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Sample records for pa-08-098 functional links

  1. A linked electron pair functional.

    PubMed

    Knowles, Peter J; Cooper, Bridgette

    2010-12-14

    A modification of the variational configuration interaction functional in the first-order interacting space for molecular electronic structure is presented. The modified functional is a fully linked expression that by construction is extensive and invariant to transformations of the underlying orbital basis and is exact for an ensemble of separated two-electron subsystems. In addition, an approximation to variational coupled cluster is generated through truncation of the exponential cluster operator. When combined, these methods demonstrate accuracy that exceeds that of the standard coupled-cluster method, in particular in situations where the reference Slater determinant is not a good approximation. PMID:21171682

  2. Linking plant and ecosystem functional biogeography

    PubMed Central

    Reichstein, Markus; Bahn, Michael; Mahecha, Miguel D.; Kattge, Jens; Baldocchi, Dennis D.

    2014-01-01

    Classical biogeographical observations suggest that ecosystems are strongly shaped by climatic constraints in terms of their structure and function. On the other hand, vegetation function feeds back on the climate system via biosphere–atmosphere exchange of matter and energy. Ecosystem-level observations of this exchange reveal very large functional biogeographical variation of climate-relevant ecosystem functional properties related to carbon and water cycles. This variation is explained insufficiently by climate control and a classical plant functional type classification approach. For example, correlations between seasonal carbon-use efficiency and climate or environmental variables remain below 0.6, leaving almost 70% of variance unexplained. We suggest that a substantial part of this unexplained variation of ecosystem functional properties is related to variations in plant and microbial traits. Therefore, to progress with global functional biogeography, we should seek to understand the link between organismic traits and flux-derived ecosystem properties at ecosystem observation sites and the spatial variation of vegetation traits given geoecological covariates. This understanding can be fostered by synergistic use of both data-driven and theory-driven ecological as well as biophysical approaches. PMID:25225392

  3. Small-Sample Equating Using a Synthetic Linking Function

    ERIC Educational Resources Information Center

    Kim, Sooyeon; von Davier, Alina A.; Haberman, Shelby

    2008-01-01

    This study addressed the sampling error and linking bias that occur with small samples in a nonequivalent groups anchor test design. We proposed a linking method called the synthetic function, which is a weighted average of the identity function and a traditional equating function (in this case, the chained linear equating function). Specifically,…

  4. Linking Long Noncoding RNA Localization and Function.

    PubMed

    Chen, Ling-Ling

    2016-09-01

    Recent studies have revealed the regulatory potential of many long noncoding RNAs (lncRNAs). Most lncRNAs, like mRNAs, are transcribed by RNA polymerase II and are capped, polyadenylated, and spliced. However, the subcellular fates of lncRNAs are distinct and the mechanisms of action are diverse. Investigating the mechanisms that determine the subcellular fate of lncRNAs has the potential to provide new insights into their biogenesis and specialized functions. PMID:27499234

  5. Introduction: Links between Social Interaction and Executive Function

    ERIC Educational Resources Information Center

    Lewis, Charlie; Carpendale, Jeremy I. M.

    2009-01-01

    The term executive function is used increasingly within developmental psychology and is often taken to refer to unfolding brain processes. We trace the origins of research on executive function to show that the link with social interaction has a long history. We suggest that a recent frenzy of research exploring methods for studying individual…

  6. The scientific process--its links, functions and problems.

    PubMed

    Kinne, O

    1988-06-01

    The scientific process comprises production, quality control, dissemination, and consumption of knowledge. Its links are represented by author, editor and referees, publisher, and user. The basic units of the scientific process are research articles, the basic substrate learned journals. The formalized scientific process provides the foundation for orderly worldwide public communication among scientists and for establishing priority in scientific findings and ideas. The functions and problems of the author-editor, editor-publisher and publisher-user connections are outlined and discussed, and suggestions are offered for reducing potentially detrimental effects of diverging link interests. PMID:3205308

  7. From Elements to Metabolism: Linking Organismal Stoichiometry to Ecosystem Function

    NASA Astrophysics Data System (ADS)

    Cohen, M. J.; Nifong, R. L.

