, Elsa; Rocks, Oliver; Panáková, Daniela; Heinemann, Udo; Wanker, Erich E.

    2016-01-01

    Interaction mapping is a powerful strategy to elucidate the biological function of protein assemblies and their regulators. Here, we report the generation of a quantitative interaction network, directly linking 14 human proteins to the AAA+ ATPase p97, an essential hexameric protein with multiple cellular functions. We show that the high-affinity interacting protein ASPL efficiently promotes p97 hexamer disassembly, resulting in the formation of stable p97:ASPL heterotetramers. High-resolution structural and biochemical studies indicate that an extended UBX domain (eUBX) in ASPL is critical for p97 hexamer disassembly and facilitates the assembly of p97:ASPL heterotetramers. This spontaneous process is accompanied by a reorientation of the D2 ATPase domain in p97 and a loss of its activity. Finally, we demonstrate that overproduction of ASPL disrupts p97 hexamer function in ERAD and that engineered eUBX polypeptides can induce cell death, providing a rationale for developing anti-cancer polypeptide inhibitors that may target p97 activity. PMID:27762274

  17. Mapping the Fresh-Salt Water Interaction in the Coastal Zone Using High Resolution Airborne Electromagnetics

    NASA Astrophysics Data System (ADS)

    Auken, E.; Pedersen, J. B. B.; Christiansen, A. V.; Foged, N.; Schaars, F.; Rolf, H.

    2016-12-01

    During the last decade airborne electromagnetics (AEM) and the accompanying data processing and inversion algorithms have undergone huge developments in terms of technology, costs, and reliability. This has expanded the scope of AEM from mainly mineral exploration to geotechnical applications and groundwater resource mapping. In this abstract we present a case with generally applicable results where AEM is used to map saltwater intrusion as well as outflow of fresh water to the sea. The survey took place on the Dutch coast in 2011 and is composed of a detailed inland coastal mapping as well as lines extending kilometres into the North Sea. It adds further complications that the area has a dense infrastructure and rapid varying dune topography causing the need for cautious data processing. We use the high resolution AEM system SkyTEM and data processing and inversion in the Aarhus Workbench. On the inland side, the results show a high resolution image of the fresh water interface and the interaction with clay layers acting as barriers. On the sea side they show a picture of freshwater plumes being pushed several hundred meters under the sea. The last mentioned information was actually the main purpose of the survey as this information could hardly be obtained by other methods and it is decisive for the total water balance of the system. The case shows an example of an AEM survey resulting in a high resolution image of the entire coastal zone. The technology is applicable in all coastal zones in the world and if applied it would lead to much improved management of the water resources in these landscapes.

  18. A Hurricane Hits Home: An Interactive Science Museum Exhibit on Ocean Mapping and Marine Debris

    NASA Astrophysics Data System (ADS)

    Butkiewicz, T.; Vasta, D. J.; Gager, N. C.; Fruth, B. W.; LeClair, J.

    2016-12-01

    As part of the outreach component for a project involving the detection and analysis of marine debris generated by Super Storm Sandy, The Center for Coastal and Ocean Mapping / Joint Hydrographic Center partnered with The Seacoast Science Center to develop an interactive museum exhibit that engages the public with a touchscreen based game revolving around the detection and identification of marine debris. "A Hurricane Hits Home" is a multi-station touchscreen exhibit geared towards children, and integrates a portion of a historical wooden shipwreck into its physical design. The game invites museum guests to examine a number of coastal regions and harbors in Sandy affected areas. It teaches visitors about modern mapping technology by having them control boats with multibeam sonars and airplanes with lidar sensors. They drag these vehicles around maps to reveal the underlying bathymetry below the satellite photos. They learn the applications and limitations of sonar and lidar by where the vehicles can and cannot collect survey data (e.g. lidar doesn't work in deep water, and the boat can't go in shallow areas). As users collect bathymetry data, they occasionally reveal marine debris objects on the seafloor. Once all the debris objects in a level have been located, the game challenges them to identify them based on their appearance in the bathymetry data. They must compare the simulated bathymetry images of the debris targets to photos of possible objects, and choose the correct matches to achieve a high score. The exhibit opened January 2016 at the Seacoast Science Center in Rye, NH.

  19. Perm-seq: Mapping Protein-DNA Interactions in Segmental Duplication and Highly Repetitive Regions of Genomes with Prior-Enhanced Read Mapping

    PubMed Central

    Zeng, Xin; Li, Bo; Welch, Rene; Rojo, Constanza; Zheng, Ye; Dewey, Colin N.; Keleş, Sündüz

    2015-01-01

    Segmental duplications and other highly repetitive regions of genomes contribute significantly to cells’ regulatory programs. Advancements in next generation sequencing enabled genome-wide profiling of protein-DNA interactions by chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq). However, interactions in highly repetitive regions of genomes have proven difficult to map since short reads of 50–100 base pairs (bps) from these regions map to multiple locations in reference genomes. Standard analytical methods discard such multi-mapping reads and the few that can accommodate them are prone to large false positive and negative rates. We developed Perm-seq, a prior-enhanced read allocation method for ChIP-seq experiments, that can allocate multi-mapping reads in highly repetitive regions of the genomes with high accuracy. We comprehensively evaluated Perm-seq, and found that our prior-enhanced approach significantly improves multi-read allocation accuracy over approaches that do not utilize additional data types. The statistical formalism underlying our approach facilitates supervising of multi-read allocation with a variety of data sources including histone ChIP-seq. We applied Perm-seq to 64 ENCODE ChIP-seq datasets from GM12878 and K562 cells and identified many novel protein-DNA interactions in segmental duplication regions. Our analysis reveals that although the protein-DNA interactions sites are evolutionarily less conserved in repetitive regions, they share the overall sequence characteristics of the protein-DNA interactions in non-repetitive regions. PMID:26484757

  20. An interactive program for computer-aided map design, display, and query: EMAPKGS2

    USGS Publications Warehouse

    Pouch, G.W.

    1997-01-01

    EMAPKGS2 is a user-friendly, PC-based electronic mapping tool for use in hydrogeologic exploration and appraisal. EMAPKGS2 allows the analyst to construct maps interactively from data stored in a relational database, perform point-oriented spatial queries such as locating all wells within a specified radius, perform geographic overlays, and export the data to other programs for further analysis. EMAPKGS2 runs under Microsoft?? Windows??? 3.1 and compatible operating systems. EMAPKGS2 is a public domain program available from the Kansas Geological Survey. EMAPKGS2 is the centerpiece of WHEAT, the Windows-based Hydrogeologic Exploration and Appraisal Toolkit, a suite of user-friendly Microsoft?? Windows??? programs for natural resource exploration and management. The principal goals in development of WHEAT have been ease of use, hardware independence, low cost, and end-user extensibility. WHEAT'S native data format is a Microsoft?? Access?? database. WHEAT stores a feature's geographic coordinates as attributes so they can be accessed easily by the user. The WHEAT programs are designed to be used in conjunction with other Microsoft?? Windows??? software to allow the natural resource scientist to perform work easily and effectively. WHEAT and EMAPKGS have been used at several of Kansas' Groundwater Management Districts and the Kansas Geological Survey on groundwater management operations, groundwater modeling projects, and geologic exploration projects. ?? 1997 Elsevier Science Ltd.

  1. Reference map technique for finite-strain elasticity and fluid-solid interaction

    NASA Astrophysics Data System (ADS)

    Kamrin, Ken; Rycroft, Chris H.; Nave, Jean-Christophe

    2012-11-01

    The reference map, defined as the inverse motion function, is utilized in an Eulerian-frame representation of continuum solid mechanics, leading to a simple, explicit finite-difference method for solids undergoing finite deformations. We investigate the accuracy and applicability of the technique for a range of finite-strain elasticity laws under various geometries and loadings. Capacity to model dynamic, static, and quasi-static conditions is shown. Specifications of the approach are demonstrated for handling irregularly shaped and/or moving boundaries, as well as shock solutions. The technique is also integrated within a fluid-solid framework using a level-set to discern phases and using a standard explicit fluid solver for the fluid phases. We employ a sharp-interface method to institute the interfacial conditions, and the resulting scheme is shown to efficiently capture fluid-solid interaction solutions in several examples.

  2. An interactive Barnes objective map analysis scheme for use with satellite and conventional data

    NASA Technical Reports Server (NTRS)

    Koch, S. E.; Desjardins, M.; Kocin, P. J.

    1983-01-01

    The Barnes (1973) objective map analysis scheme is employed to develop an interactive analysis package for assessing the impact of satellite-derived data on analyses of conventional meteorological data sets. The method permits modification of the values of input parameters in the objective analysis within objectively determined, internally set limits. The effects of the manipulations are rapidly displayed, and methods are included for assimilating the spatially clustered characteristics of satellite data and the various horizontal resolutions of the data types. Data sets from the SESAME rawinsonde wind data with uniform spatial distribution, with the same data set plus satellite cloud motion data, and a data set from the atmospheric sounder radiometer on the GOES satellite were analyzed as examples. The scheme is demonstrated to recover details after two iterations through the data.

  3. An interactive Barnes objective map analysis scheme for use with satellite and conventional data

    NASA Technical Reports Server (NTRS)

    Koch, S. E.; Desjardins, M.; Kocin, P. J.

    1983-01-01

    The Barnes (1973) objective map analysis scheme is employed to develop an interactive analysis package for assessing the impact of satellite-derived data on analyses of conventional meteorological data sets. The method permits modification of the values of input parameters in the objective analysis within objectively determined, internally set limits. The effects of the manipulations are rapidly displayed, and methods are included for assimilating the spatially clustered characteristics of satellite data and the various horizontal resolutions of the data types. Data sets from the SESAME rawinsonde wind data with uniform spatial distribution, with the same data set plus satellite cloud motion data, and a data set from the atmospheric sounder radiometer on the GOES satellite were analyzed as examples. The scheme is demonstrated to recover details after two iterations through the data.

  4. BrainMaps.org - Interactive High-Resolution Digital Brain Atlases and Virtual Microscopy.

    PubMed

    Mikula, Shawn; Stone, James M; Jones, Edward G

    2008-01-01

    BrainMaps.org is an interactive high-resolution digital brain atlas and virtual microscope that is based on over 20 million megapixels of scanned images of serial sections of both primate and non-primate brains and that is integrated with a high-speed database for querying and retrieving data about brain structure and function over the internet. Complete brain datasets for various species, including Homo sapiens, Macaca mulatta, Chlorocebus aethiops, Felis catus, Mus musculus, Rattus norvegicus, and Tyto alba, are accessible online. The methods and tools we describe are useful for both research and teaching, and can be replicated by labs seeking to increase accessibility and sharing of neuroanatomical data. These tools offer the possibility of visualizing and exploring completely digitized sections of brains at a sub-neuronal level, and can facilitate large-scale connectional tracing, histochemical and stereological analyses.

  5. Defining a microRNA-mRNA interaction map for calcineurin inhibitor induced nephrotoxicity.

    PubMed

    Benway, Christopher J; Iacomini, John

    2017-09-19

    Calcineurin inhibitors induce nephrotoxicity through poorly understood mechanisms thereby limiting their use in transplantation and other diseases. Here we define a microRNA (miRNA)-messenger RNA (mRNA) interaction map that facilitates exploration into the role of miRNAs in cyclosporine-induced nephrotoxicity (CIN) and the gene pathways they regulate. Using photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP), we isolated RNAs associated with Argonaute 2 in the RNA-Induced Silencing Complex (RISC) of cyclosporine A (CsA) treated and control human proximal tubule cells and identified mRNAs undergoing active targeting by miRNAs. CsA causes specific changes in miRNAs and mRNAs associated with RISC, thereby altering post-transcription regulation of gene expression. Pathway enrichment analysis identified canonical pathways regulated by miRNAs specifically following CsA treatment. RNA-seq performed on total RNA indicated that only a fraction of total miRNAs and mRNAs are actively targeted in the RISC indicating that PAR-CLIP more accurately defines meaningful targeting interactions. Our data also revealed a role for miRNAs in calcineurin-independent regulation of JNK and p38 MAPKs caused by targeting of MAP3K1. Together, our data provide a novel resource and unique insights into molecular pathways regulated by miRNAs in CIN. The gene pathways and miRNAs defined may represent novel targets to reduce calcineurin induced nephrotoxicity. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  6. Protein-Protein Interactions in the Yeast Pheromone Response Pathway: Ste5p Interacts with All Members of the Map Kinase Cascade

    PubMed Central

    Printen, J. A.; Sprague-Jr., G. F.

    1994-01-01

    We have used the two-hybrid system of Fields and Song to identify protein-protein interactions that occur in the pheromone response pathway of the yeast Saccharomyces cerevisiae. Pathway components Ste4p, Ste5p, Ste7p, Ste11p, Ste12p, Ste20p, Fus3p and Kss1p were tested in all pairwise combinations. All of the interactions we detected involved at least one member of the MAP kinase cascade that is a central element of the response pathway. Ste5p, a protein of unknown biochemical function, interacted with protein kinases that operate at each step of the MAP kinase cascade, specifically with Ste11p (an MEKK), Ste7p (an MEK), and Fus3p (a MAP kinase). This finding suggests that one role of Ste5p is to serve as a scaffold to facilitate interactions among members of the kinase cascade. In this role as facilitator, Ste5p may make both signal propagation and signal attenuation more efficient. Ste5p may also help minimize cross-talk with other MAP kinase cascades and thus ensure the integrity of the pheromone response pathway. We also found that both Ste11p and Ste7p interact with Fus3p and Kss1p. Finally, we detected an interaction between one of the MAP kinases, Kss1p, and a presumptive target, the transcription factor Ste12p. We failed to detect interactions of Ste4p or Ste20p with any other component of the response pathway. PMID:7851759

  7. Genetic mapping of social interaction behavior in B6/MSM consomic mouse strains.

    PubMed

    Takahashi, Aki; Tomihara, Kazuya; Shiroishi, Toshihiko; Koide, Tsuyoshi

    2010-05-01

    Genetic studies are indispensable for understanding the mechanisms by which individuals develop differences in social behavior. We report genetic mapping of social interaction behavior using inter-subspecific consomic strains established from MSM/Ms (MSM) and C57BL/6J (B6) mice. Two animals of the same strain and sex, aged 10 weeks, were introduced into a novel open-field for 10 min. Social contact was detected by an automated system when the distance between the centers of the two animals became less than approximately 12 cm. In addition, detailed behavioral observations were made of the males. The wild-derived mouse strain MSM showed significantly longer social contact as compared to B6. Analysis of the consomic panel identified two chromosomes (Chr 6 and Chr 17) with quantitative trait loci (QTL) responsible for lengthened social contact in MSM mice and two chromosomes (Chr 9 and Chr X) with QTL that inhibited social contact. Detailed behavioral analysis of males identified four additional chromosomes associated with social interaction behavior. B6 mice that contained Chr 13 from MSM showed more genital grooming and following than the parental B6 strain, whereas the presence of Chr 8 and Chr 12 from MSM resulted in a reduction of those behaviors. Longer social sniffing was observed in Chr 4 consomic strain than in B6 mice. Although the frequency was low, aggressive behavior was observed in a few pairs from consomic strains for Chrs 4, 13, 15 and 17, as well as from MSM. The social interaction test has been used as a model to measure anxiety, but genetic correlation analysis suggested that social interaction involves different aspects of anxiety than are measured by open-field test.

  8. Developing nurses' intercultural/intraprofessional communication skills using the EXCELLence in Cultural Experiential Learning and Leadership (EXCELL) Social Interaction Maps.

    PubMed

    Henderson, Saras; Barker, Michelle

    2017-09-27

    To examine how the use of Social Interaction Maps (SIMs), a tool in the EXCELL (EXCELLence in Cultural Experiential Learning and Leadership) Program can enhance the development of nurses' intercultural/intraprofessional communication skills. Nurses face communication challenges when interacting with others from similar background as well as those from a culturally and linguistically diverse (CALD) background. We used the EXCELL Program's Social Interaction Maps (SIMs) tool to foster intercultural/intraprofessional communication skills in nurses. SIMs describe verbal and non-verbal communication behaviours that model ways of communicating in a culturally appropriate manner. The Maps include four stages of an interaction, namely: Approach, Bridging, Communicating and Departing using the acronym ABCD. Qualitative approach was used with a purposeful sample of nurses enrolled in a postgraduate course. Fifteen participants were recruited. The SIM tool was taught to participants in a workshop where they engaged in sociocultural communication activities using scenarios. Participants were asked to apply SIMs in their workplaces. Six weeks later participants completed a semi-structured open-ended questionnaire and participated in a discussion forum on their experience of using SIMs. Data were content analysed. Four themes identified in the use of the SIMS were: (i) enhancing self-awareness of communication skills; (ii) promoting skills in being non-confrontational during difficult interactions; (iii) highlighting the importance of A (Approach) and B (Bridging) in interaction with others; (iv)awareness of how others interpret what is said C (Communicating), and discussing to resolve issues before closure D (Departing). Application of the EXCELL Social Interaction Mapping tool was shown to be useful in developing intercultural/intraprofessional communication skills in nurses. Professional development programs that incorporate EXCELL Social Interaction Maps can enhance nurses

  9. Usability Assessment of the Missouri Cancer Registry’s Published Interactive Mapping Reports: Round One

    PubMed Central

    Jackson-Thompson, Jeannette; Schmaltz, Chester Lee

    2017-01-01

    Background  Many users of spatial data have difficulty interpreting information in health-related spatial reports. The Missouri Cancer Registry and Research Center (MCR-ARC) has produced interactive reports for several years. These reports have never been tested for usability. Objective  The aims of this study were to: (1) conduct a multi-approach usability testing study to understand ease of use (user friendliness) and user satisfaction; and (2) evaluate the usability of MCR-ARC’s published InstantAtlas reports. Methods   An institutional review board (IRB) approved mixed methodology usability testing study using a convenience sample of health professionals. A recruiting email was sent to faculty in the Master of Public Health program and to faculty and staff in the Department of Health Management and Informatics at the University of Missouri-Columbia. The study included 7 participants. The test included a pretest questionnaire, a multi-task usability test, and the System Usability Scale (SUS). Also, the researchers collected participants’ comments about the tested maps immediately after every trial. Software was used to record the computer screen during the trial and the participants’ spoken comments. Several performance and usability metrics were measured to evaluate the usability of MCR-ARC’s published mapping reports. Results Of the 10 assigned tasks, 6 reached a 100% completion success rate, and this outcome was relative to the complexity of the tasks. The simple tasks were handled more efficiently than the complicated tasks. The SUS score ranged between 20-100 points, with an average of 62.7 points and a median of 50.5 points. The tested maps’ effectiveness outcomes were better than the efficiency and satisfaction outcomes. There was a statistically significant relationship between the subjects’ performance on the study test and the users’ previous experience with geographic information system (GIS) tools (P=.03). There were no

  10. Forest Types in the Lower Suwannee River Floodplain, Florida?-A Report and Interactive Map

    USGS Publications Warehouse

    Darst, M.R.; Light, H.M.; Lewis, L.J.; Sepulveda, A.A.

    2003-01-01

    A map of forest types in the lower Suwannee River floodplain, Florida, was created during a study conducted from 1996 to 2000 by the U.S. Geological Survey in cooperation with the Suwannee River Water Management District. The map is presented with this report on a compact disc with interactive viewing software. The forest map can be used by scientists for ecological studies in the floodplain based on land cover types and by landowners and management personnel making land use decisions. The study area is the 10-year floodplain of the lower Suwannee River from its confluence with the Santa Fe River to the lower limit of forests near the Gulf of Mexico. The floodplain is divided into three reaches: riverine (non-tidal), upper tidal, and lower tidal, due to changes in hydrology, vegetation, and soils with proximity to the coast. The 10-year floodplain covers about 21,170 hectares; nearly 88 percent of this area (18,580 hectares) is mapped as 14 major forest types. Approximately 29 percent (5,319 hectares) of these forests have been altered by agriculture or development. About 75 percent of the area of major forest types (13,994 hectares) is wetland forests and about 25 percent (4,586 hectares) is upland forests. Tidal wetland forests (8,955 hectares) cover a much greater area than riverine wetland forests (5,039 hectares). Oak/pine upland forests are present in the riverine and upper tidal reaches of the floodplain on elevations that are inundated only briefly during the highest floods. High bottomland hardwoods are present on the higher levees, ridges, and flats of the riverine reach where soils are usually sandy. Low bottomland hardwood forests are present in the riverine reach on swamp margins and low levees and flats that are flooded continuously for several weeks or longer every 1 to 3 years. Riverine swamps are present in the lowest and wettest areas of the non-tidal floodplain that are either inundated or saturated most of the time. Upper tidal bottomland

  11. An interactive mapping tool for visualizing lacunarity of laser scanned point clouds

    NASA Astrophysics Data System (ADS)

    Kania, Adam; Székely, Balázs

    2016-04-01

    Lacunarity, a measure of the spatial distribution of the empty space in a certain model or real space over large spatial scales, is found to be a useful descriptive quantity in many fields using imagery, including, among others, geology, dentistry, neurology. Its application in ecology was suggested more than 20 years ago. The main problem of its application was the lack of appropriate high resolution data. Nowadays, full-waveform laser scanning, also known as FWF LiDAR, provides the tool for mapping the vegetation in unprecedented details and accuracy. Consequently, the lacunarity concept can be revitalized, in order to study the structure of the vegetation in this sense as well. Calculation of lacunarity, even if it is done in two dimensions (2D), is still has its problems: on one hand it is a number-crunching procedure, on the other hand, it produces 4D results: at each 3D point it returns a set of data that are function of scale. These data sets are difficult to visualize, to evaluate, and to compare. In order to solve this problem, an interactive mapping tool has been conceptualized that is designed to manipulate and visualize the data, lets the user set parameters for best visualization or comparison results. The system is able to load large amounts of data, visualize them as lacunarity curves, or map view as horizontal slices or in 3D point clouds coloured according to the user's choice. Lacunarity maps are presented as a series of (usually) horizontal profiles, e.g. rasters, which cells contain color-mapped values of selected lacunarity of the point cloud. As lacunarity is usually analysed in a series of successive windows sizes, the tool can show a series of rasters with sequentially animated lacunarity maps calculated for various window sizes. A very fast switching of colour schemes is possible to facilitate rapid visual feedback to better understand underlying data patterns exposed by lacunarity functions. In the comparison mode, two sites (or two areas

  12. A genetic map in the Mimulus guttatus species complex reveals transmission ratio distortion due to heterospecific interactions.

    PubMed

    Fishman, L; Kelly, A J; Morgan, E; Willis, J H

    2001-12-01

    As part of a study of the genetics of floral adaptation and speciation in the Mimulus guttatus species complex, we constructed a genetic linkage map of an interspecific cross between M. guttatus and M. nasutus. We genotyped an F(2) mapping population (N = 526) at 255 AFLP, microsatellite, and gene-based markers and derived a framework map through repeated rounds of ordering and marker elimination. The final framework map consists of 174 marker loci on 14 linkage groups with a total map length of 1780 cM Kosambi. Genome length estimates (2011-2096 cM) indicate that this map provides thorough coverage of the hybrid genome, an important consideration for QTL mapping. Nearly half of the markers in the full data set (49%) and on the framework map (48%) exhibited significant transmission ratio distortion (alpha = 0.05). We localized a minimum of 11 transmission ratio distorting loci (TRDLs) throughout the genome, 9 of which generate an excess of M. guttatus alleles and a deficit of M. nasutus alleles. This pattern indicates that the transmission ratio distortion results from particular interactions between the heterospecific genomes and suggests that substantial genetic divergence has occurred between these Mimulus species. We discuss possible causes of the unequal representation of parental genomes in the F(2) generation.

  13. Mapping strain rate dependence of dislocation-defect interactions by atomistic simulations

    PubMed Central

    Fan, Yue; Osetskiy, Yuri N.; Yip, Sidney; Yildiz, Bilge

    2013-01-01

    Probing the mechanisms of defect–defect interactions at strain rates lower than 106 s−1 is an unresolved challenge to date to molecular dynamics (MD) techniques. Here we propose an original atomistic approach based on transition state theory and the concept of a strain-dependent effective activation barrier that is capable of simulating the kinetics of dislocation–defect interactions at virtually any strain rate, exemplified within 10−7 to 107 s−1. We apply this approach to the problem of an edge dislocation colliding with a cluster of self-interstitial atoms (SIAs) under shear deformation. Using an activation–relaxation algorithm [Kushima A, et al. (2009) J Chem Phys 130:224504], we uncover a unique strain-rate–dependent trigger mechanism that allows the SIA cluster to be absorbed during the process, leading to dislocation climb. Guided by this finding, we determine the activation barrier of the trigger mechanism as a function of shear strain, and use that in a coarse-graining rate equation formulation for constructing a mechanism map in the phase space of strain rate and temperature. Our predictions of a crossover from a defect recovery at the low strain-rate regime to defect absorption behavior in the high strain-rate regime are validated against our own independent, direct MD simulations at 105 to 107 s−1. Implications of the present approach for probing molecular-level mechanisms in strain-rate regimes previously considered inaccessible to atomistic simulations are discussed. PMID:24114271

  14. Process maps for plasma spray: Part 1: Plasma-particle interactions

    SciTech Connect

    GILMORE,DELWYN L.; NEISER JR.,RICHARD A.; WAN,YUEPENG; SAMPATH,SANJAY

    2000-01-26

    This is the first paper of a two part series based on an integrated study carried out at Sandia National Laboratories and the State University of New York at Stony Brook. The aim of the study is to develop a more fundamental understanding of plasma-particle interactions, droplet-substrate interactions, deposit formation dynamics and microstructural development as well as final deposit properties. The purpose is to create models that can be used to link processing to performance. Process maps have been developed for air plasma spray of molybdenum. Experimental work was done to investigate the importance of such spray parameters as gun current, auxiliary gas flow, and powder carrier gas flow. In-flight particle diameters, temperatures, and velocities were measured in various areas of the spray plume. Samples were produced for analysis of microstructures and properties. An empirical model was developed, relating the input parameters to the in-flight particle characteristics. Multi-dimensional numerical simulations of the plasma gas flow field and in-flight particles under different operating conditions were also performed. In addition to the parameters which were experimentally investigated, the effect of particle injection velocity was also considered. The simulation results were found to be in good general agreement with the experimental data.

  15. Mapping the Interactions between Shocks and Mixing Layers in a 3-Stream Supersonic Jet

    NASA Astrophysics Data System (ADS)

    Lewalle, Jacques; Ruscher, Christopher; Kan, Pinqing; Tenney, Andrew; Gogineni, Sivaram; Kiel, Barry

    2015-11-01

    Pressure is obtained from an LES calculation of the supersonic jet (Ma1 = 1 . 6) issuing from a rectangular nozzle in a low-subsonic co-flow; a tertiary flow, also rectangular with Ma3 = 1 insulates the primary jet from an aft-deck plate. The developing jet exhibits complex three-dimensional interactions between oblique shocks, multiple mixing layers and corner vortices, which collectively act as a skeleton for the flow. Our study is based on several plane sections through the pressure field, with short signals (0.1 s duration at 80 kHz sampling rate). Using wavelet-based band-pass filtering and cross-correlations, we map the directions of propagation of information among the various ``bones'' in the skeleton. In particular, we identify upstream propagation in some frequency bands, 3-dimensional interactions between the various shear layers, and several key bones from which the pressure signals, when taken as reference, provide dramatic phase-locking for parts of the skeleton. We acknowledge the support of AFRL through an SBIR grant.

  16. Fractionation profiling: a fast and versatile approach for mapping vesicle proteomes and protein–protein interactions

    PubMed Central

    Borner, Georg H. H.; Hein, Marco Y.; Hirst, Jennifer; Edgar, James R.; Mann, Matthias; Robinson, Margaret S.

    2014-01-01

    We developed “fractionation profiling,” a method for rapid proteomic analysis of membrane vesicles and protein particles. The approach combines quantitative proteomics with subcellular fractionation to generate signature protein abundance distribution profiles. Functionally associated groups of proteins are revealed through cluster analysis. To validate the method, we first profiled >3500 proteins from HeLa cells and identified known clathrin-coated vesicle proteins with >90% accuracy. We then profiled >2400 proteins from Drosophila S2 cells, and we report the first comprehensive insect clathrin-coated vesicle proteome. Of importance, the cluster analysis extends to all profiled proteins and thus identifies a diverse range of known and novel cytosolic and membrane-associated protein complexes. We show that it also allows the detailed compositional characterization of complexes, including the delineation of subcomplexes and subunit stoichiometry. Our predictions are presented in an interactive database. Fractionation profiling is a universal method for defining the clathrin-coated vesicle proteome and may be adapted for the analysis of other types of vesicles and particles. In addition, it provides a versatile tool for the rapid generation of large-scale protein interaction maps. PMID:25165137

  17. Bayesian model choice and search strategies for mapping interacting quantitative trait Loci.

    PubMed Central

    Yi, Nengjun; Xu, Shizhong; Allison, David B

    2003-01-01

    Most complex traits of animals, plants, and humans are influenced by multiple genetic and environmental factors. Interactions among multiple genes play fundamental roles in the genetic control and evolution of complex traits. Statistical modeling of interaction effects in quantitative trait loci (QTL) analysis must accommodate a very large number of potential genetic effects, which presents a major challenge to determining the genetic model with respect to the number of QTL, their positions, and their genetic effects. In this study, we use the methodology of Bayesian model and variable selection to develop strategies for identifying multiple QTL with complex epistatic patterns in experimental designs with two segregating genotypes. Specifically, we develop a reversible jump Markov chain Monte Carlo algorithm to determine the number of QTL and to select main and epistatic effects. With the proposed method, we can jointly infer the genetic model of a complex trait and the associated genetic parameters, including the number, positions, and main and epistatic effects of the identified QTL. Our method can map a large number of QTL with any combination of main and epistatic effects. Utility and flexibility of the method are demonstrated using both simulated data and a real data set. Sensitivity of posterior inference to prior specifications of the number and genetic effects of QTL is investigated. PMID:14573494

  18. Social interaction facilitates word learning in preverbal infants: Word-object mapping and word segmentation.

    PubMed

    Hakuno, Yoko; Omori, Takahide; Yamamoto, Jun-Ichi; Minagawa, Yasuyo

    2017-08-01

    In natural settings, infants learn spoken language with the aid of a caregiver who explicitly provides social signals. Although previous studies have demonstrated that young infants are sensitive to these signals that facilitate language development, the impact of real-life interactions on early word segmentation and word-object mapping remains elusive. We tested whether infants aged 5-6 months and 9-10 months could segment a word from continuous speech and acquire a word-object relation in an ecologically valid setting. In Experiment 1, infants were exposed to a live tutor, while in Experiment 2, another group of infants were exposed to a televised tutor. Results indicate that both younger and older infants were capable of segmenting a word and learning a word-object association only when the stimuli were derived from a live tutor in a natural manner, suggesting that real-life interaction enhances the learning of spoken words in preverbal infants. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Mapping Strain-rate Dependent Dislocation-Defect Interactions by Atomistic Simulations

    SciTech Connect

    Fan, Yue; Osetskiy, Yury N; Yip, Sidney; Yildiz-Botterud, Bilge

    2013-01-01

    Probing the mechanisms of defect-defect interactions at strain rates lower than 106 s-1 is an unresolved challenge to date to molecular dynamics (MD) techniques. Here we propose a novel atomistic approach based on transition state theory and the concept of a strain-dependent effective activation barrier that is capable of simulating the kinetics of dislocation-defect interactions at virtually any strain rate, exemplified within 10-7 to 107 s-1. We apply this approach to the problem of an edge dislocation colliding with a cluster of self-interstitial atoms (SIA) under shear deformation. Using an activation-relaxation algorithm (1), we uncover a unique strain-rate dependent trigger mechanism that allows the SIA cluster to be absorbed during the process leading to dislocation climb. Guided by this finding, we determine the activation barrier of the trigger mechanism as a function of shear strain, and use that in a coarse-graining rate equation formulation for constructing a mechanism map in the phase space of strain-rate and temperature. Our predictions of a crossover from a defect recovery at the low strain rate regime to defect absorption behavior in the high strain-rate regime are validated against our own independent, direct MD simulations at 105 to 107 s-1. Implications of the present approach for probing molecular-level mechanisms in strain-rate regimes previously considered inaccessible to atomistic simulations are discussed.

  20. Mapping of quantitative trait loci controlling adaptive traits in coastal Douglas fir. III. Quantitative trait loci-by-environment interactions.

    PubMed Central

    Jermstad, Kathleen D; Bassoni, Daniel L; Jech, Keith S; Ritchie, Gary A; Wheeler, Nicholas C; Neale, David B

    2003-01-01

    Quantitative trait loci (QTL) were mapped in the woody perennial Douglas fir (Pseudotsuga menziesii var. menziesii [Mirb.] Franco) for complex traits controlling the timing of growth initiation and growth cessation. QTL were estimated under controlled environmental conditions to identify QTL interactions with photoperiod, moisture stress, winter chilling, and spring temperatures. A three-generation mapping population of 460 cloned progeny was used for genetic mapping and phenotypic evaluations. An all-marker interval mapping method was used for scanning the genome for the presence of QTL and single-factor ANOVA was used for estimating QTL-by-environment interactions. A modest number of QTL were detected per trait, with individual QTL explaining up to 9.5% of the phenotypic variation. Two QTL-by-treatment interactions were found for growth initiation, whereas several QTL-by-treatment interactions were detected among growth cessation traits. This is the first report of QTL interactions with specific environmental signals in forest trees and will assist in the identification of candidate genes controlling these important adaptive traits in perennial plants. PMID:14668397

  1. The use of interactive graphical maps for browsing medical/health Internet information resources.

    PubMed

    Boulos, Maged N Kamel

    2003-01-10

    As online information portals accumulate metadata descriptions of Web resources, it becomes necessary to develop effective ways for visualising and navigating the resultant huge metadata repositories as well as the different semantic relationships and attributes of described Web resources. Graphical maps provide a good method to visualise, understand and navigate a world that is too large and complex to be seen directly like the Web. Several examples of maps designed as a navigational aid for Web resources are presented in this review with an emphasis on maps of medical and health-related resources. The latter include HealthCyberMap maps http://healthcybermap.semanticweb.org/, which can be classified as conceptual information space maps, and the very abstract and geometric Visual Net maps of PubMed http://pubmed.antarcti.ca/start. Information resources can be also organised and navigated based on their geographic attributes. Some of the maps presented in this review use a Kohonen Self-Organising Map algorithm, and only HealthCyberMap uses a Geographic Information System to classify Web resource data and render the maps. Maps based on familiar metaphors taken from users' everyday life are much easier to understand. Associative and pictorial map icons that enable instant recognition and comprehension are preferred to geometric ones and are key to successful maps for browsing medical/health Internet information resources.

  2. The use of interactive graphical maps for browsing medical/health Internet information resources

    PubMed Central

    Boulos, Maged N Kamel

    2003-01-01

    As online information portals accumulate metadata descriptions of Web resources, it becomes necessary to develop effective ways for visualising and navigating the resultant huge metadata repositories as well as the different semantic relationships and attributes of described Web resources. Graphical maps provide a good method to visualise, understand and navigate a world that is too large and complex to be seen directly like the Web. Several examples of maps designed as a navigational aid for Web resources are presented in this review with an emphasis on maps of medical and health-related resources. The latter include HealthCyberMap maps , which can be classified as conceptual information space maps, and the very abstract and geometric Visual Net maps of PubMed (for demos). Information resources can be also organised and navigated based on their geographic attributes. Some of the maps presented in this review use a Kohonen Self-Organising Map algorithm, and only HealthCyberMap uses a Geographic Information System to classify Web resource data and render the maps. Maps based on familiar metaphors taken from users' everyday life are much easier to understand. Associative and pictorial map icons that enable instant recognition and comprehension are preferred to geometric ones and are key to successful maps for browsing medical/health Internet information resources. PMID:12556244

  3. Influence of long-range Coulomb interaction in velocity map imaging

    NASA Astrophysics Data System (ADS)

    Barillot, T.; Brédy, R.; Celep, G.; Cohen, S.; Compagnon, I.; Concina, B.; Constant, E.; Danakas, S.; Kalaitzis, P.; Karras, G.; Lépine, F.; Loriot, V.; Marciniak, A.; Predelus-Renois, G.; Schindler, B.; Bordas, C.

    2017-07-01

    The standard velocity-map imaging (VMI) analysis relies on the simple approximation that the residual Coulomb field experienced by the photoelectron ejected from a neutral or ion system may be neglected. Under this almost universal approximation, the photoelectrons follow ballistic (parabolic) trajectories in the externally applied electric field, and the recorded image may be considered as a 2D projection of the initial photoelectron velocity distribution. There are, however, several circumstances where this approximation is not justified and the influence of long-range forces must absolutely be taken into account for the interpretation and analysis of the recorded images. The aim of this paper is to illustrate this influence by discussing two different situations involving isolated atoms or molecules where the analysis of experimental images cannot be performed without considering long-range Coulomb interactions. The first situation occurs when slow (meV) photoelectrons are photoionized from a neutral system and strongly interact with the attractive Coulomb potential of the residual ion. The result of this interaction is the formation of a more complex structure in the image, as well as the appearance of an intense glory at the center of the image. The second situation, observed also at low energy, occurs in the photodetachment from a multiply charged anion and it is characterized by the presence of a long-range repulsive potential. Then, while the standard VMI approximation is still valid, the very specific features exhibited by the recorded images can be explained only by taking into consideration tunnel detachment through the repulsive Coulomb barrier.

  4. Does the Swedish Interactive Threshold Algorithm (SITA) accurately map visual field loss attributed to vigabatrin?

    PubMed

    Conway, Miriam L; Hosking, Sarah L; Zhu, Haogang; Cubbidge, Robert P

    2014-12-23

    Vigabatrin (VGB) is an anti-epileptic medication which has been linked to peripheral constriction of the visual field. Documenting the natural history associated with continued VGB exposure is important when making decisions about the risk and benefits associated with the treatment. Due to its speed the Swedish Interactive Threshold Algorithm (SITA) has become the algorithm of choice when carrying out Full Threshold automated static perimetry. SITA uses prior distributions of normal and glaucomatous visual field behaviour to estimate threshold sensitivity. As the abnormal model is based on glaucomatous behaviour this algorithm has not been validated for VGB recipients. We aim to assess the clinical utility of the SITA algorithm for accurately mapping VGB attributed field loss. The sample comprised one randomly selected eye of 16 patients diagnosed with epilepsy, exposed to VGB therapy. A clinical diagnosis of VGB attributed visual field loss was documented in 44% of the group. The mean age was 39.3 years ± 14.5 years and the mean deviation was -4.76 dB ±4.34 dB. Each patient was examined with the Full Threshold, SITA Standard and SITA Fast algorithm. SITA Standard was on average approximately twice as fast (7.6 minutes) and SITA Fast approximately 3 times as fast (4.7 minutes) as examinations completed using the Full Threshold algorithm (15.8 minutes). In the clinical environment, the visual field outcome with both SITA algorithms was equivalent to visual field examination using the Full Threshold algorithm in terms of visual inspection of the grey scale plots , defect area and defect severity. Our research shows that both SITA algorithms are able to accurately map visual field loss attributed to VGB. As patients diagnosed with epilepsy are often vulnerable to fatigue, the time saving offered by SITA Fast means that this algorithm has a significant advantage for use with VGB recipients.

  5. COREMAP: Graphical user interface for displaying reactor core data in an interactive hexagon map

    SciTech Connect

    Muscat, F.L.; Derstine, K.L.

    1995-06-01

    COREMAP is a Graphical User Interface (GUI) designed to assist users read and check reactor core data from multidimensional neutronic simulation models in color and/or as text in an interactive 2D planar grid of hexagonal subassemblies. COREMAP is a complete GEODST/RUNDESC viewing tool which enables the user to access multi data set files (e.g. planes, moments, energy groups ,... ) and display up to two data sets simultaneously, one as color and the other as text. The user (1) controls color scale characteristics such as type (linear or logarithmic) and range limits, (2) controls the text display based upon conditional statements on data spelling, and value. (3) chooses zoom features such as core map size, number of rings and surrounding subassemblies, and (4) specifies the data selection for supplied popup subwindows which display a selection of data currently off-screen for a selected cell, as a list of data and/or as a graph. COREMAP includes a RUNDESC file editing tool which creates ``proposed`` Run-description files by point and click revisions to subassembly assignments in an existing EBRII Run-description file. COREMAP includes a fully automated printing option which creates high quality PostScript color or greyscale images of the core map independent of the monitor used, e.g. color prints can be generated with a session from a color or monochrome monitor. The automated PostScript output is an alternative to the xgrabsc based printing option. COREMAP includes a plotting option which creates graphs related to a selected cell. The user specifies the X and Y coordinates types (planes, moment, group, flux ,... ) and a parameter, P, when displaying several curves for the specified (X, Y) pair COREMAP supports hexagonal geometry reactor core configurations specified by: the GEODST file and binary Standard Interface Files and the RUNDESC ordering.

  6. Plume Tracker: Interactive mapping of volcanic sulfur dioxide emissions with high-performance radiative transfer modeling

    NASA Astrophysics Data System (ADS)

    Realmuto, Vincent J.; Berk, Alexander

    2016-11-01

    We describe the development of Plume Tracker, an interactive toolkit for the analysis of multispectral thermal infrared observations of volcanic plumes and clouds. Plume Tracker is the successor to MAP_SO2, and together these flexible and comprehensive tools have enabled investigators to map sulfur dioxide (SO2) emissions from a number of volcanoes with TIR data from a variety of airborne and satellite instruments. Our objective for the development of Plume Tracker was to improve the computational performance of the retrieval procedures while retaining the accuracy of the retrievals. We have achieved a 300 × improvement in the benchmark performance of the retrieval procedures through the introduction of innovative data binning and signal reconstruction strategies, and improved the accuracy of the retrievals with a new method for evaluating the misfit between model and observed radiance spectra. We evaluated the accuracy of Plume Tracker retrievals with case studies based on MODIS and AIRS data acquired over Sarychev Peak Volcano, and ASTER data acquired over Kilauea and Turrialba Volcanoes. In the Sarychev Peak study, the AIRS-based estimate of total SO2 mass was 40% lower than the MODIS-based estimate. This result was consistent with a 45% reduction in the AIRS-based estimate of plume area relative to the corresponding MODIS-based estimate. In addition, we found that our AIRS-based estimate agreed with an independent estimate, based on a competing retrieval technique, within a margin of ± 20%. In the Kilauea study, the ASTER-based concentration estimates from 21 May 2012 were within ± 50% of concurrent ground-level concentration measurements. In the Turrialba study, the ASTER-based concentration estimates on 21 January 2012 were in exact agreement with SO2 concentrations measured at plume altitude on 1 February 2012.

  7. Phosphorylation of the Kinase Interaction Motif in Mitogen-activated Protein (MAP) Kinase Phosphatase-4 Mediates Cross-talk between Protein Kinase A and MAP Kinase Signaling Pathways*

    PubMed Central

    Dickinson, Robin J.; Delavaine, Laurent; Cejudo-Marín, Rocío; Stewart, Graeme; Staples, Christopher J.; Didmon, Mark P.; Trinidad, Antonio Garcia; Alonso, Andrés; Pulido, Rafael; Keyse, Stephen M.

    2011-01-01

    MAP kinase phosphatase 4 (DUSP9/MKP-4) plays an essential role during placental development and is one of a subfamily of three closely related cytoplasmic dual-specificity MAPK phosphatases, which includes the ERK-specific enzymes DUSP6/MKP-3 and DUSP7/MKP-X. However, unlike DUSP6/MKP-3, DUSP9/MKP-4 also inactivates the p38α MAP kinase both in vitro and in vivo. Here we demonstrate that inactivation of both ERK1/2 and p38α by DUSP9/MKP-4 is mediated by a conserved arginine-rich kinase interaction motif located within the amino-terminal non-catalytic domain of the protein. Furthermore, DUSP9/MKP-4 is unique among these cytoplasmic MKPs in containing a conserved PKA consensus phosphorylation site 55RRXSer-58 immediately adjacent to the kinase interaction motif. DUSP9/MKP-4 is phosphorylated on Ser-58 by PKA in vitro, and phosphorylation abrogates the binding of DUSP9/MKP-4 to both ERK2 and p38α MAP kinases. In addition, although mutation of Ser-58 to either alanine or glutamic acid does not affect the intrinsic catalytic activity of DUSP9/MKP-4, phospho-mimetic (Ser-58 to Glu) substitution inhibits both the interaction of DUSP9/MKP-4 with ERK2 and p38α in vivo and its ability to dephosphorylate and inactivate these MAP kinases. Finally, the use of a phospho-specific antibody demonstrates that endogenous DUSP9/MKP-4 is phosphorylated on Ser-58 in response to the PKA agonist forskolin and is also modified in placental tissue. We conclude that DUSP9/MKP-4 is a bona fide target of PKA signaling and that attenuation of DUSP9/MKP-4 function can mediate cross-talk between the PKA pathway and MAPK signaling through both ERK1/2 and p38α in vivo. PMID:21908610

  8. Interaction between Solar Wind and Lunar Magnetic Anomalies observed by Kaguya MAP-PACE

    NASA Astrophysics Data System (ADS)

    Saito, Yoshifumi; Yokota, Shoichiro; Tanaka, Takaaki; Asamura, Kazushi; Nishino, Masaki; Yamamoto, Tadateru; Uemura, Kota; Tsunakawa, Hideo

    2010-05-01

    It is known that Moon has neither global intrinsic magnetic field nor thick atmosphere. Different from the Earth's case where the intrinsic global magnetic field prevents the solar wind from penetrating into the magnetosphere, solar wind directly impacts the lunar surface. Since the discovery of the lunar crustal magnetic field in 1960s, several papers have been published concerning the interaction between the solar wind and the lunar magnetic anomalies. MAG/ER on Lunar Prospector found heating of the solar wind electrons presumably due to the interaction between the solar wind and the lunar magnetic anomalies and the existence of the mini-magnetosphere was suggested. However, the detailed mechanism of the interaction has been unclear mainly due to the lack of the in-situ observed data of low energy ions. MAgnetic field and Plasma experiment - Plasma energy Angle and Composition Experiment (MAP-PACE) on Kaguya (SELENE) completed its ˜1.5-year observation of the low energy charged particles around the Moon on 10 June, 2009. Kaguya was launched on 14 September 2007 by H2A launch vehicle from Tanegashima Space Center in Japan. Kaguya was inserted into a circular lunar polar orbit of 100km altitude and continued observation for nearly 1.5 years till it impacted the Moon on 10 June 2009. During the last 5 months, the orbit was lowered to ˜50km-altitude between January 2009 and April 2009, and some orbits had further lower perilune altitude of ˜10km after April 2009. MAP-PACE consisted of 4 sensors: ESA (Electron Spectrum Analyzer)-S1, ESA-S2, IMA (Ion Mass Analyzer), and IEA (Ion Energy Analyzer). All the sensors performed quite well as expected from the laboratory experiment carried out before launch. Since each sensor had hemispherical field of view, two electron sensors and two ion sensors that were installed on the spacecraft panels opposite to each other could cover full 3-dimensional phase space of low energy electrons and ions. One of the ion sensors IMA was

  9. IGIS (Interactive Geologic Interpretation System) computer-aided photogeologic mapping with image processing, graphics and CAD/CAM capabilities

    SciTech Connect

    McGuffie, B.A.; Johnson, L.F.; Alley, R.E.; Lang, H.R. )

    1989-10-01

    Advances in computer technology are changing the way geologists integrate and use data. Although many geoscience disciplines are absolutely dependent upon computer processing, photogeological and map interpretation computer procedures are just now being developed. Historically, geologists collected data in the field and mapped manually on a topographic map or aerial photographic base. New software called the interactive Geologic Interpretation System (IGIS) is being developed at the Jet Propulsion Laboratory (JPL) within the National Aeronautics and Space Administration (NASA)-funded Multispectral Analysis of Sedimentary Basins Project. To complement conventional geological mapping techniques, Landsat Thematic Mapper (TM) or other digital remote sensing image data and co-registered digital elevation data are combined using computer imaging, graphics, and CAD/CAM techniques to provide tools for photogeologic interpretation, strike/dip determination, cross section construction, stratigraphic section measurement, topographic slope measurement, terrain profile generation, rotatable 3-D block diagram generation, and seismic analysis.

  10. Reconstructing Genome-Wide Protein–Protein Interaction Networks Using Multiple Strategies with Homologous Mapping

    PubMed Central

    Lo, Yu-Shu; Huang, Sing-Han; Luo, Yong-Chun; Lin, Chun-Yu; Yang, Jinn-Moon

    2015-01-01

    Background One of the crucial steps toward understanding the biological functions of a cellular system is to investigate protein–protein interaction (PPI) networks. As an increasing number of reliable PPIs become available, there is a growing need for discovering PPIs to reconstruct PPI networks of interesting organisms. Some interolog-based methods and homologous PPI families have been proposed for predicting PPIs from the known PPIs of source organisms. Results Here, we propose a multiple-strategy scoring method to identify reliable PPIs for reconstructing the mouse PPI network from two well-known organisms: human and fly. We firstly identified the PPI candidates of target organisms based on homologous PPIs, sharing significant sequence similarities (joint E-value ≤ 1 × 10−40), from source organisms using generalized interolog mapping. These PPI candidates were evaluated by our multiple-strategy scoring method, combining sequence similarities, normalized ranks, and conservation scores across multiple organisms. According to 106,825 PPI candidates in yeast derived from human and fly, our scoring method can achieve high prediction accuracy and outperform generalized interolog mapping. Experiment results show that our multiple-strategy score can avoid the influence of the protein family size and length to significantly improve PPI prediction accuracy and reflect the biological functions. In addition, the top-ranked and conserved PPIs are often orthologous/essential interactions and share the functional similarity. Based on these reliable predicted PPIs, we reconstructed a comprehensive mouse PPI network, which is a scale-free network and can reflect the biological functions and high connectivity of 292 KEGG modules, including 216 pathways and 76 structural complexes. Conclusions Experimental results show that our scoring method can improve the predicting accuracy based on the normalized rank and evolutionary conservation from multiple organisms. Our predicted

  11. Using Concept Maps as Instructional Materials to Foster the Understanding of the Atomic Model and Matter-Energy Interaction

    ERIC Educational Resources Information Center

    Aguiar, Joana G.; Correia, Paulo R. M.

    2016-01-01

    In this paper, we explore the use of concept maps (Cmaps) as instructional materials prepared by teachers, to foster the understanding of chemistry. We choose fireworks as a macroscopic event to teach basic chemical principles related to the Bohr atomic model and matter-energy interaction. During teachers' Cmap navigation, students can experience…

  12. Using Student Interactions to Foster Rule-Diagram Mapping during Problem Solving in an Intelligent Tutoring System

    ERIC Educational Resources Information Center

    Butcher, Kirsten R.; Aleven, Vincent

    2013-01-01

    In many domains, problem solving involves the application of general domain principles to specific problem representations. In 3 classroom studies with an intelligent tutoring system, we examined the impact of (learner-generated) interactions and (tutor-provided) visual cues designed to facilitate rule-diagram mapping (where students connect…

  13. Using Concept Maps as Instructional Materials to Foster the Understanding of the Atomic Model and Matter-Energy Interaction

    ERIC Educational Resources Information Center

    Aguiar, Joana G.; Correia, Paulo R. M.

    2016-01-01

    In this paper, we explore the use of concept maps (Cmaps) as instructional materials prepared by teachers, to foster the understanding of chemistry. We choose fireworks as a macroscopic event to teach basic chemical principles related to the Bohr atomic model and matter-energy interaction. During teachers' Cmap navigation, students can experience…

  14. Using Student Interactions to Foster Rule-Diagram Mapping during Problem Solving in an Intelligent Tutoring System

    ERIC Educational Resources Information Center

    Butcher, Kirsten R.; Aleven, Vincent

    2013-01-01

    In many domains, problem solving involves the application of general domain principles to specific problem representations. In 3 classroom studies with an intelligent tutoring system, we examined the impact of (learner-generated) interactions and (tutor-provided) visual cues designed to facilitate rule-diagram mapping (where students connect…

  15. Building disease-specific drug-protein connectivity maps from molecular interaction networks and PubMed abstracts.

    PubMed

    Li, Jiao; Zhu, Xiaoyan; Chen, Jake Yue

    2009-07-01

    The recently proposed concept of molecular connectivity maps enables researchers to integrate experimental measurements of genes, proteins, metabolites, and drug compounds under similar biological conditions. The study of these maps provides opportunities for future toxicogenomics and drug discovery applications. We developed a computational framework to build disease-specific drug-protein connectivity maps. We integrated gene/protein and drug connectivity information based on protein interaction networks and literature mining, without requiring gene expression profile information derived from drug perturbation experiments on disease samples. We described the development and application of this computational framework using Alzheimer's Disease (AD) as a primary example in three steps. First, molecular interaction networks were incorporated to reduce bias and improve relevance of AD seed proteins. Second, PubMed abstracts were used to retrieve enriched drug terms that are indirectly associated with AD through molecular mechanistic studies. Third and lastly, a comprehensive AD connectivity map was created by relating enriched drugs and related proteins in literature. We showed that this molecular connectivity map development approach outperformed both curated drug target databases and conventional information retrieval systems. Our initial explorations of the AD connectivity map yielded a new hypothesis that diltiazem and quinidine may be investigated as candidate drugs for AD treatment. Molecular connectivity maps derived computationally can help study molecular signature differences between different classes of drugs in specific disease contexts. To achieve overall good data coverage and quality, a series of statistical methods have been developed to overcome high levels of data noise in biological networks and literature mining results. Further development of computational molecular connectivity maps to cover major disease areas will likely set up a new model for

  16. MC EMiNEM maps the interaction landscape of the Mediator.

    PubMed

    Niederberger, Theresa; Etzold, Stefanie; Lidschreiber, Michael; Maier, Kerstin C; Martin, Dietmar E; Fröhlich, Holger; Cramer, Patrick; Tresch, Achim

    2012-01-01

    The Mediator is a highly conserved, large multiprotein complex that is involved essentially in the regulation of eukaryotic mRNA transcription. It acts as a general transcription factor by integrating regulatory signals from gene-specific activators or repressors to the RNA Polymerase II. The internal network of interactions between Mediator subunits that conveys these signals is largely unknown. Here, we introduce MC EMiNEM, a novel method for the retrieval of functional dependencies between proteins that have pleiotropic effects on mRNA transcription. MC EMiNEM is based on Nested Effects Models (NEMs), a class of probabilistic graphical models that extends the idea of hierarchical clustering. It combines mode-hopping Monte Carlo (MC) sampling with an Expectation-Maximization (EM) algorithm for NEMs to increase sensitivity compared to existing methods. A meta-analysis of four Mediator perturbation studies in Saccharomyces cerevisiae, three of which are unpublished, provides new insight into the Mediator signaling network. In addition to the known modular organization of the Mediator subunits, MC EMiNEM reveals a hierarchical ordering of its internal information flow, which is putatively transmitted through structural changes within the complex. We identify the N-terminus of Med7 as a peripheral entity, entailing only local structural changes upon perturbation, while the C-terminus of Med7 and Med19 appear to play a central role. MC EMiNEM associates Mediator subunits to most directly affected genes, which, in conjunction with gene set enrichment analysis, allows us to construct an interaction map of Mediator subunits and transcription factors.

  17. Geochemical mapping of magmatic gas water rock interactions in the aquifer of Mount Etna volcano

    NASA Astrophysics Data System (ADS)

    Brusca, L.; Aiuppa, A.; D'Alessandro, W.; Parello, F.; Allard, P.; Michel, A.

    2001-08-01

    Systematic analysis of major and minor elements in groundwaters from springs and wells on the slopes of Mt. Etna in 1995-1998 provides a detailed geochemical mapping of the aquifer of the volcano and of the interactions between magmatic gas, water bodies and their host rocks. Strong spatial correlations between the largest anomalies in pCO 2 (pH and alkalinity) K, Rb, Mg, Ca and Sr suggest a dominating control by magmatic gas (CO 2) and consequent basalt leaching by acidified waters of the shallow (meteoric) Etnean aquifer. Most groundwaters displaying this magmatic-type interaction discharge within active faulted zones on the S-SW and E lower flanks of the volcanic pile, but also in a newly recognised area on the northern flank, possibly tracking a main N-S volcano-tectonic structure. In the same time, the spatial distribution of T°C, TDS, Na, Li, Cl and B allows us to identify the existence of a deeper thermal brine with high salinity, high content of B, Cl and gases (CO 2, H 2S, CH 4) and low K/Na ratio, which is likely hosted in the sedimentary basement. This hot brine reaches the surface only at the periphery of the volcano near the Village of Paternò, where it gives rise to mud volcanoes called "Salinelle di Paternò". However, the contribution of similar brines to shallower groundwaters is also detected in other sectors to the W (Bronte, Maletto), SW (Adrano) and SE (Acireale), suggesting its possible widespread occurrence beneath Etna. This thermal brine is also closely associated with hydrocarbon fields all around the volcano and its rise, generally masked by the high outflow of the shallow aquifer, may be driven by the ascent of mixed sedimentary-magmatic gases through the main faults cutting the sedimentary basement.

  18. Mapping Region of Human Restriction Factor APOBEC3H Critical for Interaction with HIV-1 Vif.

    PubMed

    Nakashima, Masaaki; Tsuzuki, Shinya; Awazu, Hiroaki; Hamano, Akiko; Okada, Ayaka; Ode, Hirotaka; Maejima, Masami; Hachiya, Atsuko; Yokomaku, Yoshiyuki; Watanabe, Nobuhisa; Akari, Hirofumi; Iwatani, Yasumasa

    2017-04-21

    The APOBEC3 (A3) family of cellular cytidine deaminases comprises seven members (A, B, C, D, F, G, and H) that potently inhibit retroviral replication. Human immunodeficiency virus type 1 (HIV-1) Vif is a small pleiotropic protein that specifically inactivates these enzymes, targeting them for ubiquitin-mediated proteasomal degradation. A3 Vif-interaction sites are presumed to fall into three distinct types: A3C/D/F, A3G, and A3H. To date, two types of A3G and A3C/D/F sites have been well characterized, whereas the A3H Vif-binding site remains poorly defined. Here, we explore the residues critical for the A3H-type Vif interaction. To avoid technical difficulties in performing experiments with human A3H haplotype II (hapII), which is relatively resistant to HIV-1 Vif, we employed its ortholog chimpanzee A3H (cA3H), which displays high Vif sensitivity, for a comparison of sensitivity with that of A3H hapII. The Vif susceptibility of A3H hapII-cA3H chimeras and their substitution mutants revealed a single residue at position 97 as a major determinant for the difference in their Vif sensitivities. We further surveyed critical residues by structure-guided mutagenesis using an A3H structural model and thus identified eight additional residues important for Vif sensitivity, which mapped to the α3 and α4 helices of A3H. Interestingly, this area is located on a surface adjacent to the A3G and A3C/D/F interfaces and is composed of negatively charged and hydrophobic patches. These findings suggest that HIV-1 Vif has evolved to utilize three dispersed surfaces for recognizing three types of interfaces on A3 proteins under certain structural constraints.

  19. HAZPAC; an interactive map of Pacific Rim natural hazards, population, and infrastructure

    USGS Publications Warehouse

    Bemis, B.L.; Goss, H.V.; Yurkovich, E.S.; Perron, T.J.; Howell, D.G.

    2002-01-01

    This is an online version of a CD-ROM publication. The text files that describe using this publication make reference to software provided on the disc. For this online version the software can be downloaded for free from Adobe Systems and Environmental Systems Research Institute, Inc. (ESRI). Welcome to HAZPAC! HAZPAC is an interactive map about natural hazard risk in the Pacific Rim region. It is intended to communicate to a broad audience the ideas of 'Crowding the Rim,' which is an international, public-private partnership that fosters collaborative solutions for regional risks. HAZPAC, which stands for 'HAZards of the PACific,' uses Geographic Information System (GIS) technology to help people visualize the socioeconomic connections and shared hazard vulnerabilities among Pacific Rim countries, as well as to explore the general nature of risk. Please refer to the 'INTRODUCTION TO HAZPAC' section of the readme file below to determine which HAZPAC project will be right for you. Once you have decided which HAZPAC project is suitable for you, please refer to the 'GETTING STARTED' sections in the readme file for some basic information that will help you begin using HAZPAC. Also, we highly recommend that you follow the Tutorial exercises in the project-specific HAZPAC User Guides. The User Guides are PDF (Portable Document Format) files that must be read with Adobe Acrobat Reader (a free copy of Acrobat Reader is available using the link near the bottom of this page).

  20. Identification of Links Between Cellular Pathways by Genetic Interaction Mapping (GIM).

    PubMed

    Malabat, Christophe; Saveanu, Cosmin

    2016-01-01

    The yeast systematic deletion collection offered the basis for a number of different strategies that establish functional links between genes by analyzing the phenotype of cells that combine two different deletions or mutations. A distinguishing feature of the collection is the presence of molecular barcodes at each deleted locus, which can be used to quantify the presence and abundance of cells bearing a given allele in a complex mix. As a result, a large number of mutants can be tested in batch cultures, replacing tedious manipulation of thousands of individual strains with a barcode microarray readout. Barcode-based genetic screens like Genetic Interaction Mapping (GIM) thus require little investment in terms of specific equipment, are fast to perform, and allow precise measurements of double mutant growth rates for both aggravating (synthetic sick) and alleviating (epistatic) effects. We describe here protocols for preparing the pools of haploid double mutant S. cerevisiae cells, testing their composition with barcode microarrays, and analyzing the results to extract useful functional information.

  1. High-throughput genetic interaction mapping in the fission yeast Schizosaccharomyces pombe.

    PubMed

    Roguev, Assen; Wiren, Marianna; Weissman, Jonathan S; Krogan, Nevan J

    2007-10-01

    Epistasis analysis, which reports on the extent to which the function of one gene depends on the presence of a second, is a powerful tool for studying the functional organization of the cell. Systematic genome-wide studies of epistasis, however, have been limited, with the majority of data being collected in the budding yeast, Saccharomyces cerevisiae. Here we present two 'pombe epistasis mapper' strategies, PEM-1 and PEM-2, which allow for high-throughput double mutant generation in the fission yeast, S. pombe. These approaches take advantage of a previously undescribed, recessive, cycloheximide-resistance mutation. Both systems can be used for genome-wide screens or for the generation of high-density, quantitative epistatic miniarray profiles (E-MAPs). Since S. cerevisiae and S. pombe are evolutionary distant, this methodology will provide insight into conserved biological pathways that are present in S. pombe, but not S. cerevisiae, and will enable a comprehensive analysis of the conservation of genetic interaction networks.

  2. Carbon Sequestration Atlas and Interactive Maps from the Southwest Regional Partnership on Carbon Sequestration

    DOE Data Explorer

    McPherson, Brian

    In November of 2002, DOE announced a global climate change initiative involving joint government-industry partnerships working together to find sensible, low cost solutions for reducing GHG emissions. As a result, seven regional partnerships were formed; the Southwest Regional Partnership on Carbon Sequestration (SWP) is one of those. These groups are utilizing their expertise to assess sequestration technologies to capture carbon emissions, identify and evaluate appropriate storage locations, and engage a variety of stakeholders in order to increase awareness of carbon sequestration. Stakeholders in this project are made up of private industry, NGOs, the general public, and government entities. There are a total of 44 current organizations represented in the partnership including electric utilities, oil and gas companies, state governments, universities, NGOs, and tribal nations. The SWP is coordinated by New Mexico Tech and encompasses New Mexico, Arizona, Colorado, Oklahoma, Utah, and portions of Kansas, Nevada, Texas, and Wyoming. Field test sites for the region are located in New Mexico (San Juan Basin), Utah (Paradox Basin), and Texas (Permian Basin).[Taken from the SWP C02 Sequestration Atlas] The SWP makes available at this website their CO2 Sequestration Atlas and an interactive data map.

  3. An interactive mapping tool to assess individual mobility patterns in neighborhood studies.

    PubMed

    Chaix, Basile; Kestens, Yan; Perchoux, Camille; Karusisi, Noëlla; Merlo, Juan; Labadi, Karima

    2012-10-01

    As their most critical limitation, neighborhood and health studies published to date have not taken into account nonresidential activity places where individuals travel in their daily lives. However, identifying low-mobility populations residing in low-resource environments, assessing cumulative environmental exposures over multiple activity places, and identifying specific activity locations for targeting interventions are important for health promotion. Daily mobility has not been given due consideration in part because of a lack of tools to collect locational information on activity spaces. Thus, the first aim of the current article is to describe VERITAS (Visualization and Evaluation of Route Itineraries, Travel Destinations, and Activity Spaces), an interactive web mapping application that can geolocate individuals' activity places, routes between locations, and relevant areas such as experienced or perceived neighborhoods. The second aim is to formalize the theoretic grounds of a contextual expology as a subdiscipline to better assess the spatiotemporal configuration of environmental exposures. Based on activity place data, various indicators of individual patterns of movement in space (spatial behavior) are described. Successive steps are outlined for elaborating variables of multiplace environmental exposure (collection of raw locational information, selection/exclusion of locational data, defining an exposure area for measurement, and calculation). Travel and activity place network areas are discussed as a relevant construct for environmental exposure assessment. Finally, a note of caution is provided that these measures require careful handling to avoid increasing the magnitude of confounding (selective daily mobility bias).

  4. An interactive image segmentation method for lithological boundary detection: A rapid mapping tool for geologists

    NASA Astrophysics Data System (ADS)

    Vasuki, Yathunanthan; Holden, Eun-Jung; Kovesi, Peter; Micklethwaite, Steven

    2017-03-01

    Large volumes of images are collected by geoscientists using remote sensing platforms. Manual analysis of these images is a time consuming task and there is a need for fast and robust image interpretation tools. In particular the reliable mapping of lithological boundaries is a critical step for geological interpretation. In this contribution we developed an interactive image segmentation algorithm that harnesses the geologist's input and exploits automated image analysis to provide a practical tool for lithology boundary detection, using photographic images of rock surfaces. In the proposed method, the user is expected to draw rough markings to indicate the locations of different geological units in the image. Image segmentation is performed by segmenting regions based on their homogeneity in colour. This results in a high density of segmented regions which are then iteratively merged based on the colour of different geological units and the user input. Finally, a post-processing step allows the user to edit the boundaries. An experiment was conducted using photographic rock surface images collected by a UAV and a handheld digital camera. The proposed technique was applied to detect lithology boundaries. It was found that the proposed method reduced the interpretation time by a factor of four relative to manual segmentation, while achieving more than 96% similarity in boundary detection. As a result the proposed method has the potential to provide practical support for interpreting large volume of complex geological images.

  5. Interactive Web-Based Map: Applications to Large Data Sets in the Geosciences. Interactive Web-Based Map: Applications to Large Data Sets in the Geosciences.

    NASA Astrophysics Data System (ADS)

    Garbow, Z. A.; Olson, N. R.; Yuen, D. A.; Boggs, J. M.

    2001-12-01

    Current advances in computer hardware, information technology and data collection techniques have produced very large data sets, sometimes more than terabytes,in a wide variety of scientific and engineering disciplines. We must harness this opportunity to visualize and extract useful information from geophysical and geological data. We have taken the task of data-mining by using a map-like approach over the web for interrogating the humongous data, using a client-server paradigm. The spatial-data is mapped onto a two-dimensional grid from which the user ( client ) can quiz the data with the map-interface as a user extension . The data is stored on high-end compute server. The computational gateway separating the client and the server can be the front-end of an electronic publication , electronic classroom , a Grid system device or e-business. We have used a combination of JAVA, JAVA-3D and Perl for processing the data and communicating them between the client and the server. The user can interrogate the geospatial data over any particular region with arbitrary length scales and pose relevant statistical questions, such as the histogram plots and local statistics. We have applied this method for the following data sets (1.) distribution of prime numbers (2.) two-dimensional mantle convection (3.) three-dimensional mantle convection (4) high-resolution satellite reflectance data over the Upper Midwest for multiple wavelengths (5) molecular dynamics describing the flow of blood in narrow vessels. Using this map-interface concept, the user can actually interrogate these data over the web. This strategy for dissecting large data-sets can be easily applied to other areas, such as satellite geodesy and earthquake data. This mode of data-query may function in an adequately covered wireless web environment with a transfer rate of around 10 Mbit/sec .

  6. Gene-Environment Interactions Target Mitogen-activated Protein 3 Kinase 1 (MAP3K1) Signaling in Eyelid Morphogenesis*

    PubMed Central

    Mongan, Maureen; Meng, Qinghang; Wang, Jingjing; Kao, Winston W.-Y.; Puga, Alvaro; Xia, Ying

    2015-01-01

    Gene-environment interactions determine the biological outcomes through mechanisms that are poorly understood. Mouse embryonic eyelid closure is a well defined model to study the genetic control of developmental programs. Using this model, we investigated how exposure to dioxin-like environmental pollutants modifies the genetic risk of developmental abnormalities. Our studies reveal that mitogen-activated protein 3 kinase 1 (MAP3K1) signaling is a focal point of gene-environment cross-talk. Dioxin exposure, acting through the aryl hydrocarbon receptor (AHR), blocked eyelid closure in genetic mutants in which MAP3K1 signaling was attenuated but did not disturb this developmental program in either wild type or mutant mice with attenuated epidermal growth factor receptor or WNT signaling. Exposure also markedly inhibited c-Jun phosphorylation in Map3k1+/− embryonic eyelid epithelium, suggesting that dioxin-induced AHR pathways can synergize with gene mutations to inhibit MAP3K1 signaling. Our studies uncover a novel mechanism through which the dioxin-AHR axis interacts with the MAP3K1 signaling pathways during fetal development and provide strong empirical evidence that specific gene alterations can increase the risk of developmental abnormalities driven by environmental pollutant exposure. PMID:26109068

  7. 3d interaction homology: The structurally known rotamers of tyrosine derive from a surprisingly limited set of information-rich hydropathic interaction environments described by maps.

    PubMed

    Ahmed, Mostafa H; Koparde, Vishal N; Safo, Martin K; Neel Scarsdale, J; Kellogg, Glen E

    2015-06-01

    Sidechain rotamer libraries are obtained through exhaustive statistical analysis of existing crystallographic structures of proteins and have been applied in multiple aspects of structural biology, for example, crystallography of relatively low-resolution structures, in homology model building and in biomolecular NMR. Little is known, however, about the driving forces that lead to the preference or suitability of one rotamer over another. Construction of 3D hydropathic interaction maps for nearly 30,000 tyrosines reveals the environment around each, in terms of hydrophobic (π-π stacking, etc.) and polar (hydrogen bonding, etc.) interactions. After partitioning the tyrosines into backbone-dependent (ϕ, ψ) bins, a map similarity metric based on the correlation coefficient was applied to each map-map pair to build matrices suitable for clustering with k-means. The first bin (-200° ≤ ϕ < -155°; -205° ≤ ψ < -160°), representing 631 tyrosines, reduced to 14 unique hydropathic environments, with most diversity arising from favorable hydrophobic interactions with many different residue partner types. Polar interactions for tyrosine include surprisingly ubiquitous hydrogen bonding with the phenolic OH and a handful of unique environments surrounding the tyrosine backbone. The memberships of all but one of the 14 environments are dominated (>50%) by a single χ(1)/χ(2) rotamer. The last environment has weak or no interactions with the tyrosine ring and its χ(1)/χ(2) rotamer is indeterminate, which is consistent with it being composed of mostly surface residues. Each tyrosine residue attempts to fulfill its hydropathic valence and thus, structural water molecules are seen in a variety of roles throughout protein structure. © 2015 Wiley Periodicals, Inc.

  8. NeuroMap: A Spline-Based Interactive Open-Source Software for Spatiotemporal Mapping of 2D and 3D MEA Data.

    PubMed

    Abdoun, Oussama; Joucla, Sébastien; Mazzocco, Claire; Yvert, Blaise

    2011-01-01

    A major characteristic of neural networks is the complexity of their organization at various spatial scales, from microscopic local circuits to macroscopic brain-scale areas. Understanding how neural information is processed thus entails the ability to study them at multiple scales simultaneously. This is made possible using microelectrodes array (MEA) technology. Indeed, high-density MEAs provide large-scale coverage (several square millimeters) of whole neural structures combined with microscopic resolution (about 50 μm) of unit activity. Yet, current options for spatiotemporal representation of MEA-collected data remain limited. Here we present NeuroMap, a new interactive Matlab-based software for spatiotemporal mapping of MEA data. NeuroMap uses thin plate spline interpolation, which provides several assets with respect to conventional mapping methods used currently. First, any MEA design can be considered, including 2D or 3D, regular or irregular, arrangements of electrodes. Second, spline interpolation allows the estimation of activity across the tissue with local extrema not necessarily at recording sites. Finally, this interpolation approach provides a straightforward analytical estimation of the spatial Laplacian for better current sources localization. In this software, coregistration of 2D MEA data on the anatomy of the neural tissue is made possible by fine matching of anatomical data with electrode positions using rigid-deformation-based correction of anatomical pictures. Overall, NeuroMap provides substantial material for detailed spatiotemporal analysis of MEA data. The package is distributed under GNU General Public License and available at http://sites.google.com/site/neuromapsoftware.

  9. Proteins interacting with mitochondrial ATP-dependent Lon protease (MAP1) in Magnaporthe oryzae are involved in rice blast disease.

    PubMed

    Cui, Xiao; Wei, Yi; Wang, Yu-Han; Li, Jian; Wong, Fuk-Ling; Zheng, Ya-Jie; Yan, Hai; Liu, Shao-Shuai; Liu, Jin-Liang; Jia, Bao-Lei; Zhang, Shi-Hong

    2015-10-01

    The ATP-dependent Lon protease is involved in many physiological processes. In bacteria, Lon regulates pathogenesis and, in yeast, Lon protects mitochondia from oxidative damage. However, little is known about Lon in fungal phytopathogens. MAP1, a homologue of Lon in Magnaporthe oryzae, was recently identified to be important for stress resistance and pathogenesis. Here, we focus on a novel pathogenic pathway mediated by MAP1. Based on an interaction system between rice and a tandem affinity purification (TAP)-tagged MAP1 complementation strain, we identified 23 novel fungal proteins from infected leaves using a TAP approach with mass spectrometry, and confirmed that 14 of these proteins physically interact with MAP1 in vivo. Among these 14 proteins, 11 candidates, presumably localized to the mitochondria, were biochemically determined to be substrates of MAP1 hydrolysis. Deletion mutants were created and functionally analysed to further confirm the involvement of these proteins in pathogenesis. The results indicated that all mutants showed reduced conidiation and sensitivity to hydrogen peroxide. Appressorial formations were not affected, although conidia from certain mutants were morphologically altered. In addition, virulence was reduced in four mutants, enhanced (with lesions forming earlier) in two mutants and remained unchanged in one mutant. Together with the known virulence-related proteins alternative oxidase and enoyl-CoA hydratase, we propose that most of the Lon-interacting proteins are involved in the pathogenic regulation pathway mediated by MAP1 in M. oryzae. Perturbation of this pathway may represent an effective approach for the inhibition of rice blast disease. © 2015 BSPP AND JOHN WILEY & SONS LTD.

  10. MARs Tools for Interactive ANalysis (MARTIAN): Google Maps Tools for Visual Exploration of Geophysical Modeling on Mars

    NASA Astrophysics Data System (ADS)

    Dimitrova, L. L.; Haines, M.; Holt, W. E.; Schultz, R. A.; Richard, G.; Haines, A. J.

    2006-12-01

    Interactive maps of surface-breaking faults and stress models on Mars provide important tools to engage undergraduate students, educators, and scientists with current geological and geophysical research. We have developed a map based on the Google Maps API -- an Internet based tool combining DHTML and AJAX, -- which allows very large maps to be viewed over the World Wide Web. Typically, small portions of the maps are downloaded as needed, rather than the entire image at once. This set-up enables relatively fast access for users with low bandwidth. Furthermore, Google Maps provides an extensible interactive interface making it ideal for visualizing multiple data sets at the user's choice. The Google Maps API works primarily with data referenced to latitudes and longitudes, which is then mapped in Mercator projection only. We have developed utilities for general cylindrical coordinate systems by converting these coordinates into equivalent Mercator projection before including them on the map. The MARTIAN project is available at http://rock.geo.sunysb.edu/~holt/Mars/MARTIAN/. We begin with an introduction to the Martian surface using a topography model. Faults from several datasets are classified by type (extension vs. compression) and by time epoch. Deviatoric stresses due to gravitational potential energy differences, calculated from the topography and crustal thickness, can be overlain. Several quantitative measures for the fit of the stress field to the faults are also included. We provide introductory text and exercises spanning a range of topics: how are faults identified, what stress is and how it relates to faults, what gravitational potential energy is and how variations in it produce stress, how the models are created, and how these models can be evaluated and interpreted. The MARTIAN tool is used at Stony Brook University in GEO 310: Introduction to Geophysics, a class geared towards junior and senior geosciences majors. Although this project is in its

  11. Interaction between solar wind and lunar magnetic anomalies observed by MAP-PACE on Kaguya

    NASA Astrophysics Data System (ADS)

    Saito, Yoshifumi; Yokota, Shoichiro; Tanaka, Takaaki; Asamura, Kazushi; Nishino, Masaki N.; Yamamoto, Tadateru I.; Tsunakawa, Hideo

    It is well known that the Moon has neither global intrinsic magnetic field nor thick atmosphere. Different from the Earth's case where the intrinsic global magnetic field prevents the solar wind from penetrating into the magnetosphere, solar wind directly impacts the lunar surface. MAgnetic field and Plasma experiment -Plasma energy Angle and Composition Experiment (MAP-PACE) on Kaguya (SELENE) completed its 1.5-year observation of the low energy charged particles around the Moon on 10 June 2009. Kaguya was launched on 14 September 2007 by H2A launch vehicle from Tanegashima Space Center in Japan. Kaguya was inserted into a circular lunar polar orbit of 100km altitude and continued observation for nearly 1.5 years till it impacted the Moon on 10 June 2009. During the last 5 months, the orbit was lowered to 50km-altitude between January 2009 and April 2009, and some orbits had further lower perilune altitude of 10km after April 2009. MAP-PACE consisted of 4 sensors: ESA (Electron Spectrum Analyzer)-S1, ESA-S2, IMA (Ion Mass Analyzer), and IEA (Ion Energy Analyzer). Since each sensor had hemispherical field of view, two electron sensors and two ion sensors that were installed on the spacecraft panels opposite to each other could cover full 3-dimensional phase space of low energy electrons and ions. One of the ion sensors IMA was an energy mass spectrometer. IMA measured mass identified ion energy spectra that had never been obtained at 100km altitude polar orbit around the Moon. When Kaguya flew over South Pole Aitken region, where strong magnetic anomalies exist, solar wind ions reflected by magnetic anomalies were observed. These ions had much higher flux than the solar wind protons scattered at the lunar surface. The magnetically reflected ions had nearly the same energy as the incident solar wind ions while the solar wind protons scattered at the lunar surface had slightly lower energy than the incident solar wind ions. At 100km altitude, when the reflected ions

  12. RICH MAPS

    EPA Science Inventory

    Michael Goodchild recently gave eight reasons why traditional maps are limited as communication devices, and how interactive internet mapping can overcome these limitations. In the past, many authorities in cartography, from Jenks to Bertin, have emphasized the importance of sim...

  13. RICH MAPS

    EPA Science Inventory

    Michael Goodchild recently gave eight reasons why traditional maps are limited as communication devices, and how interactive internet mapping can overcome these limitations. In the past, many authorities in cartography, from Jenks to Bertin, have emphasized the importance of sim...

  14. Raman spectroscopy based toolkit for mapping bacterial social interactions relevant to human and plant health

    NASA Astrophysics Data System (ADS)

    Couvillion, Sheha Polisetti

    Bacteria interact and co-exist with other microbes and with higher organisms like plants and humans, playing a major role in their health and well being. These ubiquitous single celled organisms are so successful, because they can form organized communities, called biofilms, that protect them from environmental stressors and enable communication and cooperation among members of the community. The work described in this thesis develops a toolkit of analytical techniques centered around Raman microspectroscopy and imaging representing a powerful approach to non-invasively investigate bacterial communities, yielding molecular information at the sub-micrometer length scale. Bacterial cellular components of non-pigmented and pigmented rhizosphere strains are characterized, and regiospecific SERS is used for cases where resonantly enhanced background signals obscure the spectra. Silver nanoparticle colloids were synthesized in situ, in the presence of the cells to form a proximal coating and principal component analysis (PCA) revealed features attributed to flavins. SERS enabled in situ acquisition of Raman spectra and chemical images in highly autofluorescent P.aeruginosa biofilms. In combination with PCA, this allowed for non-invasive spatial mapping of bacterial communities and revealed differences between strains and nutrients in the secretion of virulence factor pyocyanin. The rich potential of using Raman microspectroscopy to study plant-microbe interactions is demonstrated. Effect of exposure to oxidative stress, on both the wild type Pantoea sp. YR343 and carotenoid mutant Delta crtB, was assessed by following the intensity of the 1520 cm -1 and 1126 cm-1 Raman bands, respectively, after treatment with various concentrations of H2O2. Significant changes were observed in these marker bands even at concentrations (1 mM) below the point at which the traditional plate-based viability assay shows an effect (5-10 mM), thus establishing the value of Raman

  15. Genome-wide mapping in a house mouse hybrid zone reveals hybrid sterility loci and Dobzhansky-Muller interactions

    PubMed Central

    Turner, Leslie M; Harr, Bettina

    2014-01-01

    Mapping hybrid defects in contact zones between incipient species can identify genomic regions contributing to reproductive isolation and reveal genetic mechanisms of speciation. The house mouse features a rare combination of sophisticated genetic tools and natural hybrid zones between subspecies. Male hybrids often show reduced fertility, a common reproductive barrier between incipient species. Laboratory crosses have identified sterility loci, but each encompasses hundreds of genes. We map genetic determinants of testis weight and testis gene expression using offspring of mice captured in a hybrid zone between M. musculus musculus and M. m. domesticus. Many generations of admixture enables high-resolution mapping of loci contributing to these sterility-related phenotypes. We identify complex interactions among sterility loci, suggesting multiple, non-independent genetic incompatibilities contribute to barriers to gene flow in the hybrid zone. DOI: http://dx.doi.org/10.7554/eLife.02504.001 PMID:25487987

  16. Genome-wide mapping in a house mouse hybrid zone reveals hybrid sterility loci and Dobzhansky-Muller interactions.

    PubMed

    Turner, Leslie M; Harr, Bettina

    2014-12-09

    Mapping hybrid defects in contact zones between incipient species can identify genomic regions contributing to reproductive isolation and reveal genetic mechanisms of speciation. The house mouse features a rare combination of sophisticated genetic tools and natural hybrid zones between subspecies. Male hybrids often show reduced fertility, a common reproductive barrier between incipient species. Laboratory crosses have identified sterility loci, but each encompasses hundreds of genes. We map genetic determinants of testis weight and testis gene expression using offspring of mice captured in a hybrid zone between M. musculus musculus and M. m. domesticus. Many generations of admixture enables high-resolution mapping of loci contributing to these sterility-related phenotypes. We identify complex interactions among sterility loci, suggesting multiple, non-independent genetic incompatibilities contribute to barriers to gene flow in the hybrid zone.

  17. Evolution of pleiotropy: epistatic interaction pattern supports a mechanistic model underlying variation in genotype-phenotype map.

    PubMed

    Pavlicev, Mihaela; Norgard, Elizabeth A; Fawcett, Gloria L; Cheverud, James M

    2011-07-15

    The genotype-phenotype (GP) map consists of developmental and physiological mechanisms mapping genetic onto phenotypic variation. It determines the distribution of heritable phenotypic variance on which selection can act. Comparative studies of morphology as well as of gene regulatory networks show that the GP map itself evolves, yet little is known about the actual evolutionary mechanisms involved. The study of such mechanisms requires exploring the variation in GP maps at the population level, which presently is easier to quantify by statistical genetic methods rather than by regulatory network structures. We focus on the evolution of pleiotropy, a major structural aspect of the GP map. Pleiotropic genes affect multiple traits and underlie genetic covariance between traits, often causing evolutionary constraints. Previous quantitative genetic studies have demonstrated population-level variation in pleiotropy in the form of loci, at which genotypes differ in the genetic covariation between traits. This variation can potentially fuel evolution of the GP map under selection and/or drift. Here, we propose a developmental mechanism underlying population genetic variation in covariance and test its predictions. Specifically, the mechanism predicts that the loci identified as responsible for genetic variation in pleiotropy are involved in trait-specific epistatic interactions. We test this prediction for loci affecting allometric relationships between traits in an advanced intercross between inbred mouse strains. The results consistently support the prediction. We further find a high degree of sign epistasis in these interactions, which we interpret as an indication of adaptive gene complexes within the diverged parental lines. Copyright © 2011 Wiley-Liss, Inc., A Wiley Company.

  18. Protein-protein interaction and gene co-expression maps of ARFs and Aux/IAAs in Arabidopsis

    PubMed Central

    Piya, Sarbottam; Shrestha, Sandesh K.; Binder, Brad; Stewart, C. Neal; Hewezi, Tarek

    2014-01-01

    The phytohormone auxin regulates nearly all aspects of plant growth and development. Based on the current model in Arabidopsis thaliana, Auxin/indole-3-acetic acid (Aux/IAA) proteins repress auxin-inducible genes by inhibiting auxin response transcription factors (ARFs). Experimental evidence suggests that heterodimerization between Aux/IAA and ARF proteins are related to their unique biological functions. The objective of this study was to generate the Aux/IAA-ARF protein-protein interaction map using full length sequences and locate the interacting protein pairs to specific gene co-expression networks in order to define tissue-specific responses of the Aux/IAA-ARF interactome. Pairwise interactions between 19 ARFs and 29 Aux/IAAs resulted in the identification of 213 specific interactions of which 79 interactions were previously unknown. The incorporation of co-expression profiles with protein-protein interaction data revealed a strong correlation of gene co-expression for 70% of the ARF-Aux/IAA interacting pairs in at least one tissue/organ, indicative of the biological significance of these interactions. Importantly, ARF4-8 and 19, which were found to interact with almost all Aux-Aux/IAA showed broad co-expression relationships with Aux/IAA genes, thus, formed the central hubs of the co-expression network. Our analyses provide new insights into the biological significance of ARF-Aux/IAA associations in the morphogenesis and development of various plant tissues and organs. PMID:25566309

  19. A mitochondrial-focused genetic interaction map reveals a scaffold-like complex required for inner membrane organization in mitochondria.

    PubMed

    Hoppins, Suzanne; Collins, Sean R; Cassidy-Stone, Ann; Hummel, Eric; Devay, Rachel M; Lackner, Laura L; Westermann, Benedikt; Schuldiner, Maya; Weissman, Jonathan S; Nunnari, Jodi

    2011-10-17

    To broadly explore mitochondrial structure and function as well as the communication of mitochondria with other cellular pathways, we constructed a quantitative, high-density genetic interaction map (the MITO-MAP) in Saccharomyces cerevisiae. The MITO-MAP provides a comprehensive view of mitochondrial function including insights into the activity of uncharacterized mitochondrial proteins and the functional connection between mitochondria and the ER. The MITO-MAP also reveals a large inner membrane-associated complex, which we term MitOS for mitochondrial organizing structure, comprised of Fcj1/Mitofilin, a conserved inner membrane protein, and five additional components. MitOS physically and functionally interacts with both outer and inner membrane components and localizes to extended structures that wrap around the inner membrane. We show that MitOS acts in concert with ATP synthase dimers to organize the inner membrane and promote normal mitochondrial morphology. We propose that MitOS acts as a conserved mitochondrial skeletal structure that differentiates regions of the inner membrane to establish the normal internal architecture of mitochondria.

  20. A mitochondrial-focused genetic interaction map reveals a scaffold-like complex required for inner membrane organization in mitochondria

    PubMed Central

    Hoppins, Suzanne; Collins, Sean R.; Cassidy-Stone, Ann; Hummel, Eric; DeVay, Rachel M.; Lackner, Laura L.; Westermann, Benedikt; Schuldiner, Maya

    2011-01-01

    To broadly explore mitochondrial structure and function as well as the communication of mitochondria with other cellular pathways, we constructed a quantitative, high-density genetic interaction map (the MITO-MAP) in Saccharomyces cerevisiae. The MITO-MAP provides a comprehensive view of mitochondrial function including insights into the activity of uncharacterized mitochondrial proteins and the functional connection between mitochondria and the ER. The MITO-MAP also reveals a large inner membrane–associated complex, which we term MitOS for mitochondrial organizing structure, comprised of Fcj1/Mitofilin, a conserved inner membrane protein, and five additional components. MitOS physically and functionally interacts with both outer and inner membrane components and localizes to extended structures that wrap around the inner membrane. We show that MitOS acts in concert with ATP synthase dimers to organize the inner membrane and promote normal mitochondrial morphology. We propose that MitOS acts as a conserved mitochondrial skeletal structure that differentiates regions of the inner membrane to establish the normal internal architecture of mitochondria. PMID:21987634

  1. Basaltic Magma-Water Interaction on Earth: Recognition Criteria To Aid Planetary Mapping on Mars (Invited)

    NASA Astrophysics Data System (ADS)

    Skilling, I. P.; Graettinger, A. H.; Mercurio, E.; McGarvie, D.; Edwards, B. R.

    2013-12-01

    The interaction of basaltic magma with frozen/liquid water or wet sediment is a very common process on Earth, resulting in a wide array of explosively and non-explosively generated products at the micron to kilometre scale. A variety of products and edifices on Mars have also been interpreted as having formed by such interaction, but with the exception of rootless cones, such interpretations are rarely unequivocal. This talk focuses on terrestrial process recognition criteria at a scale, orientation (vertical) and erosion level that is relevant to Mars geological mapping. In this context, we emphasise intrusions with peperite margins and wide hydrothermal haloes, steep margins of ice-contact lava flows, subaerial-subaqueous lava delta transitions, lava domains with distinctive water-cooled jointing, edifices that are dominated by slumped and rotated beds, and the presence of surrounding fluvial deposits and erosion. The most common products of magma-water interaction on Earth are subaqueously emplaced lava flows, which are dominated by pillow lavas. Though pillows are not easy to distinguish from subaerial pahoehoe toes at the resolution of most remote imagery, they are commonly associated with distinctively jointed lava domains, which are usually on a larger scale, including areas of water-cooled jointing (curvicolumnar, blocky etc), lava-filled tubes, which often display radial jointing, and steep talus deposits of joint-block breccia. Subaqueous basaltic lavas emplaced in an ice-confined environment may also display near-vertical ice-contact margins, draped by curtains of elongate pillows or cavities formed from melting of included ice-blocks. Subaerial lava flows that transition into water also develop large-scale foreset-bedding close to the angle of repose, which should be easily visible, at least in oblique imagery. As the majority of the Martian surface is more deeply eroded than most areas of terrestrial basaltic volcanism, it is important to discuss

  2. A quantitative chemotherapy genetic interaction map reveals new factors associated with PARP inhibitor resistance | Office of Cancer Genomics

    Cancer.gov

    Nearly every cancer patient is treated with chemotherapy yet our understanding of factors that dictate response and resistance to such agents remains limited. We report the generation of a quantitative chemical-genetic interaction map in human mammary epithelial cells that charts the impact of knockdown of 625 cancer and DNA repair related genes on sensitivity to 29 drugs, covering all classes of cancer chemotherapeutics.

  3. Global Mapping of Protein-Lipid Interactions by Using Modified Choline-Containing Phospholipids Metabolically Synthesized in Live Cells.

    PubMed

    Wang, Danyang; Du, Shubo; Cazenave-Gassiot, Amaury; Ge, Jingyan; Lee, Jun-Seok; Wenk, Markus R; Yao, Shao Q

    2017-05-15

    The protein-lipid interaction is an essential metabolic process that mediates cellular signaling and functions. Existing strategies for large-scale mapping studies of the protein-lipid interaction fall short in their incompatibility with metabolic incorporation or inability to remove unwanted interferences from lipidated proteins. By incorporating an alkyne-containing choline head group and a diazirine-modified fatty acid simultaneously into choline-containing phospholipids synthesized from live mammalian cells, protein-phospholipid interactions have been successfully imaged in live cells. Subsequent in situ profiling of the modified Cho phospholipid-crosslinked proteins followed by quantitative proteomics allowed identification of several hundred putative phospholipid-interacting proteins, some of which were further validated. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. A qualitative tool combining an interaction matrix and a GIS to map vulnerability to traffic induced air pollution.

    PubMed

    Mavroulidou, Maria; Hughes, Susan J; Hellawell, Emma E

    2004-04-01

    Local authorities and transport planners need fast and straightforward tools to perform their preliminary air quality assessments. Such tools are required to provide an initial impression of the local air quality and to highlight areas requiring a more rigorous investigation. This paper presents a technique to develop such a tool, for performing an initial assessment of air quality due to traffic in an urban area. The technique combines an interaction matrix methodology as developed for rock engineering systems, with Geographical Information System (GIS) map overlaying. This interaction matrix methodology incorporates a total system approach, which identifies the main parameters and quantifies the interactions between them. Weighting values for these parameters are obtained either through parametric studies, using numerical modelling, or from engineering judgement. These weightings are applied to spatial datasets for a study area using a GIS. The GIS results are presented in the form of a vulnerability map, which highlights the areas susceptible to poor air quality. This visual interpretation of the results is ideal for local authorities, who have to report to a wide range of non-specialists in the field, for example, planners, councillors and the public. The vulnerability map compares favourably with pollutant concentration patterns, obtained from an advanced dispersion model.

  5. Incorporating constraint-based shape models into an interactive system for functional brain mapping.

    PubMed

    Hinshaw, K P; Brinkley, J F

    1998-01-01

    Through intraoperative electrical stimulation mapping, it is possible to identify sites on the surface of the brain that are essential for language function. Interesting correlations have been found between the distribution of these sites and behavioral traits such as verbal IQ. In previous work, tools were developed for building a reconstruction of a patient's cortical surface and using it to recover coordinates of essential language sites. However, considerable expertise was required to produce good reconstructions. This paper describes an improved version of the mapping procedure, in which segmentation is driven by a 3-D shape model. The model-based approach provides more intuitive control over the system, allowing a trained user to complete a surface reconstruction and mapping in about two hours. This level of performance makes it feasible to gather language maps for a large number of patients, which hopefully will lead to significant new findings about language organization in the brain.

  6. Creating interactive, web-based and data-enriched maps with the Systems Biology Graphical Notation.

    PubMed

    Junker, Astrid; Rohn, Hendrik; Czauderna, Tobias; Klukas, Christian; Hartmann, Anja; Schreiber, Falk

    2012-03-01

    The Systems Biology Graphical Notation (SBGN) is an emerging standard for the uniform representation of biological processes and networks. By using examples from gene regulation and metabolism, this protocol shows the construction of SBGN maps by either manual drawing or automatic translation using the tool SBGN-ED. In addition, it discusses the enrichment of SBGN maps with different kinds of -omics data to bring numerical data into the context of these networks in order to facilitate the interpretation of experimental data. Finally, the export of such maps to public websites, including clickable images, supports the communication of results within the scientific community. With regard to the described functionalities, other tools partially overlap with SBGN-ED. However, currently, SBGN-ED is the only tool that combines all of these functions, including the representation in SBGN, data mapping and website export. This protocol aims to assist scientists with the step-by-step procedure, which altogether takes ∼90 min.

  7. Interactive Query Processing in Big Data Systems: A Cross Industry Study of MapReduce Workloads

    DTIC Science & Technology

    2012-04-02

    information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and...MapReduce behavior using existing mental models. We then describe the MapReduce work- load traces (§ 3). The next few sections present empirical evidence...system: − How uniformly or skewed are the data accesses? − How much temporal locality exists ? 2. For workload-level provisioning and load shaping: − How

  8. Interactive Mapping of the Planets: An Online Activity Using the Google Earth Platform

    NASA Astrophysics Data System (ADS)

    Osinski, G. R.; Gilbert, A.; Harrison, T. N.; Mader, M. M.; Shankar, B.; Tornabene, L. L.

    2013-12-01

    With funding from the Natural Sciences and Engineering Research Council of Canada's PromoScience program and support from the Department of Earth Sciences at The University of Western Ontario, the Centre for Planetary Science and Exploration (CPSX) has developed a new web-based initiative called Interactive Mapping of the Planets (IMAPS). Additional components include in person school visits to deliver inquiry-based workshops, week-long summer camps, and pre-prepared impact rock lending kits, all framed around the IMAPS activity. IMAPS will is now in beta testing mode and will be demonstrated in this session. The general objective of the online activity is for participants to plan and design a rover mission to Mars based on a given mission goal - e.g., to find evidence for past water flow. The activity begins with participants receiving image-analysis training to learn about the different landforms on Mars and which ones are potentially caused by water flow. They then need to pass a short test to show they can consistently identify Martian landforms. From there, the participants choose a landing site and plan a traverse - utilizing the free Google Earth plug-in - and taking into account factors such as hazards and their sites of interest. A mission control blog will provide updates on the status of their mission and a 'choose your rover' option provides the opportunity to unlock more advanced rovers by collaborating with other scientists and rating their missions. Indeed, evaluation of missions will be done using a crowd-sourcing method. In addition to being fully accessible online, CPSX will also target primary- and secondary-school grades in which astronomy and space science is taught. Teachers in K-12 classrooms will be able to sign-up for the activity ahead of time in order to receive a workshop package, which will guide them on how to use the IMAPS online activity with their class. Teachers will be able to set up groups for their classroom so that they can

  9. An Online Interactive Map Service for Displaying Ground-Water Conditions in Arizona

    USGS Publications Warehouse

    Tillman, Fred D; Leake, Stanley A.; Flynn, Marilyn E.; Cordova, Jeffrey T.; Schonauer, Kurt T.

    2007-01-01

    Monitoring the availability of the nation's ground-water supplies is of critical importance to planners and water managers. The general public also has an interest in understanding the status of ground-water conditions, especially in the semi-arid Southwestern United States where much of the water used by municipalities and agriculture comes from the subsurface. Unlike surface-water indicators such as stage or discharge, ground-water conditions may be more difficult to assess and present. Individual well observations may only represent conditions in a limited area surrounding the well and wells may be screened over single or multiple aquifers, further complicating single-well measurement interpretations. Additionally, changes in ground-water conditions may involve time scales ranging from days to many years, depending on recharge, soil properties and depth to the water table. This lack of an easily identifiable ground-water property indicative of current conditions combined with differing time scales of water-level changes makes the presentation of ground-water conditions a difficult task, particularly on a regional basis. One approach is to spatially present several indicators of ground-water conditions that address different time scales and attributes of the aquifer systems. In this report, we describe a publicly-available online interactive map service that presents several different layers of ground-water-conditions information for the alluvial basins in the Lower Colorado River Basin in Arizona (http://montezuma.wr.usgs.gov/website/azgwconditions/). These data layers include wells experiencing water-level decline, wells experiencing water-level rise, recent trends in ground-water levels, change in water level since predevelopment and change in storage since predevelopment. Recent pumpage totals and projected population numbers are also provided for ground-water basins and counties in the region of the Lower Colorado River in Arizona along with a bibliography

  10. iSOIL: Interactions between soil related sciences - Linking geophysics, soil science and digital soil mapping

    NASA Astrophysics Data System (ADS)

    Dietrich, Peter; Werban, Ulrike; Sauer, Uta

    2010-05-01

    High-resolution soil property maps are one major prerequisite for the specific protection of soil functions and restoration of degraded soils as well as sustainable land use, water and environmental management. To generate such maps the combination of digital soil mapping approaches and remote as well as proximal soil sensing techniques is most promising. However, a feasible and reliable combination of these technologies for the investigation of large areas (e.g. catchments and landscapes) and the assessment of soil degradation threats is missing. Furthermore, there is insufficient dissemination of knowledge on digital soil mapping and proximal soil sensing in the scientific community, to relevant authorities as well as prospective users. As one consequence there is inadequate standardization of techniques. At the poster we present the EU collaborative project iSOIL within the 7th framework program of the European Commission. iSOIL focuses on improving fast and reliable mapping methods of soil properties, soil functions and soil degradation risks. This requires the improvement and integration of advanced soil sampling approaches, geophysical and spectroscopic measuring techniques, as well as pedometric and pedophysical approaches. The focus of the iSOIL project is to develop new and to improve existing strategies and innovative methods for generating accurate, high resolution soil property maps. At the same time the developments will reduce costs compared to traditional soil mapping. ISOIL tackles the challenges by the integration of three major components: (i)high resolution, non-destructive geophysical (e.g. Electromagnetic Induction EMI; Ground Penetrating Radar, GPR; magnetics, seismics) and spectroscopic (e.g., Near Surface Infrared, NIR) methods, (ii)Concepts of Digital Soil Mapping (DSM) and pedometrics as well as (iii)optimized soil sampling with respect to profound soil scientific and (geo)statistical strategies. A special focus of iSOIL lies on the

  11. Comprehensive mapping of long-range interactions reveals folding principles of the human genome.

    PubMed

    Lieberman-Aiden, Erez; van Berkum, Nynke L; Williams, Louise; Imakaev, Maxim; Ragoczy, Tobias; Telling, Agnes; Amit, Ido; Lajoie, Bryan R; Sabo, Peter J; Dorschner, Michael O; Sandstrom, Richard; Bernstein, Bradley; Bender, M A; Groudine, Mark; Gnirke, Andreas; Stamatoyannopoulos, John; Mirny, Leonid A; Lander, Eric S; Dekker, Job

    2009-10-09

    We describe Hi-C, a method that probes the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing. We constructed spatial proximity maps of the human genome with Hi-C at a resolution of 1 megabase. These maps confirm the presence of chromosome territories and the spatial proximity of small, gene-rich chromosomes. We identified an additional level of genome organization that is characterized by the spatial segregation of open and closed chromatin to form two genome-wide compartments. At the megabase scale, the chromatin conformation is consistent with a fractal globule, a knot-free, polymer conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus. The fractal globule is distinct from the more commonly used globular equilibrium model. Our results demonstrate the power of Hi-C to map the dynamic conformations of whole genomes.

  12. Mapping DNA-Lac repressor interaction with ultra-fast optical tweezers

    NASA Astrophysics Data System (ADS)

    Monico, Carina; Tempestini, Alessia; Vanzi, Francesco; Pavone, Francesco S.; Capitanio, Marco

    2015-03-01

    The lac operon is a well-known example of gene expression regulation, based on the specific interaction of Lac repressor protein (LacI) with its target DNA sequence (operator). We recently developed an ultrafast force-clamp laser trap technique capable of probing molecular interactions with sub-ms temporal resolution, under controlled pN-range forces. With this technique, we tested the interaction of LacI with different DNA constructs. Based on position along the DNA sequence, the observed interactions can be interpreted as specific binding to operator sequences and transient interactions with nonspecific sequences.

  13. Double-Bottom Chaotic Map Particle Swarm Optimization Based on Chi-Square Test to Determine Gene-Gene Interactions

    PubMed Central

    Yang, Cheng-Hong; Chang, Hsueh-Wei

    2014-01-01

    Gene-gene interaction studies focus on the investigation of the association between the single nucleotide polymorphisms (SNPs) of genes for disease susceptibility. Statistical methods are widely used to search for a good model of gene-gene interaction for disease analysis, and the previously determined models have successfully explained the effects between SNPs and diseases. However, the huge numbers of potential combinations of SNP genotypes limit the use of statistical methods for analysing high-order interaction, and finding an available high-order model of gene-gene interaction remains a challenge. In this study, an improved particle swarm optimization with double-bottom chaotic maps (DBM-PSO) was applied to assist statistical methods in the analysis of associated variations to disease susceptibility. A big data set was simulated using the published genotype frequencies of 26 SNPs amongst eight genes for breast cancer. Results showed that the proposed DBM-PSO successfully determined two- to six-order models of gene-gene interaction for the risk association with breast cancer (odds ratio > 1.0; P value <0.05). Analysis results supported that the proposed DBM-PSO can identify good models and provide higher chi-square values than conventional PSO. This study indicates that DBM-PSO is a robust and precise algorithm for determination of gene-gene interaction models for breast cancer. PMID:24895547

  14. Double-bottom chaotic map particle swarm optimization based on chi-square test to determine gene-gene interactions.

    PubMed

    Yang, Cheng-Hong; Lin, Yu-Da; Chuang, Li-Yeh; Chang, Hsueh-Wei

    2014-01-01

    Gene-gene interaction studies focus on the investigation of the association between the single nucleotide polymorphisms (SNPs) of genes for disease susceptibility. Statistical methods are widely used to search for a good model of gene-gene interaction for disease analysis, and the previously determined models have successfully explained the effects between SNPs and diseases. However, the huge numbers of potential combinations of SNP genotypes limit the use of statistical methods for analysing high-order interaction, and finding an available high-order model of gene-gene interaction remains a challenge. In this study, an improved particle swarm optimization with double-bottom chaotic maps (DBM-PSO) was applied to assist statistical methods in the analysis of associated variations to disease susceptibility. A big data set was simulated using the published genotype frequencies of 26 SNPs amongst eight genes for breast cancer. Results showed that the proposed DBM-PSO successfully determined two- to six-order models of gene-gene interaction for the risk association with breast cancer (odds ratio > 1.0; P value <0.05). Analysis results supported that the proposed DBM-PSO can identify good models and provide higher chi-square values than conventional PSO. This study indicates that DBM-PSO is a robust and precise algorithm for determination of gene-gene interaction models for breast cancer.

  15. Mapping Classroom Interactions: A Spatial Approach to Analyzing Patterns of Student Participation

    ERIC Educational Resources Information Center

    Abbot, Sophia; Cook-Sather, Alison; Hein, Carola

    2014-01-01

    This article explores how mapping patterns of student participation in classroom discussion can both illuminate and complicate the dynamic relationships among identity, physical position in the classroom, student engagement, and course content. It draws on the perspectives of an undergraduate in the role of pedagogical consultant, a faculty member…

  16. Simultaneous Mapping of Interactions between Scientific and Technological Knowledge Bases: The Case of Space Communications.

    ERIC Educational Resources Information Center

    Hassan, E.

    2003-01-01

    Examines the knowledge structure of the field of space communications using bibliometric mapping techniques based on textual analysis. Presents a new approach with the aim of visualizing simultaneously the configuration of the scientific and technological knowledge bases at a worldwide level, and discusses results that show different…

  17. Mapping Classroom Interactions: A Spatial Approach to Analyzing Patterns of Student Participation

    ERIC Educational Resources Information Center

    Abbot, Sophia; Cook-Sather, Alison; Hein, Carola

    2014-01-01

    This article explores how mapping patterns of student participation in classroom discussion can both illuminate and complicate the dynamic relationships among identity, physical position in the classroom, student engagement, and course content. It draws on the perspectives of an undergraduate in the role of pedagogical consultant, a faculty member…

  18. Interactive remote data processing using Pixelize Wavelet Filtration (PWF-method) and PeriodMap analysis

    NASA Astrophysics Data System (ADS)

    Sych, Robert; Nakariakov, Valery; Anfinogentov, Sergey

    Wavelet analysis is suitable for investigating waves and oscillating in solar atmosphere, which are limited in both time and frequency. We have developed an algorithms to detect this waves by use the Pixelize Wavelet Filtration (PWF-method). This method allows to obtain information about the presence of propagating and non-propagating waves in the data observation (cube images), and localize them precisely in time as well in space. We tested the algorithm and found that the results of coronal waves detection are consistent with those obtained by visual inspection. For fast exploration of the data cube, in addition, we applied early-developed Period- Map analysis. This method based on the Fast Fourier Transform and allows on initial stage quickly to look for "hot" regions with the peak harmonic oscillations and determine spatial distribution at the significant harmonics. We propose the detection procedure of coronal waves separate on two parts: at the first part, we apply the PeriodMap analysis (fast preparation) and than, at the second part, use information about spatial distribution of oscillation sources to apply the PWF-method (slow preparation). There are two possible algorithms working with the data: in automatic and hands-on operation mode. Firstly we use multiply PWF analysis as a preparation narrowband maps at frequency subbands multiply two and/or harmonic PWF analysis for separate harmonics in a spectrum. Secondly we manually select necessary spectral subband and temporal interval and than construct narrowband maps. For practical implementation of the proposed methods, we have developed the remote data processing system at Institute of Solar-Terrestrial Physics, Irkutsk. The system based on the data processing server - http://pwf.iszf.irk.ru. The main aim of this resource is calculation in remote access through the local and/or global network (Internet) narrowband maps of wave's sources both in whole spectral band and at significant harmonics. In addition

  19. Landslide susceptibility mapping using decision-tree based CHi-squared automatic interaction detection (CHAID) and Logistic regression (LR) integration

    NASA Astrophysics Data System (ADS)

    Althuwaynee, Omar F.; Pradhan, Biswajeet; Ahmad, Noordin

    2014-06-01

    This article uses methodology based on chi-squared automatic interaction detection (CHAID), as a multivariate method that has an automatic classification capacity to analyse large numbers of landslide conditioning factors. This new algorithm was developed to overcome the subjectivity of the manual categorization of scale data of landslide conditioning factors, and to predict rainfall-induced susceptibility map in Kuala Lumpur city and surrounding areas using geographic information system (GIS). The main objective of this article is to use CHi-squared automatic interaction detection (CHAID) method to perform the best classification fit for each conditioning factor, then, combining it with logistic regression (LR). LR model was used to find the corresponding coefficients of best fitting function that assess the optimal terminal nodes. A cluster pattern of landslide locations was extracted in previous study using nearest neighbor index (NNI), which were then used to identify the clustered landslide locations range. Clustered locations were used as model training data with 14 landslide conditioning factors such as; topographic derived parameters, lithology, NDVI, land use and land cover maps. Pearson chi-squared value was used to find the best classification fit between the dependent variable and conditioning factors. Finally the relationship between conditioning factors were assessed and the landslide susceptibility map (LSM) was produced. An area under the curve (AUC) was used to test the model reliability and prediction capability with the training and validation landslide locations respectively. This study proved the efficiency and reliability of decision tree (DT) model in landslide susceptibility mapping. Also it provided a valuable scientific basis for spatial decision making in planning and urban management studies.

  20. Integrated platform for genome-wide screening and construction of high-density genetic interaction maps in mammalian cells

    PubMed Central

    Kampmann, Martin; Bassik, Michael C.; Weissman, Jonathan S.

    2013-01-01

    A major challenge of the postgenomic era is to understand how human genes function together in normal and disease states. In microorganisms, high-density genetic interaction (GI) maps are a powerful tool to elucidate gene functions and pathways. We have developed an integrated methodology based on pooled shRNA screening in mammalian cells for genome-wide identification of genes with relevant phenotypes and systematic mapping of all GIs among them. We recently demonstrated the potential of this approach in an application to pathways controlling the susceptibility of human cells to the toxin ricin. Here we present the complete quantitative framework underlying our strategy, including experimental design, derivation of quantitative phenotypes from pooled screens, robust identification of hit genes using ultra-complex shRNA libraries, parallel measurement of tens of thousands of GIs from a single double-shRNA experiment, and construction of GI maps. We describe the general applicability of our strategy. Our pooled approach enables rapid screening of the same shRNA library in different cell lines and under different conditions to determine a range of different phenotypes. We illustrate this strategy here for single- and double-shRNA libraries. We compare the roles of genes for susceptibility to ricin and Shiga toxin in different human cell lines and reveal both toxin-specific and cell line-specific pathways. We also present GI maps based on growth and ricin-resistance phenotypes, and we demonstrate how such a comparative GI mapping strategy enables functional dissection of physical complexes and context-dependent pathways. PMID:23739767

  1. University of California San Francisco (UCSF-1): Chemical-Genetic Interaction Mapping Strategy | Office of Cancer Genomics

    Cancer.gov

    The CTD2 Center at University of California San Francisco (UCSF-1) developed a chemical-genetic interaction mapping strategy to uncover the impact of cancer gene expression on responses to a panel of emerging therapeutics. To study the impact of aberrant gene activity in isolation, they developed an isogenic model of triple-negative breast cancer (TNBC) using the hormone receptor negative MCF10A non-tumorigenic cell line derived from healthy breast tissue which is diploid and largely devoid of somatic alterations.

  2. Human Interactive Analysis Using Video: Mapping the Dynamics of Complex Work Environments.

    ERIC Educational Resources Information Center

    Terrell, William R.; And Others

    1992-01-01

    Explains human interactive analysis as an architecture for using computer interactive technologies in the analysis of complex work environments. A project at the Naval Training Systems Center that used video-audio data to develop a multimedia database is described; the analysis and management of data are discussed; and decision processes are…

  3. Human Interactive Analysis Using Video: Mapping the Dynamics of Complex Work Environments.

    ERIC Educational Resources Information Center

    Terrell, William R.; And Others

    1992-01-01

    Explains human interactive analysis as an architecture for using computer interactive technologies in the analysis of complex work environments. A project at the Naval Training Systems Center that used video-audio data to develop a multimedia database is described; the analysis and management of data are discussed; and decision processes are…

  4. Interaction of Bacillus subtilis Polynucleotide Phosphorylase and RNase Y: STRUCTURAL MAPPING AND EFFECT ON mRNA TURNOVER.

    PubMed

    Salvo, Elizabeth; Alabi, Shanique; Liu, Bo; Schlessinger, Avner; Bechhofer, David H

    2016-03-25

    Polynucleotide phosphorylase (PNPase), a 3'-to-5' phosphorolytic exoribonuclease, is thought to be the primary enzyme responsible for turnover ofBacillus subtilismRNA. The role of PNPase inB. subtilismRNA decay has been analyzed previously by comparison of mRNA profiles in a wild-type strainversusa strain that is deleted forpnpA, the gene encoding PNPase. Recent studies have provided evidence for a degradosome-like complex inB. subtilisthat is built around the major decay-initiating endonuclease, RNase Y, and there is ample evidence for a strong interaction between PNPase and RNase Y. The role of the PNPase-RNase Y interaction in the exonucleolytic function of PNPase needs to be clarified. We sought to construct aB. subtilisstrain containing a catalytically active PNPase that could not interact with RNase Y. Mapping studies of the PNPase-RNase Y interaction were guided by a homology model ofB. subtilisPNPase based on the known structure of theEscherichia coliPNPase in complex with an RNase E peptide. Mutations inB. subtilisresidues predicted to be involved in RNase Y binding showed a loss of PNPase-RNase Y interaction. Two mRNAs whose decay is dependent on RNase Y and PNPase were examined in strains containing full-length PNPase that was either catalytically active but unable to interact with RNase Y, or catalytically inactive but able to interact with RNase Y. At least for these two mRNAs, disruption of the PNPase-RNase Y interaction did not appear to affect mRNA turnover. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Systematic identification and correction of annotation errors in the genetic interaction map of Saccharomyces cerevisiae

    PubMed Central

    Atias, Nir; Kupiec, Martin; Sharan, Roded

    2016-01-01

    The yeast mutant collections are a fundamental tool in deciphering genomic organization and function. Over the last decade, they have been used for the systematic exploration of ∼6 000 000 double gene mutants, identifying and cataloging genetic interactions among them. Here we studied the extent to which these data are prone to neighboring gene effects (NGEs), a phenomenon by which the deletion of a gene affects the expression of adjacent genes along the genome. Analyzing ∼90,000 negative genetic interactions observed to date, we found that more than 10% of them are incorrectly annotated due to NGEs. We developed a novel algorithm, GINGER, to identify and correct erroneous interaction annotations. We validated the algorithm using a comparative analysis of interactions from Schizosaccharomyces pombe. We further showed that our predictions are significantly more concordant with diverse biological data compared to their mis-annotated counterparts. Our work uncovered about 9500 new genetic interactions in yeast. PMID:26602688

  6. Spatial correlations and synchronization in coupled map lattices with long-range interactions

    NASA Astrophysics Data System (ADS)

    Vasconcelos, D. B.; Viana, R. L.; Lopes, S. R.; Batista, A. M.; Pinto, S. E. de S.

    2004-11-01

    We used numerical diagnostics to quantify spatial disorder, and its relation with temporal chaos, for a one-dimensional chain of coupled logistic maps with a coupling strength which varies with the lattice distance in a power-law fashion. The main tool is spatial return plots, whose properties are used to obtain information about the chaotic synchronized states of the system. A spatial correlation integral is introduced to characterize the clustering of points in the spatial return plots.

  7. MANORAA (Mapping Analogous Nuclei Onto Residue And Affinity) for identifying protein–ligand fragment interaction, pathways and SNPs

    PubMed Central

    Tanramluk, Duangrudee; Narupiyakul, Lalita; Akavipat, Ruj; Gong, Sungsam; Charoensawan, Varodom

    2016-01-01

    Protein–ligand interaction analysis is an important step of drug design and protein engineering in order to predict the binding affinity and selectivity between ligands to the target proteins. To date, there are more than 100 000 structures available in the Protein Data Bank (PDB), of which ∼30% are protein–ligand (MW below 1000 Da) complexes. We have developed the integrative web server MANORAA (Mapping Analogous Nuclei Onto Residue And Affinity) with the aim of providing a user-friendly web interface to assist structural study and design of protein–ligand interactions. In brief, the server allows the users to input the chemical fragments and present all the unique molecular interactions to the target proteins with available three-dimensional structures in the PDB. The users can also link the ligands of interest to assess possible off-target proteins, human variants and pathway information using our all-in-one integrated tools. Taken together, we envisage that the server will facilitate and improve the study of protein–ligand interactions by allowing observation and comparison of ligand interactions with multiple proteins at the same time. (http://manoraa.org). PMID:27131358

  8. Deciphering the stepwise binding mode of HRG1β to HER3 by surface plasmon resonance and interaction map.

    PubMed

    Peess, Carmen; von Proff, Leopold; Goller, Sabine; Andersson, Karl; Gerg, Michael; Malmqvist, Magnus; Bossenmaier, Birgit; Schräml, Michael

    2015-01-01

    For the development of efficient anti-cancer therapeutics against the HER receptor family it is indispensable to understand the mechanistic model of the HER receptor activation upon ligand binding. Due to its high complexity the binding mode of Heregulin 1 beta (HRG1β) with its receptor HER3 is so far not understood. Analysis of the interaction of HRG1β with surface immobilized HER3 extracellular domain by time-resolved Surface Plasmon Resonance (SPR) was so far not interpretable using any regular analysis method as the interaction was highly complex. Here, we show that Interaction Map (IM) made it possible to shed light on this interaction. IM allowed deciphering the rate limiting kinetic contributions from complex SPR sensorgrams and thereby enabling the extraction of discrete kinetic rate components from the apparently heterogeneous interactions. We could resolve details from the complex avidity-driven binding mode of HRG1β with HER3 by using a combination of SPR and IM data. Our findings contribute to the general understanding that a major conformational change of HER3 during its activation is induced by a complex sequential HRG1β docking mode.

  9. Mapping Soluble Guanylyl Cyclase and Protein Disulfide Isomerase Regions of Interaction.

    PubMed

    Heckler, Erin J; Kholodovych, Vladyslav; Jain, Mohit; Liu, Tong; Li, Hong; Beuve, Annie

    2015-01-01

    Soluble guanylyl cyclase (sGC) is a heterodimeric nitric oxide (NO) receptor that produces cyclic GMP. This signaling mechanism is a key component in the cardiovascular system. NO binds to heme in the β subunit and stimulates the catalytic conversion of GTP to cGMP several hundred fold. Several endogenous factors have been identified that modulate sGC function in vitro and in vivo. In previous work, we determined that protein disulfide isomerase (PDI) interacts with sGC in a redox-dependent manner in vitro and that PDI inhibited NO-stimulated activity in cells. To our knowledge, this was the first report of a physical interaction between sGC and a thiol-redox protein. To characterize this interaction between sGC and PDI, we first identified peptide linkages between sGC and PDI, using a lysine cross-linking reagent and recently developed mass spectrometry analysis. Together with Flag-immunoprecipitation using sGC domain deletions, wild-type (WT) and mutated PDI, regions of sGC involved in this interaction were identified. The observed data were further explored with computational modeling to gain insight into the interaction mechanism between sGC and oxidized PDI. Our results indicate that PDI interacts preferentially with the catalytic domain of sGC, thus providing a mechanism for PDI inhibition of sGC. A model in which PDI interacts with either the α or the β catalytic domain is proposed.

  10. An autoradiographic map of (3H)diprenorphine binding in rat brain: effects of social interaction

    SciTech Connect

    Panksepp, J.; Bishop, P.

    1981-10-01

    (3H)Diprenorphine binding was analyzed autoradiographically in the brains of 33 day old rat pups. A photographic atlas of diprenorphine binding in the coronal plane is provided to highlight the dispersion of opioid receptor systems through the brain. To determine whether brain opioid release may be induced by social interactions, half the animals were sacrificed following a 30 min period of social interaction while the other half were sacrificed following 30 min of social isolation. Opioid binding was higher in isolate-tested animals than socially-tested ones, suggesting that social interaction may promote endogenous brain opioid release.

  11. Chromatin Interaction Analysis with Paired-End Tag Sequencing (ChIA-PET) for Mapping Chromatin Interactions and Understanding Transcription Regulation

    PubMed Central

    Poh, Huay Mei; Peh, Su Qin; Ong, Chin Thing; Zhang, Jingyao; Ruan, Xiaoan; Ruan, Yijun

    2012-01-01

    Genomes are organized into three-dimensional structures, adopting higher-order conformations inside the micron-sized nuclear spaces 7, 2, 12. Such architectures are not random and involve interactions between gene promoters and regulatory elements 13. The binding of transcription factors to specific regulatory sequences brings about a network of transcription regulation and coordination 1, 14. Chromatin Interaction Analysis by Paired-End Tag Sequencing (ChIA-PET) was developed to identify these higher-order chromatin structures 5,6. Cells are fixed and interacting loci are captured by covalent DNA-protein cross-links. To minimize non-specific noise and reduce complexity, as well as to increase the specificity of the chromatin interaction analysis, chromatin immunoprecipitation (ChIP) is used against specific protein factors to enrich chromatin fragments of interest before proximity ligation. Ligation involving half-linkers subsequently forms covalent links between pairs of DNA fragments tethered together within individual chromatin complexes. The flanking MmeI restriction enzyme sites in the half-linkers allow extraction of paired end tag-linker-tag constructs (PETs) upon MmeI digestion. As the half-linkers are biotinylated, these PET constructs are purified using streptavidin-magnetic beads. The purified PETs are ligated with next-generation sequencing adaptors and a catalog of interacting fragments is generated via next-generation sequencers such as the Illumina Genome Analyzer. Mapping and bioinformatics analysis is then performed to identify ChIP-enriched binding sites and ChIP-enriched chromatin interactions 8. We have produced a video to demonstrate critical aspects of the ChIA-PET protocol, especially the preparation of ChIP as the quality of ChIP plays a major role in the outcome of a ChIA-PET library. As the protocols are very long, only the critical steps are shown in the video. PMID:22564980

  12. C-B4-01: Educator Experience with Group Interactive Dialogue to Educate and Activate (IDEA) Using Conversation Maps

    PubMed Central

    Sperl-Hillen, JoAnn M; Beaton, Sarah J; Fernandes, Omar; Von Worley, Ann; Hanson, Ann M; Baumer, Dorothy; Lavin-Tompkins, Jodi M

    2010-01-01

    Aims: In order to improve self- efficacy and clinical outcomes for people with diabetes, new approaches using more interactive methods of group education are being promoted. We report results of an educator evaluation of IDEA to assist others who may be interested in starting similar groups in their care settings. Methods: A qualitative analysis was conducted as part of an ongoing randomized trial comparing two different educational interventions (Group IDEA and Individual Education) to Usual Care. As part of the study, educators at HealthPartners clinics in Minneapolis, MN and ABQ Health Partners in Albuquerque, NM were trained on how to use Conversation Maps (CM). All educators completed a Likert scale questionnaire after each CM session with responses from 1–10 (10 being the best). An open- ended evaluation form was also used to solicit positive and negative opinions about the sessions. Analysis: The data consisted of 48 nurse and dietitian evaluations from two sites. The mean Likert scores of the educational experience were calculated and compared for each site and for each of the four CM topics (general information, monitoring, nutrition, and complications). All eight research team members also reviewed answers to the open-ended questions and group consensus was used to describe positive and negative themes. Results: Educator rated Likert scores of map sessions were excellent (mean scores for Maps 1, 2, 3, 4: Overall success 8.3, 7.6, 7.7, 8.8; Ease and comfort levels in facilitation 8.9, 8.9, 9.2, 9.5; Patient motivation to self-manage 7.7, 6.9, 8, 8.8). Scores did not differ significantly across sites or between maps. Positive comments on the maps outweighed the negatives. The challenges identified were: Disruptive (especially angry or negative) people; Distracting topics raised by patients and late arrivals; Variable reading levels among patients (too hard or too easy); and Not enough time to cover the content (especially nutrition). Conclusions: The IDEA

  13. Genome-wide mapping of cellular protein-RNA interactions enabled by chemical crosslinking.

    PubMed

    Li, Xiaoyu; Song, Jinghui; Yi, Chengqi

    2014-04-01

    RNA-protein interactions influence many biological processes. Identifying the binding sites of RNA-binding proteins (RBPs) remains one of the most fundamental and important challenges to the studies of such interactions. Capturing RNA and RBPs via chemical crosslinking allows stringent purification procedures that significantly remove the non-specific RNA and protein interactions. Two major types of chemical crosslinking strategies have been developed to date, i.e., UV-enabled crosslinking and enzymatic mechanism-based covalent capture. In this review, we compare such strategies and their current applications, with an emphasis on the technologies themselves rather than the biology that has been revealed. We hope such methods could benefit broader audience and also urge for the development of new methods to study RNA-RBP interactions. Copyright © 2014. Production and hosting by Elsevier Ltd.

  14. Exploring Students' Mapping Behaviors and Interactive Discourses in a Case Diagnosis Problem: Sequential Analysis of Collaborative Causal Map Drawing Processes

    ERIC Educational Resources Information Center

    Lee, Woon Jee

    2012-01-01

    The purpose of this study was to explore the nature of students' mapping and discourse behaviors while constructing causal maps to articulate their understanding of a complex, ill-structured problem. In this study, six graduate-level students were assigned to one of three pair groups, and each pair used the causal mapping software program,…

  15. Estimation and Mapping of Clouds and Rainfall Areas with an Interactive Computer.

    DTIC Science & Technology

    1982-12-01

    NITH AN INTERACTIVE COMPUTER (U) NAYAL POSTGRADUATE SCHOOL MONTEREY CA C A NELSON DEC 92 UNLSSIFIED F/G 9/2 NUC MENOMONE NONI smhhhhhhhhohh...seete o test analysis. Th. satellite imagezy was mnally evaluated and ompared to the computer guerated output. beasmbly good patterns of cloud types...ppcoved for public release; distribution unlimited Estimation and Napping of :loud anl Rainfall Areas with an Interact ive Computer by Cynthia ana Nelson

  16. Detection of epistatic interactions in association mapping populations: an example from tetraploid potato.

    PubMed

    Stich, B; Gebhardt, C

    2011-12-01

    Epistatic interactions among loci are expected to contribute substantially to variation of quantitative traits. The objectives of our research were to (i) compare a classical mixed-model approach with a combined mixed-model and analysis of variance approach for detecting epistatic interactions; (ii) examine using computer simulations the statistical power to detect additive-additive, additive-dominance and dominance-dominance epistatic interactions and (iii) detect epistatic interactions between candidate genes for resistance to leaf blight in a set of tetraploid potato clones. Our study was based on the genotypic and phenotypic data of 184 tetraploid potato cultivars as well as computer simulations. The number of significant (α* =1 × 10(-6)) epistatic interactions ranged for the three examined traits from 3 to 32. Our findings suggested that the combined mixed-model and analysis of variance approach leads in comparison with the classical mixed-model approach not to an increased rate of false-positives. The results of the computer simulations suggested that, if molecular markers are available that are in high LD (D'>0.9) with the trait-coding loci, the statistical power to detect epistatic interactions, which explain 5-10% of the phenotypic variance, was of a size that seems promising for their detection.

  17. Mapping the interacting winds of Eta Carinae: Changes Across the Apastron

    NASA Astrophysics Data System (ADS)

    Gull, Theodore R.; Madura, T.; Corcoran, M. F.; Hamaguchi, K.; Teodoro, M.

    2014-01-01

    Since the May 2009 servicing mission to repair the Hubble Space Telescope, we have systematically mapped the central 1-2" region of Eta Carinae with the 0.1"-wide, long slit of the Space Telescope Imaging Spectrograph. Six mappings of selected forbidden emission lines began in the late recovery after the 2009.1 periastron event and now extend to phase 0.85 of Eta Carina's 5.54 year period. In addition to the recovery of the high state as depicted by [Fe III] (IP=16.6 eV) strictures and the stabilization of [Fe II] (IP=7.8 eV) features, we see components of at least three wind-blown shells that expand outward at 400 to 500 km/s. Virtually all forbidden emission originates from primary wind structures. The [Fe II] shells, moving at 470 km/s, are primary wind (420 km/s) structures slightly accelerated by the fast secondary wind (Teodoro et al, 2013 ApJ 773, L16T). The [Fe III] arcs, directly photo-ionized by the secondary star, also shift outward with time. Structures in both emissions shift in a general clockwork direction consistent with the derived orbital motion by Gull et al (2009 MNRAS 396, 1308) and revised by Madura et al (2012 MNRAS 420, 2064). With the continued development of the 3D hydrodynamic models we are able to compare the changing structures and determine limits to changes in the mass loss rate over this period of time. Additional mappings, to be obtained by seven additional HST visits, are scheduled at selected orbital phases to follow major changes in ionization structue due to the drop of high ionization to low ionization across the 2014.5 periastron passage. This work is funded by NASA grants to support HST research.

  18. Novel Genes Affecting the Interaction between the Cabbage Whitefly and Arabidopsis Uncovered by Genome-Wide Association Mapping

    PubMed Central

    Broekgaarden, Colette; Bucher, Johan; Bac-Molenaar, Johanna; Keurentjes, Joost J. B.; Kruijer, Willem; Voorrips, Roeland E.; Vosman, Ben

    2015-01-01

    Plants have evolved a variety of ways to defend themselves against biotic attackers. This has resulted in the presence of substantial variation in defense mechanisms among plants, even within a species. Genome-wide association (GWA) mapping is a useful tool to study the genetic architecture of traits, but has so far only had limited exploitation in studies of plant defense. Here, we study the genetic architecture of defense against the phloem-feeding insect cabbage whitefly (Aleyrodes proletella) in Arabidopsis thaliana. We determined whitefly performance, i.e. the survival and reproduction of whitefly females, on 360 worldwide selected natural accessions and subsequently performed GWA mapping using 214,051 SNPs. Substantial variation for whitefly adult survival and oviposition rate (number of eggs laid per female per day) was observed between the accessions. We identified 39 candidate SNPs for either whitefly adult survival or oviposition rate, all with relatively small effects, underpinning the complex architecture of defense traits. Among the corresponding candidate genes, i.e. genes in linkage disequilibrium (LD) with candidate SNPs, none have previously been identified as a gene playing a role in the interaction between plants and phloem-feeding insects. Whitefly performance on knock-out mutants of a number of candidate genes was significantly affected, validating the potential of GWA mapping for novel gene discovery in plant-insect interactions. Our results show that GWA analysis is a very useful tool to gain insight into the genetic architecture of plant defense against herbivorous insects, i.e. we identified and validated several genes affecting whitefly performance that have not previously been related to plant defense against herbivorous insects. PMID:26699853

  19. Novel Genes Affecting the Interaction between the Cabbage Whitefly and Arabidopsis Uncovered by Genome-Wide Association Mapping.

    PubMed

    Broekgaarden, Colette; Bucher, Johan; Bac-Molenaar, Johanna; Keurentjes, Joost J B; Kruijer, Willem; Voorrips, Roeland E; Vosman, Ben

    2015-01-01

    Plants have evolved a variety of ways to defend themselves against biotic attackers. This has resulted in the presence of substantial variation in defense mechanisms among plants, even within a species. Genome-wide association (GWA) mapping is a useful tool to study the genetic architecture of traits, but has so far only had limited exploitation in studies of plant defense. Here, we study the genetic architecture of defense against the phloem-feeding insect cabbage whitefly (Aleyrodes proletella) in Arabidopsis thaliana. We determined whitefly performance, i.e. the survival and reproduction of whitefly females, on 360 worldwide selected natural accessions and subsequently performed GWA mapping using 214,051 SNPs. Substantial variation for whitefly adult survival and oviposition rate (number of eggs laid per female per day) was observed between the accessions. We identified 39 candidate SNPs for either whitefly adult survival or oviposition rate, all with relatively small effects, underpinning the complex architecture of defense traits. Among the corresponding candidate genes, i.e. genes in linkage disequilibrium (LD) with candidate SNPs, none have previously been identified as a gene playing a role in the interaction between plants and phloem-feeding insects. Whitefly performance on knock-out mutants of a number of candidate genes was significantly affected, validating the potential of GWA mapping for novel gene discovery in plant-insect interactions. Our results show that GWA analysis is a very useful tool to gain insight into the genetic architecture of plant defense against herbivorous insects, i.e. we identified and validated several genes affecting whitefly performance that have not previously been related to plant defense against herbivorous insects.

  20. Cross-interactions of two p38 mitogen-activated protein (MAP) kinase inhibitors and two cholecystokinin (CCK) receptor antagonists with the CCK1 receptor and p38 MAP kinase.

    PubMed

    Morel, Caroline; Ibarz, Géraldine; Oiry, Catherine; Carnazzi, Eric; Bergé, Gilbert; Gagne, Didier; Galleyrand, Jean-Claude; Martinez, Jean

    2005-06-03

    Although SB202190 and SB203580 are described as specific p38 MAP kinase inhibitors, several reports have indicated that other enzymes are also sensitive to SB203580. Using a pharmacological approach, we report for the first time that compounds SB202190 and SB203580 were able to directly and selectively interact with a G-protein-coupled receptor, namely the cholecystokinin receptor subtype CCK1, but not with the CCK2 receptor. We demonstrated that these compounds were non-competitive antagonists of the CCK1 receptor at concentrations typically used to inhibit protein kinases. By chimeric construction of the CCK2 receptor, we determined the involvement of two CCK1 receptor intracellular loops in the binding of SB202190 and SB203580. We also showed that two CCK antagonists, L364,718 and L365,260, were able to regulate p38 mitogen-activated protein (MAP) kinase activity. Using a reporter gene strategy and immunoblotting experiments, we demonstrated that both CCK antagonists inhibited selectively the enzymatic activity of p38 MAP kinase. Kinase assays suggested that this inhibition resulted from a direct interaction with both CCK antagonists. Molecular modeling simulations suggested that this interaction occurs in the ATP binding pocket of p38 MAP kinase. These results suggest that SB202190 and SB203580 bind to the CCK1 receptor and, as such, these compounds should be used with caution in models that express this receptor. We also found that L364,718 and L365,260, two CCK receptor antagonists, directly interacted with p38 MAP kinase and inhibited its activity. These findings suggest that the CCK1 receptor shares structural analogies with the p38 MAP kinase ATP binding site. They open the way to potential design of either a new family of MAP kinase inhibitors from CCK1 receptor ligand structures or new CCK1 receptor ligands based on p38 MAP kinase inhibitor structures.

  1. Towards a map of the Populus biomass protein-protein interaction network

    SciTech Connect

    Beers, Eric; Brunner, Amy; Helm, Richard; Dickerman, Allan

    2015-07-31

    Biofuels can be produced from a variety of plant feedstocks. The value of a particular feedstock for biofuels production depends in part on the degree of difficulty associated with the extraction of fermentable sugars from the plant biomass. The wood of trees is potentially a rich source fermentable sugars. However, the sugars in wood exist in a tightly cross-linked matrix of cellulose, hemicellulose, and lignin, making them largely recalcitrant to release and fermentation for biofuels production. Before breeders and genetic engineers can effectively develop plants with reduced recalcitrance to fermentation, it is necessary to gain a better understanding of the fundamental biology of the mechanisms responsible for wood formation. Regulatory, structural, and enzymatic proteins are required for the complicated process of wood formation. To function properly, proteins must interact with other proteins. Yet, very few of the protein-protein interactions necessary for wood formation are known. The main objectives of this project were to 1) identify new protein-protein interactions relevant to wood formation, and 2) perform in-depth characterizations of selected protein-protein interactions. To identify relevant protein-protein interactions, we cloned a set of approximately 400 genes that were highly expressed in the wood-forming tissue (known as secondary xylem) of poplar (Populus trichocarpa). We tested whether the proteins encoded by these biomass genes interacted with each other in a binary matrix design using the yeast two-hybrid (Y2H) method for protein-protein interaction discovery. We also tested a subset of the 400 biomass proteins for interactions with all proteins present in wood-forming tissue of poplar in a biomass library screen design using Y2H. Together, these two Y2H screens yielded over 270 interactions involving over 75 biomass proteins. For the second main objective we selected several interacting pairs or groups of interacting proteins for in

  2. Genetic interactions affecting human gene expression identified by variance association mapping

    PubMed Central

    Brown, Andrew Anand; Buil, Alfonso; Viñuela, Ana; Lappalainen, Tuuli; Zheng, Hou-Feng; Richards, J Brent; Small, Kerrin S; Spector, Timothy D; Dermitzakis, Emmanouil T; Durbin, Richard

    2014-01-01

    Non-additive interaction between genetic variants, or epistasis, is a possible explanation for the gap between heritability of complex traits and the variation explained by identified genetic loci. Interactions give rise to genotype dependent variance, and therefore the identification of variance quantitative trait loci can be an intermediate step to discover both epistasis and gene by environment effects (GxE). Using RNA-sequence data from lymphoblastoid cell lines (LCLs) from the TwinsUK cohort, we identify a candidate set of 508 variance associated SNPs. Exploiting the twin design we show that GxE plays a role in ∼70% of these associations. Further investigation of these loci reveals 57 epistatic interactions that replicated in a smaller dataset, explaining on average 4.3% of phenotypic variance. In 24 cases, more variance is explained by the interaction than their additive contributions. Using molecular phenotypes in this way may provide a route to uncovering genetic interactions underlying more complex traits. DOI: http://dx.doi.org/10.7554/eLife.01381.001 PMID:24771767

  3. Mapping and Functional Characterization of the TAF11 Interaction with TFIIA

    PubMed Central

    Robinson, M. M.; Yatherajam, G.; Ranallo, R. T.; Bric, A.; Paule, M. R.; Stargell, L. A.

    2005-01-01

    TFIIA interacts with TFIID via association with TATA binding protein (TBP) and TBP-associated factor 11 (TAF11). We previously identified a mutation in the small subunit of TFIIA (toa2-I27K) that is defective for interaction with TAF11. To further explore the functional link between TFIIA and TAF11, the toa2-I27K allele was utilized in a genetic screen to isolate compensatory mutants in TAF11. Analysis of these compensatory mutants revealed that the interaction between TAF11 and TFIIA involves two distinct regions of TAF11: the highly conserved histone fold domain and the N-terminal region. Cells expressing a TAF11 allele defective for interaction with TFIIA exhibit conditional growth phenotypes and defects in transcription. Moreover, TAF11 imparts changes to both TFIIA-DNA and TBP-DNA contacts in the context of promoter DNA. These alterations appear to enhance the formation and stabilization of the TFIIA-TBP-DNA complex. Taken together, these studies provide essential information regarding the molecular organization of the TAF11-TFIIA interaction and define a mechanistic role for this association in the regulation of gene expression in vivo. PMID:15657423

  4. Inventory and mapping of flood inundation using interactive digital image analysis techniques

    USGS Publications Warehouse

    Rohde, Wayne G.; Nelson, Charles A.; Taranik, J.V.

    1979-01-01

    LANDSAT digital data and color infra-red photographs were used in a multiphase sampling scheme to estimate the area of agricultural land affected by a flood. The LANDSAT data were classified with a maximum likelihood algorithm. Stratification of the LANDSAT data, prior to classification, greatly reduced misclassification errors. The classification results were used to prepare a map overlay showing the areal extent of flooding. These data also provided statistics required to estimate sample size in a two phase sampling scheme, and provided quick, accurate estimates of areas flooded for the first phase. The measurements made in the second phase, based on ground data and photo-interpretation, were used with two phase sampling statistics to estimate the area of agricultural land affected by flooding These results show that LANDSAT digital data can be used to prepare map overlays showing the extent of flooding on agricultural land and, with two phase sampling procedures, can provide acreage estimates with sampling errors of about 5 percent. This procedure provides a technique for rapidly assessing the areal extent of flood conditions on agricultural land and would provide a basis for designing a sampling framework to estimate the impact of flooding on crop production.

  5. Mapping Proteome-Wide Interactions of Reactive Chemicals Using Chemoproteomic Platforms

    PubMed Central

    Counihan, Jessica L.; Ford, Breanna; Nomura, Daniel K.

    2015-01-01

    A large number of pharmaceuticals, endogenous metabolites, and environmental chemicals act through covalent mechanisms with protein targets. Yet, their specific interactions with the proteome still remain poorly defined for most of these reactive chemicals. Deciphering direct protein targets of reactive small-molecules is critical in understanding their biological action, off-target effects, potential toxicological liabilities, and development of safer and more selective agents. Chemoproteomic technologies have arisen as a powerful strategy that enable the assessment of proteome-wide interactions of these irreversible agents directly in complex biological systems. We review here several chemoproteomic strategies that have facilitated our understanding of specific protein interactions of irreversibly-acting pharmaceuticals, endogenous metabolites, and environmental electrophiles to reveal novel pharmacological, biological, and toxicological mechanisms. PMID:26647369

  6. Mapping of Chikungunya Virus Interactions with Host Proteins Identified nsP2 as a Highly Connected Viral Component

    PubMed Central

    Bouraï, Mehdi; Lucas-Hourani, Marianne; Gad, Hans Henrik; Drosten, Christian; Jacob, Yves; Tafforeau, Lionel; Cassonnet, Patricia; Jones, Louis M.; Judith, Delphine; Couderc, Thérèse; Lecuit, Marc; André, Patrice; Kümmerer, Beate Mareike; Lotteau, Vincent; Desprès, Philippe; Vidalain, Pierre-Olivier

    2012-01-01

    Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that has been responsible for an epidemic outbreak of unprecedented magnitude in recent years. Since then, significant efforts have been made to better understand the biology of this virus, but we still have poor knowledge of CHIKV interactions with host cell components at the molecular level. Here we describe the extensive use of high-throughput yeast two-hybrid (HT-Y2H) assays to characterize interactions between CHIKV and human proteins. A total of 22 high-confidence interactions, which essentially involved the viral nonstructural protein nsP2, were identified and further validated in protein complementation assay (PCA). These results were integrated to a larger network obtained by extensive mining of the literature for reports on alphavirus-host interactions. To investigate the role of cellular proteins interacting with nsP2, gene silencing experiments were performed in cells infected by a recombinant CHIKV expressing Renilla luciferase as a reporter. Collected data showed that heterogeneous nuclear ribonucleoprotein K (hnRNP-K) and ubiquilin 4 (UBQLN4) participate in CHIKV replication in vitro. In addition, we showed that CHIKV nsP2 induces a cellular shutoff, as previously reported for other Old World alphaviruses, and determined that among binding partners identified by yeast two-hybrid methods, the tetratricopeptide repeat protein 7B (TTC7B) plays a significant role in this activity. Altogether, this report provides the first interaction map between CHIKV and human proteins and describes new host cell proteins involved in the replication cycle of this virus. PMID:22258240

  7. Mapping of Chikungunya virus interactions with host proteins identified nsP2 as a highly connected viral component.

    PubMed

    Bouraï, Mehdi; Lucas-Hourani, Marianne; Gad, Hans Henrik; Drosten, Christian; Jacob, Yves; Tafforeau, Lionel; Cassonnet, Patricia; Jones, Louis M; Judith, Delphine; Couderc, Thérèse; Lecuit, Marc; André, Patrice; Kümmerer, Beate Mareike; Lotteau, Vincent; Desprès, Philippe; Tangy, Frédéric; Vidalain, Pierre-Olivier

    2012-03-01

    Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that has been responsible for an epidemic outbreak of unprecedented magnitude in recent years. Since then, significant efforts have been made to better understand the biology of this virus, but we still have poor knowledge of CHIKV interactions with host cell components at the molecular level. Here we describe the extensive use of high-throughput yeast two-hybrid (HT-Y2H) assays to characterize interactions between CHIKV and human proteins. A total of 22 high-confidence interactions, which essentially involved the viral nonstructural protein nsP2, were identified and further validated in protein complementation assay (PCA). These results were integrated to a larger network obtained by extensive mining of the literature for reports on alphavirus-host interactions. To investigate the role of cellular proteins interacting with nsP2, gene silencing experiments were performed in cells infected by a recombinant CHIKV expressing Renilla luciferase as a reporter. Collected data showed that heterogeneous nuclear ribonucleoprotein K (hnRNP-K) and ubiquilin 4 (UBQLN4) participate in CHIKV replication in vitro. In addition, we showed that CHIKV nsP2 induces a cellular shutoff, as previously reported for other Old World alphaviruses, and determined that among binding partners identified by yeast two-hybrid methods, the tetratricopeptide repeat protein 7B (TTC7B) plays a significant role in this activity. Altogether, this report provides the first interaction map between CHIKV and human proteins and describes new host cell proteins involved in the replication cycle of this virus.

  8. Mapping Functional Brain Development: Building a Social Brain through Interactive Specialization

    ERIC Educational Resources Information Center

    Johnson, Mark H.; Grossmann, Tobias; Kadosh, Kathrin Cohen

    2009-01-01

    The authors review a viewpoint on human functional brain development, interactive specialization (IS), and its application to the emerging network of cortical regions referred to as the "social brain." They advance the IS view in 2 new ways. First, they extend IS into a domain to which it has not previously been applied--the emergence of social…

  9. Mapping Functional Brain Development: Building a Social Brain through Interactive Specialization

    ERIC Educational Resources Information Center

    Johnson, Mark H.; Grossmann, Tobias; Kadosh, Kathrin Cohen

    2009-01-01

    The authors review a viewpoint on human functional brain development, interactive specialization (IS), and its application to the emerging network of cortical regions referred to as the "social brain." They advance the IS view in 2 new ways. First, they extend IS into a domain to which it has not previously been applied--the emergence of social…

  10. Site-Directed Chemical Probing to map transient RNA/protein interactions.

    PubMed

    Duval, Mélodie; Marenna, Alessandra; Chevalier, Clément; Marzi, Stefano

    2017-03-15

    RNA-protein interactions are at the bases of many biological processes, forming either tight and stable functional ribonucleoprotein (RNP) complexes (i.e. the ribosome) or transitory ones, such as the complexes involving RNA chaperone proteins. To localize the sites where a protein interacts on an RNA molecule, a common simple and inexpensive biochemical method is the footprinting technique. The protein leaves its footprint on the RNA acting as a shield to protect the regions of interaction from chemical modification or cleavages obtained with chemical or enzymatic nucleases. This method has proven its efficiency to study in vitro the organization of stable RNA-protein complexes. Nevertheless, when the protein binds the RNA very dynamically, with high off-rates, protections are very often difficult to observe. For the analysis of these transient complexes, we describe an alternative strategy adapted from the Site Directed Chemical Probing (SDCP) approach and we compare it with classical footprinting. SDCP relies on the modification of the RNA binding protein to tether an RNA probe (usually Fe-EDTA) to specific protein positions. Local cleavages on the regions of interaction can be used to localize the protein and position its domains on the RNA molecule. This method has been used in the past to monitor stable complexes; we provide here a detailed protocol and a practical example of its application to the study of Escherichia coli RNA chaperone protein S1 and its transitory complexes with mRNAs. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Mapping of the interaction domains of the Crimean–Congo hemorrhagic fever virus nucleocapsid protein

    PubMed Central

    Macleod, Jesica M. Levingston; Marmor, Hannah; Frias-Staheli, Natalia

    2015-01-01

    Crimean–Congo hemorrhagic fever virus (CCHFV) is a member of the genus Nairovirus of the family Bunyaviridae, that can cause severe haemorrhagic fever in humans, with mortality rates above 30 %. CCHFV is the most widespread of the tick-borne human viruses and it is endemic in areas of central Asia, the Middle East, Africa and southern Europe. Its viral genome consists of three negative-sense RNA segments. The large segment (L) encodes a viral RNA-dependent RNA polymerase (L protein), the small segment (S) encodes the nucleocapsid protein (N protein) and the medium segment (M) encodes the envelope proteins. The N protein of bunyaviruses binds genomic RNA, forming the viral ribonucleoprotein (RNP) complex. The L protein interacts with these RNP structures, allowing the initiation of viral replication. The N protein also interacts with actin, although the regions and specific residues involved in these interactions have not yet been described. Here, by means of immunoprecipitation and immunofluorescence assays, we identified the regions within the CCHFV N protein implicated in homo-oligomerization and actin binding. We describe the interaction of the N protein with the CCHFV L protein, and identify the N- and C-terminal regions within the L protein that might be necessary for the formation of these N–L protein complexes. These results may guide the development of potent inhibitors of these complexes that could potentially block CCHFV replication. PMID:25389186

  12. Mapping interactions between myosin relay and converter domains that power muscle function.

    PubMed

    Kronert, William A; Melkani, Girish C; Melkani, Anju; Bernstein, Sanford I

    2014-05-02

    Intramolecular communication within myosin is essential for its function as motor, but the specific amino acid residue interactions required are unexplored within muscle cells. Using Drosophila melanogaster skeletal muscle myosin, we performed a novel in vivo molecular suppression analysis to define the importance of three relay loop amino acid residues (Ile(508), Asn(509), and Asp(511)) in communicating with converter domain residue Arg(759). We found that the N509K relay mutation suppressed defects in myosin ATPase, in vitro motility, myofibril stability, and muscle function associated with the R759E converter mutation. Through molecular modeling, we define a mechanism for this interaction and suggest why the I508K and D511K relay mutations fail to suppress R759E. Interestingly, I508K disabled motor function and myofibril assembly, suggesting that productive relay-converter interaction is essential for both processes. We conclude that the putative relay-converter interaction mediated by myosin residues 509 and 759 is critical for the biochemical and biophysical function of skeletal muscle myosin and the normal ultrastructural and mechanical properties of muscle.

  13. Mapping specificity landscapes of RNA-protein interactions by high throughput sequencing.

    PubMed

    Jankowsky, Eckhard; Harris, Michael E

    2017-03-02

    To function in a biological setting, RNA binding proteins (RBPs) have to discriminate between alternative binding sites in RNAs. This discrimination can occur in the ground state of an RNA-protein binding reaction, in its transition state, or in both. The extent by which RBPs discriminate at these reaction states defines RBP specificity landscapes. Here, we describe the HiTS-Kin and HiTS-EQ techniques, which combine kinetic and equilibrium binding experiments with high throughput sequencing to quantitatively assess substrate discrimination for large numbers of substrate variants at ground and transition states of RNA-protein binding reactions. We discuss experimental design, practical considerations and data analysis and outline how a combination of HiTS-Kin and HiTS-EQ allows the mapping of RBP specificity landscapes.

  14. Visual attention and action: How cueing, direct mapping, and social interactions drive orienting.

    PubMed

    Atkinson, Mark A; Simpson, Andrew A; Cole, Geoff G

    2017-08-14

    Despite considerable interest in both action perception and social attention over the last 2 decades, there has been surprisingly little investigation concerning how the manual actions of other humans orient visual attention. The present review draws together studies that have measured the orienting of attention, following observation of another's goal-directed action. Our review proposes that, in line with the literature on eye gaze, action is a particularly strong orienting cue for the visual system. However, we additionally suggest that action may orient visual attention using mechanisms, which gaze direction does not (i.e., neural direct mapping and corepresentation). Finally, we review the implications of these gaze-independent mechanisms for the study of attention to action. We suggest that our understanding of attention to action may benefit from being studied in the context of joint action paradigms, where the role of higher level action goals and social factors can be investigated.

  15. Mapping of the interaction sites of galanthamine: a quantitative analysis through pairwise potentials and quantum chemistry.

    PubMed

    Galland, Nicolas; Kone, Soleymane; Le Questel, Jean-Yves

    2012-10-01

    A quantitative analysis of the interaction sites of the anti-Alzheimer drug galanthamine with molecular probes (water and benzene molecules) representative of its surroundings in the binding site of acetylcholinesterase (AChE) has been realized through pairwise potentials calculations and quantum chemistry. This strategy allows a full and accurate exploration of the galanthamine potential energy surface of interaction. Significantly different results are obtained according to the distances of approaches between the various molecular fragments and the conformation of the galanthamine N-methyl substituent. The geometry of the most relevant complexes has then been fully optimized through MPWB1K/6-31 + G(d,p) calculations, final energies being recomputed at the LMP2/aug-cc-pVTZ(-f) level of theory. Unexpectedly, galanthamine is found to interact mainly from its hydrogen-bond donor groups. Among those, CH groups in the vicinity of the ammonium group are prominent. The trends obtained provide rationales to the predilection of the equatorial orientation of the galanthamine N-methyl substituent for binding to AChE. The analysis of the interaction energies pointed out the independence between the various interaction sites and the rigid character of galanthamine. The comparison between the cluster calculations and the crystallographic observations in galanthamine-AChE co-crystals allows the validation of the theoretical methodology. In particular, the positions of several water molecules appearing as strongly conserved in galanthamine-AChE co-crystals are predicted by the calculations. Moreover, the experimental position and orientation of lateral chains of functionally important aminoacid residues are in close agreement with the ones predicted theoretically. Our study provides relevant information for a rational drug design of galanthamine based AChE inhibitors.

  16. Mapping of the interaction sites of galanthamine: a quantitative analysis through pairwise potentials and quantum chemistry

    NASA Astrophysics Data System (ADS)

    Galland, Nicolas; Kone, Soleymane; Le Questel, Jean-Yves

    2012-10-01

    A quantitative analysis of the interaction sites of the anti-Alzheimer drug galanthamine with molecular probes (water and benzene molecules) representative of its surroundings in the binding site of acetylcholinesterase (AChE) has been realized through pairwise potentials calculations and quantum chemistry. This strategy allows a full and accurate exploration of the galanthamine potential energy surface of interaction. Significantly different results are obtained according to the distances of approaches between the various molecular fragments and the conformation of the galanthamine N-methyl substituent. The geometry of the most relevant complexes has then been fully optimized through MPWB1K/6-31 + G(d,p) calculations, final energies being recomputed at the LMP2/aug-cc-pVTZ(-f) level of theory. Unexpectedly, galanthamine is found to interact mainly from its hydrogen-bond donor groups. Among those, CH groups in the vicinity of the ammonium group are prominent. The trends obtained provide rationales to the predilection of the equatorial orientation of the galanthamine N-methyl substituent for binding to AChE. The analysis of the interaction energies pointed out the independence between the various interaction sites and the rigid character of galanthamine. The comparison between the cluster calculations and the crystallographic observations in galanthamine-AChE co-crystals allows the validation of the theoretical methodology. In particular, the positions of several water molecules appearing as strongly conserved in galanthamine-AChE co-crystals are predicted by the calculations. Moreover, the experimental position and orientation of lateral chains of functionally important aminoacid residues are in close agreement with the ones predicted theoretically. Our study provides relevant information for a rational drug design of galanthamine based AChE inhibitors.

  17. WIMAGR: An Interactive SSW IDL Tool for Mapping OVSA Legacy Microwave Interferometry Data

    NASA Astrophysics Data System (ADS)

    Nita, Gelu M.; Fleishman, Gregory D.; Gary, Dale E.

    2014-06-01

    The Owens Valley Solar Array (OVSA), which is currently the subject of a major upgrade leading to the new Expanded Owens Valley Solar Array (EOVSA), has operated between the years 2000-2007 as a 5-7 antenna solar-dedicated radio interferometer, with daily observations at typically 40 frequencies in the microwave frequency range, 1-18 GHz. Given the importance of these unique data for complementary studies with data taken during the same period by Yohkoh, RHESSI, SoHO, TRACE, Hinode and other NASA spacecraft, we have undertaken an effort to maximize their usefulness, ease of use, and longevity by creating a uniform, calibrated OVSA legacy database and community-friendly, SSW-based software, compatible with the RHESSI and EOVSA software packages. With these efforts, we can anticipate that the data will continue serving the community well into the future. In this presentation, we will introduce one of the recent upgrades of the OVSA SSW software package, WIMAGR, whose interface allows the user to generate OVSA radio maps in intensity and polarization at many available frequencies with a spatial resolution about 3” at 18 GHz, which is comparable with the spatial resolution of other imaging instruments. To illustrate the main capabilities of this software tool and its potential for promoting scientific discovery, we will present a real-time computation of a sequence of multi-frequency OVSA microwave maps and compare them with images obtained by other instruments. This work was supported in part by NSF grants AGS-1250374, and NASA grants NNX11AB49G and NNX14AC87G to New Jersey Institute of Technology

  18. Google Maps: You Are Here

    ERIC Educational Resources Information Center

    Jacobsen, Mikael

    2008-01-01

    Librarians use online mapping services such as Google Maps, MapQuest, Yahoo Maps, and others to check traffic conditions, find local businesses, and provide directions. However, few libraries are using one of Google Maps most outstanding applications, My Maps, for the creation of enhanced and interactive multimedia maps. My Maps is a simple and…

  19. Google Maps: You Are Here

    ERIC Educational Resources Information Center

    Jacobsen, Mikael

    2008-01-01

    Librarians use online mapping services such as Google Maps, MapQuest, Yahoo Maps, and others to check traffic conditions, find local businesses, and provide directions. However, few libraries are using one of Google Maps most outstanding applications, My Maps, for the creation of enhanced and interactive multimedia maps. My Maps is a simple and…

  20. Comprehensive Binary Interaction Mapping of SH2 Domains via Fluorescence Polarization Reveals Novel Functional Diversification of ErbB Receptors

    PubMed Central

    Ciaccio, Mark F.; Chuu, Chih-pin; Jones, Richard B.

    2012-01-01

    First-generation interaction maps of Src homology 2 (SH2) domains with receptor tyrosine kinase (RTK) phosphosites have previously been generated using protein microarray (PM) technologies. Here, we developed a large-scale fluorescence polarization (FP) methodology that was able to characterize interactions between SH2 domains and ErbB receptor phosphosites with higher fidelity and sensitivity than was previously achieved with PMs. We used the FP assay to query the interaction of synthetic phosphopeptides corresponding to 89 ErbB receptor intracellular tyrosine sites against 93 human SH2 domains and 2 phosphotyrosine binding (PTB) domains. From 358,944 polarization measurements, the affinities for 1,405 unique biological interactions were determined, 83% of which are novel. In contrast to data from previous reports, our analyses suggested that ErbB2 was not more promiscuous than the other ErbB receptors. Our results showed that each receptor displays unique preferences in the affinity and location of recruited SH2 domains that may contribute to differences in downstream signaling potential. ErbB1 was enriched versus the other receptors for recruitment of domains from RAS GEFs whereas ErbB2 was enriched for recruitment of domains from tyrosine and phosphatidyl inositol phosphatases. ErbB3, the kinase inactive ErbB receptor family member, was predictably enriched for recruitment of domains from phosphatidyl inositol kinases and surprisingly, was enriched for recruitment of domains from tyrosine kinases, cytoskeletal regulatory proteins, and RHO GEFs but depleted for recruitment of domains from phosphatidyl inositol phosphatases. Many novel interactions were also observed with phosphopeptides corresponding to ErbB receptor tyrosines not previously reported to be phosphorylated by mass spectrometry, suggesting the existence of many biologically relevant RTK sites that may be phosphorylated but below the detection threshold of standard mass spectrometry procedures. This

  1. Heterotic trait locus (HTL) mapping identifies intra-locus interactions that underlie reproductive hybrid vigor in Sorghum bicolor.

    PubMed

    Ben-Israel, Imri; Kilian, Benjamin; Nida, Habte; Fridman, Eyal

    2012-01-01

    Identifying intra-locus interactions underlying heterotic variation among whole-genome hybrids is a key to understanding mechanisms of heterosis and exploiting it for crop and livestock improvement. In this study, we present the development and first use of the heterotic trait locus (HTL) mapping approach to associate specific intra-locus interactions with an overdominant heterotic mode of inheritance in a diallel population using Sorghum bicolor as the model. This method combines the advantages of ample genetic diversity and the possibility of studying non-additive inheritance. Furthermore, this design enables dissecting the latter to identify specific intra-locus interactions. We identified three HTLs (3.5% of loci tested) with synergistic intra-locus effects on overdominant grain yield heterosis in 2 years of field trials. These loci account for 19.0% of the heterotic variation, including a significant interaction found between two of them. Moreover, analysis of one of these loci (hDPW4.1) in a consecutive F2 population confirmed a significant 21% increase in grain yield of heterozygous vs. homozygous plants in this locus. Notably, two of the three HTLs for grain yield are in synteny with previously reported overdominant quantitative trait loci for grain yield in maize. A mechanism for the reproductive heterosis found in this study is suggested, in which grain yield increase is achieved by releasing the compensatory tradeoffs between biomass and reproductive output, and between seed number and weight. These results highlight the power of analyzing a diverse set of inbreds and their hybrids for unraveling hitherto unknown allelic interactions mediating heterosis.

  2. Long-read ChIA-PET for base-pair-resolution mapping of haplotype-specific chromatin interactions.

    PubMed

    Li, Xingwang; Luo, Oscar Junhong; Wang, Ping; Zheng, Meizhen; Wang, Danjuan; Piecuch, Emaly; Zhu, Jacqueline Jufen; Tian, Simon Zhongyuan; Tang, Zhonghui; Li, Guoliang; Ruan, Yijun

    2017-05-01

    Chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) is a robust method for capturing genome-wide chromatin interactions. Unlike other 3C-based methods, it includes a chromatin immunoprecipitation (ChIP) step that enriches for interactions mediated by specific target proteins. This unique feature allows ChIA-PET to provide the functional specificity and higher resolution needed to detect chromatin interactions, which chromosome conformation capture (3C)/Hi-C approaches have not achieved. The original ChIA-PET protocol generates short paired-end tags (2 × 20 base pairs (bp)) to detect two genomic loci that are far apart on linear chromosomes but are in spatial proximity in the folded genome. We have improved the original approach by developing long-read ChIA-PET, in which the length of the paired-end tags is increased (up to 2 × 250 bp). The longer PET reads not only improve the tag-mapping efficiency but also increase the probability of covering phased single-nucleotide polymorphisms (SNPs), which allows haplotype-specific chromatin interactions to be identified. Here, we provide the detailed protocol for long-read ChIA-PET that includes cell fixation and lysis, chromatin fragmentation by sonication, ChIP, proximity ligation with a bridge linker, Tn5 tagmentation, PCR amplification and high-throughput sequencing. For a well-trained molecular biologist, it typically takes 6 d from cell harvesting to the completion of library construction, up to a further 36 h for DNA sequencing and <20 h for processing of raw sequencing reads.

  3. Stochastic signalling rewires the interaction map of a multiple feedback network during yeast evolution

    PubMed Central

    Hsu, Chieh; Scherrer, Simone; Buetti-Dinh, Antoine; Ratna, Prasuna; Pizzolato, Julia; Jaquet, Vincent; Becskei, Attila

    2012-01-01

    During evolution, genetic networks are rewired through strengthening or weakening their interactions to develop new regulatory schemes. In the galactose network, the GAL1/GAL3 paralogues and the GAL2 gene enhance their own expression mediated by the Gal4p transcriptional activator. The wiring strength in these feedback loops is set by the number of Gal4p binding sites. Here we show using synthetic circuits that multiplying the binding sites increases the expression of a gene under the direct control of an activator, but this enhancement is not fed back in the circuit. The feedback loops are rather activated by genes that have frequent stochastic bursts and fast RNA decay rates. In this way, rapid adaptation to galactose can be triggered even by weakly expressed genes. Our results indicate that nonlinear stochastic transcriptional responses enable feedback loops to function autonomously, or contrary to what is dictated by the strength of interactions enclosing the circuit. PMID:22353713

  4. Early Interactions of Murine Macrophages with Francisella tularensis Map to Mouse Chromosome 19

    PubMed Central

    Fink, Avner; Hassan, Musa A.; Okan, Nihal A.; Sheffer, Michal; Camejo, Ana; Saeij, Jeroen P. J.

    2016-01-01

    ABSTRACT Differences among individuals in susceptibility to infectious diseases can be modulated by host genetics. Much of the research in this field has aimed to identify loci within the host genome that are associated with these differences. In mice, A/J (AJ) and C57BL/6J (B6) mice show differential susceptibilities to various pathogens, including the intracellular pathogen Francisella tularensis. Because macrophages are the main initial target during F. tularensis infection, we explored early interactions of macrophages from these two mouse strains with F. tularensis as well as the genetic factors underlying these interactions. Our results indicate that bacterial interactions with bone marrow-derived macrophages (BMDMs) during early stages of infection are different in the AJ and B6 strains. During these early stages, bacteria are more numerous in B6 than in AJ macrophages and display differences in trafficking and early transcriptional response within these macrophages. To determine the genetic basis for these differences, we infected BMDMs isolated from recombinant inbred (RI) mice derived from reciprocal crosses between AJ and B6, and we followed early bacterial counts within these macrophages. Quantitative trait locus (QTL) analysis revealed a locus on chromosome 19 that is associated with early differences in bacterial counts in AJ versus B6 macrophages. QTL analysis of published data that measured the differential susceptibilities of the same RI mice to an in vivo challenge with F. tularensis confirmed the F. tularensis susceptibility QTL on chromosome 19. Overall, our results show that early interactions of macrophages with F. tularensis are dependent on the macrophage genetic background. PMID:26980837

  5. Mapping the Interaction Anatomy of BmP02 on Kv1.3 Channel

    PubMed Central

    Wu, B.; Wu, B. F.; Feng, Y. J.; Tao, J.; Ji, Y. H.

    2016-01-01

    The potassium channel Kv 1.3 plays a vital part in the activation of T lymphocytes and is an attractive pharmacological target for autoimmune diseases. BmP02, a 28-residue peptide isolated from Chinese scorpion (Buthus martensi Karsch) venom, is a potent and selective Kv1.3 channel blocker. However, the mechanism through which BmP02 recognizes and inhibits the Kv1.3 channel is still unclear. In the present study, a complex molecular model of Kv1.3-BmP02 was developed by docking analysis and molecular dynamics simulations. From these simulations, it appears the large β-turn (residues 10–16) of BmP02 might be the binding interface with Kv 1.3. These results were confirmed by scanning alanine mutagenesis of BmP02, which identified His9, Lys11 and Lys13, which lie within BmP02’s β-turn, as key residues for interacting with Kv1.3. Based on these results and molecular modeling, two negatively charged residues of Kv1.3, D421 and D422, located in turret region, were predicted to act as the binding site for BmP02. Mutation of these residues reduced sensitivity of Kv 1.3 to BmP02 inhibition, suggesting that electrostatic interactions play a crucial role in Kv1.3-BmP02 interaction. This study revealed the molecular basis of Kv 1.3 recognition by BmP02 venom, and provides a novel interaction model for Kv channel-specific blocker complex, which may help guide future drug-design for Kv1.3-related channelopathies. PMID:27403813

  6. A Conformal Mapping Suitable for Problems Involving Interaction Between Given Geometries and Known Far Fields.

    DTIC Science & Technology

    1984-09-01

    A conformal transformation formula using Riemann-Stieltjes integrals is derived for use with problems involving the interaction between a given finite-sized geometry and a known far field. The derivative of this transformation is non-singular in the domain considered and tends to one at infinity. A formula is derived for transformation from the unit circle to the exterior of an arbitrarily given continuous curve with bounded variation . A special case of the transformation is very similar

  7. Mapping the Interaction Anatomy of BmP02 on Kv1.3 Channel

    NASA Astrophysics Data System (ADS)

    Wu, B.; Wu, B. F.; Feng, Y. J.; Tao, J.; Ji, Y. H.

    2016-07-01

    The potassium channel Kv 1.3 plays a vital part in the activation of T lymphocytes and is an attractive pharmacological target for autoimmune diseases. BmP02, a 28-residue peptide isolated from Chinese scorpion (Buthus martensi Karsch) venom, is a potent and selective Kv1.3 channel blocker. However, the mechanism through which BmP02 recognizes and inhibits the Kv1.3 channel is still unclear. In the present study, a complex molecular model of Kv1.3-BmP02 was developed by docking analysis and molecular dynamics simulations. From these simulations, it appears the large β-turn (residues 10–16) of BmP02 might be the binding interface with Kv 1.3. These results were confirmed by scanning alanine mutagenesis of BmP02, which identified His9, Lys11 and Lys13, which lie within BmP02’s β-turn, as key residues for interacting with Kv1.3. Based on these results and molecular modeling, two negatively charged residues of Kv1.3, D421 and D422, located in turret region, were predicted to act as the binding site for BmP02. Mutation of these residues reduced sensitivity of Kv 1.3 to BmP02 inhibition, suggesting that electrostatic interactions play a crucial role in Kv1.3-BmP02 interaction. This study revealed the molecular basis of Kv 1.3 recognition by BmP02 venom, and provides a novel interaction model for Kv channel-specific blocker complex, which may help guide future drug-design for Kv1.3-related channelopathies.

  8. Mapping and identification of protein-protein interactions by two-dimensional far-Western immunoblotting.

    PubMed

    Pasquali, C; Vilbois, F; Curchod, M L; Hooft van Huijsduijnen, R; Arigoni, F

    2000-10-01

    Studies of protein-protein interactions have proved to be a useful approach to link proteins of unknown function to known cellular processes. In this study we have combined several existing methods to attempt the comprehensive identification of substrates for poorly characterized human protein tyrosine phosphatases (PTPs). We took advantage of so-called "substrate trapping" mutants, a procedure originally described by Flint et al. (Proc. Natl. Acad. Sci. USA 1997, 94, 1680-1685) to identify binding partners of cloned PTPs. This procedure was adapted to a proteome-wide approach to probe for candidate substrates in cellular extracts that were separated by two-dimensional (2-D) gel electrophoresis and blotted onto membranes. Protein-protein interactions were revealed by far-Western immunoblotting and positive binding proteins were subsequently identified from silver-stained gels using tandem mass spectrometry. With this method we were able to identify possible substrates for PTPs without using any radio-labeled cDNA or protein probes and showed that they corresponded to tyrosine phosphorylated proteins. We believe that this method could be generally applied to identify possible protein-protein interactions.

  9. Functional Mapping of Quantitative Trait Loci That Interact With the hg Mutation to Regulate Growth Trajectories in Mice

    PubMed Central

    Wu, Rongling; Ma, Chang-Xing; Hou, Wei; Corva, Pablo; Medrano, Juan F.

    2005-01-01

    The high growth (hg) mutation increases body size in mice by 30–50%. Given the complexity of the genetic regulation of animal growth, it is likely that the effect of this major locus is mediated by other quantitative trait loci (QTL) with smaller effects within a web of gene interactions. In this article, we extend our functional mapping model to characterize modifier QTL that interact with the hg locus during ontogenetic growth. Our model is derived within the maximum-likelihood context, incorporated by mathematical aspects of growth laws and implemented with the EM algorithm. In an F2 population founded by a congenic high growth (HG) line and non-HG line, a highly additive effect due to the hg gene was detected on growth trajectories. Three QTL located on chromosomes 2 and X were identified to trigger significant additive and/or dominant effects on the process of growth. The most significant finding made from our model is that these QTL interact with the hg locus to affect the shapes of the growth process. Our model provides a powerful means for understanding the genetic architecture and regulation of growth rate and body size in mammals. PMID:15965258

  10. Lunar Mapping and Modeling On-the-Go: A mobile framework for viewing and interacting with large geospatial datasets

    NASA Astrophysics Data System (ADS)

    Chang, G.; Kim, R.; Bui, B.; Sadaqathullah, S.; Law, E.; Malhotra, S.

    2012-12-01

    The Lunar Mapping and Modeling Portal (LMMP, https://www.lmmp.nasa.gov/) is a collaboration between four NASA centers, JPL, Marshall, Goddard, and Ames, along with the USGS and US Army to provide a centralized geospatial repository for storing processed lunar data collected from the Apollo missions to the latest data acquired by the Lunar Reconnaissance Orbiter (LRO). We offer various scientific and visualization tools to analyze rock and crater densities, lighting maps, thermal measurements, mineral concentrations, slope hazards, and digital elevation maps with the intention of serving not only scientists and lunar mission planners, but also the general public. The project has pioneered in leveraging new technologies and embracing new computing paradigms to create a system that is sophisticated, secure, robust, and scalable all the while being easy to use, streamlined, and modular. We have led innovations through the use of a hybrid cloud infrastructure, authentication through various sources, and utilizing an in-house GIS framework, TWMS (TiledWMS) as well as the commercial ArcGIS product from ESRI. On the client end, we also provide a Flash GUI framework as well as REST web services to interact with the portal. We have also developed a visualization framework on mobile devices, specifically Apple's iOS, which allows anyone from anywhere to interact with LMMP. At the most basic level, the framework allows users to browse LMMP's entire catalog of over 600 data imagery products ranging from global basemaps to LRO's Narrow Angle Camera (NAC) images that provide details of up to .5 meters/pixel. Users are able to view map metadata and can zoom in and out as well as pan around the entire lunar surface with the appropriate basemap. They can arbitrarily stack the maps and images on top of each other to show a layered view of the surface with layer transparency adjusted to suit the user's desired look. Once the user has selected a combination of layers, he can also

  11. Early Interactions of Murine Macrophages with Francisella tularensis Map to Mouse Chromosome 19.

    PubMed

    Fink, Avner; Hassan, Musa A; Okan, Nihal A; Sheffer, Michal; Camejo, Ana; Saeij, Jeroen P J; Kasper, Dennis L

    2016-03-15

    Differences among individuals in susceptibility to infectious diseases can be modulated by host genetics. Much of the research in this field has aimed to identify loci within the host genome that are associated with these differences. In mice, A/J (AJ) and C57BL/6J (B6) mice show differential susceptibilities to various pathogens, including the intracellular pathogen Francisella tularensis. Because macrophages are the main initial target during F. tularensis infection, we explored early interactions of macrophages from these two mouse strains with F. tularensis as well as the genetic factors underlying these interactions. Our results indicate that bacterial interactions with bone marrow-derived macrophages (BMDMs) during early stages of infection are different in the AJ and B6 strains. During these early stages, bacteria are more numerous in B6 than in AJ macrophages and display differences in trafficking and early transcriptional response within these macrophages. To determine the genetic basis for these differences, we infected BMDMs isolated from recombinant inbred (RI) mice derived from reciprocal crosses between AJ and B6, and we followed early bacterial counts within these macrophages. Quantitative trait locus (QTL) analysis revealed a locus on chromosome 19 that is associated with early differences in bacterial counts in AJ versus B6 macrophages. QTL analysis of published data that measured the differential susceptibilities of the same RI mice to an in vivo challenge with F. tularensis confirmed the F. tularensis susceptibility QTL on chromosome 19. Overall, our results show that early interactions of macrophages with F. tularensis are dependent on the macrophage genetic background. Francisella tularensis is a highly pathogenic bacterium with a very low infectious dose in humans. Some mechanisms of bacterial virulence have been elucidated, but the host genetic factors that contribute to host resistance or susceptibility are largely unknown. In this work, we

  12. Structural evolution in A ≈100 nuclei within the mapped interacting boson model based on the Gogny energy density functional

    NASA Astrophysics Data System (ADS)

    Nomura, K.; Rodríguez-Guzmán, R.; Robledo, L. M.

    2016-10-01

    The structure of even-even neutron-rich Ru, Mo, Zr, and Sr nuclei in the A ≈100 mass region is studied within the interacting boson model (IBM) with microscopic input from the self-consistent mean-field approximation based on the Gogny-D1M energy density functional. The deformation-energy surface in the quadrupole deformation space (β ,γ ) , computed within the constrained Hartree-Fock-Bogoliubov framework, is mapped onto the expectation value of the appropriately chosen IBM Hamiltonian with configuration mixing in the boson condensate state. The mapped IBM Hamiltonian is used to study the spectroscopic properties of Ru-11498, Mo-11296, Zr-11094, and Sr-10892. Several cases of γ -soft behavior are predicted in Ru and Mo nuclei while a pronounced coexistence between strongly prolate and weakly oblate deformed shapes is found for Zr and Sr nuclei. The method describes well the evolution of experimental yrast and nonyrast states as well as selected B (E 2 ) transition probabilities.

  13. NMR spectral mapping of Lipid A molecular patterns affected by interaction with the innate immune receptor CD14

    SciTech Connect

    Albright, Seth; Agrawal, Prashansa; Jain, Nitin U.

    2009-01-23

    Soluble CD14 (sCD14) is a serum glycoprotein that binds to the Lipid A moiety of lipopolysaccharides (LPS) with high affinity as part of the innate immune response to bacterial endotoxins. In order to investigate structural interactions of Lipid A with sCD14, we have prepared an isotopically labeled form of a fully active and chemically defined endotoxin, Kdo{sub 2}-Lipid A, which allowed us to carry out detailed NMR spectral mapping of this agonist ligand bound to sCD14 and identify for the first time structural regions that are strongly affected during complex formation with sCD14. These map to two adjacent areas comprising the lower portions of the sugar headgroup and upper half of the acyl chains I, III, and V, which are spatially proximal to the 1- and 4'-phosphate ends. Additionally, we have detected for the first time, presence of differential dynamic behavior for the affected resonances, suggesting a likely role for dynamics in the mechanism of Lipid A pattern recognition by sCD14.

  14. A distance-weighted interaction map reveals a previously uncharacterized layer of the Bacillus subtilis spore coat.

    PubMed

    McKenney, Peter T; Driks, Adam; Eskandarian, Haig A; Grabowski, Paul; Guberman, Jonathan; Wang, Katherine H; Gitai, Zemer; Eichenberger, Patrick

    2010-05-25

    Bacillus subtilis spores are encased in a protein assembly called the spore coat that is made up of at least 70 different proteins. Conventional electron microscopy shows the coat to be organized into two distinct layers. Because the coat is about as wide as the theoretical limit of light microscopy, quantitatively measuring the localization of individual coat proteins within the coat is challenging. We used fusions of coat proteins to green fluorescent protein to map genetic dependencies for coat assembly and to define three independent subnetworks of coat proteins. To complement the genetic data, we measured coat protein localization at subpixel resolution and integrated these two data sets to produce a distance-weighted genetic interaction map. Using these data, we predict that the coat comprises at least four spatially distinct layers, including a previously uncharacterized glycoprotein outermost layer that we name the spore crust. We found that crust assembly depends on proteins we predicted to localize to the crust. The crust may be conserved in all Bacillus spores and may play critical functions in the environment.

  15. Microscopic calculation of interacting boson model parameters by potential-energy surface mapping

    SciTech Connect

    Bentley, I.; Frauendorf, S.

    2011-06-15

    A coherent state technique is used to generate an interacting boson model (IBM) Hamiltonian energy surface which is adjusted to match a mean-field energy surface. This technique allows the calculation of IBM Hamiltonian parameters, prediction of properties of low-lying collective states, as well as the generation of probability distributions of various shapes in the ground state of transitional nuclei, the last two of which are of astrophysical interest. The results for krypton, molybdenum, palladium, cadmium, gadolinium, dysprosium, and erbium nuclei are compared with experiment.

  16. Mapping and Modeling the Extended Winds of the Massive Interacting Binary, Eta Carinae

    NASA Technical Reports Server (NTRS)

    Gull, Ted

    2010-01-01

    The combination HST/STIS high spatial and moderate spectral resolutions have revealed the massive interacting wind structure of Eta Carinae by forbidden lines of singly and doubly ionized elements. Throughout the 5.54-year period, lines of Fe++, Ne++, Ar++, S++ and N+ reveal the interacting wind structures, near critical electron densities of 10(exp 5) to 3 x 10(exp 7)cu cm, photoionized by the hot secondary, Eta Car B, Lines of Fe+ and Ni+ trace the denser (>10(exp 7)cu cm. less-ionized (< 8 eV) primary wind of Eta Car A as it wraps around the interacting binary stars. For 5 years of the 5.54 year period, the FUV radiation from Eta Car B escapes the orbital region, ionizing the boundaries of the expanding wind structures. But for three to six months, Eta Car B plunges into the primary wind approaching to within 1 to 2 AU, leading to cutoff of FUV and X-ray fluxes. The interacting wind structure, resolved out to 0.8", drops io ionization and then rebuilds as Eta Car B emerges from the primary wind envelope. Solid Particle Hydrodynamical(SPH) models have been developed extending out to 2000 AU and adapted to include FUV radiation effects of the winds. In turn, synthetic spectroimages of selected forbidden lines have been constructed and compared to the spectroimages recorded by the HST/STIS throughout 1998.0 to 2004.3, extending across the 1998 and 2003.5 minima. By this method, we show that the orbital axis of the binary system must bc within 15 degrees of the Homunculus axis of symmetry and that periastron occurs with Eta Car B passing on the far side of Eta Car B. This result ties the current binary orbit with the bipolar ejection with intervening skirt and leads to implications that the binary system influenced the mass ejection of the l840s and the lesser ejection of the 1890s.

  17. Mapping functional brain development: Building a social brain through interactive specialization.

    PubMed

    Johnson, Mark H; Grossmann, Tobias; Cohen Kadosh, Kathrin

    2009-01-01

    The authors review a viewpoint on human functional brain development, interactive specialization (IS), and its application to the emerging network of cortical regions referred to as the social brain. They advance the IS view in 2 new ways. First, they extend IS into a domain to which it has not previously been applied--the emergence of social cognition and mentalizing computations in the brain. Second, they extend the implications of the IS view from the emergence of specialized functions within a cortical region to a focus on how different cortical regions with complementary functions become orchestrated into networks during human postnatal development.

  18. Characterization of the bionano interface and mapping extrinsic interactions of the corona of nanomaterials

    NASA Astrophysics Data System (ADS)

    O'Connell, D. J.; Bombelli, F. Baldelli; Pitek, A. S.; Monopoli, M. P.; Cahill, D. J.; Dawson, K. A.

    2015-09-01

    Nanoparticles in physiological environments are known to selectively adsorb proteins and other biomolecules forming a tightly bound biomolecular `corona' on their surface. Where the exchange times of the proteins are sufficiently long, it is believed that the protein corona constitutes the particle identity in biological milieu. Here we show that proteins in the corona retain their functional characteristics and can specifically bind to cognate proteins on arrays of thousands of immobilised human proteins. The biological identity of the nanomaterial is seen to be specific to the blood plasma concentration in which they are exposed. We show that the resulting in situ nanoparticle interactome is dependent on the protein concentration in plasma, with the emergence of a small number of dominant protein-protein interactions. These interactions are those driven by proteins that are adsorbed onto the particle surface and whose binding epitopes are subsequently expressed or presented suitably on the particle surface. We suggest that, since specific tailored protein arrays for target systems and organs can be designed, their use may be an important element in an overall study of the biomolecular corona.Nanoparticles in physiological environments are known to selectively adsorb proteins and other biomolecules forming a tightly bound biomolecular `corona' on their surface. Where the exchange times of the proteins are sufficiently long, it is believed that the protein corona constitutes the particle identity in biological milieu. Here we show that proteins in the corona retain their functional characteristics and can specifically bind to cognate proteins on arrays of thousands of immobilised human proteins. The biological identity of the nanomaterial is seen to be specific to the blood plasma concentration in which they are exposed. We show that the resulting in situ nanoparticle interactome is dependent on the protein concentration in plasma, with the emergence of a small

  19. Mapping and Modeling the Extended Winds of the Massive Interacting Binary, Eta Carinae

    NASA Technical Reports Server (NTRS)

    Gull, Ted

    2010-01-01

    The combination HST/STIS high spatial and moderate spectral resolutions have revealed the massive interacting wind structure of Eta Carinae by forbidden lines of singly and doubly ionized elements. Throughout the 5.54-year period, lines of Fe++, Ne++, Ar++, S++ and N+ reveal the interacting wind structures, near critical electron densities of 10(exp 5) to 3 x 10(exp 7)cu cm, photoionized by the hot secondary, Eta Car B, Lines of Fe+ and Ni+ trace the denser (>10(exp 7)cu cm. less-ionized (< 8 eV) primary wind of Eta Car A as it wraps around the interacting binary stars. For 5 years of the 5.54 year period, the FUV radiation from Eta Car B escapes the orbital region, ionizing the boundaries of the expanding wind structures. But for three to six months, Eta Car B plunges into the primary wind approaching to within 1 to 2 AU, leading to cutoff of FUV and X-ray fluxes. The interacting wind structure, resolved out to 0.8", drops io ionization and then rebuilds as Eta Car B emerges from the primary wind envelope. Solid Particle Hydrodynamical(SPH) models have been developed extending out to 2000 AU and adapted to include FUV radiation effects of the winds. In turn, synthetic spectroimages of selected forbidden lines have been constructed and compared to the spectroimages recorded by the HST/STIS throughout 1998.0 to 2004.3, extending across the 1998 and 2003.5 minima. By this method, we show that the orbital axis of the binary system must bc within 15 degrees of the Homunculus axis of symmetry and that periastron occurs with Eta Car B passing on the far side of Eta Car B. This result ties the current binary orbit with the bipolar ejection with intervening skirt and leads to implications that the binary system influenced the mass ejection of the l840s and the lesser ejection of the 1890s.

  20. Integration of Weather Research Forecast (WRF) Hurricane model with socio-economic data in an interactive web mapping service

    NASA Astrophysics Data System (ADS)

    Boehnert, J.; Wilhelmi, O.; Sampson, K. M.

    2009-12-01

    The integration of weather forecast models and socio-economic data is key to better understanding of the weather forecast and its impact upon society. Whether the forecast is looking at a hurricane approaching land or a snow storm over an urban corridor; the public is most interested in how this weather will affect day-to-day activities, and in extreme events how it will impact human lives, property and livelihoods. The GIS program at NCAR is developing an interactive web mapping portal which will integrate weather forecasts with socio-economic and infrastructure data. This integration of data is essential to better communication of the weather models and their impact on society. As a pilot project, we are conducting a case study on hurricane Ike, which made landfall at Galveston, Texas on 13 September, 2008, with winds greater than 70 mph. There was heavy flooding and loss of electricity due to high winds. This case study is an extreme event, which we are using to demonstrate how the Weather Research Forecasts (WRF) model runs at NCAR can be used to answer questions about how storms impact society. We are integrating WRF model output with the U.S. Census and infrastructure data in a Geographic Information System (GIS) web mapping framework. In this case study, we have identified a series of questions and custom queries which can be viewed through the interactive web portal; such as who will be affected by rain greater than 5 mm/h, or which schools will be affected by winds greater than 90 mph. These types of queries demonstrate the power of GIS and the necessity of integrating weather models with other spatial data in order to improve its effectiveness and understanding for society.

  1. Genetic interaction analysis of point mutations enables interrogation of gene function at a residue-level resolution: exploring the applications of high-resolution genetic interaction mapping of point mutations.

    PubMed

    Braberg, Hannes; Moehle, Erica A; Shales, Michael; Guthrie, Christine; Krogan, Nevan J

    2014-07-01

    We have achieved a residue-level resolution of genetic interaction mapping - a technique that measures how the function of one gene is affected by the alteration of a second gene - by analyzing point mutations. Here, we describe how to interpret point mutant genetic interactions, and outline key applications for the approach, including interrogation of protein interaction interfaces and active sites, and examination of post-translational modifications. Genetic interaction analysis has proven effective for characterizing cellular processes; however, to date, systematic high-throughput genetic interaction screens have relied on gene deletions or knockdowns, which limits the resolution of gene function analysis and poses problems for multifunctional genes. Our point mutant approach addresses these issues, and further provides a tool for in vivo structure-function analysis that complements traditional biophysical methods. We also discuss the potential for genetic interaction mapping of point mutations in human cells and its application to personalized medicine.

  2. Characterization of the bionano interface and mapping extrinsic interactions of the corona of nanomaterials.

    PubMed

    O'Connell, D J; Bombelli, F Baldelli; Pitek, A S; Monopoli, M P; Cahill, D J; Dawson, K A

    2015-10-07

    Nanoparticles in physiological environments are known to selectively adsorb proteins and other biomolecules forming a tightly bound biomolecular 'corona' on their surface. Where the exchange times of the proteins are sufficiently long, it is believed that the protein corona constitutes the particle identity in biological milieu. Here we show that proteins in the corona retain their functional characteristics and can specifically bind to cognate proteins on arrays of thousands of immobilised human proteins. The biological identity of the nanomaterial is seen to be specific to the blood plasma concentration in which they are exposed. We show that the resulting in situ nanoparticle interactome is dependent on the protein concentration in plasma, with the emergence of a small number of dominant protein-protein interactions. These interactions are those driven by proteins that are adsorbed onto the particle surface and whose binding epitopes are subsequently expressed or presented suitably on the particle surface. We suggest that, since specific tailored protein arrays for target systems and organs can be designed, their use may be an important element in an overall study of the biomolecular corona.

  3. Proteochemometrics mapping of the interaction space for retroviral proteases and their substrates.

    PubMed

    Kontijevskis, Aleksejs; Petrovska, Ramona; Yahorava, Sviatlana; Komorowski, Jan; Wikberg, Jarl E S

    2009-07-15

    Understanding the complex interactions of retroviral proteases with their ligands is an important scientific challenge in efforts to achieve control of retroviral infections. Development of drug resistance because of high mutation rates and extensive polymorphisms causes major problems in treating the deadly diseases these viruses cause, and prompts efforts to identify new strategies. Here we report a comprehensive analysis of the interaction of 63 retroviral proteases from nine different viral species with their substrates and inhibitors based on publicly available data from the past 17years of retroviral research. By correlating physico-chemical descriptions of retroviral proteases and substrates to their biological activities we constructed a highly statistically valid 'proteochemometric' model for the interactome of retroviral proteases. Analysis of the model indicated amino acid positions in retroviral proteases with the highest influence on ligand activity and revealed general physicochemical properties essential for tight binding of substrates across multiple retroviral proteases. Hexapeptide inhibitors developed based on the discovered general properties effectively inhibited HIV-1 proteases in vitro, and some exhibited uniformly high inhibitory activity against all HIV-1 proteases mutants evaluated. A generalized proteochemometric model for retroviral proteases interactome has been created and analysed in this study. Our results demonstrate the feasibility of using the developed general strategy in the design of inhibitory peptides that can potentially serve as templates for drug resistance-improved HIV retardants.

  4. Protein interaction maps for complete genomes based on gene fusion events

    NASA Astrophysics Data System (ADS)

    Enright, Anton J.; Iliopoulos, Ioannis; Kyrpides, Nikos C.; Ouzounis, Christos A.

    1999-11-01

    A large-scale effort to measure, detect and analyse protein-protein interactions using experimental methods is under way. These include biochemistry such as co-immunoprecipitation or crosslinking, molecular biology such as the two-hybrid system or phage display, and genetics such as unlinked noncomplementing mutant detection. Using the two-hybrid system, an international effort to analyse the complete yeast genome is in progress. Evidently, all these approaches are tedious, labour intensive and inaccurate. From a computational perspective, the question is how can we predict that two proteins interact from structure or sequence alone. Here we present a method that identifies gene-fusion events in complete genomes, solely based on sequence comparison. Because there must be selective pressure for certain genes to be fused over the course of evolution, we are able to predict functional associations of proteins. We show that 215 genes or proteins in the complete genomes of Escherichia coli, Haemophilus influenzae and Methanococcus jannaschii are involved in 64 unique fusion events. The approach is general, and can be applied even to genes of unknown function.

  5. Trifunctional cross-linker for mapping protein-protein interaction networks and comparing protein conformational states

    PubMed Central

    Tan, Dan; Li, Qiang; Zhang, Mei-Jun; Liu, Chao; Ma, Chengying; Zhang, Pan; Ding, Yue-He; Fan, Sheng-Bo; Tao, Li; Yang, Bing; Li, Xiangke; Ma, Shoucai; Liu, Junjie; Feng, Boya; Liu, Xiaohui; Wang, Hong-Wei; He, Si-Min; Gao, Ning; Ye, Keqiong; Dong, Meng-Qiu; Lei, Xiaoguang

    2016-01-01

    To improve chemical cross-linking of proteins coupled with mass spectrometry (CXMS), we developed a lysine-targeted enrichable cross-linker containing a biotin tag for affinity purification, a chemical cleavage site to separate cross-linked peptides away from biotin after enrichment, and a spacer arm that can be labeled with stable isotopes for quantitation. By locating the flexible proteins on the surface of 70S ribosome, we show that this trifunctional cross-linker is effective at attaining structural information not easily attainable by crystallography and electron microscopy. From a crude Rrp46 immunoprecipitate, it helped identify two direct binding partners of Rrp46 and 15 protein-protein interactions (PPIs) among the co-immunoprecipitated exosome subunits. Applying it to E. coli and C. elegans lysates, we identified 3130 and 893 inter-linked lysine pairs, representing 677 and 121 PPIs. Using a quantitative CXMS workflow we demonstrate that it can reveal changes in the reactivity of lysine residues due to protein-nucleic acid interaction. DOI: http://dx.doi.org/10.7554/eLife.12509.001 PMID:26952210

  6. Mapping force of interaction between PLGA nanoparticle with cell membrane using optical tweezers

    NASA Astrophysics Data System (ADS)

    Chhajed, Suyash; Gu, Ling; Homayoni, Homa; Nguyen, Kytai; Mohanty, Samarendra

    2011-03-01

    Drug delivery using magnetic (Fe 3 O4) Poly Lactic-co-Glycolic Acid (PLGA) nanoparticles is finding increasing usage in therapeutic applications due to its biodegradability, biocompatibility and targeted localization. Since optical tweezers allow non-contact, highly sensitive force measurement, we utilized optical tweezers for studying interaction forces between the Fe 3 O4 -PLGA nanoparticles with prostate cancer PC3 cells. Presence of Fe 3 O4 within the PLGA shell allowed efficient trapping of these nanoparticles in near-IR optical tweezers. The conglomerated PLGA nanoparticles could be dispersed by use of the optical tweezers. Calibration of trapping stiffness as a function of laser beam power was carried out using equipartition theorem method, where the mean square displacement was measured with high precision using time-lapse fluorescence imaging of the nanoparticles. After the trapped PLGA nanoparticle was brought in close vicinity of the PC3 cell membrane, displacement of the nanoparticle from trap center was measured as a function of time. In short time scale (30 sec) , whiletheforceofinteractionwaswithin 0.2 pN , theforceincreasedbeyond 1 pNatlongertimescales (~ 10 min). We will present the results of the time-varying force of interactions between PLGA nanoparticles with PC3 cells using optical tweezers.

  7. Mapping the interaction of Snf1 with TORC1 in Saccharomyces cerevisiae.

    PubMed

    Zhang, Jie; Vaga, Stefania; Chumnanpuen, Pramote; Kumar, Rahul; Vemuri, Goutham N; Aebersold, Ruedi; Nielsen, Jens

    2011-11-08

    Nutrient sensing and coordination of metabolic pathways are crucial functions for all living cells, but details of the coordination under different environmental conditions remain elusive. We therefore undertook a systems biology approach to investigate the interactions between the Snf1 and the target of rapamycin complex 1 (TORC1) in Saccharomyces cerevisiae. We show that Snf1 regulates a much broader range of biological processes compared with TORC1 under both glucose- and ammonium-limited conditions. We also find that Snf1 has a role in upregulating the NADP(+)-dependent glutamate dehydrogenase (encoded by GDH3) under derepressing condition, and therefore may also have a role in ammonium assimilation and amino-acid biosynthesis, which can be considered as a convergence of Snf1 and TORC1 pathways. In addition to the accepted role of Snf1 in regulating fatty acid (FA) metabolism, we show that TORC1 also regulates FA metabolism, likely through modulating the peroxisome and β-oxidation. Finally, we conclude that direct interactions between Snf1 and TORC1 pathways are unlikely under nutrient-limited conditions and propose that TORC1 is repressed in a manner that is independent of Snf1.

  8. Identification of Odorant-Receptor Interactions by Global Mapping of the Human Odorome

    PubMed Central

    Audouze, Karine; Tromelin, Anne; Le Bon, Anne Marie; Belloir, Christine; Petersen, Rasmus Koefoed; Kristiansen, Karsten; Brunak, Søren; Taboureau, Olivier

    2014-01-01

    The human olfactory system recognizes a broad spectrum of odorants using approximately 400 different olfactory receptors (hORs). Although significant improvements of heterologous expression systems used to study interactions between ORs and odorant molecules have been made, screening the olfactory repertoire of hORs remains a tremendous challenge. We therefore developed a chemical systems level approach based on protein-protein association network to investigate novel hOR-odorant relationships. Using this new approach, we proposed and validated new bioactivities for odorant molecules and OR2W1, OR51E1 and OR5P3. As it remains largely unknown how human perception of odorants influence or prevent diseases, we also developed an odorant-protein matrix to explore global relationships between chemicals, biological targets and disease susceptibilities. We successfully experimentally demonstrated interactions between odorants and the cannabinoid receptor 1 (CB1) and the peroxisome proliferator-activated receptor gamma (PPARγ). Overall, these results illustrate the potential of integrative systems chemical biology to explore the impact of odorant molecules on human health, i.e. human odorome. PMID:24695519

  9. BDNF stimulation of protein synthesis in cortical neurons requires the MAP kinase-interacting kinase MNK1.

    PubMed

    Genheden, Maja; Kenney, Justin W; Johnston, Harvey E; Manousopoulou, Antigoni; Garbis, Spiros D; Proud, Christopher G

    2015-01-21

    Although the MAP kinase-interacting kinases (MNKs) have been known for >15 years, their roles in the regulation of protein synthesis have remained obscure. Here, we explore the involvement of the MNKs in brain-derived neurotrophic factor (BDNF)-stimulated protein synthesis in cortical neurons from mice. Using a combination of pharmacological and genetic approaches, we show that BDNF-induced upregulation of protein synthesis requires MEK/ERK signaling and the downstream kinase, MNK1, which phosphorylates eukaryotic initiation factor (eIF) 4E. Translation initiation is mediated by the interaction of eIF4E with the m(7)GTP cap of mRNA and with eIF4G. The latter interaction is inhibited by the interactions of eIF4E with partner proteins, such as CYFIP1, which acts as a translational repressor. We find that BDNF induces the release of CYFIP1 from eIF4E, and that this depends on MNK1. Finally, using a novel combination of BONCAT and SILAC, we identify a subset of proteins whose synthesis is upregulated by BDNF signaling via MNK1 in neurons. Interestingly, this subset of MNK1-sensitive proteins is enriched for functions involved in neurotransmission and synaptic plasticity. Additionally, we find significant overlap between our subset of proteins whose synthesis is regulated by MNK1 and those encoded by known FMRP-binding mRNAs. Together, our data implicate MNK1 as a key component of BDNF-mediated translational regulation in neurons. Copyright © 2015 Genheden et al.

  10. Uncovering the genetic architecture of Colletotrichum lindemuthianum resistance through QTL mapping and epistatic interaction analysis in common bean.

    PubMed

    González, Ana M; Yuste-Lisbona, Fernando J; Rodiño, A Paula; De Ron, Antonio M; Capel, Carmen; García-Alcázar, Manuel; Lozano, Rafael; Santalla, Marta

    2015-01-01

    Colletotrichum lindemuthianum is a hemibiotrophic fungal pathogen that causes anthracnose disease in common bean. Despite the genetics of anthracnose resistance has been studied for a long time, few quantitative trait loci (QTLs) studies have been conducted on this species. The present work examines the genetic basis of quantitative resistance to races 23 and 1545 of C. lindemuthianum in different organs (stem, leaf and petiole). A population of 185 recombinant inbred lines (RIL) derived from the cross PMB0225 × PHA1037 was evaluated for anthracnose resistance under natural and artificial photoperiod growth conditions. Using multi-environment QTL mapping approach, 10 and 16 main effect QTLs were identified for resistance to anthracnose races 23 and 1545, respectively. The homologous genomic regions corresponding to 17 of the 26 main effect QTLs detected were positive for the presence of resistance-associated gene cluster encoding nucleotide-binding and leucine-rich repeat (NL) proteins. Among them, it is worth noting that the main effect QTLs detected on linkage group 05 for resistance to race 1545 in stem, petiole and leaf were located within a 1.2 Mb region. The NL gene Phvul.005G117900 is located in this region, which can be considered an important candidate gene for the non-organ-specific QTL identified here. Furthermore, a total of 39 epistatic QTL (E-QTLs) (21 for resistance to race 23 and 18 for resistance to race 1545) involved in 20 epistatic interactions (eleven and nine interactions for resistance to races 23 and 1545, respectively) were identified. None of the main and epistatic QTLs detected displayed significant environment interaction effects. The present research provides essential information not only for the better understanding of the plant-pathogen interaction but also for the application of genomic assisted breeding for anthracnose resistance improvement in common bean through application of marker-assisted selection (MAS).

  11. Uncovering the genetic architecture of Colletotrichum lindemuthianum resistance through QTL mapping and epistatic interaction analysis in common bean

    PubMed Central

    González, Ana M.; Yuste-Lisbona, Fernando J.; Rodiño, A. Paula; De Ron, Antonio M.; Capel, Carmen; García-Alcázar, Manuel; Lozano, Rafael; Santalla, Marta

    2015-01-01

    Colletotrichum lindemuthianum is a hemibiotrophic fungal pathogen that causes anthracnose disease in common bean. Despite the genetics of anthracnose resistance has been studied for a long time, few quantitative trait loci (QTLs) studies have been conducted on this species. The present work examines the genetic basis of quantitative resistance to races 23 and 1545 of C. lindemuthianum in different organs (stem, leaf and petiole). A population of 185 recombinant inbred lines (RIL) derived from the cross PMB0225 × PHA1037 was evaluated for anthracnose resistance under natural and artificial photoperiod growth conditions. Using multi-environment QTL mapping approach, 10 and 16 main effect QTLs were identified for resistance to anthracnose races 23 and 1545, respectively. The homologous genomic regions corresponding to 17 of the 26 main effect QTLs detected were positive for the presence of resistance-associated gene cluster encoding nucleotide-binding and leucine-rich repeat (NL) proteins. Among them, it is worth noting that the main effect QTLs detected on linkage group 05 for resistance to race 1545 in stem, petiole and leaf were located within a 1.2 Mb region. The NL gene Phvul.005G117900 is located in this region, which can be considered an important candidate gene for the non-organ-specific QTL identified here. Furthermore, a total of 39 epistatic QTL (E-QTLs) (21 for resistance to race 23 and 18 for resistance to race 1545) involved in 20 epistatic interactions (eleven and nine interactions for resistance to races 23 and 1545, respectively) were identified. None of the main and epistatic QTLs detected displayed significant environment interaction effects. The present research provides essential information not only for the better understanding of the plant-pathogen interaction but also for the application of genomic assisted breeding for anthracnose resistance improvement in common bean through application of marker-assisted selection (MAS). PMID:25852706

  12. Mapping the Vif-A3G interaction using peptide arrays: a basis for anti-HIV lead peptides.

    PubMed

    Reingewertz, Tali H; Britan-Rosich, Elena; Rotem-Bamberger, Shahar; Viard, Mathias; Jacobs, Amy; Miller, Abigail; Lee, Ji Youn; Hwang, Jeeseong; Blumenthal, Robert; Kotler, Moshe; Friedler, Assaf

    2013-06-15

    Human apolipoprotein-B mRNA-editing catalytic polypeptide-like 3G (A3G) is a cytidine deaminase that restricts retroviruses, endogenous retro-elements and DNA viruses. A3G plays a key role in the anti-HIV-1 innate cellular immunity. The HIV-1 Vif protein counteracts A3G mainly by leading A3G towards the proteosomal machinery and by direct inhibition of its enzymatic activity. Both activities involve direct interaction between Vif and A3G. Disrupting the interaction between A3G and Vif may rescue A3G antiviral activity and inhibit HIV-1 propagation. Here, mapping the interaction sites between A3G and Vif by peptide array screening revealed distinct regions in Vif important for A3G binding, including the N-terminal domain (NTD), C-terminal domain (CTD) and residues 83-99. The Vif-binding sites in A3G included 12 different peptides that showed strong binding to either full-length Vif, Vif CTD or both. Sequence similarity was found between Vif-binding peptides from the A3G CTD and NTD. A3G peptides were synthesized and tested for their ability to counteract Vif action. A3G 211-225 inhibited HIV-1 replication in cell culture and impaired Vif dependent A3G degradation. In vivo co-localization of full-length Vif with A3G 211-225 was demonstrated by use of FRET. This peptide has the potential to serve as an anti-HIV-1 lead compound. Our results suggest a complex interaction between Vif and A3G that is mediated by discontinuous binding regions with different affinities. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Redrawing the Map of Great Britain from a Network of Human Interactions

    PubMed Central

    Ratti, Carlo; Sobolevsky, Stanislav; Calabrese, Francesco; Andris, Clio; Reades, Jonathan; Martino, Mauro; Claxton, Rob; Strogatz, Steven H.

    2010-01-01

    Do regional boundaries defined by governments respect the more natural ways that people interact across space? This paper proposes a novel, fine-grained approach to regional delineation, based on analyzing networks of billions of individual human transactions. Given a geographical area and some measure of the strength of links between its inhabitants, we show how to partition the area into smaller, non-overlapping regions while minimizing the disruption to each person's links. We tested our method on the largest non-Internet human network, inferred from a large telecommunications database in Great Britain. Our partitioning algorithm yields geographically cohesive regions that correspond remarkably well with administrative regions, while unveiling unexpected spatial structures that had previously only been hypothesized in the literature. We also quantify the effects of partitioning, showing for instance that the effects of a possible secession of Wales from Great Britain would be twice as disruptive for the human network than that of Scotland. PMID:21170390

  14. Mapping Cholesterol Interaction Sites on Serotonin Transporter through Coarse-Grained Molecular Dynamics

    PubMed Central

    Ferraro, Mariarosaria; Masetti, Matteo; Recanatini, Maurizio; Cavalli, Andrea; Bottegoni, Giovanni

    2016-01-01

    Serotonin transporter (SERT) modulates serotonergic signaling via re-uptake of serotonin in pre-synaptic cells. The inclusion in cholesterol-enriched membrane domains is crucial for SERT activity, suggesting a cross-talk between the protein and the sterol. Here, we develop a protocol to identify potential cholesterol interaction sites coupling statistical analysis to multi-microsecond coarse-grained molecular dynamics simulations of SERT in a previously validated raft-like membrane model. Six putative sites were found, including a putative CRAC motif on TM4 and a CARC motif on TM10. Among them, four hot-spots near regions related to ion binding, transport, and inhibition were detected. Our results encourage prospective studies to unravel mechanistic features of the transporter and related drug discovery implications. PMID:27907003

  15. Development of a stereo analysis algorithm for generating topographic maps using interactive techniques of the MPP

    NASA Technical Reports Server (NTRS)

    Strong, James P.

    1987-01-01

    A local area matching algorithm was developed on the Massively Parallel Processor (MPP). It is an iterative technique that first matches coarse or low resolution areas and at each iteration performs matches of higher resolution. Results so far show that when good matches are possible in the two images, the MPP algorithm matches corresponding areas as well as a human observer. To aid in developing this algorithm, a control or shell program was developed for the MPP that allows interactive experimentation with various parameters and procedures to be used in the matching process. (This would not be possible without the high speed of the MPP). With the system, optimal techniques can be developed for different types of matching problems.

  16. Mapping protein-protein interactions by localized oxidation: consequences of the reach of hydroxyl radical.

    PubMed

    Cheal, Sarah M; Ng, Mindy; Barrios, Brianda; Miao, Zheng; Kalani, Amir K; Meares, Claude F

    2009-06-02

    Hydroxyl radicals generated from a variety of methods, including not only synchrotron radiation but also Fenton reactions involving chelated iron, have become an accepted macromolecular footprinting tool. Hydroxyl radicals react with proteins via multiple mechanisms that lead to both polypeptide backbone cleavage events and side chain modifications (e.g., hydroxylation and carbonyl formation). The use of site-specifically tethered iron chelates can reveal protein-protein interactions, but the interpretation of such experiments will be strengthened by improving our understanding of how hydroxyl radicals produced at a point on a protein react with other protein sites. We have developed methods for monitoring carbonyl formation on proteins as a function of distance from a hydroxyl generator, iron-(S)-1-[p-(bromoacetamido)benzyl]EDTA (FeBABE), conjugated to an engineered cysteine residue. After activation of the chelated iron with ascorbate and peroxide produces new protein carbonyl groups, their positions can be identified using element-coded affinity tagging (ECAT), with carbonyl-specific tags {e.g., rare earth chelates of (S)-2-[4-(2-aminooxy)acetamidobenzyl]-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (AOD)} that allow for affinity purification, identification, and relative quantitation of oxidation sites using mass spectrometry. Intraprotein oxidation of single-cysteine mutants of Escherichia coli sigma(70) by tethered FeBABE was used to calibrate the reach of hydroxyl radical by comparison to the crystal structure; the application to protein-protein interactions was demonstrated using the same sigma(70) FeBABE conjugates in complexes with the RNA polymerase core enzyme. The results provide fundamental information for interpreting protein footprinting experiments in other systems.

  17. Mapping Protein-Protein Interactions by Localized Oxidation: Consequences of the Reach of Hydroxyl Radical†

    PubMed Central

    Cheal, Sarah M.; Ng, Mindy; Barrios, Brianda; Miao, Zheng; Kalani, Amir K.; Meares, Claude F.

    2009-01-01

    Hydroxyl radicals generated from a variety of methods, including not only synchrotron radiation but also Fenton reactions involving chelated iron, have become an accepted macromolecular footprinting tool. Hydroxyl radicals react with proteins via multiple mechanisms that lead to both polypeptide backbone cleavage events and side chain modifications (e.g., hydroxylation and carbonyl formation). The use of site-specifically tethered iron chelates can reveal protein-protein interactions, but the interpretation of such experiments will be strengthened by better understanding of how hydroxyl radicals produced at a point on a protein react with other protein sites. We have developed methods to monitor carbonyl formation on proteins as a function of distance from a hydroxyl generator, iron-(S)-1-[p-(bromoacetamido)benzyl]EDTA, “FeBABE”, conjugated to an engineered cysteine residue. After activation of the chelated iron with ascorbate and peroxide produces new protein carbonyl groups, their positions can be identified using element-coded affinity tagging (ECAT), with carbonyl-specific tags (e.g., rare earth chelates of ((S)-2-(4-(2-aminooxy)acetamidobenzyl)-1, 4, 7, 10-tetraazacyclododecane-N, N′, N″, N‴-tetraacetic acid, “AOD”) that allow for affinity purification, identification, and relative quantitation of oxidation sites using mass spectrometry. Intraprotein oxidation of single-cysteine mutants of E. coli σ70 by tethered FeBABE was used to calibrate the reach of hydroxyl radical by comparison to the crystal structure; the application to protein-protein interactions was demonstrated using the same σ70 FeBABE conjugates in complexes with RNA polymerase core enzyme. The results provide fundamental information for interpreting protein footprinting experiments in other systems. PMID:19354299

  18. Mapping the interaction of SmpB with ribosomes by footprinting of ribosomal RNA

    PubMed Central

    Ivanova, Natalia; Pavlov, Michael Y.; Bouakaz, Elli; Ehrenberg, Måns; Schiavone, Lovisa Holmberg

    2005-01-01

    In trans-translation transfer messenger RNA (tmRNA) and small protein B (SmpB) rescue ribosomes stalled on truncated or in other ways problematic mRNAs. SmpB promotes the binding of tmRNA to the ribosome but there is uncertainty about the number of participating SmpB molecules as well as their ribosomal location. Here, the interaction of SmpB with ribosomal subunits and ribosomes was studied by isolation of SmpB containing complexes followed by chemical modification of ribosomal RNA with dimethyl sulfate, kethoxal and hydroxyl radicals. The results show that SmpB binds 30S and 50S subunits with 1:1 molar ratios and the 70S ribosome with 2:1 molar ratio. SmpB-footprints are similar on subunits and the ribosome. In the 30S subunit, SmpB footprints nucleotides that are in the vicinity of the P-site facing the E-site, and in the 50S subunit SmpB footprints nucleotides that are located below the L7/L12 stalk in the 3D structure of the ribosome. Based on these results, we suggest a mechanism where two molecules of SmpB interact with tmRNA and the ribosome during trans-translation. The first SmpB molecule binds near the factor-binding site on the 50S subunit helping tmRNA accommodation on the ribosome, whereas the second SmpB molecule may functionally substitute for a missing anticodon stem–loop in tmRNA during later steps of trans-translation. PMID:15972795

  19. Association mapping of loci controlling genetic and environmental interaction of soybean flowering time under various photo-thermal conditions.

    PubMed

    Mao, Tingting; Li, Jinyu; Wen, Zixiang; Wu, Tingting; Wu, Cunxiang; Sun, Shi; Jiang, Bingjun; Hou, Wensheng; Li, Wenbin; Song, Qijian; Wang, Dechun; Han, Tianfu

    2017-05-26

    Soybean (Glycine max (L.) Merr.) is a short day plant. Its flowering and maturity time are controlled by genetic and environmental factors, as well the interaction between the two factors. Previous studies have shown that both genetic and environmental factors, mainly photoperiod and temperature, control flowering time of soybean. Additionally, these studies have reported gene × gene and gene × environment interactions on flowering time. However, the effects of quantitative trait loci (QTL) in response to photoperiod and temperature have not been well evaluated. The objectives of the current study were to identify the effects of loci associated with flowering time under different photo-thermal conditions and to understand the effects of interaction between loci and environment on soybean flowering. Different photoperiod and temperature combinations were obtained by adjusting sowing dates (spring sowing and summer sowing) or day-length (12 h, 16 h). Association mapping was performed on 91 soybean cultivars from different maturity groups (MG000-VIII) using 172 SSR markers and 5107 SNPs from the Illumina SoySNP6K iSelectBeadChip. The effects of the interaction between QTL and environments on flowering time were also analysed using the QTXNetwork. Large-effect loci were detected on Gm 11, Gm 16 and Gm 20 as in previous reports. Most loci associated with flowering time are sensitive to photo-thermal conditions. Number of loci associated with flowering time was more under the long day (LD) than under the short day (SD) condition. The variation of flowering time among the soybean cultivars mostly resulted from the epistasis × environment and additive × environment interactions. Among the three candidate loci, i.e. Gm04_4497001 (near GmCOL3a), Gm16_30766209 (near GmFT2a and GmFT2b) and Gm19_47514601 (E3 or GmPhyA3), the Gm04_4497001 may be the key locus interacting with other loci for controlling soybean flowering time. The effects of loci associated

  20. Cine MPR: interactive multiplanar reformatting of four-dimensional cardiac data using hardware-accelerated texture mapping.

    PubMed

    Shekhar, Raj; Zagrodsky, Vladimir

    2003-12-01

    Four-dimensional (4-D) imaging to capture the three-dimensional (3-D) structure and motion of the heart in real time is an emerging trend. We present here our method of interactive multiplanar reformatting (MPR), i.e., the ability to visualize any chosen anatomical cross section of 4-D cardiac images and to change its orientation smoothly while maintaining the original heart motion. Continuous animation to show the time-varying 3-D geometry of the heart and smooth dynamic manipulation of the reformatted planes, as well as large image size (100-300 MB), make MPR challenging. Our solution exploits the hardware acceleration of 3-D texture mapping capability of high-end commercial PC graphics boards. Customization of volume subdivision and caching concepts to periodic cardiac data allows us to use this hardware effectively and efficiently. We are able to visualize and smoothly interact with real-time 3-D ultrasound cardiac images at the desired frame rate (25 Hz). The developed methods are applicable to MPR of one or more 3-D and 4-D medical images, including 4-D cardiac images collected in a gated fashion.

  1. A MAP Kinase Kinase Interacts with SymRK and Regulates Nodule Organogenesis in Lotus japonicus[C][W

    PubMed Central

    Chen, Tao; Zhu, Hui; Ke, Danxia; Cai, Kai; Wang, Chao; Gou, Honglan; Hong, Zonglie; Zhang, Zhongming

    2012-01-01

    The symbiosis receptor kinase, SymRK, is required for root nodule development. A SymRK-interacting protein (SIP2) was found to form protein complex with SymRK in vitro and in planta. The interaction between SymRK and SIP2 is conserved in legumes. The SIP2 gene was expressed in all Lotus japonicus tissues examined. SIP2 represents a typical plant mitogen-activated protein kinase kinase (MAPKK) and exhibited autophosphorylation and transphosphorylation activities. Recombinant SIP2 protein could phosphorylate casein and the Arabidopsis thaliana MAP kinase MPK6. SymRK and SIP2 could not use one another as a substrate for phosphorylation. Instead, SymRK acted as an inhibitor of SIP2 kinase when MPK6 was used as a substrate, suggesting that SymRK may serve as a negative regulator of the SIP2 signaling pathway. Knockdown expression of SIP2 via RNA interference (RNAi) resulted in drastic reduction of nodules formed in transgenic hairy roots. A significant portion of SIP2 RNAi hairy roots failed to form a nodule. In these roots, the expression levels of SIP2 and three marker genes for infection thread and nodule primordium formation were downregulated drastically, while the expression of two other MAPKK genes were not altered. These observations demonstrate an essential role of SIP2 in the early symbiosis signaling and nodule organogenesis. PMID:22353370

  2. Assessing Systems Properties of Yeast Mitochondria through an Interaction Map of the Organelle

    PubMed Central

    Perocchi, Fabiana; Jensen, Lars J; Gagneur, Julien; Ahting, Uwe; von Mering, Christian; Bork, Peer; Prokisch, Holger; Steinmetz, Lars M

    2006-01-01

    Mitochondria carry out specialized functions; compartmentalized, yet integrated into the metabolic and signaling processes of the cell. Although many mitochondrial proteins have been identified, understanding their functional interrelationships has been a challenge. Here we construct a comprehensive network of the mitochondrial system. We integrated genome-wide datasets to generate an accurate and inclusive mitochondrial parts list. Together with benchmarked measures of protein interactions, a network of mitochondria was constructed in their cellular context, including extra-mitochondrial proteins. This network also integrates data from different organisms to expand the known mitochondrial biology beyond the information in the existing databases. Our network brings together annotated and predicted functions into a single framework. This enabled, for the entire system, a survey of mutant phenotypes, gene regulation, evolution, and disease susceptibility. Furthermore, we experimentally validated the localization of several candidate proteins and derived novel functional contexts for hundreds of uncharacterized proteins. Our network thus advances the understanding of the mitochondrial system in yeast and identifies properties of genes underlying human mitochondrial disorders. PMID:17054397

  3. IQGAP1 Scaffold-MAP Kinase Interactions Enhance Multiple Myeloma Clonogenic Growth and Self-Renewal.

    PubMed

    Gocke, Christian B; McMillan, Ross; Wang, Qiuju; Begum, Asma; Penchev, Vesselin R; Ali, Syed A; Borrello, Ivan; Huff, Carol Ann; Matsui, William

    2016-11-01

    Despite improved outcomes in newly diagnosed multiple myeloma, virtually all patients relapse and ultimately develop drug-resistant disease. Aberrant RAS/MAPK signaling is activated in the majority of relapsed/refractory multiple myeloma patients, but its biological consequences are not fully understood. Self-renewal, as defined by the long-term maintenance of clonogenic growth, is essential for disease relapse, and we examined the role of RAS/MAPK activation on multiple myeloma self-renewal by targeting IQ motif-containing GTPase-activating protein 1 (IQGAP1), an intracellular scaffold protein required for mutant RAS signaling. We found that loss of IQGAP1 expression decreased MAPK signaling, cell-cycle progression, and tumor colony formation. Similarly, a peptide mimicking the WW domain of IQGAP1 that interacts with ERK inhibited the clonogenic growth and self-renewal of multiple myeloma cell lines and primary clinical specimens in vitro as well as tumor-initiating cell frequency in immunodeficient mice. During multiple myeloma progression, self-renewal may be enhanced by aberrant RAS/MAPK signaling and inhibited by targeting IQGAP1. Mol Cancer Ther; 15(11); 2733-9. ©2016 AACR. ©2016 American Association for Cancer Research.

  4. Predicting a small molecule-kinase interaction map: A machine learning approach

    PubMed Central

    2011-01-01

    Background We present a machine learning approach to the problem of protein ligand interaction prediction. We focus on a set of binding data obtained from 113 different protein kinases and 20 inhibitors. It was attained through ATP site-dependent binding competition assays and constitutes the first available dataset of this kind. We extract information about the investigated molecules from various data sources to obtain an informative set of features. Results A Support Vector Machine (SVM) as well as a decision tree algorithm (C5/See5) is used to learn models based on the available features which in turn can be used for the classification of new kinase-inhibitor pair test instances. We evaluate our approach using different feature sets and parameter settings for the employed classifiers. Moreover, the paper introduces a new way of evaluating predictions in such a setting, where different amounts of information about the binding partners can be assumed to be available for training. Results on an external test set are also provided. Conclusions In most of the cases, the presented approach clearly outperforms the baseline methods used for comparison. Experimental results indicate that the applied machine learning methods are able to detect a signal in the data and predict binding affinity to some extent. For SVMs, the binding prediction can be improved significantly by using features that describe the active site of a kinase. For C5, besides diversity in the feature set, alignment scores of conserved regions turned out to be very useful. PMID:21708012

  5. Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin interactions.

    PubMed

    Chu, Ci; Qu, Kun; Zhong, Franklin L; Artandi, Steven E; Chang, Howard Y

    2011-11-18

    Long noncoding RNAs (lncRNAs) are key regulators of chromatin state, yet the nature and sites of RNA-chromatin interaction are mostly unknown. Here we introduce Chromatin Isolation by RNA Purification (ChIRP), where tiling oligonucleotides retrieve specific lncRNAs with bound protein and DNA sequences, which are enumerated by deep sequencing. ChIRP-seq of three lncRNAs reveal that RNA occupancy sites in the genome are focal, sequence-specific, and numerous. Drosophila roX2 RNA occupies male X-linked gene bodies with increasing tendency toward the 3' end, peaking at CES sites. Human telomerase RNA TERC occupies telomeres and Wnt pathway genes. HOTAIR lncRNA preferentially occupies a GA-rich DNA motif to nucleate broad domains of Polycomb occupancy and histone H3 lysine 27 trimethylation. HOTAIR occupancy occurs independently of EZH2, suggesting the order of RNA guidance of Polycomb occupancy. ChIRP-seq is generally applicable to illuminate the intersection of RNA and chromatin with newfound precision genome wide.

  6. Mapping the interactions and bioactivity of quercetin-(2-hydroxypropyl)-β-cyclodextrin complex.

    PubMed

    Kellici, Tahsin F; Chatziathanasiadou, Maria V; Diamantis, Dimitris; Chatzikonstantinou, Alexandra V; Andreadelis, Ioannis; Christodoulou, Eirini; Valsami, Georgia; Mavromoustakos, Thomas; Tzakos, Andreas G

    2016-09-10

    Natural products have served as a rich source for drug discovery and development. In the last decade their fruitful integration in the drug discovery pipeline declined due to their reduced bioavailability, mainly attributed to their poor aqueous solubility. We synthesized a quercetin (QUE)-(2-hydroxypropyl)-β-cyclodextrin (HP-β-CD) complex that enabled amplification of its solubility and in the same time retained its bioactivity in T24 human bladder cancer cell line. The stability of the complex and the molecular basis of the interactions developed in this host-guest complex were assayed by incorporating an array of analytical techniques and Molecular Dynamics (MD) experiments. 2D DOSY NMR experiment revealed that the diffusion coefficient of free HP-β-CD was 3.55×10(-10)m(2)s(-1) while that of QUE-HP-β-CD inclusion complex 3.09×10(-10)m(2)s(-1), indicating the formation of a complex. Solid and liquid high resolution NMR spectroscopy data showed that the most pronounced differences in chemical shifts at carbons and protons correspondingly during complexation occur in the aromatic ring Α (bearing the two phenolic hydroxyl groups meta to each other). The chemical shift differences in the aromatic ring Β (bearing the two phenolic hydroxyl groups ortho to each other) were less pronounced. The MD results confirmed the experimental data. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Association mapping for epistasis and environmental interaction of yield traits in 323 cotton cultivars under 9 different environments.

    PubMed

    Jia, Yinhua; Sun, Xiwei; Sun, Junling; Pan, Zhaoe; Wang, Xiwen; He, Shoupu; Xiao, Songhua; Shi, Weijun; Zhou, Zhongli; Pang, Baoyin; Wang, Liru; Liu, Jianguang; Ma, Jun; Du, Xiongming; Zhu, Jun

    2014-01-01

    Improving yield is a major objective for cotton breeding schemes, and lint yield and its three component traits (boll number, boll weight and lint percentage) are complex traits controlled by multiple genes and various environments. Association mapping was performed to detect markers associated with these four traits using 651 simple sequence repeats (SSRs). A mixed linear model including epistasis and environmental interaction was used to screen the loci associated with these four yield traits by 323 accessions of Gossypium hirsutum L. evaluated in nine different environments. 251 significant loci were detected to be associated with lint yield and its three components, including 69 loci with individual effects and all involved in epistasis interactions. These significant loci explain ∼ 62.05% of the phenotypic variance (ranging from 49.06% ∼ 72.29% for these four traits). It was indicated by high contribution of environmental interaction to the phenotypic variance for lint yield and boll numbers, that genetic effects of SSR loci were susceptible to environment factors. Shared loci were also observed among these four traits, which may be used for simultaneous improvement in cotton breeding for yield traits. Furthermore, consistent and elite loci were screened with -Log10 (P-value) >8.0 based on predicted effects of loci detected in different environments. There was one locus and 6 pairs of epistasis for lint yield, 4 loci and 10 epistasis for boll number, 15 loci and 2 epistasis for boll weight, and 2 loci and 5 epistasis for lint percentage, respectively. These results provided insights into the genetic basis of lint yield and its components and may be useful for marker-assisted breeding to improve cotton production.

  8. Association Mapping for Epistasis and Environmental Interaction of Yield Traits in 323 Cotton Cultivars under 9 Different Environments

    PubMed Central

    Pan, Zhaoe; Wang, Xiwen; He, Shoupu; Xiao, Songhua; Shi, Weijun; Zhou, Zhongli; Pang, Baoyin; Wang, Liru; Liu, Jianguang; Ma, Jun; Du, Xiongming; Zhu, Jun

    2014-01-01

    Improving yield is a major objective for cotton breeding schemes, and lint yield and its three component traits (boll number, boll weight and lint percentage) are complex traits controlled by multiple genes and various environments. Association mapping was performed to detect markers associated with these four traits using 651 simple sequence repeats (SSRs). A mixed linear model including epistasis and environmental interaction was used to screen the loci associated with these four yield traits by 323 accessions of Gossypium hirsutum L. evaluated in nine different environments. 251 significant loci were detected to be associated with lint yield and its three components, including 69 loci with individual effects and all involved in epistasis interactions. These significant loci explain ∼ 62.05% of the phenotypic variance (ranging from 49.06% ∼ 72.29% for these four traits). It was indicated by high contribution of environmental interaction to the phenotypic variance for lint yield and boll numbers, that genetic effects of SSR loci were susceptible to environment factors. Shared loci were also observed among these four traits, which may be used for simultaneous improvement in cotton breeding for yield traits. Furthermore, consistent and elite loci were screened with −Log10 (P-value) >8.0 based on predicted effects of loci detected in different environments. There was one locus and 6 pairs of epistasis for lint yield, 4 loci and 10 epistasis for boll number, 15 loci and 2 epistasis for boll weight, and 2 loci and 5 epistasis for lint percentage, respectively. These results provided insights into the genetic basis of lint yield and its components and may be useful for marker-assisted breeding to improve cotton production. PMID:24810754

  9. A Spatially Explicit Dual-Isotope Approach to Map Regions of Plant-Plant Interaction after Exotic Plant Invasion

    PubMed Central

    Hellmann, Christine; Werner, Christiane; Oldeland, Jens

    2016-01-01

    Understanding interactions between native and invasive plant species in field settings and quantifying the impact of invaders in heterogeneous native ecosystems requires resolving the spatial scale on which these processes take place. Therefore, functional tracers are needed that enable resolving the alterations induced by exotic plant invasion in contrast to natural variation in a spatially explicit way. 15N isoscapes, i.e., spatially referenced representations of stable nitrogen isotopic signatures, have recently provided such a tracer. However, different processes, e.g. water, nitrogen or carbon cycles, may be affected at different spatial scales. Thus multi-isotope studies, by using different functional tracers, can potentially return a more integrated picture of invader impact. This is particularly true when isoscapes are submitted to statistical methods suitable to find homogeneous subgroups in multivariate data such as cluster analysis. Here, we used model-based clustering of spatially explicit foliar δ15N and δ13C isoscapes together with N concentration of a native indicator species, Corema album, to map regions of influence in a Portuguese dune ecosystem invaded by the N2-fixing Acacia longifolia. Cluster analysis identified regions with pronounced alterations in N budget and water use efficiency in the native species, with a more than twofold increase in foliar N, and δ13C and δ15N enrichment of up to 2‰ and 8‰ closer to the invader, respectively. Furthermore, clusters of multiple functional tracers indicated a spatial shift from facilitation through N addition in the proximity of the invader to competition for resources other than N in close contact. Finding homogeneous subgroups in multi-isotope data by means of model-based cluster analysis provided an effective tool for detecting spatial structure in processes affecting plant physiology and performance. The proposed method can give an objective measure of the spatial extent of influence of

  10. Mapping and modeling the urban landscape in Bangkok, Thailand: Physical-spectral-spatial relations of population-environmental interactions

    NASA Astrophysics Data System (ADS)

    Shao, Yang

    This research focuses on the application of remote sensing, geographic information systems, statistical modeling, and spatial analysis to examine the dynamics of urban land cover, urban structure, and population-environment interactions in Bangkok, Thailand, with an emphasis on rural-to-urban migration from rural Nang Rong District, Northeast Thailand to the primate city of Bangkok. The dissertation consists of four main sections: (1) development of remote sensing image classification and change-detection methods for characterizing imperviousness for Bangkok, Thailand from 1993-2002; (2) development of 3-D urban mapping methods, using high spatial resolution IKONOS satellite images, to assess high-rises and other urban structures; (3) assessment of urban spatial structure from 2-D and 3-D perspectives; and (4) an analysis of the spatial clustering of migrants from Nang Rong District in Bangkok and the neighborhood environments of migrants' locations. Techniques are developed to improve the accuracy of the neural network classification approach for the analysis of remote sensing data, with an emphasis on the spectral unmixing problem. The 3-D building heights are derived using the shadow information on the high-resolution IKONOS image. The results from the 2-D and 3-D mapping are further examined to assess urban structure and urban feature identification. This research contributes to image processing of remotely-sensed images and urban studies. The rural-urban migration process and migrants' settlement patterns are examined using spatial statistics, GIS, and remote sensing perspectives. The results show that migrants' spatial clustering in urban space is associated with the source village and a number of socio-demographic variables. In addition, the migrants' neighborhood environments in urban setting are modeled using a set of geographic and socio-demographic variables, and the results are scale-dependent.

  11. An interactive map to assess the potential spread of Lymnaea truncatula and the free-living stages of Fasciola hepatica in Switzerland.

    PubMed

    Rapsch, Christina; Dahinden, Tobias; Heinzmann, Dominik; Torgerson, Paul R; Braun, Ueli; Deplazes, Peter; Hurni, Lorenz; Bär, Hansruedi; Knubben-Schweizer, Gabi

    2008-07-04

    The intermediate host of Fasciola hepatica is Lymnaea truncatula in Switzerland. The snail and the free-living stages of the parasite require a moderate climate and moisture for survival, reproduction, and transmission. In Switzerland, these conditions are present in many regions, resulting in a mean prevalence of bovine fasciolosis from 8.4 to 21.4%. An interactive map was created in order to demonstrate the relative risk of transmission by modelling the environmental conditions that promote the survival and reproduction of the larval stages of the parasite and the parasite's intermediate host. The map is based on temperature and rainfall data, soil conditions including ground water and forest cover in Switzerland. Extensive information on the free-living stages of F. hepatica and the intermediate host L. truncatula and how the development of these are affected by these environmental factors was used to create the interactive risk map.

  12. Fostering Primary School Students' Understanding of Cells and Other Related Concepts with Interactive Computer Animation Instruction Accompanied by Teacher and Student-Prepared Concept Maps

    ERIC Educational Resources Information Center

    Akpinar, Ercan; Ergin, Omer

    2008-01-01

    The purpose of this study was to investigate the effects of instruction (application) including interactive computer animation accompanied by teacher and student-prepared concept maps on primary students' biology achievement during instruction, as well as revealing attitudes towards science as a school subject. A quasi-experimental…

  13. Interactive Sonification of Spontaneous Movement of Children-Cross-Modal Mapping and the Perception of Body Movement Qualities through Sound.

    PubMed

    Frid, Emma; Bresin, Roberto; Alborno, Paolo; Elblaus, Ludvig

    2016-01-01

    cross-modal mapping of body motion qualities from bodily movement to sounds. Sound can be translated and understood from bodily motion, conveyed through sound visualizations in the shape of drawings and translated back from sound visualizations to audio. The work underlines the potential of using interactive sonification to communicate high-level features of human movement data.

  14. Interactive Sonification of Spontaneous Movement of Children—Cross-Modal Mapping and the Perception of Body Movement Qualities through Sound

    PubMed Central

    Frid, Emma; Bresin, Roberto; Alborno, Paolo; Elblaus, Ludvig

    2016-01-01

    cross-modal mapping of body motion qualities from bodily movement to sounds. Sound can be translated and understood from bodily motion, conveyed through sound visualizations in the shape of drawings and translated back from sound visualizations to audio. The work underlines the potential of using interactive sonification to communicate high-level features of human movement data. PMID:27891074

  15. Systematic Mapping of WNT-FZD Protein Interactions Reveals Functional Selectivity by Distinct WNT-FZD Pairs*

    PubMed Central

    Dijksterhuis, Jacomijn P.; Baljinnyam, Bolormaa; Stanger, Karen; Sercan, Hakki O.; Ji, Yun; Andres, Osler; Rubin, Jeffrey S.; Hannoush, Rami N.; Schulte, Gunnar

    2015-01-01

    The seven-transmembrane-spanning receptors of the FZD1–10 class are bound and activated by the WNT family of lipoglycoproteins, thereby inducing a complex network of signaling pathways. However, the specificity of the interaction between mammalian WNT and FZD proteins and the subsequent signaling cascade downstream of the different WNT-FZD pairs have not been systematically addressed to date. In this study, we determined the binding affinities of various WNTs for different members of the FZD family by using bio-layer interferometry and characterized their functional selectivity in a cell system. Using purified WNTs, we show that different FZD cysteine-rich domains prefer to bind to distinct WNTs with fast on-rates and slow off-rates. In a 32D cell-based system engineered to overexpress FZD2, FZD4, or FZD5, we found that WNT-3A (but not WNT-4, -5A, or -9B) activated the WNT-β-catenin pathway through FZD2/4/5 as measured by phosphorylation of LRP6 and β-catenin stabilization. Surprisingly, different WNT-FZD pairs showed differential effects on phosphorylation of DVL2 and DVL3, revealing a previously unappreciated DVL isoform selectivity by different WNT-FZD pairs in 32D cells. In summary, we present extensive mapping of WNT-FZD cysteine-rich domain interactions complemented by analysis of WNT-FZD pair functionality in a unique cell system expressing individual FZD isoforms. Differential WNT-FZD binding and selective functional readouts suggest that endogenous WNT ligands evolved with an intrinsic natural bias toward different downstream signaling pathways, a phenomenon that could be of great importance in the design of FZD-targeting drugs. PMID:25605717

  16. Construction of a Comprehensive Protein-Protein Interaction Map for Vitiligo Disease to Identify Key Regulatory Elements: A Systemic Approach.

    PubMed

    Malhotra, Anvita Gupta; Jha, Mohit; Singh, Sudha; Pandey, Khushhali M

    2017-03-13

    Vitiligo is an idiopathic disorder characterized by depigmented patches on the skin due to progressive loss of melanocytes. Several genetic, immunological, and pathophysiological investigations have established vitiligo as a polygenetic disorder with multifactorial etiology. However, no definite model explaining the interplay between these causative factors has been established hitherto. Therefore, we studied the disorder at the system level to identify the key proteins involved by exploring their molecular connectivity in terms of topological parameters. The existing research data helped us in collating 215 proteins involved in vitiligo onset or progression. Interaction study of these proteins leads to a comprehensive vitiligo map with 4845 protein nodes linked with 107,416 edges. Based on centrality measures, a backbone network with 500 nodes has been derived. This has presented a clear overview of the proteins and processes involved and the crosstalk between them. Clustering backbone proteins revealed densely connected regions inferring major molecular interaction modules essential for vitiligo. Finally, a list of top order proteins that play a key role in the disease pathomechanism has been formulated. This includes SUMO2, ESR1, COPS5, MYC, SMAD3, and Cullin proteins. While this list is in fair agreement with the available literature, it also introduces new candidate proteins that can be further explored. A subnetwork of 64 vitiligo core proteins was built by analyzing the backbone and seed protein networks. Our finding suggests that the topology, along with functional clustering, provides a deep insight into the behavior of proteins. This in turn aids in the illustration of disease condition and discovery of significant proteins involved in vitiligo.

  17. QTL mapping and epistatic interaction analysis in asparagus bean for several characterized and novel horticulturally important traits

    PubMed Central

    2013-01-01

    Background Asparagus bean (Vigna. unguiculata. ssp sesquipedalis) is a subspecies and special vegetable type of cowpea (Vigna. unguiculata L. Walp.) important in Asia. Genetic basis of horticulturally important traits of asparagus bean is still poorly understood, hindering the utilization of targeted, DNA marker-assisted breeding in this crop. Here we report the identification of quantitative trait loci (QTLs) and epistatic interactions for four horticultural traits, namely, days to first flowering (FLD), nodes to first flower (NFF), leaf senescence (LS) and pod number per plant (PN) using a recombinant inbred line (RIL) population of asparagus bean. Results A similar genetic mode of one major QTL plus a few minor QTLs was found to dominate each of the four traits, with the number of QTLs for individual traits ranging from three to four. These QTLs were distributed on 7 of the 11 chromosomes. Major QTLs for FLD, NFF and LS were co-localized on LG 11, indicative of tight linkage. Genome wide epistasis analysis detected two and one interactive locus pairs that significantly affect FLD and LS, respectively, and the epistatic QTLs for FLD appeared to work in different ways. Synteny based comparison of QTL locations revealed conservation of chromosome regions controlling these traits in related legume crops. Conclusion Major, minor, and epistatic QTLs were found to contribute to the inheritance of the FLD, NFF, LS, and PN. Positions of many of these QTLs are conserved among closely related legume species, indicating common mechanisms they share. To our best knowledge, this is the first QTL mapping report using an asparagus bean × asparagus bean intervarietal population and provides marker-trait associations for marker-assisted approaches to selection. PMID:23375055

  18. Web GIS in practice II: interactive SVG maps of diagnoses of sexually transmitted diseases by Primary Care Trust in London, 1997 – 2003

    PubMed Central

    Boulos, Maged N Kamel; Russell, Chris; Smith, Michael

    2005-01-01

    Background The rates of Sexually transmitted diseases (STDs) in England have been rising steadily since the mid 1990s, making them a major public health concern. In 2003, 672,718 people were diagnosed with an STD in England, and around one third of those cases were diagnosed in London. Results Using GeoReveal v1.1 for Windows, we produced Web-based interactive choropleth maps of diagnoses of STDs by Primary Care Trust (PCT) in London for the years from 1997 to 2003 . These maps are in Scalable Vector Graphics (SVG) format and require a freely available Adobe SVG browser plug-in to be displayed. They are based on data obtained from the House of Commons Hansard Written Answers for 15 October 2004. They show steadily rising rates of STDs in London over the covered seven-year period. Also, one can clearly see on the maps that PCTs located in central London had the highest numbers of STD diagnoses throughout the mapped seven years. A companion bar chart allows users to instantly compare the STD figure of a given PCT for a given year against the average figure for all 25 mapped PCTs for the same year, and also compare those figures across all seven years. The maps offer users a rich set of useful features and functions, including the ability to change the classification method in use, the number of ranges in the map, and the colour theme, among others. Conclusions Wizard-driven tools like GeoReveal have made it very easy to transform complex raw data into valuable decision support information products (interactive Web maps) in very little time and without requiring much expertise. The resultant interactive maps have the potential of further supporting health planners and decision makers in their planning and management tasks by allowing them to graphically interrogate data, instantly spot trends, and make quick and effective visual comparisons of geographically differentiated phenomena between different geographical areas and over time. SVG makes an ideal format for such

  19. Comprehensive mapping of protein N-glycosylation in human liver by combining hydrophilic interaction chromatography and hydrazide chemistry.

    PubMed

    Zhu, Jun; Sun, Zhen; Cheng, Kai; Chen, Rui; Ye, Mingliang; Xu, Bo; Sun, Deguang; Wang, Liming; Liu, Jing; Wang, Fangjun; Zou, Hanfa

    2014-03-07

    Although glycoproteomics is greatly developed in recent years, our knowledge about N-glycoproteome of human tissues is still very limited. In this study, we comprehensively mapped the N-glycosylation sites of human liver by combining click maltose-hydrophilic interaction chromatography (HILIC) and the improved hydrazide chemistry. The specificity could be as high as 90% for hydrazide chemistry and 80% for HILIC. Altogether, we identified 14,480 N-glycopeptides matched with N-!P-[S|T|C] sequence motif from human liver, corresponding to 2210 N-glycoproteins and 4783 N-glycosylation sites. These N-glycoproteins are widely involved into different types of biological processes, such as hepatic stellate cell activation and acute phase response of human liver, which all highly associate with the progression of liver diseases. Moreover, the exact N-glycosylation sites of some key-regulating proteins within different human liver physiological processes were also obtained, such as E-cadherin, transforming growth factor beta receptor and 29 members of G protein coupled receptors family.

  20. Structural evolution in germanium and selenium nuclei within the mapped interacting boson model based on the Gogny energy density functional

    NASA Astrophysics Data System (ADS)

    Nomura, K.; Rodríguez-Guzmán, R.; Robledo, L. M.

    2017-06-01

    The shape transitions and shape coexistence in the Ge and Se isotopes are studied within the interacting boson model (IBM) with the microscopic input from a self-consistent mean-field calculation based on the Gogny-D1M energy density functional. The mean-field energy surface as a function of the quadrupole shape variables β and γ , obtained from the constrained Hartree-Fock-Bogoliubov method, is mapped onto the expectation value of the IBM Hamiltonian with configuration mixing in the boson condensate state. The resultant Hamiltonian is used to compute excitation energies and electromagnetic properties of the selected nuclei Ge-9466 and Se-9668. Our calculation suggests that many nuclei exhibit γ softness. Coexistence between prolate and oblate shapes, as well as between spherical and γ -soft shapes, is also observed. The method provides a reasonable description of the observed systematics of the excitation energy of the low-lying energy levels and transition strengths for nuclei below the neutron shell closure N =50 , and provides predictions on the spectroscopy of neutron-rich Ge and Se isotopes with 52 ≤N ≤62 , where data are scarce or not available.

  1. An integrated protein localization and interaction map for Potato yellow dwarf virus, type species of the genus Nucleorhabdovirus

    PubMed Central

    Bandyopadhyay, Anindya; Kopperud, Kristin; Anderson, Gavin; Martin, Kathleen; Goodin, Michael

    2010-01-01

    The genome of Potato yellow dwarf virus (PYDV; Nucleorhabdovirus type species), was determined to be 12,875 nucleotides (nt). The antigenome is organized into seven open reading frames (ORFs) ordered 3′-N-X-P-Y-M-G-L-5′, which likely encode the nucleocapsid, phospho, movement, matrix, glyco and RNA-dependent RNA polymerase proteins, respectively, except for X, which is of unknown function. The ORFs are flanked by a 3′ leader RNA of 149 nt and a 5′ trailer RNA of 97 nt, and are separated by conserved intergenic junctions. Phylogenetic analyses indicated that PYDV is closely related to other leafhopper-transmitted rhabdoviruses. Functional protein assays were used to determine the subcellular localization of PYDV proteins. Surprisingly, the M protein was able to induce the intranuclear accumulation of the inner nuclear membrane in the absence of any other viral protein. Finally, bimolecular fluorescence complementation was used to generate the most comprehensive protein interaction map for a plant-adapted rhabdovirus to date. PMID:20362316

  2. An integrated protein localization and interaction map for Potato yellow dwarf virus, type species of the genus Nucleorhabdovirus

    SciTech Connect

    Bandyopadhyay, Anindya; Kopperud, Kristin; Anderson, Gavin; Martin, Kathleen; Goodin, Michael

    2010-06-20

    The genome of Potato yellow dwarf virus (PYDV; Nucleorhabdovirus type species) was determined to be 12,875 nucleotides (nt). The antigenome is organized into seven open reading frames (ORFs) ordered 3'-N-X-P-Y-M-G-L-5', which likely encode the nucleocapsid, phospho, movement, matrix, glyco and RNA-dependent RNA polymerase proteins, respectively, except for X, which is of unknown function. The ORFs are flanked by a 3' leader RNA of 149 nt and a 5' trailer RNA of 97 nt, and are separated by conserved intergenic junctions. Phylogenetic analyses indicated that PYDV is closely related to other leafhopper-transmitted rhabdoviruses. Functional protein assays were used to determine the subcellular localization of PYDV proteins. Surprisingly, the M protein was able to induce the intranuclear accumulation of the inner nuclear membrane in the absence of any other viral protein. Finally, bimolecular fluorescence complementation was used to generate the most comprehensive protein interaction map for a plant-adapted rhabdovirus to date.

  3. Genetic Interaction Mapping Reveals a Role for the SWI/SNF Nucleosome Remodeler in Spliceosome Activation in Fission Yeast

    PubMed Central

    Patrick, Kristin L.; Ryan, Colm J.; Xu, Jiewei; Lipp, Jesse J.; Nissen, Kelly E.; Roguev, Assen; Shales, Michael; Krogan, Nevan J.; Guthrie, Christine

    2015-01-01

    Although numerous regulatory connections between pre-mRNA splicing and chromatin have been demonstrated, the precise mechanisms by which chromatin factors influence spliceosome assembly and/or catalysis remain unclear. To probe the genetic network of pre-mRNA splicing in the fission yeast Schizosaccharomyces pombe, we constructed an epistatic mini-array profile (E-MAP) and discovered many new connections between chromatin and splicing. Notably, the nucleosome remodeler SWI/SNF had strong genetic interactions with components of the U2 snRNP SF3 complex. Overexpression of SF3 components in ΔSWI/SNF cells led to inefficient splicing of many fission yeast introns, predominantly those with non-consensus splice sites. Deletion of SWI/SNF decreased recruitment of the splicing ATPase Prp2, suggesting that SWI/SNF promotes co-transcriptional spliceosome assembly prior to first step catalysis. Importantly, defects in SWI/SNF as well as SF3 overexpression each altered nucleosome occupancy along intron-containing genes, illustrating that the chromatin landscape both affects—and is affected by—co-transcriptional splicing. PMID:25825871

  4. Selection in spatial working memory is independent of perceptual selective attention, but they interact in a shared spatial priority map.

    PubMed

    Hedge, Craig; Oberauer, Klaus; Leonards, Ute

    2015-11-01

    We examined the relationship between the attentional selection of perceptual information and of information in working memory (WM) through four experiments, using a spatial WM-updating task. Participants remembered the locations of two objects in a matrix and worked through a sequence of updating operations, each mentally shifting one dot to a new location according to an arrow cue. Repeatedly updating the same object in two successive steps is typically faster than switching to the other object; this object switch cost reflects the shifting of attention in WM. In Experiment 1, the arrows were presented in random peripheral locations, drawing perceptual attention away from the selected object in WM. This manipulation did not eliminate the object switch cost, indicating that the mechanisms of perceptual selection do not underlie selection in WM. Experiments 2a and 2b corroborated the independence of selection observed in Experiment 1, but showed a benefit to reaction times when the placement of the arrow cue was aligned with the locations of relevant objects in WM. Experiment 2c showed that the same benefit also occurs when participants are not able to mark an updating location through eye fixations. Together, these data can be accounted for by a framework in which perceptual selection and selection in WM are separate mechanisms that interact through a shared spatial priority map.

  5. Rydberg and valence state excitation dynamics: a velocity map imaging study involving the E-V state interaction in HBr.

    PubMed

    Zaouris, Dimitris; Kartakoullis, Andreas; Glodic, Pavle; Samartzis, Peter C; Rafn Hróðmarsson, Helgi; Kvaran, Ágúst

    2015-04-28

    Photoexcitation dynamics of the E((1)Σ(+)) (v' = 0) Rydberg state and the V((1)Σ(+)) (v') ion-pair vibrational states of HBr are investigated by velocity map imaging (VMI). H(+) photoions, produced through a number of vibrational and rotational levels of the two states were imaged and kinetic energy release (KER) and angular distributions were extracted from the data. In agreement with previous work, we found the photodissociation channels forming H*(n = 2) + Br((2)P3/2)/Br*((2)P1/2) to be dominant. Autoionization pathways leading to H(+) + Br((2)P3/2)/Br*((2)P1/2) via either HBr(+)((2)Π3/2) or HBr(+)*((2)Π1/2) formation were also present. The analysis of KER and angular distributions and comparison with rotationally and mass resolved resonance enhanced multiphoton ionization (REMPI) spectra revealed the excitation transition mechanisms and characteristics of states involved as well as the involvement of the E-V state interactions and their v' and J' dependence.

  6. Interaction of two successive Alpine deformation fronts: constraints from low-temperature thermochronology and structural mapping (NW Iberian Peninsula)

    NASA Astrophysics Data System (ADS)

    Martín-González, F.; Barbero, L.; Capote, R.; Heredia, N.; Gallastegui, G.

    2012-07-01

    The lateral termination of the Alpine-Pyrenean Orogen relief onshore is located in the NW Iberian Peninsula. It overlies a Variscan basement (Iberian Massif), where the sedimentary record of the Alpine tectonic is very scarce. Thus, the characterisation of the tectonic evolution of the lateral termination is difficult and timing and geometries of the main tectonic structures remain unclear. Combining the tectonothermal histories obtained by modelling of the apatite fission-track data (AFT) with structural mapping allows for a comparative study of the different tectonic scenarios and deformation transfer in the lateral termination of an orogen. AFT ages for the studied area vary from 53.5 ± 12.9 and 222 ± 12 Ma (from Late Triassic to Early Eocene). The beginning of the Cenozoic cooling episodes is in agreement with the infilling of the Tertiary basins (Late Eocene or Oligocene). Calculated uplift for the Alpine Orogeny is around 2,400 m. The Cantabrian Mountains were uplifted and emplaced southwards and the main period of exhumation began in the Palaeogene at rates of ~0.02 mm/a and continued during the Neogene at rates of ~0.06 mm/a. However, the Galaico-Leoneses Mountains, located to the south of the studied area, were uplifted and emplaced northwards during the Neogene, showing more rapid uplift rates of ~0.08 mm/a, suggesting that the western termination of the Alpine-Pyrenean Orogen relief is the result of the successive interaction of two Alpine deformation fronts.

  7. Genetic interaction mapping reveals a role for the SWI/SNF nucleosome remodeler in spliceosome activation in fission yeast.

    PubMed

    Patrick, Kristin L; Ryan, Colm J; Xu, Jiewei; Lipp, Jesse J; Nissen, Kelly E; Roguev, Assen; Shales, Michael; Krogan, Nevan J; Guthrie, Christine

    2015-03-01

    Although numerous regulatory connections between pre-mRNA splicing and chromatin have been demonstrated, the precise mechanisms by which chromatin factors influence spliceosome assembly and/or catalysis remain unclear. To probe the genetic network of pre-mRNA splicing in the fission yeast Schizosaccharomyces pombe, we constructed an epistatic mini-array profile (E-MAP) and discovered many new connections between chromatin and splicing. Notably, the nucleosome remodeler SWI/SNF had strong genetic interactions with components of the U2 snRNP SF3 complex. Overexpression of SF3 components in ΔSWI/SNF cells led to inefficient splicing of many fission yeast introns, predominantly those with non-consensus splice sites. Deletion of SWI/SNF decreased recruitment of the splicing ATPase Prp2, suggesting that SWI/SNF promotes co-transcriptional spliceosome assembly prior to first step catalysis. Importantly, defects in SWI/SNF as well as SF3 overexpression each altered nucleosome occupancy along intron-containing genes, illustrating that the chromatin landscape both affects--and is affected by--co-transcriptional splicing.

  8. Biochemical mapping of interactions within the intraflagellar transport (IFT) B core complex: IFT52 binds directly to four other IFT-B subunits.

    PubMed

    Taschner, Michael; Bhogaraju, Sagar; Vetter, Melanie; Morawetz, Michaela; Lorentzen, Esben

    2011-07-29

    Cilia and flagella are complex structures emanating from the surface of most eukaroytic cells and serve important functions including motility, signaling, and sensory reception. A process called intraflagellar transport (IFT) is of central importance to ciliary assembly and maintenance. The IFT complex is required for this transport and consists of two distinct multisubunit subcomplexes, IFT-A and IFT-B. Despite the importance of the IFT complex, little is known about its overall architecture. This paper presents a biochemical dissection of the molecular interactions within the IFT-B core complex. Two stable subcomplexes consisting of IFT88/70/52/46 and IFT81/74/27/25 were recombinantly co-expressed and purified. We identify a novel interaction between IFT70/52 and map the interaction domains between IFT52 and the other subunits within the IFT88/70/52/46 complex. Additionally, we show that IFT52 binds directly to the IFT81/74/27/25 complex, indicating that it could mediate the interaction between the two subcomplexes. Our data lead to an improved architectural map for the IFT-B core complex with new interactions as well as domain resolution mapping for several subunits.

  9. e2g: an interactive web-based server for efficiently mapping large EST and cDNA sets to genomic sequences.

    PubMed

    Krüger, Jan; Sczyrba, Alexander; Kurtz, Stefan; Giegerich, Robert

    2004-07-01

    e2g is a web-based server which efficiently maps large expressed sequence tag (EST) and cDNA datasets to genomic DNA. It significantly extends the volume of data that can be mapped in reasonable time, and makes this improved efficiency available as a web service. Our server hosts large collections of EST sequences (e.g. 4.1 million mouse ESTs of 1.87 Gb) in precomputed indexed data structures for efficient sequence comparison. The user can upload a genomic DNA sequence of interest and rapidly compare this to the complete collection of ESTs on the server. This delivers a mapping of the ESTs on the genomic DNA. The e2g web interface provides a graphical overview of the mapping. Alignments of the mapped EST regions with parts of the genomic sequence are visualized. Zooming functions allow the user to interactively explore the results. Mapped sequences can be downloaded for further analysis. e2g is available on the Bielefeld University Bioinformatics Server at http://bibiserv.techfak.uni-bielefeld.de/e2g/.

  10. Novel mobilizable prokaryotic two-hybrid system vectors for high-throughput protein interaction mapping in Escherichia coli by bacterial conjugation.

    PubMed

    Clarke, Paul; Cuív, Páraic O; O'Connell, Michael

    2005-02-01

    Since its initial description, the yeast two-hybrid (Y2H) system has been widely used for the detection and analysis of protein-protein interactions. Mating-based strategies have been developed permitting its application for automated proteomic interaction mapping projects using both exhaustive and high-throughput strategies. More recently, a number of prokaryotic two-hybrid (P2H) systems have been developed but, despite the many advantages such Escherichia coli-based systems have over the Y2H system, they have not yet been widely implemented for proteomic interaction mapping. This may be largely due to the fact that high-throughput strategies employing bacterial transformation are not as amenable to automation as Y2H mating-based strategies. Here, we describe the construction of novel conjugative P2H system vectors. These vectors carry a mobilization element of the IncPalpha group plasmid RP4 and can therefore be mobilized with high efficiency from an E.coli donor strain encoding all of the required transport functions in trans. We demonstrate how these vectors permit the exploitation of bacterial conjugation for technically simplified and automated proteomic interaction mapping strategies in E.coli, analogous to the mating-based strategies developed for the Y2H system.

  11. Topographical mapping of α- and β-keratins on developing chicken skin integuments: Functional interaction and evolutionary perspectives

    PubMed Central

    Wu, Ping; Ng, Chen Siang; Yan, Jie; Lai, Yung-Chih; Chen, Chih-Kuan; Lai, Yu-Ting; Wu, Siao-Man; Chen, Jiun-Jie; Luo, Weiqi; Widelitz, Randall B.; Li, Wen-Hsiung; Chuong, Cheng-Ming

    2015-01-01

    Avian integumentary organs include feathers, scales, claws, and beaks. They cover the body surface and play various functions to help adapt birds to diverse environments. These keratinized structures are mainly composed of corneous materials made of α-keratins, which exist in all vertebrates, and β-keratins, which only exist in birds and reptiles. Here, members of the keratin gene families were used to study how gene family evolution contributes to novelty and adaptation, focusing on tissue morphogenesis. Using chicken as a model, we applied RNA-seq and in situ hybridization to map α- and β-keratin genes in various skin appendages at embryonic developmental stages. The data demonstrate that temporal and spatial α- and β-keratin expression is involved in establishing the diversity of skin appendage phenotypes. Embryonic feathers express a higher proportion of β-keratin genes than other skin regions. In feather filament morphogenesis, β-keratins show intricate complexity in diverse substructures of feather branches. To explore functional interactions, we used a retrovirus transgenic system to ectopically express mutant α- or antisense β-keratin forms. α- and β-keratins show mutual dependence and mutations in either keratin type results in disrupted keratin networks and failure to form proper feather branches. Our data suggest that combinations of α- and β-keratin genes contribute to the morphological and structural diversity of different avian skin appendages, with feather-β-keratins conferring more possible composites in building intrafeather architecture complexity, setting up a platform of morphological evolution of functional forms in feathers. PMID:26598683

  12. Analysis of origin and protein-protein interaction maps suggests distinct oncogenic role of nuclear EGFR during cancer evolution

    PubMed Central

    Sharip, Ainur; Abdukhakimova, Diyora; Wang, Xiao; Kim, Alexey; Kim, Yevgeniy; Sharip, Aigul; Orakov, Askarbek; Miao, Lixia; Sun, Qinglei; Chen, Yue; Chen, Zhenbang; Xie, Yingqiu

    2017-01-01

    Receptor tyrosine kinase EGFR usually is localized on plasma membrane to induce progression of many cancers including cancers in children (Bodey et al. In Vivo. 2005, 19:931-41), but it contains a nuclear localization signal (NLS) that mediates EGFR nuclear translocation (Lin et al. Nat Cell Biol. 2001, 3:802-8). Here we report that NLS of EGFR has its old evolutionary origin. Protein-protein interaction maps suggests that nEGFR pathways are different from membrane EGFR and EGF is not found in nEGFR network while androgen receptor (AR) is found, which suggests the evolution of prostate cancer, a well-known AR driven cancer, through changes in androgen- or EGF-dependence. Database analysis suggests that nEGFR correlates with the tumor grades especially in prostate cancer patients. Structural predication analysis suggests that NLS can compromise the differential protein binding to EGFR through stretch linkers with evolutionary mutation from N to V. In experiment, elevation of nEGFR but not membrane EGFR was found in castration resistant prostate cancer cells. Finally, systems analysis of NLS and transmembrane domain (TM) suggests that NLS has old origin while NLS neighboring domain of TM has been undergone accelerated evolution. Thus nEGFR has an old origin resembling the cancer evolution but TM may interfere with NLS driven signaling for natural selection of survival to evade NLS induced aggressive cancers. Our data suggest NLS is a dynamic inducer of EGFR oncogenesis during evolution for advanced cancers. Our model provides novel insights into the evolutionary role of NLS of oncogenic kinases in cancers. PMID:28382154

  13. Identification and mapping of leaf, stem and stripe rust resistance quantitative trait loci and their interactions in durum wheat.

    PubMed

    Singh, A; Pandey, M P; Singh, A K; Knox, R E; Ammar, K; Clarke, J M; Clarke, F R; Singh, R P; Pozniak, C J; Depauw, R M; McCallum, B D; Cuthbert, R D; Randhawa, H S; Fetch, T G

    2013-02-01

    Leaf rust (Puccinia triticina Eriks.), stripe rust (Puccinia striiformis f. tritici Eriks.) and stem rust (Puccinia graminis f. sp. tritici) cause major production losses in durum wheat (Triticum turgidum L. var. durum). The objective of this research was to identify and map leaf, stripe and stem rust resistance loci from the French cultivar Sachem and Canadian cultivar Strongfield. A doubled haploid population from Sachem/Strongfield and parents were phenotyped for seedling reaction to leaf rust races BBG/BN and BBG/BP and adult plant response was determined in three field rust nurseries near El Batan, Obregon and Toluca, Mexico. Stripe rust response was recorded in 2009 and 2011 nurseries near Toluca and near Njoro, Kenya in 2010. Response to stem rust was recorded in field nurseries near Njoro, Kenya, in 2010 and 2011. Sachem was resistant to leaf, stripe and stem rust. A major leaf rust quantitative trait locus (QTL) was identified on chromosome 7B at Xgwm146 in Sachem. In the same region on 7B, a stripe rust QTL was identified in Strongfield. Leaf and stripe rust QTL around DArT marker wPt3451 were identified on chromosome 1B. On chromosome 2B, a significant leaf rust QTL was detected conferred by Strongfield, and at the same QTL, a Yr gene derived from Sachem conferred resistance. Significant stem rust resistance QTL were detected on chromosome 4B. Consistent interactions among loci for resistance to each rust type across nurseries were detected, especially for leaf rust QTL on 7B. Sachem and Strongfield offer useful sources of rust resistance genes for durum rust breeding.

  14. Interaction Between Object-Based Attention and Pertinence Values Shapes the Attentional Priority Map of a Multielement Display

    PubMed Central

    2016-01-01

    Previous studies have shown that the perceptual organization of the visual scene constrains the deployment of attention. Here we investigated how the organization of multiple elements into larger configurations alters their attentional weight, depending on the “pertinence” or behavioral importance of the elements’ features. We assessed object-based effects on distinct aspects of the attentional priority map: top-down control, reflecting the tendency to encode targets rather than distracters, and the spatial distribution of attention weights across the visual scene, reflecting the tendency to report elements belonging to the same rather than different objects. In 2 experiments participants had to report the letters in briefly presented displays containing 8 letters and digits, in which pairs of characters could be connected with a line. Quantitative estimates of top-down control were obtained using Bundesen’s Theory of Visual Attention (1990). The spatial distribution of attention weights was assessed using the “paired response index” (PRI), indicating responses for within-object pairs of letters. In Experiment 1, grouping along the task-relevant dimension (targets with targets and distracters with distracters) increased top-down control and enhanced the PRI; in contrast, task-irrelevant grouping (targets with distracters) did not affect performance. In Experiment 2, we disentangled the effect of target-target and distracter-distracter grouping: Pairwise grouping of distracters enhanced top-down control whereas pairwise grouping of targets changed the PRI. We conclude that object-based perceptual representations interact with pertinence values (of the elements’ features and location) in the computation of attention weights, thereby creating a widespread pattern of attentional facilitation across the visual scene. PMID:26752732

  15. Topographical mapping of α- and β-keratins on developing chicken skin integuments: Functional interaction and evolutionary perspectives.

    PubMed

    Wu, Ping; Ng, Chen Siang; Yan, Jie; Lai, Yung-Chih; Chen, Chih-Kuan; Lai, Yu-Ting; Wu, Siao-Man; Chen, Jiun-Jie; Luo, Weiqi; Widelitz, Randall B; Li, Wen-Hsiung; Chuong, Cheng-Ming

    2015-12-08

    Avian integumentary organs include feathers, scales, claws, and beaks. They cover the body surface and play various functions to help adapt birds to diverse environments. These keratinized structures are mainly composed of corneous materials made of α-keratins, which exist in all vertebrates, and β-keratins, which only exist in birds and reptiles. Here, members of the keratin gene families were used to study how gene family evolution contributes to novelty and adaptation, focusing on tissue morphogenesis. Using chicken as a model, we applied RNA-seq and in situ hybridization to map α- and β-keratin genes in various skin appendages at embryonic developmental stages. The data demonstrate that temporal and spatial α- and β-keratin expression is involved in establishing the diversity of skin appendage phenotypes. Embryonic feathers express a higher proportion of β-keratin genes than other skin regions. In feather filament morphogenesis, β-keratins show intricate complexity in diverse substructures of feather branches. To explore functional interactions, we used a retrovirus transgenic system to ectopically express mutant α- or antisense β-keratin forms. α- and β-keratins show mutual dependence and mutations in either keratin type results in disrupted keratin networks and failure to form proper feather branches. Our data suggest that combinations of α- and β-keratin genes contribute to the morphological and structural diversity of different avian skin appendages, with feather-β-keratins conferring more possible composites in building intrafeather architecture complexity, setting up a platform of morphological evolution of functional forms in feathers.

  16. Using GIS servers and interactive maps in spectral data sharing and administration: Case study of Ahvaz Spectral Geodatabase Platform (ASGP)

    NASA Astrophysics Data System (ADS)

    Karami, Mojtaba; Rangzan, Kazem; Saberi, Azim

    2013-10-01

    With emergence of air-borne and space-borne hyperspectral sensors, spectroscopic measurements are gaining more importance in remote sensing. Therefore, the number of available spectral reference data is constantly increasing. This rapid increase often exhibits a poor data management, which leads to ultimate isolation of data on disk storages. Spectral data without precise description of the target, methods, environment, and sampling geometry cannot be used by other researchers. Moreover, existing spectral data (in case it accompanied with good documentation) become virtually invisible or unreachable for researchers. Providing documentation and a data-sharing framework for spectral data, in which researchers are able to search for or share spectral data and documentation, would definitely improve the data lifetime. Relational Database Management Systems (RDBMS) are main candidates for spectral data management and their efficiency is proven by many studies and applications to date. In this study, a new approach to spectral data administration is presented based on spatial identity of spectral samples. This method benefits from scalability and performance of RDBMS for storage of spectral data, but uses GIS servers to provide users with interactive maps as an interface to the system. The spectral files, photographs and descriptive data are considered as belongings of a geospatial object. A spectral processing unit is responsible for evaluation of metadata quality and performing routine spectral processing tasks for newly-added data. As a result, by using internet browser software the users would be able to visually examine availability of data and/or search for data based on descriptive attributes associated to it. The proposed system is scalable and besides giving the users good sense of what data are available in the database, it facilitates participation of spectral reference data in producing geoinformation.

  17. Interaction of Antiparallel Microtubules in the Phragmoplast Is Mediated by the Microtubule-Associated Protein MAP65-3 in Arabidopsis[W

    PubMed Central

    Ho, Chin-Min Kimmy; Hotta, Takashi; Guo, Fengli; Roberson, Robert W.; Lee, Yuh-Ru Julie; Liu, Bo

    2011-01-01

    In plant cells, microtubules (MTs) in the cytokinetic apparatus phragmoplast exhibit an antiparallel array and transport Golgi-derived vesicles toward MT plus ends located at or near the division site. By transmission electron microscopy, we observed that certain antiparallel phragmoplast MTs overlapped and were bridged by electron-dense materials in Arabidopsis thaliana. Robust MT polymerization, reported by fluorescently tagged End Binding1c (EB1c), took place in the phragmoplast midline. The engagement of antiparallel MTs in the central spindle and phragmoplast was largely abolished in mutant cells lacking the MT-associated protein, MAP65-3. We found that endogenous MAP65-3 was selectively detected on the middle segments of the central spindle MTs at late anaphase. When MTs exhibited a bipolar appearance with their plus ends placed in the middle, MAP65-3 exclusively decorated the phragmoplast midline. A bacterially expressed MAP65-3 protein was able to establish the interdigitation of MTs in vitro. MAP65-3 interacted with antiparallel microtubules before motor Kinesin-12 did during the establishment of the phragmoplast MT array. Thus, MAP65-3 selectively cross-linked interdigitating MTs (IMTs) to allow antiparallel MTs to be closely engaged in the phragmoplast. Although the presence of IMTs was not essential for vesicle trafficking, they were required for the phragmoplast-specific motors Kinesin-12 and Phragmoplast-Associated Kinesin-Related Protein2 to interact with MT plus ends. In conclusion, we suggest that the phragmoplast contains IMTs and highly dynamic noninterdigitating MTs, which work in concert to bring about cytokinesis in plant cells. PMID:21873565

  18. The Application of Ligand-Mapping Molecular Dynamics Simulations to the Rational Design of Peptidic Modulators of Protein-Protein Interactions.

    PubMed

    Tan, Yaw Sing; Spring, David R; Abell, Chris; Verma, Chandra S

    2015-07-14

    A computational ligand-mapping approach to detect protein surface pockets that interact with hydrophobic moieties is presented. In this method, we incorporated benzene molecules into explicit solvent molecular dynamics simulations of various protein targets. The benzene molecules successfully identified the binding locations of hydrophobic hot-spot residues and all-hydrocarbon cross-links from known peptidic ligands. They also unveiled cryptic binding sites that are occluded by side chains and the protein backbone. Our results demonstrate that ligand-mapping molecular dynamics simulations hold immense promise to guide the rational design of peptidic modulators of protein-protein interactions, including that of stapled peptides, which show promise as an exciting new class of cell-penetrating therapeutic molecules.

  19. Autism and Intellectual Disability-Associated KIRREL3 Interacts with Neuronal Proteins MAP1B and MYO16 with Potential Roles in Neurodevelopment.

    PubMed

    Liu, Ying F; Sowell, Sarah M; Luo, Yue; Chaubey, Alka; Cameron, Richard S; Kim, Hyung-Goo; Srivastava, Anand K

    2015-01-01

    Cell-adhesion molecules of the immunoglobulin superfamily play critical roles in brain development, as well as in maintaining synaptic plasticity, the dysfunction of which is known to cause cognitive impairment. Recently dysfunction of KIRREL3, a synaptic molecule of the immunoglobulin superfamily, has been implicated in several neurodevelopmental conditions including intellectual disability, autism spectrum disorder, and in the neurocognitive delay associated with Jacobsen syndrome. However, the molecular mechanisms of its physiological actions remain largely unknown. Using a yeast two-hybrid screen, we found that the KIRREL3 extracellular domain interacts with brain expressed proteins MAP1B and MYO16 and its intracellular domain can potentially interact with ATP1B1, UFC1, and SHMT2. The interactions were confirmed by co-immunoprecipitation and colocalization analyses of proteins expressed in human embryonic kidney cells, mouse neuronal cells, and rat primary neuronal cells. Furthermore, we show KIRREL3 colocalization with the marker for the Golgi apparatus and synaptic vesicles. Previously, we have shown that KIRREL3 interacts with the X-linked intellectual disability associated synaptic scaffolding protein CASK through its cytoplasmic domain. In addition, we found a genomic deletion encompassing MAP1B in one patient with intellectual disability, microcephaly and seizures and deletions encompassing MYO16 in two unrelated patients with intellectual disability, autism and microcephaly. MAP1B has been previously implicated in synaptogenesis and is involved in the development of the actin-based membrane skeleton. MYO16 is expressed in hippocampal neurons and also indirectly affects actin cytoskeleton through its interaction with WAVE1 complex. We speculate KIRREL3 interacting proteins are potential candidates for intellectual disability and autism spectrum disorder. Moreover, our findings provide further insight into understanding the molecular mechanisms underlying

  20. Autism and Intellectual Disability-Associated KIRREL3 Interacts with Neuronal Proteins MAP1B and MYO16 with Potential Roles in Neurodevelopment

    PubMed Central

    Liu, Ying F.; Sowell, Sarah M.; Luo, Yue; Chaubey, Alka; Cameron, Richard S.; Kim, Hyung-Goo; Srivastava, Anand K.

    2015-01-01

    Cell-adhesion molecules of the immunoglobulin superfamily play critical roles in brain development, as well as in maintaining synaptic plasticity, the dysfunction of which is known to cause cognitive impairment. Recently dysfunction of KIRREL3, a synaptic molecule of the immunoglobulin superfamily, has been implicated in several neurodevelopmental conditions including intellectual disability, autism spectrum disorder, and in the neurocognitive delay associated with Jacobsen syndrome. However, the molecular mechanisms of its physiological actions remain largely unknown. Using a yeast two-hybrid screen, we found that the KIRREL3 extracellular domain interacts with brain expressed proteins MAP1B and MYO16 and its intracellular domain can potentially interact with ATP1B1, UFC1, and SHMT2. The interactions were confirmed by co-immunoprecipitation and colocalization analyses of proteins expressed in human embryonic kidney cells, mouse neuronal cells, and rat primary neuronal cells. Furthermore, we show KIRREL3 colocalization with the marker for the Golgi apparatus and synaptic vesicles. Previously, we have shown that KIRREL3 interacts with the X-linked intellectual disability associated synaptic scaffolding protein CASK through its cytoplasmic domain. In addition, we found a genomic deletion encompassing MAP1B in one patient with intellectual disability, microcephaly and seizures and deletions encompassing MYO16 in two unrelated patients with intellectual disability, autism and microcephaly. MAP1B has been previously implicated in synaptogenesis and is involved in the development of the actin-based membrane skeleton. MYO16 is expressed in hippocampal neurons and also indirectly affects actin cytoskeleton through its interaction with WAVE1 complex. We speculate KIRREL3 interacting proteins are potential candidates for intellectual disability and autism spectrum disorder. Moreover, our findings provide further insight into understanding the molecular mechanisms underlying

  1. Making large class basic histology lectures more interactive: The use of draw-along mapping techniques and associated educational activities.

    PubMed

    Kotzé, Sanet Henriët; Mole, Calvin Gerald

    2015-01-01

    At Stellenbosch University, South Africa, basic histology is taught to a combination class of almost 400 first-year medical, physiotherapy, and dietetic students. Many students often find the amount of work in basic histology lectures overwhelming and consequently loose interest. The aim was to determine if a draw-along mapping activity would focus students during large class lectures. After each lecture on three basic histology tissues, a guided draw-along mapping session covering the work from the lecture was introduced in the form of a click-advance PowerPoint presentation which was used to demonstrate the unfolding of an "ideal" map. The lecturer simultaneously drew a similar map using an overhead projector allowing the students to draw their own maps on blank sheets of paper along with the lecturer. Students remained attentive during the activity and many participated in answering informal questions posed by the lecturer as the map-making session progressed. After the last session, students completed an anonymous, voluntary questionnaire (response rate of 78%). The majority of students found the draw-along maps useful (94%) and believed that its use should be continued in the future (93%). A significant increase (P < 0.001) was found in the test results of student cohorts who were given the current intervention compared to cohorts from previous years who were given mind maps as handouts only or had no intervention. The use of the draw-along mapping sessions were successful in focusing students during large class lectures while also providing them with a useful tool for their studies. © 2015 American Association of Anatomists.

  2. Map Learning with a 3D Printed Interactive Small-Scale Model: Improvement of Space and Text Memorization in Visually Impaired Students

    PubMed Central

    Giraud, Stéphanie; Brock, Anke M.; Macé, Marc J.-M.; Jouffrais, Christophe

    2017-01-01

    Special education teachers for visually impaired students rely on tools such as raised-line maps (RLMs) to teach spatial knowledge. These tools do not fully and adequately meet the needs of the teachers because they are long to produce, expensive, and not versatile enough to provide rapid updating of the content. For instance, the same RLM can barely be used during different lessons. In addition, those maps do not provide any interactivity, which reduces students’ autonomy. With the emergence of 3D printing and low-cost microcontrollers, it is now easy to design affordable interactive small-scale models (SSMs) which are adapted to the needs of special education teachers. However, no study has previously been conducted to evaluate non-visual learning using interactive SSMs. In collaboration with a specialized teacher, we designed a SSM and a RLM representing the evolution of the geography and history of a fictitious kingdom. The two conditions were compared in a study with 24 visually impaired students regarding the memorization of the spatial layout and historical contents. The study showed that the interactive SSM improved both space and text memorization as compared to the RLM with braille legend. In conclusion, we argue that affordable home-made interactive small scale models can improve learning for visually impaired students. Interestingly, they are adaptable to any teaching situation including students with specific needs. PMID:28649209

  3. Map Learning with a 3D Printed Interactive Small-Scale Model: Improvement of Space and Text Memorization in Visually Impaired Students.

    PubMed

    Giraud, Stéphanie; Brock, Anke M; Macé, Marc J-M; Jouffrais, Christophe

    2017-01-01

    Special education teachers for visually impaired students rely on tools such as raised-line maps (RLMs) to teach spatial knowledge. These tools do not fully and adequately meet the needs of the teachers because they are long to produce, expensive, and not versatile enough to provide rapid updating of the content. For instance, the same RLM can barely be used during different lessons. In addition, those maps do not provide any interactivity, which reduces students' autonomy. With the emergence of 3D printing and low-cost microcontrollers, it is now easy to design affordable interactive small-scale models (SSMs) which are adapted to the needs of special education teachers. However, no study has previously been conducted to evaluate non-visual learning using interactive SSMs. In collaboration with a specialized teacher, we designed a SSM and a RLM representing the evolution of the geography and history of a fictitious kingdom. The two conditions were compared in a study with 24 visually impaired students regarding the memorization of the spatial layout and historical contents. The study showed that the interactive SSM improved both space and text memorization as compared to the RLM with braille legend. In conclusion, we argue that affordable home-made interactive small scale models can improve learning for visually impaired students. Interestingly, they are adaptable to any teaching situation including students with specific needs.

  4. RadMap

    EPA Pesticide Factsheets

    RadMap is an interactive desktop tool featuring a nationwide geographic information systems (GIS) map of long-term radiation monitoring locations across the United States with access to key information about the monitor and the area surrounding it.

  5. A spatially explicit multi-isotope approach to map influence regions of plant-plant interactions after exotic plant invasion

    NASA Astrophysics Data System (ADS)

    Hellmann, Christine; Oldeland, Jens; Werner, Christiane

    2015-04-01

    Exotic plant invasions impose profound alterations to native ecosystems, including changes of water, carbon and nutrient cycles. However, explicitly quantifying these impacts remains a challenge. Stable isotopes, by providing natural tracers of biogeochemical processes, can help to identify and measure such alterations in space and time. Recently, δ15N isoscapes, i.e. spatially continuous representations of isotopic values, derived from native plant foliage, enabled to accurately trace nitrogen introduced by the N2-fixing invasive Acacia longifolia into a native Portuguese dune system. It could be shown that the area of the system which was altered by the invasive species exceeded the area which was covered by the invader by far. But still, definition of clear regions of influence is to some extent ambiguous. Here, we present an approach using multiple isoscapes derived from measured foliar δ13C and δ15N values of a native, non-fixing species, Corema album. By clustering isotopic information, we obtained an objective classification of the study area. Properties and spatial position of clusters could be interpreted to distinguish areas that were or were not influenced by A. longifolia. Spatial clusters at locations where A. longifolia was present had δ15N values that were enriched, i.e. close to the atmospheric signal of 0 o compared to the depleted values of the uninvaded system (ca. -11 o). Furthermore, C. album individuals in these clusters were characterized by higher foliar N content and enriched δ13C. These results indicate that the N2-fixing A. longifolia added nitrogen to the system which originated from the atmosphere and was used by the native C. album, inducing functional changes, i.e. an increase in WUE. Additionally, clusters were identified that were presumably determined by inherent properties of the native system. Thus, combining isotope ecology with geostatistical methods is a promising approach for mapping regions of influence in multi

  6. The application of an emerging technique for protein-protein interaction interface mapping: the combination of photo-initiated cross-linking protein nanoprobes with mass spectrometry.

    PubMed

    Ptáčková, Renata; Ječmen, Tomáš; Novák, Petr; Hudeček, Jiří; Stiborová, Marie; Šulc, Miroslav

    2014-05-26

    Protein-protein interaction was investigated using a protein nanoprobe capable of photo-initiated cross-linking in combination with high-resolution and tandem mass spectrometry. This emerging experimental approach introduces photo-analogs of amino acids within a protein sequence during its recombinant expression, preserves native protein structure and is suitable for mapping the contact between two proteins. The contact surface regions involved in the well-characterized interaction between two molecules of human 14-3-3ζ regulatory protein were used as a model. The employed photo-initiated cross-linking techniques extend the number of residues shown to be within interaction distance in the contact surface of the 14-3-3ζ dimer (Gln8-Met78). The results of this study are in agreement with our previously published data from molecular dynamic calculations based on high-resolution chemical cross-linking data and Hydrogen/Deuterium exchange mass spectrometry. The observed contact is also in accord with the 14-3-3ζ X-ray crystal structure (PDB 3dhr). The results of the present work are relevant to the structural biology of transient interaction in the 14-3-3ζ protein, and demonstrate the ability of the chosen methodology (the combination of photo-initiated cross-linking protein nanoprobes and mass spectrometry analysis) to map the protein-protein interface or regions with a flexible structure.

  7. The Application of an Emerging Technique for Protein–Protein Interaction Interface Mapping: The Combination of Photo-Initiated Cross-Linking Protein Nanoprobes with Mass Spectrometry

    PubMed Central

    Ptáčková, Renata; Ječmen, Tomáš; Novák, Petr; Hudeček, Jiří; Stiborová, Marie; Šulc, Miroslav

    2014-01-01

    Protein–protein interaction was investigated using a protein nanoprobe capable of photo-initiated cross-linking in combination with high-resolution and tandem mass spectrometry. This emerging experimental approach introduces photo-analogs of amino acids within a protein sequence during its recombinant expression, preserves native protein structure and is suitable for mapping the contact between two proteins. The contact surface regions involved in the well-characterized interaction between two molecules of human 14-3-3ζ regulatory protein were used as a model. The employed photo-initiated cross-linking techniques extend the number of residues shown to be within interaction distance in the contact surface of the 14-3-3ζ dimer (Gln8–Met78). The results of this study are in agreement with our previously published data from molecular dynamic calculations based on high-resolution chemical cross-linking data and Hydrogen/Deuterium exchange mass spectrometry. The observed contact is also in accord with the 14-3-3ζ X-ray crystal structure (PDB 3dhr). The results of the present work are relevant to the structural biology of transient interaction in the 14-3-3ζ protein, and demonstrate the ability of the chosen methodology (the combination of photo-initiated cross-linking protein nanoprobes and mass spectrometry analysis) to map the protein-protein interface or regions with a flexible structure. PMID:24865487

  8. DamID-seq: Genome-wide Mapping of Protein-DNA Interactions by High Throughput Sequencing of Adenine-methylated DNA Fragments.

    PubMed

    Wu, Feinan; Olson, Brennan G; Yao, Jie

    2016-01-27

    The DNA adenine methyltransferase identification (DamID) assay is a powerful method to detect protein-DNA interactions both locally and genome-wide. It is an alternative approach to chromatin immunoprecipitation (ChIP). An expressed fusion protein consisting of the protein of interest and the E. coli DNA adenine methyltransferase can methylate the adenine base in GATC motifs near the sites of protein-DNA interactions. Adenine-methylated DNA fragments can then be specifically amplified and detected. The original DamID assay detects the genomic locations of methylated DNA fragments by hybridization to DNA microarrays, which is limited by the availability of microarrays and the density of predetermined probes. In this paper, we report the detailed protocol of integrating high throughput DNA sequencing into DamID (DamID-seq). The large number of short reads generated from DamID-seq enables detecting and localizing protein-DNA interactions genome-wide with high precision and sensitivity. We have used the DamID-seq assay to study genome-nuclear lamina (NL) interactions in mammalian cells, and have noticed that DamID-seq provides a high resolution and a wide dynamic range in detecting genome-NL interactions. The DamID-seq approach enables probing NL associations within gene structures and allows comparing genome-NL interaction maps with other functional genomic data, such as ChIP-seq and RNA-seq.

  9. Making Large Class Basic Histology Lectures More Interactive: The Use of Draw-Along Mapping Techniques and Associated Educational Activities

    ERIC Educational Resources Information Center

    Kotzé, Sanet Henriët; Mole, Calvin Gerald

    2015-01-01

    At Stellenbosch University, South Africa, basic histology is taught to a combination class of almost 400 first-year medical, physiotherapy, and dietetic students. Many students often find the amount of work in basic histology lectures overwhelming and consequently loose interest. The aim was to determine if a draw-along mapping activity would…

  10. Making Large Class Basic Histology Lectures More Interactive: The Use of Draw-Along Mapping Techniques and Associated Educational Activities

    ERIC Educational Resources Information Center

    Kotzé, Sanet Henriët; Mole, Calvin Gerald

    2015-01-01

    At Stellenbosch University, South Africa, basic histology is taught to a combination class of almost 400 first-year medical, physiotherapy, and dietetic students. Many students often find the amount of work in basic histology lectures overwhelming and consequently loose interest. The aim was to determine if a draw-along mapping activity would…

  11. An interactive program to display user-generated or file-based maps on a personal computer monitor

    USGS Publications Warehouse

    Langer, W.H.; Stephens, R.W.

    1987-01-01

    PC MAP-MAKER is an ADVANCED BASIC program written to provide users of IBM XT, IBM AT, and compatible computers with a straight-forward, flexible method to display geographical data on a color or monochrome PC (personal computer) monitor. Data can be political boundaries such as State and county boundaries; natural curvilinear features such as rivers, drainage areas, and geological contacts; and points such as well locations and mineral localities. Essentially any point defined by a latitude and longitude and any line defined by a series of latitude and longitude values can be displayed using the program. PC MAP MAKER allows users to view tabular data from U.S. Geological Survey files such as WATSTORE (National Water Data Storage and Retrieval System) in a map format in a time much shorter than required by sending the data to a line plotter. The screen image can be saved to disk for recall at a later date, and hard copies can be printed with a dot matrix printer. The program is user-friendly, using menus or prompts to guide user input. It is fully documented and structured to allow the user to tailor the program to the user 's specific needs. The documentation includes a tutorial designed to introduce users to the capabilities of the program using the State of Colorado as a demonstration map area. (Author 's abstract)

  12. Structural map of Kaposi sarcoma-associated herpesvirus RNA provides clues to molecular interactions | Center for Cancer Research

    Cancer.gov

    Scientists from CCR have generated a comprehensive structural map of Kaposi sarcoma-associated herpesvirus polyadenylated nuclear (PAN) RNA, a long non-coding RNA that helps the virus evade detection by its host’s immune system. The findings open new oppportunites to study the life cycle of this cancer-causing virus.  Learn more...

  13. Sharing our data—An overview of current (2016) USGS policies and practices for publishing data on ScienceBase and an example interactive mapping application

    USGS Publications Warehouse

    Chase, Katherine J.; Bock, Andrew R.; Sando, Roy

    2017-01-05

    This report provides an overview of current (2016) U.S. Geological Survey policies and practices related to publishing data on ScienceBase, and an example interactive mapping application to display those data. ScienceBase is an integrated data sharing platform managed by the U.S. Geological Survey. This report describes resources that U.S. Geological Survey Scientists can use for writing data management plans, formatting data, and creating metadata, as well as for data and metadata review, uploading data and metadata to ScienceBase, and sharing metadata through the U.S. Geological Survey Science Data Catalog. Because data publishing policies and practices are evolving, scientists should consult the resources cited in this paper for definitive policy information.An example is provided where, using the content of a published ScienceBase data release that is associated with an interpretive product, a simple user interface is constructed to demonstrate how the open source capabilities of the R programming language and environment can interact with the properties and objects of the ScienceBase item and be used to generate interactive maps.

  14. Multivariate PLS Modeling of Apicomplexan FabD-Ligand Interaction Space for Mapping Target-Specific Chemical Space and Pharmacophore Fingerprints

    PubMed Central

    Surolia, Avadhesha

    2015-01-01

    Biomolecular recognition underlying drug-target interactions is determined by both binding affinity and specificity. Whilst, quantification of binding efficacy is possible, determining specificity remains a challenge, as it requires affinity data for multiple targets with the same ligand dataset. Thus, understanding the interaction space by mapping the target space to model its complementary chemical space through computational techniques are desirable. In this study, active site architecture of FabD drug target in two apicomplexan parasites viz. Plasmodium falciparum (PfFabD) and Toxoplasma gondii (TgFabD) is explored, followed by consensus docking calculations and identification of fifteen best hit compounds, most of which are found to be derivatives of natural products. Subsequently, machine learning techniques were applied on molecular descriptors of six FabD homologs and sixty ligands to induce distinct multivariate partial-least square models. The biological space of FabD mapped by the various chemical entities explain their interaction space in general. It also highlights the selective variations in FabD of apicomplexan parasites with that of the host. Furthermore, chemometric models revealed the principal chemical scaffolds in PfFabD and TgFabD as pyrrolidines and imidazoles, respectively, which render target specificity and improve binding affinity in combination with other functional descriptors conducive for the design and optimization of the leads. PMID:26535573

  15. A protein interaction map for cell-cell adhesion regulators identifies DUSP23 as a novel phosphatase for β-catenin

    PubMed Central

    Gallegos, Lisa Leon; Ng, Mei Rosa; Sowa, Mathew E.; Selfors, Laura M.; White, Anne; Zervantonakis, Ioannis K.; Singh, Pragya; Dhakal, Sabin; Harper, J. Wade; Brugge, Joan S.

    2016-01-01

    Cell-cell adhesion is central to morphogenesis and maintenance of epithelial cell state. We previously identified 27 candidate cell-cell adhesion regulatory proteins (CCARPs) whose down-regulation disrupts epithelial cell-cell adhesion during collective migration. Using a protein interaction mapping strategy, we found that 18 CCARPs link to core components of adherens junctions or desmosomes. We further mapped linkages between the CCARPs and other known cell-cell adhesion proteins, including hits from recent screens uncovering novel components of E-cadherin adhesions. Mechanistic studies of one novel CCARP which links to multiple cell-cell adhesion proteins, the phosphatase DUSP23, revealed that it promotes dephosphorylation of β-catenin at Tyr 142 and enhances the interaction between α- and β-catenin. DUSP23 knockdown specifically diminished adhesion to E-cadherin without altering adhesion to fibronectin matrix proteins. Furthermore, DUSP23 knockdown produced “zipper-like” cell-cell adhesions, caused defects in transmission of polarization cues, and reduced coordination during collective migration. Thus, this study identifies multiple novel connections between proteins that regulate cell-cell interactions and provides evidence for a previously unrecognized role for DUSP23 in regulating E-cadherin adherens junctions through promoting the dephosphorylation of β-catenin. PMID:27255161

  16. A genetic interaction map of RNA-processing factors reveals links between Sem1/Dss1-containing complexes and mRNA export and splicing.

    PubMed

    Wilmes, Gwendolyn M; Bergkessel, Megan; Bandyopadhyay, Sourav; Shales, Michael; Braberg, Hannes; Cagney, Gerard; Collins, Sean R; Whitworth, Gregg B; Kress, Tracy L; Weissman, Jonathan S; Ideker, Trey; Guthrie, Christine; Krogan, Nevan J

    2008-12-05

    We used a quantitative, high-density genetic interaction map, or E-MAP (Epistatic MiniArray Profile), to interrogate the relationships within and between RNA-processing pathways. Due to their complexity and the essential roles of many of the components, these pathways have been difficult to functionally dissect. Here, we report the results for 107,155 individual interactions involving 552 mutations, 166 of which are hypomorphic alleles of essential genes. Our data enabled the discovery of links between components of the mRNA export and splicing machineries and Sem1/Dss1, a component of the 19S proteasome. In particular, we demonstrate that Sem1 has a proteasome-independent role in mRNA export as a functional component of the Sac3-Thp1 complex. Sem1 also interacts with Csn12, a component of the COP9 signalosome. Finally, we show that Csn12 plays a role in pre-mRNA splicing, which is independent of other signalosome components. Thus, Sem1 is involved in three separate and functionally distinct complexes.

  17. Interaction Between Radiating Graben-Fissure Systems and Local Geology, Ulfrun Regio, Venus: A Contribution to the Venus Global Dyke Swarm Map Project.

    NASA Astrophysics Data System (ADS)

    Studd, Duncan; Ernst, Richard; Samson, Claire; Grosfils, Eric B.; Head, James W.; Ivanov, M. A.

    This study is part of the larger Venus Global Dyke Swarm Map project, which has the goals of (1) producing a global map of graben-fissure systems, (2) assessing which systems are underlain by dyke swarms, and (3) contributing to the understanding of the tectonic and magmatic history of the planet. Graben-fissure systems on Venus are comprised of extensional lineaments, related to tectonic and/or magmatic activity. We are concentrating on the radiating systems (sometimes termed novae or radial fracture centres) which are of particular interest because they are largely ac-knowledged to be underlain by dyke swarms laterally emplaced from a magmatic centre located at the focus of the system [e.g., 1]. We have mapped the radiating graben fissure-systems in the Ulfrun Regio region of Venus using Magellan Synthetic Aperture Radar (SAR ) data at the highest resolution available (75 m/pixel). This area (200-240° E, 0-25° N) notably contains the western portion of the Hecate Chasma system, two large volcanoes (Ozza Mons and Nazit Mons), and a number of large coronae and novae. It also involves considerable deformation relating to extensional rifting and associated magmatic activity. In the Ulfrun Regio area, our mapping (over an area of 10.7 Mkm2) has identified 69 radiating systems, with diameters ranging from 20 km to greater than 2000 km. Many magmatic centres (at the foci of these radiating systems) are newly recognized, while others correspond to previously known coronae and volcanoes. We have found that it is not unusual for a single magmatic centre to exhibit multiple generations of radiating graben-fissure systems. Our graben-fissure mapping is compared with the new global geological map produced by M. Ivanov [1]. We are studying the manner in which large radiating graben-fissure systems interact with separate geological units. Radiating systems can be extensive; when crossing different geological units their surface expression varies and can manifest itself

  18. Atomic-Resolution Map of the Interactions between an Amyloid Inhibitor Protein and Amyloid Beta (Aβ) Peptides in the Monomer and Protofibril States.

    PubMed

    Algamal, Moustafa; Ahmed, Rashik; Jafari, Naeimeh; Ahsan, Bilal; Ortega, Joaquin; Melacini, Giuseppe

    2017-08-10

    Self-association of amyloid beta (Aβ) peptides is a hallmark of Alzheimer's disease and serves as a general prototype for amyloid formation. A key endogenous inhibitor of Aβ self-association is Human Serum Albumin (HSA), which binds ~90% of plasma Aβ. However, the exact molecular mechanism by which HSA binds Aβ monomers and protofibrils is not fully understood. Here, using dark-state exchange saturation transfer (DEST) NMR and relaxation experiments, complemented by morphological characterization, we mapped the HSA-Aβ interactions at atomic resolution by examining HSA's effects on Aβ monomers and soluble high-molecular weight oligomeric protofibrils. We found that HSA binds both monomeric and protofibrillar Aβ, but the affinity of HSA for Aβ monomers is lower than for Aβ protofibrils (Kd ~ sub-mM vs. μM), yet physiologically relevant owing to the ~0.6 - 0.7 mM plasma HSA concentration. In both Aβ protofibrils and monomers, HSA targets key Aβ self-recognition sites spanning the β strands found in cross-β protofibril structures, leading to a net switch from direct to tethered contacts between the monomeric Aβ and the protofibril surface. These HSA-Aβ interactions are isoform specific, as the Aβ monomer - HSA interactions were weaker for Aβ (1-42) than for Aβ (1-40). In addition, the HSA-induced perturbations of the monomer / protofibrils pseudo-equilibrium extended to the C-terminal residues in the Aβ (1-42) isoform but not in Aβ (1-40). These results provide an unprecedented view of how albumin interacts with Aβ and illustrate the potential of DEST NMR in mapping the interactions between amyloid-inhibitory proteins and amyloidogenic peptides. Copyright © 2017, The American Society for Biochemistry and Molecular Biology.

  19. The dysmorphic human-mouse homology database (DHMHD): an interactive World-Wide Web resource for gene mapping.

    PubMed Central

    Evans, C D; Searle, A G; Schinzel, A A; Winter, R M

    1996-01-01

    Genetic mapping and the examination of "candidate genes" for isolating loci associated with clinical syndromes can be greatly accelerated if there is information about where in the genome a particular locus might be situated. Such clues can come from homology to mouse mutants that have been mapped and knowledge of homology between mouse and human chromosomal segments. Further clues can come from chromosome aberrations giving a similar phenotype. However, these clues are often scattered widely in published reports, and even if they are collected together in catalogues or databases there is no rapid way of moving from one data type to another. The Dysmorphic Human and Mouse Homology Database (DHMHD) is designed to ease this data transition. DHMHD comprises detailed information from four separate sources and enables cross referencing through phenotypic and chromosome homology. The DHMHD system is a prototype which is now available online through the World-Wide Web. Images PMID:8730283

  20. Accurately mapping the location of the binding site for the interaction between hepatitis B virus X protein and cytochrome c oxidase III

    PubMed Central

    LI, DAN; DING, JIAN; CHEN, ZHIXIN; CHEN, YUN; LIN, NA; CHEN, FENGLIN; WANG, XIAOZHONG

    2015-01-01

    The hepatitis B virus (HBV) X protein (HBx) plays an important pathogenetic role in hepatocarcinoma tumorigenesis. As HBx does not have the ability to bind to double-stranded DNA (dsDNA), protein-protein interaction is crucial for HBx functions. In a previous study, we screened a novel HBx-interacting protein, the cytochrome c oxidase subunit III (COXIII). In the present study, we aimed to accurately map the location of the binding site for the interaction of HBx with COXIII. Two fragments of HBx mutants (X1 aa1-72 and X2 aa1-117) were amplified by polymerase chain reaction (PCR) and separately inserted into the pAS2-1 plasmid. PCR and gene sequencing confirmed the correct insertion of the mutant fragments in the plasmid. The tanscription of the mutant fragments in yeast cells was demonstrated by RT-PCR and western blot analysis confirmed that they were accurately translated into fusion proteins. Hybridization on solid medium and the detection of β-galactosidase (β-gal) activity indicated that the binding site for the interaction between HBx and COXIII was located between aa72 and aa117. Specific interactions between the HBxX2 protein and COXIII were verified by co-immunoprecipitation. To the best of our knowledge, this is the first study showing to demonstrate that aa72-117 in HBx is the key region for binding with COXIII. PMID:25483779

  1. Hydrogeological Mapping and Hydrological Process Modelling for understanding the interaction of surface runoff and infiltration in a karstic catchment

    NASA Astrophysics Data System (ADS)

    Stadler, Hermann; Reszler, Christian; Komma, Jürgen; Poltnig, Walter; Strobl, Elmar; Blöschl, Günter

    2013-04-01

    This paper presents a study at the interface hydrogeology - hydrology, concerning mapping of surface runoff generation areas in a karstic catchment. The governing processes range from surface runoff with subsequent infiltration to direct infiltration and further deep percolation into different karst conduits. The aim is to identify areas with a potential of surface erosion and thus, identify the hazard of solute/contaminant input into the karst system during aestival thundershowers, which can affect water quality at springs draining the karst massif. According to hydrogeological methods the emphasis of the study are field investigations based on hydrogeological mapping and field measurements in order to gain extensive knowledge about processes and their spatial distribution in the catchment to establish a site specific Dominant Process Concept (DPC). Based on the hydrogeological map, which describes the lithological units relating to their hydrogeological classification, mapping focuses on the following attributes of the overlaying loose material/debris and soils: (i) infiltration capability, (ii) soil depth (as a measure for storage capacity), and (iii) potential surface flow length. Detailed mapping is performed in the reference area, where a variety of data are acquired, such as soil grain size distribution, soil moisture through TDR measurements at characteristic points, etc. The reference area borders both end-members of the dominant surface runoff processes as described above. Geomorphologic analyses based on a 1m resolution Laserscan assist in allocating sinks and flow accumulation paths in the catchment. By a regionalisation model, developed and calibrated based on the results in the reference areas, the process disposition is transposed onto the whole study area. In a further step, a hydrological model will be set up, where model structure and parameters are identified based on above described working steps and following the DPC. The model will be

  2. Mapping Argonaute and conventional RNA-binding protein interactions with RNA at single-nucleotide resolution using HITS-CLIP and CIMS analysis

    PubMed Central

    Moore, Michael; Zhang, Chaolin; Gantman, Emily Conn; Mele, Aldo; Darnell, Jennifer C.; Darnell, Robert B.

    2014-01-01

    Summary Identifying sites where RNA binding proteins (RNABPs) interact with target RNAs opens the door to understanding the vast complexity of RNA regulation. UV-crosslinking and immunoprecipitation (CLIP) is a transformative technology in which RNAs purified from in vivo cross-linked RNA-protein complexes are sequenced to reveal footprints of RNABP:RNA contacts. CLIP combined with high throughput sequencing (HITS-CLIP) is a generalizable strategy to produce transcriptome-wide RNA binding maps with higher accuracy and resolution than standard RNA immunoprecipitation (RIP) profiling or purely computational approaches. Applying CLIP to Argonaute proteins has expanded the utility of this approach to mapping binding sites for microRNAs and other small regulatory RNAs. Finally, recent advances in data analysis take advantage of crosslinked-induced mutation sites (CIMS) to refine RNA-binding maps to single-nucleotide resolution. Once IP conditions are established, HITS-CLIP takes approximately eight days to prepare RNA for sequencing. Established pipelines for data analysis, including for CIMS, take 3-4 days. PMID:24407355

  3. BAID: The Barrow Area Information Database - an interactive web mapping portal and cyberinfrastructure for scientific activities in the vicinity of Barrow, Alaska

    NASA Astrophysics Data System (ADS)

    Cody, R. P.; Kassin, A.; Gaylord, A. G.; Tweedie, C. E.

    2013-12-01

    In 2013, the Barrow Area Information Database (BAID, www.baid.utep.edu) project resumed field operations in Barrow, AK. The Barrow area of northern Alaska is one of the most intensely researched locations in the Arctic. BAID is a cyberinfrastructure (CI) that details much of the historic and extant research undertaken within in the Barrow region in a suite of interactive web-based mapping and information portals (geobrowsers). The BAID user community and target audience for BAID is diverse and includes research scientists, science logisticians, land managers, educators, students, and the general public. BAID contains information on more than 11,000 Barrow area research sites that extend back to the 1940's and more than 640 remote sensing images and geospatial datasets. In a web-based setting, users can zoom, pan, query, measure distance, and save or print maps and query results. Data are described with metadata that meet Federal Geographic Data Committee standards and are archived at the University Corporation for Atmospheric Research Earth Observing Laboratory (EOL) where non-proprietary BAID data can be freely downloaded. Highlights for the 2013 season include the addition of more than 2000 additional research sites, providing differential global position system (dGPS) support to visiting scientists, surveying over 80 miles of coastline to document rates of erosion, training of local GIS personal, deployment of a wireless sensor network, and substantial upgrades to the BAID website and web mapping applications.

  4. Development of an expert analysis tool based on an interactive subsidence hazard map for urban land use in the city of Celaya, Mexico

    NASA Astrophysics Data System (ADS)

    Alloy, A.; Gonzalez Dominguez, F.; Nila Fonseca, A. L.; Ruangsirikulchai, A.; Gentle, J. N., Jr.; Cabral, E.; Pierce, S. A.

    2016-12-01

    Land Subsidence as a result of groundwater extraction in central Mexico's larger urban centers initiated in the 80's as a result of population and economic growth. The city of Celaya has undergone subsidence for a few decades and a consequence is the development of an active normal fault system that affects its urban infrastructure and residential areas. To facilitate its analysis and a land use decision-making process we created an online interactive map enabling users to easily obtain information associated with land subsidence. Geological and socioeconomic data of the city was collected, including fault location, population data, and other important infrastructure and structural data has been obtained from fieldwork as part of a study abroad interchange undergraduate course. The subsidence and associated faulting hazard map was created using an InSAR derived subsidence velocity map and population data from INEGI to identify hazard zones using a subsidence gradient spatial analysis approach based on a subsidence gradient and population risk matrix. This interactive map provides a simple perspective of different vulnerable urban elements. As an accessible visualization tool, it will enhance communication between scientific and socio-economic disciplines. Our project also lays the groundwork for a future expert analysis system with an open source and easily accessible Python coded, SQLite database driven website which archives fault and subsidence data along with visual damage documentation to civil structures. This database takes field notes and provides an entry form for uniform datasets, which are used to generate a JSON. Such a database is useful because it allows geoscientists to have a centralized repository and access to their observations over time. Because of the widespread presence of the subsidence phenomena throughout cities in central Mexico, the spatial analysis has been automated using the open source software R. Raster, rgeos, shapefiles, and rgdal

  5. Mapping of quantitative trait loci for temporal growth and age at maturity in coho salmon: Evidence for genotype-by-sex interactions.

    PubMed

    Kodama, Miyako; Hard, Jeffrey J; Naish, Kerry A

    2017-08-10

    Phenotypic differences between males and females are ubiquitous throughout the animal kingdom. Therefore, investigating the extent to which sex-dependent genetic effects contribute to phenotypic variation is important in understanding the evolutionary response of each sex to natural and artificial selection. Sex-specific differences in growth patterns and age at sexual maturity have been observed in a number of anadromous salmonid fishes. In these species, faster growing individuals in a given cohort often mature earlier than conspecifics, and earlier maturing individuals are often males. The aim of this study was to determine whether sex-dependent genetic effects contribute to phenotypic variation in age at sexual maturity and growth in coho salmon reared through juvenile stages to first maturity. To achieve this aim, quantitative trait loci (QTL) underlying growth-related traits and age at first maturity were mapped across four families, and interactions between offspring sex and trait were examined by investigating the significance of genotype-by-sex (QTL×sex) interactions. Several temporally expressed growth-related QTL mapped to the same position, suggesting that these regions affected growth across many months. QTL×sex interactions were widespread, indicating that the effect of QTL on age at sexual maturity and growth over the course of development in coho salmon may be under sex-specific genetic control. We also found evidence for epistatic interactions between some growth traits. Our results provide insights into the genetic architecture underlying growth-related traits in coho salmon, and have implications for understanding the genetic and evolutionary basis of important fitness-related traits. Published by Elsevier B.V.

  6. Mapping the self-interacting domains of TuMV HC-Pro and the subcellular localization of the protein.

    PubMed

    Zheng, Hongying; Yan, Fei; Lu, Yuwen; Sun, Liying; Lin, Lin; Cai, Li; Hou, Mingsheng; Chen, Jianping

    2011-02-01

    The helper component-proteinase (HC-Pro) of potyviruses is a multifunctional protein involved in aphid transmission, polyprotein processing, cell-to-cell and long-distance movement, genome amplification and symptom expression. The HC-Pros of several potyviruses interact with themselves but the key domains responsible for self-interaction are apparently not conserved. In our experiments, yeast two-hybrid assays and bimolecular fluorescence complementation showed that Turnip mosaic virus (TuMV) HC-Pro interacted with itself in yeast cells, plant cells and insect cells. It was also shown that the central and C-terminal regions of the HC-Pro participated in these self-interactions. Fluorescence microscopy showed that TuMV HC-Pro was present in the cytoplasm and formed aggregates along the ER.

  7. Mapping IR Enhancements in Closely Interacting Spiral-Spiral Pairs: I. ISO CAM and ISO SWS Observations

    NASA Technical Reports Server (NTRS)

    Xu, C.; Gao, Y.; Mazzarella, J.; Lu, N.; Sulentic, J.; Domingue, D.

    2000-01-01

    Mid-infrared (MIR) imaging and spectroscopic observations are presented for a well defined sample of eight closely interacting (CLO) pairs of spiral galaxies that have overlapping disks and show enhanced far-infrared (FIR) emission.

  8. Interactions between avian myeloblastosis reverse transcriptase and tRNATrp. Mapping of complexed tRNA with chemicals and nucleases.

    PubMed

    Garret, M; Romby, P; Giegé, R; Litvak, S

    1984-03-12

    The interactions between beef tRNATrp with avian myeloblastosis reverse transcriptase have been studied by statistical chemical modifications of phosphate (ethylnitrosourea) and cytidine (dimethyl sulfate) residues, as well as by digestion of complexed tRNA by Cobra venom nuclease and Neurospora crassa endonuclease. Results with nucleases and chemicals show that reverse transcriptase interacts preferentially with the D arm, the anticodon stem and the T psi stem. All these regions are located in the outside of the L-shaped structure of tRNA. This domain of interaction is different to that reported previously in the complex of beef tRNA with the cognate aminoacyl-tRNA synthetase (M. Garret et al.; Eur. J. Biochem. In press). Avian reverse transcriptase destabilizes the region of tRNA where most of the tertiary interactions maintaining the structure of tRNA are located.

  9. Interactions between avian myeloblastosis reverse transcriptase and tRNATrp. Mapping of complexed tRNA with chemicals and nucleases.

    PubMed Central

    Garret, M; Romby, P; Giegé, R; Litvak, S

    1984-01-01

    The interactions between beef tRNATrp with avian myeloblastosis reverse transcriptase have been studied by statistical chemical modifications of phosphate (ethylnitrosourea) and cytidine (dimethyl sulfate) residues, as well as by digestion of complexed tRNA by Cobra venom nuclease and Neurospora crassa endonuclease. Results with nucleases and chemicals show that reverse transcriptase interacts preferentially with the D arm, the anticodon stem and the T psi stem. All these regions are located in the outside of the L-shaped structure of tRNA. This domain of interaction is different to that reported previously in the complex of beef tRNA with the cognate aminoacyl-tRNA synthetase (M. Garret et al.; Eur. J. Biochem. In press). Avian reverse transcriptase destabilizes the region of tRNA where most of the tertiary interactions maintaining the structure of tRNA are located. Images PMID:6200830

  10. Mapping IR Enhancements in Closely Interacting Spiral-Spiral Pairs: I. ISO CAM and ISO SWS Observations

    NASA Technical Reports Server (NTRS)

    Xu, C.; Gao, Y.; Mazzarella, J.; Lu, N.; Sulentic, J.; Domingue, D.

    2000-01-01

    Mid-infrared (MIR) imaging and spectroscopic observations are presented for a well defined sample of eight closely interacting (CLO) pairs of spiral galaxies that have overlapping disks and show enhanced far-infrared (FIR) emission.

  11. HealthMap: a cluster randomised trial of interactive health plans and self-management support to prevent coronary heart disease in people with HIV.

    PubMed

    Dodson, Sarity; Klassen, Karen M; McDonald, Karalyn; Millard, Tanya; Osborne, Richard H; Battersby, Malcolm W; Fairley, Christopher K; Simpson, Julie A; Lorgelly, Paula; Tonkin, Andrew; Roney, Janine; Slavin, Sean; Sterjovski, Jasminka; Brereton, Margot; Lewin, Sharon R; Crooks, Levinia; Watson, Jo; Kidd, Michael R; Williams, Irith; Elliott, Julian H

    2016-03-05

    The leading causes of morbidity and mortality for people in high-income countries living with HIV are now non-AIDS malignancies, cardiovascular disease and other non-communicable diseases associated with ageing. This protocol describes the trial of HealthMap, a model of care for people with HIV (PWHIV) that includes use of an interactive shared health record and self-management support. The aims of the HealthMap trial are to evaluate engagement of PWHIV and healthcare providers with the model, and its effectiveness for reducing coronary heart disease risk, enhancing self-management, and improving mental health and quality of life of PWHIV. The study is a two-arm cluster randomised trial involving HIV clinical sites in several states in Australia. Doctors will be randomised to the HealthMap model (immediate arm) or to proceed with usual care (deferred arm). People with HIV whose doctors are randomised to the immediate arm receive 1) new opportunities to discuss their health status and goals with their HIV doctor using a HealthMap shared health record; 2) access to their own health record from home; 3) access to health coaching delivered by telephone and online; and 4) access to a peer moderated online group chat programme. Data will be collected from participating PWHIV (n = 710) at baseline, 6 months, and 12 months and from participating doctors (n = 60) at baseline and 12 months. The control arm will be offered the HealthMap intervention at the end of the trial. The primary study outcomes, measured at 12 months, are 1) 10-year risk of non-fatal acute myocardial infarction or coronary heart disease death as estimated by a Framingham Heart Study risk equation; and 2) Positive and Active Engagement in Life Scale from the Health Education Impact Questionnaire (heiQ). The study will determine the viability and utility of a novel technology-supported model of care for maintaining the health and wellbeing of people with HIV. If shown to be effective, the HealthMap model

  12. Transancestral mapping of the MHC region in systemic lupus erythematosus identifies new independent and interacting loci at MSH5, HLA-DPB1 and HLA-G

    PubMed Central

    Fernando, Michelle M A; Freudenberg, Jan; Lee, Annette; Morris, David Lester; Boteva, Lora; Rhodes, Benjamin; Gonzalez-Escribano, María Francisca; Lopez-Nevot, Miguel Angel; Navarra, Sandra V; Gregersen, Peter K; Martin, Javier; Vyse, Timothy J

    2012-01-01

    Objectives Systemic lupus erythematosus (SLE) is a chronic multisystem genetically complex autoimmune disease characterised by the production of autoantibodies to nuclear and cellular antigens, tissue inflammation and organ damage. Genome-wide association studies have shown that variants within the major histocompatibility complex (MHC) region on chromosome 6 confer the greatest genetic risk for SLE in European and Chinese populations. However, the causal variants remain elusive due to tight linkage disequilibrium across disease-associated MHC haplotypes, the highly polymorphic nature of many MHC genes and the heterogeneity of the SLE phenotype. Methods A high-density case-control single nucleotide polymorphism (SNP) study of the MHC region was undertaken in SLE cohorts of Spanish and Filipino ancestry using a custom Illumina chip in order to fine-map association signals in these haplotypically diverse populations. In addition, comparative analyses were performed between these two datasets and a northern European UK SLE cohort. A total of 1433 cases and 1458 matched controls were examined. Results Using this transancestral SNP mapping approach, novel independent loci were identified within the MHC region in UK, Spanish and Filipino patients with SLE with some evidence of interaction. These loci include HLA-DPB1, HLA-G and MSH5 which are independent of each other and HLA-DRB1 alleles. Furthermore, the established SLE-associated HLA-DRB1*15 signal was refined to an interval encompassing HLA-DRB1 and HLA-DQA1. Increased frequencies of MHC region risk alleles and haplotypes were found in the Filipino population compared with Europeans, suggesting that the greater disease burden in non-European SLE may be due in part to this phenomenon. Conclusion These data highlight the usefulness of mapping disease susceptibility loci using a transancestral approach, particularly in a region as complex as the MHC, and offer a springboard for further fine-mapping, resequencing and

  13. Coupled trivial maps.

    PubMed

    Bunimovich, L. A.; Livi, R.; Martinez-Mekler, G.; Ruffo, S.

    1992-07-01

    The first nontrivial example of coupled map lattices that admits a rigorous analysis in the whole range of the strength of space interactions is considered. This class is generated by one-dimensional maps with a globally attracting superstable periodic trajectory that are coupled by a diffusive nearest-neighbor interaction.

  14. A High-Confidence Interaction Map Identifies SIRT1 as a Mediator of Acetylation of USP22 and the SAGA Coactivator Complex

    PubMed Central

    Armour, Sean M.; Bennett, Eric J.; Braun, Craig R.; Zhang, Xiao-Yong; McMahon, Steven B.; Gygi, Steven P.; Harper, J. Wade

    2013-01-01

    Although many functions and targets have been attributed to the histone and protein deacetylase SIRT1, a comprehensive analysis of SIRT1 binding proteins yielding a high-confidence interaction map has not been established. Using a comparative statistical analysis of binding partners, we have assembled a high-confidence SIRT1 interactome. Employing this method, we identified the deubiquitinating enzyme ubiquitin-specific protease 22 (USP22), a component of the deubiquitinating module (DUBm) of the SAGA transcriptional coactivating complex, as a SIRT1-interacting partner. We found that this interaction is highly specific, requires the ZnF-UBP domain of USP22, and is disrupted by the inactivating H363Y mutation within SIRT1. Moreover, we show that USP22 is acetylated on multiple lysine residues and that alteration of a single lysine (K129) within the ZnF-UBP domain is sufficient to alter interaction of the DUBm with the core SAGA complex. Furthermore, USP22-mediated recruitment of SIRT1 activity promotes the deacetylation of individual SAGA complex components. Our results indicate an important role of SIRT1-mediated deacetylation in regulating the formation of DUBm subcomplexes within the larger SAGA complex. PMID:23382074

  15. The Gα4 G protein subunit interacts with the MAP kinase ERK2 using a D-motif that regulates developmental morphogenesis in Dictyostelium

    PubMed Central

    Nguyen, Hoai-Nghia; Hadwiger, Jeffrey A.

    2009-01-01

    G protein Gα subunits contribute to the specificity of different signal transduction pathways in Dictyostelium discoideum but Gα subunit-effector interactions have not been previously identified. The requirement of the Dictyostelium Gα4 subunit for MAP kinase (MAPK) activation and the identification of a putative MAPK docking site (D-motif) in this subunit suggested a possible interaction between the Gα4 subunit and MAPKs. In vivo association of the Gα4 subunit and ERK2 was demonstrated by pull-down and co-immunoprecipitation assays. Alteration of the D-motif reduced Gα4 subunit-ERK2 interactions but only slightly altered MAPK activation in response to folate. Expression of the Gα4 subunit with the altered D-motif in gα4− cells allowed for slug formation but not the morphogenesis associated with culmination. Expression of this mutant Gα4 subunit was sufficient to rescue chemotactic movement to folate. Alteration of the D-motif also reduced the aggregation defect associated with constitutively active Gα4 subunits. These results suggest Gα4 subunit-MAPK interactions are necessary for developmental morphogenesis but not for chemotaxis to folate. PMID:19765570

  16. Bio::Homology::InterologWalk--a Perl module to build putative protein-protein interaction networks through interolog mapping.

    PubMed

    Gallone, Giuseppe; Simpson, T Ian; Armstrong, J Douglas; Jarman, Andrew P

    2011-07-18

    Protein-protein interaction (PPI) data are widely used to generate network models that aim to describe the relationships between proteins in biological systems. The fidelity and completeness of such networks is primarily limited by the paucity of protein interaction information and by the restriction of most of these data to just a few widely studied experimental organisms. In order to extend the utility of existing PPIs, computational methods can be used that exploit functional conservation between orthologous proteins across taxa to predict putative PPIs or 'interologs'. To date most interolog prediction efforts have been restricted to specific biological domains with fixed underlying data sources and there are no software tools available that provide a generalised framework for 'on-the-fly' interolog prediction. We introduce Bio::Homology::InterologWalk, a Perl module to retrieve, prioritise and visualise putative protein-protein interactions through an orthology-walk method. The module uses orthology and experimental interaction data to generate putative PPIs and optionally collates meta-data into an Interaction Prioritisation Index that can be used to help prioritise interologs for further analysis. We show the application of our interolog prediction method to the genomic interactome of the fruit fly, Drosophila melanogaster. We analyse the resulting interaction networks and show that the method proposes new interactome members and interactions that are candidates for future experimental investigation. Our interolog prediction tool employs the Ensembl Perl API and PSICQUIC enabled protein interaction data sources to generate up to date interologs 'on-the-fly'. This represents a significant advance on previous methods for interolog prediction as it allows the use of the latest orthology and protein interaction data for all of the genomes in Ensembl. The module outputs simple text files, making it easy to customise the results by post-processing, allowing the

  17. Fine-scale chromatin interaction maps reveal the cis-regulatory landscape of human lincRNA genes

    PubMed Central

    Ma, Wenxiu; Ay, Ferhat; Lee, Choli; Gulsoy, Gunhan; Deng, Xinxian; Cook, Savannah; Hesson, Jennifer; Cavanaugh, Christopher; Ware, Carol B.; Krumm, Anton; Shendure, Jay; Blau, C. Anthony; Disteche, Christine M.; Noble, William S.; Duan, ZhiJun

    2014-01-01

    High-throughput methods based on chromosome conformation capture (3C) have greatly advanced our understanding of the three-dimensional (3D) organization of genomes but are limited in resolution by their reliance on restriction enzymes (REs). Here we describe a method called DNase Hi-C for comprehensively mapping global chromatin contacts that uses DNase I for chromatin fragmentation, leading to greatly improved efficiency and resolution compared to Hi-C. Coupling this method with DNA capture technology provides a high-throughput approach for targeted mapping of fine-scale chromatin architecture. We applied targeted DNase Hi-C to characterize the 3D organization of 998 lincRNA (long intergenic noncoding RNA) promoters in two human cell lines, thereby revealing that expression of lincRNAs is tightly controlled by complex mechanisms involving both super-enhancers and the polycomb repressive complex. Our results provide the first glimpse of a cell type-specific 3D organization of lincRNA genes. PMID:25437436

  18. Mapping the interaction network of key proteins involved in histone mRNA generation - a hydrogen/deuterium exchange study

    PubMed Central

    Skrajna, Aleksandra; Yang, Xiao-cui; Tarnowski, Krzysztof; Fituch, Kinga; Marzluff, William F.; Dominski, Zbigniew; Dadlez, Michał

    2016-01-01

    Histone pre-mRNAs are cleaved at the 3′ end by a complex that contains U7 snRNP, the FLICE-Associated Huge protein (FLASH) and Histone pre-mRNA Cleavage Complex (HCC) consisting of several polyadenylation factors. Within the complex, the N-terminus of FLASH interacts with the N-terminus of the U7 snRNP protein Lsm11 and together they recruit the HCC. FLASH through its distant C-terminus independently interacts with the C-terminal SANT/Myb-like domain of Nuclear Protein, Ataxia-Telangiectasia locus (NPAT), a transcriptional co-activator required for expression of histone genes in S-phase. To gain structural information on these interactions, we used mass spectrometry to monitor hydrogen/deuterium (H/D) exchange in various regions of FLASH, Lsm11 and NPAT alone or in the presence of their respective binding partners. Our results indicate that the FLASH-interacting domain in Lsm11 is highly dynamic, while the more downstream region required for recruiting the HCC exchanges deuterium slowly and likely folds into a stable structure. In FLASH, a stable structure is adopted by the domain that interacts with Lsm11 and this domain is further stabilized by binding Lsm11. Notably, both H/D exchange experiments and in vitro binding assays demonstrate that Lsm11, in addition to interacting with the N-terminal region of FLASH, also contacts the C-terminal SANT/Myb-like domain of FLASH, the same region that binds NPAT. However, while NPAT stabilizes this domain, Lsm11 causes its partial relaxation. These competing reactions may play a role in regulating histone gene expression in vivo. PMID:26860583

  19. Nuclear Magnetic Resonance Structural Mapping Reveals Promiscuous Interactions between Clathrin-Box Motif Sequences and the N-Terminal Domain of the Clathrin Heavy Chain

    PubMed Central

    2016-01-01

    The recruitment and organization of clathrin at endocytic sites first to form coated pits and then clathrin-coated vesicles depend on interactions between the clathrin N-terminal domain (TD) and multiple clathrin binding sequences on the cargo adaptor and accessory proteins that are concentrated at such sites. Up to four distinct protein binding sites have been proposed to be present on the clathrin TD, with each site proposed to interact with a distinct clathrin binding motif. However, an understanding of how such interactions contribute to clathrin coat assembly must take into account observations that any three of these four sites on clathrin TD can be mutationally ablated without causing loss of clathrin-mediated endocytosis. To take an unbiased approach to mapping binding sites for clathrin-box motifs on clathrin TD, we used isothermal titration calorimetry (ITC) and nuclear magnetic resonance spectroscopy. Our ITC experiments revealed that a canonical clathrin-box motif peptide from the AP-2 adaptor binds to clathrin TD with a stoichiometry of 3:1. Assignment of 90% of the total visible amide resonances in the TROSY-HSQC spectrum of 13C-, 2H-, and 15N-labeled TD40 allowed us to map these three binding sites by analyzing the chemical shift changes as clathrin-box motif peptides were titrated into clathrin TD. We found that three different clathrin-box motif peptides can each simultaneously bind not only to the previously characterized clathrin-box site but also to the W-box site and the β-arrestin splice loop site on a single TD. The promiscuity of these binding sites can help explain why their mutation does not lead to larger effects on clathrin function and suggests a mechanism by which clathrin may be transferred between different proteins during the course of an endocytic event. PMID:25844500

  20. The C4 region as a target for HIV entry inhibitors – NMR Mapping of the interacting segments of T20 and gp120

    PubMed Central

    Moseri, Adi; Biron, Zohar; Arshava, Boris; Scherf, Tali; Naider, Fred; Anglister, Jacob

    2015-01-01

    The peptide T20, which corresponds to a sequence in the C-terminal segment of the HIV-1 trans-membrane glycoprotein gp41, is a strong entry inhibitor of HIV-1. It has been assumed that T20 inhibits HIV-1 infection by binding to the trimer formed by the N-terminal helical region (HR1) of gp41, preventing the formation of a six helix bundle by the N- and C-terminal helical regions of gp41. In addition to binding to gp41, T20 was found to bind to gp120 of X4 viruses and this binding was suggested to be responsible for an alternative mechanism for HIV-1 inhibition by this peptide. In the present study, T20 also was found to bind R5 gp120. Using NMR spectroscopy, the segments of T20 that interact with both gp120 and a gp120/CD4M33 complex were mapped. A peptide corresponding to the fourth constant region of gp120, sC4, was found to partially recapitulate gp120 binding to T20 and the segment of this peptide interacting with T20 was mapped. Our conclusion is that an amphiphilic helix on the T20 C-terminus, binds through mostly hydrophobic interactions, to a non-polar gp120 surface formed primarily by the C4 region. The ten to a thousand-fold difference between the EC50 of T20 against viral fusion and the affinity of T20 to gp120 implies that binding to gp120 is not a major factor in T20 inhibition of HIV-1 fusion. Nevertheless, this hydrophobic gp120 surface could be a target for anti-HIV therapeutics. PMID:26432362

  1. Association mapping of loci controlling genetic and environmental interaction of soybean flowering time under various photo-thermal conditions

    USDA-ARS?s Scientific Manuscript database

    Soybean (Glycine max) is a short day plant. Its flowering and maturity time are controlled by genetic and environmental factors, as well as their interaction. Previous studies have shown that both genetic and environmental factors, mainly photoperiod and temperature control flowering time of soybean...

  2. Third order spectral analysis robust to mixing artifacts for mapping cross-frequency interactions in EEG/MEG.

    PubMed

    Chella, F; Marzetti, L; Pizzella, V; Zappasodi, F; Nolte, G

    2014-05-01

    We present a novel approach to the third order spectral analysis, commonly called bispectral analysis, of electroencephalographic (EEG) and magnetoencephalographic (MEG) data for studying cross-frequency functional brain connectivity. The main obstacle in estimating functional connectivity from EEG and MEG measurements lies in the signals being a largely unknown mixture of the activities of the underlying brain sources. This often constitutes a severe confounder and heavily affects the detection of brain source interactions. To overcome this problem, we previously developed metrics based on the properties of the imaginary part of coherency. Here, we generalize these properties from the linear to the nonlinear case. Specifically, we propose a metric based on an antisymmetric combination of cross-bispectra, which we demonstrate to be robust to mixing artifacts. Moreover, our metric provides complex-valued quantities that give the opportunity to study phase relationships between brain sources. The effectiveness of the method is first demonstrated on simulated EEG data. The proposed approach shows a reduced sensitivity to mixing artifacts when compared with a traditional bispectral metric. It also exhibits a better performance in extracting phase relationships between sources than the imaginary part of the cross-spectrum for delayed interactions. The method is then applied to real EEG data recorded during resting state. A cross-frequency interaction is observed between brain sources at 10Hz and 20Hz, i.e., for alpha and beta rhythms. This interaction is then projected from signal to source level by using a fit-based procedure. This approach highlights a 10-20Hz dominant interaction localized in an occipito-parieto-central network.

  3. Third order spectral analysis robust to mixing artifacts for mapping cross-frequency interactions in EEG/MEG

    PubMed Central

    Chella, F.; Marzetti, L.; Pizzella, V.; Zappasodi, F.; Nolte, G.

    2014-01-01

    We present a novel approach to the third order spectral analysis, commonly called bispectral analysis, of electroencephalographic (EEG) and magnetoencephalographic (MEG) data for studying cross-frequency functional brain connectivity. The main obstacle in estimating functional connectivity from EEG and MEG measurements lies in the signals being a largely unknown mixture of the activities of the underlying brain sources. This often constitutes a severe confounder and heavily affects the detection of brain source interactions. To overcome this problem, we previously developed metrics based on the properties of the imaginary part of coherency. Here, we generalize these properties from the linear to the nonlinear case. Specifically, we propose a metric based on an antisymmetric combination of cross-bispectra, which we demonstrate to be robust to mixing artifacts. Moreover, our metric provides complex-valued quantities that give the opportunity to study phase relationships between brain sources. The effectiveness of the method is first demonstrated on simulated EEG data. The proposed approach shows a reduced sensitivity to mixing artifacts when compared with a traditional bispectral metric. It also exhibits a better performance in extracting phase relationships between sources than the imaginary part of cross-spectrum for delayed interactions. The method is then applied to real EEG data recorded during resting state. A cross-frequency interaction is observed between brain sources at 10 Hz and 20 Hz, i.e., for alpha and beta rhythms. This interaction is then projected from signal to source level by using a fit-based procedure. This approach highlights a 10–20 Hz dominant interaction localized in an occipito-parieto-central network. PMID:24418509

  4. BAID: The Barrow Area Information Database - An Interactive Web Mapping Portal and Cyberinfrastructure Showcasing Scientific Activities in the Vicinity of Barrow, Arctic Alaska.

    NASA Astrophysics Data System (ADS)

    Escarzaga, S. M.; Cody, R. P.; Kassin, A.; Barba, M.; Gaylord, A. G.; Manley, W. F.; Mazza Ramsay, F. D.; Vargas, S. A., Jr.; Tarin, G.; Laney, C. M.; Villarreal, S.; Aiken, Q.; Collins, J. A.; Green, E.; Nelson, L.; Tweedie, C. E.

    2015-12-01

    The Barrow area of northern Alaska is one of the most intensely researched locations in the Arctic and the Barrow Area Information Database (BAID, www.barrowmapped.org) tracks and facilitates a gamut of research, management, and educational activities in the area. BAID is a cyberinfrastructure (CI) that details much of the historic and extant research undertaken within in the Barrow region in a suite of interactive web-based mapping and information portals (geobrowsers). The BAID user community and target audience for BAID is diverse and includes research scientists, science logisticians, land managers, educators, students, and the general public. BAID contains information on more than 12,000 Barrow area research sites that extend back to the 1940's and more than 640 remote sensing images and geospatial datasets. In a web-based setting, users can zoom, pan, query, measure distance, save or print maps and query results, and filter or view information by space, time, and/or other tags. Additionally, data are described with metadata that meet Federal Geographic Data Committee standards. Recent advances include the addition of more than 2000 new research sites, the addition of a query builder user interface allowing rich and complex queries, and provision of differential global position system (dGPS) and high-resolution aerial imagery support to visiting scientists. Recent field surveys include over 80 miles of coastline to document rates of erosion and the collection of high-resolution sonar data for bathymetric mapping of Elson Lagoon and near shore region of the Chukchi Sea. A network of five climate stations has been deployed across the peninsula to serve as a wireless net for the research community and to deliver near real time climatic data to the user community. Local GIS personal have also been trained to better make use of scientific data for local decision making. Links to Barrow area datasets are housed at national data archives and substantial upgrades have

  5. BAID: The Barrow Area Information Database - an interactive web mapping portal and cyberinfrastructure for scientific activities in the vicinity of Barrow, Alaska

    NASA Astrophysics Data System (ADS)

    Cody, R. P.; Kassin, A.; Gaylord, A.; Brown, J.; Tweedie, C. E.

    2012-12-01

    The Barrow area of northern Alaska is one of the most intensely researched locations in the Arctic. The Barrow Area Information Database (BAID, www.baidims.org) is a cyberinfrastructure (CI) that details much of the historic and extant research undertaken within in the Barrow region in a suite of interactive web-based mapping and information portals (geobrowsers). The BAID user community and target audience for BAID is diverse and includes research scientists, science logisticians, land managers, educators, students, and the general public. BAID contains information on more than 9,600 Barrow area research sites that extend back to the 1940's and more than 640 remote sensing images and geospatial datasets. In a web-based setting, users can zoom, pan, query, measure distance, and save or print maps and query results. Data are described with metadata that meet Federal Geographic Data Committee standards and are archived at the University Corporation for Atmospheric Research Earth Observing Laboratory (EOL) where non-proprietary BAID data can be freely downloaded. BAID has been used to: Optimize research site choice; Reduce duplication of science effort; Discover complementary and potentially detrimental research activities in an area of scientific interest; Re-establish historical research sites for resampling efforts assessing change in ecosystem structure and function over time; Exchange knowledge across disciplines and generations; Facilitate communication between western science and traditional ecological knowledge; Provide local residents access to science data that facilitates adaptation to arctic change; (and) Educate the next generation of environmental and computer scientists. This poster describes key activities that will be undertaken over the next three years to provide BAID users with novel software tools to interact with a current and diverse selection of information and data about the Barrow area. Key activities include: 1. Collecting data on research

  6. Mapping and characterization of the interaction interface between two polypyrimidine-tract binding proteins and a nova-type protein of Solanum tuberosum.

    PubMed

    Shah, Shweta; Butler, Nathaniel M; Hannapel, David J; Rao, A Gururaj

    2013-01-01

    Polypyrimidine tract-binding (PTB) proteins are RNA-binding proteins that generally contain four RNA recognition motifs (RRMs). In potato, six cDNAs encoding full-length PTB proteins have been identified. In the present study Nova1-like protein, designated StNova1, was identified as a potential interacting partner of the StPTB proteins via yeast two-hybrid screening. Nova protein is a RNA-binding protein that contains three K-homology (KH) domains. In humans, these proteins are involved in regulation of neuronal RNA metabolism but the role of Nova-like proteins in plants is poorly understood. We have validated this interaction and mapped the protein binding region on StNova1 and StPTB1 and -6 using a novel domain interaction phage display (DIPP) technique. The interaction between the two RNA-binding proteins StPTB1/6 and StNova1 is mediated through linker regions that are distinctly separated from the RRMs. Furthermore, using a random 21-mer phage-peptide library, we have identified a number of peptides with the consensus sequence motif [S/G][V/I][L/V]G that recognize the StPTB proteins. One over-represented peptide that recognizes StPTB6 contains the GVLGPWP sequence that is similar to the GIGGRYP sequence in the glycine-rich linker region between the KH2 and KH3 domains of StNova1. We show, through site-specific mutations, the importance of glycine and proline residues in StNova1-StPTB interactions.

  7. Genetic-linkage mapping of complex hereditary disorders to a whole-genome molecular-interaction network.

    PubMed

    Iossifov, Ivan; Zheng, Tian; Baron, Miron; Gilliam, T Conrad; Rzhetsky, Andrey

    2008-07-01

    Common hereditary neurodevelopmental disorders such as autism, bipolar disorder, and schizophrenia are most likely both genetically multifactorial and heterogeneous. Because of these characteristics traditional methods for genetic analysis fail when applied to such diseases. To address the problem we propose a novel probabilistic framework that combines the standard genetic linkage formalism with whole-genome molecular-interaction data to predict pathways or networks of interacting genes that contribute to common heritable disorders. We apply the model to three large genotype-phenotype data sets, identify a small number of significant candidate genes for autism (24), bipolar disorder (21), and schizophrenia (25), and predict a number of gene targets likely to be shared among the disorders.

  8. Characterization and mapping of dipolar interactions within macromolecules in tissues using a combination of DQF, MT and UTE MRI.

    PubMed

    Eliav, Uzi; Komlosh, Michal; Basser, Peter J; Navon, Gil

    2012-10-01

    This study shows that by combining a double-quantum filtered magnetization transfer (DQF-MT) with an ultra-short TE (UTE) MRI that it is possible to obtain contrast between tissue compartments based on the following characteristics: (a) the residual dipolar coupling interaction within the biomacromolecules, which depends on their structure, (b) residual dipolar interactions within water molecules, and (c) the magnetization exchange rate between biomacromolecules and water. The technique is demonstrated in rat-tail specimens, where the collagenous tissue such as tendons and the annulus pulposus of the disc are highlighted in these images, and their macromolecular properties along with those of bones and muscles can be characterized. DQF-MT UTE MRI also holds promise because collagenous tissues that are typically invisible in conventional MRI experiments produce significant signal intensities using this approach. Copyright © 2012 John Wiley & Sons, Ltd.

  9. Free energy of RNA-counterion interactions in a tight-binding model computed by a discrete space mapping

    NASA Astrophysics Data System (ADS)

    Henke, Paul S.; Mak, Chi H.

    2014-08-01

    The thermodynamic stability of a folded RNA is intricately tied to the counterions and the free energy of this interaction must be accounted for in any realistic RNA simulations. Extending a tight-binding model published previously, in this paper we investigate the fundamental structure of charges arising from the interaction between small functional RNA molecules and divalent ions such as Mg2+ that are especially conducive to stabilizing folded conformations. The characteristic nature of these charges is utilized to construct a discretely connected energy landscape that is then traversed via a novel application of a deterministic graph search technique. This search method can be incorporated into larger simulations of small RNA molecules and provides a fast and accurate way to calculate the free energy arising from the interactions between an RNA and divalent counterions. The utility of this algorithm is demonstrated within a fully atomistic Monte Carlo simulation of the P4-P6 domain of the Tetrahymena group I intron, in which it is shown that the counterion-mediated free energy conclusively directs folding into a compact structure.

  10. Free energy of RNA-counterion interactions in a tight-binding model computed by a discrete space mapping

    SciTech Connect

    Henke, Paul S.; Mak, Chi H.

    2014-08-14

    The thermodynamic stability of a folded RNA is intricately tied to the counterions and the free energy of this interaction must be accounted for in any realistic RNA simulations. Extending a tight-binding model published previously, in this paper we investigate the fundamental structure of charges arising from the interaction between small functional RNA molecules and divalent ions such as Mg{sup 2+} that are especially conducive to stabilizing folded conformations. The characteristic nature of these charges is utilized to construct a discretely connected energy landscape that is then traversed via a novel application of a deterministic graph search technique. This search method can be incorporated into larger simulations of small RNA molecules and provides a fast and accurate way to calculate the free energy arising from the interactions between an RNA and divalent counterions. The utility of this algorithm is demonstrated within a fully atomistic Monte Carlo simulation of the P4-P6 domain of the Tetrahymena group I intron, in which it is shown that the counterion-mediated free energy conclusively directs folding into a compact structure.

  11. mChIP-KAT-MS, a method to map protein interactions and acetylation sites for lysine acetyltransferases

    PubMed Central

    Mitchell, Leslie; Huard, Sylvain; Cotrut, Michael; Pourhanifeh-Lemeri, Roghayeh; Steunou, Anne-Lise; Hamza, Akil; Lambert, Jean-Philippe; Zhou, Hu; Ning, Zhibin; Basu, Amrita; Côté, Jacques; Figeys, Daniel A.; Baetz, Kristin

    2013-01-01

    Recent global proteomic and genomic studies have determined that lysine acetylation is a highly abundant posttranslational modification. The next challenge is connecting lysine acetyltransferases (KATs) to their cellular targets. We hypothesize that proteins that physically interact with KATs may not only predict the cellular function of the KATs but may be acetylation targets. We have developed a mass spectrometry-based method that generates a KAT protein interaction network from which we simultaneously identify both in vivo acetylation sites and in vitro acetylation sites. This modified chromatin-immunopurification coupled to an in vitro KAT assay with mass spectrometry (mChIP-KAT-MS) was applied to the Saccharomyces cerevisiae KAT nucleosome acetyltransferase of histone H4 (NuA4). Using mChIP-KAT-MS, we define the NuA4 interactome and in vitro-enriched acetylome, identifying over 70 previously undescribed physical interaction partners for the complex and over 150 acetyl lysine residues, of which 108 are NuA4-specific in vitro sites. Through this method we determine NuA4 acetylation of its own subunit Epl1 is a means of self-regulation and identify a unique link between NuA4 and the spindle pole body. Our work demonstrates that this methodology may serve as a valuable tool in connecting KATs with their cellular targets. PMID:23572591

  12. Yeast genetic interaction screen of human genes associated with amyotrophic lateral sclerosis: identification of MAP2K5 kinase as a potential drug target.

    PubMed

    Jo, Myungjin; Chung, Ah Young; Yachie, Nozomu; Seo, Minchul; Jeon, Hyejin; Nam, Youngpyo; Seo, Yeojin; Kim, Eunmi; Zhong, Quan; Vidal, Marc; Park, Hae Chul; Roth, Frederick P; Suk, Kyoungho

    2017-09-01

    To understand disease mechanisms, a large-scale analysis of human-yeast genetic interactions was performed. Of 1305 human disease genes assayed, 20 genes exhibited strong toxicity in yeast. Human-yeast genetic interactions were identified by en masse transformation of the human disease genes into a pool of 4653 homozygous diploid yeast deletion mutants with unique barcode sequences, followed by multiplexed barcode sequencing to identify yeast toxicity modifiers. Subsequent network analyses focusing on amyotrophic lateral sclerosis (ALS)-associated genes, such as optineurin (OPTN) and angiogenin (ANG), showed that the human orthologs of the yeast toxicity modifiers of these ALS genes are enriched for several biological processes, such as cell death, lipid metabolism, and molecular transport. When yeast genetic interaction partners held in common between human OPTN and ANG were validated in mammalian cells and zebrafish, MAP2K5 kinase emerged as a potential drug target for ALS therapy. The toxicity modifiers identified in this study may deepen our understanding of the pathogenic mechanisms of ALS and other devastating diseases. © 2017 Jo et al.; Published by Cold Spring Harbor Laboratory Press.

  13. Mapping the interactions of the single-stranded DNA binding protein of bacteriophage T4 (gp32) with DNA lattices at single nucleotide resolution: gp32 monomer binding

    PubMed Central

    Jose, Davis; Weitzel, Steven E.; Baase, Walter A.; von Hippel, Peter H.

    2015-01-01

    Combining biophysical measurements on T4 bacteriophage replication complexes with detailed structural information can illuminate the molecular mechanisms of these ‘macromolecular machines’. Here we use the low energy circular dichroism (CD) and fluorescent properties of site-specifically introduced base analogues to map and quantify the equilibrium binding interactions of short (8 nts) ssDNA oligomers with gp32 monomers at single nucleotide resolution. We show that single gp32 molecules interact most directly and specifically near the 3′-end of these ssDNA oligomers, thus defining the polarity of gp32 binding with respect to the ssDNA lattice, and that only 2–3 nts are directly involved in this tight binding interaction. The loss of exciton coupling in the CD spectra of dimer 2-AP (2-aminopurine) probes at various positions in the ssDNA constructs, together with increases in fluorescence intensity, suggest that gp32 binding directly extends the sugar-phosphate backbone of this ssDNA oligomer, particularly at the 3′-end and facilitates base unstacking along the entire 8-mer lattice. These results provide a model (and ‘DNA map’) for the isolated gp32 binding to ssDNA targets, which serves as the nucleation step for the cooperative binding that occurs at transiently exposed ssDNA sequences within the functioning T4 DNA replication complex. PMID:26275775

  14. Mapping the interactions of the single-stranded DNA binding protein of bacteriophage T4 (gp32) with DNA lattices at single nucleotide resolution: polynucleotide binding and cooperativity

    PubMed Central

    Jose, Davis; Weitzel, Steven E.; Baase, Walter A.; Michael, Miya M.; von Hippel, Peter H.

    2015-01-01

    We here use our site-specific base analog mapping approach to study the interactions and binding equilibria of cooperatively-bound clusters of the single-stranded DNA binding protein (gp32) of the T4 DNA replication complex with longer ssDNA (and dsDNA) lattices. We show that in cooperatively bound clusters the binding free energy appears to be equi-partitioned between the gp32 monomers of the cluster, so that all bind to the ssDNA lattice with comparable affinity, but also that the outer domains of the gp32 monomers at the ends of the cluster can fluctuate on and off the lattice and that the clusters of gp32 monomers can slide along the ssDNA. We also show that at very low binding densities gp32 monomers bind to the ssDNA lattice at random, but that cooperatively bound gp32 clusters bind preferentially at the 5′-end of the ssDNA lattice. We use these results and the gp32 monomer-binding results of the companion paper to propose a detailed model for how gp32 might bind to and interact with ssDNA lattices in its various binding modes, and also consider how these clusters might interact with other components of the T4 DNA replication complex. PMID:26275774

  15. Complete genome sequence and integrated protein localization and interaction map for alfalfa dwarf virus, which combines properties of both cytoplasmic and nuclear plant rhabdoviruses

    SciTech Connect

    Bejerman, Nicolás; Giolitti, Fabián; Breuil, Soledad de; Trucco, Verónica; Nome, Claudia; Lenardon, Sergio; Dietzgen, Ralf G.

    2015-09-15

    Summary: We have determined the full-length 14,491-nucleotide genome sequence of a new plant rhabdovirus, alfalfa dwarf virus (ADV). Seven open reading frames (ORFs) were identified in the antigenomic orientation of the negative-sense, single-stranded viral RNA, in the order 3′-N-P-P3-M-G-P6-L-5′. The ORFs are separated by conserved intergenic regions and the genome coding region is flanked by complementary 3′ leader and 5′ trailer sequences. Phylogenetic analysis of the nucleoprotein amino acid sequence indicated that this alfalfa-infecting rhabdovirus is related to viruses in the genus Cytorhabdovirus. When transiently expressed as GFP fusions in Nicotiana benthamiana leaves, most ADV proteins accumulated in the cell periphery, but unexpectedly P protein was localized exclusively in the nucleus. ADV P protein was shown to have a homotypic, and heterotypic nuclear interactions with N, P3 and M proteins by bimolecular fluorescence complementation. ADV appears unique in that it combines properties of both cytoplasmic and nuclear plant rhabdoviruses. - Highlights: • The complete genome of alfalfa dwarf virus is obtained. • An integrated localization and interaction map for ADV is determined. • ADV has a genome sequence similarity and evolutionary links with cytorhabdoviruses. • ADV protein localization and interaction data show an association with the nucleus. • ADV combines properties of both cytoplasmic and nuclear plant rhabdoviruses.

  16. Improved detection of gene-microbe interactions in the mouse skin microbiota using high-resolution QTL mapping of 16S rRNA transcripts.

    PubMed

    Belheouane, Meriem; Gupta, Yask; Künzel, Sven; Ibrahim, Saleh; Baines, John F

    2017-06-06

    Recent studies highlight the utility of quantitative trait locus (QTL) mapping for determining the contribution of host genetics to interindividual variation in the microbiota. We previously demonstrated that similar to the gut microbiota, abundances of bacterial taxa in the skin are significantly influenced by host genetic variation. In this study, we analyzed the skin microbiota of mice from the 15th generation of an advanced intercross line using a novel approach of extending bacterial trait mapping to both the 16S rRNA gene copy (DNA) and transcript (RNA) levels, which reflect relative bacterial cell number and activity, respectively. Remarkably, the combination of highly recombined individuals and 53,203 informative SNPs allowed the identification of genomic intervals as small as <0.1 megabases containing single genes. Furthermore, the inclusion of 16S rRNA transcript-level mapping dramatically increased the number of significant associations detected, with five versus 21 significant SNP-bacterial trait associations based on DNA- compared to RNA-level profiling, respectively. Importantly, the genomic intervals identified contain many genes involved in skin inflammation and cancer and are further supported by the bacterial traits they influence, which in some cases have known genotoxic or probiotic capabilities. These results indicate that profiling based on the relative activity levels of bacterial community members greatly enhances the capability of detecting interactions between the host and its associated microbes. Finally, the identification of several genes involved in skin cancer suggests that similar to colon carcinogenesis, the resident microbiota may play a role in skin cancer susceptibility and its potential prevention and/or treatment.

  17. BAID: The Barrow Area Information Database - an interactive web mapping portal and cyberinfrastructure for scientific activities in the vicinity of Barrow, Alaska.

    NASA Astrophysics Data System (ADS)

    Cody, R. P.; Kassin, A.; Kofoed, K. B.; Copenhaver, W.; Laney, C. M.; Gaylord, A. G.; Collins, J. A.; Tweedie, C. E.

    2014-12-01

    The Barrow area of northern Alaska is one of the most intensely researched locations in the Arctic and the Barrow Area Information Database (BAID, www.barrowmapped.org) tracks and facilitates a gamut of research, management, and educational activities in the area. BAID is a cyberinfrastructure (CI) that details much of the historic and extant research undertaken within in the Barrow region in a suite of interactive web-based mapping and information portals (geobrowsers). The BAID user community and target audience for BAID is diverse and includes research scientists, science logisticians, land managers, educators, students, and the general public. BAID contains information on more than 12,000 Barrow area research sites that extend back to the 1940's and more than 640 remote sensing images and geospatial datasets. In a web-based setting, users can zoom, pan, query, measure distance, save or print maps and query results, and filter or view information by space, time, and/or other tags. Data are described with metadata that meet Federal Geographic Data Committee standards and are archived at the University Corporation for Atmospheric Research Earth Observing Laboratory (EOL) where non-proprietary BAID data can be freely downloaded. Recent advances include the addition of more than 2000 new research sites, provision of differential global position system (dGPS) and Unmanned Aerial Vehicle (UAV) support to visiting scientists, surveying over 80 miles of coastline to document rates of erosion, training of local GIS personal to better make use of science in local decision making, deployment and near real time connectivity to a wireless micrometeorological sensor network, links to Barrow area datasets housed at national data archives and substantial upgrades to the BAID website and web mapping applications.

  18. Intervention Mapping Approach in the Design of an Interactive Mobile Health Application to Improve Self-care in Heart Failure.

    PubMed

    Athilingam, Ponrathi; Clochesy, John M; Labrador, Miguel A

    2017-09-08

    Heart failure is a complex syndrome among older adults who may experience and interpret symptoms differently. These differences in symptom interpretation may influence decision-making in symptom management. A well-informed and motivated person may develop the knowledge and skills needed to successfully manage symptoms. Therefore, the patient-centered mobile health application HeartMapp was designed to engage patients with heart failure in self-care management by offering tailored alerts and feedback using mobile phones. The main objective of this article is to describe the six-step intervention mapping approach including (1) the initial needs assessment, (2) proximal program objective, (3) selection of theory-based methods, (4) the translation of objectives into an actual program plan for mobile health intervention, (5) adaptation and implementation plan, and (6) evaluation plan that assisted the team in the development of a conceptual framework and intervention program matrix during the development of HeartMapp. The HeartMapp intervention takes the information, motivation, and behavioral skills model as the theoretical underpinning, with "patient engagement" as the key mediator in achieving targeted and persistent self-care behavioral changes in patients with heart failure. The HeartMapp intervention is proposed to improve self-care management and long-term outcomes.

  19. Site-directed mutagenesis maps interactions that enhance cognate and limit promiscuous catalysis by an alkaline phosphatase superfamily phosphodiesterase.

    PubMed

    Wiersma-Koch, Helen; Sunden, Fanny; Herschlag, Daniel

    2013-12-23

    Catalytic promiscuity, an evolutionary concept, also provides a powerful tool for gaining mechanistic insights into enzymatic reactions. Members of the alkaline phosphatase (AP) superfamily are highly amenable to such investigation, with several members having been shown to exhibit promiscuous activity for the cognate reactions of other superfamily members. Previous work has shown that nucleotide pyrophosphatase/phosphodiesterase (NPP) exhibits a >10⁶-fold preference for the hydrolysis of phosphate diesters over phosphate monoesters, and that the reaction specificity is reduced 10³-fold when the size of the substituent on the transferred phosphoryl group of phosphate diester substrates is reduced to a methyl group. Here we show additional specificity contributions from the binding pocket for this substituent (herein termed the R' substituent) that account for an additional ~250-fold differential specificity with the minimal methyl substituent. Removal of four hydrophobic side chains suggested on the basis of structural inspection to interact favorably with R' substituents decreases phosphate diester reactivity 10⁴-fold with an optimal diester substrate (R' = 5'-deoxythymidine) and 50-fold with a minimal diester substrate (R' = CH₃). These mutations also enhance the enzyme's promiscuous phosphate monoesterase activity by nearly an order of magnitude, an effect that is traced by mutation to the reduction of unfavorable interactions with the two residues closest to the nonbridging phosphoryl oxygen atoms. The quadruple R' pocket mutant exhibits the same activity toward phosphate diester and phosphate monoester substrates that have identical leaving groups, with substantial rate enhancements of ~10¹¹-fold. This observation suggests that the Zn²⁺ bimetallo core of AP superfamily enzymes, which is equipotent in phosphate monoester and diester catalysis, has the potential to become specialized for the hydrolysis of each class of phosphate esters via addition

  20. Epitope mapping of anti-human transferrin monoclonal antibodies: potential uses for transferrin-transferrin receptor interaction studies.

    PubMed

    Perera, Yasser; García, Darién; Guirola, Osmany; Huerta, Vivian; García, Yanet; Muñoz, Yasmiana

    2008-01-01

    Human transferrin (hTf) is an 80 kDa glycoprotein involved in iron transport from the absorption sites to the sites of storage and utilization. Additionally, transferrin also plays a relevant role as a bacteriostatic agent preventing uncontrolled bacterial growth in the host. In this work we describe a well-characterized Mabs panel in terms of precise epitope localization and estimate affinity for the two major hTf isoforms. We found at least four antigenic regions in the hTf molecule, narrowed down the interacting antigen residues within three of such regions, and located them on a molecular model of hTf. Two of the antigenic regions partially overlap with previously described transferrin-binding sites for both human receptor (antigenic region I: containing amino acid residues from Asp-69 to Asn-76 at the N-lobe) and bacterial receptors from two pathogenic species (antigenic region III: amino acid residues from Leu-665 to Ser-672 at the C-lobe). Hence, such monoclonal antibodies (Mabs) could be used as an additional tool for conformational studies and/or the characterization of the interaction between hTf and both types of receptor molecules.

  1. Evaluation and mapping of the DNA binding and oligomerization domains of the IE2 regulatory protein of human cytomegalovirus using yeast one and two hybrid interaction assays.

    PubMed

    Ahn, J H; Chiou, C J; Hayward, G S

    1998-03-27

    The 86-kDa IE2 nuclear phosphoprotein encoded by the human cytomegalovirus (HCMV) major immediate-early (MIE) gene behaves as both a non-specific transactivator of viral and cellular gene expression and as a specific DNA-binding protein targeted to the cis-repression sequence (CRS) at the cap site of its own promoter/enhancer region. Although the IE2 protein produced in bacteria has been shown to bind to the 14-bp palindromic CRS motif and IE2 synthesized in vitro forms stable dimers in solution through the conserved C-terminus of the protein, there is no direct evidence as yet that the intracellular mammalian forms of IE2 do so. Here, we show that the intact HCMV IE2 protein both binds to CRS DNA and dimerizes in yeast cells. In a one-hybrid assay system, a GAL4/IE2 fusion protein expressed in yeast cells activated target HIS3 expression only when CRS sites were located upstream of the GAL1 minimal promoter, but failed to do so on mutant CRS sites, demonstrating a requirement for sequence-specific DNA-binding by IE2. Examination of a series of deletion and triple amino acid point mutations in the C-terminal half of IE2 mapped the domains required for DNA-binding in yeast to the entire region between codons 313 and 579, whereas in the previous in-vitro study with truncated bacterial GST fusion proteins, it was mapped to between codons 346 and 579. Transient co-transfection assays with deleted IE2 effector genes in Vero cells showed that the extra segment of IE2 between codons 313 and 346 is also required for both autoregulation and transactivation activity in mammalian cells. In a two-hybrid assay to study IE2 self-interations, we generated both GAL4 DNA-binding (DB) and activation domain (A)/IE2 fusion proteins and showed that IE2 could also dimerize or oligomerize through the C-terminus of the protein in yeast cells. Domains required for this interaction were all mapped to within the region between codons 388 and 542, which is coincident with the domain mapped

  2. Geomorphic Mapping and Paleoterrain Generation for use in Modeling Holocene (8,000 1,500 yr) Agropastoral Landuse and Landscape Interactions in Southeast Spain

    NASA Astrophysics Data System (ADS)

    Arrowsmith, J. R.; Dimaggio, E. N.; Barton, C. M.; Sarjoughian, H. S.; Fall, P.; Falconer, S. E.; Ullah, I. I.

    2006-12-01

    Dramatic changes in land use were associated with the rise of agriculture in the mid Holo