WorldWideScience

Sample records for biological function analyses

  1. Analyses in zebrafish embryos reveal that nanotoxicity profiles are dependent on surface-functionalization controlled penetrance of biological membranes.

    Science.gov (United States)

    Paatero, Ilkka; Casals, Eudald; Niemi, Rasmus; Özliseli, Ezgi; Rosenholm, Jessica M; Sahlgren, Cecilia

    2017-08-21

    Mesoporous silica nanoparticles (MSNs) are extensively explored as drug delivery systems, but in depth understanding of design-toxicity relationships is still scarce. We used zebrafish (Danio rerio) embryos to study toxicity profiles of differently surface functionalized MSNs. Embryos with the chorion membrane intact, or dechoroniated embryos, were incubated or microinjected with amino (NH 2 -MSNs), polyethyleneimine (PEI-MSNs), succinic acid (SUCC-MSNs) or polyethyleneglycol (PEG-MSNs) functionalized MSNs. Toxicity was assessed by viability and cardiovascular function. NH 2 -MSNs, SUCC-MSNs and PEG-MSNs were well tolerated, 50 µg/ml PEI-MSNs induced 100% lethality 48 hours post fertilization (hpf). Dechoroniated embryos were more sensitive and 10 µg/ml PEI-MSNs reduced viability to 5% at 96hpf. Sensitivity to PEG- and SUCC-, but not NH 2 -MSNs, was also enhanced. Typically cardiovascular toxicity was evident prior to lethality. Confocal microscopy revealed that PEI-MSNs penetrated into the embryos whereas PEG-, NH2- and SUCC-MSNs remained aggregated on the skin surface. Direct exposure of inner organs by microinjecting NH 2 -MSNs and PEI-MSNs demonstrated that the particles displayed similar toxicity indicating that functionalization affects the toxicity profile by influencing penetrance through biological barriers. The data emphasize the need for careful analyses of toxicity mechanisms in relevant models and constitute an important knowledge step towards the development of safer and sustainable nanotherapies.

  2. Functions in Biological Kind Classification

    Science.gov (United States)

    Lombrozo, Tania; Rehder, Bob

    2012-01-01

    Biological traits that serve functions, such as a zebra's coloration (for camouflage) or a kangaroo's tail (for balance), seem to have a special role in conceptual representations for biological kinds. In five experiments, we investigate whether and why functional features are privileged in biological kind classification. Experiment 1…

  3. Methods for Functional Connectivity Analyses

    Science.gov (United States)

    2012-12-13

    motor , or hand motor function (green, red, or blue shading, respectively). Thus, this work produced the first comprehensive analysis of ECoG...Computer Engineering, University of Texas at El Paso , TX, USA 3Department of Neurology, Albany Medical College, Albany, NY, USA 4Department of Computer...Department of Health, Albany, NY, USA bDepartment of Electrical and Computer Engineering, University of Texas at El Paso , TX, USA cDepartment of Neurology

  4. The relativity of biological function.

    Science.gov (United States)

    Laubichler, Manfred D; Stadler, Peter F; Prohaska, Sonja J; Nowick, Katja

    2015-12-01

    Function is a central concept in biological theories and explanations. Yet discussions about function are often based on a narrow understanding of biological systems and processes, such as idealized molecular systems or simple evolutionary, i.e., selective, dynamics. Conflicting conceptions of function continue to be used in the scientific literature to support certain claims, for instance about the fraction of "functional DNA" in the human genome. Here we argue that all biologically meaningful interpretations of function are necessarily context dependent. This implies that they derive their meaning as well as their range of applicability only within a specific theoretical and measurement context. We use this framework to shed light on the current debate about functional DNA and argue that without considering explicitly the theoretical and measurement contexts all attempts to integrate biological theories are prone to fail.

  5. Functional enrichment analyses and construction of functional similarity networks with high confidence function prediction by PFP

    Directory of Open Access Journals (Sweden)

    Kihara Daisuke

    2010-05-01

    Full Text Available Abstract Background A new paradigm of biological investigation takes advantage of technologies that produce large high throughput datasets, including genome sequences, interactions of proteins, and gene expression. The ability of biologists to analyze and interpret such data relies on functional annotation of the included proteins, but even in highly characterized organisms many proteins can lack the functional evidence necessary to infer their biological relevance. Results Here we have applied high confidence function predictions from our automated prediction system, PFP, to three genome sequences, Escherichia coli, Saccharomyces cerevisiae, and Plasmodium falciparum (malaria. The number of annotated genes is increased by PFP to over 90% for all of the genomes. Using the large coverage of the function annotation, we introduced the functional similarity networks which represent the functional space of the proteomes. Four different functional similarity networks are constructed for each proteome, one each by considering similarity in a single Gene Ontology (GO category, i.e. Biological Process, Cellular Component, and Molecular Function, and another one by considering overall similarity with the funSim score. The functional similarity networks are shown to have higher modularity than the protein-protein interaction network. Moreover, the funSim score network is distinct from the single GO-score networks by showing a higher clustering degree exponent value and thus has a higher tendency to be hierarchical. In addition, examining function assignments to the protein-protein interaction network and local regions of genomes has identified numerous cases where subnetworks or local regions have functionally coherent proteins. These results will help interpreting interactions of proteins and gene orders in a genome. Several examples of both analyses are highlighted. Conclusion The analyses demonstrate that applying high confidence predictions from PFP

  6. A Calculus for Modelling, Simulating and Analysing Compartmentalized Biological Systems

    DEFF Research Database (Denmark)

    Mardare, Radu Iulian; Ihekwaba, Adoha

    2007-01-01

    A. Ihekwaba, R. Mardare. A Calculus for Modelling, Simulating and Analysing Compartmentalized Biological Systems. Case study: NFkB system. In Proc. of International Conference of Computational Methods in Sciences and Engineering (ICCMSE), American Institute of Physics, AIP Proceedings, N 2...

  7. The biological function of consciousness

    Directory of Open Access Journals (Sweden)

    Brian eEarl

    2014-08-01

    Full Text Available This research is an investigation of whether consciousness—one’s ongoing experience—influences one’s behavior and, if so, how. Analysis of the components, structure, properties, and temporal sequences of consciousness has established that, (1 contrary to one’s intuitive understanding, consciousness does not have an active, executive role in determining behavior; (2 consciousness does have a biological function; and (3 consciousness is solely information in various forms. Consciousness is associated with a flexible response mechanism (FRM for decision-making, planning, and generally responding in nonautomatic ways. The FRM generates responses by manipulating information and, to function effectively, its data input must be restricted to task-relevant information. The properties of consciousness correspond to the various input requirements of the FRM; and when important information is missing from consciousness, functions of the FRM are adversely affected; both of which indicate that consciousness is the input data to the FRM. Qualitative and quantitative information (shape, size, location, etc., is incorporated into the input data by a qualia array of colors, sounds, and so on, which makes the input conscious. This view of the biological function of consciousness provides an explanation why we have experiences; why we have emotional and other feelings, and why their loss is associated with poor decision-making; why blindsight patients do not spontaneously initiate responses to events in their blind field; why counter-habitual actions are only possible when the intended action is in mind; and the reason for inattentional blindness.

  8. Pegasys: software for executing and integrating analyses of biological sequences

    Directory of Open Access Journals (Sweden)

    Lett Drew

    2004-04-01

    Full Text Available Abstract Background We present Pegasys – a flexible, modular and customizable software system that facilitates the execution and data integration from heterogeneous biological sequence analysis tools. Results The Pegasys system includes numerous tools for pair-wise and multiple sequence alignment, ab initio gene prediction, RNA gene detection, masking repetitive sequences in genomic DNA as well as filters for database formatting and processing raw output from various analysis tools. We introduce a novel data structure for creating workflows of sequence analyses and a unified data model to store its results. The software allows users to dynamically create analysis workflows at run-time by manipulating a graphical user interface. All non-serial dependent analyses are executed in parallel on a compute cluster for efficiency of data generation. The uniform data model and backend relational database management system of Pegasys allow for results of heterogeneous programs included in the workflow to be integrated and exported into General Feature Format for further analyses in GFF-dependent tools, or GAME XML for import into the Apollo genome editor. The modularity of the design allows for new tools to be added to the system with little programmer overhead. The database application programming interface allows programmatic access to the data stored in the backend through SQL queries. Conclusions The Pegasys system enables biologists and bioinformaticians to create and manage sequence analysis workflows. The software is released under the Open Source GNU General Public License. All source code and documentation is available for download at http://bioinformatics.ubc.ca/pegasys/.

  9. Structure and function in biology

    International Nuclear Information System (INIS)

    Hirs, C.H.W.

    1976-01-01

    A summary is given of the history of the developments of structural chemistry in biology beginning with the work of the bacteriologist Ehrlich leading to a comprehensive examination of the influence of size and configuration on the interaction between specific antibodies and side-chain determinants. Recent developments include the recognition of a higher order of specificity in the interaction of proteins with one another

  10. Synthetic biology analysed tools for discussion and evaluation

    CERN Document Server

    2016-01-01

    Synthetic biology is a dynamic, young, ambitious, attractive, and heterogeneous scientific discipline. It is constantly developing and changing, which makes societal evaluation of this emerging new science a challenging task, prone to misunderstandings. Synthetic biology is difficult to capture, and confusion arises not only regarding which part of synthetic biology the discussion is about, but also with respect to the underlying concepts in use. This book offers a useful toolbox to approach this complex and fragmented field. It provides a biological access to the discussion using a 'layer' model that describes the connectivity of synthetic or semisynthetic organisms and cells to the realm of natural organisms derived by evolution. Instead of directly reviewing the field as a whole, firstly our book addresses the characteristic features of synthetic biology that are relevant to the societal discussion. Some of these features apply only to parts of synthetic biology, whereas others are relevant to synthetic bi...

  11. A Unifying Theory of Biological Function.

    Science.gov (United States)

    van Hateren, J H

    2017-01-01

    A new theory that naturalizes biological function is explained and compared with earlier etiological and causal role theories. Etiological (or selected effects) theories explain functions from how they are caused over their evolutionary history. Causal role theories analyze how functional mechanisms serve the current capacities of their containing system. The new proposal unifies the key notions of both kinds of theories, but goes beyond them by explaining how functions in an organism can exist as factors with autonomous causal efficacy. The goal-directedness and normativity of functions exist in this strict sense as well. The theory depends on an internal physiological or neural process that mimics an organism's fitness, and modulates the organism's variability accordingly. The structure of the internal process can be subdivided into subprocesses that monitor specific functions in an organism. The theory matches well with each intuition on a previously published list of intuited ideas about biological functions, including intuitions that have posed difficulties for other theories.

  12. Functional model of biological neural networks.

    Science.gov (United States)

    Lo, James Ting-Ho

    2010-12-01

    A functional model of biological neural networks, called temporal hierarchical probabilistic associative memory (THPAM), is proposed in this paper. THPAM comprises functional models of dendritic trees for encoding inputs to neurons, a first type of neuron for generating spike trains, a second type of neuron for generating graded signals to modulate neurons of the first type, supervised and unsupervised Hebbian learning mechanisms for easy learning and retrieving, an arrangement of dendritic trees for maximizing generalization, hardwiring for rotation-translation-scaling invariance, and feedback connections with different delay durations for neurons to make full use of present and past informations generated by neurons in the same and higher layers. These functional models and their processing operations have many functions of biological neural networks that have not been achieved by other models in the open literature and provide logically coherent answers to many long-standing neuroscientific questions. However, biological justifications of these functional models and their processing operations are required for THPAM to qualify as a macroscopic model (or low-order approximate) of biological neural networks.

  13. A functional overview of conservation biological control

    DEFF Research Database (Denmark)

    Begg, Graham S; Cook, Samantha M; Dye, Richard

    2017-01-01

    Conservation biological control (CBC) is a sustainable approach to pest management that can contribute to a reduction in pesticide use as part of an Integrated Pest Management (IPM) strategy. CBC is based on the premise that countering habitat loss and environmental disturbance associated...... CBC prescriptions have proved elusive. To tackle this, we consolidate existing knowledge of CBC using a simple conceptual model that organises the functional elements of CBC into a common, unifying framework. We identify and integrate the key biological processes affecting natural enemies...... and their biological control function across local and regional scales, and consider the interactions, interdependencies and constraints that determine the outcome of CBC strategies. Conservation measures are often effective in supporting natural enemy populations but their success cannot be guaranteed; the greatest...

  14. Network Analyses in Systems Biology: New Strategies for Dealing with Biological Complexity

    DEFF Research Database (Denmark)

    Green, Sara; Serban, Maria; Scholl, Raphael

    2018-01-01

    of biological networks using tools from graph theory to the application of dynamical systems theory to understand the behavior of complex biological systems. We show how network approaches support and extend traditional mechanistic strategies but also offer novel strategies for dealing with biological...... strategies? When and how can network and mechanistic approaches interact in productive ways? In this paper we address these questions by focusing on how biological networks are represented and analyzed in a diverse class of case studies. Our examples span from the investigation of organizational properties...

  15. Functional biology of sympatric krill species

    DEFF Research Database (Denmark)

    Agersted, Mette Dalgaard; Nielsen, Torkel Gissel

    2016-01-01

    Here we compare the functional biology of the sympatric krill species, Meganyctiphanes norvegica and Thysanoessa inermis. For M. norvegica, we investigated functional responses on diatoms and copepods, together with prey size spectra on plankton ,400 mm and copepods in the size range 500–3220 mm....... For T. inermis, only prey size spectrum on plankton ,400 mm were investigated. The prey size ranges of both species include organisms ,400 mm, and they consequently graze on several trophic levels. However, T. inermis feed on cells ,10 mm equivalent spherical diameter (ESD), whereas M. norvegica only...

  16. Marine Carotenoids: Biological Functions and Commercial Applications

    Science.gov (United States)

    Vílchez, Carlos; Forján, Eduardo; Cuaresma, María; Bédmar, Francisco; Garbayo, Inés; Vega, José M.

    2011-01-01

    Carotenoids are the most common pigments in nature and are synthesized by all photosynthetic organisms and fungi. Carotenoids are considered key molecules for life. Light capture, photosynthesis photoprotection, excess light dissipation and quenching of singlet oxygen are among key biological functions of carotenoids relevant for life on earth. Biological properties of carotenoids allow for a wide range of commercial applications. Indeed, recent interest in the carotenoids has been mainly for their nutraceutical properties. A large number of scientific studies have confirmed the benefits of carotenoids to health and their use for this purpose is growing rapidly. In addition, carotenoids have traditionally been used in food and animal feed for their color properties. Carotenoids are also known to improve consumer perception of quality; an example is the addition of carotenoids to fish feed to impart color to farmed salmon. PMID:21556162

  17. Distinct signaling roles of ceramide species in yeast revealed through systematic perturbation and systems biology analyses.

    Science.gov (United States)

    Montefusco, David J; Chen, Lujia; Matmati, Nabil; Lu, Songjian; Newcomb, Benjamin; Cooper, Gregory F; Hannun, Yusuf A; Lu, Xinghua

    2013-10-29

    Ceramide, the central molecule of sphingolipid metabolism, is an important bioactive molecule that participates in various cellular regulatory events and that has been implicated in disease. Deciphering ceramide signaling is challenging because multiple ceramide species exist, and many of them may have distinct functions. We applied systems biology and molecular approaches to perturb ceramide metabolism in the yeast Saccharomyces cerevisiae and inferred causal relationships between ceramide species and their potential targets by combining lipidomic, genomic, and transcriptomic analyses. We found that during heat stress, distinct metabolic mechanisms controlled the abundance of different groups of ceramide species and provided experimental support for the importance of the dihydroceramidase Ydc1 in mediating the decrease in dihydroceramides during heat stress. Additionally, distinct groups of ceramide species, with different N-acyl chains and hydroxylations, regulated different sets of functionally related genes, indicating that the structural complexity of these lipids produces functional diversity. The transcriptional modules that we identified provide a resource to begin to dissect the specific functions of ceramides.

  18. Uncovering Biological Network Function via Graphlet Degree Signatures

    Directory of Open Access Journals (Sweden)

    Nataša Pržulj

    2008-01-01

    Full Text Available Motivation: Proteins are essential macromolecules of life and thus understanding their function is of great importance. The number of functionally unclassified proteins is large even for simple and well studied organisms such as baker’s yeast. Methods for determining protein function have shifted their focus from targeting specific proteins based solely on sequence homology to analyses of the entire proteome based on protein-protein interaction (PPI networks. Since proteins interact to perform a certain function, analyzing structural properties of PPI networks may provide useful clues about the biological function of individual proteins, protein complexes they participate in, and even larger subcellular machines.Results: We design a sensitive graph theoretic method for comparing local structures of node neighborhoods that demonstrates that in PPI networks, biological function of a node and its local network structure are closely related. The method summarizes a protein’s local topology in a PPI network into the vector of graphlet degrees called the signature of the protein and computes the signature similarities between all protein pairs. We group topologically similar proteins under this measure in a PPI network and show that these protein groups belong to the same protein complexes, perform the same biological functions, are localized in the same subcellular compartments, and have the same tissue expressions. Moreover, we apply our technique on a proteome-scale network data and infer biological function of yet unclassified proteins demonstrating that our method can provide valuable guidelines for future experimental research such as disease protein prediction.Availability: Data is available upon request.

  19. Neurotrophin Propeptides: Biological Functions and Molecular Mechanisms.

    Science.gov (United States)

    Rafieva, Lola M; Gasanov, Eugene V

    2016-01-01

    Neurotrophins constitute a family of growth factors that play a key role in the regulation of the development and function of the central and peripheral nervous systems. A common feature of all the neurotrophins is their synthesis in cells as long precursors (pre-pro-neurotrophins) that contain an N-terminal signal peptide, a following propeptide and the mature neurotrophin. Although the signal peptide functions have been well studied, the role of neurotrophin propeptides is not so clear. Here, we briefly summarize the biochemistry of neurotrophin propeptides, including their role as folding-assistants for the mature factor and their role in processing and in secretion of neurotrophins. In the main part of the review we summarize our current state of knowledge of the biological activity of neurotrophin propeptides, their possible mechanisms of action, and their potential influence on the activity of the mature neurotrophins.

  20. FUNCTION IN BIOLOGY: ETIOLOGICAL AND ORGANIZATIONAL PERSPECTIVES

    Directory of Open Access Journals (Sweden)

    Charbel Niño El-Hani

    2009-10-01

    Full Text Available ABSTRACT. In this paper, we argue for a taxonomy of approaches to function based on different epistemological perspectives assumed with regard to the treatment of this central concept in the life sciences. We distinguish between etiological and organizational perspectives on function, analyzing two distinct theories related to each perspective: Wright’s selectionist etiological approach and Godfrey-Smith’s modern history theory of functions, in the case of the etiological perspective; and Cummins’ functional analysis and Collier’s interactivist approach to function, among organizational accounts. We explain differences and similarities between these theories and the broader perspectives on function, arguing for a particular way of understanding the consensus without unity in debates about function. While explaining the accounts of function, we also deal with the relationship between this concept and other important biological concepts, such as adaptation, selection, complexity, and autonomy. We also advance an argument for the limits and prospects of the explanatory role of function in evolution. By arguing that changes in functionality are always grounded on changes in systems’ organization, we show that function can never explain the origins of traits. Nevertheless, it can explain the spread of traits in populations, but only when we are dealing with functionally novel traits. Finally, we stress that organizational accounts of function are needed to understand how new functions appear by means of changes in systems’ organization. KEYWORDS: Function; Teleology; Explanation; Etiology; Organization.   RESUMEN. En este artículo, argumentamos a favor de una taxonomía de abordajes sobre función basada en diferentes perspectivas epistemológicas a cerca del tratamiento de este concepto central en las ciencias de la vida. Distinguimos entre perspectivas etiológicas y organizacionales sobre función, analizando dos teorías distintas

  1. Progressing From Initially Ambiguous Functional Analyses: Three Case Examples

    OpenAIRE

    Tiger, Jeffrey H.; Fisher, Wayne W.; Toussaint, Karen A.; Kodak, Tiffany

    2009-01-01

    Most often functional analyses are initiated using a standard set of test conditions, similar to those described by Iwata, Dorsey, Slifer, Bauman, and Richman (1982/1994). These test conditions involve the careful manipulation of motivating operations, discriminative stimuli, and reinforcement contingencies to determine the events related to the occurrence and maintenance of problem behavior. Some individuals display problem behavior that is occasioned and reinforced by idiosyncratic or other...

  2. The functional biology of human milk oligosaccharides.

    Science.gov (United States)

    Bode, Lars

    2015-11-01

    Human milk oligosaccharides (HMOs) are a group of complex sugars that are highly abundant in human milk, but currently not present in infant formula. More than a hundred different HMOs have been identified so far. The amount and composition of HMOs are highly variable between women, and each structurally defined HMO might have a distinct functionality. HMOs are not digested by the infant and serve as metabolic substrates for select microbes, contributing to shape the infant gut microbiome. HMOs act as soluble decoy receptors that block the attachment of viral, bacterial or protozoan parasite pathogens to epithelial cell surface sugars, which may help prevent infectious diseases in the gut and also the respiratory and urinary tracts. HMOs are also antimicrobials that act as bacteriostatic or bacteriocidal agents. In addition, HMOs alter host epithelial and immune cell responses with potential benefits for the neonate. The article reviews current knowledge as well as future challenges and opportunities related to the functional biology of HMOs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Use and misuse of temperature normalisation in meta-analyses of thermal responses of biological traits

    Directory of Open Access Journals (Sweden)

    Dimitrios - Georgios Kontopoulos

    2018-02-01

    Full Text Available There is currently unprecedented interest in quantifying variation in thermal physiology among organisms, especially in order to understand and predict the biological impacts of climate change. A key parameter in this quantification of thermal physiology is the performance or value of a rate, across individuals or species, at a common temperature (temperature normalisation. An increasingly popular model for fitting thermal performance curves to data—the Sharpe-Schoolfield equation—can yield strongly inflated estimates of temperature-normalised rate values. These deviations occur whenever a key thermodynamic assumption of the model is violated, i.e., when the enzyme governing the performance of the rate is not fully functional at the chosen reference temperature. Using data on 1,758 thermal performance curves across a wide range of species, we identify the conditions that exacerbate this inflation. We then demonstrate that these biases can compromise tests to detect metabolic cold adaptation, which requires comparison of fitness or rate performance of different species or genotypes at some fixed low temperature. Finally, we suggest alternative methods for obtaining unbiased estimates of temperature-normalised rate values for meta-analyses of thermal performance across species in climate change impact studies.

  4. A real-time transfer function analyser program for PFR

    International Nuclear Information System (INIS)

    McWilliam, D.

    1980-03-01

    A transfer function analyser software package has been produced which is believed to constitute a significant advance over others reported in the literature. The main advantages of the system are its operating speed, especially at low frequencies, which is due to its use of part-cycle integration and its high degree of interactive operator control. The driving sine wave, the return signals and the computed vector diagrams are displayed on TV type visual display units. Data output is by means of an incremental graph plotter or an IBM typewriter. (author)

  5. The Structure and Function of Biological Networks

    Science.gov (United States)

    Wu, Daniel Duanqing

    2010-01-01

    Biology has been revolutionized in recent years by an explosion in the availability of data. Transforming this new wealth of data into meaningful biological insights and clinical breakthroughs requires a complete overhaul both in the questions being asked and the methodologies used to answer them. A major challenge in organizing and understanding…

  6. DMPD: Structural and functional analyses of bacterial lipopolysaccharides. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 12106784 Structural and functional analyses of bacterial lipopolysaccharides. Carof...html) (.csml) Show Structural and functional analyses of bacterial lipopolysaccharides. PubmedID 12106784 Title Structural and functi...onal analyses of bacterial lipopolysaccharides. Authors

  7. Feedback dynamics and cell function: Why systems biology is called Systems Biology.

    Science.gov (United States)

    Wolkenhauer, Olaf; Mesarovic, Mihajlo

    2005-05-01

    A new paradigm, like Systems Biology, should challenge the way research has been conducted previously. This Opinion article aims to present Systems Biology, not as the application of engineering principles to biology but as a merger of systems- and control theory with molecular- and cell biology. In our view, the central dogma of Systems Biology is that it is system dynamics that gives rise to the functioning and function of cells. The concepts of feedback regulation and control of pathways and the coordination of cell function are emphasized as an important area of Systems Biology research. The hurdles and risks for this area are discussed from the perspective of dynamic pathway modelling. Most of all, the aim of this article is to promote mathematical modelling and simulation as a part of molecular- and cell biology. Systems Biology is a success if it is widely accepted that there is nothing more practical than a good theory.

  8. Marine Carotenoids: Biological Functions and Commercial Applications

    NARCIS (Netherlands)

    Vilchez, C.; Forján, E.; Cuaresma, M.; Bédmar, F.; Garbayo, I.; Vega, J.M.

    2011-01-01

    Carotenoids are the most common pigments in nature and are synthesized by all photosynthetic organisms and fungi. Carotenoids are considered key molecules for life. Light capture, photosynthesis photoprotection, excess light dissipation and quenching of singlet oxygen are among key biological

  9. Evaluation of the divided attention condition during functional analyses.

    Science.gov (United States)

    Fahmie, Tara A; Iwata, Brian A; Harper, Jill M; Querim, Angie C

    2013-01-01

    A common condition included in most functional analyses (FAs) is the attention condition, in which the therapist ignores the client by engaging in a solitary activity (antecedent event) but delivers attention to the client contingent on problem behavior (consequent event). The divided attention condition is similar, except that the antecedent event consists of the therapist conversing with an adult confederate. We compared the typical and divided attention conditions to determine whether behavior in general (Study 1) and problem behavior in particular (Study 2) were more sensitive to one of the test conditions. Results showed that the divided attention condition resulted in faster acquisition or more efficient FA results for 2 of 9 subjects, suggesting that the divided attention condition could be considered a preferred condition when resources are available. © Society for the Experimental Analysis of Behavior.

  10. IMRT optimization with pseudo-biologic objective function

    International Nuclear Information System (INIS)

    Yi, B. Y.; Ahn, S. D.; Kim, J. H.; Lee, S. W.; Choi, E. K.

    2002-01-01

    The pseudo-biologic objective function has been proposed for the IMRT optimization. It is similar to the biological objective function in mathematical shape, but uses physical parameters. The pseudo-biologic objective function concept is consisted of the target coverage index (TCI) and the organ score index (OSI), was introduced. The TCI was expressed as the sum of all of the weighted bins of target dose volume histogram (DVH). The weights were given as the normal distribution of which the average is 100 % and the standard deviation is ±. The OSI was expressed as similar way. The average of the normal distribution was 0% of the dose and that of standard deviation was selected as a function of limiting dose and its importance. The objective function could be calculated as the product of the TCI and OSI's. The RTP Tool Box (RTB) was used for this study. The constraints applied in the optimization was intuitively clinical experience based numbers, while the physical objective function asks just numbers which are not necessarily based on the clinic, and the parameters for the biologic objective functions are uncertain. The OSI's from the pseudo-biological function showed better results than from the physical functions, while TCI's showed similar tendency. We could show that the pseudo-biologic function can be used for an IMRT objective function on behalf of the biological objective function

  11. Event-based text mining for biology and functional genomics

    Science.gov (United States)

    Thompson, Paul; Nawaz, Raheel; McNaught, John; Kell, Douglas B.

    2015-01-01

    The assessment of genome function requires a mapping between genome-derived entities and biochemical reactions, and the biomedical literature represents a rich source of information about reactions between biological components. However, the increasingly rapid growth in the volume of literature provides both a challenge and an opportunity for researchers to isolate information about reactions of interest in a timely and efficient manner. In response, recent text mining research in the biology domain has been largely focused on the identification and extraction of ‘events’, i.e. categorised, structured representations of relationships between biochemical entities, from the literature. Functional genomics analyses necessarily encompass events as so defined. Automatic event extraction systems facilitate the development of sophisticated semantic search applications, allowing researchers to formulate structured queries over extracted events, so as to specify the exact types of reactions to be retrieved. This article provides an overview of recent research into event extraction. We cover annotated corpora on which systems are trained, systems that achieve state-of-the-art performance and details of the community shared tasks that have been instrumental in increasing the quality, coverage and scalability of recent systems. Finally, several concrete applications of event extraction are covered, together with emerging directions of research. PMID:24907365

  12. Functional Analysis in Public Schools: A Summary of 90 Functional Analyses

    Science.gov (United States)

    Mueller, Michael M.; Nkosi, Ajamu; Hine, Jeffrey F.

    2011-01-01

    Several review and epidemiological studies have been conducted over recent years to inform behavior analysts of functional analysis outcomes. None to date have closely examined demographic and clinical data for functional analyses conducted exclusively in public school settings. The current paper presents a data-based summary of 90 functional…

  13. Function-Based Algorithms for Biological Sequences

    Science.gov (United States)

    Mohanty, Pragyan Sheela P.

    2015-01-01

    Two problems at two different abstraction levels of computational biology are studied. At the molecular level, efficient pattern matching algorithms in DNA sequences are presented. For gene order data, an efficient data structure is presented capable of storing all gene re-orderings in a systematic manner. A common characteristic of presented…

  14. Genetic analyses of the stability of executive functioning during childhood.

    NARCIS (Netherlands)

    Polderman, T.J.C.; Posthuma, D.; de Sonneville, L.M.J.; Stins, J.F.; Verhulst, F.C.; Boomsma, D.I.

    2007-01-01

    Executive functioning is an umbrella term for several related cognitive functions like selective- and sustained attention, working memory, and inhibition. Little is known about the stability of executive functioning during childhood. In this study the longitudinal stability of executive functioning

  15. Function of dynamic models in systems biology: linking structure to behaviour.

    Science.gov (United States)

    Knüpfer, Christian; Beckstein, Clemens

    2013-10-08

    Dynamic models in Systems Biology are used in computational simulation experiments for addressing biological questions. The complexity of the modelled biological systems and the growing number and size of the models calls for computer support for modelling and simulation in Systems Biology. This computer support has to be based on formal representations of relevant knowledge fragments. In this paper we describe different functional aspects of dynamic models. This description is conceptually embedded in our "meaning facets" framework which systematises the interpretation of dynamic models in structural, functional and behavioural facets. Here we focus on how function links the structure and the behaviour of a model. Models play a specific role (teleological function) in the scientific process of finding explanations for dynamic phenomena. In order to fulfil this role a model has to be used in simulation experiments (pragmatical function). A simulation experiment always refers to a specific situation and a state of the model and the modelled system (conditional function). We claim that the function of dynamic models refers to both the simulation experiment executed by software (intrinsic function) and the biological experiment which produces the phenomena under investigation (extrinsic function). We use the presented conceptual framework for the function of dynamic models to review formal accounts for functional aspects of models in Systems Biology, such as checklists, ontologies, and formal languages. Furthermore, we identify missing formal accounts for some of the functional aspects. In order to fill one of these gaps we propose an ontology for the teleological function of models. We have thoroughly analysed the role and use of models in Systems Biology. The resulting conceptual framework for the function of models is an important first step towards a comprehensive formal representation of the functional knowledge involved in the modelling and simulation process

  16. Sobol method application in dimensional sensitivity analyses of different AFM cantilevers for biological particles

    Science.gov (United States)

    Korayem, M. H.; Taheri, M.; Ghahnaviyeh, S. D.

    2015-08-01

    Due to the more delicate nature of biological micro/nanoparticles, it is necessary to compute the critical force of manipulation. The modeling and simulation of reactions and nanomanipulator dynamics in a precise manipulation process require an exact modeling of cantilevers stiffness, especially the stiffness of dagger cantilevers because the previous model is not useful for this investigation. The stiffness values for V-shaped cantilevers can be obtained through several methods. One of them is the PBA method. In another approach, the cantilever is divided into two sections: a triangular head section and two slanted rectangular beams. Then, deformations along different directions are computed and used to obtain the stiffness values in different directions. The stiffness formulations of dagger cantilever are needed for this sensitivity analyses so the formulations have been driven first and then sensitivity analyses has been started. In examining the stiffness of the dagger-shaped cantilever, the micro-beam has been divided into two triangular and rectangular sections and by computing the displacements along different directions and using the existing relations, the stiffness values for dagger cantilever have been obtained. In this paper, after investigating the stiffness of common types of cantilevers, Sobol sensitivity analyses of the effects of various geometric parameters on the stiffness of these types of cantilevers have been carried out. Also, the effects of different cantilevers on the dynamic behavior of nanoparticles have been studied and the dagger-shaped cantilever has been deemed more suitable for the manipulation of biological particles.

  17. Fibroblast Growth Factors: Biology, Function, and Application for Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Ye-Rang Yun

    2010-01-01

    Full Text Available Fibroblast growth factors (FGFs that signal through FGF receptors (FGFRs regulate a broad spectrum of biological functions, including cellular proliferation, survival, migration, and differentiation. The FGF signal pathways are the RAS/MAP kinase pathway, PI3 kinase/AKT pathway, and PLCγ pathway, among which the RAS/MAP kinase pathway is known to be predominant. Several studies have recently implicated the in vitro biological functions of FGFs for tissue regeneration. However, to obtain optimal outcomes in vivo, it is important to enhance the half-life of FGFs and their biological stability. Future applications of FGFs are expected when the biological functions of FGFs are potentiated through the appropriate use of delivery systems and scaffolds. This review will introduce the biology and cellular functions of FGFs and deal with the biomaterials based delivery systems and their current applications for the regeneration of tissues, including skin, blood vessel, muscle, adipose, tendon/ligament, cartilage, bone, tooth, and nerve tissues.

  18. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

    Science.gov (United States)

    Scott, Robert A; Lagou, Vasiliki; Welch, Ryan P; Wheeler, Eleanor; Montasser, May E; Luan, Jian’an; Mägi, Reedik; Strawbridge, Rona J; Rehnberg, Emil; Gustafsson, Stefan; Kanoni, Stavroula; Rasmussen-Torvik, Laura J; Yengo, Loïc; Lecoeur, Cecile; Shungin, Dmitry; Sanna, Serena; Sidore, Carlo; Johnson, Paul C D; Jukema, J Wouter; Johnson, Toby; Mahajan, Anubha; Verweij, Niek; Thorleifsson, Gudmar; Hottenga, Jouke-Jan; Shah, Sonia; Smith, Albert V; Sennblad, Bengt; Gieger, Christian; Salo, Perttu; Perola, Markus; Timpson, Nicholas J; Evans, David M; Pourcain, Beate St; Wu, Ying; Andrews, Jeanette S; Hui, Jennie; Bielak, Lawrence F; Zhao, Wei; Horikoshi, Momoko; Navarro, Pau; Isaacs, Aaron; O’Connell, Jeffrey R; Stirrups, Kathleen; Vitart, Veronique; Hayward, Caroline; Esko, Tönu; Mihailov, Evelin; Fraser, Ross M; Fall, Tove; Voight, Benjamin F; Raychaudhuri, Soumya; Chen, Han; Lindgren, Cecilia M; Morris, Andrew P; Rayner, Nigel W; Robertson, Neil; Rybin, Denis; Liu, Ching-Ti; Beckmann, Jacques S; Willems, Sara M; Chines, Peter S; Jackson, Anne U; Kang, Hyun Min; Stringham, Heather M; Song, Kijoung; Tanaka, Toshiko; Peden, John F; Goel, Anuj; Hicks, Andrew A; An, Ping; Müller-Nurasyid, Martina; Franco-Cereceda, Anders; Folkersen, Lasse; Marullo, Letizia; Jansen, Hanneke; Oldehinkel, Albertine J; Bruinenberg, Marcel; Pankow, James S; North, Kari E; Forouhi, Nita G; Loos, Ruth J F; Edkins, Sarah; Varga, Tibor V; Hallmans, Göran; Oksa, Heikki; Antonella, Mulas; Nagaraja, Ramaiah; Trompet, Stella; Ford, Ian; Bakker, Stephan J L; Kong, Augustine; Kumari, Meena; Gigante, Bruna; Herder, Christian; Munroe, Patricia B; Caulfield, Mark; Antti, Jula; Mangino, Massimo; Small, Kerrin; Miljkovic, Iva; Liu, Yongmei; Atalay, Mustafa; Kiess, Wieland; James, Alan L; Rivadeneira, Fernando; Uitterlinden, Andre G; Palmer, Colin N A; Doney, Alex S F; Willemsen, Gonneke; Smit, Johannes H; Campbell, Susan; Polasek, Ozren; Bonnycastle, Lori L; Hercberg, Serge; Dimitriou, Maria; Bolton, Jennifer L; Fowkes, Gerard R; Kovacs, Peter; Lindström, Jaana; Zemunik, Tatijana; Bandinelli, Stefania; Wild, Sarah H; Basart, Hanneke V; Rathmann, Wolfgang; Grallert, Harald; Maerz, Winfried; Kleber, Marcus E; Boehm, Bernhard O; Peters, Annette; Pramstaller, Peter P; Province, Michael A; Borecki, Ingrid B; Hastie, Nicholas D; Rudan, Igor; Campbell, Harry; Watkins, Hugh; Farrall, Martin; Stumvoll, Michael; Ferrucci, Luigi; Waterworth, Dawn M; Bergman, Richard N; Collins, Francis S; Tuomilehto, Jaakko; Watanabe, Richard M; de Geus, Eco J C; Penninx, Brenda W; Hofman, Albert; Oostra, Ben A; Psaty, Bruce M; Vollenweider, Peter; Wilson, James F; Wright, Alan F; Hovingh, G Kees; Metspalu, Andres; Uusitupa, Matti; Magnusson, Patrik K E; Kyvik, Kirsten O; Kaprio, Jaakko; Price, Jackie F; Dedoussis, George V; Deloukas, Panos; Meneton, Pierre; Lind, Lars; Boehnke, Michael; Shuldiner, Alan R; van Duijn, Cornelia M; Morris, Andrew D; Toenjes, Anke; Peyser, Patricia A; Beilby, John P; Körner, Antje; Kuusisto, Johanna; Laakso, Markku; Bornstein, Stefan R; Schwarz, Peter E H; Lakka, Timo A; Rauramaa, Rainer; Adair, Linda S; Smith, George Davey; Spector, Tim D; Illig, Thomas; de Faire, Ulf; Hamsten, Anders; Gudnason, Vilmundur; Kivimaki, Mika; Hingorani, Aroon; Keinanen-Kiukaanniemi, Sirkka M; Saaristo, Timo E; Boomsma, Dorret I; Stefansson, Kari; van der Harst, Pim; Dupuis, Josée; Pedersen, Nancy L; Sattar, Naveed; Harris, Tamara B; Cucca, Francesco; Ripatti, Samuli; Salomaa, Veikko; Mohlke, Karen L; Balkau, Beverley; Froguel, Philippe; Pouta, Anneli; Jarvelin, Marjo-Riitta; Wareham, Nicholas J; Bouatia-Naji, Nabila; McCarthy, Mark I; Franks, Paul W; Meigs, James B; Teslovich, Tanya M; Florez, Jose C; Langenberg, Claudia; Ingelsson, Erik; Prokopenko, Inga; Barroso, Inês

    2012-01-01

    Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have raised the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q fasting insulin showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional follow-up of these newly discovered loci will further improve our understanding of glycemic control. PMID:22885924

  19. Functionalized Nanodiamonds for Biological and Medical Applications.

    Science.gov (United States)

    Lai, Lin; Barnard, Amanda S

    2015-02-01

    Nanodiamond is a promising material for biological and medical applications, owning to its relatively inexpensive and large-scale synthesis, unique structure, and superior optical properties. However, most biomedical applications, such as drug delivery and bio-imaging, are dependent upon the precise control of the surfaces, and can be significantly affected by the type, distribution and stability of chemical funtionalisations of the nanodiamond surface. In this paper, recent studies on nanodiamonds and their biomedical applications by conjugating with different chemicals are reviewed, while highlighting the critical importance of surface chemical states for various applications.

  20. Extending and Applying Spartan to Perform Temporal Sensitivity Analyses for Predicting Changes in Influential Biological Pathways in Computational Models.

    Science.gov (United States)

    Alden, Kieran; Timmis, Jon; Andrews, Paul S; Veiga-Fernandes, Henrique; Coles, Mark

    2017-01-01

    Through integrating real time imaging, computational modelling, and statistical analysis approaches, previous work has suggested that the induction of and response to cell adhesion factors is the key initiating pathway in early lymphoid tissue development, in contrast to the previously accepted view that the process is triggered by chemokine mediated cell recruitment. These model derived hypotheses were developed using spartan, an open-source sensitivity analysis toolkit designed to establish and understand the relationship between a computational model and the biological system that model captures. Here, we extend the functionality available in spartan to permit the production of statistical analyses that contrast the behavior exhibited by a computational model at various simulated time-points, enabling a temporal analysis that could suggest whether the influence of biological mechanisms changes over time. We exemplify this extended functionality by using the computational model of lymphoid tissue development as a time-lapse tool. By generating results at twelve- hour intervals, we show how the extensions to spartan have been used to suggest that lymphoid tissue development could be biphasic, and predict the time-point when a switch in the influence of biological mechanisms might occur.

  1. Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Atsushi Takata

    2018-01-01

    Full Text Available Recent studies have established important roles of de novo mutations (DNMs in autism spectrum disorders (ASDs. Here, we analyze DNMs in 262 ASD probands of Japanese origin and confirm the “de novo paradigm” of ASDs across ethnicities. Based on this consistency, we combine the lists of damaging DNMs in our and published ASD cohorts (total number of trios, 4,244 and perform integrative bioinformatics analyses. Besides replicating the findings of previous studies, our analyses highlight ATP-binding genes and fetal cerebellar/striatal circuits. Analysis of individual genes identified 61 genes enriched for damaging DNMs, including ten genes for which our dataset now contributes to statistical significance. Screening of compounds altering the expression of genes hit by damaging DNMs reveals a global downregulating effect of valproic acid, a known risk factor for ASDs, whereas cardiac glycosides upregulate these genes. Collectively, our integrative approach provides deeper biological and potential medical insights into ASDs.

  2. Distinguishing between "function" and "effect" in genome biology.

    Science.gov (United States)

    Doolittle, W Ford; Brunet, Tyler D P; Linquist, Stefan; Gregory, T Ryan

    2014-05-09

    Much confusion in genome biology results from conflation of possible meanings of the word "function." We suggest that, in this connection, attention should be paid to evolutionary biologists and philosophers who have previously dealt with this problem. We need only decide that although all genomic structures have effects, only some of them should be said to have functions. Although it will very often be difficult or impossible to establish function (strictly defined), it should not automatically be assumed. We enjoin genomicists in particular to pay greater attention to parsing biological effects. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  3. A Unifying Theory of Biological Function

    NARCIS (Netherlands)

    van Hateren, J. H.

    2017-01-01

    A new theory that naturalizes biological function is explained and compared with earlier etiological and causal role theories. Etiological (or selected effects) theories explain functions from how they are caused over their evolutionary history. Causal role theories analyze how functional mechanisms

  4. Explaining Biological Functionality: Is Control Theory Enough ...

    African Journals Online (AJOL)

    I argue that the etiological approach, as understood in terms of control theory, suffers from a problem of symmetry, by which function can equally well be placed in the environment as in the organism. Focusing on the autonomy view, I note that it can be understood to some degree in terms of control theory in its version called ...

  5. Functional mapping in biology and medicine

    International Nuclear Information System (INIS)

    McEachron, D.L.

    1986-01-01

    This book contains 10 selections. Some of the titles are: Two Views of Functional Mapping and Autoradiography; Quantitative Analysis of Autoradiographs; Hardware and Software Design Considerations in Engineering an Image Processing Workstation: Autoradiographic Analysis with DUMAS and the BRAIN Autoradiograph Analysis Software Package (with 1 color plate); and Quantitative Autoradiography and in vitro Radioligand Binding

  6. A Compilation of MATLAB Scripts and Functions for MACGMC Analyses

    Science.gov (United States)

    Murthy, Pappu L. N.; Bednarcyk, Brett A.; Mital, Subodh K.

    2017-01-01

    The primary aim of the current effort is to provide scripts that automate many of the repetitive pre- and post-processing tasks associated with composite materials analyses using the Micromechanics Analysis Code with the Generalized Method of Cells. This document consists of a compilation of hundreds of scripts that were developed in MATLAB (The Mathworks, Inc., Natick, MA) programming language and consolidated into 16 MATLAB functions. (MACGMC). MACGMC is a composite material and laminate analysis software code developed at NASA Glenn Research Center. The software package has been built around the generalized method of cells (GMC) family of micromechanics theories. The computer code is developed with a user-friendly framework, along with a library of local inelastic, damage, and failure models. Further, application of simulated thermo-mechanical loading, generation of output results, and selection of architectures to represent the composite material have been automated to increase the user friendliness, as well as to make it more robust in terms of input preparation and code execution. Finally, classical lamination theory has been implemented within the software, wherein GMC is used to model the composite material response of each ply. Thus, the full range of GMC composite material capabilities is available for analysis of arbitrary laminate configurations as well. The pre-processing tasks include generation of a multitude of different repeating unit cells (RUCs) for CMCs and PMCs, visualization of RUCs from MACGMC input and output files and generation of the RUC section of a MACGMC input file. The post-processing tasks include visualization of the predicted composite response, such as local stress and strain contours, damage initiation and progression, stress-strain behavior, and fatigue response. In addition to the above, several miscellaneous scripts have been developed that can be used to perform repeated Monte-Carlo simulations to enable probabilistic

  7. Towards Integration of Biological and Physiological Functions at Multiple Levels

    Directory of Open Access Journals (Sweden)

    Taishin eNomura

    2010-12-01

    Full Text Available An aim of systems physiology today can be stated as to establish logical and quantitative bridges between phenomenological attributes of physiological entities such as cells and organs and physical attributes of biological entities, i.e., biological molecules, allowing us to describe and better understand physiological functions in terms of underlying biological functions. This article illustrates possible schema that can be used for promoting systems physiology by integrating quantitative knowledge of biological and physiological functions at multiple levels of time and space with the use of information technology infrastructure. Emphasis will be made for systematic, modular, hierarchical, and standardized descriptions of mathematical models of the functions and advantages for the use of them.

  8. Genomic Functionalization: The Next Revolution In Biology

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Peter [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Schoeniger, Joseph S. [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Imbro, Paula M. [Sandia National Lab. (SNL-CA), Livermore, CA (United States)

    2014-07-01

    We have implemented a ligand-alignment algorithm into our developed computational pipeline for identifying specificity-determining features (SDFs) in protein-ligand complexes. Given a set of protein-ligand complex structures, the algorithm aligns the complexes by ligand rather than by the C -RMSD or standard approach, providing a single reference frame for extracting SDFs. We anticipate that this ligand-alignment capability will be highly useful for protein function prediction. We already have a database containing > 20 K ligand-protein complex crystal structures taken from the Protein Data Bank. By aligning these proteins to single reference frames using ligand alignment, we can submit the complexes to our pipeline for SDF extraction. The SDFs derived from this training procedure can be used as thumbprints that are hallmarks of individual enzyme classes. These SDF thumbprints may then serve as guides to the prediction of function of new unknown proteins.

  9. Dispensing processes impact apparent biological activity as determined by computational and statistical analyses.

    Directory of Open Access Journals (Sweden)

    Sean Ekins

    Full Text Available Dispensing and dilution processes may profoundly influence estimates of biological activity of compounds. Published data show Ephrin type-B receptor 4 IC50 values obtained via tip-based serial dilution and dispensing versus acoustic dispensing with direct dilution differ by orders of magnitude with no correlation or ranking of datasets. We generated computational 3D pharmacophores based on data derived by both acoustic and tip-based transfer. The computed pharmacophores differ significantly depending upon dispensing and dilution methods. The acoustic dispensing-derived pharmacophore correctly identified active compounds in a subsequent test set where the tip-based method failed. Data from acoustic dispensing generates a pharmacophore containing two hydrophobic features, one hydrogen bond donor and one hydrogen bond acceptor. This is consistent with X-ray crystallography studies of ligand-protein interactions and automatically generated pharmacophores derived from this structural data. In contrast, the tip-based data suggest a pharmacophore with two hydrogen bond acceptors, one hydrogen bond donor and no hydrophobic features. This pharmacophore is inconsistent with the X-ray crystallographic studies and automatically generated pharmacophores. In short, traditional dispensing processes are another important source of error in high-throughput screening that impacts computational and statistical analyses. These findings have far-reaching implications in biological research.

  10. Dynamic Biological Functioning Important for Simulating and Stabilizing Ocean Biogeochemistry

    Science.gov (United States)

    Buchanan, P. J.; Matear, R. J.; Chase, Z.; Phipps, S. J.; Bindoff, N. L.

    2018-04-01

    The biogeochemistry of the ocean exerts a strong influence on the climate by modulating atmospheric greenhouse gases. In turn, ocean biogeochemistry depends on numerous physical and biological processes that change over space and time. Accurately simulating these processes is fundamental for accurately simulating the ocean's role within the climate. However, our simulation of these processes is often simplistic, despite a growing understanding of underlying biological dynamics. Here we explore how new parameterizations of biological processes affect simulated biogeochemical properties in a global ocean model. We combine 6 different physical realizations with 6 different biogeochemical parameterizations (36 unique ocean states). The biogeochemical parameterizations, all previously published, aim to more accurately represent the response of ocean biology to changing physical conditions. We make three major findings. First, oxygen, carbon, alkalinity, and phosphate fields are more sensitive to changes in the ocean's physical state. Only nitrate is more sensitive to changes in biological processes, and we suggest that assessment protocols for ocean biogeochemical models formally include the marine nitrogen cycle to assess their performance. Second, we show that dynamic variations in the production, remineralization, and stoichiometry of organic matter in response to changing environmental conditions benefit the simulation of ocean biogeochemistry. Third, dynamic biological functioning reduces the sensitivity of biogeochemical properties to physical change. Carbon and nitrogen inventories were 50% and 20% less sensitive to physical changes, respectively, in simulations that incorporated dynamic biological functioning. These results highlight the importance of a dynamic biology for ocean properties and climate.

  11. X-ray structure analyses of biological molecules and particles in Japan. A brief history and future prospect

    International Nuclear Information System (INIS)

    Nakasako, Masayoshi; Yamamoto, Masaki

    2015-01-01

    In Japan, X-ray structure analyses of molecules and particles from biology started in the 1970s. The structure analysis methods have been developed through the innovation of various techniques in advance, and have contributed for understanding the elementary and microscopic processes in life. Here we summarize briefly the history of X-ray structure analyses for structural biology in Japan and think about the prospect. (author)

  12. Assessing Ecological Impacts of Shrimp and Sewage Effluent: Biological Indicators with Standard Water Quality Analyses

    Science.gov (United States)

    Jones, A. B.; O'Donohue, M. J.; Udy, J.; Dennison, W. C.

    2001-01-01

    Despite evidence linking shrimp farming to several cases of environmental degradation, there remains a lack of ecologically meaningful information about the impacts of effluent on receiving waters. The aim of this study was to determine the biological impact of shrimp farm effluent, and to compare and distinguish its impacts from treated sewage effluent. Analyses included standard water quality/sediment parameters, as well as biological indicators including tissue nitrogen (N) content, stable isotope ratio of nitrogen (δ 15N), and amino acid composition of inhabitant seagrasses, mangroves and macroalgae. The study area consisted of two tidal creeks, one receiving effluent from a sewage treatment plant and the other from an intensive shrimp farm. The creeks discharged into the western side of Moreton Bay, a sub-tropical coastal embayment on the east coast of Australia. Characterization of water quality revealed significant differences between the creeks, and with unimpacted eastern Moreton Bay. The sewage creek had higher concentrations of dissolved nutrients (predominantly NO-3/NO-2 and PO3-4, compared to NH+4 in the shrimp creek). In contrast, the shrimp creek was more turbid and had higher phytoplankton productivity. Beyond 750 m from the creek mouths, water quality parameters were indistinguishable from eastern Moreton Bay values. Biological indicators detected significant impacts up to 4 km beyond the creek mouths (reference site). Elevated plant δ 15N values ranged from 10·4-19·6‰ at the site of sewage discharge to 2·9-4·5‰ at the reference site. The free amino acid concentration and composition of seagrass and macroalgae was used to distinguish between the uptake of sewage and shrimp derived N. Proline (seagrass) and serine (macroalgae) were high in sewage impacted plants and glutamine (seagrass) and alanine (macroalgae) were high in plants impacted by shrimp effluent. The δ 15N isotopic signatures and free amino acid composition of inhabitant

  13. Gene Discovery and Functional Analyses in the Model Plant Arabidopsis

    DEFF Research Database (Denmark)

    Feng, Cai-ping; Mundy, J.

    2006-01-01

    The present mini-review describes newer methods and strategies, including transposon and T-DNA insertions, TILLING, Deleteagene, and RNA interference, to functionally analyze genes of interest in the model plant Arabidopsis. The relative advantages and disadvantages of the systems are also discus...

  14. Computer assisted functional analysis. Computer gestuetzte funktionelle Analyse

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, H A.E.; Roesler, H

    1982-01-01

    The latest developments in computer-assisted functional analysis (CFA) in nuclear medicine are presented in about 250 papers of the 19th international annual meeting of the Society of Nuclear Medicine (Bern, September 1981). Apart from the mathematical and instrumental aspects of CFA, computerized emission tomography is given particular attention. Advances in nuclear medical diagnosis in the fields of radiopharmaceuticals, cardiology, angiology, neurology, ophthalmology, pulmonology, gastroenterology, nephrology, endocrinology, oncology and osteology are discussed.

  15. Plant ion channels: gene families, physiology, and functional genomics analyses.

    Science.gov (United States)

    Ward, John M; Mäser, Pascal; Schroeder, Julian I

    2009-01-01

    Distinct potassium, anion, and calcium channels in the plasma membrane and vacuolar membrane of plant cells have been identified and characterized by patch clamping. Primarily owing to advances in Arabidopsis genetics and genomics, and yeast functional complementation, many of the corresponding genes have been identified. Recent advances in our understanding of ion channel genes that mediate signal transduction and ion transport are discussed here. Some plant ion channels, for example, ALMT and SLAC anion channel subunits, are unique. The majority of plant ion channel families exhibit homology to animal genes; such families include both hyperpolarization- and depolarization-activated Shaker-type potassium channels, CLC chloride transporters/channels, cyclic nucleotide-gated channels, and ionotropic glutamate receptor homologs. These plant ion channels offer unique opportunities to analyze the structural mechanisms and functions of ion channels. Here we review gene families of selected plant ion channel classes and discuss unique structure-function aspects and their physiological roles in plant cell signaling and transport.

  16. Development of Standards for NanoSIMS Analyses of Biological Materials

    Energy Technology Data Exchange (ETDEWEB)

    Davission, M L; Weber, P K; Pett-Ridge, J; Singer, S

    2008-07-31

    NanoSIMS is a powerful analytical technique for investigating element distributions at the nanometer scale, but quantifying elemental abundances requires appropriate standards, which are not readily available for biological materials. Standards for trace element analyses have been extensively developed for secondary ion mass spectrometry (SIMS) in the semiconductor industry and in the geological sciences. The three primary approaches for generating standards for SIMS are: (1) ion implantation (2) using previously characterized natural materials, and (3) preparing synthetic substances. Ion implantation is a reliable method for generating trace element standards, but it is expensive, which limits investigation of the analytical issues discussed above. It also requires low background levels of the elements of interest. Finding or making standard materials has the potential to provide more flexibility than ion implantation, but realizing homogeneity at the nano-scale is in itself a significant challenge. In this study, we experiment with all three approaches, but with an emphasis toward synthetic organic polymers in order to reduce costs, increase flexibility, and achieve a wide dynamic concentration range. This emphasis serves to meet the major challenge for biological samples of identifying matrix matched, homogeneous material. Biological samples themselves are typically heterogeneous at the scale of microns to 100s of microns, and therefore they are poor SIMS standards. Therefore, we focused on identifying 'biological-like' materials--either natural or synthetic--that can be used for standards. The primary criterion is that the material be as compositionally similar to biological samples as possible (primarily C, H, O, and N). For natural material we adsorbed organic colloids consisting of peptidoglycan (i.e., amino sugars), activated charcoal, and humic acids. Experiments conducted with Si on peptidoglycan showed low affinity as SiO{sub 2}, yet its

  17. Soil microbial community structure in diverse land use systems:A comparative study using Biolog,DGGE,and PLFA analyses

    Institute of Scientific and Technical Information of China (English)

    XUE Dong; YAO Huai-Ying; GE De-Yong; HUANG Chang-Yong

    2008-01-01

    Biolog,16S rRNA gene denaturing gradient gel electrophoresis (DGGE),and phospholipid fatty acid (PLFA) analyses were used to assess soil microbial community characteristics in a chronosequence of tea garden systems (8-,50-,and 90year-old tea gardens),an adjacent wasteland,and a 90-year-old forest.Biolog analysis showed that the average well color development (AWCD) of all carbon sources and the functional diversity based on the Shannon index decreased (P<0.05)in the following order:wasteland>forest>tea garden.For the DGGE analysis,the genetic diversity based on the Shannon index was significantly lower in the tea garden soils than in the wasteland.However,compared to the 90-year-old forest,the tea garden soils showed significantly higher genetic diversity.PLFA analysis showed that the ratio of Gram positive bacteria to Gram negative bacteria was significantly higher in the tea garden soils than in the wasteland,and the highest value was found in the 90-year-old forest.Both the fungal PLFA and the ratio of fungi to bacteria were significantly higher in the three tea garden soils than in the wasteland and forest,indicating that fungal PLFA was significantly affected by land-use change.Based on cluster analysis of the soil microbial community structure,all three analytical methods showed that land-use change had a greater effect on soil microbial community structure than tea garden age.

  18. Synthesis, spectroscopic characterization, biological screenings, DNA binding study and POM analyses of transition metal carboxylates

    Science.gov (United States)

    Uddin, Noor; Sirajuddin, Muhammad; Uddin, Nizam; Tariq, Muhammad; Ullah, Hameed; Ali, Saqib; Tirmizi, Syed Ahmed; Khan, Abdur Rehman

    2015-04-01

    This article contains the synthesis of a novel carboxylic acid derivative, its transition metal complexes and evaluation of biological applications. Six carboxylate complexes of transition metals, Zn(II) and Hg(II), have been successfully synthesized and characterized by FT-IR and NMR (1H, 13C). The ligand, HL, (4-[(2,6-Diethylphenyl)amino]-4-oxobutanoic acid) was also characterized by single crystal X-ray analysis. The complexation occurs via oxygen atoms of the carboxylate moiety. FT-IR date show the bidentate nature of the carboxylate moiety of the ligand as the Δν value in all complexes is less than that of the free ligand. The ligand and its complexes were screened for antifungal and antileishmanial activities. The results showed that the ligand and its complexes are active with few exceptions. UV-visible spectroscopy and viscometry results reveal that the ligand and its complexes interact with the DNA via intercalative mode of interaction. A new and efficient strategy to identify the pharmacophores and anti-pharmacophores sites in carboxylate derivatives for the antibacterial/antifungal activity using Petra, Osiris and Molinspiration (POM) analyses was also carried out.

  19. Biological pathways and genetic mechanisms involved in social functioning.

    Science.gov (United States)

    Ordoñana, Juan R; Bartels, Meike; Boomsma, Dorret I; Cella, David; Mosing, Miriam; Oliveira, Joao R; Patrick, Donald L; Veenhoven, Ruut; Wagner, Gert G; Sprangers, Mirjam A G

    2013-08-01

    To describe the major findings in the literature regarding associations between biological and genetic factors and social functioning, paying special attention to: (1) heritability studies on social functioning and related concepts; (2) hypothesized biological pathways and genetic variants that could be involved in social functioning, and (3) the implications of these results for quality-of-life research. A search of Web of Science and PubMed databases was conducted using combinations of the following keywords: genetics, twins, heritability, social functioning, social adjustment, social interaction, and social dysfunction. Variability in the definitions and measures of social functioning was extensive. Moderate to high heritability was reported for social functioning and related concepts, including prosocial behavior, loneliness, and extraversion. Disorders characterized by impairments in social functioning also show substantial heritability. Genetic variants hypothesized to be involved in social functioning are related to the network of brain structures and processes that are known to affect social cognition and behavior. Better knowledge and understanding about the impact of genetic factors on social functioning is needed to help us to attain a more comprehensive view of health-related quality-of-life (HRQOL) and will ultimately enhance our ability to identify those patients who are vulnerable to poor social functioning.

  20. The functioning and behaviour of biological parents of children ...

    African Journals Online (AJOL)

    Parenting a child with ADHD may intensify parental stress through functional impairment notwithstanding the diagnosis of ADHD. Methods: Eighty-one biological parents of children diagnosed with attention-deficit/ hyperactivity disorder were screened using self-reporting measurements. ADHD self-report scale (ASRS-V 1.1) ...

  1. Evolutionary cell biology: functional insight from "endless forms most beautiful".

    Science.gov (United States)

    Richardson, Elisabeth; Zerr, Kelly; Tsaousis, Anastasios; Dorrell, Richard G; Dacks, Joel B

    2015-12-15

    In animal and fungal model organisms, the complexities of cell biology have been analyzed in exquisite detail and much is known about how these organisms function at the cellular level. However, the model organisms cell biologists generally use include only a tiny fraction of the true diversity of eukaryotic cellular forms. The divergent cellular processes observed in these more distant lineages are still largely unknown in the general scientific community. Despite the relative obscurity of these organisms, comparative studies of them across eukaryotic diversity have had profound implications for our understanding of fundamental cell biology in all species and have revealed the evolution and origins of previously observed cellular processes. In this Perspective, we will discuss the complexity of cell biology found across the eukaryotic tree, and three specific examples of where studies of divergent cell biology have altered our understanding of key functional aspects of mitochondria, plastids, and membrane trafficking. © 2015 Richardson et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  2. Analyses of Brucella pathogenesis, host immunity, and vaccine targets using systems biology and bioinformatics

    Directory of Open Access Journals (Sweden)

    Yongqun eHe

    2012-02-01

    Full Text Available Brucella is a Gram-negative, facultative intracellular bacterium that causes zoonotic brucellosis in humans and various animals. Out of ten classified Brucella species, B. melitensis, B. abortus, B. suis, and B. canis are pathogenic to humans. In the past decade, the mechanisms of Brucella pathogenesis and host immunity have been extensively investigated using the cutting edge systems biology and bioinformatics approaches. This article provides a comprehensive review of the applications of Omics (including genomics, transcriptomics, and proteomics and bioinformatics technologies for the analysis of Brucella pathogenesis, host immune responses, and vaccine targets. Based on more than 30 sequenced Brucella genomes, comparative genomics is able to identify gene variations among Brucella strains that help to explain host specificity and virulence differences among Brucella species. Diverse transcriptomics and proteomics gene expression studies have been conducted to analyze gene expression profiles of wild type Brucella strains and mutants under different laboratory conditions. High throughput Omics analyses of host responses to infections with virulent or attenuated Brucella strains have been focused on responses by mouse and cattle macrophages, bovine trophoblastic cells, mouse and boar splenocytes, and ram buffy coat. Differential serum responses in humans and rams to Brucella infections have been analyzed using high throughput serum antibody screening technology. The Vaxign reverse vaccinology has been used to predict many Brucella vaccine targets. More than 180 Brucella virulence factors and their gene interaction networks have been identified using advanced literature mining methods. The recent development of community-based Vaccine Ontology and Brucellosis Ontology provides an efficient way for Brucella data integration, exchange, and computer-assisted automated reasoning.

  3. Analyses of Brucella Pathogenesis, Host Immunity, and Vaccine Targets using Systems Biology and Bioinformatics

    Science.gov (United States)

    He, Yongqun

    2011-01-01

    Brucella is a Gram-negative, facultative intracellular bacterium that causes zoonotic brucellosis in humans and various animals. Out of 10 classified Brucella species, B. melitensis, B. abortus, B. suis, and B. canis are pathogenic to humans. In the past decade, the mechanisms of Brucella pathogenesis and host immunity have been extensively investigated using the cutting edge systems biology and bioinformatics approaches. This article provides a comprehensive review of the applications of Omics (including genomics, transcriptomics, and proteomics) and bioinformatics technologies for the analysis of Brucella pathogenesis, host immune responses, and vaccine targets. Based on more than 30 sequenced Brucella genomes, comparative genomics is able to identify gene variations among Brucella strains that help to explain host specificity and virulence differences among Brucella species. Diverse transcriptomics and proteomics gene expression studies have been conducted to analyze gene expression profiles of wild type Brucella strains and mutants under different laboratory conditions. High throughput Omics analyses of host responses to infections with virulent or attenuated Brucella strains have been focused on responses by mouse and cattle macrophages, bovine trophoblastic cells, mouse and boar splenocytes, and ram buffy coat. Differential serum responses in humans and rams to Brucella infections have been analyzed using high throughput serum antibody screening technology. The Vaxign reverse vaccinology has been used to predict many Brucella vaccine targets. More than 180 Brucella virulence factors and their gene interaction networks have been identified using advanced literature mining methods. The recent development of community-based Vaccine Ontology and Brucellosis Ontology provides an efficient way for Brucella data integration, exchange, and computer-assisted automated reasoning. PMID:22919594

  4. Linking structural features of protein complexes and biological function.

    Science.gov (United States)

    Sowmya, Gopichandran; Breen, Edmond J; Ranganathan, Shoba

    2015-09-01

    Protein-protein interaction (PPI) establishes the central basis for complex cellular networks in a biological cell. Association of proteins with other proteins occurs at varying affinities, yet with a high degree of specificity. PPIs lead to diverse functionality such as catalysis, regulation, signaling, immunity, and inhibition, playing a crucial role in functional genomics. The molecular principle of such interactions is often elusive in nature. Therefore, a comprehensive analysis of known protein complexes from the Protein Data Bank (PDB) is essential for the characterization of structural interface features to determine structure-function relationship. Thus, we analyzed a nonredundant dataset of 278 heterodimer protein complexes, categorized into major functional classes, for distinguishing features. Interestingly, our analysis has identified five key features (interface area, interface polar residue abundance, hydrogen bonds, solvation free energy gain from interface formation, and binding energy) that are discriminatory among the functional classes using Kruskal-Wallis rank sum test. Significant correlations between these PPI interface features amongst functional categories are also documented. Salt bridges correlate with interface area in regulator-inhibitors (r = 0.75). These representative features have implications for the prediction of potential function of novel protein complexes. The results provide molecular insights for better understanding of PPIs and their relation to biological functions. © 2015 The Protein Society.

  5. Milk protein tailoring to improve functional and biological properties

    Directory of Open Access Journals (Sweden)

    JEAN-MARC CHOBERT

    2012-01-01

    Full Text Available Proteins are involved in every aspects of life: structure, motion, catalysis, recognition and regulation. Today's highly sophisticated science of the modifications of proteins has ancient roots. The tailoring of proteins for food and medical uses precedes the beginning of what is called biochemistry. Chemical modification of proteins was pursued early in the twentieth century as an analytical procedure for side-chain amino acids. Later, methods were developed for specific inactivation of biologically active proteins and titration of their essential groups. Enzymatic modifications were mainly developed in the seventies when many more enzymes became economically available. Protein engineering has become a valuable tool for creating or improving proteins for practical use and has provided new insights into protein structure and function. The actual and potential use of milk proteins as food ingredients has been a popular topic for research over the past 40 years. With today's sophisticated analytical, biochemical and biological research tools, the presence of compounds with biological activity has been demonstrated. Improvements in separation techniques and enzyme technology have enabled efficient and economic isolation and modification of milk proteins, which has made possible their use as functional foods, dietary supplements, nutraceuticals and medical foods. In this review, some chemical and enzymatic modifications of milk proteins are described, with particular focus on their functional and biological properties.

  6. Nuclear analyses in biology and medical science. Measuring on nucleii in stead of atoms

    International Nuclear Information System (INIS)

    De Goeij, J.J.M.

    1996-01-01

    A brief overview is given of the use of nuclear analyses in life sciences. Features of nuclear analytical methods (NAMs) are grouped into four categories: physical basis, isotopic analyses rather than elemental analyses, no interference of electronic and molecular structure, and penetrating character of nuclear radiation. Obstacles in applying NAMs in the life sciences are outlined. 1 tab

  7. Knowledge base and functionality of concepts of some Filipino biology teachers in five biology topics

    Science.gov (United States)

    Barquilla, Manuel B.

    2018-01-01

    This mixed research, is a snapshot of some Filipino Biology teachers' knowledge structure and how their concepts of the five topics in Biology (Photosynthesis, Cellular Respiration, human reproductive system, Mendelian genetics and NonMendelian genetics) functions and develops inside a biology classroom. The study focuses on the six biology teachers and a total of 222 students in their respective classes. Of the Six (6) teachers, three (3) are under the Science curriculum and the other three (3) are under regular curriculum in both public and private schools in Iligan city and Lanao del Norte, Philippines. The study utilized classroom discourses, concept maps, interpretative case-study method, bracketing method, and concept analysis for qualitative part; the quantitative part uses a nonparametric statistical tool, Kendall's tau Coefficient for determining relationship and congruency while measures of central tendencies and dispersion (mean, and standard deviation) for concept maps scores interpretation. Knowledge Base of Biology teachers were evaluated by experts in field of specialization having a doctorate program (e.g. PhD in Genetics) and PhD Biology candidates. The data collection entailed seven (7) months immersion: one (1) month for preliminary phase for the researcher to gain teachers' and students' confidence and the succeeding six (6) months for main observation and data collection. The evaluation of teachers' knowledge base by experts indicated that teachers' knowledge of (65%) is lower than the minimum (75%) recommended by ABD-el-Khalick and Boujaoude (1997). Thus, the experts believe that content knowledge of the teachers is hardly adequate for their teaching assignment. Moreover, the teachers in this study do not systematically use reallife situation to apply the concepts they teach. They can identify concepts too abstract for their student; however, they seldom use innovative ways to bring the discussion to their students' level of readiness and

  8. Progress in the biological function of alpha-enolase

    Directory of Open Access Journals (Sweden)

    Hong Ji

    2016-03-01

    Full Text Available Alpha-enolase (ENO1, also known as 2-phospho-D-glycerate hydrolase, is a metalloenzyme that catalyzes the conversion of 2-phosphoglyceric acid to phosphoenolpyruvic acid in the glycolytic pathway. It is a multifunctional glycolytic enzyme involved in cellular stress, bacterial and fungal infections, autoantigen activities, the occurrence and metastasis of cancer, parasitic infections, and the growth, development and reproduction of organisms. This article mainly reviews the basic characteristics and biological functions of ENO1.

  9. SU-E-T-54: Benefits of Biological Cost Functions

    International Nuclear Information System (INIS)

    Demirag, N

    2014-01-01

    Purpose: To verify the benefits of the biological cost functions. Methods: TG166 patients were used for the test case scenarios. Patients were planned using Monaco V5.0 (CMS/Elekta, St.Louis, MO) Monaco has 3 biological and 8 physical CFs. In this study the plans were optimized using 3 different scenarios. 1- Biological CFs only 2-Physical CFs only 3- Combination of Physical and Biological CFsMonaco has 3 biological CFs. Target EUD used for the targets, derived from the poisson cell kill model, has an α value that controls the cold spots inside the target. α values used in the optimization were 0.5 and 0.8. if cold spots needs to be penalized α value increased. Serial CF: it's called serial to mimic the behaviour of the serial organs, if a high k value like 12 or 14 is used it controls the maximum dose. Serial CF has a k parameter that is used to shape the whole dvh curve. K value ranges between 1–20. k:1 is used to control the mean dose, lower k value controls the mean dose, higher k value controls the higher dose, using 2 serial CFs with different k values controls the whole DVH. Paralel CF controls the percentage of the volume that tolerates higher doses than the reference dose to mimic the behaviour of the paralel organs. Results: It was possible to achive clinically accepted plans in all 3 scenarios. The benefit of the biological cost functions were to control the mean dose for target and OAR, to shape the DVH curve using one EUD value and one k value simplifies the optimization process. Using the biological CFs alone, it was hard to control the dose at a point. Conclusion: Biological CFs in Monaco doesn't require the ntcp/tcp values from the labs and useful to shape the whole dvh curve. I work as an applications support specialist for Elekta and I am a Ph.D. Student in Istanbul University for radiation therapy physics

  10. Construction of Biologically Functional Bacterial Plasmids In Vitro

    Science.gov (United States)

    Cohen, Stanley N.; Chang, Annie C. Y.; Boyer, Herbert W.; Helling, Robert B.