    2014-12-01

    Metabolism is an integrative metric of ecosystem function and energetics, synthesizing the relative contributions of multiple inputs, processes, and interactions. Stoichiometry is a framework based on elemental ratios for understanding how organisms interact within ecosystems. Linking the two has the potential to yield fresh insight about how ecosystems utilize elements and energy. We sought to quantify the link between the stoichiometry of ecosystem metabolism, specifically the C:N:P ratios of integrated autotrophic assimilation, and the stoichiometric tissue ratios observed in the dominant autotrophs. Using high frequency in situ nutrient sensors we estimated the assimilatory fluxes of C, N, and P in multiple spring-fed rivers of varying autotrophic species composition. We measured autotroph cover in each spring river, collected composite vegetation samples, and evaluated tissue stoichiometry; as expected, we observed large differences in C:N and N:P between algal and vascular plant taxa. We observed associations between measured tissue stoichiometry and elemental ratios at the ecosystem scale, suggesting that aggregated assimilatory fluxes may be useful for partitioning primary production and linking organismal nutrient content to the stoichiometry of ecosystem metabolism.

  8. Herbivorous fishes, ecosystem function and mobile links on coral reefs

    NASA Astrophysics Data System (ADS)

    Welsh, J. Q.; Bellwood, D. R.

    2014-06-01

    Understanding large-scale movement of ecologically important taxa is key to both species and ecosystem management. Those species responsible for maintaining functional connectivity between habitats are often called mobile links and are regarded as essential elements of resilience. By providing connectivity, they support resilience across spatial scales. Most marine organisms, including fishes, have long-term, biogeographic-scale connectivity through larval movement. Although most reef species are highly site attached after larval settlement, some taxa may also be able to provide rapid, reef-scale connectivity as adults. On coral reefs, the identity of such taxa and the extent of their mobility are not yet known. We use acoustic telemetry to monitor the movements of Kyphosus vaigiensis, one of the few reef fishes that feeds on adult brown macroalgae. Unlike other benthic herbivorous fish species, it also exhibits large-scale (>2 km) movements. Individual K. vaigiensis cover, on average, a 2.5 km length of reef (11 km maximum) each day. These large-scale movements suggest that this species may act as a mobile link, providing functional connectivity, should the need arise, and helping to support functional processes across habitats and spatial scales. An analysis of published studies of home ranges in reef fishes found a consistent relationship between home range size and body length. K. vaigiensis is the sole herbivore to depart significantly from the expected home range-body size relationship, with home range sizes more comparable to exceptionally mobile large pelagic predators rather than other reef herbivores. While the large-scale movements of K. vaigiensis reveal its potential capacity to enhance resilience over large areas, it also emphasizes the potential limitations of small marine reserves to protect some herbivore populations.

  9. Spatial Colocalization and Functional Link of Purinosomes with Mitochondria

    PubMed Central

    French, Jarrod B.; Jones, Sara A.; Deng, Huayun; Pedley, Anthony M.; Kim, Doory; Chan, Chung Yu; Hu, Haibei; Pugh, Raymond J.; Zhao, Hong; Zhang, Youxin; Huang, Tony Jun; Fang, Ye; Zhuang, Xiaowei; Benkovic, Stephen J.

    2016-01-01

    Purine biosynthetic enzymes organize into dynamic cellular bodies called purinosomes. Little is known about the spatiotemporal control of these structures. Using super-resolution microscopy, we demonstrated that purinosomes colocalized with mitochondria, and these results were supported by isolation of purinosome enzymes with mitochondria. Moreover, the number of purinosome containing cells responded to dysregulation of mitochondrial function and metabolism. To explore the role of intracellular signaling, we performed a kinome screen using a label-free assay and identified that mTOR influenced purinosome assembly. mTOR inhibition disrupted purinosome-mitochondria colocalization and suppressed purinosome formation stimulated by mitochondria dysregulation. Collectively, our data suggests an mTOR-mediated link between purinosomes and mitochondria and suggests a general means by which mTOR regulates nucleotide metabolism by spatiotemporal control over protein association. PMID:26912862

  10. Improving nonlinear modeling capabilities of functional link adaptive filters.

    PubMed

    Comminiello, Danilo; Scarpiniti, Michele; Scardapane, Simone; Parisi, Raffaele; Uncini, Aurelio

    2015-09-01

    The functional link adaptive filter (FLAF) represents an effective solution for online nonlinear modeling problems. In this paper, we take into account a FLAF-based architecture, which separates the adaptation of linear and nonlinear elements, and we focus on the nonlinear branch to improve the modeling performance. In particular, we propose a new model that involves an adaptive combination of filters downstream of the nonlinear expansion. Such combination leads to a cooperative behavior of the whole architecture, thus yielding a performance improvement, particularly in the presence of strong nonlinearities. An advanced architecture is also proposed involving the adaptive combination of multiple filters on the nonlinear branch. The proposed models are assessed in different nonlinear modeling problems, in which their effectiveness and capabilities are shown. PMID:26057613

  11. Nrf2 links epidermal barrier function with antioxidant defense.

    PubMed

    Schäfer, Matthias; Farwanah, Hany; Willrodt, Ann-Helen; Huebner, Aaron J; Sandhoff, Konrad; Roop, Dennis; Hohl, Daniel; Bloch, Wilhelm; Werner, Sabine

    2012-05-01

    The skin provides an efficient permeability barrier and protects from microbial invasion and oxidative stress. Here, we show that these essential functions are linked through the Nrf2 transcription factor. To test the hypothesis that activation of Nrf2 provides skin protection under stress conditions, we determined the consequences of pharmacological or genetic activation of Nrf2 in keratinocytes. Surprisingly, mice with enhanced Nrf2 activity in keratinocytes developed epidermal thickening, hyperkeratosis and inflammation resembling lamellar ichthyosis. This resulted from upregulation of the cornified envelope proteins small proline-rich proteins (Sprr) 2d and 2h and of secretory leukocyte peptidase inhibitor (Slpi), which we identified as novel Nrf2 targets in keratinocytes. Since Sprrs are potent scavengers of reactive oxygen species and since Slpi has antimicrobial activities, their upregulation contributes to Nrf2's protective function. However, it also caused corneocyte fragility and impaired desquamation, followed by alterations in the epidermal lipid barrier, inflammation and overexpression of mitogens that induced keratinocyte hyperproliferation. These results identify an unexpected role of Nrf2 in epidermal barrier function, which needs to be considered for pharmacological use of Nrf2 activators. PMID:22383093

  12. Linking biological soil crust diversity to ecological functions

    NASA Astrophysics Data System (ADS)

    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.

  13. Mitochondrial function in the brain links anxiety with social subordination

    PubMed Central

    Hollis, Fiona; van der Kooij, Michael A.; Zanoletti, Olivia; Lozano, Laura; Cantó, Carles; Sandi, Carmen

    2015-01-01

    Dominance hierarchies are integral aspects of social groups, yet whether personality traits may predispose individuals to a particular rank remains unclear. Here we show that trait anxiety directly influences social dominance in male outbred rats and identify an important mediating role for mitochondrial function in the nucleus accumbens. High-anxious animals that are prone to become subordinate during a social encounter with a low-anxious rat exhibit reduced mitochondrial complex I and II proteins and respiratory capacity as well as decreased ATP and increased ROS production in the nucleus accumbens. A causal link for these findings is indicated by pharmacological approaches. In a dyadic contest between anxiety-matched animals, microinfusion of specific mitochondrial complex I or II inhibitors into the nucleus accumbens reduced social rank, mimicking the low probability to become dominant observed in high-anxious animals. Conversely, intraaccumbal infusion of nicotinamide, an amide form of vitamin B3 known to enhance brain energy metabolism, prevented the development of a subordinate status in high-anxious individuals. We conclude that mitochondrial function in the nucleus accumbens is crucial for social hierarchy establishment and is critically involved in the low social competitiveness associated with high anxiety. Our findings highlight a key role for brain energy metabolism in social behavior and point to mitochondrial function in the nucleus accumbens as a potential marker and avenue of treatment for anxiety-related social disorders. PMID:26621716

  14. Mitochondrial function in the brain links anxiety with social subordination.

    PubMed

    Hollis, Fiona; van der Kooij, Michael A; Zanoletti, Olivia; Lozano, Laura; Cantó, Carles; Sandi, Carmen

    2015-12-15

    Dominance hierarchies are integral aspects of social groups, yet whether personality traits may predispose individuals to a particular rank remains unclear. Here we show that trait anxiety directly influences social dominance in male outbred rats and identify an important mediating role for mitochondrial function in the nucleus accumbens. High-anxious animals that are prone to become subordinate during a social encounter with a low-anxious rat exhibit reduced mitochondrial complex I and II proteins and respiratory capacity as well as decreased ATP and increased ROS production in the nucleus accumbens. A causal link for these findings is indicated by pharmacological approaches. In a dyadic contest between anxiety-matched animals, microinfusion of specific mitochondrial complex I or II inhibitors into the nucleus accumbens reduced social rank, mimicking the low probability to become dominant observed in high-anxious animals. Conversely, intraaccumbal infusion of nicotinamide, an amide form of vitamin B3 known to enhance brain energy metabolism, prevented the development of a subordinate status in high-anxious individuals. We conclude that mitochondrial function in the nucleus accumbens is crucial for social hierarchy establishment and is critically involved in the low social competitiveness associated with high anxiety. Our findings highlight a key role for brain energy metabolism in social behavior and point to mitochondrial function in the nucleus accumbens as a potential marker and avenue of treatment for anxiety-related social disorders. PMID:26621716

  15. Linking geophysics and soil function modelling - two examples

    NASA Astrophysics Data System (ADS)

    Krüger, J.; Franko, U.; Werban, U.; Dietrich, P.; Behrens, T.; Schmidt, K.; Fank, J.; Kroulik, M.

    2011-12-01

    iSOIL - "Interactions between soil related sciences - Linking geophysics, soil science and digital soil mapping" is a Collaborative Project (Grant Agreement number 211386) co-funded by the Research DG of the European Commission within the RTD activities of the FP7 Thematic Priority Environment. The iSOIL project aims at reliable mapping of soil properties and soil functions with various methods including geophysical, spectroscopic and monitoring techniques. The general procedure contains three steps (i) geophysical monitoring, (ii) generation of soil property maps and (iii) process modelling. The objective of this work is to demonstrate the methodological procedure on two different examples. Example A focuses on the turnover conditions for soil organic matter (SOM) since many soil functions in a direct or indirect way depend on SOM and SOM depletion is amongst the worst soil threats. Example B deals with the dynamics of soil water and the direct influence on crop biomass production. The applied CANDY model (Franko et al. 1995) was developed to describe dynamics of soil organic matter and mineral nitrogen as well as soil water and temperature. The new module PLUS extends CANDY to simulate crop biomass production based on environmental influences (Krüger et al. 2011). The methodological procedure of example A illustrates a model application for a field site in the Czech Republic using generated soil maps from combined geophysical data. Modelling requires a complete set of soil parameters. Combining measured soil properties and data of geophysical measurements (electrical conductivity and gamma spectrometry) is the basis for digital soil mapping which provided data about clay, silt and sand as well as SOC content. With these data pedotransfer functions produce detailed soil input data (e.g. bulk and particle density, field capacity, wilting point, saturated conductivity) for the rooted soil profile. CANDY calculated different indicators for SOM and gave hints about

  16. Linking soil functions to carbon fluxes and stocks

    NASA Astrophysics Data System (ADS)

    Olesen, Jørgen E.

    2014-05-01

    Farming practices causing declining returns and inputs of carbon (C) to soils pose threats to sustainable soil functioning by reducing availability of organic matter for soil microbial activities and by affecting soil structure, and soil C stocks that contribute to regulating greenhouse gas emissions. Declines in soil C also affect availability and storage capacity of a range of essential plant nutrients thus affecting needs for external inputs. Soil degradation is considered a serious problem in Europe and a large part of the degradation is caused by agricultural activity with intensive cultivation in arable and mixed farming system contributing to several soil threats. About 45% of European soils are estimated to have low SOM content, principally in southern Europe, but also in areas of France, UK and Germany. The European SOC stocks follow a clear north to south gradient with cooler temperatures favouring higher stocks. However, SOC stocks strongly depend on soil and land management, and there is thus a potential to both increase and lose SOC, although the potential to increase SOC strongly depends on incentives and structures for implementing improved management. Understanding the role of soil C may be better conceptualised by using a soil C flow and stocks concept to assess the impact of C management on crop productivity, soil organic C stocks and other ecosystem services. This concept distinguishes C flows and stocks, which may be hypothesized to have distinctly different effects on biological, chemical and physical soil functions. By separating the roles of carbon flows from the role of carbon stocks, it may become possible to better identify critical levels not only of soil carbon stocks, but also critical levels of carbon inputs, which directly relate to needs for crop and soil management measures. Such critical soil carbon stocks may be linked to soil mineralogy through complexed organic carbon on clay and silt surfaces. Critical levels of soil carbon

  17. Linking geophysics and soil function modelling - biomass production

    NASA Astrophysics Data System (ADS)

    Krüger, J.; Franko, U.; Werban, U.; Fank, J.

    2012-04-01

    The iSOIL project aims at reliable mapping of soil properties and soil functions with various methods including geophysical, spectroscopic and monitoring techniques. The general procedure contains three steps (i) geophysical monitoring, (ii) generation of soil property maps and (iii) process modelling. The objective of this work is to demonstrate the mentioned procedure with a focus on process modelling. It deals with the dynamics of soil water and the direct influence on crop biomass production. The new module PLUS extends CANDY to simulate crop biomass production based on environmental influences. A soil function modelling with an adapted model parameterisation based on data of ground penetration radar (GPR) and conductivity (EM38) was realized. This study shows an approach to handle heterogeneity of soil properties with geophysical data used for biomass production modelling. The Austrian field site Wagna is characterised by highly heterogenic soil with fluvioglacial gravel sediments. The variation of thickness of topsoil above a sandy subsoil with gravels strongly influences the soil water balance. EM38, mounted on a mobile platform, enables to rapidly scan large areas whereas GPR requires a greater logistical effort. However, GPR can detect exact soil horizon depth between topsoil and subsoil, the combination of both results in a detailed large scale soil map. The combined plot-specific GPR and field site EM38 measurements extends the soil input data and improves the model performance of CANDY PLUS for plant biomass production (Krüger et al. 2011). The example demonstrates how geophysics provides a surplus of data for agroecosystem modelling which identifies and contributes alternative options for agricultural management decisions. iSOIL - "Interactions between soil related sciences - Linking geophysics, soil science and digital soil mapping" is a Collaborative Project (Grant Agreement number 211386) co-funded by the Research DG of the European Commission

  18. Optimizing Linked Perceptual Class Formation and Transfer of Function

    ERIC Educational Resources Information Center

    Fields, Lanny; Garruto, Michelle

    2009-01-01

    A linked perceptual class consists of two distinct perceptual classes, A' and B', the members of which have become related to each other. For example, a linked perceptual class might be composed of many pictures of a woman (one perceptual class) and the sounds of that woman's voice (the other perceptual class). In this case, any sound of the…

  19. Hepatic Inflammation and Fibrosis: Functional Links and Key Pathways

    PubMed Central

    Seki, Ekihiro; Schwabe, Robert F.

    2014-01-01

    Inflammation is one of the most characteristic features of chronic liver disease of viral, alcoholic, fatty and autoimmune origin. Inflammation is typically present in all disease stages, and associated with the development of fibrosis, cirrhosis and hepatocellular carcinoma. In the past decade, numerous studies have contributed to improved understanding of the links between hepatic inflammation and fibrosis. Here, we review mechanisms that link inflammation with the development of liver fibrosis, focusing on the role of inflammatory mediators in hepatic stellate cell (HSC) activation and HSC survival during fibrogenesis and fibrosis regression. We will summarize the contributions of different inflammatory cells, including hepatic macrophages, T- and B-lymphocytes, NK cells and platelets, as well as key effectors such as cytokines, chemokines, and damage-associated molecular patterns. Furthermore, we will discuss the relevance of inflammatory signaling pathways for clinical liver disease and for the development of anti-fibrogenic strategies. PMID:25066777

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

    PubMed

    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. PMID:26131659

  1. Polyimide aerogels cross-linked through amine functionalized polyoligomeric silsesquioxane.

    PubMed

    Guo, Haiquan; Meador, Mary Ann B; McCorkle, Linda; Quade, Derek J; Guo, Jiao; Hamilton, Bart; Cakmak, Miko; Sprowl, Guilherme

    2011-02-01

    We report the first synthesis of polyimide aerogels cross-linked through a polyhedral oligomeric silsesquioxane, octa(aminophenyl)silsesquioxane (OAPS). Gels formed from polyamic acid solutions of 3,3',4,4'-biphenyltetracarboxylic dianhydride (BPDA), bisaniline-p-xylidene (BAX) and OAPS were chemically imidized and dried using supercritical CO(2) extraction to give aerogels having density around 0.1 g/cm(3). The aerogels are greater than 90 % porous, have high surface areas (230 to 280 m(2)/g) and low thermal conductivity (14 mW/m-K at room temperature). Notably, the polyimide aerogels cross-linked with OAPS have higher modulus than polymer reinforced silica aerogels of similar density and can be fabricated as both monoliths and thin films. Thin films of the aerogel are flexible and foldable making them an ideal insulation for space suits, and inflatable structures for habitats or decelerators for planetary re-entry, as well as more down to earth applications. PMID:21294517

  2. Linking species functional roles to their network roles.

    PubMed

    Coux, Camille; Rader, Romina; Bartomeus, Ignasi; Tylianakis, Jason M

    2016-07-01

    Species roles in ecological networks combine to generate their architecture, which contributes to their stability. Species trait diversity also affects ecosystem functioning and resilience, yet it remains unknown whether species' contributions to functional diversity relate to their network roles. Here, we use 21 empirical pollen transport networks to characterise this relationship. We found that, apart from a few abundant species, pollinators with original traits either had few interaction partners or interacted most frequently with a subset of these partners. This suggests that narrowing of interactions to a subset of the plant community accompanies pollinator niche specialisation, congruent with our hypothesised trade-off between having unique traits vs. being able to interact with many mutualist partners. Conversely, these effects were not detected in plants, potentially because key aspects of their flowering traits are conserved at a family level. Relating functional and network roles can provide further insight into mechanisms underlying ecosystem functioning. PMID:27169359

  3. Soil-borne microbiome: linking diversity to function.

    PubMed

    Mendes, Lucas W; Tsai, Siu M; Navarrete, Acácio A; de Hollander, Mattias; van Veen, Johannes A; Kuramae, Eiko E

    2015-07-01

    Soil microorganisms are sensitive to environment disturbances, and such alterations have consequences on microbial diversity and functions. Our hypothesis is that alpha diversity of microbial communities and functional diversity decrease from undisturbed to disturbed soils, with consequences for functional redundancy in the soil ecosystem. To test this hypothesis, we used soil DNA shotgun metagenomics approach to assess the soil microbiome in a chronosequence of land-use from a native tropical forest, followed by deforestation and cultivation of soybean croplands and pasture in different seasons. Agriculture and pasture soils were among the most diverse and presented higher functional redundancy, which is important to maintain the ecosystem functioning after the forest conversion. On the other hand, the ecosystem equilibrium in forest is maintained based on a lower alpha diversity but higher abundance of microorganisms. Our results indicate that land-use change alters the structure and composition of microbial communities; however, ecosystem functionality is overcome by different strategies based on the abundance and diversity of the communities. PMID:25586384

  4. Cognitive Function is Linked to Adherence to Bariatric Postoperative Guidelines

    PubMed Central

    Spitznagel, Mary Beth; Galioto, Rachel; Limbach, Kristen; Gunstad, John; Heinberg, Leslie

    2013-01-01

    Background Impairment in cognitive function is found in a significant subset of individuals undergoing bariatric surgery and recent work shows this impairment is associated with smaller postoperative weight loss. Reduced cognitive function could contribute to poorer adherence to postoperative guidelines, though this has not been previously examined. Objectives The current study examined the relationship between cognitive function and adherence to bariatric postoperative guidelines. We expected that higher cognitive function would be associated with better adherence to postoperative guidelines. Setting Data were collected through the bariatric service of a major medical center. Methods Thirty-seven bariatric surgery patients completed cognitive testing and a self-report measure of adherence to postoperative bariatric guidelines during their 4–6 week postoperative appointment. Results Strong correlations were observed between adherence to postoperative guidelines and cognitive indices of attention, executive function, and memory. Conclusions Results demonstrate that cognitive performance is strongly associated with adherence to postoperative guidelines shortly after bariatric surgery. Further work is needed to clarify if this relationship is present at later postoperative stages, and the degree to which this relationship mediates postoperative weight loss outcomes. PMID:23791534

  5. Olfactory Cilia: Linking Sensory Cilia Function and Human Disease

    PubMed Central

    Jenkins, Paul M.; McEwen, Dyke P.

    2009-01-01

    The olfactory system gives us an awareness of our immediate environment by allowing us to detect airborne stimuli. The components necessary for detection of these odorants are compartmentalized in the cilia of olfactory sensory neurons. Cilia are microtubule-based organelles, which can be found projecting from the surface of almost any mammalian cell, and are critical for proper olfactory function. Mislocalization of ciliary proteins and/or the loss of cilia cause impaired olfactory function, which is now recognized as a clinical manifestation of a broad class of human diseases, termed ciliopathies. Future work investigating the mechanisms of olfactory cilia function will provide us important new information regarding the pathogenesis of human sensory perception diseases. PMID:19406873

  6. Linking structure and function: Information processing in the brain

    SciTech Connect

    Gremillion, M.A.V.

    1990-01-01

    Traditionally, theories of function in neuroscience have emerged from physiology. Physiologists have suggested a number of means by which information in the brain can be processed, yet the principles underlying the generation of these phenomena are not well understood. A complex systems approach would be to examine the overall structure and function of the system and to attempt to establish a common framework for information processing interactions. This paper will use the structure-function relationship as a basis for exploring units of information processing. It will examine the brain as a whole, first providing the non-specialists with an short overview of the structure and some of the functions or outputs of the brain. It then very briefly reviews three of the prominent theoretical concepts that have emerged in the last few decades: receptive fields, feature extraction, and parallel processing. Next, it addresses the question of information processing and outlines the structures which have traditionally been proposed to be the basic unit of information processing. An alternative unit on which information processing in the brain might be based is then proposed, and data outlined to support it. Finally, the implications of this different mode of processing are discussed, both for the brain and for other complex systems. 40 refs., 4 figs., 2 tabs.

  7. Morphology and behaviour: functional links in development and evolution

    PubMed Central

    Bertossa, Rinaldo C.

    2011-01-01

    Development and evolution of animal behaviour and morphology are frequently addressed independently, as reflected in the dichotomy of disciplines dedicated to their study distinguishing object of study (morphology versus behaviour) and perspective (ultimate versus proximate). Although traits are known to develop and evolve semi-independently, they are matched together in development and evolution to produce a unique functional phenotype. Here I highlight similarities shared by both traits, such as the decisive role played by the environment for their ontogeny. Considering the widespread developmental and functional entanglement between both traits, many cases of adaptive evolution are better understood when proximate and ultimate explanations are integrated. A field integrating these perspectives is evolutionary developmental biology (evo-devo), which studies the developmental basis of phenotypic diversity. Ultimate aspects in evo-devo studies—which have mostly focused on morphological traits—could become more apparent when behaviour, ‘the integrator of form and function’, is integrated into the same framework of analysis. Integrating a trait such as behaviour at a different level in the biological hierarchy will help to better understand not only how behavioural diversity is produced, but also how levels are connected to produce functional phenotypes and how these evolve. A possible framework to accommodate and compare form and function at different levels of the biological hierarchy is outlined. At the end, some methodological issues are discussed. PMID:21690124

  8. Can Chemical Diversity Provide a Link to Ecosystem Function?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Biodiversity indices – whether to count or differentiate – reflect the purpose for which they are designed. Diversity in litter-mix experiments has been traditionally described by species or functional group richness. The lack of predictability in decomposition or mineralization response to these di...

  9. Controlled degradation of hydrogels using multi-functional cross-linking molecules.

    PubMed

    Lee, Kuen Yong; Bouhadir, Kamal H; Mooney, David J

    2004-06-01

    Hydrogels, chemically cross-linked or physically entangled, have found a number of applications as novel delivery vehicles of drugs and cells. However, the narrow ranges of degradation rates and mechanical strength currently available from many hydrogels limits their applications. We have hypothesized that utilization of multi-functional cross-linking molecules to form hydrogels could provide a wider range and tighter control over the degradation rates and mechanical stiffness of gels than bi-functional cross-linking molecules. To address the possibility, we isolated alpha-L-guluronate residues of sodium alginate, and oxidized them to prepare poly(aldehyde guluronate) (PAG). Hydrogels were formed with either poly(acrylamide-co-hydrazide) (PAH) as a multi-functional cross-linking molecule or adipic acid dihydrazide (AAD) as a bi-functional cross-linking molecule. The initial properties and degradation behavior of both PAG gel types were monitored. PAG/PAH hydrogels showed higher mechanical stiffness before degradation and degraded more slowly than PAG/AAD gels, at the same concentration of cross-linking functional groups. The enhanced mechanical stiffness and prolonged degradation behavior could be attributed to the multiple attachment points of PAH in the gel at the same concentration of functional groups. This approach to regulating gel properties with multifunctional cross-linking molecules could be broadly used in hydrogels. PMID:14751730

  10. Effects on Scale Linking of Different Definitions of Criterion Functions for the IRT Characteristic Curve Methods

    ERIC Educational Resources Information Center

    Kim, Seonghoon; Kolen, Michael J.

    2007-01-01

    Under item response theory, the characteristic curve methods (Haebara and Stocking-Lord methods) are used to link two ability scales from separate calibrations. The linking methods use their respective criterion functions that can be defined differently according to the symmetry- and distribution-related schemes. The symmetry-related scheme…

  11. Linked Sex Differences in Cognition and Functional Connectivity in Youth.

    PubMed

    Satterthwaite, Theodore D; Wolf, Daniel H; Roalf, David R; Ruparel, Kosha; Erus, Guray; Vandekar, Simon; Gennatas, Efstathios D; Elliott, Mark A; Smith, Alex; Hakonarson, Hakon; Verma, Ragini; Davatzikos, Christos; Gur, Raquel E; Gur, Ruben C

    2015-09-01

    Sex differences in human cognition are marked, but little is known regarding their neural origins. Here, in a sample of 674 human participants ages 9-22, we demonstrate that sex differences in cognitive profiles are related to multivariate patterns of resting-state functional connectivity MRI (rsfc-MRI). Males outperformed females on motor and spatial cognitive tasks; females were faster in tasks of emotion identification and nonverbal reasoning. Sex differences were also prominent in the rsfc-MRI data at multiple scales of analysis, with males displaying more between-module connectivity, while females demonstrated more within-module connectivity. Multivariate pattern analysis using support vector machines classified subject sex on the basis of their cognitive profile with 63% accuracy (P < 0.001), but was more accurate using functional connectivity data (71% accuracy; P < 0.001). Moreover, the degree to which a given participant's cognitive profile was "male" or "female" was significantly related to the masculinity or femininity of their pattern of brain connectivity (P = 2.3 × 10(-7)). This relationship was present even when considering males and female separately. Taken together, these results demonstrate for the first time that sex differences in patterns of cognition are in part represented on a neural level through divergent patterns of brain connectivity. PMID:24646613

  12. Linking vegetation structure, function and physiology through spectroscopic remote sensing

    NASA Astrophysics Data System (ADS)

    Serbin, S.; