Sample records for visualizing complex biochemical

  1. Visualization of Proton and Electron Transfer Processes of a Biochemical Reaction by μSR

    NASA Astrophysics Data System (ADS)

    Kiyotani, Tamiko; Kobayashi, Masayoshi; Tanaka, Ichiro; Niimura, Nobuo

    For the last several years, we have discussed and conducted experiments toward realization of visualization of electron and proton transfer process in an enzyme reaction using muon. As the first step for exploring the useful application of the μSR for the biological system, which is "μSR in Biology". A first μSR experiment on biochemical reaction was conducted using the complex of a digestive enzyme, a kind of serine-protease and the inhibitor at J-PARC and PSI.

  2. The Curriculum Prerequisite Network: Modeling the Curriculum as a Complex System

    ERIC Educational Resources Information Center

    Aldrich, Preston R.

    2015-01-01

    This article advances the prerequisite network as a means to visualize the hidden structure in an academic curriculum. Networks have been used to represent a variety of complex systems ranging from social systems to biochemical pathways and protein interactions. Here, I treat the academic curriculum as a complex system with nodes representing…

  3. A grid layout algorithm for automatic drawing of biochemical networks.

    PubMed

    Li, Weijiang; Kurata, Hiroyuki

    2005-05-01

    Visualization is indispensable in the research of complex biochemical networks. Available graph layout algorithms are not adequate for satisfactorily drawing such networks. New methods are required to visualize automatically the topological architectures and facilitate the understanding of the functions of the networks. We propose a novel layout algorithm to draw complex biochemical networks. A network is modeled as a system of interacting nodes on squared grids. A discrete cost function between each node pair is designed based on the topological relation and the geometric positions of the two nodes. The layouts are produced by minimizing the total cost. We design a fast algorithm to minimize the discrete cost function, by which candidate layouts can be produced efficiently. A simulated annealing procedure is used to choose better candidates. Our algorithm demonstrates its ability to exhibit cluster structures clearly in relatively compact layout areas without any prior knowledge. We developed Windows software to implement the algorithm for CADLIVE. All materials can be freely downloaded from http://kurata21.bio.kyutech.ac.jp/grid/grid_layout.htm; http://www.cadlive.jp/ http://kurata21.bio.kyutech.ac.jp/grid/grid_layout.htm; http://www.cadlive.jp/

  4. [The influence of C-taurine antioxidant complex on biochemical blood parameters in the process of treatment of patients with diabetes mellitus of type II with nonproliferative diabetic retinopathy].

    PubMed

    Lekishvili, S E

    2014-02-01

    The purpose of this investigation is to study the effect of C- taurine complex of antioxidants on blood biochemical parameters in the process of treatment of patients with diabetes mellitus of type II with NPDR. 68 patients (136 eyes) were enrolled in the study. The monitoring of the patient lasted for 3 months. The character of changes of the basic visual functions has been examined. The patients were divided into 2 groups (main and control). Treatment of patients with main group conducted antioxidant complex Taurine + Vitamin C for 42 days. namely. Thus, we have revealed antioxidant activity of the combination of taurine and vitamin C with positive effect on the indexes of carbohydrate, lipid metabolism and hepatoprotective characteristics in patients with diabetes mellitus type II with NPDR. Taking into consideration the peculiarities of correlation relationships between functional, clinical and biochemical parameters and the results of experimental studies on animal it is acceptable to use Taurine complex + Vitamin C as part of conservative treatment of patients with diabetes mellitus type II with NPDR.

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

    Hartmann, Anja, E-mail: hartmann@ipk-gatersleben.de; Schreiber, Falk; Martin-Luther-University Halle-Wittenberg, Halle

    The characterization of biological systems with respect to their behavior and functionality based on versatile biochemical interactions is a major challenge. To understand these complex mechanisms at systems level modeling approaches are investigated. Different modeling formalisms allow metabolic models to be analyzed depending on the question to be solved, the biochemical knowledge and the availability of experimental data. Here, we describe a method for an integrative analysis of the structure and dynamics represented by qualitative and quantitative metabolic models. Using various formalisms, the metabolic model is analyzed from different perspectives. Determined structural and dynamic properties are visualized in the contextmore » of the metabolic model. Interaction techniques allow the exploration and visual analysis thereby leading to a broader understanding of the behavior and functionality of the underlying biological system. The System Biology Metabolic Model Framework (SBM{sup 2} – Framework) implements the developed method and, as an example, is applied for the integrative analysis of the crop plant potato.« less

  6. BNDB - the Biochemical Network Database.

    PubMed

    Küntzer, Jan; Backes, Christina; Blum, Torsten; Gerasch, Andreas; Kaufmann, Michael; Kohlbacher, Oliver; Lenhof, Hans-Peter

    2007-10-02

    Technological advances in high-throughput techniques and efficient data acquisition methods have resulted in a massive amount of life science data. The data is stored in numerous databases that have been established over the last decades and are essential resources for scientists nowadays. However, the diversity of the databases and the underlying data models make it difficult to combine this information for solving complex problems in systems biology. Currently, researchers typically have to browse several, often highly focused, databases to obtain the required information. Hence, there is a pressing need for more efficient systems for integrating, analyzing, and interpreting these data. The standardization and virtual consolidation of the databases is a major challenge resulting in a unified access to a variety of data sources. We present the Biochemical Network Database (BNDB), a powerful relational database platform, allowing a complete semantic integration of an extensive collection of external databases. BNDB is built upon a comprehensive and extensible object model called BioCore, which is powerful enough to model most known biochemical processes and at the same time easily extensible to be adapted to new biological concepts. Besides a web interface for the search and curation of the data, a Java-based viewer (BiNA) provides a powerful platform-independent visualization and navigation of the data. BiNA uses sophisticated graph layout algorithms for an interactive visualization and navigation of BNDB. BNDB allows a simple, unified access to a variety of external data sources. Its tight integration with the biochemical network library BN++ offers the possibility for import, integration, analysis, and visualization of the data. BNDB is freely accessible at http://www.bndb.org.

  7. An affinity-structure database of helix-turn-helix: DNA complexes with a universal coordinate system.

    PubMed

    AlQuraishi, Mohammed; Tang, Shengdong; Xia, Xide

    2015-11-19

    Molecular interactions between proteins and DNA molecules underlie many cellular processes, including transcriptional regulation, chromosome replication, and nucleosome positioning. Computational analyses of protein-DNA interactions rely on experimental data characterizing known protein-DNA interactions structurally and biochemically. While many databases exist that contain either structural or biochemical data, few integrate these two data sources in a unified fashion. Such integration is becoming increasingly critical with the rapid growth of structural and biochemical data, and the emergence of algorithms that rely on the synthesis of multiple data types to derive computational models of molecular interactions. We have developed an integrated affinity-structure database in which the experimental and quantitative DNA binding affinities of helix-turn-helix proteins are mapped onto the crystal structures of the corresponding protein-DNA complexes. This database provides access to: (i) protein-DNA structures, (ii) quantitative summaries of protein-DNA binding affinities using position weight matrices, and (iii) raw experimental data of protein-DNA binding instances. Critically, this database establishes a correspondence between experimental structural data and quantitative binding affinity data at the single basepair level. Furthermore, we present a novel alignment algorithm that structurally aligns the protein-DNA complexes in the database and creates a unified residue-level coordinate system for comparing the physico-chemical environments at the interface between complexes. Using this unified coordinate system, we compute the statistics of atomic interactions at the protein-DNA interface of helix-turn-helix proteins. We provide an interactive website for visualization, querying, and analyzing this database, and a downloadable version to facilitate programmatic analysis. This database will facilitate the analysis of protein-DNA interactions and the development of programmatic computational methods that capitalize on integration of structural and biochemical datasets. The database can be accessed at http://ProteinDNA.hms.harvard.edu.

  8. Visual format for detection of Mycobacterium tuberculosis and M. bovis in clinical samples using molecular beacons.

    PubMed

    Kumar, Parameet; Nath, Kapili; Rath, Bimba; Sen, Manas K; Vishalakshi, Potharuju; Chauhan, Devender S; Katoch, Vishwa M; Singh, Sarman; Tyagi, Sanjay; Sreenivas, Vishnubhatla; Prasad, Hanumanthappa K

    2009-09-01

    A real-time polymerase chain reaction (PCR) assay for the direct identification of Mycobacterium tuberculosis and M. bovis using molecular beacons was developed. The assay was modified for use in regular thermal cyclers. Molecular beacons that were specific for M. tuberculosis (Tb-B) and M. bovis (Bo-B) were designed. The fluorescence of the target PCR product-molecular beacon probe complex was detected visually using a transilluminator. The results were then compared with those of conventional multiplex PCR (CM-PCR) assays and biochemical identification. The detection limit of Tb-B and Bo-B beacons was 500 fg and 50 fg by the visual format and real-time PCR assay, respectively, compared with 5 pg by CM-PCR assay. Pulmonary and extrapulmonary samples were examined. The agreement between culture and the two assays was very good in sputum samples and fair in extrapulmonary samples. The agreement between clinical diagnoses with the two assays was moderate in extrapulmonary samples. There was very good agreement between CM-PCR and visual format assays for all samples used in the study. Concordance in the identification of isolates by the visual, CM-PCR assay, and biochemical identification was seen. Hence, the use of molecular beacon detection of M. tuberculosis and M. bovis in clinical samples is feasible by setting up two asymmetric PCRs concurrently. The assay is sensitive, specific, simple to interpret, and takes less than 3 hours to complete.

  9. Visual Format for Detection of Mycobacterium tuberculosis and M. bovis in Clinical Samples Using Molecular Beacons

    PubMed Central

    Kumar, Parameet; Nath, Kapili; Rath, Bimba; Sen, Manas K.; Vishalakshi, Potharuju; Chauhan, Devender S.; Katoch, Vishwa M.; Singh, Sarman; Tyagi, Sanjay; Sreenivas, Vishnubhatla; Prasad, Hanumanthappa K.

    2009-01-01

    A real-time polymerase chain reaction (PCR) assay for the direct identification of Mycobacterium tuberculosis and M. bovis using molecular beacons was developed. The assay was modified for use in regular thermal cyclers. Molecular beacons that were specific for M. tuberculosis (Tb-B) and M. bovis (Bo-B) were designed. The fluorescence of the target PCR product-molecular beacon probe complex was detected visually using a transilluminator. The results were then compared with those of conventional multiplex PCR (CM-PCR) assays and biochemical identification. The detection limit of Tb-B and Bo-B beacons was 500 fg and 50 fg by the visual format and real-time PCR assay, respectively, compared with 5 pg by CM-PCR assay. Pulmonary and extrapulmonary samples were examined. The agreement between culture and the two assays was very good in sputum samples and fair in extrapulmonary samples. The agreement between clinical diagnoses with the two assays was moderate in extrapulmonary samples. There was very good agreement between CM-PCR and visual format assays for all samples used in the study. Concordance in the identification of isolates by the visual, CM-PCR assay, and biochemical identification was seen. Hence, the use of molecular beacon detection of M. tuberculosis and M. bovis in clinical samples is feasible by setting up two asymmetric PCRs concurrently. The assay is sensitive, specific, simple to interpret, and takes less than 3 hours to complete. PMID:19661384

  10. Methods for the visualization and analysis of extracellular matrix protein structure and degradation.

    PubMed

    Leonard, Annemarie K; Loughran, Elizabeth A; Klymenko, Yuliya; Liu, Yueying; Kim, Oleg; Asem, Marwa; McAbee, Kevin; Ravosa, Matthew J; Stack, M Sharon

    2018-01-01

    This chapter highlights methods for visualization and analysis of extracellular matrix (ECM) proteins, with particular emphasis on collagen type I, the most abundant protein in mammals. Protocols described range from advanced imaging of complex in vivo matrices to simple biochemical analysis of individual ECM proteins. The first section of this chapter describes common methods to image ECM components and includes protocols for second harmonic generation, scanning electron microscopy, and several histological methods of ECM localization and degradation analysis, including immunohistochemistry, Trichrome staining, and in situ zymography. The second section of this chapter details both a common transwell invasion assay and a novel live imaging method to investigate cellular behavior with respect to collagen and other ECM proteins of interest. The final section consists of common electrophoresis-based biochemical methods that are used in analysis of ECM proteins. Use of the methods described herein will enable researchers to gain a greater understanding of the role of ECM structure and degradation in development and matrix-related diseases such as cancer and connective tissue disorders. © 2018 Elsevier Inc. All rights reserved.

  11. An affinity-structure database of helix-turn-helix: DNA complexes with a universal coordinate system

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

    AlQuraishi, Mohammed; Tang, Shengdong; Xia, Xide

    Molecular interactions between proteins and DNA molecules underlie many cellular processes, including transcriptional regulation, chromosome replication, and nucleosome positioning. Computational analyses of protein-DNA interactions rely on experimental data characterizing known protein-DNA interactions structurally and biochemically. While many databases exist that contain either structural or biochemical data, few integrate these two data sources in a unified fashion. Such integration is becoming increasingly critical with the rapid growth of structural and biochemical data, and the emergence of algorithms that rely on the synthesis of multiple data types to derive computational models of molecular interactions. We have developed an integrated affinity-structure database inmore » which the experimental and quantitative DNA binding affinities of helix-turn-helix proteins are mapped onto the crystal structures of the corresponding protein-DNA complexes. This database provides access to: (i) protein-DNA structures, (ii) quantitative summaries of protein-DNA binding affinities using position weight matrices, and (iii) raw experimental data of protein-DNA binding instances. Critically, this database establishes a correspondence between experimental structural data and quantitative binding affinity data at the single basepair level. Furthermore, we present a novel alignment algorithm that structurally aligns the protein-DNA complexes in the database and creates a unified residue-level coordinate system for comparing the physico-chemical environments at the interface between complexes. Using this unified coordinate system, we compute the statistics of atomic interactions at the protein-DNA interface of helix-turn-helix proteins. We provide an interactive website for visualization, querying, and analyzing this database, and a downloadable version to facilitate programmatic analysis. Lastly, this database will facilitate the analysis of protein-DNA interactions and the development of programmatic computational methods that capitalize on integration of structural and biochemical datasets. The database can be accessed at http://ProteinDNA.hms.harvard.edu.« less

  12. An affinity-structure database of helix-turn-helix: DNA complexes with a universal coordinate system

    DOE PAGES

    AlQuraishi, Mohammed; Tang, Shengdong; Xia, Xide

    2015-11-19

    Molecular interactions between proteins and DNA molecules underlie many cellular processes, including transcriptional regulation, chromosome replication, and nucleosome positioning. Computational analyses of protein-DNA interactions rely on experimental data characterizing known protein-DNA interactions structurally and biochemically. While many databases exist that contain either structural or biochemical data, few integrate these two data sources in a unified fashion. Such integration is becoming increasingly critical with the rapid growth of structural and biochemical data, and the emergence of algorithms that rely on the synthesis of multiple data types to derive computational models of molecular interactions. We have developed an integrated affinity-structure database inmore » which the experimental and quantitative DNA binding affinities of helix-turn-helix proteins are mapped onto the crystal structures of the corresponding protein-DNA complexes. This database provides access to: (i) protein-DNA structures, (ii) quantitative summaries of protein-DNA binding affinities using position weight matrices, and (iii) raw experimental data of protein-DNA binding instances. Critically, this database establishes a correspondence between experimental structural data and quantitative binding affinity data at the single basepair level. Furthermore, we present a novel alignment algorithm that structurally aligns the protein-DNA complexes in the database and creates a unified residue-level coordinate system for comparing the physico-chemical environments at the interface between complexes. Using this unified coordinate system, we compute the statistics of atomic interactions at the protein-DNA interface of helix-turn-helix proteins. We provide an interactive website for visualization, querying, and analyzing this database, and a downloadable version to facilitate programmatic analysis. Lastly, this database will facilitate the analysis of protein-DNA interactions and the development of programmatic computational methods that capitalize on integration of structural and biochemical datasets. The database can be accessed at http://ProteinDNA.hms.harvard.edu.« less

  13. Development of a Paradigm to Assess Nutritive and Biochemical Substances in Humans: A Preliminary Report on the Effects of Tyrosine upon Altitude- and Cold-Induced Stress Responses

    DTIC Science & Technology

    1987-03-01

    3/4 hours. Performance tests evaluated simple and choice reaction time to visual stimuli, vigilance, and processing of symbolic, numerical, verbal...minimize the adverse consequences of these stressors. Tyrosine enhanced performance (e.g. complex information processing , vigilance, and reaction time... processes inherent in many real-world tasks. For example, Map Compass requires association of Wsi PL AFCm uA O-SV CHETCLtISS) direction and degree

  14. Accessible methods for the dynamic time-scale decomposition of biochemical systems.

    PubMed

    Surovtsova, Irina; Simus, Natalia; Lorenz, Thomas; König, Artjom; Sahle, Sven; Kummer, Ursula

    2009-11-01

    The growing complexity of biochemical models asks for means to rationally dissect the networks into meaningful and rather independent subnetworks. Such foregoing should ensure an understanding of the system without any heuristics employed. Important for the success of such an approach is its accessibility and the clarity of the presentation of the results. In order to achieve this goal, we developed a method which is a modification of the classical approach of time-scale separation. This modified method as well as the more classical approach have been implemented for time-dependent application within the widely used software COPASI. The implementation includes different possibilities for the representation of the results including 3D-visualization. The methods are included in COPASI which is free for academic use and available at www.copasi.org. irina.surovtsova@bioquant.uni-heidelberg.de Supplementary data are available at Bioinformatics online.

  15. Structural and functional impairment of endocytic pathways by retinitis pigmentosa mutant rhodopsin-arrestin complexes

    PubMed Central

    Chuang, Jen-Zen; Vega, Carrie; Jun, Wenjin; Sung, Ching-Hwa

    2004-01-01

    Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous degenerative eye disease. Mutations at Arg135 of rhodopsin are associated with a severe form of autosomal dominant RP. This report presents evidence that Arg135 mutant rhodopsins (e.g., R135L, R135G, and R135W) are hyperphosphorylated and bind with high affinity to visual arrestin. Mutant rhodopsin recruits the cytosolic arrestin to the plasma membrane, and the rhodopsin-arrestin complex is internalized into the endocytic pathway. Furthermore, the rhodopsin-arrestin complexes alter the morphology of endosomal compartments and severely damage receptor-mediated endocytic functions. The biochemical and cellular defects of Arg135 mutant rhodopsins are distinct from those previously described for class I and class II RP mutations, and, hence, we propose that they be named class III. Impaired endocytic activity may underlie the pathogenesis of RP caused by class III rhodopsin mutations. PMID:15232620

  16. Using simple manipulatives to improve student comprehension of a complex biological process: protein synthesis.

    PubMed

    Guzman, Karen; Bartlett, John

    2012-01-01

    Biological systems and living processes involve a complex interplay of biochemicals and macromolecular structures that can be challenging for undergraduate students to comprehend and, thus, misconceptions abound. Protein synthesis, or translation, is an example of a biological process for which students often hold many misconceptions. This article describes an exercise that was developed to illustrate the process of translation using simple objects to represent complex molecules. Animations, 3D physical models, computer simulations, laboratory experiments and classroom lectures are also used to reinforce the students' understanding of translation, but by focusing on the simple manipulatives in this exercise, students are better able to visualize concepts that can elude them when using the other methods. The translation exercise is described along with suggestions for background material, questions used to evaluate student comprehension and tips for using the manipulatives to identify common misconceptions. Copyright © 2012 Wiley Periodicals, Inc.

  17. PyContact: Rapid, Customizable, and Visual Analysis of Noncovalent Interactions in MD Simulations.

    PubMed

    Scheurer, Maximilian; Rodenkirch, Peter; Siggel, Marc; Bernardi, Rafael C; Schulten, Klaus; Tajkhorshid, Emad; Rudack, Till

    2018-02-06

    Molecular dynamics (MD) simulations have become ubiquitous in all areas of life sciences. The size and model complexity of MD simulations are rapidly growing along with increasing computing power and improved algorithms. This growth has led to the production of a large amount of simulation data that need to be filtered for relevant information to address specific biomedical and biochemical questions. One of the most relevant molecular properties that can be investigated by all-atom MD simulations is the time-dependent evolution of the complex noncovalent interaction networks governing such fundamental aspects as molecular recognition, binding strength, and mechanical and structural stability. Extracting, evaluating, and visualizing noncovalent interactions is a key task in the daily work of structural biologists. We have developed PyContact, an easy-to-use, highly flexible, and intuitive graphical user interface-based application, designed to provide a toolkit to investigate biomolecular interactions in MD trajectories. PyContact is designed to facilitate this task by enabling identification of relevant noncovalent interactions in a comprehensible manner. The implementation of PyContact as a standalone application enables rapid analysis and data visualization without any additional programming requirements, and also preserves full in-program customization and extension capabilities for advanced users. The statistical analysis representation is interactively combined with full mapping of the results on the molecular system through the synergistic connection between PyContact and VMD. We showcase the capabilities and scientific significance of PyContact by analyzing and visualizing in great detail the noncovalent interactions underlying the ion permeation pathway of the human P2X 3 receptor. As a second application, we examine the protein-protein interaction network of the mechanically ultrastable cohesin-dockering complex. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  18. Classification of Chemical Compounds to Support Complex Queries in a Pathway Database

    PubMed Central

    Weidemann, Andreas; Kania, Renate; Peiss, Christian; Rojas, Isabel

    2004-01-01

    Data quality in biological databases has become a topic of great discussion. To provide high quality data and to deal with the vast amount of biochemical data, annotators and curators need to be supported by software that carries out part of their work in an (semi-) automatic manner. The detection of errors and inconsistencies is a part that requires the knowledge of domain experts, thus in most cases it is done manually, making it very expensive and time-consuming. This paper presents two tools to partially support the curation of data on biochemical pathways. The tool enables the automatic classification of chemical compounds based on their respective SMILES strings. Such classification allows the querying and visualization of biochemical reactions at different levels of abstraction, according to the level of detail at which the reaction participants are described. Chemical compounds can be classified in a flexible manner based on different criteria. The support of the process of data curation is provided by facilitating the detection of compounds that are identified as different but that are actually the same. This is also used to identify similar reactions and, in turn, pathways. PMID:18629066

  19. MetaMapp: mapping and visualizing metabolomic data by integrating information from biochemical pathways and chemical and mass spectral similarity

    PubMed Central

    2012-01-01

    Background Exposure to environmental tobacco smoke (ETS) leads to higher rates of pulmonary diseases and infections in children. To study the biochemical changes that may precede lung diseases, metabolomic effects on fetal and maternal lungs and plasma from rats exposed to ETS were compared to filtered air control animals. Genome- reconstructed metabolic pathways may be used to map and interpret dysregulation in metabolic networks. However, mass spectrometry-based non-targeted metabolomics datasets often comprise many metabolites for which links to enzymatic reactions have not yet been reported. Hence, network visualizations that rely on current biochemical databases are incomplete and also fail to visualize novel, structurally unidentified metabolites. Results We present a novel approach to integrate biochemical pathway and chemical relationships to map all detected metabolites in network graphs (MetaMapp) using KEGG reactant pair database, Tanimoto chemical and NIST mass spectral similarity scores. In fetal and maternal lungs, and in maternal blood plasma from pregnant rats exposed to environmental tobacco smoke (ETS), 459 unique metabolites comprising 179 structurally identified compounds were detected by gas chromatography time of flight mass spectrometry (GC-TOF MS) and BinBase data processing. MetaMapp graphs in Cytoscape showed much clearer metabolic modularity and complete content visualization compared to conventional biochemical mapping approaches. Cytoscape visualization of differential statistics results using these graphs showed that overall, fetal lung metabolism was more impaired than lungs and blood metabolism in dams. Fetuses from ETS-exposed dams expressed lower lipid and nucleotide levels and higher amounts of energy metabolism intermediates than control animals, indicating lower biosynthetic rates of metabolites for cell division, structural proteins and lipids that are critical for in lung development. Conclusions MetaMapp graphs efficiently visualizes mass spectrometry based metabolomics datasets as network graphs in Cytoscape, and highlights metabolic alterations that can be associated with higher rate of pulmonary diseases and infections in children prenatally exposed to ETS. The MetaMapp scripts can be accessed at http://metamapp.fiehnlab.ucdavis.edu. PMID:22591066

  20. Single-molecule visualization of a formin-capping protein ‘decision complex' at the actin filament barbed end

    PubMed Central

    Bombardier, Jeffrey P.; Eskin, Julian A.; Jaiswal, Richa; Corrêa, Ivan R.; Xu, Ming-Qun; Goode, Bruce L.; Gelles, Jeff

    2015-01-01

    Precise control of actin filament length is essential to many cellular processes. Formins processively elongate filaments, whereas capping protein (CP) binds to barbed ends and arrests polymerization. While genetic and biochemical evidence has indicated that these two proteins function antagonistically, the mechanism underlying the antagonism has remained unresolved. Here we use multi-wavelength single-molecule fluorescence microscopy to observe the fully reversible formation of a long-lived ‘decision complex' in which a CP dimer and a dimer of the formin mDia1 simultaneously bind the barbed end. Further, mDia1 displaced from the barbed end by CP can randomly slide along the filament and later return to the barbed end to re-form the complex. Quantitative kinetic analysis reveals that the CP-mDia1 antagonism that we observe in vitro occurs through the decision complex. Our observations suggest new molecular mechanisms for the control of actin filament length and for the capture of filament barbed ends in cells. PMID:26566078

  1. Visual perception and imagery: a new molecular hypothesis.

    PubMed

    Bókkon, I

    2009-05-01

    Here, we put forward a redox molecular hypothesis about the natural biophysical substrate of visual perception and visual imagery. This hypothesis is based on the redox and bioluminescent processes of neuronal cells in retinotopically organized cytochrome oxidase-rich visual areas. Our hypothesis is in line with the functional roles of reactive oxygen and nitrogen species in living cells that are not part of haphazard process, but rather a very strict mechanism used in signaling pathways. We point out that there is a direct relationship between neuronal activity and the biophoton emission process in the brain. Electrical and biochemical processes in the brain represent sensory information from the external world. During encoding or retrieval of information, electrical signals of neurons can be converted into synchronized biophoton signals by bioluminescent radical and non-radical processes. Therefore, information in the brain appears not only as an electrical (chemical) signal but also as a regulated biophoton (weak optical) signal inside neurons. During visual perception, the topological distribution of photon stimuli on the retina is represented by electrical neuronal activity in retinotopically organized visual areas. These retinotopic electrical signals in visual neurons can be converted into synchronized biophoton signals by radical and non-radical processes in retinotopically organized mitochondria-rich areas. As a result, regulated bioluminescent biophotons can create intrinsic pictures (depictive representation) in retinotopically organized cytochrome oxidase-rich visual areas during visual imagery and visual perception. The long-term visual memory is interpreted as epigenetic information regulated by free radicals and redox processes. This hypothesis does not claim to solve the secret of consciousness, but proposes that the evolution of higher levels of complexity made the intrinsic picture representation of the external visual world possible by regulated redox and bioluminescent reactions in the visual system during visual perception and visual imagery.

  2. Biochemistry Instructors' Views toward Developing and Assessing Visual Literacy in Their Courses

    ERIC Educational Resources Information Center

    Linenberger, Kimberly J.; Holme, Thomas A.

    2015-01-01

    Biochemistry instructors are inundated with various representations from which to choose to depict biochemical phenomena. Because of the immense amount of visual know-how needed to be an expert biochemist in the 21st century, there have been calls for instructors to develop biochemistry students' visual literacy. However, visual literacy has…

  3. A collaborative visual analytics suite for protein folding research.

    PubMed

    Harvey, William; Park, In-Hee; Rübel, Oliver; Pascucci, Valerio; Bremer, Peer-Timo; Li, Chenglong; Wang, Yusu

    2014-09-01

    Molecular dynamics (MD) simulation is a crucial tool for understanding principles behind important biochemical processes such as protein folding and molecular interaction. With the rapidly increasing power of modern computers, large-scale MD simulation experiments can be performed regularly, generating huge amounts of MD data. An important question is how to analyze and interpret such massive and complex data. One of the (many) challenges involved in analyzing MD simulation data computationally is the high-dimensionality of such data. Given a massive collection of molecular conformations, researchers typically need to rely on their expertise and prior domain knowledge in order to retrieve certain conformations of interest. It is not easy to make and test hypotheses as the data set as a whole is somewhat "invisible" due to its high dimensionality. In other words, it is hard to directly access and examine individual conformations from a sea of molecular structures, and to further explore the entire data set. There is also no easy and convenient way to obtain a global view of the data or its various modalities of biochemical information. To this end, we present an interactive, collaborative visual analytics tool for exploring massive, high-dimensional molecular dynamics simulation data sets. The most important utility of our tool is to provide a platform where researchers can easily and effectively navigate through the otherwise "invisible" simulation data sets, exploring and examining molecular conformations both as a whole and at individual levels. The visualization is based on the concept of a topological landscape, which is a 2D terrain metaphor preserving certain topological and geometric properties of the high dimensional protein energy landscape. In addition to facilitating easy exploration of conformations, this 2D terrain metaphor also provides a platform where researchers can visualize and analyze various properties (such as contact density) overlayed on the top of the 2D terrain. Finally, the software provides a collaborative environment where multiple researchers can assemble observations and biochemical events into storyboards and share them in real time over the Internet via a client-server architecture. The software is written in Scala and runs on the cross-platform Java Virtual Machine. Binaries and source code are available at http://www.aylasoftware.org and have been released under the GNU General Public License. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Biochemical Visual Literacy with Constructive Alignment: Outcomes, Assessment, and Activities

    ERIC Educational Resources Information Center

    Herraez, Angel; Costa, Manuel Joao

    2013-01-01

    Several contributions in "Biochemistry and Molecular Biology Education" have highlighted the role of visualization tools and the importance of developing students' visual literacy in biochemistry education. In this forum, the authors suggest that more focus is needed on the assessment of student learning, and they advance…

  5. Biochemical, histological and behavioural aspects of visual function during early development of rainbow trout

    USGS Publications Warehouse

    Carvalho, Paulo S. M.; Noltie, Douglas B.; Tillitt, D.E.

    2004-01-01

    Retinal structure and concentration of retinoids involved in phototransduction changed during early development of rainbow trout Oncorhynchus mykiss, correlating with improvements in visual function. A test chamber was used to evaluate the presence of optokinetic or optomotor responses and to assess the functionality of the integrated cellular, physiological and biochemical components of the visual system. The results indicated that in rainbow trout optomotor responses start at 10 days post-hatch, and demonstrated for the first time that increases in acuity, sensitivity to low light as well as in motion detection abilities occur from this stage until exogenous feeding starts. The structure of retinal cells such as cone ellipsoids increased in length as photopic visual acuity improved, and rod densities increased concurrently with improvements in scotopic thresholds (2.2 log10 units). An increase in the concentrations of the chromophore all-trans-retinal correlated with improvements of all behavioural measures of visual function during the same developmental phase. ?? 2004 The Fisheries Society of the British Isles.

  6. Complexity and performance of on-chip biochemical assays

    NASA Astrophysics Data System (ADS)

    Kopf-Sill, Anne R.; Nikiforov, Theo; Bousse, Luc J.; Nagle, Rob; Parce, J. W.

    1997-03-01

    The use of microchips for performing biochemical processes has the potential to reduce reagent use and thus assay costs, increase throughput, and automate complex processes. We are building a multifunctional platform that provides sensing and actuation functions for a variety of microchip- based biochemical and analytical processes. Here we describe recent experiments that include on-chip dilution, reagent mixing, reaction, separation, and detection for important classes of biochemical assays. Issues in chip design and control are discussed.

  7. Visualizing the phage T4 activated transcription complex of DNA and E. coli RNA polymerase

    PubMed Central

    James, Tamara D.; Cardozo, Timothy; Abell, Lauren E.; Hsieh, Meng-Lun; Jenkins, Lisa M. Miller; Jha, Saheli S.; Hinton, Deborah M.

    2016-01-01

    The ability of RNA polymerase (RNAP) to select the right promoter sequence at the right time is fundamental to the control of gene expression in all organisms. However, there is only one crystallized structure of a complete activator/RNAP/DNA complex. In a process called σ appropriation, bacteriophage T4 activates a class of phage promoters using an activator (MotA) and a co-activator (AsiA), which function through interactions with the σ70 subunit of RNAP. We have developed a holistic, structure-based model for σ appropriation using multiple experimentally determined 3D structures (Escherichia coli RNAP, the Thermus aquaticus RNAP/DNA complex, AsiA /σ70 Region 4, the N-terminal domain of MotA [MotANTD], and the C-terminal domain of MotA [MotACTD]), molecular modeling, and extensive biochemical observations indicating the position of the proteins relative to each other and to the DNA. Our results visualize how AsiA/MotA redirects σ, and therefore RNAP activity, to T4 promoter DNA, and demonstrate at a molecular level how the tactful interaction of transcriptional factors with even small segments of RNAP can alter promoter specificity. Furthermore, our model provides a rational basis for understanding how a mutation within the β subunit of RNAP (G1249D), which is far removed from AsiA or MotA, impairs σ appropriation. PMID:27458207

  8. Exploring the remote sensing of foliar biochemical concentrations with AVIRIS data

    NASA Technical Reports Server (NTRS)

    Smith, Geoffrey M.; Curran, Paul J.

    1992-01-01

    Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) data shows promise for the estimation of foliar biochemical concentrations at the scale of the canopy. There are, however, several problems associated with the use of AVIRIS data in this way and these are detailed in recent Plant Biochemical Workshop Report. The research reported was concentrated upon three of these problems: field sampling of forest canopies, wet laboratory assay of foliar chemicals, and the visualization of AVIRIS data.

  9. MEGADOCK-Web: an integrated database of high-throughput structure-based protein-protein interaction predictions.

    PubMed

    Hayashi, Takanori; Matsuzaki, Yuri; Yanagisawa, Keisuke; Ohue, Masahito; Akiyama, Yutaka

    2018-05-08

    Protein-protein interactions (PPIs) play several roles in living cells, and computational PPI prediction is a major focus of many researchers. The three-dimensional (3D) structure and binding surface are important for the design of PPI inhibitors. Therefore, rigid body protein-protein docking calculations for two protein structures are expected to allow elucidation of PPIs different from known complexes in terms of 3D structures because known PPI information is not explicitly required. We have developed rapid PPI prediction software based on protein-protein docking, called MEGADOCK. In order to fully utilize the benefits of computational PPI predictions, it is necessary to construct a comprehensive database to gather prediction results and their predicted 3D complex structures and to make them easily accessible. Although several databases exist that provide predicted PPIs, the previous databases do not contain a sufficient number of entries for the purpose of discovering novel PPIs. In this study, we constructed an integrated database of MEGADOCK PPI predictions, named MEGADOCK-Web. MEGADOCK-Web provides more than 10 times the number of PPI predictions than previous databases and enables users to conduct PPI predictions that cannot be found in conventional PPI prediction databases. In MEGADOCK-Web, there are 7528 protein chains and 28,331,628 predicted PPIs from all possible combinations of those proteins. Each protein structure is annotated with PDB ID, chain ID, UniProt AC, related KEGG pathway IDs, and known PPI pairs. Additionally, MEGADOCK-Web provides four powerful functions: 1) searching precalculated PPI predictions, 2) providing annotations for each predicted protein pair with an experimentally known PPI, 3) visualizing candidates that may interact with the query protein on biochemical pathways, and 4) visualizing predicted complex structures through a 3D molecular viewer. MEGADOCK-Web provides a huge amount of comprehensive PPI predictions based on docking calculations with biochemical pathways and enables users to easily and quickly assess PPI feasibilities by archiving PPI predictions. MEGADOCK-Web also promotes the discovery of new PPIs and protein functions and is freely available for use at http://www.bi.cs.titech.ac.jp/megadock-web/ .

  10. Benchmarking a Visual-Basic based multi-component one-dimensional reactive transport modeling tool

    NASA Astrophysics Data System (ADS)

    Torlapati, Jagadish; Prabhakar Clement, T.

    2013-01-01

    We present the details of a comprehensive numerical modeling tool, RT1D, which can be used for simulating biochemical and geochemical reactive transport problems. The code can be run within the standard Microsoft EXCEL Visual Basic platform, and it does not require any additional software tools. The code can be easily adapted by others for simulating different types of laboratory-scale reactive transport experiments. We illustrate the capabilities of the tool by solving five benchmark problems with varying levels of reaction complexity. These literature-derived benchmarks are used to highlight the versatility of the code for solving a variety of practical reactive transport problems. The benchmarks are described in detail to provide a comprehensive database, which can be used by model developers to test other numerical codes. The VBA code presented in the study is a practical tool that can be used by laboratory researchers for analyzing both batch and column datasets within an EXCEL platform.

  11. PathFinder: reconstruction and dynamic visualization of metabolic pathways.

    PubMed

    Goesmann, Alexander; Haubrock, Martin; Meyer, Folker; Kalinowski, Jörn; Giegerich, Robert

    2002-01-01

    Beyond methods for a gene-wise annotation and analysis of sequenced genomes new automated methods for functional analysis on a higher level are needed. The identification of realized metabolic pathways provides valuable information on gene expression and regulation. Detection of incomplete pathways helps to improve a constantly evolving genome annotation or discover alternative biochemical pathways. To utilize automated genome analysis on the level of metabolic pathways new methods for the dynamic representation and visualization of pathways are needed. PathFinder is a tool for the dynamic visualization of metabolic pathways based on annotation data. Pathways are represented as directed acyclic graphs, graph layout algorithms accomplish the dynamic drawing and visualization of the metabolic maps. A more detailed analysis of the input data on the level of biochemical pathways helps to identify genes and detect improper parts of annotations. As an Relational Database Management System (RDBMS) based internet application PathFinder reads a list of EC-numbers or a given annotation in EMBL- or Genbank-format and dynamically generates pathway graphs.

  12. Meal-Insulin Cycle: A Visual Summary of the Biochemical Events between Meals

    ERIC Educational Resources Information Center

    Kalogiannis, Stavros

    2017-01-01

    In the present article, a scheme that summarizes the biochemical events occurring in the human body after the consumption of a meal is proposed. The scheme illustrates the metabolic sequence as a series of counteracting components occupying opposite positions in a cycle, indicating their opposite actions or physiological states, such as meal…

  13. [Signal reception and processing by the retina].

    PubMed

    Eysel, U

    2007-01-01

    Phototransduction occurs in the retina, which, as an outsourced part of the brain, fulfills important tasks in neuronal processing for image analysis relevant to perception. Interlinked biochemical cycles with immense amplification factors transform the electromagnetic waves of light into neuronal activity, and photochemical adaptation allows adjustment to light intensities of over more than 10 logarithmic units. Beginning with its dual system of photoreceptors with highly sensible rods and a color sensitive cone system, the retina, with between 50 and 100 main cell types, is characterized by complex neuronal circuits. The resulting center-surround antagonism of the receptive fields serves, amongst other things, to amplify intensity and color contrasts. Specialized ganglion cell types give rise to parallel signaling pathways into the higher visual centers of the brain.

  14. ChloroKB: A Web Application for the Integration of Knowledge Related to Chloroplast Metabolic Network1[OPEN

    PubMed Central

    Gloaguen, Pauline; Alban, Claude; Ravanel, Stéphane; Seigneurin-Berny, Daphné; Matringe, Michel; Ferro, Myriam; Bruley, Christophe; Rolland, Norbert; Vandenbrouck, Yves

    2017-01-01

    Higher plants, as autotrophic organisms, are effective sources of molecules. They hold great promise for metabolic engineering, but the behavior of plant metabolism at the network level is still incompletely described. Although structural models (stoichiometry matrices) and pathway databases are extremely useful, they cannot describe the complexity of the metabolic context, and new tools are required to visually represent integrated biocurated knowledge for use by both humans and computers. Here, we describe ChloroKB, a Web application (http://chlorokb.fr/) for visual exploration and analysis of the Arabidopsis (Arabidopsis thaliana) metabolic network in the chloroplast and related cellular pathways. The network was manually reconstructed through extensive biocuration to provide transparent traceability of experimental data. Proteins and metabolites were placed in their biological context (spatial distribution within cells, connectivity in the network, participation in supramolecular complexes, and regulatory interactions) using CellDesigner software. The network contains 1,147 reviewed proteins (559 localized exclusively in plastids, 68 in at least one additional compartment, and 520 outside the plastid), 122 proteins awaiting biochemical/genetic characterization, and 228 proteins for which genes have not yet been identified. The visual presentation is intuitive and browsing is fluid, providing instant access to the graphical representation of integrated processes and to a wealth of refined qualitative and quantitative data. ChloroKB will be a significant support for structural and quantitative kinetic modeling, for biological reasoning, when comparing novel data with established knowledge, for computer analyses, and for educational purposes. ChloroKB will be enhanced by continuous updates following contributions from plant researchers. PMID:28442501

  15. The Stereochemistry of Biochemical Molecules: A Subject to Revisit

    ERIC Educational Resources Information Center

    Centelles, Josep J.; Imperial, Santiago

    2005-01-01

    Although Fischer's convention for stereoisomers is useful for simple molecules, the stereochemistry of complex biochemical molecules is often poorly indicated in textbooks. This article reports on errors in stereochemistry of complex hydrosoluble vitamin B12 molecule. Twenty-five popular biochemistry textbooks were examined for their treatment of…

  16. Catalytic mechanism of a retinoid isomerase essential for vertebrate vision

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

    Kiser, Philip D.; Zhang, Jianye; Badiee, Mohsen

    Visual function in vertebrates is dependent on the membrane-bound retinoid isomerase RPE65, an essential component of the retinoid cycle pathway that regenerates 11-cis-retinal for rod and cone opsins. The mechanism by which RPE65 catalyzes stereoselective retinoid isomerization has remained elusive because of uncertainty about how retinoids bind to its active site. Here we present crystal structures of RPE65 in complex with retinoid-mimetic compounds, one of which is in clinical trials for the treatment of age-related macular degeneration. The structures reveal the active site retinoid-binding cavity located near the membrane-interacting surface of the enzyme as well as an Fe-bound palmitate ligandmore » positioned in an adjacent pocket. With the geometry of the RPE65–substrate complex clarified, we delineate a mechanism of catalysis that reconciles the extensive biochemical and structural research on this enzyme. Finally, these data provide molecular foundations for understanding a key process in vision and pharmacological inhibition of RPE65 with small molecules.« less

  17. Catalytic mechanism of a retinoid isomerase essential for vertebrate vision

    DOE PAGES

    Kiser, Philip D.; Zhang, Jianye; Badiee, Mohsen; ...

    2015-04-20

    Visual function in vertebrates is dependent on the membrane-bound retinoid isomerase RPE65, an essential component of the retinoid cycle pathway that regenerates 11-cis-retinal for rod and cone opsins. The mechanism by which RPE65 catalyzes stereoselective retinoid isomerization has remained elusive because of uncertainty about how retinoids bind to its active site. Here we present crystal structures of RPE65 in complex with retinoid-mimetic compounds, one of which is in clinical trials for the treatment of age-related macular degeneration. The structures reveal the active site retinoid-binding cavity located near the membrane-interacting surface of the enzyme as well as an Fe-bound palmitate ligandmore » positioned in an adjacent pocket. With the geometry of the RPE65–substrate complex clarified, we delineate a mechanism of catalysis that reconciles the extensive biochemical and structural research on this enzyme. Finally, these data provide molecular foundations for understanding a key process in vision and pharmacological inhibition of RPE65 with small molecules.« less

  18. Catalytic mechanism of a retinoid isomerase essential for vertebrate vision

    PubMed Central

    Kiser, Philip D.; Zhang, Jianye; Badiee, Mohsen; Li, Qingjiang; Shi, Wuxian; Sui, Xuewu; Golczak, Marcin; Tochtrop, Gregory P.; Palczewski, Krzysztof

    2015-01-01

    Visual function in vertebrates is dependent on the membrane-bound retinoid isomerase, RPE65, an essential component of the retinoid cycle pathway that regenerates 11-cis-retinal for rod and cone opsins. The mechanism by which RPE65 catalyzes stereoselective retinoid isomerization has remained elusive due to uncertainty about how retinoids bind to its active site. Here we present crystal structures of RPE65 in complex with retinoid-mimetic compounds, one of which is in clinical trials for treatment of age-related macular degeneration. The structures reveal the active site retinoid-binding cavity located near the membrane-interacting surface of the enzyme as well as an Fe-bound palmitate ligand positioned in an adjacent pocket. With the geometry of the RPE65-substrate complex clarified we delineate a mechanism of catalysis that reconciles the extensive biochemical and structural research on this enzyme. These data provide molecular foundations for understanding a key process in vision and pharmacological inhibition of RPE65 with small molecules. PMID:25894083

  19. Single-molecule visualization of Saccharomyces cerevisiae leading-strand synthesis reveals dynamic interaction between MTC and the replisome

    PubMed Central

    Lewis, Jacob S.; Spenkelink, Lisanne M.; Schauer, Grant D.; Hill, Flynn R.; Georgescu, Roxanna E.; O’Donnell, Michael E.; van Oijen, Antoine M.

    2017-01-01

    The replisome, the multiprotein system responsible for genome duplication, is a highly dynamic complex displaying a large number of different enzyme activities. Recently, the Saccharomyces cerevisiae minimal replication reaction has been successfully reconstituted in vitro. This provided an opportunity to uncover the enzymatic activities of many of the components in a eukaryotic system. Their dynamic behavior and interactions in the context of the replisome, however, remain unclear. We use a tethered-bead assay to provide real-time visualization of leading-strand synthesis by the S. cerevisiae replisome at the single-molecule level. The minimal reconstituted leading-strand replisome requires 24 proteins, forming the CMG helicase, the Pol ε DNA polymerase, the RFC clamp loader, the PCNA sliding clamp, and the RPA single-stranded DNA binding protein. We observe rates and product lengths similar to those obtained from ensemble biochemical experiments. At the single-molecule level, we probe the behavior of two components of the replication progression complex and characterize their interaction with active leading-strand replisomes. The Minichromosome maintenance protein 10 (Mcm10), an important player in CMG activation, increases the number of productive replication events in our assay. Furthermore, we show that the fork protection complex Mrc1–Tof1–Csm3 (MTC) enhances the rate of the leading-strand replisome threefold. The introduction of periods of fast replication by MTC leads to an average rate enhancement of a factor of 2, similar to observations in cellular studies. We observe that the MTC complex acts in a dynamic fashion with the moving replisome, leading to alternating phases of slow and fast replication. PMID:28923950

  20. Sequence-controlled RNA self-processing: computational design, biochemical analysis, and visualization by AFM

    PubMed Central

    Petkovic, Sonja; Badelt, Stefan; Flamm, Christoph; Delcea, Mihaela

    2015-01-01

    Reversible chemistry allowing for assembly and disassembly of molecular entities is important for biological self-organization. Thus, ribozymes that support both cleavage and formation of phosphodiester bonds may have contributed to the emergence of functional diversity and increasing complexity of regulatory RNAs in early life. We have previously engineered a variant of the hairpin ribozyme that shows how ribozymes may have circularized or extended their own length by forming concatemers. Using the Vienna RNA package, we now optimized this hairpin ribozyme variant and selected four different RNA sequences that were expected to circularize more efficiently or form longer concatemers upon transcription. (Two-dimensional) PAGE analysis confirms that (i) all four selected ribozymes are catalytically active and (ii) high yields of cyclic species are obtained. AFM imaging in combination with RNA structure prediction enabled us to calculate the distributions of monomers and self-concatenated dimers and trimers. Our results show that computationally optimized molecules do form reasonable amounts of trimers, which has not been observed for the original system so far, and we demonstrate that the combination of theoretical prediction, biochemical and physical analysis is a promising approach toward accurate prediction of ribozyme behavior and design of ribozymes with predefined functions. PMID:25999318

  1. Biochemical Reconstitution of the WAVE Regulatory Complex

    PubMed Central

    Chen, Baoyu; Padrick, Shae B.; Henry, Lisa; Rosen, Michael K.

    2014-01-01

    The WAVE regulatory complex (WRC) is a 400-KDa heteropentameric protein assembly that plays a central role in controlling actin cytoskeletal dynamics in many cellular processes. The WRC acts by integrating diverse cellular cues and stimulating the actin nucleating activity of the Arp2/3 complex at membranes. Biochemical and biophysical studies of the underlying mechanisms of these processes require large amounts of purified WRC. Recent success in recombinant expression, reconstitution, purification and crystallization of the WRC has greatly advanced our understanding of the inhibition, activation and membrane recruitment mechanisms of this complex. But many important questions remain to be answered. Here we summarize and update the methods developed in our laboratory, which allow reliable and flexible production of tens of milligrams of recombinant WRC of crystallographic quality, sufficient for many biochemical and structural studies. PMID:24630101

  2. Biochemical and genetic analysis of Leigh syndrome patients in Korea.

    PubMed

    Chae, Jong-Hee; Lee, Jin Sook; Kim, Ki Joong; Hwang, Yong Seung; Hirano, Michio

    2008-06-01

    Sixteen Korean patients with Leigh syndrome were identified at the Seoul National University Children's Hospital in 2001-2006. Biochemical or molecular defects were identified in 14 patients (87.5%). Thirteen patients had respiratory chain enzyme defects; 9 had complex I deficiency, and 4 had combined defects of complex I+III+IV. Based on the biochemical defects, targeted genetic studies in 4 patients with complex I deficiency revealed two heteroplasmic mitochondrial DNA mutations in ND genes. One patient had the mitochondrial DNA T8993G point mutation. No mitochondrial DNA defects were identified in 11 (68.7%) of our LS patients, who probably have mutations in nuclear DNA. Although a limited study based in a single tertiary medical center, our findings suggest that isolated complex I deficiency may be the most common cause of Leigh syndrome in Korea.

  3. [Functional indices of the participants of the satellite experiments of the "Mars-500" project in the north of Russia in different seasons of a year].

    PubMed

    Solonin, Iu G; Markov, A L; Boĭko, E R; Potolitsyna, N N; Parshukova, O I

    2014-01-01

    17 male northerners participating in the satellite experiments of the '"Mars-500" project passed through the morphological, physiometric, psychological and biochemical studies. The prenosological health indices in different seasons were calculated using the hardware-software complex "Ecosan-2007". Seasonal sinusoidal fluctuations were detected for the thermoregulation (body and skin temperature), lipids metabolism (cholesterol, HDL and LDL levels in the blood), circulation regulation under physical exercise (the increase of "double product" and its recovery time). In the majority of the participants the unfavorable deviations of body mass index, "power" and "life" indices, simple visual-motor reaction time, Kerdo vegetative index, physical health levels and regulatory systems activity index (in comparison with the mid-latitude standards) were found.

  4. OCT of early dental caries: a comparative study with histology and Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Hewko, Mark D.; Choo-Smith, Lin-P'ing; Ko, Alex C.; Leonardi, Lorenzo; Dong, Cecilia C.; Cleghorn, Blaine; Sowa, Michael G.

    2005-03-01

    Early dental caries result from destruction of the tooth's outer mineral matrix by acid-forming bacteria found in dental plaques. Early caries begin as surface disruptions where minerals are leached from the teeth resulting in regions of decreased mineral matrix integrity. Visually, these early carious regions appear as white spots due to the higher backscattering of incident light. With age these areas may become stained by organic compounds. Optical coherence tomography (OCT) examination of human teeth demonstrates a difference in penetration depth of the OCT signal into the carious region in comparison with sound enamel. However, while OCT demonstrates a structural difference in the enamel in the region of the caries, this technique provides little insight into the source of this difference. Raman spectroscopy provides biochemical measures derived from hydroxyapatite within the enamel as well as information on the crystallinity of the enamel matrix. The differences in the biochemical and morphological features of early caries and intact sound enamel are compared. Histological thin sections confirm the observations by OCT morphological imaging while Raman spectroscopy allows for biochemical identification of carious regions by a non-destructive method. Visual examination and conventional radiographic imaging of the intact tooth are used in clinical assessment prior to optical measurements. The combination of OCT, Raman spectroscopy and thin section histology aid in determining the changes that give rise to the visual white spot lesions.

  5. Visual Complexity and Affect: Ratings Reflect More Than Meets the Eye.

    PubMed

    Madan, Christopher R; Bayer, Janine; Gamer, Matthias; Lonsdorf, Tina B; Sommer, Tobias

    2017-01-01

    Pictorial stimuli can vary on many dimensions, several aspects of which are captured by the term 'visual complexity.' Visual complexity can be described as, "a picture of a few objects, colors, or structures would be less complex than a very colorful picture of many objects that is composed of several components." Prior studies have reported a relationship between affect and visual complexity, where complex pictures are rated as more pleasant and arousing. However, a relationship in the opposite direction, an effect of affect on visual complexity, is also possible; emotional arousal and valence are known to influence selective attention and visual processing. In a series of experiments, we found that ratings of visual complexity correlated with affective ratings, and independently also with computational measures of visual complexity. These computational measures did not correlate with affect, suggesting that complexity ratings are separately related to distinct factors. We investigated the relationship between affect and ratings of visual complexity, finding an 'arousal-complexity bias' to be a robust phenomenon. Moreover, we found this bias could be attenuated when explicitly indicated but did not correlate with inter-individual difference measures of affective processing, and was largely unrelated to cognitive and eyetracking measures. Taken together, the arousal-complexity bias seems to be caused by a relationship between arousal and visual processing as it has been described for the greater vividness of arousing pictures. The described arousal-complexity bias is also of relevance from an experimental perspective because visual complexity is often considered a variable to control for when using pictorial stimuli.

  6. Visual Complexity and Affect: Ratings Reflect More Than Meets the Eye

    PubMed Central

    Madan, Christopher R.; Bayer, Janine; Gamer, Matthias; Lonsdorf, Tina B.; Sommer, Tobias

    2018-01-01

    Pictorial stimuli can vary on many dimensions, several aspects of which are captured by the term ‘visual complexity.’ Visual complexity can be described as, “a picture of a few objects, colors, or structures would be less complex than a very colorful picture of many objects that is composed of several components.” Prior studies have reported a relationship between affect and visual complexity, where complex pictures are rated as more pleasant and arousing. However, a relationship in the opposite direction, an effect of affect on visual complexity, is also possible; emotional arousal and valence are known to influence selective attention and visual processing. In a series of experiments, we found that ratings of visual complexity correlated with affective ratings, and independently also with computational measures of visual complexity. These computational measures did not correlate with affect, suggesting that complexity ratings are separately related to distinct factors. We investigated the relationship between affect and ratings of visual complexity, finding an ‘arousal-complexity bias’ to be a robust phenomenon. Moreover, we found this bias could be attenuated when explicitly indicated but did not correlate with inter-individual difference measures of affective processing, and was largely unrelated to cognitive and eyetracking measures. Taken together, the arousal-complexity bias seems to be caused by a relationship between arousal and visual processing as it has been described for the greater vividness of arousing pictures. The described arousal-complexity bias is also of relevance from an experimental perspective because visual complexity is often considered a variable to control for when using pictorial stimuli. PMID:29403412

  7. Integrated web visualizations for protein-protein interaction databases.

    PubMed

    Jeanquartier, Fleur; Jean-Quartier, Claire; Holzinger, Andreas

    2015-06-16

    Understanding living systems is crucial for curing diseases. To achieve this task we have to understand biological networks based on protein-protein interactions. Bioinformatics has come up with a great amount of databases and tools that support analysts in exploring protein-protein interactions on an integrated level for knowledge discovery. They provide predictions and correlations, indicate possibilities for future experimental research and fill the gaps to complete the picture of biochemical processes. There are numerous and huge databases of protein-protein interactions used to gain insights into answering some of the many questions of systems biology. Many computational resources integrate interaction data with additional information on molecular background. However, the vast number of diverse Bioinformatics resources poses an obstacle to the goal of understanding. We present a survey of databases that enable the visual analysis of protein networks. We selected M=10 out of N=53 resources supporting visualization, and we tested against the following set of criteria: interoperability, data integration, quantity of possible interactions, data visualization quality and data coverage. The study reveals differences in usability, visualization features and quality as well as the quantity of interactions. StringDB is the recommended first choice. CPDB presents a comprehensive dataset and IntAct lets the user change the network layout. A comprehensive comparison table is available via web. The supplementary table can be accessed on http://tinyurl.com/PPI-DB-Comparison-2015. Only some web resources featuring graph visualization can be successfully applied to interactive visual analysis of protein-protein interaction. Study results underline the necessity for further enhancements of visualization integration in biochemical analysis tools. Identified challenges are data comprehensiveness, confidence, interactive feature and visualization maturing.

  8. ChloroKB: A Web Application for the Integration of Knowledge Related to Chloroplast Metabolic Network.

    PubMed

    Gloaguen, Pauline; Bournais, Sylvain; Alban, Claude; Ravanel, Stéphane; Seigneurin-Berny, Daphné; Matringe, Michel; Tardif, Marianne; Kuntz, Marcel; Ferro, Myriam; Bruley, Christophe; Rolland, Norbert; Vandenbrouck, Yves; Curien, Gilles

    2017-06-01

    Higher plants, as autotrophic organisms, are effective sources of molecules. They hold great promise for metabolic engineering, but the behavior of plant metabolism at the network level is still incompletely described. Although structural models (stoichiometry matrices) and pathway databases are extremely useful, they cannot describe the complexity of the metabolic context, and new tools are required to visually represent integrated biocurated knowledge for use by both humans and computers. Here, we describe ChloroKB, a Web application (http://chlorokb.fr/) for visual exploration and analysis of the Arabidopsis ( Arabidopsis thaliana ) metabolic network in the chloroplast and related cellular pathways. The network was manually reconstructed through extensive biocuration to provide transparent traceability of experimental data. Proteins and metabolites were placed in their biological context (spatial distribution within cells, connectivity in the network, participation in supramolecular complexes, and regulatory interactions) using CellDesigner software. The network contains 1,147 reviewed proteins (559 localized exclusively in plastids, 68 in at least one additional compartment, and 520 outside the plastid), 122 proteins awaiting biochemical/genetic characterization, and 228 proteins for which genes have not yet been identified. The visual presentation is intuitive and browsing is fluid, providing instant access to the graphical representation of integrated processes and to a wealth of refined qualitative and quantitative data. ChloroKB will be a significant support for structural and quantitative kinetic modeling, for biological reasoning, when comparing novel data with established knowledge, for computer analyses, and for educational purposes. ChloroKB will be enhanced by continuous updates following contributions from plant researchers. © 2017 American Society of Plant Biologists. All Rights Reserved.

  9. Symportin 1 chaperones 5S RNP assembly during ribosome biogenesis by occupying an essential rRNA-binding site

    PubMed Central

    Calviño, Fabiola R.; Kharde, Satyavati; Ori, Alessandro; Hendricks, Astrid; Wild, Klemens; Kressler, Dieter; Bange, Gert; Hurt, Ed; Beck, Martin; Sinning, Irmgard

    2015-01-01

    During 60S biogenesis, mature 5S RNP consisting of 5S RNA, RpL5 and RpL11, assembles into a pre-60S particle, where docking relies on RpL11 interacting with helix 84 (H84) of the 25S RNA. How 5S RNP is assembled for recruitment into the pre-60S is not known. Here we report the crystal structure of a ternary symportin Syo1–RpL5-N–RpL11 complex and provide biochemical and structural insights into 5S RNP assembly. Syo1 guards the 25S RNA-binding surface on RpL11 and competes with H84 for binding. Pull-down experiments show that H84 releases RpL11 from the ternary complex, but not in the presence of 5S RNA. Crosslinking mass spectrometry visualizes structural rearrangements on incorporation of 5S RNA into the Syo1–RpL5–RpL11 complex supporting the formation of a pre-5S RNP. Our data underline the dual role of Syo1 in ribosomal protein transport and as an assembly platform for 5S RNP. PMID:25849277

  10. Symportin 1 chaperones 5S RNP assembly during ribosome biogenesis by occupying an essential rRNA-binding site.

    PubMed

    Calviño, Fabiola R; Kharde, Satyavati; Ori, Alessandro; Hendricks, Astrid; Wild, Klemens; Kressler, Dieter; Bange, Gert; Hurt, Ed; Beck, Martin; Sinning, Irmgard

    2015-04-07

    During 60S biogenesis, mature 5S RNP consisting of 5S RNA, RpL5 and RpL11, assembles into a pre-60S particle, where docking relies on RpL11 interacting with helix 84 (H84) of the 25S RNA. How 5S RNP is assembled for recruitment into the pre-60S is not known. Here we report the crystal structure of a ternary symportin Syo1-RpL5-N-RpL11 complex and provide biochemical and structural insights into 5S RNP assembly. Syo1 guards the 25S RNA-binding surface on RpL11 and competes with H84 for binding. Pull-down experiments show that H84 releases RpL11 from the ternary complex, but not in the presence of 5S RNA. Crosslinking mass spectrometry visualizes structural rearrangements on incorporation of 5S RNA into the Syo1-RpL5-RpL11 complex supporting the formation of a pre-5S RNP. Our data underline the dual role of Syo1 in ribosomal protein transport and as an assembly platform for 5S RNP.

  11. Evolution and the complexity of bacteriophages.

    PubMed

    Serwer, Philip

    2007-03-13

    The genomes of both long-genome (> 200 Kb) bacteriophages and long-genome eukaryotic viruses have cellular gene homologs whose selective advantage is not explained. These homologs add genomic and possibly biochemical complexity. Understanding their significance requires a definition of complexity that is more biochemically oriented than past empirically based definitions. Initially, I propose two biochemistry-oriented definitions of complexity: either decreased randomness or increased encoded information that does not serve immediate needs. Then, I make the assumption that these two definitions are equivalent. This assumption and recent data lead to the following four-part hypothesis that explains the presence of cellular gene homologs in long bacteriophage genomes and also provides a pathway for complexity increases in prokaryotic cells: (1) Prokaryotes underwent evolutionary increases in biochemical complexity after the eukaryote/prokaryote splits. (2) Some of the complexity increases occurred via multi-step, weak selection that was both protected from strong selection and accelerated by embedding evolving cellular genes in the genomes of bacteriophages and, presumably, also archaeal viruses (first tier selection). (3) The mechanisms for retaining cellular genes in viral genomes evolved under additional, longer-term selection that was stronger (second tier selection). (4) The second tier selection was based on increased access by prokaryotic cells to improved biochemical systems. This access was achieved when DNA transfer moved to prokaryotic cells both the more evolved genes and their more competitive and complex biochemical systems. I propose testing this hypothesis by controlled evolution in microbial communities to (1) determine the effects of deleting individual cellular gene homologs on the growth and evolution of long genome bacteriophages and hosts, (2) find the environmental conditions that select for the presence of cellular gene homologs, (3) determine which, if any, bacteriophage genes were selected for maintaining the homologs and (4) determine the dynamics of homolog evolution. This hypothesis is an explanation of evolutionary leaps in general. If accurate, it will assist both understanding and influencing the evolution of microbes and their communities. Analysis of evolutionary complexity increase for at least prokaryotes should include analysis of genomes of long-genome bacteriophages.

  12. 2,3,7,8-TCDD effects on visual structure and function in swim-up rainbow trout

    USGS Publications Warehouse

    Carvalho, Paulo S. M.

    2004-01-01

    An understanding of mechanisms of contaminant effects across levels of biological organization is essential in ecotoxicology if we are to generate predictive models for population-level effects. We applied a suite of biochemical, histological, and behavioral end points related to visual structure and function and foraging behavior to evaluate effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) on swim-up rainbow trout. We detected a dose-dependent decrease in densities of retinal ganglion cells (RGC), key retinal neurons that link the eye with the brain. These changes resulted in corresponding deficits in visual/motor function including reductions in visual acuity and in scotopic and photopic thresholds due to TCDD. The loss of RGCs suggests an increase in convergence of synapses from photoreceptors to RGCs as a cellular mechanism for the visual deficits. Dose-dependent increases in immunohistochemical detection of CYP1A protein in the vasculature of the brain and eye choroid was proportional with decreased ganglion cell densities in the retina. TCDD-induced AHR-regulated effects on these tissues might be involved in the detected decrease in ganglion cell densities. Prey capture rate decreased after TCDD exposure only at the highest treatment groups evaluated. Collectively, these results show that TCDD causes biochemical and structural changes in the eye and brain of rainbow trout that are associated with behavioral deficits leading to decreased individual fitness.

  13. Improving Marine Ecosystem Models with Biochemical Tracers

    NASA Astrophysics Data System (ADS)

    Pethybridge, Heidi R.; Choy, C. Anela; Polovina, Jeffrey J.; Fulton, Elizabeth A.

    2018-01-01

    Empirical data on food web dynamics and predator-prey interactions underpin ecosystem models, which are increasingly used to support strategic management of marine resources. These data have traditionally derived from stomach content analysis, but new and complementary forms of ecological data are increasingly available from biochemical tracer techniques. Extensive opportunities exist to improve the empirical robustness of ecosystem models through the incorporation of biochemical tracer data and derived indices, an area that is rapidly expanding because of advances in analytical developments and sophisticated statistical techniques. Here, we explore the trophic information required by ecosystem model frameworks (species, individual, and size based) and match them to the most commonly used biochemical tracers (bulk tissue and compound-specific stable isotopes, fatty acids, and trace elements). Key quantitative parameters derived from biochemical tracers include estimates of diet composition, niche width, and trophic position. Biochemical tracers also provide powerful insight into the spatial and temporal variability of food web structure and the characterization of dominant basal and microbial food web groups. A major challenge in incorporating biochemical tracer data into ecosystem models is scale and data type mismatches, which can be overcome with greater knowledge exchange and numerical approaches that transform, integrate, and visualize data.

  14. Biochemical Characterization of Cone Cyclic Nucleotide-gated (CNG) Channel Using the Infrared Fluorescence Detection System

    PubMed Central

    Ding, Xi-Qin; Matveev, Alexander; Singh, Anil; Komori, Naoka; Matsumoto, Hiroyuki

    2012-01-01

    Cone vision mediated by photoreceptor cyclic nucleotide-gated (CNG) channel is essential for central and color vision and visual acuity. Cone CNG channel is composed of two structurally related subunit types, CNGA3 and CNGB3. Naturally occurring mutations in cone CNG channel are associated with a variety of cone diseases including achromatopsia, progressive cone dystrophy, and some maculopathies. Nevertheless, our understanding of the structure of cone CNG channel is quite limited. This is, in part, due to the challenge of studying cones in a rod-dominant mammalian retina. We have demonstrated a robust expression of cone CNG channel and lack of rod CNG channel in the cone-dominant Nrl−/− retina and shown that the Nrl−/− mouse line is a valuable model to study cone CNG channel. This work examined the complex structure of cone CNG channel using infrared fluorescence Western detection combined with chemical cross-linking and blue native-PAGE. Our results suggest that the native cone CNG channel is a heterotetrameric complex likely at a stoichiometry of three CNGA3 and one CNGB3. PMID:22183405

  15. Single-molecule studies of multi-protein machines

    NASA Astrophysics Data System (ADS)

    van Oijen, Antoine

    2010-03-01

    Advances in optical imaging and molecular manipulation techniques have made it possible to observe individual enzymes and record molecular movies that provide new insight into their dynamics and reaction mechanisms. In a biological context, most of these enzymes function in concert with other enzymes in multi-protein complexes, so an important future direction will be the utilization of single-molecule techniques to unravel the orchestration of large macromolecular assemblies. Our group is developing the single-molecule tools that will make it possible to study biochemical pathways of arbitrary complexity at the single-molecule level. I will discuss results of single-molecule experiments on the replisome, the molecular machinery that is responsible for replication of DNA. We stretch individual DNA molecules and use their elastic properties to obtain dynamic information on the proteins that unwind the double helix and copy its genetic information. Furthermore, we visualize fluorescently labeled components of the replisome and thus obtain information on stochiometry and exchange kinetics. This simultaneous observation of catalytic activity and composition allows us to gain deeper insight into the structure-function relationship of the replisome.

  16. A novel subunit structure of Clostridium botulinum serotype D toxin complex with three extended arms.

    PubMed

    Hasegawa, Kimiko; Watanabe, Toshihiro; Suzuki, Tomonori; Yamano, Akihito; Oikawa, Tetsuo; Sato, Yasuhiko; Kouguchi, Hirokazu; Yoneyama, Tohru; Niwa, Koichi; Ikeda, Toshihiko; Ohyama, Tohru

    2007-08-24

    The botulinum neurotoxins (BoNTs) are the most potent toxins known in nature, causing the lethal disease known as botulism in humans and animals. The BoNTs act by inhibiting neurotransmitter release from cholinergic synapses. Clostridium botulinum strains produce large BoNTs toxin complexes, which include auxiliary non-toxic proteins that appear not only to protect BoNTs from the hostile environment of the digestive tract but also to assist BoNT translocation across the intestinal mucosal layer. In this study, we visualize for the first time a series of botulinum serotype D toxin complexes using negative stain transmission electron microscopy (TEM). The complexes consist of the 150-kDa BoNT, 130-kDa non-toxic non-hemagglutinin (NTNHA), and three kinds of hemagglutinin (HA) subcomponents: 70-kDa HA-70, 33-kDa HA-33, and 17-kDa HA-17. These components assemble sequentially to form the complex. A novel TEM image of the mature L-TC revealed an ellipsoidal-shaped structure with "three arms" attached. The "body" section was comprised of a single BoNT, a single NTNHA and three HA-70 molecules. The arm section consisted of a complex of HA-33 and HA-17 molecules. We determined the x-ray crystal structure of the complex formed by two HA-33 plus one HA-17. On the basis of the TEM image and biochemical results, we propose a novel 14-mer subunit model for the botulinum toxin complex. This unique model suggests how non-toxic components make up a "delivery vehicle" for BoNT.

  17. Preparation of wholemount mouse intestine for high-resolution three-dimensional imaging using two-photon microscopy.

    PubMed

    Appleton, P L; Quyn, A J; Swift, S; Näthke, I

    2009-05-01

    Visualizing overall tissue architecture in three dimensions is fundamental for validating and integrating biochemical, cell biological and visual data from less complex systems such as cultured cells. Here, we describe a method to generate high-resolution three-dimensional image data of intact mouse gut tissue. Regions of highest interest lie between 50 and 200 mum within this tissue. The quality and usefulness of three-dimensional image data of tissue with such depth is limited owing to problems associated with scattered light, photobleaching and spherical aberration. Furthermore, the highest-quality oil-immersion lenses are designed to work at a maximum distance of

  18. Visual Complexity and Pictorial Memory: A Fifteen Year Research Perspective.

    ERIC Educational Resources Information Center

    Berry, Louis H.

    For 15 years an ongoing research project at the University of Pittsburgh has focused on the effects of variations in visual complexity and color on the storage and retrieval of visual information by learners. Research has shown that visual materials facilitate instruction, but has not fully delineated the interactions of visual complexity and…

  19. [A study of biomechanical method for urine test based on color difference estimation].

    PubMed

    Wang, Chunhong; Zhou, Yue; Zhao, Hongxia; Zhou, Fengkun

    2008-02-01

    The biochemical analysis of urine is an important inspection and diagnosis method in hospitals. The conventional method of urine analysis covers mainly colorimetric visual appraisement and automation detection, in which the colorimetric visual appraisement technique has been superseded basically, and the automation detection method is adopted in hospital; moreover, the price of urine biochemical analyzer on market is around twenty thousand RMB yuan (Y), which is hard to enter into ordinary families. It is known that computer vision system is not subject to the physiological and psychological influence of person, its appraisement standard is objective and steady. Therefore, according to the color theory, we have established a computer vision system, which can carry through collection, management, display, and appraisement of color difference between the color of standard threshold value and the color of urine test paper after reaction with urine liquid, and then the level of an illness can be judged accurately. In this paper, we introduce the Urine Test Biochemical Analysis method, which is new and can be popularized in families. Experimental result shows that this test method is easy-to-use and cost-effective. It can realize the monitoring of a whole course and can find extensive applications.

  20. Automated visualization of rule-based models

    PubMed Central

    Tapia, Jose-Juan; Faeder, James R.

    2017-01-01

    Frameworks such as BioNetGen, Kappa and Simmune use “reaction rules” to specify biochemical interactions compactly, where each rule specifies a mechanism such as binding or phosphorylation and its structural requirements. Current rule-based models of signaling pathways have tens to hundreds of rules, and these numbers are expected to increase as more molecule types and pathways are added. Visual representations are critical for conveying rule-based models, but current approaches to show rules and interactions between rules scale poorly with model size. Also, inferring design motifs that emerge from biochemical interactions is an open problem, so current approaches to visualize model architecture rely on manual interpretation of the model. Here, we present three new visualization tools that constitute an automated visualization framework for rule-based models: (i) a compact rule visualization that efficiently displays each rule, (ii) the atom-rule graph that conveys regulatory interactions in the model as a bipartite network, and (iii) a tunable compression pipeline that incorporates expert knowledge and produces compact diagrams of model architecture when applied to the atom-rule graph. The compressed graphs convey network motifs and architectural features useful for understanding both small and large rule-based models, as we show by application to specific examples. Our tools also produce more readable diagrams than current approaches, as we show by comparing visualizations of 27 published models using standard graph metrics. We provide an implementation in the open source and freely available BioNetGen framework, but the underlying methods are general and can be applied to rule-based models from the Kappa and Simmune frameworks also. We expect that these tools will promote communication and analysis of rule-based models and their eventual integration into comprehensive whole-cell models. PMID:29131816

  1. Thermodynamic considerations on Ca2+-induced biochemical reactions in living cells

    NASA Astrophysics Data System (ADS)

    Lucia, Umberto; Ponzetto, Antonio

    2016-02-01

    Cells can be regarded as complex engines that execute a series of chemical reactions. Energy transformations, thermo-electro-chemical processes and transport phenomena can occur across cell membranes. Different, related thermo-electro-biochemical behaviour can occur between health and disease states. Analysis of the irreversibility related to ion fluxes can represent a new approach to study and control the biochemical behaviour of living cells.

  2. Predicting beauty: fractal dimension and visual complexity in art.

    PubMed

    Forsythe, A; Nadal, M; Sheehy, N; Cela-Conde, C J; Sawey, M

    2011-02-01

    Visual complexity has been known to be a significant predictor of preference for artistic works for some time. The first study reported here examines the extent to which perceived visual complexity in art can be successfully predicted using automated measures of complexity. Contrary to previous findings the most successful predictor of visual complexity was Gif compression. The second study examined the extent to which fractal dimension could account for judgments of perceived beauty. The fractal dimension measure accounts for more of the variance in judgments of perceived beauty in visual art than measures of visual complexity alone, particularly for abstract and natural images. Results also suggest that when colour is removed from an artistic image observers are unable to make meaningful judgments as to its beauty. ©2010 The British Psychological Society.

  3. Perimetric Complexity of Binary Digital Images: Notes on Calculation and Relation to Visual Complexity

    NASA Technical Reports Server (NTRS)

    Watson, Andrew B.

    2011-01-01

    Perimetric complexity is a measure of the complexity of binary pictures. It is defined as the sum of inside and outside perimeters of the foreground, squared, divided by the foreground area, divided by 4p . Difficulties arise when this definition is applied to digital images composed of binary pixels. In this paper we identify these problems and propose solutions. Perimetric complexity is often used as a measure of visual complexity, in which case it should take into account the limited resolution of the visual system. We propose a measure of visual perimetric complexity that meets this requirement.

  4. Effect of pattern complexity on the visual span for Chinese and alphabet characters

    PubMed Central

    Wang, Hui; He, Xuanzi; Legge, Gordon E.

    2014-01-01

    The visual span for reading is the number of letters that can be recognized without moving the eyes and is hypothesized to impose a sensory limitation on reading speed. Factors affecting the size of the visual span have been studied using alphabet letters. There may be common constraints applying to recognition of other scripts. The aim of this study was to extend the concept of the visual span to Chinese characters and to examine the effect of the greater complexity of these characters. We measured visual spans for Chinese characters and alphabet letters in the central vision of bilingual subjects. Perimetric complexity was used as a metric to quantify the pattern complexity of binary character images. The visual span tests were conducted with four sets of stimuli differing in complexity—lowercase alphabet letters and three groups of Chinese characters. We found that the size of visual spans decreased with increasing complexity, ranging from 10.5 characters for alphabet letters to 4.5 characters for the most complex Chinese characters studied. A decomposition analysis revealed that crowding was the dominant factor limiting the size of the visual span, and the amount of crowding increased with complexity. Errors in the spatial arrangement of characters (mislocations) had a secondary effect. We conclude that pattern complexity has a major effect on the size of the visual span, mediated in large part by crowding. Measuring the visual span for Chinese characters is likely to have high relevance to understanding visual constraints on Chinese reading performance. PMID:24993020

  5. Subunit Organisation of In Vitro Reconstituted HOPS and CORVET Multisubunit Membrane Tethering Complexes

    PubMed Central

    Guo, Zhong; Johnston, Wayne; Kovtun, Oleksiy; Mureev, Sergey; Bröcker, Cornelia; Ungermann, Christian; Alexandrov, Kirill

    2013-01-01

    Biochemical and structural analysis of macromolecular protein assemblies remains challenging due to technical difficulties in recombinant expression, engineering and reconstitution of multisubunit complexes. Here we use a recently developed cell-free protein expression system based on the protozoan Leishmania tarentolae to produce in vitro all six subunits of the 600 kDa HOPS and CORVET membrane tethering complexes. We demonstrate that both subcomplexes and the entire HOPS complex can be reconstituted in vitro resulting in a comprehensive subunit interaction map. To our knowledge this is the largest eukaryotic protein complex in vitro reconstituted to date. Using the truncation and interaction analysis, we demonstrate that the complex is assembled through short hydrophobic sequences located in the C-terminus of the individual Vps subunits. Based on this data we propose a model of the HOPS and CORVET complex assembly that reconciles the available biochemical and structural data. PMID:24312556

  6. Complement activation and choriocapillaris loss in early AMD: Implications for pathophysiology and therapy

    PubMed Central

    Whitmore, S.Scott; Sohn, Elliott H.; Chirco, Kathleen R.; Drack, Arlene V.; Stone, Edwin M.; Tucker, Budd A.; Mullins, Robert F.

    2015-01-01

    Age-related macular degeneration (AMD) is a common and devastating disease that can result in severe visual dysfunction. Over the last decade, great progress has been made in identifying genetic variants that contribute to AMD, many of which lie in genes involved in the complement cascade. In this review we discuss the significance of complement activation in AMD, particularly with respect to the formation of the membrane attack complex in the aging choriocapillaris. We review the clinical, histological and biochemical data that indicate that vascular loss in the choroid occurs very early in the pathogenesis of AMD, and discuss the potential impact of vascular dropout on the retinal pigment epithelium, Bruch's membrane and the photoreceptor cells. Finally, we present a hypothesis for the pathogenesis of early AMD and consider the implications of this model on the development of new therapies. PMID:25486088

  7. Complement activation and choriocapillaris loss in early AMD: implications for pathophysiology and therapy.

    PubMed

    Whitmore, S Scott; Sohn, Elliott H; Chirco, Kathleen R; Drack, Arlene V; Stone, Edwin M; Tucker, Budd A; Mullins, Robert F

    2015-03-01

    Age-related macular degeneration (AMD) is a common and devastating disease that can result in severe visual dysfunction. Over the last decade, great progress has been made in identifying genetic variants that contribute to AMD, many of which lie in genes involved in the complement cascade. In this review we discuss the significance of complement activation in AMD, particularly with respect to the formation of the membrane attack complex in the aging choriocapillaris. We review the clinical, histological and biochemical data that indicate that vascular loss in the choroid occurs very early in the pathogenesis of AMD, and discuss the potential impact of vascular dropout on the retinal pigment epithelium, Bruch's membrane and the photoreceptor cells. Finally, we present a hypothesis for the pathogenesis of early AMD and consider the implications of this model on the development of new therapies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Molecular Imaging of Apoptosis: From Micro to Macro

    PubMed Central

    Zeng, Wenbin; Wang, Xiaobo; Xu, Pengfei; Liu, Gang; Eden, Henry S.; Chen, Xiaoyuan

    2015-01-01

    Apoptosis, or programmed cell death, is involved in numerous human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer, and is often confused with other types of cell death. Therefore strategies that enable visualized detection of apoptosis would be of enormous benefit in the clinic for diagnosis, patient management, and development of new therapies. In recent years, improved understanding of the apoptotic machinery and progress in imaging modalities have provided opportunities for researchers to formulate microscopic and macroscopic imaging strategies based on well-defined molecular markers and/or physiological features. Correspondingly, a large collection of apoptosis imaging probes and approaches have been documented in preclinical and clinical studies. In this review, we mainly discuss microscopic imaging assays and macroscopic imaging probes, ranging in complexity from simple attachments of reporter moieties to proteins that interact with apoptotic biomarkers, to rationally designed probes that target biochemical changes. Their clinical translation will also be our focus. PMID:25825597

  9. A linear framework for time-scale separation in nonlinear biochemical systems.

    PubMed

    Gunawardena, Jeremy

    2012-01-01

    Cellular physiology is implemented by formidably complex biochemical systems with highly nonlinear dynamics, presenting a challenge for both experiment and theory. Time-scale separation has been one of the few theoretical methods for distilling general principles from such complexity. It has provided essential insights in areas such as enzyme kinetics, allosteric enzymes, G-protein coupled receptors, ion channels, gene regulation and post-translational modification. In each case, internal molecular complexity has been eliminated, leading to rational algebraic expressions among the remaining components. This has yielded familiar formulas such as those of Michaelis-Menten in enzyme kinetics, Monod-Wyman-Changeux in allostery and Ackers-Johnson-Shea in gene regulation. Here we show that these calculations are all instances of a single graph-theoretic framework. Despite the biochemical nonlinearity to which it is applied, this framework is entirely linear, yet requires no approximation. We show that elimination of internal complexity is feasible when the relevant graph is strongly connected. The framework provides a new methodology with the potential to subdue combinatorial explosion at the molecular level.

  10. Design of experiments for identification of complex biochemical systems with applications to mitochondrial bioenergetics.

    PubMed

    Vinnakota, Kalyan C; Beard, Daniel A; Dash, Ranjan K

    2009-01-01

    Identification of a complex biochemical system model requires appropriate experimental data. Models constructed on the basis of data from the literature often contain parameters that are not identifiable with high sensitivity and therefore require additional experimental data to identify those parameters. Here we report the application of a local sensitivity analysis to design experiments that will improve the identifiability of previously unidentifiable model parameters in a model of mitochondrial oxidative phosphorylation and tricaboxylic acid cycle. Experiments were designed based on measurable biochemical reactants in a dilute suspension of purified cardiac mitochondria with experimentally feasible perturbations to this system. Experimental perturbations and variables yielding the most number of parameters above a 5% sensitivity level are presented and discussed.

  11. Visual Complexity in Orthographic Learning: Modeling Learning across Writing System Variations

    ERIC Educational Resources Information Center

    Chang, Li-Yun; Plaut, David C.; Perfetti, Charles A.

    2016-01-01

    The visual complexity of orthographies varies across writing systems. Prior research has shown that complexity strongly influences the initial stage of reading development: the perceptual learning of grapheme forms. This study presents a computational simulation that examines the degree to which visual complexity leads to grapheme learning…

  12. Nicholas Cleveland | NREL

    Science.gov Websites

    tools for complex sample analysis Affiliated Research Programs Biochemical Catalysis Working Group The synthesis Catalyst characterization Catalyst testing and reaction screening Analysis of complex organics

  13. MetaMapR: pathway independent metabolomic network analysis incorporating unknowns.

    PubMed

    Grapov, Dmitry; Wanichthanarak, Kwanjeera; Fiehn, Oliver

    2015-08-15

    Metabolic network mapping is a widely used approach for integration of metabolomic experimental results with biological domain knowledge. However, current approaches can be limited by biochemical domain or pathway knowledge which results in sparse disconnected graphs for real world metabolomic experiments. MetaMapR integrates enzymatic transformations with metabolite structural similarity, mass spectral similarity and empirical associations to generate richly connected metabolic networks. This open source, web-based or desktop software, written in the R programming language, leverages KEGG and PubChem databases to derive associations between metabolites even in cases where biochemical domain or molecular annotations are unknown. Network calculation is enhanced through an interface to the Chemical Translation System, which allows metabolite identifier translation between >200 common biochemical databases. Analysis results are presented as interactive visualizations or can be exported as high-quality graphics and numerical tables which can be imported into common network analysis and visualization tools. Freely available at http://dgrapov.github.io/MetaMapR/. Requires R and a modern web browser. Installation instructions, tutorials and application examples are available at http://dgrapov.github.io/MetaMapR/. ofiehn@ucdavis.edu. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Traffic Signs in Complex Visual Environments

    DOT National Transportation Integrated Search

    1982-11-01

    The effects of sign luminance on detection and recognition of traffic control devices is mediated through contrast with the immediate surround. Additionally, complex visual scenes are known to degrade visual performance with targets well above visual...

  15. Channel-transporter complexes: an emerging theme in cell signaling.

    PubMed

    Abbott, Geoffrey W

    2016-11-01

    In a recent edition of Biochemical Journal, Mistry et al. described the discovery of a novel protein complex, formed from the epithelial sodium channel (ENaC) and the sodium chloride cotransporter (NCC) [Mistry et al. (2016) Biochem. J. 473, 3237–3252]. The importance of these two proteins in the regulation of salt balance and blood pressure has long been known, as has their overlapping expression in the distal convoluted tubule of the kidney. The new study by Mistry et al. now demonstrates their physical interaction in the kidney and when heterologously co-expressed. Furthermore, the authors demonstrate some degree of functional co-dependence between ENaC and NCC, with pharmacological inhibition of the latter diminishing activity of the former when the two are co-assembled. This novel and potentially important interaction adds to a growing number of recently identified channel-transporter ('chansporter') complexes, which together constitute an emerging theme in cell signaling. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  16. T1ρ MR Imaging of Human Musculoskeletal System

    PubMed Central

    Wang, Ligong; Regatte, Ravinder R.

    2014-01-01

    Magnetic resonance imaging (MRI) offers the direct visualization of human musculoskeletal (MSK) system, especially all diarthrodial tissues including cartilage, bone, menisci, ligaments, tendon, hip, synovium etc. Conventional MR imaging techniques based on T1- and T2-weighted, proton density (PD) contrast are inconclusive in quantifying early biochemically degenerative changes in MSK system in general and articular cartilage in particular. In recent years, quantitative MR parameter mapping techniques have been used to quantify the biochemical changes in articular cartilage with a special emphasis on evaluating joint injury, cartilage degeneration, and soft tissue repair. In this article, we will focus on cartilage biochemical composition, basic principles of T1ρ MR imaging, implementation of T1ρ pulse sequences, biochemical validation, and summarize the potential applications of T1ρ MR imaging technique in MSK diseases including osteoarthritis (OA), anterior cruciate ligament (ACL) injury, and knee joint repair. Finally, we will also review the potential advantages, challenges, and future prospects of T1ρ MR imaging for widespread clinical translation. PMID:24935818

  17. T₁ρ MRI of human musculoskeletal system.

    PubMed

    Wang, Ligong; Regatte, Ravinder R

    2015-03-01

    Magnetic resonance imaging (MRI) offers the direct visualization of the human musculoskeletal (MSK) system, especially all diarthrodial tissues including cartilage, bone, menisci, ligaments, tendon, hip, synovium, etc. Conventional MRI techniques based on T1 - and T2 -weighted, proton density (PD) contrast are inconclusive in quantifying early biochemically degenerative changes in MSK system in general and articular cartilage in particular. In recent years, quantitative MR parameter mapping techniques have been used to quantify the biochemical changes in articular cartilage, with a special emphasis on evaluating joint injury, cartilage degeneration, and soft tissue repair. In this article we focus on cartilage biochemical composition, basic principles of T1ρ MRI, implementation of T1ρ pulse sequences, biochemical validation, and summarize the potential applications of the T1ρ MRI technique in MSK diseases including osteoarthritis (OA), anterior cruciate ligament (ACL) injury, and knee joint repair. Finally, we also review the potential advantages, challenges, and future prospects of T1ρ MRI for widespread clinical translation. © 2014 Wiley Periodicals, Inc.

  18. Complexity reduction of biochemical rate expressions.

    PubMed

    Schmidt, Henning; Madsen, Mads F; Danø, Sune; Cedersund, Gunnar

    2008-03-15

    The current trend in dynamical modelling of biochemical systems is to construct more and more mechanistically detailed and thus complex models. The complexity is reflected in the number of dynamic state variables and parameters, as well as in the complexity of the kinetic rate expressions. However, a greater level of complexity, or level of detail, does not necessarily imply better models, or a better understanding of the underlying processes. Data often does not contain enough information to discriminate between different model hypotheses, and such overparameterization makes it hard to establish the validity of the various parts of the model. Consequently, there is an increasing demand for model reduction methods. We present a new reduction method that reduces complex rational rate expressions, such as those often used to describe enzymatic reactions. The method is a novel term-based identifiability analysis, which is easy to use and allows for user-specified reductions of individual rate expressions in complete models. The method is one of the first methods to meet the classical engineering objective of improved parameter identifiability without losing the systems biology demand of preserved biochemical interpretation. The method has been implemented in the Systems Biology Toolbox 2 for MATLAB, which is freely available from http://www.sbtoolbox2.org. The Supplementary Material contains scripts that show how to use it by applying the method to the example models, discussed in this article.

  19. Predicting perceived visual complexity of abstract patterns using computational measures: The influence of mirror symmetry on complexity perception

    PubMed Central

    Leder, Helmut

    2017-01-01

    Visual complexity is relevant for many areas ranging from improving usability of technical displays or websites up to understanding aesthetic experiences. Therefore, many attempts have been made to relate objective properties of images to perceived complexity in artworks and other images. It has been argued that visual complexity is a multidimensional construct mainly consisting of two dimensions: A quantitative dimension that increases complexity through number of elements, and a structural dimension representing order negatively related to complexity. The objective of this work is to study human perception of visual complexity utilizing two large independent sets of abstract patterns. A wide range of computational measures of complexity was calculated, further combined using linear models as well as machine learning (random forests), and compared with data from human evaluations. Our results confirm the adequacy of existing two-factor models of perceived visual complexity consisting of a quantitative and a structural factor (in our case mirror symmetry) for both of our stimulus sets. In addition, a non-linear transformation of mirror symmetry giving more influence to small deviations from symmetry greatly increased explained variance. Thus, we again demonstrate the multidimensional nature of human complexity perception and present comprehensive quantitative models of the visual complexity of abstract patterns, which might be useful for future experiments and applications. PMID:29099832

  20. Visual complexity: a review.

    PubMed

    Donderi, Don C

    2006-01-01

    The idea of visual complexity, the history of its measurement, and its implications for behavior are reviewed, starting with structuralism and Gestalt psychology at the beginning of the 20th century and ending with visual complexity theory, perceptual learning theory, and neural circuit theory at the beginning of the 21st. Evidence is drawn from research on single forms, form and texture arrays and visual displays. Form complexity and form probability are shown to be linked through their reciprocal relationship in complexity theory, which is in turn shown to be consistent with recent developments in perceptual learning and neural circuit theory. Directions for further research are suggested.

  1. Visualization and Semiquantitative Study of the Distribution of Major Components in Wheat Straw in Mesoscopic Scale using Fourier Transform Infrared Microspectroscopic Imaging.

    PubMed

    Yang, Zengling; Mei, Jiaqi; Liu, Zhiqiang; Huang, Guangqun; Huang, Guan; Han, Lujia

    2018-06-19

    Understanding the biochemical heterogeneity of plant tissue linked to crop straw anatomy is attractive to plant researchers and researchers in the field of biomass refinery. This study provides an in situ analysis and semiquantitative visualization of major components distribution in internodal transverse sections of wheat straw based on Fourier transform infrared (FTIR) microspectroscopic imaging, with a fast non-negativity-constrained least squares (fast NNLS) fitting. This paper investigates changes in biochemical components of tissue during stages of elongation, booting, heading, flowering, grain-filling, milk-ripening, dough, and full-ripening. Visualization analysis was carried out with reference spectra for five components (microcrystalline cellulose, xylan, lignin, pectin, and starch) of wheat straw. Our result showed that (a) the cellulose and lignin distribution is consistent with that from tissue-dyeing with safranin O-fast green and (b) the distribution of cellulose, lignin, and starch is consistent with chemical images for characteristic wavelength at 1432, 1507, and 987 cm -1 , respectively, showing no interference from the other components analyzed. With the validation from biochemical images using characteristic wavelength and tissue-dyeing techniques, further semiquantitative analysis in local tissues based on fast NNLS was carried out, and the result showed that (a) the contents of cellulose in various tissues are very different, with most in parenchyma tissue and least in the epidermis and (b) during plant development, the fluctuation of each component in tissues follows nearly the same trend, especially within vascular bundles and parenchyma tissue. Thus, FTIR microspectroscopic imaging combined with suitable chemometric methods can be successfully applied to study chemical distributions within the internodes transverse sections of wheat straw, providing semiquantitative chemical information.

  2. Interaction of glutaric aciduria type 1-related glutaryl-CoA dehydrogenase with mitochondrial matrix proteins.

    PubMed

    Schmiesing, Jessica; Schlüter, Hartmut; Ullrich, Kurt; Braulke, Thomas; Mühlhausen, Chris

    2014-01-01

    Glutaric aciduria type 1 (GA1) is an inherited neurometabolic disorder caused by mutations in the GCDH gene encoding glutaryl-CoA dehydrogenase (GCDH), which forms homo- and heteromeric complexes in the mitochondrial matrix. GA1 patients are prone to the development of encephalopathic crises which lead to an irreversible disabling dystonic movement disorder. The clinical and biochemical manifestations of GA1 vary considerably and lack correlations to the genotype. Using an affinity chromatography approach we report here for the first time on the identification of mitochondrial proteins interacting directly with GCDH. Among others, dihydrolipoamide S-succinyltransferase (DLST) involved in the formation of glutaryl-CoA, and the β-subunit of the electron transfer flavoprotein (ETFB) serving as electron acceptor, were identified as GCDH binding partners. We have adapted the yellow fluorescent protein-based fragment complementation assay and visualized the oligomerization of GCDH as well as its direct interaction with DLST and ETFB in mitochondria of living cells. These data suggest that GCDH is a constituent of multimeric mitochondrial dehydrogenase complexes, and the characterization of their interrelated functions may provide new insights into the regulation of lysine oxidation and the pathophysiology of GA1.

  3. Interaction of Glutaric Aciduria Type 1-Related glutaryl-CoA Dehydrogenase with Mitochondrial Matrix Proteins

    PubMed Central

    Schmiesing, Jessica; Schlüter, Hartmut; Ullrich, Kurt; Braulke, Thomas; Mühlhausen, Chris

    2014-01-01

    Glutaric aciduria type 1 (GA1) is an inherited neurometabolic disorder caused by mutations in the GCDH gene encoding glutaryl-CoA dehydrogenase (GCDH), which forms homo- and heteromeric complexes in the mitochondrial matrix. GA1 patients are prone to the development of encephalopathic crises which lead to an irreversible disabling dystonic movement disorder. The clinical and biochemical manifestations of GA1 vary considerably and lack correlations to the genotype. Using an affinity chromatography approach we report here for the first time on the identification of mitochondrial proteins interacting directly with GCDH. Among others, dihydrolipoamide S-succinyltransferase (DLST) involved in the formation of glutaryl-CoA, and the β-subunit of the electron transfer flavoprotein (ETFB) serving as electron acceptor, were identified as GCDH binding partners. We have adapted the yellow fluorescent protein-based fragment complementation assay and visualized the oligomerization of GCDH as well as its direct interaction with DLST and ETFB in mitochondria of living cells. These data suggest that GCDH is a constituent of multimeric mitochondrial dehydrogenase complexes, and the characterization of their interrelated functions may provide new insights into the regulation of lysine oxidation and the pathophysiology of GA1. PMID:24498361

  4. Muscle morphology and mitochondrial investigations of a family with autosomal dominant cerebellar ataxia and retinal degeneration mapped to chromosome 3p12-p21.1.

    PubMed

    Forsgren, L; Libelius, R; Holmberg, M; von Döbeln, U; Wibom, R; Heijbel, J; Sandgren, O; Holmgren, G

    1996-12-01

    The autosomal dominant cerebellar ataxias (ADCA) are a group of neurodegenerative disorders with ataxia and dysarthria as early and dominant signs. In ADCA type II, retinal degeneration causes severe visual impairment. ADCA type II has recently been mapped to chromosome 3p by three independent groups. In the family with ADCA type II studied here, the disease has been mapped to chromosome 3p12-p21.1. Histochemical examination of muscle biopsies in 5 cases showed slight neurogenic atrophy and irregular lobulated appearance or focal decreases of enzyme activity when staining for NADH dehydrogenase, succinic dehydrogenase and cytochrome oxidase. Ragged-red fibres were scarce. Electron microscopic examination showed uneven distribution of mitochondria with large fibre areas devoid of mitochondria and/or large subsarcolemmal accumulations of small rounded mitochondria, and frequent autophagic vacuoles. These vacuoles contained remnants of multiple small rounded organelles, possibly mitochondria, and had a remarkably consistent ultrastructural appearance. Biochemical investigation of mitochondrial function showed reduced activity of complex IV and slightly reduced activity of complex I in the respiratory chain in a severely affected child while no abnormalities were found in his affected uncle.

  5. Measurement Frontiers in Molecular Biology

    NASA Astrophysics Data System (ADS)

    Laderman, Stephen

    2009-03-01

    Developments of molecular measurements and manipulations have long enabled forefront research in evolution, genetics, biological development and its dysfunction, and the impact of external factors on the behavior of cells. Measurement remains at the heart of exciting and challenging basic and applied problems in molecular and cell biology. Methods to precisely determine the identity and abundance of particular molecules amongst a complex mixture of similar and dissimilar types require the successful design and integration of multiple steps involving biochemical manipulations, separations, physical probing, and data processing. Accordingly, today's most powerful methods for characterizing life at the molecular level depend on coordinated advances in applied physics, biochemistry, chemistry, computer science, and engineering. This is well illustrated by recent approaches to the measurement of DNA, RNA, proteins, and intact cells. Such successes underlie well founded visions of how molecular biology can further assist in answering compelling scientific questions and in enabling the development of remarkable advances in human health. These visions, in turn, are motivating the interdisciplinary creation of even more comprehensive measurements. As a further and closely related consequence, they are motivating innovations in the conceptual and practical approaches to organizing and visualizing large, complex sets of interrelated experimental results and distilling from those data compelling, informative conclusions.

  6. New fluorescent probes for visual proteins. Part II. 5-(Oxo)penta-2,4-dienyl-p-(N,N-dimethylamino)benzoate.

    PubMed

    Papper, Vladislav; Kharlanov, Vladimir; Schädel, Sandra; Maretzki, Dieter; Rettig, Wolfgang

    2003-12-01

    A new dual-fluorescent compound, 5-(oxo)penta-2,4-dienyl-p-(N,N-dimethylamino)benzoate (1), a derivative of dimethylaminobenzoic acid, has been synthesised and studied photophysically. This compound continues the series of potential fluorescent probes for visual and proton-pumping opsin proteins. The photophysical behaviour of this molecule, including charge-transfer interaction in the ground state and dual-fluorescence emission, is similar to that of the previously studied analogue cis-3-(oxo)propenyl-p-(N,N-dimethylamino)benzoate (cis-2). The presence of several theoretically calculated conformers of compound 2 was suggested to be responsible for the observed strongly red-shifted absorption and excitation wavelength dependence. These photophysical anomalies were also observed for molecule 1, though the models put forward to explain them in the cases of 1 and 2 are rather different. Based on theoretical calculations and experimental results, we propose that some of the stable conformers might be connected with either a charge-transfer complex or mesomeric interactions in the ground state. Upon changing the electronic nature of the oxo-pentadienyl acceptor moiety, e.g. protonation, chemical or biochemical reaction, the charge-transfer absorption disappears, which leads to a dramatic increase in the fluorescence quantum yield.

  7. Using NMR-based metabolomics to monitor the biochemical composition of agricultural soils: a pilot study

    USDA-ARS?s Scientific Manuscript database

    NMR-based metabolomics plays a major role studying complex living systems. However, very few studies describe the application of this technique to the evaluation of soil metabolome. Here, we introduce a protocol for analyzing the biochemical compounds from agricultural soils where the microbial comm...

  8. Biochemical identification of Argonaute 2 as the sole protein required for RNA-induced silencing complex activity

    PubMed Central

    Rand, Tim A.; Ginalski, Krzysztof; Grishin, Nick V.; Wang, Xiaodong

    2004-01-01

    RNA interference is carried out by the small double-stranded RNA-induced silencing complex (RISC). The RISC-bound small RNA guides the RISC complex to identify and cleave mRNAs with complementary sequences. The proteins that make up the RISC complex and cleave mRNA have not been unequivocally defined. Here, we report the biochemical purification of RISC activity to homogeneity from Drosophila Schnieder 2 cell extracts. Argonaute 2 (Ago-2) is the sole protein component present in the purified, functional RISC. By using a bioinformatics method that combines sequence-profile analysis with predicted protein secondary structure, we found homology between the PIWI domain of Ago-2 and endonuclease V and identified potential active-site amino acid residues within the PIWI domain of Ago-2. PMID:15452342

  9. Biochemical identification of Argonaute 2 as the sole protein required for RNA-induced silencing complex activity.

    PubMed

    Rand, Tim A; Ginalski, Krzysztof; Grishin, Nick V; Wang, Xiaodong

    2004-10-05

    RNA interference is carried out by the small double-stranded RNA-induced silencing complex (RISC). The RISC-bound small RNA guides the RISC complex to identify and cleave mRNAs with complementary sequences. The proteins that make up the RISC complex and cleave mRNA have not been unequivocally defined. Here, we report the biochemical purification of RISC activity to homogeneity from Drosophila Schnieder 2 cell extracts. Argonaute 2 (Ago-2) is the sole protein component present in the purified, functional RISC. By using a bioinformatics method that combines sequence-profile analysis with predicted protein secondary structure, we found homology between the PIWI domain of Ago-2 and endonuclease V and identified potential active-site amino acid residues within the PIWI domain of Ago-2.

  10. Human infrared vision is triggered by two-photon chromophore isomerization

    PubMed Central

    Palczewska, Grazyna; Vinberg, Frans; Stremplewski, Patrycjusz; Bircher, Martin P.; Salom, David; Komar, Katarzyna; Zhang, Jianye; Cascella, Michele; Wojtkowski, Maciej; Kefalov, Vladimir J.; Palczewski, Krzysztof

    2014-01-01

    Vision relies on photoactivation of visual pigments in rod and cone photoreceptor cells of the retina. The human eye structure and the absorption spectra of pigments limit our visual perception of light. Our visual perception is most responsive to stimulating light in the 400- to 720-nm (visible) range. First, we demonstrate by psychophysical experiments that humans can perceive infrared laser emission as visible light. Moreover, we show that mammalian photoreceptors can be directly activated by near infrared light with a sensitivity that paradoxically increases at wavelengths above 900 nm, and display quadratic dependence on laser power, indicating a nonlinear optical process. Biochemical experiments with rhodopsin, cone visual pigments, and a chromophore model compound 11-cis-retinyl-propylamine Schiff base demonstrate the direct isomerization of visual chromophore by a two-photon chromophore isomerization. Indeed, quantum mechanics modeling indicates the feasibility of this mechanism. Together, these findings clearly show that human visual perception of near infrared light occurs by two-photon isomerization of visual pigments. PMID:25453064

  11. Distribution of different surface modified carbon dots in pumpkin seedlings.

    PubMed

    Qian, Kun; Guo, Huiyuan; Chen, Guangcai; Ma, Chuanxin; Xing, Baoshan

    2018-05-22

    The distribution of surface modified carbon dots (CDs) in the pumpkin seedlings was studied by visualization techniques and their potential phytotoxicity was investigated at both the physiological and biochemical levels. The average size of carbon dots was approximately 4 nm. The fluorescent peaks of bared CDs, CD-PEI and CD-PAA were between 420 nm and 500 nm, indicating CDs could emit blue and green fluorescence. Fluorescent images showed that all three types of CDs could accumulate in the pumpkin roots and translocate to the shoots, although the distribution pattern of each CDs was obviously different. At the biochemical level, the elevated antioxidant enzymes in pumpkin roots suggest that all the CDs could potentially trigger the antioxidant defense systems in pumpkin seedlings. Additionally, such alteration was greater in the roots than in the shoots. Our study represents a new perspective on CD visualization in plant tissues and provide useful information for the potential toxicity of different types of CDs to terrestrial plants, which is of importance to agricultural application.

  12. Visual Complexity: A Review

    ERIC Educational Resources Information Center

    Donderi, Don C.

    2006-01-01

    The idea of visual complexity, the history of its measurement, and its implications for behavior are reviewed, starting with structuralism and Gestalt psychology at the beginning of the 20th century and ending with visual complexity theory, perceptual learning theory, and neural circuit theory at the beginning of the 21st. Evidence is drawn from…

  13. Hierarchical thinking in network biology: the unbiased modularization of biochemical networks.

    PubMed

    Papin, Jason A; Reed, Jennifer L; Palsson, Bernhard O

    2004-12-01

    As reconstructed biochemical reaction networks continue to grow in size and scope, there is a growing need to describe the functional modules within them. Such modules facilitate the study of biological processes by deconstructing complex biological networks into conceptually simple entities. The definition of network modules is often based on intuitive reasoning. As an alternative, methods are being developed for defining biochemical network modules in an unbiased fashion. These unbiased network modules are mathematically derived from the structure of the whole network under consideration.

  14. Widening the Heterogeneity of Leigh Syndrome: Clinical, Biochemical, and Neuroradiologic Features in a Patient Harboring a NDUFA10 Mutation.

    PubMed

    Minoia, Francesca; Bertamino, Marta; Picco, Paolo; Severino, Mariasavina; Rossi, Andrea; Fiorillo, Chiara; Minetti, Carlo; Nesti, Claudia; Santorelli, Filippo Maria; Di Rocco, Maja

    2017-01-01

    Leigh syndrome (LS) is an early-onset progressive neurodegenerative disorder, characterized by a wide clinical and genetic heterogeneity, and is the most frequent disorder of mitochondrial energy production in children. Beside its great variability in clinical, biochemical, and genetic features, LS is pathologically uniformly characterized by multifocal bilateral and symmetric spongiform degeneration of the basal ganglia, brainstem, thalamus, cerebellum, spinal cord, and optic nerves. Isolated complex I deficiency is the most common defect identified in Leigh syndrome. In 2011, the first child with a mutation of NDUFA10 gene, coding for an accessory subunits of complex I, was described. Here, we present an additional description of a child with Leigh syndrome harboring a homozygous mutation in NDUFA10, providing insights in clinical, biochemical, and neuroradiologic features for future earlier recognition.

  15. Multiple Ion Binding Equilibria, Reaction Kinetics, and Thermodynamics in Dynamic Models of Biochemical Pathways

    PubMed Central

    Vinnakota, Kalyan C.; Wu, Fan; Kushmerick, Martin J.; Beard, Daniel A.

    2009-01-01

    The operation of biochemical systems in vivo and in vitro is strongly influenced by complex interactions between biochemical reactants and ions such as H+, Mg2+, K+, and Ca2+. These are important second messengers in metabolic and signaling pathways that directly influence the kinetics and thermodynamics of biochemical systems. Herein we describe the biophysical theory and computational methods to account for multiple ion binding to biochemical reactants and demonstrate the crucial effects of ion binding on biochemical reaction kinetics and thermodynamics. In simulations of realistic systems, the concentrations of these ions change with time due to dynamic buffering and competitive binding. In turn, the effective thermodynamic properties vary as functions of cation concentrations and important environmental variables such as temperature and overall ionic strength. Physically realistic simulations of biochemical systems require incorporating all of these phenomena into a coherent mathematical description. Several applications to physiological systems are demonstrated based on this coherent simulation framework. PMID:19216922

  16. An integrated modelling framework for neural circuits with multiple neuromodulators.

    PubMed

    Joshi, Alok; Youssofzadeh, Vahab; Vemana, Vinith; McGinnity, T M; Prasad, Girijesh; Wong-Lin, KongFatt

    2017-01-01

    Neuromodulators are endogenous neurochemicals that regulate biophysical and biochemical processes, which control brain function and behaviour, and are often the targets of neuropharmacological drugs. Neuromodulator effects are generally complex partly owing to the involvement of broad innervation, co-release of neuromodulators, complex intra- and extrasynaptic mechanism, existence of multiple receptor subtypes and high interconnectivity within the brain. In this work, we propose an efficient yet sufficiently realistic computational neural modelling framework to study some of these complex behaviours. Specifically, we propose a novel dynamical neural circuit model that integrates the effective neuromodulator-induced currents based on various experimental data (e.g. electrophysiology, neuropharmacology and voltammetry). The model can incorporate multiple interacting brain regions, including neuromodulator sources, simulate efficiently and easily extendable to large-scale brain models, e.g. for neuroimaging purposes. As an example, we model a network of mutually interacting neural populations in the lateral hypothalamus, dorsal raphe nucleus and locus coeruleus, which are major sources of neuromodulator orexin/hypocretin, serotonin and norepinephrine/noradrenaline, respectively, and which play significant roles in regulating many physiological functions. We demonstrate that such a model can provide predictions of systemic drug effects of the popular antidepressants (e.g. reuptake inhibitors), neuromodulator antagonists or their combinations. Finally, we developed user-friendly graphical user interface software for model simulation and visualization for both fundamental sciences and pharmacological studies. © 2017 The Authors.

  17. An integrated modelling framework for neural circuits with multiple neuromodulators

    PubMed Central

    Vemana, Vinith

    2017-01-01

    Neuromodulators are endogenous neurochemicals that regulate biophysical and biochemical processes, which control brain function and behaviour, and are often the targets of neuropharmacological drugs. Neuromodulator effects are generally complex partly owing to the involvement of broad innervation, co-release of neuromodulators, complex intra- and extrasynaptic mechanism, existence of multiple receptor subtypes and high interconnectivity within the brain. In this work, we propose an efficient yet sufficiently realistic computational neural modelling framework to study some of these complex behaviours. Specifically, we propose a novel dynamical neural circuit model that integrates the effective neuromodulator-induced currents based on various experimental data (e.g. electrophysiology, neuropharmacology and voltammetry). The model can incorporate multiple interacting brain regions, including neuromodulator sources, simulate efficiently and easily extendable to large-scale brain models, e.g. for neuroimaging purposes. As an example, we model a network of mutually interacting neural populations in the lateral hypothalamus, dorsal raphe nucleus and locus coeruleus, which are major sources of neuromodulator orexin/hypocretin, serotonin and norepinephrine/noradrenaline, respectively, and which play significant roles in regulating many physiological functions. We demonstrate that such a model can provide predictions of systemic drug effects of the popular antidepressants (e.g. reuptake inhibitors), neuromodulator antagonists or their combinations. Finally, we developed user-friendly graphical user interface software for model simulation and visualization for both fundamental sciences and pharmacological studies. PMID:28100828

  18. Stable isotope probing to study functional components of complex microbial ecosystems.

    PubMed

    Mazard, Sophie; Schäfer, Hendrik

    2014-01-01

    This protocol presents a method of dissecting the DNA or RNA of key organisms involved in a specific biochemical process within a complex ecosystem. Stable isotope probing (SIP) allows the labelling and separation of nucleic acids from community members that are involved in important biochemical transformations, yet are often not the most numerically abundant members of a community. This pure culture-independent technique circumvents limitations of traditional microbial isolation techniques or data mining from large-scale whole-community metagenomic studies to tease out the identities and genomic repertoires of microorganisms participating in biological nutrient cycles. SIP experiments can be applied to virtually any ecosystem and biochemical pathway under investigation provided a suitable stable isotope substrate is available. This versatile methodology allows a wide range of analyses to be performed, from fatty-acid analyses, community structure and ecology studies, and targeted metagenomics involving nucleic acid sequencing. SIP experiments provide an effective alternative to large-scale whole-community metagenomic studies by specifically targeting the organisms or biochemical transformations of interest, thereby reducing the sequencing effort and time-consuming bioinformatics analyses of large datasets.

  19. Visualizing Antimicrobials in Bacterial Biofilms: Three-Dimensional Biochemical Imaging Using TOF-SIMS.

    PubMed

    Davies, Sarah K; Fearn, Sarah; Allsopp, Luke P; Harrison, Freya; Ware, Ecaterina; Diggle, Stephen P; Filloux, Alain; McPhail, David S; Bundy, Jacob G

    2017-01-01

    Bacterial biofilms are groups of bacteria that exist within a self-produced extracellular matrix, adhering to each other and usually to a surface. They grow on medical equipment and inserts such as catheters and are responsible for many persistent infections throughout the body, as they can have high resistance to many antimicrobials. Pseudomonas aeruginosa is an opportunistic pathogen that can cause both acute and chronic infections and is used as a model for research into biofilms. Direct biochemical methods of imaging of molecules in bacterial biofilms are of high value in gaining a better understanding of the fundamental biology of biofilms and biochemical gradients within them. Time of flight-secondary-ion mass spectrometry (TOF-SIMS) is one approach, which combines relatively high spatial resolution and sensitivity and can perform depth profiling analysis. It has been used to analyze bacterial biofilms but has not yet been used to study the distribution of antimicrobials (including antibiotics and the antimicrobial metal gallium) within biofilms. Here we compared two methods of imaging of the interior structure of P. aeruginosa in biological samples using TOF-SIMS, looking at both antimicrobials and endogenous biochemicals: cryosectioning of tissue samples and depth profiling to give pseudo-three-dimensional (pseudo-3D) images. The sample types included both simple biofilms grown on glass slides and bacteria growing in tissues in an ex vivo pig lung model. The two techniques for the 3D imaging of biofilms are potentially valuable complementary tools for analyzing bacterial infection. IMPORTANCE Modern analytical techniques are becoming increasingly important in the life sciences; imaging mass spectrometry offers the opportunity to gain unprecedented amounts of information on the distribution of chemicals in samples-both xenobiotics and endogenous compounds. In particular, simultaneous imaging of antibiotics (and other antimicrobial compounds) and bacterium-derived metabolites in complex biological samples could be very important in the future for helping to understand how sample matrices impact the survival of bacteria under antibiotic challenge. We have shown that an imaging mass spectrometric technique, TOF-SIMS, will be potentially extremely valuable for this kind of research in the future.

  20. Biomarkers of a five-domain translational substrate for schizophrenia and schizoaffective psychosis.

    PubMed

    Fryar-Williams, Stephanie; Strobel, Jörg E

    2015-01-01

    The Mental Health Biomarker Project (2010-2014) selected commercial biochemistry markers related to monoamine synthesis and metabolism and measures of visual and auditory processing performance. Within a case-control discovery design with exclusion criteria designed to produce a highly characterised sample, results from 67 independently DSM IV-R-diagnosed cases of schizophrenia and schizoaffective disorder were compared with those from 67 control participants selected from a local hospital, clinic and community catchment area. Participants underwent protocol-based diagnostic-checking, functional-rating, biological sample-collection for thirty candidate markers and sensory-processing assessment. Fifteen biomarkers were identified on ROC analysis. Using these biomarkers, odds ratios, adjusted for a case-control design, indicated that schizophrenia and schizoaffective disorder were highly associated with dichotic listening disorder, delayed visual processing, low visual span, delayed auditory speed of processing, low reverse digit span as a measure of auditory working memory and elevated levels of catecholamines. Other nutritional and biochemical biomarkers were identified as elevated hydroxyl pyrroline-2-one as a marker of oxidative stress, vitamin D, B6 and folate deficits with elevation of serum B12 and free serum copper to zinc ratio. When individual biomarkers were ranked by odds ratio and correlated with clinical severity, five functional domains of visual processing, auditory processing, oxidative stress, catecholamines and nutritional-biochemical variables were formed. When the strengths of their inter-domain relationships were predicted by Lowess (non-parametric) regression, predominant bidirectional relationships were found between visual processing and catecholamine domains. At a cellular level, the nutritional-biochemical domain exerted a pervasive influence on the auditory domain as well as on all other domains. The findings of this biomarker research point towards a much-required advance in Psychiatry: quantification of some theoretically-understandable, translationally-informative, treatment-relevant underpinnings of serious mental illness. This evidence reveals schizophrenia and schizoaffective disorder in a somewhat different manner, as a conglomerate of several disorders many of which are not currently being assessed-for or treated in clinical settings. Currently available remediation techniques for these underlying conditions have potential to reduce treatment-resistance, relapse-prevention, cost burden and social stigma in these conditions. If replicated and validated in prospective trials, such findings will improve progress-monitoring and treatment-response for schizophrenia and schizoaffective disorder.

  1. Comparison of biochemical values in serum and plasma, fresh and frozen plasma, and hemolyzed samples from orange-winged Amazon parrots (Amazona amazonica).

    PubMed

    Hawkins, Michelle G; Kass, Philip H; Zinkl, Joseph G; Tell, Lisa A

    2006-06-01

    To the authors' knowledge, on the basis of sample type, storage condition, or hemolysis, differences in serum and plasma biochemical values have not been evaluated in orange-winged Amazon parrots (Amazona amazonica). The purpose of this study was to compare values for biochemical analytes in serum vs plasma, fresh vs frozen plasma, and nonhemolyzed vs hemolyzed samples in orange-winged Amazon parrots. We also compared differences in serum and plasma yield from whole-blood aliquots. Fifteen biochemical analytes were evaluated in paired serum and plasma, fresh and frozen plasma, nonhemolyzed and hemolyzed serum and plasma samples from orange-winged Amazon parrots (n = 10) using a wet reagent analyzer. Hemolysis was assessed qualitatively (visually) and quantitatively (hemoglobin [Hgb] measured spectrophotometrically). Serum and plasma yields from 500-microl whole-blood aliquots were determined from centrifuged samples. Analyte values significantly differed among sample groups, but were still within published reference intervals, with the exception of increases in potassium concentration in markedly hemolyzed serum and plasma samples. Clinically important changes in hemolyzed serum and plasma samples included increases in potassium, phosphorus, and albumin concentrations and lactate dehydrogenase activity. The degree of hemolysis assigned qualitatively did not correlate with quantitative Hgb concentration. A significantly greater yield of plasma (288 +/- 13 microL) than serum (241 +/- 44 microL) was obtained. Significant differences may occur in different sample types, however, only changes in potassium, phosphorus, albumin, and lactate dehydrogenase values in hemolyzed samples were considered clinically relevant. Lack of agreement between qualitative and quantitative Hgb concentration indicates the unreliability of visual estimation. Based on higher sample yield, and lack of clinically relevant differences from serum, plasma is a better sample choice for clinical chemistry analysis in birds.

  2. Automated analysis of information processing, kinetic independence and modular architecture in biochemical networks using MIDIA.

    PubMed

    Bowsher, Clive G

    2011-02-15

    Understanding the encoding and propagation of information by biochemical reaction networks and the relationship of such information processing properties to modular network structure is of fundamental importance in the study of cell signalling and regulation. However, a rigorous, automated approach for general biochemical networks has not been available, and high-throughput analysis has therefore been out of reach. Modularization Identification by Dynamic Independence Algorithms (MIDIA) is a user-friendly, extensible R package that performs automated analysis of how information is processed by biochemical networks. An important component is the algorithm's ability to identify exact network decompositions based on both the mass action kinetics and informational properties of the network. These modularizations are visualized using a tree structure from which important dynamic conditional independence properties can be directly read. Only partial stoichiometric information needs to be used as input to MIDIA, and neither simulations nor knowledge of rate parameters are required. When applied to a signalling network, for example, the method identifies the routes and species involved in the sequential propagation of information between its multiple inputs and outputs. These routes correspond to the relevant paths in the tree structure and may be further visualized using the Input-Output Path Matrix tool. MIDIA remains computationally feasible for the largest network reconstructions currently available and is straightforward to use with models written in Systems Biology Markup Language (SBML). The package is distributed under the GNU General Public License and is available, together with a link to browsable Supplementary Material, at http://code.google.com/p/midia. Further information is at www.maths.bris.ac.uk/~macgb/Software.html.

  3. An integrated cell-free metabolic platform for protein production and synthetic biology

    PubMed Central

    Jewett, Michael C; Calhoun, Kara A; Voloshin, Alexei; Wuu, Jessica J; Swartz, James R

    2008-01-01

    Cell-free systems offer a unique platform for expanding the capabilities of natural biological systems for useful purposes, i.e. synthetic biology. They reduce complexity, remove structural barriers, and do not require the maintenance of cell viability. Cell-free systems, however, have been limited by their inability to co-activate multiple biochemical networks in a single integrated platform. Here, we report the assessment of biochemical reactions in an Escherichia coli cell-free platform designed to activate natural metabolism, the Cytomim system. We reveal that central catabolism, oxidative phosphorylation, and protein synthesis can be co-activated in a single reaction system. Never before have these complex systems been shown to be simultaneously activated without living cells. The Cytomim system therefore promises to provide the metabolic foundation for diverse ab initio cell-free synthetic biology projects. In addition, we describe an improved Cytomim system with enhanced protein synthesis yields (up to 1200 mg/l in 2 h) and lower costs to facilitate production of protein therapeutics and biochemicals that are difficult to make in vivo because of their toxicity, complexity, or unusual cofactor requirements. PMID:18854819

  4. In vivo biochemical analyses reveal distinct roles of β-importins and eEF1A in tRNA subcellular traffic

    PubMed Central

    Huang, Hsiao-Yun

    2015-01-01

    Bidirectional tRNA movement between the nucleus and the cytoplasm serves multiple biological functions. To gain a biochemical understanding of the mechanisms for tRNA subcellular dynamics, we developed in vivo β-importin complex coimmunoprecipitation (co-IP) assays using budding yeast. Our studies provide the first in vivo biochemical evidence that two β-importin family members, Los1 (exportin-t) and Msn5 (exportin-5), serve overlapping but distinct roles in tRNA nuclear export. Los1 assembles complexes with RanGTP and tRNA. Both intron-containing pre-tRNAs and spliced tRNAs, regardless of whether they are aminoacylated, assemble into Los1–RanGTP complexes, documenting that Los1 participates in both primary nuclear export and re-export of tRNAs to the cytoplasm. In contrast, β-importin Msn5 preferentially assembles with RanGTP and spliced, aminoacylated tRNAs, documenting its role in tRNA nuclear re-export. Tef1/2 (the yeast form of translation elongation factor 1α [eEF1A]) aids the specificity of Msn5 for aminoacylated tRNAs to form a quaternary complex consisting of Msn5, RanGTP, aminoacylated tRNA, and Tef1/2. Assembly and/or stability of this quaternary complex requires Tef1/2, thereby facilitating efficient re-export of aminoacylated tRNAs to the cytoplasm. PMID:25838545

  5. An Integrated Qualitative and Quantitative Biochemical Model Learning Framework Using Evolutionary Strategy and Simulated Annealing.

    PubMed

    Wu, Zujian; Pang, Wei; Coghill, George M

    2015-01-01

    Both qualitative and quantitative model learning frameworks for biochemical systems have been studied in computational systems biology. In this research, after introducing two forms of pre-defined component patterns to represent biochemical models, we propose an integrative qualitative and quantitative modelling framework for inferring biochemical systems. In the proposed framework, interactions between reactants in the candidate models for a target biochemical system are evolved and eventually identified by the application of a qualitative model learning approach with an evolution strategy. Kinetic rates of the models generated from qualitative model learning are then further optimised by employing a quantitative approach with simulated annealing. Experimental results indicate that our proposed integrative framework is feasible to learn the relationships between biochemical reactants qualitatively and to make the model replicate the behaviours of the target system by optimising the kinetic rates quantitatively. Moreover, potential reactants of a target biochemical system can be discovered by hypothesising complex reactants in the synthetic models. Based on the biochemical models learned from the proposed framework, biologists can further perform experimental study in wet laboratory. In this way, natural biochemical systems can be better understood.

  6. Conceptual analysis of Physiology of vision in Ayurveda.

    PubMed

    Balakrishnan, Praveen; Ashwini, M J

    2014-07-01

    The process by which the world outside is seen is termed as visual process or physiology of vision. There are three phases in this visual process: phase of refraction of light, phase of conversion of light energy into electrical impulse and finally peripheral and central neurophysiology. With the advent of modern instruments step by step biochemical changes occurring at each level of the visual process has been deciphered. Many investigations have emerged to track these changes and helping to diagnose the exact nature of the disease. Ayurveda has described this physiology of vision based on the functions of vata and pitta. Philosophical textbook of ayurveda, Tarka Sangraha, gives certain basics facts of visual process. This article discusses the second and third phase of visual process. Step by step analysis of the visual process through the spectacles of ayurveda amalgamated with the basics of philosophy from Tarka Sangraha has been analyzed critically to generate a concrete idea regarding the physiology and hence thereby interpret the pathology on the grounds of ayurveda based on the investigative reports.

  7. Assessment of Molecular Construction in Undergraduate Biochemistry

    ERIC Educational Resources Information Center

    Booth, Deborah; Bateman, Robert C., Jr.; Sirochman, Rudy; Richardson, David C.; Richardson, Jane S.; Weiner, Steven W.; Farwell, Mary; Putnam-Evans, Cindy

    2005-01-01

    White and group used a two question, open-ended tests to separately evaluate students' learning of specific biochemical concepts in the general biology lecture and laboratory, in the first performance assessment of molecular visualization in teaching biochemistry. Two studies were devoted to protein structure using globins followed by one…

  8. The use of audio-visual methods in radiology and physics courses

    NASA Astrophysics Data System (ADS)

    Holmberg, Peter

    1987-03-01

    Today's medicine utilizes sophisticated equipment for radiological, biochemical and microbiological investigation procedures and analyses. Hence it is necessary that physicians have adequate scientific and technical knowledge of the apparatus they are using so that the equipment can be used in the most effective way. Partly this knowledge is obtained from science-orientated courses in the preclinical stage of the study program for medical students. To increase the motivation to study science-courses (medical physics) audio-visual methods are used to describe diagnostic and therapeutic procedures in the clinical routines.

  9. Computational Chemical Imaging for Cardiovascular Pathology: Chemical Microscopic Imaging Accurately Determines Cardiac Transplant Rejection

    PubMed Central

    Tiwari, Saumya; Reddy, Vijaya B.; Bhargava, Rohit; Raman, Jaishankar

    2015-01-01

    Rejection is a common problem after cardiac transplants leading to significant number of adverse events and deaths, particularly in the first year of transplantation. The gold standard to identify rejection is endomyocardial biopsy. This technique is complex, cumbersome and requires a lot of expertise in the correct interpretation of stained biopsy sections. Traditional histopathology cannot be used actively or quickly during cardiac interventions or surgery. Our objective was to develop a stain-less approach using an emerging technology, Fourier transform infrared (FT-IR) spectroscopic imaging to identify different components of cardiac tissue by their chemical and molecular basis aided by computer recognition, rather than by visual examination using optical microscopy. We studied this technique in assessment of cardiac transplant rejection to evaluate efficacy in an example of complex cardiovascular pathology. We recorded data from human cardiac transplant patients’ biopsies, used a Bayesian classification protocol and developed a visualization scheme to observe chemical differences without the need of stains or human supervision. Using receiver operating characteristic curves, we observed probabilities of detection greater than 95% for four out of five histological classes at 10% probability of false alarm at the cellular level while correctly identifying samples with the hallmarks of the immune response in all cases. The efficacy of manual examination can be significantly increased by observing the inherent biochemical changes in tissues, which enables us to achieve greater diagnostic confidence in an automated, label-free manner. We developed a computational pathology system that gives high contrast images and seems superior to traditional staining procedures. This study is a prelude to the development of real time in situ imaging systems, which can assist interventionists and surgeons actively during procedures. PMID:25932912

  10. Current status of the use of modalities in wound care: electrical stimulation and ultrasound therapy.

    PubMed

    Ennis, William J; Lee, Claudia; Plummer, Malgorzata; Meneses, Patricio

    2011-01-01

    Wound healing is a complex pathway that requires cells, an appropriate biochemical environment (i.e., cytokines, chemokines), an extracellular matrix, perfusion, and the application of both macrostrain and microstrain. The process is both biochemically complex and energy dependent. Healing can be assisted in difficult cases through the use of physical modalities. In the current literature, there is much debate over which treatment modality, dosage level, and timing is optimal. The mechanism of action for both electrical stimulation and ultrasound are reviewed along with possible clinical applications for the plastic surgeon.

  11. Declarative memory impairments following a military combat course: parallel neuropsychological and biochemical investigations.

    PubMed

    Piérard, Christophe; Béracochéa, Daniel; Pérès, Michel; Jouanin, Jean-Claude; Liscia, Pierrette; Satabin, Pascale; Martin, Serge; Testylier, Guy; Guézennec, Charles Yannick; Beaumont, Maurice

    2004-01-01

    The aim of this study was to investigate the impact on several forms of memory and metabolism of a 5-day combat course including heavy and continuous physical activities and sleep deprivation. Mnemonic performance and biochemical parameters of 21 male soldiers were examined before and at the end of the course. Our results showed that short-term memory (memory span, visual memory, audiovisual association) and long-term memory were significantly impaired, whereas short-term spatial memory and planning tasks were spared. Parallel biochemical analysis showed an adaptation of energy metabolism. The observed decrease in glycaemia may be partly responsible for the long-term memory impairment, whereas the decreases in plasma cholinesterases and choline may be involved in the short-term memory deterioration. However, there are also many other reasons for the observed memory changes, one of them being chronic sleep deprivation. Copyright 2004 S. Karger AG, Basel

  12. Synthesis, structural and biochemical activity studies of a new hexadentate Schiff base ligand and its Cu(II), Ni(II), and Co(II) complexes

    NASA Astrophysics Data System (ADS)

    Ekmekcioglu, Pinar; Karabocek, Nevin; Karabocek, Serdar; Emirik, Mustafa

    2015-11-01

    A new Schiff base ligand (H2L) and its metal complexes have been prepared and characterized by elemental analysis, magnetic moment and spectral studies. The comparative in-vitro antimicrobial activities against various pathogens with reference to known antibiotics activity under the standard control of different concentrations revealed that the metal complexes (6-8) showed enhanced antimicrobial activities in general as compared to free ligand. As an exception, the free ligand showed better activity against Trichoderma. The antifungal activity experiments were performed in triplicate. The order of biochemical activity for metal complexes were observed as in the following. CuL > CoL > NiL, which is exactly same as the order of stability constants of these complexes. Additionally, we performed DFT and TD-DFT calculation for free ligand and Cu(II) complex to support the experimental data. The geometries of the Cu(II) complex have been optimized using the B3LYP level of theory. The theoretical calculations confirm that the copper (II) center exhibits a distorted square pyramidal geometry which is favored by experimental results.

  13. Structure of soybean serine acetyltransferase and formation of the cysteine regulatory complex as a molecular chaperone

    USDA-ARS?s Scientific Manuscript database

    Serine acetyltransferase (SAT) catalyzes the limiting reaction in plant and microbial biosynthesis of cysteine. In addition to its enzymatic function, SAT forms a macromolecular complex with O-acetylserine sulfhydrylase (OASS). Formation of the cysteine regulatory complex (CRC) is a critical biochem...

  14. Complex Functions with GeoGebra

    ERIC Educational Resources Information Center

    Breda, Ana Maria D'azevedo; Dos Santos, José Manuel Dos Santos

    2016-01-01

    Complex functions, generally feature some interesting peculiarities, seen as extensions of real functions. The visualization of complex functions properties usually requires the simultaneous visualization of two-dimensional spaces. The multiple Windows of GeoGebra, combined with its ability of algebraic computation with complex numbers, allow the…

  15. Peptide-MHC-based nanomedicines for autoimmunity function as T-cell receptor microclustering devices

    NASA Astrophysics Data System (ADS)

    Singha, Santiswarup; Shao, Kun; Yang, Yang; Clemente-Casares, Xavier; Solé, Patricia; Clemente, Antonio; Blanco, Jesús; Dai, Qin; Song, Fayi; Liu, Shang Wan; Yamanouchi, Jun; Umeshappa, Channakeshava Sokke; Nanjundappa, Roopa Hebbandi; Detampel, Pascal; Amrein, Matthias; Fandos, César; Tanguay, Robert; Newbigging, Susan; Serra, Pau; Khadra, Anmar; Chan, Warren C. W.; Santamaria, Pere

    2017-07-01

    We have shown that nanoparticles (NPs) can be used as ligand-multimerization platforms to activate specific cellular receptors in vivo. Nanoparticles coated with autoimmune disease-relevant peptide-major histocompatibility complexes (pMHC) blunted autoimmune responses by triggering the differentiation and expansion of antigen-specific regulatory T cells in vivo. Here, we define the engineering principles impacting biological activity, detail a synthesis process yielding safe and stable compounds, and visualize how these nanomedicines interact with cognate T cells. We find that the triggering properties of pMHC-NPs are a function of pMHC intermolecular distance and involve the sustained assembly of large antigen receptor microclusters on murine and human cognate T cells. These compounds show no off-target toxicity in zebrafish embryos, do not cause haematological, biochemical or histological abnormalities, and are rapidly captured by phagocytes or processed by the hepatobiliary system. This work lays the groundwork for the design of ligand-based NP formulations to re-program in vivo cellular responses using nanotechnology.

  16. Hormones and the neuromuscular control of courtship in the golden-collared manakin (Manacus vitellinus)

    PubMed Central

    Schlinger, Barney A.; Barske, Julia; Day, Lainy; Fusani, Leonida; Fuxjager, Matthew J.

    2014-01-01

    Many animals engage in spectacular courtship displays, likely recruiting specialized neural, hormonal and muscular systems to facilitate these performances. Male golden-collared manakins (Manacus vitellinus) of Panamanian rainforests perform physically elaborate courtship displays that include novel forms of visual and acoustic signaling. We study the behavioral neuroendocrinology of this male’s courtship, combining field behavioral observations with anatomical, biochemical and molecular laboratory-based studies. Seasonally, male courtship is activated by testosterone with little correspondence between testosterone levels and display intensity. Females prefer males whose displays are exceptionally frequent, fast and accurate. The activation of androgen receptors (AR) is crucial for optimal display performance, with AR expressed at elevated levels in several neuromuscular tissues. Apparently, courtship enlists an elaborate androgen-dependent network that includes spinal motoneurons, skeletal muscles and somatosensory systems. This work highlights the value of studying non-traditional species to illuminate physiological adaptations and, hopefully, stimulates future research on other species with complex behaviors. PMID:23624091

  17. Cytology of pollutant metals in marine invertebrates: A review of microanalytical applications

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

    Nott, J.A.

    1991-03-01

    x-ray microanalysis (XRMA) is customized for investigations of the metabolic and detoxification strategies of heavy metals taken by marine organisms from polluted environments. Sites of uptake, intracellular accumulation, transport and excretion are visualized, analysed and quantified. Cryopreparation techniques are required to prevent the translocation or loss from specimens of soluble metal species. In marine invertebrates, metals are detoxified by systems of chemical binding and intracellular compartmentalization. XRMA investigations have concentrated on marine molluscs and crustaceans and even within these restricted groups there are marked inter-species differences in the biochemical and cytological processes which reduce metal bioavailability. Some detoxification systems alsomore » protect the carnivores which ingest the metal-laden tissues of the prey. This results in the bioreduction of metals along a food chain. These processes are investigated by XRMA which can be tuned to observe the complex interactions which operate at all levels within and between the biota and polluted environments. 90 refs.« less

  18. Profiling Synaptic Proteins Identifies Regulators of Insulin Secretion and Lifespan

    PubMed Central

    Kaplan, Joshua M.

    2008-01-01

    Cells are organized into distinct compartments to perform specific tasks with spatial precision. In neurons, presynaptic specializations are biochemically complex subcellular structures dedicated to neurotransmitter secretion. Activity-dependent changes in the abundance of presynaptic proteins are thought to endow synapses with different functional states; however, relatively little is known about the rules that govern changes in the composition of presynaptic terminals. We describe a genetic strategy to systematically analyze protein localization at Caenorhabditis elegans presynaptic specializations. Nine presynaptic proteins were GFP-tagged, allowing visualization of multiple presynaptic structures. Changes in the distribution and abundance of these proteins were quantified in 25 mutants that alter different aspects of neurotransmission. Global analysis of these data identified novel relationships between particular presynaptic components and provides a new method to compare gene functions by identifying shared protein localization phenotypes. Using this strategy, we identified several genes that regulate secretion of insulin-like growth factors (IGFs) and influence lifespan in a manner dependent on insulin/IGF signaling. PMID:19043554

  19. The Study of Learners' Preference for Visual Complexity on Small Screens of Mobile Computers Using Neural Networks

    ERIC Educational Resources Information Center

    Wang, Lan-Ting; Lee, Kun-Chou

    2014-01-01

    The vision plays an important role in educational technologies because it can produce and communicate quite important functions in teaching and learning. In this paper, learners' preference for the visual complexity on small screens of mobile computers is studied by neural networks. The visual complexity in this study is divided into five…

  20. A systems biology approach toward understanding seed composition in soybean.

    PubMed

    Li, Ling; Hur, Manhoi; Lee, Joon-Yong; Zhou, Wenxu; Song, Zhihong; Ransom, Nick; Demirkale, Cumhur Yusuf; Nettleton, Dan; Westgate, Mark; Arendsee, Zebulun; Iyer, Vidya; Shanks, Jackie; Nikolau, Basil; Wurtele, Eve Syrkin

    2015-01-01

    The molecular, biochemical, and genetic mechanisms that regulate the complex metabolic network of soybean seed development determine the ultimate balance of protein, lipid, and carbohydrate stored in the mature seed. Many of the genes and metabolites that participate in seed metabolism are unknown or poorly defined; even more remains to be understood about the regulation of their metabolic networks. A global omics analysis can provide insights into the regulation of seed metabolism, even without a priori assumptions about the structure of these networks. With the future goal of predictive biology in mind, we have combined metabolomics, transcriptomics, and metabolic flux technologies to reveal the global developmental and metabolic networks that determine the structure and composition of the mature soybean seed. We have coupled this global approach with interactive bioinformatics and statistical analyses to gain insights into the biochemical programs that determine soybean seed composition. For this purpose, we used Plant/Eukaryotic and Microbial Metabolomics Systems Resource (PMR, http://www.metnetdb.org/pmr, a platform that incorporates metabolomics data to develop hypotheses concerning the organization and regulation of metabolic networks, and MetNet systems biology tools http://www.metnetdb.org for plant omics data, a framework to enable interactive visualization of metabolic and regulatory networks. This combination of high-throughput experimental data and bioinformatics analyses has revealed sets of specific genes, genetic perturbations and mechanisms, and metabolic changes that are associated with the developmental variation in soybean seed composition. Researchers can explore these metabolomics and transcriptomics data interactively at PMR.

  1. Synthesis, structure, biochemical, and docking studies of a new dinitrosyl iron complex [Fe2(μ-SC4H3SCH2)2(NO)4

    NASA Astrophysics Data System (ADS)

    Davidovich, P. B.; Fischer, A. I.; Korchagin, D. V.; Panchuk, V. V.; Shchukarev, A. V.; Garabadzhiu, A. V.; Belyaev, A. N.

    2015-07-01

    A new dinitrosyl iron complex of binuclear structure [Fe2(μ-S-2-methylthiophene)2(NO)4] was first synthesized and structurally characterized by XRD and theoretical methods. Using caspase-3 as an example it was shown that [Fe2(μ-S-2-methylthiophene)2(NO)4] and its analog [Fe2(μ-S-2-methylfurane)2(NO)4] can inhibit the action of active site cysteine proteins; the difference in inhibitory activity was explained by molecular docking studies. Biochemical and in silico studies give grounds that the biological activity of dinitrosyl iron complexes is a μ-SR bridging ligand structure function. Thus the rational design strategy of [Fe2(μ-SR)2(NO)4] complexes can be applied to make NO prodrugs with high affinity to therapeutically significant targets involved in cancer and inflammation.

  2. Rac1 GTPase activates the WAVE regulatory complex through two distinct binding sites.

    PubMed

    Chen, Baoyu; Chou, Hui-Ting; Brautigam, Chad A; Xing, Wenmin; Yang, Sheng; Henry, Lisa; Doolittle, Lynda K; Walz, Thomas; Rosen, Michael K

    2017-09-26

    The Rho GTPase Rac1 activates the WAVE regulatory complex (WRC) to drive Arp2/3 complex-mediated actin polymerization, which underpins diverse cellular processes. Here we report the structure of a WRC-Rac1 complex determined by cryo-electron microscopy. Surprisingly, Rac1 is not located at the binding site on the Sra1 subunit of the WRC previously identified by mutagenesis and biochemical data. Rather, it binds to a distinct, conserved site on the opposite end of Sra1. Biophysical and biochemical data on WRC mutants confirm that Rac1 binds to both sites, with the newly identified site having higher affinity and both sites required for WRC activation. Our data reveal that the WRC is activated by simultaneous engagement of two Rac1 molecules, suggesting a mechanism by which cells may sense the density of active Rac1 at membranes to precisely control actin assembly.

  3. Visual analysis and exploration of complex corporate shareholder networks

    NASA Astrophysics Data System (ADS)

    Tekušová, Tatiana; Kohlhammer, Jörn

    2008-01-01

    The analysis of large corporate shareholder network structures is an important task in corporate governance, in financing, and in financial investment domains. In a modern economy, large structures of cross-corporation, cross-border shareholder relationships exist, forming complex networks. These networks are often difficult to analyze with traditional approaches. An efficient visualization of the networks helps to reveal the interdependent shareholding formations and the controlling patterns. In this paper, we propose an effective visualization tool that supports the financial analyst in understanding complex shareholding networks. We develop an interactive visual analysis system by combining state-of-the-art visualization technologies with economic analysis methods. Our system is capable to reveal patterns in large corporate shareholder networks, allows the visual identification of the ultimate shareholders, and supports the visual analysis of integrated cash flow and control rights. We apply our system on an extensive real-world database of shareholder relationships, showing its usefulness for effective visual analysis.

  4. Mathematical treatment of isotopologue and isotopomer speciation and fractionation in biochemical kinetics

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

    Maggi, F.M.; Riley, W.J.

    2009-11-01

    We present a mathematical treatment of the kinetic equations that describe isotopologue and isotopomer speciation and fractionation during enzyme-catalyzed biochemical reactions. These equations, presented here with the name GEBIK (general equations for biochemical isotope kinetics) and GEBIF (general equations for biochemical isotope fractionation), take into account microbial biomass and enzyme dynamics, reaction stoichiometry, isotope substitution number, and isotope location within each isotopologue and isotopomer. In addition to solving the complete GEBIK and GEBIF, we also present and discuss two approximations to the full solutions under the assumption of biomass-free and enzyme steady-state, and under the quasi-steady-state assumption as applied tomore » the complexation rate. The complete and approximate approaches are applied to observations of biological denitrification in soils. Our analysis highlights that the full GEBIK and GEBIF provide a more accurate description of concentrations and isotopic compositions of substrates and products throughout the reaction than do the approximate forms. We demonstrate that the isotopic effects of a biochemical reaction depend, in the most general case, on substrate and complex concentrations and, therefore, the fractionation factor is a function of time. We also demonstrate that inverse isotopic effects can occur for values of the fractionation factor smaller than 1, and that reactions that do not discriminate isotopes do not necessarily imply a fractionation factor equal to 1.« less

  5. The Effects of Visual Complexity for Japanese Kanji Processing with High and Low Frequencies

    ERIC Educational Resources Information Center

    Tamaoka, Katsuo; Kiyama, Sachiko

    2013-01-01

    The present study investigated the effects of visual complexity for kanji processing by selecting target kanji from different stroke ranges of visually simple (2-6 strokes), medium (8-12 strokes), and complex (14-20 strokes) kanji with high and low frequencies. A kanji lexical decision task in Experiment 1 and a kanji naming task in Experiment 2…

  6. Distinguishing between biochemical and cellular function: Are there peptide signatures for cellular function of proteins?

    PubMed

    Jain, Shruti; Bhattacharyya, Kausik; Bakshi, Rachit; Narang, Ankita; Brahmachari, Vani

    2017-04-01

    The genome annotation and identification of gene function depends on conserved biochemical activity. However, in the cell, proteins with the same biochemical function can participate in different cellular pathways and cannot complement one another. Similarly, two proteins of very different biochemical functions are put in the same class of cellular function; for example, the classification of a gene as an oncogene or a tumour suppressor gene is not related to its biochemical function, but is related to its cellular function. We have taken an approach to identify peptide signatures for cellular function in proteins with known biochemical function. ATPases as a test case, we classified ATPases (2360 proteins) and kinases (517 proteins) from the human genome into different cellular function categories such as transcriptional, replicative, and chromatin remodelling proteins. Using publicly available tool, MEME, we identify peptide signatures shared among the members of a given category but not between cellular functional categories; for example, no motif sharing is seen between chromatin remodelling and transporter ATPases, similarly between receptor Serine/Threonine Kinase and Receptor Tyrosine Kinase. There are motifs shared within each category with significant E value and high occurrence. This concept of signature for cellular function was applied to developmental regulators, the polycomb and trithorax proteins which led to the prediction of the role of INO80, a chromatin remodelling protein, in development. This has been experimentally validated earlier for its role in homeotic gene regulation and its interaction with regulatory complexes like the Polycomb and Trithorax complex. Proteins 2017; 85:682-693. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. Visualizing Chemical Interaction Dynamics of Confined DNA Molecules

    NASA Astrophysics Data System (ADS)

    Henkin, Gilead; Berard, Daniel; Stabile, Frank; Leslie, Sabrina

    We present a novel nanofluidic approach to controllably introducing reagent molecules to interact with confined biopolymers and visualizing the reaction dynamics in real time. By dynamically deforming a flow cell using CLiC (Convex Lens-induced Confinement) microscopy, we are able to tune reaction chamber dimensions from micrometer to nanometer scales. We apply this gentle deformation to load and extend DNA polymers within embedded nanotopographies and visualize their interactions with other molecules in solution. Quantifying the change in configuration of polymers within embedded nanotopographies in response to binding/unbinding of reagent molecules provides new insights into their consequent change in physical properties. CLiC technology enables an ultra sensitive, massively parallel biochemical analysis platform which can acces a broader range of interaction parameters than existing devices.

  8. Metabonomics and medicine: the Biochemical Oracle.

    PubMed

    Mitchell, Steve; Holmes, Elaine; Carmichael, Paul

    2002-10-01

    Occasionally, a new idea emerges that has the potential to revolutionize an entire field of scientific endeavour. It is now within our grasp to be able to detect subtle perturbations within the phenomenally complex biochemical matrix of living organisms. The discipline of metabonomics promises an all-encompassing approach to understanding total, yet fundamental, changes occurring in disease processes, drug toxicity and cell function.

  9. CAP/ACMG proficiency testing for biochemical genetics laboratories: a summary of performance.

    PubMed

    Oglesbee, Devin; Cowan, Tina M; Pasquali, Marzia; Wood, Timothy C; Weck, Karen E; Long, Thomas; Palomaki, Glenn E

    2018-01-01

    PurposeTesting for inborn errors of metabolism is performed by clinical laboratories worldwide, each utilizing laboratory-developed procedures. We sought to summarize performance in the College of American Pathologists' (CAP) proficiency testing (PT) program and identify opportunities for improving laboratory quality. When evaluating PT data, we focused on a subset of laboratories that have participated in at least one survey since 2010.MethodsAn analysis of laboratory performance (2004 to 2014) on the Biochemical Genetics PT Surveys, a program administered by CAP and the American College of Medical Genetics and Genomics. Analytical and interpretive performance was evaluated for four tests: amino acids, organic acids, acylcarnitines, and mucopolysaccharides.ResultsSince 2010, 150 laboratories have participated in at least one of four PT surveys. Analytic sensitivities ranged from 88.2 to 93.4%, while clinical sensitivities ranged from 82.4 to 91.0%. Performance was higher for US participants and for more recent challenges. Performance was lower for challenges with subtle findings or complex analytical patterns.ConclusionUS clinical biochemical genetics laboratory proficiency is satisfactory, with a minority of laboratories accounting for the majority of errors. Our findings underscore the complex nature of clinical biochemical genetics testing and highlight the necessity of continuous quality management.

  10. Computational multiscale modeling in protein--ligand docking.

    PubMed

    Taufer, Michela; Armen, Roger; Chen, Jianhan; Teller, Patricia; Brooks, Charles

    2009-01-01

    In biological systems, the binding of small molecule ligands to proteins is a crucial process for almost every aspect of biochemistry and molecular biology. Enzymes are proteins that function by catalyzing specific biochemical reactions that convert reactants into products. Complex organisms are typically composed of cells in which thousands of enzymes participate in complex and interconnected biochemical pathways. Some enzymes serve as sequential steps in specific pathways (such as energy metabolism), while others function to regulate entire pathways and cellular functions [1]. Small molecule ligands can be designed to bind to a specific enzyme and inhibit the biochemical reaction. Inhibiting the activity of key enzymes may result in the entire biochemical pathways being turned on or off [2], [3]. Many small molecule drugs marketed today function in this generic way as enzyme inhibitors. If research identifies a specific enzyme as being crucial to the progress of disease, then this enzyme may be targeted with an inhibitor, which may slow down or reverse the progress of disease. In this way, enzymes are targeted from specific pathogens (e.g., virus, bacteria, fungi) for infectious diseases [4], [5], and human enzymes are targeted for noninfectious diseases such as cardiovascular disease, cancer, diabetes, and neurodegenerative diseases [6].

  11. In vivo biochemical analyses reveal distinct roles of β-importins and eEF1A in tRNA subcellular traffic.

    PubMed

    Huang, Hsiao-Yun; Hopper, Anita K

    2015-04-01

    Bidirectional tRNA movement between the nucleus and the cytoplasm serves multiple biological functions. To gain a biochemical understanding of the mechanisms for tRNA subcellular dynamics, we developed in vivo β-importin complex coimmunoprecipitation (co-IP) assays using budding yeast. Our studies provide the first in vivo biochemical evidence that two β-importin family members, Los1 (exportin-t) and Msn5 (exportin-5), serve overlapping but distinct roles in tRNA nuclear export. Los1 assembles complexes with RanGTP and tRNA. Both intron-containing pre-tRNAs and spliced tRNAs, regardless of whether they are aminoacylated, assemble into Los1-RanGTP complexes, documenting that Los1 participates in both primary nuclear export and re-export of tRNAs to the cytoplasm. In contrast, β-importin Msn5 preferentially assembles with RanGTP and spliced, aminoacylated tRNAs, documenting its role in tRNA nuclear re-export. Tef1/2 (the yeast form of translation elongation factor 1α [eEF1A]) aids the specificity of Msn5 for aminoacylated tRNAs to form a quaternary complex consisting of Msn5, RanGTP, aminoacylated tRNA, and Tef1/2. Assembly and/or stability of this quaternary complex requires Tef1/2, thereby facilitating efficient re-export of aminoacylated tRNAs to the cytoplasm. © 2015 Huang and Hopper; Published by Cold Spring Harbor Laboratory Press.

  12. Combining Flux Balance and Energy Balance Analysis for Large-Scale Metabolic Network: Biochemical Circuit Theory for Analysis of Large-Scale Metabolic Networks

    NASA Technical Reports Server (NTRS)

    Beard, Daniel A.; Liang, Shou-Dan; Qian, Hong; Biegel, Bryan (Technical Monitor)

    2001-01-01

    Predicting behavior of large-scale biochemical metabolic networks represents one of the greatest challenges of bioinformatics and computational biology. Approaches, such as flux balance analysis (FBA), that account for the known stoichiometry of the reaction network while avoiding implementation of detailed reaction kinetics are perhaps the most promising tools for the analysis of large complex networks. As a step towards building a complete theory of biochemical circuit analysis, we introduce energy balance analysis (EBA), which compliments the FBA approach by introducing fundamental constraints based on the first and second laws of thermodynamics. Fluxes obtained with EBA are thermodynamically feasible and provide valuable insight into the activation and suppression of biochemical pathways.

  13. Promising New Photon Detection Concepts for High-Resolution Clinical and Preclinical PET

    PubMed Central

    Levin, Craig S.

    2013-01-01

    The ability of PET to visualize and quantify regions of low concentration of PET tracer representing subtle cellular and molecular signatures of disease depends on relatively complex biochemical, biologic, and physiologic factors that are challenging to control, as well as on instrumentation performance parameters that are, in principle, still possible to improve on. Thus, advances to the latter can somewhat offset barriers of the former. PET system performance parameters such as spatial resolution, contrast resolution, and photon sensitivity contribute significantly to PET’s ability to visualize and quantify lower concentrations of signal in the presence of background. In this report we present some technology innovations under investigation toward improving these PET system performance parameters. We focus particularly on a promising advance known as 3-dimensional position-sensitive detectors, which are detectors capable of distinguishing and measuring the position, energy, and arrival time of individual interactions of multi-interaction photon events in 3 dimensions. If successful, these new strategies enable enhancements such as the detection of fewer diseased cells in tissue or the ability to characterize lower-abundance molecular targets within cells. Translating these advanced capabilities to the clinic might allow expansion of PET’s roles in disease management, perhaps to earlier stages of disease. In preclinical research, such enhancements enable more sensitive and accurate studies of disease biology in living subjects. PMID:22302960

  14. Schizophrenia: an integrative approach to modelling a complex disorder

    PubMed Central

    Robertson, George S.; Hori, Sarah E.; Powell, Kelly J.

    2006-01-01

    The discovery of candidate susceptibility genes for schizophrenia and the generation of mice lacking proteins that reproduce biochemical processes that are disrupted in this mental illness offer unprecedented opportunities for improved modelling of this complex disorder. Several lines of evidence indicate that obstetrical complications, as well as fetal or neonatal exposure to viral infection, are predisposing events for some forms of schizophrenia. These environmental events can be modelled in animals, resulting in some of the characteristic features of schizophrenia; however, animal models have yet to be developed that encompass both environmental and genetic aspects of this mental illness. A large number of candidate schizophrenia susceptibility genes have been identified that encode proteins implicated in the regulation of synaptic plasticity, neurotransmission, neuronal migration, cell adherence, signal transduction, energy metabolism and neurite outgrowth. In support of the importance of these processes in schizophrenia, mice that have reduced levels or completely lack proteins that control glutamatergic neurotransmission, neuronal migration, cell adherence, signal transduction, neurite outgrowth and synaptic plasticity display many features reminiscent of schizophrenia. In the present review, we discuss strategies for modelling schizophrenia that involve treating mice that bear these mutations in a variety of ways to better model both environmental and genetic factors responsible for this complex mental illness according to a “two-hit hypothesis.” Because rodents are able to perform complex cognitive tasks using odour but not visual or auditory cues, we hypothesize that olfactory-based tests of cognitive performance should be used to search for novel therapeutics that ameliorate the cognitive deficits that are a feature of this devastating mental disorder. PMID:16699601

  15. Biochemical and molecular diagnosis of tyrosinemia type I with two novel FAH mutations in a Hong Kong chinese patient: recommendation for expanded newborn screening in Hong Kong.

    PubMed

    Mak, Chloe Miu; Lam, Ching-Wan; Chim, Stella; Siu, Tak-Shing; Ng, King-Fai; Tam, Sidney

    2013-01-01

    Tyrosinemia type I is an autosomal recessive disorder in tyrosine metabolism. In areas without expanded newborn screening, patients present with acute hepatorenal failure in early infancy. Diagnosis can be elusive when clinical presentation is non-specific and biochemical abnormalities are masked by secondary changes. This is the first Hong Kong Chinese report. A two-month-old Chinese male infant with unremarkable antenatal and postnatal history presented with progressive abdominal distension for three days. He suffered from end-stage liver failure, hypoglycemia and hepatic encephalopathy. Diagnostic work-up was complicated starting from rule-out sepsis, intestinal obstruction, volvulus, peritonitis, septic ileus, poisoning to metabolic diseases. Clinical, biochemical and genetic data was described. The patient showed increases in multiple plasma amino acids including tyrosine, phenylalanine and methionine, and hyper-excretions of 4-hydroxyphenyl-acetate, -pyruvate, and -lactate, as well as N-acetyltyrosine which could be seen in liver failure due to both tyrosinemia type I and non-metabolic conditions. Because of the volatile nature, succinylacetone was almost undetectable. The diagnosis was confirmed by genetic analysis of FAH with two novel mutations, viz. NM_000137.2:c.1063-1G>A and NM_000137.2:c.1035_1037del. Living-related liver transplantation was done. However, the patient still suffered many complications after the severe metabolic insult with hypoxic ischemic encephalopathy, cerebral atrophy, global developmental delay and cortical visual impairment. Because of the lack of expanded newborn screening in Hong Kong, this child unfortunately presented in the most severe form of tyrosinemia type I. Expanded newborn screening can save life and reduce the burden of diagnostic complexity. This illustrates the need for expanded newborn screening in Hong Kong. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  16. Metabolomics, Standards, and Metabolic Modeling for Synthetic Biology in Plants

    PubMed Central

    Hill, Camilla Beate; Czauderna, Tobias; Klapperstück, Matthias; Roessner, Ute; Schreiber, Falk

    2015-01-01

    Life on earth depends on dynamic chemical transformations that enable cellular functions, including electron transfer reactions, as well as synthesis and degradation of biomolecules. Biochemical reactions are coordinated in metabolic pathways that interact in a complex way to allow adequate regulation. Biotechnology, food, biofuel, agricultural, and pharmaceutical industries are highly interested in metabolic engineering as an enabling technology of synthetic biology to exploit cells for the controlled production of metabolites of interest. These approaches have only recently been extended to plants due to their greater metabolic complexity (such as primary and secondary metabolism) and highly compartmentalized cellular structures and functions (including plant-specific organelles) compared with bacteria and other microorganisms. Technological advances in analytical instrumentation in combination with advances in data analysis and modeling have opened up new approaches to engineer plant metabolic pathways and allow the impact of modifications to be predicted more accurately. In this article, we review challenges in the integration and analysis of large-scale metabolic data, present an overview of current bioinformatics methods for the modeling and visualization of metabolic networks, and discuss approaches for interfacing bioinformatics approaches with metabolic models of cellular processes and flux distributions in order to predict phenotypes derived from specific genetic modifications or subjected to different environmental conditions. PMID:26557642

  17. Effects of Radiographic Contrast Media on the Micromorphology of the Junctional Complex of Erythrocytes Visualized by Immunocytology

    PubMed Central

    Franke, Ralf-Peter; Krüger, Anne; Scharnweber, Tim; Wenzel, Folker; Jung, Friedrich

    2014-01-01

    Effects of radiographic contrast media (RCM) application were demonstrated in vitro and in vivo where the injection of RCM into the A. axillaris of patients with coronary artery disease was followed by a significant and RCM-dependent decrease of erythrocyte velocity in downstream skin capillaries. Another study in pigs revealed that the deceleration of erythrocytes coincided with a significant reduction of the oxygen partial pressure in the myocardium—supplied by the left coronary artery—after the administration of RCM into this artery. Further reports showed RCM dependent alterations of erythrocytes like echinocyte formation and exocytosis, sequestration of actin or band 3 and the buckling of endothelial cells coinciding with a formation of interendothelial fenestrations leading to areas devoid of endothelial cells. Key to morphological alterations of erythrocytes is the membrane cytoskeleton, which is linked to the band 3 in the erythrocyte membrane via the junctional complex. Fundamental observations regarding the cell biological and biochemical aspects of the structure and function of the cell membrane and the membrane cytoskeleton of erythrocytes have been reported. This review focuses on recent results gained, e.g., by advanced confocal laser scanning microscopy of different double-stained structural elements of the erythrocyte membrane cytoskeleton. PMID:25222553

  18. PRince: a web server for structural and physicochemical analysis of protein-RNA interface.

    PubMed

    Barik, Amita; Mishra, Abhishek; Bahadur, Ranjit Prasad

    2012-07-01

    We have developed a web server, PRince, which analyzes the structural features and physicochemical properties of the protein-RNA interface. Users need to submit a PDB file containing the atomic coordinates of both the protein and the RNA molecules in complex form (in '.pdb' format). They should also mention the chain identifiers of interacting protein and RNA molecules. The size of the protein-RNA interface is estimated by measuring the solvent accessible surface area buried in contact. For a given protein-RNA complex, PRince calculates structural, physicochemical and hydration properties of the interacting surfaces. All these parameters generated by the server are presented in a tabular format. The interacting surfaces can also be visualized with software plug-in like Jmol. In addition, the output files containing the list of the atomic coordinates of the interacting protein, RNA and interface water molecules can be downloaded. The parameters generated by PRince are novel, and users can correlate them with the experimentally determined biophysical and biochemical parameters for better understanding the specificity of the protein-RNA recognition process. This server will be continuously upgraded to include more parameters. PRince is publicly accessible and free for use. Available at http://www.facweb.iitkgp.ernet.in/~rbahadur/prince/home.html.

  19. Next Generation Tissue Engineering of Orthopedic Soft Tissue-to-Bone Interfaces.

    PubMed

    Boys, Alexander J; McCorry, Mary Clare; Rodeo, Scott; Bonassar, Lawrence J; Estroff, Lara A

    2017-09-01

    Soft tissue-to-bone interfaces are complex structures that consist of gradients of extracellular matrix materials, cell phenotypes, and biochemical signals. These interfaces, called entheses for ligaments, tendons, and the meniscus, are crucial to joint function, transferring mechanical loads and stabilizing orthopedic joints. When injuries occur to connected soft tissue, the enthesis must be re-established to restore function, but due to structural complexity, repair has proven challenging. Tissue engineering offers a promising solution for regenerating these tissues. This prospective review discusses methodologies for tissue engineering the enthesis, outlined in three key design inputs: materials processing methods, cellular contributions, and biochemical factors.

  20. Next Generation Tissue Engineering of Orthopedic Soft Tissue-to-Bone Interfaces

    PubMed Central

    Boys, Alexander J.; McCorry, Mary Clare; Rodeo, Scott; Bonassar, Lawrence J.; Estroff, Lara A.

    2017-01-01

    Soft tissue-to-bone interfaces are complex structures that consist of gradients of extracellular matrix materials, cell phenotypes, and biochemical signals. These interfaces, called entheses for ligaments, tendons, and the meniscus, are crucial to joint function, transferring mechanical loads and stabilizing orthopedic joints. When injuries occur to connected soft tissue, the enthesis must be re-established to restore function, but due to structural complexity, repair has proven challenging. Tissue engineering offers a promising solution for regenerating these tissues. This prospective review discusses methodologies for tissue engineering the enthesis, outlined in three key design inputs: materials processing methods, cellular contributions, and biochemical factors. PMID:29333332

  1. Fornix and medial temporal lobe lesions lead to comparable deficits in complex visual perception.

    PubMed

    Lech, Robert K; Koch, Benno; Schwarz, Michael; Suchan, Boris

    2016-05-04

    Recent research dealing with the structures of the medial temporal lobe (MTL) has shifted away from exclusively investigating memory-related processes and has repeatedly incorporated the investigation of complex visual perception. Several studies have demonstrated that higher level visual tasks can recruit structures like the hippocampus and perirhinal cortex in order to successfully perform complex visual discriminations, leading to a perceptual-mnemonic or representational view of the medial temporal lobe. The current study employed a complex visual discrimination paradigm in two patients suffering from brain lesions with differing locations and origin. Both patients, one with extensive medial temporal lobe lesions (VG) and one with a small lesion of the anterior fornix (HJK), were impaired in complex discriminations while showing otherwise mostly intact cognitive functions. The current data confirmed previous results while also extending the perceptual-mnemonic theory of the MTL to the main output structure of the hippocampus, the fornix. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Tailored information for cancer patients on the Internet: effects of visual cues and language complexity on information recall and satisfaction.

    PubMed

    van Weert, Julia C M; van Noort, Guda; Bol, Nadine; van Dijk, Liset; Tates, Kiek; Jansen, Jesse

    2011-09-01

    This study was designed to investigate the effects of visual cues and language complexity on satisfaction and information recall using a personalised website for lung cancer patients. In addition, age effects were investigated. An experiment using a 2 (complex vs. non-complex language)×3 (text only vs. photograph vs. drawing) factorial design was conducted. In total, 200 respondents without cancer were exposed to one of the six conditions. Respondents were more satisfied with the comprehensibility of both websites when they were presented with a visual cue. A significant interaction effect was found between language complexity and photograph use such that satisfaction with comprehensibility improved when a photograph was added to the complex language condition. Next, an interaction effect was found between age and satisfaction, which indicates that adding a visual cue is more important for older adults than younger adults. Finally, respondents who were exposed to a website with less complex language showed higher recall scores. The use of visual cues enhances satisfaction with the information presented on the website, and the use of non-complex language improves recall. The results of the current study can be used to improve computer-based information systems for patients. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  3. Using complex auditory-visual samples to produce emergent relations in children with autism.

    PubMed

    Groskreutz, Nicole C; Karsina, Allen; Miguel, Caio F; Groskreutz, Mark P

    2010-03-01

    Six participants with autism learned conditional relations between complex auditory-visual sample stimuli (dictated words and pictures) and simple visual comparisons (printed words) using matching-to-sample training procedures. Pre- and posttests examined potential stimulus control by each element of the complex sample when presented individually and emergence of additional conditional relations and oral labeling. Tests revealed class-consistent performance for all participants following training.

  4. Sub-Chronic Neuropathological and Biochemical Changes in Mouse Visual System after Repetitive Mild Traumatic Brain Injury

    PubMed Central

    Tzekov, Radouil; Dawson, Clint; Orlando, Megan; Mouzon, Benoit; Reed, Jon; Evans, James; Crynen, Gogce; Mullan, Michael; Crawford, Fiona

    2016-01-01

    Repetitive mild traumatic brain injury (r-mTBI) results in neuropathological and biochemical consequences in the human visual system. Using a recently developed mouse model of r-mTBI, with control mice receiving repetitive anesthesia alone (r-sham) we assessed the effects on the retina and optic nerve using histology, immunohistochemistry, proteomic and lipidomic analyses at 3 weeks post injury. Retina tissue was used to determine retinal ganglion cell (RGC) number, while optic nerve tissue was examined for cellularity, myelin content, protein and lipid changes. Increased cellularity and areas of demyelination were clearly detectable in optic nerves in r-mTBI, but not in r-sham. These changes were accompanied by a ~25% decrease in the total number of Brn3a-positive RGCs. Proteomic analysis of the optic nerves demonstrated various changes consistent with a negative effect of r-mTBI on major cellular processes like depolymerization of microtubules, disassembly of filaments and loss of neurons, manifested by decrease of several proteins, including neurofilaments (NEFH, NEFM, NEFL), tubulin (TUBB2A, TUBA4A), microtubule-associated proteins (MAP1A, MAP1B), collagen (COL6A1, COL6A3) and increased expression of other proteins, including heat shock proteins (HSP90B1, HSPB1), APOE and cathepsin D. Lipidomic analysis showed quantitative changes in a number of phospholipid species, including a significant increase in the total amount of lysophosphatidylcholine (LPC), including the molecular species 16:0, a known demyelinating agent. The overall amount of some ether phospholipids, like ether LPC, ether phosphatidylcholine and ether lysophosphatidylethanolamine were also increased, while the majority of individual molecular species of ester phospholipids, like phosphatidylcholine and phosphatidylethanolamine, were decreased. Results from the biochemical analysis correlate well with changes detected by histological and immunohistochemical methods and indicate the involvement of several important molecular pathways. This will allow future identification of therapeutic targets for improving the visual consequences of r-mTBI. PMID:27088355

  5. Centrifugal multiplexing fixed-volume dispenser on a plastic lab-on-a-disk for parallel biochemical single-end-point assays

    PubMed Central

    La, Moonwoo; Park, Sang Min; Kim, Dong Sung

    2015-01-01

    In this study, a multiple sample dispenser for precisely metered fixed volumes was successfully designed, fabricated, and fully characterized on a plastic centrifugal lab-on-a-disk (LOD) for parallel biochemical single-end-point assays. The dispenser, namely, a centrifugal multiplexing fixed-volume dispenser (C-MUFID) was designed with microfluidic structures based on the theoretical modeling about a centrifugal circumferential filling flow. The designed LODs were fabricated with a polystyrene substrate through micromachining and they were thermally bonded with a flat substrate. Furthermore, six parallel metering and dispensing assays were conducted at the same fixed-volume (1.27 μl) with a relative variation of ±0.02 μl. Moreover, the samples were metered and dispensed at different sub-volumes. To visualize the metering and dispensing performances, the C-MUFID was integrated with a serpentine micromixer during parallel centrifugal mixing tests. Parallel biochemical single-end-point assays were successfully conducted on the developed LOD using a standard serum with albumin, glucose, and total protein reagents. The developed LOD could be widely applied to various biochemical single-end-point assays which require different volume ratios of the sample and reagent by controlling the design of the C-MUFID. The proposed LOD is feasible for point-of-care diagnostics because of its mass-producible structures, reliable metering/dispensing performance, and parallel biochemical single-end-point assays, which can identify numerous biochemical. PMID:25610516

  6. "Chemical transformers" from nanoparticle ensembles operated with logic.

    PubMed

    Motornov, Mikhail; Zhou, Jian; Pita, Marcos; Gopishetty, Venkateshwarlu; Tokarev, Ihor; Katz, Evgeny; Minko, Sergiy

    2008-09-01

    The pH-responsive nanoparticles were coupled with information-processing enzyme-based systems to yield "smart" signal-responsive hybrid systems with built-in Boolean logic. The enzyme systems performed AND/OR logic operations, transducing biochemical input signals into reversible structural changes (signal-directed self-assembly) of the nanoparticle assemblies, thus resulting in the processing and amplification of the biochemical signals. The hybrid system mimics biological systems in effective processing of complex biochemical information, resulting in reversible changes of the self-assembled structures of the nanoparticles. The bioinspired approach to the nanostructured morphing materials could be used in future self-assembled molecular robotic systems.

  7. Visualizing biological reaction intermediates with DNA curtains

    NASA Astrophysics Data System (ADS)

    Zhao, Yiling; Jiang, Yanzhou; Qi, Zhi

    2017-04-01

    Single-molecule approaches have tremendous potential analyzing dynamic biological reaction with heterogeneity that cannot be effectively accessed via traditional ensemble-level biochemical approaches. The approach of deoxyribonucleic acid (DNA) curtains developed by Dr Eric Greene and his research team at Columbia University is a high-throughput single-molecule technique that utilizes fluorescent imaging to visualize protein-DNA interactions directly and allows the acquisition of statistically relevant information from hundreds or even thousands of individual reactions. This review aims to summarize the past, present, and future of DNA curtains, with an emphasis on its applications to solve important biological questions.

  8. MetExploreViz: web component for interactive metabolic network visualization.

    PubMed

    Chazalviel, Maxime; Frainay, Clément; Poupin, Nathalie; Vinson, Florence; Merlet, Benjamin; Gloaguen, Yoann; Cottret, Ludovic; Jourdan, Fabien

    2017-09-15

    MetExploreViz is an open source web component that can be easily embedded in any web site. It provides features dedicated to the visualization of metabolic networks and pathways and thus offers a flexible solution to analyze omics data in a biochemical context. Documentation and link to GIT code repository (GPL 3.0 license)are available at this URL: http://metexplore.toulouse.inra.fr/metexploreViz/doc /. Tutorial is available at this URL. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  9. Exploring lipids with nonlinear optical microscopy in multiple biological systems

    NASA Astrophysics Data System (ADS)

    Alfonso-Garcia, Alba

    Lipids are crucial biomolecules for the well being of humans. Altered lipid metabolism may give rise to a variety of diseases that affect organs from the cardiovascular to the central nervous system. A deeper understanding of lipid metabolic processes would spur medical research towards developing precise diagnostic tools, treatment methods, and preventive strategies for reducing the impact of lipid diseases. Lipid visualization remains a complex task because of the perturbative effect exerted by traditional biochemical assays and most fluorescence markers. Coherent Raman scattering (CRS) microscopy enables interrogation of biological samples with minimum disturbance, and is particularly well suited for label-free visualization of lipids, providing chemical specificity without compromising on spatial resolution. Hyperspectral imaging yields large datasets that benefit from tailored multivariate analysis. In this thesis, CRS microscopy was combined with Raman spectroscopy and other label-free nonlinear optical techniques to analyze lipid metabolism in multiple biological systems. We used nonlinear Raman techniques to characterize Meibum secretions in the progression of dry eye disease, where the lipid and protein contributions change in ratio and phase segregation. We employed similar tools to examine lipid droplets in mice livers aboard a spaceflight mission, which lose their retinol content contributing to the onset of nonalcoholic fatty-liver disease. We also focused on atherosclerosis, a disease that revolves around lipid-rich plaques in arterial walls. We examined the lipid content of macrophages, whose variable phenotype gives rise to contrasting healing and inflammatory activities. We also proposed new label-free markers, based on lifetime imaging, for macrophage phenotype, and to detect products of lipid oxidation. Cholesterol was also detected in hepatitis C virus infected cells, and in specific strains of age-related macular degeneration diseased cells by spontaneous Raman spectroscopy. We used synthesized highly-deuterated cholesterol to track its compartmentalization in adrenal cells, revealing heterogeneous lipid droplet content. These examples illustrate the potential of label-free nonlinear optical microscopy for unveiling complex physiological processes by direct visualization of lipids. Detailed image analysis and combined microscopy modalities will continue to reveal and quantify fundamental biology that will support the advance of biomedicine.

  10. Complex Digital Visual Systems

    ERIC Educational Resources Information Center

    Sweeny, Robert W.

    2013-01-01

    This article identifies possibilities for data visualization as art educational research practice. The author presents an analysis of the relationship between works of art and digital visual culture, employing aspects of network analysis drawn from the work of Barabási, Newman, and Watts (2006) and Castells (1994). Describing complex network…

  11. Right hemispheric dominance of visual phenomena evoked by intracerebral stimulation of the human visual cortex.

    PubMed

    Jonas, Jacques; Frismand, Solène; Vignal, Jean-Pierre; Colnat-Coulbois, Sophie; Koessler, Laurent; Vespignani, Hervé; Rossion, Bruno; Maillard, Louis

    2014-07-01

    Electrical brain stimulation can provide important information about the functional organization of the human visual cortex. Here, we report the visual phenomena evoked by a large number (562) of intracerebral electrical stimulations performed at low-intensity with depth electrodes implanted in the occipito-parieto-temporal cortex of 22 epileptic patients. Focal electrical stimulation evoked primarily visual hallucinations with various complexities: simple (spot or blob), intermediary (geometric forms), or complex meaningful shapes (faces); visual illusions and impairments of visual recognition were more rarely observed. With the exception of the most posterior cortical sites, the probability of evoking a visual phenomenon was significantly higher in the right than the left hemisphere. Intermediary and complex hallucinations, illusions, and visual recognition impairments were almost exclusively evoked by stimulation in the right hemisphere. The probability of evoking a visual phenomenon decreased substantially from the occipital pole to the most anterior sites of the temporal lobe, and this decrease was more pronounced in the left hemisphere. The greater sensitivity of the right occipito-parieto-temporal regions to intracerebral electrical stimulation to evoke visual phenomena supports a predominant role of right hemispheric visual areas from perception to recognition of visual forms, regardless of visuospatial and attentional factors. Copyright © 2013 Wiley Periodicals, Inc.

  12. Dimensionality of visual complexity in computer graphics scenes

    NASA Astrophysics Data System (ADS)

    Ramanarayanan, Ganesh; Bala, Kavita; Ferwerda, James A.; Walter, Bruce

    2008-02-01

    How do human observers perceive visual complexity in images? This problem is especially relevant for computer graphics, where a better understanding of visual complexity can aid in the development of more advanced rendering algorithms. In this paper, we describe a study of the dimensionality of visual complexity in computer graphics scenes. We conducted an experiment where subjects judged the relative complexity of 21 high-resolution scenes, rendered with photorealistic methods. Scenes were gathered from web archives and varied in theme, number and layout of objects, material properties, and lighting. We analyzed the subject responses using multidimensional scaling of pooled subject responses. This analysis embedded the stimulus images in a two-dimensional space, with axes that roughly corresponded to "numerosity" and "material / lighting complexity". In a follow-up analysis, we derived a one-dimensional complexity ordering of the stimulus images. We compared this ordering with several computable complexity metrics, such as scene polygon count and JPEG compression size, and did not find them to be very correlated. Understanding the differences between these measures can lead to the design of more efficient rendering algorithms in computer graphics.

  13. Conceptual analysis of Physiology of vision in Ayurveda

    PubMed Central

    Balakrishnan, Praveen; Ashwini, M. J.

    2014-01-01

    The process by which the world outside is seen is termed as visual process or physiology of vision. There are three phases in this visual process: phase of refraction of light, phase of conversion of light energy into electrical impulse and finally peripheral and central neurophysiology. With the advent of modern instruments step by step biochemical changes occurring at each level of the visual process has been deciphered. Many investigations have emerged to track these changes and helping to diagnose the exact nature of the disease. Ayurveda has described this physiology of vision based on the functions of vata and pitta. Philosophical textbook of ayurveda, Tarka Sangraha, gives certain basics facts of visual process. This article discusses the second and third phase of visual process. Step by step analysis of the visual process through the spectacles of ayurveda amalgamated with the basics of philosophy from Tarka Sangraha has been analyzed critically to generate a concrete idea regarding the physiology and hence thereby interpret the pathology on the grounds of ayurveda based on the investigative reports. PMID:25336853

  14. Evolution of an RNP assembly system: A minimal SMN complex facilitates formation of UsnRNPs in Drosophila melanogaster

    PubMed Central

    Kroiss, Matthias; Schultz, Jörg; Wiesner, Julia; Chari, Ashwin; Sickmann, Albert; Fischer, Utz

    2008-01-01

    In vertebrates, assembly of spliceosomal uridine-rich small nuclear ribonucleoproteins (UsnRNPs) is mediated by the SMN complex, a macromolecular entity composed of the proteins SMN and Gemins 2–8. Here we have studied the evolution of this machinery using complete genome assemblies of multiple model organisms. The SMN complex has gained complexity in evolution by a blockwise addition of Gemins onto an ancestral core complex composed of SMN and Gemin2. In contrast to this overall evolutionary trend to more complexity in metazoans, orthologs of most Gemins are missing in dipterans. In accordance with these bioinformatic data a previously undescribed biochemical purification strategy elucidated that the dipteran Drosophila melanogaster contains an SMN complex of remarkable simplicity. Surprisingly, this minimal complex not only mediates the assembly reaction in a manner very similar to its vertebrate counterpart, but also prevents misassembly onto nontarget RNAs. Our data suggest that only a minority of Gemins are required for the assembly reaction per se, whereas others may serve additional functions in the context of UsnRNP biogenesis. The evolution of the SMN complex is an interesting example of how the simplification of a biochemical process contributes to genome compaction. PMID:18621711

  15. Managing Construction Operations Visually: 3-D Techniques for Complex Topography and Restricted Visibility

    ERIC Educational Resources Information Center

    Rodriguez, Walter; Opdenbosh, Augusto; Santamaria, Juan Carlos

    2006-01-01

    Visual information is vital in planning and managing construction operations, particularly, where there is complex terrain topography and salvage operations with limited accessibility and visibility. From visually-assessing site operations and preventing equipment collisions to simulating material handling activities to supervising remotes sites…

  16. The KUPNetViz: a biological network viewer for multiple -omics datasets in kidney diseases.

    PubMed

    Moulos, Panagiotis; Klein, Julie; Jupp, Simon; Stevens, Robert; Bascands, Jean-Loup; Schanstra, Joost P

    2013-07-24

    Constant technological advances have allowed scientists in biology to migrate from conventional single-omics to multi-omics experimental approaches, challenging bioinformatics to bridge this multi-tiered information. Ongoing research in renal biology is no exception. The results of large-scale and/or high throughput experiments, presenting a wealth of information on kidney disease are scattered across the web. To tackle this problem, we recently presented the KUPKB, a multi-omics data repository for renal diseases. In this article, we describe KUPNetViz, a biological graph exploration tool allowing the exploration of KUPKB data through the visualization of biomolecule interactions. KUPNetViz enables the integration of multi-layered experimental data over different species, renal locations and renal diseases to protein-protein interaction networks and allows association with biological functions, biochemical pathways and other functional elements such as miRNAs. KUPNetViz focuses on the simplicity of its usage and the clarity of resulting networks by reducing and/or automating advanced functionalities present in other biological network visualization packages. In addition, it allows the extrapolation of biomolecule interactions across different species, leading to the formulations of new plausible hypotheses, adequate experiment design and to the suggestion of novel biological mechanisms. We demonstrate the value of KUPNetViz by two usage examples: the integration of calreticulin as a key player in a larger interaction network in renal graft rejection and the novel observation of the strong association of interleukin-6 with polycystic kidney disease. The KUPNetViz is an interactive and flexible biological network visualization and exploration tool. It provides renal biologists with biological network snapshots of the complex integrated data of the KUPKB allowing the formulation of new hypotheses in a user friendly manner.

  17. The KUPNetViz: a biological network viewer for multiple -omics datasets in kidney diseases

    PubMed Central

    2013-01-01

    Background Constant technological advances have allowed scientists in biology to migrate from conventional single-omics to multi-omics experimental approaches, challenging bioinformatics to bridge this multi-tiered information. Ongoing research in renal biology is no exception. The results of large-scale and/or high throughput experiments, presenting a wealth of information on kidney disease are scattered across the web. To tackle this problem, we recently presented the KUPKB, a multi-omics data repository for renal diseases. Results In this article, we describe KUPNetViz, a biological graph exploration tool allowing the exploration of KUPKB data through the visualization of biomolecule interactions. KUPNetViz enables the integration of multi-layered experimental data over different species, renal locations and renal diseases to protein-protein interaction networks and allows association with biological functions, biochemical pathways and other functional elements such as miRNAs. KUPNetViz focuses on the simplicity of its usage and the clarity of resulting networks by reducing and/or automating advanced functionalities present in other biological network visualization packages. In addition, it allows the extrapolation of biomolecule interactions across different species, leading to the formulations of new plausible hypotheses, adequate experiment design and to the suggestion of novel biological mechanisms. We demonstrate the value of KUPNetViz by two usage examples: the integration of calreticulin as a key player in a larger interaction network in renal graft rejection and the novel observation of the strong association of interleukin-6 with polycystic kidney disease. Conclusions The KUPNetViz is an interactive and flexible biological network visualization and exploration tool. It provides renal biologists with biological network snapshots of the complex integrated data of the KUPKB allowing the formulation of new hypotheses in a user friendly manner. PMID:23883183

  18. Methods for Discovery of Novel Cellulosomal Cellulases Using Genomics and Biochemical Tools.

    PubMed

    Ben-David, Yonit; Dassa, Bareket; Bensoussan, Lizi; Bayer, Edward A; Moraïs, Sarah

    2018-01-01

    Cell wall degradation by cellulases is extensively explored owing to its potential contribution to biofuel production. The cellulosome is an extracellular multienzyme complex that can degrade the plant cell wall very efficiently, and cellulosomal enzymes are therefore of great interest. The cellulosomal cellulases are defined as enzymes that contain a dockerin module, which can interact with a cohesin module contained in multiple copies in a noncatalytic protein, termed scaffoldin. The assembly of the cellulosomal cellulases into the cellulosomal complex occurs via specific protein-protein interactions. Cellulosome systems have been described initially only in several anaerobic cellulolytic bacteria. However, owing to ongoing genome sequencing and metagenomic projects, the discovery of novel cellulosome-producing bacteria and the description of their cellulosomal genes have dramatically increased in the recent years. In this chapter, methods for discovery of novel cellulosomal cellulases from a DNA sequence by bioinformatics and biochemical tools are described. Their biochemical characterization is also described, including both the enzymatic activity of the putative cellulases and their assembly into mature designer cellulosomes.

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

    Jeffries, H P

    The principal hypothesis addressed in this study states that community variability is related to fatty acid structure. As a test of this idea, the zooplankton in three regimes of increasing physical severity (Block Island Sound, Narragansett Bay and Green Hill Pond) are being compared. Measurements were made on the physical environment, on standing crop and on fatty acid composition in both the phytoplankton-microzooplankton and macrozooplankton. Fatty acid variation in these communities displays a unique trajectory in time at each location. Environmental change and biochemical variability are directly related. The resulting biochemical message is complex but apparently highly informative. Patterns ofmore » variation in some fatty acids are affected most strongly by physical environmental parameters whereas the variation of other fatty acids is more responsive to differences in species composition, diversity and food web relationships. Taken together, these two aspects of biochemical pattern appear to characterize complex species assemblages. The result offers a new strategem for convenient assessment of the ever changing state in a natural community.« less

  20. The Story of the Calvin Cycle: Bringing Carbon Fixation to Life

    ERIC Educational Resources Information Center

    Firooznia, Fardad

    2007-01-01

    A fun, simple, musical role-playing exercise that allows students to actively step through and visualize the biochemical steps of the Calvin cycle. This musical can easily be completed in about 15 minutes with more than enough time during a 50-minute class period to review the steps and clarify the process further.

  1. Monitoring environmental stress in forest trees using biochemical and physiological markers

    Treesearch

    R. Minocha; S.C. Minocha; S. Long

    2003-01-01

    Our objective was to determine the usefulness of polyamines, particularly putrescine, and amino acids such as arginine, as foliar indicators of abiotic stress in visually asymptomatic trees. An evaluation of apparently healthy trees is essential in developing risk assessment and stress remediation strategies for forest trees prior to the onset of obvious decline....

  2. Balanced Biochemical Reactions: A New Approach to Unify Chemical and Biochemical Thermodynamics

    PubMed Central

    Sabatini, Antonio; Vacca, Alberto; Iotti, Stefano

    2012-01-01

    A novel procedure is presented which, by balancing elements and electric charge of biochemical reactions which occur at constant pH and pMg, allows assessing the thermodynamics properties of reaction ΔrG ′0, ΔrH ′0, ΔrS ′0 and the change in binding of hydrogen and magnesium ions of these reactions. This procedure of general applicability avoids the complex calculations required by the use of the Legendre transformed thermodynamic properties of formation ΔfG ′0, ΔfH ′0 and ΔfS ′0 hitherto considered an obligatory prerequisite to deal with the thermodynamics of biochemical reactions. As a consequence, the term “conditional” is proposed in substitution of “Legendre transformed” to indicate these thermodynamics properties. It is also shown that the thermodynamic potential G is fully adequate to give a criterion of spontaneous chemical change for all biochemical reactions and then that the use of the Legendre transformed G′ is unnecessary. The procedure proposed can be applied to any biochemical reaction, making possible to re-unify the two worlds of chemical and biochemical thermodynamics, which so far have been treated separately. PMID:22247780

  3. MONALISA for stochastic simulations of Petri net models of biochemical systems.

    PubMed

    Balazki, Pavel; Lindauer, Klaus; Einloft, Jens; Ackermann, Jörg; Koch, Ina

    2015-07-10

    The concept of Petri nets (PN) is widely used in systems biology and allows modeling of complex biochemical systems like metabolic systems, signal transduction pathways, and gene expression networks. In particular, PN allows the topological analysis based on structural properties, which is important and useful when quantitative (kinetic) data are incomplete or unknown. Knowing the kinetic parameters, the simulation of time evolution of such models can help to study the dynamic behavior of the underlying system. If the number of involved entities (molecules) is low, a stochastic simulation should be preferred against the classical deterministic approach of solving ordinary differential equations. The Stochastic Simulation Algorithm (SSA) is a common method for such simulations. The combination of the qualitative and semi-quantitative PN modeling and stochastic analysis techniques provides a valuable approach in the field of systems biology. Here, we describe the implementation of stochastic analysis in a PN environment. We extended MONALISA - an open-source software for creation, visualization and analysis of PN - by several stochastic simulation methods. The simulation module offers four simulation modes, among them the stochastic mode with constant firing rates and Gillespie's algorithm as exact and approximate versions. The simulator is operated by a user-friendly graphical interface and accepts input data such as concentrations and reaction rate constants that are common parameters in the biological context. The key features of the simulation module are visualization of simulation, interactive plotting, export of results into a text file, mathematical expressions for describing simulation parameters, and up to 500 parallel simulations of the same parameter sets. To illustrate the method we discuss a model for insulin receptor recycling as case study. We present a software that combines the modeling power of Petri nets with stochastic simulation of dynamic processes in a user-friendly environment supported by an intuitive graphical interface. The program offers a valuable alternative to modeling, using ordinary differential equations, especially when simulating single-cell experiments with low molecule counts. The ability to use mathematical expressions provides an additional flexibility in describing the simulation parameters. The open-source distribution allows further extensions by third-party developers. The software is cross-platform and is licensed under the Artistic License 2.0.

  4. Visual Short-Term Memory Capacity for Simple and Complex Objects

    ERIC Educational Resources Information Center

    Luria, Roy; Sessa, Paola; Gotler, Alex; Jolicoeur, Pierre; Dell'Acqua, Roberto

    2010-01-01

    Does the capacity of visual short-term memory (VSTM) depend on the complexity of the objects represented in memory? Although some previous findings indicated lower capacity for more complex stimuli, other results suggest that complexity effects arise during retrieval (due to errors in the comparison process with what is in memory) that is not…

  5. Conditions for duality between fluxes and concentrations in biochemical networks

    PubMed Central

    Fleming, Ronan M.T.; Vlassis, Nikos; Thiele, Ines; Saunders, Michael A.

    2016-01-01

    Mathematical and computational modelling of biochemical networks is often done in terms of either the concentrations of molecular species or the fluxes of biochemical reactions. When is mathematical modelling from either perspective equivalent to the other? Mathematical duality translates concepts, theorems or mathematical structures into other concepts, theorems or structures, in a one-to-one manner. We present a novel stoichiometric condition that is necessary and sufficient for duality between unidirectional fluxes and concentrations. Our numerical experiments, with computational models derived from a range of genome-scale biochemical networks, suggest that this flux-concentration duality is a pervasive property of biochemical networks. We also provide a combinatorial characterisation that is sufficient to ensure flux-concentration duality. The condition prescribes that, for every two disjoint sets of molecular species, there is at least one reaction complex that involves species from only one of the two sets. When unidirectional fluxes and molecular species concentrations are dual vectors, this implies that the behaviour of the corresponding biochemical network can be described entirely in terms of either concentrations or unidirectional fluxes. PMID:27345817

  6. Conditions for duality between fluxes and concentrations in biochemical networks

    DOE PAGES

    Fleming, Ronan M. T.; Vlassis, Nikos; Thiele, Ines; ...

    2016-06-23

    Mathematical and computational modelling of biochemical networks is often done in terms of either the concentrations of molecular species or the fluxes of biochemical reactions. When is mathematical modelling from either perspective equivalent to the other? Mathematical duality translates concepts, theorems or mathematical structures into other concepts, theorems or structures, in a one-to-one manner. We present a novel stoichiometric condition that is necessary and sufficient for duality between unidirectional fluxes and concentrations. Our numerical experiments, with computational models derived from a range of genome-scale biochemical networks, suggest that this flux-concentration duality is a pervasive property of biochemical networks. We alsomore » provide a combinatorial characterisation that is sufficient to ensure flux-concentration duality.The condition prescribes that, for every two disjoint sets of molecular species, there is at least one reaction complex that involves species from only one of the two sets. When unidirectional fluxes and molecular species concentrations are dual vectors, this implies that the behaviour of the corresponding biochemical network can be described entirely in terms of either concentrations or unidirectional fluxes« less

  7. Conditions for duality between fluxes and concentrations in biochemical networks

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

    Fleming, Ronan M. T.; Vlassis, Nikos; Thiele, Ines

    Mathematical and computational modelling of biochemical networks is often done in terms of either the concentrations of molecular species or the fluxes of biochemical reactions. When is mathematical modelling from either perspective equivalent to the other? Mathematical duality translates concepts, theorems or mathematical structures into other concepts, theorems or structures, in a one-to-one manner. We present a novel stoichiometric condition that is necessary and sufficient for duality between unidirectional fluxes and concentrations. Our numerical experiments, with computational models derived from a range of genome-scale biochemical networks, suggest that this flux-concentration duality is a pervasive property of biochemical networks. We alsomore » provide a combinatorial characterisation that is sufficient to ensure flux-concentration duality.The condition prescribes that, for every two disjoint sets of molecular species, there is at least one reaction complex that involves species from only one of the two sets. When unidirectional fluxes and molecular species concentrations are dual vectors, this implies that the behaviour of the corresponding biochemical network can be described entirely in terms of either concentrations or unidirectional fluxes« less

  8. Structure of the Deactive State of Mammalian Respiratory Complex I.

    PubMed

    Blaza, James N; Vinothkumar, Kutti R; Hirst, Judy

    2018-02-06

    Complex I (NADH:ubiquinone oxidoreductase) is central to energy metabolism in mammalian mitochondria. It couples NADH oxidation by ubiquinone to proton transport across the energy-conserving inner membrane, catalyzing respiration and driving ATP synthesis. In the absence of substrates, active complex I gradually enters a pronounced resting or deactive state. The active-deactive transition occurs during ischemia and is crucial for controlling how respiration recovers upon reperfusion. Here, we set a highly active preparation of Bos taurus complex I into the biochemically defined deactive state, and used single-particle electron cryomicroscopy to determine its structure to 4.1 Å resolution. We show that the deactive state arises when critical structural elements that form the ubiquinone-binding site become disordered, and we propose reactivation is induced when substrate binding to the NADH-reduced enzyme templates their reordering. Our structure both rationalizes biochemical data on the deactive state and offers new insights into its physiological and cellular roles. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Examining Practice in Secondary Visual Arts Education

    ERIC Educational Resources Information Center

    Mitchell, Donna Mathewson

    2015-01-01

    Teaching in secondary visual arts classrooms is complex and challenging work. While it is implicated in much research, the complexity of the lived experience of secondary visual arts teaching has rarely been the subject of sustained and synthesized research. In this paper, the potential of practice as a concept to examine and represent secondary…

  10. Metabolic Mapping of the Brain's Response to Visual Stimulation: Studies in Humans.

    ERIC Educational Resources Information Center

    Phelps, Michael E.; Kuhl, David E.

    1981-01-01

    Studies demonstrate increasing glucose metabolic rates in human primary (PVC) and association (AVC) visual cortex as complexity of visual scenes increase. AVC increased more rapidly with scene complexity than PVC and increased local metabolic activities above control subject with eyes closed; indicates wide range and metabolic reserve of visual…

  11. The Effects of Pictorial Complexity and Cognitive Style on Visual Recall Memory.

    ERIC Educational Resources Information Center

    Jesky, Romaine R.; Berry, Louis H.

    The effect of the interaction between cognitive style differences (field dependence/field independence) and various degrees of visual complexity on pictorial recall memory was explored using three sets of visuals in three different formats--line drawing, black and white, and color. The subjects were 86 undergraduate students enrolled in two core…

  12. Camouflage and visual perception

    PubMed Central

    Troscianko, Tom; Benton, Christopher P.; Lovell, P. George; Tolhurst, David J.; Pizlo, Zygmunt

    2008-01-01

    How does an animal conceal itself from visual detection by other animals? This review paper seeks to identify general principles that may apply in this broad area. It considers mechanisms of visual encoding, of grouping and object encoding, and of search. In most cases, the evidence base comes from studies of humans or species whose vision approximates to that of humans. The effort is hampered by a relatively sparse literature on visual function in natural environments and with complex foraging tasks. However, some general constraints emerge as being potentially powerful principles in understanding concealment—a ‘constraint’ here means a set of simplifying assumptions. Strategies that disrupt the unambiguous encoding of discontinuities of intensity (edges), and of other key visual attributes, such as motion, are key here. Similar strategies may also defeat grouping and object-encoding mechanisms. Finally, the paper considers how we may understand the processes of search for complex targets in complex scenes. The aim is to provide a number of pointers towards issues, which may be of assistance in understanding camouflage and concealment, particularly with reference to how visual systems can detect the shape of complex, concealed objects. PMID:18990671

  13. Congenital Chromosomal Syndromes—A Model for Pathogenesis

    PubMed Central

    Rohde, Russell A.

    1965-01-01

    The origin of anomalies in the chromosomal syndromes is believed to be both polyetiologic and polypathogenetic. Whereas some malformations quite clearly appear to result from single gene mutations or from genic imbalance due to individual monosomic or trisomic loci, other anomalies (singly or in complex patterns) are better interpreted as originating from disturbances in particular biochemical pathways which affect the development of a variety of traits. Additional phenogenetic studies and the use of sophisticated biochemical analysis in persons with complex patterns of anomalies should provide a truer understanding of disease mechanisms and provide guidance for future studies which are aimed at the treatment and prevention of these intriguing misadventures of Nature. PMID:5318572

  14. Reduction of Complexity: An Aspect of Network Visualization

    DTIC Science & Technology

    2006-12-01

    research is to identify strategies for the visualization of network information. Distinction can be made between visual communication and visual...exploration (MacEachern 1994). Visual communication deals with how to visualize results of different kinds of analysis, i.e., visualization in the case

  15. Assessment of the patellofemoral cartilage: Correlation of knee pain score with magnetic resonance cartilage grading and magnetization transfer ratio asymmetry of glycosaminoglycan chemical exchange saturation transfer.

    PubMed

    Lee, Young Han; Yang, Jaemoon; Jeong, Ha-Kyu; Suh, Jin-Suck

    2017-01-01

    Biochemical imaging of glycosaminoglycan chemical exchange saturation transfer (gagCEST) could predict the depletion of glycosaminoglycans (GAG) in early osteoarthritis. The purpose of this study was to evaluate the relationship between the magnetization transfer ratio asymmetry (MTR asym ) of gagCEST images and visual analog scale (VAS) pain scores in the knee joint. This retrospective study was approved by the institutional review board. A phantom study was performed using hyaluronic acid to validate the MTR asym values of gagCEST images. Knee magnetic resonance (MR) images of 22 patients (male, 9; female, 13; mean age, 50.3years; age range; 25-79years) with knee pain were included in this study. The MR imaging (MRI) protocol involved standard knee MRI as well as gagCEST imaging, which allowed region-of-interest analyses of the patellar facet and femoral trochlea. The MTR asym at 1.0ppm was calculated at each region. The cartilages of the patellar facets and femoral trochlea were graded according to the Outerbridge classification system. Data regarding the VAS scores of knee pain were collected from the electronic medical records of the patients. Statistical analysis was performed using Spearman's correlation. The results of the phantom study revealed excellent correlation between the MTR asym values and the concentration of GAGs (r=0.961; p=0.003). The cartilage grades on the MR images showed significant negative correlation with the MTR asym values in the patellar facet and femoral trochlea (r=-0.460; p=0.031 and r=-0.543; p=0.009, respectively). The VAS pain scores showed significant negative correlation with the MTR asym values in the patellar facet and femoral trochlea (r=-0.435; p=0.043 and r=-0.671; p=0.001, respectively). The pain scores were associated with the morphological and biochemical changes in articular cartilages visualized on knee MR images. The biochemical changes, visualized in terms of the MTR asym values of the gagCEST images, exhibited greater correlation with the pain scores than the morphological changes visualized on conventional MR images; these results provide evidence supporting the theory regarding the association of patellofemoral osteoarthritis with knee pain scores. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. A lightning strike to the head causing a visual cortex defect with simple and complex visual hallucinations

    PubMed Central

    Kleiter, Ingo; Luerding, Ralf; Diendorfer, Gerhard; Rek, Helga; Bogdahn, Ulrich; Schalke, Berthold

    2007-01-01

    The case of a 23‐year‐old mountaineer who was hit by a lightning strike to the occiput causing a large central visual field defect and bilateral tympanic membrane ruptures is described. Owing to extreme agitation, the patient was set to a drug‐induced coma for 3 days. After extubation, she experienced simple and complex visual hallucinations for several days, but otherwise recovered largely. Neuropsychological tests revealed deficits in fast visual detection tasks and non‐verbal learning, and indicated a right temporal lobe dysfunction, consistent with a right temporal focus on electroencephalography. Four months after the accident, she developed a psychological reaction consisting of nightmares with reappearance of the complex visual hallucinations and a depressive syndrome. Using the European Cooperation for Lightning Detection network, a meteorological system for lightning surveillance, the exact geographical location and nature of the lightning flash were retrospectively retraced. PMID:17369595

  17. A lightning strike to the head causing a visual cortex defect with simple and complex visual hallucinations

    PubMed Central

    Kleiter, Ingo; Luerding, Ralf; Diendorfer, Gerhard; Rek, Helga; Bogdahn, Ulrich; Schalke, Berthold

    2009-01-01

    The case of a 23-year-old mountaineer who was hit by a lightning strike to the occiput causing a large central visual field defect and bilateral tympanic membrane ruptures is described. Owing to extreme agitation, the patient was sent into a drug-induced coma for 3 days. After extubation, she experienced simple and complex visual hallucinations for several days, but otherwise largely recovered. Neuropsychological tests revealed deficits in fast visual detection tasks and non-verbal learning and indicated a right temporal lobe dysfunction, consistent with a right temporal focus on electroencephalography. At 4 months after the accident, she developed a psychological reaction consisting of nightmares, with reappearance of the complex visual hallucinations and a depressive syndrome. Using the European Cooperation for Lightning Detection network, a meteorological system for lightning surveillance, the exact geographical location and nature of the lightning strike were retrospectively retraced PMID:21734915

  18. Alien life: how would we know?

    NASA Astrophysics Data System (ADS)

    Boden, Margaret A.

    2003-04-01

    To recognize alien life, we would have to be clear about the defining criteria of "life". Metabolism - in other words, biochemical fine-tuning - is one of these criteria. Three senses of metabolism are distinguished. The weakest allows strong artificial life (A-life): virtual creatures having physical existence in computer electronics, but not bodies, are classed as "alive". The second excludes strong A-life but allows that some non-biochemical A-life robots could be classed as alive. The third, which stresses the body's self-production by energy budgeting and self-equilibrating energy exchanges of some (necessary) complexity, excludes both strong A-life and living non-biochemical robots.

  19. Effects of emotional tone and visual complexity on processing health information in prescription drug advertising.

    PubMed

    Norris, Rebecca L; Bailey, Rachel L; Bolls, Paul D; Wise, Kevin R

    2012-01-01

    This experiment explored how the emotional tone and visual complexity of direct-to-consumer (DTC) drug advertisements affect the encoding and storage of specific risk and benefit statements about each of the drugs in question. Results are interpreted under the limited capacity model of motivated mediated message processing framework. Findings suggest that DTC drug ads should be pleasantly toned and high in visual complexity in order to maximize encoding and storage of risk and benefit information.

  20. Psycho acoustical Measures in Individuals with Congenital Visual Impairment.

    PubMed

    Kumar, Kaushlendra; Thomas, Teenu; Bhat, Jayashree S; Ranjan, Rajesh

    2017-12-01

    In congenital visual impaired individuals one modality is impaired (visual modality) this impairment is compensated by other sensory modalities. There is evidence that visual impaired performed better in different auditory task like localization, auditory memory, verbal memory, auditory attention, and other behavioural tasks when compare to normal sighted individuals. The current study was aimed to compare the temporal resolution, frequency resolution and speech perception in noise ability in individuals with congenital visual impaired and normal sighted. Temporal resolution, frequency resolution, and speech perception in noise were measured using MDT, GDT, DDT, SRDT, and SNR50 respectively. Twelve congenital visual impaired participants with age range of 18 to 40 years were taken and equal in number with normal sighted participants. All the participants had normal hearing sensitivity with normal middle ear functioning. Individual with visual impairment showed superior threshold in MDT, SRDT and SNR50 as compared to normal sighted individuals. This may be due to complexity of the tasks; MDT, SRDT and SNR50 are complex tasks than GDT and DDT. Visual impairment showed superior performance in auditory processing and speech perception with complex auditory perceptual tasks.

  1. The B3 Subunit of the Cone Cyclic Nucleotide-gated Channel Regulates the Light Responses of Cones and Contributes to the Channel Structural Flexibility*

    PubMed Central

    Ding, Xi-Qin; Thapa, Arjun; Ma, Hongwei; Xu, Jianhua; Elliott, Michael H.; Rodgers, Karla K.; Smith, Marci L.; Wang, Jin-Shan; Pittler, Steven J.; Kefalov, Vladimir J.

    2016-01-01

    Cone photoreceptor cyclic nucleotide-gated (CNG) channels play a pivotal role in cone phototransduction, which is a process essential for daylight vision, color vision, and visual acuity. Mutations in the cone channel subunits CNGA3 and CNGB3 are associated with human cone diseases, including achromatopsia, cone dystrophies, and early onset macular degeneration. Mutations in CNGB3 alone account for 50% of reported cases of achromatopsia. This work investigated the role of CNGB3 in cone light response and cone channel structural stability. As cones comprise only 2–3% of the total photoreceptor population in the wild-type mouse retina, we used Cngb3−/−/Nrl−/− mice with CNGB3 deficiency on a cone-dominant background in our study. We found that, in the absence of CNGB3, CNGA3 was able to travel to the outer segments, co-localize with cone opsin, and form tetrameric complexes. Electroretinogram analyses revealed reduced cone light response amplitude/sensitivity and slower response recovery in Cngb3−/−/Nrl−/− mice compared with Nrl−/− mice. Absence of CNGB3 expression altered the adaptation capacity of cones and severely compromised function in bright light. Biochemical analysis demonstrated that CNGA3 channels lacking CNGB3 were more resilient to proteolysis than CNGA3/CNGB3 channels, suggesting a hindered structural flexibility. Thus, CNGB3 regulates cone light response kinetics and the channel structural flexibility. This work advances our understanding of the biochemical and functional role of CNGB3 in cone photoreceptors. PMID:26893377

  2. Multifunctional receptor model for dioxin and related compound toxic action: possible thyroid hormone-responsive effector-linked site.

    PubMed Central

    McKinney, J D

    1989-01-01

    Molecular/theoretical modeling studies have revealed that thyroid hormones and toxic chlorinated aromatic hydrocarbons of environmental significance (for which dioxin or TCDD is the prototype) have similar structural properties that could be important in molecular recognition in biochemical systems. These molecular properties include a somewhat rigid, sterically accessible and polarizable aromatic ring and size-limited, hydrophobic lateral substituents, usually contained in opposite adjoining rings of a diphenyl compound. These molecular properties define the primary binding groups thought to be important in molecular recognition of both types of structures in biochemical systems. Similar molecular reactivities are supported by the demonstration of effective specific binding of thyroid hormones and chlorinated aromatic hydrocarbons with four different proteins, enzymes, or receptor preparations that are known or suspected to be involved in the expression of thyroid hormone activity. These binding interactions represent both aromatic-aromatic (stacking) and molecular cleft-type recognition processes. A multiple protein or multifunctional receptor-ligand binding mechanism model is proposed as a way of visualizing the details and possible role of both the stacking and cleft type molecular recognition factors in the expression of biological activity. The model suggests a means by which hormone-responsive effector-linked sites (possible protein-protein-DNA complexes) can maintain highly structurally specific control of hormone action. Finally, the model also provides a theoretical basis for the design and conduct of further biological experimentation on the molecular mechanism(s) of action of toxic chlorinated aromatic hydrocarbons and thyroid hormones. Images FIGURE 3. A FIGURE 3. B FIGURE 3. C FIGURE 3. D PMID:2551666

  3. A Model Incorporating Some of the Mechanical and Biochemical Factors Underlying Clot Formation and Dissolution in Flowing Blood

    DOE PAGES

    Anand, M.; Rajagopal, K.; Rajagopal, K. R.

    2003-01-01

    Multiple interacting mechanisms control the formation and dissolution of clots to maintain blood in a state of delicate balance. In addition to a myriad of biochemical reactions, rheological factors also play a crucial role in modulating the response of blood to external stimuli. To date, a comprehensive model for clot formation and dissolution, that takes into account the biochemical, medical and rheological factors, has not been put into place, the existing models emphasizing either one or the other of the factors. In this paper, after discussing the various biochemical, physiologic and rheological factors at some length, we develop a modelmore » for clot formation and dissolution that incorporates many of the relevant crucial factors that have a bearing on the problem. The model, though just a first step towards understanding a complex phenomenon, goes further than previous models in integrating the biochemical, physiologic and rheological factors that come into play.« less

  4. Structural and biochemical characterization of the inhibitor complexes of XMRV protease

    PubMed Central

    Li, Mi; Gustchina, Alla; Matúz, Krisztina; Tözsér, Jozsef; Namwong, Sirilak; Goldfarb, Nathan E.; Dunn, Ben M.; Wlodawer, Alexander

    2012-01-01

    Summary Interactions between the protease (PR) encoded by the xenotropic murine leukemia virus-related virus (XMRV) and a number of potential inhibitors have been investigated by biochemical and structural techniques. It was observed that several inhibitors used clinically against HIV PR exhibit nanomolar or even subnanomolar values of Ki, depending on exact experimental conditions. TL-3, a universal inhibitor of retroviral proteases, as well as some inhibitors originally shown to inhibit plasmepsins were also quite potent, whereas inhibition by pepstatin A was considerably weaker. Crystal structures of the complexes of XMRV PR with TL-3, amprenavir, and pepstatin A were solved at high resolution and compared to the structures of these inhibitors complexed with other retropepsins. Whereas TL-3 and amprenavir bind in a predictable manner spanning the substrate-binding site of the enzyme, two molecules of pepstatin A bind simultaneously in an unprecedented manner, leaving the catalytic water molecule in place. PMID:21951660

  5. Memory for Complex Visual Objects but Not for Allocentric Locations during the First Year of Life

    ERIC Educational Resources Information Center

    Dupierrix, Eve; Hillairet de Boisferon, Anne; Barbeau, Emmanuel; Pascalis, Olivier

    2015-01-01

    Although human infants demonstrate early competence to retain visual information, memory capacities during infancy remain largely undocumented. In three experiments, we used a Visual Paired Comparison (VPC) task to examine abilities to encode identity (Experiment 1) and spatial properties (Experiments 2a and 2b) of unfamiliar complex visual…

  6. Designing Epigenome Editors: Considerations of Biochemical and Locus Specificities.

    PubMed

    Sen, Dilara; Keung, Albert J

    2018-01-01

    The advent of locus-specific protein recruitment technologies has enabled a new class of studies in chromatin biology. Epigenome editors enable biochemical modifications of chromatin at almost any specific endogenous locus. Their locus specificity unlocks unique information including the functional roles of distinct modifications at specific genomic loci. Given the growing interest in using these tools for biological and translational studies, there are many specific design considerations depending on the scientific question or clinical need. Here we present and discuss important design considerations and challenges regarding the biochemical and locus specificities of epigenome editors. These include how to account for the complex biochemical diversity of chromatin; control for potential interdependency of epigenome editors and their resultant modifications; avoid sequestration effects; quantify the locus specificity of epigenome editors; and improve locus specificity by considering concentration, affinity, avidity, and sequestration effects.

  7. Evidence for light perception in a bioluminescent organ

    PubMed Central

    Tong, Deyan; Rozas, Natalia S.; Oakley, Todd H.; Mitchell, Jane; Colley, Nansi J.; McFall-Ngai, Margaret J.

    2009-01-01

    Here we show that bioluminescent organs of the squid Euprymna scolopes possess the molecular, biochemical, and physiological capability for light detection. Transcriptome analyses revealed expression of genes encoding key visual transduction proteins in light-organ tissues, including the same isoform of opsin that occurs in the retina. Electroretinograms demonstrated that the organ responds physiologically to light, and immunocytochemistry experiments localized multiple proteins of visual transduction cascades to tissues housing light-producing bacterial symbionts. These data provide evidence that the light-organ tissues harboring the symbionts serve as extraocular photoreceptors, with the potential to perceive directly the bioluminescence produced by their bacterial partners. PMID:19509343

  8. The distribution of RNA polymerase in Escherichia coli is dynamic and sensitive to environmental cues | Center for Cancer Research

    Cancer.gov

    Despite extensive genetic, biochemical and structural studies on Escherichia coli RNA polymerase (RNAP), little is known about its location and distribution in response to environmental changes. To visualize the RNAP by fluorescence microscopy in E. coli under different physiological conditions, we constructed a functional rpoC-gfp gene fusion on the chromosome.

  9. Comparison of Germination and Viability Tests for Southern Hardwood Seed

    Treesearch

    F. T. Bonner; J. L. Gammage

    1967-01-01

    This paper summarizes a 3-year evaluation of 10 methods for testing germinability and viability of the seed of six species of southern hardwood. In five of the methods, the seeds were germinated. In the others, visual, biochemical, or physical properties were the criteria. Cutting tests were best for sweetgum and Nuttall oak seed, while cutting or water germination...

  10. Pathway collages: personalized multi-pathway diagrams.

    PubMed

    Paley, Suzanne; O'Maille, Paul E; Weaver, Daniel; Karp, Peter D

    2016-12-13

    Metabolic pathway diagrams are a classical way of visualizing a linked cascade of biochemical reactions. However, to understand some biochemical situations, viewing a single pathway is insufficient, whereas viewing the entire metabolic network results in information overload. How do we enable scientists to rapidly construct personalized multi-pathway diagrams that depict a desired collection of interacting pathways that emphasize particular pathway interactions? We define software for constructing personalized multi-pathway diagrams called pathway-collages using a combination of manual and automatic layouts. The user specifies a set of pathways of interest for the collage from a Pathway/Genome Database. Layouts for the individual pathways are generated by the Pathway Tools software, and are sent to a Javascript Pathway Collage application implemented using Cytoscape.js. That application allows the user to re-position pathways; define connections between pathways; change visual style parameters; and paint metabolomics, gene expression, and reaction flux data onto the collage to obtain a desired multi-pathway diagram. We demonstrate the use of pathway collages in two application areas: a metabolomics study of pathogen drug response, and an Escherichia coli metabolic model. Pathway collages enable facile construction of personalized multi-pathway diagrams.

  11. Simulation studies in biochemical signaling and enzyme reactions

    NASA Astrophysics Data System (ADS)

    Nelatury, Sudarshan R.; Vagula, Mary C.

    2014-06-01

    Biochemical pathways characterize various biochemical reaction schemes that involve a set of species and the manner in which they are connected. Determination of schematics that represent these pathways is an important task in understanding metabolism and signal transduction. Examples of these Pathways are: DNA and protein synthesis, and production of several macro-molecules essential for cell survival. A sustained feedback mechanism arises in gene expression and production of mRNA that lead to protein synthesis if the protein so synthesized serves as a transcription factor and becomes a repressor of the gene expression. The cellular regulations are carried out through biochemical networks consisting of reactions and regulatory proteins. Systems biology is a relatively new area that attempts to describe the biochemical pathways analytically and develop reliable mathematical models for the pathways. A complete understanding of chemical reaction kinetics is prohibitively hard thanks to the nonlinear and highly complex mechanisms that regulate protein formation, but attempting to numerically solve some of the governing differential equations seems to offer significant insight about their biochemical picture. To validate these models, one can perform simple experiments in the lab. This paper introduces fundamental ideas in biochemical signaling and attempts to take first steps into the understanding of biochemical oscillations. Initially, the two-pool model of calcium is used to describe the dynamics behind the oscillations. Later we present some elementary results showing biochemical oscillations arising from solving differential equations of Elowitz and Leibler using MATLAB software.

  12. Juxtaposed Polycomb complexes co-regulate vertebral identity.

    PubMed

    Kim, Se Young; Paylor, Suzanne W; Magnuson, Terry; Schumacher, Armin

    2006-12-01

    Best known as epigenetic repressors of developmental Hox gene transcription, Polycomb complexes alter chromatin structure by means of post-translational modification of histone tails. Depending on the cellular context, Polycomb complexes of diverse composition and function exhibit cooperative interaction or hierarchical interdependency at target loci. The present study interrogated the genetic, biochemical and molecular interaction of BMI1 and EED, pivotal constituents of heterologous Polycomb complexes, in the regulation of vertebral identity during mouse development. Despite a significant overlap in dosage-sensitive homeotic phenotypes and co-repression of a similar set of Hox genes, genetic analysis implicated eed and Bmi1 in parallel pathways, which converge at the level of Hox gene regulation. Whereas EED and BMI1 formed separate biochemical entities with EzH2 and Ring1B, respectively, in mid-gestation embryos, YY1 engaged in both Polycomb complexes. Strikingly, methylated lysine 27 of histone H3 (H3-K27), a mediator of Polycomb complex recruitment to target genes, stably associated with the EED complex during the maintenance phase of Hox gene repression. Juxtaposed EED and BMI1 complexes, along with YY1 and methylated H3-K27, were detected in upstream regulatory regions of Hoxc8 and Hoxa5. The combined data suggest a model wherein epigenetic and genetic elements cooperatively recruit and retain juxtaposed Polycomb complexes in mammalian Hox gene clusters toward co-regulation of vertebral identity.

  13. Optimizing Cognitive Load for Learning from Computer-Based Science Simulations

    ERIC Educational Resources Information Center

    Lee, Hyunjeong; Plass, Jan L.; Homer, Bruce D.

    2006-01-01

    How can cognitive load in visual displays of computer simulations be optimized? Middle-school chemistry students (N = 257) learned with a simulation of the ideal gas law. Visual complexity was manipulated by separating the display of the simulations in two screens (low complexity) or presenting all information on one screen (high complexity). The…

  14. Similarity, Not Complexity, Determines Visual Working Memory Performance

    ERIC Educational Resources Information Center

    Jackson, Margaret C.; Linden, David E. J.; Roberts, Mark V.; Kriegeskorte, Nikolaus; Haenschel, Corinna

    2015-01-01

    A number of studies have shown that visual working memory (WM) is poorer for complex versus simple items, traditionally accounted for by higher information load placing greater demands on encoding and storage capacity limits. Other research suggests that it may not be complexity that determines WM performance per se, but rather increased…

  15. Pituitary apoplexy in a teenager--case report.

    PubMed

    Chao, Chen-Cheng; Lin, Chun-Ju

    2014-06-01

    Pituitary apoplexy is a rare clinical emergency which results from hemorrhage or infarction in the pituitary gland. We present a 14-year-old girl with pituitary apoplexy and review the literature. Our patient experienced blurred vision, nausea, and headache. Her best-corrected visual acuity was 20/200 and 20/20. Confrontation test visual field testing revealed bitemporal hemianopsia. Brain imaging demonstrated a suprasellar mass. The microscopic endonasal transsphenoidal approach only found 5-10 mL brownish fluid-like material. Pathology confirmed no malignancy. Pituitary apoplexy was diagnosed. Her nausea and headache gradually improved. Six months after operation, her best-corrected visual acuity had improved to 20/30 and 20/20. Although pituitary apoplexy is rare in pediatric patients, prompt evaluation including detailed ophthalmic examination, biochemical evaluation, endocrine workup, and image study are very important. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Software complex for geophysical data visualization

    NASA Astrophysics Data System (ADS)

    Kryukov, Ilya A.; Tyugin, Dmitry Y.; Kurkin, Andrey A.; Kurkina, Oxana E.

    2013-04-01

    The effectiveness of current research in geophysics is largely determined by the degree of implementation of the procedure of data processing and visualization with the use of modern information technology. Realistic and informative visualization of the results of three-dimensional modeling of geophysical processes contributes significantly into the naturalness of physical modeling and detailed view of the phenomena. The main difficulty in this case is to interpret the results of the calculations: it is necessary to be able to observe the various parameters of the three-dimensional models, build sections on different planes to evaluate certain characteristics and make a rapid assessment. Programs for interpretation and visualization of simulations are spread all over the world, for example, software systems such as ParaView, Golden Software Surfer, Voxler, Flow Vision and others. However, it is not always possible to solve the problem of visualization with the help of a single software package. Preprocessing, data transfer between the packages and setting up a uniform visualization style can turn into a long and routine work. In addition to this, sometimes special display modes for specific data are required and existing products tend to have more common features and are not always fully applicable to certain special cases. Rendering of dynamic data may require scripting languages that does not relieve the user from writing code. Therefore, the task was to develop a new and original software complex for the visualization of simulation results. Let us briefly list of the primary features that are developed. Software complex is a graphical application with a convenient and simple user interface that displays the results of the simulation. Complex is also able to interactively manage the image, resize the image without loss of quality, apply a two-dimensional and three-dimensional regular grid, set the coordinate axes with data labels and perform slice of data. The feature of geophysical data is their size. Detailed maps used in the simulations are large, thus rendering in real time can be difficult task even for powerful modern computers. Therefore, the performance of the software complex is an important aspect of this work. Complex is based on the latest version of graphic API: Microsoft - DirectX 11, which reduces overhead and harness the power of modern hardware. Each geophysical calculation is the adjustment of the mathematical model for a particular case, so the architecture of the complex visualization is created with the scalability and the ability to customize visualization objects, for better visibility and comfort. In the present study, software complex 'GeoVisual' was developed. One of the main features of this research is the use of bleeding-edge techniques of computer graphics in scientific visualization. The research was supported by The Ministry of education and science of Russian Federation, project 14.B37.21.0642.

  17. An extended family of novel vertebrate photopigments is widely expressed and displays a diversity of function

    PubMed Central

    Davies, Wayne I.L.; Tamai, T. Katherine; Zheng, Lei; Fu, Josephine K.; Rihel, Jason; Foster, Russell G.; Whitmore, David; Hankins, Mark W.

    2015-01-01

    Light affects animal physiology and behavior more than simply through classical visual, image-forming pathways. Nonvisual photoreception regulates numerous biological systems, including circadian entrainment, DNA repair, metabolism, and behavior. However, for the majority of these processes, the photoreceptive molecules involved are unknown. Given the diversity of photophysiological responses, the question arises whether a single photopigment or a greater diversity of proteins within the opsin superfamily detect photic stimuli. Here, a functional genomics approach identified the full complement of photopigments in a highly light-sensitive model vertebrate, the zebrafish (Danio rerio), and characterized their tissue distribution, expression levels, and biochemical properties. The results presented here reveal the presence of 42 distinct genes encoding 10 classical visual photopigments and 32 nonvisual opsins, including 10 novel opsin genes comprising four new pigment classes. Consistent with the presence of light-entrainable circadian oscillators in zebrafish, all adult tissues examined expressed two or more opsins, including several novel opsins. Spectral and electrophysiological analyses of the new opsins demonstrate that they form functional photopigments, each with unique chromophore-binding and wavelength specificities. This study has revealed a remarkable number and diversity of photopigments in zebrafish, the largest number so far discovered for any vertebrate. Found in amphibians, reptiles, birds, and all three mammalian clades, most of these genes are not restricted to teleosts. Therefore, nonvisual light detection is far more complex than initially appreciated, which has significant biological implications in understanding photoreception in vertebrates. PMID:26450929

  18. Time-dependent morphological and biochemical changes following cutaneous thermal burn injury and their modulation by copper nicotinate complex: an animal model.

    PubMed

    Nassar, Muammar A Y; Eldien, Heba M Saad; Tawab, Hanem S Abdel; Saleem, Tahia H; Omar, Hossam M; Nassar, Ahmed Y; Hussein, Mahmoud Rezk Abdelwahed

    2012-10-01

    Thermal tissue injury is partly mediated by reactive oxygen metabolites. Oxygen free radicals are contributory to local tissue damage following thermal injury and accordingly an interventional therapy using antioxidants may be beneficial. Copper nicotinate complex can scavenge reactive oxygen species (i.e., has antioxidant activity). To examine time-related morphological and biochemical changes following skin thermal injury and their modulation by copper nicotinate complex. An animal model composed of 80 albino rats was established. Ten rats (nonburn group) served as a control group. Seventy rats (burn group) were anesthetized, given a 10% total body surface area, full-thickness burn. Ten rats (from the postburn group) were sacrificed after 24 h (without treatment, i.e., untreated-burn group). The remaining rats were divided into three subgroups (20 rats, each) and were treated topically either with soft paraffin, moist exposed burn ointment (MEBO, a standard therapeutic treatment for burns), or copper nicotinate complex. Five animals from each subgroup were sacrificed every week over a period of 4 weeks. The morphological and biochemical changes were evaluated and compared among the different groups. High levels of the plasma and skin nitiric oxide (marker of oxidative stress) were observed in the untreated-burn group. These levels were significantly low following the application of copper nicotinate complex. Low levels of plasma and skin superoxide dismutase (marker of oxidative stress) and plasma ceruloplasmin were observed in the untreated-burn group. These levels were significantly high following copper nicotinate complex treatment. The total and differential leukocyte counts were low following the onset of the thermal injury. They gradually returned to normal levels over a 4-week period following the application of MEBO or copper nicotinate complex. Compared to untreated-burn group, postburn-healing changes (resolution of the inflammatory reaction, reepithelization of the epidermis, angiogenesis, deposition of collagen fibers, and recovery of the subcellualr organelles) were significantly accelerated following the application of either MEBO or copper nicotinate complex. Application of copper nicotinate complex was associated with improved healing of the thermal burns of the skin. The underlying molecular changes underlying these effects await further investigations.

  19. Pederin-type pathways of uncultivated bacterial symbionts: analysis of o-methyltransferases and generation of a biosynthetic hybrid.

    PubMed

    Zimmermann, Katrin; Engeser, Marianne; Blunt, John W; Munro, Murray H G; Piel, Jörn

    2009-03-04

    The complex polyketide pederin is a potent antitumor agent isolated from Paederus spp. rove beetles. We have previously isolated a set of genes from a bacterial endosymbiont that are good candidates for pederin biosynthesis. To biochemically study this pathway, we expressed three methyltransferases from the putative pederin pathway and used the partially unmethylated analogue mycalamide A from the marine sponge Mycale hentscheli as test substrate. Analysis by high-resolution MS/MS and NMR revealed that PedO regiospecifically methylates the marine compound to generate the nonnatural hybrid compound 18-O-methylmycalamide A with increased cytotoxicity. To our knowledge, this is the first biochemical evidence that invertebrates can obtain defensive complex polyketides from bacterial symbionts.

  20. Leigh syndrome caused by mutations in the flavoprotein (Fp) subunit of succinate dehydrogenase (SDHA).

    PubMed

    Horváth, R; Abicht, A; Holinski-Feder, E; Laner, A; Gempel, K; Prokisch, H; Lochmüller, H; Klopstock, T; Jaksch, M

    2006-01-01

    Detailed clinical, neuroradiological, histological, biochemical, and genetic investigations were undertaken in a child suffering from Leigh syndrome. The clinical symptoms started at age five months and led to a severe progressive neurodegenerative disorder causing epilepsy, psychomotor retardation, and tetraspasticity. Biochemical measurement of skeletal muscle showed a severe decrease in mitochondrial complex II. Sequencing of SDHA revealed compound heterozygosity for a nonsense mutation in exon 4 (W119X) and a missense mutation in exon 3 (A83V), both absent in normal controls. In six additional patients--five with Leigh or Leigh-like syndrome and one with neuropathy and ataxia associated with isolated deficiency of complex II--mutations in SDHA were not detected, indicating genetic heterogeneity.

  1. iview: an interactive WebGL visualizer for protein-ligand complex.

    PubMed

    Li, Hongjian; Leung, Kwong-Sak; Nakane, Takanori; Wong, Man-Hon

    2014-02-25

    Visualization of protein-ligand complex plays an important role in elaborating protein-ligand interactions and aiding novel drug design. Most existing web visualizers either rely on slow software rendering, or lack virtual reality support. The vital feature of macromolecular surface construction is also unavailable. We have developed iview, an easy-to-use interactive WebGL visualizer of protein-ligand complex. It exploits hardware acceleration rather than software rendering. It features three special effects in virtual reality settings, namely anaglyph, parallax barrier and oculus rift, resulting in visually appealing identification of intermolecular interactions. It supports four surface representations including Van der Waals surface, solvent excluded surface, solvent accessible surface and molecular surface. Moreover, based on the feature-rich version of iview, we have also developed a neat and tailor-made version specifically for our istar web platform for protein-ligand docking purpose. This demonstrates the excellent portability of iview. Using innovative 3D techniques, we provide a user friendly visualizer that is not intended to compete with professional visualizers, but to enable easy accessibility and platform independence.

  2. Monitoring Interactions and Dynamics of Endogenous Beta-catenin With Intracellular Nanobodies in Living Cells*

    PubMed Central

    Traenkle, Bjoern; Emele, Felix; Anton, Roman; Poetz, Oliver; Haeussler, Ragna S.; Maier, Julia; Kaiser, Philipp D.; Scholz, Armin M.; Nueske, Stefan; Buchfellner, Andrea; Romer, Tina; Rothbauer, Ulrich

    2015-01-01

    β-catenin is the key component of the canonical Wnt pathway and plays a crucial role in a multitude of developmental and homeostatic processes. The different tasks of β-catenin are orchestrated by its subcellular localization and participation in multiprotein complexes. To gain a better understanding of β-catenin's role in living cells we have generated a new set of single domain antibodies, referred to as nanobodies, derived from heavy chain antibodies of camelids. We selected nanobodies recognizing the N-terminal, core or C-terminal domain of β-catenin and applied these new high-affinity binders as capture molecules in sandwich immunoassays and co-immunoprecipitations of endogenous β-catenin complexes. In addition, we engineered intracellularly functional anti-β-catenin chromobodies by combining the binding moieties of the nanobodies with fluorescent proteins. For the first time, we were able to visualize the subcellular localization and nuclear translocation of endogenous β-catenin in living cells using these chromobodies. Moreover, the chromobody signal allowed us to trace the accumulation of diffusible, hypo-phosphorylated β-catenin in response to compound treatment in real time using High Content Imaging. The anti-β-catenin nanobodies and chromobodies characterized in this study are versatile tools that enable a novel and unique approach to monitor the dynamics of subcellular β-catenin in biochemical and cell biological assays. PMID:25595278

  3. Cooperative ethylene receptor signaling

    PubMed Central

    Liu, Qian; Wen, Chi-Kuang

    2012-01-01

    The gaseous plant hormone ethylene is perceived by a family of five ethylene receptor members in the dicotyledonous model plant Arabidopsis. Genetic and biochemical studies suggest that the ethylene response is suppressed by ethylene receptor complexes, but the biochemical nature of the receptor signal is unknown. Without appropriate biochemical measures to trace the ethylene receptor signal and quantify the signal strength, the biological significance of the modulation of ethylene responses by multiple ethylene receptors has yet to be fully addressed. Nevertheless, the ethylene receptor signal strength can be reflected by degrees in alteration of various ethylene response phenotypes and in expression levels of ethylene-inducible genes. This mini-review highlights studies that have advanced our understanding of cooperative ethylene receptor signaling. PMID:22827938

  4. Fascin-mediated propulsion of Listeria monocytogenes independent of frequent nucleation by the Arp2/3 complex.

    PubMed

    Brieher, William M; Coughlin, Margaret; Mitchison, Timothy J

    2004-04-26

    Actin-dependent propulsion of Listeria monocytogenes is thought to require frequent nucleation of actin polymerization by the Arp2/3 complex. We demonstrate that L. monocytogenes motility can be separated into an Arp2/3-dependent nucleation phase and an Arp2/3-independent elongation phase. Elongation-based propulsion requires a unique set of biochemical factors in addition to those required for Arp2/3-dependent motility. We isolated fascin from brain extracts as the only soluble factor required in addition to actin during the elongation phase for this type of movement. The nucleation reaction assembles a comet tail of branched actin filaments directly behind the bacterium. The elongation-based reaction generates a hollow cylinder of parallel bundles that attach along the sides of the bacterium. Bacteria move faster in the elongation reaction than in the presence of Arp2/3, and the rate is limited by the concentration of G-actin. The biochemical and structural differences between the two motility reactions imply that each operates through distinct biochemical and biophysical mechanisms.

  5. Building simple multiscale visualizations of outcrop geology using virtual reality modeling language (VRML)

    NASA Astrophysics Data System (ADS)

    Thurmond, John B.; Drzewiecki, Peter A.; Xu, Xueming

    2005-08-01

    Geological data collected from outcrop are inherently three-dimensional (3D) and span a variety of scales, from the megascopic to the microscopic. This presents challenges in both interpreting and communicating observations. The Virtual Reality Modeling Language provides an easy way for geoscientists to construct complex visualizations that can be viewed with free software. Field data in tabular form can be used to generate hierarchical multi-scale visualizations of outcrops, which can convey the complex relationships between a variety of data types simultaneously. An example from carbonate mud-mounds in southeastern New Mexico illustrates the embedding of three orders of magnitude of observation into a single visualization, for the purpose of interpreting depositional facies relationships in three dimensions. This type of raw data visualization can be built without software tools, yet is incredibly useful for interpreting and communicating data. Even simple visualizations can aid in the interpretation of complex 3D relationships that are frequently encountered in the geosciences.

  6. Temporal Structure and Complexity Affect Audio-Visual Correspondence Detection

    PubMed Central

    Denison, Rachel N.; Driver, Jon; Ruff, Christian C.

    2013-01-01

    Synchrony between events in different senses has long been considered the critical temporal cue for multisensory integration. Here, using rapid streams of auditory and visual events, we demonstrate how humans can use temporal structure (rather than mere temporal coincidence) to detect multisensory relatedness. We find psychophysically that participants can detect matching auditory and visual streams via shared temporal structure for crossmodal lags of up to 200 ms. Performance on this task reproduced features of past findings based on explicit timing judgments but did not show any special advantage for perfectly synchronous streams. Importantly, the complexity of temporal patterns influences sensitivity to correspondence. Stochastic, irregular streams – with richer temporal pattern information – led to higher audio-visual matching sensitivity than predictable, rhythmic streams. Our results reveal that temporal structure and its complexity are key determinants for human detection of audio-visual correspondence. The distinctive emphasis of our new paradigms on temporal patterning could be useful for studying special populations with suspected abnormalities in audio-visual temporal perception and multisensory integration. PMID:23346067

  7. Enhanced visual performance in obsessive compulsive personality disorder.

    PubMed

    Ansari, Zohreh; Fadardi, Javad Salehi

    2016-12-01

    Visual performance is considered as commanding modality in human perception. We tested whether Obsessive-compulsive personality disorder (OCPD) people do differently in visual performance tasks than people without OCPD. One hundred ten students of Ferdowsi University of Mashhad and non-student participants were tested by Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II), among whom 18 (mean age = 29.55; SD = 5.26; 84% female) met the criteria for OCPD classification; controls were 20 persons (mean age = 27.85; SD = 5.26; female = 84%), who did not met the OCPD criteria. Both groups were tested on a modified Flicker task for two dimensions of visual performance (i.e., visual acuity: detecting the location of change, complexity, and size; and visual contrast sensitivity). The OCPD group had responded more accurately on pairs related to size, complexity, and contrast, but spent more time to detect a change on pairs related to complexity and contrast. The OCPD individuals seem to have more accurate visual performance than non-OCPD controls. The findings support the relationship between personality characteristics and visual performance within the framework of top-down processing model. © 2016 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

  8. A Multilevel Gamma-Clustering Layout Algorithm for Visualization of Biological Networks

    PubMed Central

    Hruz, Tomas; Lucas, Christoph; Laule, Oliver; Zimmermann, Philip

    2013-01-01

    Visualization of large complex networks has become an indispensable part of systems biology, where organisms need to be considered as one complex system. The visualization of the corresponding network is challenging due to the size and density of edges. In many cases, the use of standard visualization algorithms can lead to high running times and poorly readable visualizations due to many edge crossings. We suggest an approach that analyzes the structure of the graph first and then generates a new graph which contains specific semantic symbols for regular substructures like dense clusters. We propose a multilevel gamma-clustering layout visualization algorithm (MLGA) which proceeds in three subsequent steps: (i) a multilevel γ-clustering is used to identify the structure of the underlying network, (ii) the network is transformed to a tree, and (iii) finally, the resulting tree which shows the network structure is drawn using a variation of a force-directed algorithm. The algorithm has a potential to visualize very large networks because it uses modern clustering heuristics which are optimized for large graphs. Moreover, most of the edges are removed from the visual representation which allows keeping the overview over complex graphs with dense subgraphs. PMID:23864855

  9. Influence of Biochemical Features of Burkholderia pseudomallei Strains on Identification Reliability by Vitek 2 System.

    PubMed

    Zakharova, Irina B; Lopasteyskaya, Yana A; Toporkov, Andrey V; Viktorov, Dmitry V

    2018-01-01

    Burkholderia pseudomallei is a Gram-negative saprophytic soil bacterium that causes melioidosis, a potentially fatal disease endemic in wet tropical areas. The currently available biochemical identification systems can misidentify some strains of B. pseudomallei . The aim of the present study was to identify the biochemical features of B. pseudomallei , which can affect its correct identification by Vitek 2 system. The biochemical patterns of 40 B. pseudomallei strains were obtained using Vitek 2 GN cards. The average contribution of biochemical tests in overall dissimilarities between correctly and incorrectly identified strains was assessed using nonmetric multidimensional scaling. It was found ( R statistic of 0.836, P = 0.001) that a combination of negative N-acetyl galactosaminidase, β-N-acetyl glucosaminidase, phosphatase, and positive D-cellobiase (dCEL), tyrosine arylamidase (TyrA), and L-proline arylamidase (ProA) tests leads to low discrimination of B. pseudomallei , whereas a set of positive dCEL and negative N-acetyl galactosaminidase, TyrA, and ProA determines the wrong identification of B. pseudomallei as Burkholderia cepacia complex. The further expansion of the Vitek 2 identification keys is needed for correct identification of atypical or regionally distributed biochemical profiles of B. pseudomallei .

  10. Decoding complex flow-field patterns in visual working memory.

    PubMed

    Christophel, Thomas B; Haynes, John-Dylan

    2014-05-01

    There has been a long history of research on visual working memory. Whereas early studies have focused on the role of lateral prefrontal cortex in the storage of sensory information, this has been challenged by research in humans that has directly assessed the encoding of perceptual contents, pointing towards a role of visual and parietal regions during storage. In a previous study we used pattern classification to investigate the storage of complex visual color patterns across delay periods. This revealed coding of such contents in early visual and parietal brain regions. Here we aim to investigate whether the involvement of visual and parietal cortex is also observable for other types of complex, visuo-spatial pattern stimuli. Specifically, we used a combination of fMRI and multivariate classification to investigate the retention of complex flow-field stimuli defined by the spatial patterning of motion trajectories of random dots. Subjects were trained to memorize the precise spatial layout of these stimuli and to retain this information during an extended delay. We used a multivariate decoding approach to identify brain regions where spatial patterns of activity encoded the memorized stimuli. Content-specific memory signals were observable in motion sensitive visual area MT+ and in posterior parietal cortex that might encode spatial information in a modality independent manner. Interestingly, we also found information about the memorized visual stimulus in somatosensory cortex, suggesting a potential crossmodal contribution to memory. Our findings thus indicate that working memory storage of visual percepts might be distributed across unimodal, multimodal and even crossmodal brain regions. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. [Sound improves distinction of low intensities of light in the visual cortex of a rabbit].

    PubMed

    Polianskiĭ, V B; Alymkulov, D E; Evtikhin, D V; Chernyshev, B V

    2011-01-01

    Electrodes were implanted into cranium above the primary visual cortex of four rabbits (Orictolagus cuniculus). At the first stage, visual evoked potentials (VEPs) were recorded in response to substitution of threshold visual stimuli (0.28 and 0.31 cd/m2). Then the sound (2000 Hz, 84 dB, duration 40 ms) was added simultaneously to every visual stimulus. Single sounds (without visual stimuli) did not produce a VEP-response. It was found that the amplitude ofVEP component N1 (85-110 ms) in response to complex stimuli (visual and sound) increased 1.6 times as compared to "simple" visual stimulation. At the second stage, paired substitutions of 8 different visual stimuli (range 0.38-20.2 cd/m2) by each other were performed. Sensory spaces of intensity were reconstructed on the basis of factor analysis. Sensory spaces of complexes were reconstructed in a similar way for simultaneous visual and sound stimulation. Comparison of vectors representing the stimuli in the spaces showed that the addition of a sound led to a 1.4-fold expansion of the space occupied by smaller intensities (0.28; 1.02; 3.05; 6.35 cd/m2). Also, the addition of the sound led to an arrangement of intensities in an ascending order. At the same time, the sound 1.33-times narrowed the space of larger intensities (8.48; 13.7; 16.8; 20.2 cd/m2). It is suggested that the addition of a sound improves a distinction of smaller intensities and impairs a dis- tinction of larger intensities. Sensory spaces revealed by complex stimuli were two-dimensional. This fact can be a consequence of integration of sound and light in a unified complex at simultaneous stimulation.

  12. Connecting the dots between genes, biochemistry, and disease susceptibility: systems biology modeling in human genetics.

    PubMed

    Moore, Jason H; Boczko, Erik M; Summar, Marshall L

    2005-02-01

    Understanding how DNA sequence variations impact human health through a hierarchy of biochemical and physiological systems is expected to improve the diagnosis, prevention, and treatment of common, complex human diseases. We have previously developed a hierarchical dynamic systems approach based on Petri nets for generating biochemical network models that are consistent with genetic models of disease susceptibility. This modeling approach uses an evolutionary computation approach called grammatical evolution as a search strategy for optimal Petri net models. We have previously demonstrated that this approach routinely identifies biochemical network models that are consistent with a variety of genetic models in which disease susceptibility is determined by nonlinear interactions between two or more DNA sequence variations. We review here this approach and then discuss how it can be used to model biochemical and metabolic data in the context of genetic studies of human disease susceptibility.

  13. CADLIVE toolbox for MATLAB: automatic dynamic modeling of biochemical networks with comprehensive system analysis.

    PubMed

    Inoue, Kentaro; Maeda, Kazuhiro; Miyabe, Takaaki; Matsuoka, Yu; Kurata, Hiroyuki

    2014-09-01

    Mathematical modeling has become a standard technique to understand the dynamics of complex biochemical systems. To promote the modeling, we had developed the CADLIVE dynamic simulator that automatically converted a biochemical map into its associated mathematical model, simulated its dynamic behaviors and analyzed its robustness. To enhance the feasibility by CADLIVE and extend its functions, we propose the CADLIVE toolbox available for MATLAB, which implements not only the existing functions of the CADLIVE dynamic simulator, but also the latest tools including global parameter search methods with robustness analysis. The seamless, bottom-up processes consisting of biochemical network construction, automatic construction of its dynamic model, simulation, optimization, and S-system analysis greatly facilitate dynamic modeling, contributing to the research of systems biology and synthetic biology. This application can be freely downloaded from http://www.cadlive.jp/CADLIVE_MATLAB/ together with an instruction.

  14. Learning Science in a Virtual Reality Application: The Impacts of Animated-Virtual Actors' Visual Complexity

    ERIC Educational Resources Information Center

    Kartiko, Iwan; Kavakli, Manolya; Cheng, Ken

    2010-01-01

    As the technology in computer graphics advances, Animated-Virtual Actors (AVAs) in Virtual Reality (VR) applications become increasingly rich and complex. Cognitive Theory of Multimedia Learning (CTML) suggests that complex visual materials could hinder novice learners from attending to the lesson properly. On the other hand, previous studies have…

  15. Sibling Curves 3: Imaginary Siblings and Tracing Complex Roots

    ERIC Educational Resources Information Center

    Harding, Ansie; Engelbrecht, Johann

    2009-01-01

    Visualizing complex roots of a quadratic equation has been a quest since the inception of the Argand plane in the 1800s. Many algebraic and numerical methods exist for calculating complex roots of an equation, but few visual methods exist. Following on from papers by Harding and Engelbrecht (A. Harding and J. Engelbrecht, "Sibling curves and…

  16. Measuring Search Efficiency in Complex Visual Search Tasks: Global and Local Clutter

    ERIC Educational Resources Information Center

    Beck, Melissa R.; Lohrenz, Maura C.; Trafton, J. Gregory

    2010-01-01

    Set size and crowding affect search efficiency by limiting attention for recognition and attention against competition; however, these factors can be difficult to quantify in complex search tasks. The current experiments use a quantitative measure of the amount and variability of visual information (i.e., clutter) in highly complex stimuli (i.e.,…

  17. Programmable chemical reaction networks: emulating regulatory functions in living cells using a bottom-up approach.

    PubMed

    van Roekel, Hendrik W H; Rosier, Bas J H M; Meijer, Lenny H H; Hilbers, Peter A J; Markvoort, Albert J; Huck, Wilhelm T S; de Greef, Tom F A

    2015-11-07

    Living cells are able to produce a wide variety of biological responses when subjected to biochemical stimuli. It has become apparent that these biological responses are regulated by complex chemical reaction networks (CRNs). Unravelling the function of these circuits is a key topic of both systems biology and synthetic biology. Recent progress at the interface of chemistry and biology together with the realisation that current experimental tools are insufficient to quantitatively understand the molecular logic of pathways inside living cells has triggered renewed interest in the bottom-up development of CRNs. This builds upon earlier work of physical chemists who extensively studied inorganic CRNs and showed how a system of chemical reactions can give rise to complex spatiotemporal responses such as oscillations and pattern formation. Using purified biochemical components, in vitro synthetic biologists have started to engineer simplified model systems with the goal of mimicking biological responses of intracellular circuits. Emulation and reconstruction of system-level properties of intracellular networks using simplified circuits are able to reveal key design principles and molecular programs that underlie the biological function of interest. In this Tutorial Review, we present an accessible overview of this emerging field starting with key studies on inorganic CRNs followed by a discussion of recent work involving purified biochemical components. Finally, we review recent work showing the versatility of programmable biochemical reaction networks (BRNs) in analytical and diagnostic applications.

  18. A framework for stochastic simulations and visualization of biological electron-transfer dynamics

    NASA Astrophysics Data System (ADS)

    Nakano, C. Masato; Byun, Hye Suk; Ma, Heng; Wei, Tao; El-Naggar, Mohamed Y.

    2015-08-01

    Electron transfer (ET) dictates a wide variety of energy-conversion processes in biological systems. Visualizing ET dynamics could provide key insight into understanding and possibly controlling these processes. We present a computational framework named VizBET to visualize biological ET dynamics, using an outer-membrane Mtr-Omc cytochrome complex in Shewanella oneidensis MR-1 as an example. Starting from X-ray crystal structures of the constituent cytochromes, molecular dynamics simulations are combined with homology modeling, protein docking, and binding free energy computations to sample the configuration of the complex as well as the change of the free energy associated with ET. This information, along with quantum-mechanical calculations of the electronic coupling, provides inputs to kinetic Monte Carlo (KMC) simulations of ET dynamics in a network of heme groups within the complex. Visualization of the KMC simulation results has been implemented as a plugin to the Visual Molecular Dynamics (VMD) software. VizBET has been used to reveal the nature of ET dynamics associated with novel nonequilibrium phase transitions in a candidate configuration of the Mtr-Omc complex due to electron-electron interactions.

  19. Charles Bonnet Syndrome in a Patient With Right Medial Occipital Lobe Infarction: Epileptic or Deafferentation Phenomenon?

    PubMed

    Kumral, Emre; Uluakay, Arzu; Dönmez, İlknur

    2015-07-01

    Charles Bonnet syndrome (CBS) is an uncommon disorder characterized by complex and recurrent visual hallucinations in patients with visual pathway pathologic defects. To describe a patient who experienced complex visual hallucinations following infarction in the right occipital lobe and epileptic seizure who was diagnosed as having CBS. A 65-year-old man presented acute ischemic stroke caused by artery to artery embolism involving the right occipital lobe. Following ischemic stroke, complex visual hallucinations in the left visual field not associated with loss of consciousness or delusion developed in the patient. Hallucinations persisted for >1 month and during hallucination, no electrographic seizures were recorded through 24 hours of videoelectroencephalographic monitoring. CBS may develop in a patient with occipital lobe infarction following an embolic event. CBS associated with medial occipital lobe infarction and epilepsy may coexist and reflects the abnormal functioning of an integrated neuronal network.

  20. Molecular gearing systems

    DOE PAGES

    Gakh, Andrei A.; Sachleben, Richard A.; Bryan, Jeff C.

    1997-11-01

    The race to create smaller devices is fueling much of the research in electronics. The competition has intensified with the advent of microelectromechanical systems (MEMS), in which miniaturization is already reaching the dimensional limits imposed by physics of current lithographic techniques. Also, in the realm of biochemistry, evidence is accumulating that certain enzyme complexes are capable of very sophisticated modes of motion. Complex synergistic biochemical complexes driven by sophisticated biomechanical processes are quite common. Their biochemical functions are based on the interplay of mechanical and chemical processes, including allosteric effects. In addition, the complexity of this interplay far exceeds thatmore » of typical chemical reactions. Understanding the behavior of artificial molecular devices as well as complex natural molecular biomechanical systems is difficult. Fortunately, the problem can be successfully resolved by direct molecular engineering of simple molecular systems that can mimic desired mechanical or electronic devices. These molecular systems are called technomimetics (the name is derived, by analogy, from biomimetics). Several classes of molecular systems that can mimic mechanical, electronic, or other features of macroscopic devices have been successfully synthesized by conventional chemical methods during the past two decades. In this article we discuss only one class of such model devices: molecular gearing systems.« less

  1. Mi2, an auto-antigen for dermatomyositis, is an ATP-dependent nucleosome remodeling factor.

    PubMed

    Wang, H B; Zhang, Y

    2001-06-15

    Dynamic changes in chromatin structure play an important role in transcription regulation. Recent studies have revealed two mechanisms that alter chromatin structure. One involves ATP-dependent chromatin remodeling, and the other involves acetylation of the core histone tails. We have previously purified and characterized a multi-subunit protein complex, NuRD, which possesses both nucleosome remodeling and histone deacetylase activities. Despite extensive biochemical characterization of the complex, little is known about the functions of its individual components. In this study, we focused on Mi2, a component of the NuRD complex. We found that, similar to the native NuRD complex, recombinant Mi2 is a DNA-dependent, nucleosome-stimulated ATPase. Kinetic analysis of the ATP hydrolysis reaction indicated that the differential stimulation of the Mi2 ATPase by DNA and nucleosomes were primarily due to their differential effects on the turnover number of the reaction. Furthermore, we demonstrated that recombinant Mi2 is an efficient nucleosome remodeling factor when compared to that of the native NuRD complex. Our results define the biochemical function of Mi2 and set the stage for understanding the mechanism of nucleosome remodeling in a defined reconstituted system.

  2. Mi2, an auto-antigen for dermatomyositis, is an ATP-dependent nucleosome remodeling factor

    PubMed Central

    Wang, Heng-Bin; Zhang, Yi

    2001-01-01

    Dynamic changes in chromatin structure play an important role in transcription regulation. Recent studies have revealed two mechanisms that alter chromatin structure. One involves ATP-dependent chromatin remodeling, and the other involves acetylation of the core histone tails. We have previously purified and characterized a multi-subunit protein complex, NuRD, which possesses both nucleosome remodeling and histone deacetylase activities. Despite extensive biochemical characterization of the complex, little is known about the functions of its individual components. In this study, we focused on Mi2, a component of the NuRD complex. We found that, similar to the native NuRD complex, recombinant Mi2 is a DNA-dependent, nucleosome-stimulated ATPase. Kinetic analysis of the ATP hydrolysis reaction indicated that the differential stimulation of the Mi2 ATPase by DNA and nucleosomes were primarily due to their differential effects on the turnover number of the reaction. Furthermore, we demonstrated that recombinant Mi2 is an efficient nucleosome remodeling factor when compared to that of the native NuRD complex. Our results define the biochemical function of Mi2 and set the stage for understanding the mechanism of nucleosome remodeling in a defined reconstituted system. PMID:11410659

  3. Isolation of viral ribonucleoprotein complexes from infected cells by tandem affinity purification.

    PubMed

    Mayer, Daniel; Baginsky, Sacha; Schwemmle, Martin

    2005-11-01

    The biochemical purification and analysis of viral ribonucleoprotein complexes (RNPs) of negative-strand RNA viruses is hampered by the lack of suitable tags that facilitate specific enrichment of these complexes. We therefore tested whether fusion of the tandem-affinity-purification (TAP) tag to the main component of viral RNPs, the nucleoprotein, might allow the isolation of these RNPs from cells. We constitutively expressed TAP-tagged nucleoprotein of Borna disease virus (BDV) in cells persistently infected with this virus. The TAP-tagged bait was efficiently incorporated into viral RNPs, did not interfere with BDV replication and was also packaged into viral particles. Native purification of the tagged protein complexes from BDV-infected cells by two consecutive affinity columns resulted in the isolation of several viral proteins, which were identified by MS analysis as the matrix protein, the two forms of the nucleoprotein and the phosphoprotein. In addition to the viral proteins, RT-PCR analysis revealed the presence of viral genomic RNA. Introduction of further protease cleavage sites within the TAP-tag significantly increased the purification yield. These results demonstrate that purification of TAP-tagged viral RNPs is possible and efficient, and may therefore provide new avenues for biochemical and functional studies of these complexes.

  4. Relationships among foliar chemistry, foliar polyamines, and soil chemistry in red spruce trees growing across the northeastern United States

    Treesearch

    Rakesh Minocha; Walter C. Shortle; Gregory B. Lawrence; Mark B. David; Subhash C. Minocha

    1997-01-01

    Forest trees are constantly exposed to various types of natural and anthropogenic stressors. A major long-term goal of our research is to develop a set of early physiological and biochemical markers of stress in trees before the appearance of visual symptoms. Six red spruce (Picea rubens Sarg.) stands from the northeastern United States were selected...

  5. Metabolism. Part III: Lipids.

    ERIC Educational Resources Information Center

    Bodner, George M.

    1986-01-01

    Describes the metabolic processes of complex lipids, including saponification, activation and transport, and the beta-oxidation spiral. Discusses fatty acid degradation in regard to biochemical energy and ketone bodies. (TW)

  6. A 3D puzzle approach to building protein-DNA structures.

    PubMed

    Hinton, Deborah M

    2017-03-15

    Despite recent advances in structural analysis, it is still challenging to obtain a high-resolution structure for a complex of RNA polymerase, transcriptional factors, and DNA. However, using biochemical constraints, 3D printed models of available structures, and computer modeling, one can build biologically relevant models of such supramolecular complexes.

  7. Using Simple Manipulatives to Improve Student Comprehension of a Complex Biological Process: Protein Synthesis

    ERIC Educational Resources Information Center

    Guzman, Karen; Bartlett, John

    2012-01-01

    Biological systems and living processes involve a complex interplay of biochemicals and macromolecular structures that can be challenging for undergraduate students to comprehend and, thus, misconceptions abound. Protein synthesis, or translation, is an example of a biological process for which students often hold many misconceptions. This article…

  8. Complex structure of the fission yeast SREBP-SCAP binding domains reveals an oligomeric organization.

    PubMed

    Gong, Xin; Qian, Hongwu; Shao, Wei; Li, Jingxian; Wu, Jianping; Liu, Jun-Jie; Li, Wenqi; Wang, Hong-Wei; Espenshade, Peter; Yan, Nieng

    2016-11-01

    Sterol regulatory element-binding protein (SREBP) transcription factors are master regulators of cellular lipid homeostasis in mammals and oxygen-responsive regulators of hypoxic adaptation in fungi. SREBP C-terminus binds to the WD40 domain of SREBP cleavage-activating protein (SCAP), which confers sterol regulation by controlling the ER-to-Golgi transport of the SREBP-SCAP complex and access to the activating proteases in the Golgi. Here, we biochemically and structurally show that the carboxyl terminal domains (CTD) of Sre1 and Scp1, the fission yeast SREBP and SCAP, form a functional 4:4 oligomer and Sre1-CTD forms a dimer of dimers. The crystal structure of Sre1-CTD at 3.5 Å and cryo-EM structure of the complex at 5.4 Å together with in vitro biochemical evidence elucidate three distinct regions in Sre1-CTD required for Scp1 binding, Sre1-CTD dimerization and tetrameric formation. Finally, these structurally identified domains are validated in a cellular context, demonstrating that the proper 4:4 oligomeric complex formation is required for Sre1 activation.

  9. "Structure and dynamics in complex chemical systems: Gaining new insights through recent advances in time-resolved spectroscopies.” ACS Division of Physical Chemistry Symposium presented at the Fall National ACS Meeting in Boston, MA, August 2015

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

    Crawford, Daniel

    8-Session Symposium on STRUCTURE AND DYNAMICS IN COMPLEX CHEMICAL SYSTEMS: GAINING NEW INSIGHTS THROUGH RECENT ADVANCES IN TIME-RESOLVED SPECTROSCOPIES. The intricacy of most chemical, biochemical, and material processes and their applications are underscored by the complex nature of the environments in which they occur. Substantial challenges for building a global understanding of a heterogeneous system include (1) identifying unique signatures associated with specific structural motifs within the heterogeneous distribution, and (2) resolving the significance of each of multiple time scales involved in both small- and large-scale nuclear reorganization. This symposium focuses on the progress in our understanding of dynamics inmore » complex systems driven by recent innovations in time-resolved spectroscopies and theoretical developments. Such advancement is critical for driving discovery at the molecular level facilitating new applications. Broad areas of interest include: Structural relaxation and the impact of structure on dynamics in liquids, interfaces, biochemical systems, materials, and other heterogeneous environments.« less

  10. Linear analysis near a steady-state of biochemical networks: control analysis, correlation metrics and circuit theory.

    PubMed

    Heuett, William J; Beard, Daniel A; Qian, Hong

    2008-05-15

    Several approaches, including metabolic control analysis (MCA), flux balance analysis (FBA), correlation metric construction (CMC), and biochemical circuit theory (BCT), have been developed for the quantitative analysis of complex biochemical networks. Here, we present a comprehensive theory of linear analysis for nonequilibrium steady-state (NESS) biochemical reaction networks that unites these disparate approaches in a common mathematical framework and thermodynamic basis. In this theory a number of relationships between key matrices are introduced: the matrix A obtained in the standard, linear-dynamic-stability analysis of the steady-state can be decomposed as A = SRT where R and S are directly related to the elasticity-coefficient matrix for the fluxes and chemical potentials in MCA, respectively; the control-coefficients for the fluxes and chemical potentials can be written in terms of RTBS and STBS respectively where matrix B is the inverse of A; the matrix S is precisely the stoichiometric matrix in FBA; and the matrix eAt plays a central role in CMC. One key finding that emerges from this analysis is that the well-known summation theorems in MCA take different forms depending on whether metabolic steady-state is maintained by flux injection or concentration clamping. We demonstrate that if rate-limiting steps exist in a biochemical pathway, they are the steps with smallest biochemical conductances and largest flux control-coefficients. We hypothesize that biochemical networks for cellular signaling have a different strategy for minimizing energy waste and being efficient than do biochemical networks for biosynthesis. We also discuss the intimate relationship between MCA and biochemical systems analysis (BSA).

  11. The Hetero-Hexameric Nature of a Chloroplast AAA+ FtsH Protease Contributes to Its Thermodynamic Stability

    PubMed Central

    Ziv, Tamar; Adam, Zach; Prag, Gali

    2012-01-01

    FtsH is an evolutionary conserved membrane-bound metalloprotease complex. While in most prokaryotes FtsH is encoded by a single gene, multiple FtsH genes are found in eukaryotes. Genetic and biochemical data suggest that the Arabidopsis chloroplast FtsH is a hetero-hexamer. This raises the question why photosynthetic organisms require a heteromeric complex, whereas in most bacteria a homomeric one is sufficient. To gain structural information of the possible complexes, the Arabidopsis FtsH2 (type B) and FtsH5 (type A) were modeled. An in silico study with mixed models of FtsH2/5 suggests that heteromeric hexamer structure with ratio of 4∶2 is more likely to exists. Specifically, calculation of the buried surface area at the interfaces between neighboring subunits revealed that a hetero-complex should be thermodynamically more stable than a homo-hexamer, due to the presence of additional hydrophobic and hydrophilic interactions. To biochemically assess this model, we generated Arabidopsis transgenic plants, expressing epitope-tagged FtsH2 and immuno-purified the protein. Mass-spectrometry analysis showed that FtsH2 is associated with FtsH1, FtsH5 and FtsH8. Interestingly, we found that ‘type B’ subunits (FtsH2 and FtsH8) were 2–3 fold more abundant than ‘type A’ (FtsH1 and FtsH5). The biochemical data corroborate the in silico model and suggest that the thylakoid FtsH hexamer is composed of two ‘type A’ and four ‘type B’ subunits. PMID:22558304

  12. BIOCHEMICAL INDICATORS OF HEPATOTOXICITY IN BLOOD SERUM OF RATS UNDER THE EFFECT OF NOVEL 4-THIAZOLIDINONE DERIVATIVES AND DOXORUBICIN AND THEIR COMPLEXES WITH POLYETHYLENEGLYCOL-CONTAINING NANOSCALE POLYMERIC CARRIER.

    PubMed

    Kobylinska, L I; Havrylyuk, D Ya; Ryabtseva, A O; Mitina, N E; Zaichenko, O S; Lesyk, R B; Zimenkovsky, B S; Stoika, R S

    2015-01-01

    The aim of this study was to compare the effect of new synthetic 4-tiazolidinone derivatives (compounds 3882, 3288 and 3833) and doxorubicin (positive control) in free form and in their complexes with synthetic polyethyleneglycol-containing nanoscale polymeric carrier on the biochemical indicators of hepatotoxicity in blood serum of rats. The activity of enzymes considered as the markers of hepatotoxicity, as well as. the concentration of total protein, urea and creatinine were measured in blood serum of rats. It was found that after injection of investigated compounds the activities ofalanine aminotransferase, alkaline phosphatase and α-amylase increased in comparison to control. Doxorubicin injection was accompanied by 4-fold increase in the activity of γ-glutamyltransferase, and injection ofcompound 3833 led to 2.5-fold elevation ofthe activity of this enzyme. Complexation ofthese antineoplastic derivatives with a synthetic nanocarrier lowered the activity ofthe investigated enzymes substantially if compared to the effect of these compounds infreeform. The most evident decrease was measured for α-amylase, γ-glutamyltransferase and lactate dehydrogenase activities. The normalization of concentrations of total protein, urea and creatinine in blood serum of rats treated with complexes of the studied compounds with a polymeric carrier comparing with their introduction infreeform was also detected. Thus, the immobilization by novel polymeric carrier of anticancer drugs possessing high general toxicity in the treated organism mitigates their toxic effect, which is evident as normalization of specific biochemical indicators of the hepatodestructive effects of the anticancer drugs.

  13. Rainbows, graticules, and logos…oh my!

    NASA Astrophysics Data System (ADS)

    Pisut, D.; MacIntosh, E.; McDougall, C.

    2016-12-01

    Data visualizations are meant to simplify the complex. However, visualizations in geosciences are often made more complex than need be. Color palettes that hide Earth system dynamics or even cannot be seen; annotations that clutter the display more than provide context; logos that only add meaningless acronyms and other visual distraction. We will share lessons learned on how tweaking these and other components of visualizations improve the usability and comprehension for multiple audiences - especially since the best practices for one audience (e.g., television) do not necessarily translate to other audiences (e.g., print, education, web, etc).

  14. Visual Constructive and Visual-Motor Skills in Deaf Native Signers

    ERIC Educational Resources Information Center

    Hauser, Peter C.; Cohen, Julie; Dye, Matthew W. G.; Bavelier, Daphne

    2007-01-01

    Visual constructive and visual-motor skills in the deaf population were investigated by comparing performance of deaf native signers (n = 20) to that of hearing nonsigners (n = 20) on the Beery-Buktenica Developmental Test of Visual-Motor Integration, Rey-Osterrieth Complex Figure Test, Wechsler Memory Scale Visual Reproduction subtest, and…

  15. A Complex Story: Universal Preference vs. Individual Differences Shaping Aesthetic Response to Fractals Patterns.

    PubMed

    Street, Nichola; Forsythe, Alexandra M; Reilly, Ronan; Taylor, Richard; Helmy, Mai S

    2016-01-01

    Fractal patterns offer one way to represent the rough complexity of the natural world. Whilst they dominate many of our visual experiences in nature, little large-scale perceptual research has been done to explore how we respond aesthetically to these patterns. Previous research (Taylor et al., 2011) suggests that the fractal patterns with mid-range fractal dimensions (FDs) have universal aesthetic appeal. Perceptual and aesthetic responses to visual complexity have been more varied with findings suggesting both linear (Forsythe et al., 2011) and curvilinear (Berlyne, 1970) relationships. Individual differences have been found to account for many of the differences we see in aesthetic responses but some, such as culture, have received little attention within the fractal and complexity research fields. This two-study article aims to test preference responses to FD and visual complexity, using a large cohort (N = 443) of participants from around the world to allow universality claims to be tested. It explores the extent to which age, culture and gender can predict our preferences for fractally complex patterns. Following exploratory analysis that found strong correlations between FD and visual complexity, a series of linear mixed-effect models were implemented to explore if each of the individual variables could predict preference. The first tested a linear complexity model (likelihood of selecting the more complex image from the pair of images) and the second a mid-range FD model (likelihood of selecting an image within mid-range). Results show that individual differences can reliably predict preferences for complexity across culture, gender and age. However, in fitting with current findings the mid-range models show greater consistency in preference not mediated by gender, age or culture. This article supports the established theory that the mid-range fractal patterns appear to be a universal construct underlying preference but also highlights the fragility of universal claims by demonstrating individual differences in preference for the interrelated concept of visual complexity. This highlights a current stalemate in the field of empirical aesthetics.

  16. Brief Report: Effect of Spatial Complexity on Visual Short-Term Memory and Self-Reported Autistic-Like Traits in Typically Developed Individuals

    ERIC Educational Resources Information Center

    Takahashi, Junichi; Gyoba, Jiro; Yamawaki, Nozomi

    2013-01-01

    This report examines effects of the spatial complexity of configurations on visual short-term memory (VSTM) capacity for individuals from the general population differing on autism-spectrum quotient (AQ) scores. During each trial, nine-line segments with various orientations were arrayed in simple or complex configurations and presented in both…

  17. In the working memory of the beholder: Art appreciation is enhanced when visual complexity is compatible with working memory.

    PubMed

    Sherman, Aleksandra; Grabowecky, Marcia; Suzuki, Satoru

    2015-08-01

    What shapes art appreciation? Much research has focused on the importance of visual features themselves (e.g., symmetry, natural scene statistics) and of the viewer's experience and expertise with specific artworks. However, even after taking these factors into account, there are considerable individual differences in art preferences. Our new result suggests that art preference is also influenced by the compatibility between visual properties and the characteristics of the viewer's visual system. Specifically, we have demonstrated, using 120 artworks from diverse periods, cultures, genres, and styles, that art appreciation is increased when the level of visual complexity within an artwork is compatible with the viewer's visual working memory capacity. The result highlights the importance of the interaction between visual features and the beholder's general visual capacity in shaping art appreciation. (c) 2015 APA, all rights reserved).

  18. Optical Coherence Tomography and Autofluorescence Imaging of Human Tonsil

    PubMed Central

    Pahlevaninezhad, Hamid; Lee, Anthony M. D.; Rosin, Miriam; Sun, Ivan; Zhang, Lewei; Hakimi, Mehrnoush; MacAulay, Calum; Lane, Pierre M.

    2014-01-01

    For the first time, we present co-registered autofluorescence imaging and optical coherence tomography (AF/OCT) of excised human palatine tonsils to evaluate the capabilities of OCT to visualize tonsil tissue components. Despite limited penetration depth, OCT can provide detailed structural information about tonsil tissue with much higher resolution than that of computed tomography, magnetic resonance imaging, and Ultrasound. Different tonsil tissue components such as epithelium, dense connective tissue, lymphoid nodules, and crypts can be visualized by OCT. The co-registered AF imaging can provide matching biochemical information. AF/OCT scans may provide a non-invasive tool for detecting tonsillar cancers and for studying the natural history of their development. PMID:25542010

  19. Advanced morphological and biochemical magnetic resonance imaging of cartilage repair procedures in the knee joint at 3 Tesla.

    PubMed

    Welsch, Goetz H; Mamisch, Tallal C; Hughes, Timothy; Domayer, Stephan; Marlovits, Stefan; Trattnig, Siegfried

    2008-09-01

    Morphological and biochemical magnetic resonance imaging (MRI) is due to high field MR systems, advanced coil technology, and sophisticated sequence protocols capable of visualizing articular cartilage in vivo with high resolution in clinical applicable scan time. Several conventional two-dimensional (2D) and three-dimensional (3D) approaches show changes in cartilage structure. Furthermore newer isotropic 3D sequences show great promise in improving cartilage imaging and additionally in diagnosing surrounding pathologies within the knee joint. Functional MR approaches are additionally able to provide a specific measure of the composition of cartilage. Cartilage physiology and ultra-structure can be determined, changes in cartilage macromolecules can be detected, and cartilage repair tissue can thus be assessed and potentially differentiated. In cartilage defects and following nonsurgical and surgical cartilage repair, morphological MRI provides the basis for diagnosis and follow-up evaluation, whereas biochemical MRI provides a deeper insight into the composition of cartilage and cartilage repair tissue. A combination of both, together with clinical evaluation, may represent a desirable multimodal approach in the future, also available in routine clinical use.

  20. New pharmacologic approaches to treating diabetic retinopathy.

    PubMed

    Ryan, Gina J

    2007-09-01

    The goal of treatment of diabetic retinopathy, limitations of laser photocoagulation, endpoints used in clinical studies of diabetic retinopathy treatments, and the mechanism of action, efficacy, and safety of several new and emerging therapies targeting the biochemical pathways that link chronic hyperglycemia with microvascular damage in patients with diabetic retinopathy are discussed. Improving or preserving vision is the primary goal of treatment for diabetic retinopathy. Limitations of laser photocoagulation include a lack of efficacy in some cases, discomfort from the procedure, the need for repeated treatment, and a risk of retinal damage and scarring. Visual acuity, quality of life, and macular thickness are used as endpoints in clinical studies of diabetic retinopathy treatments. Microvascular damage in patients with chronic hyperglycemia is mediated by interrelated pathways involving aldose reductase, advanced glycation end products, protein kinase C (PKC), and vascular endothelial growth factor (VEGF). Oral aldose reductase inhibitors have been studied with some success only in patients with diabetic peripheral neuropathy. The oral PKC inhibitor midostaurin and oral selective PKC beta inhibitor ruboxistaurin appear promising for improving or maintaining visual acuity, with gastrointestinal complaints the most commonly reported adverse effects. Intra-vitreal injection of corticosteroids or VEGF inhibitors is associated with short-lived improvement in or maintenance of visual acuity, a need for repeated injection, and a risk of local adverse effects. A variety of promising new therapies for diabetic retinopathy targeting the biochemical pathways that cause microvascular damage are under investigation. Additional clinical research is needed to determine the role of these new therapies in treating diabetic retinopathy.

  1. Environmental influences on neural systems of relational complexity

    PubMed Central

    Kalbfleisch, M. Layne; deBettencourt, Megan T.; Kopperman, Rebecca; Banasiak, Meredith; Roberts, Joshua M.; Halavi, Maryam

    2013-01-01

    Constructivist learning theory contends that we construct knowledge by experience and that environmental context influences learning. To explore this principle, we examined the cognitive process relational complexity (RC), defined as the number of visual dimensions considered during problem solving on a matrix reasoning task and a well-documented measure of mature reasoning capacity. We sought to determine how the visual environment influences RC by examining the influence of color and visual contrast on RC in a neuroimaging task. To specify the contributions of sensory demand and relational integration to reasoning, our participants performed a non-verbal matrix task comprised of color, no-color line, or black-white visual contrast conditions parametrically varied by complexity (relations 0, 1, 2). The use of matrix reasoning is ecologically valid for its psychometric relevance and for its potential to link the processing of psychophysically specific visual properties with various levels of RC during reasoning. The role of these elements is important because matrix tests assess intellectual aptitude based on these seemingly context-less exercises. This experiment is a first step toward examining the psychophysical underpinnings of performance on these types of problems. The importance of this is increased in light of recent evidence that intelligence can be linked to visual discrimination. We submit three main findings. First, color and black-white visual contrast (BWVC) add demand at a basic sensory level, but contributions from color and from BWVC are dissociable in cortex such that color engages a “reasoning heuristic” and BWVC engages a “sensory heuristic.” Second, color supports contextual sense-making by boosting salience resulting in faster problem solving. Lastly, when visual complexity reaches 2-relations, color and visual contrast relinquish salience to other dimensions of problem solving. PMID:24133465

  2. A review of uncertainty visualization within the IPCC reports

    NASA Astrophysics Data System (ADS)

    Nocke, Thomas; Reusser, Dominik; Wrobel, Markus

    2015-04-01

    Results derived from climate model simulations confront non-expert users with a variety of uncertainties. This gives rise to the challenge that the scientific information must be communicated such that it can be easily understood, however, the complexity of the science behind is still incorporated. With respect to the assessment reports of the IPCC, the situation is even more complicated, because heterogeneous sources and multiple types of uncertainties need to be compiled together. Within this work, we systematically (1) analyzed the visual representation of uncertainties in the IPCC AR4 and AR5 reports, and (2) executed a questionnaire to evaluate how different user groups such as decision-makers and teachers understand these uncertainty visualizations. Within the first step, we classified visual uncertainty metaphors for spatial, temporal and abstract representations. As a result, we clearly identified a high complexity of the IPCC visualizations compared to standard presentation graphics, sometimes even integrating two or more uncertainty classes / measures together with the "certain" (mean) information. Further we identified complex written uncertainty explanations within image captions even within the "summary reports for policy makers". In the second step, based on these observations, we designed a questionnaire to investigate how non-climate experts understand these visual representations of uncertainties, how visual uncertainty coding might hinder the perception of the "non-uncertain" data, and if alternatives for certain IPCC visualizations exist. Within the talk/poster, we will present first results from this questionnaire. Summarizing, we identified a clear trend towards complex images within the latest IPCC reports, with a tendency to incorporate as much as possible information into the visual representations, resulting in proprietary, non-standard graphic representations that are not necessarily easy to comprehend on one glimpse. We conclude that further translation is required to (visually) present the IPCC results to non-experts, providing tailored static and interactive visualization solutions for different user groups.

  3. Biochemical characterization of native Usher protein complexes from a vesicular subfraction of tracheal epithelial cells.

    PubMed

    Zallocchi, Marisa; Sisson, Joseph H; Cosgrove, Dominic

    2010-02-16

    Usher syndrome is the major cause of deaf/blindness in the world. It is a genetic heterogeneous disorder, with nine genes already identified as causative for the disease. We noted expression of all known Usher proteins in bovine tracheal epithelial cells and exploited this system for large-scale biochemical analysis of Usher protein complexes. The dissected epithelia were homogenized in nondetergent buffer and sedimented on sucrose gradients. At least two complexes were evident after the first gradient: one formed by specific isoforms of CDH23, PCDH15, and VLGR-1 and a different one at the top of the gradient that included all of the Usher proteins and rab5, a transport vesicle marker. TEM analysis of these top fractions found them enriched in 100-200 nm vesicles, confirming a vesicular association of the Usher complex(es). Immunoisolation of these vesicles confirmed some of the associations already predicted and identified novel interactions. When the vesicles are lysed in the presence of phenylbutyrate, most of the Usher proteins cosediment into the gradient at a sedimentation coefficient of approximately 50 S, correlating with a predicted molecular mass of 2 x 10(6) Da. Although it is still unclear whether there is only one complex or several independent complexes that are trafficked within distinct vesicular pools, this work shows for the first time that native Usher protein complexes occur in vivo. This complex(es) is present primarily in transport vesicles at the apical pole of tracheal epithelial cells, predicting that Usher proteins may be directionally transported as complexes in hair cells and photoreceptors.

  4. BIOCHEMICAL CHARACTERIZATION OF NATIVE USHER PROTEIN COMPLEXES FROM A VESICULAR SUBFRACTION OF TRACHEAL EPITHELIAL CELLS†

    PubMed Central

    Zallocchi, Marisa; Sisson, Joseph H.; Cosgrove, Dominic

    2010-01-01

    Usher syndrome is the major cause of deaf/blindness in the world. It is a genetic heterogeneous disorder, with nine genes already identified as causative for the disease. We noted expression of all known Usher proteins in bovine tracheal epithelial cells, and exploited this system for large-scale biochemical analysis of Usher protein complexes. The dissected epithelia were homogenized in non-detergent buffer, and sedimented on sucrose gradients. At least two complexes were evident after the first gradient: one formed by specific isoforms of CDH23, PCDH15 and VLGR-1, and a different one at the top of the gradient that included all the Usher proteins and rab5, a transport vesicle marker. TEM analysis of these top fractions found them enriched in 100–200 nm vesicles, confirming a vesicular association of the Usher complex(es). Immunoisolation of these vesicles confirmed some of the associations already predicted and identified novel interactions. When the vesicles are lysed in the presence of phenylbutyrate, most of the Usher proteins co-sediment into the gradient at a sedimentation coefficient of approximately 50S, correlating with a predicted molecular mass of 2 × 106 Daltons. Although it is still unclear whether there is only one complex or several independent complexes that are trafficked within distinct vesicular pools, this work shows for the first time that native Usher proteins complexes occur in vivo. This complex(es) is present primarily in transport vesicles at the apical pole of tracheal epithelial cells, predicting that Usher proteins may be directionally transported as complexes in hair cells and photoreceptors. PMID:20058854

  5. CMS-G from Beta vulgaris ssp. maritima is maintained in natural populations despite containing an atypical cytochrome c oxidase.

    PubMed

    Meyer, Etienne H; Lehmann, Caroline; Boivin, Stéphane; Brings, Lea; De Cauwer, Isabelle; Bock, Ralph; Kühn, Kristina; Touzet, Pascal

    2018-02-23

    While mitochondrial mutants of the respiratory machinery are rare and often lethal, cytoplasmic male sterility (CMS), a mitochondrially inherited trait that results in pollen abortion, is frequently encountered in wild populations. It generates a breeding system called gynodioecy. In Beta vulgaris ssp. maritima , a gynodioecious species, we found CMS-G to be widespread across the distribution range of the species. Despite the sequencing of the mitochondrial genome of CMS-G, the mitochondrial sterilizing factor causing CMS-G is still unknown. By characterizing biochemically CMS-G, we found that the expression of several mitochondrial proteins is altered in CMS-G plants. In particular, Cox1, a core subunit of the cytochrome c oxidase (complex IV), is larger but can still assemble into complex IV. However, the CMS-G-specific complex IV was only detected as a stabilized dimer. We did not observe any alteration of the affinity of complex IV for cytochrome c ; however, in CMS-G, complex IV capacity is reduced. Our results show that CMS-G is maintained in many natural populations despite being associated with an atypical complex IV. We suggest that the modified complex IV could incur the associated cost predicted by theoretical models to maintain gynodioecy in wild populations. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  6. Brain signal complexity rises with repetition suppression in visual learning.

    PubMed

    Lafontaine, Marc Philippe; Lacourse, Karine; Lina, Jean-Marc; McIntosh, Anthony R; Gosselin, Frédéric; Théoret, Hugo; Lippé, Sarah

    2016-06-21

    Neuronal activity associated with visual processing of an unfamiliar face gradually diminishes when it is viewed repeatedly. This process, known as repetition suppression (RS), is involved in the acquisition of familiarity. Current models suggest that RS results from interactions between visual information processing areas located in the occipito-temporal cortex and higher order areas, such as the dorsolateral prefrontal cortex (DLPFC). Brain signal complexity, which reflects information dynamics of cortical networks, has been shown to increase as unfamiliar faces become familiar. However, the complementarity of RS and increases in brain signal complexity have yet to be demonstrated within the same measurements. We hypothesized that RS and brain signal complexity increase occur simultaneously during learning of unfamiliar faces. Further, we expected alteration of DLPFC function by transcranial direct current stimulation (tDCS) to modulate RS and brain signal complexity over the occipito-temporal cortex. Participants underwent three tDCS conditions in random order: right anodal/left cathodal, right cathodal/left anodal and sham. Following tDCS, participants learned unfamiliar faces, while an electroencephalogram (EEG) was recorded. Results revealed RS over occipito-temporal electrode sites during learning, reflected by a decrease in signal energy, a measure of amplitude. Simultaneously, as signal energy decreased, brain signal complexity, as estimated with multiscale entropy (MSE), increased. In addition, prefrontal tDCS modulated brain signal complexity over the right occipito-temporal cortex during the first presentation of faces. These results suggest that although RS may reflect a brain mechanism essential to learning, complementary processes reflected by increases in brain signal complexity, may be instrumental in the acquisition of novel visual information. Such processes likely involve long-range coordinated activity between prefrontal and lower order visual areas. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Methods of Model Reduction for Large-Scale Biological Systems: A Survey of Current Methods and Trends.

    PubMed

    Snowden, Thomas J; van der Graaf, Piet H; Tindall, Marcus J

    2017-07-01

    Complex models of biochemical reaction systems have become increasingly common in the systems biology literature. The complexity of such models can present a number of obstacles for their practical use, often making problems difficult to intuit or computationally intractable. Methods of model reduction can be employed to alleviate the issue of complexity by seeking to eliminate those portions of a reaction network that have little or no effect upon the outcomes of interest, hence yielding simplified systems that retain an accurate predictive capacity. This review paper seeks to provide a brief overview of a range of such methods and their application in the context of biochemical reaction network models. To achieve this, we provide a brief mathematical account of the main methods including timescale exploitation approaches, reduction via sensitivity analysis, optimisation methods, lumping, and singular value decomposition-based approaches. Methods are reviewed in the context of large-scale systems biology type models, and future areas of research are briefly discussed.

  8. Biochemical Characterization of Glutamate Racemase-A New Candidate Drug Target against Burkholderia cenocepacia Infections.

    PubMed

    Israyilova, Aygun; Buroni, Silvia; Forneris, Federico; Scoffone, Viola Camilla; Shixaliyev, Namiq Q; Riccardi, Giovanna; Chiarelli, Laurent Roberto

    2016-01-01

    The greatest obstacle for the treatment of cystic fibrosis patients infected with the Burkholderia species is their intrinsic antibiotic resistance. For this reason, there is a need to develop new effective compounds. Glutamate racemase, an essential enzyme for the biosynthesis of the bacterial cell wall, is an excellent candidate target for the design of new antibacterial drugs. To this aim, we recombinantly produced and characterized glutamate racemase from Burkholderia cenocepacia J2315. From the screening of an in-house library of compounds, two Zn (II) and Mn (III) 1,3,5-triazapentadienate complexes were found to efficiently inhibit the glutamate racemase activity with IC50 values of 35.3 and 10.0 μM, respectively. Using multiple biochemical approaches, the metal complexes have been shown to affect the enzyme activity by binding to the enzyme-substrate complex and promoting the formation of an inhibited dimeric form of the enzyme. Our results corroborate the value of glutamate racemase as a good target for the development of novel inhibitors against Burkholderia.

  9. CTCF and cohesin regulate chromatin loop stability with distinct dynamics

    PubMed Central

    Hansen, Anders S; Pustova, Iryna; Cattoglio, Claudia; Tjian, Robert; Darzacq, Xavier

    2017-01-01

    Folding of mammalian genomes into spatial domains is critical for gene regulation. The insulator protein CTCF and cohesin control domain location by folding domains into loop structures, which are widely thought to be stable. Combining genomic and biochemical approaches we show that CTCF and cohesin co-occupy the same sites and physically interact as a biochemically stable complex. However, using single-molecule imaging we find that CTCF binds chromatin much more dynamically than cohesin (~1–2 min vs. ~22 min residence time). Moreover, after unbinding, CTCF quickly rebinds another cognate site unlike cohesin for which the search process is long (~1 min vs. ~33 min). Thus, CTCF and cohesin form a rapidly exchanging 'dynamic complex' rather than a typical stable complex. Since CTCF and cohesin are required for loop domain formation, our results suggest that chromatin loops are dynamic and frequently break and reform throughout the cell cycle. DOI: http://dx.doi.org/10.7554/eLife.25776.001 PMID:28467304

  10. Cross-modal links among vision, audition, and touch in complex environments.

    PubMed

    Ferris, Thomas K; Sarter, Nadine B

    2008-02-01

    This study sought to determine whether performance effects of cross-modal spatial links that were observed in earlier laboratory studies scale to more complex environments and need to be considered in multimodal interface design. It also revisits the unresolved issue of cross-modal cuing asymmetries. Previous laboratory studies employing simple cues, tasks, and/or targets have demonstrated that the efficiency of processing visual, auditory, and tactile stimuli is affected by the modality, lateralization, and timing of surrounding cues. Very few studies have investigated these cross-modal constraints in the context of more complex environments to determine whether they scale and how complexity affects the nature of cross-modal cuing asymmetries. Amicroworld simulation of battlefield operations with a complex task set and meaningful visual, auditory, and tactile stimuli was used to investigate cuing effects for all cross-modal pairings. Significant asymmetric performance effects of cross-modal spatial links were observed. Auditory cues shortened response latencies for collocated visual targets but visual cues did not do the same for collocated auditory targets. Responses to contralateral (rather than ipsilateral) targets were faster for tactually cued auditory targets and each visual-tactile cue-target combination, suggesting an inhibition-of-return effect. The spatial relationships between multimodal cues and targets significantly affect target response times in complex environments. The performance effects of cross-modal links and the observed cross-modal cuing asymmetries need to be examined in more detail and considered in future interface design. The findings from this study have implications for the design of multimodal and adaptive interfaces and for supporting attention management in complex, data-rich domains.

  11. IP-Based Video Modem Extender Requirements

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

    Pierson, L G; Boorman, T M; Howe, R E

    2003-12-16

    Visualization is one of the keys to understanding large complex data sets such as those generated by the large computing resources purchased and developed by the Advanced Simulation and Computing program (aka ASCI). In order to be convenient to researchers, visualization data must be distributed to offices and large complex visualization theaters. Currently, local distribution of the visual data is accomplished by distance limited modems and RGB switches that simply do not scale to hundreds of users across the local, metropolitan, and WAN distances without incurring large costs in fiber plant installation and maintenance. Wide Area application over the DOEmore » Complex is infeasible using these limited distance RGB extenders. On the other hand, Internet Protocols (IP) over Ethernet is a scalable well-proven technology that can distribute large volumes of data over these distances. Visual data has been distributed at lower resolutions over IP in industrial applications. This document describes requirements of the ASCI program in visual signal distribution for the purpose of identifying industrial partners willing to develop products to meet ASCI's needs.« less

  12. Atypical Balance between Occipital and Fronto-Parietal Activation for Visual Shape Extraction in Dyslexia

    PubMed Central

    Zhang, Ying; Whitfield-Gabrieli, Susan; Christodoulou, Joanna A.; Gabrieli, John D. E.

    2013-01-01

    Reading requires the extraction of letter shapes from a complex background of text, and an impairment in visual shape extraction would cause difficulty in reading. To investigate the neural mechanisms of visual shape extraction in dyslexia, we used functional magnetic resonance imaging (fMRI) to examine brain activation while adults with or without dyslexia responded to the change of an arrow’s direction in a complex, relative to a simple, visual background. In comparison to adults with typical reading ability, adults with dyslexia exhibited opposite patterns of atypical activation: decreased activation in occipital visual areas associated with visual perception, and increased activation in frontal and parietal regions associated with visual attention. These findings indicate that dyslexia involves atypical brain organization for fundamental processes of visual shape extraction even when reading is not involved. Overengagement in higher-order association cortices, required to compensate for underengagment in lower-order visual cortices, may result in competition for top-down attentional resources helpful for fluent reading. PMID:23825653

  13. How Do Structure and Charge Affect Metal-Complex Binding to DNA? An Upper-Division Integrated Laboratory Project Using Cyclic Voltammetry

    ERIC Educational Resources Information Center

    Kulczynska, Agnieszka; Johnson, Reed; Frost, Tony; Margerum, Lawrence D.

    2011-01-01

    An advanced undergraduate laboratory project is described that integrates inorganic, analytical, physical, and biochemical techniques to reveal differences in binding between cationic metal complexes and anionic DNA (herring testes). Students were guided to formulate testable hypotheses based on the title question and a list of different metal…

  14. On the Validity of the Name teyahalee as Applied to a Member of the Plethodon glutinosus Complex (Caudata: Plethodontidae): A New Name

    Treesearch

    Nelson G. Hairston

    1993-01-01

    The name Plethudon teyahalee (Hairston) cannot be applied to the member of the P. glutinosus complex as designated by Highton (1983). Biochemical data show that the population from which the type of teyahelee was taken consists of hybrids between local populations representing the P. jordani...

  15. Often Ignored Facts about the Control of the 2-Oxoglutarate Dehydrogenase Complex

    ERIC Educational Resources Information Center

    Strumilo, Slawomir

    2005-01-01

    Information about the control of the activity of the 2-oxoglutarate dehydrogenase complex (OGDHC), a key enzyme in the citric acid cycle, is not well covered in the biochemical education literature, especially as it concerns the allosteric regulation of OGDHC by adenine nucleotide and ortophosphate. From experimental work published during the last…

  16. Chemistry and biology of the initial steps in vision: the Friedenwald lecture.

    PubMed

    Palczewski, Krzysztof

    2014-10-22

    Visual transduction is the process in the eye whereby absorption of light in the retina is translated into electrical signals that ultimately reach the brain. The first challenge presented by visual transduction is to understand its molecular basis. We know that maintenance of vision is a continuous process requiring the activation and subsequent restoration of a vitamin A-derived chromophore through a series of chemical reactions catalyzed by enzymes in the retina and retinal pigment epithelium (RPE). Diverse biochemical approaches that identified key proteins and reactions were essential to achieve a mechanistic understanding of these visual processes. The three-dimensional arrangements of these enzymes' polypeptide chains provide invaluable insights into their mechanisms of action. A wealth of information has already been obtained by solving high-resolution crystal structures of both rhodopsin and the retinoid isomerase from pigment RPE (RPE65). Rhodopsin, which is activated by photoisomerization of its 11-cis-retinylidene chromophore, is a prototypical member of a large family of membrane-bound proteins called G protein-coupled receptors (GPCRs). RPE65 is a retinoid isomerase critical for regeneration of the chromophore. Electron microscopy (EM) and atomic force microscopy have provided insights into how certain proteins are assembled to form much larger structures such as rod photoreceptor cell outer segment membranes. A second challenge of visual transduction is to use this knowledge to devise therapeutic approaches that can prevent or reverse conditions leading to blindness. Imaging modalities like optical coherence tomography (OCT) and scanning laser ophthalmoscopy (SLO) applied to appropriate animal models as well as human retinal imaging have been employed to characterize blinding diseases, monitor their progression, and evaluate the success of therapeutic agents. Lately two-photon (2-PO) imaging, together with biochemical assays, are revealing functional aspects of vision at a new molecular level. These multidisciplinary approaches combined with suitable animal models and inbred mutant species can be especially helpful in translating provocative cell and tissue culture findings into therapeutic options for further development in animals and eventually in humans. A host of different approaches and techniques is required for substantial progress in understanding fundamental properties of the visual system. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  17. The Visual Orientation Memory of "Drosophila" Requires Foraging (PKG) Upstream of Ignorant (RSK2) in Ring Neurons of the Central Complex

    ERIC Educational Resources Information Center

    Kuntz, Sara; Poeck, Burkhard; Sokolowski, Marla B.; Strauss, Roland

    2012-01-01

    Orientation and navigation in a complex environment requires path planning and recall to exert goal-driven behavior. Walking "Drosophila" flies possess a visual orientation memory for attractive targets which is localized in the central complex of the adult brain. Here we show that this type of working memory requires the cGMP-dependent protein…

  18. 25 Years of Tension over Actin Binding to the Cadherin Cell Adhesion Complex: The Devil is in the Details.

    PubMed

    Nelson, W James; Weis, William I

    2016-07-01

    Over the past 25 years, there has been a conceptual (re)evolution in understanding how the cadherin cell adhesion complex, which contains F-actin-binding proteins, binds to the actin cytoskeleton. There is now good synergy between structural, biochemical, and cell biological results that the cadherin-catenin complex binds to F-actin under force. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Results of medical studies during long-term manned flights on the orbital Salyut-6 and Soyuz complex

    NASA Technical Reports Server (NTRS)

    Yegorov, A. D. (Compiler)

    1979-01-01

    Results of tests made on the crews of the Salyut-6 and Soyuz complex are presented. The basic results of studies made before, during and after 96-day and 140-day flights are presented in 5 sections: characteristics of flight conditions in the orbital complex; the cardiovascular system; the motor sphere and vestibular analyzer; biochemical, hematologic and immunologic studies; and recovery measures in the readaptation period.

  20. Unlocking Proteomic Heterogeneity in Complex Diseases through Visual Analytics

    PubMed Central

    Bhavnani, Suresh K.; Dang, Bryant; Bellala, Gowtham; Divekar, Rohit; Visweswaran, Shyam; Brasier, Allan; Kurosky, Alex

    2015-01-01

    Despite years of preclinical development, biological interventions designed to treat complex diseases like asthma often fail in phase III clinical trials. These failures suggest that current methods to analyze biomedical data might be missing critical aspects of biological complexity such as the assumption that cases and controls come from homogeneous distributions. Here we discuss why and how methods from the rapidly evolving field of visual analytics can help translational teams (consisting of biologists, clinicians, and bioinformaticians) to address the challenge of modeling and inferring heterogeneity in the proteomic and phenotypic profiles of patients with complex diseases. Because a primary goal of visual analytics is to amplify the cognitive capacities of humans for detecting patterns in complex data, we begin with an overview of the cognitive foundations for the field of visual analytics. Next, we organize the primary ways in which a specific form of visual analytics called networks have been used to model and infer biological mechanisms, which help to identify the properties of networks that are particularly useful for the discovery and analysis of proteomic heterogeneity in complex diseases. We describe one such approach called subject-protein networks, and demonstrate its application on two proteomic datasets. This demonstration provides insights to help translational teams overcome theoretical, practical, and pedagogical hurdles for the widespread use of subject-protein networks for analyzing molecular heterogeneities, with the translational goal of designing biomarker-based clinical trials, and accelerating the development of personalized approaches to medicine. PMID:25684269

  1. Visual Function Changes after Laser Exposure.

    DTIC Science & Technology

    1984-04-01

    degeneration induced by prolonged exposure to flourescent light. Using the ERG as a criterion response Noell et al (5) showed that the damage action...without photoreceptors. Exp Neurol 1972;34:446-454 15. Bennett 11H, Dyer RF, Dunn JD. Light-induced retinal degeneration : effect upon light-dark...20. Lemmon V, Anderson VV. Behavioral effects of retinal degeneration . Exp Neurol 1979;63:35-49 21. Wright A, Sperling HG. Psychophysical biochemical

  2. Absence of Complex I Implicates Rearrangement of the Respiratory Chain in European Mistletoe.

    PubMed

    Senkler, Jennifer; Rugen, Nils; Eubel, Holger; Hegermann, Jan; Braun, Hans-Peter

    2018-05-21

    The mitochondrial oxidative phosphorylation (OXPHOS) system, which is based on the presence of five protein complexes, is in the very center of cellular ATP production. Complexes I to IV are components of the respiratory electron transport chain that drives proton translocation across the inner mitochondrial membrane. The resulting proton gradient is used by complex V (the ATP synthase complex) for the phosphorylation of ADP. Occurrence of complexes I to V is highly conserved in eukaryotes, with exceptions being restricted to unicellular parasites that take up energy-rich compounds from their hosts. Here we present biochemical evidence that the European mistletoe (Viscum album), an obligate semi-parasite living on branches of trees, has a highly unusual OXPHOS system. V. album mitochondria completely lack complex I and have greatly reduced amounts of complexes II and V. At the same time, the complexes III and IV form remarkably stable respiratory supercomplexes. Furthermore, complexome profiling revealed the presence of 150 kDa complexes that include type II NAD(P)H dehydrogenases and an alternative oxidase. Although the absence of complex I genes in mitochondrial genomes of mistletoe species has recently been reported, this is the first biochemical proof that these genes have not been transferred to the nuclear genome and that this respiratory complex indeed is not assembled. As a consequence, the whole respiratory chain is remodeled. Our results demonstrate that, in the context of parasitism, multicellular life can cope with lack of one of the OXPHOS complexes and give new insights into the life strategy of mistletoe species. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Perceptual Visual Grouping under Inattention: Electrophysiological Functional Imaging

    ERIC Educational Resources Information Center

    Razpurker-Apfeld, Irene; Pratt, Hillel

    2008-01-01

    Two types of perceptual visual grouping, differing in complexity of shape formation, were examined under inattention. Fourteen participants performed a similarity judgment task concerning two successive briefly presented central targets surrounded by task-irrelevant simple and complex grouping patterns. Event-related potentials (ERPs) were…

  4. Influence of Biochemical Features of Burkholderia pseudomallei Strains on Identification Reliability by Vitek 2 System

    PubMed Central

    Zakharova, Irina B; Lopasteyskaya, Yana A; Toporkov, Andrey V; Viktorov, Dmitry V

    2018-01-01

    Background: Burkholderia pseudomallei is a Gram-negative saprophytic soil bacterium that causes melioidosis, a potentially fatal disease endemic in wet tropical areas. The currently available biochemical identification systems can misidentify some strains of B. pseudomallei. The aim of the present study was to identify the biochemical features of B. pseudomallei, which can affect its correct identification by Vitek 2 system. Materials and Methods: The biochemical patterns of 40 B. pseudomallei strains were obtained using Vitek 2 GN cards. The average contribution of biochemical tests in overall dissimilarities between correctly and incorrectly identified strains was assessed using nonmetric multidimensional scaling. Results: It was found (R statistic of 0.836, P = 0.001) that a combination of negative N-acetyl galactosaminidase, β-N-acetyl glucosaminidase, phosphatase, and positive D-cellobiase (dCEL), tyrosine arylamidase (TyrA), and L-proline arylamidase (ProA) tests leads to low discrimination of B. pseudomallei, whereas a set of positive dCEL and negative N-acetyl galactosaminidase, TyrA, and ProA determines the wrong identification of B. pseudomallei as Burkholderia cepacia complex. Conclusion: The further expansion of the Vitek 2 identification keys is needed for correct identification of atypical or regionally distributed biochemical profiles of B. pseudomallei. PMID:29563716

  5. Fractal Analysis of Radiologists Visual Scanning Pattern in Screening Mammography

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

    Alamudun, Folami T; Yoon, Hong-Jun; Hudson, Kathy

    2015-01-01

    Several investigators have investigated radiologists visual scanning patterns with respect to features such as total time examining a case, time to initially hit true lesions, number of hits, etc. The purpose of this study was to examine the complexity of the radiologists visual scanning pattern when viewing 4-view mammographic cases, as they typically do in clinical practice. Gaze data were collected from 10 readers (3 breast imaging experts and 7 radiology residents) while reviewing 100 screening mammograms (24 normal, 26 benign, 50 malignant). The radiologists scanpaths across the 4 mammographic views were mapped to a single 2-D image plane. Then,more » fractal analysis was applied on the derived scanpaths using the box counting method. For each case, the complexity of each radiologist s scanpath was estimated using fractal dimension. The association between gaze complexity, case pathology, case density, and radiologist experience was evaluated using 3 factor fixed effects ANOVA. ANOVA showed that case pathology, breast density, and experience level are all independent predictors of the visual scanning pattern complexity. Visual scanning patterns are significantly different for benign and malignant cases than for normal cases as well as when breast parenchyma density changes.« less

  6. Auditory-musical processing in autism spectrum disorders: a review of behavioral and brain imaging studies.

    PubMed

    Ouimet, Tia; Foster, Nicholas E V; Tryfon, Ana; Hyde, Krista L

    2012-04-01

    Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by atypical social and communication skills, repetitive behaviors, and atypical visual and auditory perception. Studies in vision have reported enhanced detailed ("local") processing but diminished holistic ("global") processing of visual features in ASD. Individuals with ASD also show enhanced processing of simple visual stimuli but diminished processing of complex visual stimuli. Relative to the visual domain, auditory global-local distinctions, and the effects of stimulus complexity on auditory processing in ASD, are less clear. However, one remarkable finding is that many individuals with ASD have enhanced musical abilities, such as superior pitch processing. This review provides a critical evaluation of behavioral and brain imaging studies of auditory processing with respect to current theories in ASD. We have focused on auditory-musical processing in terms of global versus local processing and simple versus complex sound processing. This review contributes to a better understanding of auditory processing differences in ASD. A deeper comprehension of sensory perception in ASD is key to better defining ASD phenotypes and, in turn, may lead to better interventions. © 2012 New York Academy of Sciences.

  7. Shape and color conjunction stimuli are represented as bound objects in visual working memory.

    PubMed

    Luria, Roy; Vogel, Edward K

    2011-05-01

    The integrated object view of visual working memory (WM) argues that objects (rather than features) are the building block of visual WM, so that adding an extra feature to an object does not result in any extra cost to WM capacity. Alternative views have shown that complex objects consume additional WM storage capacity so that it may not be represented as bound objects. Additionally, it was argued that two features from the same dimension (i.e., color-color) do not form an integrated object in visual WM. This led some to argue for a "weak" object view of visual WM. We used the contralateral delay activity (the CDA) as an electrophysiological marker of WM capacity, to test those alternative hypotheses to the integrated object account. In two experiments we presented complex stimuli and color-color conjunction stimuli, and compared performance in displays that had one object but varying degrees of feature complexity. The results supported the integrated object account by showing that the CDA amplitude corresponded to the number of objects regardless of the number of features within each object, even for complex objects or color-color conjunction stimuli. Copyright © 2010 Elsevier Ltd. All rights reserved.

  8. SVP-like MADS-box protein from Carya cathayensis forms higher-order complexes.

    PubMed

    Wang, Jingjing; Hou, Chuanming; Huang, Jianqin; Wang, Zhengjia; Xu, Yingwu

    2015-03-01

    To properly regulate plant flowering time and construct floral pattern, MADS-domain containing transcription factors must form multimers including homo- and hetero-dimers. They are also active in forming hetero-higher-order complexes with three to five different molecules. However, it is not well known if a MADS-box protein can also form homo-higher-order complex. In this study a biochemical approach is utilized to provide insight into the complex formation for an SVP-like MADS-box protein cloned from hickory. The results indicated that the protein is a heterogeneous higher-order complex with the peak population containing over 20 monomers. Y2H verified the protein to form homo-complex in yeast cells. Western blot of the hickory floral bud sample revealed that the protein exists in higher-order polymers in native. Deletion assays indicated that the flexible C-terminal residues are mainly responsible for the higher-order polymer formation and the heterogeneity. Current results provide direct biochemical evidences for an active MADS-box protein to be a high order complex, much higher than a quartermeric polymer. Analysis suggests that a MADS-box subset may be able to self-assemble into large complexes, and thereby differentiate one subfamily from the other in a higher-order structural manner. Present result is a valuable supplement to the action of mechanism for MADS-box proteins in plant development. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  9. Linear analysis near a steady-state of biochemical networks: Control analysis, correlation metrics and circuit theory

    PubMed Central

    Heuett, William J; Beard, Daniel A; Qian, Hong

    2008-01-01

    Background Several approaches, including metabolic control analysis (MCA), flux balance analysis (FBA), correlation metric construction (CMC), and biochemical circuit theory (BCT), have been developed for the quantitative analysis of complex biochemical networks. Here, we present a comprehensive theory of linear analysis for nonequilibrium steady-state (NESS) biochemical reaction networks that unites these disparate approaches in a common mathematical framework and thermodynamic basis. Results In this theory a number of relationships between key matrices are introduced: the matrix A obtained in the standard, linear-dynamic-stability analysis of the steady-state can be decomposed as A = SRT where R and S are directly related to the elasticity-coefficient matrix for the fluxes and chemical potentials in MCA, respectively; the control-coefficients for the fluxes and chemical potentials can be written in terms of RTBS and STBS respectively where matrix B is the inverse of A; the matrix S is precisely the stoichiometric matrix in FBA; and the matrix eAt plays a central role in CMC. Conclusion One key finding that emerges from this analysis is that the well-known summation theorems in MCA take different forms depending on whether metabolic steady-state is maintained by flux injection or concentration clamping. We demonstrate that if rate-limiting steps exist in a biochemical pathway, they are the steps with smallest biochemical conductances and largest flux control-coefficients. We hypothesize that biochemical networks for cellular signaling have a different strategy for minimizing energy waste and being efficient than do biochemical networks for biosynthesis. We also discuss the intimate relationship between MCA and biochemical systems analysis (BSA). PMID:18482450

  10. Interactive Visualization of Complex Seismic Data and Models Using Bokeh

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

    Chai, Chengping; Ammon, Charles J.; Maceira, Monica

    Visualizing multidimensional data and models becomes more challenging as the volume and resolution of seismic data and models increase. But thanks to the development of powerful and accessible computer systems, a model web browser can be used to visualize complex scientific data and models dynamically. In this paper, we present four examples of seismic model visualization using an open-source Python package Bokeh. One example is a visualization of a surface-wave dispersion data set, another presents a view of three-component seismograms, and two illustrate methods to explore a 3D seismic-velocity model. Unlike other 3D visualization packages, our visualization approach has amore » minimum requirement on users and is relatively easy to develop, provided you have reasonable programming skills. Finally, utilizing familiar web browsing interfaces, the dynamic tools provide us an effective and efficient approach to explore large data sets and models.« less

  11. Interactive Visualization of Complex Seismic Data and Models Using Bokeh

    DOE PAGES

    Chai, Chengping; Ammon, Charles J.; Maceira, Monica; ...

    2018-02-14

    Visualizing multidimensional data and models becomes more challenging as the volume and resolution of seismic data and models increase. But thanks to the development of powerful and accessible computer systems, a model web browser can be used to visualize complex scientific data and models dynamically. In this paper, we present four examples of seismic model visualization using an open-source Python package Bokeh. One example is a visualization of a surface-wave dispersion data set, another presents a view of three-component seismograms, and two illustrate methods to explore a 3D seismic-velocity model. Unlike other 3D visualization packages, our visualization approach has amore » minimum requirement on users and is relatively easy to develop, provided you have reasonable programming skills. Finally, utilizing familiar web browsing interfaces, the dynamic tools provide us an effective and efficient approach to explore large data sets and models.« less

  12. Evaluation of a technique to simplify depictions of visually complex aeronautical procedures for NextGen

    DOT National Transportation Integrated Search

    2013-10-04

    Performance based navigation supports the design of more precise flight procedures. However, these new procedures can be visually complex, which may impact the usability of charts that depict the procedures. The purpose of the study was to evaluate w...

  13. The effect of visual taskload on critical flicker frequency (CFF) change during performance of a complex monitoring task.

    DOT National Transportation Integrated Search

    1985-10-01

    The present study examined the effect of differing levels of visual taskload on critical flicker frequency (CFF) change during performance of a complex monitoring task. The task employed was designed to functionally simulate the general task characte...

  14. Interhemispheric Resource Sharing: Decreasing Benefits with Increasing Processing Efficiency

    ERIC Educational Resources Information Center

    Maertens, M.; Pollmann, S.

    2005-01-01

    Visual matches are sometimes faster when stimuli are presented across visual hemifields, compared to within-field matching. Using a cued geometric figure matching task, we investigated the influence of computational complexity vs. processing efficiency on this bilateral distribution advantage (BDA). Computational complexity was manipulated by…

  15. Biophysical and biochemical constraints imposed by salt stress: learning from halophytes

    PubMed Central

    Duarte, Bernardo; Sleimi, Noomene; Caçador, Isabel

    2014-01-01

    Soil salinization is one of the most important factors impacting plant productivity. About 3.6 billion of the world’s 5.2 billion ha of agricultural dry land, have already suffered erosion, degradation, and salinization. Halophytes are typically considered as plants able to complete their life cycle in environments where the salt concentration is above 200 mM NaCl. Salinity adjustment is a complex phenomenon but essential mechanism to overcome salt stress, with both biophysical and biochemical implications. At this level, halophytes evolved in several directions, adopting different strategies. Otherwise, the lack of adaptation to a salt environment would negatively affect their electron transduction pathways and the entire energetic metabolism, the foundation of every plant photosynthesis and biomass production. The maintenance of ionic homeostasis is in the basis of all cellular counteractive measures, in particular in terms of redox potential and energy transduction. In the present work the biophysical mechanisms underlying energy capture and transduction in halophytes are discussed alongside with their relation with biochemical counteractive mechanisms, integrating data from photosynthetic light harvesting complexes, electron transport chains to the quinone pools, carbon fixation, and energy dissipation metabolism. PMID:25566311

  16. Biochemical and physiological bases for the use of carbon and nitrogen isotopes in environmental and ecological studies

    NASA Astrophysics Data System (ADS)

    Ohkouchi, Naohiko; Ogawa, Nanako O.; Chikaraishi, Yoshito; Tanaka, Hiroyuki; Wada, Eitaro

    2015-12-01

    We review the biochemical and physiological bases of the use of carbon and nitrogen isotopic compositions as an approach for environmental and ecological studies. Biochemical processes commonly observed in the biosphere, including the decarboxylation and deamination of amino acids, are the key factors in this isotopic approach. The principles drawn from the isotopic distributions disentangle the complex dynamics of the biosphere and allow the interactions between the geosphere and biosphere to be analyzed in detail. We also summarize two recently examined topics with new datasets: the isotopic compositions of individual biosynthetic products (chlorophylls and amino acids) and those of animal organs for further pursuing the basis of the methodology. As a tool for investigating complex systems, compound-specific isotopic analysis compensates the intrinsic disadvantages of bulk isotopic signatures. Chlorophylls provide information about the particular processes of various photoautotrophs, whereas amino acids provide a precise measure of the trophic positions of heterotrophs. The isotopic distributions of carbon and nitrogen in a single organism as well as in the whole biosphere are strongly regulated, so that their major components such as amino acids are coordinated appropriately rather than controlled separately.

  17. How low can you go? Changing the resolution of novel complex objects in visual working memory according to task demands

    PubMed Central

    Allon, Ayala S.; Balaban, Halely; Luria, Roy

    2014-01-01

    In three experiments we manipulated the resolution of novel complex objects in visual working memory (WM) by changing task demands. Previous studies that investigated the trade-off between quantity and resolution in visual WM yielded mixed results for simple familiar stimuli. We used the contralateral delay activity as an electrophysiological marker to directly track the deployment of visual WM resources while participants preformed a change-detection task. Across three experiments we presented the same novel complex items but changed the task demands. In Experiment 1 we induced a medium resolution task by using change trials in which a random polygon changed to a different type of polygon and replicated previous findings showing that novel complex objects are represented with higher resolution relative to simple familiar objects. In Experiment 2 we induced a low resolution task that required distinguishing between polygons and other types of stimulus categories, but we failed in finding a corresponding decrease in the resolution of the represented item. Finally, in Experiment 3 we induced a high resolution task that required discriminating between highly similar polygons with somewhat different contours. This time, we observed an increase in the item’s resolution. Our findings indicate that the resolution for novel complex objects can be increased but not decreased according to task demands, suggesting that minimal resolution is required in order to maintain these items in visual WM. These findings support studies claiming that capacity and resolution in visual WM reflect different mechanisms. PMID:24734026

  18. Interactive visualization of public health indicators to support policymaking: An exploratory study

    PubMed Central

    Zakkar, Moutasem; Sedig, Kamran

    2017-01-01

    Purpose The purpose of this study is to examine the use of interactive visualizations to represent data/information related to social determinants of health and public health indicators, and to investigate the benefits of such visualizations for health policymaking. Methods: The study developed a prototype for an online interactive visualization tool that represents the social determinants of health. The study participants explored and used the tool. The tool was evaluated using the informal user experience evaluation method. This method involves the prospective users of a tool to use and play with it and their feedback to be collected through interviews. Results: Using visualizations to represent and interact with health indicators has advantages over traditional representation techniques that do not allow users to interact with the information. Communicating healthcare indicators to policymakers is a complex task because of the complexity of the indicators, diversity of audiences, and different audience needs. This complexity can lead to information misinterpretation, which occurs when users of the health data ignore or do not know why, where, and how the data has been produced, or where and how it can be used. Conclusions: Public health policymaking is a complex process, and data is only one element among others needed in this complex process. Researchers and healthcare organizations should conduct a strategic evaluation to assess the usability of interactive visualizations and decision support tools before investing in these tools. Such evaluation should take into consideration the cost, ease of use, learnability, and efficiency of those tools, and the factors that influence policymaking. PMID:29026455

  19. An egalitarian network model for the emergence of simple and complex cells in visual cortex

    PubMed Central

    Tao, Louis; Shelley, Michael; McLaughlin, David; Shapley, Robert

    2004-01-01

    We explain how simple and complex cells arise in a large-scale neuronal network model of the primary visual cortex of the macaque. Our model consists of ≈4,000 integrate-and-fire, conductance-based point neurons, representing the cells in a small, 1-mm2 patch of an input layer of the primary visual cortex. In the model the local connections are isotropic and nonspecific, and convergent input from the lateral geniculate nucleus confers cortical cells with orientation and spatial phase preference. The balance between lateral connections and lateral geniculate nucleus drive determines whether individual neurons in this recurrent circuit are simple or complex. The model reproduces qualitatively the experimentally observed distributions of both extracellular and intracellular measures of simple and complex response. PMID:14695891

  20. Chess players' eye movements reveal rapid recognition of complex visual patterns: Evidence from a chess-related visual search task.

    PubMed

    Sheridan, Heather; Reingold, Eyal M

    2017-03-01

    To explore the perceptual component of chess expertise, we monitored the eye movements of expert and novice chess players during a chess-related visual search task that tested anecdotal reports that a key differentiator of chess skill is the ability to visualize the complex moves of the knight piece. Specifically, chess players viewed an array of four minimized chessboards, and they rapidly searched for the target board that allowed a knight piece to reach a target square in three moves. On each trial, there was only one target board (i.e., the "Yes" board), and for the remaining "lure" boards, the knight's path was blocked on either the first move (the "Easy No" board) or the second move (i.e., "the Difficult No" board). As evidence that chess experts can rapidly differentiate complex chess-related visual patterns, the experts (but not the novices) showed longer first-fixation durations on the "Yes" board relative to the "Difficult No" board. Moreover, as hypothesized, the task strongly differentiated chess skill: Reaction times were more than four times faster for the experts relative to novices, and reaction times were correlated with within-group measures of expertise (i.e., official chess ratings, number of hours of practice). These results indicate that a key component of chess expertise is the ability to rapidly recognize complex visual patterns.

  1. High-definition Fourier Transform Infrared (FT-IR) Spectroscopic Imaging of Human Tissue Sections towards Improving Pathology

    PubMed Central

    Nguyen, Peter L.; Davidson, Bennett; Akkina, Sanjeev; Guzman, Grace; Setty, Suman; Kajdacsy-Balla, Andre; Walsh, Michael J.

    2015-01-01

    High-definition Fourier Transform Infrared (FT-IR) spectroscopic imaging is an emerging approach to obtain detailed images that have associated biochemical information. FT-IR imaging of tissue is based on the principle that different regions of the mid-infrared are absorbed by different chemical bonds (e.g., C=O, C-H, N-H) within cells or tissue that can then be related to the presence and composition of biomolecules (e.g., lipids, DNA, glycogen, protein, collagen). In an FT-IR image, every pixel within the image comprises an entire Infrared (IR) spectrum that can give information on the biochemical status of the cells that can then be exploited for cell-type or disease-type classification. In this paper, we show: how to obtain IR images from human tissues using an FT-IR system, how to modify existing instrumentation to allow for high-definition imaging capabilities, and how to visualize FT-IR images. We then present some applications of FT-IR for pathology using the liver and kidney as examples. FT-IR imaging holds exciting applications in providing a novel route to obtain biochemical information from cells and tissue in an entirely label-free non-perturbing route towards giving new insight into biomolecular changes as part of disease processes. Additionally, this biochemical information can potentially allow for objective and automated analysis of certain aspects of disease diagnosis. PMID:25650759

  2. Crystallographic and Molecular Dynamics Simulation Analysis of Escherichia Coli Dihydroneopterin Aldolase

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

    Blaszczyk, Jaroslaw; Lu, Zhenwei; Li, Yue

    2014-09-01

    To understand the structural basis for the biochemical differences and further investigate the catalytic mechanism of DHNA, we have determined the structure of EcDHNA complexed with NP at 1.07-Å resolution [PDB:2O90], built an atomic model of EcDHNA complexed with the substrate DHNP, and performed molecular dynamics (MD) simulation analysis of the substrate complex. EcDHNA has the same fold as SaDHNA and also forms an octamer that consists of two tetramers, but the packing of one tetramer with the other is significantly different between the two enzymes. Furthermore, the structures reveal significant differences in the vicinity of the active site, particularlymore » in the loop that connects strands β3 and β4, mainly due to the substitution of nearby residues. The building of an atomic model of the complex of EcDHNA and the substrate DHNP and the MD simulation of the complex show that some of the hydrogen bonds between the substrate and the enzyme are persistent, whereas others are transient. The substrate binding model and MD simulation provide the molecular basis for the biochemical behaviors of the enzyme, including noncooperative substrate binding, indiscrimination of a pair of epimers as the substrates, proton wire switching during catalysis, and formation of epimerization product.« less

  3. Human RAD50 makes a functional DNA-binding complex.

    PubMed

    Kinoshita, Eri; van Rossum-Fikkert, Sari; Sanchez, Humberto; Kertokalio, Aryandi; Wyman, Claire

    2015-06-01

    The MRE11-RAD50-NBS1 (MRN) complex has several distinct functions in DNA repair including important roles in both non-homologous end-joining (NHEJ) and homologous recombination (HR). The biochemical activities of MR(N) have been well characterized implying specific functional roles for the components. The arrangement of proteins in the complex implies interdependence of their biochemical activities making it difficult to separate specific functions. We obtained purified human RAD50 and observed that it binds ATP, undergoes ATP-dependent conformational changes as well as having ATPase activity. Scanning force microscopy analysis clearly showed that RAD50 binds DNA although not as oligomers. RAD50 alone was not functional in tethering DNA molecules. ATP increased formation of RAD50 multimers which were however globular lacking extended coiled coils, in contrast to the MR complex where ATP induced oligomers have obvious coiled coils protruding from a central domain. These results suggest that MRE11 is important in maintaining the structural arrangement of RAD50 in the protein complex and perhaps has a role in reinforcing proper alignment of the coiled coils in the ATP-bound state. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  4. The Development and Activity-Dependent Expression of Aggrecan in the Cat Visual Cortex

    PubMed Central

    Sengpiel, F.; Beaver, C. J.; Crocker-Buque, A.; Kelly, G. M.; Matthews, R. T.; Mitchell, D. E.

    2013-01-01

    The Cat-301 monoclonal antibody identifies aggrecan, a chondroitin sulfate proteoglycan in the cat visual cortex and dorsal lateral geniculate nucleus (dLGN). During development, aggrecan expression increases in the dLGN with a time course that matches the decline in plasticity. Moreover, examination of tissue from selectively visually deprived cats shows that expression is activity dependent, suggesting a role for aggrecan in the termination of the sensitive period. Here, we demonstrate for the first time that the onset of aggrecan expression in area 17 also correlates with the decline in experience-dependent plasticity in visual cortex and that this expression is experience dependent. Dark rearing until 15 weeks of age dramatically reduced the density of aggrecan-positive neurons in the extragranular layers, but not in layer IV. This effect was reversible as dark-reared animals that were subsequently exposed to light showed normal numbers of Cat-301-positive cells. The reduction in aggrecan following certain early deprivation regimens is the first biochemical correlate of the functional changes to the γ-aminobutyric acidergic system that have been reported following early deprivation in cats. PMID:22368089

  5. Macular pigment and its contribution to visual performance and experience

    PubMed Central

    Loughman, James; Davison, Peter A.; Nolan, John M.; Akkali, Mukunda C.; Beatty, Stephen

    2010-01-01

    There is now a consensus, based on histological, biochemical and spectral absorption data, that the yellow colour observed at the macula lutea is a consequence of the selective accumulation of dietary xanthophylls in the central retina of the living eye. Scientific research continues to explore the function(s) of MP in the human retina, with two main hypotheses premised on its putative capacity to (1) protect the retina from (photo)-oxidative damage by means of its optical filtration and/or antioxidant properties, the so-called protective hypothesis and (2) influence the quality of visual performance by means of selective short wavelength light absorption prior to photoreceptor light capture, thereby attenuating the effects of chromatic aberration and light scatter, the so-called acuity and visibility hypotheses. The current epidemic of age-related macular degeneration has directed researchers to investigate the protective hypothesis of MP, while there has been a conspicuous lack of work designed to investigate the role of MP in visual performance. The aim of this review is to present and critically appraise the current literature germane to the contribution of MP, if any, to visual performance and experience.

  6. Elementary Teachers' Selection and Use of Visual Models

    ERIC Educational Resources Information Center

    Lee, Tammy D.; Jones, M. Gail

    2018-01-01

    As science grows in complexity, science teachers face an increasing challenge of helping students interpret models that represent complex science systems. Little is known about how teachers select and use models when planning lessons. This mixed methods study investigated the pedagogical approaches and visual models used by elementary in-service…

  7. Attention Guidance in Learning from a Complex Animation: Seeing Is Understanding?

    ERIC Educational Resources Information Center

    de Koning, Bjorn B.; Tabbers, Huib K.; Rikers, Remy M. J. P.; Paas, Fred

    2010-01-01

    To examine how visual attentional resources are allocated when learning from a complex animation about the cardiovascular system, eye movements were registered in the absence and presence of visual cues. Cognitive processing was assessed using cued retrospective reporting, whereas comprehension and transfer tests measured the quality of the…

  8. Presentation Media, Information Complexity, and Learning Outcomes

    ERIC Educational Resources Information Center

    Andres, Hayward P.; Petersen, Candice

    2002-01-01

    Cognitive processing limitations restrict the number of complex information items held and processed in human working memory. To overcome such limitations, a verbal working memory channel is used to construct an if-then proposition representation of facts and a visual working memory channel is used to construct a visual imagery of geometric…

  9. Concept Mapping: A Graphical System for Understanding the Relationship between Concepts. ERIC Digest.

    ERIC Educational Resources Information Center

    Plotnick, Eric

    This ERIC Digest discusses concept mapping, a technique for representing the structure of information visually. Concept mapping can be used to brainstorm, design complex structures, communicate complex ideas, aid learning by explicitly integrating new and old knowledge, and assess understanding or diagnose misunderstanding. Visual representation…

  10. Investigating Complexity Using Excel and Visual Basic.

    ERIC Educational Resources Information Center

    Zetie, K. P.

    2001-01-01

    Shows how some of the simple ideas in complexity can be investigated using a spreadsheet and a macro written in Visual Basic. Shows how the sandpile model of Bak, Chao, and Wiesenfeld can be simulated and animated. The model produces results that cannot easily be predicted from its properties. (Author/MM)

  11. Analysis of DNA interactions using single-molecule force spectroscopy.

    PubMed

    Ritzefeld, Markus; Walhorn, Volker; Anselmetti, Dario; Sewald, Norbert

    2013-06-01

    Protein-DNA interactions are involved in many biochemical pathways and determine the fate of the corresponding cell. Qualitative and quantitative investigations on these recognition and binding processes are of key importance for an improved understanding of biochemical processes and also for systems biology. This review article focusses on atomic force microscopy (AFM)-based single-molecule force spectroscopy and its application to the quantification of forces and binding mechanisms that lead to the formation of protein-DNA complexes. AFM and dynamic force spectroscopy are exciting tools that allow for quantitative analysis of biomolecular interactions. Besides an overview on the method and the most important immobilization approaches, the physical basics of the data evaluation is described. Recent applications of AFM-based force spectroscopy to investigate DNA intercalation, complexes involving DNA aptamers and peptide- and protein-DNA interactions are given.

  12. Complexity of generic biochemical circuits: topology versus strength of interactions.

    PubMed

    Tikhonov, Mikhail; Bialek, William

    2016-12-06

    The historical focus on network topology as a determinant of biological function is still largely maintained today, illustrated by the rise of structure-only approaches to network analysis. However, biochemical circuits and genetic regulatory networks are defined both by their topology and by a multitude of continuously adjustable parameters, such as the strength of interactions between nodes, also recognized as important. Here we present a class of simple perceptron-based Boolean models within which comparing the relative importance of topology versus interaction strengths becomes a quantitatively well-posed problem. We quantify the intuition that for generic networks, optimization of interaction strengths is a crucial ingredient of achieving high complexity, defined here as the number of fixed points the network can accommodate. We propose a new methodology for characterizing the relative role of parameter optimization for topologies of a given class.

  13. Development of interactive graphic user interfaces for modeling reaction-based biogeochemical processes in batch systems with BIOGEOCHEM

    NASA Astrophysics Data System (ADS)

    Chang, C.; Li, M.; Yeh, G.

    2010-12-01

    The BIOGEOCHEM numerical model (Yeh and Fang, 2002; Fang et al., 2003) was developed with FORTRAN for simulating reaction-based geochemical and biochemical processes with mixed equilibrium and kinetic reactions in batch systems. A complete suite of reactions including aqueous complexation, adsorption/desorption, ion-exchange, redox, precipitation/dissolution, acid-base reactions, and microbial mediated reactions were embodied in this unique modeling tool. Any reaction can be treated as fast/equilibrium or slow/kinetic reaction. An equilibrium reaction is modeled with an implicit finite rate governed by a mass action equilibrium equation or by a user-specified algebraic equation. A kinetic reaction is modeled with an explicit finite rate with an elementary rate, microbial mediated enzymatic kinetics, or a user-specified rate equation. None of the existing models has encompassed this wide array of scopes. To ease the input/output learning curve using the unique feature of BIOGEOCHEM, an interactive graphic user interface was developed with the Microsoft Visual Studio and .Net tools. Several user-friendly features, such as pop-up help windows, typo warning messages, and on-screen input hints, were implemented, which are robust. All input data can be real-time viewed and automated to conform with the input file format of BIOGEOCHEM. A post-processor for graphic visualizations of simulated results was also embedded for immediate demonstrations. By following data input windows step by step, errorless BIOGEOCHEM input files can be created even if users have little prior experiences in FORTRAN. With this user-friendly interface, the time effort to conduct simulations with BIOGEOCHEM can be greatly reduced.

  14. Protecting the retinal neurons from glaucoma: lowering ocular pressure is not enough.

    PubMed

    Pascale, Alessia; Drago, Filippo; Govoni, Stefano

    2012-07-01

    The retina is theater of a number of biochemical reactions allowing, within its layers, the conversion of light impulses into electrical signals. The axons of the last neuronal elements, the ganglion cells, form the optic nerve and transfer the signals to the brain. Therefore, an appropriate cellular communication, not only within the different retinal cells, but also between the retina itself and the other brain structures, is fundamental. One of the most diffuse pathologies affecting retinal function and communication, which thus reverberates in the whole visual system, is glaucoma. This insidious disease is characterized by a progressive optic nerve degeneration and sight loss which may finally lead to irreversible blindness. Nevertheless, the progressive nature of this pathology offers an opportunity for therapeutic intervention. To better understand the cellular processes implicated in the development of glaucoma useful to envision a targeted pharmacological strategy, this manuscript first examines the complex cellular and functional organization of the retina and subsequently identifies the targets sensitive to neurodegeneration. Within this context, high ocular pressure represents a key risk factor. However, recent literature findings highlight the concept that lowering ocular pressure is not enough to prevent/slow down glaucomatous damage, suggesting the importance of combining the hypotensive treatment with other pharmacological approaches, such as the use of neuroprotectants. Therefore, this important and more novel aspect is extensively considered in this review, also emphasizing the idea that the neuroprotective strategy should be extended to the entire visual system and not restricted to the retina. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Beyond the real world: attention debates in auditory mismatch negativity.

    PubMed

    Chung, Kyungmi; Park, Jin Young

    2018-04-11

    The aim of this study was to address the potential for the auditory mismatch negativity (aMMN) to be used in applied event-related potential (ERP) studies by determining whether the aMMN would be an attention-dependent ERP component and could be differently modulated across visual tasks or virtual reality (VR) stimuli with different visual properties and visual complexity levels. A total of 80 participants, aged 19-36 years, were assigned to either a reading-task (21 men and 19 women) or a VR-task (22 men and 18 women) group. Two visual-task groups of healthy young adults were matched in age, sex, and handedness. All participants were instructed to focus only on the given visual tasks and ignore auditory change detection. While participants in the reading-task group read text slides, those in the VR-task group viewed three 360° VR videos in a random order and rated how visually complex the given virtual environment was immediately after each VR video ended. Inconsistent with the finding of a partial significant difference in perceived visual complexity in terms of brightness of virtual environments, both visual properties of distance and brightness showed no significant differences in the modulation of aMMN amplitudes. A further analysis was carried out to compare elicited aMMN amplitudes of a typical MMN task and an applied VR task. No significant difference in the aMMN amplitudes was found across the two groups who completed visual tasks with different visual-task demands. In conclusion, the aMMN is a reliable ERP marker of preattentive cognitive processing for auditory deviance detection.

  16. A Complex Story: Universal Preference vs. Individual Differences Shaping Aesthetic Response to Fractals Patterns

    PubMed Central

    Street, Nichola; Forsythe, Alexandra M.; Reilly, Ronan; Taylor, Richard; Helmy, Mai S.

    2016-01-01

    Fractal patterns offer one way to represent the rough complexity of the natural world. Whilst they dominate many of our visual experiences in nature, little large-scale perceptual research has been done to explore how we respond aesthetically to these patterns. Previous research (Taylor et al., 2011) suggests that the fractal patterns with mid-range fractal dimensions (FDs) have universal aesthetic appeal. Perceptual and aesthetic responses to visual complexity have been more varied with findings suggesting both linear (Forsythe et al., 2011) and curvilinear (Berlyne, 1970) relationships. Individual differences have been found to account for many of the differences we see in aesthetic responses but some, such as culture, have received little attention within the fractal and complexity research fields. This two-study article aims to test preference responses to FD and visual complexity, using a large cohort (N = 443) of participants from around the world to allow universality claims to be tested. It explores the extent to which age, culture and gender can predict our preferences for fractally complex patterns. Following exploratory analysis that found strong correlations between FD and visual complexity, a series of linear mixed-effect models were implemented to explore if each of the individual variables could predict preference. The first tested a linear complexity model (likelihood of selecting the more complex image from the pair of images) and the second a mid-range FD model (likelihood of selecting an image within mid-range). Results show that individual differences can reliably predict preferences for complexity across culture, gender and age. However, in fitting with current findings the mid-range models show greater consistency in preference not mediated by gender, age or culture. This article supports the established theory that the mid-range fractal patterns appear to be a universal construct underlying preference but also highlights the fragility of universal claims by demonstrating individual differences in preference for the interrelated concept of visual complexity. This highlights a current stalemate in the field of empirical aesthetics. PMID:27252634

  17. Testing the Usability of Interactive Visualizations for Complex Problem-Solving: Findings Related to Improving Interfaces and Help.

    ERIC Educational Resources Information Center

    Mirel, Barbara

    2001-01-01

    Conducts a scenario-based usability test with 10 data analysts using visual querying (visually analyzing data with interactive graphics). Details a range of difficulties found in visual selection that, at times, gave rise to inaccurate selections, invalid conclusions, and misguided decisions. Argues that support for visual selection must be built…

  18. An integrative top-down and bottom-up qualitative model construction framework for exploration of biochemical systems.

    PubMed

    Wu, Zujian; Pang, Wei; Coghill, George M

    Computational modelling of biochemical systems based on top-down and bottom-up approaches has been well studied over the last decade. In this research, after illustrating how to generate atomic components by a set of given reactants and two user pre-defined component patterns, we propose an integrative top-down and bottom-up modelling approach for stepwise qualitative exploration of interactions among reactants in biochemical systems. Evolution strategy is applied to the top-down modelling approach to compose models, and simulated annealing is employed in the bottom-up modelling approach to explore potential interactions based on models constructed from the top-down modelling process. Both the top-down and bottom-up approaches support stepwise modular addition or subtraction for the model evolution. Experimental results indicate that our modelling approach is feasible to learn the relationships among biochemical reactants qualitatively. In addition, hidden reactants of the target biochemical system can be obtained by generating complex reactants in corresponding composed models. Moreover, qualitatively learned models with inferred reactants and alternative topologies can be used for further web-lab experimental investigations by biologists of interest, which may result in a better understanding of the system.

  19. Analytical considerations and dimensionless analysis for a description of particle interactions in high pressure processes

    NASA Astrophysics Data System (ADS)

    Rauh, Cornelia; Delgado, Antonio

    2010-12-01

    High pressures of up to several hundreds of MPa are utilized in a wide range of applications in chemical, bio-, and food engineering, aiming at selective control of (bio-)chemical reactions. Non-uniformity of process conditions may threaten the safety and quality of the resulting products because processing conditions such as pressure, temperature, and treatment history are crucial for the course of (bio-)chemical reactions. Therefore, thermofluid-dynamical phenomena during the high pressure process have to be examined, and numerical tools to predict process uniformity and to optimize the processes have to be developed. Recently applied mathematical models and numerical simulations of laboratory and industrial scale high pressure processes investigating the mentioned crucial phenomena are based on continuum balancing models of thermofluid dynamics. Nevertheless, biological systems are complex fluids containing the relevant (bio-)chemical compounds (enzymes and microorganisms). These compounds are particles that interact with the surrounding medium and between each other. This contribution deals with thermofluid-dynamical interactions of the relevant particulate (bio-)chemical compounds (enzymes and microorganisms) with the surrounding fluid. By consideration of characteristic time and length scales and particle forces, the motion of the (bio-)chemical compounds is characterized.

  20. Beyond Ball-and-Stick: Students' Processing of Novel STEM Visualizations

    ERIC Educational Resources Information Center

    Hinze, Scott R.; Rapp, David N.; Williamson, Vickie M.; Shultz, Mary Jane; Deslongchamps, Ghislain; Williamson, Kenneth C.

    2013-01-01

    Students are frequently presented with novel visualizations introducing scientific concepts and processes normally unobservable to the naked eye. Despite being unfamiliar, students are expected to understand and employ the visualizations to solve problems. Domain experts exhibit more competency than novices when using complex visualizations, but…

  1. The evaluative imaging of mental models - Visual representations of complexity

    NASA Technical Reports Server (NTRS)

    Dede, Christopher

    1989-01-01

    The paper deals with some design issues involved in building a system that could visually represent the semantic structures of training materials and their underlying mental models. In particular, hypermedia-based semantic networks that instantiate classification problem solving strategies are thought to be a useful formalism for such representations; the complexity of these web structures can be best managed through visual depictions. It is also noted that a useful approach to implement in these hypermedia models would be some metrics of conceptual distance.

  2. Enzyme-substrate and enzyme-inhibitor complexes of triose phosphate isomerase studied by 31P nuclear magnetic resonance.

    PubMed Central

    Campbell, I D; Jones, R B; Kiener, P A; Waley, S G

    1979-01-01

    The complex formed between the enzyme triose phosphate isomerase (EC 5.3.1.1.), from rabbit and chicken muscle, and its substrate dihydroxyacetone phosphate was studied by 31P n.m.r. Two other enzyme-ligant complexes examined were those formed by glycerol 3-phosphate (a substrate analogue) and by 2-phosphoglycollate (potential transition-state analogue). Separate resonances were observed in the 31P n.m.r. spectrum for free and bound 2-phosphoglycollate, and this sets an upper limit to the rate constant for dissociation of the enzyme-inhibitor complex; the linewidth of the resonance assigned to the bound inhibitor provided further kinetic information. The position of this resonance did not vary with pH but remained close to that of the fully ionized form of the free 2-phosphoglycollate. It is the fully ionized form of this ligand that binds to the enzyme. The proton uptake that accompanies binding shows protonation of a group on the enzyme. On the basis of chemical and crystallographic information [Hartman (1971) Biochemistry 10, 146--154; Miller & Waley (1971) Biochem. J. 123, 163--170; De la Mare, Coulson, Knowles, Priddle & Offord )1972) Biochem. J. 129, 321--331; Phillips, Rivers, Sternberg, Thornton & Wilson (1977) Biochem. Soc. Trans. 5, 642--647] this group is believed to be glutamate-165. On the other hand, the position of the resonance of D-glycerol 3 phosphate (sn-glycerol 1-phosphate) in the enzyme-ligand complex changes with pH, and both monoanion and dianon of the ligand bind, although dianion binds better. The substrate, dihydroxyacetone phosphate, behaves essentially like glycerol 3-phosphate. The experiments with dihydroxy-acetone phosphate and triose phosphate isomerase have to be carried out at 1 degree C because at 37 degrees C there is conversion into methyl glyoxal and orthophosphate. The mechanismof the enzymic reaction and the reasons for rate-enhancement are considered, and aspects of the pH-dependence are discussed in an Appendix. PMID:38777

  3. Polarization-Difference Imaging: Biophysical Mechanisms and Engineering Applications to Visibility Enhancement in Scattering Media

    DTIC Science & Technology

    1993-07-01

    to neglect the variation in refractive Average refractive index. Using refractometry and dif. index along they axis, so that the assumed index...output. photoreceptor calls studied by refractometry and interference microscopy," J. Biophys. Biochem. Cytolol. 3, 15-33 (1957). curves) indicate...of rhodopsin in the visual Science 300, 540-52 (1978). receptor membrane," Nature (London) 386, 39-43 (1972) 26. R. Borer and S. Joseph, " Refractometry

  4. Neuropeptides in the desert ant Cataglyphis fortis: Mass spectrometric analysis, localization, and age-related changes.

    PubMed

    Schmitt, Franziska; Vanselow, Jens T; Schlosser, Andreas; Wegener, Christian; Rössler, Wolfgang

    2017-03-01

    Cataglyphis desert ants exhibit an age-related polyethism, with ants performing tasks in the dark nest for the first ∼4 weeks of their adult life before they switch to visually based long-distance navigation to forage. Although behavioral and sensory aspects of this transition have been studied, the internal factors triggering the behavioral changes are largely unknown. We suggest the neuropeptide families allatostatin A (AstA), allatotropin (AT), short neuropeptide F (sNPF), and tachykinin (TK) as potential candidates. Based on a neuropeptidomic analysis in Camponotus floridanus, nano-LC-ESI MS/MS was used to identify these neuropeptides biochemically in Cataglyphis fortis. Furthermore, we show that all identified peptide families are present in the central brain and ventral ganglia of C. fortis whereas in the retrocerebral complex only sNPF could be detected. Immunofluorescence staining against AstA, AT, and TK in the brain revealed arborizations of AstA- and TK-positive neurons in primary sensory processing centers and higher order integration centers, whereas AT immunoreactivity was restricted to the central complex, the antennal mechanosensory and motor center, and the protocerebrum. For artificially dark-kept ants, we found that TK distribution changed markedly in the central complex from days 1 and 7 to day 14 after eclosion. Based on functional studies in Drosophila, this age-related variation of TK is suggestive of a modulatory role in locomotion behavior in C. fortis. We conclude that the general distribution and age-related changes in neuropeptides indicate a modulatory role in sensory input regions and higher order processing centers in the desert ant brain. J. Comp. Neurol. 525:901-918, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Influence of social presence on eye movements in visual search tasks.

    PubMed

    Liu, Na; Yu, Ruifeng

    2017-12-01

    This study employed an eye-tracking technique to investigate the influence of social presence on eye movements in visual search tasks. A total of 20 male subjects performed visual search tasks in a 2 (target presence: present vs. absent) × 2 (task complexity: complex vs. simple) × 2 (social presence: alone vs. a human audience) within-subject experiment. Results indicated that the presence of an audience could evoke a social facilitation effect on response time in visual search tasks. Compared with working alone, the participants made fewer and shorter fixations, larger saccades and shorter scan path in simple search tasks and more and longer fixations, smaller saccades and longer scan path in complex search tasks when working with an audience. The saccade velocity and pupil diameter in the audience-present condition were larger than those in the working-alone condition. No significant change in target fixation number was observed between two social presence conditions. Practitioner Summary: This study employed an eye-tracking technique to examine the influence of social presence on eye movements in visual search tasks. Results clarified the variation mechanism and characteristics of oculomotor scanning induced by social presence in visual search.

  6. Visual analytics in medical education: impacting analytical reasoning and decision making for quality improvement.

    PubMed

    Vaitsis, Christos; Nilsson, Gunnar; Zary, Nabil

    2015-01-01

    The medical curriculum is the main tool representing the entire undergraduate medical education. Due to its complexity and multilayered structure it is of limited use to teachers in medical education for quality improvement purposes. In this study we evaluated three visualizations of curriculum data from a pilot course, using teachers from an undergraduate medical program and applying visual analytics methods. We found that visual analytics can be used to positively impacting analytical reasoning and decision making in medical education through the realization of variables capable to enhance human perception and cognition on complex curriculum data. The positive results derived from our evaluation of a medical curriculum and in a small scale, signify the need to expand this method to an entire medical curriculum. As our approach sustains low levels of complexity it opens a new promising direction in medical education informatics research.

  7. Remembering Complex Objects in Visual Working Memory: Do Capacity Limits Restrict Objects or Features?

    PubMed Central

    Hardman, Kyle; Cowan, Nelson

    2014-01-01

    Visual working memory stores stimuli from our environment as representations that can be accessed by high-level control processes. This study addresses a longstanding debate in the literature about whether storage limits in visual working memory include a limit to the complexity of discrete items. We examined the issue with a number of change-detection experiments that used complex stimuli which possessed multiple features per stimulus item. We manipulated the number of relevant features of the stimulus objects in order to vary feature load. In all of our experiments, we found that increased feature load led to a reduction in change-detection accuracy. However, we found that feature load alone could not account for the results, but that a consideration of the number of relevant objects was also required. This study supports capacity limits for both feature and object storage in visual working memory. PMID:25089739

  8. Testing Limits on Matte Surface Color Perception in Three-Dimensional Scenes with Complex Light Fields

    PubMed Central

    Doerschner, K.; Boyaci, H.; Maloney, L. T.

    2007-01-01

    We investigated limits on the human visual system’s ability to discount directional variation in complex lights field when estimating Lambertian surface color. Directional variation in the light field was represented in the frequency domain using spherical harmonics. The bidirectional reflectance distribution function of a Lambertian surface acts as a low-pass filter on directional variation in the light field. Consequently, the visual system needs to discount only the low-pass component of the incident light corresponding to the first nine terms of a spherical harmonics expansion (Basri & Jacobs, 2001; Ramamoorthi & Hanrahan, 2001) to accurately estimate surface color. We test experimentally whether the visual system discounts directional variation in the light field up to this physical limit. Our results are consistent with the claim that the visual system can compensate for all of the complexity in the light field that affects the appearance of Lambertian surfaces. PMID:18053846

  9. Visualizing Parallel Computer System Performance

    NASA Technical Reports Server (NTRS)

    Malony, Allen D.; Reed, Daniel A.

    1988-01-01

    Parallel computer systems are among the most complex of man's creations, making satisfactory performance characterization difficult. Despite this complexity, there are strong, indeed, almost irresistible, incentives to quantify parallel system performance using a single metric. The fallacy lies in succumbing to such temptations. A complete performance characterization requires not only an analysis of the system's constituent levels, it also requires both static and dynamic characterizations. Static or average behavior analysis may mask transients that dramatically alter system performance. Although the human visual system is remarkedly adept at interpreting and identifying anomalies in false color data, the importance of dynamic, visual scientific data presentation has only recently been recognized Large, complex parallel system pose equally vexing performance interpretation problems. Data from hardware and software performance monitors must be presented in ways that emphasize important events while eluding irrelevant details. Design approaches and tools for performance visualization are the subject of this paper.

  10. KinMap: a web-based tool for interactive navigation through human kinome data.

    PubMed

    Eid, Sameh; Turk, Samo; Volkamer, Andrea; Rippmann, Friedrich; Fulle, Simone

    2017-01-05

    Annotations of the phylogenetic tree of the human kinome is an intuitive way to visualize compound profiling data, structural features of kinases or functional relationships within this important class of proteins. The increasing volume and complexity of kinase-related data underlines the need for a tool that enables complex queries pertaining to kinase disease involvement and potential therapeutic uses of kinase inhibitors. Here, we present KinMap, a user-friendly online tool that facilitates the interactive navigation through kinase knowledge by linking biochemical, structural, and disease association data to the human kinome tree. To this end, preprocessed data from freely-available sources, such as ChEMBL, the Protein Data Bank, and the Center for Therapeutic Target Validation platform are integrated into KinMap and can easily be complemented by proprietary data. The value of KinMap will be exemplarily demonstrated for uncovering new therapeutic indications of known kinase inhibitors and for prioritizing kinases for drug development efforts. KinMap represents a new generation of kinome tree viewers which facilitates interactive exploration of the human kinome. KinMap enables generation of high-quality annotated images of the human kinome tree as well as exchange of kinome-related data in scientific communications. Furthermore, KinMap supports multiple input and output formats and recognizes alternative kinase names and links them to a unified naming scheme, which makes it a useful tool across different disciplines and applications. A web-service of KinMap is freely available at http://www.kinhub.org/kinmap/ .

  11. Nano-scale characterization of the dynamics of the chloroplast Toc translocon.

    PubMed

    Reddick, L Evan; Chotewutmontri, Prakitchai; Crenshaw, Will; Dave, Ashita; Vaughn, Michael; Bruce, Barry D

    2008-01-01

    Translocons are macromolecular nano-scale machines that facilitate the selective translocation of proteins across membranes. Although common in function, different translocons have evolved diverse molecular mechanisms for protein translocation. Subcellular organelles of endosymbiotic origin such as the chloroplast and mitochondria had to evolve/acquire translocons capable of importing proteins whose genes were transferred to the host genome. These gene products are expressed on cytosolic ribosomes as precursor proteins and targeted back to the organelle by an N-terminal extension called the transit peptide or presequence. In chloroplasts the transit peptide is specifically recognized by the Translocon of the Outer Chloroplast membrane (Toc) which is composed of receptor GTPases that potentially function as gate-like switches, where GTP binding and hydrolysis somehow facilitate preprotein binding and translocation. Compared to other translocons, the dynamics of the Toc translocon are probably more complex and certainly less understood. We have developed biochemical/biophysical, imaging, and computational techniques to probe the dynamics of the Toc translocon at the nanoscale. In this chapter we provide detailed protocols for kinetic and binding analysis of precursor interactions in organeller, measurement of the activity and nucleotide binding of the Toc GTPases, native electrophoretic analysis of the assembly/organization of the Toc complex, visualization of the distribution and mobility of Toc apparatus on the surface of chloroplasts, and conclude with the identification and molecular modeling Toc75 POTRA domains. With these new methodologies we discuss future directions of the field.

  12. Learner differences and learning outcomes in an introductory biochemistry class: attitude toward images, visual cognitive skills, and learning approach.

    PubMed

    Milner, Rachel E

    2014-01-01

    The practice of using images in teaching is widespread, and in science education images are used so extensively that some have argued they are now the "main vehicle of communication" (C. Ferreira, A. Arroio Problems Educ. 21st Century 2009, 16, 48-53). Although this phenomenon is especially notable in the field of biochemistry, we know little about the role and importance of images in communicating concepts to students in the classroom. This study reports the development of a scale to assess students' attitude toward biochemical images, particularly their willingness and ability to use the images to support their learning. In addition, because it is argued that images are central in the communication of biochemical concepts, we investigated three "learner differences" which might impact learning outcomes in this kind of classroom environment: attitude toward images, visual cognitive skills, and learning approach. Overall, the students reported a positive attitude toward the images, the majority agreeing that they liked images and considered them useful. However, the participants also reported that verbal explanations were more important than images in helping them to understand the concepts. In keeping with this we found that there was no relationship between learning outcomes and the students' self-reported attitude toward images or visual cognitive skills. In contrast, learning outcomes were significantly correlated with the students' self-reported approach to learning. These findings suggest that images are not necessarily the main vehicle of communication in a biochemistry classroom and that verbal explanations and encouragement of a deep learning approach are important considerations in improving our pedagogical approach. © 2013 International Union of Biochemistry and Molecular Biology, Inc.

  13. Beyond Control Panels: Direct Manipulation for Visual Analytics

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

    Endert, Alexander; Bradel, Lauren; North, Chris

    2013-07-19

    Information Visualization strives to provide visual representations through which users can think about and gain insight into information. By leveraging the visual and cognitive systems of humans, complex relationships and phenomena occurring within datasets can be uncovered by exploring information visually. Interaction metaphors for such visualizations are designed to enable users direct control over the filters, queries, and other parameters controlling how the data is visually represented. Through the evolution of information visualization, more complex mathematical and data analytic models are being used to visualize relationships and patterns in data – creating the field of Visual Analytics. However, the expectationsmore » for how users interact with these visualizations has remained largely unchanged – focused primarily on the direct manipulation of parameters of the underlying mathematical models. In this article we present an opportunity to evolve the methodology for user interaction from the direct manipulation of parameters through visual control panels, to interactions designed specifically for visual analytic systems. Instead of focusing on traditional direct manipulation of mathematical parameters, the evolution of the field can be realized through direct manipulation within the visual representation – where users can not only gain insight, but also interact. This article describes future directions and research challenges that fundamentally change the meaning of direct manipulation with regards to visual analytics, advancing the Science of Interaction.« less

  14. Familiarity Enhances Visual Working Memory for Faces

    ERIC Educational Resources Information Center

    Jackson, Margaret C.; Raymond, Jane E.

    2008-01-01

    Although it is intuitive that familiarity with complex visual objects should aid their preservation in visual working memory (WM), empirical evidence for this is lacking. This study used a conventional change-detection procedure to assess visual WM for unfamiliar and famous faces in healthy adults. Across experiments, faces were upright or…

  15. Using Visual Organizers to Enhance EFL Instruction

    ERIC Educational Resources Information Center

    Kang, Shumin

    2004-01-01

    Visual organizers are visual frameworks such as figures, diagrams, charts, etc. used to present structural knowledge spatially in a given area with the intention of enhancing comprehension and learning. Visual organizers are effective in terms of helping to elicit, explain, and communicate information because they can clarify complex concepts into…

  16. Physical Models that Provide Guidance in Visualization Deconstruction in an Inorganic Context

    ERIC Educational Resources Information Center

    Schiltz, Holly K.; Oliver-Hoyo, Maria T.

    2012-01-01

    Three physical model systems have been developed to help students deconstruct the visualization needed when learning symmetry and group theory. The systems provide students with physical and visual frames of reference to facilitate the complex visualization involved in symmetry concepts. The permanent reflection plane demonstration presents an…

  17. Metabolism and Weight Loss: How You Burn Calories

    MedlinePlus

    ... you eat and drink into energy. During this complex biochemical process, calories in food and beverages are ... About 10 percent of the calories from the carbohydrates and protein you eat are used during the ...

  18. Enhanced Pure-Tone Pitch Discrimination among Persons with Autism but not Asperger Syndrome

    ERIC Educational Resources Information Center

    Bonnel, Anna; McAdams, Stephen; Smith, Bennett; Berthiaume, Claude; Bertone, Armando; Ciocca, Valter; Burack, Jacob A.; Mottron, Laurent

    2010-01-01

    Persons with Autism spectrum disorders (ASD) display atypical perceptual processing in visual and auditory tasks. In vision, Bertone, Mottron, Jelenic, and Faubert (2005) found that enhanced and diminished visual processing is linked to the level of neural complexity required to process stimuli, as proposed in the neural complexity hypothesis.…

  19. Subliminal perception of complex visual stimuli.

    PubMed

    Ionescu, Mihai Radu

    2016-01-01

    Rationale: Unconscious perception of various sensory modalities is an active subject of research though its function and effect on behavior is uncertain. Objective: The present study tried to assess if unconscious visual perception could occur with more complex visual stimuli than previously utilized. Methods and Results: Videos containing slideshows of indifferent complex images with interspersed frames of interest of various durations were presented to 24 healthy volunteers. The perception of the stimulus was evaluated with a forced-choice questionnaire while awareness was quantified by self-assessment with a modified awareness scale annexed to each question with 4 categories of awareness. At values of 16.66 ms of stimulus duration, conscious awareness was not possible and answers regarding the stimulus were random. At 50 ms, nonrandom answers were coupled with no self-reported awareness suggesting unconscious perception of the stimulus. At larger durations of stimulus presentation, significantly correct answers were coupled with a certain conscious awareness. Discussion: At values of 50 ms, unconscious perception is possible even with complex visual stimuli. Further studies are recommended with a focus on a range of interest of stimulus duration between 50 to 16.66 ms.

  20. Acquisition of Chinese characters: the effects of character properties and individual differences among second language learners

    PubMed Central

    Kuo, Li-Jen; Kim, Tae-Jin; Yang, Xinyuan; Li, Huiwen; Liu, Yan; Wang, Haixia; Hyun Park, Jeong; Li, Ying

    2015-01-01

    In light of the dramatic growth of Chinese learners worldwide and a need for cross-linguistic research on Chinese literacy development, this study drew upon theories of visual complexity effect (Su and Samuels, 2010) and dual-coding processing (Sadoski and Paivio, 2013) and investigated (a) the effects of character properties (i.e., visual complexity and radical presence) on character acquisition and (b) the relationship between individual learner differences in radical awareness and character acquisition. Participants included adolescent English-speaking beginning learners of Chinese in the U.S. Following Kuo et al. (2014), a novel character acquisition task was used to investigate the process of acquiring the meaning of new characters. Results showed that (a) characters with radicals and with less visual complexity were easier to acquire than characters without radicals and with greater visual complexity; and (b) individual differences in radical awareness were associated with the acquisition of all types of characters, but the association was more pronounced with the acquisition of characters with radicals. Theoretical and practical implications of the findings were discussed. PMID:26379562

  1. Bingo! Externally-Supported Performance Intervention for Deficient Visual Search in Normal Aging, Parkinson’s Disease and Alzheimer’s Disease

    PubMed Central

    Laudate, Thomas M.; Neargarder, Sandy; Dunne, Tracy E.; Sullivan, Karen D.; Joshi, Pallavi; Gilmore, Grover C.; Riedel, Tatiana M.; Cronin-Golomb, Alice

    2011-01-01

    External support may improve task performance regardless of an individual’s ability to compensate for cognitive deficits through internally-generated mechanisms. We investigated if performance of a complex, familiar visual search task (the game of bingo) could be enhanced in groups with suboptimal vision by providing external support through manipulation of task stimuli. Participants were 19 younger adults, 14 individuals with probable Alzheimer’s disease (AD), 13 AD-matched healthy adults, 17 non-demented individuals with Parkinson’s disease (PD), and 20 PD-matched healthy adults. We varied stimulus contrast, size, and visual complexity during game play. The externally-supported performance interventions of increased stimulus size and decreased complexity resulted in improvements in performance by all groups. Performance improvement through increased stimulus size and decreased complexity was demonstrated by all groups. AD also obtained benefit from increasing contrast, presumably by compensating for their contrast sensitivity deficit. The general finding of improved performance across healthy and afflicted groups suggests the value of visual support as an easy-to-apply intervention to enhance cognitive performance. PMID:22066941

  2. A low complexity visualization tool that helps to perform complex systems analysis

    NASA Astrophysics Data System (ADS)

    Beiró, M. G.; Alvarez-Hamelin, J. I.; Busch, J. R.

    2008-12-01

    In this paper, we present an extension of large network visualization (LaNet-vi), a tool to visualize large scale networks using the k-core decomposition. One of the new features is how vertices compute their angular position. While in the later version it is done using shell clusters, in this version we use the angular coordinate of vertices in higher k-shells, and arrange the highest shell according to a cliques decomposition. The time complexity goes from O(n\\sqrt n) to O(n) upon bounds on a heavy-tailed degree distribution. The tool also performs a k-core-connectivity analysis, highlighting vertices that are not k-connected; e.g. this property is useful to measure robustness or quality of service (QoS) capabilities in communication networks. Finally, the actual version of LaNet-vi can draw labels and all the edges using transparencies, yielding an accurate visualization. Based on the obtained figure, it is possible to distinguish different sources and types of complex networks at a glance, in a sort of 'network iris-print'.

  3. Complex patterns of divergence among green-sensitive (RH2a) African cichlid opsins revealed by Clade model analyses

    PubMed Central

    2012-01-01

    Background Gene duplications play an important role in the evolution of functional protein diversity. Some models of duplicate gene evolution predict complex forms of paralog divergence; orthologous proteins may diverge as well, further complicating patterns of divergence among and within gene families. Consequently, studying the link between protein sequence evolution and duplication requires the use of flexible substitution models that can accommodate multiple shifts in selection across a phylogeny. Here, we employed a variety of codon substitution models, primarily Clade models, to explore how selective constraint evolved following the duplication of a green-sensitive (RH2a) visual pigment protein (opsin) in African cichlids. Past studies have linked opsin divergence to ecological and sexual divergence within the African cichlid adaptive radiation. Furthermore, biochemical and regulatory differences between the RH2aα and RH2aβ paralogs have been documented. It thus seems likely that selection varies in complex ways throughout this gene family. Results Clade model analysis of African cichlid RH2a opsins revealed a large increase in the nonsynonymous-to-synonymous substitution rate ratio (ω) following the duplication, as well as an even larger increase, one consistent with positive selection, for Lake Tanganyikan cichlid RH2aβ opsins. Analysis using the popular Branch-site models, by contrast, revealed no such alteration of constraint. Several amino acid sites known to influence spectral and non-spectral aspects of opsin biochemistry were found to be evolving divergently, suggesting that orthologous RH2a opsins may vary in terms of spectral sensitivity and response kinetics. Divergence appears to be occurring despite intronic gene conversion among the tandemly-arranged duplicates. Conclusions Our findings indicate that variation in selective constraint is associated with both gene duplication and divergence among orthologs in African cichlid RH2a opsins. At least some of this variation may reflect an adaptive response to differences in light environment. Interestingly, these patterns only became apparent through the use of Clade models, not through the use of the more widely employed Branch-site models; we suggest that this difference stems from the increased flexibility associated with Clade models. Our results thus bear both on studies of cichlid visual system evolution and on studies of gene family evolution in general. PMID:23078361

  4. Expansion of signal transduction by G proteins The second 15 years or so: From 3 to 16 α subunits plus βγ dimers

    PubMed Central

    Birnbaumer, Lutz

    2007-01-01

    The first 15 years, or so, brought the realization that there existed a G protein coupled signal transduction mechanism by which hormone receptors regulate adenylyl cyclases and the light receptor rhodopsin activates visual phosphodiesterase. Three G proteins, Gs, Gi and transducin (T) had been characterized as αβγ heterotrimers, and Gsα-GTP and Tα-GTP had been identified as the sigaling arms of Gs and T. These discoveries were made using classical biochemical approaches, and culminated in the purification of these G proteins. The second 15 years, or so, are the subject of the present review. This time coincided with the advent of powerful recombinant DNA techniques. Combined with the classical approaches, the field expanded the repertoire of G proteins from 3 to 16, discovered the superfamily of seven transmembrane G protein coupled receptors (GPCRs) – which is not addressed in this article – and uncovered an amazing repertoire of effector functions regulated not only by αGTP complexes but also by βγ dimers. Emphasis is placed in presenting how the field developed with the hope of conveying why many of the new findings were made. PMID:17258171

  5. A transgenic rat with ubiquitous expression of firefly luciferase gene

    NASA Astrophysics Data System (ADS)

    Hakamata, Yoji; Murakami, Takashi; Kobayashi, Eiji

    2006-02-01

    In vivo imaging strategies provide cellular and molecular events in real time that helps us to understand biological processes in living animals. The development of molecular tags such as green fluorescent proteins and luciferase from the firefly Photinus pyralis has lead to a revolution in the visualization of complex biochemical processes. We developed a novel inbred transgenic rat strain containing firefly luciferase based on the transgenic (Tg) technique in rats. This Tg rat expressed the luciferase gene ubiquitously under control of the ROSA26 promoter. Cellular immune responsiveness against the luciferase protein was evaluated using conventional skin grafting and resulted in the long-term acceptance of Tg rat skin on wild-type rats. Strikingly, organ transplant with heart and small bowel demonstrated organ viability and graft survival, suggesting that cells from luciferase-Tg are transplantable to track their fate. Taking advantage of the less immunogenic luciferase, we also tested the role of hepatocyte-infusion in a liver injury model, and bone marrow-derived cells in a skin defect model. Employed in conjunction with modern advances in optical imaging, this luciferase-Tg rat system provides an innovative animal tool and a new means of facilitating biomedical research such as in the case of regeneration medicine.

  6. NIR DLP hyperspectral imaging system for medical applications

    NASA Astrophysics Data System (ADS)

    Wehner, Eleanor; Thapa, Abhas; Livingston, Edward; Zuzak, Karel

    2011-03-01

    DLP® hyperspectral reflectance imaging in the visible range has been previously shown to quantify hemoglobin oxygenation in subsurface tissues, 1 mm to 2 mm deep. Extending the spectral range into the near infrared reflects biochemical information from deeper subsurface tissues. Unlike any other illumination method, the digital micro-mirror device, DMD, chip is programmable, allowing the user to actively illuminate with precisely predetermined spectra of illumination with a minimum bandpass of approximately 10 nm. It is possible to construct active spectral-based illumination that includes but is not limited to containing sharp cutoffs to act as filters or forming complex spectra, varying the intensity of light at discrete wavelengths. We have characterized and tested a pure NIR, 760 nm to 1600 nm, DLP hyperspectral reflectance imaging system. In its simplest application, the NIR system can be used to quantify the percentage of water in a subject, enabling edema visualization. It can also be used to map vein structure in a patient in real time. During gall bladder surgery, this system could be invaluable in imaging bile through fatty tissue, aiding surgeons in locating the common bile duct in real time without injecting any contrast agents.

  7. Spatiotemporal dynamics of DNA repair proteins following laser microbeam induced DNA damage – When is a DSB not a DSB?☆

    PubMed Central

    Reynolds, Pamela; Botchway, Stanley W.; Parker, Anthony W.; O’Neill, Peter

    2013-01-01

    The formation of DNA lesions poses a constant threat to cellular stability. Repair of endogenously and exogenously produced lesions has therefore been extensively studied, although the spatiotemporal dynamics of the repair processes has yet to be fully understood. One of the most recent advances to study the kinetics of DNA repair has been the development of laser microbeams to induce and visualize recruitment and loss of repair proteins to base damage in live mammalian cells. However, a number of studies have produced contradictory results that are likely caused by the different laser systems used reflecting in part the wavelength dependence of the damage induced. Additionally, the repair kinetics of laser microbeam induced DNA lesions have generally lacked consideration of the structural and chemical complexity of the DNA damage sites, which are known to greatly influence their reparability. In this review, we highlight the key considerations when embarking on laser microbeam experiments and interpreting the real time data from laser microbeam irradiations. We compare the repair kinetics from live cell imaging with biochemical and direct quantitative cellular measurements for DNA repair. PMID:23688615

  8. Noninvasive imaging of intracellular lipid metabolism in macrophages by Raman microscopy in combination with stable isotopic labeling.

    PubMed

    Matthäus, Christian; Krafft, Christoph; Dietzek, Benjamin; Brehm, Bernhard R; Lorkowski, Stefan; Popp, Jürgen

    2012-10-16

    Monocyte-derived macrophages play a key role in atherogenesis because their transformation into foam cells is responsible for deposition of lipids in plaques within arterial walls. The appearance of cytosolic lipid droplets is a hallmark of macrophage foam cell formation, and the molecular basics involved in this process are not well understood. Of particular interest is the intracellular fate of different individual lipid species, such as fatty acids or cholesterol. Here, we utilize Raman microscopy to image the metabolism of such lipids and to trace their subsequent storage patterns. The combination of microscopic information with Raman spectroscopy provides a powerful molecular imaging method, which allows visualization at the diffraction limit of the employed laser light and biochemical characterization through associated spectral information. In order to distinguish the molecules of interest from other naturally occurring lipids spectroscopically, deuterium labels were introduced. Intracellular distribution and metabolic changes were observed for serum albumin-complexed palmitic and oleic acid and cholesterol and quantitatively evaluated by monitoring the increase in CD scattering intensities at 0.5, 1, 3, 6, 24, 30, and 36 h. This approach may also allow for investigating the cellular trafficking of other molecules, such as nutrients, metabolites, and drugs.

  9. New advances in probing cell–extracellular matrix interactions

    PubMed Central

    2017-01-01

    The extracellular matrix (ECM) provides structural and biochemical support to cells within tissues. An emerging body of evidence has established that the ECM plays a key role in cell mechanotransduction – the study of coupling between mechanical inputs and cellular phenotype – through either mediating transmission of forces to the cells, or presenting mechanical cues that guide cellular behaviors. Recent progress in cell mechanotransduction research has been facilitated by advances of experimental tools, particularly microtechnologies, engineered biomaterials, and imaging and analytical methods. Microtechnologies have enabled the design and fabrication of controlled physical microenvironments for the study and measurement of cell–ECM interactions. Advances in engineered biomaterials have allowed researchers to develop synthetic ECMs that mimic tissue microenvironments and investigate the impact of altered physicochemical properties on various cellular processes. Finally, advanced imaging and spectroscopy techniques have facilitated the visualization of the complex interaction between cells and ECM in vitro and in living tissues. This review will highlight the application of recent innovations in these areas to probing cell–ECM interactions. We believe cross-disciplinary approaches, combining aspects of the different technologies reviewed here, will inspire innovative ideas to further elucidate the secrets of ECM-mediated cell control. PMID:28352896

  10. Non-visualized pregnancy losses are prognostically important for unexplained recurrent miscarriage.

    PubMed

    Kolte, A M; van Oppenraaij, R H; Quenby, S; Farquharson, R G; Stephenson, M; Goddijn, M; Christiansen, O B

    2014-05-01

    Are non-visualized pregnancy losses (biochemical pregnancy loss and failed pregnancy of unknown location combined) in the reproductive history of women with unexplained recurrent miscarriage (RM) negatively associated with the chance of live birth in a subsequent pregnancy? Non-visualized pregnancy losses contribute negatively to the chance for live birth: each non-visualized pregnancy loss confers a relative risk (RR) for live birth of 0.90 (95% CI 0.83; 0.97), equivalent to the RR conferred by each additional clinical miscarriage. The number of clinical miscarriages prior to referral is an important determinant for live birth in women with RM, whereas the significance of non-visualized pregnancy losses is unknown. A retrospective cohort study comprising 587 women with RM seen in a tertiary RM unit 2000-2010. Data on the outcome of the first pregnancy after referral were analysed for 499 women. The study was conducted in the RM Unit at Rigshospitalet, Copenhagen, Denmark. We included all women with unexplained RM, defined as ≥3 consecutive clinical miscarriages or non-visualized pregnancy losses following spontaneous conception or homologous insemination. The category 'non-visualized pregnancy losses' combines biochemical pregnancy loss (positive hCG, no ultrasound performed) and failed PUL (pregnancy of unknown location, positive hCG, but on ultrasound, no pregnancy location established). Demographics were collected, including BMI, age at first pregnancy after referral and outcome of pregnancies prior to referral. Using our own records and records from other Danish hospitals, we verified the outcome of the first pregnancy after referral. For each non-visualized pregnancy loss and miscarriage in the women's reproductive history, the RR for live birth in the first pregnancy after referral was determined by robust Poisson regression analysis, adjusting for risk factors for negative pregnancy outcome. Non-visualized pregnancy losses constituted 37% of reported pregnancies prior to referral among women with RM. Each additional non-visualized pregnancy loss conferred an RR for live birth of 0.90 (95% CI 0.83; 0.97), which was not statistically significantly different from the corresponding RR of 0.87 (95% CI 0.80; 0.94) conferred by each clinical miscarriage. Among women with ≥2 clinical miscarriages, a reduced RR for live birth was also shown: 0.82 (95% CI 0.74; 0.92) for each clinical miscarriage and 0.89 (95% CI 0.80; 0.98) for each non-visualized pregnancy loss, respectively. Surgically treated ectopic pregnancies (EPs) were significantly more common for women with primary RM and no confirmed clinical miscarriages, compared with women with primary RM and ≥1 clinical miscarriage (22 versus 6%, difference 16% (95% CI 9.1%; 28.7%); RR for ectopic pregnancy was 4.0 (95% CI 1.92; 8.20). RM was defined as ≥3 consecutive pregnancy losses before 12 weeks' gestation, and we included only women with unexplained RM after thorough evaluation. It is uncertain whether the findings apply to other definitions of RM and among women with known causes for their miscarriages. To our knowledge, this is the first comprehensive investigation of prior non-visualized pregnancy losses and their prognostic significance for live birth in a subsequent pregnancy in women with unexplained RM. We show that a prior non-visualized pregnancy loss has a negative prognostic impact on subsequent live birth and is thus clinically significant. None. N/A.

  11. Selective transfer of visual working memory training on Chinese character learning.

    PubMed

    Opitz, Bertram; Schneiders, Julia A; Krick, Christoph M; Mecklinger, Axel

    2014-01-01

    Previous research has shown a systematic relationship between phonological working memory capacity and second language proficiency for alphabetic languages. However, little is known about the impact of working memory processes on second language learning in a non-alphabetic language such as Mandarin Chinese. Due to the greater complexity of the Chinese writing system we expect that visual working memory rather than phonological working memory exerts a unique influence on learning Chinese characters. This issue was explored in the present experiment by comparing visual working memory training with an active (auditory working memory training) control condition and a passive, no training control condition. Training induced modulations in language-related brain networks were additionally examined using functional magnetic resonance imaging in a pretest-training-posttest design. As revealed by pre- to posttest comparisons and analyses of individual differences in working memory training gains, visual working memory training led to positive transfer effects on visual Chinese vocabulary learning compared to both control conditions. In addition, we found sustained activation after visual working memory training in the (predominantly visual) left infero-temporal cortex that was associated with behavioral transfer. In the control conditions, activation either increased (active control condition) or decreased (passive control condition) without reliable behavioral transfer effects. This suggests that visual working memory training leads to more efficient processing and more refined responses in brain regions involved in visual processing. Furthermore, visual working memory training boosted additional activation in the precuneus, presumably reflecting mental image generation of the learned characters. We, therefore, suggest that the conjoint activity of the mid-fusiform gyrus and the precuneus after visual working memory training reflects an interaction of working memory and imagery processes with complex visual stimuli that fosters the coherent synthesis of a percept from a complex visual input in service of enhanced Chinese character learning. © 2013 Published by Elsevier Ltd.

  12. Laser nano-surgery for neuronal manipulation (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Sarker, Hori Pada; Chudal, Lalit; Mahapatra, Vasu; Kim, Young-tae; Mohanty, Samarendra K.

    2016-03-01

    Optical manipulation has enabled study of bio-chemical and bio-mechanical properties of the cells. Laser nanosurgery by ultrafast laser beam with appropriate laser parameters provides spatially-targeted manipulation of neurons in a minimal invasiveness manner with high efficiency. We utilized femto-second laser nano-surgery for both axotomy and sub-axotomy of rat cortical neurons. Degeneration and regeneration after axotomy was studied with and without external growth-factor(s) and biochemical(s). Further, axonal injury was studied as a function of pulse energy, exposure and site of injury. The ability to study the response of neurons to localized injury opens up opportunities for screening potential molecules for repair and regeneration after nerve injury. Sub-axotomy enabled transient opening of axonal membrane for optical delivery of impermeable molecules to the axoplasm. Fast resealing of the axonal membrane after sub-axotomy without significant long-term damage to axon (monitored by its growth) was observed. We will present these experimental results along with theoretical simulation of injury due to laser nano-surgery and delivery via the transient pore. Targeted delivery of proteins such as antibodies, genes encoding reporter proteins, ion-channels and voltage indicators will allow visualization, activation and detection of the neuronal structure and function.

  13. Visual Complexity Attenuates Emotional Processing in Psychopathy: Implications for Fear-Potentiated Startle Deficits

    PubMed Central

    Sadeh, Naomi; Verona, Edelyn

    2012-01-01

    A long-standing debate is the extent to which psychopathy is characterized by a fundamental deficit in attention or emotion. We tested the hypothesis that the interplay of emotional and attentional systems is critical for understanding processing deficits in psychopathy. Sixty-three offenders were assessed using the Psychopathy Checklist: Screening Version. Event-related brain potentials (ERPs) and fear-potentiated startle (FPS) were collected while participants viewed pictures selected to disentangle an existing confound between perceptual complexity and emotional content in the pictures typically used to study fear deficits in psychopathy. As predicted, picture complexity moderated emotional processing deficits. Specifically, the affective-interpersonal features of psychopathy were associated with greater allocation of attentional resources to processing emotional stimuli at initial perception (visual N1) but only when picture stimuli were visually-complex. Despite this, results for the late positive potential indicated that emotional pictures were less attentionally engaging and held less motivational significance for individuals high in affective-interpersonal traits. This deficient negative emotional processing was observed later in their reduced defensive fear reactivity (FPS) to high-complexity unpleasant pictures. In contrast, the impulsive-antisocial features of psychopathy were associated with decreased sensitivity to picture complexity (visual N1) and unrelated to emotional processing as assessed by ERP and FPS. These findings are the first to demonstrate that picture complexity moderates FPS deficits and implicate the interplay of attention and emotional systems as deficient in psychopathy. PMID:22187225

  14. Truncated somatostatin receptor 5 may modulate therapy response to somatostatin analogues--Observations in two patients with acromegaly and severe headache.

    PubMed

    Marina, Djordje; Burman, Pia; Klose, Marianne; Casar-Borota, Olivera; Luque, Raúl M; Castaño, Justo P; Feldt-Rasmussen, Ulla

    2015-10-01

    Somatotropinomas have unique "fingerprints" of somatostatin receptor (sst) expression, which are targets in treatment of acromegaly with somatostatin analogues (SSAs). However, a significant expression of sst is not always related to the biochemical response to SSAs. Headache is a common complaint in acromegaly and considered a clinical marker of disease activity. SSAs are reported to have an own analgesic effect, but the sst involved are unknown. We investigated sst expression in two acromegalic patients with severe headache and no biochemical effects of octreotide, but a good response to pasireotide. We searched the literature for determinants of biochemical and analgesic effects of SSAs in somatotropinomas. Case 1 had no biochemical or analgesic effects of octreotide, a semi-selective SSA, but a rapid and significant effect of pasireotide, a pan-SSA. Case 2 demonstrated discordance between analgesic and biochemical effects of octreotide, in that headache disappeared, but without biochemical improvement. In contrast, pasireotide normalized insulin-like growth factor 1. Both adenomas were sparsely granulated and had strong membranous expressions of sst2a in 50-75% and sst5 in 75-100% of tumor cells. The truncated sst5 variant TMD4 (sst5TMD4) showed expression in 20-57% of tumor cells. A poor biochemical response to octreotide may be associated with tumor expression of a truncated sst5 variant, despite abundant sst2a expression, suggesting an influence from variant sst5 on common sst signaling pathways. Furthermore, unrelated analgesic and biochemical effects of SSAs supported a complex pathogenesis of acromegaly-associated headache. Finally, assessment of truncated sst5 in addition to full length sst could be important for a choice of postoperative SSA treatment in somatotropinomas. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. The development of visual speech perception in Mandarin Chinese-speaking children.

    PubMed

    Chen, Liang; Lei, Jianghua

    2017-01-01

    The present study aimed to investigate the development of visual speech perception in Chinese-speaking children. Children aged 7, 13 and 16 were asked to visually identify both consonant and vowel sounds in Chinese as quickly and accurately as possible. Results revealed (1) an increase in accuracy of visual speech perception between ages 7 and 13 after which the accuracy rate either stagnates or drops; and (2) a U-shaped development pattern in speed of perception with peak performance in 13-year olds. Results also showed that across all age groups, the overall levels of accuracy rose, whereas the response times fell for simplex finals, complex finals and initials. These findings suggest that (1) visual speech perception in Chinese is a developmental process that is acquired over time and is still fine-tuned well into late adolescence; (2) factors other than cross-linguistic differences in phonological complexity and degrees of reliance on visual information are involved in development of visual speech perception.

  16. Dissociating visual form from lexical frequency using Japanese.

    PubMed

    Twomey, Tae; Kawabata Duncan, Keith J; Hogan, John S; Morita, Kenji; Umeda, Kazumasa; Sakai, Katsuyuki; Devlin, Joseph T

    2013-05-01

    In Japanese, the same word can be written in either morphographic Kanji or syllabographic Hiragana and this provides a unique opportunity to disentangle a word's lexical frequency from the frequency of its visual form - an important distinction for understanding the neural information processing in regions engaged by reading. Behaviorally, participants responded more quickly to high than low frequency words and to visually familiar relative to less familiar words, independent of script. Critically, the imaging results showed that visual familiarity, as opposed to lexical frequency, had a strong effect on activation in ventral occipito-temporal cortex. Activation here was also greater for Kanji than Hiragana words and this was not due to their inherent differences in visual complexity. These findings can be understood within a predictive coding framework in which vOT receives bottom-up information encoding complex visual forms and top-down predictions from regions encoding non-visual attributes of the stimulus. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Photosynthetic and biochemical mechanisms of an EMS-mutagenized cowpea associated with its resistance to cowpea severe mosaic virus.

    PubMed

    Souza, Pedro F N; Silva, Fredy D A; Carvalho, Fabricio E L; Silveira, Joaquim A G; Vasconcelos, Ilka M; Oliveira, Jose T A

    2017-01-01

    The seed treatment of a CPSMV-susceptible cowpea genotype with the mutagenic agent EMS generated mutagenized resistant plantlets that respond to the virus challenge by activating biochemical and physiological defense mechanisms. Cowpea is an important crop that makes major nutritional contributions particularly to the diet of the poor population worldwide. However, its production is low, because cowpea is naturally exposed to several abiotic and biotic stresses, including viral agents. Cowpea severe mosaic virus (CPSMV) drastically affects cowpea grain production. This study was conducted to compare photosynthetic and biochemical parameters of a CPSMV-susceptible cowpea (CE-31 genotype) and its derived ethyl methanesulfonate-mutagenized resistant plantlets, both challenged with CPSMV, to shed light on the mechanisms of virus resistance. CPSMV inoculation was done in the fully expanded secondary leaves, 15 days after planting. At 7 days post-inoculation, in vivo photosynthetic parameters were measured and leaves collected for biochemical analysis. CPSMV-inoculated mutagenized-resistant cowpea plantlets (MCPI) maintained higher photosynthesis index, chlorophyll, and carotenoid contents in relation to the susceptible (CE-31) CPSMV-inoculated cowpea (CPI). Visually, the MCPI leaves did not exhibit any viral symptoms neither the presence of the virus as examined by RT-PCR. In addition, MCPI showed higher SOD, GPOX, chitinase, and phenylalanine ammonia lyase activities, H 2 O 2 , phenolic contents, and cell wall lignifications, but lower CAT and APX activities in comparison to CPI. All together, these photosynthetic and biochemical changes might have contributed for the CPSMS resistance of MCPI. Contrarily, CPI plantlets showed CPSMV accumulation, severe disease symptoms, reduction in the photosynthesis-related parameters, chlorophyll, carotenoid, phenolic compound, and H 2 O 2 contents, in addition to increased β-1,3-glucanase, and catalase activities that might have favored viral infection.

  18. Live Cell Genomics: RNA Exon-Specific RNA-Binding Protein Isolation.

    PubMed

    Bell, Thomas J; Eberwine, James

    2015-01-01

    RNA-binding proteins (RBPs) are essential regulatory proteins that control all modes of RNA processing and regulation. New experimental approaches to isolate these indispensable proteins under in vivo conditions are needed to advance the field of RBP biology. Historically, in vitro biochemical approaches to isolate RBP complexes have been useful and productive, but biological relevance of the identified RBP complexes can be imprecise or erroneous. Here we review an inventive experimental to isolate RBPs under the in vivo conditions. The method is called peptide nucleic acid (PNA)-assisted identification of RBP (PAIR) technology and it uses cell-penetrating peptides (CPPs) to deliver photo-activatible RBP-capture molecule to the cytoplasm of the live cells. The PAIR methodology provides two significant advantages over the most commonly used approaches: (1) it overcomes the in vitro limitation of standard biochemical approaches and (2) the PAIR RBP-capture molecule is highly selective and adaptable which allows investigators to isolate exon-specific RBP complexes. Most importantly, the in vivo capture conditions and selectivity of the RBP-capture molecule yield biologically accurate and relevant RBP data.

  19. Single-molecule pull-down (SiMPull) for new-age biochemistry: methodology and biochemical applications of single-molecule pull-down (SiMPull) for probing biomolecular interactions in crude cell extracts.

    PubMed

    Aggarwal, Vasudha; Ha, Taekjip

    2014-11-01

    Macromolecular interactions play a central role in many biological processes. Protein-protein interactions have mostly been studied by co-immunoprecipitation, which cannot provide quantitative information on all possible molecular connections present in the complex. We will review a new approach that allows cellular proteins and biomolecular complexes to be studied in real-time at the single-molecule level. This technique is called single-molecule pull-down (SiMPull), because it integrates principles of conventional immunoprecipitation with the powerful single-molecule fluorescence microscopy. SiMPull is used to count how many of each protein is present in the physiological complexes found in cytosol and membranes. Concurrently, it serves as a single-molecule biochemical tool to perform functional studies on the pulled-down proteins. In this review, we will focus on the detailed methodology of SiMPull, its salient features and a wide range of biological applications in comparison with other biosensing tools. © 2014 WILEY Periodicals, Inc.

  20. Structural and Functional Impacts of ER Coactivator Sequential Recruitment.

    PubMed

    Yi, Ping; Wang, Zhao; Feng, Qin; Chou, Chao-Kai; Pintilie, Grigore D; Shen, Hong; Foulds, Charles E; Fan, Guizhen; Serysheva, Irina; Ludtke, Steven J; Schmid, Michael F; Hung, Mien-Chie; Chiu, Wah; O'Malley, Bert W

    2017-09-07

    Nuclear receptors recruit multiple coactivators sequentially to activate transcription. This "ordered" recruitment allows different coactivator activities to engage the nuclear receptor complex at different steps of transcription. Estrogen receptor (ER) recruits steroid receptor coactivator-3 (SRC-3) primary coactivator and secondary coactivators, p300/CBP and CARM1. CARM1 recruitment lags behind the binding of SRC-3 and p300 to ER. Combining cryo-electron microscopy (cryo-EM) structure analysis and biochemical approaches, we demonstrate that there is a close crosstalk between early- and late-recruited coactivators. The sequential recruitment of CARM1 not only adds a protein arginine methyltransferase activity to the ER-coactivator complex, it also alters the structural organization of the pre-existing ERE/ERα/SRC-3/p300 complex. It induces a p300 conformational change and significantly increases p300 HAT activity on histone H3K18 residues, which, in turn, promotes CARM1 methylation activity on H3R17 residues to enhance transcriptional activity. This study reveals a structural role for a coactivator sequential recruitment and biochemical process in ER-mediated transcription. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Ran1 functions to control the Cdc10/Sct1 complex through Puc1.

    PubMed Central

    Caligiuri, M; Connolly, T; Beach, D

    1997-01-01

    We have undertaken a biochemical analysis of the regulation of the G1/S-phase transition and commitment to the cell cycle in the fission yeast Schizosaccharomyces pombe. The execution of Start requires the activity of the Cdc2 protein kinase and the Sct1/Cdc10 transcription complex. Progression through G1 also requires the Ran1 protein kinase whose inactivation leads to activation of the meiotic pathway under conditions normally inhibitory to this process. We have found that in addition to Cdc2, Sct1/Cdc10 complex formation requires Ran1. We demonstrate that the Puc1 cyclin associates with Ran1 and Cdc10 in vivo and that the Ran1 protein kinase functions to control the association between Puc1 and Cdc10. In addition, we present evidence that the phosphorylation state of Cdc10 is altered upon inactivation of Ran1. These results provide biochemical evidence that demonstrate one mechanism by which the Ran1 protein kinase serves to control cell fate through Cdc10 and Puc1. Images PMID:9201720

  2. Structural and biochemical characterization of the inhibitor complexes of xenotropic murine leukemia virus-related virus protease.

    PubMed

    Li, Mi; Gustchina, Alla; Matúz, Krisztina; Tözsér, Jozsef; Namwong, Sirilak; Goldfarb, Nathan E; Dunn, Ben M; Wlodawer, Alexander

    2011-11-01

    Interactions between the protease (PR) encoded by the xenotropic murine leukemia virus-related virus and a number of potential inhibitors have been investigated by biochemical and structural techniques. It was observed that several inhibitors used clinically against HIV PR exhibit nanomolar or even subnanomolar values of K(i) , depending on the exact experimental conditions. Both TL-3, a universal inhibitor of retroviral PRs, and some inhibitors originally shown to inhibit plasmepsins were also quite potent, whereas inhibition by pepstatin A was considerably weaker. Crystal structures of the complexes of xenotropic murine leukemia virus-related virus PR with TL-3, amprenavir and pepstatin A were solved at high resolution and compared with the structures of complexes of these inhibitors with other retropepsins. Whereas TL-3 and amprenavir bound in a predictable manner, spanning the substrate-binding site of the enzyme, two molecules of pepstatin A bound simultaneously in an unprecedented manner, leaving the catalytic water molecule in place. Journal compilation © 2011 FEBS. No claim to original US government works.

  3. Probing Dominant Negative Behavior of Glucocorticoid Receptor β through a Hybrid Structural and Biochemical Approach

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

    Min, Jungki; Perera, Lalith; Krahn, Juno M.

    ABSTRACT Glucocorticoid receptor β (GRβ) is associated with glucocorticoid resistance via dominant negative regulation of GRα. To better understand how GRβ functions as a dominant negative inhibitor of GRα at a molecular level, we determined the crystal structure of the ligand binding domain of GRβ complexed with the antagonist RU-486. The structure reveals that GRβ binds RU-486 in the same ligand binding pocket as GRα, and the unique C-terminal amino acids of GRβ are mostly disordered. Binding energy analysis suggests that these C-terminal residues of GRβ do not contribute to RU-486 binding. Intriguingly, the GRβ/RU-486 complex binds corepressor peptide withmore » affinity similar to that of a GRα/RU-486 complex, despite the lack of helix 12. Our biophysical and biochemical analyses reveal that in the presence of RU-486, GRβ is found in a conformation that favors corepressor binding, potentially antagonizing GRα function. This study thus presents an unexpected molecular mechanism by which GRβ could repress transcription.« less

  4. Diversity of bile salts in fish and amphibians: evolution of a complex biochemical pathway.

    PubMed

    Hagey, Lee R; Møller, Peter R; Hofmann, Alan F; Krasowski, Matthew D

    2010-01-01

    Bile salts are the major end metabolites of cholesterol and are also important in lipid and protein digestion, as well as shaping of the gut microflora. Previous studies had demonstrated variation of bile salt structures across vertebrate species. We greatly extend prior surveys of bile salt variation in fish and amphibians, particularly in analysis of the biliary bile salts of Agnatha and Chondrichthyes. While there is significant structural variation of bile salts across all fish orders, bile salt profiles are generally stable within orders of fish and do not correlate with differences in diet. This large data set allowed us to infer evolutionary changes in the bile salt synthetic pathway. The hypothesized ancestral bile salt synthetic pathway, likely exemplified in extant hagfish, is simpler and much shorter than the pathway of most teleost fish and terrestrial vertebrates. Thus, the bile salt synthetic pathway has become longer and more complex throughout vertebrate evolution. Analysis of the evolution of bile salt synthetic pathways provides a rich model system for the molecular evolution of a complex biochemical pathway in vertebrates.

  5. Genetic and biochemical impairment of mitochondrial complex I activity in a family with Leber hereditary optic neuropathy and hereditary spastic dystonia

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

    De Vries, D.D.; Oost, B.A. van; Went, L.N.

    1996-04-01

    A rare form of Leber hereditary optic neuropathy (LHON) that is associated with hereditary spastic dystonia has been studied in a large Dutch family. Neuropathy and ophthalmological lesions were present together in some family members, whereas only one type of abnormality was found in others. mtDNA mutations previously reported in LHON were not present. Sequence analysis of the protein-coding mitochondrial genes revealed two previously unreported mtDNA mutations. A heteroplasmic A{yields}G transition at nucleotide position 11696 in the ND4 gene resulted in the substitution of an isoleucine for valine at amino acid position 312. A second mutation, a homoplasmic T{yields}A transitionmore » at nucleotide position 14596 in the ND6 gene, resulted in the substitution of a methionine for the isoleucine at amino acid residue 26. Biochemical analysis of a muscle biopsy revealed a severe complex I deficiency, providing a link between these unique mtDNA mutations and this rare, complex phenotype including Leber optic neuropathy. 80 refs., 2 figs., 3 tabs.« less

  6. Palmitoylation is required for the production of a soluble multimeric Hedgehog protein complex and long-range signaling in vertebrates

    PubMed Central

    Chen, Miao-Hsueh; Li, Ya-Jun; Kawakami, Takatoshi; Xu, Shan-Mei; Chuang, Pao-Tien

    2004-01-01

    Hedgehog (Hh) signaling plays a major role in multiple aspects of embryonic development. A key issue in Hh signaling is to elucidate the molecular mechanism by which a Hh protein morphogen gradient is formed despite its membrane association. In this study, we used a combination of genetic, cellular, and biochemical approaches to address the role of lipid modifications in long-range vertebrate Hh signaling. Our molecular analysis of knockout mice deficient in Skn, the murine homolog of the Drosophila ski gene, which catalyzes Hh palmitoylation, and gene-targeted mice producing a nonpalmitoylated form of Shh indicates that Hh palmitoylation is essential for its activity as well as the generation of a protein gradient in the developing embryos. Furthermore, our biochemical data show that Hh lipid modifications are required for producing a soluble multimeric protein complex, which constitutes the major active component for Hh signaling. These results suggest that soluble Hh multimeric complex travels in the morphogenetic field to activate Hh signaling in distant Hh-responsive cells. PMID:15075292

  7. Functional vision and cognition in infants with congenital disorders of the peripheral visual system.

    PubMed

    Dale, Naomi; Sakkalou, Elena; O'Reilly, Michelle; Springall, Clare; De Haan, Michelle; Salt, Alison

    2017-07-01

    To investigate how vision relates to early development by studying vision and cognition in a national cohort of 1-year-old infants with congenital disorders of the peripheral visual system and visual impairment. This was a cross-sectional observational investigation of a nationally recruited cohort of infants with 'simple' and 'complex' congenital disorders of the peripheral visual system. Entry age was 8 to 16 months. Vision level (Near Detection Scale) and non-verbal cognition (sensorimotor understanding, Reynell Zinkin Scales) were assessed. Parents completed demographic questionnaires. Of 90 infants (49 males, 41 females; mean 13mo, standard deviation [SD] 2.5mo; range 7-17mo); 25 (28%) had profound visual impairment (light perception at best) and 65 (72%) had severe visual impairment (basic 'form' vision). The Near Detection Scale correlated significantly with sensorimotor understanding developmental quotients in the 'total', 'simple', and 'complex' groups (all p<0.001). Age and vision accounted for 48% of sensorimotor understanding variance. Infants with profound visual impairment, especially in the 'complex' group with congenital disorders of the peripheral visual system with known brain involvement, showed the greatest cognitive delay. Lack of vision is associated with delayed early-object manipulative abilities and concepts; 'form' vision appeared to support early developmental advance. This paper provides baseline characteristics for cross-sectional and longitudinal follow-up investigations in progress. A methodological strength of the study was the representativeness of the cohort according to national epidemiological and population census data. © 2017 Mac Keith Press.

  8. Universal dynamical properties preclude standard clustering in a large class of biochemical data.

    PubMed

    Gomez, Florian; Stoop, Ralph L; Stoop, Ruedi

    2014-09-01

    Clustering of chemical and biochemical data based on observed features is a central cognitive step in the analysis of chemical substances, in particular in combinatorial chemistry, or of complex biochemical reaction networks. Often, for reasons unknown to the researcher, this step produces disappointing results. Once the sources of the problem are known, improved clustering methods might revitalize the statistical approach of compound and reaction search and analysis. Here, we present a generic mechanism that may be at the origin of many clustering difficulties. The variety of dynamical behaviors that can be exhibited by complex biochemical reactions on variation of the system parameters are fundamental system fingerprints. In parameter space, shrimp-like or swallow-tail structures separate parameter sets that lead to stable periodic dynamical behavior from those leading to irregular behavior. We work out the genericity of this phenomenon and demonstrate novel examples for their occurrence in realistic models of biophysics. Although we elucidate the phenomenon by considering the emergence of periodicity in dependence on system parameters in a low-dimensional parameter space, the conclusions from our simple setting are shown to continue to be valid for features in a higher-dimensional feature space, as long as the feature-generating mechanism is not too extreme and the dimension of this space is not too high compared with the amount of available data. For online versions of super-paramagnetic clustering see http://stoop.ini.uzh.ch/research/clustering. Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Advanced in Visualization of 3D Time-Dependent CFD Solutions

    NASA Technical Reports Server (NTRS)

    Lane, David A.; Lasinski, T. A. (Technical Monitor)

    1995-01-01

    Numerical simulations of complex 3D time-dependent (unsteady) flows are becoming increasingly feasible because of the progress in computing systems. Unfortunately, many existing flow visualization systems were developed for time-independent (steady) solutions and do not adequately depict solutions from unsteady flow simulations. Furthermore, most systems only handle one time step of the solutions individually and do not consider the time-dependent nature of the solutions. For example, instantaneous streamlines are computed by tracking the particles using one time step of the solution. However, for streaklines and timelines, particles need to be tracked through all time steps. Streaklines can reveal quite different information about the flow than those revealed by instantaneous streamlines. Comparisons of instantaneous streamlines with dynamic streaklines are shown. For a complex 3D flow simulation, it is common to generate a grid system with several millions of grid points and to have tens of thousands of time steps. The disk requirement for storing the flow data can easily be tens of gigabytes. Visualizing solutions of this magnitude is a challenging problem with today's computer hardware technology. Even interactive visualization of one time step of the flow data can be a problem for some existing flow visualization systems because of the size of the grid. Current approaches for visualizing complex 3D time-dependent CFD solutions are described. The flow visualization system developed at NASA Ames Research Center to compute time-dependent particle traces from unsteady CFD solutions is described. The system computes particle traces (streaklines) by integrating through the time steps. This system has been used by several NASA scientists to visualize their CFD time-dependent solutions. The flow visualization capabilities of this system are described, and visualization results are shown.

  10. Multisensory object perception in infancy: 4-month-olds perceive a mistuned harmonic as a separate auditory and visual object

    PubMed Central

    A. Smith, Nicholas; A. Folland, Nicholas; Martinez, Diana M.; Trainor, Laurel J.

    2017-01-01

    Infants learn to use auditory and visual information to organize the sensory world into identifiable objects with particular locations. Here we use a behavioural method to examine infants' use of harmonicity cues to auditory object perception in a multisensory context. Sounds emitted by different objects sum in the air and the auditory system must figure out which parts of the complex waveform belong to different sources (auditory objects). One important cue to this source separation is that complex tones with pitch typically contain a fundamental frequency and harmonics at integer multiples of the fundamental. Consequently, adults hear a mistuned harmonic in a complex sound as a distinct auditory object (Alain et al., 2003). Previous work by our group demonstrated that 4-month-old infants are also sensitive to this cue. They behaviourally discriminate a complex tone with a mistuned harmonic from the same complex with in-tune harmonics, and show an object-related event-related potential (ERP) electrophysiological (EEG) response to the stimulus with mistuned harmonics. In the present study we use an audiovisual procedure to investigate whether infants perceive a complex tone with an 8% mistuned harmonic as emanating from two objects, rather than merely detecting the mistuned cue. We paired in-tune and mistuned complex tones with visual displays that contained either one or two bouncing balls. Four-month-old infants showed surprise at the incongruous pairings, looking longer at the display of two balls when paired with the in-tune complex and at the display of one ball when paired with the mistuned harmonic complex. We conclude that infants use harmonicity as a cue for source separation when integrating auditory and visual information in object perception. PMID:28346869

  11. Abiogenic synthesis of nucleotides on the surface of small space bodies with high energy particles

    NASA Astrophysics Data System (ADS)

    Simakov, M. B.; Kuzicheva, E. A.; Antropov, A. E.; Dodonova, N. Ya

    Abiotic formation of such complex biochemical compounds as nucleotides and oligopeptides on the surface of interstellar and interplanetary dust particles (IDP) by cosmic radiation was examined. In order to study the formation of organic compounds on IDPs, solid films prepared from nucleososide and inorganic phosphate were irradiated with high energy protons. Irradiated products were analyzed with HPLC. The natural nucleotides were detected. The main products were 5' AMP (3.2%) and 2'3' cAMP (2.7%). The results were compared with others experiments on the action of ultraviolet radiation with different wavelengths, γ-radiation and heat on solid mixtures of biologically significant compounds. The experiment on abiogenic synthesis of nucleotides on board of space satellite "BION-11" was compared also. The present results suggest that a considerable amount of complex biochemical compounds formed in extraterrestrial environments could have been supplied to the primitive earth before the origin of life.

  12. Computational modelling of oxygenation processes in enzymes and biomimetic model complexes.

    PubMed

    de Visser, Sam P; Quesne, Matthew G; Martin, Bodo; Comba, Peter; Ryde, Ulf

    2014-01-11

    With computational resources becoming more efficient and more powerful and at the same time cheaper, computational methods have become more and more popular for studies on biochemical and biomimetic systems. Although large efforts from the scientific community have gone into exploring the possibilities of computational methods for studies on large biochemical systems, such studies are not without pitfalls and often cannot be routinely done but require expert execution. In this review we summarize and highlight advances in computational methodology and its application to enzymatic and biomimetic model complexes. In particular, we emphasize on topical and state-of-the-art methodologies that are able to either reproduce experimental findings, e.g., spectroscopic parameters and rate constants, accurately or make predictions of short-lived intermediates and fast reaction processes in nature. Moreover, we give examples of processes where certain computational methods dramatically fail.

  13. Amyloid Precursor Protein Processing and Alzheimer’s Disease

    PubMed Central

    O’Brien, Richard J.; Wong, Philip C.

    2011-01-01

    Alzheimer’s disease (AD), the leading cause of dementia worldwide, is characterized by the accumulation of the β-amyloid peptide (Aβ) within the brain along with hyperphosphorylated and cleaved forms of the microtubule-associated protein tau. Genetic, biochemical, and behavioral research suggest that physiologic generation of the neurotoxic Aβ peptide from sequential amyloid precursor protein (APP) proteolysis is the crucial step in the development of AD. APP is a single-pass transmembrane protein expressed at high levels in the brain and metabolized in a rapid and highly complex fashion by a series of sequential proteases, including the intramembranous γ-secretase complex, which also process other key regulatory molecules. Why Aβ accumulates in the brains of elderly individuals is unclear but could relate to changes in APP metabolism or Aβ elimination. Lessons learned from biochemical and genetic studies of APP processing will be crucial to the development of therapeutic targets to treat AD. PMID:21456963

  14. Ancestral gene reconstruction and synthesis of ancient rhodopsins in the laboratory.

    PubMed

    Chang, Belinda S W

    2003-08-01

    Laboratory synthesis of ancestral proteins offers an intriguing opportunity to study the past directly. The development of Bayesian methods to infer ancestral sequences, combined with advances in models of molecular evolution, and synthetic gene technology make this an increasingly promising approach in evolutionary studies of molecular function. Visual pigments form the first step in the biochemical cascade of events in the retina in all animals known to possess visual capabilities. In vertebrates, the necessity of spanning a dynamic range of light intensities of many orders of magnitude has given rise to two different types of photoreceptors, rods specialized for dim-light conditions, and cones for daylight and color vision. These photoreceptors contain different types of visual pigment genes. Reviewed here are methods of inferring ancestral sequences, chemical synthesis of artificial ancestral genes in the laboratory, and applications to the evolution of vertebrate visual systems and the experimental recreation of an archosaur rod visual pigment. The ancestral archosaurs gave rise to several notable lineages of diapsid reptiles, including the birds and the dinosaurs, and would have existed over 200 MYA. What little is known of their physiology comes from fossil remains, and inference based on the biology of their living descendants. Despite its age, an ancestral archosaur pigment was successfully recreated in the lab, and showed interesting properties of its wavelength sensitivity that may have implications for the visual capabilities of the ancestral archosaurs in dim light.

  15. Conveying Clinical Reasoning Based on Visual Observation via Eye-Movement Modelling Examples

    ERIC Educational Resources Information Center

    Jarodzka, Halszka; Balslev, Thomas; Holmqvist, Kenneth; Nystrom, Marcus; Scheiter, Katharina; Gerjets, Peter; Eika, Berit

    2012-01-01

    Complex perceptual tasks, like clinical reasoning based on visual observations of patients, require not only conceptual knowledge about diagnostic classes but also the skills to visually search for symptoms and interpret these observations. However, medical education so far has focused very little on how visual observation skills can be…

  16. Functional MRI evidence for the importance of visual short-term memory in logographic reading.

    PubMed

    Koyama, Maki S; Stein, John F; Stoodley, Catherine J; Hansen, Peter C

    2011-02-01

    Logographic symbols are visually complex, and thus children's abilities for visual short-term memory (VSTM) predict their reading competence in logographic systems. In the present study, we investigated the importance of VSTM in logographic reading in adults, both behaviorally and by means of fMRI. Outside the scanner, VSTM predicted logographic Kanji reading in native Japanese adults (n=45), a finding consistent with previous observations in Japanese children. In the scanner, participants (n=15) were asked to perform a visual one-back task. For this fMRI experiment, we took advantage of the unique linguistic characteristic of the Japanese writing system, whereby syllabic Kana and logographic Kanji can share the same sound and meaning, but differ only in the complexity of their visual features. Kanji elicited greater activation than Kana in the cerebellum and two regions associated with VSTM, the lateral occipital complex and the superior intraparietal sulcus, bilaterally. The same regions elicited the highest activation during the control condition (an unfamiliar, unpronounceable script to the participants), presumably due to the increased VSTM demands for processing the control script. In addition, individual differences in VSTM performance (outside the scanner) significantly predicted blood oxygen level-dependent signal changes in the identified VSTM regions, during the Kanji and control conditions, but not during the Kana condition. VSTM appears to play an important role in reading logographic words, even in skilled adults, as evidenced at the behavioral and neural level, most likely due to the increased VSTM/visual attention demands necessary for processing complex visual features inherent in logographic symbols. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd. No claim to original US government works.

  17. The Application of Current User Interface Technology to Interactive Wargaming Systems.

    DTIC Science & Technology

    1987-09-01

    components is essential to the Macintosh interface. Apple states that "Consistent visual communication is very powerful in delivering complex messages...interface. A visual interface uses visual objects as the basis of communication. "A visual communication object is some combination S. of text and...graphics used for communication under a system of inter- pretation, or visual language." The benefit of visual communication is V 45 "When humans are faced

  18. Live imaging of apoptotic cells in zebrafish

    PubMed Central

    van Ham, Tjakko J.; Mapes, James; Kokel, David; Peterson, Randall T.

    2010-01-01

    Many debilitating diseases, including neurodegenerative diseases, involve apoptosis. Several methods have been developed for visualizing apoptotic cells in vitro or in fixed tissues, but few tools are available for visualizing apoptotic cells in live animals. Here we describe a genetically encoded fluorescent reporter protein that labels apoptotic cells in live zebrafish embryos. During apoptosis, the phospholipid phosphatidylserine (PS) is exposed on the outer leaflet of the plasma membrane. The calcium-dependent protein Annexin V (A5) binds PS with high affinity, and biochemically purified, fluorescently labeled A5 probes have been widely used to detect apoptosis in vitro. Here we show that secreted A5 fused to yellow fluorescent protein specifically labels apoptotic cells in living zebrafish. We use this fluorescent probe to characterize patterns of apoptosis in living zebrafish larvae and to visualize neuronal cell death at single-cell resolution in vivo.—Van Ham, T. J., Mapes, J., Kokel, D., Peterson, R. T. Live imaging of apoptotic cells in zebrafish. PMID:20601526

  19. A standard-enabled workflow for synthetic biology.

    PubMed

    Myers, Chris J; Beal, Jacob; Gorochowski, Thomas E; Kuwahara, Hiroyuki; Madsen, Curtis; McLaughlin, James Alastair; Mısırlı, Göksel; Nguyen, Tramy; Oberortner, Ernst; Samineni, Meher; Wipat, Anil; Zhang, Michael; Zundel, Zach

    2017-06-15

    A synthetic biology workflow is composed of data repositories that provide information about genetic parts, sequence-level design tools to compose these parts into circuits, visualization tools to depict these designs, genetic design tools to select parts to create systems, and modeling and simulation tools to evaluate alternative design choices. Data standards enable the ready exchange of information within such a workflow, allowing repositories and tools to be connected from a diversity of sources. The present paper describes one such workflow that utilizes, among others, the Synthetic Biology Open Language (SBOL) to describe genetic designs, the Systems Biology Markup Language to model these designs, and SBOL Visual to visualize these designs. We describe how a standard-enabled workflow can be used to produce types of design information, including multiple repositories and software tools exchanging information using a variety of data standards. Recently, the ACS Synthetic Biology journal has recommended the use of SBOL in their publications. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  20. Structured illumination microscopy for dual-modality 3D sub-diffraction resolution fluorescence and refractive-index reconstruction

    PubMed Central

    Chowdhury, Shwetadwip; Eldridge, Will J.; Wax, Adam; Izatt, Joseph A.

    2017-01-01

    Though structured illumination (SI) microscopy is a popular imaging technique conventionally associated with fluorescent super-resolution, recent works have suggested its applicability towards sub-diffraction resolution coherent imaging with quantitative endogenous biological contrast. Here, we demonstrate that SI can efficiently integrate together the principles of fluorescent super-resolution and coherent synthetic aperture to achieve 3D dual-modality sub-diffraction resolution, fluorescence and refractive-index (RI) visualizations of biological samples. We experimentally demonstrate this framework by introducing a SI microscope capable of 3D sub-diffraction resolution fluorescence and RI imaging, and verify its biological visualization capabilities by experimentally reconstructing 3D RI/fluorescence visualizations of fluorescent calibration microspheres as well as alveolar basal epithelial adenocarcinoma (A549) and human colorectal adenocarcinmoa (HT-29) cells, fluorescently stained for F-actin. This demonstration may suggest SI as an especially promising imaging technique to enable future biological studies that explore synergistically operating biophysical/biochemical and molecular mechanisms at sub-diffraction resolutions. PMID:29296504

  1. sbml-diff: A Tool for Visually Comparing SBML Models in Synthetic Biology.

    PubMed

    Scott-Brown, James; Papachristodoulou, Antonis

    2017-07-21

    We present sbml-diff, a tool that is able to read a model of a biochemical reaction network in SBML format and produce a range of diagrams showing different levels of detail. Each diagram type can be used to visualize a single model or to visually compare two or more models. The default view depicts species as ellipses, reactions as rectangles, rules as parallelograms, and events as diamonds. A cartoon view replaces the symbols used for reactions on the basis of the associated Systems Biology Ontology terms. An abstract view represents species as ellipses and draws edges between them to indicate whether a species increases or decreases the production or degradation of another species. sbml-diff is freely licensed under the three-clause BSD license and can be downloaded from https://github.com/jamesscottbrown/sbml-diff and used as a python package called from other software, as a free-standing command-line application, or online using the form at http://sysos.eng.ox.ac.uk/tebio/upload.

  2. Readers' Use of Analogic and Visual Aids for Understanding and Remembering Complex Prose.

    ERIC Educational Resources Information Center

    Hayes, David A.

    A study researched the differential uses readers make of analogic and visual prompts for understanding and remembering complex prose. Fifty-two eleventh grade students with average and above average reading ability enrolled in a comprehensive high school in central Georgia participated in the study. They were ranked according to their ability to…

  3. The Role of Derivative Suffix Productivity in the Visual Word Recognition of Complex Words

    ERIC Educational Resources Information Center

    Lázaro, Miguel; Sainz, Javier; Illera, Víctor

    2015-01-01

    In this article we present two lexical decision experiments that examine the role of base frequency and of derivative suffix productivity in visual recognition of Spanish words. In the first experiment we find that complex words with productive derivative suffixes result in lower response times than those with unproductive derivative suffixes.…

  4. [The influence of tobacco-smoke components on alpha-ketopropionic acid in the pulp of front and rear teeth of chronic smokers].

    PubMed

    Zurabashvili, D; Chanturia, I; Kapanadze, L; Danelia, G

    2010-02-01

    The composition of cigarette-smoke is relatively well known in spite of its tremendous complexity. But the analysis of cigarette smoke toxicological influence on biochemical components of tooth enamel, dentine and pulpe is not completely study. The present study was designed to characterize the pulpe biochemical component (alpha-ketopropionic acide) by acute serous pulpit. The total number of 140 patients, age 35-40 (Tobacco-smokers 80, non-smokers - 60) have been investigated. The results suggested, that tobacco-smokers chisel tooth and molars contains less alpha-ketopropionic acide than non-smokers individuals. These studies support the hypothesis of cigarette smoke important role in the tooth support mechanisms. The biochemical activity and function of tooth proteins and amino acids composition must by compared to concentration of tobacco-smoke components.

  5. Metatranscriptomic analysis of diverse microbial communities reveals core metabolic pathways and microbiome-specific functionality.

    PubMed

    Jiang, Yue; Xiong, Xuejian; Danska, Jayne; Parkinson, John

    2016-01-12

    Metatranscriptomics is emerging as a powerful technology for the functional characterization of complex microbial communities (microbiomes). Use of unbiased RNA-sequencing can reveal both the taxonomic composition and active biochemical functions of a complex microbial community. However, the lack of established reference genomes, computational tools and pipelines make analysis and interpretation of these datasets challenging. Systematic studies that compare data across microbiomes are needed to demonstrate the ability of such pipelines to deliver biologically meaningful insights on microbiome function. Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. Metatranscriptomic datasets exhibited distinct taxonomic and functional signatures. From a metabolic perspective, we identified a common core of enzymes involved in amino acid, energy and nucleotide metabolism and also identified microbiome-specific pathways such as phosphonate metabolism (deep sea) and glycan degradation pathways (cow rumen). Integrating taxonomic and functional annotations within a novel visualization framework revealed the contribution of different taxa to metabolic pathways, allowing the identification of taxa that contribute unique functions. The application of a single, standard pipeline confirms that the rich taxonomic and functional diversity observed across microbiomes is not simply an artefact of different analysis pipelines but instead reflects distinct environmental influences. At the same time, our findings show how microbiome complexity and availability of reference genomes can impact comprehensive annotation of metatranscriptomes. Consequently, beyond the application of standardized pipelines, additional caution must be taken when interpreting their output and performing downstream, microbiome-specific, analyses. The pipeline used in these analyses along with a tutorial has been made freely available for download from our project website: http://www.compsysbio.org/microbiome .

  6. Cross-cultural differences for three visual memory tasks in Brazilian children.

    PubMed

    Santos, F H; Mello, C B; Bueno, O F A; Dellatolas, G

    2005-10-01

    Norms for three visual memory tasks, including Corsi's block tapping test and the BEM 144 complex figures and visual recognition, were developed for neuropsychological assessment in Brazilian children. The tasks were measured in 127 children ages 7 to 10 years from rural and urban areas of the States of São Paulo and Minas Gerais. Analysis indicated age-related but not sex-related differences. A cross-cultural effect was observed in relation to copying and recall of Complex pictures. Different performances between rural and urban children were noted.

  7. Molecular Investigations of the Structure and Function of the Protein Phosphatase 1:Spinophilin:Inhibitor-2 Heterotrimeric Complex

    PubMed Central

    Dancheck, Barbara; Ragusa, Michael J.; Allaire, Marc; Nairn, Angus C.; Page, Rebecca; Peti, Wolfgang

    2011-01-01

    Regulation of the major ser/thr phosphatase Protein Phosphatase 1 (PP1) is controlled by a diverse array of targeting and inhibitor proteins. Though many PP1 regulatory proteins share at least one PP1 binding motif, usually the RVxF motif, it was recently discovered that certain pairs of targeting and inhibitor proteins bind PP1 simultaneously to form PP1 heterotrimeric complexes. To date, structural information for these heterotrimeric complexes, and, in turn, how they direct PP1 activity is entirely lacking. Using a combination of NMR spectroscopy, biochemistry and small angle X-ray scattering (SAXS), we show that major structural rearrangements in both spinophilin (targeting) and Inhibitor-2 (I-2, inhibitor) are essential for the formation of the heterotrimeric PP1:spinophilin:I-2 (PSI) complex. The RVxF motif of I-2 is released from PP1 during the formation of PSI, making the less prevalent SILK motif of I-2 essential for complex stability. The release of the I-2 RVxF motif allows for enhanced flexibility of both I-2 and spinophilin in the heterotrimeric complex. In addition, we used inductively coupled plasma atomic emission spectroscopy to show that PP1 contains two metals in both heterodimeric complexes (PP1:spinophilin and PP1:I2) and PSI, demonstrating that PSI retains the biochemical characteristics of the PP1:I2 holoenzyme. Finally, we combined the NMR and biochemical data with SAXS and molecular dynamics simulations to generate a structural model of the full heterotrimeric PSI complex. Collectively, these data reveal the molecular events that enable PP1 heterotrimeric complexes to exploit both the targeting and inhibitory features of the PP1-regulatory proteins to form multi-functional PP1 holoenzymes. PMID:21218781

  8. Microbial oxidative sulfur metabolism: biochemical evidence of the membrane-bound heterodisulfide reductase-like complex of the bacterium Aquifex aeolicus.

    PubMed

    Boughanemi, Souhela; Lyonnet, Jordan; Infossi, Pascale; Bauzan, Marielle; Kosta, Artémis; Lignon, Sabrina; Giudici-Orticoni, Marie-Thérèse; Guiral, Marianne

    2016-08-01

    The Hdr (heterodisulfide reductase)-like enzyme is predicted, from gene transcript profiling experiments previously published, to be essential in oxidative sulfur metabolism in a number of bacteria and archaea. Nevertheless, no biochemical and physicochemical data are available so far about this enzyme. Genes coding for it were identified in Aquifex aeolicus, a Gram-negative, hyperthermophilic, chemolithoautotrophic and microaerophilic bacterium that uses inorganic sulfur compounds as electron donor to grow. We provide biochemical evidence that this Hdr-like enzyme is present in this sulfur-oxidizing prokaryote (cultivated with thiosulfate or elemental sulfur). We demonstrate, by immunolocalization and cell fractionation, that Hdr-like enzyme is associated, presumably monotopically, with the membrane fraction. We show by co-immunoprecipitation assay or partial purification, that the Hdr proteins form a stable complex composed of at least five subunits, HdrA, HdrB1, HdrB2, HdrC1 and HdrC2, present in two forms of high molecular mass on native gel (∼240 and 450 kDa). These studies allow us to propose a revised model for dissimilatory sulfur oxidation pathways in A. aeolicus, with Hdr predicted to generate sulfite. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. The Nucleosome Remodeling and Deacetylase (NuRD) Complex in Development and Disease

    PubMed Central

    Basta, Jeannine; Rauchman, Michael

    2014-01-01

    The Nucleosome Remodeling and Deacetylase (NuRD) complex is one of the major chromatin remodeling complexes found in cells. It plays an important role in regulating gene transcription, genome integrity and cell cycle progression. Through its impact on these basic cellular processes, increasing evidence indicates that alterations in the activity of this macromolecular complex can lead to developmental defects, oncogenesis and accelerated ageing. Recent genetic and biochemical studies have elucidated the mechanisms of NuRD action in modifying the chromatin landscape. These advances have the potential to lead to new therapeutic approaches to birth defects and cancer. PMID:24880148

  10. Conservation and Divergence in the Candida Species Biofilm Matrix Mannan-Glucan Complex Structure, Function, and Genetic Control

    PubMed Central

    Dominguez, Eddie; Zarnowski, Robert; Sanchez, Hiram; Covelli, Antonio S.; Westler, William M.; Azadi, Parastoo; Nett, Jeniel

    2018-01-01

    ABSTRACT Candida biofilms resist the effects of available antifungal therapies. Prior studies with Candida albicans biofilms show that an extracellular matrix mannan-glucan complex (MGCx) contributes to antifungal sequestration, leading to drug resistance. Here we implement biochemical, pharmacological, and genetic approaches to explore a similar mechanism of resistance for the three most common clinically encountered non-albicans Candida species (NAC). Our findings reveal that each Candida species biofilm synthesizes a mannan-glucan complex and that the antifungal-protective function of this complex is conserved. Structural similarities extended primarily to the polysaccharide backbone (α-1,6-mannan and β-1,6-glucan). Surprisingly, biochemical analysis uncovered stark differences in the branching side chains of the MGCx among the species. Consistent with the structural analysis, similarities in the genetic control of MGCx production for each Candida species also appeared limited to the synthesis of the polysaccharide backbone. Each species appears to employ a unique subset of modification enzymes for MGCx synthesis, likely accounting for the observed side chain diversity. Our results argue for the conservation of matrix function among Candida spp. While biogenesis is preserved at the level of the mannan-glucan complex backbone, divergence emerges for construction of branching side chains. Thus, the MGCx backbone represents an ideal drug target for effective pan-Candida species biofilm therapy. PMID:29615504

  11. The aerobic respiratory chain of the acidophilic archaeon Ferroplasma acidiphilum: A membrane-bound complex oxidizing ferrous iron.

    PubMed

    Castelle, Cindy J; Roger, Magali; Bauzan, Marielle; Brugna, Myriam; Lignon, Sabrina; Nimtz, Manfred; Golyshina, Olga V; Giudici-Orticoni, Marie-Thérèse; Guiral, Marianne

    2015-08-01

    The extremely acidophilic archaeon Ferroplasma acidiphilum is found in iron-rich biomining environments and is an important micro-organism in naturally occurring microbial communities in acid mine drainage. F. acidiphilum is an iron oxidizer that belongs to the order Thermoplasmatales (Euryarchaeota), which harbors the most extremely acidophilic micro-organisms known so far. At present, little is known about the nature or the structural and functional organization of the proteins in F. acidiphilum that impact the iron biogeochemical cycle. We combine here biochemical and biophysical techniques such as enzyme purification, activity measurements, proteomics and spectroscopy to characterize the iron oxidation pathway(s) in F. acidiphilum. We isolated two respiratory membrane protein complexes: a 850 kDa complex containing an aa3-type cytochrome oxidase and a blue copper protein, which directly oxidizes ferrous iron and reduces molecular oxygen, and a 150 kDa cytochrome ba complex likely composed of a di-heme cytochrome and a Rieske protein. We tentatively propose that both of these complexes are involved in iron oxidation respiratory chains, functioning in the so-called uphill and downhill electron flow pathways, consistent with autotrophic life. The cytochrome ba complex could possibly play a role in regenerating reducing equivalents by a reverse ('uphill') electron flow. This study constitutes the first detailed biochemical investigation of the metalloproteins that are potentially directly involved in iron-mediated energy conservation in a member of the acidophilic archaea of the genus Ferroplasma. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Influence of visual clutter on the effect of navigated safety inspection: a case study on elevator installation.

    PubMed

    Liao, Pin-Chao; Sun, Xinlu; Liu, Mei; Shih, Yu-Nien

    2018-01-11

    Navigated safety inspection based on task-specific checklists can increase the hazard detection rate, theoretically with interference from scene complexity. Visual clutter, a proxy of scene complexity, can theoretically impair visual search performance, but its impact on the effect of safety inspection performance remains to be explored for the optimization of navigated inspection. This research aims to explore whether the relationship between working memory and hazard detection rate is moderated by visual clutter. Based on a perceptive model of hazard detection, we: (a) developed a mathematical influence model for construction hazard detection; (b) designed an experiment to observe the performance of hazard detection rate with adjusted working memory under different levels of visual clutter, while using an eye-tracking device to observe participants' visual search processes; (c) utilized logistic regression to analyze the developed model under various visual clutter. The effect of a strengthened working memory on the detection rate through increased search efficiency is more apparent in high visual clutter. This study confirms the role of visual clutter in construction-navigated inspections, thus serving as a foundation for the optimization of inspection planning.

  13. Characterization of Visual Scanning Patterns in Air Traffic Control

    PubMed Central

    McClung, Sarah N.; Kang, Ziho

    2016-01-01

    Characterization of air traffic controllers' (ATCs') visual scanning strategies is a challenging issue due to the dynamic movement of multiple aircraft and increasing complexity of scanpaths (order of eye fixations and saccades) over time. Additionally, terminologies and methods are lacking to accurately characterize the eye tracking data into simplified visual scanning strategies linguistically expressed by ATCs. As an intermediate step to automate the characterization classification process, we (1) defined and developed new concepts to systematically filter complex visual scanpaths into simpler and more manageable forms and (2) developed procedures to map visual scanpaths with linguistic inputs to reduce the human judgement bias during interrater agreement. The developed concepts and procedures were applied to investigating the visual scanpaths of expert ATCs using scenarios with different aircraft congestion levels. Furthermore, oculomotor trends were analyzed to identify the influence of aircraft congestion on scan time and number of comparisons among aircraft. The findings show that (1) the scanpaths filtered at the highest intensity led to more consistent mapping with the ATCs' linguistic inputs, (2) the pattern classification occurrences differed between scenarios, and (3) increasing aircraft congestion caused increased scan times and aircraft pairwise comparisons. The results provide a foundation for better characterizing complex scanpaths in a dynamic task and automating the analysis process. PMID:27239190

  14. Fractal analysis of radiologists' visual scanning pattern in screening mammography

    NASA Astrophysics Data System (ADS)

    Alamudun, Folami T.; Yoon, Hong-Jun; Hudson, Kathy; Morin-Ducote, Garnetta; Tourassi, Georgia

    2015-03-01

    Several researchers have investigated radiologists' visual scanning patterns with respect to features such as total time examining a case, time to initially hit true lesions, number of hits, etc. The purpose of this study was to examine the complexity of the radiologists' visual scanning pattern when viewing 4-view mammographic cases, as they typically do in clinical practice. Gaze data were collected from 10 readers (3 breast imaging experts and 7 radiology residents) while reviewing 100 screening mammograms (24 normal, 26 benign, 50 malignant). The radiologists' scanpaths across the 4 mammographic views were mapped to a single 2-D image plane. Then, fractal analysis was applied on the composite 4- view scanpaths. For each case, the complexity of each radiologist's scanpath was measured using fractal dimension estimated with the box counting method. The association between the fractal dimension of the radiologists' visual scanpath, case pathology, case density, and radiologist experience was evaluated using fixed effects ANOVA. ANOVA showed that the complexity of the radiologists' visual search pattern in screening mammography is dependent on case specific attributes (breast parenchyma density and case pathology) as well as on reader attributes, namely experience level. Visual scanning patterns are significantly different for benign and malignant cases than for normal cases. There is also substantial inter-observer variability which cannot be explained only by experience level.

  15. Integrating mechanisms of visual guidance in naturalistic language production.

    PubMed

    Coco, Moreno I; Keller, Frank

    2015-05-01

    Situated language production requires the integration of visual attention and linguistic processing. Previous work has not conclusively disentangled the role of perceptual scene information and structural sentence information in guiding visual attention. In this paper, we present an eye-tracking study that demonstrates that three types of guidance, perceptual, conceptual, and structural, interact to control visual attention. In a cued language production experiment, we manipulate perceptual (scene clutter) and conceptual guidance (cue animacy) and measure structural guidance (syntactic complexity of the utterance). Analysis of the time course of language production, before and during speech, reveals that all three forms of guidance affect the complexity of visual responses, quantified in terms of the entropy of attentional landscapes and the turbulence of scan patterns, especially during speech. We find that perceptual and conceptual guidance mediate the distribution of attention in the scene, whereas structural guidance closely relates to scan pattern complexity. Furthermore, the eye-voice span of the cued object and its perceptual competitor are similar; its latency mediated by both perceptual and structural guidance. These results rule out a strict interpretation of structural guidance as the single dominant form of visual guidance in situated language production. Rather, the phase of the task and the associated demands of cross-modal cognitive processing determine the mechanisms that guide attention.

  16. Characterization of Visual Scanning Patterns in Air Traffic Control.

    PubMed

    McClung, Sarah N; Kang, Ziho

    2016-01-01

    Characterization of air traffic controllers' (ATCs') visual scanning strategies is a challenging issue due to the dynamic movement of multiple aircraft and increasing complexity of scanpaths (order of eye fixations and saccades) over time. Additionally, terminologies and methods are lacking to accurately characterize the eye tracking data into simplified visual scanning strategies linguistically expressed by ATCs. As an intermediate step to automate the characterization classification process, we (1) defined and developed new concepts to systematically filter complex visual scanpaths into simpler and more manageable forms and (2) developed procedures to map visual scanpaths with linguistic inputs to reduce the human judgement bias during interrater agreement. The developed concepts and procedures were applied to investigating the visual scanpaths of expert ATCs using scenarios with different aircraft congestion levels. Furthermore, oculomotor trends were analyzed to identify the influence of aircraft congestion on scan time and number of comparisons among aircraft. The findings show that (1) the scanpaths filtered at the highest intensity led to more consistent mapping with the ATCs' linguistic inputs, (2) the pattern classification occurrences differed between scenarios, and (3) increasing aircraft congestion caused increased scan times and aircraft pairwise comparisons. The results provide a foundation for better characterizing complex scanpaths in a dynamic task and automating the analysis process.

  17. Does linear separability really matter? Complex visual search is explained by simple search

    PubMed Central

    Vighneshvel, T.; Arun, S. P.

    2013-01-01

    Visual search in real life involves complex displays with a target among multiple types of distracters, but in the laboratory, it is often tested using simple displays with identical distracters. Can complex search be understood in terms of simple searches? This link may not be straightforward if complex search has emergent properties. One such property is linear separability, whereby search is hard when a target cannot be separated from its distracters using a single linear boundary. However, evidence in favor of linear separability is based on testing stimulus configurations in an external parametric space that need not be related to their true perceptual representation. We therefore set out to assess whether linear separability influences complex search at all. Our null hypothesis was that complex search performance depends only on classical factors such as target-distracter similarity and distracter homogeneity, which we measured using simple searches. Across three experiments involving a variety of artificial and natural objects, differences between linearly separable and nonseparable searches were explained using target-distracter similarity and distracter heterogeneity. Further, simple searches accurately predicted complex search regardless of linear separability (r = 0.91). Our results show that complex search is explained by simple search, refuting the widely held belief that linear separability influences visual search. PMID:24029822

  18. Photochemistry in Organized Media.

    ERIC Educational Resources Information Center

    Fendler, Janos H.

    1983-01-01

    Describes common artificially produced organized media such as colloids, surfactants, and polymers and their usefulness in studying complex biochemical processes. Discusses selected recent photophysical and photochemical exploitations of these systems, including artificial photosynthesis, in situ generation of colloidal gold and platinum,…

  19. Vitamins and endurance training. Food for running or faddish claims?

    PubMed

    van der Beek, E J

    1985-01-01

    The inter-relationship of food and physical performance, food is considered as a conglomerate of nutrients and man is depicted as a kind of organic pudding. This 'machine' concept of human performance in combination with the mysticism surrounding vitamins, has led to the faddish belief that additional vitamins are necessary to improve physical performance by means of supercharging the metabolic processes in the body. Various vitamins and their dietary recommendations as well as the indicators for vitamin status are discussed. It is concluded that a marginal or subclinical deficiency state can be defined as an intermediate between optimal vitamin status and frank clinical deficiency. Marginal deficiency is characterised by biochemical values deviating from statistically derived reference limits as well as the absence of clinical signs and symptoms of vitamin deficiency. Besides the static, mostly biochemical, indicators of vitamin status, more functional indicators are considered, among them work capacity. An extensive historical review on depletion studies, epidemiological surveys and supplementation studies is presented. It is concluded that a restricted intake of some B-complex vitamins-individually and in combination-of approximately less than 35 to 45% of the recommended dietary allowance may lead to decreased endurance capacity within a few weeks. Studies on ascorbic acid (vitamin C) depletion and fat-soluble vitamin A deficiency have noted no decrease of endurance capacity. However, in a few recent epidemiological surveys, biochemical vitamin C deficiency was actually shown to decrease aerobic power. Although the general conclusion is that a reduced water-soluble vitamin intake decreases endurance capacity, it is believed that further controlled experimentation is needed with B-complex vitamins and vitamin C individually. Furthermore, usually employed reference limits for vitamins need reappraisal translating them into impairment limits. With respect to the available evidence, it can be concluded that supplementation of diet with either single or multivitamin preparations containing B-complex vitamins, vitamin C or E does not improve physical performance in athletes with a normal biochemical vitamin balance resulting from a well-balanced diet. Although vitamin supplementation does not seem to produce any effect when the diet is adequate, it is possible that vitamin B-complex supplementation is useful in sports with a high energy expenditure, because of the unavoidable consumption of 'empty calories' i.e. food products with a low nutrient density. The side effects of megavitamin supplementation are discussed briefly.

  20. Idiosyncratic characteristics of saccadic eye movements when viewing different visual environments.

    PubMed

    Andrews, T J; Coppola, D M

    1999-08-01

    Eye position was recorded in different viewing conditions to assess whether the temporal and spatial characteristics of saccadic eye movements in different individuals are idiosyncratic. Our aim was to determine the degree to which oculomotor control is based on endogenous factors. A total of 15 naive subjects viewed five visual environments: (1) The absence of visual stimulation (i.e. a dark room); (2) a repetitive visual environment (i.e. simple textured patterns); (3) a complex natural scene; (4) a visual search task; and (5) reading text. Although differences in visual environment had significant effects on eye movements, idiosyncrasies were also apparent. For example, the mean fixation duration and size of an individual's saccadic eye movements when passively viewing a complex natural scene covaried significantly with those same parameters in the absence of visual stimulation and in a repetitive visual environment. In contrast, an individual's spatio-temporal characteristics of eye movements during active tasks such as reading text or visual search covaried together, but did not correlate with the pattern of eye movements detected when viewing a natural scene, simple patterns or in the dark. These idiosyncratic patterns of eye movements in normal viewing reveal an endogenous influence on oculomotor control. The independent covariance of eye movements during different visual tasks shows that saccadic eye movements during active tasks like reading or visual search differ from those engaged during the passive inspection of visual scenes.

  1. Optimal Cytoplasmic Transport in Viral Infections

    PubMed Central

    D'Orsogna, Maria R.; Chou, Tom

    2009-01-01

    For many viruses, the ability to infect eukaryotic cells depends on their transport through the cytoplasm and across the nuclear membrane of the host cell. During this journey, viral contents are biochemically processed into complexes capable of both nuclear penetration and genomic integration. We develop a stochastic model of viral entry that incorporates all relevant aspects of transport, including convection along microtubules, biochemical conversion, degradation, and nuclear entry. Analysis of the nuclear infection probabilities in terms of the transport velocity, degradation, and biochemical conversion rates shows how certain values of key parameters can maximize the nuclear entry probability of the viral material. The existence of such “optimal” infection scenarios depends on the details of the biochemical conversion process and implies potentially counterintuitive effects in viral infection, suggesting new avenues for antiviral treatment. Such optimal parameter values provide a plausible transport-based explanation of the action of restriction factors and of experimentally observed optimal capsid stability. Finally, we propose a new interpretation of how genetic mutations unrelated to the mechanism of drug action may nonetheless confer novel types of overall drug resistance. PMID:20046829

  2. Stoichiometric network theory for nonequilibrium biochemical systems.

    PubMed

    Qian, Hong; Beard, Daniel A; Liang, Shou-dan

    2003-02-01

    We introduce the basic concepts and develop a theory for nonequilibrium steady-state biochemical systems applicable to analyzing large-scale complex isothermal reaction networks. In terms of the stoichiometric matrix, we demonstrate both Kirchhoff's flux law sigma(l)J(l)=0 over a biochemical species, and potential law sigma(l) mu(l)=0 over a reaction loop. They reflect mass and energy conservation, respectively. For each reaction, its steady-state flux J can be decomposed into forward and backward one-way fluxes J = J+ - J-, with chemical potential difference deltamu = RT ln(J-/J+). The product -Jdeltamu gives the isothermal heat dissipation rate, which is necessarily non-negative according to the second law of thermodynamics. The stoichiometric network theory (SNT) embodies all of the relevant fundamental physics. Knowing J and deltamu of a biochemical reaction, a conductance can be computed which directly reflects the level of gene expression for the particular enzyme. For sufficiently small flux a linear relationship between J and deltamu can be established as the linear flux-force relation in irreversible thermodynamics, analogous to Ohm's law in electrical circuits.

  3. Petri net modeling of high-order genetic systems using grammatical evolution.

    PubMed

    Moore, Jason H; Hahn, Lance W

    2003-11-01

    Understanding how DNA sequence variations impact human health through a hierarchy of biochemical and physiological systems is expected to improve the diagnosis, prevention, and treatment of common, complex human diseases. We have previously developed a hierarchical dynamic systems approach based on Petri nets for generating biochemical network models that are consistent with genetic models of disease susceptibility. This modeling approach uses an evolutionary computation approach called grammatical evolution as a search strategy for optimal Petri net models. We have previously demonstrated that this approach routinely identifies biochemical network models that are consistent with a variety of genetic models in which disease susceptibility is determined by nonlinear interactions between two DNA sequence variations. In the present study, we evaluate whether the Petri net approach is capable of identifying biochemical networks that are consistent with disease susceptibility due to higher order nonlinear interactions between three DNA sequence variations. The results indicate that our model-building approach is capable of routinely identifying good, but not perfect, Petri net models. Ideas for improving the algorithm for this high-dimensional problem are presented.

  4. A cellular and metabolic assessment of the thermal stress responses in the endemic gastropod Benedictia limnaeoides ongurensis from Lake Baikal.

    PubMed

    Axenov-Gribanov, Denis V; Bedulina, Daria S; Shatilina, Zhanna M; Lubyaga, Yulia A; Vereshchagina, Kseniya P; Timofeyev, Maxim A

    2014-01-01

    Our objective was to determine if the Lake Baikal endemic gastropod Benedictia limnaeoides ongurensis, which inhabits in stable cold waters expresses a thermal stress response. We hypothesized that the evolution of this species in the stable cold waters of Lake Baikal resulted in a reduction of its thermal stress-response mechanisms at the biochemical and cellular levels. Contrary to our hypothesis, our results show that exposure to a thermal challenge activates the cellular and biochemical mechanisms of thermal resistance, such as heat shock proteins and antioxidative enzymes, and alters energetic metabolism in B. limnaeoides ongurensis. Thermal stress caused the elevation of heat shock protein 70 and the products of anaerobic glycolysis together with the depletion of glucose and phosphagens in the studied species. Thus, a temperature increase activates the complex biochemical system of stress response and alters the energetic metabolism in this endemic Baikal gastropod. It is concluded that the deepwater Lake Baikal endemic gastropod B. limnaeoides ongurensis retains the ability to activate well-developed biochemical stress-response mechanisms when exposed to a thermal challenge. © 2013.

  5. Intact Visual Discrimination of Complex and Feature-Ambiguous Stimuli in the Absence of Perirhinal Cortex

    ERIC Educational Resources Information Center

    Squire, Larry R.; Levy, Daniel A.; Shrager, Yael

    2005-01-01

    The perirhinal cortex is known to be important for memory, but there has recently been interest in the possibility that it might also be involved in visual perceptual functions. In four experiments, we assessed visual discrimination ability and visual discrimination learning in severely amnesic patients with large medial temporal lobe lesions that…

  6. Visual Thinking Strategies: Teachers' Reflections on Closely Reading Complex Visual Texts within the Disciplines

    ERIC Educational Resources Information Center

    Cappello, Marva; Walker, Nancy T.

    2016-01-01

    The authors offer a new perspective on close reading that uses a range of multimodal texts to capitalize on the visual nature of contemporary society and to support literacy within the academic disciplines. Specifically, a qualitative study explored teachers' perspectives on the use of Visual Thinking Strategies (VTS), a practice borrowed from…

  7. Perchlorate mixed-ligand copper(II) complexes of beta-diketone and ethylene diamine derivatives: thermal, spectroscopic and biochemical studies.

    PubMed

    El-Ayaan, Usama; El-Metwally, Nashwa M; Youssef, Magdy M; El Bialy, Serry A A

    2007-12-31

    The present work carried out a study on perchlorate mixed-ligand copper(II) complexes which have been synthesized from ethylenediamine derivatives (3a-c) and beta-diketones. These complexes, namely [Cu(DA-Cl)(acac)H(2)O]ClO(4)4, [Cu(DA-Cl)(bzac)H(2)O]H(2)O.ClO(4)5, [Cu(DA-OMe)(acac)H(2)O]ClO(4)6, [Cu(DA-OMe)(bzac)H(2)O]ClO(4)7, [Cu(DA-H)(acac)H(2)O]2H(2)O.ClO(4)8 and [Cu(DA-H)(bzac)H(2)O]ClO(4)9 (where acac, acetylacetonate and bzac, benzoylacetonate) were characterized by elemental analysis, spectral (IR and UV-vis) and magnetic moment measurements. Thermal properties and decomposition kinetics of all complexes are investigated. The interpretation, mathematical analysis and evaluation of kinetic parameters (E, A, DeltaH, DeltaS and DeltaG) of all thermal decomposition stages have been evaluated using Coats-Redfern equation. The biochemical studies showed that, the diamines 3a-c have powerful effects on degradation of DNA and protein. The antibacterial screening demonstrated that, the diamine (DA-Cl), 3b has the maximum and broad activities against Gram +ve and Gram -ve bacterial strains.

  8. Biochemical indicators of nephrotoxicity in blood serum of rats treated with novel 4-thiazolidinone derivatives or their complexes with polyethylene glycol-containing nanoscale polymeric carrier

    PubMed

    Kоbyli nska, L I; Havrylyuk, D Ya; Mitina, N E; Zaichenko, A S; Lesyk, R B; Zіme nkovsky, B S; Stoika, R S

    2016-01-01

    The aim of this study was to compare the effect of new synthetic 4-thiazolidinone derivatives (potential anticancer compounds denoted as 3882, 3288 and 3833) and doxorubicin (positive control) in free form and in their complexes with synthetic polyethylene glycol-containing nanoscale polymeric carrier on the biochemical indicators of nephrotoxicity in blood serum of rats. The concentration of total protein, urea, creatinine, glucose, ions of sodium, potassium, calcium, iron and chloride was measured. It was found that after injection of the investigated compounds, the concentration of sodium cations and chloride anions in blood serum was increased compared with control (untreated animals). Doxorubicin’s injection was accompanied by a decrease in the concentration of iron cations. The concentration of total protein, urea and creatinine decreased under the influence of the studied compounds. Complexation of these аntineoplastic substances with a synthetic polymeric nanocarrier lowered the concentration of the investigated metabolites substantially compared to the effect of these compounds in free form. The normalization of concentration of total protein, urea and creatinine in blood serum of rats treated with complexes of the studied compounds with the polymeric carrier comparing with increased concentration of these indicators at the introduction of such compounds in free form was found.

  9. Endoplasmic reticulum stress-responsive transcription factor ATF6α directs recruitment of the Mediator of RNA polymerase II transcription and multiple histone acetyltransferase complexes.

    PubMed

    Sela, Dotan; Chen, Lu; Martin-Brown, Skylar; Washburn, Michael P; Florens, Laurence; Conaway, Joan Weliky; Conaway, Ronald C

    2012-06-29

    The basic leucine zipper transcription factor ATF6α functions as a master regulator of endoplasmic reticulum (ER) stress response genes. Previous studies have established that, in response to ER stress, ATF6α translocates to the nucleus and activates transcription of ER stress response genes upon binding sequence specifically to ER stress response enhancer elements in their promoters. In this study, we investigate the biochemical mechanism by which ATF6α activates transcription. By exploiting a combination of biochemical and multidimensional protein identification technology-based mass spectrometry approaches, we have obtained evidence that ATF6α functions at least in part by recruiting to the ER stress response enhancer elements of ER stress response genes a collection of RNA polymerase II coregulatory complexes, including the Mediator and multiple histone acetyltransferase complexes, among which are the Spt-Ada-Gcn5 acetyltransferase (SAGA) and Ada-Two-A-containing (ATAC) complexes. Our findings shed new light on the mechanism of action of ATF6α, and they outline a straightforward strategy for applying multidimensional protein identification technology mass spectrometry to determine which RNA polymerase II transcription factors and coregulators are recruited to promoters and other regulatory elements to control transcription.

  10. Visualizing Terrestrial and Aquatic Systems in 3-D

    EPA Science Inventory

    The environmental modeling community has a long-standing need for affordable, easy-to-use tools that support 3-D visualization of complex spatial and temporal model output. The Visualization of Terrestrial and Aquatic Systems project (VISTAS) aims to help scientists produce effe...

  11. Cranial Nerve II

    PubMed Central

    Gillig, Paulette Marie; Sanders, Richard D.

    2009-01-01

    This article contains a brief review of the anatomy of the visual system, a survey of diseases of the retina, optic nerve and lesions of the optic chiasm, and other visual field defects of special interest to the psychiatrist. It also includes a presentation of the corticothalamic mechanisms, differential diagnosis, and various manifestations of visual illusions, and simple and complex visual hallucinations, as well as the differential diagnoses of these various visual phenomena. PMID:19855858

  12. Remembering complex objects in visual working memory: do capacity limits restrict objects or features?

    PubMed

    Hardman, Kyle O; Cowan, Nelson

    2015-03-01

    Visual working memory stores stimuli from our environment as representations that can be accessed by high-level control processes. This study addresses a longstanding debate in the literature about whether storage limits in visual working memory include a limit to the complexity of discrete items. We examined the issue with a number of change-detection experiments that used complex stimuli that possessed multiple features per stimulus item. We manipulated the number of relevant features of the stimulus objects in order to vary feature load. In all of our experiments, we found that increased feature load led to a reduction in change-detection accuracy. However, we found that feature load alone could not account for the results but that a consideration of the number of relevant objects was also required. This study supports capacity limits for both feature and object storage in visual working memory. PsycINFO Database Record (c) 2015 APA, all rights reserved.

  13. The scope and control of attention as separate aspects of working memory.

    PubMed

    Shipstead, Zach; Redick, Thomas S; Hicks, Kenny L; Engle, Randall W

    2012-01-01

    The present study examines two varieties of working memory (WM) capacity task: visual arrays (i.e., a measure of the amount of information that can be maintained in working memory) and complex span (i.e., a task that taps WM-related attentional control). Using previously collected data sets we employ confirmatory factor analysis to demonstrate that visual arrays and complex span tasks load on separate, but correlated, factors. A subsequent series of structural equation models and regression analyses demonstrate that these factors contribute both common and unique variance to the prediction of general fluid intelligence (Gf). However, while visual arrays does contribute uniquely to higher cognition, its overall correlation to Gf is largely mediated by variance associated with the complex span factor. Thus we argue that visual arrays performance is not strictly driven by a limited-capacity storage system (e.g., the focus of attention; Cowan, 2001), but may also rely on control processes such as selective attention and controlled memory search.

  14. Fast and Precise Emulation of Stochastic Biochemical Reaction Networks With Amplified Thermal Noise in Silicon Chips.

    PubMed

    Kim, Jaewook; Woo, Sung Sik; Sarpeshkar, Rahul

    2018-04-01

    The analysis and simulation of complex interacting biochemical reaction pathways in cells is important in all of systems biology and medicine. Yet, the dynamics of even a modest number of noisy or stochastic coupled biochemical reactions is extremely time consuming to simulate. In large part, this is because of the expensive cost of random number and Poisson process generation and the presence of stiff, coupled, nonlinear differential equations. Here, we demonstrate that we can amplify inherent thermal noise in chips to emulate randomness physically, thus alleviating these costs significantly. Concurrently, molecular flux in thermodynamic biochemical reactions maps to thermodynamic electronic current in a transistor such that stiff nonlinear biochemical differential equations are emulated exactly in compact, digitally programmable, highly parallel analog "cytomorphic" transistor circuits. For even small-scale systems involving just 80 stochastic reactions, our 0.35-μm BiCMOS chips yield a 311× speedup in the simulation time of Gillespie's stochastic algorithm over COPASI, a fast biochemical-reaction software simulator that is widely used in computational biology; they yield a 15 500× speedup over equivalent MATLAB stochastic simulations. The chip emulation results are consistent with these software simulations over a large range of signal-to-noise ratios. Most importantly, our physical emulation of Poisson chemical dynamics does not involve any inherently sequential processes and updates such that, unlike prior exact simulation approaches, they are parallelizable, asynchronous, and enable even more speedup for larger-size networks.

  15. Visualizing Complex Environments in the Geo- and BioSciences

    NASA Astrophysics Data System (ADS)

    Prabhu, A.; Fox, P. A.; Zhong, H.; Eleish, A.; Ma, X.; Zednik, S.; Morrison, S. M.; Moore, E. K.; Muscente, D.; Meyer, M.; Hazen, R. M.

    2017-12-01

    Earth's living and non-living components have co-evolved for 4 billion years through numerous positive and negative feedbacks. Earth and life scientists have amassed vast amounts of data in diverse fields related to planetary evolution through deep time-mineralogy and petrology, paleobiology and paleontology, paleotectonics and paleomagnetism, geochemistry and geochrononology, genomics and proteomics, and more. Integrating the data from these complimentary disciplines is very useful in gaining an understanding of the evolution of our planet's environment. The integrated data however, represent many extremely complex environments. In order to gain insights and make discoveries using this data, it is important for us to model and visualize these complex environments. As part of work in understanding the "Co-Evolution of Geo and Biospheres using Data Driven Methodologies," we have developed several visualizations to help represent the information stored in the datasets from complimentary disciplines. These visualizations include 2D and 3D force directed Networks, Chord Diagrams, 3D Klee Diagrams. Evolving Network Diagrams, Skyline Diagrams and Tree Diagrams. Combining these visualizations with the results of machine learning and data analysis methods leads to a powerful way to discover patterns and relationships about the Earth's past and today's changing environment.

  16. Affective facilitation of early visual cortex during rapid picture presentation at 6 and 15 Hz

    PubMed Central

    Bekhtereva, Valeria

    2015-01-01

    The steady-state visual evoked potential (SSVEP), a neurophysiological marker of attentional resource allocation with its generators in early visual cortex, exhibits enhanced amplitude for emotional compared to neutral complex pictures. Emotional cue extraction for complex images is linked to the N1-EPN complex with a peak latency of ∼140–160 ms. We tested whether neural facilitation in early visual cortex with affective pictures requires emotional cue extraction of individual images, even when a stream of images of the same valence category is presented. Images were shown at either 6 Hz (167 ms, allowing for extraction) or 15 Hz (67 ms per image, causing disruption of processing by the following image). Results showed SSVEP amplitude enhancement for emotional compared to neutral images at a presentation rate of 6 Hz but no differences at 15 Hz. This was not due to featural differences between the two valence categories. Results strongly suggest that individual images need to be displayed for sufficient time allowing for emotional cue extraction to drive affective neural modulation in early visual cortex. PMID:25971598

  17. MemAxes: Visualization and Analytics for Characterizing Complex Memory Performance Behaviors.

    PubMed

    Gimenez, Alfredo; Gamblin, Todd; Jusufi, Ilir; Bhatele, Abhinav; Schulz, Martin; Bremer, Peer-Timo; Hamann, Bernd

    2018-07-01

    Memory performance is often a major bottleneck for high-performance computing (HPC) applications. Deepening memory hierarchies, complex memory management, and non-uniform access times have made memory performance behavior difficult to characterize, and users require novel, sophisticated tools to analyze and optimize this aspect of their codes. Existing tools target only specific factors of memory performance, such as hardware layout, allocations, or access instructions. However, today's tools do not suffice to characterize the complex relationships between these factors. Further, they require advanced expertise to be used effectively. We present MemAxes, a tool based on a novel approach for analytic-driven visualization of memory performance data. MemAxes uniquely allows users to analyze the different aspects related to memory performance by providing multiple visual contexts for a centralized dataset. We define mappings of sampled memory access data to new and existing visual metaphors, each of which enabling a user to perform different analysis tasks. We present methods to guide user interaction by scoring subsets of the data based on known performance problems. This scoring is used to provide visual cues and automatically extract clusters of interest. We designed MemAxes in collaboration with experts in HPC and demonstrate its effectiveness in case studies.

  18. Thinking graphically: Connecting vision and cognition during graph comprehension.

    PubMed

    Ratwani, Raj M; Trafton, J Gregory; Boehm-Davis, Deborah A

    2008-03-01

    Task analytic theories of graph comprehension account for the perceptual and conceptual processes required to extract specific information from graphs. Comparatively, the processes underlying information integration have received less attention. We propose a new framework for information integration that highlights visual integration and cognitive integration. During visual integration, pattern recognition processes are used to form visual clusters of information; these visual clusters are then used to reason about the graph during cognitive integration. In 3 experiments, the processes required to extract specific information and to integrate information were examined by collecting verbal protocol and eye movement data. Results supported the task analytic theories for specific information extraction and the processes of visual and cognitive integration for integrative questions. Further, the integrative processes scaled up as graph complexity increased, highlighting the importance of these processes for integration in more complex graphs. Finally, based on this framework, design principles to improve both visual and cognitive integration are described. PsycINFO Database Record (c) 2008 APA, all rights reserved

  19. Origin of Complexity in Multicellular Organisms

    NASA Astrophysics Data System (ADS)

    Furusawa, Chikara; Kaneko, Kunihiko

    2000-06-01

    Through extensive studies of dynamical system modeling cellular growth and reproduction, we find evidence that complexity arises in multicellular organisms naturally through evolution. Without any elaborate control mechanism, these systems can exhibit complex pattern formation with spontaneous cell differentiation. Such systems employ a ``cooperative'' use of resources and maintain a larger growth speed than simple cell systems, which exist in a homogeneous state and behave ``selfishly.'' The relevance of the diversity of chemicals and reaction dynamics to the growth of a multicellular organism is demonstrated. Chaotic biochemical dynamics are found to provide the multipotency of stem cells.

  20. Modeling protein complexes with BiGGER.

    PubMed

    Krippahl, Ludwig; Moura, José J; Palma, P Nuno

    2003-07-01

    This article describes the method and results of our participation in the Critical Assessment of PRediction of Interactions (CAPRI) experiment, using the protein docking program BiGGER (Bimolecular complex Generation with Global Evaluation and Ranking) (Palma et al., Proteins 2000;39:372-384). Of five target complexes (CAPRI targets 2, 4, 5, 6, and 7), only one was successfully predicted (target 6), but BiGGER generated reasonable models for targets 4, 5, and 7, which could have been identified if additional biochemical information had been available. Copyright 2003 Wiley-Liss, Inc.

  1. Interactive and coordinated visualization approaches for biological data analysis.

    PubMed

    Cruz, António; Arrais, Joel P; Machado, Penousal

    2018-03-26

    The field of computational biology has become largely dependent on data visualization tools to analyze the increasing quantities of data gathered through the use of new and growing technologies. Aside from the volume, which often results in large amounts of noise and complex relationships with no clear structure, the visualization of biological data sets is hindered by their heterogeneity, as data are obtained from different sources and contain a wide variety of attributes, including spatial and temporal information. This requires visualization approaches that are able to not only represent various data structures simultaneously but also provide exploratory methods that allow the identification of meaningful relationships that would not be perceptible through data analysis algorithms alone. In this article, we present a survey of visualization approaches applied to the analysis of biological data. We focus on graph-based visualizations and tools that use coordinated multiple views to represent high-dimensional multivariate data, in particular time series gene expression, protein-protein interaction networks and biological pathways. We then discuss how these methods can be used to help solve the current challenges surrounding the visualization of complex biological data sets.

  2. Decoding the time-course of object recognition in the human brain: From visual features to categorical decisions.

    PubMed

    Contini, Erika W; Wardle, Susan G; Carlson, Thomas A

    2017-10-01

    Visual object recognition is a complex, dynamic process. Multivariate pattern analysis methods, such as decoding, have begun to reveal how the brain processes complex visual information. Recently, temporal decoding methods for EEG and MEG have offered the potential to evaluate the temporal dynamics of object recognition. Here we review the contribution of M/EEG time-series decoding methods to understanding visual object recognition in the human brain. Consistent with the current understanding of the visual processing hierarchy, low-level visual features dominate decodable object representations early in the time-course, with more abstract representations related to object category emerging later. A key finding is that the time-course of object processing is highly dynamic and rapidly evolving, with limited temporal generalisation of decodable information. Several studies have examined the emergence of object category structure, and we consider to what degree category decoding can be explained by sensitivity to low-level visual features. Finally, we evaluate recent work attempting to link human behaviour to the neural time-course of object processing. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. The cognitive science of visual-spatial displays: implications for design.

    PubMed

    Hegarty, Mary

    2011-07-01

    This paper reviews cognitive science perspectives on the design of visual-spatial displays and introduces the other papers in this topic. It begins by classifying different types of visual-spatial displays, followed by a discussion of ways in which visual-spatial displays augment cognition and an overview of the perceptual and cognitive processes involved in using displays. The paper then argues for the importance of cognitive science methods to the design of visual displays and reviews some of the main principles of display design that have emerged from these approaches to date. Cognitive scientists have had good success in characterizing the performance of well-defined tasks with relatively simple visual displays, but many challenges remain in understanding the use of complex displays for ill-defined tasks. Current research exemplified by the papers in this topic extends empirical approaches to new displays and domains, informs the development of general principles of graphic design, and addresses current challenges in display design raised by the recent explosion in availability of complex data sets and new technologies for visualizing and interacting with these data. Copyright © 2011 Cognitive Science Society, Inc.

  4. Reading with sounds: sensory substitution selectively activates the visual word form area in the blind.

    PubMed

    Striem-Amit, Ella; Cohen, Laurent; Dehaene, Stanislas; Amedi, Amir

    2012-11-08

    Using a visual-to-auditory sensory-substitution algorithm, congenitally fully blind adults were taught to read and recognize complex images using "soundscapes"--sounds topographically representing images. fMRI was used to examine key questions regarding the visual word form area (VWFA): its selectivity for letters over other visual categories without visual experience, its feature tolerance for reading in a novel sensory modality, and its plasticity for scripts learned in adulthood. The blind activated the VWFA specifically and selectively during the processing of letter soundscapes relative to both textures and visually complex object categories and relative to mental imagery and semantic-content controls. Further, VWFA recruitment for reading soundscapes emerged after 2 hr of training in a blind adult on a novel script. Therefore, the VWFA shows category selectivity regardless of input sensory modality, visual experience, and long-term familiarity or expertise with the script. The VWFA may perform a flexible task-specific rather than sensory-specific computation, possibly linking letter shapes to phonology. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. How cortical neurons help us see: visual recognition in the human brain

    PubMed Central

    Blumberg, Julie; Kreiman, Gabriel

    2010-01-01

    Through a series of complex transformations, the pixel-like input to the retina is converted into rich visual perceptions that constitute an integral part of visual recognition. Multiple visual problems arise due to damage or developmental abnormalities in the cortex of the brain. Here, we provide an overview of how visual information is processed along the ventral visual cortex in the human brain. We discuss how neurophysiological recordings in macaque monkeys and in humans can help us understand the computations performed by visual cortex. PMID:20811161

  6. Data-Driven Healthcare: Challenges and Opportunities for Interactive Visualization.

    PubMed

    Gotz, David; Borland, David

    2016-01-01

    The healthcare industry's widespread digitization efforts are reshaping one of the largest sectors of the world's economy. This transformation is enabling systems that promise to use ever-improving data-driven evidence to help doctors make more precise diagnoses, institutions identify at risk patients for intervention, clinicians develop more personalized treatment plans, and researchers better understand medical outcomes within complex patient populations. Given the scale and complexity of the data required to achieve these goals, advanced data visualization tools have the potential to play a critical role. This article reviews a number of visualization challenges unique to the healthcare discipline.

  7. The Effect of Visual Information on the Manual Approach and Landing

    NASA Technical Reports Server (NTRS)

    Wewerinke, P. H.

    1982-01-01

    The effect of visual information in combination with basic display information on the approach performance. A pre-experimental model analysis was performed in terms of the optimal control model. The resulting aircraft approach performance predictions were compared with the results of a moving base simulator program. The results illustrate that the model provides a meaningful description of the visual (scene) perception process involved in the complex (multi-variable, time varying) manual approach task with a useful predictive capability. The theoretical framework was shown to allow a straight-forward investigation of the complex interaction of a variety of task variables.

  8. An efficient algorithm for computing fixed length attractors based on bounded model checking in synchronous Boolean networks with biochemical applications.

    PubMed

    Li, X Y; Yang, G W; Zheng, D S; Guo, W S; Hung, W N N

    2015-04-28

    Genetic regulatory networks are the key to understanding biochemical systems. One condition of the genetic regulatory network under different living environments can be modeled as a synchronous Boolean network. The attractors of these Boolean networks will help biologists to identify determinant and stable factors. Existing methods identify attractors based on a random initial state or the entire state simultaneously. They cannot identify the fixed length attractors directly. The complexity of including time increases exponentially with respect to the attractor number and length of attractors. This study used the bounded model checking to quickly locate fixed length attractors. Based on the SAT solver, we propose a new algorithm for efficiently computing the fixed length attractors, which is more suitable for large Boolean networks and numerous attractors' networks. After comparison using the tool BooleNet, empirical experiments involving biochemical systems demonstrated the feasibility and efficiency of our approach.

  9. Thermodynamics of Computational Copying in Biochemical Systems

    NASA Astrophysics Data System (ADS)

    Ouldridge, Thomas E.; Govern, Christopher C.; ten Wolde, Pieter Rein

    2017-04-01

    Living cells use readout molecules to record the state of receptor proteins, similar to measurements or copies in typical computational devices. But is this analogy rigorous? Can cells be optimally efficient, and if not, why? We show that, as in computation, a canonical biochemical readout network generates correlations; extracting no work from these correlations sets a lower bound on dissipation. For general input, the biochemical network cannot reach this bound, even with arbitrarily slow reactions or weak thermodynamic driving. It faces an accuracy-dissipation trade-off that is qualitatively distinct from and worse than implied by the bound, and more complex steady-state copy processes cannot perform better. Nonetheless, the cost remains close to the thermodynamic bound unless accuracy is extremely high. Additionally, we show that biomolecular reactions could be used in thermodynamically optimal devices under exogenous manipulation of chemical fuels, suggesting an experimental system for testing computational thermodynamics.

  10. Adiabatic coarse-graining and simulations of stochastic biochemical networks

    PubMed Central

    Sinitsyn, N. A.; Hengartner, Nicolas; Nemenman, Ilya

    2009-01-01

    We propose a universal approach for analysis and fast simulations of stiff stochastic biochemical networks, which rests on elimination of fast chemical species without a loss of information about mesoscopic, non-Poissonian fluctuations of the slow ones. Our approach is similar to the Born–Oppenheimer approximation in quantum mechanics and follows from the stochastic path integral representation of the cumulant generating function of reaction events. In applications with a small number of chemical reactions, it produces analytical expressions for cumulants of chemical fluxes between the slow variables. This allows for a low-dimensional, interpretable representation and can be used for high-accuracy, low-complexity coarse-grained numerical simulations. As an example, we derive the coarse-grained description for a chain of biochemical reactions and show that the coarse-grained and the microscopic simulations agree, but the former is 3 orders of magnitude faster. PMID:19525397

  11. THE RHODOPSIN-TRANSDUCIN COMPLEX HOUSES TWO DISTINCT RHODOPSIN MOLECULES

    PubMed Central

    Jastrzebska, Beata; Ringler, Philipe; Palczewski, Krzysztof; Engel, Andreas

    2013-01-01

    Upon illumination the visual receptor rhodopsin (Rho) transitions to the activated form Rho*, which binds the heterotrimeric G protein, transducin (Gt) causing GDP to GTP exchange and Gt dissociation. Using succinylated concanavalin A (sConA) as a probe, we visualized native Rho dimers solubilized in 1 mM n-dodecyl-β-D-maltoside (DDM) and Rho monomers 5 mM in DDM. By nucleotide depletion and affinity chromatography together with crosslinking and size exclusion chromatography, we trapped and purified nucleotide-free Rho*•Gt and sConA-Rho*•Gt complexes kept in solution by either DDM or lauryl-maltose-neopentyl-glycol (LMNG). The 3-D envelope calculated from projections of negatively stained Rho*•Gt-LMNG complexes accommodated two Rho molecules, one Gt heterotrimer and a detergent belt. Visualization of triple sConA-Rho*•Gt complexes unequivocally demonstrated a pentameric assembly of the Rho*•Gt complex in which the photoactivated Rho* dimer serves as a platform for binding the Gt heterotrimer. Importantly, individual monomers of the Rho* dimer in the heteropentameric complex exhibited different capabilities to be regenerated with either 11-cis or 9-cis-retinal. PMID:23458690

  12. Design and implementation of bimolecular fluorescence complementation (BiFC) assays for the visualization of protein interactions in living cells.

    PubMed

    Kerppola, Tom K

    2006-01-01

    Bimolecular fluorescence complementation (BiFC) analysis enables direct visualization of protein interactions in living cells. The BiFC assay is based on the discoveries that two non-fluorescent fragments of a fluorescent protein can form a fluorescent complex and that the association of the fragments can be facilitated when they are fused to two proteins that interact with each other. BiFC must be confirmed by parallel analysis of proteins in which the interaction interface has been mutated. It is not necessary for the interaction partners to juxtapose the fragments within a specific distance of each other because they can associate when they are tethered to a complex with flexible linkers. It is also not necessary for the interaction partners to form a complex with a long half-life or a high occupancy since the fragments can associate in a transient complex and un-associated fusion proteins do not interfere with detection of the complex. Many interactions can be visualized when the fusion proteins are expressed at levels comparable to their endogenous counterparts. The BiFC assay has been used for the visualization of interactions between many types of proteins in different subcellular locations and in different cell types and organisms. It is technically straightforward and can be performed using a regular fluorescence microscope and standard molecular biology and cell culture reagents.

  13. Learning invariance from natural images inspired by observations in the primary visual cortex.

    PubMed

    Teichmann, Michael; Wiltschut, Jan; Hamker, Fred

    2012-05-01

    The human visual system has the remarkable ability to largely recognize objects invariant of their position, rotation, and scale. A good interpretation of neurobiological findings involves a computational model that simulates signal processing of the visual cortex. In part, this is likely achieved step by step from early to late areas of visual perception. While several algorithms have been proposed for learning feature detectors, only few studies at hand cover the issue of biologically plausible learning of such invariance. In this study, a set of Hebbian learning rules based on calcium dynamics and homeostatic regulations of single neurons is proposed. Their performance is verified within a simple model of the primary visual cortex to learn so-called complex cells, based on a sequence of static images. As a result, the learned complex-cell responses are largely invariant to phase and position.

  14. Preliminary Investigation of Visual Attention to Human Figures in Photographs: Potential Considerations for the Design of Aided AAC Visual Scene Displays

    ERIC Educational Resources Information Center

    Wilkinson, Krista M.; Light, Janice

    2011-01-01

    Purpose: Many individuals with complex communication needs may benefit from visual aided augmentative and alternative communication systems. In visual scene displays (VSDs), language concepts are embedded into a photograph of a naturalistic event. Humans play a central role in communication development and might be important elements in VSDs.…

  15. A foreground object features-based stereoscopic image visual comfort assessment model

    NASA Astrophysics Data System (ADS)

    Jin, Xin; Jiang, G.; Ying, H.; Yu, M.; Ding, S.; Peng, Z.; Shao, F.

    2014-11-01

    Since stereoscopic images provide observers with both realistic and discomfort viewing experience, it is necessary to investigate the determinants of visual discomfort. By considering that foreground object draws most attention when human observing stereoscopic images. This paper proposes a new foreground object based visual comfort assessment (VCA) metric. In the first place, a suitable segmentation method is applied to disparity map and then the foreground object is ascertained as the one having the biggest average disparity. In the second place, three visual features being average disparity, average width and spatial complexity of foreground object are computed from the perspective of visual attention. Nevertheless, object's width and complexity do not consistently influence the perception of visual comfort in comparison with disparity. In accordance with this psychological phenomenon, we divide the whole images into four categories on the basis of different disparity and width, and exert four different models to more precisely predict its visual comfort in the third place. Experimental results show that the proposed VCA metric outperformance other existing metrics and can achieve a high consistency between objective and subjective visual comfort scores. The Pearson Linear Correlation Coefficient (PLCC) and Spearman Rank Order Correlation Coefficient (SROCC) are over 0.84 and 0.82, respectively.

  16. Ictal visual hallucinations due to frontal lobe epilepsy in a patient with bipolar disorder☆

    PubMed Central

    Manfioli, Valeria; Saladini, Marina; Cagnin, Annachiara

    2013-01-01

    In ictal psychosis with complex visual hallucinations (VHs), widespread functional changes of cortical networks have been suggested. We describe the clinical and EEG findings of a patient with bipolar disorder who manifested complex VHs associated with intense emotional symptoms caused by frontal epileptic seizures. This description highlights the challenges of diagnosing the epileptic nature of new psychotic phenomena in patients with previous psychiatric disorders and shines light into the role of the frontal cortex in the genesis of complex VHs. PMID:25667849

  17. Nursing students learning the pharmacology of diabetes mellitus with complexity-based computerized models: A quasi-experimental study.

    PubMed

    Dubovi, Ilana; Dagan, Efrat; Sader Mazbar, Ola; Nassar, Laila; Levy, Sharona T

    2018-02-01

    Pharmacology is a crucial component of medications administration in nursing, yet nursing students generally find it difficult and self-rate their pharmacology skills as low. To evaluate nursing students learning pharmacology with the Pharmacology Inter-Leaved Learning-Cells environment, a novel approach to modeling biochemical interactions using a multiscale, computer-based model with a complexity perspective based on a small set of entities and simple rules. This environment represents molecules, organelles and cells to enhance the understanding of cellular processes, and combines these cells at a higher scale to obtain whole-body interactions. Sophomore nursing students who learned the pharmacology of diabetes mellitus with the Pharmacology Inter-Leaved Learning-Cells environment (experimental group; n=94) or via a lecture-based curriculum (comparison group; n=54). A quasi-experimental pre- and post-test design was conducted. The Pharmacology-Diabetes-Mellitus questionnaire and the course's final exam were used to evaluate students' knowledge of the pharmacology of diabetes mellitus. Conceptual learning was significantly higher for the experimental than for the comparison group for the course final exam scores (unpaired t=-3.8, p<0.001) and for the Pharmacology-Diabetes-Mellitus questionnaire (U=942, p<0.001). The largest effect size for the Pharmacology-Diabetes-Mellitus questionnaire was for the medication action subscale. Analysis of complex-systems component reasoning revealed a significant difference for micro-macro transitions between the levels (F(1, 82)=6.9, p<0.05). Learning with complexity-based computerized models is highly effective and enhances the understanding of moving between micro and macro levels of the biochemical phenomena, this is then related to better understanding of medication actions. Moreover, the Pharmacology Inter-Leaved Learning-Cells approach provides a more general reasoning scheme for biochemical processes, which enhances pharmacology learning beyond the specific topic learned. The present study implies that deeper understanding of pharmacology will support nursing students' clinical decisions and empower their proficiency in medications administration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Science information systems: Visualization

    NASA Technical Reports Server (NTRS)

    Wall, Ray J.

    1991-01-01

    Future programs in earth science, planetary science, and astrophysics will involve complex instruments that produce data at unprecedented rates and volumes. Current methods for data display, exploration, and discovery are inadequate. Visualization technology offers a means for the user to comprehend, explore, and examine complex data sets. The goal of this program is to increase the effectiveness and efficiency of scientists in extracting scientific information from large volumes of instrument data.

  19. A review of visual perception mechanisms that regulate rapid adaptive camouflage in cuttlefish.

    PubMed

    Chiao, Chuan-Chin; Chubb, Charles; Hanlon, Roger T

    2015-09-01

    We review recent research on the visual mechanisms of rapid adaptive camouflage in cuttlefish. These neurophysiologically complex marine invertebrates can camouflage themselves against almost any background, yet their ability to quickly (0.5-2 s) alter their body patterns on different visual backgrounds poses a vexing challenge: how to pick the correct body pattern amongst their repertoire. The ability of cuttlefish to change appropriately requires a visual system that can rapidly assess complex visual scenes and produce the motor responses-the neurally controlled body patterns-that achieve camouflage. Using specifically designed visual backgrounds and assessing the corresponding body patterns quantitatively, we and others have uncovered several aspects of scene variation that are important in regulating cuttlefish patterning responses. These include spatial scale of background pattern, background intensity, background contrast, object edge properties, object contrast polarity, object depth, and the presence of 3D objects. Moreover, arm postures and skin papillae are also regulated visually for additional aspects of concealment. By integrating these visual cues, cuttlefish are able to rapidly select appropriate body patterns for concealment throughout diverse natural environments. This sensorimotor approach of studying cuttlefish camouflage thus provides unique insights into the mechanisms of visual perception in an invertebrate image-forming eye.

  20. Targeting Transcription Elongation Machinery for Breast Cancer Therapy

    DTIC Science & Technology

    2017-05-01

    be performed to evaluate the pausing index for RNA Pol II. The potential role of a Super Enhancer will also be tested by knocking down the mediator...generation of all the cell lines stably knocking out the components of various P-TEFb complexes and performed some of the biochemical experiments...assessing the changes in P-TEFb complex formation upon knocking down or overexpression of various components. Funding Support: NIH Has there been a

  1. [The muzzle and biochemical genetic markers as supplementary breed characteristics in cattle].

    PubMed

    Tarasiuk, S I; Glazko, V I; Trofimenko, A L

    1997-01-01

    The comparative analysis of characteristics of three different cattle breeds (Brown Carpathian, Pinzgauer, Red Polish) on the 5 molecular-genetic markers and 5 muzzle dermatoglyphic types was carried out. It was indicated, that one characteristic can not be use as a breed-specific one but only their complex. The main aspect of search of this complex is the use of characteristics which mark different structure-functional systems of whole organism.

  2. Final anatomic and visual outcomes appear independent of duration of silicone oil intraocular tamponade in complex retinal detachment surgery.

    PubMed

    Rhatigan, Maedbh; McElnea, Elizabeth; Murtagh, Patrick; Stephenson, Kirk; Harris, Elaine; Connell, Paul; Keegan, David

    2018-01-01

    To report anatomic and visual outcomes following silicone oil removal in a cohort of patients with complex retinal detachment, to determine association between duration of tamponade and outcomes and to compare patients with oil removed and those with oil in situ in terms of demographic, surgical and visual factors. We reported a four years retrospective case series of 143 patients with complex retinal detachments who underwent intraocular silicone oil tamponade. Analysis between anatomic and visual outcomes, baseline demographics, duration of tamponade and number of surgical procedures were carried out using Fisher's exact test and unpaired two-tailed t -test. One hundred and six patients (76.2%) had undergone silicone oil removal at the time of review with 96 patients (90.6%) showing retinal reattachment following oil removal. Duration of tamponade was not associated with final reattachment rate or with a deterioration in best corrected visual acuity (BCVA). Patients with oil removed had a significantly better baseline and final BCVA compared to those under oil tamponade ( P =0.0001, <0.0001 respectively). Anatomic and visual outcomes in this cohort are in keeping with those reported in the literature. Favorable outcomes were seen with oil removal but duration of oil tamponade does not affect final attachment rate with modern surgical techniques and should be managed on a case by case basis.

  3. Learning of goal-relevant and -irrelevant complex visual sequences in human V1.

    PubMed

    Rosenthal, Clive R; Mallik, Indira; Caballero-Gaudes, Cesar; Sereno, Martin I; Soto, David

    2018-06-12

    Learning and memory are supported by a network involving the medial temporal lobe and linked neocortical regions. Emerging evidence indicates that primary visual cortex (i.e., V1) may contribute to recognition memory, but this has been tested only with a single visuospatial sequence as the target memorandum. The present study used functional magnetic resonance imaging to investigate whether human V1 can support the learning of multiple, concurrent complex visual sequences involving discontinous (second-order) associations. Two peripheral, goal-irrelevant but structured sequences of orientated gratings appeared simultaneously in fixed locations of the right and left visual fields alongside a central, goal-relevant sequence that was in the focus of spatial attention. Pseudorandom sequences were introduced at multiple intervals during the presentation of the three structured visual sequences to provide an online measure of sequence-specific knowledge at each retinotopic location. We found that a network involving the precuneus and V1 was involved in learning the structured sequence presented at central fixation, whereas right V1 was modulated by repeated exposure to the concurrent structured sequence presented in the left visual field. The same result was not found in left V1. These results indicate for the first time that human V1 can support the learning of multiple concurrent sequences involving complex discontinuous inter-item associations, even peripheral sequences that are goal-irrelevant. Copyright © 2018. Published by Elsevier Inc.

  4. Morphological analysis of the pancreas and liver in diabetic KK-A(y) mice treated with zinc and oxovanadium complexes.

    PubMed

    Moroki, Takayasu; Yoshikawa, Yutaka; Yoshizawa, Katsuhiko; Tsubura, Airo; Yasui, Hiroyuki

    2014-09-01

    The relationship between biometals, such as zinc (Zn(2+)), vanadium, copper, cobalt, and magnesium ions, and diabetes therapy has been recognized for several years. In particular, the antidiabetic activities of Zn(2+) and oxovanadium (VO(2+)) complexes have been measured using biochemical approaches. In the present study, diabetic KK-A(y) mice were treated with bis(1-oxy-2-pyridine-thiolato)Zn(2+) (Zn(opt)2) and bis(1-oxy-2-pyridine-thiolato)VO(2+) (VO(opt)2) for 4 weeks, and the antidiabetic activities of these metal complexes were evaluated using biochemical and morphological methods. Additionally, zinc gluconate (Zn(glc)2) and bis(ethylmaltolato)VO(2+) (VO(emal)2) were used as reference compounds. Pancreatic islet cells were smaller, and there was a tendency towards a lower islet cell area ratio in Zn(opt)2-treated mice compared with nontreated KK-A(y) mice. Furthermore, plasma insulin concentrations were significantly reduced to 27.2% of insulin concentrations in nontreated KK-A(y) mice. These results suggest that Zn(opt)2 administration provides morphological and biochemical improvements in hyperinsulinaemia. In contrast, in mice that received Zn(glc)2 and VO(2+) complexes, the islet cell size and islet cell area ratio did not differ from those in nontreated controls. Zn(opt)2- and VO(opt)2-treated mice exhibited significantly lower fat deposition and fat deposition area ratio in the liver (63.6% and 65.8% of nontreated KK-A(y) mice, respectively) compared to those observed in nontreated KK-A(y) mice. The differences in morphological improvements of the pancreas and liver owing to Zn(opt)2 or VO(opt)2 treatment may be explained by differences in the sites of actions of Zn(2+) and VO(2+) complexes in different organs in KK-A(y) mice. In conclusion, Zn(opt)2 exhibited superior antidiabetic effects over those of VO(opt)2, and this was owing to greater amelioration of the morphological parameters of the liver and pancreas.

  5. "Soft docking": matching of molecular surface cubes.

    PubMed

    Jiang, F; Kim, S H

    1991-05-05

    Molecular recognition is achieved through the complementarity of molecular surface structures and energetics with, most commonly, associated minor conformational changes. This complementarity can take many forms: charge-charge interaction, hydrogen bonding, van der Waals' interaction, and the size and shape of surfaces. We describe a method that exploits these features to predict the sites of interactions between two cognate molecules given their three-dimensional structures. We have developed a "cube representation" of molecular surface and volume which enables us not only to design a simple algorithm for a six-dimensional search but also to allow implicitly the effects of the conformational changes caused by complex formation. The present molecular docking procedure may be divided into two stages. The first is the selection of a population of complexes by geometric "soft docking", in which surface structures of two interacting molecules are matched with each other, allowing minor conformational changes implicitly, on the basis of complementarity in size and shape, close packing, and the absence of steric hindrance. The second is a screening process to identify a subpopulation with many favorable energetic interactions between the buried surface areas. Once the size of the subpopulation is small, one may further screen to find the correct complex based on other criteria or constraints obtained from biochemical, genetic, and theoretical studies, including visual inspection. We have tested the present method in two ways. First is a control test in which we docked the components of a molecular complex of known crystal structure available in the Protein Data Bank (PDB). Two molecular complexes were used: (1) a ternary complex of dihydrofolate reductase, NADPH and methotrexate (3DFR in PDB) and (2) a binary complex of trypsin and trypsin inhibitor (2PTC in PDB). The components of each complex were taken apart at an arbitrary relative orientation and then docked together again. The results show that the geometric docking alone is sufficient to determine the correct docking solutions in these ideal cases, and that the cube representation of the molecules does not degrade the docking process in the search for the correct solution. The second is the more realistic experiment in which we docked the crystal structures of uncomplexed molecules and then compared the structures of docked complexes with the crystal structures of the corresponding complexes. This is to test the capability of our method in accommodating the effects of the conformational changes in the binding sites of the molecules in docking.(ABSTRACT TRUNCATED AT 400 WORDS)

  6. The measles virus N(TAIL)-XD complex: an illustrative example of fuzziness.

    PubMed

    Longhi, Sonia

    2012-01-01

    In this chapter, I focus on the biochemical and structural characterization of the complex between the intrinsically disordered C-terminal domain of the measles virus nucleoprotein (N(TAIL)) and the C-terminal X domain (XD) of the viral phosphoprotein (P). I summarize the main experimental data available so far pointing out the prevalently disordered nature of N(TAIL) even after complex formation and the role of the flexible C-terminal appendage in the binding reaction. I finally discuss the possible functional role of these residual disordered regions within the complex in terms of their ability to capture other regulatory, binding partners.

  7. [Dinitrosyl iron complexes are endogenous signaling agents in animal and human cells and tissues (a hypothesis)].

    PubMed

    Vanin, A F

    2004-01-01

    The hypothesis was advanced that dinitrosyl iron complexes generated in animal and human cells and tissues producing nitric oxide can function as endogenous universal regulators of biochemical and physiological processes. This function is realized by the ability of dinitrosyl iron complexes to act as donors of free nitric oxide molecules interacting with the heme groups of proteins, nitrosonium ions, or Fe+(NO+)2 interacting with the thiol groups of proteins. The effect of dinitrosyl iron complexes on the activity of some enzymes and the expression of the genome at the translation and transcription levels was considered.

  8. Toward structural elucidation of the gamma-secretase complex

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

    Li, H.; Wolfe, M. S.; Selkoe, D. J.

    2009-03-11

    {gamma}-Secretase is an intramembrane protease complex that mediates the Notch signaling pathway and the production of amyloid {beta}-proteins. As such, this enzyme has emerged as an important target for development of novel therapeutics for Alzheimer disease and cancer. Great progress has been made in the identification and characterization of the membrane complex and its biological functions. One major challenge now is to illuminate the structure of this fascinating and important protease at atomic resolution. Here, we review recent progress on biochemical and biophysical probing of the structure of the four-component complex and discuss obstacles and potential pathways toward elucidating itsmore » detailed structure.« less

  9. The role of complex carbohydrate catabolism in the pathogenesis of invasive streptococci

    PubMed Central

    Shelburne, Samuel A.; Davenport, Michael T.; Keith, David B.; Musser, James M.

    2009-01-01

    Historically, the study of bacterial catabolism of complex carbohydrates has contributed to understanding basic bacterial physiology. Recently, however, genome-wide screens of streptococcal pathogenesis have identified genes encoding proteins involved in complex carbohydrate catabolism as participating in pathogen infectivity. Subsequent studies have focused on specific mechanisms by which carbohydrate utilization proteins might contribute to the ability of streptococci to colonize and infect the host. Moreover, transcriptome and biochemical analyses have uncovered novel regulatory pathways by which streptococci link environmental carbohydrate availability to virulence factor production. Herein we review new insights into the role of complex carbohydrates in streptococcal host-pathogen interaction. PMID:18508271

  10. Physiology and biochemistry of honey bees

    USDA-ARS?s Scientific Manuscript database

    Despite their tremendous economic importance, honey bees are not a typical model system for studying general questions of insect physiology. This is primarily due to the fact that honey bees live in complex social settings which impact their physiological and biochemical characteristics. Not surpris...

  11. Different Roles for Honey Bee Mushroom Bodies and Central Complex in Visual Learning of Colored Lights in an Aversive Conditioning Assay

    PubMed Central

    Plath, Jenny A.; Entler, Brian V.; Kirkerud, Nicholas H.; Schlegel, Ulrike; Galizia, C. Giovanni; Barron, Andrew B.

    2017-01-01

    The honey bee is an excellent visual learner, but we know little about how and why it performs so well, or how visual information is learned by the bee brain. Here we examined the different roles of two key integrative regions of the brain in visual learning: the mushroom bodies and the central complex. We tested bees' learning performance in a new assay of color learning that used electric shock as punishment. In this assay a light field was paired with electric shock. The other half of the conditioning chamber was illuminated with light of a different wavelength and not paired with shocks. The unrestrained bee could run away from the light stimulus and thereby associate one wavelength with punishment, and the other with safety. We compared learning performance of bees in which either the central complex or mushroom bodies had been transiently inactivated by microinjection of the reversible anesthetic procaine. Control bees learned to escape the shock-paired light field and to spend more time in the safe light field after a few trials. When ventral lobe neurons of the mushroom bodies were silenced, bees were no longer able to associate one light field with shock. By contrast, silencing of one collar region of the mushroom body calyx did not alter behavior in the learning assay in comparison to control treatment. Bees with silenced central complex neurons did not leave the shock-paired light field in the middle trials of training, even after a few seconds of being shocked. We discussed how mushroom bodies and the central complex both contribute to aversive visual learning with an operant component. PMID:28611605

  12. Collagenous extracellular matrix of cartilage submitted to mechanical forces studied by second harmonic generation microscopy.

    PubMed

    Werkmeister, Elisabeth; de Isla, Natalia; Netter, Patrick; Stoltz, Jean-François; Dumas, Dominique

    2010-01-01

    Osteoarthritis is a degenerative pathology leading to degradation of the extracellular matrix (ECM). Similar effects can be visualized when applying mechanical or biochemical constraints on cartilaginous tissue. Here, we characterized modification of the ECM appearing under mechanical compression and/or biochemical action (hypoxia environment, nitric oxide and collagenase action). In recent decades, multiphoton microscopy has proved its interest for observing living, thick and opaque biological tissues. Thus, the main components of the cartilaginous ECM can be observed without fluorescent labeling. In particular, the collagen network emits strong second harmonic generation (SHG) signal which could be collected at half of the excitation wavelength. Combining autofluorescence and SHG signal detection enables to obtain complementary structural information. Here, we proved that multiphoton microscopy represents an appropriate tool for ex vitro cartilage imaging. First, we showed that SHG signal specifically comes from collagen (collagenase digestion). Further, we verified that the use of an appropriate band-pass filter enables to reject the autofluorescence from the ECM. Once this specificity was shown, we followed modification of the cartilage ECM submitted to mechanical or biochemical constraints (compression, enzymatic digestion). By performing textural analysis of SHG images (Haralick's method), we showed the restructuration of the collagen network according to constraints.

  13. Linking Automated Data Analysis and Visualization with Applications in Developmental Biology and High-Energy Physics

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

    Ruebel, Oliver

    2009-11-20

    Knowledge discovery from large and complex collections of today's scientific datasets is a challenging task. With the ability to measure and simulate more processes at increasingly finer spatial and temporal scales, the increasing number of data dimensions and data objects is presenting tremendous challenges for data analysis and effective data exploration methods and tools. Researchers are overwhelmed with data and standard tools are often insufficient to enable effective data analysis and knowledge discovery. The main objective of this thesis is to provide important new capabilities to accelerate scientific knowledge discovery form large, complex, and multivariate scientific data. The research coveredmore » in this thesis addresses these scientific challenges using a combination of scientific visualization, information visualization, automated data analysis, and other enabling technologies, such as efficient data management. The effectiveness of the proposed analysis methods is demonstrated via applications in two distinct scientific research fields, namely developmental biology and high-energy physics.Advances in microscopy, image analysis, and embryo registration enable for the first time measurement of gene expression at cellular resolution for entire organisms. Analysis of high-dimensional spatial gene expression datasets is a challenging task. By integrating data clustering and visualization, analysis of complex, time-varying, spatial gene expression patterns and their formation becomes possible. The analysis framework MATLAB and the visualization have been integrated, making advanced analysis tools accessible to biologist and enabling bioinformatic researchers to directly integrate their analysis with the visualization. Laser wakefield particle accelerators (LWFAs) promise to be a new compact source of high-energy particles and radiation, with wide applications ranging from medicine to physics. To gain insight into the complex physical processes of particle acceleration, physicists model LWFAs computationally. The datasets produced by LWFA simulations are (i) extremely large, (ii) of varying spatial and temporal resolution, (iii) heterogeneous, and (iv) high-dimensional, making analysis and knowledge discovery from complex LWFA simulation data a challenging task. To address these challenges this thesis describes the integration of the visualization system VisIt and the state-of-the-art index/query system FastBit, enabling interactive visual exploration of extremely large three-dimensional particle datasets. Researchers are especially interested in beams of high-energy particles formed during the course of a simulation. This thesis describes novel methods for automatic detection and analysis of particle beams enabling a more accurate and efficient data analysis process. By integrating these automated analysis methods with visualization, this research enables more accurate, efficient, and effective analysis of LWFA simulation data than previously possible.« less

  14. Through Green Eyes: Complex Visual Culture and Post-Literacy

    ERIC Educational Resources Information Center

    Dobrin, Sidney I.

    2010-01-01

    By way of reclamation of the metaphor "green," this paper contends that research regarding the relationships between children's literatures and cultures and environmental experience requires a reinvigorated consideration of the role of the visual. The heightened importance of visual texts is made evident via three primary, contemporary conditions…

  15. Using Scientific Visualization to Represent Soil Hydrology Dynamics

    ERIC Educational Resources Information Center

    Dolliver, H. A. S.; Bell, J. C.

    2006-01-01

    Understanding the relationships between soil, landscape, and hydrology is important for making sustainable land management decisions. In this study, scientific visualization was explored as a means to visually represent the complex spatial and temporal variations in the hydrologic status of soils. Soil hydrology data was collected at seven…

  16. Identifying Secondary-School Students' Difficulties When Reading Visual Representations Displayed in Physics Simulations

    ERIC Educational Resources Information Center

    López, Víctor; Pintó, Roser

    2017-01-01

    Computer simulations are often considered effective educational tools, since their visual and communicative power enable students to better understand physical systems and phenomena. However, previous studies have found that when students read visual representations some reading difficulties can arise, especially when these are complex or dynamic…

  17. Using Real-Life Experiences to Teach Computer Concepts

    ERIC Educational Resources Information Center

    Read, Alexis

    2012-01-01

    Teaching computer concepts to individuals with visual impairments (that is, those who are blind or visually impaired) presents some unique challenges. Students often have difficulty remembering to perform certain steps or have difficulty remembering specific keystrokes when using computers. Many cannot visualize the way in which complex computing…

  18. Grief and Needs of Adults with Acquired Visual Impairments

    ERIC Educational Resources Information Center

    Murray, Shirley A.; McKay, Robert C.; Nieuwoudt, Johan M.

    2010-01-01

    This report aims to illuminate the complex phenomenon of grief and the needs experienced throughout the time course of their impairments by adults with acquired visual impairments. The study applied a phenomenological research strategy using 10 case studies of South African adults, visually impaired within and beyond six years. Qualitative…

  19. Detection of differentially expressed genes in broiler pectoralis major muscle affected by White Striping - Wooden Breast myopathies.

    PubMed

    Zambonelli, Paolo; Zappaterra, Martina; Soglia, Francesca; Petracci, Massimiliano; Sirri, Federico; Cavani, Claudio; Davoli, Roberta

    2016-12-01

    White Striping and Wooden Breast (WS/WB) are abnormalities increasingly occurring in the fillets of high breast yield and growth rate chicken hybrids. These defects lead to consistent economic losses for poultry meat industry, as affected broiler fillets present an impaired visual appearance that negatively affects consumers' acceptability. Previous studies have highlighted in affected fillets a severely damaged muscle, showing profound inflammation, fibrosis, and lipidosis. The present study investigated the differentially expressed genes and pathways linked to the compositional changes observed in WS/WB breast muscles, in order to outline a more complete framework of the gene networks related to the occurrence of this complex pathological picture. The biochemical composition was performed on 20 pectoralis major samples obtained from high breast yield and growth rate broilers (10 affected vs. 10 normal) and 12 out of the 20 samples were used for the microarray gene expression profiling (6 affected vs. 6 normal). The obtained results indicate strong changes in muscle mineral composition, coupled to an increased deposition of fat. In addition, 204 differentially expressed genes (DEG) were found: 102 up-regulated and 102 down-regulated in affected breasts. The gene expression pathways found more altered in WS/WB muscles are those related to muscle development, polysaccharide metabolic processes, proteoglycans synthesis, inflammation, and calcium signaling pathway. On the whole, the findings suggest that a multifactorial and complex etiology is associated with the occurrence of WS/WB muscle abnormalities, contributing to further defining the transcription patterns associated with these myopathies. © 2016 Poultry Science Association Inc.

  20. An insight into the active site of a type I DNA topoisomerase from the kinetoplastid protozoan Leishmania donovani

    PubMed Central

    Das, Aditi; Mandal, Chhabinath; Dasgupta, Arindam; Sengupta, Tanushri; Majumder, Hemanta K.

    2002-01-01

    DNA topoisomerases are ubiquitous enzymes that govern the topological interconversions of DNA thereby playing a key role in many aspects of nucleic acid metabolism. Recently determined crystal structures of topoisomerase fragments, representing nearly all the known subclasses, have been solved. The type IB enzymes are structurally distinct from other known topoisomerases but are similar to a class of enzymes referred to as tyrosine recombinases. A putative topoisomerase I open reading frame from the kinetoplastid Leishmania donovani was reported which shared a substantial degree of homology with type IB topoisomerases but having a variable C-terminus. Here we present a molecular model of the above parasite gene product, using the human topoisomerase I crystal structure in complex with a 22 bp oligonucleotide as a template. Our studies indicate that the overall structure of the parasite protein is similar to the human enzyme; however, major differences occur in the C-terminal loop, which harbors a serine in place of the usual catalytic tyrosine. Most other structural themes common to type IB topoisomerases, including secondary structural folds, hinged clamps that open and close to bind DNA, nucleophilic attack on the scissile DNA strand and formation of a ternary complex with the topoisomerase I inhibitor camptothecin could be visualized in our homology model. The validity of serine acting as the nucleophile in the case of the parasite protein model was corroborated with our biochemical mapping of the active site with topoisomerase I enzyme purified from L.donovani promastigotes. PMID:11809893

  1. Mitochondrial respiratory chain Complex I defects in Fanconi anemia complementation group A.

    PubMed

    Ravera, Silvia; Vaccaro, Daniele; Cuccarolo, Paola; Columbaro, Marta; Capanni, Cristina; Bartolucci, Martina; Panfoli, Isabella; Morelli, Alessandro; Dufour, Carlo; Cappelli, Enrico; Degan, Paolo

    2013-10-01

    Fanconi anemia (FA) is a rare and complex inherited blood disorder of the child. At least 15 genes are associated with the disease. The highest frequency of mutations belongs to groups A, C and G. Genetic instability and cytokine hypersensitivity support the selection of leukemic over non-leukemic stem cells. FA cellular phenotype is characterized by alterations in red-ox state, mitochondrial functionality and energy metabolism as reported in the past however a clear picture of the altered biochemical phenotype in FA is still elusive and the final biochemical defect(s) still unknown. Here we report an analysis of the respiratory fluxes in FANCA primary fibroblasts, lymphocytes and lymphoblasts. FANCA mutants show defective respiration through Complex I, diminished ATP production and metabolic sufferance with an increased AMP/ATP ratio. Respiration in FANCC mutants is normal. Treatment with N-acetyl-cysteine (NAC) restores oxygen consumption to normal level. Defective respiration in FANCA mutants appear correlated with the FA pro-oxidative phenotype which is consistent with the altered morphology of FANCA mitochondria. Electron microscopy measures indeed show profound alterations in mitochondrial ultrastructure and shape. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  2. Association of Membrane Rafts and Postsynaptic Density: Proteomics, Biochemical, and Ultrastructural Analyses

    PubMed Central

    Suzuki, Tatsuo; Zhang, Jingping; Miyazawa, Shoko; Liu, Qian; Farzan, Michael R.; Yao, Wei-Dong

    2011-01-01

    Postsynaptic membrane rafts are believed to play important roles in synaptic signaling, plasticity, and maintenance. However, their molecular identities remain elusive. Further, how they interact with the well-established signaling specialization, the postsynaptic density (PSD), is poorly understood. We previously detected a number of conventional PSD proteins in detergent-resistant membranes (DRMs). Here, we have performed LC-MS/MS (liquid chromatography coupled with tandem mass spectrometry) analyses on postsynaptic membrane rafts and PSDs. Our comparative analysis identified an extensive overlap of protein components in the two structures. This overlapping could be explained, at least partly, by a physical association of the two structures. Meanwhile, a significant number of proteins displayed biased distributions to either rafts or PSDs, suggesting distinct roles for the two postsynaptic specializations. Using biochemical and electron microscopic methods, we directly detected membrane raft-PSD complexes. In vitro reconstitution experiments indicated that the formation of raft-PSD complexes was not due to the artificial reconstruction of once-solubilized membrane components and PSD structures, supporting that these complexes occurred in vivo. Taking together, our results provide evidence that postsynaptic membrane rafts and PSDs may be physically associated. Such association could be important in postsynaptic signal integration, synaptic function, and maintenance. PMID:21797867

  3. Predictive hypotheses are ineffectual in resolving complex biochemical systems.

    PubMed

    Fry, Michael

    2018-03-20

    Scientific hypotheses may either predict particular unknown facts or accommodate previously-known data. Although affirmed predictions are intuitively more rewarding than accommodations of established facts, opinions divide whether predictive hypotheses are also epistemically superior to accommodation hypotheses. This paper examines the contribution of predictive hypotheses to discoveries of several bio-molecular systems. Having all the necessary elements of the system known beforehand, an abstract predictive hypothesis of semiconservative mode of DNA replication was successfully affirmed. However, in defining the genetic code whose biochemical basis was unclear, hypotheses were only partially effective and supplementary experimentation was required for its conclusive definition. Markedly, hypotheses were entirely inept in predicting workings of complex systems that included unknown elements. Thus, hypotheses did not predict the existence and function of mRNA, the multiple unidentified components of the protein biosynthesis machinery, or the manifold unknown constituents of the ubiquitin-proteasome system of protein breakdown. Consequently, because of their inability to envision unknown entities, predictive hypotheses did not contribute to the elucidation of cation theories remained the sole instrument to explain complex bio-molecular systems, the philosophical question of alleged advantage of predictive over accommodative hypotheses became inconsequential.

  4. Hyperthyroidism and atrial myxoma--an intriguing cardio-endocrine association.

    PubMed

    Kumar, Gautam; Chow, John T; Klarich, Kyle W; Dean, Diana S

    2007-12-01

    A 65-year-old woman presented with dyspnea and bilateral leg edema for 1 week, worsening fatigue for 1 month, and a 7-lb weight loss over the last summer. She was clinically and biochemically hyperthyroid. Echocardiography revealed a left atrial myxoma measuring 6.2 x 3.3 cm protruding into the mitral orifice and left ventricle during diastole. She was treated for Graves' disease with Iodine-131. Six weeks later, her left atrial myxoma measuring 10.1 x 6.2 x 2.4 cm was resected. She became euthyroid before surgery and then biochemically hypothyroid 6 weeks after radioiodine treatment, for which she subsequently required thyroxine replacement. Atrial myxomas are the most common primary cardiac neoplasms. At least 5% to 10% can be attributed to Carney's complex. More than two-thirds of patients with Carney's complex develop one or more cardiac myxomas. Although atrial myxomas in Carney's complex are histologically indistinguishable from the sporadic form, their clinical presentation and course is distinct. This is the first case of newly diagnosed Graves' disease that has been reported in association with an atrial myxoma. The features discussed in this article help differentiate between syndromic and sporadic atrial myxomas.

  5. Clinical instrumentation and applications of Raman spectroscopy

    PubMed Central

    Pence, Isaac

    2016-01-01

    Clinical diagnostic devices provide new sources of information that give insight about the state of health which can then be used to manage patient care. These tools can be as simple as an otoscope to better visualize the ear canal or as complex as a wireless capsule endoscope to monitor the gastrointestinal tract. It is with tools such as these that medical practitioners can determine when a patient is healthy and to make an appropriate diagnosis when he/she is not. The goal of diagnostic medicine then is to efficiently determine the presence and cause of disease in order to provide the most appropriate intervention. The earliest form of medical diagnostics relied on the eye – direct visual observation of the interaction of light with the sample. This technique was espoused by Hippocrates in his 5th century BCE work Epidemics, in which the pallor of a patient’s skin and the coloring of the bodily fluids could be indicative of health. In the last hundred years, medical diagnosis has moved from relying on visual inspection to relying on numerous technological tools that are based on various types of interaction of the sample with different types of energy – light, ultrasound, radio waves, X-rays etc. Modern advances in science and technology have depended on enhancing technologies for the detection of these interactions for improved visualization of human health. Optical methods have been focused on providing this information in the micron to millimeter scale while ultrasound, X-ray, and radio waves have been key in aiding in the millimeter to centimeter scale. While a few optical technologies have achieved the status of medical instruments, many remain in the research and development phase despite persistent efforts by many researchers in the translation of these methods for clinical care. Of these, Raman spectroscopy has been described as a sensitive method that can provide biochemical information about tissue state while maintaining the capability of delivering this information in real-time, non-invasively, and in an automated manner. This review presents the various instrumentation considerations relevant to the clinical implementation of Raman spectroscopy and reviews a subset of interesting applications that have successfully demonstrated the efficacy of this technique for clinical diagnostics and monitoring in large (n ≥ 50) in vivo human studies. PMID:26999370

  6. ViSEN: methodology and software for visualization of statistical epistasis networks

    PubMed Central

    Hu, Ting; Chen, Yuanzhu; Kiralis, Jeff W.; Moore, Jason H.

    2013-01-01

    The non-linear interaction effect among multiple genetic factors, i.e. epistasis, has been recognized as a key component in understanding the underlying genetic basis of complex human diseases and phenotypic traits. Due to the statistical and computational complexity, most epistasis studies are limited to interactions with an order of two. We developed ViSEN to analyze and visualize epistatic interactions of both two-way and three-way. ViSEN not only identifies strong interactions among pairs or trios of genetic attributes, but also provides a global interaction map that shows neighborhood and clustering structures. This visualized information could be very helpful to infer the underlying genetic architecture of complex diseases and to generate plausible hypotheses for further biological validations. ViSEN is implemented in Java and freely available at https://sourceforge.net/projects/visen/. PMID:23468157

  7. A visual-environment simulator with variable contrast

    NASA Astrophysics Data System (ADS)

    Gusarova, N. F.; Demin, A. V.; Polshchikov, G. V.

    1987-01-01

    A visual-environment simulator is proposed in which the image contrast can be varied continuously up to the reversal of the image. Contrast variability can be achieved by using two independently adjustable light sources to simultaneously illuminate the carrier of visual information (e.g., a slide or a cinematographic film). It is shown that such a scheme makes it possible to adequately model a complex visual environment.

  8. Computational Cellular Dynamics Based on the Chemical Master Equation: A Challenge for Understanding Complexity

    PubMed Central

    Liang, Jie; Qian, Hong

    2010-01-01

    Modern molecular biology has always been a great source of inspiration for computational science. Half a century ago, the challenge from understanding macromolecular dynamics has led the way for computations to be part of the tool set to study molecular biology. Twenty-five years ago, the demand from genome science has inspired an entire generation of computer scientists with an interest in discrete mathematics to join the field that is now called bioinformatics. In this paper, we shall lay out a new mathematical theory for dynamics of biochemical reaction systems in a small volume (i.e., mesoscopic) in terms of a stochastic, discrete-state continuous-time formulation, called the chemical master equation (CME). Similar to the wavefunction in quantum mechanics, the dynamically changing probability landscape associated with the state space provides a fundamental characterization of the biochemical reaction system. The stochastic trajectories of the dynamics are best known through the simulations using the Gillespie algorithm. In contrast to the Metropolis algorithm, this Monte Carlo sampling technique does not follow a process with detailed balance. We shall show several examples how CMEs are used to model cellular biochemical systems. We shall also illustrate the computational challenges involved: multiscale phenomena, the interplay between stochasticity and nonlinearity, and how macroscopic determinism arises from mesoscopic dynamics. We point out recent advances in computing solutions to the CME, including exact solution of the steady state landscape and stochastic differential equations that offer alternatives to the Gilespie algorithm. We argue that the CME is an ideal system from which one can learn to understand “complex behavior” and complexity theory, and from which important biological insight can be gained. PMID:24999297

  9. Computational Cellular Dynamics Based on the Chemical Master Equation: A Challenge for Understanding Complexity.

    PubMed

    Liang, Jie; Qian, Hong

    2010-01-01

    Modern molecular biology has always been a great source of inspiration for computational science. Half a century ago, the challenge from understanding macromolecular dynamics has led the way for computations to be part of the tool set to study molecular biology. Twenty-five years ago, the demand from genome science has inspired an entire generation of computer scientists with an interest in discrete mathematics to join the field that is now called bioinformatics. In this paper, we shall lay out a new mathematical theory for dynamics of biochemical reaction systems in a small volume (i.e., mesoscopic) in terms of a stochastic, discrete-state continuous-time formulation, called the chemical master equation (CME). Similar to the wavefunction in quantum mechanics, the dynamically changing probability landscape associated with the state space provides a fundamental characterization of the biochemical reaction system. The stochastic trajectories of the dynamics are best known through the simulations using the Gillespie algorithm. In contrast to the Metropolis algorithm, this Monte Carlo sampling technique does not follow a process with detailed balance. We shall show several examples how CMEs are used to model cellular biochemical systems. We shall also illustrate the computational challenges involved: multiscale phenomena, the interplay between stochasticity and nonlinearity, and how macroscopic determinism arises from mesoscopic dynamics. We point out recent advances in computing solutions to the CME, including exact solution of the steady state landscape and stochastic differential equations that offer alternatives to the Gilespie algorithm. We argue that the CME is an ideal system from which one can learn to understand "complex behavior" and complexity theory, and from which important biological insight can be gained.

  10. MacroBac: New Technologies for Robust and Efficient Large-Scale Production of Recombinant Multiprotein Complexes.

    PubMed

    Gradia, Scott D; Ishida, Justin P; Tsai, Miaw-Sheue; Jeans, Chris; Tainer, John A; Fuss, Jill O

    2017-01-01

    Recombinant expression of large, multiprotein complexes is essential and often rate limiting for determining structural, biophysical, and biochemical properties of DNA repair, replication, transcription, and other key cellular processes. Baculovirus-infected insect cell expression systems are especially well suited for producing large, human proteins recombinantly, and multigene baculovirus systems have facilitated studies of multiprotein complexes. In this chapter, we describe a multigene baculovirus system called MacroBac that uses a Biobricks-type assembly method based on restriction and ligation (Series 11) or ligation-independent cloning (Series 438). MacroBac cloning and assembly is efficient and equally well suited for either single subcloning reactions or high-throughput cloning using 96-well plates and liquid handling robotics. MacroBac vectors are polypromoter with each gene flanked by a strong polyhedrin promoter and an SV40 poly(A) termination signal that minimize gene order expression level effects seen in many polycistronic assemblies. Large assemblies are robustly achievable, and we have successfully assembled as many as 10 genes into a single MacroBac vector. Importantly, we have observed significant increases in expression levels and quality of large, multiprotein complexes using a single, multigene, polypromoter virus rather than coinfection with multiple, single-gene viruses. Given the importance of characterizing functional complexes, we believe that MacroBac provides a critical enabling technology that may change the way that structural, biophysical, and biochemical research is done. © 2017 Elsevier Inc. All rights reserved.

  11. [Imaging Mass Spectrometry in Histopathologic Analysis].

    PubMed

    Yamazaki, Fumiyoshi; Seto, Mitsutoshi

    2015-04-01

    Matrix-assisted laser desorption/ionization (MALDI)-imaging mass spectrometry (IMS) enables visualization of the distribution of a range of biomolecules by integrating biochemical information from mass spectrometry with positional information from microscopy. IMS identifies a target molecule. In addition, IMS enables global analysis of biomolecules containing unknown molecules by detecting the ratio of the molecular weight to electric charge without any target, which makes it possible to identify novel molecules. IMS generates data on the distribution of lipids and small molecules in tissues, which is difficult to visualize with either conventional counter-staining or immunohistochemistry. In this review, we firstly introduce the principle of imaging mass spectrometry and recent advances in the sample preparation method. Secondly, we present findings regarding biological samples, especially pathological ones. Finally, we discuss the limitations and problems of the IMS technique and clinical application, such as in drug development.

  12. Visual short-term memory capacity for simple and complex objects.

    PubMed

    Luria, Roy; Sessa, Paola; Gotler, Alex; Jolicoeur, Pierre; Dell'Acqua, Roberto

    2010-03-01

    Does the capacity of visual short-term memory (VSTM) depend on the complexity of the objects represented in memory? Although some previous findings indicated lower capacity for more complex stimuli, other results suggest that complexity effects arise during retrieval (due to errors in the comparison process with what is in memory) that is not related to storage limitations of VSTM, per se. We used ERPs to track neuronal activity specifically related to retention in VSTM by measuring the sustained posterior contralateral negativity during a change detection task (which required detecting if an item was changed between a memory and a test array). The sustained posterior contralateral negativity, during the retention interval, was larger for complex objects than for simple objects, suggesting that neurons mediating VSTM needed to work harder to maintain more complex objects. This, in turn, is consistent with the view that VSTM capacity depends on complexity.

  13. Crystal structure of the Xpo1p nuclear export complex bound to the SxFG/PxFG repeats of the nucleoporin Nup42p.

    PubMed

    Koyama, Masako; Hirano, Hidemi; Shirai, Natsuki; Matsuura, Yoshiyuki

    2017-10-01

    Xpo1p (yeast CRM1) is the major nuclear export receptor that carries a plethora of proteins and ribonucleoproteins from the nucleus to cytoplasm. The passage of the Xpo1p nuclear export complex through nuclear pore complexes (NPCs) is facilitated by interactions with nucleoporins (Nups) containing extensive repeats of phenylalanine-glycine (so-called FG repeats), although the precise role of each Nup in the nuclear export reaction remains incompletely understood. Here we report structural and biochemical characterization of the interactions between the Xpo1p nuclear export complex and the FG repeats of Nup42p, a nucleoporin localized at the cytoplasmic face of yeast NPCs and has characteristic SxFG/PxFG sequence repeat motif. The crystal structure of Xpo1p-PKI-Nup42p-Gsp1p-GTP complex identified three binding sites for the SxFG/PxFG repeats on HEAT repeats 14-20 of Xpo1p. Mutational analyses of Nup42p showed that the conserved serines and prolines in the SxFG/PxFG repeats contribute to Xpo1p-Nup42p binding. Our structural and biochemical data suggest that SxFG/PxFG-Nups such as Nup42p and Nup159p at the cytoplasmic face of NPCs provide high-affinity docking sites for the Xpo1p nuclear export complex in the terminal stage of NPC passage and that subsequent disassembly of the nuclear export complex facilitates recycling of free Xpo1p back to the nucleus. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  14. Plasma adiponectin complexes have distinct biochemical characteristics.

    PubMed

    Schraw, Todd; Wang, Zhao V; Halberg, Nils; Hawkins, Meredith; Scherer, Philipp E

    2008-05-01

    Adipocytes release the secretory protein adiponectin in a number of different higher-order complexes. Once synthesized and assembled in the secretory pathway of the adipocyte, these complexes circulate as biochemically distinct and stable entities with little evidence of interchange between the different forms that include a high-molecular-weight (HMW) species, a hexamer (low-molecular-weight form), and a trimeric form of the complexes. Here, we validate a high-resolution gel filtration method that reproducibly separates the three complexes in recombinant adiponectin and adiponectin from human and murine samples. We demonstrate that the HMW form is prominently reduced in male vs. female subjects and in obese, insulin-resistant vs. lean, insulin-sensitive individuals. A direct comparison of human and mouse adiponectin demonstrates that the trimer is generally more abundant in human serum. Furthermore, when the production of adiponectin is reduced, either by obesity or in mice carrying only a single functional allele of the adiponectin locus, then the amount of the HMW form is selectively reduced in circulation. The complex distribution of adiponectin can be regulated in several ways. Both mouse and human HMW adiponectin are very stable under basic conditions but are exquisitely labile under acidic conditions below pH 7. Murine and human adiponectin HMW forms also display differential susceptibility to the presence of calcium in the buffer. A mutant form of adiponectin unable to bind calcium is less susceptible to changes in calcium concentrations. However, the lack of calcium binding results in a destabilization of the structure. Disulfide bond formation (at position C39) is also important for complex formation. A mutant form of adiponectin lacking C39 prominently forms HMW and trimer but not the low-molecular-weight form. Injection of adiponectin with a fluorescent label reveals that over time, the various complexes do not interconvert in vivo. The stability of adiponectin complexes highlights that the production and secretion of these forms from fat cells has a major influence on the circulating levels of each complex.

  15. C-SPADE: a web-tool for interactive analysis and visualization of drug screening experiments through compound-specific bioactivity dendrograms

    PubMed Central

    Alam, Zaid; Peddinti, Gopal

    2017-01-01

    Abstract The advent of polypharmacology paradigm in drug discovery calls for novel chemoinformatic tools for analyzing compounds’ multi-targeting activities. Such tools should provide an intuitive representation of the chemical space through capturing and visualizing underlying patterns of compound similarities linked to their polypharmacological effects. Most of the existing compound-centric chemoinformatics tools lack interactive options and user interfaces that are critical for the real-time needs of chemical biologists carrying out compound screening experiments. Toward that end, we introduce C-SPADE, an open-source exploratory web-tool for interactive analysis and visualization of drug profiling assays (biochemical, cell-based or cell-free) using compound-centric similarity clustering. C-SPADE allows the users to visually map the chemical diversity of a screening panel, explore investigational compounds in terms of their similarity to the screening panel, perform polypharmacological analyses and guide drug-target interaction predictions. C-SPADE requires only the raw drug profiling data as input, and it automatically retrieves the structural information and constructs the compound clusters in real-time, thereby reducing the time required for manual analysis in drug development or repurposing applications. The web-tool provides a customizable visual workspace that can either be downloaded as figure or Newick tree file or shared as a hyperlink with other users. C-SPADE is freely available at http://cspade.fimm.fi/. PMID:28472495

  16. In search of cellular control: signal transduction in context

    NASA Technical Reports Server (NTRS)

    Ingber, D.

    1998-01-01

    The field of molecular cell biology has experienced enormous advances over the last century by reducing the complexity of living cells into simpler molecular components and binding interactions that are amenable to rigorous biochemical analysis. However, as our tools become more powerful, there is a tendency to define mechanisms by what we can measure. The field is currently dominated by efforts to identify the key molecules and sequences that mediate the function of critical receptors, signal transducers, and molecular switches. Unfortunately, these conventional experimental approaches ignore the importance of supramolecular control mechanisms that play a critical role in cellular regulation. Thus, the significance of individual molecular constituents cannot be fully understood when studied in isolation because their function may vary depending on their context within the structural complexity of the living cell. These higher-order regulatory mechanisms are based on the cell's use of a form of solid-state biochemistry in which molecular components that mediate biochemical processing and signal transduction are immobilized on insoluble cytoskeletal scaffolds in the cytoplasm and nucleus. Key to the understanding of this form of cellular regulation is the realization that chemistry is structure and hence, recognition of the the importance of architecture and mechanics for signal integration and biochemical control. Recent work that has unified chemical and mechanical signaling pathways provides a glimpse of how this form of higher-order cellular control may function and where paths may lie in the future.

  17. Complex bud architecture and cell‐specific chemical patterns enable supercooling of Picea abies bud primordia

    PubMed Central

    Munkler, Caspar; Resnyak, Anna; Zimmermann, Sonja; Tuong, Tan D.; Gierlinger, Notburga; Müller, Thomas; Livingston, David P.; Neuner, Gilbert

    2017-01-01

    Abstract Bud primordia of Picea abies, despite a frozen shoot, stay ice free down to −50 °C by a mechanism termed supercooling whose biophysical and biochemical requirements are poorly understood. Bud architecture was assessed by 3D—reconstruction, supercooling and freezing patterns by infrared video thermography, freeze dehydration and extraorgan freezing by water potential measurements, and cell‐specific chemical patterns by Raman microscopy and mass spectrometry imaging. A bowl‐like ice barrier tissue insulates primordia from entrance by intrinsic ice. Water repellent and densely packed bud scales prevent extrinsic ice penetration. At −18 °C, break‐down of supercooling was triggered by intrinsic ice nucleators whereas the ice barrier remained active. Temperature‐dependent freeze dehydration (−0.1 MPa K−1) caused accumulation of extraorgan ice masses that by rupture of the shoot, pith tissue are accommodated in large voids. The barrier tissue has exceptionally pectin‐rich cell walls and intercellular spaces, and the cell lumina were lined or filled with proteins, especially near the primordium. Primordial cells close to the barrier accumulate di, tri and tetrasaccharides. Bud architecture efficiently prevents ice penetration, but ice nucleators become active inside the primordium below a temperature threshold. Biochemical patterns indicate a complex cellular interplay enabling supercooling and the necessity for cell‐specific biochemical analysis. PMID:28960368

  18. Endogenous Biologically Inspired Art of Complex Systems.

    PubMed

    Ji, Haru; Wakefield, Graham

    2016-01-01

    Since 2007, Graham Wakefield and Haru Ji have looked to nature for inspiration as they have created a series of "artificial natures," or interactive visualizations of biologically inspired complex systems that can evoke nature-like aesthetic experiences within mixed-reality art installations. This article describes how they have applied visualization, sonification, and interaction design in their work with artificial ecosystems and organisms using specific examples from their exhibited installations.

  19. Visual cortical areas of the mouse: comparison of parcellation and network structure with primates

    PubMed Central

    Laramée, Marie-Eve; Boire, Denis

    2015-01-01

    Brains have evolved to optimize sensory processing. In primates, complex cognitive tasks must be executed and evolution led to the development of large brains with many cortical areas. Rodents do not accomplish cognitive tasks of the same level of complexity as primates and remain with small brains both in relative and absolute terms. But is a small brain necessarily a simple brain? In this review, several aspects of the visual cortical networks have been compared between rodents and primates. The visual system has been used as a model to evaluate the level of complexity of the cortical circuits at the anatomical and functional levels. The evolutionary constraints are first presented in order to appreciate the rules for the development of the brain and its underlying circuits. The organization of sensory pathways, with their parallel and cross-modal circuits, is also examined. Other features of brain networks, often considered as imposing constraints on the development of underlying circuitry, are also discussed and their effect on the complexity of the mouse and primate brain are inspected. In this review, we discuss the common features of cortical circuits in mice and primates and see how these can be useful in understanding visual processing in these animals. PMID:25620914

  20. Visual cortical areas of the mouse: comparison of parcellation and network structure with primates.

    PubMed

    Laramée, Marie-Eve; Boire, Denis

    2014-01-01

    Brains have evolved to optimize sensory processing. In primates, complex cognitive tasks must be executed and evolution led to the development of large brains with many cortical areas. Rodents do not accomplish cognitive tasks of the same level of complexity as primates and remain with small brains both in relative and absolute terms. But is a small brain necessarily a simple brain? In this review, several aspects of the visual cortical networks have been compared between rodents and primates. The visual system has been used as a model to evaluate the level of complexity of the cortical circuits at the anatomical and functional levels. The evolutionary constraints are first presented in order to appreciate the rules for the development of the brain and its underlying circuits. The organization of sensory pathways, with their parallel and cross-modal circuits, is also examined. Other features of brain networks, often considered as imposing constraints on the development of underlying circuitry, are also discussed and their effect on the complexity of the mouse and primate brain are inspected. In this review, we discuss the common features of cortical circuits in mice and primates and see how these can be useful in understanding visual processing in these animals.

  1. Raised visual detection thresholds depend on the level of complexity of cognitive foveal loading.

    PubMed

    Plainis, S; Murray, I J; Chauhan, K

    2001-01-01

    The objective of the study was to measure the interactions between visual thresholds for a simple light (the secondary task) presented peripherally and a simultaneously performed cognitive task (the primary task) presented foveally The primary task was highly visible but varied according to its cognitive complexity. Interactions between the tasks were determined by measuring detection thresholds for the peripheral task and accuracy of performance of the foveal task. Effects were measured for 5, 10, 20, and 30 deg eccentricity of the peripherally presented light and for three levels of cognitive complexity. Mesopic conditions (0.5 lx) were used. As expected, the concurrent presentation of the foveal cognitive task reduced peripheral sensitivity. Moreover, performance of the foveal task was adversely affected when conducting the peripheral task. Performance on both tasks was reduced as the level of complexity of the cognitive task increased. There were qualitative differences in task interactions between the central 10 deg and at greater eccentricities. Within 10 deg there was a disproportionate effect of eccentricity, previously interpreted as the 'tunnel-vision' model of visual field narrowing. Interactions outside 10 deg were less affected by eccentricity. These results are discussed in terms of the known neurophysiological characteristics of the primary visual pathway.

  2. User evaluations of design complexity: the impact of visual perceptions for effective online health communication.

    PubMed

    Lazard, Allison; Mackert, Michael

    2014-10-01

    This paper highlights the influential role of design complexity for users' first impressions of health websites. An experimental design was utilized to investigate whether a website's level of design complexity impacts user evaluations. An online questionnaire measured the hypothesized impact of design complexity on predictors of message effectiveness. Findings reveal that increased design complexity was positively associated with higher levels of perceived design esthetics, attitude toward the website, perceived message comprehensibility, perceived ease of use, perceived usefulness, perceived message quality, perceived informativeness, and perceived visual informativeness. This research gives further evidence that design complexity should be considered an influential variable for health communicators to effectively reach their audiences, as it embodies the critical first step for message evaluation via electronic platforms. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Biochemical characterization of the THIN-B metallo-beta-lactamase of Janthinobacterium lividum.

    PubMed

    Docquier, Jean-Denis; Lopizzo, Teresa; Liberatori, Sabrina; Prenna, Manuela; Thaller, Maria Cristina; Frère, Jean-Marie; Rossolini, Gian Maria

    2004-12-01

    The THIN-B metallo-beta-lactamase, a subclass B3 enzyme produced by the environmental species Janthinobacterium lividum, was overproduced in Escherichia coli by means of a T7-based expression system. The enzyme was purified (>95%) by two ion-exchange chromatography steps and subjected to biochemical analysis. The native THIN-B enzyme is a monomeric protein of 31 kDa. It exhibits the highest catalytic efficiencies with carbapenem substrates and cephalosporins, except for cephaloridine, which acts as a poor inactivator. Individual rate constants for inactivation by chelators were measured, suggesting that inactivation occurred by a mechanism involving formation of a ternary complex.

  4. Biochemical Characterization of the THIN-B Metallo-β-Lactamase of Janthinobacterium lividum

    PubMed Central

    Docquier, Jean-Denis; Lopizzo, Teresa; Liberatori, Sabrina; Prenna, Manuela; Thaller, Maria Cristina; Frère, Jean-Marie; Rossolini, Gian Maria

    2004-01-01

    The THIN-B metallo-β-lactamase, a subclass B3 enzyme produced by the environmental species Janthinobacterium lividum, was overproduced in Escherichia coli by means of a T7-based expression system. The enzyme was purified (>95%) by two ion-exchange chromatography steps and subjected to biochemical analysis. The native THIN-B enzyme is a monomeric protein of 31 kDa. It exhibits the highest catalytic efficiencies with carbapenem substrates and cephalosporins, except for cephaloridine, which acts as a poor inactivator. Individual rate constants for inactivation by chelators were measured, suggesting that inactivation occurred by a mechanism involving formation of a ternary complex. PMID:15561856

  5. Activity-based metagenomic screening and biochemical characterization of bovine ruminal protozoan glycoside hydrolases.

    PubMed

    Findley, Seth D; Mormile, Melanie R; Sommer-Hurley, Andrea; Zhang, Xue-Cheng; Tipton, Peter; Arnett, Krista; Porter, James H; Kerley, Monty; Stacey, Gary

    2011-11-01

    The rumen, the foregut of herbivorous ruminant animals such as cattle, functions as a bioreactor to process complex plant material. Among the numerous and diverse microbes involved in ruminal digestion are the ruminal protozoans, which are single-celled, ciliated eukaryotic organisms. An activity-based screen was executed to identify genes encoding fibrolytic enzymes present in the metatranscriptome of a bovine ruminal protozoan-enriched cDNA expression library. Of the four novel genes identified, two were characterized in biochemical assays. Our results provide evidence for the effective use of functional metagenomics to retrieve novel enzymes from microbial populations that cannot be maintained in axenic cultures.

  6. Numerical simulations of a reduced model for blood coagulation

    NASA Astrophysics Data System (ADS)

    Pavlova, Jevgenija; Fasano, Antonio; Sequeira, Adélia

    2016-04-01

    In this work, the three-dimensional numerical resolution of a complex mathematical model for the blood coagulation process is presented. The model was illustrated in Fasano et al. (Clin Hemorheol Microcirc 51:1-14, 2012), Pavlova et al. (Theor Biol 380:367-379, 2015). It incorporates the action of the biochemical and cellular components of blood as well as the effects of the flow. The model is characterized by a reduction in the biochemical network and considers the impact of the blood slip at the vessel wall. Numerical results showing the capacity of the model to predict different perturbations in the hemostatic system are discussed.

  7. Biochemical and High Throughput Microscopic Assessment of Fat Mass in Caenorhabditis Elegans

    PubMed Central

    Pino, Elizabeth C.; Webster, Christopher M.; Carr, Christopher E.; Soukas, Alexander A.

    2013-01-01

    The nematode C. elegans has emerged as an important model for the study of conserved genetic pathways regulating fat metabolism as it relates to human obesity and its associated pathologies. Several previous methodologies developed for the visualization of C. elegans triglyceride-rich fat stores have proven to be erroneous, highlighting cellular compartments other than lipid droplets. Other methods require specialized equipment, are time-consuming, or yield inconsistent results. We introduce a rapid, reproducible, fixative-based Nile red staining method for the accurate and rapid detection of neutral lipid droplets in C. elegans. A short fixation step in 40% isopropanol makes animals completely permeable to Nile red, which is then used to stain animals. Spectral properties of this lipophilic dye allow it to strongly and selectively fluoresce in the yellow-green spectrum only when in a lipid-rich environment, but not in more polar environments. Thus, lipid droplets can be visualized on a fluorescent microscope equipped with simple GFP imaging capability after only a brief Nile red staining step in isopropanol. The speed, affordability, and reproducibility of this protocol make it ideally suited for high throughput screens. We also demonstrate a paired method for the biochemical determination of triglycerides and phospholipids using gas chromatography mass-spectrometry. This more rigorous protocol should be used as confirmation of results obtained from the Nile red microscopic lipid determination. We anticipate that these techniques will become new standards in the field of C. elegans metabolic research. PMID:23568026

  8. Common neural substrates for visual working memory and attention.

    PubMed

    Mayer, Jutta S; Bittner, Robert A; Nikolić, Danko; Bledowski, Christoph; Goebel, Rainer; Linden, David E J

    2007-06-01

    Humans are severely limited in their ability to memorize visual information over short periods of time. Selective attention has been implicated as a limiting factor. Here we used functional magnetic resonance imaging to test the hypothesis that this limitation is due to common neural resources shared by visual working memory (WM) and selective attention. We combined visual search and delayed discrimination of complex objects and independently modulated the demands on selective attention and WM encoding. Participants were presented with a search array and performed easy or difficult visual search in order to encode one or three complex objects into visual WM. Overlapping activation for attention-demanding visual search and WM encoding was observed in distributed posterior and frontal regions. In the right prefrontal cortex and bilateral insula blood oxygen-level-dependent activation additively increased with increased WM load and attentional demand. Conversely, several visual, parietal and premotor areas showed overlapping activation for the two task components and were severely reduced in their WM load response under the condition with high attentional demand. Regions in the left prefrontal cortex were selectively responsive to WM load. Areas selectively responsive to high attentional demand were found within the right prefrontal and bilateral occipital cortex. These results indicate that encoding into visual WM and visual selective attention require to a high degree access to common neural resources. We propose that competition for resources shared by visual attention and WM encoding can limit processing capabilities in distributed posterior brain regions.

  9. Toward the establishment of design guidelines for effective 3D perspective interfaces

    NASA Astrophysics Data System (ADS)

    Fitzhugh, Elisabeth; Dixon, Sharon; Aleva, Denise; Smith, Eric; Ghrayeb, Joseph; Douglas, Lisa

    2009-05-01

    The propagation of information operation technologies, with correspondingly vast amounts of complex network information to be conveyed, significantly impacts operator workload. Information management research is rife with efforts to develop schemes to aid operators to identify, review, organize, and retrieve the wealth of available data. Data may take on such distinct forms as intelligence libraries, logistics databases, operational environment models, or network topologies. Increased use of taxonomies and semantic technologies opens opportunities to employ network visualization as a display mechanism for diverse information aggregations. The broad applicability of network visualizations is still being tested, but in current usage, the complexity of densely populated abstract networks suggests the potential utility of 3D. Employment of 2.5D in network visualization, using classic perceptual cues, creates a 3D experience within a 2D medium. It is anticipated that use of 3D perspective (2.5D) will enhance user ability to visually inspect large, complex, multidimensional networks. Current research for 2.5D visualizations demonstrates that display attributes, including color, shape, size, lighting, atmospheric effects, and shadows, significantly impact operator experience. However, guidelines for utilization of attributes in display design are limited. This paper discusses pilot experimentation intended to identify potential problem areas arising from these cues and determine how best to optimize perceptual cue settings. Development of optimized design guidelines will ensure that future experiments, comparing network displays with other visualizations, are not confounded or impeded by suboptimal attribute characterization. Current experimentation is anticipated to support development of cost-effective, visually effective methods to implement 3D in military applications.

  10. Viewing the dynamics and control of visual attention through the lens of electrophysiology

    PubMed Central

    Woodman, Geoffrey F.

    2013-01-01

    How we find what we are looking for in complex visual scenes is a seemingly simple ability that has taken half a century to unravel. The first study to use the term visual search showed that as the number of objects in a complex scene increases, observers’ reaction times increase proportionally (Green and Anderson, 1956). This observation suggests that our ability to process the objects in the scenes is limited in capacity. However, if it is known that the target will have a certain feature attribute, for example, that it will be red, then only an increase in the number of red items increases reaction time. This observation suggests that we can control which visual inputs receive the benefit of our limited capacity to recognize the objects, such as those defined by the color red, as the items we seek. The nature of the mechanisms that underlie these basic phenomena in the literature on visual search have been more difficult to definitively determine. In this paper, I discuss how electrophysiological methods have provided us with the necessary tools to understand the nature of the mechanisms that give rise to the effects observed in the first visual search paper. I begin by describing how recordings of event-related potentials from humans and nonhuman primates have shown us how attention is deployed to possible target items in complex visual scenes. Then, I will discuss how event-related potential experiments have allowed us to directly measure the memory representations that are used to guide these deployments of attention to items with target-defining features. PMID:23357579

  11. Origins and identities of key manure odor components

    USDA-ARS?s Scientific Manuscript database

    Odor is just one of many environmental issues associated with animal manures. Odor arises from a number of different locations in animal production systems, but the chemistry and biochemical origin is similar across sites. A complex mixture of volatile organic compounds (VOC) and inorganic compoun...

  12. Ganglioside biochemistry.

    PubMed

    Kolter, Thomas

    2012-01-01

    Gangliosides are sialic acid-containing glycosphingolipids. They occur especially on the cellular surfaces of neuronal cells, where they form a complex pattern, but are also found in many other cell types. The paper provides a general overview on their structures, occurrence, and metabolism. Key functional, biochemical, and pathobiochemical aspects are summarized.

  13. Complex signal-based optical coherence tomography angiography enables in vivo visualization of choriocapillaris in human choroid

    NASA Astrophysics Data System (ADS)

    Chu, Zhongdi; Chen, Chieh-Li; Zhang, Qinqin; Pepple, Kathryn; Durbin, Mary; Gregori, Giovanni; Wang, Ruikang K.

    2017-12-01

    The choriocapillaris (CC) plays an essential role in maintaining the normal functions of the human eye. There is increasing interest in the community to develop an imaging technique for visualizing the CC, yet this remains underexplored due to technical limitations. We propose an approach for the visualization of the CC in humans via a complex signal-based optical microangiography (OMAG) algorithm, based on commercially available spectral domain optical coherence tomography (SD-OCT). We show that the complex signal-based OMAG was superior to both the phase and amplitude signal-based approaches in detailing the vascular lobules previously seen with histological analysis. With this improved ability to visualize the lobular vascular networks, it is possible to identify the feeding arterioles and draining venules around the lobules, which is important in understanding the role of the CC in the pathogenesis of ocular diseases. With built-in FastTrac™ and montage scanning capabilities, we also demonstrate wide-field SD-OCT angiograms of the CC with a field of view at 9×11 mm2.

  14. Working memory capacity and the scope and control of attention.

    PubMed

    Shipstead, Zach; Harrison, Tyler L; Engle, Randall W

    2015-08-01

    Complex span and visual arrays are two common measures of working memory capacity that are respectively treated as measures of attention control and storage capacity. A recent analysis of these tasks concluded that (1) complex span performance has a relatively stronger relationship to fluid intelligence and (2) this is due to the requirement that people engage control processes while performing this task. The present study examines the validity of these conclusions by examining two large data sets that include a more diverse set of visual arrays tasks and several measures of attention control. We conclude that complex span and visual arrays account for similar amounts of variance in fluid intelligence. The disparity relative to the earlier analysis is attributed to the present study involving a more complete measure of the latent ability underlying the performance of visual arrays. Moreover, we find that both types of working memory task have strong relationships to attention control. This indicates that the ability to engage attention in a controlled manner is a critical aspect of working memory capacity, regardless of the type of task that is used to measure this construct.

  15. Novel and simple route to fabricate fully biocompatible plasmonic mushroom arrays adhered on silk biopolymer

    NASA Astrophysics Data System (ADS)

    Park, Joonhan; Choi, Yunkyoung; Lee, Myungjae; Jeon, Heonsu; Kim, Sunghwan

    2014-12-01

    A fully biocompatible plasmonic quasi-3D nanostructure is demonstrated by a simple and reliable fabrication method using strong adhesion between gold and silk fibroin. The quasi-3D nature gives rise to complex photonic responses in reflectance that are prospectively useful in bio/chemical sensing applications. Laser interference lithography is utilized to fabricate large-area plasmonic nanostructures.A fully biocompatible plasmonic quasi-3D nanostructure is demonstrated by a simple and reliable fabrication method using strong adhesion between gold and silk fibroin. The quasi-3D nature gives rise to complex photonic responses in reflectance that are prospectively useful in bio/chemical sensing applications. Laser interference lithography is utilized to fabricate large-area plasmonic nanostructures. Electronic supplementary information (ESI) available: The incident angle dependence of reflectance spectra and the atomic force microscopy image of the Au nanoparticle array on a silk film after 1 hour of ultrasonication. See DOI: 10.1039/c4nr05172f

  16. Efficient Constant-Time Complexity Algorithm for Stochastic Simulation of Large Reaction Networks.

    PubMed

    Thanh, Vo Hong; Zunino, Roberto; Priami, Corrado

    2017-01-01

    Exact stochastic simulation is an indispensable tool for a quantitative study of biochemical reaction networks. The simulation realizes the time evolution of the model by randomly choosing a reaction to fire and update the system state according to a probability that is proportional to the reaction propensity. Two computationally expensive tasks in simulating large biochemical networks are the selection of next reaction firings and the update of reaction propensities due to state changes. We present in this work a new exact algorithm to optimize both of these simulation bottlenecks. Our algorithm employs the composition-rejection on the propensity bounds of reactions to select the next reaction firing. The selection of next reaction firings is independent of the number reactions while the update of propensities is skipped and performed only when necessary. It therefore provides a favorable scaling for the computational complexity in simulating large reaction networks. We benchmark our new algorithm with the state of the art algorithms available in literature to demonstrate its applicability and efficiency.

  17. Short-term regulation of the alpha-ketoglutarate dehydrogenase complex by energy-linked and some other effectors.

    PubMed

    Strumilo, S

    2005-07-01

    The question of regulation of alpha-ketoglutarate dehydrogenase complex (KGDHC) has been considered in the biochemical literature very rarely. Moreover, such information is not usually accurate, especially in biochemical textbooks. From the mini-review of research works published during the last 25 years, the following basic view is clear: a) animal KGDHC is very sensitive to ADP, P(i), and Ca2+; b) these positive effectors increase manifold the affinity of KGDHC to alpha-ketoglutarate; c) KGDHC is inhibited by ATP, NADH, and succinyl-CoA; d) the ATP effect is realized in several ways, probably mainly via opposition versus ADP activation; e) NADH, besides inhibiting dihydrolipoamide dehydrogenase component competitively versus NAD+, decreases the affinity of alpha-ketoglutarate dehydrogenase to substrate and inactivates it; f) thioredoxin protects KGDHC from self-inactivation during catalysis; g) bacterial and plant KGDHC is activated by AMP instead of ADP. These main effects form the basis of short-term regulation of KGDHC.

  18. A new nanostructured Silicon biosensor for diagnostics of bovine leucosis

    NASA Astrophysics Data System (ADS)

    Luchenko, A. I.; Melnichenko, M. M.; Starodub, N. F.; Shmyryeva, O. M.

    2010-08-01

    In this report we propose a new instrumental method for the biochemical diagnostics of the bovine leucosis through the registration of the formation of the specific immune complex (antigen-antibody) with the help of biosensor based on the nano-structured silicon. The principle of the measurements is based on the determination of the photosensitivity of the surface. In spite of the existed traditional methods of the biochemical diagnostics of the bovine leucosis the proposed approach may provide the express control of the milk quality as direct on the farm and during the process raw materials. The proposed variant of the biosensor based on the nano-structured silicon may be applied for the determination of the concentration of different substances which may form the specific complex in the result of the bioaffine reactions. A new immune technique based on the nanostructured silicon and intended for the quantitative determination of some toxic substances is offered. The sensitivity of such biosensor allows determining T-2 mycotoxin at the concentration of 10 ng/ml during several minutes.

  19. European spruce bark beetle (Ips typographus, L.) green attack affects foliar reflectance and biochemical properties

    NASA Astrophysics Data System (ADS)

    Abdullah, Haidi; Darvishzadeh, Roshanak; Skidmore, Andrew K.; Groen, Thomas A.; Heurich, Marco

    2018-02-01

    The European spruce bark beetle Ips typographus, L. (hereafter bark beetle), causes major economic loss to the forest industry in Europe, especially in Norway Spruce (Picea abies). To minimise economic loss and preclude a mass outbreak, early detection of bark beetle infestation (so-called ;green attack; stage - a period at which trees are yet to show visual signs of infestation stress) is, therefore, a crucial step in the management of Norway spruce stands. It is expected that a bark beetle infestation at the green attack stage affects a tree's physiological and chemical status. However, the concurrent effect on key foliar biochemical such as foliar nitrogen and chlorophyll as well as spectral responses are not well documented in the literature. Therefore, in this study, the early detection of bark beetle green attacks is investigated by examining foliar biochemical and spectral properties (400-2000 nm). We also assessed whether bark beetle infestation affects the estimation accuracy of foliar biochemicals. An extensive field survey was conducted in the Bavarian Forest National Park (BFNP), Germany, in the early summer of 2015 to collect leaf samples from 120 healthy and green attacked trees. The spectra of the leaf samples were measured using an ASD FieldSpec3 equipped with an integrating sphere. Significant differences (p < 0.05) between healthy and infested needle samples were found in the mean reflectance spectra, with the most pronounced differences being observed in the NIR and SWIR regions between 730 and 1370 nm. Furthermore, significant differences (p < 0.05) were found in the biochemical compositions (chlorophyll and nitrogen concentration) of healthy versus green attacked samples. Our results further demonstrate that the estimation accuracy of foliar chlorophyll and nitrogen concentrations, utilising partial least square regression model, was lower for the infested compared to the healthy trees. We show that early stage of infestation reduces not only foliar biochemical content but also their retrieval accuracy. Our results further indicate that remote sensing measurements can be successfully used for the early detection of the bark beetle infestation. We demonstrated that bark beetle infestation at the green attack stage effects leaf spectral response as well as leaf biochemical properties and their retrievals from hyperspectral measurements.

  20. Biochemical characterization and phylogenetic analysis based on 16S rRNA sequences for V-factor dependent members of Pasteurellaceae derived from laboratory rats.

    PubMed

    Hayashimoto, Nobuhito; Ueno, Masami; Tkakura, Akira; Itoh, Toshio

    2007-06-01

    Phylogenetic analysis based on 16S rRNA sequences with sequence data of some bacterial species of Pasteurellaceae related to rodents deposited in GenBank was performed along with biochemical characterization for the 20 strains of V-factor dependent members of Pasteurellaceae derived from laboratory rats to obtain basic information and to investigate the taxonomic positions. The results of biochemical tests for all strains were identical except for three tests, the ornithine decarboxylase test, and fermentation tests of D(+) mannose and D(+) xylose. The biochemical properties of 8 of 20 strains that showed negative results for the fermentation test of D(+) xylose agreed with those of Haemophilus parainfluenzae complex. By phylogenetic analysis, the strains were divided into two clusters that agreed with the results of the fermentation test of xylose (group I: negative reaction for xylose, group II: positive reaction for xylose). The clusters were independent of other bacterial species of Pasteurellaceae tested. The sequences of the strains in group I showed 99.7-99.8% similarity and the strains in group II showed 99.3-99.7% similarity. None of the strains in group I had a close relation with Haemophilus parainfluenzae by phylogenetic analysis, although they showed the same biochemical properties. In conclusion, the strains had characteristic biochemical properties and formed two independent groups within the "rodent cluster" of Pasteurellaceae that differed in the results of the fermentation test of xylose. Therefore, they seemed to be hitherto undescribed taxa in Pasteurellaceae.

  1. Fractal Analysis of Visual Search Activity for Mass Detection During Mammographic Screening

    DOE PAGES

    Alamudun, Folami T.; Yoon, Hong-Jun; Hudson, Kathy; ...

    2017-02-21

    Purpose: The objective of this study was to assess the complexity of human visual search activity during mammographic screening using fractal analysis and to investigate its relationship with case and reader characteristics. Methods: The study was performed for the task of mammographic screening with simultaneous viewing of four coordinated breast views as typically done in clinical practice. Eye-tracking data and diagnostic decisions collected for 100 mammographic cases (25 normal, 25 benign, 50 malignant) and 10 readers (three board certified radiologists and seven radiology residents), formed the corpus data for this study. The fractal dimension of the readers’ visual scanning patternsmore » was computed with the Minkowski–Bouligand box-counting method and used as a measure of gaze complexity. Individual factor and group-based interaction ANOVA analysis was performed to study the association between fractal dimension, case pathology, breast density, and reader experience level. The consistency of the observed trends depending on gaze data representation was also examined. Results: Case pathology, breast density, reader experience level, and individual reader differences are all independent predictors of the visual scanning pattern complexity when screening for breast cancer. No higher order effects were found to be significant. Conclusions: Fractal characterization of visual search behavior during mammographic screening is dependent on case properties and image reader characteristics.« less

  2. Nonuniform Changes in the Distribution of Visual Attention from Visual Complexity and Action: A Driving Simulation Study.

    PubMed

    Park, George D; Reed, Catherine L

    2015-02-01

    Researchers acknowledge the interplay between action and attention, but typically consider action as a response to successful attentional selection or the correlation of performance on separate action and attention tasks. We investigated how concurrent action with spatial monitoring affects the distribution of attention across the visual field. We embedded a functional field of view (FFOV) paradigm with concurrent central object recognition and peripheral target localization tasks in a simulated driving environment. Peripheral targets varied across 20-60 deg eccentricity at 11 radial spokes. Three conditions assessed the effects of visual complexity and concurrent action on the size and shape of the FFOV: (1) with no background, (2) with driving background, and (3) with driving background and vehicle steering. The addition of visual complexity slowed task performance and reduced the FFOV size but did not change the baseline shape. In contrast, the addition of steering produced not only shrinkage of the FFOV, but also changes in the FFOV shape. Nonuniform performance decrements occurred in proximal regions used for the central task and for steering, independent of interference from context elements. Multifocal attention models should consider the role of action and account for nonhomogeneities in the distribution of attention. © 2015 SAGE Publications.

  3. Resolving the neural dynamics of visual and auditory scene processing in the human brain: a methodological approach

    PubMed Central

    Teng, Santani

    2017-01-01

    In natural environments, visual and auditory stimulation elicit responses across a large set of brain regions in a fraction of a second, yielding representations of the multimodal scene and its properties. The rapid and complex neural dynamics underlying visual and auditory information processing pose major challenges to human cognitive neuroscience. Brain signals measured non-invasively are inherently noisy, the format of neural representations is unknown, and transformations between representations are complex and often nonlinear. Further, no single non-invasive brain measurement technique provides a spatio-temporally integrated view. In this opinion piece, we argue that progress can be made by a concerted effort based on three pillars of recent methodological development: (i) sensitive analysis techniques such as decoding and cross-classification, (ii) complex computational modelling using models such as deep neural networks, and (iii) integration across imaging methods (magnetoencephalography/electroencephalography, functional magnetic resonance imaging) and models, e.g. using representational similarity analysis. We showcase two recent efforts that have been undertaken in this spirit and provide novel results about visual and auditory scene analysis. Finally, we discuss the limits of this perspective and sketch a concrete roadmap for future research. This article is part of the themed issue ‘Auditory and visual scene analysis’. PMID:28044019

  4. Local spatio-temporal analysis in vision systems

    NASA Astrophysics Data System (ADS)

    Geisler, Wilson S.; Bovik, Alan; Cormack, Lawrence; Ghosh, Joydeep; Gildeen, David

    1994-07-01

    The aims of this project are the following: (1) develop a physiologically and psychophysically based model of low-level human visual processing (a key component of which are local frequency coding mechanisms); (2) develop image models and image-processing methods based upon local frequency coding; (3) develop algorithms for performing certain complex visual tasks based upon local frequency representations, (4) develop models of human performance in certain complex tasks based upon our understanding of low-level processing; and (5) develop a computational testbed for implementing, evaluating and visualizing the proposed models and algorithms, using a massively parallel computer. Progress has been substantial on all aims. The highlights include the following: (1) completion of a number of psychophysical and physiological experiments revealing new, systematic and exciting properties of the primate (human and monkey) visual system; (2) further development of image models that can accurately represent the local frequency structure in complex images; (3) near completion in the construction of the Texas Active Vision Testbed; (4) development and testing of several new computer vision algorithms dealing with shape-from-texture, shape-from-stereo, and depth-from-focus; (5) implementation and evaluation of several new models of human visual performance; and (6) evaluation, purchase and installation of a MasPar parallel computer.

  5. Resolving the neural dynamics of visual and auditory scene processing in the human brain: a methodological approach.

    PubMed

    Cichy, Radoslaw Martin; Teng, Santani

    2017-02-19

    In natural environments, visual and auditory stimulation elicit responses across a large set of brain regions in a fraction of a second, yielding representations of the multimodal scene and its properties. The rapid and complex neural dynamics underlying visual and auditory information processing pose major challenges to human cognitive neuroscience. Brain signals measured non-invasively are inherently noisy, the format of neural representations is unknown, and transformations between representations are complex and often nonlinear. Further, no single non-invasive brain measurement technique provides a spatio-temporally integrated view. In this opinion piece, we argue that progress can be made by a concerted effort based on three pillars of recent methodological development: (i) sensitive analysis techniques such as decoding and cross-classification, (ii) complex computational modelling using models such as deep neural networks, and (iii) integration across imaging methods (magnetoencephalography/electroencephalography, functional magnetic resonance imaging) and models, e.g. using representational similarity analysis. We showcase two recent efforts that have been undertaken in this spirit and provide novel results about visual and auditory scene analysis. Finally, we discuss the limits of this perspective and sketch a concrete roadmap for future research.This article is part of the themed issue 'Auditory and visual scene analysis'. © 2017 The Authors.

  6. Graphing Powers and Roots of Complex Numbers.

    ERIC Educational Resources Information Center

    Embse, Charles Vonder

    1993-01-01

    Using De Moivre's theorem and a parametric graphing utility, examines powers and roots of complex numbers and allows students to establish connections between the visual and numerical representations of complex numbers. Provides a program to numerically verify the roots of complex numbers. (MDH)

  7. Proteome-wide Subcellular Topologies of E. coli Polypeptides Database (STEPdb)*

    PubMed Central

    Orfanoudaki, Georgia; Economou, Anastassios

    2014-01-01

    Cell compartmentalization serves both the isolation and the specialization of cell functions. After synthesis in the cytoplasm, over a third of all proteins are targeted to other subcellular compartments. Knowing how proteins are distributed within the cell and how they interact is a prerequisite for understanding it as a whole. Surface and secreted proteins are important pathogenicity determinants. Here we present the STEP database (STEPdb) that contains a comprehensive characterization of subcellular localization and topology of the complete proteome of Escherichia coli. Two widely used E. coli proteomes (K-12 and BL21) are presented organized into thirteen subcellular classes. STEPdb exploits the wealth of genetic, proteomic, biochemical, and functional information on protein localization, secretion, and targeting in E. coli, one of the best understood model organisms. Subcellular annotations were derived from a combination of bioinformatics prediction, proteomic, biochemical, functional, topological data and extensive literature re-examination that were refined through manual curation. Strong experimental support for the location of 1553 out of 4303 proteins was based on 426 articles and some experimental indications for another 526. Annotations were provided for another 320 proteins based on firm bioinformatic predictions. STEPdb is the first database that contains an extensive set of peripheral IM proteins (PIM proteins) and includes their graphical visualization into complexes, cellular functions, and interactions. It also summarizes all currently known protein export machineries of E. coli K-12 and pairs them, where available, with the secretory proteins that use them. It catalogs the Sec- and TAT-utilizing secretomes and summarizes their topological features such as signal peptides and transmembrane regions, transmembrane topologies and orientations. It also catalogs physicochemical and structural features that influence topology such as abundance, solubility, disorder, heat resistance, and structural domain families. Finally, STEPdb incorporates prediction tools for topology (TMHMM, SignalP, and Phobius) and disorder (IUPred) and implements the BLAST2STEP that performs protein homology searches against the STEPdb. PMID:25210196

  8. Scalable Parameter Estimation for Genome-Scale Biochemical Reaction Networks

    PubMed Central

    Kaltenbacher, Barbara; Hasenauer, Jan

    2017-01-01

    Mechanistic mathematical modeling of biochemical reaction networks using ordinary differential equation (ODE) models has improved our understanding of small- and medium-scale biological processes. While the same should in principle hold for large- and genome-scale processes, the computational methods for the analysis of ODE models which describe hundreds or thousands of biochemical species and reactions are missing so far. While individual simulations are feasible, the inference of the model parameters from experimental data is computationally too intensive. In this manuscript, we evaluate adjoint sensitivity analysis for parameter estimation in large scale biochemical reaction networks. We present the approach for time-discrete measurement and compare it to state-of-the-art methods used in systems and computational biology. Our comparison reveals a significantly improved computational efficiency and a superior scalability of adjoint sensitivity analysis. The computational complexity is effectively independent of the number of parameters, enabling the analysis of large- and genome-scale models. Our study of a comprehensive kinetic model of ErbB signaling shows that parameter estimation using adjoint sensitivity analysis requires a fraction of the computation time of established methods. The proposed method will facilitate mechanistic modeling of genome-scale cellular processes, as required in the age of omics. PMID:28114351

  9. Organization of biogeochemical nitrogen pathways with switch-like adjustment in fluctuating soil redox conditions

    PubMed Central

    Lamba, Sanjay; Bera, Soumen; Rashid, Mubasher; Medvinsky, Alexander B.; Acquisti, Claudia; Li, Bai-Lian

    2017-01-01

    Nitrogen is cycled throughout ecosystems by a suite of biogeochemical processes. The high complexity of the nitrogen cycle resides in an intricate interplay between reversible biochemical pathways alternatively and specifically activated in response to diverse environmental cues. Despite aggressive research, how the fundamental nitrogen biochemical processes are assembled and maintained in fluctuating soil redox conditions remains elusive. Here, we address this question using a kinetic modelling approach coupled with dynamical systems theory and microbial genomics. We show that alternative biochemical pathways play a key role in keeping nitrogen conversion and conservation properties invariant in fluctuating environments. Our results indicate that the biochemical network holds inherent adaptive capacity to stabilize ammonium and nitrate availability, and that the bistability in the formation of ammonium is linked to the transient upregulation of the amo-hao mediated nitrification pathway. The bistability is maintained by a pair of complementary subsystems acting as either source or sink type systems in response to soil redox fluctuations. It is further shown how elevated anthropogenic pressure has the potential to break down the stability of the system, altering substantially ammonium and nitrate availability in the soil, with dramatic effects on biodiversity. PMID:28280580

  10. Efficient visual object and word recognition relies on high spatial frequency coding in the left posterior fusiform gyrus: evidence from a case-series of patients with ventral occipito-temporal cortex damage.

    PubMed

    Roberts, Daniel J; Woollams, Anna M; Kim, Esther; Beeson, Pelagie M; Rapcsak, Steven Z; Lambon Ralph, Matthew A

    2013-11-01

    Recent visual neuroscience investigations suggest that ventral occipito-temporal cortex is retinotopically organized, with high acuity foveal input projecting primarily to the posterior fusiform gyrus (pFG), making this region crucial for coding high spatial frequency information. Because high spatial frequencies are critical for fine-grained visual discrimination, we hypothesized that damage to the left pFG should have an adverse effect not only on efficient reading, as observed in pure alexia, but also on the processing of complex non-orthographic visual stimuli. Consistent with this hypothesis, we obtained evidence that a large case series (n = 20) of patients with lesions centered on left pFG: 1) Exhibited reduced sensitivity to high spatial frequencies; 2) demonstrated prolonged response latencies both in reading (pure alexia) and object naming; and 3) were especially sensitive to visual complexity and similarity when discriminating between novel visual patterns. These results suggest that the patients' dual reading and non-orthographic recognition impairments have a common underlying mechanism and reflect the loss of high spatial frequency visual information normally coded in the left pFG.

  11. Vibrotactile Feedback for Brain-Computer Interface Operation

    PubMed Central

    Cincotti, Febo; Kauhanen, Laura; Aloise, Fabio; Palomäki, Tapio; Caporusso, Nicholas; Jylänki, Pasi; Mattia, Donatella; Babiloni, Fabio; Vanacker, Gerolf; Nuttin, Marnix; Marciani, Maria Grazia; Millán, José del R.

    2007-01-01

    To be correctly mastered, brain-computer interfaces (BCIs) need an uninterrupted flow of feedback to the user. This feedback is usually delivered through the visual channel. Our aim was to explore the benefits of vibrotactile feedback during users' training and control of EEG-based BCI applications. A protocol for delivering vibrotactile feedback, including specific hardware and software arrangements, was specified. In three studies with 33 subjects (including 3 with spinal cord injury), we compared vibrotactile and visual feedback, addressing: (I) the feasibility of subjects' training to master their EEG rhythms using tactile feedback; (II) the compatibility of this form of feedback in presence of a visual distracter; (III) the performance in presence of a complex visual task on the same (visual) or different (tactile) sensory channel. The stimulation protocol we developed supports a general usage of the tactors; preliminary experimentations. All studies indicated that the vibrotactile channel can function as a valuable feedback modality with reliability comparable to the classical visual feedback. Advantages of using a vibrotactile feedback emerged when the visual channel was highly loaded by a complex task. In all experiments, vibrotactile feedback felt, after some training, more natural for both controls and SCI users. PMID:18354734

  12. An enhanced data visualization method for diesel engine malfunction classification using multi-sensor signals.

    PubMed

    Li, Yiqing; Wang, Yu; Zi, Yanyang; Zhang, Mingquan

    2015-10-21

    The various multi-sensor signal features from a diesel engine constitute a complex high-dimensional dataset. The non-linear dimensionality reduction method, t-distributed stochastic neighbor embedding (t-SNE), provides an effective way to implement data visualization for complex high-dimensional data. However, irrelevant features can deteriorate the performance of data visualization, and thus, should be eliminated a priori. This paper proposes a feature subset score based t-SNE (FSS-t-SNE) data visualization method to deal with the high-dimensional data that are collected from multi-sensor signals. In this method, the optimal feature subset is constructed by a feature subset score criterion. Then the high-dimensional data are visualized in 2-dimension space. According to the UCI dataset test, FSS-t-SNE can effectively improve the classification accuracy. An experiment was performed with a large power marine diesel engine to validate the proposed method for diesel engine malfunction classification. Multi-sensor signals were collected by a cylinder vibration sensor and a cylinder pressure sensor. Compared with other conventional data visualization methods, the proposed method shows good visualization performance and high classification accuracy in multi-malfunction classification of a diesel engine.

  13. Exploratory Climate Data Visualization and Analysis Using DV3D and UVCDAT

    NASA Technical Reports Server (NTRS)

    Maxwell, Thomas

    2012-01-01

    Earth system scientists are being inundated by an explosion of data generated by ever-increasing resolution in both global models and remote sensors. Advanced tools for accessing, analyzing, and visualizing very large and complex climate data are required to maintain rapid progress in Earth system research. To meet this need, NASA, in collaboration with the Ultra-scale Visualization Climate Data Analysis Tools (UVCOAT) consortium, is developing exploratory climate data analysis and visualization tools which provide data analysis capabilities for the Earth System Grid (ESG). This paper describes DV3D, a UV-COAT package that enables exploratory analysis of climate simulation and observation datasets. OV3D provides user-friendly interfaces for visualization and analysis of climate data at a level appropriate for scientists. It features workflow inte rfaces, interactive 40 data exploration, hyperwall and stereo visualization, automated provenance generation, and parallel task execution. DV30's integration with CDAT's climate data management system (COMS) and other climate data analysis tools provides a wide range of high performance climate data analysis operations. DV3D expands the scientists' toolbox by incorporating a suite of rich new exploratory visualization and analysis methods for addressing the complexity of climate datasets.

  14. An Enhanced Data Visualization Method for Diesel Engine Malfunction Classification Using Multi-Sensor Signals

    PubMed Central

    Li, Yiqing; Wang, Yu; Zi, Yanyang; Zhang, Mingquan

    2015-01-01

    The various multi-sensor signal features from a diesel engine constitute a complex high-dimensional dataset. The non-linear dimensionality reduction method, t-distributed stochastic neighbor embedding (t-SNE), provides an effective way to implement data visualization for complex high-dimensional data. However, irrelevant features can deteriorate the performance of data visualization, and thus, should be eliminated a priori. This paper proposes a feature subset score based t-SNE (FSS-t-SNE) data visualization method to deal with the high-dimensional data that are collected from multi-sensor signals. In this method, the optimal feature subset is constructed by a feature subset score criterion. Then the high-dimensional data are visualized in 2-dimension space. According to the UCI dataset test, FSS-t-SNE can effectively improve the classification accuracy. An experiment was performed with a large power marine diesel engine to validate the proposed method for diesel engine malfunction classification. Multi-sensor signals were collected by a cylinder vibration sensor and a cylinder pressure sensor. Compared with other conventional data visualization methods, the proposed method shows good visualization performance and high classification accuracy in multi-malfunction classification of a diesel engine. PMID:26506347

  15. Probing mammalian spermine oxidase enzyme-substrate complex through molecular modeling, site-directed mutagenesis and biochemical characterization.

    PubMed

    Tavladoraki, Paraskevi; Cervelli, Manuela; Antonangeli, Fabrizio; Minervini, Giovanni; Stano, Pasquale; Federico, Rodolfo; Mariottini, Paolo; Polticelli, Fabio

    2011-04-01

    Spermine oxidase (SMO) and acetylpolyamine oxidase (APAO) are FAD-dependent enzymes that are involved in the highly regulated pathways of polyamine biosynthesis and degradation. Polyamine content is strictly related to cell growth, and dysfunctions in polyamine metabolism have been linked with cancer. Specific inhibitors of SMO and APAO would allow analyzing the precise role of these enzymes in polyamine metabolism and related pathologies. However, none of the available polyamine oxidase inhibitors displays the desired characteristics of selective affinity and specificity. In addition, repeated efforts to obtain structural details at the atomic level on these two enzymes have all failed. In the present study, in an effort to better understand structure-function relationships, SMO enzyme-substrate complex has been probed through a combination of molecular modeling, site-directed mutagenesis and biochemical studies. Results obtained indicate that SMO binds spermine in a similar conformation as that observed in the yeast polyamine oxidase FMS1-spermine complex and demonstrate a major role for residues His82 and Lys367 in substrate binding and catalysis. In addition, the SMO enzyme-substrate complex highlights the presence of an active site pocket with highly polar characteristics, which may explain the different substrate specificity of SMO with respect to APAO and provide the basis for the design of specific inhibitors for SMO and APAO.

  16. Cell type-specific recruitment of Drosophila Lin-7 to distinct MAGUK-based protein complexes defines novel roles for Sdt and Dlg-S97.

    PubMed

    Bachmann, André; Timmer, Marco; Sierralta, Jimena; Pietrini, Grazia; Gundelfinger, Eckart D; Knust, Elisabeth; Thomas, Ulrich

    2004-04-15

    Stardust (Sdt) and Discs-Large (Dlg) are membrane-associated guanylate kinases (MAGUKs) involved in the organization of supramolecular protein complexes at distinct epithelial membrane compartments in Drosophila. Loss of either Sdt or Dlg affects epithelial development with severe effects on apico-basal polarity. Moreover, Dlg is required for the structural and functional integrity of synaptic junctions. Recent biochemical and cell culture studies have revealed that various mammalian MAGUKs can interact with mLin-7/Veli/MALS, a small PDZ-domain protein. To substantiate these findings for their in vivo significance with regard to Sdt- and Dlg-based protein complexes, we analyzed the subcellular distribution of Drosophila Lin-7 (DLin-7) and performed genetic and biochemical assays to characterize its interaction with either of the two MAGUKs. In epithelia, Sdt mediates the recruitment of DLin-7 to the subapical region, while at larval neuromuscular junctions, a particular isoform of Dlg, Dlg-S97, is required for postsynaptic localization of DLin-7. Ectopic expression of Dlg-S97 in epithelia, however, was not sufficient to induce a redistribution of DLin-7. These results imply that the recruitment of DLin-7 to MAGUK-based protein complexes is defined by cell-type specific mechanisms and that DLin-7 acts downstream of Sdt in epithelia and downstream of Dlg at synapses.

  17. Reinforcing Visual Grouping Cues to Communicate Complex Informational Structure.

    PubMed

    Bae, Juhee; Watson, Benjamin

    2014-12-01

    In his book Multimedia Learning [7], Richard Mayer asserts that viewers learn best from imagery that provides them with cues to help them organize new information into the correct knowledge structures. Designers have long been exploiting the Gestalt laws of visual grouping to deliver viewers those cues using visual hierarchy, often communicating structures much more complex than the simple organizations studied in psychological research. Unfortunately, designers are largely practical in their work, and have not paused to build a complex theory of structural communication. If we are to build a tool to help novices create effective and well structured visuals, we need a better understanding of how to create them. Our work takes a first step toward addressing this lack, studying how five of the many grouping cues (proximity, color similarity, common region, connectivity, and alignment) can be effectively combined to communicate structured text and imagery from real world examples. To measure the effectiveness of this structural communication, we applied a digital version of card sorting, a method widely used in anthropology and cognitive science to extract cognitive structures. We then used tree edit distance to measure the difference between perceived and communicated structures. Our most significant findings are: 1) with careful design, complex structure can be communicated clearly; 2) communicating complex structure is best done with multiple reinforcing grouping cues; 3) common region (use of containers such as boxes) is particularly effective at communicating structure; and 4) alignment is a weak structural communicator.

  18. Changes in visual quality, physiological and biochemical parameters assessed during the postharvest storage at chilling or non-chilling temperatures of three sweet basil (Ocimum basilicum L.) cultivars.

    PubMed

    Fratianni, Florinda; Cefola, Maria; Pace, Bernardo; Cozzolino, Rosaria; De Giulio, Beatrice; Cozzolino, Autilia; d'Acierno, Antonio; Coppola, Raffaele; Logrieco, Antonio Francesco; Nazzaro, Filomena

    2017-08-15

    Leaves of three different sweet basil (Ocimum basilicum L.) cultivars (Italico a foglia larga, Cammeo, and Italiano classico) packed in macro-perforated polyethylene bags were stored at chilling (4°C) or non-chilling temperature (12°C) for 9days. During storage, visual quality, physiological (respiration rate, ethylene production, ammonium content) and chemical (antioxidant activity, total polyphenols and polyphenol profile) parameters were measured. Detached leaves stored at chilling temperature showed visual symptoms related to chilling injury, while ethylene production and ammonium content resulted associated to cultivar sensibility to damage at low temperature. Storage at 4°C caused a depletion in polyphenols content and antioxidant capability, which was preserved at 12°C. Regarding the polyphenols profile, stressful storage conditions did not enhance the phenolic metabolism. However, leaves stored at 12°C did not loss a significant amount of metabolites respect to fresh leaves, suggesting the possibility to extend the storability after the expiration date, for a possible recovery of bioactive compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Types of Creativity and Visualization in Teams of Different Educational Specialization

    ERIC Educational Resources Information Center

    Blazhenkova, Olesya; Kozhevnikov, Maria

    2016-01-01

    This research is the first to examine different types of creativity dimensions in relation to different types of visualization on a team level, by comparing adolescences' teams of different specialization (visual artist, scientists, and humanities) during a complex creative task in an ecologically valid educational setting First, the difference…

  20. SOCR "Motion Charts": An Efficient, Open-Source, Interactive and Dynamic Applet for Visualizing Longitudinal Multivariate Data

    ERIC Educational Resources Information Center

    Al-Aziz, Jameel; Christou, Nicolas; Dinov, Ivo D.

    2010-01-01

    The amount, complexity and provenance of data have dramatically increased in the past five years. Visualization of observed and simulated data is a critical component of any social, environmental, biomedical or scientific quest. Dynamic, exploratory and interactive visualization of multivariate data, without preprocessing by dimensionality…

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