    1973-01-01

    The construction of new plasmid DNA species by in vitro joining of restriction endonuclease-generated fragments of separate plasmids is described. Newly constructed plasmids that are inserted into Escherichia coli by transformation are shown to be biologically functional replicons that possess genetic properties and nucleotide base sequences from both of the parent DNA molecules. Functional plasmids can be obtained by reassociation of endonuclease-generated fragments of larger replicons, as well as by joining of plasmid DNA molecules of entirely different origins. Images PMID:4594039

  11. Biological properties of extracellular vesicles and their physiological functions

    Science.gov (United States)

    Yáñez-Mó, María; Siljander, Pia R.-M.; Andreu, Zoraida; Zavec, Apolonija Bedina; Borràs, Francesc E.; Buzas, Edit I.; Buzas, Krisztina; Casal, Enriqueta; Cappello, Francesco; Carvalho, Joana; Colás, Eva; Silva, Anabela Cordeiro-da; Fais, Stefano; Falcon-Perez, Juan M.; Ghobrial, Irene M.; Giebel, Bernd; Gimona, Mario; Graner, Michael; Gursel, Ihsan; Gursel, Mayda; Heegaard, Niels H. H.; Hendrix, An; Kierulf, Peter; Kokubun, Katsutoshi; Kosanovic, Maja; Kralj-Iglic, Veronika; Krämer-Albers, Eva-Maria; Laitinen, Saara; Lässer, Cecilia; Lener, Thomas; Ligeti, Erzsébet; Linē, Aija; Lipps, Georg; Llorente, Alicia; Lötvall, Jan; Manček-Keber, Mateja; Marcilla, Antonio; Mittelbrunn, Maria; Nazarenko, Irina; Hoen, Esther N.M. Nolte-‘t; Nyman, Tuula A.; O'Driscoll, Lorraine; Olivan, Mireia; Oliveira, Carla; Pállinger, Éva; del Portillo, Hernando A.; Reventós, Jaume; Rigau, Marina; Rohde, Eva; Sammar, Marei; Sánchez-Madrid, Francisco; Santarém, N.; Schallmoser, Katharina; Ostenfeld, Marie Stampe; Stoorvogel, Willem; Stukelj, Roman; Van der Grein, Susanne G.; Vasconcelos, M. Helena; Wauben, Marca H. M.; De Wever, Olivier

    2015-01-01

    In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system. PMID:25979354

  12. Biological properties of extracellular vesicles and their physiological functions

    Directory of Open Access Journals (Sweden)

    María Yáñez-Mó

    2015-05-01

    Full Text Available In the past decade, extracellular vesicles (EVs have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.

  13. “Multi-Omics” Analyses of the Development and Function of Natural Killer Cells

    Directory of Open Access Journals (Sweden)

    Yonggang Zhou

    2017-09-01

    Full Text Available For over four decades, our understanding of natural killer (NK cells has evolved from the original description of cluster of differentiation (CD56+CD3− to establishing NK cells as an important subset of innate lymphocytes in the host’s surveillance against viral infections and malignancy. The progress of research on the fundamental properties and therapeutic prospects for translational medicine using NK cells excites immunologists and clinicians. Over the past decade, numerous advances in “-omics”-scale methods and new technological approaches have addressed many essential questions in the biology of NK cells. We now have further understanding of the overall molecular mechanisms of action that determine the development, function, plasticity, diversity, and immune reactivity of NK cells. These findings are summarized here, and our view on how to study NK cells using “multi-omics” is highlighted. We also describe “-omics” analyses of the relationships between NK cells and viral infection, tumorigenesis, and autoimmune diseases. Ultimately, a deeper and more comprehensive understanding of NK cells in multiple conditions will provide more effective strategies to manipulate NK cells for the treatment of human disease.

  14. Biomarkers of Aging: From Function to Molecular Biology

    Directory of Open Access Journals (Sweden)

    Karl-Heinz Wagner

    2016-06-01

    Full Text Available Aging is a major risk factor for most chronic diseases and functional impairments. Within a homogeneous age sample there is a considerable variation in the extent of disease and functional impairment risk, revealing a need for valid biomarkers to aid in characterizing the complex aging processes. The identification of biomarkers is further complicated by the diversity of biological living situations, lifestyle activities and medical treatments. Thus, there has been no identification of a single biomarker or gold standard tool that can monitor successful or healthy aging. Within this short review the current knowledge of putative biomarkers is presented, focusing on their application to the major physiological mechanisms affected by the aging process including physical capability, nutritional status, body composition, endocrine and immune function. This review emphasizes molecular and DNA-based biomarkers, as well as recent advances in other biomarkers such as microRNAs, bilirubin or advanced glycation end products.

  15. Determining the impacts of trawling on benthic function in European waters : a biological traits approach

    DEFF Research Database (Denmark)

    Bolam, Stefan; Kenny, Andrew; Garcia, Clement

    characteristics, have allowed us to better understand the interactions between the benthic fauna and their environment at a functional level. We present the initial findings of work conducted under the auspices of the EU-funded project ‘BENTHIS’ which aims to improve our understanding of the impacts of trawling...... on benthic ecosystem functioning over much larger spatial scales than previously undertaken. Biological traits information from 887 stations across European waters (Norwegian, UK, Belgian, Dutch, Danish waters, the Mediterranean and Black Sea) were analysed to: i) quantify the relationships between infaunal...

  16. Chemometric and Statistical Analyses of ToF-SIMS Spectra of Increasingly Complex Biological Samples

    Energy Technology Data Exchange (ETDEWEB)

    Berman, E S; Wu, L; Fortson, S L; Nelson, D O; Kulp, K S; Wu, K J

    2007-10-24

    Characterizing and classifying molecular variation within biological samples is critical for determining fundamental mechanisms of biological processes that will lead to new insights including improved disease understanding. Towards these ends, time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used to examine increasingly complex samples of biological relevance, including monosaccharide isomers, pure proteins, complex protein mixtures, and mouse embryo tissues. The complex mass spectral data sets produced were analyzed using five common statistical and chemometric multivariate analysis techniques: principal component analysis (PCA), linear discriminant analysis (LDA), partial least squares discriminant analysis (PLSDA), soft independent modeling of class analogy (SIMCA), and decision tree analysis by recursive partitioning. PCA was found to be a valuable first step in multivariate analysis, providing insight both into the relative groupings of samples and into the molecular basis for those groupings. For the monosaccharides, pure proteins and protein mixture samples, all of LDA, PLSDA, and SIMCA were found to produce excellent classification given a sufficient number of compound variables calculated. For the mouse embryo tissues, however, SIMCA did not produce as accurate a classification. The decision tree analysis was found to be the least successful for all the data sets, providing neither as accurate a classification nor chemical insight for any of the tested samples. Based on these results we conclude that as the complexity of the sample increases, so must the sophistication of the multivariate technique used to classify the samples. PCA is a preferred first step for understanding ToF-SIMS data that can be followed by either LDA or PLSDA for effective classification analysis. This study demonstrates the strength of ToF-SIMS combined with multivariate statistical and chemometric techniques to classify increasingly complex biological samples

  17. Ultra-Structure database design methodology for managing systems biology data and analyses

    Directory of Open Access Journals (Sweden)

    Hemminger Bradley M

    2009-08-01

    Full Text Available Abstract Background Modern, high-throughput biological experiments generate copious, heterogeneous, interconnected data sets. Research is dynamic, with frequently changing protocols, techniques, instruments, and file formats. Because of these factors, systems designed to manage and integrate modern biological data sets often end up as large, unwieldy databases that become difficult to maintain or evolve. The novel rule-based approach of the Ultra-Structure design methodology presents a potential solution to this problem. By representing both data and processes as formal rules within a database, an Ultra-Structure system constitutes a flexible framework that enables users to explicitly store domain knowledge in both a machine- and human-readable form. End users themselves can change the system's capabilities without programmer intervention, simply by altering database contents; no computer code or schemas need be modified. This provides flexibility in adapting to change, and allows integration of disparate, heterogenous data sets within a small core set of database tables, facilitating joint analysis and visualization without becoming unwieldy. Here, we examine the application of Ultra-Structure to our ongoing research program for the integration of large proteomic and genomic data sets (proteogenomic mapping. Results We transitioned our proteogenomic mapping information system from a traditional entity-relationship design to one based on Ultra-Structure. Our system integrates tandem mass spectrum data, genomic annotation sets, and spectrum/peptide mappings, all within a small, general framework implemented within a standard relational database system. General software procedures driven by user-modifiable rules can perform tasks such as logical deduction and location-based computations. The system is not tied specifically to proteogenomic research, but is rather designed to accommodate virtually any kind of biological research. Conclusion We find

  18. Metabolomics for functional genomics, systems biology, and biotechnology.

    Science.gov (United States)

    Saito, Kazuki; Matsuda, Fumio

    2010-01-01

    Metabolomics now plays a significant role in fundamental plant biology and applied biotechnology. Plants collectively produce a huge array of chemicals, far more than are produced by most other organisms; hence, metabolomics is of great importance in plant biology. Although substantial improvements have been made in the field of metabolomics, the uniform annotation of metabolite signals in databases and informatics through international standardization efforts remains a challenge, as does the development of new fields such as fluxome analysis and single cell analysis. The principle of transcript and metabolite cooccurrence, particularly transcriptome coexpression network analysis, is a powerful tool for decoding the function of genes in Arabidopsis thaliana. This strategy can now be used for the identification of genes involved in specific pathways in crops and medicinal plants. Metabolomics has gained importance in biotechnology applications, as exemplified by quantitative loci analysis, prediction of food quality, and evaluation of genetically modified crops. Systems biology driven by metabolome data will aid in deciphering the secrets of plant cell systems and their application to biotechnology.

  19. Biological substantiation of antipsychotic-associated pneumonia: Systematic literature review and computational analyses.

    Science.gov (United States)

    Sultana, Janet; Calabró, Marco; Garcia-Serna, Ricard; Ferrajolo, Carmen; Crisafulli, Concetta; Mestres, Jordi; Trifirò', Gianluca

    2017-01-01

    Antipsychotic (AP) safety has been widely investigated. However, mechanisms underlying AP-associated pneumonia are not well-defined. The aim of this study was to investigate the known mechanisms of AP-associated pneumonia through a systematic literature review, confirm these mechanisms using an independent data source on drug targets and attempt to identify novel AP drug targets potentially linked to pneumonia. A search was conducted in Medline and Web of Science to identify studies exploring the association between pneumonia and antipsychotic use, from which information on hypothesized mechanism of action was extracted. All studies had to be in English and had to concern AP use as an intervention in persons of any age and for any indication, provided that the outcome was pneumonia. Information on the study design, population, exposure, outcome, risk estimate and mechanism of action was tabulated. Public repositories of pharmacology and drug safety data were used to identify the receptor binding profile and AP safety events. Cytoscape was then used to map biological pathways that could link AP targets and off-targets to pneumonia. The literature search yielded 200 articles; 41 were included in the review. Thirty studies reported a hypothesized mechanism of action, most commonly activation/inhibition of cholinergic, histaminergic and dopaminergic receptors. In vitro pharmacology data confirmed receptor affinities identified in the literature review. Two targets, thromboxane A2 receptor (TBXA2R) and platelet activating factor receptor (PTAFR) were found to be novel AP target receptors potentially associated with pneumonia. Biological pathways constructed using Cytoscape identified plausible biological links potentially leading to pneumonia downstream of TBXA2R and PTAFR. Innovative approaches for biological substantiation of drug-adverse event associations may strengthen evidence on drug safety profiles and help to tailor pharmacological therapies to patient risk

  20. Analyses of Brucella Pathogenesis, Host Immunity, and Vaccine Targets using Systems Biology and Bioinformatics

    OpenAIRE

    He, Yongqun

    2012-01-01

    Brucella is a Gram-negative, facultative intracellular bacterium that causes zoonotic brucellosis in humans and various animals. Out of 10 classified Brucella species, B. melitensis, B. abortus, B. suis, and B. canis are pathogenic to humans. In the past decade, the mechanisms of Brucella pathogenesis and host immunity have been extensively investigated using the cutting edge systems biology and bioinformatics approaches. This article provides a comprehensive review of the applications of Omi...

  1. Structure, function, and behaviour of computational models in systems biology.

    Science.gov (United States)

    Knüpfer, Christian; Beckstein, Clemens; Dittrich, Peter; Le Novère, Nicolas

    2013-05-31

    Systems Biology develops computational models in order to understand biological phenomena. The increasing number and complexity of such "bio-models" necessitate computer support for the overall modelling task. Computer-aided modelling has to be based on a formal semantic description of bio-models. But, even if computational bio-models themselves are represented precisely in terms of mathematical expressions their full meaning is not yet formally specified and only described in natural language. We present a conceptual framework - the meaning facets - which can be used to rigorously specify the semantics of bio-models. A bio-model has a dual interpretation: On the one hand it is a mathematical expression which can be used in computational simulations (intrinsic meaning). On the other hand the model is related to the biological reality (extrinsic meaning). We show that in both cases this interpretation should be performed from three perspectives: the meaning of the model's components (structure), the meaning of the model's intended use (function), and the meaning of the model's dynamics (behaviour). In order to demonstrate the strengths of the meaning facets framework we apply it to two semantically related models of the cell cycle. Thereby, we make use of existing approaches for computer representation of bio-models as much as possible and sketch the missing pieces. The meaning facets framework provides a systematic in-depth approach to the semantics of bio-models. It can serve two important purposes: First, it specifies and structures the information which biologists have to take into account if they build, use and exchange models. Secondly, because it can be formalised, the framework is a solid foundation for any sort of computer support in bio-modelling. The proposed conceptual framework establishes a new methodology for modelling in Systems Biology and constitutes a basis for computer-aided collaborative research.

  2. Scavenger Receptor CD163 and Its Biological Functions

    Directory of Open Access Journals (Sweden)

    Gabriela Onofre

    2009-01-01

    Full Text Available CD163 is a member of scavenger receptor super family class B of the first subgroup. It is mapped to the region p13 on chromosome 12. Five different isoforms of CD163 have been described, which differ in the structure of their cytoplasmic domains and putative phosporylation sites. This scavenger receptor is selectively expressed on cells of monocytes and macrophages lineage exclusively. CD163 immunological function is essentially homeostatic. It also has other functions because participates in adhesion to endothelial cells, in tolerance induction and tissues regeneration. Other very important function of CD163 is the clearance of hemoglobin in its cell-free form and participation in anti-inflammation in its soluble form, exhibiting cytokine-like functions. We review the biological functions of CD163 which have been discovered until now. It seems apparent from this review that CD163 scavenger receptor can be used as biomarker in different diseases and as a valuable diagnostic parameter for prognosis of many diseases especially inflammatory disorders and sepsis.

  3. STAT6: its role in interleukin 4-mediated biological functions.

    Science.gov (United States)

    Takeda, K; Kishimoto, T; Akira, S

    1997-05-01

    Interleukin (IL) 4 is known to be a cytokine which plays a central role in the regulation of immune response. Studies on cytokine signal transduction have clarified the mechanism by which IL4 exerts its functions. Two cytoplasmic proteins, signal transducer and activator of transcription (STAT) 6 and IL4-induced phosphotyrosine substrate/insulin receptor substrate 2 (4PS/IRS2), are activated in IL4 signal transduction. Recent studies from STAT6-deficient mice have revealed the essential role of STAT6 in IL4-mediated biological actions. In addition, STAT6 has also been demonstrated to be important for the functions mediated by IL13, which is related to IL4. IL4 and IL13 have been shown to induce the production of IgE, which is a major mediator in an allergic response. These findings indicate that STAT6 activation is involved in IL4- and IL13-mediated disorders such as allergy.

  4. Effect of biological factors during functional scintigraphy of the heart

    Energy Technology Data Exchange (ETDEWEB)

    Breuel, H P; Emrich, D; Luig, H [Goettingen Univ. (F.R. Germany). Abt. fuer Nuklearmedizin

    1976-07-01

    The parameters relating to functional scintigraphy of the heart (average circulation time, peak time) depend not only on the method (injection technique, radiopharmaceutical), but also on biological factors. Failure to take these into consideration may result in an erroneous interpretation of the findings. Circulation time in normal children aged 6 to 14 years, as determined by isotope methods is significantly shorter than in normal adults. Patients with compensated heart disease, as well trained athletes, show significant increase in all portions of the circulation time, when compared with normals of similar ages. This indicates that deviation in the haemodynamics of the circulation as shown by functional scintigraphy, can only be interpreted in the light of clinical findings.

  5. Functions of MicroRNAs in Cardiovascular Biology and Disease

    Science.gov (United States)

    Hata, Akiko

    2015-01-01

    In 1993, lin-4 was discovered as a critical modulator of temporal development in Caenorhabditis elegans and, most notably, as the first in the class of small, single-stranded noncoding RNAs now defined as microRNAs (miRNAs). Another eight years elapsed before miRNA expression was detected in mammalian cells. Since then, explosive advancements in the field of miRNA biology have elucidated the basic mechanism of miRNA biogenesis, regulation, and gene-regulatory function. The discovery of this new class of small RNAs has augmented the complexity of gene-regulatory programs as well as the understanding of developmental and pathological processes in the cardiovascular system. Indeed, the contributions of miRNAs in cardiovascular development and function have been widely explored, revealing the extensive role of these small regulatory RNAs in cardiovascular physiology. PMID:23157557

  6. Carotenoids from Marine Organisms: Biological Functions and Industrial Applications

    Directory of Open Access Journals (Sweden)

    Christian Galasso

    2017-11-01

    Full Text Available As is the case for terrestrial organisms, carotenoids represent the most common group of pigments in marine environments. They are generally biosynthesized by all autotrophic marine organisms, such as bacteria and archaea, algae and fungi. Some heterotrophic organisms also contain carotenoids probably accumulated from food or partly modified through metabolic reactions. These natural pigments are divided into two chemical classes: carotenes (such as lycopene and α- and β-carotene that are composed of hydrogen and carbon; xanthophylls (such as astaxanthin, fucoxanthin and lutein, which are constituted by hydrogen, carbon and oxygen. Carotenoids, as antioxidant compounds, assume a key role in the protection of cells. In fact, quenching of singlet oxygen, light capture and photosynthesis protection are the most relevant biological functions of carotenoids. The present review aims at describing (i the biological functions of carotenoids and their benefits for human health, (ii the most common carotenoids from marine organisms and (iii carotenoids having large success in pharmaceutical, nutraceutical and cosmeceutical industries, highlighting the scientific progress in marine species cultivation for natural pigments production.

  7. Biological response to purification and acid functionalization of carbon nanotubes

    Science.gov (United States)

    Figarol, Agathe; Pourchez, Jérémie; Boudard, Delphine; Forest, Valérie; Tulliani, Jean-Marc; Lecompte, Jean-Pierre; Cottier, Michèle; Bernache-Assollant, Didier; Grosseau, Philippe

    2014-07-01

    Acid functionalization has been considered as an easy way to enhance the dispersion and biodegradation of carbon nanotubes (CNT). However, inconsistencies between toxicity studies of acid functionalized CNT remain unexplained. This could be due to a joint effect of the main physicochemical modifications resulting from an acid functionalization: addition of surface acid groups and purification from catalytic metallic impurities. In this study, the impact on CNT biotoxicity of these two physiochemical features was assessed separately. The in vitro biological response of RAW 264.7 macrophages was evaluated after exposure to 15-240 µg mL-1 of two types of multi-walled CNT. For each type of CNT (small: 20 nm diameter, and big: 90 nm diameter), three different surface chemical properties were studied (total of six CNT samples): pristine, acid functionalized and desorbed. Desorbed CNT were purified by the acid functionalization but presented a very low amount of surface acid groups due to a thermal treatment under vacuum. A Janus effect of acid functionalization with two opposite impacts is highlighted. The CNT purification decreased the overall toxicity, while the surface acid groups intensified it when present at a specific threshold. These acid groups especially amplified the pro-inflammatory response. The threshold mechanism which seemed to regulate the impact of acid groups should be further studied to determine its value and potential link to the other physicochemical state of the CNT. The results suggest that, for a safer-design approach, the benefit-risk balance of an acid functionalization has to be considered, depending on the CNT primary state of purification. Further research should be conducted in this direction.

  8. Kidney function changes with aging in adults: comparison between cross-sectional and longitudinal data analyses in renal function assessment.

    Science.gov (United States)

    Chung, Sang M; Lee, David J; Hand, Austin; Young, Philip; Vaidyanathan, Jayabharathi; Sahajwalla, Chandrahas

    2015-12-01

    The study evaluated whether the renal function decline rate per year with age in adults varies based on two primary statistical analyses: cross-section (CS), using one observation per subject, and longitudinal (LT), using multiple observations per subject over time. A total of 16628 records (3946 subjects; age range 30-92 years) of creatinine clearance and relevant demographic data were used. On average, four samples per subject were collected for up to 2364 days (mean: 793 days). A simple linear regression and random coefficient models were selected for CS and LT analyses, respectively. The renal function decline rates per year were 1.33 and 0.95 ml/min/year for CS and LT analyses, respectively, and were slower when the repeated individual measurements were considered. The study confirms that rates are different based on statistical analyses, and that a statistically robust longitudinal model with a proper sampling design provides reliable individual as well as population estimates of the renal function decline rates per year with age in adults. In conclusion, our findings indicated that one should be cautious in interpreting the renal function decline rate with aging information because its estimation was highly dependent on the statistical analyses. From our analyses, a population longitudinal analysis (e.g. random coefficient model) is recommended if individualization is critical, such as a dose adjustment based on renal function during a chronic therapy. Copyright © 2015 John Wiley & Sons, Ltd.

  9. Ab initio computational study of vincristine as a biological active compound: NMR and NBO analyses

    Directory of Open Access Journals (Sweden)

    Shiva Joohari

    2015-06-01

    Full Text Available Vincristine is a biological active alkaloid that has been used clinically against a variety of neoplasms. In the current study we have theoretically investigated the magnetic properties of titled compound to predict physical and chemical properties of vincristine as a biological inhibitor. Ab initio computation using HF and B3LYP with 3-21G(d and 6-31G(d level of theory have been performed and then magnetic shielding tensor (, ppm, shielding asymmetry (, magnetic shielding anisotropy (aniso, ppm, the skew of a tensor (K, chemical shift anisotropy ( and chemical shift ( were calculated to indicate the details of the interaction mechanism between microtubules and vincristine. Moreover, EHOMO, ELUMO and Ebg were evaluated. The maximum and minimum values of Ebg were found in HF/3-21g and B3LYP/3-21g respectively. It was also uggested that O24, O37, O49 and O55 with minimum values of iso, are active sites of titled compound. Furthermore the calculated chemical shifts were compared with experimental data in DMSO and CDCl3 solvents.

  10. Challenges of analysing suspected over exposed subjects using biological dosimetry at Sri Ramachandra University

    International Nuclear Information System (INIS)

    Vijayalakshimi, J.; Venkatachalam, P.; Solomon, F.D. Paul

    2016-01-01

    Biological dosimetry based on the analysis of dicentric chromosomes has become a routine component of the radiological protection programmes and has a valuable role to contribute in suspected over exposed subjects who perform diagnostic and therapeutic procedures. The Department of Human Genetics, Sri Ramachandra University, Porur, Chennai, has been involved in the standardization of chromosomal aberration analysis as a biological dosimeter for investigating accidental ionising radiation exposure since 1998. Our laboratory has been accredited since 2007 by Atomic Energy Regulatory Board. The initial process was to establish the in vitro dose response curve for various type of low LET ionizing radiation. Since accreditation, a total of 61 subjects have been referred to Sri Ramachandra University from SRRC, Kalpakkam. Brief social/medical history and informed consent are being obtained prior to blood samplings. The dose estimates expressed in sievert (Sv) measured by Thermoluminescence badges was in the range of 0.05-2779.05 mSv. Chromosomal aberration assay was used for analysis which allows direct detection of aberration in peripheral blood lymphocytes. The test was performed as per the standard operating protocol on peripheral blood lymphocyte. Currently the dose response curve for the automated scoring process in under way and we hope to improve upon quality and turnaround time using the automation available. Future challenge would be to establish an in vitro dose response curve with automated scoring technique and developing inter-laboratory comparison of dose response generated using automation

  11. Use of FISH-translocations analyses for retrospective biological dosimetry: How stable are stable chromosome aberrations?

    International Nuclear Information System (INIS)

    Darroudi, F.

    2000-01-01

    Chromosome aberrations, in particular dicentrics, in peripheral blood lymphocytes are used to estimate the absorbed dose immediately following a radiation accident. However, difficulties for dose estimation arise with old exposures, due to a decline of cells containing unstable dicentric aberrations. The fluorescence in situ hybridisation (FISH) technique employing chromosome specific DNA libraries to 'paint' individual human chromosomes has opened new perspectives for rapid and reliable detection of stable chromosome aberrations such as translocations. The inherent stability of translocations over cell generations has enabled them to be used as a biodosemeter. However, due to the limited life of circulating T-lymphocytes, a level of uncertainty exists on the long-term persistence of stable translocations. The objectives of the present work are to present the current state of knowledge on the stability of translocations detected by FISH. The following aspects have been considered; (1) experience so far of retrospective biological dosimetry in humans following accidental and occupational over-exposure, (2) animal studies using mice and monkeys, (3) the influence of subsequent cell divisions on the yield and persistence of translocations following in vitro irradiation of human lymphocytes, and (4) the needs for further work to standardise and validate the use of FISH as a biological dosemeter, and to investigate the influence of various parameters such as radiation quality, dose rate and the discrimination of sub-types of translocations on persistence. (author)

  12. Integrative analyses of miRNA and proteomics identify potential biological pathways associated with onset of pulmonary fibrosis in the bleomycin rat model

    International Nuclear Information System (INIS)

    Fukunaga, Satoki; Kakehashi, Anna; Sumida, Kayo; Kushida, Masahiko; Asano, Hiroyuki; Gi, Min; Wanibuchi, Hideki

    2015-01-01

    To determine miRNAs and their predicted target proteins regulatory networks which are potentially involved in onset of pulmonary fibrosis in the bleomycin rat model, we conducted integrative miRNA microarray and iTRAQ-coupled LC-MS/MS proteomic analyses, and evaluated the significance of altered biological functions and pathways. We observed that alterations of miRNAs and proteins are associated with the early phase of bleomycin-induced pulmonary fibrosis, and identified potential target pairs by using ingenuity pathway analysis. Using the data set of these alterations, it was demonstrated that those miRNAs, in association with their predicted target proteins, are potentially involved in canonical pathways reflective of initial epithelial injury and fibrogenic processes, and biofunctions related to induction of cellular development, movement, growth, and proliferation. Prediction of activated functions suggested that lung cells acquire proliferative, migratory, and invasive capabilities, and resistance to cell death especially in the very early phase of bleomycin-induced pulmonary fibrosis. The present study will provide new insights for understanding the molecular pathogenesis of idiopathic pulmonary fibrosis. - Highlights: • We analyzed bleomycin-induced pulmonary fibrosis in the rat. • Integrative analyses of miRNA microarray and proteomics were conducted. • We determined the alterations of miRNAs and their potential target proteins. • The alterations may control biological functions and pathways in pulmonary fibrosis. • Our result may provide new insights of pulmonary fibrosis

  13. Integrative analyses of miRNA and proteomics identify potential biological pathways associated with onset of pulmonary fibrosis in the bleomycin rat model

    Energy Technology Data Exchange (ETDEWEB)

    Fukunaga, Satoki [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 3-1-98 Kasugade-Naka, Konohana-ku, Osaka 554-8558 (Japan); Kakehashi, Anna [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Sumida, Kayo; Kushida, Masahiko; Asano, Hiroyuki [Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 3-1-98 Kasugade-Naka, Konohana-ku, Osaka 554-8558 (Japan); Gi, Min [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Wanibuchi, Hideki, E-mail: wani@med.osaka-cu.ac.jp [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan)

    2015-08-01

    To determine miRNAs and their predicted target proteins regulatory networks which are potentially involved in onset of pulmonary fibrosis in the bleomycin rat model, we conducted integrative miRNA microarray and iTRAQ-coupled LC-MS/MS proteomic analyses, and evaluated the significance of altered biological functions and pathways. We observed that alterations of miRNAs and proteins are associated with the early phase of bleomycin-induced pulmonary fibrosis, and identified potential target pairs by using ingenuity pathway analysis. Using the data set of these alterations, it was demonstrated that those miRNAs, in association with their predicted target proteins, are potentially involved in canonical pathways reflective of initial epithelial injury and fibrogenic processes, and biofunctions related to induction of cellular development, movement, growth, and proliferation. Prediction of activated functions suggested that lung cells acquire proliferative, migratory, and invasive capabilities, and resistance to cell death especially in the very early phase of bleomycin-induced pulmonary fibrosis. The present study will provide new insights for understanding the molecular pathogenesis of idiopathic pulmonary fibrosis. - Highlights: • We analyzed bleomycin-induced pulmonary fibrosis in the rat. • Integrative analyses of miRNA microarray and proteomics were conducted. • We determined the alterations of miRNAs and their potential target proteins. • The alterations may control biological functions and pathways in pulmonary fibrosis. • Our result may provide new insights of pulmonary fibrosis.

  14. Electroencephalographic power and coherence analyses suggest altered brain function in abstinent male heroin-dependent patients

    NARCIS (Netherlands)

    Franken, Ingmar H. A.; Stam, Cornelis J.; Hendriks, Vincent M.; van den Brink, Wim

    2004-01-01

    Previous studies have shown that drug abuse is associated with altered brain function. However, studies of heroin abuse-related brain dysfunctions are scarce. Electroencephalographic ( EEG) power and coherence analyses are two important tools for examining the effects of drugs on brain function. In

  15. Influence of assessment setting on the results of functional analyses of problem behavior

    NARCIS (Netherlands)

    Lang, R.B.; Sigafoos, J.; Lancioni, G.E.; Didden, H.C.M.; Rispoli, M.

    2010-01-01

    Analogue functional analyses are widely used to identify the operant function of problem behavior in individuals with developmental disabilities. Because problem behavior often occurs across multiple settings (e.g., homes, schools, outpatient clinics), it is important to determine whether the

  16. AFM imaging of functionalized carbon nanotubes on biological membranes

    International Nuclear Information System (INIS)

    Lamprecht, C; Danzberger, J; Rangl, M; Gruber, H J; Hinterdorfer, P; Kienberger, F; Ebner, A; Liashkovich, I; Neves, V; Heister, E; Coley, H M; McFadden, J; Flahaut, E

    2009-01-01

    Multifunctional carbon nanotubes are promising for biomedical applications as their nano-size, together with their physical stability, gives access into the cell and various cellular compartments including the nucleus. However, the direct and label-free detection of carbon nanotube uptake into cells is a challenging task. The atomic force microscope (AFM) is capable of resolving details of cellular surfaces at the nanometer scale and thus allows following of the docking of carbon nanotubes to biological membranes. Here we present topographical AFM images of non-covalently functionalized single walled (SWNT) and double walled carbon nanotubes (DWNT) immobilized on different biological membranes, such as plasma membranes and nuclear envelopes, as well as on a monolayer of avidin molecules. We were able to visualize DWNT on the nuclear membrane while at the same time resolving individual nuclear pore complexes. Furthermore, we succeeded in localizing individual SWNT at the border of incubated cells and in identifying bundles of DWNT on cell surfaces by AFM imaging.

  17. Biological activity of lactoferrin-functionalized biomimetic hydroxyapatite nanocrystals

    Directory of Open Access Journals (Sweden)

    Nocerino N

    2014-03-01

    Full Text Available Nunzia Nocerino,1 Andrea Fulgione,1 Marco Iannaccone,1 Laura Tomasetta,1 Flora Ianniello,1 Francesca Martora,1 Marco Lelli,2 Norberto Roveri,2 Federico Capuano,3 Rosanna Capparelli1 1Department of Agriculture Special Biotechnology Center Federico II, CeBIOTEC Biotechnology, University of Naples Federico II, Naples, 2Department of Chemistry, G Ciamician, Alma Mater Studiorum, University of Bologna, Bologna, 3Department of Food Inspection IZS ME, Naples, Italy Abstract: The emergence of bacterial strains resistant to antibiotics is a general public health problem. Progress in developing new molecules with antimicrobial properties has been made. In this study, we evaluated the biological activity of a hybrid nanocomposite composed of synthetic biomimetic hydroxyapatite surface-functionalized by lactoferrin (LF-HA. We evaluated the antimicrobial, anti-inflammatory, and antioxidant properties of LF-HA and found that the composite was active against both Gram-positive and Gram-negative bacteria, and that it modulated proinflammatory and anti-inflammatory responses and enhanced antioxidant properties as compared with LF alone. These results indicate the possibility of using LF-HA as an antimicrobial system and biomimetic hydroxyapatite as a candidate for innovative biomedical applications. Keywords: lactoferrin, hydroxyapatite nanocrystals, biomimetism, biological activity, drug delivery

  18. Click Chemistry Mediated Functionalization of Vertical Nanowires for Biological Applications.

    Science.gov (United States)

    Vutti, Surendra; Schoffelen, Sanne; Bolinsson, Jessica; Buch-Månson, Nina; Bovet, Nicolas; Nygård, Jesper; Martinez, Karen L; Meldal, Morten

    2016-01-11

    Semiconductor nanowires (NWs) are gaining significant importance in various biological applications, such as biosensing and drug delivery. Efficient and controlled immobilization of biomolecules on the NW surface is crucial for many of these applications. Here, we present for the first time the use of the Cu(I) -catalyzed alkyne-azide cycloaddition and its strain-promoted variant for the covalent functionalization of vertical NWs with peptides and proteins. The potential of the approach was demonstrated in two complementary applications of measuring enzyme activity and protein binding, which is of general interest for biological studies. The attachment of a peptide substrate provided NW arrays for the detection of protease activity. In addition, green fluorescent protein was immobilized in a site-specific manner and recognized by antibody binding to demonstrate the proof-of-concept for the use of covalently modified NWs for diagnostic purposes using minute amounts of material. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Linking biological soil crust diversity to ecological functions

    Science.gov (United States)

    Glaser, Karin; Borchhardt, Nadine; Schulz, Karoline; Mikhailyuk, Tatiana; Baumann, Karen; Leinweber, Peter; Ulf, Karsten

    2016-04-01

    Biological soil crusts (BSCs) are an association of different microorganisms and soil particles in the top millimeters of the soil. They are formed by algae, cyanobacteria, microfungi, bacteria, bryophytes and lichens in various compositions. Our aim was to determine and compare the biodiversity of all occurring organisms in biogeographically different habitats, ranging from polar (both Arctic and Antarctic), subpolar (Scandinavia), temperate (Germany) to dry regions (Chile). The combination of microscopy and molecular techniques (next-generation sequencing) revealed highly diverse crust communities, whose composition clustered by region and correlates with habitat characteristics such as water content. The BSC biodiversity was then linked to the ecological function of the crusts. The functional role of the BSCs in the biogeochemical cycles of carbon, nitrogen and phosphorous is evaluated using an array of state of the art soil chemistry methods including Py-FIMS (pyrolysis field ionization mass spectrometry) and XANES (x-ray absorbance near edge structure). Total P as well as P fractions were quantified in all BSCs, adjacent soil underneath and comparable nearby soil of BSC-free areas revealing a remarkable accumulation of total phosphorous and a distinct pattern of P fractions in the crust. Further, we observed an indication of a different P-speciation composition in the crust compared with BSC-free soil. The data allow answering the question whether BSCs act as sink or source for these compounds, and how biodiversity controls the biogeochemical function of BSCs.

  20. A Synthetic Biology Framework for Programming Eukaryotic Transcription Functions

    Science.gov (United States)

    Khalil, Ahmad S.; Lu, Timothy K.; Bashor, Caleb J.; Ramirez, Cherie L.; Pyenson, Nora C.; Joung, J. Keith; Collins, James J.

    2013-01-01

    SUMMARY Eukaryotic transcription factors (TFs) perform complex and combinatorial functions within transcriptional networks. Here, we present a synthetic framework for systematically constructing eukaryotic transcription functions using artificial zinc fingers, modular DNA-binding domains found within many eukaryotic TFs. Utilizing this platform, we construct a library of orthogonal synthetic transcription factors (sTFs) and use these to wire synthetic transcriptional circuits in yeast. We engineer complex functions, such as tunable output strength and transcriptional cooperativity, by rationally adjusting a decomposed set of key component properties, e.g., DNA specificity, affinity, promoter design, protein-protein interactions. We show that subtle perturbations to these properties can transform an individual sTF between distinct roles (activator, cooperative factor, inhibitory factor) within a transcriptional complex, thus drastically altering the signal processing behavior of multi-input systems. This platform provides new genetic components for synthetic biology and enables bottom-up approaches to understanding the design principles of eukaryotic transcriptional complexes and networks. PMID:22863014

  1. Biological effects of simple changes in functionality on rhodium metalloinsertors

    Science.gov (United States)

    Weidmann, Alyson G.; Komor, Alexis C.; Barton, Jacqueline K.

    2013-01-01

    DNA mismatch repair (MMR) is crucial to ensuring the fidelity of the genome. The inability to correct single base mismatches leads to elevated mutation rates and carcinogenesis. Using metalloinsertors–bulky metal complexes that bind with high specificity to mismatched sites in the DNA duplex–our laboratory has adopted a new chemotherapeutic strategy through the selective targeting of MMR-deficient cells, that is, those that have a propensity for cancerous transformation. Rhodium metalloinsertors display inhibitory effects selectively in cells that are deficient in the MMR machinery, consistent with this strategy. However, a highly sensitive structure–function relationship is emerging with the development of new complexes that highlights the importance of subcellular localization. We have found that small structural modifications, for example a hydroxyl versus a methyl functional group, can yield profound differences in biological function. Despite similar binding affinities and selectivities for DNA mismatches, only one metalloinsertor shows selective inhibition of cellular proliferation in MMR-deficient versus -proficient cells. Studies of whole-cell, nuclear and mitochondrial uptake reveal that this selectivity depends upon targeting DNA mismatches in the cell nucleus. PMID:23776288

  2. Preservation of pathological tissue specimens by freeze-drying for immunohistochemical staining and various molecular biological analyses.

    Science.gov (United States)

    Matsuo, S; Sugiyama, T; Okuyama, T; Yoshikawa, K; Honda, K; Takahashi, R; Maeda, S

    1999-05-01

    Conditions of preserving DNA, RNA and protein in pathological specimens are of great importance as degradation of such macromolecules would critically affect results of molecular biological analysis. The feasibility of freeze-drying as a means of preserving pathological tissue samples for molecular analysis has previously been shown. In the present study, further tests on long-term storage conditions and analyses of freeze-dried samples by polymerase chain reaction (PCR), reverse transcriptase (RT)-PCR, western blotting and immunohistochemistry are reported. Rat chromosomal DNA of freeze-dried samples stored for 4 years showed slight degradation while RNA degradation was more prominently seen at an earlier stage of storage. However, these 4 year DNA and RNA samples were still able to serve as a template for some PCR and RT-PCR analyses, respectively. Overexpression of c-erbB-2 and p53 protein was demonstrated by western blotting and immunohistochemical staining using freeze-dried human breast cancer tissues. Although macromolecules in freeze-dried samples degrade to some extent during the preservation period, they should still be of value for certain molecular biological analyses and morphological examination; hence, providing more convenient and inexpensive ways of pathological tissue storage.

  3. Chemical and Biological Analyses of the Essential Oils and Main Constituents of Piper Species

    Directory of Open Access Journals (Sweden)

    Leonor Laura Leon

    2012-02-01

    Full Text Available The essential oils obtained from leaves of Piper duckei and Piper demeraranum by hydrodistillation were analyzed by gas chromatography-mass spectrometry. The main constituents found in P. demeraranum oil were limonene (19.3% and β-elemene (33.1% and in P. duckei oil the major components found were germacrene D (14.7% and trans-caryophyllene (27.1%. P. demeraranum and P. duckei oils exhibited biological activity, with IC50 values between 15 to 76 μg mL−1 against two Leishmania species, P. duckei oil being the most active. The cytotoxicity of the essential oils on mice peritoneal macrophage cells was insignificant, compared with the toxicity of pentamidine. The main mono- and sesquiterpene, limonene (IC50 = 278 μM and caryophyllene (IC50 = 96 μM, were tested against the strains of Leishmania amazonensis, and the IC50 values of these compounds were lower than those found for the essential oils of the Piper species. The HET-CAM test was used to evaluate the irritation potential of these oils as topical products, showing that these oils can be used as auxiliary medication in cases of cutaneous leishmaniasis, with less side effects and lower costs.

  4. Transferability of results of cost utility analyses for biologicals in inflammatory conditions for Central and Eastern European countries.

    Science.gov (United States)

    Gulácsi, László; Rencz, Fanni; Péntek, Márta; Brodszky, Valentin; Lopert, Ruth; Hevér, Noémi V; Baji, Petra

    2014-05-01

    Several Central and Eastern European (CEE) countries require cost-utility analyses (CUAs) to support reimbursement formulary listing. However, CUAs informed by local evidence are often unavailable, and the cost-effectiveness of the several currently reimbursed biologicals is unclear. To estimate the cost-effectiveness as multiples of per capita GDP/quality adjusted life years (QALY) of four biologicals (infliximab, etanercept, adalimumab, golimumab) currently reimbursed in six CEE countries in six inflammatory rheumatoid and bowel disease conditions. Systematic literature review of published cost-utility analyses in the selected conditions, using the United Kingdom (UK) as reference country and with study selection criteria set to optimize the transfer of results to the CEEs. Prices in each CEE country were pro-rated against UK prices using purchasing power parity (PPP)-adjusted per capita GDP, and local GDP per capita/QALY ratios estimated. Central and Eastern European countries list prices were 144-333% higher than pro rata prices. Out of 85 CUAs identified by previous systematic literature reviews, 15 were selected as a convenience sample for estimating the cost-effectiveness of biologicals in the CEE countries in terms of per capita GDP/QALY. Per capita GDP/QALY values varied from 0.42 to 6.4 across countries and conditions (Bulgaria: 0.97-6.38; Czech Republic: 0.42-2.76; Hungary: 0.54-3.54; Poland: 0.59-3.90; Romania: 0.77-5.07; Slovakia: 0.55-3.61). While results must be interpreted with caution, calculating pro rata (cost-effective) prices and per capita GDP/QALY ratios based on CUAs can aid reimbursement decision-making in the absence of analyses using local data.

  5. Morphometric analyses of hominoid crania, probabilities of conspecificity and an approximation of a biological species constant.

    Science.gov (United States)

    Thackeray, J F; Dykes, S

    2016-02-01

    Thackeray has previously explored the possibility of using a morphometric approach to quantify the "amount" of variation within species and to assess probabilities of conspecificity when two fossil specimens are compared, instead of "pigeon-holing" them into discrete species. In an attempt to obtain a statistical (probabilistic) definition of a species, Thackeray has recognized an approximation of a biological species constant (T=-1.61) based on the log-transformed standard error of the coefficient m (log sem) in regression analysis of cranial and other data from pairs of specimens of conspecific extant species, associated with regression equations of the form y=mx+c where m is the slope and c is the intercept, using measurements of any specimen A (x axis), and any specimen B of the same species (y axis). The log-transformed standard error of the co-efficient m (log sem) is a measure of the degree of similarity between pairs of specimens, and in this study shows central tendency around a mean value of -1.61 and standard deviation 0.10 for modern conspecific specimens. In this paper we focus attention on the need to take into account the range of difference in log sem values (Δlog sem or "delta log sem") obtained from comparisons when specimen A (x axis) is compared to B (y axis), and secondly when specimen A (y axis) is compared to B (x axis). Thackeray's approach can be refined to focus on high probabilities of conspecificity for pairs of specimens for which log sem is less than -1.61 and for which Δlog sem is less than 0.03. We appeal for the adoption of a concept here called "sigma taxonomy" (as opposed to "alpha taxonomy"), recognizing that boundaries between species are not always well defined. Copyright © 2015 Elsevier GmbH. All rights reserved.

  6. Phylogeny, Functional Annotation, and Protein Interaction Network Analyses of the Xenopus tropicalis Basic Helix-Loop-Helix Transcription Factors

    Directory of Open Access Journals (Sweden)

    Wuyi Liu

    2013-01-01

    Full Text Available The previous survey identified 70 basic helix-loop-helix (bHLH proteins, but it was proved to be incomplete, and the functional information and regulatory networks of frog bHLH transcription factors were not fully known. Therefore, we conducted an updated genome-wide survey in the Xenopus tropicalis genome project databases and identified 105 bHLH sequences. Among the retrieved 105 sequences, phylogenetic analyses revealed that 103 bHLH proteins belonged to 43 families or subfamilies with 46, 26, 11, 3, 15, and 4 members in the corresponding supergroups. Next, gene ontology (GO enrichment analyses showed 65 significant GO annotations of biological processes and molecular functions and KEGG pathways counted in frequency. To explore the functional pathways, regulatory gene networks, and/or related gene groups coding for Xenopus tropicalis bHLH proteins, the identified bHLH genes were put into the databases KOBAS and STRING to get the signaling information of pathways and protein interaction networks according to available public databases and known protein interactions. From the genome annotation and pathway analysis using KOBAS, we identified 16 pathways in the Xenopus tropicalis genome. From the STRING interaction analysis, 68 hub proteins were identified, and many hub proteins created a tight network or a functional module within the protein families.

  7. Pectin: cell biology and prospects for functional analysis.

    Science.gov (United States)

    Willats, W G; McCartney, L; Mackie, W; Knox, J P

    2001-09-01

    Pectin is a major component of primary cell walls of all land plants and encompasses a range of galacturonic acid-rich polysaccharides. Three major pectic polysaccharides (homogalacturonan, rhamnogalacturonan-I and rhamnogalacturonan-II) are thought to occur in all primary cell walls. This review surveys what is known about the structure and function of these pectin domains. The high degree of structural complexity and heterogeneity of the pectic matrix is produced both during biosynthesis in the endomembrane system and as a result of the action of an array of wall-based pectin-modifying enzymes. Recent developments in analytical techniques and in the generation of anti-pectin probes have begun to place the structural complexity of pectin in cell biological and developmental contexts. The in muro de-methyl-esterification of homogalacturonan by pectin methyl esterases is emerging as a key process for the local modulation of matrix properties. Rhamnogalacturonan-I comprises a highly diverse population of spatially and developmentally regulated polymers, whereas rhamnogalacturonan-II appears to be a highly conserved and stable pectic domain. Current knowledge of biosynthetic enzymes, plant and microbial pectinases and the interactions of pectin with other cell wall components and the impact of molecular genetic approaches are reviewed in terms of the functional analysis of pectic polysaccharides in plant growth and development.

  8. Sample heterogeneity in unipolar depression as assessed by functional connectivity analyses is dominated by general disease effects.

    Science.gov (United States)

    Feder, Stephan; Sundermann, Benedikt; Wersching, Heike; Teuber, Anja; Kugel, Harald; Teismann, Henning; Heindel, Walter; Berger, Klaus; Pfleiderer, Bettina

    2017-11-01

    Combinations of resting-state fMRI and machine-learning techniques are increasingly employed to develop diagnostic models for mental disorders. However, little is known about the neurobiological heterogeneity of depression and diagnostic machine learning has mainly been tested in homogeneous samples. Our main objective was to explore the inherent structure of a diverse unipolar depression sample. The secondary objective was to assess, if such information can improve diagnostic classification. We analyzed data from 360 patients with unipolar depression and 360 non-depressed population controls, who were subdivided into two independent subsets. Cluster analyses (unsupervised learning) of functional connectivity were used to generate hypotheses about potential patient subgroups from the first subset. The relationship of clusters with demographical and clinical measures was assessed. Subsequently, diagnostic classifiers (supervised learning), which incorporated information about these putative depression subgroups, were trained. Exploratory cluster analyses revealed two weakly separable subgroups of depressed patients. These subgroups differed in the average duration of depression and in the proportion of patients with concurrently severe depression and anxiety symptoms. The diagnostic classification models performed at chance level. It remains unresolved, if subgroups represent distinct biological subtypes, variability of continuous clinical variables or in part an overfitting of sparsely structured data. Functional connectivity in unipolar depression is associated with general disease effects. Cluster analyses provide hypotheses about potential depression subtypes. Diagnostic models did not benefit from this additional information regarding heterogeneity. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Functional anthology of intrinsic disorder. 1. Biological processes and functions of proteins with long disordered regions.

    Science.gov (United States)

    Xie, Hongbo; Vucetic, Slobodan; Iakoucheva, Lilia M; Oldfield, Christopher J; Dunker, A Keith; Uversky, Vladimir N; Obradovic, Zoran

    2007-05-01

    Identifying relationships between function, amino acid sequence, and protein structure represents a major challenge. In this study, we propose a bioinformatics approach that identifies functional keywords in the Swiss-Prot database that correlate with intrinsic disorder. A statistical evaluation is employed to rank the significance of these correlations. Protein sequence data redundancy and the relationship between protein length and protein structure were taken into consideration to ensure the quality of the statistical inferences. Over 200,000 proteins from the Swiss-Prot database were analyzed using this approach. The predictions of intrinsic disorder were carried out using PONDR VL3E predictor of long disordered regions that achieves an accuracy of above 86%. Overall, out of the 710 Swiss-Prot functional keywords that were each associated with at least 20 proteins, 238 were found to be strongly positively correlated with predicted long intrinsically disordered regions, whereas 302 were strongly negatively correlated with such regions. The remaining 170 keywords were ambiguous without strong positive or negative correlation with the disorder predictions. These functions cover a large variety of biological activities and imply that disordered regions are characterized by a wide functional repertoire. Our results agree well with literature findings, as we were able to find at least one illustrative example of functional disorder or order shown experimentally for the vast majority of keywords showing the strongest positive or negative correlation with intrinsic disorder. This work opens a series of three papers, which enriches the current view of protein structure-function relationships, especially with regards to functionalities of intrinsically disordered proteins, and provides researchers with a novel tool that could be used to improve the understanding of the relationships between protein structure and function. The first paper of the series describes our

  10. Functional Anthology of Intrinsic Disorder. I. Biological Processes and Functions of Proteins with Long Disordered Regions

    Science.gov (United States)

    Xie, Hongbo; Vucetic, Slobodan; Iakoucheva, Lilia M.; Oldfield, Christopher J.; Dunker, A. Keith; Uversky, Vladimir N.; Obradovic, Zoran

    2008-01-01

    Identifying relationships between function, amino acid sequence and protein structure represents a major challenge. In this study we propose a bioinformatics approach that identifies functional keywords in the Swiss-Prot database that correlate with intrinsic disorder. A statistical evaluation is employed to rank the significance of these correlations. Protein sequence data redundancy and the relationship between protein length and protein structure were taken into consideration to ensure the quality of the statistical inferences. Over 200,000 proteins from Swiss-Prot database were analyzed using this approach. The predictions of intrinsic disorder were carried out using PONDR VL3E predictor of long disordered regions that achieves an accuracy of above 86%. Overall, out of the 710 Swiss-Prot functional keywords that were each associated with at least 20 proteins, 238 were found to be strongly positively correlated with predicted long intrinsically disordered regions, whereas 302 were strongly negatively correlated with such regions. The remaining 170 keywords were ambiguous without strong positive or negative correlation with the disorder predictions. These functions cover a large variety of biological activities and imply that disordered regions are characterized by a wide functional repertoire. Our results agree well with literature findings, as we were able to find at least one illustrative example of functional disorder or order shown experimentally for the vast majority of keywords showing the strongest positive or negative correlation with intrinsic disorder. This work opens a series of three papers, which enriches the current view of protein structure-function relationships, especially with regards to functionalities of intrinsically disordered proteins and provides researchers with a novel tool that could be used to improve the understanding of the relationships between protein structure and function. The first paper of the series describes our statistical

  11. Lessons we learned from high-throughput and top-down systems biology analyses about glioma stem cells.

    Science.gov (United States)

    Mock, Andreas; Chiblak, Sara; Herold-Mende, Christel

    2014-01-01

    A growing body of evidence suggests that glioma stem cells (GSCs) account for tumor initiation, therapy resistance, and the subsequent regrowth of gliomas. Thus, continuous efforts have been undertaken to further characterize this subpopulation of less differentiated tumor cells. Although we are able to enrich GSCs, we still lack a comprehensive understanding of GSC phenotypes and behavior. The advent of high-throughput technologies raised hope that incorporation of these newly developed platforms would help to tackle such questions. Since then a couple of comparative genome-, transcriptome- and proteome-wide studies on GSCs have been conducted giving new insights in GSC biology. However, lessons had to be learned in designing high-throughput experiments and some of the resulting conclusions fell short of expectations because they were performed on only a few GSC lines or at one molecular level instead of an integrative poly-omics approach. Despite these shortcomings, our knowledge of GSC biology has markedly expanded due to a number of survival-associated biomarkers as well as glioma-relevant signaling pathways and therapeutic targets being identified. In this article we review recent findings obtained by comparative high-throughput analyses of GSCs. We further summarize fundamental concepts of systems biology as well as its applications for glioma stem cell research.

  12. Analysing Symbolic Expressions in Secondary School Chemistry: Their Functions and Implications for Pedagogy

    Science.gov (United States)

    Liu, Yu; Taber, Keith S.

    2016-01-01

    Symbolic expressions are essential resources for producing knowledge, yet they are a source of learning difficulties in chemistry education. This study aims to employ social semiotics to analyse the symbolic representation of chemistry from two complementary perspectives, referred to here as contextual (i.e., historical) and functional. First, the…

  13. Redox Biology in Neurological Function, Dysfunction, and Aging.

    Science.gov (United States)

    Franco, Rodrigo; Vargas, Marcelo R

    2018-04-23

    Reduction oxidation (redox) reactions are central to life and when altered, they can promote disease progression. In the brain, redox homeostasis is recognized to be involved in all aspects of central nervous system (CNS) development, function, aging, and disease. Recent studies have uncovered the diverse nature by which redox reactions and homeostasis contribute to brain physiology, and when dysregulated to pathological consequences. Redox reactions go beyond what is commonly described as oxidative stress and involve redox mechanisms linked to signaling and metabolism. In contrast to the nonspecific nature of oxidative damage, redox signaling involves specific oxidation/reduction reactions that regulate a myriad of neurological processes such as neurotransmission, homeostasis, and degeneration. This Forum is focused on the role of redox metabolism and signaling in the brain. Six review articles from leading scientists in the field that appraise the role of redox metabolism and signaling in different aspects of brain biology including neurodevelopment, neurotransmission, aging, neuroinflammation, neurodegeneration, and neurotoxicity are included. An original research article exemplifying these concepts uncovers a novel link between oxidative modifications, redox signaling, and neurodegeneration. This Forum highlights the recent advances in the field and we hope it encourages future research aimed to understand the mechanisms by which redox metabolism and signaling regulate CNS physiology and pathophysiology. Antioxid. Redox Signal. 00, 000-000.

  14. Function and regulation of lipid biology in Caenorhabditis elegans aging

    Directory of Open Access Journals (Sweden)

    Nicole Shangming Hou

    2012-05-01

    Full Text Available Rapidly expanding aging populations and a concomitant increase in the prevalence of age-related diseases are global health problems today. Over the past three decades, a large body of work has led to the identification of genes and regulatory networks that affect longevity and health span, often benefitting from the tremendous power of genetics in vertebrate and invertebrate model organisms. Interestingly, many of these factors appear linked to lipids, important molecules that participate in cellular signaling, energy metabolism, and structural compartmentalization. Despite the putative link between lipids and longevity, the role of lipids in aging remains poorly understood. Emerging data from the model organism Caenorhabditis elegans suggest that lipid composition may change during aging, as several pathways that influence aging also regulate lipid metabolism enzymes; moreover, some of these enzymes apparently play key roles in the pathways that affect the rate of aging. By understanding how lipid biology is regulated during C. elegans aging, and how it impacts molecular, cellular and organismal function, we may gain insight into novel ways to delay aging using genetic or pharmacological interventions. In the present review we discuss recent insights into the roles of lipids in C. elegans aging, including regulatory roles played by lipids themselves, the regulation of lipid metabolic enzymes, and the roles of lipid metabolism genes in the pathways that affect aging.

  15. Analyses of Dynein Heavy Chain Mutations Reveal Complex Interactions Between Dynein Motor Domains and Cellular Dynein Functions

    Science.gov (United States)

    Sivagurunathan, Senthilkumar; Schnittker, Robert R.; Razafsky, David S.; Nandini, Swaran; Plamann, Michael D.; King, Stephen J.

    2012-01-01

    Cytoplasmic dynein transports cargoes for a variety of crucial cellular functions. However, since dynein is essential in most eukaryotic organisms, the in-depth study of the cellular function of dynein via genetic analysis of dynein mutations has not been practical. Here, we identify and characterize 34 different dynein heavy chain mutations using a genetic screen of the ascomycete fungus Neurospora crassa, in which dynein is nonessential. Interestingly, our studies show that these mutations segregate into five different classes based on the in vivo localization of the mutated dynein motors. Furthermore, we have determined that the different classes of dynein mutations alter vesicle trafficking, microtubule organization, and nuclear distribution in distinct ways and require dynactin to different extents. In addition, biochemical analyses of dynein from one mutant strain show a strong correlation between its in vitro biochemical properties and the aberrant intracellular function of that altered dynein. When the mutations were mapped to the published dynein crystal structure, we found that the three-dimensional structural locations of the heavy chain mutations were linked to particular classes of altered dynein functions observed in cells. Together, our data indicate that the five classes of dynein mutations represent the entrapment of dynein at five separate points in the dynein mechanochemical and transport cycles. We have developed N. crassa as a model system where we can dissect the complexities of dynein structure, function, and interaction with other proteins with genetic, biochemical, and cell biological studies. PMID:22649085

  16. Phytochrome from Green Plants: Properties and biological Function

    Energy Technology Data Exchange (ETDEWEB)

    Quail, Peter H.

    2014-07-25

    Pfr conformer reverses this activity upon initial light exposure, inducing the switch to photomorphogenic development. This reversal involves light-triggered translocation of the photoactivated phy molecule into the nucleus where it interacts with PIF-family members, inducing rapid phosphorylation and degradation of the PIFs via the ubiquitin-proteasome system. This degradation in turn elicits rapid alterations in gene expression that drive the deetiolation transition. This project has made considerable progress in defining phy-PIF signaling activity in controlling the SAR. The biological functions of the multiple PIF-family members in controlling the SAR, including dissection of the relative contributions of the individual PIFs to this process, as well as to diurnal growth-control oscillations, have been investigated using higher-order pif-mutant combinations. Using microarray analysis of a quadruple pif mutant we have defined the shade-induced, PIF-regulated transcriptional network genome-wide. This has revealed that a dynamic antagonism between the phys and PIFs generates selective reciprocal responses during deetiolation and the SAR in a rapidly light-responsive transcriptional network. Using integrated RNA-seq and ChIP-seq analysis of higher order pif-mutant combinations, we have defined the direct gene-targets of PIF transcriptional regulation, and have obtained evidence that this regulation involves differential direct targeting of rapidly light-responsive genes by the individual PIF-family members. This project has provided significant advances in our understanding of the molecular mechanisms by which the phy-PIF photosensory signaling pathway regulates an important bioenergy-related plant response to the light environment. The identification of molecular targets in the primary transcriptional-regulatory circuitry of this pathway has the potential to enable genetic or reverse-genetic manipulation of the partitioning of carbon between reproductive and

  17. Individual-based analyses reveal limited functional overlap in a coral reef fish community.

    Science.gov (United States)

    Brandl, Simon J; Bellwood, David R

    2014-05-01

    Detailed knowledge of a species' functional niche is crucial for the study of ecological communities and processes. The extent of niche overlap, functional redundancy and functional complementarity is of particular importance if we are to understand ecosystem processes and their vulnerability to disturbances. Coral reefs are among the most threatened marine systems, and anthropogenic activity is changing the functional composition of reefs. The loss of herbivorous fishes is particularly concerning as the removal of algae is crucial for the growth and survival of corals. Yet, the foraging patterns of the various herbivorous fish species are poorly understood. Using a multidimensional framework, we present novel individual-based analyses of species' realized functional niches, which we apply to a herbivorous coral reef fish community. In calculating niche volumes for 21 species, based on their microhabitat utilization patterns during foraging, and computing functional overlaps, we provide a measurement of functional redundancy or complementarity. Complementarity is the inverse of redundancy and is defined as less than 50% overlap in niche volumes. The analyses reveal extensive complementarity with an average functional overlap of just 15.2%. Furthermore, the analyses divide herbivorous reef fishes into two broad groups. The first group (predominantly surgeonfishes and parrotfishes) comprises species feeding on exposed surfaces and predominantly open reef matrix or sandy substrata, resulting in small niche volumes and extensive complementarity. In contrast, the second group consists of species (predominantly rabbitfishes) that feed over a wider range of microhabitats, penetrating the reef matrix to exploit concealed surfaces of various substratum types. These species show high variation among individuals, leading to large niche volumes, more overlap and less complementarity. These results may have crucial consequences for our understanding of herbivorous processes on

  18. Coupling Front-End Separations, Ion Mobility Spectrometry, and Mass Spectrometry For Enhanced Multidimensional Biological and Environmental Analyses

    Science.gov (United States)

    Zheng, Xueyun; Wojcik, Roza; Zhang, Xing; Ibrahim, Yehia M.; Burnum-Johnson, Kristin E.; Orton, Daniel J.; Monroe, Matthew E.; Moore, Ronald J.; Smith, Richard D.; Baker, Erin S.

    2017-01-01

    Ion mobility spectrometry (IMS) is a widely used analytical technique for rapid molecular separations in the gas phase. Though IMS alone is useful, its coupling with mass spectrometry (MS) and front-end separations is extremely beneficial for increasing measurement sensitivity, peak capacity of complex mixtures, and the scope of molecular information available from biological and environmental sample analyses. In fact, multiple disease screening and environmental evaluations have illustrated that the IMS-based multidimensional separations extract information that cannot be acquired with each technique individually. This review highlights three-dimensional separations using IMS-MS in conjunction with a range of front-end techniques, such as gas chromatography, supercritical fluid chromatography, liquid chromatography, solid-phase extractions, capillary electrophoresis, field asymmetric ion mobility spectrometry, and microfluidic devices. The origination, current state, various applications, and future capabilities of these multidimensional approaches are described in detail to provide insight into their uses and benefits. PMID:28301728

  19. Coupling Front-End Separations, Ion Mobility Spectrometry, and Mass Spectrometry For Enhanced Multidimensional Biological and Environmental Analyses

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Xueyun; Wojcik, Roza; Zhang, Xing; Ibrahim, Yehia M.; Burnum-Johnson, Kristin E.; Orton, Daniel J.; Monroe, Matthew E.; Moore, Ronald J.; Smith, Richard D.; Baker, Erin M.

    2017-06-12

    Ion mobility spectrometry (IMS) is a widely used analytical technique for rapid molecular separations in the gas phase. IMS alone is useful, but its coupling with mass spectrometry (MS) and front-end separations has been extremely beneficial for increasing measurement sensitivity, peak capacity of complex mixtures, and the scope of molecular information in biological and environmental sample analyses. Multiple studies in disease screening and environmental evaluations have even shown these IMS-based multidimensional separations extract information not possible with each technique individually. This review highlights 3-dimensional separations using IMS-MS in conjunction with a range of front-end techniques, such as gas chromatography (GC), supercritical fluid chromatography (SFC), liquid chromatography (LC), solid phase extractions (SPE), capillary electrophoresis (CE), field asymmetric ion mobility spectrometry (FAIMS), and microfluidic devices. The origination, current state, various applications, and future capabilities for these multidimensional approaches are described to provide insight into the utility and potential of each technique.

  20. Using analyses of amino Acid coevolution to understand protein structure and function.

    Science.gov (United States)

    Ashenberg, Orr; Laub, Michael T

    2013-01-01

    Determining which residues of a protein contribute to a specific function is a difficult problem. Analyses of amino acid covariation within a protein family can serve as a useful guide by identifying residues that are functionally coupled. Covariation analyses have been successfully used on several different protein families to identify residues that work together to promote folding, enable protein-protein interactions, or contribute to an enzymatic activity. Covariation is a statistical signal that can be measured in a multiple sequence alignment of homologous proteins. As sequence databases have expanded dramatically, covariation analyses have become easier and more powerful. In this chapter, we describe how functional covariation arises during the evolution of proteins and how this signal can be distinguished from various background signals. We discuss the basic methodology for performing amino acid covariation analysis, using bacterial two-component signal transduction proteins as an example. We provide practical suggestions for each step of the process including assembly of protein sequences, construction of a multiple sequence alignment, measurement of covariation, and analysis of results. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Comparative analyses identified species-specific functional roles in oral microbial genomes

    Science.gov (United States)

    Chen, Tsute; Gajare, Prasad; Olsen, Ingar; Dewhirst, Floyd E.

    2017-01-01

    ABSTRACT The advent of next generation sequencing is producing more genomic sequences for various strains of many human oral microbial species and allows for insightful functional comparisons at both intra- and inter-species levels. This study performed in-silico functional comparisons for currently available genomic sequences of major species associated with periodontitis including Aggregatibacter actinomycetemcomitans (AA), Porphyromonas gingivalis (PG), Treponema denticola (TD), and Tannerella forsythia (TF), as well as several cariogenic and commensal streptococcal species. Complete or draft sequences were annotated with the RAST to infer structured functional subsystems for each genome. The subsystems profiles were clustered to groups of functions with similar patterns. Functional enrichment and depletion were evaluated based on hypergeometric distribution to identify subsystems that are unique or missing between two groups of genomes. Unique or missing metabolic pathways and biological functions were identified in different species. For example, components involved in flagellar motility were found only in the motile species TD, as expected, with few exceptions scattered in several streptococcal species, likely associated with chemotaxis. Transposable elements were only found in the two Bacteroidales species PG and TF, and half of the AA genomes. Genes involved in CRISPR were prevalent in most oral species. Furthermore, prophage related subsystems were also commonly found in most species except for PG and Streptococcus mutans, in which very few genomes contain prophage components. Comparisons between pathogenic (P) and nonpathogenic (NP) genomes also identified genes potentially important for virulence. Two such comparisons were performed between AA (P) and several A. aphrophilus (NP) strains, and between S. mutans + S. sobrinus (P) and other oral streptococcal species (NP). This comparative genomics approach can be readily used to identify functions unique to

  2. Membrane Binding of Recoverin: From Mechanistic Understanding to Biological Functionality

    Czech Academy of Sciences Publication Activity Database

    Timr, S.; Pleskot, Roman; Kadlec, J.; Kohagen, M.; Magarkar, A.; Jungwirth, P.

    2017-01-01

    Roč. 3, č. 8 (2017), s. 868-874 ISSN 2374-7943 Institutional support: RVO:61389030 Keywords : recoverin * membrane * myristoyl Subject RIV: CF - Physical ; Theoretical Chemistry OBOR OECD: Cell biology Impact factor: 7.481, year: 2016

  3. Functional analyses of cellulose synthase genes in flax (Linum usitatissimum) by virus-induced gene silencing.

    Science.gov (United States)

    Chantreau, Maxime; Chabbert, Brigitte; Billiard, Sylvain; Hawkins, Simon; Neutelings, Godfrey

    2015-12-01

    Flax (Linum usitatissimum) bast fibres are located in the stem cortex where they play an important role in mechanical support. They contain high amounts of cellulose and so are used for linen textiles and in the composite industry. In this study, we screened the annotated flax genome and identified 14 distinct cellulose synthase (CESA) genes using orthologous sequences previously identified. Transcriptomics of 'primary cell wall' and 'secondary cell wall' flax CESA genes showed that some were preferentially expressed in different organs and stem tissues providing clues as to their biological role(s) in planta. The development for the first time in flax of a virus-induced gene silencing (VIGS) approach was used to functionally evaluate the biological role of different CESA genes in stem tissues. Quantification of transcript accumulation showed that in many cases, silencing not only affected targeted CESA clades, but also had an impact on other CESA genes. Whatever the targeted clade, inactivation by VIGS affected plant growth. In contrast, only clade 1- and clade 6-targeted plants showed modifications in outer-stem tissue organization and secondary cell wall formation. In these plants, bast fibre number and structure were severely impacted, suggesting that the targeted genes may play an important role in the establishment of the fibre cell wall. Our results provide new fundamental information about cellulose biosynthesis in flax that should facilitate future plant improvement/engineering. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  4. The functional and biological properties of whey proteins: prospects for the development of functional foods

    Directory of Open Access Journals (Sweden)

    H. J. T. KORHONEN

    2008-12-01

    Full Text Available Advances in processing technologies and the accumulation of scientific data on the functional and biological properties of whey components have contributed to the growing commercial valuation of cheese whey over the last decade. New membrane separation and chromatographic techniques have made it possible to fractionate and enrich various components of whey more efficiently than before. The specific properties of these components can now be examined in greater detail and new applications developed accordingly. The utilisation of cheese whey is evolving into a new industry producing a multitude of purified ingredients for numerous purposes. The most significant areas of R&D related to whey proteins include functional foods, the rheological properties of foodstuffs, and biopharmaceuticals.

  5. Lung function in idiopathic pulmonary fibrosis - extended analyses of the IFIGENIA trial

    Directory of Open Access Journals (Sweden)

    Verschakelen Johny

    2009-10-01

    Full Text Available Abstract Background The randomized placebo-controlled IFIGENIA-trial demonstrated that therapy with high-dose N-acetylcysteine (NAC given for one year, added to prednisone and azathioprine, significantly ameliorates (i.e. slows down disease progression in terms of vital capacity (VC (+9% and diffusing capacity (DLco (+24% in idiopathic pulmonary fibrosis (IPF. To better understand the clinical implications of these findings we performed additional, explorative analyses of the IFGENIA data set. Methods We analysed effects of NAC on VC, DLco, a composite physiologic index (CPI, and mortality in the 155 study-patients. Results In trial completers the functional indices did not change significantly with NAC, whereas most indices deteriorated with placebo; in non-completers the majority of indices worsened but decline was generally less pronounced in most indices with NAC than with placebo. Most categorical analyses of VC, DLco and CPI also showed favourable changes with NAC. The effects of NAC on VC, DLco and CPI were significantly better if the baseline CPI was 50 points or lower. Conclusion This descriptive analysis confirms and extends the favourable effects of NAC on lung function in IPF and emphasizes the usefulness of VC, DLco, and the CPI for the evaluation of a therapeutic effect. Most importantly, less progressed disease as indicated by a CPI of 50 points or lower at baseline was more responsive to therapy in this study. Trial Registration Registered at http://www.ClinicalTrials.gov; number NCT00639496.

  6. Characterization and functional analyses of the human G protein-coupled receptor kinase 4 gene promoter.

    Science.gov (United States)

    Hasenkamp, Sandra; Telgmann, Ralph; Staessen, Jan A; Hagedorn, Claudia; Dördelmann, Corinna; Bek, Martin; Brand-Herrmann, Stefan-Martin; Brand, Eva

    2008-10-01

    The G protein-coupled receptor kinase 4 is involved in renal sodium handling and blood pressure regulation. Missense variants have already been tested functionally and are associated with hypertension, but no data on promoter analyses are yet available. We scanned 94 hypertensive white subjects for genetic variation and performed promoter reporter gene analyses in HEK293T, COS7, and SaOs-2 cells. Transient transfections with various full lengths and wild-type deletion constructs revealed that 1851 bp of the flanking region and 275 bp of the 5'-untranslated region were sufficient for transcriptional activities and composed a powerful cis-active element in the distal 293 bp. The -1702T and +2T alleles resulted in drastic general reductions of promoter function, whereas an activity increasing effect of +268C was cell type specific. Electrophoretic mobility-shift assay, supershift, and cotransfection analyses of transcription factor binding sites predicted in silico (Alibaba2.1/Transfac7) resulted in allele-specific binding patterns of nuclear proteins and identified the participation of CCAAT/enhancer-binding protein transcription factor family members. The G protein-coupled receptor kinase 4 core promoter resides in the first 1851 bp upstream of its transcription start site. The 4 identified genetic variants within this region exert allele-specific impact on both cell type- and stimulation-dependent transcription and may affect the expression balance of renal G protein-coupled receptor kinase 4.

  7. Operational and biological analyses of branched water-adjustment and combined treatment of wastewater from a chemical industrial park.

    Science.gov (United States)

    Xu, Ming; Cao, Jiashun; Li, Chao; Tu, Yong; Wu, Haisuo; Liu, Weijing

    2018-01-01

    The combined biological processes of branched water-adjustment, chemical precipitation, hydrolysis acidification, secondary sedimentation, Anoxic/Oxic and activated carbon treatment were used for chemical industrial wastewater treatment in the Taihu Lake Basin. Full-scale treatment resulted in effluent chemical oxygen demand, total nitrogen, NH 3 -N and total phosphorus of 35.1, 5.20, 3.10 and 0.15 mg/L, respectively, with a total removal efficiency of 91.1%, 67.1%, 70.5% and 89.3%, respectively. In this process, short-circuited organic carbon from brewery wastewater was beneficial for denitrification and second-sulfate reduction. The concentration of effluent fluoride was 6.22 mg/L, which also met the primary standard. Gas Chromatography-Mass Spectrometry analysis revealed that many types of refractory compounds were present in the inflow. Microbial community analysis performed in the summer by PCR-denaturing gradient gel electrophoresis and MiSeq demonstrated that certain special functional bacteria, such as denitrificans, phosphorus-accumulating bacteria, sulfate- and perhafnate-reducing bacteria, aromatic compound-degrading bacteria and organic fluoride-degrading bacteria, present in the bio-tanks were responsible for the acceptable specific biological pollutant reduction achieved.

  8. Core microbial functional activities in ocean environments revealed by global metagenomic profiling analyses.

    Directory of Open Access Journals (Sweden)

    Ari J S Ferreira

    Full Text Available Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world's oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light.

  9. Core microbial functional activities in ocean environments revealed by global metagenomic profiling analyses.

    KAUST Repository

    Ferreira, Ari J S

    2014-06-12

    Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world\\'s oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs) of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light.

  10. Core microbial functional activities in ocean environments revealed by global metagenomic profiling analyses.

    KAUST Repository

    Ferreira, Ari J S; Siam, Rania; Setubal, Joã o C; Moustafa, Ahmed; Sayed, Ahmed; Chambergo, Felipe S; Dawe, Adam S; Ghazy, Mohamed A; Sharaf, Hazem; Ouf, Amged; Alam, Intikhab; Abdel-Haleem, Alyaa M; Lehvä slaiho, Heikki; Ramadan, Eman; Antunes, André ; Stingl, Ulrich; Archer, John A.C.; Jankovic, Boris R; Sogin, Mitchell; Bajic, Vladimir B.; El-Dorry, Hamza

    2014-01-01

    Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world's oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs) of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light.

  11. Lipid polymorphism and the functional roles of lipids in biological membranes

    NARCIS (Netherlands)

    Cullis, P.R.; Kruijff, B. de

    1979-01-01

    The reasons for the great variety of lipids found in biological membranes, and the relations between lipid composition and membrane function pose major unsolved problems in membrane biology. Perhaps the only major functional role of lipids which may be regarded as firmly established involves the

  12. Exploring candidate biological functions by Boolean Function Networks for Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Maria Simak

    Full Text Available The great amount of gene expression data has brought a big challenge for the discovery of Gene Regulatory Network (GRN. For network reconstruction and the investigation of regulatory relations, it is desirable to ensure directness of links between genes on a map, infer their directionality and explore candidate biological functions from high-throughput transcriptomic data. To address these problems, we introduce a Boolean Function Network (BFN model based on techniques of hidden Markov model (HMM, likelihood ratio test and Boolean logic functions. BFN consists of two consecutive tests to establish links between pairs of genes and check their directness. We evaluate the performance of BFN through the application to S. cerevisiae time course data. BFN produces regulatory relations which show consistency with succession of cell cycle phases. Furthermore, it also improves sensitivity and specificity when compared with alternative methods of genetic network reverse engineering. Moreover, we demonstrate that BFN can provide proper resolution for GO enrichment of gene sets. Finally, the Boolean functions discovered by BFN can provide useful insights for the identification of control mechanisms of regulatory processes, which is the special advantage of the proposed approach. In combination with low computational complexity, BFN can serve as an efficient screening tool to reconstruct genes relations on the whole genome level. In addition, the BFN approach is also feasible to a wide range of time course datasets.

  13. Design of Functional Polyesters for Electronic and Biological Applications

    OpenAIRE

    Nelson, Ashley Marie

    2015-01-01

    Melt polymerization and novel monomers enabled the synthesis of polyesters for electronic and biological applications. Inspiration from nature and a passion for environmental preservation instigated an emphasis on the incorporation of renewable resources into polymeric materials. Critical analysis of current research surrounding bisphenol-A replacements and ioncontaining segmented polyurethanes aided in identifying benchmark polymers, including limitations, challenges, and future needs. Struc...

  14. Oxidative metabolites of lycopene and their biological functions

    Science.gov (United States)

    To gain a better understanding of the beneficial biological activities of lycopene on cancer prevention, a greater knowledge of the metabolism of lycopene is needed. In particular, the identification of lycopene metabolites and oxidation products in vivo; the importance of tissue specific lycopene c...

  15. Click chemistry mediated functionalization of vertical nanowires for biological applications

    DEFF Research Database (Denmark)

    Vutti, Surendra; Schoffelen, Sanne; Bolinsson, Jessica

    2016-01-01

    is of general interest for biological studies. The attachment of a peptide substrate provided NW arrays for the detection of protease activity. In addition, green fluorescent protein was immobilized in a site-specific manner and recognized by antibody binding to demonstrate the proof-of-concept for the use...

  16. Procurement of a Nanoindenter for Structure-Function Analyses of Biologically Inspired High Performance Composite Materials

    Science.gov (United States)

    2012-01-13

    abalone shell (Figures 3, 4). Here, we can see that the damage is significantly mitigated in the nacreous regions while cracks formed in the Calcitic...properties. Page 5 / 11 Identifying the crack propagation mechanisms helps to identify new designs for impact resistant materials, so the...human tooth from dentin – dentin/ enamel junction – enamel . It is clear that higher resolution scans are necessary to interrogate local structure

  17. Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

    Directory of Open Access Journals (Sweden)

    Wenbo Tang

    Full Text Available Genome-wide association studies (GWAS have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function.We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1 in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis.The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7. In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8 at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively.In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function.

  18. Recent Advances in Momordica charantia: Functional Components and Biological Activities

    Directory of Open Access Journals (Sweden)

    Shuo Jia

    2017-11-01

    Full Text Available Momordica charantia L. (M. charantia, a member of the Cucurbitaceae family, is widely distributed in tropical and subtropical regions of the world. It has been used in folk medicine for the treatment of diabetes mellitus, and its fruit has been used as a vegetable for thousands of years. Phytochemicals including proteins, polysaccharides, flavonoids, triterpenes, saponins, ascorbic acid and steroids have been found in this plant. Various biological activities of M. charantia have been reported, such as antihyperglycemic, antibacterial, antiviral, antitumor, immunomodulation, antioxidant, antidiabetic, anthelmintic, antimutagenic, antiulcer, antilipolytic, antifertility, hepatoprotective, anticancer and anti-inflammatory activities. However, both in vitro and in vivo studies have also demonstrated that M. charantia may also exert toxic or adverse effects under different conditions. This review addresses the chemical constituents of M. charantia and discusses their pharmacological activities as well as their adverse effects, aimed at providing a comprehensive overview of the phytochemistry and biological activities of M. charantia.

  19. Recent Advances in Momordica charantia: Functional Components and Biological Activities.

    Science.gov (United States)

    Jia, Shuo; Shen, Mingyue; Zhang, Fan; Xie, Jianhua

    2017-11-28

    Momordica charantia L. ( M. charantia ), a member of the Cucurbitaceae family, is widely distributed in tropical and subtropical regions of the world. It has been used in folk medicine for the treatment of diabetes mellitus, and its fruit has been used as a vegetable for thousands of years. Phytochemicals including proteins, polysaccharides, flavonoids, triterpenes, saponins, ascorbic acid and steroids have been found in this plant. Various biological activities of M. charantia have been reported, such as antihyperglycemic, antibacterial, antiviral, antitumor, immunomodulation, antioxidant, antidiabetic, anthelmintic, antimutagenic, antiulcer, antilipolytic, antifertility, hepatoprotective, anticancer and anti-inflammatory activities. However, both in vitro and in vivo studies have also demonstrated that M. charantia may also exert toxic or adverse effects under different conditions. This review addresses the chemical constituents of M. charantia and discusses their pharmacological activities as well as their adverse effects, aimed at providing a comprehensive overview of the phytochemistry and biological activities of M. charantia .

  20. The effects of ropivacaine hydrochloride on platelet function: an assessment using the platelet function analyser (PFA-100).

    LENUS (Irish Health Repository)

    Porter, J

    2012-02-03

    Amide local anaesthetics impair blood clotting in a concentration-dependent manner by inhibition of platelet function and enhanced fibrinolysis. We hypothesised that the presence of ropivacaine in the epidural space could decrease the efficacy of an epidural blood patch, as this technique requires that the injected blood can clot in order to be effective. Ropivacaine is an aminoamide local anaesthetic used increasingly for epidural analgesia during labour. The concentration of local anaesthetic in blood achieved in the epidural space during the performance of an epidural blood patch is likely to be the greatest which occurs (intentionally) in any clinical setting. This study was undertaken to investigate whether concentrations of ropivacaine in blood, which could occur: (i) clinically in the epidural space and (ii) in plasma during an epidural infusion of ropivacaine, alter platelet function. A platelet function analyser (Dade PFA-100, Miami) was employed to assess the effects of ropivacaine-treated blood on platelet function. The greater concentrations of ropivacaine studied (3.75 and 1.88 mg x ml(-1)), which correspond to those which could occur in the epidural space, produced significant inhibition of platelet aggregation. We conclude that the presence of ropivacaine in the epidural space may decrease the efficacy of an early or prophylactic epidural blood patch.

  1. Statistical and extra-statistical considerations in differential item functioning analyses

    Directory of Open Access Journals (Sweden)

    G. K. Huysamen

    2004-10-01

    Full Text Available This article briefly describes the main procedures for performing differential item functioning (DIF analyses and points out some of the statistical and extra-statistical implications of these methods. Research findings on the sources of DIF, including those associated with translated tests, are reviewed. As DIF analyses are oblivious of correlations between a test and relevant criteria, the elimination of differentially functioning items does not necessarily improve predictive validity or reduce any predictive bias. The implications of the results of past DIF research for test development in the multilingual and multi-cultural South African society are considered. Opsomming Hierdie artikel beskryf kortliks die hoofprosedures vir die ontleding van differensiële itemfunksionering (DIF en verwys na sommige van die statistiese en buite-statistiese implikasies van hierdie metodes. ’n Oorsig word verskaf van navorsingsbevindings oor die bronne van DIF, insluitend dié by vertaalde toetse. Omdat DIF-ontledings nie die korrelasies tussen ’n toets en relevante kriteria in ag neem nie, sal die verwydering van differensieel-funksionerende items nie noodwendig voorspellingsgeldigheid verbeter of voorspellingsydigheid verminder nie. Die implikasies van vorige DIF-navorsingsbevindings vir toetsontwikkeling in die veeltalige en multikulturele Suid-Afrikaanse gemeenskap word oorweeg.

  2. Structural and functional analyses of the putrescine binding protein PotF from Xanthomonas citri

    Energy Technology Data Exchange (ETDEWEB)

    Santana, L.D.F.; Balan, A. [Laboratorio Nacional de Biociencias - LNBIO, Campinas, SP (Brazil)

    2012-07-01

    Full text: The focus of our group is to determinate the role of ABC transporters in the physiology and growth of Xanthomonas citri, a phytopathogenic bacteria that infects citrus plants causing significant losses for the economy. One of the ABC transporters identified in the X. citri genome and that was showed to be active during the infection in Citrus sinensis plants was the putrescine transporter. This transporter consists of two internal membrane proteins PotG and PotH that form a pore, a cytoplasmic protein that gives energy for the transport and the periplasmic-binding protein PotF, which is responsible for the affinity and specificity of the system. Its function is associated to the microbial carcinogenesis, biofilm formation, escape from phagolysosomes, bacteriocin production, toxin activity and protection from oxidative and acid stress. In this work, we show for the first time, the expression, purification, functional and structural analyses of the X. citri PotF protein. The PotF was expressed from Escherichia coli cells strain Arctic, as a 40 kDa soluble protein, after induction of IPTG for twenty four hours at thirteen deg C. Using immobilized metal affinity chromatography for purification, the protein was eluted in the fractions with 10-500 mM of imidazole. To test the folding and cability to bind putrescine, spectroscopic analyses were performed using circular dichroism and intrinsic fluorescence. The data showed that PotF suffers conformational changes in presence of ligands and in different pH, suggesting a possible interaction with the tested ligand. Moreover, based on bioinformatics studies and molecular modeling analyses, we showed that X. citri PotF is highly conserved when compared to orthologs present in other bacteria, including the residues that form the ligand-binding site. The production of PotF in a soluble and stable form will allow us to start the crystallization trials in attempt to solve its structure. (author)

  3. Structural and functional analyses of the putrescine binding protein PotF from Xanthomonas citri

    International Nuclear Information System (INIS)

    Santana, L.D.F.; Balan, A.

    2012-01-01

    Full text: The focus of our group is to determinate the role of ABC transporters in the physiology and growth of Xanthomonas citri, a phytopathogenic bacteria that infects citrus plants causing significant losses for the economy. One of the ABC transporters identified in the X. citri genome and that was showed to be active during the infection in Citrus sinensis plants was the putrescine transporter. This transporter consists of two internal membrane proteins PotG and PotH that form a pore, a cytoplasmic protein that gives energy for the transport and the periplasmic-binding protein PotF, which is responsible for the affinity and specificity of the system. Its function is associated to the microbial carcinogenesis, biofilm formation, escape from phagolysosomes, bacteriocin production, toxin activity and protection from oxidative and acid stress. In this work, we show for the first time, the expression, purification, functional and structural analyses of the X. citri PotF protein. The PotF was expressed from Escherichia coli cells strain Arctic, as a 40 kDa soluble protein, after induction of IPTG for twenty four hours at thirteen deg C. Using immobilized metal affinity chromatography for purification, the protein was eluted in the fractions with 10-500 mM of imidazole. To test the folding and cability to bind putrescine, spectroscopic analyses were performed using circular dichroism and intrinsic fluorescence. The data showed that PotF suffers conformational changes in presence of ligands and in different pH, suggesting a possible interaction with the tested ligand. Moreover, based on bioinformatics studies and molecular modeling analyses, we showed that X. citri PotF is highly conserved when compared to orthologs present in other bacteria, including the residues that form the ligand-binding site. The production of PotF in a soluble and stable form will allow us to start the crystallization trials in attempt to solve its structure. (author)

  4. Heavy water effects on the structure, functions and behavior of biological systems

    International Nuclear Information System (INIS)

    Buzgariu, Wanda; Caloianu, Maria; Moldovan, Lucia; Titescu, G.

    2003-01-01

    The H 2 O substitution for D 2 O either in environment or in the culture medium of the living systems generates changes in their main functions and composition. In this paper some of the heavy water effects in biological systems such as structural and functional changes were reviewed: normal cell architecture alterations, cell division and membrane functions disturbance, muscular contractility and the perturbations of biological oscillators such as circadian rhythm, heart rate, respiratory cycle, tidal and ultradian rhythm. (authors)

  5. Inferring biological functions of guanylyl cyclases with computational methods

    KAUST Repository

    Alquraishi, May Majed; Meier, Stuart Kurt

    2013-01-01

    A number of studies have shown that functionally related genes are often co-expressed and that computational based co-expression analysis can be used to accurately identify functional relationships between genes and by inference, their encoded proteins. Here we describe how a computational based co-expression analysis can be used to link the function of a specific gene of interest to a defined cellular response. Using a worked example we demonstrate how this methodology is used to link the function of the Arabidopsis Wall-Associated Kinase-Like 10 gene, which encodes a functional guanylyl cyclase, to host responses to pathogens. © Springer Science+Business Media New York 2013.

  6. Inferring biological functions of guanylyl cyclases with computational methods

    KAUST Repository

    Alquraishi, May Majed

    2013-09-03

    A number of studies have shown that functionally related genes are often co-expressed and that computational based co-expression analysis can be used to accurately identify functional relationships between genes and by inference, their encoded proteins. Here we describe how a computational based co-expression analysis can be used to link the function of a specific gene of interest to a defined cellular response. Using a worked example we demonstrate how this methodology is used to link the function of the Arabidopsis Wall-Associated Kinase-Like 10 gene, which encodes a functional guanylyl cyclase, to host responses to pathogens. © Springer Science+Business Media New York 2013.

  7. Mining Functional Modules in Heterogeneous Biological Networks Using Multiplex PageRank Approach.

    Science.gov (United States)

    Li, Jun; Zhao, Patrick X

    2016-01-01

    Identification of functional modules/sub-networks in large-scale biological networks is one of the important research challenges in current bioinformatics and systems biology. Approaches have been developed to identify functional modules in single-class biological networks; however, methods for systematically and interactively mining multiple classes of heterogeneous biological networks are lacking. In this paper, we present a novel algorithm (called mPageRank) that utilizes the Multiplex PageRank approach to mine functional modules from two classes of biological networks. We demonstrate the capabilities of our approach by successfully mining functional biological modules through integrating expression-based gene-gene association networks and protein-protein interaction networks. We first compared the performance of our method with that of other methods using simulated data. We then applied our method to identify the cell division cycle related functional module and plant signaling defense-related functional module in the model plant Arabidopsis thaliana. Our results demonstrated that the mPageRank method is effective for mining sub-networks in both expression-based gene-gene association networks and protein-protein interaction networks, and has the potential to be adapted for the discovery of functional modules/sub-networks in other heterogeneous biological networks. The mPageRank executable program, source code, the datasets and results of the presented two case studies are publicly and freely available at http://plantgrn.noble.org/MPageRank/.

  8. Histological and molecular-biological analyses of poly(3-hydroxybutyrate) (PHB) patches for enhancement of bone regeneration.

    Science.gov (United States)

    Gredes, Tomasz; Gedrange, Tomasz; Hinüber, Claudia; Gelinsky, Michael; Kunert-Keil, Christiane

    2015-05-01

    Tissue engineered cell-seeded constructs with poly(3)hydroxybutyrate (PHB) induced ectopic bone formation after implantation into the back muscle of rats. The objective of our in vivo study was to evaluate the osteogenic potential of pure PHB patches in surgically created cranial defects. For this, PHB patches were analyzed after implantation in surgically created defects on the cranium of adult male rats. After healing periods of 4, 8 and 12 weeks, the bone tissue specimens containing PHB patches were processed and analyzed histologically as well as molecular-biologically. After 4 weeks, the PHB patches were completely embedded in connective tissue. Eight weeks after PHB insertion, bone regeneration proceeding from bearing bone was found in 50% of all treated animals, whereas all PHB treated cavities showed both bone formation and embedding of the patches in bone 12 weeks after surgery. Furthermore, all slices showed pronounced development of blood vessels. Histomorphometric analysis presented a regenerated bone mean value between 46.4 ± 16.1% and 54.2 ± 19.3% after 4-12 weeks of healing. Caveolin-1 staining in capillary-like structures showed a 1.16-1.38 fold increased expression in PHB treated defects compared to controls. Real-time RT-PCR analyses showed significantly lower expressions of Alpl, Col1a1 and VEGFA in cranium defects after treatment with PHB patches compared to untreated bony defects of the same cranium. Within the limits of the presented animal investigation, it could conclude that the tested PHB patches featured a good biocompatibility and an osteoconductive character. Copyright © 2014 Elsevier GmbH. All rights reserved.

  9. The lectins: properties, functions, and applications in biology and medicine

    National Research Council Canada - National Science Library

    Liener, Irvin E; Sharon, Nathan; Goldstein, Irwin J

    1986-01-01

    ... (Editors). The Enzymology of Post-Translational Modification of Proteins, Volume 1, 1980. Volume 2, 1985 W A I YIU CHEUNG (Editor). Calcium and Cell Function, Volume I: Calmodulin, 1980. Volume II, ...

  10. Evolutionary Analyses Suggest a Function of MxB Immunity Proteins Beyond Lentivirus Restriction.

    Directory of Open Access Journals (Sweden)

    Patrick S Mitchell

    2015-12-01

    Full Text Available Viruses impose diverse and dynamic challenges on host defenses. Diversifying selection of codons and gene copy number variation are two hallmarks of genetic innovation in antiviral genes engaged in host-virus genetic conflicts. The myxovirus resistance (Mx genes encode interferon-inducible GTPases that constitute a major arm of the cell-autonomous defense against viral infection. Unlike the broad antiviral activity of MxA, primate MxB was recently shown to specifically inhibit lentiviruses including HIV-1. We carried out detailed evolutionary analyses to investigate whether genetic conflict with lentiviruses has shaped MxB evolution in primates. We found strong evidence for diversifying selection in the MxB N-terminal tail, which contains molecular determinants of MxB anti-lentivirus specificity. However, we found no overlap between previously-mapped residues that dictate lentiviral restriction and those that have evolved under diversifying selection. Instead, our findings are consistent with MxB having a long-standing and important role in the interferon response to viral infection against a broader range of pathogens than is currently appreciated. Despite its critical role in host innate immunity, we also uncovered multiple functional losses of MxB during mammalian evolution, either by pseudogenization or by gene conversion from MxA genes. Thus, although the majority of mammalian genomes encode two Mx genes, this apparent stasis masks the dramatic effects that recombination and diversifying selection have played in shaping the evolutionary history of Mx genes. Discrepancies between our study and previous publications highlight the need to account for recombination in analyses of positive selection, as well as the importance of using sequence datasets with appropriate depth of divergence. Our study also illustrates that evolutionary analyses of antiviral gene families are critical towards understanding molecular principles that govern host

  11. Analysing the relationship between traumatic biographical events and the current structural functioning of personality.

    Science.gov (United States)

    Schiltz, L; Schiltz, J

    2008-01-01

    We present the general structure of a multi-annual research project. Our general expectancy concerns the possibilities of arts psychotherapy as a means of launching the blocked process of subjectivation with people suffering from exclusion, precarity and marginalization. The research project follows a complex research design with a sequential strategy, the first part consisting in an integrated psychosocial and clinical study using a mixed methodology. We constructed special rating scales for the analysis of the data of a semi-structured biographical interview and also for the holistic interpretation of the Rotter Blank Sentences Test, separating the associations to sentences beginning with the third and first person. The correlations between two sets of variables (biographical interview and Rotter test) were computed for the total experimental group (N=206), and for clinical subgroups. We shall analyse the matrices of correlations (Spearman's Rho) with the help of optimal scaling procedures (OVERALS). The links between traumatic biographical events and responses to the 3rd, respectively 1st person items of the Rotter test are interpreted in terms of unconscious versus conscious psychological processes and allow us analysing the expression of defence mechanisms and coping strategies. The results of the study are discussed in the light of the recent traumatogenic hypothesis of borderline functioning.

  12. Relationships of Functional Tests Following ACL Reconstruction: Exploratory Factor Analyses of the Lower Extremity Assessment Protocol.

    Science.gov (United States)

    DiFabio, Melissa; Slater, Lindsay V; Norte, Grant; Goetschius, John; Hart, Joseph M; Hertel, Jay

    2018-03-01

    After ACL reconstruction (ACLR), deficits are often assessed using a variety of functional tests, which can be time consuming. It is unknown whether these tests provide redundant or unique information. To explore relationships between components of a battery of functional tests, the Lower Extremity Assessment Protocol (LEAP) was created to aid in developing the most informative, concise battery of tests for evaluating ACLR patients. Descriptive, cross-sectional. Laboratory. 76 ACLR patients (6.86±3.07 months postoperative) and 54 healthy participants. Isokinetic knee flexion and extension at 90 and 180 degrees/second, maximal voluntary isometric contraction for knee extension and flexion, single leg balance, 4 hopping tasks (single, triple, crossover, and 6-meter timed hop), and a bilateral drop vertical jump that was scored with the Landing Error Scoring System (LESS). Peak torque, average torque, average power, total work, fatigue indices, center of pressure area and velocity, hop distance and time, and LESS score. A series of factor analyses were conducted to assess grouping of functional tests on the LEAP for each limb in the ACLR and healthy groups and limb symmetry indices (LSI) for both groups. Correlations were run between measures that loaded on retained factors. Isokinetic and isometric strength tests for knee flexion and extension, hopping, balance, and fatigue index were identified as unique factors for all limbs. The LESS score loaded with various factors across the different limbs. The healthy group LSI analysis produced more factors than the ACLR LSI analysis. Individual measures within each factor had moderate to strong correlations. Isokinetic and isometric strength, hopping, balance, and fatigue index provided unique information. Within each category of measures, not all tests may need to be included for a comprehensive functional assessment of ACLR patients due to the high amount of shared variance between them.

  13. Single-wavelength functional photoacoustic microscopy in biological tissue.

    Science.gov (United States)

    Danielli, Amos; Favazza, Christopher P; Maslov, Konstantin; Wang, Lihong V

    2011-03-01

    Recently, we developed a reflection-mode relaxation photoacoustic microscope, based on saturation intensity, to measure picosecond relaxation times using a nanosecond laser. Here, using the different relaxation times of oxygenated and deoxygenated hemoglobin molecules, both possessing extremely low fluorescence quantum yields, the oxygen saturation was quantified in vivo with single-wavelength photoacoustic microscopy. All previous functional photoacoustic microscopy measurements required imaging with multiple-laser-wavelength measurements to quantify oxygen saturation. Eliminating the need for multiwavelength measurements removes the influence of spectral properties on oxygenation calculations and improves the portability and cost-effectiveness of functional or molecular photoacoustic microscopy.

  14. Chemically-functionalized microcantilevers for detection of chemical, biological and explosive material

    Science.gov (United States)

    Pinnaduwage, Lal A [Knoxville, TN; Thundat, Thomas G [Knoxville, TN; Brown, Gilbert M [Knoxville, TN; Hawk, John Eric [Olive Branch, MS; Boiadjiev, Vassil I [Knoxville, TN

    2007-04-24

    A chemically functionalized cantilever system has a cantilever coated on one side thereof with a reagent or biological species which binds to an analyte. The system is of particular value when the analyte is a toxic chemical biological warfare agent or an explosive.

  15. Biological markers for kidney injury and renal function in the intensive care unit

    NARCIS (Netherlands)

    Royakkers, A.A.N.M.

    2014-01-01

    The purpose of the investigations described in this thesis was to seek for answers to two relevant questions in ICUs in resource-rich settings, i.e., can new biological markers play a role in early recognition of AKI, and can new biological markers predict recovery of renal function in patients who

  16. Theoretical study for a digital transfer function analyser; Etude theorique pour un transferometre digital

    Energy Technology Data Exchange (ETDEWEB)

    Freycenon, J [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1964-07-01

    This study deals with the harmonic analysis of the instantaneous counting rate of a pulse train. This arises from using a fission chamber for reactivity to power transfer function measurements by oscillation methods in reactors. The systematical errors due to the sampling process are computed. The integration carried out when sampling the signal modifies the formulae of the Nyquist theorem on spectrum folding. The statistical errors due to the noise are analysed: it is shown that the bandwidth of the spectral window applied to the noise frequency spectrum is equal to the inverse of the time duration of the experiment. A dead time of 25 per cent of the sampling time does not increase appreciably the bandwidth. A new method is proposed afterwards yielding very approximate results of the Fourier analysis during the experiment. The systematical errors arising from the measuring process are determined, and it is shown that the bandwidth of the corresponding spectral window is still given by the inverse of the time duration of the experiment. (author) [French] Cette etude se rapporte a l'analyse harmonique de la valeur instantanee du taux de comptage d'une suite d'impulsions. On rencontre ce probleme dans l'utilisation de chambres a fission pour les mesures de fonction de transfert reactivite-puissance par la methode d'oscillation dans les piles. On calcule l'erreur systematique due au processus d'echantillonnage ou l'integration operee modifie les formules classiques de recouvrement du spectre. On analyse ensuite les erreurs statistiques dues au bruit de fond. On montre que la largeur de bande de la fenetre spectrale appliquee au spectre de puissance du bruit est donnee par l'inverse du temps de mesure. Un temps mort de 25 pour cent du temps de prelevement n'accroit pas sensiblement cette largeur de bande. On propose ensuite un procede simple qui permet d'obtenir, en cours d'experience, des resultats tres approches de l'analyse de Fourier. On determine les erreurs

  17. Exosome function: from tumor immunology to pathogen biology.

    Science.gov (United States)

    Schorey, Jeffrey S; Bhatnagar, Sanchita

    2008-06-01

    Exosomes are the newest family member of 'bioactive vesicles' that function to promote intercellular communication. Exosomes are derived from the fusion of multivesicular bodies with the plasma membrane and extracellular release of the intraluminal vesicles. Recent studies have focused on the biogenesis and composition of exosomes as well as regulation of exosome release. Exosomes have been shown to be released by cells of hematopoietic and non-hematopoietic origin, yet their function remains enigmatic. Much of the prior work has focused on exosomes as a source of tumor antigens and in presentation of tumor antigens to T cells. However, new studies have shown that exosomes might also promote cell-to-cell spread of infectious agents. Moreover, exosomes isolated from cells infected with various intracellular pathogens, including Mycobacterium tuberculosis and Toxoplasma gondii, have been shown to contain microbial components and can promote antigen presentation and macrophage activation, suggesting that exosomes may function in immune surveillance. In this review, we summarize our understanding of exosome biogenesis but focus primarily on new insights into exosome function. We also discuss their possible use as disease biomarkers and vaccine candidates.

  18. Advancing Functional Metagenomics using Synthetic Biology from Soil to Sequence

    DEFF Research Database (Denmark)

    van der Helm, Eric

    as ‘functional metagenomics’, the DNA of these bacteria can be recovered from the environment and used by host-bacteria which can be grown in a lab. This allows us to make use of the capabilities of the billions of bacteria that a represent in the environment without actually growing them but by making use...

  19. Single-wavelength functional photoacoustic microscopy in biological tissue

    OpenAIRE

    Danielli, Amos; Favazza, Christopher P.; Maslov, Konstantin; Wang, Lihong V.

    2011-01-01

    Recently, we developed a reflection-mode relaxation photoacoustic microscope, based on saturation intensity, to measure picosecond relaxation times using a nanosecond laser. Here, using the different relaxation times of oxygenated and deoxygenated hemoglobin molecules, both possessing extremely low fluorescence quantum yields, the oxygen saturation was quantified in vivo with single-wavelength photoacoustic microscopy. All previous functional photoacoustic microscopy measurements required ima...

  20. Preliminary biological evaluation of a urea-functionalized dendrimer

    International Nuclear Information System (INIS)

    Stephan, H.; Syhre, R.; Spies, H.; Johannsen, B.; Zessin, J.; Steinbach, J.; Klein, L.; Werner, N.; Voegtle, F.

    2002-01-01

    A new third generation ethylurea-functionalized polypropyleneamine dendrimer was prepared. After labelling this dendrimer with 11-carbon the biodistribution in rats was studied. The highest level of radioactivity was found in the liver (30-35% ID). The 11 C-labelled dendrimer was well tolerated by the rats. (orig.)

  1. Functional proteomic analyses of Bothrops atrox venom reveals phenotypes associated with habitat variation in the Amazon.

    Science.gov (United States)

    Sousa, Leijiane F; Portes-Junior, José A; Nicolau, Carolina A; Bernardoni, Juliana L; Nishiyama, Milton Y; Amazonas, Diana R; Freitas-de-Sousa, Luciana A; Mourão, Rosa Hv; Chalkidis, Hipócrates M; Valente, Richard H; Moura-da-Silva, Ana M

    2017-04-21

    Venom variability is commonly reported for venomous snakes including Bothrops atrox. Here, we compared the composition of venoms from B. atrox snakes collected at Amazonian conserved habitats (terra-firme upland forest and várzea) and human modified areas (pasture and degraded areas). Venom samples were submitted to shotgun proteomic analysis as a whole or compared after fractionation by reversed-phase chromatography. Whole venom proteomes revealed a similar composition among the venoms with predominance of SVMPs, CTLs, and SVSPs and intermediate amounts of PLA 2 s and LAAOs. However, when distribution of particular isoforms was analyzed by either method, the venom from várzea snakes showed a decrease in hemorrhagic SVMPs and an increase in SVSPs, and procoagulant SVMPs and PLA 2 s. These differences were validated by experimental approaches including both enzymatic and in vivo assays, and indicated restrictions in respect to antivenom efficacy to variable components. Thus, proteomic analysis at the isoform level combined to in silico prediction of functional properties may indicate venom biological activity. These results also suggest that the prevalence of functionally distinct isoforms contributes to the variability of the venoms and could reflect the adaptation of B. atrox to distinct prey communities in different Amazon habitats. In this report, we compared isoforms present in venoms from snakes collected at different Amazonian habitats. By means of a species venom gland transcriptome and the in silico functional prediction of each isoform, we were able to predict the principal venom activities in vitro and in animal models. We also showed remarkable differences in the venom pools from snakes collected at the floodplain (várzea habitat) compared to other habitats. Not only was this venom less hemorrhagic and more procoagulant, when compared to the venom pools from the other three habitats studied, but also this enhanced procoagulant activity was not

  2. The functionality of biological knowledge in the workplace. Integrating school and workplace learning about reproduction

    NARCIS (Netherlands)

    Mazereeuw, M.

    2013-01-01

    This thesis reports on a design research project about a learning, supervising and teaching strategy to enable students in agricultural preparatory vocational secondary education (VMBO) to recognize the functionality of biological knowledge of reproduction in work placement sites. Although

  3. MicroRNA functional network in pancreatic cancer: From biology to ...

    Indian Academy of Sciences (India)

    [Wang J and Sen S 2011 MicroRNA functional network in pancreatic cancer: From biology to biomarkers of disease. ... growth factor type I receptor; INSR, insulin receptor; IPA, Ingenuity Pathway Analysis; IPMN, ..... Prostate cancer signalling.

  4. Characterization of Aeromonas hydrophila wound pathotypes by comparative genomic and functional analyses of virulence genes.

    Science.gov (United States)

    Grim, Christopher J; Kozlova, Elena V; Sha, Jian; Fitts, Eric C; van Lier, Christina J; Kirtley, Michelle L; Joseph, Sandeep J; Read, Timothy D; Burd, Eileen M; Tall, Ben D; Joseph, Sam W; Horneman, Amy J; Chopra, Ashok K; Shak, Joshua R

    2013-04-23

    Aeromonas hydrophila has increasingly been implicated as a virulent and antibiotic-resistant etiologic agent in various human diseases. In a previously published case report, we described a subject with a polymicrobial wound infection that included a persistent and aggressive strain of A. hydrophila (E1), as well as a more antibiotic-resistant strain of A. hydrophila (E2). To better understand the differences between pathogenic and environmental strains of A. hydrophila, we conducted comparative genomic and functional analyses of virulence-associated genes of these two wound isolates (E1 and E2), the environmental type strain A. hydrophila ATCC 7966(T), and four other isolates belonging to A. aquariorum, A. veronii, A. salmonicida, and A. caviae. Full-genome sequencing of strains E1 and E2 revealed extensive differences between the two and strain ATCC 7966(T). The more persistent wound infection strain, E1, harbored coding sequences for a cytotoxic enterotoxin (Act), a type 3 secretion system (T3SS), flagella, hemolysins, and a homolog of exotoxin A found in Pseudomonas aeruginosa. Corresponding phenotypic analyses with A. hydrophila ATCC 7966(T) and SSU as reference strains demonstrated the functionality of these virulence genes, with strain E1 displaying enhanced swimming and swarming motility, lateral flagella on electron microscopy, the presence of T3SS effector AexU, and enhanced lethality in a mouse model of Aeromonas infection. By combining sequence-based analysis and functional assays, we characterized an A. hydrophila pathotype, exemplified by strain E1, that exhibited increased virulence in a mouse model of infection, likely because of encapsulation, enhanced motility, toxin secretion, and cellular toxicity. Aeromonas hydrophila is a common aquatic bacterium that has increasingly been implicated in serious human infections. While many determinants of virulence have been identified in Aeromonas, rapid identification of pathogenic versus nonpathogenic

  5. 3D Printing Polymers with Supramolecular Functionality for Biological Applications.

    Science.gov (United States)

    Pekkanen, Allison M; Mondschein, Ryan J; Williams, Christopher B; Long, Timothy E

    2017-09-11

    Supramolecular chemistry continues to experience widespread growth, as fine-tuned chemical structures lead to well-defined bulk materials. Previous literature described the roles of hydrogen bonding, ionic aggregation, guest/host interactions, and π-π stacking to tune mechanical, viscoelastic, and processing performance. The versatility of reversible interactions enables the more facile manufacturing of molded parts with tailored hierarchical structures such as tissue engineered scaffolds for biological applications. Recently, supramolecular polymers and additive manufacturing processes merged to provide parts with control of the molecular, macromolecular, and feature length scales. Additive manufacturing, or 3D printing, generates customizable constructs desirable for many applications, and the introduction of supramolecular interactions will potentially increase production speed, offer a tunable surface structure for controlling cell/scaffold interactions, and impart desired mechanical properties through reinforcing interlayer adhesion and introducing gradients or self-assembled structures. This review details the synthesis and characterization of supramolecular polymers suitable for additive manufacture and biomedical applications as well as the use of supramolecular polymers in additive manufacturing for drug delivery and complex tissue scaffold formation. The effect of supramolecular assembly and its dynamic behavior offers potential for controlling the anisotropy of the printed objects with exquisite geometrical control. The potential for supramolecular polymers to generate well-defined parts, hierarchical structures, and scaffolds with gradient properties/tuned surfaces provides an avenue for developing next-generation biomedical devices and tissue scaffolds.

  6. Functional nanostructured platforms for chemical and biological sensing

    Science.gov (United States)

    Létant, S. E.

    2006-05-01

    The central goal of our work is to combine semiconductor nanotechnology and surface functionalization in order to build platforms for the selective detection of bio-organisms ranging in size from bacteria (micron range) down to viruses, as well as for the detection of chemical agents (nanometer range). We will show on three porous silicon platforms how pore geometry and pore wall chemistry can be combined and optimized to capture and detect specific targets. We developed a synthetic route allowing to directly anchor proteins on silicon surfaces and illustrated the relevance of this technique by immobilizing live enzymes onto electrochemically etched luminescent nano-porous silicon. The powerful association of the specific enzymes with the transducing matrix led to a selective hybrid platform for chemical sensing. We also used light-assisted electrochemistry to produce periodic arrays of through pores on pre-patterned silicon membranes with controlled diameters ranging from many microns down to tens of nanometers. We demonstrated the first covalently functionalized silicon membranes and illustrated their selective capture abilities with antibody-coated micro-beads. These engineered membranes are extremely versatile and could be adapted to specifically recognize the external fingerprints (size and coat composition) of target bio-organisms. Finally, we fabricated locally functionalized single nanopores using a combination of focused ion beam drilling and ion beam assisted oxide deposition. We showed how a silicon oxide ring can be grown around a single nanopore and how it can be functionalized with DNA probes to detect single viral-sized beads. The next step for this platform is the detection of whole viruses and bacteria.

  7. The biology and function of exosomes in cancer

    OpenAIRE

    Kalluri, Raghu

    2016-01-01

    Humans circulate quadrillions of exosomes at all times. Exosomes are a class of extracellular vesicles released by all cells, with a size range of 40?150 nm and a lipid bilayer membrane. Exosomes contain DNA, RNA, and proteins. Exosomes likely remove excess and/or unnecessary constituents from the cells, functioning like garbage bags, although their precise physiological role remains unknown. Additionally, exosomes may mediate specific cell-to-cell communication and activate signaling pathway...

  8. Biology and Function of Fetal and Pediatric Skin

    OpenAIRE

    Leung, Alice; Balaji, Swathi; Keswani, Sundeep G

    2013-01-01

    The development of the integumentary system is a series of events, which start in utero and continue throughout life. Although at birth, skin in full-term infants is anatomically mature, functional maturity develops during the first year of life. Pediatric skin transitions again with the onset of puberty. At each stage, there are changes in transepidermal water loss, skin hydration, and skin acidity that define the specific period of development.

  9. Biological factors of natural and artificial ecosystems stable (unstable) functioning

    Science.gov (United States)

    Pechurkin, Nikolai S.

    The problem of sustainable development of humanity on Earth and the problem of supporting human life in space have the same scientific and methodological bases. The key to solve both problems is a long term maintenance of balanced material cycle. As a whole, natural or artificial ecosystems are to be more closed than open, but their elements (links of systems) are to be substantially open in interactions with each other. Prolonged stable interactions of different links have to have unique joint results - closed material cycling or biotic turnover. It is necessary to include, at least, three types of main links into any system to support real material cycling: producers, consumers, reducers. Producer links are now under studies in many laboratories. It is evident that the higher productivity of link, the lower link stability. Especially, it concerns with parasite impact to plants. As usual, artificial ecosystems are more simple (incomplete) than natural ecosystems, sometimes, they have not enough links for prolonged stable functioning. For example, life support system for space flight can be incomplete in consumer link, having only some crew persons, instead of interacting populations of consumers. As for reducer link, it is necessary to "organize" a special coordinated work of microbial biocenoses to fulfill proper cycling. Possible evolution of links, their self development is a matter of special attention for the maintenance of prolonged stable functioning. It's the most danger for systems with populations of quickly reproducing, so-called, R - strategists, according to symbols of logistic equation. From another side, quick reproduction of R - strategists is able to increase artificial ecosystems and their links functioning. After some damages of system, R - strategist's link can be quickly "self repaired" up to level of normal functioning. Some experimental data of this kind and mathematical models are to be discussed in the paper. This work is supported by

  10. Genome-wide identification and function analyses of heat shock transcription factors in potato

    Directory of Open Access Journals (Sweden)

    Ruimin eTang

    2016-04-01

    Full Text Available Heat shock transcription factors (Hsfs play vital roles in the regulation of tolerance to various stresses in living organisms. To dissect the mechanisms of the Hsfs in potato adaptation to abiotic stresses, genome and transcriptome analyses of Hsf gene family were investigated in Solanum tuberosum L. Twenty-seven StHsf members were identified by bioinformatics and phylogenetic analyses and were classified into A, B and C groups according to their structural and phylogenetic features. StHsfs in the same class shared similar gene structures and conserved motifs. The chromosomal location analysis showed that 27 Hsfs were located in 10 of 12 chromosomes (except chromosome 1 and chromosome 5 and that 18 of these genes formed 9 paralogous pairs. Expression profiles of StHsfs in 12 different organs and tissues uncovered distinct spatial expression patterns of these genes and their potential roles in the process of growth and development. Promoter and quantitative real-time polymerase chain reaction (qRT-PCR detections of StHsfs were conducted and demonstrated that these genes were all responsive to various stresses. StHsf004, StHsf007, StHsf009, StHsf014 and StHsf019 were constitutively expressed under non-stress conditions, and some specific Hsfs became the predominant Hsfs in response to different abiotic stresses, indicating their important and diverse regulatory roles in adverse conditions. A co-expression network between StHsfs and StHsf-co-expressed genes was generated based on the publicly-available potato transcriptomic databases and identified key candidate StHsfs for further functional studies.

  11. Biological functions of iduronic acid in chondroitin/dermatan sulfate.

    Science.gov (United States)

    Thelin, Martin A; Bartolini, Barbara; Axelsson, Jakob; Gustafsson, Renata; Tykesson, Emil; Pera, Edgar; Oldberg, Åke; Maccarana, Marco; Malmstrom, Anders

    2013-05-01

    The presence of iduronic acid in chondroitin/dermatan sulfate changes the properties of the polysaccharides because it generates a more flexible chain with increased binding potentials. Iduronic acid in chondroitin/dermatan sulfate influences multiple cellular properties, such as migration, proliferation, differentiation, angiogenesis and the regulation of cytokine/growth factor activities. Under pathological conditions such as wound healing, inflammation and cancer, iduronic acid has diverse regulatory functions. Iduronic acid is formed by two epimerases (i.e. dermatan sulfate epimerase 1 and 2) that have different tissue distribution and properties. The role of iduronic acid in chondroitin/dermatan sulfate is highlighted by the vast changes in connective tissue features in patients with a new type of Ehler-Danlos syndrome: adducted thumb-clubfoot syndrome. Future research aims to understand the roles of the two epimerases and their interplay with the sulfotransferases involved in chondroitin sulfate/dermatan sulfate biosynthesis. Furthermore, a better definition of chondroitin/dermatan sulfate functions using different knockout models is needed. In this review, we focus on the two enzymes responsible for iduronic acid formation, as well as the role of iduronic acid in health and disease. © 2013 The Authors Journal compilation © 2013 FEBS.

  12. Development of biological functional material and product from Nelumbo nucifera

    International Nuclear Information System (INIS)

    Jeong, Il Yun; Park, Yong Dae; Jin, Chang Hyun; Choi, Dae Seong

    2008-01-01

    The solvent extracts of Nelumbo nucifera G. were investigated for the activities of antioxidant, whitening, anti-wrinkle and antimicrobial effects to apply as a functional ingredient for cosmetic products. The electron donating ability of irradiated NN-L extract was above 85% at the concentration of 50ppm. The superoxide dismutase(SOD)-like activity of irradiated NN-L extract was about 76% at 1,000ppm concentration. The xanthine oxidase inhibitory effect of irradiated NN-L extract was about 15% at 1,000ppm. The tyrosinase inhibitory effect of irradiated NN-L extract was about 18% at 1,000ppm. Anti-wrinkle effect, the elastase inhibition activity of irradiated NN-L extract was about 45% at 1,000ppm concentration. All these findings suggested that Nelumbo nucifera G. has a great potential as a cosmeceutical ingredient

  13. The biology and function of exosomes in cancer.

    Science.gov (United States)

    Kalluri, Raghu

    2016-04-01

    Humans circulate quadrillions of exosomes at all times. Exosomes are a class of extracellular vesicles released by all cells, with a size range of 40-150 nm and a lipid bilayer membrane. Exosomes contain DNA, RNA, and proteins. Exosomes likely remove excess and/or unnecessary constituents from the cells, functioning like garbage bags, although their precise physiological role remains unknown. Additionally, exosomes may mediate specific cell-to-cell communication and activate signaling pathways in cells they fuse or interact with. Exosomes are detected in the tumor microenvironment, and emerging evidence suggests that they play a role in facilitating tumorigenesis by regulating angiogenesis, immunity, and metastasis. Circulating exosomes can be used as liquid biopsies and noninvasive biomarkers for early detection, diagnosis, and treatment of cancer patients.

  14. The functions of biological diversity in an age of extinction.

    Science.gov (United States)

    Naeem, Shahid; Duffy, J Emmett; Zavaleta, Erika

    2012-06-15

    Ecosystems worldwide are rapidly losing taxonomic, phylogenetic, genetic, and functional diversity as a result of human appropriation of natural resources, modification of habitats and climate, and the spread of pathogenic, exotic, and domestic plants and animals. Twenty years of intense theoretical and empirical research have shown that such biotic impoverishment can markedly alter the biogeochemical and dynamic properties of ecosystems, but frontiers remain in linking this research to the complexity of wild nature, and in applying it to pressing environmental issues such as food, water, energy, and biosecurity. The question before us is whether these advances can take us beyond merely invoking the precautionary principle of conserving biodiversity to a predictive science that informs practical and specific solutions to mitigate and adapt to its loss.

  15. Development of biological functional material and product from Nelumbo nucifera

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Il Yun; Park, Yong Dae; Jin, Chang Hyun; Choi, Dae Seong

    2008-01-15

    The solvent extracts of Nelumbo nucifera G. were investigated for the activities of antioxidant, whitening, anti-wrinkle and antimicrobial effects to apply as a functional ingredient for cosmetic products. The electron donating ability of irradiated NN-L extract was above 85% at the concentration of 50ppm. The superoxide dismutase(SOD)-like activity of irradiated NN-L extract was about 76% at 1,000ppm concentration. The xanthine oxidase inhibitory effect of irradiated NN-L extract was about 15% at 1,000ppm. The tyrosinase inhibitory effect of irradiated NN-L extract was about 18% at 1,000ppm. Anti-wrinkle effect, the elastase inhibition activity of irradiated NN-L extract was about 45% at 1,000ppm concentration. All these findings suggested that Nelumbo nucifera G. has a great potential as a cosmeceutical ingredient.

  16. Biological function of activation-induced cytidine deaminase (AID

    Directory of Open Access Journals (Sweden)

    Ritu Kumar

    2014-10-01

    Full Text Available Activation-induced Cytidine Deaminase (AID is an essential regulator of B cell diversification, but its full range of action has until recently been an enigma. Based on homology, it was originally proposed to be an RNA-editing enzyme, but so far, no RNA substrates are known. Rather, it functions by deaminating cytidine, and in this manner, coupled with base-excision repair or mismatch repair machinery, it is a natural mutator. This allows it to play a central role in adaptive immunity, whereby it initiates the processes of class switch recombination and somatic hypermutation to help generate a diverse and high-affinity repertoire of immunoglobulin isotypes. More recently, it has been appreciated that methylated cytidine, already known as a key epigenetic mark on DNA controlling gene expression, can also be a target for AID modification. Coupled with repair machinery, this can facilitate the active removal of methylated DNA. This activity can impact the process of cellular reprogramming, including transition of a somatic cell to pluripotency, which requires major reshuffling of epigenetic memory. Thus, seemingly disparate roles for AID in controlling immune diversity and epigenetic memory have a common mechanistic basis. However, the very activity that is so useful for B cell diversity and cellular reprogramming is dangerous for the integrity of the genome. Thus, AID expression and activity is tightly regulated, and deregulation is associated with diseases including cancer. Here, we review the range of AID functions with a focus on its mechanisms of action and regulation. Major questions remain to be answered concerning how and when AID is targeted to specific loci and how this impacts development and disease.

  17. The practical impact of differential item functioning analyses in a health-related quality of life instrument

    DEFF Research Database (Denmark)

    Scott, Neil W; Fayers, Peter M; Aaronson, Neil K

    2009-01-01

    Differential item functioning (DIF) analyses are commonly used to evaluate health-related quality of life (HRQoL) instruments. There is, however, a lack of consensus as to how to assess the practical impact of statistically significant DIF results.......Differential item functioning (DIF) analyses are commonly used to evaluate health-related quality of life (HRQoL) instruments. There is, however, a lack of consensus as to how to assess the practical impact of statistically significant DIF results....

  18. Selenium and arsenic in biology: their chemical forms and biological functions.

    Science.gov (United States)

    Shibata, Y; Morita, M; Fuwa, K

    1992-01-01

    Based on the recent development of analytical methods, sensitive systems for the analysis and speciation of selenium and arsenic have been established. A palladium addition technique was developed for the accurate determination of selenium in biological samples using graphite furnace atomic absorption analysis. For the speciation of the elements, combined methods of HPLC either with ICP-AES or with ICP-MS were found to work well. These systems were applied to the elucidation of the chemical form of the elements in natural samples. Some chemical properties of the selenium-mercury complex in dolphin liver were elucidated: i.e., it was a cationic, water-soluble, low molecular weight compound containing selenium and mercury in a 1:1 molar ratio, and was shown to be different from a known selenium-mercury complex, bis(methylmercuric)selenide. The major selenium compound excreted in human urine was revealed to be other than any of those previously identified (TMSe, selenate, and selenite). TMSe, a suspected major metabolite in urine, was found, if at all, in low levels. The major water-soluble, and lipid-soluble arsenic compounds in a brown seaweed, U. pinnatifida (WAKAME), were rigorously identified, and the results were compared with other data on marine algae and animals. The major organic arsenic compounds (termed "arseno-sugars") in marine algae commonly contain 5-deoxy-5-dimethylarsinyl-ribofuranoside moiety. There are various kinds of arseno-sugar derivatives containing different side-chains attached to the anomeric position of the sugar, and the distribution of each arsenic species seems to be related to algal species. The arseno-sugar (A-XI) is present in every alga so far examined, is metabolized to lipids, and possibly may play some specific role in the algal cells. On the other hand, the major arsenic compound in fish, crustacea and molluscs has been identified as arsenobetaine, which is an arseno-analog of glycinebetaine, a very common osmo-regulator in

  19. Structural and functional analyses of DNA-sensing and immune activation by human cGAS.

    Science.gov (United States)

    Kato, Kazuki; Ishii, Ryohei; Goto, Eiji; Ishitani, Ryuichiro; Tokunaga, Fuminori; Nureki, Osamu

    2013-01-01

    The detection of cytosolic DNA, derived from pathogens or host cells, by cytosolic receptors is essential for appropriate host immune responses. Cyclic GMP-AMP synthase (cGAS) is a newly identified cytosolic DNA receptor that produces cyclic GMP-AMP, which activates stimulator of interferon genes (STING), resulting in TBK1-IRF3 pathway activation followed by the production of type I interferons. Here we report the crystal structure of human cGAS. The structure revealed that a cluster of lysine and arginine residues forms the positively charged DNA binding surface of human cGAS, which is important for the STING-dependent immune activation. A structural comparison with other previously determined cGASs and our functional analyses suggested that a conserved zinc finger motif and a leucine residue on the DNA binding surface are crucial for the DNA-specific immune response of human cGAS, consistent with previous work. These structural features properly orient the DNA binding to cGAS, which is critical for DNA-induced cGAS activation and STING-dependent immune activation. Furthermore, we showed that the cGAS-induced activation of STING also involves the activation of the NF-κB and IRF3 pathways. Our results indicated that cGAS is a DNA sensor that efficiently activates the host immune system by inducing two distinct pathways.

  20. Structural and functional analyses of DNA-sensing and immune activation by human cGAS.

    Directory of Open Access Journals (Sweden)

    Kazuki Kato

    Full Text Available The detection of cytosolic DNA, derived from pathogens or host cells, by cytosolic receptors is essential for appropriate host immune responses. Cyclic GMP-AMP synthase (cGAS is a newly identified cytosolic DNA receptor that produces cyclic GMP-AMP, which activates stimulator of interferon genes (STING, resulting in TBK1-IRF3 pathway activation followed by the production of type I interferons. Here we report the crystal structure of human cGAS. The structure revealed that a cluster of lysine and arginine residues forms the positively charged DNA binding surface of human cGAS, which is important for the STING-dependent immune activation. A structural comparison with other previously determined cGASs and our functional analyses suggested that a conserved zinc finger motif and a leucine residue on the DNA binding surface are crucial for the DNA-specific immune response of human cGAS, consistent with previous work. These structural features properly orient the DNA binding to cGAS, which is critical for DNA-induced cGAS activation and STING-dependent immune activation. Furthermore, we showed that the cGAS-induced activation of STING also involves the activation of the NF-κB and IRF3 pathways. Our results indicated that cGAS is a DNA sensor that efficiently activates the host immune system by inducing two distinct pathways.

  1. Biological Functions of the Secretome of Neisseria meningitidis

    Directory of Open Access Journals (Sweden)

    Jan Tommassen

    2017-06-01

    Full Text Available Neisseria meningitidis is a Gram-negative bacterial pathogen that normally resides as a commensal in the human nasopharynx but occasionally causes disease with high mortality and morbidity. To interact with its environment, it transports many proteins across the outer membrane to the bacterial cell surface and into the extracellular medium for which it deploys the common and well-characterized autotransporter, two-partner and type I secretion mechanisms, as well as a recently discovered pathway for the surface exposure of lipoproteins. The surface-exposed and secreted proteins serve roles in host-pathogen interactions, including adhesion to host cells and extracellular matrix proteins, evasion of nutritional immunity imposed by iron-binding proteins of the host, prevention of complement activation, neutralization of antimicrobial peptides, degradation of immunoglobulins, and permeabilization of epithelial layers. Furthermore, they have roles in interbacterial interactions, including the formation and dispersal of biofilms and the suppression of the growth of bacteria competing for the same niche. Here, we will review the protein secretion systems of N. meningitidis and focus on the functions of the secreted proteins.

  2. Functionalized diamond nanopowder for phosphopeptides enrichment from complex biological fluids

    Energy Technology Data Exchange (ETDEWEB)

    Hussain, Dilshad [Division of Analytical Chemistry, Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800 (Pakistan); Najam-ul-Haq, Muhammad, E-mail: najamulhaq@bzu.edu.pk [Division of Analytical Chemistry, Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800 (Pakistan); Institute of Analytical Chemistry and Radiochemistry, Leopold-Franzens University, Innrain 80-82, A-6020 Innsbruck (Austria); Jabeen, Fahmida; Ashiq, Muhammad N.; Athar, Muhammad [Division of Analytical Chemistry, Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800 (Pakistan); Rainer, Matthias; Huck, Christian W.; Bonn, Guenther K. [Institute of Analytical Chemistry and Radiochemistry, Leopold-Franzens University, Innrain 80-82, A-6020 Innsbruck (Austria)

    2013-05-02

    Graphical abstract: -- Highlights: •Derivatization of diamond nanopowder as IMAC and RP. •Characterization with SEM, EDX and FT-IR. •Phosphopeptide enrichment from standard as well as real samples. •Desalting and human serum profiling with reproducible results. •MALDI-MS analysis with database identification. -- Abstract: Diamond is known for its high affinity and biocompatibility towards biomolecules and is used exclusively in separation sciences and life science research. In present study, diamond nanopowder is derivatized as Immobilized Metal Ion Affinity Chromatographic (IMAC) material for the phosphopeptides enrichment and as Reversed Phase (C-18) media for the desalting of complex mixtures and human serum profiling through MALDI-TOF-MS. Functionalized diamond nanopowder is characterized by Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) spectroscopy. Diamond-IMAC is applied to the standard protein (β-casein), spiked human serum, egg yolk and non-fat milk for the phosphopeptides enrichment. Results show the selectivity of synthesized IMAC-diamond immobilized with Fe{sup 3+} and La{sup 3+} ions. To comprehend the elaborated use, diamond-IMAC is also applied to the serum samples from gall bladder carcinoma for the potential biomarkers. Database search is carried out by the Mascot program ( (www.matrixscience.com)) for the assignment of phosphorylation sites. Diamond nanopowder is thus a separation media with multifunctional use and can be applied to cancer protein profiling for the diagnosis and biomarker identification.

  3. Biological catalysis of the hydrological cycle: life's thermodynamic function

    Science.gov (United States)

    Michaelian, K.

    2011-01-01

    Darwinian theory depicts life as being overwhelmingly consumed by a fight for survival in a hostile environment. However, from a thermodynamic perspective, life is a dynamic out of equilibrium process, stabilizing and coevolving in concert with its abiotic environment. The living component of the biosphere on the surface of the Earth of greatest biomass, the plants and cyanobacteria, are involved in the transpiration of a vast amount of water. Transpiration is part of the global water cycle, and it is this cycle that distinguishes Earth from its apparently life barren neighboring planets, Venus and Mars. The dissipation of sunlight into heat by organic molecules in the biosphere and its coupling to the water cycle (as well as other abiotic processes), is by far the greatest entropy producing process occurring on Earth. Life, from this perspective, can be viewed as performing an important thermodynamic function; acting as a dynamic catalyst by aiding irreversible abiotic process such as the water cycle, hurricanes, and ocean and wind currents to produce entropy. The role of animals in this view is that of unwitting but dedicated servants of the plants and cyanobacteria, helping them to grow and to spread into initially inhospitable areas.

  4. Towards understanding the biological function of hopanoids (Invited)

    Science.gov (United States)

    Doughty, D. M.; Hunter, R.; Summons, R. E.; Newman, D. K.

    2010-12-01

    Rhodopseudomonas palustris TIE-1 expresses bacterial hopanoid lipids that are structurally similar and evolutionarily related to eukaryotic sterols. The genome of R. palustris TIE-1 contains two copies of the hpnN gene (hpnN1 and hpnN2) that are orthologs of genes encoding eukaryotic sterol and lipid transporters. Hopanoid localization to the outer membrane was found to be dependent upon hpnN1. Since the cell cycle of R. palustris TIE-1 is obligately bimodal with each cell division resulting in the generation of one mother and one swarmer cell, evidence was obtained that hopanoids where specifically localized to the outer membrane of mother cells. The sequestration of hopanoids to the mother cells was also disrupted by the deletion of the hpnN1 gene. Mutants lacking the hopanoid transporters were able to grow normally at 30 °C but showed decreased growth at 38 °C. The hopanoid transporter mutant formed cellular filaments when grown at elevated temperature. Because sedimentary steranes and hopanes comprise some of the earliest evidence for the emergence of distinct bacteria and eukaryotic phyla, a better appreciation of the function of hopanoids will improve our ability to interpret the evolution of life on Earth.

  5. The reflection of life functional entailment and imminence in relational biology

    CERN Document Server

    Louie, A H

    2013-01-01

    A. H. Louie’s The Reflection of Life: Functional Entailment and Imminence in Relational Biology is a continuation of the exploratory journey in relational biology which began with his 2009 monograph More Than Life Itself: A Synthetic Continuation in Relational Biology. The theme of his first book was ‘What is life?’; the theme of this sequel is “How do two life forms interact?” Biology is a subject concerned with organization of relations. Relational biology is the approach that advocates ‘function dictates structure”, rather than ‘structure implies function’. It is mathematics decoded into biological realizations. The book demonstrates some of the powers of the approach of relational biology, and illustrates how pertinent problems in biology can be better addressed this way. In the first volume the theory was developed by using partially ordered sets, lattices, simulations, models, Aristotle’s four causes, graphs, categories, simple and complex systems, anticipatory systems, and metabolis...

  6. A systematic literature review on reviews and meta-analyses of biologically based CAM-practices for cancer patients

    DEFF Research Database (Denmark)

    Paludan-Müller, Christine; Lunde, Anita; Johannessen, Helle

    2010-01-01

    levels of evidence and were excluded from further evaluation. Among the 32 high-quality reviews the most reviewed practices were soy/plant hormones (7), Chinese herbal medicine (7), antioxidants (5) and mistletoe (4). Fifteen of the 32 reviews included data on the efficacy of biologically-based CAM......-practices against cancer, but none of the reviews concluded a positive effect on the cancer. Reviews including data on quality of life (10) and/or reduction of side effects (12) showed promising, but yet insufficient evidence for Chinese herbal medicine against pain  and side effects of chemotherapy, and mistletoe......Purpose To provide an overview and evaluate the evidence of biologically based CAM-practices for cancer patients. Methods Pubmed, Social Science Citation Index, AMED and the Cochrane library were systematically searched for reviews on effects of biologically based CAM-practices, including herbal...

  7. Functional analyses of ATM, ATR and Fanconi anemia proteins in lung carcinoma

    International Nuclear Information System (INIS)

    Beumer, Jan H.; Fu, Katherine Y.; Anyang, Bean N.; Siegfried, Jill M.; Bakkenist, Christopher J.

    2015-01-01

    ATM and ATR are kinases implicated in a myriad of DNA-damage responses. ATM kinase inhibition radiosensitizes cells and selectively kills cells with Fanconi anemia (FA) gene mutations. ATR kinase inhibition sensitizes cells to agents that induce replication stress and selectively kills cells with ATM and TP53 mutations. ATM mutations and FANCF promoter-methylation are reported in lung carcinomas. We undertook functional analyses of ATM, ATR, Chk1 and FA proteins in lung cancer cell lines. We included Calu6 that is reported to be FANCL-deficient. In addition, the cancer genome atlas (TCGA) database was interrogated for alterations in: 1) ATM, MRE11A, RAD50 and NBN; 2) ATR, ATRIP and TOPBP1; and 3) 15 FA genes. No defects in ATM, ATR or Chk1 kinase activation, or FANCD2 monoubiquitination were identified in the lung cancer cell lines examined, including Calu6, and major alterations in these pathways were not identified in the TCGA database. Cell lines were radiosensitized by ATM kinase inhibitor KU60019, but no cell killing by ATM kinase inhibitor alone was observed. While no synergy between gemcitabine or carboplatin and ATR kinase inhibitor ETP-46464 was observed, synergy between gemcitabine and Chk1 kinase inhibitor UCN-01 was observed in 54 T, 201 T and H460, and synergy between carboplatin and Chk1 kinase inhibitor was identified in 201 T and 239 T. No interactions between ATM, ATR and FA activation were observed by either ATM or ATR kinase inhibition in the lung cancer cell lines. Analyses of ATM serine 1981 and Chk1 serine 345 phosphorylation, and FANCD2 monoubiquitination revealed that ATM and ATR kinase activation and FA pathway signaling are intact in the lung cancer cell lines examined. As such, these posttranslational modifications may have utility as biomarkers for the integrity of DNA damage signaling pathways in lung cancer. Different sensitization profiles between gemcitabine and carboplatin and ATR kinase inhibitor ETP-46464 and Chk1 kinase inhibitor

  8. Revealing complex function, process and pathway interactions with high-throughput expression and biological annotation data.

    Science.gov (United States)

    Singh, Nitesh Kumar; Ernst, Mathias; Liebscher, Volkmar; Fuellen, Georg; Taher, Leila

    2016-10-20

    The biological relationships both between and within the functions, processes and pathways that operate within complex biological systems are only poorly characterized, making the interpretation of large scale gene expression datasets extremely challenging. Here, we present an approach that integrates gene expression and biological annotation data to identify and describe the interactions between biological functions, processes and pathways that govern a phenotype of interest. The product is a global, interconnected network, not of genes but of functions, processes and pathways, that represents the biological relationships within the system. We validated our approach on two high-throughput expression datasets describing organismal and organ development. Our findings are well supported by the available literature, confirming that developmental processes and apoptosis play key roles in cell differentiation. Furthermore, our results suggest that processes related to pluripotency and lineage commitment, which are known to be critical for development, interact mainly indirectly, through genes implicated in more general biological processes. Moreover, we provide evidence that supports the relevance of cell spatial organization in the developing liver for proper liver function. Our strategy can be viewed as an abstraction that is useful to interpret high-throughput data and devise further experiments.

  9. Proteomic and Functional Analyses of the Virion Transmembrane Proteome of Cyprinid Herpesvirus 3.

    Science.gov (United States)

    Vancsok, Catherine; Peñaranda, M Michelle D; Raj, V Stalin; Leroy, Baptiste; Jazowiecka-Rakus, Joanna; Boutier, Maxime; Gao, Yuan; Wilkie, Gavin S; Suárez, Nicolás M; Wattiez, Ruddy; Gillet, Laurent; Davison, Andrew J; Vanderplasschen, Alain F C

    2017-11-01

    Virion transmembrane proteins (VTPs) mediate key functions in the herpesvirus infectious cycle. Cyprinid herpesvirus 3 (CyHV-3) is the archetype of fish alloherpesviruses. The present study was devoted to CyHV-3 VTPs. Using mass spectrometry approaches, we identified 16 VTPs of the CyHV-3 FL strain. Mutagenesis experiments demonstrated that eight of these proteins are essential for viral growth in vitro (open reading frame 32 [ORF32], ORF59, ORF81, ORF83, ORF99, ORF106, ORF115, and ORF131), and eight are nonessential (ORF25, ORF64, ORF65, ORF108, ORF132, ORF136, ORF148, and ORF149). Among the nonessential proteins, deletion of ORF25, ORF132, ORF136, ORF148, or ORF149 affects viral replication in vitro , and deletion of ORF25, ORF64, ORF108, ORF132, or ORF149 impacts plaque size. Lack of ORF148 or ORF25 causes attenuation in vivo to a minor or major extent, respectively. The safety and efficacy of a virus lacking ORF25 were compared to those of a previously described vaccine candidate deleted for ORF56 and ORF57 (Δ56-57). Using quantitative PCR, we demonstrated that the ORF25 deleted virus infects fish through skin infection and then spreads to internal organs as reported previously for the wild-type parental virus and the Δ56-57 virus. However, compared to the parental wild-type virus, the replication of the ORF25-deleted virus was reduced in intensity and duration to levels similar to those observed for the Δ56-57 virus. Vaccination of fish with a virus lacking ORF25 was safe but had low efficacy at the doses tested. This characterization of the virion transmembrane proteome of CyHV-3 provides a firm basis for further research on alloherpesvirus VTPs. IMPORTANCE Virion transmembrane proteins play key roles in the biology of herpesviruses. Cyprinid herpesvirus 3 (CyHV-3) is the archetype of fish alloherpesviruses and the causative agent of major economic losses in common and koi carp worldwide. In this study of the virion transmembrane proteome of CyHV-3, the

  10. Soft robotic arm inspired by the octopus: I. From biological functions to artificial requirements

    International Nuclear Information System (INIS)

    Margheri, L; Laschi, C; Mazzolai, B

    2012-01-01

    Octopuses are molluscs that belong to the group Cephalopoda. They lack joints and rigid links, and as a result, their arms possess virtually limitless freedom of movement. These flexible appendages exhibit peculiar biomechanical features such as stiffness control, compliance, and high flexibility and dexterity. Studying the capabilities of the octopus arm is a complex task that presents a challenge for both biologists and roboticists, the latter of whom draw inspiration from the octopus in designing novel technologies within soft robotics. With this idea in mind, in this study, we used new, purposively developed methods of analysing the octopus arm in vivo to create new biologically inspired design concepts. Our measurements showed that the octopus arm can elongate by 70% in tandem with a 23% diameter reduction and exhibits an average pulling force of 40 N. The arm also exhibited a 20% mean shortening at a rate of 17.1 mm s −1 and a longitudinal stiffening rate as high as 2 N (mm s) −1 . Using histology and ultrasounds, we investigated the functional morphology of the internal tissues, including the sinusoidal arrangement of the nerve cord and the local insertion points of the longitudinal and transverse muscle fibres. The resulting information was used to create novel design principles and specifications that can in turn be used in developing a new soft robotic arm. (paper)

  11. Soft robotic arm inspired by the octopus: I. From biological functions to artificial requirements.

    Science.gov (United States)

    Margheri, L; Laschi, C; Mazzolai, B

    2012-06-01

    Octopuses are molluscs that belong to the group Cephalopoda. They lack joints and rigid links, and as a result, their arms possess virtually limitless freedom of movement. These flexible appendages exhibit peculiar biomechanical features such as stiffness control, compliance, and high flexibility and dexterity. Studying the capabilities of the octopus arm is a complex task that presents a challenge for both biologists and roboticists, the latter of whom draw inspiration from the octopus in designing novel technologies within soft robotics. With this idea in mind, in this study, we used new, purposively developed methods of analysing the octopus arm in vivo to create new biologically inspired design concepts. Our measurements showed that the octopus arm can elongate by 70% in tandem with a 23% diameter reduction and exhibits an average pulling force of 40 N. The arm also exhibited a 20% mean shortening at a rate of 17.1 mm s(-1) and a longitudinal stiffening rate as high as 2 N (mm s)(-1). Using histology and ultrasounds, we investigated the functional morphology of the internal tissues, including the sinusoidal arrangement of the nerve cord and the local insertion points of the longitudinal and transverse muscle fibres. The resulting information was used to create novel design principles and specifications that can in turn be used in developing a new soft robotic arm.

  12. Function and significance of bell beaker pottery according to data from residue analyses

    Directory of Open Access Journals (Sweden)

    Guerra Doce, Elisa

    2006-06-01

    Full Text Available Traditionally, Bell Beakers have been thought to contain alcoholic beverages which were consumed in the course of male feasting ceremonies. Recent residue analyses have shed some light on the question of their function. However, whilst beer and mead have been identified from certain examples, not all Beakers were drinking cups. Some were used as reduction pots to smelt copper ores, others have some organic residues associated with food, and still others were employed as funerary urns. Yet, while the evidence points to a diversity of uses, it is argued that an ideological connection can be observed. Beakers were probably a special form of pottery with a ritual character, related to activities that imply some kind of transformation.

    Los vasos campaniformes suelen relacionarse con el consumo de bebidas alcohólicas durante la celebración de banquetes ceremoniales de exaltación masculina. Si bien las analíticas de residuos han identificado cerveza e hidromiel en unos cuantos ejemplares, no todos los campaniformes desempeñaron esta misma función. Algunos hicieron las veces de vasijas-horno para reducir el mineral de cobre, en otros se han detectado restos de alimentos y también se emplearon como urnas funerarias. A pesar de esta diversidad de usos, creemos que existe una conexión ideológica entre ellos, de tal manera que habría que considerar a los campaniformes como una cerámica singular con un carácter ritual, destinada a actividades que conllevan algún tipo de transformación.

  13. Sharing Structure and Function in Biological Design with SBOL 2.0.

    Science.gov (United States)

    Roehner, Nicholas; Beal, Jacob; Clancy, Kevin; Bartley, Bryan; Misirli, Goksel; Grünberg, Raik; Oberortner, Ernst; Pocock, Matthew; Bissell, Michael; Madsen, Curtis; Nguyen, Tramy; Zhang, Michael; Zhang, Zhen; Zundel, Zach; Densmore, Douglas; Gennari, John H; Wipat, Anil; Sauro, Herbert M; Myers, Chris J

    2016-06-17

    The Synthetic Biology Open Language (SBOL) is a standard that enables collaborative engineering of biological systems across different institutions and tools. SBOL is developed through careful consideration of recent synthetic biology trends, real use cases, and consensus among leading researchers in the field and members of commercial biotechnology enterprises. We demonstrate and discuss how a set of SBOL-enabled software tools can form an integrated, cross-organizational workflow to recapitulate the design of one of the largest published genetic circuits to date, a 4-input AND sensor. This design encompasses the structural components of the system, such as its DNA, RNA, small molecules, and proteins, as well as the interactions between these components that determine the system's behavior/function. The demonstrated workflow and resulting circuit design illustrate the utility of SBOL 2.0 in automating the exchange of structural and functional specifications for genetic parts, devices, and the biological systems in which they operate.

  14. Active Interaction Mapping as a tool to elucidate hierarchical functions of biological processes.

    Science.gov (United States)

    Farré, Jean-Claude; Kramer, Michael; Ideker, Trey; Subramani, Suresh

    2017-07-03

    Increasingly, various 'omics data are contributing significantly to our understanding of novel biological processes, but it has not been possible to iteratively elucidate hierarchical functions in complex phenomena. We describe a general systems biology approach called Active Interaction Mapping (AI-MAP), which elucidates the hierarchy of functions for any biological process. Existing and new 'omics data sets can be iteratively added to create and improve hierarchical models which enhance our understanding of particular biological processes. The best datatypes to further improve an AI-MAP model are predicted computationally. We applied this approach to our understanding of general and selective autophagy, which are conserved in most eukaryotes, setting the stage for the broader application to other cellular processes of interest. In the particular application to autophagy-related processes, we uncovered and validated new autophagy and autophagy-related processes, expanded known autophagy processes with new components, integrated known non-autophagic processes with autophagy and predict other unexplored connections.

  15. X-ray diffraction and infrared spectroscopy analyses on the crystallinity of engineered biological hydroxyapatite for medical application

    Science.gov (United States)

    Poralan, G. M., Jr.; Gambe, J. E.; Alcantara, E. M.; Vequizo, R. M.

    2015-06-01

    Biological hydroxyapatite (BHAp) derived from thermally-treated fish bones was successfully produced. However, the obtained biological HAp was amorphous and thus making it unfavorable for medical application. Consequently, this research exploits and engineers the crystallinity of BHAp powders by addition of CaCO3 and investigates its degree of crystallinity using XRD and IR spectroscopy. On XRD, the HAp powders with [Ca]/[P] ratios 1.42, 1.46, 1.61 and 1.93 have degree of crystallinity equal to 58.08, 72.13, 85.79, 75.85% and crystal size equal to 0.67, 0.74, 0.75, 0.72 nm, respectively. The degree of crystallinity and crystal size of the obtained calcium deficient biological HAp powders increase as their [Ca]/[P] ratio approaches the stoichiometric ratio by addition of CaCO3 as source of Ca2+ ions. These results show the possibility of engineering the crystallinity and crystal size of biological HAp by addition of CaCO3. Moreover, the splitting factor of PO4 vibration matches the result with % crystallinity on XRD. Also, the area of phosphate-substitution site of PO4 vibration shows linear relationship (R2 = 0.994) with crystal size calculated from XRD. It is worth noting that the crystallinity of the biological HAp with [Ca]/[P] ratios 1.42 and 1.48 fall near the range 60-70% for highly resorbable HAp used in the medical application.

  16. Diurnal rhythmicity in biological processes involved in bioavailability of functional food factors.

    Science.gov (United States)

    Tsurusaki, Takashi; Sakakibara, Hiroyuki; Aoshima, Yoshiki; Yamazaki, Shunsuke; Sakono, Masanobu; Shimoi, Kayoko

    2013-05-01

    In the past few decades, many types of functional factors have been identified in dietary foods; for example, flavonoids are major groups widely distributed in the plant kingdom. However, the absorption rates of the functional food factors are usually low, and many of these are difficult to be absorbed in the intact forms because of metabolization by biological processes during absorption. To gain adequate beneficial effects, it is therefore mandatory to know whether functional food factors are absorbed in sufficient quantity, and then reach target organs while maintaining beneficial effects. These are the reasons why the bioavailability of functional food factors has been well investigated using rodent models. Recently, many of the biological processes have been reported to follow diurnal rhythms recurring every 24 h. Therefore, absorption and metabolism of functional food factors influenced by the biological processes may vary with time of day. Consequently, the evaluation of the bioavailability of functional food factors using rodent models should take into consideration the timing of consumption. In this review, we provide a perspective overview of the diurnal rhythm of biological processes involved in the bioavailability of functional food factors, particularly flavonoids.

  17. N-acylation of phosphatidylethanolamine and its biological functions in mammals

    DEFF Research Database (Denmark)

    Wellner, Niels; Diep, Thi Ai; Janfelt, Christian

    2013-01-01

    N-acylphosphatidylethanolamine (NAPE) and N-acylplasmenylethanolamine (pNAPE) are widely found phospholipids, and they are precursors for N-acylethanolamines, a group of compounds that has a variety of biological effects and encompasses the endocannabinoid anandamide. NAPE and pNAPE are synthesiz...... reviews the metabolism, occurrence and assay of NAPE and pNAPE, and discusses the putative biological functions in mammals of these phospholipids. This article is part of a Special Issue entitled Phospholipids and Phospholipid Metabolism....

  18. Functional assays and metagenomic analyses reveals differences between the microbial communities inhabiting the soil horizons of a Norway spruce plantation.

    Directory of Open Access Journals (Sweden)

    Stéphane Uroz

    Full Text Available In temperate ecosystems, acidic forest soils are among the most nutrient-poor terrestrial environments. In this context, the long-term differentiation of the forest soils into horizons may impact the assembly and the functions of the soil microbial communities. To gain a more comprehensive understanding of the ecology and functional potentials of these microbial communities, a suite of analyses including comparative metagenomics was applied on independent soil samples from a spruce plantation (Breuil-Chenue, France. The objectives were to assess whether the decreasing nutrient bioavailability and pH variations that naturally occurs between the organic and mineral horizons affects the soil microbial functional biodiversity. The 14 Gbp of pyrosequencing and Illumina sequences generated in this study revealed complex microbial communities dominated by bacteria. Detailed analyses showed that the organic soil horizon was significantly enriched in sequences related to Bacteria, Chordata, Arthropoda and Ascomycota. On the contrary the mineral horizon was significantly enriched in sequences related to Archaea. Our analyses also highlighted that the microbial communities inhabiting the two soil horizons differed significantly in their functional potentials according to functional assays and MG-RAST analyses, suggesting a functional specialisation of these microbial communities. Consistent with this specialisation, our shotgun metagenomic approach revealed a significant increase in the relative abundance of sequences related glycoside hydrolases in the organic horizon compared to the mineral horizon that was significantly enriched in glycoside transferases. This functional stratification according to the soil horizon was also confirmed by a significant correlation between the functional assays performed in this study and the functional metagenomic analyses. Together, our results suggest that the soil stratification and particularly the soil resource

  19. Composite Structural Motifs of Binding Sites for Delineating Biological Functions of Proteins

    Science.gov (United States)

    Kinjo, Akira R.; Nakamura, Haruki

    2012-01-01

    Most biological processes are described as a series of interactions between proteins and other molecules, and interactions are in turn described in terms of atomic structures. To annotate protein functions as sets of interaction states at atomic resolution, and thereby to better understand the relation between protein interactions and biological functions, we conducted exhaustive all-against-all atomic structure comparisons of all known binding sites for ligands including small molecules, proteins and nucleic acids, and identified recurring elementary motifs. By integrating the elementary motifs associated with each subunit, we defined composite motifs that represent context-dependent combinations of elementary motifs. It is demonstrated that function similarity can be better inferred from composite motif similarity compared to the similarity of protein sequences or of individual binding sites. By integrating the composite motifs associated with each protein function, we define meta-composite motifs each of which is regarded as a time-independent diagrammatic representation of a biological process. It is shown that meta-composite motifs provide richer annotations of biological processes than sequence clusters. The present results serve as a basis for bridging atomic structures to higher-order biological phenomena by classification and integration of binding site structures. PMID:22347478

  20. To What Extent Do Biology Textbooks Contribute to Scientific Literacy? Criteria for Analysing Science-Technology-Society-Environment Issues

    Science.gov (United States)

    Calado, Florbela M.; Scharfenberg, Franz-Josef; Bogner, Franz X.

    2015-01-01

    Our article proposes a set of six criteria for analysing science-technology-society-environment (STSE) issues in regular textbooks as to how they are expected to contribute to students' scientific literacy. We chose genetics and gene technology as fields prolific in STSE issues. We derived our criteria (including 26 sub-criteria) from a literature…

  1. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

    DEFF Research Database (Denmark)

    Scott, Robert A; Lagou, Vasiliki; Welch, Ryan P

    2012-01-01

    Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes...

  2. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

    NARCIS (Netherlands)

    Scott, Robert A.; Lagou, Vasiliki; Welch, Ryan P.; Wheeler, Eleanor; Montasser, May E.; Luan, Jian'an; Mägi, Reedik; Strawbridge, Rona J.; Rehnberg, Emil; Gustafsson, Stefan; Kanoni, Stavroula; Rasmussen-Torvik, Laura J.; Yengo, Loïc; Lecoeur, Cecile; Shungin, Dmitry; Sanna, Serena; Sidore, Carlo; Johnson, Paul C. D.; Jukema, J. Wouter; Johnson, Toby; Mahajan, Anubha; Verweij, Niek; Thorleifsson, Gudmar; Hottenga, Jouke-Jan; Shah, Sonia; Smith, Albert V.; Sennblad, Bengt; Gieger, Christian; Salo, Perttu; Perola, Markus; Timpson, Nicholas J.; Evans, David M.; Pourcain, Beate St; Wu, Ying; Andrews, Jeanette S.; Hui, Jennie; Bielak, Lawrence F.; Zhao, Wei; Horikoshi, Momoko; Navarro, Pau; Isaacs, Aaron; O'Connell, Jeffrey R.; Stirrups, Kathleen; Vitart, Veronique; Hayward, Caroline; Esko, Tõnu; Mihailov, Evelin; Fraser, Ross M.; Fall, Tove; Voight, Benjamin F.; Raychaudhuri, Soumya; Chen, Han; Lindgren, Cecilia M.; Morris, Andrew P.; Rayner, Nigel W.; Robertson, Neil; Rybin, Denis; Liu, Ching-Ti; Beckmann, Jacques S.; Willems, Sara M.; Chines, Peter S.; Jackson, Anne U.; Kang, Hyun Min; Stringham, Heather M.; Song, Kijoung; Tanaka, Toshiko; Peden, John F.; Goel, Anuj; Hicks, Andrew A.; An, Ping; Müller-Nurasyid, Martina; Franco-Cereceda, Anders; Folkersen, Lasse; Marullo, Letizia; Jansen, Hanneke; Oldehinkel, Albertine J.; Bruinenberg, Marcel; Pankow, James S.; North, Kari E.; Forouhi, Nita G.; Loos, Ruth J. F.; Edkins, Sarah; Varga, Tibor V.; Hallmans, Göran; Oksa, Heikki; Antonella, Mulas; Nagaraja, Ramaiah; Trompet, Stella; Ford, Ian; Bakker, Stephan J. L.; Kong, Augustine; Kumari, Meena; Gigante, Bruna; Herder, Christian; Munroe, Patricia B.; Caulfield, Mark; Antti, Jula; Mangino, Massimo; Small, Kerrin; Miljkovic, Iva; Liu, Yongmei; Atalay, Mustafa; Kiess, Wieland; James, Alan L.; Rivadeneira, Fernando; Uitterlinden, Andre G.; Palmer, Colin N. A.; Doney, Alex S. F.; Willemsen, Gonneke; Smit, Johannes H.; Campbell, Susan; Polasek, Ozren; Bonnycastle, Lori L.; Hercberg, Serge; Dimitriou, Maria; Bolton, Jennifer L.; Fowkes, Gerard R.; Kovacs, Peter; Lindström, Jaana; Zemunik, Tatijana; Bandinelli, Stefania; Wild, Sarah H.; Basart, Hanneke V.; Rathmann, Wolfgang; Grallert, Harald; Maerz, Winfried; Kleber, Marcus E.; Boehm, Bernhard O.; Peters, Annette; Pramstaller, Peter P.; Province, Michael A.; Borecki, Ingrid B.; Hastie, Nicholas D.; Rudan, Igor; Campbell, Harry; Watkins, Hugh; Farrall, Martin; Stumvoll, Michael; Ferrucci, Luigi; Waterworth, Dawn M.; Bergman, Richard N.; Collins, Francis S.; Tuomilehto, Jaakko; Watanabe, Richard M.; de Geus, Eco J. C.; Penninx, Brenda W.; Hofman, Albert; Oostra, Ben A.; Psaty, Bruce M.; Vollenweider, Peter; Wilson, James F.; Wright, Alan F.; Hovingh, G. Kees; Metspalu, Andres; Uusitupa, Matti; Magnusson, Patrik K. E.; Kyvik, Kirsten O.; Kaprio, Jaakko; Price, Jackie F.; Dedoussis, George V.; Deloukas, Panos; Meneton, Pierre; Lind, Lars; Boehnke, Michael; Shuldiner, Alan R.; van Duijn, Cornelia M.; Morris, Andrew D.; Toenjes, Anke; Peyser, Patricia A.; Beilby, John P.; Körner, Antje; Kuusisto, Johanna; Laakso, Markku; Bornstein, Stefan R.; Schwarz, Peter E. H.; Lakka, Timo A.; Rauramaa, Rainer; Adair, Linda S.; Smith, George Davey; Spector, Tim D.; Illig, Thomas; de Faire, Ulf; Hamsten, Anders; Gudnason, Vilmundur; Kivimaki, Mika; Hingorani, Aroon; Keinanen-Kiukaanniemi, Sirkka M.; Saaristo, Timo E.; Boomsma, Dorret I.; Stefansson, Kari; van der Harst, Pim; Dupuis, Josée; Pedersen, Nancy L.; Sattar, Naveed; Harris, Tamara B.; Cucca, Francesco; Ripatti, Samuli; Salomaa, Veikko; Mohlke, Karen L.; Balkau, Beverley; Froguel, Philippe; Pouta, Anneli; Jarvelin, Marjo-Riitta; Wareham, Nicholas J.; Bouatia-Naji, Nabila; McCarthy, Mark I.; Franks, Paul W.; Meigs, James B.; Teslovich, Tanya M.; Florez, Jose C.; Langenberg, Claudia; Ingelsson, Erik; Prokopenko, Inga; Barroso, Inês

    2012-01-01

    Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes

  3. Biologic variability and correlation of platelet function testing in healthy dogs.

    Science.gov (United States)

    Blois, Shauna L; Lang, Sean T; Wood, R Darren; Monteith, Gabrielle

    2015-12-01

    Platelet function tests are influenced by biologic variability, including inter-individual (CVG ) and intra-individual (CVI ), as well as analytic (CVA ) variability. Variability in canine platelet function testing is unknown, but if excessive, would make it difficult to interpret serial results. Additionally, the correlation between platelet function tests is poor in people, but not well described in dogs. The aims were to: (1) identify the effect of variation in preanalytic factors (venipuncture, elapsed time until analysis) on platelet function tests; (2) calculate analytic and biologic variability of adenosine diphosphate (ADP) and arachidonic acid (AA)-induced thromboelastograph platelet mapping (TEG-PM), ADP-, AA-, and collagen-induced whole blood platelet aggregometry (WBA), and collagen/ADP and collagen/epinephrine platelet function analysis (PFA-CADP, PFA-CEPI); and (3) determine the correlation between these variables. In this prospective observational trial, platelet function was measured once every 7 days, for 4 consecutive weeks, in 9 healthy dogs. In addition, CBC, TEG-PM, WBA, and PFA were performed. Overall coefficients of variability ranged from 13.3% to 87.8% for the platelet function tests. Biologic variability was highest for AA-induced maximum amplitude generated during TEG-PM (MAAA; CVG = 95.3%, CVI = 60.8%). Use of population-based reference intervals (RI) was determined appropriate only for PFA-CADP (index of individuality = 10.7). There was poor correlation between most platelet function tests. Use of population-based RI appears inappropriate for most platelet function tests, and tests poorly correlate with one another. Future studies on biologic variability and correlation of platelet function tests should be performed in dogs with platelet dysfunction and those treated with antiplatelet therapy. © 2015 American Society for Veterinary Clinical Pathology.

  4. Effects of Computer-Based Training on Procedural Modifications to Standard Functional Analyses

    Science.gov (United States)

    Schnell, Lauren K.; Sidener, Tina M.; DeBar, Ruth M.; Vladescu, Jason C.; Kahng, SungWoo

    2018-01-01

    Few studies have evaluated methods for training decision-making when functional analysis data are undifferentiated. The current study evaluated computer-based training to teach 20 graduate students to arrange functional analysis conditions, analyze functional analysis data, and implement procedural modifications. Participants were exposed to…

  5. The relationship between oral health status and biological and psychosocial function in the bedridden elderly.

    Science.gov (United States)

    Hanada, N; Tada, A

    2001-01-01

    The present study was conducted in order to determine what item of biological and psychosocial function is related to oral health status in the bedridden elderly. The subjects were 94 elderly individuals (30 males, 64 females) who had been admitted to a nursing home in Chiba city, Japan. We assessed the number of remaining teeth and the number of functional teeth as oral health status variables. Biological and psychosocial function levels were determined using the functional independence measure method developed by the State University of New York at Buffalo. More than 70% of subjects had less than ten remaining teeth. Almost all subjects needed prosthesis treatment. More than 50% of subjects had 27 or less functional teeth. Mann-Whitney U-test and logistic regression models showed that 'expression' was concerned with the number of remaining teeth and 'bladder management', 'locomotion', 'transfers' were related to the number of functional teeth. These data suggest close relation between oral health status and biological and psychosocial function levels in the bedridden elderly.

  6. Integrative functional genomic analyses implicate specific molecular pathways and circuits in autism

    OpenAIRE

    Parikshak, Neelroop N.; Luo, Rui; Zhang, Alice; Won, Hyejung; Lowe, Jennifer K.; Chandran, Vijayendran; Horvath, Steve; Geschwind, Daniel H.

    2013-01-01

    Genetic studies have identified dozens of autism spectrum disorder (ASD) susceptibility genes, raising two critical questions: 1) do these genetic loci converge on specific biological processes, and 2) where does the phenotypic specificity of ASD arise, given its genetic overlap with intellectual disability (ID)? To address this, we mapped ASD and ID risk genes onto co-expression networks representing developmental trajectories and transcriptional profiles representing fetal and adult cortica...

  7. [Recent advances of synthetic biology for production of functional ingredients in Chinese materia medica].

    Science.gov (United States)

    Su, Xin-Yao; Xue, Jian-Ping; Wang, Cai-Xia

    2016-11-01

    The functional ingredients in Chinese materia medica are the main active substance for traditional Chinese medicine and most of them are secondary metabolites derivatives. Until now,the main method to obtain those functional ingredients is through direct extraction from the Chinese materia medica. However, the income is very low because of the high extraction costs and the decreased medicinal plants. Synthetic biology technology, as a new and microbial approach, can be able to carry out large-scale production of functional ingredients and greatly ease the shortage of traditional Chinese medicine ingredients. This review mainly focused on the recent advances in synthetic biology for the functional ingredients production. Copyright© by the Chinese Pharmaceutical Association.

  8. Metagenomic and functional analyses of the consequences of reduction of bacterial diversity on soil functions and bioremediation in diesel-contaminated microcosms

    OpenAIRE

    Jung, Jaejoon; Philippot, Laurent

    2016-01-01

    The relationship between microbial biodiversity and soil function is an important issue in ecology, yet most studies have been performed in pristine ecosystems. Here, we assess the role of microbial diversity in ecological function and remediation strategies in diesel-contaminated soils. Soil microbial diversity was manipulated using a removal by dilution approach and microbial functions were determined using both metagenomic analyses and enzymatic assays. A shift from Proteobacteria- to Acti...

  9. Significance of functional disease-causal/susceptible variants identified by whole-genome analyses for the understanding of human diseases.

    Science.gov (United States)

    Hitomi, Yuki; Tokunaga, Katsushi

    2017-01-01

    Human genome variation may cause differences in traits and disease risks. Disease-causal/susceptible genes and variants for both common and rare diseases can be detected by comprehensive whole-genome analyses, such as whole-genome sequencing (WGS), using next-generation sequencing (NGS) technology and genome-wide association studies (GWAS). Here, in addition to the application of an NGS as a whole-genome analysis method, we summarize approaches for the identification of functional disease-causal/susceptible variants from abundant genetic variants in the human genome and methods for evaluating their functional effects in human diseases, using an NGS and in silico and in vitro functional analyses. We also discuss the clinical applications of the functional disease causal/susceptible variants to personalized medicine.

  10. PANTHER version 6: protein sequence and function evolution data with expanded representation of biological pathways

    OpenAIRE

    Mi, Huaiyu; Guo, Nan; Kejariwal, Anish; Thomas, Paul D.

    2006-01-01

    PANTHER is a freely available, comprehensive software system for relating protein sequence evolution to the evolution of specific protein functions and biological roles. Since 2005, there have been three main improvements to PANTHER. First, the sequences used to create evolutionary trees are carefully selected to provide coverage of phylogenetic as well as functional information. Second, PANTHER is now a member of the InterPro Consortium, and the PANTHER hidden markov Models (HMMs) are distri...

  11. Metagenomics and in situ analyses reveal Propionivibrio spp. to be abundant GAO in biological wastewater treatment systems

    DEFF Research Database (Denmark)

    McIlroy, Simon Jon; Albertsen, Mads; Stokholm-Bjerregaard, Mikkel

    Enhanced biological phosphorus removal (EBPR) is widely applied for phosphorus removal from wastewater. The process relies on polyphosphate-accumulating organisms (PAOs) that are able to take up phosphorus in excess of what is needed for growth. However, glycogen-accumulating organisms (GAOs) may...... reduce the EBPR efficiency as they compete for substrates with PAOs, but do not store excess polyphosphate. “Candidatus Accumulibacter” is widely considered to be the important PAO. In this study a laboratory scale sequencing batch reactor was operated for EBPR for the enrichment of “Ca. Accumulibacter......”. Applying the PAOmix probe set, routinely applied to target the “Ca. Accumulibacter”, suggested a PAO enrichment of 70% of the biovolume by FISH. Known GAOs were detected in low abundance with FISH (PAO and GAO...

  12. Late-stage diversification of biologically active pyridazinones via a direct C-H functionalization strategy.

    Science.gov (United States)

    Li, Wei; Fan, Zhoulong; Geng, Kaijun; Xu, Youjun; Zhang, Ao

    2015-01-14

    Divergent C-H functionalization reactions (arylation, carboxylation, olefination, thiolation, acetoxylation, halogenation, naphthylation) using a pyridazinone moiety as an internal directing group were successfully established. This approach offers a late-stage, ortho-selective diversification of a biologically active pyridazinone scaffold. Seven series of novel pyridazinone analogues were synthesized conveniently as the synthetic precursors of potential sortase A (SrtA) inhibitors.

  13. Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function

    NARCIS (Netherlands)

    D.B. Hancock (Dana); M. Eijgelsheim (Mark); J.B. Wilk (Jemma); S.A. Gharib (Sina); L.R. Loehr (Laura); K. Marciante (Kristin); N. Franceschini (Nora); Y.M.T.A. van Durme; T.H. Chen; R.G. Barr (Graham); M.B. Schabath (Matthew); D.J. Couper (David); G.G. Brusselle (Guy); B.M. Psaty (Bruce); P. Tikka-Kleemola (Päivi); J.I. Rotter (Jerome); A.G. Uitterlinden (André); A. Hofman (Albert); N.M. Punjabi (Naresh); F. Rivadeneira Ramirez (Fernando); A.C. Morrison (Alanna); P.L. Enright (Paul); K.E. North (Kari); S.R. Heckbert (Susan); T. Lumley (Thomas); B.H.Ch. Stricker (Bruno); G.T. O'Connor (George); S.J. London (Stephanie)

    2010-01-01

    textabstractSpirometric measures of lung function are heritable traits that reflect respiratory health and predict morbidity and mortality. We meta-analyzed genome-wide association studies for two clinically important lung-function measures: forced expiratory volume in the first second (FEV1) and

  14. A promising future for integrative biodiversity research: an increased role of scale-dependency and functional biology

    Science.gov (United States)

    Schmitz, L.

    2016-01-01

    Studies into the complex interaction between an organism and changes to its biotic and abiotic environment are fundamental to understanding what regulates biodiversity. These investigations occur at many phylogenetic, temporal and spatial scales and within a variety of biological and geological disciplines but often in relative isolation. This issue focuses on what can be achieved when ecological mechanisms are integrated into analyses of deep-time biodiversity patterns through the union of fossil and extant data and methods. We expand upon this perspective to argue that, given its direct relevance to the current biodiversity crisis, greater integration is needed across biodiversity research. We focus on the need to understand scaling effects, how lower-level ecological and evolutionary processes scale up and vice versa, and the importance of incorporating functional biology. Placing function at the core of biodiversity research is fundamental, as it establishes how an organism interacts with its abiotic and biotic environment and it is functional diversity that ultimately determines important ecosystem processes. To achieve full integration, concerted and ongoing efforts are needed to build a united and interactive community of biodiversity researchers, with education and interdisciplinary training at its heart. PMID:26977068

  15. A promising future for integrative biodiversity research: an increased role of scale-dependency and functional biology.

    Science.gov (United States)

    Price, S A; Schmitz, L

    2016-04-05

    Studies into the complex interaction between an organism and changes to its biotic and abiotic environment are fundamental to understanding what regulates biodiversity. These investigations occur at many phylogenetic, temporal and spatial scales and within a variety of biological and geological disciplines but often in relative isolation. This issue focuses on what can be achieved when ecological mechanisms are integrated into analyses of deep-time biodiversity patterns through the union of fossil and extant data and methods. We expand upon this perspective to argue that, given its direct relevance to the current biodiversity crisis, greater integration is needed across biodiversity research. We focus on the need to understand scaling effects, how lower-level ecological and evolutionary processes scale up and vice versa, and the importance of incorporating functional biology. Placing function at the core of biodiversity research is fundamental, as it establishes how an organism interacts with its abiotic and biotic environment and it is functional diversity that ultimately determines important ecosystem processes. To achieve full integration, concerted and ongoing efforts are needed to build a united and interactive community of biodiversity researchers, with education and interdisciplinary training at its heart. © 2016 The Author(s).

  16. A biologically inspired psychometric function for accuracy of visual identification as a function of exposure duration

    DEFF Research Database (Denmark)

    Petersen, Anders; Andersen, Tobias

    , all of these having a temporal offset included, as well as the ex-Gaussian, and finally a new psychometric function, motivated from single-neuron studies by (Albrecht, Geisler, Frazor & Crane, 2002). The new psychometric function stands out by having a nonmonotonous hazard rate which is initially...

  17. Evaluating the Accuracy of Results for Teacher Implemented Trial-Based Functional Analyses.

    Science.gov (United States)

    Rispoli, Mandy; Ninci, Jennifer; Burke, Mack D; Zaini, Samar; Hatton, Heather; Sanchez, Lisa

    2015-09-01

    Trial-based functional analysis (TBFA) allows for the systematic and experimental assessment of challenging behavior in applied settings. The purposes of this study were to evaluate a professional development package focused on training three Head Start teachers to conduct TBFAs with fidelity during ongoing classroom routines. To assess the accuracy of the TBFA results, the effects of a function-based intervention derived from the TBFA were compared with the effects of a non-function-based intervention. Data were collected on child challenging behavior and appropriate communication. An A-B-A-C-D design was utilized in which A represented baseline, and B and C consisted of either function-based or non-function-based interventions counterbalanced across participants, and D represented teacher implementation of the most effective intervention. Results showed that the function-based intervention produced greater decreases in challenging behavior and greater increases in appropriate communication than the non-function-based intervention for all three children. © The Author(s) 2015.

  18. End-systolic stress-velocity relation and circumferential fiber velocity shortening for analysing left ventricular function in mice

    Energy Technology Data Exchange (ETDEWEB)

    Fayssoil, A. [Cardiologie, Hopital europeen Georges Pompidou, 20, rue le blanc, Paris (France)], E-mail: fayssoil2000@yahoo.fr; Renault, G. [CNRS UMR 8104, Inserm, U567, Institut Cochin, Universite Paris Descartes, Paris (France); Fougerousse, F. [Genethon, RD, Evry (France)

    2009-08-15

    Traditionally, analysing left ventricular (LV) performance relies on echocardiography by evaluating shortening fraction (SF) in mice. SF is influenced by load conditions. End-systolic stress-velocity (ESSV) relation and circumferential fiber velocity (VcF) shortening are more relevant parameters for evaluating systolic function regardless load conditions particularly in mice's models of heart failure.

  19. Sum rule and hydrodynamic analyses of the velocity autocorrelation function in strongly coupled plasmas

    International Nuclear Information System (INIS)

    Nagano, Seido; Ichimaru, Setsuo

    1980-01-01

    The memory function for the velocity autocorrelation function in a strongly coupled, one-component plasma is analyzed in the short time and long time domains, respectively, with the aid of the frequency-moment sum rules and the hydrodynamic consideration evoking the idea of the generalized Stokes friction. A series of interpolation schemes with successively improved accuracies are then introduced. Numerical investigations of those interpolation schemes clarify the physical origin of the three different types of the velocity autocorrelation function observed in the molecular dynamics simulation at different regimes of the coupling constant. (author)

  20. An Innovative Approach to Functionality Testing of Analysers in the Clinical Laboratory

    OpenAIRE

    Stockmann, Wolfgang; Engeldinger, Werner; Kunst, Albert; McGovern, Margaret

    2008-01-01

    The established protocols for evaluating new analytical systems produce indispensable information with regard to quality characteristics, but in general they fail to analyse the system performance under routine-like conditions. We describe a model which allows the testing of a new analytical system under conditions close to the routine in a controlled and systematic manner by using an appropriate software tool. Performing routine simulation experiments, either reflecting imprecision or method...

  1. Cotyledonary somatic embryos of Pinus pinaster Ait. most closely resemble fresh, maturing cotyledonary zygotic embryos: biological, carbohydrate and proteomic analyses.

    Science.gov (United States)

    Morel, Alexandre; Trontin, Jean-François; Corbineau, Françoise; Lomenech, Anne-Marie; Beaufour, Martine; Reymond, Isabelle; Le Metté, Claire; Ader, Kevin; Harvengt, Luc; Cadene, Martine; Label, Philippe; Teyssier, Caroline; Lelu-Walter, Marie-Anne

    2014-11-01

    Cotyledonary somatic embryos (SEs) of maritime pine are routinely matured for 12 weeks before being germinated and converted to plantlets. Although regeneration success is highly dependent on SEs quality, the date of harvesting is currently determined mainly on the basis of morphological features. This empirical method does not provide any accurate information about embryo quality with respect to storage compounds (proteins, carbohydrates). We first analyzed SEs matured for 10, 12 and 14 weeks by carrying out biological (dry weight, water content) and biochemical measurements (total protein and carbohydrate contents). No difference could be found between collection dates, suggesting that harvesting SEs after 12 weeks is appropriate. Cotyledonary SEs were then compared to various stages, from fresh to fully desiccated, in the development of cotyledonary zygotic embryos (ZEs). We identified profiles that were similar using hierarchical ascendant cluster analysis (HCA). Fresh and dehydrated ZEs could be distinguished, and SEs clustered with fresh ZEs. Both types of embryo exhibited similar carbohydrate and protein contents and signatures. This high level of similarity (94.5 %) was further supported by proteome profiling. Highly expressed proteins included storage, stress-related, late embryogenesis abundant and energy metabolism proteins. By comparing overexpressed proteins in developing and cotyledonary SEs or ZEs, some (23 proteins) could be identified as candidate biomarkers for the late, cotyledonary stage. This is the first report of useful generic protein markers for monitoring embryo development in maritime pine. Our results also suggest that improvements of SEs quality may be achieved if the current maturation conditions are refined.

  2. Synchrotron radiation. 4. Analyses of biological samples using synchrotron radiation. 3. Research on radiation damage to DNA using synchrotron radiation

    International Nuclear Information System (INIS)

    Takakura, Kaoru

    1998-01-01

    This review described how the synchrotron radiation (SR) is used to solve problems unknown hitherto in radiation biology. Historically, the target substance of UV light in bacterial death was suggested to be nucleic acid in 1930. Researches on the radiation damage to DNA were begun at around 1960 and have mainly used UV light, X-ray and γray. Soft X-ray and vacuum UV whose energy covering from several eV to scores of keV have not been used since UV and X-ray lack the energy of this range. This is one of reasons why detailed process leading to radiation-induced death, carcinogenicity and mutation has not been known hitherto. RS possesses wide range of energy, i.e., from UV to hard X-ray, of high intensity, which is helpful for studying the unknown problems. The RS studies were begun in nineteen-seventies. Those include the action spectrum studies and atomic target studies. In the former, the course of the effect, e.g., the mechanism of DNA double strand breakage, can be elucidated. In the latter, photon of known energy can be irradiated to the specified atom like phosphorus in DNA which elucidating the precise physicochemical process of the breakage. Use of RS in these studies is thought still meaningful in future. (K.H.) 62 refs

  3. Functional Analyses of Bitter Taste Receptors in Domestic Cats (Felis catus.

    Directory of Open Access Journals (Sweden)

    Weiwei Lei

    Full Text Available Cats are obligate carnivores and under most circumstances eat only animal products. Owing to the pseudogenization of one of two subunits of the sweet receptor gene, they are indifferent to sweeteners, presumably having no need to detect plant-based sugars in their diet. Following this reasoning and a recent report of a positive correlation between the proportion of dietary plants and the number of Tas2r (bitter receptor genes in vertebrate species, we tested the hypothesis that if bitter perception exists primarily to protect animals from poisonous plant compounds, the genome of the domestic cat (Felis catus should have lost functional bitter receptors and they should also have reduced bitter receptor function. To test functionality of cat bitter receptors, we expressed cat Tas2R receptors in cell-based assays. We found that they have at least 7 functional receptors with distinct receptive ranges, showing many similarities, along with some differences, with human bitter receptors. To provide a comparative perspective, we compared the cat repertoire of intact receptors with those of a restricted number of members of the order Carnivora, with a range of dietary habits as reported in the literature. The numbers of functional bitter receptors in the terrestrial Carnivora we examined, including omnivorous and herbivorous species, were roughly comparable to that of cats thereby providing no strong support for the hypothesis that a strict meat diet influences bitter receptor number or function. Maintenance of bitter receptor function in terrestrial obligate carnivores may be due to the presence of bitter compounds in vertebrate and invertebrate prey, to the necessary role these receptors play in non-oral perception, or to other unknown factors. We also found that the two aquatic Carnivora species examined had fewer intact bitter receptors. Further comparative studies of factors driving numbers and functions of bitter taste receptors will aid in

  4. Functional Analyses of Bitter Taste Receptors in Domestic Cats (Felis catus).

    Science.gov (United States)

    Lei, Weiwei; Ravoninjohary, Aurore; Li, Xia; Margolskee, Robert F; Reed, Danielle R; Beauchamp, Gary K; Jiang, Peihua

    2015-01-01

    Cats are obligate carnivores and under most circumstances eat only animal products. Owing to the pseudogenization of one of two subunits of the sweet receptor gene, they are indifferent to sweeteners, presumably having no need to detect plant-based sugars in their diet. Following this reasoning and a recent report of a positive correlation between the proportion of dietary plants and the number of Tas2r (bitter receptor) genes in vertebrate species, we tested the hypothesis that if bitter perception exists primarily to protect animals from poisonous plant compounds, the genome of the domestic cat (Felis catus) should have lost functional bitter receptors and they should also have reduced bitter receptor function. To test functionality of cat bitter receptors, we expressed cat Tas2R receptors in cell-based assays. We found that they have at least 7 functional receptors with distinct receptive ranges, showing many similarities, along with some differences, with human bitter receptors. To provide a comparative perspective, we compared the cat repertoire of intact receptors with those of a restricted number of members of the order Carnivora, with a range of dietary habits as reported in the literature. The numbers of functional bitter receptors in the terrestrial Carnivora we examined, including omnivorous and herbivorous species, were roughly comparable to that of cats thereby providing no strong support for the hypothesis that a strict meat diet influences bitter receptor number or function. Maintenance of bitter receptor function in terrestrial obligate carnivores may be due to the presence of bitter compounds in vertebrate and invertebrate prey, to the necessary role these receptors play in non-oral perception, or to other unknown factors. We also found that the two aquatic Carnivora species examined had fewer intact bitter receptors. Further comparative studies of factors driving numbers and functions of bitter taste receptors will aid in understanding the forces

  5. Comparative Analyses of Aryl Hydrocarbon Receptor Structure, Function, and Evolution in Marine Mammals

    Science.gov (United States)

    2007-02-01

    function in early vertebrates: inducibility of cytochrome P450 1A in agnathan and elasmobranch fish . Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 120...J.Y., A.G. McArthur and J.J. Stegeman. 2005b. Characterization of a cetacean aromatase (CYP19) and the phylogeny and functional conservation of... phylogeny of cetaceans prompts revision of morphological transformations. Trends in Ecology and Evolution 10:328-334. Nei, M., P. Xu and G. Glazko

  6. Cross-biome metagenomic analyses of soil microbial communities and their functional attributes.

    Science.gov (United States)

    Fierer, Noah; Leff, Jonathan W; Adams, Byron J; Nielsen, Uffe N; Bates, Scott Thomas; Lauber, Christian L; Owens, Sarah; Gilbert, Jack A; Wall, Diana H; Caporaso, J Gregory

    2012-12-26

    For centuries ecologists have studied how the diversity and functional traits of plant and animal communities vary across biomes. In contrast, we have only just begun exploring similar questions for soil microbial communities despite soil microbes being the dominant engines of biogeochemical cycles and a major pool of living biomass in terrestrial ecosystems. We used metagenomic sequencing to compare the composition and functional attributes of 16 soil microbial communities collected from cold deserts, hot deserts, forests, grasslands, and tundra. Those communities found in plant-free cold desert soils typically had the lowest levels of functional diversity (diversity of protein-coding gene categories) and the lowest levels of phylogenetic and taxonomic diversity. Across all soils, functional beta diversity was strongly correlated with taxonomic and phylogenetic beta diversity; the desert microbial communities were clearly distinct from the nondesert communities regardless of the metric used. The desert communities had higher relative abundances of genes associated with osmoregulation and dormancy, but lower relative abundances of genes associated with nutrient cycling and the catabolism of plant-derived organic compounds. Antibiotic resistance genes were consistently threefold less abundant in the desert soils than in the nondesert soils, suggesting that abiotic conditions, not competitive interactions, are more important in shaping the desert microbial communities. As the most comprehensive survey of soil taxonomic, phylogenetic, and functional diversity to date, this study demonstrates that metagenomic approaches can be used to build a predictive understanding of how microbial diversity and function vary across terrestrial biomes.

  7. Short term recovery of soil biological functions in a new vineyard cultivated in organic farming

    Science.gov (United States)

    Costantini, Edoardo; Agnelli, Alessandro; Fabiani, Arturo; Gagnarli, Elena; Mocali, Stefano; Priori, Simone; Simoni, Sauro; Valboa, Giuseppe

    2014-05-01

    Deep earthwork activities carried out before vineyard plantation completely upset soil profile and characteristics. The resulting soil features are often much more similar to the underlying substratum than original soil profile. The time needed to recover soil functions is ecologically relevant and affects vine phenology and grape yield, particularly in organic viticulture. The general aim of this research work was to investigate the time needed to recover soil functions after the earthworks made before vine plantation. This study compared for a four years period physical and chemical properties, microbial and mesofauna communities, in new and old vineyards, cultivated on the same soil type. The experiment was conducted in a farm of the Chianti Classico district (Central Italy), on hills of high altitude (400-500 m a.s.l.) on clayey-calcareous flysches, with stony and calcareous soils (Haplic Cambisol (Calcaric, Skeletic)). The reference vine cultivar was Sangiovese. The older vineyard was planted in 2000, after slope reshaping by bulldozing and back hoe ploughing down to about 0.8-1.0 m. The new vineyard was planted in 2011 after an equivalent earthwork carried out in the summer of 2009. Both vineyards were organically managed and only compost at the rate of 1,000 kg ha-1 -a was added every year. The new vineyard was periodically cultivated by mechanical tillage, while the older only at alternate rows. Soil samples from the first 15 cm depth were collected in 4 replicates in the younger as well as in the older vineyard during the springtime of 2010-2013; in the older vineyard, two samples were from the periodically cultivated swaths and two under permanent grass cover. Samples were analysed for physical (particle size, field capacity, wilting point), chemical (pH, electrical conductivity, lime, active lime, organic carbon, total nitrogen), microbiological (soil respiration, microbial biomass, DGGE), and mesofauna features (abundance, taxa richness, BSQ index and

  8. Single amino acid substitution in important hemoglobinopathies does not disturb molecular function and biological process

    Directory of Open Access Journals (Sweden)

    Viroj Wiwanitkit

    2008-06-01

    Full Text Available Viroj WiwanitkitDepartment of Laboratory Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, ThailandAbstract: Hemoglobin is an important protein found in the red cells of many animals. In humans, the hemoglobin is mainly distributed in the red blood cell. Single amino acid substitution is the main pathogenesis of most hemoglobin disorders. Here, the author used a new gene ontology technology to predict the molecular function and biological process of four important hemoglobin disorders with single substitution. The four studied important abnormal hemoglobins (Hb with single substitution included Hb S, Hb E, Hb C, and Hb J-Baltimore. Using the GoFigure server, the molecular function and biological process in normal and abnormal hemoglobins was predicted. Compared with normal hemoglobin, all studied abnormal hemoglobins had the same function and biological process. This indicated that the overall function of oxygen transportation is not disturbed in the studied hemoglobin disorders. Clinical findings of oxygen depletion in abnormal hemoglobin should therefore be due to the other processes rather than genomics, proteomics, and expression levels.Keywords: hemoglobin, amino acid, substitution, function

  9. Genome-wide functional genomic and transcriptomic analyses for genes regulating sensitivity to vorinostat.

    Science.gov (United States)

    Falkenberg, Katrina J; Gould, Cathryn M; Johnstone, Ricky W; Simpson, Kaylene J

    2014-01-01

    Identification of mechanisms of resistance to histone deacetylase inhibitors, such as vorinostat, is important in order to utilise these anticancer compounds more efficiently in the clinic. Here, we present a dataset containing multiple tiers of stringent siRNA screening for genes that when knocked down conferred sensitivity to vorinostat-induced cell death. We also present data from a miRNA overexpression screen for miRNAs contributing to vorinostat sensitivity. Furthermore, we provide transcriptomic analysis using massively parallel sequencing upon knockdown of 14 validated vorinostat-resistance genes. These datasets are suitable for analysis of genes and miRNAs involved in cell death in the presence and absence of vorinostat as well as computational biology approaches to identify gene regulatory networks.

  10. Radiotoxicological analyses of 239+240Pu and 241Am in biological samples by anion-exchange and extraction chromatography: a preliminary study for internal contamination evaluations

    International Nuclear Information System (INIS)

    Ridone, S.; Arginelli, D.; Bortoluzzi, S.; Canuto, G.; Montalto, M.; Nocente, M.; Vegro, M.

    2006-01-01

    Many biological samples (urines and faeces) have been analysed by means of chromatographic extraction columns, utilising two different resins (AG 1-X2 resin chloride and T.R.U.), in order to detect the possible internal contamination of 239 + 240 Pu and 241 Am, for some workers of a reprocessing nuclear plant in the decommissioning phase. The results obtained show on one hand the great suitability of the first resin for the determination of plutonium, and on the other the great selectivity of the second one for the determination of americium

  11. The leukemia-specific fusion gene ETV6/RUNX1 perturbs distinct key biological functions primarily by gene repression.

    Directory of Open Access Journals (Sweden)

    Gerhard Fuka

    Full Text Available BACKGROUND: ETV6/RUNX1 (E/R (also known as TEL/AML1 is the most frequent gene fusion in childhood acute lymphoblastic leukemia (ALL and also most likely the crucial factor for disease initiation; its role in leukemia propagation and maintenance, however, remains largely elusive. To address this issue we performed a shRNA-mediated knock-down (KD of the E/R fusion gene and investigated the ensuing consequences on genome-wide gene expression patterns and deducible regulatory functions in two E/R-positive leukemic cell lines. FINDINGS: Microarray analyses identified 777 genes whose expression was substantially altered. Although approximately equal proportions were either up- (KD-UP or down-regulated (KD-DOWN, the effects on biological processes and pathways differed considerably. The E/R KD-UP set was significantly enriched for genes included in the "cell activation", "immune response", "apoptosis", "signal transduction" and "development and differentiation" categories, whereas in the E/R KD-DOWN set only the "PI3K/AKT/mTOR signaling" and "hematopoietic stem cells" categories became evident. Comparable expression signatures obtained from primary E/R-positive ALL samples underline the relevance of these pathways and molecular functions. We also validated six differentially expressed genes representing the categories "stem cell properties", "B-cell differentiation", "immune response", "cell adhesion" and "DNA damage" with RT-qPCR. CONCLUSION: Our analyses provide the first preliminary evidence that the continuous expression of the E/R fusion gene interferes with key regulatory functions that shape the biology of this leukemia subtype. E/R may thus indeed constitute the essential driving force for the propagation and maintenance of the leukemic process irrespective of potential consequences of associated secondary changes. Finally, these findings may also provide a valuable source of potentially attractive therapeutic targets.

  12. Analysing innovation policy indicators through a functional approach: the aeronautic industry case

    Energy Technology Data Exchange (ETDEWEB)

    Haddad, C.R.; Uriona Maldonado, M.

    2016-07-01

    Developing countries face different problems than developed countries and the use of the same indicator to evaluate and compare both regions can lead to misleading conclusions. Traditional indicators, such as R&D and patents may not capture the whole dynamic of a system, as they are used to compare systems focusing on its current structure. Many authors have been discussing the processes underlying industry transformation, innovation, and economic growth to access a system performance, i.e. the functions of innovation systems. Therefore, the purpose of this paper is to analyze these functions as indicators to measure the performance of the system in order to identify policy issues. In order to do that, we analyze the case of the aeronautic sectoral system of innovation of a region in Brazil. The functional approach helped us to better capture the dynamic of the system, by not restricting our analysis to the system’s structure. (Author)

  13. Analyses of functional brain connectivity; Untersuchungen zur funktionellen Konnektivitaet des Gehirns

    Energy Technology Data Exchange (ETDEWEB)

    Stephan, K.E.

    2003-03-01

    This dissertation includes two independent studies that investigate two complementary aspects of functional connectivity in the Macaque and the human brain. In the first study, a computational meta-analysis of published electrophysiological data on context-independent functional brain connectivity was conducted by means of three independent methods. The second study investigated the effects of the atypical antipsychotic substance olanzapine on the functional connectivity of the cerebellum during a simple motor task (self-paced finger tapping). Six schizophrenic patients and six control subjects matched for age and sex were investigated by functional magnetic resonance imaging (fMRI) twice. This study provided the first experimental data on the effects of atypical antipsychotic agents on functional brain connectivity and demonstrated pronounced olanzapine-dependent changes of functional couplings between cerebellum, thalamus, and prefrontal cortex. (orig.) [German] In der hier vorgelegten Arbeit werden zwei komplementaere Aspekte der funktionellen Konnektivitaet - im Gehirn des Makaken und Menschen anhand zweier separater Studien untersucht. In der ersten Studie wurde mittels dreier unabhaengiger Methoden eine Metaanalyse publizierter elektrophysiologischer Daten zur kontextunabhaengigen funktionellen Konnektivitaet des Makakenkortex durchgefuehrt. Diese Studie erbrachte damit zum ersten Mal den Nachweis einer funktionellen Small World-Netzwerkstruktur des Primatenkortex. In der zweiten Studie wurde der Effekt des atypischen Neuroleptikums Olanzapin auf die funktionelle Konnektivitaet des Zerebellums im Kontext einer einfachen motorischen Aufgabe (selbstgesteuertes Fingertrapping) untersucht. Sechs schizophrene Patienten, die Neuroleptika-naiv bzw. -entwoehnt waren, sowie sechs alters- und geschlechtsentprechende Kontrollprobanden wurden im Abstand von jeweils drei Wochen mit funktioneller Magnetresonanztomografie (fMRT) untersucht. Diese Studie lieferte die ersten

  14. Biological Sampling and Analysis in Sinclair and Dyes Inlets, Washington: Chemical Analyses for 2007 Puget Sound Biota Study

    Energy Technology Data Exchange (ETDEWEB)

    Brandenberger, Jill M.; Suslick, Carolynn R.; Johnston, Robert K.

    2008-10-09

    Evaluating spatial and temporal trends in contaminant residues in Puget Sound fish and macroinvertebrates are the objectives of the Puget Sound Ambient Monitoring Program (PSAMP). In a cooperative effort between the ENVironmental inVESTment group (ENVVEST) and Washington State Department of Fish and Wildlife, additional biota samples were collected during the 2007 PSAMP biota survey and analyzed for chemical residues and stable isotopes of carbon (δ13C) and nitrogen (δ15N). Approximately three specimens of each species collected from Sinclair Inlet, Georgia Basin, and reference locations in Puget Sound were selected for whole body chemical analysis. The muscle tissue of specimens selected for chemical analyses were also analyzed for δ13C and δ15N to provide information on relative trophic level and food sources. This data report summarizes the chemical residues for the 2007 PSAMP fish and macro-invertebrate samples. In addition, six Spiny Dogfish (Squalus acanthias) samples were necropsied to evaluate chemical residue of various parts of the fish (digestive tract, liver, embryo, muscle tissue), as well as, a weight proportional whole body composite (WBWC). Whole organisms were homogenized and analyzed for silver, arsenic, cadmium, chromium, copper, nickel, lead, zinc, mercury, 19 polychlorinated biphenyl (PCB) congeners, PCB homologues, percent moisture, percent lipids, δ13C, and δ15N.

  15. The bottom-up approach to defining life : deciphering the functional organization of biological cells via multi-objective representation of biological complexity from molecules to cells

    Directory of Open Access Journals (Sweden)

    Sathish ePeriyasamy

    2013-12-01

    Full Text Available In silico representation of cellular systems needs to represent the adaptive dynamics of biological cells, recognizing a cell’s multi-objective topology formed by spatially and temporally cohesive intracellular structures. The design of these models needs to address the hierarchical and concurrent nature of cellular functions and incorporate the ability to self-organise in response to transitions between healthy and pathological phases, and adapt accordingly. The functions of biological systems are constantly evolving, due to the ever changing demands of their environment. Biological systems meet these demands by pursuing objectives, aided by their constituents, giving rise to biological functions. A biological cell is organised into an objective/task hierarchy. These objective hierarchy corresponds to the nested nature of temporally cohesive structures and representing them will facilitate in studying pleiotropy and polygeny by modeling causalities propagating across multiple interconnected intracellular processes. Although biological adaptations occur in physiological, developmental and reproductive timescales, the paper is focused on adaptations that occur within physiological timescales, where the biomolecular activities contributing to functional organisation, play a key role in cellular physiology. The paper proposes a multi-scale and multi-objective modelling approach from the bottom-up by representing temporally cohesive structures for multi-tasking of intracellular processes. Further the paper characterises the properties and constraints that are consequential to the organisational and adaptive dynamics in biological cells.

  16. The contribution of town functions to the development of rural areas: empirical analyses for Ethiopia

    NARCIS (Netherlands)

    Tadesse Woeldesenbet, T.

    2012-01-01

    Rural areas in many developing countries often lack infrastructure and institutions. However, rural towns and towns possess some of the major services that rural and town households can use to advance their economic activities. The study of the contribution that towns and their functions make to

  17. Analyses of soil microbial community compositions and functional genes reveal potential consequences of natural forest succession.

    Science.gov (United States)

    Cong, Jing; Yang, Yunfeng; Liu, Xueduan; Lu, Hui; Liu, Xiao; Zhou, Jizhong; Li, Diqiang; Yin, Huaqun; Ding, Junjun; Zhang, Yuguang

    2015-05-06

    The succession of microbial community structure and function is a central ecological topic, as microbes drive the Earth's biogeochemical cycles. To elucidate the response and mechanistic underpinnings of soil microbial community structure and metabolic potential relevant to natural forest succession, we compared soil microbial communities from three adjacent natural forests: a coniferous forest (CF), a mixed broadleaf forest (MBF) and a deciduous broadleaf forest (DBF) on Shennongjia Mountain in central China. In contrary to plant communities, the microbial taxonomic diversity of the DBF was significantly (P the DBF. Furthermore, a network analysis of microbial carbon and nitrogen cycling genes showed the network for the DBF samples was relatively large and tight, revealing strong couplings between microbes. Soil temperature, reflective of climate regimes, was important in shaping microbial communities at both taxonomic and functional gene levels. As a first glimpse of both the taxonomic and functional compositions of soil microbial communities, our results suggest that microbial community structure and function potentials will be altered by future environmental changes, which have implications for forest succession.

  18. Differential item functioning (DIF) analyses of health-related quality of life instruments using logistic regression

    DEFF Research Database (Denmark)

    Scott, Neil W.; Fayers, Peter M.; Aaronson, Neil K.

    2010-01-01

    Differential item functioning (DIF) methods can be used to determine whether different subgroups respond differently to particular items within a health-related quality of life (HRQoL) subscale, after allowing for overall subgroup differences in that scale. This article reviews issues that arise...

  19. Flexible gateway constructs for functional analyses of genes in plant pathogenic fungi

    NARCIS (Netherlands)

    Mehrabi, Rahim; Mirzadi Gohari, Amir; Silva, da Gilvan Ferreira; Steinberg, Gero; Kema, Gert H.J.; Wit, de Pierre J.G.M.

    2015-01-01

    Genetic manipulation of fungi requires quick, low-cost, efficient, high-throughput and molecular tools. In this paper, we report 22 entry constructs as new molecular tools based on the Gateway technology facilitating rapid construction of binary vectors that can be used for functional analysis of

  20. Replicated landscape genetic and network analyses reveal wide variation in functional connectivity for American pikas.

    Science.gov (United States)

    Castillo, Jessica A; Epps, Clinton W; Jeffress, Mackenzie R; Ray, Chris; Rodhouse, Thomas J; Schwalm, Donelle

    2016-09-01

    Landscape connectivity is essential for maintaining viable populations, particularly for species restricted to fragmented habitats or naturally arrayed in metapopulations and facing rapid climate change. The importance of assessing both structural connectivity (physical distribution of favorable habitat patches) and functional connectivity (how species move among habitat patches) for managing such species is well understood. However, the degree to which functional connectivity for a species varies among landscapes, and the resulting implications for conservation, have rarely been assessed. We used a landscape genetics approach to evaluate resistance to gene flow and, thus, to determine how landscape and climate-related variables influence gene flow for American pikas (Ochotona princeps) in eight federally managed sites in the western United States. We used empirically derived, individual-based landscape resistance models in conjunction with predictive occupancy models to generate patch-based network models describing functional landscape connectivity. Metareplication across landscapes enabled identification of limiting factors for dispersal that would not otherwise have been apparent. Despite the cool microclimates characteristic of pika habitat, south-facing aspects consistently represented higher resistance to movement, supporting the previous hypothesis that exposure to relatively high temperatures may limit dispersal in American pikas. We found that other barriers to dispersal included areas with a high degree of topographic relief, such as cliffs and ravines, as well as streams and distances greater than 1-4 km depending on the site. Using the empirically derived network models of habitat patch connectivity, we identified habitat patches that were likely disproportionately important for maintaining functional connectivity, areas in which habitat appeared fragmented, and locations that could be targeted for management actions to improve functional connectivity

  1. The Widespread Prevalence and Functional Significance of Silk-Like Structural Proteins in Metazoan Biological Materials.

    Directory of Open Access Journals (Sweden)

    Carmel McDougall

    Full Text Available In nature, numerous mechanisms have evolved by which organisms fabricate biological structures with an impressive array of physical characteristics. Some examples of metazoan biological materials include the highly elastic byssal threads by which bivalves attach themselves to rocks, biomineralized structures that form the skeletons of various animals, and spider silks that are renowned for their exceptional strength and elasticity. The remarkable properties of silks, which are perhaps the best studied biological materials, are the result of the highly repetitive, modular, and biased amino acid composition of the proteins that compose them. Interestingly, similar levels of modularity/repetitiveness and similar bias in amino acid compositions have been reported in proteins that are components of structural materials in other organisms, however the exact nature and extent of this similarity, and its functional and evolutionary relevance, is unknown. Here, we investigate this similarity and use sequence features common to silks and other known structural proteins to develop a bioinformatics-based method to identify similar proteins from large-scale transcriptome and whole-genome datasets. We show that a large number of proteins identified using this method have roles in biological material formation throughout the animal kingdom. Despite the similarity in sequence characteristics, most of the silk-like structural proteins (SLSPs identified in this study appear to have evolved independently and are restricted to a particular animal lineage. Although the exact function of many of these SLSPs is unknown, the apparent independent evolution of proteins with similar sequence characteristics in divergent lineages suggests that these features are important for the assembly of biological materials. The identification of these characteristics enable the generation of testable hypotheses regarding the mechanisms by which these proteins assemble and direct the

  2. Multistable Microactuators Functioning on the Basis of Electromagnetic Lorentz Force: Nonlinear Structural and Electrothermal Analyses

    International Nuclear Information System (INIS)

    Han, Jeong Sam

    2010-01-01

    In this paper, the design and nonlinear simulation of a multistable electromagnetic microactuator, which provides four stable equilibrium positions within its operating range, have been discussed. Quadstable actuator motion has been made possible by using both X- and Y-directional bistable structures with snapping curved beams. Two pairs of the curved beams are attached to an inner frame in both X- and Y-directions to realize independent bistable behavior in each direction. For the actuation of the actuator at the micrometer scale, an electromagnetic actuation method in which Lorentz force is taken into consideration was used. By using this method, micrometer-stroke quadstability in a plane parallel to a substrate was possible. The feasibility of designing an actuator that can realize quadstable motion by using the electromagnetic actuation method has been thoroughly clarified by performing nonlinear static and dynamic analyses and electrothermal coupled-field analysis of the multistable microactuator

  3. Overview of a surface-ripened cheese community functioning by meta-omics analyses.

    Directory of Open Access Journals (Sweden)

    Eric Dugat-Bony

    Full Text Available Cheese ripening is a complex biochemical process driven by microbial communities composed of both eukaryotes and prokaryotes. Surface-ripened cheeses are widely consumed all over the world and are appreciated for their characteristic flavor. Microbial community composition has been studied for a long time on surface-ripened cheeses, but only limited knowledge has been acquired about its in situ metabolic activities. We applied metagenomic, metatranscriptomic and biochemical analyses to an experimental surface-ripened cheese composed of nine microbial species during four weeks of ripening. By combining all of the data, we were able to obtain an overview of the cheese maturation process and to better understand the metabolic activities of the different community members and their possible interactions. Furthermore, differential expression analysis was used to select a set of biomarker genes, providing a valuable tool that can be used to monitor the cheese-making process.

  4. Longitudinal and Cross-sectional Analyses of Lung Function in Toluene Diisocyanate Production Workers.

    Science.gov (United States)

    Wang, Mei Lin; Storey, Eileen; Cassidy, Laura D; Doney, Brent; Conner, Patrick R; Collins, James J; Carson, Michael; Molenaar, Don

    2017-12-01

    The aim of this study was to investigate lung function among toluene diisocyanate (TDI) production workers. One hundred ninety-seven U.S workers performed spirometry from 2006 through 2012. Results were compared within the study cohort and with U.S. population measures. A mixed-effects model assessed factors affecting repeated forced expiratory volume in 1 second (FEV1) measurements. The cohort's mean FEV1 and forced vital capacity (FVC) percent reference values, although greater than 90%, were significantly lower and the prevalence of abnormal spirometry (predominantly restrictive pattern) was significantly higher than in the U.S. Differences in lung function among workers with higher cumulative TDI exposure were in the direction of an exposure effect, but not significant. We found little evidence of an adverse effect of TDI exposure on longitudinal spirometry in these workers. The association between TDI exposure and the increasing prevalence of a restrictive pattern needs further exploration.

  5. Multilevel functional genomics data integration as a tool for understanding physiology: a network biology perspective.

    Science.gov (United States)

    Davidsen, Peter K; Turan, Nil; Egginton, Stuart; Falciani, Francesco

    2016-02-01

    The overall aim of physiological research is to understand how living systems function in an integrative manner. Consequently, the discipline of physiology has since its infancy attempted to link multiple levels of biological organization. Increasingly this has involved mathematical and computational approaches, typically to model a small number of components spanning several levels of biological organization. With the advent of "omics" technologies, which can characterize the molecular state of a cell or tissue (intended as the level of expression and/or activity of its molecular components), the number of molecular components we can quantify has increased exponentially. Paradoxically, the unprecedented amount of experimental data has made it more difficult to derive conceptual models underlying essential mechanisms regulating mammalian physiology. We present an overview of state-of-the-art methods currently used to identifying biological networks underlying genomewide responses. These are based on a data-driven approach that relies on advanced computational methods designed to "learn" biology from observational data. In this review, we illustrate an application of these computational methodologies using a case study integrating an in vivo model representing the transcriptional state of hypoxic skeletal muscle with a clinical study representing muscle wasting in chronic obstructive pulmonary disease patients. The broader application of these approaches to modeling multiple levels of biological data in the context of modern physiology is discussed. Copyright © 2016 the American Physiological Society.

  6. Teleology then and now: the question of Kant's relevance for contemporary controversies over function in biology.

    Science.gov (United States)

    Zammito, John

    2006-12-01

    'Naturalism' is the aspiration of contemporary philosophy of biology, and Kant simply cannot be refashioned into a naturalist. Instead, epistemological 'deflation' was the decisive feature of Kant's treatment of the 'biomedical' science in his day, so it is not surprising that this might attract some philosophers of science to him today. A certain sense of impasse in the contemporary 'function talk' seems to motivate renewed interest in Kant. Kant--drawing on his eighteenth-century predecessors-provided a discerning and powerful characterization of what biologists had to explain in organic form. His difference from the rest is that he opined that it was impossible to explain it. Its 'inscrutability' was intrinsic. The third Critique essentially proposed the reduction of biology to a kind of pre-scientific descriptivism, doomed never to attain authentic scientificity, to have its 'Newton of the blade of grass'. By contrast, for Locke, and a fortiori for Buffon and his followers, 'intrinsic purposiveness' was a fact of the matter about concrete biological phenomena; the features of internal self-regulation were hypotheses arising out of actual research practice. The difference comes most vividly to light once we recognize Kant's distinction of the concept of organism from the concept of life. If biology must conceptualize self-organization as actual in the world, Kant's regulative/constitutive distinction is pointless in practice and the (naturalist) philosophy of biology has urgent work to undertake for which Kant turns out not to be very helpful.

  7. TCA Cycle and Mitochondrial Membrane Potential Are Necessary for Diverse Biological Functions.

    Science.gov (United States)

    Martínez-Reyes, Inmaculada; Diebold, Lauren P; Kong, Hyewon; Schieber, Michael; Huang, He; Hensley, Christopher T; Mehta, Manan M; Wang, Tianyuan; Santos, Janine H; Woychik, Richard; Dufour, Eric; Spelbrink, Johannes N; Weinberg, Samuel E; Zhao, Yingming; DeBerardinis, Ralph J; Chandel, Navdeep S

    2016-01-21

    Mitochondrial metabolism is necessary for the maintenance of oxidative TCA cycle function and mitochondrial membrane potential. Previous attempts to decipher whether mitochondria are necessary for biological outcomes have been hampered by genetic and pharmacologic methods that simultaneously disrupt multiple functions linked to mitochondrial metabolism. Here, we report that inducible depletion of mitochondrial DNA (ρ(ο) cells) diminished respiration, oxidative TCA cycle function, and the mitochondrial membrane potential, resulting in diminished cell proliferation, hypoxic activation of HIF-1, and specific histone acetylation marks. Genetic reconstitution only of the oxidative TCA cycle function specifically in these inducible ρ(ο) cells restored metabolites, resulting in re-establishment of histone acetylation. In contrast, genetic reconstitution of the mitochondrial membrane potential restored ROS, which were necessary for hypoxic activation of HIF-1 and cell proliferation. These results indicate that distinct mitochondrial functions associated with respiration are necessary for cell proliferation, epigenetics, and HIF-1 activation. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Differential item functioning (DIF) analyses of health-related quality of life instruments using logistic regression

    DEFF Research Database (Denmark)

    Scott, Neil W; Fayers, Peter M; Aaronson, Neil K

    2010-01-01

    Differential item functioning (DIF) methods can be used to determine whether different subgroups respond differently to particular items within a health-related quality of life (HRQoL) subscale, after allowing for overall subgroup differences in that scale. This article reviews issues that arise ...... when testing for DIF in HRQoL instruments. We focus on logistic regression methods, which are often used because of their efficiency, simplicity and ease of application....

  9. Optimisation of a machine learning algorithm in human locomotion using principal component and discriminant function analyses

    OpenAIRE

    Bisele, M; Bencsik, M; Lewis, MGC; Barnett, CT

    2017-01-01

    Assessment methods in human locomotion often involve the description of normalised graphical profiles and/or the extraction of discrete variables. Whilst useful, these approaches may not represent the full complexity of gait data. Multivariate statistical methods, such as Principal Component Analysis (PCA) and Discriminant Function Analysis (DFA), have been adopted since they have the potential to overcome these data handling issues. The aim of the current study was to develop and optimise a ...

  10. Item response theory analyses of the Delis-Kaplan Executive Function System card sorting subtest.

    Science.gov (United States)

    Spencer, Mercedes; Cho, Sun-Joo; Cutting, Laurie E

    2018-02-02

    In the current study, we examined the dimensionality of the 16-item Card Sorting subtest of the Delis-Kaplan Executive Functioning System assessment in a sample of 264 native English-speaking children between the ages of 9 and 15 years. We also tested for measurement invariance for these items across age and gender groups using item response theory (IRT). Results of the exploratory factor analysis indicated that a two-factor model that distinguished between verbal and perceptual items provided the best fit to the data. Although the items demonstrated measurement invariance across age groups, measurement invariance was violated for gender groups, with two items demonstrating differential item functioning for males and females. Multigroup analysis using all 16 items indicated that the items were more effective for individuals whose IRT scale scores were relatively high. A single-group explanatory IRT model using 14 non-differential item functioning items showed that for perceptual ability, females scored higher than males and that scores increased with age for both males and females; for verbal ability, the observed increase in scores across age differed for males and females. The implications of these findings are discussed.

  11. Characteristics of microbial community functional structure of a biological coking wastewater treatment system.

    Science.gov (United States)

    Joshi, Dev Raj; Zhang, Yu; Zhang, Hong; Gao, Yingxin; Yang, Min

    2018-01-01

    Nitrogenous heterocyclic compounds are key pollutants in coking wastewater; however, the functional potential of microbial communities for biodegradation of such contaminants during biological treatment is still elusive. Herein, a high throughput functional gene array (GeoChip 5.0) in combination with Illumina HiSeq2500 sequencing was used to compare and characterize the microbial community functional structure in a long run (500days) bench scale bioreactor treating coking wastewater, with a control system treating synthetic wastewater. Despite the inhibitory toxic pollutants, GeoChip 5.0 detected almost all key functional gene (average 61,940 genes) categories in the coking wastewater sludge. With higher abundance, aromatic ring cleavage dioxygenase genes including multi ring1,2diox; one ring2,3diox; catechol represented significant functional potential for degradation of aromatic pollutants which was further confirmed by Illumina HiSeq2500 analysis results. Response ratio analysis revealed that three nitrogenous compound degrading genes- nbzA (nitro-aromatics), tdnB (aniline), and scnABC (thiocyanate) were unique for coking wastewater treatment, which might be strong cause to increase ammonia level during the aerobic process. Additionally, HiSeq2500 elucidated carbozole and isoquinoline degradation genes in the system. These findings expanded our understanding on functional potential of microbial communities to remove organic nitrogenous pollutants; hence it will be useful in optimization strategies for biological treatment of coking wastewater. Copyright © 2017. Published by Elsevier B.V.

  12. Adult Diffuse Astrocytoma in the Medulla Oblongata: Molecular Biological Analyses Including H3F3A Mutation of Histone H3.3.

    Science.gov (United States)

    Uekawa, Ken; Nakamura, Hideo; Shinojima, Naoki; Takezaki, Tatsuya; Yano, Shigetoshi; Kuratsu, Jun-Ichi

    2016-04-01

    Unlike in children, brain stem gliomas in adult are rare and still poorly understood. In addition, most adult brain stem gliomas result predominantly in the pons and are less often found in the medulla oblongata. Here, we report a case of an adult glioma in the medulla oblongata and its molecular biological features. A 46-year-old male presented with gait disturbance, paresthesia, and dysphagia. Magnetic resonance imaging (MRI) showed a diffuse hyper-intensive lesion in the medulla oblongata on a T 2 -weighted image without gadolinium contrast enhancement. We performed an open biopsy and the lesion was pathologically diagnosed as a diffuse astrocytoma. Molecular biological analyses revealed the absence of histone H3.3 mutation (H3F3A K27M), and presence of methylation of O-6-methylguanine-DNA methyltransferase (MGMT) promoter and a mutation in isocitrate dehydrogenase 1 (IDH-1). The patient received local radiotherapy and temozolomide chemotherapy. The patient's symptoms were ameliorated, and MRI showed no tumor growth at 6 months after the initial treatment. Biopsy for brain stem lesions is generally thought to have risk of complications, but if performed minimally, it is useful to diagnose and determine treatment strategy. Obtaining patient characteristics and molecular biological features will provide insight towards therapeutic treatment for adult brain stem gliomas.

  13. Form and function: Perspectives on structural biology and resources for the future

    International Nuclear Information System (INIS)

    Vaughan, D.

    1990-12-01

    The purpose of this study is largely to explore and expand on the thesis that biological structures and their functions are suited to. Form indeed follows function and if we are to understand the workings of a living system, with all that such an understanding promises, we must first seek to describe the structure of its parts. Descriptions of a few achievements of structural biology lay the groundwork, but the substance of this booklet is a discussion of important questions yet unanswered and opportunities just beyond our grasp. The concluding pages then outline a course of action in which the Department of Energy would exercise its responsibility to develop the major resources needed to extend our reach and to answer some of those unanswered questions. 22 figs

  14. Mediating objects: scientific and public functions of models in nineteenth-century biology.

    Science.gov (United States)

    Ludwig, David

    2013-01-01

    The aim of this article is to examine the scientific and public functions of two- and three-dimensional models in the context of three episodes from nineteenth-century biology. I argue that these models incorporate both data and theory by presenting theoretical assumptions in the light of concrete data or organizing data through theoretical assumptions. Despite their diverse roles in scientific practice, they all can be characterized as mediators between data and theory. Furthermore, I argue that these different mediating functions often reflect their different audiences that included specialized scientists, students, and the general public. In this sense, models in nineteenth-century biology can be understood as mediators between theory, data, and their diverse audiences.

  15. PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance.

    Science.gov (United States)

    van Oers, Johanna M M; Roa, Sergio; Werling, Uwe; Liu, Yiyong; Genschel, Jochen; Hou, Harry; Sellers, Rani S; Modrich, Paul; Scharff, Matthew D; Edelmann, Winfried

    2010-07-27

    The DNA mismatch repair protein PMS2 was recently found to encode a novel endonuclease activity. To determine the biological functions of this activity in mammals, we generated endonuclease-deficient Pms2E702K knock-in mice. Pms2EK/EK mice displayed increased genomic mutation rates and a strong cancer predisposition. In addition, class switch recombination, but not somatic hypermutation, was impaired in Pms2EK/EK B cells, indicating a specific role in Ig diversity. In contrast to Pms2-/- mice, Pms2EK/EK male mice were fertile, indicating that this activity is dispensable in spermatogenesis. Therefore, the PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance and tumor suppression.

  16. Automated quantitative assessment of proteins' biological function in protein knowledge bases.

    Science.gov (United States)

    Mayr, Gabriele; Lepperdinger, Günter; Lackner, Peter

    2008-01-01

    Primary protein sequence data are archived in databases together with information regarding corresponding biological functions. In this respect, UniProt/Swiss-Prot is currently the most comprehensive collection and it is routinely cross-examined when trying to unravel the biological role of hypothetical proteins. Bioscientists frequently extract single entries and further evaluate those on a subjective basis. In lieu of a standardized procedure for scoring the existing knowledge regarding individual proteins, we here report about a computer-assisted method, which we applied to score the present knowledge about any given Swiss-Prot entry. Applying this quantitative score allows the comparison of proteins with respect to their sequence yet highlights the comprehension of functional data. pfs analysis may be also applied for quality control of individual entries or for database management in order to rank entry listings.

  17. Automated Quantitative Assessment of Proteins' Biological Function in Protein Knowledge Bases

    Directory of Open Access Journals (Sweden)

    Gabriele Mayr

    2008-01-01

    Full Text Available Primary protein sequence data are archived in databases together with information regarding corresponding biological functions. In this respect, UniProt/Swiss-Prot is currently the most comprehensive collection and it is routinely cross-examined when trying to unravel the biological role of hypothetical proteins. Bioscientists frequently extract single entries and further evaluate those on a subjective basis. In lieu of a standardized procedure for scoring the existing knowledge regarding individual proteins, we here report about a computer-assisted method, which we applied to score the present knowledge about any given Swiss-Prot entry. Applying this quantitative score allows the comparison of proteins with respect to their sequence yet highlights the comprehension of functional data. pfs analysis may be also applied for quality control of individual entries or for database management in order to rank entry listings.

  18. The functional biology and trophic role of krill (Thysanoessa raschii) in a Greenlandic fjord

    DEFF Research Database (Denmark)

    Agersted, Mette Dalgaard; Nielsen, Torkel Gissel; Munk, Peter

    2011-01-01

    Despite being a key zooplankton group, knowledge on krill biology from the Arctic is inadequate. The present study examine the functional biology and evaluate the trophic role of krill in the GodthAyenbsfjord (64 degrees N, 51 degrees W) SW Greenland, through a combination of fieldwork...... and laboratory experiments. Krill biomass was highest in the middle fjord and inner fjord, whereas no krill was found offshore. The dominating species Thysanoessa raschii revealed a type III functional response when fed with the diatom Thalassiosira weissflogii. At food saturation, T. raschii exhibited a daily...... ration of 1% body C d(-1). Furthermore, T. raschii was capable of exploiting plankton cells from 5 to 400 mu m, covering several trophic levels of the pelagic food web. The calculated grazing impact by T. raschii on the fjord plankton community was negligible. However, the schooling and migratory...

  19. PreproVIP-derived peptides in the human female genital tract: expression and biological function

    DEFF Research Database (Denmark)

    Bredkjoer, H E; Palle, C; Ekblad, E

    1997-01-01

    The aim of the study was to elucidate the localization, distribution, colocalization and biological effect of preproVIP-derived peptides in the human female genital tract. Radioimmunoassays applying antisera against the five functional domains of the VIP precursor in combination with immunohistoc......The aim of the study was to elucidate the localization, distribution, colocalization and biological effect of preproVIP-derived peptides in the human female genital tract. Radioimmunoassays applying antisera against the five functional domains of the VIP precursor in combination...... with immunohistochemistry were used. The effect of preproVIP 22-79, preproVIP 111-122 and preproVIP 156-170 on genital smooth muscle activity in the Fallopian tube was investigated in vitro and compared to that of VIP. All the preproVIP-derived peptides were expressed throughout the genital tract in neuronal elements...

  20. Form and function: Perspectives on structural biology and resources for the future

    Energy Technology Data Exchange (ETDEWEB)

    Vaughan, D. (ed.)

    1990-12-01

    The purpose of this study is largely to explore and expand on the thesis that biological structures and their functions are suited to. Form indeed follows function and if we are to understand the workings of a living system, with all that such an understanding promises, we must first seek to describe the structure of its parts. Descriptions of a few achievements of structural biology lay the groundwork, but the substance of this booklet is a discussion of important questions yet unanswered and opportunities just beyond our grasp. The concluding pages then outline a course of action in which the Department of Energy would exercise its responsibility to develop the major resources needed to extend our reach and to answer some of those unanswered questions. 22 figs.

  1. Tongue and Taste Organ Biology and Function: Homeostasis Maintained by Hedgehog Signaling.

    Science.gov (United States)

    Mistretta, Charlotte M; Kumari, Archana

    2017-02-10

    The tongue is an elaborate complex of heterogeneous tissues with taste organs of diverse embryonic origins. The lingual taste organs are papillae, composed of an epithelium that includes specialized taste buds, the basal lamina, and a lamina propria core with matrix molecules, fibroblasts, nerves, and vessels. Because taste organs are dynamic in cell biology and sensory function, homeostasis requires tight regulation in specific compartments or niches. Recently, the Hedgehog (Hh) pathway has emerged as an essential regulator that maintains lingual taste papillae, taste bud and progenitor cell proliferation and differentiation, and neurophysiological function. Activating or suppressing Hh signaling, with genetic models or pharmacological agents used in cancer treatments, disrupts taste papilla and taste bud integrity and can eliminate responses from taste nerves to chemical stimuli but not to touch or temperature. Understanding Hh regulation of taste organ homeostasis contributes knowledge about the basic biology underlying taste disruptions in patients treated with Hh pathway inhibitors.

  2. Effects of Physical Exercise on Cognitive Functioning and Wellbeing: Biological and Psychological Benefits

    Directory of Open Access Journals (Sweden)

    Laura Mandolesi

    2018-04-01

    Full Text Available Much evidence shows that physical exercise (PE is a strong gene modulator that induces structural and functional changes in the brain, determining enormous benefit on both cognitive functioning and wellbeing. PE is also a protective factor for neurodegeneration. However, it is unclear if such protection is granted through modifications to the biological mechanisms underlying neurodegeneration or through better compensation against attacks. This concise review addresses the biological and psychological positive effects of PE describing the results obtained on brain plasticity and epigenetic mechanisms in animal and human studies, in order to clarify how to maximize the positive effects of PE while avoiding negative consequences, as in the case of exercise addiction.

  3. Functional analyses of multiple lichenin-degrading enzymes from the rumen bacterium Ruminococcus albus 8.

    Science.gov (United States)

    Iakiviak, Michael; Mackie, Roderick I; Cann, Isaac K O

    2011-11-01

    Ruminococcus albus 8 is a fibrolytic ruminal bacterium capable of utilization of various plant cell wall polysaccharides. A bioinformatic analysis of a partial genome sequence of R. albus revealed several putative enzymes likely to hydrolyze glucans, including lichenin, a mixed-linkage polysaccharide of glucose linked together in β-1,3 and β-1,4 glycosidic bonds. In the present study, we demonstrate the capacity of four glycoside hydrolases (GHs), derived from R. albus, to hydrolyze lichenin. Two of the genes encoded GH family 5 enzymes (Ra0453 and Ra2830), one gene encoded a GH family 16 enzyme (Ra0505), and the last gene encoded a GH family 3 enzyme (Ra1595). Each gene was expressed in Escherichia coli, and the recombinant protein was purified to near homogeneity. Upon screening on a wide range of substrates, Ra0453, Ra2830, and Ra0505 displayed different hydrolytic properties, as they released unique product profiles. The Ra1595 protein, predicted to function as a β-glucosidase, preferred cleavage of a nonreducing end glucose when linked by a β-1,3 glycosidic bond to the next glucose residue. The major product of Ra0505 hydrolysis of lichenin was predicted to be a glucotriose that was degraded only by Ra0453 to glucose and cellobiose. Most importantly, the four enzymes functioned synergistically to hydrolyze lichenin to glucose, cellobiose, and cellotriose. This lichenin-degrading enzyme mix should be of utility as an additive to feeds administered to monogastric animals, especially those high in fiber.

  4. Structural and functional analyses of human cerebral cortex using a surface-based atlas

    Science.gov (United States)

    Van Essen, D. C.; Drury, H. A.

    1997-01-01

    We have analyzed the geometry, geography, and functional organization of human cerebral cortex using surface reconstructions and cortical flat maps of the left and right hemispheres generated from a digital atlas (the Visible Man). The total surface area of the reconstructed Visible Man neocortex is 1570 cm2 (both hemispheres), approximately 70% of which is buried in sulci. By linking the Visible Man cerebrum to the Talairach stereotaxic coordinate space, the locations of activation foci reported in neuroimaging studies can be readily visualized in relation to the cortical surface. The associated spatial uncertainty was empirically shown to have a radius in three dimensions of approximately 10 mm. Application of this approach to studies of visual cortex reveals the overall patterns of activation associated with different aspects of visual function and the relationship of these patterns to topographically organized visual areas. Our analysis supports a distinction between an anterior region in ventral occipito-temporal cortex that is selectively involved in form processing and a more posterior region (in or near areas VP and V4v) involved in both form and color processing. Foci associated with motion processing are mainly concentrated in a region along the occipito-temporal junction, the ventral portion of which overlaps with foci also implicated in form processing. Comparisons between flat maps of human and macaque monkey cerebral cortex indicate significant differences as well as many similarities in the relative sizes and positions of cortical regions known or suspected to be homologous in the two species.

  5. RESPONDING AND ANALYSING: STAGES OF TEACHING FUNCTIONAL GRAMMAR IN INDONESIAN CONTEXT

    Directory of Open Access Journals (Sweden)

    Lala Bumela

    2014-07-01

    Full Text Available Abstract: This paper offers an alternative to the teaching of a functional grammar course in Indonesian TEFL tertiary level context. An issue raised here is whether the course should directly require students to undertake textual analysis or provide them first with subjective reading experiences.  This issue is inspired by Jones and Lock¹s approach to teaching grammar in context (2011. This paper reports on a study that focused on two related phases of dealing with texts: responding and analyzing.  In the first phase, students were encouraged to take a personalised approach in responding to written English texts.  They had the freedom to decide whether the texts were meaningful for them in certain ways. Mckee (2003 and Lehtonen (2000 posit that as the sole decision maker in meaning negotiation, readers perceive the meaningfulness of texts in very diverse ways. In the second phase of the study, the students undertook an individual analysis of different text types.  This study reveals that a successful textual analysis is determined by how students make sense of the texts. The analysis of context of situation, for example, becomes meaningful to students after they demonstrate a proper position as a reader.  This, in turn, helps them in gaining insights into the structure and grammar of those texts.   Keywords: systemic functional linguistics, genre-based approach, textual analysis

  6. Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis

    DEFF Research Database (Denmark)

    Loft, N D; Skov, L; Iversen, L

    2017-01-01

    Biological agents including anti-tumor necrosis factor (anti-TNF; adalimumab, infliximab, etanercept) and anti-interleukin-12/13 (IL12/23; ustekinumab) are essential for treatment of patients with severe psoriasis. However, a significant proportion of the patients do not respond to a specific...... of ustekinumab treatment. Associations between genetic variants and treatment outcomes (drug survival and Psoriasis Area Severity Index reduction) were assessed using logistic regression analyses (crude and adjusted for gender, age, psoriatic arthritis and previous treatment). After correction for multiple...

  7. Paul Langerhans: a prilgrim "traveling" from functional histology to marine biology.

    Science.gov (United States)

    Raica, Marius; Cimpean, Anca Maria

    2017-06-01

    The nineteenth century was the time of a real revolution in science and medicine. A lot of seminal discoveries in medicine and biology were done in this time, and many of them were coincident with the introduction of the compound microscope by Hermann van Deijl and the standard histological technique by Paul Ehrlich. The main tissue types and individual cells were characterized and originally classified more than hundred years ago, although less attention was paid to their basic functions. This was mainly due to the modality of tissue specimen processing that allowed particularly detailed descriptive studies. Even so, we can notice some attempts to correlate the structure with the function. The German scientist Paul Langerhans, well-known for the discovery of Langerhans islets of the pancreas and Langerhans cells from the epidermis, tried to change the conventional fate of morphological studies introducing in his works functional hypothesis based on traditional microscopic observations even from the beginning of his scientific career. Paul Langerhans was a complex personality of the second half of the nineteenth century, not only in medicine, but also in other fields of biology. In the present review, presented is the life and research activity of Paul Langerhans, not only because of the importance of his discoveries, but also for perspectives that were opened by these findings in unexpected fields of medicine and biology.

  8. Functional and comparative genomics analyses of pmp22 in medaka fish

    Directory of Open Access Journals (Sweden)

    Kawarabayasi Yutaka

    2009-06-01

    Full Text Available Abstract Background Pmp22, a member of the junction protein family Claudin/EMP/PMP22, plays an important role in myelin formation. Increase of pmp22 transcription causes peripheral neuropathy, Charcot-Marie-Tooth disease type1A (CMT1A. The pathophysiological phenotype of CMT1A is aberrant axonal myelination which induces a reduction in nerve conduction velocity (NCV. Several CMT1A model rodents have been established by overexpressing pmp22. Thus, it is thought that pmp22 expression must be tightly regulated for correct myelin formation in mammals. Interestingly, the myelin sheath is also present in other jawed vertebrates. The purpose of this study is to analyze the evolutionary conservation of the association between pmp22 transcription level and vertebrate myelin formation, and to find the conserved non-coding sequences for pmp22 regulation by comparative genomics analyses between jawed fishes and mammals. Results A transgenic pmp22 over-expression medaka fish line was established. The transgenic fish had approximately one fifth the peripheral NCV values of controls, and aberrant myelination of transgenic fish in the peripheral nerve system (PNS was observed. We successfully confirmed that medaka fish pmp22 has the same exon-intron structure as mammals, and identified some known conserved regulatory motifs. Furthermore, we found novel conserved sequences in the first intron and 3'UTR. Conclusion Medaka fish undergo abnormalities in the PNS when pmp22 transcription increases. This result indicates that an adequate pmp22 transcription level is necessary for correct myelination of jawed vertebrates. Comparison of pmp22 orthologs between distantly related species identifies evolutionary conserved sequences that contribute to precise regulation of pmp22 expression.

  9. Liver function in Huntington's disease assessed by blood biochemical analyses in a clinical setting

    DEFF Research Database (Denmark)

    Nielsen, Signe Marie Borch; Vinther-Jensen, Tua; Nielsen, Jørgen E.

    2016-01-01

    dysfunction are seen. Blood levels of a wide range of hormones, metabolites and proteins have been analyzed in HD patients, identifying several changes associated with the disease. However, a comprehensive panel of liver function tests (LFT) has not been performed. We investigated a cohort of manifest......Huntington's disease (HD) is a dominantly inherited, progressive neurological disorder caused by a CAG repeat elongation in the huntingtin gene. In addition to motor-, psychiatric- A nd cognitive dysfunction, peripheral disease manifestations in the form of metabolic changes and cellular...... and premanifest HD gene-expansion carriers and controls, using a clinically applied panel of LFTs. Here, we demonstrate that the level of alkaline phosphatase is increased in manifest HD gene-expansion carriers compared to premanifest HD gene-expansion carriers and correlate with increased disease severity...

  10. Some applications of neutron activation analysis in plant biology and agronomy; Quelques applications de l'analyse par radioactivation neutronique en biologie vegetale et en agronomie

    Energy Technology Data Exchange (ETDEWEB)

    Fourcy, A [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires

    1966-06-01

    Plants materials are not so commonly analysed by radioactivation than biological extracts of medical importance. With help of concrete examples, applications of neutrons activation analysis to the determination of some metals (Mn, Cu, Co, Fe, Zn, and K) in plant materials, are proposed. Samples are activated in a swimming-pool reactor at the thermal flux of 5.10{sup 12} n.cm{sup -2}s{sup -1} for a time varying between few minutes and several days according to the element being analysed. The induced radioactivity is measured by spectrometry, with radiochemical separation ( Cu, Co, Fe, Zn and K) or without separation in best cases (Mn,Cu, K). Described dosages are related to: manganese in a graminaceous plant, copper in vine treatments, cobalt, iron and zinc in animal feeding, potassium in a radiological experiment. (author) [French] Les produits vegetaux sont beaucoup moins souvent soumis a l'analyse par activation que les extraits biologiques d'interet medical. En s'appuyant sur des cas concrets, nous proposons des applications de l'analyse par activation neutronique au dosage de differents metaux (Mn, Cu, Co, Fe, Zn, et K) dans la matiere vegetale. Les echantillons sont actives en pile piscine au flux thermique de 5.10{sup 12} n.cm{sup -2} s{sup -1} pendant des temps variant de quelques minutes a plusieurs jours selon les elements a analyser. le comptage de la radioactivite induite est effectue par spectrometrie gamma apres separation radiochimique (Cu, Co, Fe, Zn, et K) ou sans separation dans les cas favorables (Mn, Cu, K). Les dosages decrits concernent: le manganese dans une graminee, le cuivre en viticulture, le cobalt, le fer, et le zinc dans un aliment du betail, le potassium dans une experience de radioecologie. (auteur)

  11. A Bayesian spatial model for neuroimaging data based on biologically informed basis functions.

    Science.gov (United States)

    Huertas, Ismael; Oldehinkel, Marianne; van Oort, Erik S B; Garcia-Solis, David; Mir, Pablo; Beckmann, Christian F; Marquand, Andre F

    2017-11-01

    The dominant approach to neuroimaging data analysis employs the voxel as the unit of computation. While convenient, voxels lack biological meaning and their size is arbitrarily determined by the resolution of the image. Here, we propose a multivariate spatial model in which neuroimaging data are characterised as a linearly weighted combination of multiscale basis functions which map onto underlying brain nuclei or networks or nuclei. In this model, the elementary building blocks are derived to reflect the functional anatomy of the brain during the resting state. This model is estimated using a Bayesian framework which accurately quantifies uncertainty and automatically finds the most accurate and parsimonious combination of basis functions describing the data. We demonstrate the utility of this framework by predicting quantitative SPECT images of striatal dopamine function and we compare a variety of basis sets including generic isotropic functions, anatomical representations of the striatum derived from structural MRI, and two different soft functional parcellations of the striatum derived from resting-state fMRI (rfMRI). We found that a combination of ∼50 multiscale functional basis functions accurately represented the striatal dopamine activity, and that functional basis functions derived from an advanced parcellation technique known as Instantaneous Connectivity Parcellation (ICP) provided the most parsimonious models of dopamine function. Importantly, functional basis functions derived from resting fMRI were more accurate than both structural and generic basis sets in representing dopamine function in the striatum for a fixed model order. We demonstrate the translational validity of our framework by constructing classification models for discriminating parkinsonian disorders and their subtypes. Here, we show that ICP approach is the only basis set that performs well across all comparisons and performs better overall than the classical voxel-based approach

  12. Genetic and functional analyses demonstrate a role for abnormal glycinergic signaling in autism.

    Science.gov (United States)

    Pilorge, M; Fassier, C; Le Corronc, H; Potey, A; Bai, J; De Gois, S; Delaby, E; Assouline, B; Guinchat, V; Devillard, F; Delorme, R; Nygren, G; Råstam, M; Meier, J C; Otani, S; Cheval, H; James, V M; Topf, M; Dear, T N; Gillberg, C; Leboyer, M; Giros, B; Gautron, S; Hazan, J; Harvey, R J; Legendre, P; Betancur, C

    2016-07-01

    Autism spectrum disorder (ASD) is a common neurodevelopmental condition characterized by marked genetic heterogeneity. Recent studies of rare structural and sequence variants have identified hundreds of loci involved in ASD, but our knowledge of the overall genetic architecture and the underlying pathophysiological mechanisms remains incomplete. Glycine receptors (GlyRs) are ligand-gated chloride channels that mediate inhibitory neurotransmission in the adult nervous system but exert an excitatory action in immature neurons. GlyRs containing the α2 subunit are highly expressed in the embryonic brain, where they promote cortical interneuron migration and the generation of excitatory projection neurons. We previously identified a rare microdeletion of the X-linked gene GLRA2, encoding the GlyR α2 subunit, in a boy with autism. The microdeletion removes the terminal exons of the gene (GLRA2(Δex8-9)). Here, we sequenced 400 males with ASD and identified one de novo missense mutation, p.R153Q, absent from controls. In vitro functional analysis demonstrated that the GLRA2(Δex8)(-)(9) protein failed to localize to the cell membrane, while the R153Q mutation impaired surface expression and markedly reduced sensitivity to glycine. Very recently, an additional de novo missense mutation (p.N136S) was reported in a boy with ASD, and we show that this mutation also reduced cell-surface expression and glycine sensitivity. Targeted glra2 knockdown in zebrafish induced severe axon-branching defects, rescued by injection of wild type but not GLRA2(Δex8-9) or R153Q transcripts, providing further evidence for their loss-of-function effect. Glra2 knockout mice exhibited deficits in object recognition memory and impaired long-term potentiation in the prefrontal cortex. Taken together, these results implicate GLRA2 in non-syndromic ASD, unveil a novel role for GLRA2 in synaptic plasticity and learning and memory, and link altered glycinergic signaling to social and cognitive

  13. Statistical improvements in functional magnetic resonance imaging analyses produced by censoring high-motion data points.

    Science.gov (United States)

    Siegel, Joshua S; Power, Jonathan D; Dubis, Joseph W; Vogel, Alecia C; Church, Jessica A; Schlaggar, Bradley L; Petersen, Steven E

    2014-05-01

    Subject motion degrades the quality of task functional magnetic resonance imaging (fMRI) data. Here, we test two classes of methods to counteract the effects of motion in task fMRI data: (1) a variety of motion regressions and (2) motion censoring ("motion scrubbing"). In motion regression, various regressors based on realignment estimates were included as nuisance regressors in general linear model (GLM) estimation. In motion censoring, volumes in which head motion exceeded a threshold were withheld from GLM estimation. The effects of each method were explored in several task fMRI data sets and compared using indicators of data quality and signal-to-noise ratio. Motion censoring decreased variance in parameter estimates within- and across-subjects, reduced residual error in GLM estimation, and increased the magnitude of statistical effects. Motion censoring performed better than all forms of motion regression and also performed well across a variety of parameter spaces, in GLMs with assumed or unassumed response shapes. We conclude that motion censoring improves the quality of task fMRI data and can be a valuable processing step in studies involving populations with even mild amounts of head movement. Copyright © 2013 Wiley Periodicals, Inc.

  14. Functional evolution of ADAMTS genes: Evidence from analyses of phylogeny and gene organization

    Directory of Open Access Journals (Sweden)

    Van Meir Erwin G

    2005-02-01

    Full Text Available Abstract Background The ADAMTS (A Disintegrin-like and Metalloprotease with Thrombospondin motifs proteins are a family of metalloproteases with sequence similarity to the ADAM proteases, that contain the thrombospondin type 1 sequence repeat motifs (TSRs common to extracellular matrix proteins. ADAMTS proteins have recently gained attention with the discovery of their role in a variety of diseases, including tissue and blood disorders, cancer, osteoarthritis, Alzheimer's and the genetic syndromes Weill-Marchesani syndrome (ADAMTS10, thrombotic thrombocytopenic purpura (ADAMTS13, and Ehlers-Danlos syndrome type VIIC (ADAMTS2 in humans and belted white-spotting mutation in mice (ADAMTS20. Results Phylogenetic analysis and comparison of the exon/intron organization of vertebrate (Homo, Mus, Fugu, chordate (Ciona and invertebrate (Drosophila and Caenorhabditis ADAMTS homologs has elucidated the evolutionary relationships of this important gene family, which comprises 19 members in humans. Conclusions The evolutionary history of ADAMTS genes in vertebrate genomes has been marked by rampant gene duplication, including a retrotransposition that gave rise to a distinct ADAMTS subfamily (ADAMTS1, -4, -5, -8, -15 that may have distinct aggrecanase and angiogenesis functions.

  15. Experiment and density functional theory analyses of GdTaO4 single crystal

    Science.gov (United States)

    Ding, Shoujun; Kinross, Ashlie; Wang, Xiaofei; Yang, Huajun; Zhang, Qingli; Liu, Wenpeng; Sun, Dunlu

    2018-05-01

    GdTaO4 is a type of excellent materials that can be used as scintillation, laser matrix as well as self-activated phosphor has generated significant interest. Whereas its band structure, electronic structure and optical properties are still need elucidation. To solve this intriguing problem, high-quality GdTaO4 single crystal (M-type) was grown successfully using Czochralski method. Its structure as well as optical properties was determined in experiment. Moreover, a systematic theoretical calculation based on the density function theory methods were performed on M-type and M‧-type GdTaO4 and their band structure, density of state as well as optical properties were obtained. Combine with the performed experiment results, the calculated results were proved with high reliability. Hence, the calculated results obtained in this work could provide a deep understanding of GdTaO4 material, which also useful for the further investigation on GdTaO4 material.

  16. Optimisation of a machine learning algorithm in human locomotion using principal component and discriminant function analyses.

    Science.gov (United States)

    Bisele, Maria; Bencsik, Martin; Lewis, Martin G C; Barnett, Cleveland T

    2017-01-01

    Assessment methods in human locomotion often involve the description of normalised graphical profiles and/or the extraction of discrete variables. Whilst useful, these approaches may not represent the full complexity of gait data. Multivariate statistical methods, such as Principal Component Analysis (PCA) and Discriminant Function Analysis (DFA), have been adopted since they have the potential to overcome these data handling issues. The aim of the current study was to develop and optimise a specific machine learning algorithm for processing human locomotion data. Twenty participants ran at a self-selected speed across a 15m runway in barefoot and shod conditions. Ground reaction forces (BW) and kinematics were measured at 1000 Hz and 100 Hz, respectively from which joint angles (°), joint moments (N.m.kg-1) and joint powers (W.kg-1) for the hip, knee and ankle joints were calculated in all three anatomical planes. Using PCA and DFA, power spectra of the kinematic and kinetic variables were used as a training database for the development of a machine learning algorithm. All possible combinations of 10 out of 20 participants were explored to find the iteration of individuals that would optimise the machine learning algorithm. The results showed that the algorithm was able to successfully predict whether a participant ran shod or barefoot in 93.5% of cases. To the authors' knowledge, this is the first study to optimise the development of a machine learning algorithm.

  17. Model tests and numerical analyses on horizontal impedance functions of inclined single piles embedded in cohesionless soil

    Science.gov (United States)

    Goit, Chandra Shekhar; Saitoh, Masato

    2013-03-01

    Horizontal impedance functions of inclined single piles are measured experimentally for model soil-pile systems with both the effects of local soil nonlinearity and resonant characteristics. Two practical pile inclinations of 5° and 10° in addition to a vertical pile embedded in cohesionless soil and subjected to lateral harmonic pile head loadings for a wide range of frequencies are considered. Results obtained with low-to-high amplitude of lateral loadings on model soil-pile systems encased in a laminar shear box show that the local nonlinearities have a profound impact on the horizontal impedance functions of piles. Horizontal impedance functions of inclined piles are found to be smaller than the vertical pile and the values decrease as the angle of pile inclination increases. Distinct values of horizontal impedance functions are obtained for the `positive' and `negative' cycles of harmonic loadings, leading to asymmetric force-displacement relationships for the inclined piles. Validation of these experimental results is carried out through three-dimensional nonlinear finite element analyses, and the results from the numerical models are in good agreement with the experimental data. Sensitivity analyses conducted on the numerical models suggest that the consideration of local nonlinearity at the vicinity of the soil-pile interface influence the response of the soil-pile systems.

  18. Working memory circuit as a function of increasing age in healthy adolescence: A systematic review and meta-analyses.

    Science.gov (United States)

    Andre, Julia; Picchioni, Marco; Zhang, Ruibin; Toulopoulou, Timothea

    2016-01-01

    Working memory ability matures through puberty and early adulthood. Deficits in working memory are linked to the risk of onset of neurodevelopmental disorders such as schizophrenia, and there is a significant temporal overlap between the peak of first episode psychosis risk and working memory maturation. In order to characterize the normal working memory functional maturation process through this critical phase of cognitive development we conducted a systematic review and coordinate based meta-analyses of all the available primary functional magnetic resonance imaging studies (n = 382) that mapped WM function in healthy adolescents (10-17 years) and young adults (18-30 years). Activation Likelihood Estimation analyses across all WM tasks revealed increased activation with increasing subject age in the middle frontal gyrus (BA6) bilaterally, the left middle frontal gyrus (BA10), the left precuneus and left inferior parietal gyri (BA7; 40). Decreased activation with increasing age was found in the right superior frontal (BA8), left junction of postcentral and inferior parietal (BA3/40), and left limbic cingulate gyrus (BA31). These results suggest that brain activation during adolescence increased with age principally in higher order cortices, part of the core working memory network, while reductions were detected in more diffuse and potentially more immature neural networks. Understanding the process by which the brain and its cognitive functions mature through healthy adulthood may provide us with new clues to understanding the vulnerability to neurodevelopmental disorders.

  19. Working memory circuit as a function of increasing age in healthy adolescence: A systematic review and meta-analyses

    Directory of Open Access Journals (Sweden)

    Julia Andre

    2016-01-01

    Full Text Available Working memory ability matures through puberty and early adulthood. Deficits in working memory are linked to the risk of onset of neurodevelopmental disorders such as schizophrenia, and there is a significant temporal overlap between the peak of first episode psychosis risk and working memory maturation. In order to characterize the normal working memory functional maturation process through this critical phase of cognitive development we conducted a systematic review and coordinate based meta-analyses of all the available primary functional magnetic resonance imaging studies (n = 382 that mapped WM function in healthy adolescents (10–17 years and young adults (18–30 years. Activation Likelihood Estimation analyses across all WM tasks revealed increased activation with increasing subject age in the middle frontal gyrus (BA6 bilaterally, the left middle frontal gyrus (BA10, the left precuneus and left inferior parietal gyri (BA7; 40. Decreased activation with increasing age was found in the right superior frontal (BA8, left junction of postcentral and inferior parietal (BA3/40, and left limbic cingulate gyrus (BA31. These results suggest that brain activation during adolescence increased with age principally in higher order cortices, part of the core working memory network, while reductions were detected in more diffuse and potentially more immature neural networks. Understanding the process by which the brain and its cognitive functions mature through healthy adulthood may provide us with new clues to understanding the vulnerability to neurodevelopmental disorders.

  20. Functional analyses of the three simian hemorrhagic fever virus nonstructural protein 1 papain-like proteases.

    Science.gov (United States)

    Vatter, Heather A; Di, Han; Donaldson, Eric F; Radu, Gertrud U; Maines, Taronna R; Brinton, Margo A

    2014-08-01

    The N-terminal region of simian hemorrhagic fever virus (SHFV) nonstructural polyprotein 1a is predicted to encode three papain-like proteases (PLP1α, PLP1β, and PLP1γ). Catalytic residues and cleavage sites for each of the SHFV PLP1s were predicted by alignment of the SHFV PLP1 region sequences with each other as well as with those of other arteriviruses, and the predicted catalytic residues were shown to be proximal by homology modeling of the SHFV nsp1s on porcine respiratory and reproductive syndrome virus (PRRSV) nsp1 crystal structures. The functionality of the predicted catalytic Cys residues and cleavage sites was tested by analysis of the autoproteolytic products generated in in vitro transcription/translation reactions done with wild-type or mutant SHFV nsp1 constructs. Cleavage sites were also analyzed by mass spectroscopy analysis of selected immunoprecipitated cleavage products. The data showed that each of the three SHFV PLP1s is an active protease. Cys63 was identified as the catalytic Cys of SHFV PLP1α and is adjacent to an Ala instead of the canonical Tyr observed in other arterivirus PLP1s. SHFV PLP1γ is able to cleave at both downstream and upstream nsp1 junction sites. Although intermediate precursor polyproteins as well as alternative products generated by each of the SHFV PLP1s cleaving at sites within the N-terminal region of nsp1β were produced in the in vitro reactions, Western blotting of SHFV-infected, MA104 cell lysates with SHFV nsp1 protein-specific antibodies detected only the three mature nsp1 proteins. SHFV is unique among arteriviruses in having three N-terminal papain-like protease 1 (PLP1) domains. Other arteriviruses encode one or two active PLP1s. This is the first functional study of the SHFV PLP1s. Analysis of the products of in vitro autoprocessing of an N-terminal SHFV nonstructural 1a polypeptide fragment showed that each of the three SHFV PLP1s is active, and the predicted catalytic Cys residues and cleavage sites

  1. Establishment of mitochondrial pyruvate carrier 1 (MPC1) gene knockout mice with preliminary gene function analyses

    Science.gov (United States)

    Li, Xiaoli; Li, Yaqing; Han, Gaoyang; Li, Xiaoran; Ji, Yasai; Fan, Zhirui; Zhong, Yali; Cao, Jing; Zhao, Jing; Mariusz, Goscinski; Zhang, Mingzhi; Wen, Jianguo; Nesland, Jahn M.; Suo, Zhenhe

    2016-01-01

    Pyruvate plays a critical role in the mitochondrial tricarboxylic acid (TCA) cycle, and it is the center product for the synthesis of amino acids, carbohydrates and fatty acids. Pyruvate transported across the inner mitochondrial membrane appears to be essential in anabolic and catabolic intermediary metabolism. The mitochondrial pyruvate carrier (MPC) mounted in the inner membrane of mitochondria serves as the channel to facilitate pyruvate permeating. In mammals, the MPC is formed by two paralogous subunits, MPC1 and MPC2. It is known that complete ablation of MPC2 in mice causes death on the 11th or 12th day of the embryonic period. However, MPC1 deletion and the knowledge of gene function in vivo are lacking. Using the new technology of gene manipulation known as Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated 9 (CRISPR/Cas9) systems, we gained stable MPC1 gene heterozygous mutation mice models, and the heterozygous mutations could be stably maintained in their offsprings. Only one line with homozygous 27 bases deletion in the first exon was established, but no offsprings could be obtained after four months of mating experiments, indicating infertility of the mice with such homozygous deletion. The other line of MPC1 knockout (KO) mice was only heterozygous, which mutated in the first exon with a terminator shortly afterwards. These two lines of MPC1 KO mice showed lower fertility and significantly higher bodyweight in the females. We concluded that heterozygous MPC1 KO weakens fertility and influences the metabolism of glucose and fatty acid and bodyweight in mice. PMID:27835892

  2. Molecular cloning, functional identification and expressional analyses of FasL in Tilapia, Oreochromis niloticus.

    Science.gov (United States)

    Ma, Tai-yang; Wu, Jin-ying; Gao, Xiao-ke; Wang, Jing-yuan; Zhan, Xu-liang; Li, Wen-sheng

    2014-10-01

    FasL is the most extensively studied apoptosis ligand. In 2000, tilapia FasL was identified using anti-human FasL monoclonal antibody by Evans's research group. Recently, a tilapia FasL-like protein of smaller molecule weight was predicted in Genbank (XM_003445156.2). Based on several clues drawn from previous studies, we cast doubt on the authenticity of the formerly identified tilapia FasL. Conversely, using reverse transcription polymerase chain reaction (RT-PCR), the existence of the predicted FasL-like was verified at the mRNA level (The Genbank accession number of the FasL mRNA sequence we cloned is KM008610). Through multiple alignments, this FasL-like protein was found to be highly similar to the FasL of the Japanese flounder. Moreover, we artificially expressed the functional region of the predicted protein and later confirmed its apoptosis-inducing activity using a methyl thiazolyl tetrazolium (MTT) assay, Annexin-V/Propidium iodide (PI) double staining, and DNA fragment detection. Supported by these evidences, we suggest that the predicted protein is the authentic tilapia FasL. To advance this research further, tilapia FasL mRNA and its protein across different tissues were quantified. High expression levels were identified in the tilapia immune system and sites where active cell turnover conservatively occurs. In this regard, FasL may assume an active role in the immune system and cell homeostasis maintenance in tilapia, similar to that shown in other species. In addition, because the distribution pattern of FasL mRNA did not synchronize with that of the protein, post-transcriptional expression regulation is suggested. Such regulation may be dominated by potential adenylate- and uridylate-rich elements (AREs) featuring AUUUA repeats found in the 3' untranslated region (UTR) of tilapia FasL mRNA. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Clinical history and biologic age predicted falls better than objective functional tests.

    Science.gov (United States)

    Gerdhem, Paul; Ringsberg, Karin A M; Akesson, Kristina; Obrant, Karl J

    2005-03-01

    Fall risk assessment is important because the consequences, such as a fracture, may be devastating. The objective of this study was to find the test or tests that best predicted falls in a population-based sample of elderly women. The fall-predictive ability of a questionnaire, a subjective estimate of biologic age and objective functional tests (gait, balance [Romberg and sway test], thigh muscle strength, and visual acuity) were compared in 984 randomly selected women, all 75 years of age. A recalled fall was the most important predictor for future falls. Only recalled falls and intake of psycho-active drugs independently predicted future falls. Women with at least five of the most important fall predictors (previous falls, conditions affecting the balance, tendency to fall, intake of psychoactive medication, inability to stand on one leg, high biologic age) had an odds ratio of 11.27 (95% confidence interval 4.61-27.60) for a fall (sensitivity 70%, specificity 79%). The more time-consuming objective functional tests were of limited importance for fall prediction. A simple clinical history, the inability to stand on one leg, and a subjective estimate of biologic age were more important as part of the fall risk assessment.

  4. Antisense oligodeoxynucleotide inhibition as a potent diagnostic tool for gene function in plant biology

    Energy Technology Data Exchange (ETDEWEB)

    Jansson, Christer; Sun, Chuanxin; Ghebramedhin, Haile; Hoglund, Anna-Stina; Jansson, Christer

    2008-01-15

    Antisense oligodeoxynucleotide (ODN) inhibition emerges as an effective means for probing gene function in plant cells. Employing this method we have established the importance of the SUSIBA2 transcription factor for regulation of starch synthesis in barley endosperm, and arrived at a model for the role of the SUSIBAs in sugar signaling and source-sink commutation during cereal endosperm development. In this addendum we provide additional data demonstrating the suitability of the antisense ODN technology in studies on starch branching enzyme activities in barley leaves. We also comment on the mechanism for ODN uptake in plant cells. Antisense ODNs are short (12-25 nt-long) stretches of single-stranded ODNs that hybridize to the cognate mRNA in a sequence-specific manner, thereby inhibiting gene expression. They are naturally occurring in both prokaryotes and eukaryotes where they partake in gene regulation and defense against viral infection. The mechanisms for antisense ODN inhibition are not fully understood but it is generally considered that the ODN either sterically interferes with translation or promotes transcript degradation by RNase H activation. The earliest indication of the usefulness of antisense ODN technology for the purposes of molecular biology and medical therapy was the demonstration in 1978 that synthetic ODNs complementary to Raos sarcoma virus could inhibit virus replication in tissue cultures of chick embryo fibroblasts. Since then the antisense ODN technology has been widely used in animal sciences and as an important emerging therapeutic approach in clinical medicine. However, antisense ODN inhibition has been an under-exploited strategy for plant tissues, although the prospects for plant cells in suspension cultures to take up single-stranded ODNs was reported over a decade ago. In 2001, two reports from Malho and coworker demonstrated the use of cationic-complexed antisense ODNs to suppress expression of genes encoding pollen

  5. Functional profiles reveal unique ecological roles of various biological soil crust organisms

    Science.gov (United States)

    Bowker, M.A.; Mau, R.L.; Maestre, F.T.; Escolar, C.; Castillo-Monroy, A. P.

    2011-01-01

    1. At the heart of the body of research on biodiversity effects on ecosystem function is the debate over whether different species tend to be functionally singular or redundant. When we consider ecosystem multi-function, the provision of multiple ecosystem functions simultaneously, we may find that seemingly redundant species may in fact play unique roles in ecosystems. 2. Over the last few decades, the significance of biological soil crusts (BSCs) as ecological boundaries and ecosystem engineers, and their multi-functional nature, has become increasingly well documented. We compiled 'functional profiles' of the organisms in this understudied community, to determine whether functional singularity emerges when multiple ecosystem functions are considered. 3. In two data sets, one representing multiple sites around the semi-arid regions of Spain (regional scale), and another from a single site in central Spain (local scale), we examined correlations between the abundance or frequency of BSC species in a community, and multiple surrogates of ecosystem functioning. There was a wide array of apparent effects of species on specific functions. 4. Notably, in gypsiferous soils and at regional scale, we found that indicators of carbon (C) and phosphorus cycling were apparently suppressed and promoted by the lichens Diploschistes diacapsis and Squamarina lentigera, respectively. The moss Pleurochaete squarrosa appears to promote C cycling in calcareous soils at this spatial scale. At the local scale in gypsiferous soils, D. diacapsis positively correlated with carbon cycling, but negatively with nitrogen cycling, whereas numerous lichens exhibited the opposite profile. 5. We found a high degree of functional singularity, i.e. that species were highly individualistic in their effects on multiple functions. Many functional attributes were not easily predictable from existing functional grouping systems based primarily on morphology. 6. Our results suggest that maintaining

  6. Functional soil microbial diversity across Europe estimated by EEA, MicroResp and BIOLOG

    DEFF Research Database (Denmark)

    Winding, Anne; Rutgers, Michiel; Creamer, Rachel

    consisting of 81 soil samples covering five Biogeograhical Zones and three land-uses in order to test the sensitivity, ease and cost of performance and biological significance of the data output. The techniques vary in how close they are to in situ functions; dependency on growth during incubation......Soil microorganisms are abundant and essential for the bio-geochemical processes of soil, soil quality and soil ecosystem services. All this is dependent on the actual functions the microbial communities are performing in the soil. Measuring soil respiration has for many years been the basis...... of estimating soil microbial activity. However, today several techniques are in use for determining microbial functional diversity and assessing soil biodiversity: Methods based on CO2 development by the microbes such as substrate induced respiration (SIR) on specific substrates have lead to the development...

  7. Patterns of use and impact of standardised MedDRA query analyses on the safety evaluation and review of new drug and biologics license applications.

    Science.gov (United States)

    Chang, Lin-Chau; Mahmood, Riaz; Qureshi, Samina; Breder, Christopher D

    2017-01-01

    Standardised MedDRA Queries (SMQs) have been developed since the early 2000's and used by academia, industry, public health, and government sectors for detecting safety signals in adverse event safety databases. The purpose of the present study is to characterize how SMQs are used and the impact in safety analyses for New Drug Application (NDA) and Biologics License Application (BLA) submissions to the United States Food and Drug Administration (USFDA). We used the PharmaPendium database to capture SMQ use in Summary Basis of Approvals (SBoAs) of drugs and biologics approved by the USFDA. Characteristics of the drugs and the SMQ use were employed to evaluate the role of SMQ safety analyses in regulatory decisions and the veracity of signals they revealed. A comprehensive search of the SBoAs yielded 184 regulatory submissions approved from 2006 to 2015. Search strategies more frequently utilized restrictive searches with "narrow terms" to enhance specificity over strategies using "broad terms" to increase sensitivity, while some involved modification of search terms. A majority (59%) of 1290 searches used descriptive statistics, however inferential statistics were utilized in 35% of them. Commentary from reviewers and supervisory staff suggested that a small, yet notable percentage (18%) of 1290 searches supported regulatory decisions. The searches with regulatory impact were found in 73 submissions (40% of the submissions investigated). Most searches (75% of 227 searches) with regulatory implications described how the searches were confirmed, indicating prudence in the decision-making process. SMQs have an increasing role in the presentation and review of safety analysis for NDAs/BLAs and their regulatory reviews. This study suggests that SMQs are best used for screening process, with descriptive statistics, description of SMQ modifications, and systematic verification of cases which is crucial for drawing regulatory conclusions.

  8. Patterns of use and impact of standardised MedDRA query analyses on the safety evaluation and review of new drug and biologics license applications.

    Directory of Open Access Journals (Sweden)

    Lin-Chau Chang

    Full Text Available Standardised MedDRA Queries (SMQs have been developed since the early 2000's and used by academia, industry, public health, and government sectors for detecting safety signals in adverse event safety databases. The purpose of the present study is to characterize how SMQs are used and the impact in safety analyses for New Drug Application (NDA and Biologics License Application (BLA submissions to the United States Food and Drug Administration (USFDA.We used the PharmaPendium database to capture SMQ use in Summary Basis of Approvals (SBoAs of drugs and biologics approved by the USFDA. Characteristics of the drugs and the SMQ use were employed to evaluate the role of SMQ safety analyses in regulatory decisions and the veracity of signals they revealed.A comprehensive search of the SBoAs yielded 184 regulatory submissions approved from 2006 to 2015. Search strategies more frequently utilized restrictive searches with "narrow terms" to enhance specificity over strategies using "broad terms" to increase sensitivity, while some involved modification of search terms. A majority (59% of 1290 searches used descriptive statistics, however inferential statistics were utilized in 35% of them. Commentary from reviewers and supervisory staff suggested that a small, yet notable percentage (18% of 1290 searches supported regulatory decisions. The searches with regulatory impact were found in 73 submissions (40% of the submissions investigated. Most searches (75% of 227 searches with regulatory implications described how the searches were confirmed, indicating prudence in the decision-making process.SMQs have an increasing role in the presentation and review of safety analysis for NDAs/BLAs and their regulatory reviews. This study suggests that SMQs are best used for screening process, with descriptive statistics, description of SMQ modifications, and systematic verification of cases which is crucial for drawing regulatory conclusions.

  9. A Gaussian mixture model based cost function for parameter estimation of chaotic biological systems

    Science.gov (United States)

    Shekofteh, Yasser; Jafari, Sajad; Sprott, Julien Clinton; Hashemi Golpayegani, S. Mohammad Reza; Almasganj, Farshad

    2015-02-01

    As we know, many biological systems such as neurons or the heart can exhibit chaotic behavior. Conventional methods for parameter estimation in models of these systems have some limitations caused by sensitivity to initial conditions. In this paper, a novel cost function is proposed to overcome those limitations by building a statistical model on the distribution of the real system attractor in state space. This cost function is defined by the use of a likelihood score in a Gaussian mixture model (GMM) which is fitted to the observed attractor generated by the real system. Using that learned GMM, a similarity score can be defined by the computed likelihood score of the model time series. We have applied the proposed method to the parameter estimation of two important biological systems, a neuron and a cardiac pacemaker, which show chaotic behavior. Some simulated experiments are given to verify the usefulness of the proposed approach in clean and noisy conditions. The results show the adequacy of the proposed cost function.

  10. A New Triangular Hybrid Displacement Function Element for Static and Free Vibration Analyses of Mindlin-Reissner Plate

    Directory of Open Access Journals (Sweden)

    Jun-Bin Huang

    Full Text Available Abstract A new 3-node triangular hybrid displacement function Mindlin-Reissner plate element is developed. Firstly, the modified variational functional of complementary energy for Mindlin-Reissner plate, which is eventually expressed by a so-called displacement function F, is proposed. Secondly, the locking-free formulae of Timoshenko’s beam theory are chosen as the deflection, rotation, and shear strain along each element boundary. Thirdly, seven fundamental analytical solutions of the displacement function F are selected as the trial functions for the assumed resultant fields, so that the assumed resultant fields satisfy all governing equations in advance. Finally, the element stiffness matrix of the new element, denoted by HDF-P3-7β, is derived from the modified principle of complementary energy. Together with the diagonal inertia matrix of the 3-node triangular isoparametric element, the proposed element is also successfully generalized to the free vibration problems. Numerical results show that the proposed element exhibits overall remarkable performance in all benchmark problems, especially in the free vibration analyses.

  11. Integration of multiscale dendritic spine structure and function data into systems biology models

    Directory of Open Access Journals (Sweden)

    James J Mancuso

    2014-11-01

    Full Text Available Comprising 1011 neurons with 1014 synaptic connections the human brain is the ultimate systems biology puzzle. An increasing body of evidence highlights the observation that changes in brain function, both normal and pathological, consistently correlate with dynamic changes in neuronal anatomy. Anatomical changes occur on a full range of scales from the trafficking of individual proteins, to alterations in synaptic morphology both individually and on a systems level, to reductions in long distance connectivity and brain volume. The major sites of contact for synapsing neurons are dendritic spines, which provide an excellent metric for the number and strength of signaling connections between elements of functional neuronal circuits. A comprehensive model of anatomical changes and their functional consequences would be a holy grail for the field of systems neuroscience but its realization appears far on the horizon. Various imaging technologies have advanced to allow for multi-scale visualization of brain plasticity and pathology, but computational analysis of the massive big data sets involved forms the bottleneck toward the creation of multiscale models of brain structure and function. While a full accounting of techniques and progress toward a comprehensive model of brain anatomy and function is beyond the scope of this or any other single paper, this review serves to highlight the opportunities for analysis of neuronal spine anatomy and function provided by new imaging technologies and the high-throughput application of older technologies while surveying the strengths and weaknesses of currently available computational analytical tools and room for future improvement.

  12. Synthesis, characterization, and in vitro biological evaluation of highly stable diversely functionalized superparamagnetic iron oxide nanoparticles

    International Nuclear Information System (INIS)

    Bhattacharya, Dipsikha; Sahu, Sumanta K.; Banerjee, Indranil; Das, Manasmita; Mishra, Debashish; Maiti, Tapas K.; Pramanik, Panchanan

    2011-01-01

    In this article, we report the design and synthesis of a series of well-dispersed superparamagnetic iron oxide nanoparticles (SPIONs) using chitosan as a surface modifying agent to develop a potential T 2 contrast probe for magnetic resonance imaging (MRI). The amine, carboxyl, hydroxyl, and thiol functionalities were introduced on chitosan-coated magnetic probe via simple reactions with small reactive organic molecules to afford a series of biofunctionalized nanoparticles. Physico-chemical characterizations of these functionalized nanoparticles were performed by TEM, XRD, DLS, FTIR, and VSM. The colloidal stability of these functionalized iron oxide nanoparticles was investigated in presence of phosphate buffer saline, high salt concentrations and different cell media for 1 week. MRI analysis of human cervical carcinoma (HeLa) cell lines treated with nanoparticles elucidated that the amine-functionalized nanoparticles exhibited higher amount of signal darkening and lower T 2 relaxation in comparison to the others. The cellular internalization efficacy of these functionalized SPIONs was also investigated with HeLa cancer cell line by magnetically activated cell sorting (MACS) and fluorescence microscopy and results established selectively higher internalization efficacy of amine-functionalized nanoparticles to cancer cells. These positive attributes demonstrated that these nanoconjugates can be used as a promising platform for further in vitro and in vivo biological evaluations.

  13. Synthesis and Characterization of Rhodamine B-ethylenediamine-hyaluronan Acid as Potential Biological Functional Materials

    Science.gov (United States)

    Li, Y. L.; Wang, W. X.; Wang, Y.; Zhang, W. B.; Gong, H. M.; Liu, M. X.

    2018-05-01

    The purpose of this study is to synthesize and characterize fluorescent polymers, rhodamine B-ethylenediamine-hyaluronan acid (RhB-EA-HA). RhB-EA-HA was successfully synthesized by ester ammonolysis reaction and amidation reaction. Moreover, the structural properties of RhB-EA-HA were characterized by 1H-NMR spectra, UV-vis spectrometry and Fourier transform infrared spectroscopy (FT-IR). RhB-EA-HA can be grafted on the surface of silica nanomaterials, which may be potential biological functional materials for drug delivery system.

  14. Functional knowledge transfer for high-accuracy prediction of under-studied biological processes.

    Directory of Open Access Journals (Sweden)

    Christopher Y Park

    Full Text Available A key challenge in genetics is identifying the functional roles of genes in pathways. Numerous functional genomics techniques (e.g. machine learning that predict protein function have been developed to address this question. These methods generally build from existing annotations of genes to pathways and thus are often unable to identify additional genes participating in processes that are not already well studied. Many of these processes are well studied in some organism, but not necessarily in an investigator's organism of interest. Sequence-based search methods (e.g. BLAST have been used to transfer such annotation information between organisms. We demonstrate that functional genomics can complement traditional sequence similarity to improve the transfer of gene annotations between organisms. Our method transfers annotations only when functionally appropriate as determined by genomic data and can be used with any prediction algorithm to combine transferred gene function knowledge with organism-specific high-throughput data to enable accurate function prediction. We show that diverse state-of-art machine learning algorithms leveraging functional knowledge transfer (FKT dramatically improve their accuracy in predicting gene-pathway membership, particularly for processes with little experimental knowledge in an organism. We also show that our method compares favorably to annotation transfer by sequence similarity. Next, we deploy FKT with state-of-the-art SVM classifier to predict novel genes to 11,000 biological processes across six diverse organisms and expand the coverage of accurate function predictions to processes that are often ignored because of a dearth of annotated genes in an organism. Finally, we perform in vivo experimental investigation in Danio rerio and confirm the regulatory role of our top predicted novel gene, wnt5b, in leftward cell migration during heart development. FKT is immediately applicable to many bioinformatics

  15. A Rapid and Efficient Method for Purifying High Quality Total RNA from Peaches (Prunus persica for Functional Genomics Analyses

    Directory of Open Access Journals (Sweden)

    LEE MEISEL

    2005-01-01

    Full Text Available Prunus persica has been proposed as a genomic model for deciduous trees and the Rosaceae family. Optimized protocols for RNA isolation are necessary to further advance studies in this model species such that functional genomics analyses may be performed. Here we present an optimized protocol to rapidly and efficiently purify high quality total RNA from peach fruits (Prunus persica. Isolating high-quality RNA from fruit tissue is often difficult due to large quantities of polysaccharides and polyphenolic compounds that accumulate in this tissue and co-purify with the RNA. Here we demonstrate that a modified version of the method used to isolate RNA from pine trees and the woody plant Cinnamomun tenuipilum is ideal for isolating high quality RNA from the fruits of Prunus persica. This RNA may be used for many functional genomic based experiments such as RT-PCR and the construction of large-insert cDNA libraries.

  16. Genome-wide analyses and functional classification of proline repeat-rich proteins: potential role of eIF5A in eukaryotic evolution.

    Directory of Open Access Journals (Sweden)

    Ajeet Mandal

    Full Text Available The eukaryotic translation factor, eIF5A has been recently reported as a sequence-specific elongation factor that facilitates peptide bond formation at consecutive prolines in Saccharomyces cerevisiae, as its ortholog elongation factor P (EF-P does in bacteria. We have searched the genome databases of 35 representative organisms from six kingdoms of life for PPP (Pro-Pro-Pro and/or PPG (Pro-Pro-Gly-encoding genes whose expression is expected to depend on eIF5A. We have made detailed analyses of proteome data of 5 selected species, Escherichia coli, Saccharomyces cerevisiae, Drosophila melanogaster, Mus musculus and Homo sapiens. The PPP and PPG motifs are low in the prokaryotic proteomes. However, their frequencies markedly increase with the biological complexity of eukaryotic organisms, and are higher in newly derived proteins than in those orthologous proteins commonly shared in all species. Ontology classifications of S. cerevisiae and human genes encoding the highest level of polyprolines reveal their strong association with several specific biological processes, including actin/cytoskeletal associated functions, RNA splicing/turnover, DNA binding/transcription and cell signaling. Previously reported phenotypic defects in actin polarity and mRNA decay of eIF5A mutant strains are consistent with the proposed role for eIF5A in the translation of the polyproline-containing proteins. Of all the amino acid tandem repeats (≥3 amino acids, only the proline repeat frequency correlates with functional complexity of the five organisms examined. Taken together, these findings suggest the importance of proline repeat-rich proteins and a potential role for eIF5A and its hypusine modification pathway in the course of eukaryotic evolution.

  17. Functional and gene network analyses of transcriptional signatures characterizing pre-weaned bovine mammary parenchyma or fat pad uncovered novel inter-tissue signaling networks during development

    Directory of Open Access Journals (Sweden)

    Lewin Harris A

    2010-05-01

    Full Text Available Abstract Background The neonatal bovine mammary fat pad (MFP surrounding the mammary parenchyma (PAR is thought to exert proliferative effects on the PAR through secretion of local modulators of growth induced by systemic hormones. We used bioinformatics to characterize transcriptomics differences between PAR and MFP from ~65 d old Holstein heifers. Data were mined to uncover potential crosstalk through the analyses of signaling molecules preferentially expressed in one tissue relative to the other. Results Over 9,000 differentially expressed genes (DEG; False discovery rate ≤ 0.05 were found of which 1,478 had a ≥1.5-fold difference between PAR and MFP. Within the DEG highly-expressed in PAR vs. MFP (n = 736 we noted significant enrichment of functions related to cell cycle, structural organization, signaling, and DNA/RNA metabolism. Only actin cytoskeletal signaling was significant among canonical pathways. DEG more highly-expressed in MFP vs. PAR (n = 742 belong to lipid metabolism, signaling, cell movement, and immune-related functions. Canonical pathways associated with metabolism and signaling, particularly immune- and metabolism-related were significantly-enriched. Network analysis uncovered a central role of MYC, TP53, and CTNNB1 in controlling expression of DEG highly-expressed in PAR vs. MFP. Similar analysis suggested a central role for PPARG, KLF2, EGR2, and EPAS1 in regulating expression of more highly-expressed DEG in MFP vs. PAR. Gene network analyses revealed putative inter-tissue crosstalk between cytokines and growth factors preferentially expressed in one tissue (e.g., ANGPTL1, SPP1, IL1B in PAR vs. MFP; ADIPOQ, IL13, FGF2, LEP in MFP vs. PAR with DEG preferentially expressed in the other tissue, particularly transcription factors or pathways (e.g., MYC, TP53, and actin cytoskeletal signaling in PAR vs. MFP; PPARG and LXR/RXR Signaling in MFP vs. PAR. Conclusions Functional analyses underscored a reciprocal influence in

  18. Meta-analyses of cognitive and motor function in youth aged 16 years and younger who subsequently develop schizophrenia.

    Science.gov (United States)

    Dickson, H; Laurens, K R; Cullen, A E; Hodgins, S

    2012-04-01

    Previous reviews have reported cognitive and motor deficits in childhood and adolescence among individuals who later develop schizophrenia. However, these reviews focused exclusively on studies of individuals with affected relatives or on population/birth cohorts, incorporated studies with estimated measures of pre-morbid intelligence, or included investigations that examined symptomatic at-risk participants or participants 18 years or older. Thus, it remains unclear whether cognitive and motor deficits constitute robust antecedents of schizophrenia. Meta-analyses were conducted on published studies that examined cognitive or motor function in youth aged 16 years or younger who later developed schizophrenia or a schizophrenia spectrum disorder (SSD) and those who did not. Twenty-three studies fulfilled the following inclusion criteria: (1) written in English; (2) prospective investigations of birth or genetic high-risk cohorts, or follow-back investigations of population samples; (3) objective measures of cognitive or motor performance at age 16 or younger; (4) results provided for individuals who did and who did not develop schizophrenia/SSD later in life; and (5) sufficient data to calculate effect sizes. Four domains of function were examined: IQ; Motor Function; General Academic Achievement; and Mathematics Achievement. Meta-analyses showed that, by age 16, individuals who subsequently developed schizophrenia/SSD displayed significant deficits in IQ (d=0.51) and motor function (d=0.56), but not in general academic achievement (d=0.25) or mathematics achievement (d=0.21). Subsidiary analysis indicated that the IQ deficit was present by age 13. These results demonstrate that deficits in IQ and motor performance precede the prodrome and the onset of illness.

  19. Cross-cultural and sex differences in the Emotional Skills and Competence Questionnaire scales: Challenges of differential item functioning analyses

    Directory of Open Access Journals (Sweden)

    Bo Molander

    2009-11-01

    Full Text Available University students in Croatia, Slovenia, and Sweden (N = 1129 were examined by means of the Emotional Skills and Competence Questionnaire (Takšić, 1998. Results showed a significant effect for the sex factor only on the total-score scale, women scoring higher than men, but significant effects were obtained for country, as well as for sex, on the Express and Label (EL and Perceive and Understand (PU subscales. Sweden showed higher scores than Croatia and Slovenia on the EL scale, and Slovenia showed higher scores than Croatia and Sweden on the PU scale. In subsequent analyses of differential item functioning (DIF, comparisons were carried out for pairs of countries. The analyses revealed that a large proportion of the items in the total-score scale were potentially biased, most so for the Croatian-Swedish comparison, less for the Slovenian-Swedish comparison, and least for the Croatian-Slovenian comparison. These findings give doubts about the validity of mean score differences in comparisons of countries. However, DIF analyses of sex differences within each country show very few DIF items, indicating that the ESCQ instrument works well within each cultural/linguistic setting. Possible explanations of the findings are discussed, and improvements for future studies are suggested.

  20. Item response theory analysis of the life orientation test-revised: age and gender differential item functioning analyses.

    Science.gov (United States)

    Steca, Patrizia; Monzani, Dario; Greco, Andrea; Chiesi, Francesca; Primi, Caterina

    2015-06-01

    This study is aimed at testing the measurement properties of the Life Orientation Test-Revised (LOT-R) for the assessment of dispositional optimism by employing item response theory (IRT) analyses. The LOT-R was administered to a large sample of 2,862 Italian adults. First, confirmatory factor analyses demonstrated the theoretical conceptualization of the construct measured by the LOT-R as a single bipolar dimension. Subsequently, IRT analyses for polytomous, ordered response category data were applied to investigate the items' properties. The equivalence of the items across gender and age was assessed by analyzing differential item functioning. Discrimination and severity parameters indicated that all items were able to distinguish people with different levels of optimism and adequately covered the spectrum of the latent trait. Additionally, the LOT-R appears to be gender invariant and, with minor exceptions, age invariant. Results provided evidence that the LOT-R is a reliable and valid measure of dispositional optimism. © The Author(s) 2014.

  1. An impedance function approach for soil-structure interaction analyses including structure-to-structure interaction effects

    International Nuclear Information System (INIS)

    Gantayat, A.; Kamil, H.

    1981-01-01

    The dynamic soil-structure and structure-to-structure interaction effects may be determined in one of the two ways: by modeling the entire soil-structure system by a finite-element model, or by using a frequency-dependent (or frequency-independent) impedance function approach. In seismic design of nuclear power plant structures, the normal practice is to use the first approach because of its simplicity and easy availability of computer codes to perform such analyses. However, in the finite-element approach, because of the size and cost restrictions, the three-dimensional behavior of the entire soil-structure system and the radiation damping in soil are only approximately included by using a two-dimensional finite-element mesh. In using the impedance function approach, the soil-structure analyses can be performed in four steps: (a) determination of the dynamic properties of the fixed base superstructure, (b) determination of foundation and structure impedance matrices and input motions, (c) evaluation of foundation motion, (d) analysis of the fixed base superstructure using computed foundation motion. (orig./RW)

  2. Carcinogenesis: alterations in reciprocal interactions of normal functional structure of biologic systems.

    Science.gov (United States)

    Davydyan, Garri

    2015-12-01

    The evolution of biologic systems (BS) includes functional mechanisms that in some conditions may lead to the development of cancer. Using mathematical group theory and matrix analysis, previously, it was shown that normally functioning BS are steady functional structures regulated by three basis regulatory components: reciprocal links (RL), negative feedback (NFB) and positive feedback (PFB). Together, they form an integrative unit maintaining system's autonomy and functional stability. It is proposed that phylogenetic development of different species is implemented by the splitting of "rudimentary" characters into two relatively independent functional parts that become encoded in chromosomes. The functional correlate of splitting mechanisms is RL. Inversion of phylogenetic mechanisms during ontogenetic development leads cell differentiation until cells reach mature states. Deterioration of reciprocal structure in the genome during ontogenesis gives rise of pathological conditions characterized by unsteadiness of the system. Uncontrollable cell proliferation and invasive cell growth are the leading features of the functional outcomes of malfunctioning systems. The regulatory element responsible for these changes is RL. In matrix language, pathological regulation is represented by matrices having positive values of diagonal elements ( TrA  > 0) and also positive values of matrix determinant ( detA  > 0). Regulatory structures of that kind can be obtained if the negative entry of the matrix corresponding to RL is replaced with the positive one. To describe not only normal but also pathological states of BS, a unit matrix should be added to the basis matrices representing RL, NFB and PFB. A mathematical structure corresponding to the set of these four basis functional patterns (matrices) is a split quaternion (coquaternion). The structure and specific role of basis elements comprising four-dimensional linear space of split quaternions help to understand what

  3. Importance of N-Glycosylation on CD147 for Its Biological Functions

    Science.gov (United States)

    Bai, Yang; Huang, Wan; Ma, Li-Tian; Jiang, Jian-Li; Chen, Zhi-Nan

    2014-01-01

    Glycosylation of glycoproteins is one of many molecular changes that accompany malignant transformation. Post-translational modifications of proteins are closely associated with the adhesion, invasion, and metastasis of tumor cells. CD147, a tumor-associated antigen that is highly expressed on the cell surface of various tumors, is a potential target for cancer diagnosis and therapy. A significant biochemical property of CD147 is its high level of glycosylation. Studies on the structure and function of CD147 glycosylation provide valuable clues to the development of targeted therapies for cancer. Here, we review current understanding of the glycosylation characteristics of CD147 and the glycosyltransferases involved in the biosynthesis of CD147 N-glycans. Finally, we discuss proteins regulating CD147 glycosylation and the biological functions of CD147 glycosylation. PMID:24739808

  4. Importance of N-Glycosylation on CD147 for Its Biological Functions

    Directory of Open Access Journals (Sweden)

    Yang Bai

    2014-04-01

    Full Text Available Glycosylation of glycoproteins is one of many molecular changes that accompany malignant transformation. Post-translational modifications of proteins are closely associated with the adhesion, invasion, and metastasis of tumor cells. CD147, a tumor-associated antigen that is highly expressed on the cell surface of various tumors, is a potential target for cancer diagnosis and therapy. A significant biochemical property of CD147 is its high level of glycosylation. Studies on the structure and function of CD147 glycosylation provide valuable clues to the development of targeted therapies for cancer. Here, we review current understanding of the glycosylation characteristics of CD147 and the glycosyltransferases involved in the biosynthesis of CD147 N-glycans. Finally, we discuss proteins regulating CD147 glycosylation and the biological functions of CD147 glycosylation.

  5. The RNAi Universe in Fungi: A Varied Landscape of Small RNAs and Biological Functions.

    Science.gov (United States)

    Torres-Martínez, Santiago; Ruiz-Vázquez, Rosa M

    2017-09-08

    RNA interference (RNAi) is a conserved eukaryotic mechanism that uses small RNA molecules to suppress gene expression through sequence-specific messenger RNA degradation, translational repression, or transcriptional inhibition. In filamentous fungi, the protective function of RNAi in the maintenance of genome integrity is well known. However, knowledge of the regulatory role of RNAi in fungi has had to wait until the recent identification of different endogenous small RNA classes, which are generated by distinct RNAi pathways. In addition, RNAi research on new fungal models has uncovered the role of small RNAs and RNAi pathways in the regulation of diverse biological functions. In this review, we give an up-to-date overview of the different classes of small RNAs and RNAi pathways in fungi and their roles in the defense of genome integrity and regulation of fungal physiology and development, as well as in the interaction of fungi with biotic and abiotic environments.

  6. Structural and Conformational Chemistry from Electrochemical Molecular Machines. Replicating Biological Functions. A Review.

    Science.gov (United States)

    Otero, Toribio F

    2017-12-14

    Each constitutive chain of a conducting polymer electrode acts as a reversible multi-step electrochemical molecular motor: reversible reactions drive reversible conformational movements of the chain. The reaction-driven cooperative actuation of those molecular machines generates, or destroys, inside the film the free volume required to lodge/expel balancing counterions and solvent: reactions drive reversible film volume variations, which basic structural components are here identified and quantified from electrochemical responses. The content of the reactive dense gel (chemical molecular machines, ions and water) mimics that of the intracellular matrix in living functional cells. Reaction-driven properties (composition-dependent properties) and devices replicate biological functions and organs. An emerging technological world of soft, wet, reaction-driven, multifunctional and biomimetic devices and the concomitant zoomorphic or anthropomorphic robots is presented. © 2017 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Microstructure, mechanical properties, and biological response to functionally graded HA coatings

    International Nuclear Information System (INIS)

    Rabiei, Afsaneh; Blalock, Travis; Thomas, Brent; Cuomo, Jerry; Yang, Y.; Ong, Joo

    2007-01-01

    Hydroxyapatite (HA) [Ca 10 (PO 4 ) 6 (OH) 2 ] is the primary mineral content, representing 43% by weight, of bone. Applying a thin layer of HA, to the surface of a metal implant, can promote osseointegration and increase the mechanical stability of the implant. In this study, a biocompatible coating comprising an HA film with functionally graded crystallinity is being deposited on a heated substrate in an Ion Beam Assisted Deposition (IBAD) system. The microstructure of the film was studied using Transmission Electron Microscopy techniques. Finally, initial cell adhesion and cell differentiation on the coating was evaluated using ATCC CRL 1486 human embryonic palatal mesenchymal cell, an osteoblast precursor cell line. The results have shown superior mechanical properties and biological response to the functionally graded HA film

  8. Enzymes for ecdysteroid biosynthesis: their biological functions in insects and beyond.

    Science.gov (United States)

    Niwa, Ryusuke; Niwa, Yuko S

    2014-01-01

    Steroid hormones are responsible for the coordinated regulation of many aspects of biological processes in multicellular organisms. Since the last century, many studies have identified and characterized steroidogenic enzymes in vertebrates, including mammals. However, much less is known about invertebrate steroidogenic enzymes. In the last 15 years, a number of steroidogenic enzymes and their functions have been characterized in ecdysozoan animals, especially in the fruit fly Drosophila melanogaster. In this review, we summarize the latest knowledge of enzymes crucial for synthesizing ecdysteroids, the principal insect steroid hormones. We also discuss the functional conservation and diversity of ecdysteroidogenic enzymes in other insects and even non-insect species, such as nematodes, vertebrates, and lower eukaryotes.

  9. Strategies for the chemical and biological functionalization of scaffolds for cardiac tissue engineering: a review.

    Science.gov (United States)

    Tallawi, Marwa; Rosellini, Elisabetta; Barbani, Niccoletta; Cascone, Maria Grazia; Rai, Ranjana; Saint-Pierre, Guillaume; Boccaccini, Aldo R

    2015-07-06

    The development of biomaterials for cardiac tissue engineering (CTE) is challenging, primarily owing to the requirement of achieving a surface with favourable characteristics that enhances cell attachment and maturation. The biomaterial surface plays a crucial role as it forms the interface between the scaffold (or cardiac patch) and the cells. In the field of CTE, synthetic polymers (polyglycerol sebacate, polyethylene glycol, polyglycolic acid, poly-l-lactide, polyvinyl alcohol, polycaprolactone, polyurethanes and poly(N-isopropylacrylamide)) have been proven to exhibit suitable biodegradable and mechanical properties. Despite the fact that they show the required biocompatible behaviour, most synthetic polymers exhibit poor cell attachment capability. These synthetic polymers are mostly hydrophobic and lack cell recognition sites, limiting their application. Therefore, biofunctionalization of these biomaterials to enhance cell attachment and cell material interaction is being widely investigated. There are numerous approaches for functionalizing a material, which can be classified as mechanical, physical, chemical and biological. In this review, recent studies reported in the literature to functionalize scaffolds in the context of CTE, are discussed. Surface, morphological, chemical and biological modifications are introduced and the results of novel promising strategies and techniques are discussed.

  10. Embryonic stem cell interactomics: the beginning of a long road to biological function.

    Science.gov (United States)

    Yousefi, Maram; Hajihoseini, Vahid; Jung, Woojin; Hosseinpour, Batol; Rassouli, Hassan; Lee, Bonghee; Baharvand, Hossein; Lee, KiYoung; Salekdeh, Ghasem Hosseini

    2012-12-01

    Embryonic stem cells (ESCs) are capable of unlimited self-renewal while maintaining pluripotency. They are of great interest in regenerative medicine due to their ability to differentiate into all cell types of the three embryonic germ layers. Recently, induced pluripotent stem cells (iPSCs) have shown similarities to ESCs and thus promise great therapeutic potential in regenerative medicine. Despite progress in stem cell biology, our understanding of the exact mechanisms by which pluripotency and self-renewal are established and maintained is largely unknown. A better understanding of these processes may lead to discovery of alternative ways for reprogramming, differentiation and more reliable applications of stem cells in therapies. It has become evident that proteins generally function as members of large complexes that are part of a more complex network. Therefore, the identification of protein-protein interactions (PPI) is an efficient strategy for understanding protein function and regulation. Systematic genome-wide and pathway-specific PPI analysis of ESCs has generated a network of ESC proteins, including major transcription factors. These PPI networks of ESCs may contribute to a mechanistic understanding of self-renewal and pluripotency. In this review we describe different experimental approaches for the identification of PPIs along with various databases. We discuss biological findings and technical challenges encountered with interactome studies of pluripotent stem cells, and provide insight into how interactomics is likely to develop.

  11. Biological adaptations for functional features of language in the face of cultural evolution.

    Science.gov (United States)

    Christiansen, Morten H; Reali, Florencia; Chater, Nick

    2011-04-01

    Although there may be no true language universals, it is nonetheless possible to discern several family resemblance patterns across the languages of the world. Recent work on the cultural evolution of language indicates the source of these patterns is unlikely to be an innate universal grammar evolved through biological adaptations for arbitrary linguistic features. Instead, it has been suggested that the patterns of resemblance emerge because language has been shaped by the brain, with individual languages representing different but partially overlapping solutions to the same set of nonlinguistic constraints. Here, we use computational simulations to investigate whether biological adaptation for functional features of language, deriving from cognitive and communicative constraints, may nonetheless be possible alongside rapid cultural evolution. Specifically, we focus on the Baldwin effect as an evolutionary mechanism by which previously learned linguistic features might become innate through natural selection across many generations of language users. The results indicate that cultural evolution of language does not necessarily prevent functional features of language from becoming genetically fixed, thus potentially providing a particularly informative source of constraints on cross-linguistic resemblance patterns.

  12. Biology of bone and how it orchestrates the form and function of the skeleton

    Science.gov (United States)

    Sommerfeldt, D. W.; Rubin, C. T.

    2001-01-01

    The principal role of the skeleton is to provide structural support for the body. While the skeleton also serves as the body's mineral reservoir, the mineralized structure is the very basis of posture, opposes muscular contraction resulting in motion, withstands functional load bearing, and protects internal organs. Although the mass and morphology of the skeleton is defined, to some extent, by genetic determinants, it is the tissue's ability to remodel--the local resorption and formation of bone--which is responsible for achieving this intricate balance between competing responsibilities. The aim of this review is to address bone's form-function relationship, beginning with extensive research in the musculoskeletal disciplines, and focusing on several recent cellular and molecular discoveries which help understand the complex interdependence of bone cells, growth factors, physical stimuli, metabolic demands, and structural responsibilities. With a clinical and spine-oriented audience in mind, the principles of bone cell and molecular biology and physiology are presented, and an attempt has been made to incorporate epidemiologic data and therapeutic implications. Bone research remains interdisciplinary by nature, and a deeper understanding of bone biology will ultimately lead to advances in the treatment of diseases and injuries to bone itself.

  13. Characterization of Aeromonas hydrophila Wound Pathotypes by Comparative Genomic and Functional Analyses of Virulence Genes

    Science.gov (United States)

    Grim, Christopher J.; Kozlova, Elena V.; Sha, Jian; Fitts, Eric C.; van Lier, Christina J.; Kirtley, Michelle L.; Joseph, Sandeep J.; Read, Timothy D.; Burd, Eileen M.; Tall, Ben D.; Joseph, Sam W.; Horneman, Amy J.; Chopra, Ashok K.; Shak, Joshua R.

    2013-01-01

    ABSTRACT Aeromonas hydrophila has increasingly been implicated as a virulent and antibiotic-resistant etiologic agent in various human diseases. In a previously published case report, we described a subject with a polymicrobial wound infection that included a persistent and aggressive strain of A. hydrophila (E1), as well as a more antibiotic-resistant strain of A. hydrophila (E2). To better understand the differences between pathogenic and environmental strains of A. hydrophila, we conducted comparative genomic and functional analyses of virulence-associated genes of these two wound isolates (E1 and E2), the environmental type strain A. hydrophila ATCC 7966T, and four other isolates belonging to A. aquariorum, A. veronii, A. salmonicida, and A. caviae. Full-genome sequencing of strains E1 and E2 revealed extensive differences between the two and strain ATCC 7966T. The more persistent wound infection strain, E1, harbored coding sequences for a cytotoxic enterotoxin (Act), a type 3 secretion system (T3SS), flagella, hemolysins, and a homolog of exotoxin A found in Pseudomonas aeruginosa. Corresponding phenotypic analyses with A. hydrophila ATCC 7966T and SSU as reference strains demonstrated the functionality of these virulence genes, with strain E1 displaying enhanced swimming and swarming motility, lateral flagella on electron microscopy, the presence of T3SS effector AexU, and enhanced lethality in a mouse model of Aeromonas infection. By combining sequence-based analysis and functional assays, we characterized an A. hydrophila pathotype, exemplified by strain E1, that exhibited increased virulence in a mouse model of infection, likely because of encapsulation, enhanced motility, toxin secretion, and cellular toxicity. PMID:23611906

  14. Role of soil biology and soil functions in relation to land use intensity.

    Science.gov (United States)

    Bondi, Giulia; Wall, David; Bacher, Matthias; Emmet-Booth, Jeremy; Graça, Jessica; Marongiu, Irene; Creamer, Rachel

    2017-04-01

    The delivery of the ecosystem's functions is predominantly controlled by soil biology. The biology found in a gram of soil contains more than ten thousand individual species of bacteria and fungi (Torsvik et al., 1990). Understanding the role and the requirements of these organisms is essential for the protection and the sustainable use of soils. Soil biology represents the engine of all the processes occurring in the soil and it supports the ecosystem services such as: 1) nutrient mineralisation 2) plant production 3) water purification and regulation and 4) carbon cycling and storage. During the last years land management type and intensity have been identified as major drivers for microbial performance in soil. For this reason land management needs to be appropriately studied to understand the role of soil biology within this complex interplay of functions. We aimed to study whether and how land management drives soil biological processes and related functions. To reach this objective we built a land use intensity index (LUI) able to quantify the impact of the common farming practices carried out in Irish grassland soils. The LUI is derived from a detailed farmer questionnaire on grassland management practices at 38 farms distributed in the five major agro-climatic regions of Ireland defined by Holden and Brereton (2004). Soils were classified based on their drainage status according to the Irish Soil Information System by Creamer et al. (2014). This detailed questionnaire is then summarised into 3 management intensity components: (i) intensity of Fertilisation (Fi), (ii) frequency of Mowing (Mi) and (iii) intensity of Livestock Grazing (Gi). Sites were sampled to assess the impact of land management intensity on microbial community structure and enzyme behaviour in relation to nitrogen, phosphorus and carbon cycling. Preliminary results for enzymes linked to C and N cycles showed higher activity in relation to low grazing pressure (low Gi). Enzymes linked to P

  15. Evaluation of jaw and neck muscle activities while chewing using EMG-EMG transfer function and EMG-EMG coherence function analyses in healthy subjects.

    Science.gov (United States)

    Ishii, Tomohiro; Narita, Noriyuki; Endo, Hiroshi

    2016-06-01

    This study aims to quantitatively clarify the physiological features in rhythmically coordinated jaw and neck muscle EMG activities while chewing gum using EMG-EMG transfer function and EMG-EMG coherence function analyses in 20 healthy subjects. The chewing side masseter muscle EMG signal was used as the reference signal, while the other jaw (non-chewing side masseter muscle, bilateral anterior temporal muscles, and bilateral anterior digastric muscles) and neck muscle (bilateral sternocleidomastoid muscles) EMG signals were used as the examined signals in EMG-EMG transfer function and EMG-EMG coherence function analyses. Chewing-related jaw and neck muscle activities were aggregated in the first peak of the power spectrum in rhythmic chewing. The gain in the peak frequency represented the power relationships between jaw and neck muscle activities during rhythmic chewing. The phase in the peak frequency represented the temporal relationships between the jaw and neck muscle activities, while the non-chewing side neck muscle presented a broad range of distributions across jaw closing and opening phases. Coherence in the peak frequency represented the synergistic features in bilateral jaw closing muscles and chewing side neck muscle activities. The coherence and phase in non-chewing side neck muscle activities exhibited a significant negative correlation. From above, the bilateral coordination between the jaw and neck muscle activities is estimated while chewing when the non-chewing side neck muscle is synchronously activated with the jaw closing muscles, while the unilateral coordination is estimated when the non-chewing side neck muscle is irregularly activated in the jaw opening phase. Thus, the occurrence of bilateral or unilateral coordinated features in the jaw and neck muscle activities may correspond to the phase characteristics in the non-chewing side neck muscle activities during rhythmical chewing. Considering these novel findings in healthy subjects, EMG

  16. Post Hoc Analyses of Randomized Clinical Trial for the Effect of Clopidogrel Added to Aspirin on Kidney Function.

    Science.gov (United States)

    Ikeme, Jesse C; Pergola, Pablo E; Scherzer, Rebecca; Shlipak, Michael G; Benavente, Oscar R; Peralta, Carmen A

    2017-07-07

    Despite the high burden of CKD, few specific therapies are available that can halt disease progression. In animal models, clopidogrel has emerged as a potential therapy to preserve kidney function. The effect of clopidogrel on kidney function in humans has not been established. The Secondary Prevention of Small Subcortical Strokes Study randomized participants with prior lacunar stroke to treatment with aspirin or aspirin plus clopidogrel. We compared annual eGFR decline and incidence of rapid eGFR decline (≥30% from baseline) using generalized estimating equations and interval-censored proportional hazards regression, respectively. We also stratified our analyses by baseline eGFR, systolic BP target, and time after randomization. At randomization, median age was 62 (interquartile range, 55-71) years old; 36% had a history of diabetes, 90% had hypertension, and the median eGFR was 81 (interquartile range, 65-94) ml/min per 1 m 2 . Persons receiving aspirin plus clopidogrel had an average annual change in kidney function of -1.39 (95% confidence interval, -1.15 to -1.62) ml/min per 1.73 m 2 per year compared with -1.52 (95% confidence interval, -1.30 to -1.74) ml/min per 1.73 m 2 per year among persons receiving aspirin only ( P =0.42). Rapid kidney function decline occurred in 21% of participants receiving clopidogrel plus aspirin compared with 22% of participants receiving aspirin plus placebo (hazard ratio, 0.94; 95% confidence interval, 0.79 to 1.10; P =0.42). Findings did not vary by baseline eGFR, time after randomization, or systolic BP target (all P values for interaction were >0.3). We found no effect of clopidogrel added to aspirin compared with aspirin alone on kidney function decline among persons with prior lacunar stroke. Copyright © 2017 by the American Society of Nephrology.

  17. Unsupervised Learning and Pattern Recognition of Biological Data Structures with Density Functional Theory and Machine Learning.

    Science.gov (United States)

    Chen, Chien-Chang; Juan, Hung-Hui; Tsai, Meng-Yuan; Lu, Henry Horng-Shing

    2018-01-11

    By introducing the methods of machine learning into the density functional theory, we made a detour for the construction of the most probable density function, which can be estimated by learning relevant features from the system of interest. Using the properties of universal functional, the vital core of density functional theory, the most probable cluster numbers and the corresponding cluster boundaries in a studying system can be simultaneously and automatically determined and the plausibility is erected on the Hohenberg-Kohn theorems. For the method validation and pragmatic applications, interdisciplinary problems from physical to biological systems were enumerated. The amalgamation of uncharged atomic clusters validated the unsupervised searching process of the cluster numbers and the corresponding cluster boundaries were exhibited likewise. High accurate clustering results of the Fisher's iris dataset showed the feasibility and the flexibility of the proposed scheme. Brain tumor detections from low-dimensional magnetic resonance imaging datasets and segmentations of high-dimensional neural network imageries in the Brainbow system were also used to inspect the method practicality. The experimental results exhibit the successful connection between the physical theory and the machine learning methods and will benefit the clinical diagnoses.

  18. How biological soil crusts became recognized as a functional unit: a selective history

    Science.gov (United States)

    Lange, Otto L.; Belnap, Jayne

    2016-01-01

    It is surprising that despite the world-wide distribution and general importance of biological soil crusts (biocrusts), scientific recognition and functional analysis of these communities is a relatively young field of science. In this chapter, we sketch the historical lines that led to the recognition of biocrusts as a community with important ecosystem functions. The idea of biocrusts as a functional ecological community has come from two main scientific branches: botany and soil science. For centuries, botanists have long recognized that multiple organisms colonize the soil surface in the open and often dry areas occurring between vascular plants. Much later, after the initial taxonomic and phyto-sociological descriptions were made, soil scientists and agronomists observed that these surface organisms interacted with soils in ways that changed the soil structure. In the 1970’s, research on these communities as ecological units that played an important functional role in drylands began in earnest, and these studies have continued to this day. Here, we trace the history of these studies from the distant past until 1990, when biocrusts became well-known to scientists and the public.

  19. Metagenomic and functional analyses of the consequences of reduction of bacterial diversity on soil functions and bioremediation in diesel-contaminated microcosms.

    Science.gov (United States)

    Jung, Jaejoon; Philippot, Laurent; Park, Woojun

    2016-03-14

    The relationship between microbial biodiversity and soil function is an important issue in ecology, yet most studies have been performed in pristine ecosystems. Here, we assess the role of microbial diversity in ecological function and remediation strategies in diesel-contaminated soils. Soil microbial diversity was manipulated using a removal by dilution approach and microbial functions were determined using both metagenomic analyses and enzymatic assays. A shift from Proteobacteria- to Actinobacteria-dominant communities was observed when species diversity was reduced. Metagenomic analysis showed that a large proportion of functional gene categories were significantly altered by the reduction in biodiversity. The abundance of genes related to the nitrogen cycle was significantly reduced in the low-diversity community, impairing denitrification. In contrast, the efficiency of diesel biodegradation was increased in the low-diversity community and was further enhanced by addition of red clay as a stimulating agent. Our results suggest that the relationship between microbial diversity and ecological function involves trade-offs among ecological processes, and should not be generalized as a positive, neutral, or negative relationship.

  20. Evaluation of functionality and biological response of the multilayer flow modulator in porcine animal models.

    Science.gov (United States)

    Sultan, Sherif; Kavanagh, Edel P; Hynes, Niamh; Diethrich, Edward B

    2016-02-01

    This study outlines the use of non-aneurysmal porcine animal models to study device functionality and biological response of the Multilayer Flow Modulator (MFM) (Cardiatis, Isnes, Belgium), with an emphasis on preclinical device functionality and biological response characteristics in an otherwise healthy aorta. Twelve animals were implanted with the study device in the abdominal aorta, in 6 animals for 1 month and 6 animals for 6 months. Upon completion of the study period, each animal underwent a necropsy to examine how the implanted device had affected the artery and surrounding tissue. Neointima and stenosis formation were recorded via morphometry, and endothelialization via histopathological analysis. The MFM devices were delivered to their respective implantation sites without difficulty. Six of the implanted stents were oversized with percentages ranging from 2.6% to 18.8%. Statistical analysis was carried out and showed no significance between the regular sized stent group and oversized stent group for neointimal area (P=0.17), neointimal thickness (P=0.17), and percentage area stenosis (P=0.65). Histopathological findings showed in most areas flattened endothelium like cells lined the luminal surface of the neointima. Scanning electron microscopy also showed the devices were well tolerated, inciting only a minimal neointimal covering and little fibrin or platelet deposition. Neointimal thickness of 239.7±55.6 μm and 318.3±130.4 μm, and percentage area stenosis of 9.6±2.6% and 12.6±5% were recorded at 1 and 6 months respectively. No statistical differences were found between these results. The MFM devices were delivered to their respective implantation sites without difficulty and incited little neointimal and stenosis formation in the aorta, affirming its functionality and biocompatibility.

  1. Virtual Agonist-antagonist Mechanisms Produce Biological Muscle-like Functions: An Application for Robot Joint Control

    DEFF Research Database (Denmark)

    Xiong, Xiaofeng; Wörgötter, Florentin; Manoonpong, Poramate

    2014-01-01

    Purpose – Biological muscles of animals have a surprising variety of functions, i.e., struts, springs, and brakes. According to this, the purpose of this paper is to apply virtual agonist-antagonist mechanisms to robot joint control allowing for muscle-like functions and variably compliant joint......, variably compliant joint motions can be produced without mechanically bulky and complex mechanisms or complex force/toque sensing at each joint. Moreover, through tuning the damping coefficient of the VAAM, the functions of the VAAM are comparable to biological muscles. Originality/value – The model (i.......e., VAAM) provides a way forward to emulate muscle-like functions that are comparable to those found in physiological experiments of biological muscles. Based on these muscle-like functions, the robotic joints can easily achieve variable compliance that does not require complex physical components...

  2. Food web functioning of the benthopelagic community in a deep-sea seamount based on diet and stable isotope analyses

    Science.gov (United States)

    Preciado, Izaskun; Cartes, Joan E.; Punzón, Antonio; Frutos, Inmaculada; López-López, Lucía; Serrano, Alberto

    2017-03-01

    Trophic interactions in the deep-sea fish community of the Galicia Bank seamount (NE Atlantic) were inferred by using stomach contents analyses (SCA) and stable isotope analyses (SIA) of 27 fish species and their main prey items. Samples were collected during three surveys performed in 2009, 2010 and 2011 between 625 and 1800 m depth. Three main trophic guilds were determined using SCA data: pelagic, benthopelagic and benthic feeders, respectively. Vertically migrating macrozooplankton and meso-bathypelagic shrimps were identified to play a key role as pelagic prey for the deep sea fish community of the Galicia Bank. Habitat overlap was hardly detected; as a matter of fact, when species coexisted most of them evidenced a low dietary overlap, indicating a high degree of resource partitioning. A high potential competition, however, was observed among benthopelagic feeders, i.e.: Etmopterus spinax, Hoplostethus mediterraneus and Epigonus telescopus. A significant correlation was found between δ15N and δ13C for all the analysed species. When calculating Trophic Levels (TLs) for the main fish species, using both the SCA and SIA approaches, some discrepancies arose: TLs calculated from SIA were significantly higher than those obtained from SCA, probably indicating a higher consumption of benthic-suprabenthic prey in the previous months. During the summer, food web functioning in the Galicia Bank was more influenced by the assemblages dwelling in the water column than by deep-sea benthos, which was rather scarce in the summer samples. These discrepancies demonstrate the importance of using both approaches, SCA (snapshot of diet) and SIA (assimilated food in previous months), when attempting trophic studies, if an overview of food web dynamics in different compartments of the ecosystem is to be obtained.

  3. Size-dependent electro-magneto-elastic bending analyses of the shear-deformable axisymmetric functionally graded circular nanoplates

    Science.gov (United States)

    Arefi, Mohammad; Zenkour, Ashraf M.

    2017-10-01

    This paper develops nonlocal elasticity equations and magneto-electro-elastic relations to size-dependent electro-magneto-elastic bending analyses of the functionally graded axisymmetric circular nanoplates based on the first-order shear deformation theory. All material properties are graded along the thickness direction based on exponential varying. It is assumed that a circular nanoplate is made from piezo-magnetic materials. The energy method and Ritz approach is employed for the derivation of governing equations of electro-magneto-elastic bending and the solution of the problem, respectively. The nanoplate is subjected to applied electric and magnetic potentials at top and transverse loads while it is rested on Pasternak's foundation. Some important numerical results are presented in various figures to show the influence of applied electric and magnetic potentials, small scale parameter and inhomogeneous index of an exponentially graded nanoplate.

  4. SCALE: A modular code system for performing standardized computer analyses for licensing evaluation: Functional modules, F9-F11

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    This Manual represents Revision 5 of the user documentation for the modular code system referred to as SCALE. The history of the SCALE code system dates back to 1969 when the current Computational Physics and Engineering Division at Oak Ridge National Laboratory (ORNL) began providing the transportation package certification staff at the U.S. Atomic Energy Commission with computational support in the use of the new KENO code for performing criticality safety assessments with the statistical Monte Carlo method. From 1969 to 1976 the certification staff relied on the ORNL staff to assist them in the correct use of codes and data for criticality, shielding, and heat transfer analyses of transportation packages. However, the certification staff learned that, with only occasional use of the codes, it was difficult to become proficient in performing the calculations often needed for an independent safety review. Thus, shortly after the move of the certification staff to the U.S. Nuclear Regulatory Commission (NRC), the NRC staff proposed the development of an easy-to-use analysis system that provided the technical capabilities of the individual modules with which they were familiar. With this proposal, the concept of the Standardized Computer Analyses for Licensing Evaluation (SCALE) code system was born. This volume consists of the section of the manual dealing with three of the functional modules in the code. Those are the Morse-SGC for the SCALE system, Heating 7.2, and KENO V.a. The manual describes the latest released versions of the codes.

  5. SCALE: A modular code system for performing standardized computer analyses for licensing evaluation: Functional modules, F9-F11

    International Nuclear Information System (INIS)

    1997-03-01

    This Manual represents Revision 5 of the user documentation for the modular code system referred to as SCALE. The history of the SCALE code system dates back to 1969 when the current Computational Physics and Engineering Division at Oak Ridge National Laboratory (ORNL) began providing the transportation package certification staff at the U.S. Atomic Energy Commission with computational support in the use of the new KENO code for performing criticality safety assessments with the statistical Monte Carlo method. From 1969 to 1976 the certification staff relied on the ORNL staff to assist them in the correct use of codes and data for criticality, shielding, and heat transfer analyses of transportation packages. However, the certification staff learned that, with only occasional use of the codes, it was difficult to become proficient in performing the calculations often needed for an independent safety review. Thus, shortly after the move of the certification staff to the U.S. Nuclear Regulatory Commission (NRC), the NRC staff proposed the development of an easy-to-use analysis system that provided the technical capabilities of the individual modules with which they were familiar. With this proposal, the concept of the Standardized Computer Analyses for Licensing Evaluation (SCALE) code system was born. This volume consists of the section of the manual dealing with three of the functional modules in the code. Those are the Morse-SGC for the SCALE system, Heating 7.2, and KENO V.a. The manual describes the latest released versions of the codes

  6. The use of mass spectrometry for analysing metabolite biomarkers in epidemiology: methodological and statistical considerations for application to large numbers of biological samples.

    Science.gov (United States)

    Lind, Mads V; Savolainen, Otto I; Ross, Alastair B

    2016-08-01

    Data quality is critical for epidemiology, and as scientific understanding expands, the range of data available for epidemiological studies and the types of tools used for measurement have also expanded. It is essential for the epidemiologist to have a grasp of the issues involved with different measurement tools. One tool that is increasingly being used for measuring biomarkers in epidemiological cohorts is mass spectrometry (MS), because of the high specificity and sensitivity of MS-based methods and the expanding range of biomarkers that can be measured. Further, the ability of MS to quantify many biomarkers simultaneously is advantageously compared to single biomarker methods. However, as with all methods used to measure biomarkers, there are a number of pitfalls to consider which may have an impact on results when used in epidemiology. In this review we discuss the use of MS for biomarker analyses, focusing on metabolites and their application and potential issues related to large-scale epidemiology studies, the use of MS "omics" approaches for biomarker discovery and how MS-based results can be used for increasing biological knowledge gained from epidemiological studies. Better understanding of the possibilities and possible problems related to MS-based measurements will help the epidemiologist in their discussions with analytical chemists and lead to the use of the most appropriate statistical tools for these data.

  7. Genome-wide linkage, exome sequencing and functional analyses identify ABCB6 as the pathogenic gene of dyschromatosis universalis hereditaria.

    Directory of Open Access Journals (Sweden)

    Hong Liu

    Full Text Available As a genetic disorder of abnormal pigmentation, the molecular basis of dyschromatosis universalis hereditaria (DUH had remained unclear until recently when ABCB6 was reported as a causative gene of DUH.We performed genome-wide linkage scan using Illumina Human 660W-Quad BeadChip and exome sequencing analyses using Agilent SureSelect Human All Exon Kits in a multiplex Chinese DUH family to identify the pathogenic mutations and verified the candidate mutations using Sanger sequencing. Quantitative RT-PCR and Immunohistochemistry was performed to verify the expression of the pathogenic gene, Zebrafish was also used to confirm the functional role of ABCB6 in melanocytes and pigmentation.Genome-wide linkage (assuming autosomal dominant inheritance mode and exome sequencing analyses identified ABCB6 as the disease candidate gene by discovering a coding mutation (c.1358C>T; p.Ala453Val that co-segregates with the disease phenotype. Further mutation analysis of ABCB6 in four other DUH families and two sporadic cases by Sanger sequencing confirmed the mutation (c.1358C>T; p.Ala453Val and discovered a second, co-segregating coding mutation (c.964A>C; p.Ser322Lys in one of the four families. Both mutations were heterozygous in DUH patients and not present in the 1000 Genome Project and dbSNP database as well as 1,516 unrelated Chinese healthy controls. Expression analysis in human skin and mutagenesis interrogation in zebrafish confirmed the functional role of ABCB6 in melanocytes and pigmentation. Given the involvement of ABCB6 mutations in coloboma, we performed ophthalmological examination of the DUH carriers of ABCB6 mutations and found ocular abnormalities in them.Our study has advanced our understanding of DUH pathogenesis and revealed the shared pathological mechanism between pigmentary DUH and ocular coloboma.

  8. Proteomic and functional analyses of the venom of Porthidium lansbergii lansbergii (Lansberg's hognose viper) from the Atlantic Department of Colombia.

    Science.gov (United States)

    Jiménez-Charris, Eliécer; Montealegre-Sanchez, Leonel; Solano-Redondo, Luis; Mora-Obando, Diana; Camacho, Erika; Castro-Herrera, Fernando; Fierro-Pérez, Leonardo; Lomonte, Bruno

    2015-01-30

    largely unknown. This study provides the first combined proteomic and functional analyses of the venom of this pitviper, which may contribute to a better understanding of the features of envenomings by this species. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. The role of ontologies in biological and biomedical research: a functional perspective

    KAUST Repository

    Hoehndorf, Robert

    2015-04-10

    Ontologies are widely used in biological and biomedical research. Their success lies in their combination of four main features present in almost all ontologies: provision of standard identifiers for classes and relations that represent the phenomena within a domain; provision of a vocabulary for a domain; provision of metadata that describes the intended meaning of the classes and relations in ontologies; and the provision of machine-readable axioms and definitions that enable computational access to some aspects of the meaning of classes and relations. While each of these features enables applications that facilitate data integration, data access and analysis, a great potential lies in the possibility of combining these four features to support integrative analysis and interpretation of multimodal data. Here, we provide a functional perspective on ontologies in biology and biomedicine, focusing on what ontologies can do and describing how they can be used in support of integrative research. We also outline perspectives for using ontologies in data-driven science, in particular their application in structured data mining and machine learning applications.

  10. Green leaf volatiles: biosynthesis, biological functions and their applications in biotechnology.

    Science.gov (United States)

    ul Hassan, Muhammad Naeem; Zainal, Zamri; Ismail, Ismanizan

    2015-08-01

    Plants have evolved numerous constitutive and inducible defence mechanisms to cope with biotic and abiotic stresses. These stresses induce the expression of various genes to activate defence-related pathways that result in the release of defence chemicals. One of these defence mechanisms is the oxylipin pathway, which produces jasmonates, divinylethers and green leaf volatiles (GLVs) through the peroxidation of polyunsaturated fatty acids (PUFAs). GLVs have recently emerged as key players in plant defence, plant-plant interactions and plant-insect interactions. Some GLVs inhibit the growth and propagation of plant pathogens, including bacteria, viruses and fungi. In certain cases, GLVs released from plants under herbivore attack can serve as aerial messengers to neighbouring plants and to attract parasitic or parasitoid enemies of the herbivores. The plants that perceive these volatile signals are primed and can then adapt in preparation for the upcoming challenges. Due to their 'green note' odour, GLVs impart aromas and flavours to many natural foods, such as vegetables and fruits, and therefore, they can be exploited in industrial biotechnology. The aim of this study was to review the progress and recent developments in research on the oxylipin pathway, with a specific focus on the biosynthesis and biological functions of GLVs and their applications in industrial biotechnology. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  11. The role of ontologies in biological and biomedical research: a functional perspective

    KAUST Repository

    Hoehndorf, Robert; Schofield, P. N.; Gkoutos, G. V.

    2015-01-01

    Ontologies are widely used in biological and biomedical research. Their success lies in their combination of four main features present in almost all ontologies: provision of standard identifiers for classes and relations that represent the phenomena within a domain; provision of a vocabulary for a domain; provision of metadata that describes the intended meaning of the classes and relations in ontologies; and the provision of machine-readable axioms and definitions that enable computational access to some aspects of the meaning of classes and relations. While each of these features enables applications that facilitate data integration, data access and analysis, a great potential lies in the possibility of combining these four features to support integrative analysis and interpretation of multimodal data. Here, we provide a functional perspective on ontologies in biology and biomedicine, focusing on what ontologies can do and describing how they can be used in support of integrative research. We also outline perspectives for using ontologies in data-driven science, in particular their application in structured data mining and machine learning applications.

  12. Exploring new biological functions of amyloids: bacteria cell agglutination mediated by host protein aggregation.

    Directory of Open Access Journals (Sweden)

    Marc Torrent

    Full Text Available Antimicrobial proteins and peptides (AMPs are important effectors of the innate immune system that play a vital role in the prevention of infections. Recent advances have highlighted the similarity between AMPs and amyloid proteins. Using the Eosinophil Cationic Protein as a model, we have rationalized the structure-activity relationships between amyloid aggregation and antimicrobial activity. Our results show how protein aggregation can induce bacteria agglutination and cell death. Using confocal and total internal reflection fluorescence microscopy we have tracked the formation in situ of protein amyloid-like aggregates at the bacteria surface and on membrane models. In both cases, fibrillar aggregates able to bind to amyloid diagnostic dyes were detected. Additionally, a single point mutation (Ile13 to Ala can suppress the protein amyloid behavior, abolishing the agglutinating activity and impairing the antimicrobial action. The mutant is also defective in triggering both leakage and lipid vesicle aggregation. We conclude that ECP aggregation at the bacterial surface is essential for its cytotoxicity. Hence, we propose here a new prospective biological function for amyloid-like aggregates with potential biological relevance.

  13. Enhanced surface functionality via plasma modification and plasma deposition techniques to create more biologically relevant materials

    Science.gov (United States)

    Shearer, Jeffrey C.

    Functionalizing nanoparticles and other unusually shaped substrates to create more biologically relevant materials has become central to a wide range of research programs. One of the primary challenges in this field is creating highly functionalized surfaces without modifying the underlying bulk material. Traditional wet chemistry techniques utilize thin film depositions to functionalize nanomaterials with oxygen and nitrogen containing functional groups, such as --OH and --NHx. These functional groups can serve to create surfaces that are amenable to cell adhesion or can act as reactive groups for further attachment of larger structures, such as macromolecules or antiviral agents. Additional layers, such as SiO2, are often added between the nanomaterial and the functionalized coating to act as a barrier films, adhesion layers, and to increase overall hydrophilicity. However, some wet chemistry techniques can damage the bulk material during processing. This dissertation examines the use of plasma processing as an alternative method for producing these highly functionalized surfaces on nanoparticles and polymeric scaffolds through the use of plasma modification and plasma enhanced chemical vapor deposition techniques. Specifically, this dissertation will focus on (1) plasma deposition of SiO2 barrier films on nanoparticle substrates; (2) surface functionalization of amine and alcohol groups through (a) plasma co-polymerization and (b) plasma modification; and (3) the design and construction of plasma hardware to facilitate plasma processing of nanoparticles and polymeric scaffolds. The body of work presented herein first examines the fabrication of composite nanoparticles by plasma processing. SiOxC y and hexylamine films were coated onto TiO2 nanoparticles to demonstrate enhanced water dispersion properties. Continuous wave and pulsed allyl alcohol plasmas were used to produce highly functionalized Fe2 O3 supported nanoparticles. Specifically, film composition was

  14. FUSE: a profit maximization approach for functional summarization of biological networks

    Directory of Open Access Journals (Sweden)

    Seah Boon-Siew

    2012-03-01

    Full Text Available Abstract Background The availability of large-scale curated protein interaction datasets has given rise to the opportunity to investigate higher level organization and modularity within the protein interaction network (PPI using graph theoretic analysis. Despite the recent progress, systems level analysis of PPIS remains a daunting task as it is challenging to make sense out of the deluge of high-dimensional interaction data. Specifically, techniques that automatically abstract and summarize PPIS at multiple resolutions to provide high level views of its functional landscape are still lacking. We present a novel data-driven and generic algorithm called FUSE (Functional Summary Generator that generates functional maps of a PPI at different levels of organization, from broad process-process level interactions to in-depth complex-complex level interactions, through a pro t maximization approach that exploits Minimum Description Length (MDL principle to maximize information gain of the summary graph while satisfying the level of detail constraint. Results We evaluate the performance of FUSE on several real-world PPIS. We also compare FUSE to state-of-the-art graph clustering methods with GO term enrichment by constructing the biological process landscape of the PPIS. Using AD network as our case study, we further demonstrate the ability of FUSE to quickly summarize the network and identify many different processes and complexes that regulate it. Finally, we study the higher-order connectivity of the human PPI. Conclusion By simultaneously evaluating interaction and annotation data, FUSE abstracts higher-order interaction maps by reducing the details of the underlying PPI to form a functional summary graph of interconnected functional clusters. Our results demonstrate its effectiveness and superiority over state-of-the-art graph clustering methods with GO term enrichment.

  15. FUSE: a profit maximization approach for functional summarization of biological networks.

    Science.gov (United States)

    Seah, Boon-Siew; Bhowmick, Sourav S; Dewey, C Forbes; Yu, Hanry

    2012-03-21

    The availability of large-scale curated protein interaction datasets has given rise to the opportunity to investigate higher level organization and modularity within the protein interaction network (PPI) using graph theoretic analysis. Despite the recent progress, systems level analysis of PPIS remains a daunting task as it is challenging to make sense out of the deluge of high-dimensional interaction data. Specifically, techniques that automatically abstract and summarize PPIS at multiple resolutions to provide high level views of its functional landscape are still lacking. We present a novel data-driven and generic algorithm called FUSE (Functional Summary Generator) that generates functional maps of a PPI at different levels of organization, from broad process-process level interactions to in-depth complex-complex level interactions, through a pro t maximization approach that exploits Minimum Description Length (MDL) principle to maximize information gain of the summary graph while satisfying the level of detail constraint. We evaluate the performance of FUSE on several real-world PPIS. We also compare FUSE to state-of-the-art graph clustering methods with GO term enrichment by constructing the biological process landscape of the PPIS. Using AD network as our case study, we further demonstrate the ability of FUSE to quickly summarize the network and identify many different processes and complexes that regulate it. Finally, we study the higher-order connectivity of the human PPI. By simultaneously evaluating interaction and annotation data, FUSE abstracts higher-order interaction maps by reducing the details of the underlying PPI to form a functional summary graph of interconnected functional clusters. Our results demonstrate its effectiveness and superiority over state-of-the-art graph clustering methods with GO term enrichment.

  16. Ab Initio Calculations of the Electronic Structures and Biological Functions of Protein Molecules

    Science.gov (United States)

    Zheng, Haoping

    2003-04-01

    The self-consistent cluster-embedding (SCCE) calculation method reduces the computational effort from M3 to about M1 (M is the number of atoms in the system) with unchanged calculation precision. So the ab initio, all-electron calculation of the electronic structure and biological function of protein molecule becomes a reality, which will promote new proteomics considerably. The calculated results of two real protein molecules, the trypsin inhibitor from the seeds of squash Cucurbita maxima (CMTI-I, 436 atoms) and the Ascaris trypsin inhibitor (912 atoms, two three-dimensional structures), are presented. The reactive sites of the inhibitors are determined and explained. The precision of structure determination of inhibitors are tested theoretically.

  17. Functional biology and ecological role of krill in Northern marine ecosystems

    DEFF Research Database (Denmark)

    Agersted, Mette Dalgaard

    Krill is an understudied key group of zooplankton, which transfers energy through the food web by linking lower and higher trophic levels. Furthermore, krill play an important role in the biological pump by transporting carbon out of the euphotic zone to depth by diel vertical migration (DVM...... to be the key factor determining the trophic position of a species, where the largest species had the highest trophic position. The species were feeding on the same food items, which could lead to competition for food. However, there is a difference between the two functional groups, represented by M. norvegica...... for the two dominating species within the fjord, T. inermis and T. raschii. The krill grazed community at this time of year. Yet, the grazing impact was similar to the copepods’, which are normally...

  18. Detection of Metabolism Function of Microbial Community of Corpses by Biolog-Eco Method.

    Science.gov (United States)

    Jiang, X Y; Wang, J F; Zhu, G H; Ma, M Y; Lai, Y; Zhou, H

    2016-06-01

    To detect the changes of microbial community functional diversity of corpses with different postmortem interval (PMI) and to evaluate forensic application value for estimating PMI. The cultivation of microbial community from the anal swabs of a Sus scrofa and a human corpse placed in field environment from 0 to 240 h after death was performed using the Biolog-Eco Microplate and the variations of the absorbance values were also monitored. Combined with the technology of forensic pathology and flies succession, the metabolic characteristics and changes of microbial community on the decomposed corpse under natural environment were also observed. The diversity of microbial metabolism function was found to be negatively correlated with the number of maggots in the corpses. The freezing processing had the greatest impact on average well color development value at 0 h and the impact almost disappeared after 48 h. The diversity of microbial metabolism of the samples became relatively unstable after 192 h. The principal component analysis showed that 31 carbon sources could be consolidated for 5 principal components (accumulative contribution ratio >90%).The carbon source tsquare-analysis showed that N -acetyl- D -glucosamine and L -serine were the dominant carbon sources for estimating the PMI (0=240 h) of the Sus scrofa and human corpse. The Biolog-Eco method can be used to reveal the metabolic differences of the carbon resources utilization of the microbial community on the corpses during 0-240 h after death, which could provide a new basis for estimating the PMI. Copyright© by the Editorial Department of Journal of Forensic Medicine

  19. [Historic and functional biology: the inadequacy of a system theory of evolution].

    Science.gov (United States)

    Regelmann, J P

    1982-01-01

    In the first half of the 20th century neo-Kantianism in a broad sense proved itself the main conceptual and methodological background of the central European biology. As such it contributed much to the victory on the typological, idealistic-morphological and psycho-vitalistic interpretations of life. On the other hand it could not give tools to the biologists for working out a strictly darwinian evolution theory. Kant's theory of organism was conceived without evolution as a theory of the internal functionality of the organism. There was only some 'play' with the evolutionary differentiation of the species. Since then the disputes around the work of August Weismann, a synthetical evolution theory which is now behind time, arose. This theory developed from coinciding claims, elaborated by geneticists, mathematicians, and by biologists studying development, natural history and systematics. This was done under a strong influence of marxist ideas. Through the interweaving of such different approaches it was possible for this evolutionary synthesis to influence successfully the development of evolution research during more than 40 years. Philosophically speaking modern evolution theory means therefore an aversion, even a positive abolition of Kantian positions. A number of biologists however--as L. von Bertalanffy--refused to adhere to a misinterpreted Kantian methodology and oriented themselves to an approach via system theory, which obtained a place in evolution research. In fact this is a Kantian approach as well. They only repeated the Kantian dilemma of the evolution which can also be found in Lamarck and Hegel. The system theory of the functionality of the organism never reaches to the level of the evolving species, but remains always on the level of epigenetic thinking, because of its philosophical origin. This paper points out the consequences of this still current dilemma. At the same time an all-enclosing reflection on the methodological, epistemological and

  20. RNA-seq analyses reveal insights into the function of respiratory nitrate reductase of the diazotroph Herbaspirillum seropedicae.

    Science.gov (United States)

    Bonato, Paloma; Batista, Marcelo B; Camilios-Neto, Doumit; Pankievicz, Vânia C S; Tadra-Sfeir, Michelle Z; Monteiro, Rose Adele; Pedrosa, Fabio O; Souza, Emanuel M; Chubatsu, Leda S; Wassem, Roseli; Rigo, Liu Un

    2016-09-01

    Herbaspirillum seropedicae is a nitrogen-fixing β-proteobacterium that associates with roots of gramineous plants. In silico analyses revealed that H. seropedicae genome has genes encoding a putative respiratory (NAR) and an assimilatory nitrate reductase (NAS). To date, little is known about nitrate metabolism in H. seropedicae, and, as this bacterium cannot respire nitrate, the function of NAR remains unknown. This study aimed to investigate the function of NAR in H. seropedicae and how it metabolizes nitrate in a low aerated-condition. RNA-seq transcriptional profiling in the presence of nitrate allowed us to pinpoint genes important for nitrate metabolism in H. seropedicae, including nitrate transporters and regulatory proteins. Additionally, both RNA-seq data and physiological characterization of a mutant in the catalytic subunit of NAR (narG mutant) showed that NAR is not required for nitrate assimilation but is required for: (i) production of high levels of nitrite, (ii) production of NO and (iii) dissipation of redox power, which in turn lead to an increase in carbon consumption. In addition, wheat plants showed an increase in shoot dry weight only when inoculated with H. seropedicae wild type, but not with the narG mutant, suggesting that NAR is important to H. seropedicae-wheat interaction. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    Guan-Feng Wang

    2015-02-01

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

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

    Science.gov (United States)

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

    2015-02-01

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

  3. Phenotypic and functional analyses show stem cell-derived hepatocyte-like cells better mimic fetal rather than adult hepatocytes.

    Science.gov (United States)

    Baxter, Melissa; Withey, Sarah; Harrison, Sean; Segeritz, Charis-Patricia; Zhang, Fang; Atkinson-Dell, Rebecca; Rowe, Cliff; Gerrard, Dave T; Sison-Young, Rowena; Jenkins, Roz; Henry, Joanne; Berry, Andrew A; Mohamet, Lisa; Best, Marie; Fenwick, Stephen W; Malik, Hassan; Kitteringham, Neil R; Goldring, Chris E; Piper Hanley, Karen; Vallier, Ludovic; Hanley, Neil A

    2015-03-01

    Hepatocyte-like cells (HLCs), differentiated from pluripotent stem cells by the use of soluble factors, can model human liver function and toxicity. However, at present HLC maturity and whether any deficit represents a true fetal state or aberrant differentiation is unclear and compounded by comparison to potentially deteriorated adult hepatocytes. Therefore, we generated HLCs from multiple lineages, using two different protocols, for direct comparison with fresh fetal and adult hepatocytes. Protocols were developed for robust differentiation. Multiple transcript, protein and functional analyses compared HLCs to fresh human fetal and adult hepatocytes. HLCs were comparable to those of other laboratories by multiple parameters. Transcriptional changes during differentiation mimicked human embryogenesis and showed more similarity to pericentral than periportal hepatocytes. Unbiased proteomics demonstrated greater proximity to liver than 30 other human organs or tissues. However, by comparison to fresh material, HLC maturity was proven by transcript, protein and function to be fetal-like and short of the adult phenotype. The expression of 81% phase 1 enzymes in HLCs was significantly upregulated and half were statistically not different from fetal hepatocytes. HLCs secreted albumin and metabolized testosterone (CYP3A) and dextrorphan (CYP2D6) like fetal hepatocytes. In seven bespoke tests, devised by principal components analysis to distinguish fetal from adult hepatocytes, HLCs from two different source laboratories consistently demonstrated fetal characteristics. HLCs from different sources are broadly comparable with unbiased proteomic evidence for faithful differentiation down the liver lineage. This current phenotype mimics human fetal rather than adult hepatocytes. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  4. [The hyperiricosuria as an indicator of derangement of biologic functions of endoecology and adaptation, biologic reactions of excretion, inflammation and arterial tension].

    Science.gov (United States)

    Titov, V N; Oshchepkova, E V; Dmitriev, V A; Gushchina, O V; Shiriaeva, Iu K; Iashin, A Ia

    2012-04-01

    During millions years in all animals allantoine (oxidized by uricase uric acid) was catabolite of purines and ascorbic acid was an acceptor of active forms of oxygen. The proximal tubules of nephron reabsorbed the trace amounts of uric acid Then during phylogenesis the primates had a mutation of ascorbic acid gen minus. Later on occurred a second spontaneous mutation and uricase gen minus and uric acid became catabolites of purines. In absence of ascorbic acid synthesis ions of urates became a major capturers of active forms of oxygen and all uric acid as before underwent the reabsorption. Later the carriers were formed which began in epithelium of proximal tubules to secrete all uric acid into urine. At every incident of "littering" of intercellular medium with endogenic flogogens (impairment of biologic function of endoecology) under compensatory development of biologic reaction of inflammation the need in inactivation of active forms of oxygen increases. Hence later on in phylogenesis one more stage was formed--post secretory reabsorption of uric acid In the biologic reaction of inflammation epithelium of proximal tubules initiates retentional hyperiricosuria. The general antioxidant activity of human blood plasma in 60% is presented by urates' ions. The excretion of uric acid includes 4 stages: filtration, full reabsorption, secretion and post secretory reabsorption. In phylogenesis these stages formed in sequence. The mild hyperiricosuria is most frequently considered as a non-specific indicator of activation of biologic reaction of inflammation. The productive hyperiricosuria develops more infrequently under surplus of meat food and cytolysis syndrome (intensification of cell loss in vivo). Under concentration of uric acid more than 400 mkmol/l part of urates circulates in intercellular medium in the form of crystals. The microcrystals of uric acid (biologic "litter") initiate the syndrome of systemic inflammatory response as an endogenic flogogen

  5. SCALE: A modular code system for performing standardized computer analyses for licensing evaluation: Functional modules F1-F8

    International Nuclear Information System (INIS)

    1997-03-01

    This Manual represents Revision 5 of the user documentation for the modular code system referred to as SCALE. The history of the SCALE code system dates back to 1969 when the current Computational Physics and Engineering Division at Oak Ridge National Laboratory (ORNL) began providing the transportation package certification staff at the U.S. Atomic Energy Commission with computational support in the use of the new KENO code for performing criticality safety assessments with the statistical Monte Carlo method. From 1969 to 1976 the certification staff relied on the ORNL staff to assist them in the correct use of codes and data for criticality, shielding, and heat transfer analyses of transportation packages. However, the certification staff learned that, with only occasional use of the codes, it was difficult to become proficient in performing the calculations often needed for an independent safety review. Thus, shortly after the move of the certification staff to the U.S. Nuclear Regulatory Commission (NRC), the NRC staff proposed the development of an easy-to-use analysis system that provided the technical capabilities of the individual modules with which they were familiar. With this proposal, the concept of the Standardized Computer Analyses for Licensing Evaluation (SCALE) code system was born. This volume consists of the section of the manual dealing with eight of the functional modules in the code. Those are: BONAMI - resonance self-shielding by the Bondarenko method; NITAWL-II - SCALE system module for performing resonance shielding and working library production; XSDRNPM - a one-dimensional discrete-ordinates code for transport analysis; XSDOSE - a module for calculating fluxes and dose rates at points outside a shield; KENO IV/S - an improved monte carlo criticality program; COUPLE; ORIGEN-S - SCALE system module to calculate fuel depletion, actinide transmutation, fission product buildup and decay, and associated radiation source terms; ICE

  6. SCALE: A modular code system for performing standardized computer analyses for licensing evaluation: Functional modules F1-F8

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    This Manual represents Revision 5 of the user documentation for the modular code system referred to as SCALE. The history of the SCALE code system dates back to 1969 when the current Computational Physics and Engineering Division at Oak Ridge National Laboratory (ORNL) began providing the transportation package certification staff at the U.S. Atomic Energy Commission with computational support in the use of the new KENO code for performing criticality safety assessments with the statistical Monte Carlo method. From 1969 to 1976 the certification staff relied on the ORNL staff to assist them in the correct use of codes and data for criticality, shielding, and heat transfer analyses of transportation packages. However, the certification staff learned that, with only occasional use of the codes, it was difficult to become proficient in performing the calculations often needed for an independent safety review. Thus, shortly after the move of the certification staff to the U.S. Nuclear Regulatory Commission (NRC), the NRC staff proposed the development of an easy-to-use analysis system that provided the technical capabilities of the individual modules with which they were familiar. With this proposal, the concept of the Standardized Computer Analyses for Licensing Evaluation (SCALE) code system was born. This volume consists of the section of the manual dealing with eight of the functional modules in the code. Those are: BONAMI - resonance self-shielding by the Bondarenko method; NITAWL-II - SCALE system module for performing resonance shielding and working library production; XSDRNPM - a one-dimensional discrete-ordinates code for transport analysis; XSDOSE - a module for calculating fluxes and dose rates at points outside a shield; KENO IV/S - an improved monte carlo criticality program; COUPLE; ORIGEN-S - SCALE system module to calculate fuel depletion, actinide transmutation, fission product buildup and decay, and associated radiation source terms; ICE.

  7. Re-evaluating concepts of biological function in clinical medicine: towards a new naturalistic theory of disease.

    Science.gov (United States)

    Chin-Yee, Benjamin; Upshur, Ross E G

    2017-08-01

    Naturalistic theories of disease appeal to concepts of biological function, and use the notion of dysfunction as the basis of their definitions. Debates in the philosophy of biology demonstrate how attributing functions in organisms and establishing the function-dysfunction distinction is by no means straightforward. This problematization of functional ascription has undermined naturalistic theories and led some authors to abandon the concept of dysfunction, favoring instead definitions based in normative criteria or phenomenological approaches. Although this work has enhanced our understanding of disease and illness, we need not necessarily abandon naturalistic concepts of function and dysfunction in the disease debate. This article attempts to move towards a new naturalistic theory of disease that overcomes the limitations of previous definitions and offers advantages in the clinical setting. Our approach involves a re-evaluation of concepts of biological function employed by naturalistic theories. Drawing on recent insights from the philosophy of biology, we develop a contextual and evaluative account of function that is better suited to clinical medicine and remains consistent with contemporary naturalism. We also show how an updated naturalistic view shares important affinities with normativist and phenomenological positions, suggesting a possibility for consilience in the disease debate.

  8. Optimization of polysaccharides extraction from watermelon rinds: Structure, functional and biological activities.

    Science.gov (United States)

    Romdhane, Molka Ben; Haddar, Anissa; Ghazala, Imen; Jeddou, Khawla Ben; Helbert, Claire Boisset; Ellouz-Chaabouni, Semia

    2017-02-01

    In the present work, optimization of hot water extraction, structural characteristics, functional properties, and biological activities of polysaccharides extracted from watermelon rinds (WMRP) were investigated. The physicochemical characteristics and the monosaccharide composition of these polysaccharides were then determined using chemical composition analysis, Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM) and gas chromatography-flame ionization detection (GC-FID). SEM images showed that extracted polysaccharides had a rough surface with many cavities. GC-FID results proved that galactose was the dominant sugar in the extracted polysaccharides, followed by arabinose, glucose, galacturonic acid, rhamnose, mannose, xylose and traces of glucuronic acid. The findings revealed that WMRP displayed excellent antihypertensive and antioxidant activities. Those polysaccharides had also a protection effect against hydroxyl radical-induced DNA damage. Functional properties of extracted polysaccharides were also evaluated. WMRP showed good interfacial dose-dependent proprieties. Overall, the results suggested that WMRP presents a promising natural source of antioxidants and antihypertensive agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. A postprocessing method in the HMC framework for predicting gene function based on biological instrumental data

    Science.gov (United States)

    Feng, Shou; Fu, Ping; Zheng, Wenbin

    2018-03-01

    Predicting gene function based on biological instrumental data is a complicated and challenging hierarchical multi-label classification (HMC) problem. When using local approach methods to solve this problem, a preliminary results processing method is usually needed. This paper proposed a novel preliminary results processing method called the nodes interaction method. The nodes interaction method revises the preliminary results and guarantees that the predictions are consistent with the hierarchy constraint. This method exploits the label dependency and considers the hierarchical interaction between nodes when making decisions based on the Bayesian network in its first phase. In the second phase, this method further adjusts the results according to the hierarchy constraint. Implementing the nodes interaction method in the HMC framework also enhances the HMC performance for solving the gene function prediction problem based on the Gene Ontology (GO), the hierarchy of which is a directed acyclic graph that is more difficult to tackle. The experimental results validate the promising performance of the proposed method compared to state-of-the-art methods on eight benchmark yeast data sets annotated by the GO.

  10. Functionalized polypyrrole film: synthesis, characterization, and potential applications in chemical and biological sensors.

    Science.gov (United States)

    Dong, Hua; Cao, Xiaodong; Li, Chang Ming

    2009-07-01

    In this paper, we report the synthesis of a carboxyl-functionalized polypyrrole derivative, a poly(pyrrole-N-propanoic acid) (PPPA) film, by electrochemical polymerization, and the investigation of its basic properties via traditional characterization techniques such as confocal-Raman, FTIR, SEM, AFM, UV-vis, fluorescence microscopy, and contact-angle measurements. The experimental data show that the as-prepared PPPA film exhibits a hydrophilic nanoporous structure, abundant -COOH functional groups in the polymer backbone, and high fluorescent emission under laser excitation. On the basis of these unique properties, further experiments were conducted to demonstrate three potential applications of the PPPA film in chemical and biological sensors: a permeable and permselective membrane, a membrane with specific recognition sites for biomolecule immobilization, and a fluorescent conjugated polymer for amplification of fluorescence quenching. Specifically, the permeability and permselectivity of ion species through the PPPA film are detected by means of rotating-disk-electrode voltammetry; the specific recognition sites on the film surface are confirmed with protein immobilization, and the amplification of fluorescence quenching is measured by the addition of a quenching agent with fluorescence microscopy. The results are in good agreement with our expectations.

  11. Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells

    Directory of Open Access Journals (Sweden)

    Rinaldo Florencio-Silva

    2015-01-01

    Full Text Available Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines and systemic (e.g., calcitonin and estrogens factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells. For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts. Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology. It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue. In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling.

  12. Unexpected functional similarities between gatekeeper tumour suppressor genes and proto-oncogenes revealed by systems biology.

    Science.gov (United States)

    Zhao, Yongzhong; Epstein, Richard J

    2011-05-01

    Familial tumor suppressor genes comprise two subgroups: caretaker genes (CTs) that repair DNA, and gatekeeper genes (GKs) that trigger cell death. Since GKs may also induce cell cycle delay and thus enhance cell survival by facilitating DNA repair, we hypothesized that the prosurvival phenotype of GKs could be selected during cancer progression, and we used a multivariable systems biology approach to test this. We performed multidimensional data analysis, non-negative matrix factorization and logistic regression to compare the features of GKs with those of their putative antagonists, the proto-oncogenes (POs), as well as with control groups of CTs and functionally unrelated congenital heart disease genes (HDs). GKs and POs closely resemble each other, but not CTs or HDs, in terms of gene structure (Pexpression level and breadth (Pimplied suggest a common functional attribute that is strongly negatively selected-that is, a shared phenotype that enhances cell survival. The counterintuitive finding of similar evolutionary pressures affecting GKs and POs raises an intriguing possibility: namely, that cancer microevolution is accelerated by an epistatic cascade in which upstream suppressor gene defects subvert the normal bifunctionality of wild-type GKs by constitutively shifting the phenotype away from apoptosis towards survival. If correct, this interpretation would explain the hitherto unexplained phenomenon of frequent wild-type GK (for example, p53) overexpression in tumors.

  13. Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells.

    Science.gov (United States)

    Florencio-Silva, Rinaldo; Sasso, Gisela Rodrigues da Silva; Sasso-Cerri, Estela; Simões, Manuel Jesus; Cerri, Paulo Sérgio

    2015-01-01

    Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines) and systemic (e.g., calcitonin and estrogens) factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells. For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts. Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology. It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue. In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling.

  14. Structural and functional biological materials: Abalone nacre, sharp materials, and abalone foot adhesion

    Science.gov (United States)

    Lin, Albert Yu-Min

    A three-part study of lessons from nature is presented through the examination of various biological materials, with an emphasis on materials from the mollusk Haliotis rufescens, commonly referred to as the red abalone. The three categories presented are: structural hierarchy, self-assembly, and functionality. Ocean mollusk shells are composed of aragonite/calcite crystals interleaved with layers of a visco-elastic protein, having dense, tailored structures with excellent mechanical properties. The complex nano-laminate structure of this bio-composite material is characterized and related to its mechanical properties. Three levels of structural hierarchy are identified: macroscale mesolayers separating larger regions of tiled aragonite, microscale organization of 0.5 mum by 10 mum aragonite bricks; nanoscale mineral bridges passing through 30 nm layers of organic matrix separating individual aragonite tiles. Composition and growth mechanisms of this nanostructure were observed through close examination of laboratory-grown samples using scanning electron microscopy (SEM), Raman spectroscopy, and transmission electron microscopy (TEM). Glass slides and nacre pucks were implanted onto the growth surface of living abalone and removed periodically to observe trends in nacre deposition. Various deproteinization and demineralization experiments are used to explore the inorganic and organic components of the nacre's structure. The organic component of the shell is characterized by atomic force microscopy (AFM). The functionality of various biological materials is described and investigated. Two specific types of functionality are characterized, the ability of some materials to cut and puncture through sharp designs, and the ability for some materials to be used as attachment devices. Aspects of cutting materials employed by a broad range of animals were characterized and compared. In respect to the attachment mechanisms the foot of the abalone and the tree frog were

  15. Functional connectivity of coral reef fishes in a tropical seascape assessed by compound-specific stable isotope analyses

    KAUST Repository

    McMahon, Kelton W.

    2011-01-01

    The ecological integrity of tropical habitats, including mangroves, seagrass beds and coral reefs, is coming under increasing pressure from human activities. Many coral reef fish species are thought to use mangroves and seagrass beds as juvenile nurseries before migrating to coral reefs as adults. Identifying essential habitats and preserving functional linkages among these habitats is likely necessary to promote ecosystem health and sustainable fisheries on coral reefs. This necessitates quantitative assessment of functional connectivity among essential habitats at the seascape level. This thesis presents the development and first application of a method for tracking fish migration using amino acid (AA) δ13C analysis in otoliths. In a controlled feeding experiment with fish reared on isotopically distinct diets, we showed that essential AAs exhibited minimal trophic fractionation between consumer and diet, providing a δ13C record of the baseline isoscape. We explored the potential for geochemical signatures in otoliths of snapper to act as natural tags of residency in seagrass beds, mangroves and coral reefs in the Red Sea, Caribbean Sea and Eastern Pacific Ocean. The δ13C values of otolith essential AAs varied as a function of habitat type and provided a better tracer of residence in juvenile nursery habitats than conventional bulk stable isotope analyses (SIA). Using our otolith AA SIA approach, we quantified the relative contribution of coastal wetlands and reef habitats to Lutjanus ehrenbergii populations on coastal, shelf and oceanic coral reefs in the Red Sea. L. ehrenbergii made significant ontogenetic migrations, traveling more than 30 km from juvenile nurseries to coral reefs and across deep open water. Coastal wetlands were important nurseries for L. ehrenbergii; however, there was significant plasticity in L. ehrenbergii juvenile habitat requirements. Seascape configuration played an important role in determining the functional connectivity of L

  16. Multi-functional photonic crystal sensors enabled by biological silica (Conference Presentation)

    Science.gov (United States)

    Wang, Alan X.

    2017-02-01

    Diatoms are microalgae found in every habitat where water is present. They produce 40% of the ocean's yearly production of organic carbon and 20% of the oxygen that we breathe. Their abundance and wide distribution make them ideal materials for a wide range of applications as living organisms. In our previous work, we have demonstrated that diatom biosilica with self-assembled silver nanoparticles (Ag NPs) can be used as ultra-sensitive, low-cost substrates for surface-enhanced Raman scattering (SERS) sensing. The enhancement comes from the photonic crystal enhancement of diatom frustules that could improve the hot-spots of Ag NPs. In this work, we report the unique micro-fluidic flow, analyte concentration effect, and thin layer chromatography (TLC) on diatom biosilica, which enables selection, separation, detection, and analysis of complex chemical and biological samples. Particularly, we show that the microscopic fluidic flow induced by the evaporation of liquid droplet can concentrate the analyte and achieve label-free sensing of single molecule detection of R6G and label-free sensing of 4.5×10-17g trinitrotoluene (TNT) from only 200 nano-liter solution. We also demonstrated a facile method for instant on-site separation and detection of analytes by TLC in tandem with SERS spectroscopy using high density diatom thin film. This lab-on-chip technology has been successfully applied for label-free detection of polycyclic aromatic hydrocarbons from human plasma and histamine from salmon fish. Our research suggests that such cost-effective, multi-functional photonic crystal sensors enabled by diatom biosilica opens a new route for lab-on-chip systems and possess significant engineering potentials for chemical and biological sensing.

  17. Decreased functional diversity and biological pest control in conventional compared to organic crop fields.

    Directory of Open Access Journals (Sweden)

    Jochen Krauss

    Full Text Available Organic farming is one of the most successful agri-environmental schemes, as humans benefit from high quality food, farmers from higher prices for their products and it often successfully protects biodiversity. However there is little knowledge if organic farming also increases ecosystem services like pest control. We assessed 30 triticale fields (15 organic vs. 15 conventional and recorded vascular plants, pollinators, aphids and their predators. Further, five conventional fields which were treated with insecticides were compared with 10 non-treated conventional fields. Organic fields had five times higher plant species richness and about twenty times higher pollinator species richness compared to conventional fields. Abundance of pollinators was even more than one-hundred times higher on organic fields. In contrast, the abundance of cereal aphids was five times lower in organic fields, while predator abundances were three times higher and predator-prey ratios twenty times higher in organic fields, indicating a significantly higher potential for biological pest control in organic fields. Insecticide treatment in conventional fields had only a short-term effect on aphid densities while later in the season aphid abundances were even higher and predator abundances lower in treated compared to untreated conventional fields. Our data indicate that insecticide treatment kept aphid predators at low abundances throughout the season, thereby significantly reducing top-down control of aphid populations. Plant and pollinator species richness as well as predator abundances and predator-prey ratios were higher at field edges compared to field centres, highlighting the importance of field edges for ecosystem services. In conclusion organic farming increases biodiversity, including important functional groups like plants, pollinators and predators which enhance natural pest control. Preventative insecticide application in conventional fields has only short

  18. Decreased functional diversity and biological pest control in conventional compared to organic crop fields.

    Science.gov (United States)

    Krauss, Jochen; Gallenberger, Iris; Steffan-Dewenter, Ingolf

    2011-01-01

    Organic farming is one of the most successful agri-environmental schemes, as humans benefit from high quality food, farmers from higher prices for their products and it often successfully protects biodiversity. However there is little knowledge if organic farming also increases ecosystem services like pest control. We assessed 30 triticale fields (15 organic vs. 15 conventional) and recorded vascular plants, pollinators, aphids and their predators. Further, five conventional fields which were treated with insecticides were compared with 10 non-treated conventional fields. Organic fields had five times higher plant species richness and about twenty times higher pollinator species richness compared to conventional fields. Abundance of pollinators was even more than one-hundred times higher on organic fields. In contrast, the abundance of cereal aphids was five times lower in organic fields, while predator abundances were three times higher and predator-prey ratios twenty times higher in organic fields, indicating a significantly higher potential for biological pest control in organic fields. Insecticide treatment in conventional fields had only a short-term effect on aphid densities while later in the season aphid abundances were even higher and predator abundances lower in treated compared to untreated conventional fields. Our data indicate that insecticide treatment kept aphid predators at low abundances throughout the season, thereby significantly reducing top-down control of aphid populations. Plant and pollinator species richness as well as predator abundances and predator-prey ratios were higher at field edges compared to field centres, highlighting the importance of field edges for ecosystem services. In conclusion organic farming increases biodiversity, including important functional groups like plants, pollinators and predators which enhance natural pest control. Preventative insecticide application in conventional fields has only short-term effects on aphid

  19. Subtypes of familial hemophagocytic lymphohistiocytosis in Japan based on genetic and functional analyses of cytotoxic T lymphocytes.

    Directory of Open Access Journals (Sweden)

    Kozo Nagai

    Full Text Available BACKGROUND: Familial hemophagocytic lymphohistiocytosis (FHL is a rare disease of infancy or early childhood. To clarify the incidence and subtypes of FHL in Japan, we performed genetic and functional analyses of cytotoxic T lymphocytes (CTLs in Japanese patients with FHL. DESIGN AND METHODS: Among the Japanese children with hemophagocytic lymphohistiocytosis (HLH registered at our laboratory, those with more than one of the following findings were eligible for study entry under a diagnosis of FHL: positive for known genetic mutations, a family history of HLH, and impaired CTL-mediated cytotoxicity. Mutations of the newly identified causative gene for FHL5, STXBP2, and the cytotoxicity and degranulation activity of CTLs in FHL patients, were analyzed. RESULTS: Among 31 FHL patients who satisfied the above criteria, PRF1 mutation was detected in 17 (FHL2 and UNC13D mutation was in 10 (FHL3. In 2 other patients, 3 novel mutations of STXBP2 gene were confirmed (FHL5. Finally, the remaining 2 were classified as having FHL with unknown genetic mutations. In all FHL patients, CTL-mediated cytotoxicity was low or deficient, and degranulation activity was also low or absent except FHL2 patients. In 2 patients with unknown genetic mutations, the cytotoxicity and degranulation activity of CTLs appeared to be deficient in one patient and moderately impaired in the other. CONCLUSIONS: FHL can be diagnosed and classified on the basis of CTL-mediated cytotoxicity, degranulation activity, and genetic analysis. Based on the data obtained from functional analysis of CTLs, other unknown gene(s responsible for FHL remain to be identified.

  20. Effects of Red Wine Vinegar Beverage on the Colonic Tissue of Rodents: Biochemical, Functional and Pharmacological Analyses.

    Science.gov (United States)

    Enkhsaikhan, Azjargal; Takahara, Akira; Nakamura, Yuji; Goto, Ai; Chiba, Koki; Lubna, Nur Jaharat; Hagiwara-Nagasawa, Mihoko; Izumi-Nakaseko, Hiroko; Ando, Kentaro; Naito, Atsuhiko T; Sugiyama, Atsushi

    2018-01-01

    A beverage made of red wine vinegar and grape juice (Yamanashi-no-megumi™) was developed as a supplemental fluid containing polyphenols, which has been clinically shown to enhance the colonic transit. In this study, we assessed the mechanism of its prokinetic action by analyzing the effects on both the colonic phosphodiesterase activity of rats (n=4) and the isolated colonic strip preparation of guinea pigs (n=4). The 7% (v/v) solution of the beverage significantly decreased the phosphodiesterase activity by 9% (n=4). The beverage in concentrations of 0.7, 2.1 and 7% (v/v) relaxed the colonic strips pre-contracted by 1 µmol/L of carbachol in a concentration-related manner with 50, 58 and 79%, each response of which was diminished to 11, 19 and 46%, respectively in the presence of 100 µmol/L of L-nitro-arginine methyl ester. These results obtained by biochemical, functional and pharmacological analyses suggest that the beverage could relax the colon through both cAMP-associated and nitric oxide-dependent pathways, which may partly explain clinically observed prokinetic effect of the beverage.

  1. Functional Analyses of a Novel CITED2 Nonsynonymous Mutation in Chinese Tibetan Patients with Congenital Heart Disease.

    Science.gov (United States)

    Liu, Shiming; Su, Zhaobing; Tan, Sainan; Ni, Bin; Pan, Hong; Liu, Beihong; Wang, Jing; Xiao, Jianmin; Chen, Qiuhong

    2017-08-01

    CITED2 gene is an important cardiac transcription factor that plays a fundamental role in the formation and development of embryonic cardiovascular. Previous studies have showed that knock-out of CITED2 in mice might result in various cardiac malformations. However, the mechanisms of CITED2 mutation on congenital heart disease (CHD) in Chinese Tibetan population are still poorly understood. In the present study, 187 unrelated Tibetan patients with CHD and 200 unrelated Tibetan healthy controls were screened for variants in the CITED2 gene; we subsequently identified one potential disease-causing mutation p.G143A in a 6-year-old girl with PDA and functional analyses of the mutation were carried out. Our study showed that the novel mutation of CITED2 significantly enhanced the expression activity of vascular endothelial growth factor (VEGF) under the role of co-receptor hypoxia inducible factor 1-aipha (HIF-1A), which is closely related with embryonic cardiac development. As a result, CITED2 gene mutation may play a significant role in the development of pediatric congenital heart disease.

  2. Supernatant from bifidobacterium differentially modulates transduction signaling pathways for biological functions of human dendritic cells.

    Directory of Open Access Journals (Sweden)

    Cyrille Hoarau

    Full Text Available BACKGROUND: Probiotic bacteria have been shown to modulate immune responses and could have therapeutic effects in allergic and inflammatory disorders. However, the signaling pathways engaged by probiotics are poorly understood. We have previously reported that a fermentation product from Bifidobacterium breve C50 (BbC50sn could induce maturation, high IL-10 production and prolonged survival of DCs via a TLR2 pathway. We therefore studied the roles of mitogen-activated protein kinases (MAPK, glycogen synthase kinase-3 (GSK3 and phosphatidylinositol 3-kinase (PI3K pathways on biological functions of human monocyte-derived DCs treated with BbC50sn. METHODOLOGY/PRINCIPAL FINDINGS: DCs were differentiated from human monocytes with IL-4 and GM-CSF for 5 days and cultured with BbC50sn, lipopolysaccharide (LPS or Zymosan, with or without specific inhibitors of p38MAPK (SB203580, ERK (PD98059, PI3K (LY294002 and GSK3 (SB216763. We found that 1 the PI3K pathway was positively involved in the prolonged DC survival induced by BbC50sn, LPS and Zymosan in contrast to p38MAPK and GSK3 which negatively regulated DC survival; 2 p38MAPK and PI3K were positively involved in DC maturation, in contrast to ERK and GSK3 which negatively regulated DC maturation; 3 ERK and PI3K were positively involved in DC-IL-10 production, in contrast to GSK3 that was positively involved in DC-IL-12 production whereas p38MAPK was positively involved in both; 4 BbC50sn induced a PI3K/Akt phosphorylation similar to Zymosan and a p38MAPK phosphorylation similar to LPS. CONCLUSION/SIGNIFICANCE: We report for the first time that a fermentation product of a bifidobacteria can differentially activate MAPK, GSK3 and PI3K in order to modulate DC biological functions. These results give new insights on the fine-tuned balance between the maintenance of normal mucosal homeostasis to commensal and probiotic bacteria and the specific inflammatory immune responses to pathogen bacteria.

  3. Biological function evaluation and effects of laser micro-pore burn-denatured acellular dermal matrix.

    Science.gov (United States)

    Zhang, Youlai; Zeng, Yuanlin; Xin, Guohua; Zou, Lijin; Ding, Yuewei; Duyin, Jiang

    2018-03-01

    In the field of burns repairs, many problems exist in the shortage of donor skin, the expense of allograft or xenograft skin, temporary substitution and unsatisfactory extremity function after wound healing. Previous studies showed that burn-denatured skin could return to normal dermis formation and function. This study investigates the application of laser micro-pore burn-denatured acellular dermis matrix (DADM) from an escharotomy in the repair of burn wounds and evaluates the biological properties and wound repair effects of DADM in implantation experiments in Kunming mice. Specific-pathogen-free (SPF) Kunming mice were used in this study. A deep II° burn wound was created on the dorsum of the mice by an electric heated water bath. The full-thickness wound tissue was harvested. The necrotic tissue and subcutaneous tissue were removed. The denatured dermis was preserved and treated with 0.25% trypsin, 0.5% Triton X-100. The DADM was drilled by laser micro-pore. The biological properties and grafting effects of laser micro-pore burn-DADM were evaluated by morphology, cytokine expression levels and subcutaneous implantation experiments in Kunming mice. We found statistical significance (Ppore burn-DADM (experimental group) compared to the control group (no laser micro-pore burn-DADM). Cytokine expression level was different in the dermal matrixes harvested at various time points after burn (24h, 48h, 72h and infected wound group). Comparing the dermal matrix from 24h burn tissue to infected wound tissue, the expression level of IL-6, MMP-24, VE-cadherin and VEGF were decreased. We found no inflammatory cells infiltration in the dermal matrix were observed in both experimental and control groups (24h burn group), while the obviously vascular infiltration and fiber fusion were observed in the experimental group after subcutaneous implantation experiments. There was better bio-performance, low immunogenicity and better dermal incorporation after treated by laser

  4. Nitrification inhibition as measured by RNA- and DNA-based function-specific assays and microbial community structure analyses

    Science.gov (United States)

    Abstract: The biological removal of ammonia in conventional wastewater treatment plants (WWTPs) is performed by promoting nitrification, which transforms ammonia into nitrate, which in turn is converted into nitrogen gas by denitrifying bacteria. The first step in nitrification, ...

  5. Invited review: Caseins and the casein micelle: their biological functions, structures, and behavior in foods.

    Science.gov (United States)

    Holt, C; Carver, J A; Ecroyd, H; Thorn, D C

    2013-10-01

    A typical casein micelle contains thousands of casein molecules, most of which form thermodynamically stable complexes with nanoclusters of amorphous calcium phosphate. Like many other unfolded proteins, caseins have an actual or potential tendency to assemble into toxic amyloid fibrils, particularly at the high concentrations found in milk. Fibrils do not form in milk because an alternative aggregation pathway is followed that results in formation of the casein micelle. As a result of forming micelles, nutritious milk can be secreted and stored without causing either pathological calcification or amyloidosis of the mother's mammary tissue. The ability to sequester nanoclusters of amorphous calcium phosphate in a stable complex is not unique to caseins. It has been demonstrated using a number of noncasein secreted phosphoproteins and may be of general physiological importance in preventing calcification of other biofluids and soft tissues. Thus, competent noncasein phosphoproteins have similar patterns of phosphorylation and the same type of flexible, unfolded conformation as caseins. The ability to suppress amyloid fibril formation by forming an alternative amorphous aggregate is also not unique to caseins and underlies the action of molecular chaperones such as the small heat-shock proteins. The open structure of the protein matrix of casein micelles is fragile and easily perturbed by changes in its environment. Perturbations can cause the polypeptide chains to segregate into regions of greater and lesser density. As a result, the reliable determination of the native structure of casein micelles continues to be extremely challenging. The biological functions of caseins, such as their chaperone activity, are determined by their composition and flexible conformation and by how the casein polypeptide chains interact with each other. These same properties determine how caseins behave in the manufacture of many dairy products and how they can be used as functional

  6. Carbohydrate/glycan-binding specificity of legume lectins in respect to their proposed biological functions

    Directory of Open Access Journals (Sweden)

    Márcio Viana Ramos

    2000-01-01

    Full Text Available The lectins, proteins which specifically recognize carbohydrate moieties, have been extensively studied in many biochemical and structural aspects in order to establish the molecular basis of this non-catalytic event. On the other hand, their clinical and agricultural potentials have been growing fast. Although lectins, mainly those from legume plants, had been investigated for biological properties, studies about the physiological functions of lectins are scarce in literature. Therefore, despite the accumulated data on lectins (as proteins, the role played by these signalizing molecules is poorly discussed. In the light of our accumulated results on legume lectins, specially those obtained from plants belonging to the Diocleinae sub-tribe and available data in literature, we discuss here the main hypothesis of their functions according to their carbohydrate/glycan-binding specificity.As lectinas, proteinas que especificamente reconhecem estruturas que contém carboidratos, têm sido extensivamente estudadas em muitos aspectos bioquímicos e estruturais, objetivando estabelecer as bases moleculares deste evento não-catalítico. Por outro lado, os potenciais clínicos e agriculturais destas proteínas têm crescido rapidamente. Embora as lectinas, principalmente aquelas de legumes tenham sido bastante investigadas em suas propriedades biológicas, estudos sobre as funcões fisiológicas de lectinas são escassos na literatura. Além disto, a despeito da quantidade de dados acumulados sobre lectinas (como proteínas, o papel desempenhado por estas moléculas de sinalização é pobremente discutido. Valendo-se de nossos estudos sobre lectinas de leguminosas, principalmente da sub-tribo Diocleinae, e outros dados presentes na literatura, discutimos aqui, as principais hipóteses de suas funções com base na especificidade por carboidratos e glicanos complexos.

  7. Melanocyte biology and function with reference to oral melanin hyperpigmentation in HIV-seropositive subjects.

    Science.gov (United States)

    Feller, Liviu; Chandran, Rakesh; Kramer, Beverley; Khammissa, Razia A G; Altini, Mario; Lemmer, Johan

    2014-09-01

    The color of normal skin and of oral mucosa is not determined by the number of melanocytes in the epithelium but rather by their melanogenic activity. Pigmented biopolymers or melanins are synthesized in melanosomes. Tyrosinase is the critical enzyme in the biosynthesis of both brown/black eumelanin and yellow/red pheomelanin. The number of the melanosomes within the melanocytes, the type of melanin within the melanosomes, and the efficacy of the transfer of melanosomes from the melanocytes to the neighboring keratinocytes all play an important role in tissue pigmentation. Melanin production is regulated by locally produced factors including proopiomelanocortin and its derivative peptides, particularly alpha-melanocyte-stimulating hormone (α-MSH), melanocortin 1 receptor (MC1R), adrenergic and cholinergic agents, growth factors, cytokines, and nitric oxide. Both eumelanin and pheomelanin can be produced by the same melanocytes, and the proportion of the two melanin types is influenced by the degree of functional activity of the α-MSH/MC1R intracellular pathway. The cause of HIV oral melanosis is not fully understood but may be associated with HIV-induced cytokine dysregulation, with the medications commonly prescribed to HIV-seropositive persons, and with adrenocortical dysfunction, which is not uncommon in HIV-seropositive subjects with AIDS. The purpose of this article is to discuss some aspects of melanocyte biology and HIV-associated oral melanin hyperpigmentation.

  8. Ants: Major Functional Elements in Fruit Agro-Ecosystems and Biological Control Agents

    Directory of Open Access Journals (Sweden)

    Lamine Diamé

    2017-12-01

    Full Text Available Ants are a very diverse taxonomic group. They display remarkable social organization that has enabled them to be ubiquitous throughout the world. They make up approximately 10% of the world’s animal biomass. Ants provide ecosystem services in agrosystems by playing a major role in plant pollination, soil bioturbation, bioindication, and the regulation of crop-damaging insects. Over recent decades, there have been numerous studies in ant ecology and the focus on tree cropping systems has given added importance to ant ecology knowledge. The only missing point in this knowledge is the reasons underlying difference between the positive and negative effects of ants in tree cropping systems. This review article provides an overview of knowledge of the roles played by ants in orchards as functional elements, and on the potential of Oecophylla weaver ants as biological control agents. It also shows the potential and relevance of using ants as an agro-ecological diagnosis tool in orchards. Lastly, it demonstrates the potential elements which may determine the divergent negative and positive of their effects on cropping systems.

  9. Structural changes in PVDF fibers due to electrospinning and its effect on biological function

    International Nuclear Information System (INIS)

    Damaraju, Sita M; Wu, Siliang; Jaffe, Michael; Arinzeh, Treena Livingston

    2013-01-01

    Polyvinylidine fluoride (PVDF) is being investigated as a potential scaffold for bone tissue engineering because of its proven biocompatibility and piezoelectric property, wherein it can generate electrical activity when mechanically deformed. In this study, PVDF scaffolds were prepared by electrospinning using different voltages (12–30 kV), evaluated for the presence of the piezoelectric β-crystal phase and its effect on biological function. Electrospun PVDF was compared with unprocessed/raw PVDF, films and melt-spun fibers for the presence of the piezoelectric β-phase using differential scanning calorimetry, Fourier transform infrared spectroscopy and x-ray diffraction. The osteogenic differentiation of human mesenchymal stem cells (MSCs) was evaluated on scaffolds electrospun at 12 and 25 kV (PVDF-12 kV and PVDF-25 kV, respectively) and compared to tissue culture polystyrene (TCP). Electrospinning PVDF resulted in the formation of the piezoelectric β-phase with the highest β-phase fraction of 72% for electrospun PVDF at 25 kV. MSCs cultured on both the scaffolds were well attached as indicated by a spread morphology. Cells on PVDF-25 kV scaffolds had the greatest alkaline phosphatase activity and early mineralization by day 10 as compared to TCP and PVDF-12 kV. The results demonstrate the potential for the use of PVDF scaffolds for bone tissue engineering applications. (paper)

  10. A novel biological function of soluble biglycan: Induction of erythropoietin production and polycythemia.

    Science.gov (United States)

    Frey, Helena; Moreth, Kristin; Hsieh, Louise Tzung-Harn; Zeng-Brouwers, Jinyang; Rathkolb, Birgit; Fuchs, Helmut; Gailus-Durner, Valérie; Iozzo, Renato V; de Angelis, Martin Hrabě; Schaefer, Liliana

    2017-06-01

    Secondary polycythemia, a disease characterized by a selective increase in circulating mature erythrocytes, is caused by enhanced erythropoietin (Epo) concentrations triggered by hypoxia-inducible factor-2α (HIF-2α). While mechanisms of hypoxia-dependent stabilization of HIF-2α protein are well established, data regarding oxygen-independent regulation of HIF-2α are sparse. In this study, we generated a novel transgenic mouse model, in which biglycan was constitutively overexpressed and secreted by hepatocytes (BGN Tg ), thereby providing a constant source of biglycan released into the blood stream. We discovered that although the mice were apparently normal, they harbored an increase in mature circulating erythrocytes. In addition to erythrocytosis, the BGN Tg mice showed elevated hemoglobin concentrations, hematocrit values and enhanced total iron binding capacity, revealing a clinical picture of polycythemia. In BGN Tg mice markedly enhanced Epo mRNA expression was observed in the liver and kidney, while elevated Epo protein levels were found in liver, kidney and blood. Mechanistically, we showed that the transgenic animals had an abundance of HIF-2α protein in the liver and kidney. Finally, by transiently overexpressing circulating biglycan in mice deficient in various Toll-like receptors (TLRs), we determined that this novel function of biglycan to promote Epo synthesis was specifically mediated by a selective interaction with TLR2. Thus, we discovered a novel biological pathway of soluble biglycan inducing HIF-2α protein stabilization and Epo production presumably in an oxygen-independent manner, ultimately giving rise to secondary polycythemia.

  11. Improved normal tissue sparing in head and neck radiotherapy using biological cost function based-IMRT.

    Science.gov (United States)

    Anderson, N; Lawford, C; Khoo, V; Rolfo, M; Joon, D L; Wada, M

    2011-12-01

    Intensity-modulated radiotherapy (IMRT) has reduced the impact of acute and late toxicities associated with head and neck radiotherapy. Treatment planning system (TPS) advances in biological cost function based optimization (BBO) and improved segmentation techniques have increased organ at risk (OAR) sparing compared to conventional dose-based optimization (DBO). A planning study was undertaken to compare OAR avoidance in DBO and BBO treatment planning. Simultaneous integrated boost treatment plans were produced for 10 head and neck patients using both planning systems. Plans were compared for tar get coverage and OAR avoidance. Comparisons were made using the BBO TPS Monte Carlo dose engine to eliminate differences due to inherent algorithms. Target coverage (V95%) was maintained for both solutions. BBO produced lower OAR doses, with statistically significant improvement to left (12.3%, p = 0.005) and right parotid mean dose (16.9%, p = 0.004), larynx V50_Gy (71.0%, p = 0.005), spinal cord (21.9%, p < 0.001) and brain stem dose maximums (31.5%, p = 0.002). This study observed improved OAR avoidance with BBO planning. Further investigations will be undertaken to review any clinical benefit of this improved planned dosimetry.

  12. Functional and Expression Analyses of the Pneumocystis MAT Genes Suggest Obligate Sexuality through Primary Homothallism within Host Lungs

    Directory of Open Access Journals (Sweden)

    S. Richard

    2018-02-01

    Full Text Available Fungi of the genus Pneumocystis are obligate parasites that colonize mammals’ lungs and are host species specific. Pneumocystis jirovecii and Pneumocystis carinii infect, respectively, humans and rats. They can turn into opportunistic pathogens in immunosuppressed hosts, causing severe pneumonia. Their cell cycle is poorly known, mainly because of the absence of an established method of culture in vitro. It is thought to include both asexual and sexual phases. Comparative genomic analysis suggested that their mode of sexual reproduction is primary homothallism involving a single mating type (MAT locus encompassing plus and minus genes (matMc, matMi, and matPi; Almeida et al., mBio 6:e02250-14, 2015. Thus, each strain would be capable of sexual reproduction alone (self-fertility. However, this is a working hypothesis derived from computational analyses that is, in addition, based on the genome sequences of single isolates. Here, we tested this hypothesis in the wet laboratory. The function of the P. jirovecii and P. carinii matMc genes was ascertained by restoration of sporulation in the corresponding mutant of fission yeast. Using PCR, we found the same single MAT locus in all P. jirovecii isolates and showed that all three MAT genes are often concomitantly expressed during pneumonia. Extensive homology searches did not identify other types of MAT transcription factors in the genomes or cis-acting motifs flanking the MAT locus that could have been involved in MAT switching or silencing. Our observations suggest that Pneumocystis sexuality through primary homothallism is obligate within host lungs to complete the cell cycle, i.e., produce asci necessary for airborne transmission to new hosts.

  13. Single Fluorescent Molecules as Nano-Illuminators for Biological Structure and Function

    Science.gov (United States)

    Moerner, W. E.

    2011-03-01

    Since the first optical detection and spectroscopy of a single molecule in a solid (Phys. Rev. Lett. {62}, 2535 (1989)), much has been learned about the ability of single molecules to probe local nanoenvironments and individual behavior in biological and nonbiological materials in the absence of ensemble averaging that can obscure heterogeneity. Because each single fluorophore acts a light source roughly 1 nm in size, microscopic imaging of individual fluorophores leads naturally to superlocalization, or determination of the position of the molecule with precision beyond the optical diffraction limit, simply by digitization of the point-spread function from the single emitter. For example, the shape of single filaments in a living cell can be extracted simply by allowing a single molecule to move through the filament (PNAS {103}, 10929 (2006)). The addition of photoinduced control of single-molecule emission allows imaging beyond the diffraction limit (super-resolution) and a new array of acronyms (PALM, STORM, F-PALM etc.) and advances have appeared. We have used the native blinking and switching of a common yellow-emitting variant of green fluorescent protein (EYFP) reported more than a decade ago (Nature {388}, 355 (1997)) to achieve sub-40 nm super-resolution imaging of several protein structures in the bacterium Caulobacter crescentus: the quasi-helix of the actin-like protein MreB (Nat. Meth. {5}, 947 (2008)), the cellular distribution of the DNA binding protein HU (submitted), and the recently discovered division spindle composed of ParA filaments (Nat. Cell Biol. {12}, 791 (2010)). Even with these advances, better emitters would provide more photons and improved resolution, and a new photoactivatable small-molecule emitter has recently been synthesized and targeted to specific structures in living cells to provide super-resolution images (JACS {132}, 15099 (2010)). Finally, a new optical method for extracting three-dimensional position information based on

  14. Mediational Analyses of the Effects of Responsive Teaching on the Developmental Functioning of Preschool Children with Disabilities

    Science.gov (United States)

    Karaaslan, Ozcan; Mahoney, Gerald

    2015-01-01

    Mediational analyses were conducted with data from two small randomized control trials of the Responsive Teaching (RT) parent-mediated developmental intervention which used nearly identical intervention and control procedures. The purpose of these analyses was to determine whether or how the changes in maternal responsiveness and children's…

  15. Connecting Structure-Property and Structure-Function Relationships across the Disciplines of Chemistry and Biology: Exploring Student Perceptions

    Science.gov (United States)

    Kohn, Kathryn P.; Underwood, Sonia M.; Cooper, Melanie M.

    2018-01-01

    While many university students take science courses in multiple disciplines, little is known about how they perceive common concepts from different disciplinary perspectives. Structure-property and structure-function relationships have long been considered important explanatory concepts in the disciplines of chemistry and biology, respectively.…

  16. Perchlorate exposure and association with iron homeostasis and other biological functions among NHANES 2005-2008 subjects

    Science.gov (United States)

    Perchlorate exposure and association with iron homeostasis and other biological functions among NHANES 2005-2008 subjects Schreinemachers DM, Ghio AJ, Cascio WE, Sobus JR. U.S. EPA, RTP, NC, USA Perchlorate (ClO4-), an environmental pollutant, is a known thyroid toxicant and...

  17. Prokaryotic regulatory systems biology: Common principles governing the functional architectures of Bacillus subtilis and Escherichia coli unveiled by the natural decomposition approach.

    Science.gov (United States)

    Freyre-González, Julio A; Treviño-Quintanilla, Luis G; Valtierra-Gutiérrez, Ilse A; Gutiérrez-Ríos, Rosa María; Alonso-Pavón, José A

    2012-10-31

    Escherichia coli and Bacillus subtilis are two of the best-studied prokaryotic model organisms. Previous analyses of their transcriptional regulatory networks have shown that they exhibit high plasticity during evolution and suggested that both converge to scale-free-like structures. Nevertheless, beyond this suggestion, no analyses have been carried out to identify the common systems-level components and principles governing these organisms. Here we show that these two phylogenetically distant organisms follow a set of common novel biologically consistent systems principles revealed by the mathematically and biologically founded natural decomposition approach. The discovered common functional architecture is a diamond-shaped, matryoshka-like, three-layer (coordination, processing, and integration) hierarchy exhibiting feedback, which is shaped by four systems-level components: global transcription factors (global TFs), locally autonomous modules, basal machinery and intermodular genes. The first mathematical criterion to identify global TFs, the κ-value, was reassessed on B. subtilis and confirmed its high predictive power by identifying all the previously reported, plus three potential, master regulators and eight sigma factors. The functionally conserved cores of modules, basal cell machinery, and a set of non-orthologous common physiological global responses were identified via both orthologous genes and non-orthologous conserved functions. This study reveals novel common systems principles maintained between two phylogenetically distant organisms and provides a comparison of their lifestyle adaptations. Our results shed new light on the systems-level principles and the fundamental functions required by bacteria to sustain life. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Proteome-wide Structural Analysis of PTM Hotspots Reveals Regulatory Elements Predicted to Impact Biological Function and Disease.

    Science.gov (United States)

    Torres, Matthew P; Dewhurst, Henry; Sundararaman, Niveda

    2016-11-01

    Post-translational modifications (PTMs) regulate protein behavior through modulation of protein-protein interactions, enzymatic activity, and protein stability essential in the translation of genotype to phenotype in eukaryotes. Currently, less than 4% of all eukaryotic PTMs are reported to have biological function - a statistic that continues to decrease with an increasing rate of PTM detection. Previously, we developed SAPH-ire (Structural Analysis of PTM Hotspots) - a method for the prioritization of PTM function potential that has been used effectively to reveal novel PTM regulatory elements in discrete protein families (Dewhurst et al., 2015). Here, we apply SAPH-ire to the set of eukaryotic protein families containing experimental PTM and 3D structure data - capturing 1,325 protein families with 50,839 unique PTM sites organized into 31,747 modified alignment positions (MAPs), of which 2010 (∼6%) possess known biological function. Here, we show that using an artificial neural network model (SAPH-ire NN) trained to identify MAP hotspots with biological function results in prediction outcomes that far surpass the use of single hotspot features, including nearest neighbor PTM clustering methods. We find the greatest enhancement in prediction for positions with PTM counts of five or less, which represent 98% of all MAPs in the eukaryotic proteome and 90% of all MAPs found to have biological function. Analysis of the top 1092 MAP hotspots revealed 267 of truly unknown function (containing 5443 distinct PTMs). Of these, 165 hotspots could be mapped to human KEGG pathways for normal and/or disease physiology. Many high-ranking hotspots were also found to be disease-associated pathogenic sites of amino acid substitution despite the lack of observable PTM in the human protein family member. Taken together, these experiments demonstrate that the functional relevance of a PTM can be predicted very effectively by neural network models, revealing a large but testable

  19. Revealing the functions of the transketolase enzyme isoforms in Rhodopseudomonas palustris using a systems biology approach.

    Directory of Open Access Journals (Sweden)

    Chia-Wei Hu

    Full Text Available BACKGROUND: Rhodopseudomonas palustris (R. palustris is a purple non-sulfur anoxygenic phototrophic bacterium that belongs to the class of proteobacteria. It is capable of absorbing atmospheric carbon dioxide and converting it to biomass via the process of photosynthesis and the Calvin-Benson-Bassham (CBB cycle. Transketolase is a key enzyme involved in the CBB cycle. Here, we reveal the functions of transketolase isoforms I and II in R. palustris using a systems biology approach. METHODOLOGY/PRINCIPAL FINDINGS: By measuring growth ability, we found that transketolase could enhance the autotrophic growth and biomass production of R. palustris. Microarray and real-time quantitative PCR revealed that transketolase isoforms I and II were involved in different carbon metabolic pathways. In addition, immunogold staining demonstrated that the two transketolase isoforms had different spatial localizations: transketolase I was primarily associated with the intracytoplasmic membrane (ICM but transketolase II was mostly distributed in the cytoplasm. Comparative proteomic analysis and network construction of transketolase over-expression and negative control (NC strains revealed that protein folding, transcriptional regulation, amino acid transport and CBB cycle-associated carbon metabolism were enriched in the transketolase I over-expressed strain. In contrast, ATP synthesis, carbohydrate transport, glycolysis-associated carbon metabolism and CBB cycle-associated carbon metabolism were enriched in the transketolase II over-expressed strain. Furthermore, ATP synthesis assays showed a significant increase in ATP synthesis in the transketolase II over-expressed strain. A PEPCK activity assay showed that PEPCK activity was higher in transketolase over-expressed strains than in the negative control strain. CONCLUSIONS/SIGNIFICANCE: Taken together, our results indicate that the two isoforms of transketolase in R. palustris could affect photoautotrophic growth

  20. Rapidly restoring biological soil crusts and ecosystem functions in a severely disturbed desert ecosystem.

    Science.gov (United States)

    Chiquoine, Lindsay P; Abella, Scott R; Bowker, Matthew A

    2016-06-01

    Restoring biological soil crusts (biocrusts) in degraded drylands can contribute to recovery of ecosystem functions that have global implications, including erosion resistance and nutrient cycling. To examine techniques for restoring biocrusts, we conducted a replicated, factorial experiment on recently abandoned road surfaces by applying biocrust inoculation (salvaged and stored dry for two years), salvaged topsoil, an abiotic soil amendment (wood shavings), and planting of a dominant perennial shrub (Ambrosia dumosa). Eighteen months after treatments, we measured biocrust abundance and species composition, soil chlorophyll a content and fertility, and soil resistance to erosion. Biocrust addition significantly accelerated biocrust recovery on disturbed soils, including increasing lichen and moss cover and cyanobacteria colonization. Compared to undisturbed controls, inoculated plots had similar lichen and moss composition, recovered 43% of total cyanobacteria density, had similar soil chlorophyll content, and exhibited recovery of soil fertility and soil stability. Inoculation was the only treatment that generated lichen and moss cover. Topsoil application resulted in partial recovery of the cyanobacteria community and soil properties. Compared to untreated disturbed plots, topsoil application without inoculum increased cyanobacteria density by 186% and moderately improved soil chlorophyll and ammonium content and soil stability. Topsoil application produced 22% and 51% of the cyanobacteria density g⁻¹ soil compared to undisturbed and inoculated plots, respectively. Plots not treated with either topsoil or inoculum had significantly lower cyanobacteria density, soil chlorophyll and ammonium concentrations, and significantly higher soil nitrate concentration. Wood shavings and Ambrosia had no influence on biocrust lichen and moss species recovery but did affect cyanobacteria composition and soil fertility. Inoculation of severely disturbed soil with native

  1. Biological oscillations for learning walking coordination: dynamic recurrent neural network functionally models physiological central pattern generator.

    Science.gov (United States)

    Hoellinger, Thomas; Petieau, Mathieu; Duvinage, Matthieu; Castermans, Thierry; Seetharaman, Karthik; Cebolla, Ana-Maria; Bengoetxea, Ana; Ivanenko, Yuri; Dan, Bernard; Cheron, Guy

    2013-01-01

    The existence of dedicated neuronal modules such as those organized in the cerebral cortex, thalamus, basal ganglia, cerebellum, or spinal cord raises the question of how these functional modules are coordinated for appropriate motor behavior. Study of human locomotion offers an interesting field for addressing this central question. The coordination of the elevation of the 3 leg segments under a planar covariation rule (Borghese et al., 1996) was recently modeled (Barliya et al., 2009) by phase-adjusted simple oscillators shedding new light on the understanding of the central pattern generator (CPG) processing relevant oscillation signals. We describe the use of a dynamic recurrent neural network (DRNN) mimicking the natural oscillatory behavior of human locomotion for reproducing the planar covariation rule in both legs at different walking speeds. Neural network learning was based on sinusoid signals integrating frequency and amplitude features of the first three harmonics of the sagittal elevation angles of the thigh, shank, and foot of each lower limb. We verified the biological plausibility of the neural networks. Best results were obtained with oscillations extracted from the first three harmonics in comparison to oscillations outside the harmonic frequency peaks. Physiological replication steadily increased with the number of neuronal units from 1 to 80, where similarity index reached 0.99. Analysis of synaptic weighting showed that the proportion of inhibitory connections consistently increased with the number of neuronal units in the DRNN. This emerging property in the artificial neural networks resonates with recent advances in neurophysiology of inhibitory neurons that are involved in central nervous system oscillatory activities. The main message of this study is that this type of DRNN may offer a useful model of physiological central pattern generator for gaining insights in basic research and developing clinical applications.

  2. Functional near infrared spectroscopy as a potential biological assessment of addiction recovery: preliminary findings.

    Science.gov (United States)

    Dempsey, Jared P; Harris, Kitty S; Shumway, Sterling T; Kimball, Thomas G; Herrera, J Caleb; Dsauza, Cynthia M; Bradshaw, Spencer D

    2015-03-01

    Addiction science has primarily utilized self-report, continued substance use, and relapse factors to explore the process of recovery. However, the entry into successful abstinence substantially reduces our assessment abilities. Advances in neuroscience may be the key to objective understanding, treating, and monitoring long-term success in addiction recovery. To explore functional near infrared spectroscopy (fNIR) as a viable technique in the assessment of addiction-cue reactivity. Specifically, prefrontal cortex (PFC) activation to alcohol cues was explored among formally alcohol-dependent individuals, across varying levels of successful abstinence. The aim of the investigation was to identify patterns of PFC activation change consistent with duration of abstinence. A total of 15 formally alcohol-dependent individuals, with abstinence durations ranging from 1 month to 10 years, viewed alcohol images during fNIR PFC assessment. Participants also subjectively rated the same images for affect and arousal level. Subjective ratings of alcohol cues did not significantly correlate with duration of abstinence. As expected, days of abstinence did not significantly correlate with neutral cue fNIR reactivity. However, for alcohol cues, fNIR results showed increased days of abstinence was associated with decreased activation within the dorsolateral and dorsomedial prefrontal cortex regions. The present results suggest that fNIR may be a viable tool in the assessment of addiction-cue reactivity. RESULTS also support previous findings on the importance of dorsolateral and dorsomedial PFC in alcohol-cue activation. The findings build upon these past results suggesting that fNIR-assessed activation may represent a robust biological marker of successful addiction recovery.

  3. Functionalization of titanium with chitosan via silanation: evaluation of biological and mechanical performances.

    Directory of Open Access Journals (Sweden)

    Pauline Renoud

    Full Text Available Complications in dentistry and orthopaedic surgery are mainly induced by peri-implant bacterial infections and current implant devices do not prevent such infections. The coating of antibacterial molecules such as chitosan on its surface would give the implant bioactive properties. The major challenge of this type of coating is the attachment of chitosan to a metal substrate. In this study, we propose to investigate the functionalization of titanium with chitosan via a silanation. Firstly, the surface chemistry and mechanical properties of such coating were evaluated. We also verified if the coated chitosan retained its biocompatibility with the peri-implant cells, as well as its antibacterial properties. FTIR and Tof-SIMS analyses confirmed the presence of chitosan on the titanium surface. This coating showed great scratch resistance and was strongly adhesive to the substrate. These mechanical properties were consistent with an implantology application. The Chitosan-coated surfaces showed strong inhibition of Actinomyces naeslundii growth; they nonetheless showed a non significant inhibition against Porphyromonas gingivalis after 32 hours in liquid media. The chitosan-coating also demonstrated good biocompatibility to NIH3T3 fibroblasts. Thus this method of covalent coating provides a biocompatible material with improved bioactive properties. These results proved that covalent coating of chitosan has significant potential in biomedical device implantation.

  4. The development of peptide-based interfacial biomaterials for generating biological functionality on the surface of bioinert materials.

    Science.gov (United States)

    Meyers, Steven R; Khoo, Xiaojuan; Huang, Xin; Walsh, Elisabeth B; Grinstaff, Mark W; Kenan, Daniel J

    2009-01-01

    Biomaterials used in implants have traditionally been selected based on their mechanical properties, chemical stability, and biocompatibility. However, the durability and clinical efficacy of implantable biomedical devices remain limited in part due to the absence of appropriate biological interactions at the implant interface and the lack of integration into adjacent tissues. Herein, we describe a robust peptide-based coating technology capable of modifying the surface of existing biomaterials and medical devices through the non-covalent binding of modular biofunctional peptides. These peptides contain at least one material binding sequence and at least one biologically active sequence and thus are termed, "Interfacial Biomaterials" (IFBMs). IFBMs can simultaneously bind the biomaterial surface while endowing it with desired biological functionalities at the interface between the material and biological realms. We demonstrate the capabilities of model IFBMs to convert native polystyrene, a bioinert surface, into a bioactive surface that can support a range of cell activities. We further distinguish between simple cell attachment with insufficient integrin interactions, which in some cases can adversely impact downstream biology, versus biologically appropriate adhesion, cell spreading, and cell survival mediated by IFBMs. Moreover, we show that we can use the coating technology to create spatially resolved patterns of fluorophores and cells on substrates and that these patterns retain their borders in culture.

  5. Synthesis, characterization and functionalization of silicon nanoparticle based hybrid nanomaterials for photovoltaic and biological applications

    Science.gov (United States)

    Xu, Zejing

    Silicon nanoparticles are attractive candidates for biological, photovoltaic and energy storage applications due to their size dependent optoelectronic properties. These include tunable light emission, high brightness, and stability against photo-bleaching relative to organic dyes (see Chapter 1). The preparation and characterization of silicon nanoparticle based hybrid nanomaterials and their relevance to photovoltaic and biological applications are described. The surface-passivated silicon nanoparticles were produced in one step from the reactive high-energy ball milling (RHEBM) of silicon wafers with various organic ligands. The surface structure and optical properties of the passivated silicon nanoparticles were systematically characterized. Fast approaches for purifying and at the same time size separating the silicon nanoparticles using a gravity GPC column were developed. The hydrodynamic diameter and size distribution of these size-separated silicon nanoparticles were determined using GPC and Diffusion Ordered NMR Spectroscopy (DOSY) as fast, reliable alternative approaches to TEM. Water soluble silicon nanoparticles were synthesized by grafting PEG polymers onto functionalized silicon nanoparticles with distal alkyne or azide moieties. The surface-functionalized silicon nanoparticles were produced from the reactive high-energy ball milling (RHEBM) of silicon wafers with a mixture of either 5-chloro-1-pentyne in 1-pentyne or 1,7 octadiyne in 1-hexyne to afford air and water stable chloroalkyl or alkynyl terminated nanoparticles, respectively. Nanoparticles with the ω-chloroalkyl substituents were easily converted to ω-azidoalkyl groups through the reaction of the silicon nanoparticles with sodium azide in DMF. The azido terminated nanoparticles were then grafted with monoalkynyl-PEG polymers using a copper catalyzed alkyne-azide cycloaddition (CuAAC) reaction to afford core-shell silicon nanoparticles with a covalently attached PEG shell. Covalently

  6. Proteome-wide Structural Analysis of PTM Hotspots Reveals Regulatory Elements Predicted to Impact Biological Function and Disease*

    Science.gov (United States)

    Dewhurst, Henry; Sundararaman, Niveda

    2016-01-01

    Post-translational modifications (PTMs) regulate protein behavior through modulation of protein-protein interactions, enzymatic activity, and protein stability essential in the translation of genotype to phenotype in eukaryotes. Currently, less than 4% of all eukaryotic PTMs are reported to have biological function - a statistic that continues to decrease with an increasing rate of PTM detection. Previously, we developed SAPH-ire (Structural Analysis of PTM Hotspots) - a method for the prioritization of PTM function potential that has been used effectively to reveal novel PTM regulatory elements in discrete protein families (Dewhurst et al., 2015). Here, we apply SAPH-ire to the set of eukaryotic protein families containing experimental PTM and 3D structure data - capturing 1,325 protein families with 50,839 unique PTM sites organized into 31,747 modified alignment positions (MAPs), of which 2010 (∼6%) possess known biological function. Here, we show that using an artificial neural network model (SAPH-ire NN) trained to identify MAP hotspots with biological function results in prediction outcomes that far surpass the use of single hotspot features, including nearest neighbor PTM clustering methods. We find the greatest enhancement in prediction for positions with PTM counts of five or less, which represent 98% of all MAPs in the eukaryotic proteome and 90% of all MAPs found to have biological function. Analysis of the top 1092 MAP hotspots revealed 267 of truly unknown function (containing 5443 distinct PTMs). Of these, 165 hotspots could be mapped to human KEGG pathways for normal and/or disease physiology. Many high-ranking hotspots were also found to be disease-associated pathogenic sites of amino acid substitution despite the lack of observable PTM in the human protein family member. Taken together, these experiments demonstrate that the functional relevance of a PTM can be predicted very effectively by neural network models, revealing a large but testable

  7. Life sciences payloads analyses and technical program planning studies. [project planning of space missions of space shuttles in aerospace medicine and space biology

    Science.gov (United States)

    1976-01-01

    Contractural requirements, project planning, equipment specifications, and technical data for space shuttle biological experiment payloads are presented. Topics discussed are: (1) urine collection and processing on the space shuttle, (2) space processing of biochemical and biomedical materials, (3) mission simulations, and (4) biomedical equipment.

  8. Functionalized gold nanoparticle supported sensory mechanisms applied in detection of chemical and biological threat agents: A review

    International Nuclear Information System (INIS)

    Upadhyayula, Venkata K.K.

    2012-01-01

    Highlights: ► Smart sensors are needed for detection of chemical and biological threat agents. ► Smart sensors detect analytes with rapid speed, high sensitivity and selectivity. ► Functionalized gold nanoparticles (GNPs) can potentially smart sense threat agents. ► Functionalized GNPs support multiple analytical methods for sensing threat agents. ► Threat agents of all types can be detected using functionalized GNPs. - Abstract: There is a great necessity for development of novel sensory concepts supportive of smart sensing capabilities in defense and homeland security applications for detection of chemical and biological threat agents. A smart sensor is a detection device that can exhibit important features such as speed, sensitivity, selectivity, portability, and more importantly, simplicity in identifying a target analyte. Emerging nanomaterial based sensors, particularly those developed by utilizing functionalized gold nanoparticles (GNPs) as a sensing component potentially offer many desirable features needed for threat agent detection. The sensitiveness of physical properties expressed by GNPs, e.g. color, surface plasmon resonance, electrical conductivity and binding affinity are significantly enhanced when they are subjected to functionalization with an appropriate metal, organic or biomolecular functional groups. This sensitive nature of functionalized GNPs can be potentially exploited in the design of threat agent detection devices with smart sensing capabilities. In the presence of a target analyte (i.e., a chemical or biological threat agent) a change proportional to concentration of the analyte is observed, which can be measured either by colorimetric, fluorimetric, electrochemical or spectroscopic means. This article provides a review of how functionally modified gold colloids are applied in the detection of a broad range of threat agents, including radioactive substances, explosive compounds, chemical warfare agents, biotoxins, and

  9. Functionalized gold nanoparticle supported sensory mechanisms applied in detection of chemical and biological threat agents: A review

    Energy Technology Data Exchange (ETDEWEB)

    Upadhyayula, Venkata K.K., E-mail: Upadhyayula.Venkata@epa.gov [Oak Ridge Institute of Science and Education (ORISE), MC-100-44, PO Box 117, Oak Ridge, TN 37831 (United States)

    2012-02-17

    Highlights: Black-Right-Pointing-Pointer Smart sensors are needed for detection of chemical and biological threat agents. Black-Right-Pointing-Pointer Smart sensors detect analytes with rapid speed, high sensitivity and selectivity. Black-Right-Pointing-Pointer Functionalized gold nanoparticles (GNPs) can potentially smart sense threat agents. Black-Right-Pointing-Pointer Functionalized GNPs support multiple analytical methods for sensing threat agents. Black-Right-Pointing-Pointer Threat agents of all types can be detected using functionalized GNPs. - Abstract: There is a great necessity for development of novel sensory concepts supportive of smart sensing capabilities in defense and homeland security applications for detection of chemical and biological threat agents. A smart sensor is a detection device that can exhibit important features such as speed, sensitivity, selectivity, portability, and more importantly, simplicity in identifying a target analyte. Emerging nanomaterial based sensors, particularly those developed by utilizing functionalized gold nanoparticles (GNPs) as a sensing component potentially offer many desirable features needed for threat agent detection. The sensitiveness of physical properties expressed by GNPs, e.g. color, surface plasmon resonance, electrical conductivity and binding affinity are significantly enhanced when they are subjected to functionalization with an appropriate metal, organic or biomolecular functional groups. This sensitive nature of functionalized GNPs can be potentially exploited in the design of threat agent detection devices with smart sensing capabilities. In the presence of a target analyte (i.e., a chemical or biological threat agent) a change proportional to concentration of the analyte is observed, which can be measured either by colorimetric, fluorimetric, electrochemical or spectroscopic means. This article provides a review of how functionally modified gold colloids are applied in the detection of a broad

  10. Permeating disciplines: Overcoming barriers between molecular simulations and classical structure-function approaches in biological ion transport.

    Science.gov (United States)

    Howard, Rebecca J; Carnevale, Vincenzo; Delemotte, Lucie; Hellmich, Ute A; Rothberg, Brad S

    2018-04-01

    Ion translocation across biological barriers is a fundamental requirement for life. In many cases, controlling this process-for example with neuroactive drugs-demands an understanding of rapid and reversible structural changes in membrane-embedded proteins, including ion channels and transporters. Classical approaches to electrophysiology and structural biology have provided valuable insights into several such proteins over macroscopic, often discontinuous scales of space and time. Integrating these observations into meaningful mechanistic models now relies increasingly on computational methods, particularly molecular dynamics simulations, while surfacing important challenges in data management and conceptual alignment. Here, we seek to provide contemporary context, concrete examples, and a look to the future for bridging disciplinary gaps in biological ion transport. This article is part of a Special Issue entitled: Beyond the Structure-Function Horizon of Membrane Proteins edited by Ute Hellmich, Rupak Doshi and Benjamin McIlwain. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. No effects of functional exercise therapy on walking biomechanics in patients with knee osteoarthritis: exploratory outcome analyses from a randomised trial

    OpenAIRE

    Henriksen, Marius; Klokker, Louise; Bartholdy, Cecilie; Schjoedt-Jorgensen, Tanja; Bandak, Elisabeth; Bliddal, Henning

    2017-01-01

    Aim To assess the effects of a functional and individualised exercise programme on gait biomechanics during walking in people with knee OA. Methods Sixty participants were randomised to 12 weeks of facility-based functional and individualised neuromuscular exercise therapy (ET), 3 sessions per week supervised by trained physical therapists, or a no attention control group (CG). Three-dimensional gait analyses were used, from which a comprehensive list of conventional gait variables were extra...

  12. Coral Reef Health Indices versus the Biological, Ecological and Functional Diversity of Fish and Coral Assemblages in the Caribbean Sea.

    Science.gov (United States)

    Díaz-Pérez, Leopoldo; Rodríguez-Zaragoza, Fabián Alejandro; Ortiz, Marco; Cupul-Magaña, Amílcar Leví; Carriquiry, Jose D; Ríos-Jara, Eduardo; Rodríguez-Troncoso, Alma Paola; García-Rivas, María Del Carmen

    2016-01-01

    This study evaluated the relationship between the indices known as the Reef Health Index (RHI) and two-dimensional Coral Health Index (2D-CHI) and different representative metrics of biological, ecological and functional diversity of fish and corals in 101 reef sites located across seven zones in the western Caribbean Sea. Species richness and average taxonomic distinctness were used to asses biological estimation; while ecological diversity was evaluated with the indices of Shannon diversity and Pielou´s evenness, as well as by taxonomic diversity and distinctness. Functional diversity considered the number of functional groups, the Shannon diversity and the functional Pielou´s evenness. According to the RHI, 57.15% of the zones were classified as presenting a "poor" health grade, while 42.85% were in "critical" grade. Based on the 2D-CHI, 28.5% of the zones were in "degraded" condition and 71.5% were "very degraded". Differences in fish and coral diversity among sites and zones were demonstrated using permutational ANOVAs. Differences between the two health indices (RHI and 2D-CHI) and some indices of biological, ecological and functional diversity of fish and corals were observed; however, only the RHI showed a correlation between the health grades and the species and functional group richness of fish at the scale of sites, and with the species and functional group richness and Shannon diversity of the fish assemblages at the scale of zones. None of the health indices were related to the metrics analyzed for the coral diversity. In general, our study suggests that the estimation of health indices should be complemented with classic community indices, or should at least include diversity indices of fish and corals, in order to improve the accuracy of the estimated health status of coral reefs in the western Caribbean Sea.

  13. Transcript and hormone analyses reveal the involvement of ABA-signalling, hormone crosstalk and genotype-specific biological processes in cold-shock response in wheat

    Czech Academy of Sciences Publication Activity Database

    Kalapos, S.; Dobrev, Petre; Nagy, T.; Vítámvás, P.; Gyorgyey, J.; Kocsy, G.; Marincs, F.; Galiba, G.

    2016-01-01

    Roč. 253, DEC (2016), s. 86-97 ISSN 0168-9452 Institutional support: RVO:61389030 Keywords : complex phytohormone responses * abscisic-acid biosynthesis * frost-resistance * stress responses * gene-expression * chromosome 5a * triticum-monococcum * regulatory network * basal resistance * abiotic stresses * ABA-Signalling * Carbon metabolism * Freezing-tolerance * Gene ontology * Plant hormones * Short-term cold-shock * Triticum aestivum Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.437, year: 2016

  14. Understanding the Biological Roles of Pectins in Plants through Physiological and Functional Characterizations of Plant and Fungal Mutants

    DEFF Research Database (Denmark)

    Stranne, Maria

    The plant cell wall is a dynamic structure and it is involved in regulating a number of physiological features of plants such as physical strength, growth, cell differentiation, intercellular communication, water movement and defense responses. Pectins constitute a major class of plant cell wall...... polysaccharides and consist of backbones rich in galacturonic acids, which are decorated with a range of functional groups including acetyl esters and arabinan sidechains. Although much effort has been made to uncover biological functions of pectins in plants and remarkable progresses have taken place, many...... aspects remain elusive. Studies described in this thesis aimed at gaining new insights into the biological roles of pectin acetylation and arabinosylation in the model plant Arabidopsis thaliana. The thesis consists of four chapters: physiological characterization of cell wall mutants affected in cell...

  15. Excited states in biological systems

    International Nuclear Information System (INIS)

    Cilento, G.; Zinner, K.; Bechara, E.J.H.; Duran, N.; Baptista, R.C. de; Shimizu, Y.; Augusto, O.; Faljoni-Alario, A.; Vidigal, C.C.C.; Oliveira, O.M.M.F.; Haun, M.

    1979-01-01

    Some aspects of bioluminescence related to bioenergetics are discussed: 1. chemical generation of excited species, by means of two general processes: electron transference and cyclic - and linear peroxide cleavage; 2. biological systems capable of generating excited states and 3. biological functions of these states, specially the non-emissive ones (tripletes). The production and the role of non-emissive excited states in biological systems are analysed, the main purpose of the study being the search for non-emissive states. Experiences carried out in biological systems are described; results and conclusions are given. (M.A.) [pt

  16. Network class superposition analyses.

    Directory of Open Access Journals (Sweden)

    Carl A B Pearson

    Full Text Available Networks are often used to understand a whole system by modeling the interactions among its pieces. Examples include biomolecules in a cell interacting to provide some primary function, or species in an environment forming a stable community. However, these interactions are often unknown; instead, the pieces' dynamic states are known, and network structure must be inferred. Because observed function may be explained by many different networks (e.g., ≈ 10(30 for the yeast cell cycle process, considering dynamics beyond this primary function means picking a single network or suitable sample: measuring over all networks exhibiting the primary function is computationally infeasible. We circumvent that obstacle by calculating the network class ensemble. We represent the ensemble by a stochastic matrix T, which is a transition-by-transition superposition of the system dynamics for each member of the class. We present concrete results for T derived from boolean time series dynamics on networks obeying the Strong Inhibition rule, by applying T to several traditional questions about network dynamics. We show that the distribution of the number of point attractors can be accurately estimated with T. We show how to generate Derrida plots based on T. We show that T-based Shannon entropy outperforms other methods at selecting experiments to further narrow the network structure. We also outline an experimental test of predictions based on T. We motivate all of these results in terms of a popular molecular biology boolean network model for the yeast cell cycle, but the methods and analyses we introduce are general. We conclude with open questions for T, for example, application to other models, computational considerations when scaling up to larger systems, and other potential analyses.

  17. Discovering and validating biological hypotheses from coherent patterns in functional genomics data

    Energy Technology Data Exchange (ETDEWEB)

    Joachimiak, Marcin Pawel

    2008-08-12

    The area of transcriptomics analysis is among the more established in computational biology, having evolved in both technology and experimental design. Transcriptomics has a strong impetus to develop sophisticated computational methods due to the large amounts of available whole-genome datasets for many species and because of powerful applications in regulatory network reconstruction as well as elucidation and modeling of cellular transcriptional responses. While gene expression microarray data can be noisy and comparisons across experiments challenging, there are a number of sophisticated methods that aid in arriving at statistically and biologically significant conclusions. As such, computational transcriptomics analysis can provide guidance for analysis of results from newer experimental technologies. More recently, search methods have been developed to identify modules of genes, which exhibit coherent expression patterns in only a subset of experimental conditions. The latest advances in these methods allow to integrate multiple data types anddatasets, both experimental and computational, within a single statistical framework accounting for data confidence and relevance to specific biological questions. Such frameworks provide a unified environment for the exploration of specific biological hypothesis and for the discovery of coherent data patterns along with the evidence supporting them.

  18. Functionalization and microfluidic integration of silicon nanowire biologically gated field effect transistors

    DEFF Research Database (Denmark)

    Pfreundt, Andrea

    This thesis deals with the development of a novel biosensor for the detection of biomolecules based on a silicon nanowire biologically gated field-effect transistor and its integration into a point-of-care device. The sensor and electrical on-chip integration was developed in a different project...

  19. Functionalization and microfluidic integration of silicon nanowire biologically gated field effect transistors

    DEFF Research Database (Denmark)

    Pfreundt, Andrea; Svendsen, Winnie Edith; Dimaki, Maria

    2016-01-01

    This thesis deals with the development of a novel biosensor for the detection of biomolecules based on a silicon nanowire biologically gated field-effect transistor and its integration into a point-of-care device. The sensor and electrical on-chip integration was developed in a different project...

  20. Systems Biology-Derived Biomarkers to Predict Progression of Renal Function Decline in Type 2 Diabetes

    NARCIS (Netherlands)

    Mayer, Gert; Heerspink, Hiddo J. L.; Aschauer, Constantin; Heinzel, Andreas; Heinze, Georg; Kainz, Alexander; Sunzenauer, Judith; Perco, Paul; de Zeeuw, Dick; Rossing, Peter; Pena, Michelle; Oberbauer, Rainer

    OBJECTIVE: Chronic kidney disease (CKD) in diabetes has a complex molecular and likely multifaceted pathophysiology. We aimed to validate a panel of biomarkers identified using a systems biology approach to predict the individual decline of estimated glomerular filtration rate (eGFR) in a large

  1. Analyses of the influencing factors of soil microbial functional gene diversity in tropical rainforest based on GeoChip 5.0.

    Science.gov (United States)

    Cong, Jing; Liu, Xueduan; Lu, Hui; Xu, Han; Li, Yide; Deng, Ye; Li, Diqiang; Zhang, Yuguang

    2015-09-01

    To examine soil microbial functional gene diversity and causative factors in tropical rainforests, we used a microarray-based metagenomic tool named GeoChip 5.0 to profile it. We found that high microbial functional gene diversity and different soil microbial metabolic potential for biogeochemical processes were considered to exist in tropical rainforest. Soil available nitrogen was the most associated with soil microbial functional gene structure. Here, we mainly describe the experiment design, the data processing, and soil biogeochemical analyses attached to the study in details, which could be published on BMC microbiology Journal in 2015, whose raw data have been deposited in NCBI's Gene Expression Omnibus (accession number GSE69171).

  2. Resting State Functional Connectivity in Mild Traumatic Brain Injury at the Acute Stage: Independent Component and Seed-Based Analyses

    Science.gov (United States)

    Iraji, Armin; Benson, Randall R.; Welch, Robert D.; O'Neil, Brian J.; Woodard, John L.; Imran Ayaz, Syed; Kulek, Andrew; Mika, Valerie; Medado, Patrick; Soltanian-Zadeh, Hamid; Liu, Tianming; Haacke, E. Mark

    2015-01-01

    Abstract Mild traumatic brain injury (mTBI) accounts for more than 1 million emergency visits each year. Most of the injured stay in the emergency department for a few hours and are discharged home without a specific follow-up plan because of their negative clinical structural imaging. Advanced magnetic resonance imaging (MRI), particularly functional MRI (fMRI), has been reported as being sensitive to functional disturbances after brain injury. In this study, a cohort of 12 patients with mTBI were prospectively recruited from the emergency department of our local Level-1 trauma center for an advanced MRI scan at the acute stage. Sixteen age- and sex-matched controls were also recruited for comparison. Both group-based and individual-based independent component analysis of resting-state fMRI (rsfMRI) demonstrated reduced functional connectivity in both posterior cingulate cortex (PCC) and precuneus regions in comparison with controls, which is part of the default mode network (DMN). Further seed-based analysis confirmed reduced functional connectivity in these two regions and also demonstrated increased connectivity between these regions and other regions of the brain in mTBI. Seed-based analysis using the thalamus, hippocampus, and amygdala regions further demonstrated increased functional connectivity between these regions and other regions of the brain, particularly in the frontal lobe, in mTBI. Our data demonstrate alterations of multiple brain networks at the resting state, particularly increased functional connectivity in the frontal lobe, in response to brain concussion at the acute stage. Resting-state functional connectivity of the DMN could serve as a potential biomarker for improved detection of mTBI in the acute setting. PMID:25285363

  3. Surface functionalization of bioactive glasses with natural molecules of biological significance, Part I: Gallic acid as model molecule

    Science.gov (United States)

    Zhang, Xin; Ferraris, Sara; Prenesti, Enrico; Verné, Enrica

    2013-12-01

    Gallic acid (3,4,5-trihydroxybenzoic acid, GA) and its derivatives are a group of biomolecules (polyphenols) obtained from plants. They have effects which are potentially beneficial to heath, for example they are antioxidant, anticarcinogenic and antibacterial, as recently investigated in many fields such as medicine, food and plant sciences. The main drawbacks of these molecules are both low stability and bioavailability. In this research work the opportunity to graft GA to bioactive glasses is investigated, in order to deliver the undamaged biological molecule into the body, using the biomaterial surfaces as a localized carrier. GA was considered for functionalization since it is a good model molecule for polyphenols and presents several interesting biological activities, like antibacterial, antioxidant and anticarcinogenic properties. Two different silica based bioactive glasses (SCNA and CEL2), with different reactivity, were employed as substrates. UV photometry combined with the Folin&Ciocalteu reagent was adopted to test the concentration of GA in uptake solution after functionalization. This test verified how much GA consumption occurred with surface modification and it was also used on solid samples to test the presence of GA on functionalized glasses. XPS and SEM-EDS techniques were employed to characterize the modification of material surface properties and functional group composition before and after functionalization.

  4. A methodology for evaluating weighting functions using MCNP and its application to PWR ex-core analyses

    International Nuclear Information System (INIS)

    Pecchia, Marco; Vasiliev, Alexander; Ferroukhi, Hakim; Pautz, Andreas

    2017-01-01

    Highlights: • Evaluation of neutron source importance for a given tally. • Assessment of ex-core detector response plus its uncertainty. • Direct use of neutron track evaluated by a Monte Carlo neutron transport code. - Abstract: The ex-core neutron detectors are commonly used to control reactor power in light water reactors. Therefore, it is relevant to understand the importance of a neutron source to the ex-core detectors response. In mathematical terms, this information is conveniently represented by the so called weighting functions. A new methodology based on the MCNP code for evaluating the weighting functions starting from the neutron history database is presented in this work. A simultaneous evaluation of the weighting functions in a user-given Cartesian coverage mesh is the main advantage of the method. The capability to generate weighting functions simultaneously in both spatial and energy ranges is the innovative part of this work. Then, an interpolation tool complements the methodology, allowing the generation of weighting functions up to the pin-by-pin fuel segment, where a direct evaluation is not possible due to low statistical precision. A comparison to reference results provides a verification of the methodology. Finally, an application to investigate the role of ex-core detectors spatial location and core burnup for a Swiss nuclear power plant is provided.

  5. Bayesian uncertainty analysis for complex systems biology models: emulation, global parameter searches and evaluation of gene functions.

    Science.gov (United States)

    Vernon, Ian; Liu, Junli; Goldstein, Michael; Rowe, James; Topping, Jen; Lindsey, Keith

    2018-01-02

    Many mathematical models have now been employed across every area of systems biology. These models increasingly involve large numbers of unknown parameters, have complex structure which can result in substantial evaluation time relative to the needs of the analysis, and need to be compared to observed data of various forms. The correct analysis of such models usually requires a global parameter search, over a high dimensional parameter space, that incorporates and respects the most important sources of uncertainty. This can be an extremely difficult task, but it is essential for any meaningful inference or prediction to be made about any biological system. It hence represents a fundamental challenge for the whole of systems biology. Bayesian statistical methodology for the uncertainty analysis of complex models is introduced, which is designed to address the high dimensional global parameter search problem. Bayesian emulators that mimic the systems biology model but which are extremely fast to evaluate are embeded within an iterative history match: an efficient method to search high dimensional spaces within a more formal statistical setting, while incorporating major sources of uncertainty. The approach is demonstrated via application to a model of hormonal crosstalk in Arabidopsis root development, which has 32 rate parameters, for which we identify the sets of rate parameter values that lead to acceptable matches between model output and observed trend data. The multiple insights into the model's structure that this analysis provides are discussed. The methodology is applied to a second related model, and the biological consequences of the resulting comparison, including the evaluation of gene functions, are described. Bayesian uncertainty analysis for complex models using both emulators and history matching is shown to be a powerful technique that can greatly aid the study of a large class of systems biology models. It both provides insight into model behaviour

  6. Mechanical and biological properties of the micro-/nano-grain functionally graded hydroxyapatite bioceramics for bone tissue engineering.

    Science.gov (United States)

    Zhou, Changchun; Deng, Congying; Chen, Xuening; Zhao, Xiufen; Chen, Ying; Fan, Yujiang; Zhang, Xingdong

    2015-08-01

    Functionally graded materials (FGM) open the promising approach for bone tissue repair. In this study, a novel functionally graded hydroxyapatite (HA) bioceramic with micrograin and nanograin structure was fabricated. Its mechanical properties were tailored by composition of micrograin and nanograin. The dynamic mechanical analysis (DMA) indicated that the graded HA ceramics had similar mechanical property compared to natural bones. Their cytocompatibility was evaluated via fluorescent microscopy and MTT colorimetric assay. The viability and proliferation of rabbit bone marrow mesenchymal stem cells (BMSCs) on ceramics indicated that this functionally graded HA ceramic had better cytocompatibility than conventional HA ceramic. This study demonstrated that functionally graded HA ceramics create suitable structures to satisfy both the mechanical and biological requirements of bone tissues. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Petrologic, morphologic and functional analyses of ground and abrasive stone tools from Rug Bair, Ovche Pole valley

    International Nuclear Information System (INIS)

    Boev, Blazho; Dimitrovska, Vasilka

    2011-01-01

    This paper represents the results of the ground and abrasive stone tools analyses based on the finds collected during the excavation of Rug Bair undertaken in 1970, and today stored in the Museum and Institute for Protection of Shtip. The studies were made possible with the help from the Faculty of Natural and Technical Sciences, Shtip, Republic of Macedonia. Through the stone material, an attempt was made a more comprehensive picture of the raw material, petrologic, technical and typo logical characteristics of the Neolithic stone industry at this site to be gained as well as its relationship with related simultaneously industries. (Author)

  8. Resting State Functional Connectivity in Mild Traumatic Brain Injury at the Acute Stage: Independent Component and Seed-Based Analyses

    OpenAIRE

    Iraji, Armin; Benson, Randall R.; Welch, Robert D.; O'Neil, Brian J.; Woodard, John L.; Imran Ayaz, Syed; Kulek, Andrew; Mika, Valerie; Medado, Patrick; Soltanian-Zadeh, Hamid; Liu, Tianming; Haacke, E. Mark; Kou, Zhifeng

    2015-01-01

    Mild traumatic brain injury (mTBI) accounts for more than 1 million emergency visits each year. Most of the injured stay in the emergency department for a few hours and are discharged home without a specific follow-up plan because of their negative clinical structural imaging. Advanced magnetic resonance imaging (MRI), particularly functional MRI (fMRI), has been reported as being sensitive to functional disturbances after brain injury. In this study, a cohort of 12 patients with mTBI were pr...

  9. Analyses of advanced rice anther transcriptomes reveal global tapetum secretory functions and potential proteins for lipid exine formation.

    Science.gov (United States)

    Huang, Ming-Der; Wei, Fu-Jin; Wu, Cheng-Cheih; Hsing, Yue-Ie Caroline; Huang, Anthony H C

    2009-02-01

    The anthers in flowers perform important functions in sexual reproduction. Several recent studies used microarrays to study anther transcriptomes to explore genes controlling anther development. To analyze the secretion and other functions of the tapetum, we produced transcriptomes of anthers of rice (Oryza sativa subsp. japonica) at six progressive developmental stages and pollen with sequencing-by-synthesis technology. The transcriptomes included at least 18,000 unique transcripts, about 25% of which had antisense transcripts. In silico anther-minus-pollen subtraction produced transcripts largely unique to the tapetum; these transcripts include all the reported tapetum-specific transcripts of orthologs in other species. The differential developmental profiles of the transcripts and their antisense transcripts signify extensive regulation of gene expression in the anther, especially the tapetum, during development. The transcriptomes were used to dissect two major cell/biochemical functions of the tapetum. First, we categorized and charted the developmental profiles of all transcripts encoding secretory proteins present in the cellular exterior; these transcripts represent about 12% and 30% of the those transcripts having more than 100 and 1,000 transcripts per million, respectively. Second, we successfully selected from hundreds of transcripts several transcripts encoding potential proteins for lipid exine synthesis during early anther development. These proteins include cytochrome P450, acyltransferases, and lipid transfer proteins in our hypothesized mechanism of exine synthesis in and export from the tapetum. Putative functioning of these proteins in exine formation is consistent with proteins and metabolites detected in the anther locule fluid obtained by micropipetting.

  10. Thyroid Autoimmunity and Function after Treatment with Biological Antirheumatic Agents in Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Bliddal, Sofie; Borresen, Stina Willemoes; Feldt-Rasmussen, Ulla

    2017-01-01

    With the increased pro-inflammatory response in both rheumatoid arthritis and thyroid autoimmune diseases, treatment with biological antirheumatic agents (BAAs) of the former may affect the course of the latter. In hepatitis C and cancer patients, treatment with biological agents substantially...... increases the risk of developing thyroid autoimmunity. As the use of BAAs in the treatment of rheumatoid arthritis is increasing, this review aimed to investigate if such use affected thyroid status in rheumatoid arthritis patients. We conducted a systematic literature search and included six studies...... status: a reduction of thyroid peroxidase and thyroglobulin antibody concentrations, and a reduction of thyrotropin levels in hypothyroid patients. Despite the small number of studies, they presented compliant data. The BAAs used in rheumatoid arthritis thus did not seem to negatively affect thyroid...

  11. Recent Progress in Synthesis and Functionalization of Multimodal Fluorescent-Magnetic Nanoparticles for Biological Applications

    Directory of Open Access Journals (Sweden)

    Raquel Serrano García

    2018-01-01

    Full Text Available There is a great interest in the development of new nanomaterials for multimodal imaging applications in biology and medicine. Multimodal fluorescent-magnetic based nanomaterials deserve particular attention as they can be used as diagnostic and drug delivery tools, which could facilitate the diagnosis and treatment of cancer and many other diseases. This review focuses on the recent developments of magnetic-fluorescent nanocomposites and their biomedical applications. The recent advances in synthetic strategies and approaches for the preparation of fluorescent-magnetic nanocomposites are presented. The main biomedical uses of multimodal fluorescent-magnetic nanomaterials, including biological imaging, cancer therapy and drug delivery, are discussed, and prospects of this field are outlined.

  12. Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis

    DEFF Research Database (Denmark)

    Loft, N D; Skov, L; Iversen, L.

    2018-01-01

    Biological agents including anti-tumor necrosis factor (anti-TNF; adalimumab, infliximab, etanercept) and anti-interleukin-12/13 (IL12/23; ustekinumab) are essential for treatment of patients with severe psoriasis. However, a significant proportion of the patients do not respond to a specific tre...... with ustekinumab.The Pharmacogenomics Journal advance online publication, 11 July 2017; doi:10.1038/tpj.2017.31....

  13. Bio-templated CdSe quantum dots green synthesis in the functional protein, lysozyme, and biological activity investigation

    International Nuclear Information System (INIS)

    Wang, Qisui; Li, Song; Liu, Peng; Min, Xinmin

    2012-01-01

    Bifunctional fluorescence (CdSe Quantum Dots) – protein (Lysozyme) nanocomposites were synthesized at room temperature by a protein-directed, solution-phase, green-synthetic method. Fluorescence (FL) and absorption spectra showed that CdSe QDs were prepared successfully with Lyz. The average particle size and crystalline structure of QDs were investigated by high-resolution transmission electron microscopy (HRTEM) and X-ray diffraction (XRD), respectively. With attenuated total reflection-fourier transform infrared (ATR-FTIR) spectra and thermogravimetric (TG) analysis, it was confirmed that there is interaction between QDs and amide I, amide II groups in Lyz. FL polarization was measured and FL imaging was done to monitor whether QDs could be responsible for possible changes in the conformation and activity of Lyz. Interestingly, the results showed Lyz still retain the biological activity after formation of QDs, but the secondary structure of the Lyz was changed. And the advantage of this synthesis method is producing excellent fluorescent QDs with specifically biological function. -- Highlights: ► Lysozyme-directed green synthesis of CdSe quantum dots. ► Lysozyme still retain the biological activity after formation of CdSe. ► The method is the production of fluorescent QDs with highly specific and functions.

  14. AGROBEST: an efficient Agrobacterium-mediated transient expression method for versatile gene function analyses in Arabidopsis seedlings

    Science.gov (United States)

    2014-01-01

    Background Transient gene expression via Agrobacterium-mediated DNA transfer offers a simple and fast method to analyze transgene functions. Although Arabidopsis is the most-studied model plant with powerful genetic and genomic resources, achieving highly efficient and consistent transient expression for gene function analysis in Arabidopsis remains challenging. Results We developed a highly efficient and robust Agrobacterium-mediated transient expression system, named AGROBEST (Agrobacterium-mediated enhanced seedling transformation), which achieves versatile analysis of diverse gene functions in intact Arabidopsis seedlings. Using β-glucuronidase (GUS) as a reporter for Agrobacterium-mediated transformation assay, we show that the use of a specific disarmed Agrobacterium strain with vir gene pre-induction resulted in homogenous GUS staining in cotyledons of young Arabidopsis seedlings. Optimization with AB salts in plant culture medium buffered with acidic pH 5.5 during Agrobacterium infection greatly enhanced the transient expression levels, which were significantly higher than with two existing methods. Importantly, the optimized method conferred 100% infected seedlings with highly increased transient expression in shoots and also transformation events in roots of ~70% infected seedlings in both the immune receptor mutant efr-1 and wild-type Col-0 seedlings. Finally, we demonstrated the versatile applicability of the method for examining transcription factor action and circadian reporter-gene regulation as well as protein subcellular localization and protein–protein interactions in physiological contexts. Conclusions AGROBEST is a simple, fast, reliable, and robust transient expression system enabling high transient expression and transformation efficiency in Arabidopsis seedlings. Demonstration of the proof-of-concept experiments elevates the transient expression technology to the level of functional studies in Arabidopsis seedlings in addition to previous

  15. The Triumph of Function over Form The Role of Analytic Philosophy in Planning and Analysing Modern Architecture

    Directory of Open Access Journals (Sweden)

    Borbala Jasz

    2017-07-01

    Full Text Available The most dominant dialectical succession of architectural thinking during the 20th Century was between form and function. The latter of these two modern ways of architectural thinking is based on the results of Carnapian Neopositivism. The keywords of this philosophical school, that are empiricism, logic, verification, unity of language and science, could still be applied to interpreting modern architecture. I will explain the antecedents and the first connection between analytic philosophy and architecture, and some characteristic points of their influence during the 20th Century: the triumph of function over form as analogous to triumph of analytic philosophy over metaphysics.After the theoretic grounding of the form-function debate, I am going to focus first on the characteristic appearance of form: the Façadism of Socialist Realism in the architecture of East-Central Europe. Second, I will explain that architectural tendencies of classical modernism did not disappear in this period, they were just hidden in case of public buildings or migrated to the industrial planning. Third, I am going to claim that after this socialist realist gap, the architectural theory and planning tendencies of the interwar period – especially the work of Le Corbusier – returned and continued.

  16. The W22 genome: a foundation for maize functional genomics and transposon biology

    Science.gov (United States)

    The maize W22 inbred has served as a platform for maize genetics since the mid twentieth century. To streamline maize genome analyses, we have sequenced and de novo assembled a W22 reference genome using small-read sequencing technologies. We show that significant structural heterogeneity exists in ...

  17. From transcriptome to biological function: environmental stress in an ectothermic vertebrate, the coral reef fish Pomacentrus moluccensis

    Directory of Open Access Journals (Sweden)

    Ward Alister C

    2007-10-01

    Full Text Available Abstract Background Our understanding of the importance of transcriptional regulation for biological function is continuously improving. We still know, however, comparatively little about how environmentally induced stress affects gene expression in vertebrates, and the consistency of transcriptional stress responses to different types of environmental stress. In this study, we used a multi-stressor approach to identify components of a common stress response as well as components unique to different types of environmental stress. We exposed individuals of the coral reef fish Pomacentrus moluccensis to hypoxic, hyposmotic, cold and heat shock and measured the responses of approximately 16,000 genes in liver. We also compared winter and summer responses to heat shock to examine the capacity for such responses to vary with acclimation to different ambient temperatures. Results We identified a series of gene functions that were involved in all stress responses examined here, suggesting some common effects of stress on biological function. These common responses were achieved by the regulation of largely independent sets of genes; the responses of individual genes varied greatly across different stress types. In response to heat exposure over five days, a total of 324 gene loci were differentially expressed. Many heat-responsive genes had functions associated with protein turnover, metabolism, and the response to oxidative stress. We were also able to identify groups of co-regulated genes, the genes within which shared similar functions. Conclusion This is the first environmental genomic study to measure gene regulation in response to different environmental stressors in a natural population of a warm-adapted ectothermic vertebrate. We have shown that different types of environmental stress induce expression changes in genes with similar gene functions, but that the responses of individual genes vary between stress types. The functions of heat

  18. Self-assembly and stability of double rosette nanostructures with biological functionalities

    NARCIS (Netherlands)

    ten Cate, M.G.J.; Omerovic, Merdan; Oshovsky, G.; Crego Calama, Mercedes; Reinhoudt, David

    2005-01-01

    The syntheses of calix[4]arene dimelamines that are functionalized with alkyl, aminoalkyl, ureido, pyridyl, carbohydrate, amino acid and peptide functionalities, and their self-assembly with barbituric acid or cyanuric acid derivatives into well-defined hydrogen-bonded nanostructures are described.

  19. Novel function of polyaniline for biological environments: Cultivation of paramecium in the presence of polyaniline

    Science.gov (United States)

    Goto, Hiromasa

    2014-03-01

    The reduced form of polyaniline (PANI, emeraldine base) functions as water purification to extend the lives of paramecia. The emeraldine base can absorb discharged waste from the planktons such as nitrogenous compounds and salts. This is a new function of π-conjugated polymers for micro-organisms.

  20. Novel function of polyaniline for biological environments: Cultivation of paramecium in the presence of polyaniline

    International Nuclear Information System (INIS)

    Goto, Hiromasa

    2014-01-01

    The reduced form of polyaniline (PANI, emeraldine base) functions as water purification to extend the lives of paramecia. The emeraldine base can absorb discharged waste from the planktons such as nitrogenous compounds and salts. This is a new function of π-conjugated polymers for micro-organisms

  1. The relationship between the connecting peptide of recombined single chain insulin and its biological function

    Institute of Scientific and Technical Information of China (English)

    HUANG; Yiding; (

    2001-01-01

    [1]Straus, D. S., Growth-stimulatory of insulin in vitro and in vivo, Endocr. Rev., 1984, 5(2): 356-369.[2]Svenningsen, A. F., Kanje, M., Insulin and the insulin-like growth factors I and II are mitogenic to cultured rat sciatic nerve segments and stimulate [3H] thuymidine incorporation through their respective receptors, Glia, 1996, 18(1): 68-72.[3]Ogihara, S., Yamada, M., Saito, T. et al., Insulin potentiates mitogenic effect of epidermal growth factor on cultured guinea pig gastric mucous cells, Am. J. Physiol., 1996, 271(1 Pt 1): G104-121.[4]Steiner, D. F., Oyer, P. E., The biosynthesis of insulin and a probable precursor of insulin by a human islet cell adenoma, Proc. Nalt. Acad. Sci. USA, 1967, 57(2): 473-480.[5]King, G. L., Kahn, C. R., The growth-promoting effects of insulin, in Growth and Maturation Factors(ed. Guroff, G.), New York: John Wiley & Sons, 1984, 223-265.[6]Peavy, D. E., Brunner, M. R., Duckworth, W. C. et al., Receptor binding and biological potency of several split forms (conversion intermediates) of human proinsulin, Studies in cultured IM-9 lymphocytes and in vivo and in vitro in rats, J. Biol. Chem., 1985, 260: 13989-13994.[7]Derewenda, U., Derewenda, Z., Dodson, E. J. et al., X-ray analysis of the single chain B29-A1 peptide-linked insulin molecule. A completely inactive analogue, J. Mol. Biol., 1991, 220: 425-433.[8]Hua, Q. X., Shoelson, S. E., Kochoyan, M. et al., Receptor binding redefined by a structural switch in a mutant human insulin, Nature, 1991, 354: 238-241.[9]Hua, Q. X., Gozani, S. N., Chance, R. E. et al., Structure of a protein in a kinetic trap, Nat. Struc. Boil, 1995, 2: 129-138.[10]Kristensen, C., Andersen, A. S., Hach, M., A single-chain insulin-like growth factor I/insulin hybrid binds with high affinity to the insulin receptor, Biochem. J., 1995, 305: 981-986.[11]Humbel, R. E., Insulin-like growth factors I and II, Euro. J. Biochem., 1990, 190: 445-462.[12]Cooke, R. M

  2. Biological half-life of iodine in adults with intact thyroid function and in athyreotic persons

    Energy Technology Data Exchange (ETDEWEB)

    Kramer, G.H.; Hauck, B.M.; Chamberlain, M.J

    2002-07-01

    A joint project between the Human Monitoring Laboratory (HML) and the Ottawa Hospital has measured the retention of {sup 131}I in patients who have received the radioiodine diagnostically. Thirty-nine subjects with intact thyroid glands and nine athyreotic subjects were measured in the HML's whole-body/thyroid counter to determine the retention of {sup 131}I following its medical administration. The average biological half-life of {sup 131}I in 26 euthyroid subjects was found to be 66.1{+-}6.3 days which may be statistically significantly lower than the ICRP recommended value of 80 days. Nine hyperthyroid patients had a mean biological half-life of 38.2{+-}8.6 days and in three hypothyroid patients the corresponding value was 29.3{+-}8.8 days. Thyroid {sup 131}I uptake was measured in a conventional clinical fashion at the Ottawa Hospital Civic campus 24 h after oral administration of the radioiodine using a collimated thick sodium iodide detector placed over the neck arteriorly. Measured values were 0.144{+-}0.009, 0.314{+-}0.035 and 0.045{+-}0.010 of the administered dose in euthyroid, hyperthyroid and hypothyroid patients respectively. The euthyroid range at the hospital is 0.06-0.22. Uptake was significantly lower for the euthyroid group than the ICRP value of 0.3. The radioiodine retention in athyreotic subjects followed a two compartment model with biological half-lives of 1.0{+-}0.2 days and 18.4{+-}1.1. days. (author)

  3. Biological aspects and life table of Uroleucon ambrosiae (Thomas, 1878) as a function of temperature

    OpenAIRE

    Auad Alexander Machado; Moraes Jair Campos de

    2003-01-01

    The aphid Uroleucon ambrosiae (Thomas) is considered a pest of hidroponically-grown lettuce, but basic and applied information on its control are scarce in Brazil. The aim of this study was to determine the effect of different temperatures on biological aspects and life history of U. ambrosiae (Thomas) developing on hydroponic lettuce (Lactuca sativa L.) crop. Newly emerged nymphs were placed on 4-cm discs of hydroponic lettuce, var. Verônica, which were maintained on 5-cm Petri dishes, at te...

  4. Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis

    DEFF Research Database (Denmark)

    Loft, N D; Skov, L; Iversen, L

    2017-01-01

    Biological agents including anti-tumor necrosis factor (anti-TNF; adalimumab, infliximab, etanercept) and anti-interleukin-12/13 (IL12/23; ustekinumab) are essential for treatment of patients with severe psoriasis. However, a significant proportion of the patients do not respond to a specific tre...... with ustekinumab.The Pharmacogenomics Journal advance online publication, 11 July 2017; doi:10.1038/tpj.2017.31....... with response to ustekinumab treatment (qhigh interferon-γ levels may be favorable when treating psoriasis...

  5. No effects of functional exercise therapy on walking biomechanics in patients with knee osteoarthritis: exploratory outcome analyses from a randomised trial.

    Science.gov (United States)

    Henriksen, Marius; Klokker, Louise; Bartholdy, Cecilie; Schjoedt-Jorgensen, Tanja; Bandak, Elisabeth; Bliddal, Henning

    2016-01-01

    To assess the effects of a functional and individualised exercise programme on gait biomechanics during walking in people with knee OA. Sixty participants were randomised to 12 weeks of facility-based functional and individualised neuromuscular exercise therapy (ET), 3 sessions per week supervised by trained physical therapists, or a no attention control group (CG). Three-dimensional gait analyses were used, from which a comprehensive list of conventional gait variables were extracted (totally 52 kinematic, kinetic and spatiotemporal variables). According to the protocol, the analyses were based on the 'Per-Protocol' population (defined as participants following the protocol with complete and valid gait analyses). Analysis of covariance adjusting for the level at baseline was used to determine differences between groups (95% CIs) in the changes from baseline at follow-up. The per-protocol population included 46 participants (24 ET/22 CG). There were no group differences in the analysed gait variables, except for a significant group difference in the second peak knee flexor moment and second peak vertical ground reaction force. While plausible we have limited confidence in the findings due to multiple statistical tests and lack of biomechanical logics. Therefore we conclude that a 12-week supervised individualised neuromuscular exercise programme has no effects on gait biomechanics. Future studies should focus on exercise programmes specifically designed to alter gait patterns, or include other measures of mobility, such as walking on stairs or inclined surfaces. ClinicalTrials.gov: NCT01545258.

  6. Transcriptomic and Functional Analyses Reveal That PpGLK1 Regulates Chloroplast Development in Peach (Prunus persica

    Directory of Open Access Journals (Sweden)

    Min Chen

    2018-01-01

    Full Text Available Peach is an ideal species for fruit tree research because of its small, fully sequenced genome. Chloroplast development is dependent on the tight cooperation between the nuclear and plastid genomes, and is regulated by GLK transcription factors. In this work, the pigment content was monitored and the chloroplast-to-chromoplast conversion during the fruit ripening was visualized by transmission electron microscopy. Localization and expression analyses showed that PpGLK1 was located in the nucleus and expressed mainly in the leaves and fruit skin. A transcriptome analysis showed that PpGLK1 and its target genes were significantly differentially expressed in ripening peach fruit skin. PpGLK1 silencing affected chlorophyll accumulation in peach leaves and fruits. Overexpression of PpGLK1 rescued the phenotypes of the Arabidopsis Atglk1Atglk2 double mutant and the tomato uniform ripening mutant. The results of a yeast two-hybrid analysis showed that PpGLK1 is autoactivated and that PpGLK1 (301-542 a.a. interacted with PpARF5. Together, our results indicate that PpGLK1 regulates chloroplast development in green tissues in peach. Therefore, it may be a promising target gene for improving the production and quality of peach by genetic engineering and breeding approaches.

  7. The unique architecture and function of cellulose-interacting proteins in oomycetes revealed by genomic and structural analyses

    Directory of Open Access Journals (Sweden)

    Larroque Mathieu

    2012-11-01

    provides insight into the evolution and biological roles of CBM1-containing proteins from oomycetes. We show that while CBM1s from fungi and oomycetes are similar, they team up with different protein domains, either in proteins implicated in the degradation of plant cell wall components in the case of fungi or in proteins involved in adhesion to polysaccharidic substrates in the case of oomycetes. This work highlighted the unique role and evolution of CBM1 proteins in oomycete among the Stramenopile lineage.

  8. A graphical user interface (GUI) toolkit for the calculation of three-dimensional (3D) multi-phase biological effective dose (BED) distributions including statistical analyses.

    Science.gov (United States)

    Kauweloa, Kevin I; Gutierrez, Alonso N; Stathakis, Sotirios; Papanikolaou, Niko; Mavroidis, Panayiotis

    2016-07-01

    A toolkit has been developed for calculating the 3-dimensional biological effective dose (BED) distributions in multi-phase, external beam radiotherapy treatments such as those applied in liver stereotactic body radiation therapy (SBRT) and in multi-prescription treatments. This toolkit also provides a wide range of statistical results related to dose and BED distributions. MATLAB 2010a, version 7.10 was used to create this GUI toolkit. The input data consist of the dose distribution matrices, organ contour coordinates, and treatment planning parameters from the treatment planning system (TPS). The toolkit has the capability of calculating the multi-phase BED distributions using different formulas (denoted as true and approximate). Following the calculations of the BED distributions, the dose and BED distributions can be viewed in different projections (e.g. coronal, sagittal and transverse). The different elements of this toolkit are presented and the important steps for the execution of its calculations are illustrated. The toolkit is applied on brain, head & neck and prostate cancer patients, who received primary and boost phases in order to demonstrate its capability in calculating BED distributions, as well as measuring the inaccuracy and imprecision of the approximate BED distributions. Finally, the clinical situations in which the use of the present toolkit would have a significant clinical impact are indicated. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Socio-sexual functioning in autism spectrum disorder: A systematic review and meta-analyses of existing literature.

    Science.gov (United States)

    Hancock, Grace I P; Stokes, Mark A; Mesibov, Gary B

    2017-11-01

    Socio-sexual functioning encompasses an individual's interests, behaviors, and knowledge with respect to sexual, romantic, and social aspects of life. An individual's understanding of these domains is developed through a range of informal and formal avenues of sexual health education. The current model demonstrated this and proposed that, compared to typically developing individuals, those with ASD develop socio-sexual functioning differently due to having less peer engagement, less relationship experience, more parental guidance, greater use of online materials, receive less school-based sexual health education, and more support from wellbeing services. Systematic review and meta-analysis of existing literature revealed that individuals with ASD have greater difficultly adhering to privacy norms, engage in less social behavior, are described as engaging in less appropriate sexual behavior, have greater concerns about themselves, and receive less sexual health education. Having fewer opportunities for appropriate informal and formal sexual health education leaves them at a double disadvantage from others who are receiving this information from both of these avenues. Some of the current meta-analytic results are cautioned by large l-square statistics which suggest that a degree of variance is being caused by extraneous factors. Further empirical research in this area is needed to overcome current design and sample limitations. Finally, the Sexual Behavior Scale was the most commonly utilized tool in the meta-analyzed studies, thus comprehensive evaluation of its functioning is warranted. The importance of work in this area is highlighted by the central role of social and sexual wellbeing on one's quality of life. Autism Res 2017, 10: 1823-1833. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Review of existing literature revealed that individuals with ASD have greater difficultly adhering to privacy norms, engage in less social behavior

  10. Biological functioning of PAH-polluted and thermal desorption-treated soils assessed by fauna and microbial bioindicators.

    Science.gov (United States)

    Cébron, Aurélie; Cortet, Jérôme; Criquet, Stéven; Biaz, Asmaa; Calvert, Virgile; Caupert, Cécile; Pernin, Céline; Leyval, Corinne

    2011-11-01

    A large number of soil bioindicators were used to assess biological diversity and activity in soil polluted with polycyclic aromatic hydrocarbons (PAHs) and the same soil after thermal desorption (TD) treatment. Abundance and biodiversity of bacteria, fungi, protozoa, nematodes and microarthropods, as well as functional parameters such as enzymatic activities and soil respiration, were assessed during a two year period of in situ monitoring. We investigated the influence of vegetation (spontaneous vegetation and Medicago sativa) and TD treatment on biological functioning. Multivariate analysis was performed to analyze the whole data set. A principal response curve (PRC) technique was used to evaluate the different treatments (various vegetation and contaminated vs. TD soil) contrasted with control (bare) soil over time. Our results indicated the value of using a number of complementary bioindicators, describing both diversity and functions, to assess the influence of vegetation on soil and discriminate polluted from thermal desorption (TD)-treated soil. Plants had an influence on the abundance and activity of all organisms examined in our study, favoring the whole trophic chain development. However, although TD-treated soil had a high abundance and diversity of microorganisms and fauna, enzymatic activities were weak because of the strong physical and chemical modifications of this soil. Copyright © 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  11. Minimal information: an urgent need to assess the functional reliability of recombinant proteins used in biological experiments

    Directory of Open Access Journals (Sweden)

    de Marco Ario

    2008-07-01

    Full Text Available Abstract Structural characterization of proteins used in biological experiments is largely neglected. In most publications, the information available is totally insufficient to judge the functionality of the proteins used and, therefore, the significance of identified protein-protein interactions (was the interaction specific or due to unspecific binding of misfolded protein regions? or reliability of kinetic and thermodynamic data (how much protein was in its native form?. As a consequence, the results of single experiments might not only become questionable, but the whole reliability of systems biology, built on these fundaments, would be weakened. The introduction of Minimal Information concerning purified proteins to add as metadata to the main body of a manuscript would render straightforward the assessment of their functional and structural qualities and, consequently, of results obtained using these proteins. Furthermore, accepted standards for protein annotation would simplify data comparison and exchange. This article has been envisaged as a proposal for aggregating scientists who share the opinion that the scientific community needs a platform for Minimum Information for Protein Functionality Evaluation (MIPFE.

  12. The Pectin Methylesterase Gene Complement of Phytophthora sojae: Structural and Functional Analyses, and the Evolutionary Relationships with Its Oomycete Homologs.

    Science.gov (United States)

    Horowitz, Brent B; Ospina-Giraldo, Manuel D

    2015-01-01

    Phytophthora sojae is an oomycete pathogen that causes the disease known as root and stem rot in soybean plants, frequently leading to massive economic damage. Additionally, P. sojae is increasingly being utilized as a model for phytopathogenic oomycete research. Despite the economic and scientific importance of P. sojae, the mechanism by which it penetrates the host roots is not yet fully understood. It has been found that oomycetes are not capable of penetrating the cell wall solely through mechanical force, suggesting that alternative factors facilitate breakdown of the host cell wall. Pectin methylesterases have been suggested to be important for Phytophthora pathogenicity, but no data exist on their role in the P. sojae infection process. We have scanned the newly revised version of the annotated P. sojae genome for the presence of putative pectin methylesterases genes and conducted a sequence analysis of all gene models found. We also searched for potential regulatory motifs in the promoter region of the proposed P. sojae models, and investigated the gene expression levels throughout the early course of infection on soybean plants. We found that P. sojae contains a large repertoire of pectin methylesterase-coding genes and that most of these genes display similar motifs in the promoter region, indicating the possibility of a shared regulatory mechanism. Phylogenetic analyses confirmed the evolutionary relatedness of the pectin methylesterase-coding genes within and across Phytophthora spp. In addition, the gene duplication events that led to the emergence of this gene family appear to have occurred prior to many speciation events in the genus Phytophthora. Our results also indicate that the highest levels of expression occurred in the first 24 hours post inoculation, with expression falling after this time. Our study provides evidence that pectin methylesterases may be important for the early action of the P. sojae infection process.

  13. The Pectin Methylesterase Gene Complement of Phytophthora sojae: Structural and Functional Analyses, and the Evolutionary Relationships with Its Oomycete Homologs.

    Directory of Open Access Journals (Sweden)

    Brent B Horowitz

    Full Text Available Phytophthora sojae is an oomycete pathogen that causes the disease known as root and stem rot in soybean plants, frequently leading to massive economic damage. Additionally, P. sojae is increasingly being utilized as a model for phytopathogenic oomycete research. Despite the economic and scientific importance of P. sojae, the mechanism by which it penetrates the host roots is not yet fully understood. It has been found that oomycetes are not capable of penetrating the cell wall solely through mechanical force, suggesting that alternative factors facilitate breakdown of the host cell wall. Pectin methylesterases have been suggested to be important for Phytophthora pathogenicity, but no data exist on their role in the P. sojae infection process. We have scanned the newly revised version of the annotated P. sojae genome for the presence of putative pectin methylesterases genes and conducted a sequence analysis of all gene models found. We also searched for potential regulatory motifs in the promoter region of the proposed P. sojae models, and investigated the gene expression levels throughout the early course of infection on soybean plants. We found that P. sojae contains a large repertoire of pectin methylesterase-coding genes and that most of these genes display similar motifs in the promoter region, indicating the possibility of a shared regulatory mechanism. Phylogenetic analyses confirmed the evolutionary relatedness of the pectin methylesterase-coding genes within and across Phytophthora spp. In addition, the gene duplication events that led to the emergence of this gene family appear to have occurred prior to many speciation events in the genus Phytophthora. Our results also indicate that the highest levels of expression occurred in the first 24 hours post inoculation, with expression falling after this time. Our study provides evidence that pectin methylesterases may be important for the early action of the P. sojae infection process.

  14. Functionalization of Self-Organized Nanoparticles for Biological Targeting and Active Drug Release

    DEFF Research Database (Denmark)

    Jølck, Rasmus Irming

    Functional nanomaterials have attracted much attention due to the unique properties of these nanoconstructs. In recognition of the huge potential within this field, much research has been devoted to develop sophisticated nanoparticles for medical diagnostics, sensors, contrast agents, vaccines an...

  15. In silico determination of intracellular glycosylation and phosphorylation sites in human selectins: Implications for biological function

    DEFF Research Database (Denmark)

    Ahmad, I.; Hoessli, D.C.; Gupta, Ramneek

    2007-01-01

    Post-translational modifications provide the proteins with the possibility to perform functions in addition to those determined by their primary sequence. However, analysis of multifunctional protein structures in the environment of cells and body fluids is made especially difficult by the presence...... both modifications are likely to occur can also be predicted (YinYang sites), to suggest further functional versatility. Structural modifications of hydroxyl groups of P-, E-, and L-selectins have been predicted and possible functions resulting from such modifications are proposed. Functional changes...... of the three selectins are based on the assumption that transitory and reversible protein modifications by phosphate and O-GlcNAc cause specific conformational changes and generate binding sites for other proteins. The computer-assisted prediction of glycosylation and phosphorylation sites in selectins should...

  16. Complexity of cancer protease biology: Cathepsin K expression and function in cancer progression

    NARCIS (Netherlands)

    Verbovšek, Urška; van Noorden, Cornelis J. F.; Lah, Tamara T.

    2015-01-01

    Proteases, including lysosomal cathepsins, are functionally involved in many processes in cancer progression from its initiation to invasion and metastatic spread. Only recently, cathepsin K (CatK), the cysteine protease originally reported as a collagenolytic protease produced by osteoclasts,

  17. A functional approach for research on cognitive control: Analysing cognitive control tasks and their effects in terms of operant conditioning.

    Science.gov (United States)

    Liefooghe, Baptist; De Houwer, Jan

    2016-02-01

    Cognitive control is an important mental ability that is examined using a multitude of cognitive control tasks and effects. The present paper presents the first steps in the elaboration of a functional approach, which aims to uncover the communalities and differences between different cognitive control tasks and their effects. Based on the idea that responses in cognitive control tasks qualify as operant behaviour, we propose to reinterpret cognitive control tasks in terms of operant contingencies and cognitive control effects as instances of moderated stimulus control. We illustrate how our approach can be used to uncover communalities between topographically different cognitive control tasks and can lead to novel questions about the processes underlying cognitive control. © 2015 International Union of Psychological Science.

  18. Load time functions (LTF) for large commercial aircraft based on Riera approach and finite element analyses – a parametric study

    International Nuclear Information System (INIS)

    Iliev, A.

    2013-01-01

    Conclusions: In cases of a complex geometry of the target structure a careful evaluation of the predefined load time function should be performed. Special attention should be paid on different deceleration of airplane parts and their equivalent load forces. In cases of cylindrical structures with relatively small diameter (in comparison to the airplane wing spread), the impact of the engines should be investigated separately. When auxiliary structures are surrounding the reactor containment, the impact load will be reduced due to initial destruction of part of the airplane in the surrounding auxiliary structures. For the case study, this reduction was found to be non-significant. However if important equipment is situated in surrounding auxiliary buildings, engines may provide higher equivalent forces compared to normal planar target structure

  19. Aerodynamic and cephalometric analyses of velopharyngeal structure and function following re-pushback surgery for secondary correction in cleft palate.

    Science.gov (United States)

    Nakamura, Norifumi; Ogata, Yuko; Sasaguri, Masaaki; Suzuki, Akira; Kikuta, Rumiko; Ohishi, Masamichi

    2003-01-01

    The goal of this study was to clarify the efficacy of and indication for re-pushback surgery as secondary treatment for cleft palate. Fifteen patients treated by re-pushback surgery involving intravelar veloplasty (IVV) with buccal mucosal grafting on the nasal surface and followed up more than 6 months were enrolled in this study. Pre- and postoperative velopharyngeal functions were analyzed by perceptual voice analysis, blowing ratio, and nasalance scores during phonation of /i/ and /tsu/. Cephalometric analysis was used to evaluate the relationship between velopharyngeal structure and the outcome of re-pushback surgery. Control data were obtained from the longitudinal files of normal 10-year-old children in Kyushu University Dental Hospital. Eight of 15 patients obtained complete velopharyngeal closure (complete group), five patients improved remarkably (improved group), and no effective result was seen in two patients (ineffective group). Nasality disappeared or remarkably improved after the operation in 13 patients. Effective surgical results were found in 86.7% of the patients. Partial flap necrosis was seen in two patients in whom re-pushback surgery was performed using mucosal palatal flaps instead of mucoperiosteal flaps. Preoperative velar length and the length/depth ratio of the re-pushback group were significantly smaller than the controls, but there was no difference after the operation. Furthermore, the preoperative length/depth ratio of the complete group (ranged more than 100%) was significantly greater than those of the other two groups (ranged less than 100%). Re-pushback surgery by IVV with free mucous grafting on the nasal surface was effective in managing velopharyngeal incompetence secondarily, improving velopharyngeal structure and function.

  20. Abnormal Resting-State Functional Connectivity in Patients with Chronic Fatigue Syndrome: Results of Seed and Data-Driven Analyses.

    Science.gov (United States)

    Gay, Charles W; Robinson, Michael E; Lai, Song; O'Shea, Andrew; Craggs, Jason G; Price, Donald D; Staud, Roland

    2016-02-01

    Although altered resting-state functional connectivity (FC) is a characteristic of many chronic pain conditions, it has not yet been evaluated in patients with chronic fatigue. Our objective was to investigate the association between fatigue and altered resting-state FC in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Thirty-six female subjects, 19 ME/CFS and 17 healthy controls, completed a fatigue inventory before undergoing functional magnetic resonance imaging. Two methods, (1) data driven and (2) model based, were used to estimate and compare the intraregional FC between both groups during the resting state (RS). The first approach using independent component analysis was applied to investigate five RS networks: the default mode network, salience network (SN), left frontoparietal networks (LFPN) and right frontoparietal networks, and the sensory motor network (SMN). The second approach used a priori selected seed regions demonstrating abnormal regional cerebral blood flow (rCBF) in ME/CFS patients at rest. In ME/CFS patients, Method-1 identified decreased intrinsic connectivity among regions within the LFPN. Furthermore, the FC of the left anterior midcingulate with the SMN and the connectivity of the left posterior cingulate cortex with the SN were significantly decreased. For Method-2, five distinct clusters within the right parahippocampus and occipital lobes, demonstrating significant rCBF reductions in ME/CFS patients, were used as seeds. The parahippocampal seed and three occipital lobe seeds showed altered FC with other brain regions. The degree of abnormal connectivity correlated with the level of self-reported fatigue. Our results confirm altered RS FC in patients with ME/CFS, which was significantly correlated with the severity of their chronic fatigue.

  1. Mechanistic Insight into Bunyavirus-Induced Membrane Fusion from Structure-Function Analyses of the Hantavirus Envelope Glycoprotein Gc.

    Directory of Open Access Journals (Sweden)

    Pablo Guardado-Calvo

    2016-10-01

    Full Text Available Hantaviruses are zoonotic viruses transmitted to humans by persistently infected rodents, giving rise to serious outbreaks of hemorrhagic fever with renal syndrome (HFRS or of hantavirus pulmonary syndrome (HPS, depending on the virus, which are associated with high case fatality rates. There is only limited knowledge about the organization of the viral particles and in particular, about the hantavirus membrane fusion glycoprotein Gc, the function of which is essential for virus entry. We describe here the X-ray structures of Gc from Hantaan virus, the type species hantavirus and responsible for HFRS, both in its neutral pH, monomeric pre-fusion conformation, and in its acidic pH, trimeric post-fusion form. The structures confirm the prediction that Gc is a class II fusion protein, containing the characteristic β-sheet rich domains termed I, II and III as initially identified in the fusion proteins of arboviruses such as alpha- and flaviviruses. The structures also show a number of features of Gc that are distinct from arbovirus class II proteins. In particular, hantavirus Gc inserts residues from three different loops into the target membrane to drive fusion, as confirmed functionally by structure-guided mutagenesis on the HPS-inducing Andes virus, instead of having a single "fusion loop". We further show that the membrane interacting region of Gc becomes structured only at acidic pH via a set of polar and electrostatic interactions. Furthermore, the structure reveals that hantavirus Gc has an additional N-terminal "tail" that is crucial in stabilizing the post-fusion trimer, accompanying the swapping of domain III in the quaternary arrangement of the trimer as compared to the standard class II fusion proteins. The mechanistic understandings derived from these data are likely to provide a unique handle for devising treatments against these human pathogens.

  2. A systemic gene silencing method suitable for high throughput, reverse genetic analyses of gene function in fern gametophytes

    Directory of Open Access Journals (Sweden)

    Tanurdzic Milos

    2004-04-01

    Full Text Available Abstract Background Ceratopteris richardii is a useful experimental system for studying gametophyte development and sexual reproduction in plants. However, few tools for cloning mutant genes or disrupting gene function exist for this species. The feasibility of systemic gene silencing as a reverse genetics tool was examined in this study. Results Several DNA constructs targeting a Ceratopteris protoporphyrin IX magnesium chelatase (CrChlI gene that is required for chlorophyll biosynthesis were each introduced into young gametophytes by biolistic delivery. Their transient expression in individual cells resulted in a colorless cell phenotype that affected most cells of the mature gametophyte, including the meristem and gametangia. The colorless phenotype was associated with a 7-fold decrease in the abundance of the endogenous transcript. While a construct designed to promote the transient expression of a CrChlI double stranded, potentially hairpin-forming RNA was found to be the most efficient in systemically silencing the endogenous gene, a plasmid containing the CrChlI cDNA insert alone was sufficient to induce silencing. Bombarded, colorless hermaphroditic gametophytes produced colorless embryos following self-fertilization, demonstrating that the silencing signal could be transmitted through gametogenesis and fertilization. Bombardment of young gametophytes with constructs targeting the Ceratopteris filamentous temperature sensitive (CrFtsZ and uroporphyrin dehydrogenase (CrUrod genes also produced the expected mutant phenotypes. Conclusion A method that induces the systemic silencing of target genes in the Ceratopteris gametophyte is described. It provides a simple, inexpensive and rapid means to test the functions of genes involved in gametophyte development, especially those involved in cellular processes common to all plants.

  3. Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function.

    Science.gov (United States)

    Chasman, Daniel I; Fuchsberger, Christian; Pattaro, Cristian; Teumer, Alexander; Böger, Carsten A; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Taliun, Daniel; Li, Man; Gao, Xiaoyi; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C; O'Seaghdha, Conall M; Glazer, Nicole; Isaacs, Aaron; Liu, Ching-Ti; Smith, Albert V; O'Connell, Jeffrey R; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Johnson, Andrew D; Gierman, Hinco J; Feitosa, Mary F; Hwang, Shih-Jen; Atkinson, Elizabeth J; Lohman, Kurt; Cornelis, Marilyn C; Johansson, Asa; Tönjes, Anke; Dehghan, Abbas; Lambert, Jean-Charles; Holliday, Elizabeth G; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y; Murgia, Federico; Trompet, Stella; Imboden, Medea; Coassin, Stefan; Pistis, Giorgio; Harris, Tamara B; Launer, Lenore J; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D; Boerwinkle, Eric; Schmidt, Helena; Cavalieri, Margherita; Rao, Madhumathi; Hu, Frank; Demirkan, Ayse; Oostra, Ben A; de Andrade, Mariza; Turner, Stephen T; Ding, Jingzhong; Andrews, Jeanette S; Freedman, Barry I; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Meisinger, Christa; Gieger, Christian; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G; Rivadeneira, Fernando; Aulchenko, Yurii S; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Ketkar, Shamika; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K; Portas, Laura; Ford, Ian; Buckley, Brendan M; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Kim, Stuart K; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J Wouter; Probst-Hensch, Nicole M; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Siscovick, David S; van Duijn, Cornelia M; Borecki, Ingrid B; Kardia, Sharon L R; Liu, Yongmei; Curhan, Gary C; Rudan, Igor; Gyllensten, Ulf; Wilson, James F; Franke, Andre; Pramstaller, Peter P; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M; Parsa, Afshin; Bochud, Murielle; Heid, Iris M; Kao, W H Linda; Fox, Caroline S; Köttgen, Anna

    2012-12-15

    In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P = 5.6 × 10(-9)) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 × 10(-4)-2.2 × 10(-7). Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general.

  4. Genomic and in Situ Analyses Reveal the Micropruina spp. as Abundant Fermentative Glycogen Accumulating Organisms in Enhanced Biological Phosphorus Removal Systems

    Directory of Open Access Journals (Sweden)

    Simon J. McIlroy

    2018-05-01

    Full Text Available Enhanced biological phosphorus removal (EBPR involves the cycling of biomass through carbon-rich (feast and carbon-deficient (famine conditions, promoting the activity of polyphosphate accumulating organisms (PAOs. However, several alternate metabolic strategies, without polyphosphate storage, are possessed by other organisms, which can compete with the PAO for carbon at the potential expense of EBPR efficiency. The most studied are the glycogen accumulating organisms (GAOs, which utilize aerobically stored glycogen to energize anaerobic substrate uptake and storage. In full-scale systems the Micropruina spp. are among the most abundant of the proposed GAO, yet little is known about their ecophysiology. In the current study, genomic and metabolomic studies were performed on Micropruina glycogenica str. Lg2T and compared to the in situ physiology of members of the genus in EBPR plants using state-of-the-art single cell techniques. The Micropruina spp. were observed to take up carbon, including sugars and amino acids, under anaerobic conditions, which were partly fermented to lactic acid, acetate, propionate, and ethanol, and partly stored as glycogen for potential aerobic use. Fermentation was not directly demonstrated for the abundant members of the genus in situ, but was strongly supported by the confirmation of anaerobic uptake of carbon and glycogen storage in the absence of detectable polyhydroxyalkanoates or polyphosphate reserves. This physiology is markedly different from the classical GAO model. The amount of carbon stored by fermentative organisms has potentially important implications for phosphorus removal – as they compete for substrates with the Tetrasphaera PAO and stored carbon is not made available to the “Candidatus Accumulibacter” PAO under anaerobic conditions. This study shows that the current models of the competition between PAO and GAO are too simplistic and may need to be revised to take into account the impact of

  5. Radiotoxicological analyses of {sup 239+240}Pu and {sup 241}Am in biological samples by anion-exchange and extraction chromatography: a preliminary study for internal contamination evaluations

    Energy Technology Data Exchange (ETDEWEB)

    Ridone, S.; Arginelli, D.; Bortoluzzi, S.; Canuto, G.; Montalto, M.; Nocente, M.; Vegro, M. [Italian National Agency for New Technologies, Energy and the Environment (ENEA), Research Centre of Saluggia, Radiation Protection Institute, Saluggia, VC (Italy)

    2006-07-01

    Many biological samples (urines and faeces) have been analysed by means of chromatographic extraction columns, utilising two different resins (AG 1-X2 resin chloride and T.R.U.), in order to detect the possible internal contamination of {sup 239{sup +}}{sup 240}Pu and {sup 241}Am, for some workers of a reprocessing nuclear plant in the decommissioning phase. The results obtained show on one hand the great suitability of the first resin for the determination of plutonium, and on the other the great selectivity of the second one for the determination of americium.

  6. A Tricky Trait: Applying the Fruits of the "Function Debate" in the Philosophy of Biology to the "Venom Debate" in the Science of Toxinology.

    Science.gov (United States)

    Jackson, Timothy N W; Fry, Bryan G

    2016-09-07

    The "function debate" in the philosophy of biology and the "venom debate" in the science of toxinology are conceptually related. Venom systems are complex multifunctional traits that have evolved independently numerous times throughout the animal kingdom. No single concept of function, amongst those popularly defended, appears adequate to describe these systems in all their evolutionary contexts and extant variations. As such, a pluralistic view of function, previously defended by some philosophers of biology, is most appropriate. Venom systems, like many other functional traits, exist in nature as points on a continuum and the boundaries between "venomous" and "non-venomous" species may not always be clearly defined. This paper includes a brief overview of the concept of function, followed by in-depth discussion of its application to venom systems. A sound understanding of function may aid in moving the venom debate forward. Similarly, consideration of a complex functional trait such as venom may be of interest to philosophers of biology.

  7. Changes in number and function of the lymphocyte populations as a biological indicator for ionizing radiation

    International Nuclear Information System (INIS)

    Dehos, A.; Hinz, G.; Schwarz, E.R.

    1986-01-01

    Siegal and Siegal reported that the number of immunoglobulin producing cells, especially after higher doses of ionizing radiation on isolated mononuclear cells decreases considerably. However, if non-irradiated B cells are cultivated with irradiated (16 Gy) T cells, a significant increase of immunoglobulin production due to the non-irradiated B cells can be observed. Siegal and Siegal described a similar result when they combined and cultivated non-irradiated with irradiated mononuclear cells. The immunoglobulin producing cells decreased in a lower and increased in a higher dose range. The two results can be explained by the fact that Tg cells which act as suppressor cells are relatively sensitive to radiation while Tm cells which are helper cells in this test are relatively resistant. According to these results, B lymphocytes are the most sensitive of the lymphocyte subpopulations. The aim of the project is to clarify whether the mentioned effects are suitable for 'biological dosimetry'. (orig./MG)

  8. synthesis and characterization of some poly functionalized heterocyclic derivatives of expected biological activity

    International Nuclear Information System (INIS)

    El-sayed, M.S.

    2001-01-01

    The present work was aimed and designed to fulfil The following objectives : 1- Continuation of the effort done by our research group in the field of chemistry of pyridinethione derivatives and their biological activities. 2- Synthesis of several new heterocyclic derivatives containing N and/or S using the laboratory available reagents. 3- Establishment of the structures of the newly synthesized heterocyclic compounds by the data of IR, 1 H-NMR, mass spectra in addition to the elemental analysis. 4- Synthesis of some of these heterocyclic derivatives via alternative routs and this used as a tool to confirm the structures of the newly synthesized heterocyclic derivatives. 5- study of the most probable mechanisms leading to the formation of the new heterocyclic derivatives. 6- The antimicrobial activity of some of the newly synthesized heterocyclic derivatives was tested against several types of organisms

  9. School belongingness and mental health functioning across the primary-secondary transition in a mainstream sample: multi-group cross-lagged analyses.

    Science.gov (United States)

    Vaz, Sharmila; Falkmer, Marita; Parsons, Richard; Passmore, Anne Elizabeth; Parkin, Timothy; Falkmer, Torbjörn

    2014-01-01

    The relationship between school belongingness and mental health functioning before and after the primary-secondary school transition has not been previously investigated in students with and without disabilities. This study used a prospective longitudinal design to test the bi-directional relationships between these constructs, by surveying 266 students with and without disabilities and their parents, 6-months before and after the transition to secondary school. Cross-lagged multi-group analyses found student perception of belongingness in the final year of primary school to contribute to change in their mental health functioning a year later. The beneficial longitudinal effects of school belongingness on subsequent mental health functioning were evident in all student subgroups; even after accounting for prior mental health scores and the cross-time stability in mental health functioning and school belongingness scores. Findings of the current study substantiate the role of school contextual influences on early adolescent mental health functioning. They highlight the importance for primary and secondary schools to assess students' school belongingness and mental health functioning and transfer these records as part of the transition process, so that appropriate scaffolds are in place to support those in need. Longer term longitudinal studies are needed to increase the understanding of the temporal sequencing between school belongingness and mental health functioning of all mainstream students.

  10. School Belongingness and Mental Health Functioning across the Primary-Secondary Transition in a Mainstream Sample: Multi-Group Cross-Lagged Analyses

    Science.gov (United States)

    Vaz, Sharmila; Falkmer, Marita; Parsons, Richard; Passmore, Anne Elizabeth; Parkin, Timothy; Falkmer, Torbjörn

    2014-01-01

    The relationship between school belongingness and mental health functioning before and after the primary-secondary school transition has not been previously investigated in students with and without disabilities. This study used a prospective longitudinal design to test the bi-directional relationships between these constructs, by surveying 266 students with and without disabilities and their parents, 6-months before and after the transition to secondary school. Cross-lagged multi-group analyses found student perception of belongingness in the final year of primary school to contribute to change in their mental health functioning a year later. The beneficial longitudinal effects of school belongingness on subsequent mental health functioning were evident in all student subgroups; even after accounting for prior mental health scores and the cross-time stability in mental health functioning and school belongingness scores. Findings of the current study substantiate the role of school contextual influences on early adolescent mental health functioning. They highlight the importance for primary and secondary schools to assess students’ school belongingness and mental health functioning and transfer these records as part of the transition process, so that appropriate scaffolds are in place to support those in need. Longer term longitudinal studies are needed to increase the understanding of the temporal sequencing between school belongingness and mental health functioning of all mainstream students. PMID:24967580

  11. School belongingness and mental health functioning across the primary-secondary transition in a mainstream sample: multi-group cross-lagged analyses.

    Directory of Open Access Journals (Sweden)

    Sharmila Vaz

    Full Text Available The relationship between school belongingness and mental health functioning before and after the primary-secondary school transition has not been previously investigated in students with and without disabilities. This study used a prospective longitudinal design to test the bi-directional relationships between these constructs, by surveying 266 students with and without disabilities and their parents, 6-months before and after the transition to secondary school. Cross-lagged multi-group analyses found student perception of belongingness in the final year of primary school to contribute to change in their mental health functioning a year later. The beneficial longitudinal effects of school belongingness on subsequent mental health functioning were evident in all student subgroups; even after accounting for prior mental health scores and the cross-time stability in mental health functioning and school belongingness scores. Findings of the current study substantiate the role of school contextual influences on early adolescent mental health functioning. They highlight the importance for primary and secondary schools to assess students' school belongingness and mental health functioning and transfer these records as part of the transition process, so that appropriate scaffolds are in place to support those in need. Longer term longitudinal studies are needed to increase the understanding of the temporal sequencing between school belongingness and mental health functioning of all mainstream students.

  12. Biological aspects and life table of Uroleucon ambrosiae (Thomas, 1878 as a function of temperature

    Directory of Open Access Journals (Sweden)

    Auad Alexander Machado

    2003-01-01

    Full Text Available The aphid Uroleucon ambrosiae (Thomas is considered a pest of hidroponically-grown lettuce, but basic and applied information on its control are scarce in Brazil. The aim of this study was to determine the effect of different temperatures on biological aspects and life history of U. ambrosiae (Thomas developing on hydroponic lettuce (Lactuca sativa L. crop. Newly emerged nymphs were placed on 4-cm discs of hydroponic lettuce, var. Verônica, which were maintained on 5-cm Petri dishes, at temperatures of 15, 20 and 25ºC and 14 h photophase, and inside a greenhouse, within micro-cages at room temperature. The duration of development in all nymphal stages varied inversely to temperature. Nymphs maintained at 20ºC and 25ºC, had similar development period. However, at fluctuating greenhouse temperatures (daily mean = 21ºC, different results were obtained, which was also true for the pre-reproductive, reproductive and post-reproductive periods. Daily and total fertilities at 20ºC were better in comparison to the other treatments. The highest mortality rate of aphids occurred under greenhouse conditions. The production of 1.28 nymphs per female per day, the time needed for the population to double in size (TD=2.77days, and the intrinsic rate of population increase (r m=0.25, were similar for in insects maintained at 20 and 25ºC. On the other hand, time interval between generations (T and the net reproductive rate (Ro were higher at 20ºC. In the greenhouse, even though T was similar to laboratory conditions at 20 and 25ºC, the R0, r m and l parameters were lower and TD was higher. Based on biological aspects, fertility and life expectancy tables, constant temperature of 20ºC is the most suitable for U. ambrosiae.

  13. Functional and modular analyses of diverse endoglucanases from Ruminococcus albus 8, a specialist plant cell wall degrading bacterium.

    Science.gov (United States)

    Iakiviak, Michael; Devendran, Saravanan; Skorupski, Anna; Moon, Young Hwan; Mackie, Roderick I; Cann, Isaac

    2016-07-21

    Ruminococcus albus 8 is a specialist plant cell wall degrading ruminal bacterium capable of utilizing hemicellulose and cellulose. Cellulose degradation requires a suite of enzymes including endoglucanases, exoglucanases, and β-glucosidases. The enzymes employed by R. albus 8 in degrading cellulose are yet to be completely elucidated. Through bioinformatic analysis of a draft genome sequence of R. albus 8, seventeen putatively cellulolytic genes were identified. The genes were heterologously expressed in E. coli, and purified to near homogeneity. On biochemical analysis with cellulosic substrates, seven of the gene products (Ra0185, Ra0259, Ra0325, Ra0903, Ra1831, Ra2461, and Ra2535) were identified as endoglucanases, releasing predominantly cellobiose and cellotriose. Each of the R. albus 8 endoglucanases, except for Ra0259 and Ra0325, bound to the model crystalline cellulose Avicel, confirming functional carbohydrate binding modules (CBMs). The polypeptides for Ra1831 and Ra2535 were found to contain distantly related homologs of CBM65. Mutational analysis of residues within the CBM65 of Ra1831 identified key residues required for binding. Phylogenetic analysis of the endoglucanases revealed three distinct subfamilies of glycoside hydrolase family 5 (GH5). Our results demonstrate that this fibrolytic bacterium uses diverse GH5 catalytic domains appended with different CBMs, including novel forms of CBM65, to degrade cellulose.

  14. Comparative genomic and functional analyses: unearthing the diversity and specificity of nematicidal factors in Pseudomonas putida strain 1A00316

    Science.gov (United States)

    Guo, Jing; Jing, Xueping; Peng, Wen-Lei; Nie, Qiyu; Zhai, Yile; Shao, Zongze; Zheng, Longyu; Cai, Minmin; Li, Guangyu; Zuo, Huaiyu; Zhang, Zhitao; Wang, Rui-Ru; Huang, Dian; Cheng, Wanli; Yu, Ziniu; Chen, Ling-Ling; Zhang, Jibin

    2016-01-01

    We isolated Pseudomonas putida (P. putida) strain 1A00316 from Antarctica. This bacterium has a high efficiency against Meloidogyne incognita (M. incognita) in vitro and under greenhouse conditions. The complete genome of P. putida 1A00316 was sequenced using PacBio single molecule real-time (SMRT) technology. A comparative genomic analysis of 16 Pseudomonas strains revealed that although P. putida 1A00316 belonged to P. putida, it was phenotypically more similar to nematicidal Pseudomonas fluorescens (P. fluorescens) strains. We characterized the diversity and specificity of nematicidal factors in P. putida 1A00316 with comparative genomics and functional analysis, and found that P. putida 1A00316 has diverse nematicidal factors including protein alkaline metalloproteinase AprA and two secondary metabolites, hydrogen cyanide and cyclo-(l-isoleucyl-l-proline). We show for the first time that cyclo-(l-isoleucyl-l-proline) exhibit nematicidal activity in P. putida. Interestingly, our study had not detected common nematicidal factors such as 2,4-diacetylphloroglucinol (2,4-DAPG) and pyrrolnitrin in P. putida 1A00316. The results of the present study reveal the diversity and specificity of nematicidal factors in P. putida strain 1A00316. PMID:27384076

  15. Resurrecting Brinley Plots for a Novel Use: Meta-Analyses of Functional Brain Imaging Data in Older Adults

    Directory of Open Access Journals (Sweden)

    Ann M. Peiffer

    2008-01-01

    Full Text Available By plotting response times of young and older adults across a variety of tasks, Brinley spurred investigation and debate into the theory of general cognitive slowing. Though controversial, Brinley plots can assess between-task differences, the impact of increasing task demand, and the relationship between responses in two groups of subjects. Since a relationship exists between response times and the blood-oxygen level dependent (BOLD signal of functional MRI (fMRI, Brinley's plotting method could be applied as a meta-analysis tool in fMRI studies of aging. Here, fledgling “Peiffer plots” are discussed for their potential impact on understanding general cognitive brain activity in aging. Preliminary results suggest that general cognitive slowing may be localized at the sensorimotor transformation in the precentral gyrus. Although this meta-analysis method is naturally used with imaging studies of aging, theoretically it may be applied to other study pairs (e.g., schizophrenic versus normal or imaging datasets (e.g., PET.

  16. Genome-Wide Comparative Functional Analyses Reveal Adaptations of Salmonella sv. Newport to a Plant Colonization Lifestyle

    Directory of Open Access Journals (Sweden)

    Marcos H. de Moraes

    2018-05-01

    Full Text Available Outbreaks of salmonellosis linked to the consumption of vegetables have been disproportionately associated with strains of serovar Newport. We tested the hypothesis that strains of sv. Newport have evolved unique adaptations to persistence in plants that are not shared by strains of other Salmonella serovars. We used a genome-wide mutant screen to compare growth in tomato fruit of a sv. Newport strain from an outbreak traced to tomatoes, and a sv. Typhimurium strain from animals. Most genes in the sv. Newport strain that were selected during persistence in tomatoes were shared with, and similarly selected in, the sv. Typhimurium strain. Many of their functions are linked to central metabolism, including amino acid biosynthetic pathways, iron acquisition, and maintenance of cell structure. One exception was a greater need for the core genes involved in purine metabolism in sv. Typhimurium than in sv. Newport. We discovered a gene, papA, that was unique to sv. Newport and contributed to the strain’s fitness in tomatoes. The papA gene was present in about 25% of sv. Newport Group III genomes and generally absent from other Salmonella genomes. Homologs of papA were detected in the genomes of Pantoea, Dickeya, and Pectobacterium, members of the Enterobacteriacea family that can colonize both plants and animals.

  17. Differential CLE peptide perception by plant receptors implicated from structural and functional analyses of TDIF-TDR interactions

    Energy Technology Data Exchange (ETDEWEB)

    Li, Zhijie; Chakraborty, Sayan; Xu, Guozhou; Kobe, Bostjan

    2017-04-06

    Tracheary Element Differentiation Inhibitory Factor (TDIF) belongs to the family of post-translationally modified CLE (CLAVATA3/embryo surrounding region (ESR)-related) peptide hormones that control root growth and define the delicate balance between stem cell proliferation and differentiation in SAM (shoot apical meristem) or RAM (root apical meristem). In Arabidopsis, Tracheary Element Differentiation Inhibitory Factor Receptor (TDR) and its ligand TDIF signaling pathway is involved in the regulation of procambial cell proliferation and inhibiting its differentiation into xylem cells. Here we present the crystal structures of the extracellular domains (ECD) of TDR alone and in complex with its ligand TDIF resolved at 2.65 Åand 2.75 Å respectively. These structures provide insights about the ligand perception and specific interactions between the CLE peptides and their cognate receptors. Our in vitro biochemical studies indicate that the interactions between the ligands and the receptors at the C-terminal anchoring site provide conserved binding. While the binding interactions occurring at the N-terminal anchoring site dictate differential binding specificities between different ligands and receptors. Our studies will open different unknown avenues of TDR-TDIF signaling pathways that will enhance our knowledge in this field highlighting the receptor ligand interaction, receptor activation, signaling network, modes of action and will serve as a structure function relationship model between the ligand and the receptor for various similar leucine-rich repeat receptor-like kinases (LRR-RLKs).

  18. Functional and genomic analyses of FOXP3-transduced Jurkat-T cells as regulatory T (Treg)-like cells

    International Nuclear Information System (INIS)

    Kim, Joon-Young; Kim, Han-Jong; Hurt, Elaine M.; Chen, Xin; Howard, O.M. Zack; Farrar, William L.

    2007-01-01

    FOXP3, a forkhead transcription factor is essential for the development and function of CD4 + CD25 + regulatory T cells (Tregs). In contrast to conversion of murine naive T cells to Tregs by transduction of Foxp3, it is controversial whether ectopic expression of FOXP3 in human CD4 + T cells is sufficient for acquisition of suppressive activity. Here, we show that retroviral transduction of FOXP3 induces a Treg phenotype in human leukemic CD4 + Jurkat-T cells, evidenced by increased expression of Treg-associated cell surface markers as well as inhibition of cytokine production. Furthermore, FOXP3-transduced Jurkat-T cells suppress the proliferation of human CD4 + CD25 - T cells. Additionally, DNA microarray analysis identifies Treg-related genes regulated by FOXP3. Our study demonstrates that enforced expression of FOXP3 confers Treg-like properties on Jurkat-T cells, which can be a convenient and efficient Treg-like cell model for further study to identify Treg cell surface markers and target genes regulated by FOXP3

  19. Trends in IT Innovation to Build a Next Generation Bioinformatics Solution to Manage and Analyse Biological Big Data Produced by NGS Technologies

    Directory of Open Access Journals (Sweden)

    Alexandre G. de Brevern

    2015-01-01

    Full Text Available Sequencing the human genome began in 1994, and 10 years of work were necessary in order to provide a nearly complete sequence. Nowadays, NGS technologies allow sequencing of a whole human genome in a few days. This deluge of data challenges scientists in many ways, as they are faced with data management issues and analysis and visualization drawbacks due to the limitations of current bioinformatics tools. In this paper, we describe how the NGS Big Data revolution changes the way of managing and analysing data. We present how biologists are confronted with abundance of methods, tools, and data formats. To overcome these problems, focus on Big Data Information Technology innovations from web and business intelligence. We underline the interest of NoSQL databases, which are much more efficient than relational databases. Since Big Data leads to the loss of interactivity with data during analysis due to high processing time, we describe solutions from the Business Intelligence that allow one to regain interactivity whatever the volume of data is. We illustrate this point with a focus on the Amadea platform. Finally, we discuss visualization challenges posed by Big Data and present the latest innovations with JavaScript graphic libraries.

  20. Trends in IT Innovation to Build a Next Generation Bioinformatics Solution to Manage and Analyse Biological Big Data Produced by NGS Technologies

    Science.gov (United States)

    de Brevern, Alexandre G.; Meyniel, Jean-Philippe; Fairhead, Cécile; Neuvéglise, Cécile; Malpertuy, Alain

    2015-01-01

    Sequencing the human genome began in 1994, and 10 years of work were necessary in order to provide a nearly complete sequence. Nowadays, NGS technologies allow sequencing of a whole human genome in a few days. This deluge of data challenges scientists in many ways, as they are faced with data management issues and analysis and visualization drawbacks due to the limitations of current bioinformatics tools. In this paper, we describe how the NGS Big Data revolution changes the way of managing and analysing data. We present how biologists are confronted with abundance of methods, tools, and data formats. To overcome these problems, focus on Big Data Information Technology innovations from web and business intelligence. We underline the interest of NoSQL databases, which are much more efficient than relational databases. Since Big Data leads to the loss of interactivity with data during analysis due to high processing time, we describe solutions from the Business Intelligence that allow one to regain interactivity whatever the volume of data is. We illustrate this point with a focus on the Amadea platform. Finally, we discuss visualization challenges posed by Big Data and present the latest innovations with JavaScript graphic libraries. PMID:26125026

  1. Trends in IT Innovation to Build a Next Generation Bioinformatics Solution to Manage and Analyse Biological Big Data Produced by NGS Technologies.

    Science.gov (United States)

    de Brevern, Alexandre G; Meyniel, Jean-Philippe; Fairhead, Cécile; Neuvéglise, Cécile; Malpertuy, Alain

    2015-01-01

    Sequencing the human genome began in 1994, and 10 years of work were necessary in order to provide a nearly complete sequence. Nowadays, NGS technologies allow sequencing of a whole human genome in a few days. This deluge of data challenges scientists in many ways, as they are faced with data management issues and analysis and visualization drawbacks due to the limitations of current bioinformatics tools. In this paper, we describe how the NGS Big Data revolution changes the way of managing and analysing data. We present how biologists are confronted with abundance of methods, tools, and data formats. To overcome these problems, focus on Big Data Information Technology innovations from web and business intelligence. We underline the interest of NoSQL databases, which are much more efficient than relational databases. Since Big Data leads to the loss of interactivity with data during analysis due to high processing time, we describe solutions from the Business Intelligence that allow one to regain interactivity whatever the volume of data is. We illustrate this point with a focus on the Amadea platform. Finally, we discuss visualization challenges posed by Big Data and present the latest innovations with JavaScript graphic libraries.

  2. Ruminant Metabolic Systems Biology: Reconstruction and Integration of Transcriptome Dynamics Underlying Functional Responses of Tissues to Nutrition and Physiological Statea

    Science.gov (United States)

    Bionaz, Massimo; Loor, Juan J.

    2012-01-01

    High-throughput ‘omics’ data analysis via bioinformatics is one key component of the systems biology approach. The systems approach is particularly well-suited for the study of the interactions between nutrition and physiological state with tissue metabolism and functions during key life stages of organisms such as the transition from pregnancy to lactation in mammals, ie, the peripartal period. In modern dairy cows with an unprecedented genetic potential for milk synthesis, the nature of the physiologic and metabolic adaptations during the peripartal period is multifaceted and involves key tissues such as liver, adipose, and mammary. In order to understand such adaptation, we have reviewed several works performed in our and other labs. In addition, we have used a novel bioinformatics approach, Dynamic Impact Approach (DIA), in combination with partly previously published data to help interpret longitudinal biological adaptations of bovine liver, adipose, and mammary tissue to lactation using transcriptomics datasets. Use of DIA with transcriptomic data from those tissues during normal physiological adaptations and in animals fed different levels of energy prepartum allowed visualization and integration of most-impacted metabolic pathways around the time of parturition. The DIA is a suitable tool for applying the integrative systems biology approach. The ultimate goal is to visualize the complexity of the systems at study and uncover key molecular players involved in the tissue’s adaptations to physiological state or nutrition. PMID:22807626

  3. [The Functional Role of Exosomes in Cancer Biology and Their Potential as Biomarkers and Therapeutic Targets of Cancer].

    Science.gov (United States)

    Naito, Yutaka; Yoshioka, Yusuke; Ochiya, Takahiro

    2015-06-01

    Intercellular communication plays an important role in the regulation of various cellular events. In particular, cancer cells and the surrounding cells communicate with each other, and this intercellular communication triggers cancer initiation and progression through the secretion of molecules, including growth factors and cytokines. Recent advances in cancer biology have indicated that small membrane vesicles, termed exosomes, also serve as regulatory agents in intercellular communications. Exosomes contain functional cellular components, including proteins and microRNAs (miRNAs), and they transfer these components to recipient cells. This exosome-mediated intercellular communication leads to increased growth, invasion, and metastasis of cancer. Thus, researchers regard exosomes as important cues to understanding the molecular mechanisms of cancer biology. Indeed, several lines of evidence have demonstrated that exosomes can explain multiple aspects of cancer biology. In addition, increasing evidence suggests that exosomes and their specific molecules are also attractive for use as biomarkers and therapeutic targets in cancer. Recent reports showed the efficacy of a novel diagnosis by detecting component molecules of cancer-derived exosomes, including miRNAs and membrane proteins. Furthermore, clinical trials that test the application of exosomes for cancer therapy have already been reported. From these points of view, we will summarize experimental data that support the role of exosomes in cancer progression and the potential of exosomes for use in novel diagnostic and therapeutic approaches for cancer.

  4. Nerve Regeneration: Understanding Biology and Its Influence on Return of Function After Nerve Transfers.

    Science.gov (United States)

    Gordon, Tessa

    2016-05-01

    Poor functional outcomes are frequent after peripheral nerve injuries despite the regenerative support of Schwann cells. Motoneurons and, to a lesser extent, sensory neurons survive the injuries but outgrowth of axons across the injury site is slow. The neuronal regenerative capacity and the support of regenerating axons by the chronically denervated Schwann cells progressively declines with time and distance of the injury from the denervated targets. Strategies, including brief low-frequency electrical stimulation that accelerates target reinnervation and functional recovery, and the insertion of cross-bridges between a donor nerve and a recipient denervated nerve stump, are effective in promoting functional outcomes after complete and incomplete injuries. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. [Scientific bases for the development of functional meat products with combined biological activity].

    Science.gov (United States)

    Palanca, V; Rodríguez, E; Señoráns, J; Reglero, G

    2006-01-01

    The scientific evidences on the relationship between food and health have given place to a new food market of rapid growth in the last years: the market of the functional food. Though the interest of maintaining or improving the state of health by means of the consumption of traditional food with bioactive ingredients added is undoubtedly high, the Spanish population, increasingly formed and informed, is unwilling to consume functional food, until these possess a scientific rigorous base. This article presents a review of the scientific bases that support the development of functional meat products with balanced ratio omega-6/omega-3 and a combination of synergic antioxidants, among them an extract of rosemary obtained by means of extraction with supercritical CO2.

  6. New MRI technologies. Diffusion MRI and its application to functional neuroimaging and analyses of white matter integrity

    International Nuclear Information System (INIS)

    Kobayashi, Tetsuo

    2010-01-01

    Described is the technological aspect of MRI, MR diffusion-weighted imaging (MR-DWI), principles of its measurement and application for imaging the cerebral function and for aiding the quantitative diagnosis of brain diseases. The author explains the principle of MR imaging process; diffusion properties of water molecules, MR-DWI based on them and DW-fMRI of the brain; MR-diffusion tensor imaging (MR-DTI), its analysis and color acquisition, and tracking of white matter nerve fibers; analysis of white matter lesions by the tracking; and the new tracking method at the chiasm of nerve fascicles. The usual fMRI reflects the blood oxygen level depending (BOLD) signals whereas recently attracted DW-fMRI, the volume changes of nerve cells concomitant to nerve activation accompanying apparent changes of water diffusion coefficients in and out of cells which occur faster than BOLD signs, resulting in higher resolution of time and space. However, DWI requires the higher intensity of static magnetic field like 3T. MR-DTI acquires the anisotropic diffusion of water molecules using MR-DWI technique with application of 6 or more motion probing gradients, thus makes it possible to track the running directions of nerve fibers and capillary vessels, and is proposed to be a useful mean of specific fiber tracking in the white matter when displayed by 3 different colors exhibiting the directions like the right/left (x axis, red), anterior/posterior (y, green) and upper/lower (z, blue) sides of head. Recently, MR-DWI and MR-DTI have been found usable for pathogenic studies of brain diseases such as dementia. Tensor anisotropy is apparently lowered at the chiasm of nerve fascicles, the cause of tracking error, for which authors have developed a new method using the similarity of directional vector, not of tensor, before and behind the chiasm. As exemplified, MRI technology is further advancing even at present. (T.T.)

  7. Analyses of functions of an anti-PD-L1/TGFβR2 bispecific fusion protein (M7824).

    Science.gov (United States)

    Jochems, Caroline; Tritsch, Sarah R; Pellom, Samuel Troy; Su, Zhen; Soon-Shiong, Patrick; Wong, Hing C; Gulley, James L; Schlom, Jeffrey

    2017-09-26

    M7824 (MSB0011359C) is a novel first-in-class bifunctional fusion protein consisting of a fully human IgG1 anti-PD-L1 monoclonal antibody (with structural similarities to avelumab) linked to the extracellular domain of two TGFβ receptor 2 (TGFβR2) molecules serving as a TGFβ Trap. Avelumab has demonstrated clinical activity in a range of human cancers and has been approved by the Food and Drug Administration for the therapy of Merkel cell and bladder carcinomas. Preclinical studies have shown this anti-PD-L1 is capable of mediating antibody-dependent cell-mediated cytotoxicity (ADCC). In the studies reported here, it is shown that M7824 is also capable of mediating ADCC of a wide range of human carcinoma cells in vitro , employing natural killer (NK) cells as effectors, albeit not as potent as anti-PD-L1 employing some tumor cells as targets. The addition of the IL-15 superagonist fusion protein complex ALT-803 enhanced the ADCC capacity of both anti-PD-L1 and M7824, and to levels that both agents now demonstrated similar levels of ADCC of tumor cells. TGFβ is a known immunosuppressive entity. Studies reported here show TGFβ1 induced reduction of several NK activation markers as well as reduction of endogenous NK lytic activity and NK-mediated ADCC of tumor cells. These phenomena could be reduced or mitigated, however, by M7824, but not by anti-PD-L1. M7824, but not anti-PD-L1, was also shown to reduce the immunosuppressive activity of regulatory T cells on human CD4 + T-cell proliferation. These studies thus demonstrate the dual functionalities of M7824 and provide the rationale for its further clinical development.

  8. Analyses of the influencing factors of soil microbial functional gene diversity in tropical rainforest based on GeoChip 5.0

    Directory of Open Access Journals (Sweden)

    Jing Cong

    2015-09-01

    Full Text Available To examine soil microbial functional gene diversity and causative factors in tropical rainforests, we used a microarray-based metagenomic tool named GeoChip 5.0 to profile it. We found that high microbial functional gene diversity and different soil microbial metabolic potential for biogeochemical processes were considered to exist in tropical rainforest. Soil available nitrogen was the most associated with soil microbial functional gene structure. Here, we mainly describe the experiment design, the data processing, and soil biogeochemical analyses attached to the study in details, which could be published on BMC microbiology Journal in 2015, whose raw data have been deposited in NCBI's Gene Expression Omnibus (accession number GSE69171.

  9. The fine-grained metaphysics of artifactual and biological functional kinds

    NARCIS (Netherlands)

    Carrara, M.; Vermaas, P.E.

    2008-01-01

    In this paper we consider the emerging position in metaphysics that artifact functions characterize real kinds of artifacts. We analyze how it can circumvent an objection by David Wiggins (Sameness and substance renewed, 2001, 87) and then argue that this position, in comparison to expert judgments,

  10. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer.

    Science.gov (United States)

    Fasano, Alessio

    2011-01-01

    The primary functions of the gastrointestinal tract have traditionally been perceived to be limited to the digestion and absorption of nutrients and to electrolytes and water homeostasis. A more attentive analysis of the anatomic and functional arrangement of the gastrointestinal tract, however, suggests that another extremely important function of this organ is its ability to regulate the trafficking of macromolecules between the environment and the host through a barrier mechanism. Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self antigens. Zonulin is the only physiological modulator of intercellular tight junctions described so far that is involved in trafficking of macromolecules and, therefore, in tolerance/immune response balance. When the finely tuned zonulin pathway is deregulated in genetically susceptible individuals, both intestinal and extraintestinal autoimmune, inflammatory, and neoplastic disorders can occur. This new paradigm subverts traditional theories underlying the development of these diseases and suggests that these processes can be arrested if the interplay between genes and environmental triggers is prevented by reestablishing the zonulin-dependent intestinal barrier function. This review is timely given the increased interest in the role of a "leaky gut" in the pathogenesis of several pathological conditions targeting both the intestine and extraintestinal organs.

  11. Phenotypic and functional analyses of NK and NKT-like populations during the early stages of chikungunya infection.

    Science.gov (United States)

    Thanapati, Subrat; Das, Rumki; Tripathy, Anuradha S

    2015-01-01

    The aim of this study was to characterize NK (CD56(+)CD3(-)) and NKT-like cell (CD56(+)CD3(+)) responses early after chikungunya infection. Expression profiling and functional analysis of T/NK/NKT-like cells were performed on samples from 56 acute and 31 convalescent chikungunya patients and 56 control individuals. The percentages of NK cells were high in both patient groups, whereas NKT-like cell percentages were high only in the convalescent group. The percentages of NKp30(+)CD3(-)CD56(+), NKp30(+)CD3(+)CD56(+), CD244(+)CD3(-)CD56(+), and CD244(+)CD3(+)CD56(+)cells were high, whereas the percentages of NKG2D(+)CD3(-)CD56(+) and NKG2D(+)CD3(+)CD56(+)cells were low in both patient groups. The percentages of NKp44(+)CD3(-)CD56(+) cells were high in both patient groups, whereas the percentages of NKp44(+)CD3(+)CD56(+) cells were higher in the acute group than in convalescent and control groups. The percentages of NKp46(+)CD3(-)CD56(+) cells were high in both patient groups. Higher percentages of perforin(+)CD3(-)CD56(+) and perforin(+)CD3(+)CD56(+) cells were observed in acute and convalescent patients, respectively. Higher cytotoxic activity was observed in acute patients than in controls. IFN-γ expression on NK cells of convalescent patients and on NKT-like cells of both patient groups was indicative of the regulatory role of NK and NKT-like cells. Collectively, these data showed that higher expression of activating receptors on NK/NKT-like cells and perforin(+) NK cells in acute patients could be responsible for increased cytotoxicity. The observed expression of perforin(+) NK cells in the acute phase and IFN-γ(+) NKT-like cells in the subsequent convalescent stage showed that NK/NKT-like cells mount an early and efficient response to chikungunya virus. Further study of the molecular mechanisms that limit viral dissemination/establishment of chronic disease will aid in understanding how NK/NKT-like cells control chikungunya infection.

  12. The dimer interface of the membrane type 1 matrix metalloproteinase hemopexin domain: crystal structure and biological functions.

    Science.gov (United States)

    Tochowicz, Anna; Goettig, Peter; Evans, Richard; Visse, Robert; Shitomi, Yasuyuki; Palmisano, Ralf; Ito, Noriko; Richter, Klaus; Maskos, Klaus; Franke, Daniel; Svergun, Dmitri; Nagase, Hideaki; Bode, Wolfram; Itoh, Yoshifumi

    2011-03-04

    Homodimerization is an essential step for membrane type 1 matrix metalloproteinase (MT1-MMP) to activate proMMP-2 and to degrade collagen on the cell surface. To uncover the molecular basis of the hemopexin (Hpx) domain-driven dimerization of MT1-MMP, a crystal structure of the Hpx domain was solved at 1.7 Å resolution. Two interactions were identified as potential biological dimer interfaces in the crystal structure, and mutagenesis studies revealed that the biological dimer possesses a symmetrical interaction where blades II and III of molecule A interact with blades III and II of molecule B. The mutations of amino acids involved in the interaction weakened the dimer interaction of Hpx domains in solution, and incorporation of these mutations into the full-length enzyme significantly inhibited dimer-dependent functions on the cell surface, including proMMP-2 activation, collagen degradation, and invasion into the three-dimensional collagen matrix, whereas dimer-independent functions, including gelatin film degradation and two-dimensional cell migration, were not affected. These results shed light on the structural basis of MT1-MMP dimerization that is crucial to promote cellular invasion.

  13. The EBI Search engine: providing search and retrieval functionality for biological data from EMBL-EBI.

    Science.gov (United States)

    Squizzato, Silvano; Park, Young Mi; Buso, Nicola; Gur, Tamer; Cowley, Andrew; Li, Weizhong; Uludag, Mahmut; Pundir, Sangya; Cham, Jennifer A; McWilliam, Hamish; Lopez, Rodrigo

    2015-07-01

    The European Bioinformatics Institute (EMBL-EBI-https://www.ebi.ac.uk) provides free and unrestricted access to data across all major areas of biology and biomedicine. Searching and extracting knowledge across these domains requires a fast and scalable solution that addresses the requirements of domain experts as well as casual users. We present the EBI Search engine, referred to here as 'EBI Search', an easy-to-use fast text search and indexing system with powerful data navigation and retrieval capabilities. API integration provides access to analytical tools, allowing users to further investigate the results of their search. The interconnectivity that exists between data resources at EMBL-EBI provides easy, quick and precise navigation and a better understanding of the relationship between different data types including sequences, genes, gene products, proteins, protein domains, protein families, enzymes and macromolecular structures, together with relevant life science literature. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  14. Using synthetic biology to distinguish and overcome regulatory and functional barriers related to nitrogen fixation.

    Directory of Open Access Journals (Sweden)

    Xia Wang

    Full Text Available Biological nitrogen fixation is a complex process requiring multiple genes working in concert. To date, the Klebsiella pneumoniae nif gene cluster, divided into seven operons, is one of the most studied systems. Its nitrogen fixation capacity is subject to complex cascade regulation and physiological limitations. In this report, the entire K. pneumoniae nif gene cluster was reassembled as operon-based BioBrick parts in Escherichia coli. It provided ~100% activity of native K. pneumoniae system. Based on the expression levels of these BioBrick parts, a T7 RNA polymerase-LacI expression system was used to replace the σ(54-dependent promoters located upstream of nif operons. Expression patterns of nif operons were critical for the maximum activity of the recombinant system. By mimicking these expression levels with variable-strength T7-dependent promoters, ~42% of the nitrogenase activity of the σ(54-dependent nif system was achieved in E. coli. When the newly constructed T7-dependent nif system was challenged with different genetic and physiological conditions, it bypassed the original complex regulatory circuits, with minor physiological limitations. Therefore, we have successfully replaced the nif regulatory elements with a simple expression system that may provide the first step for further research of introducing nif genes into eukaryotic organelles, which has considerable potentials in agro-biotechnology.

  15. Covariance Association Test (CVAT) Identifies Genetic Markers Associated with Schizophrenia in Functionally Associated Biological Processes.

    Science.gov (United States)

    Rohde, Palle Duun; Demontis, Ditte; Cuyabano, Beatriz Castro Dias; Børglum, Anders D; Sørensen, Peter

    2016-08-01

    Schizophrenia is a psychiatric disorder with large personal and social costs, and understanding the genetic etiology is important. Such knowledge can be obtained by testing the association between a disease phenotype and individual genetic markers; however, such single-marker methods have limited power to detect genetic markers with small effects. Instead, aggregating genetic markers based on biological information might increase the power to identify sets of genetic markers of etiological significance. Several set test methods have been proposed: Here we propose a new set test derived from genomic best linear unbiased prediction (GBLUP), the covariance association test (CVAT). We compared the performance of CVAT to other commonly used set tests. The comparison was conducted using a simulated study population having the same genetic parameters as for schizophrenia. We found that CVAT was among the top performers. When extending CVAT to utilize a mixture of SNP effects, we found an increase in power to detect the causal sets. Applying the methods to a Danish schizophrenia case-control data set, we found genomic evidence for association of schizophrenia with vitamin A metabolism and immunological responses, which previously have been implicated with schizophrenia based on experimental and observational studies. Copyright © 2016 by the Genetics Society of America.

  16. Ecology and functional roles of biological soil crusts in semi-arid ecosystems of Spain

    Science.gov (United States)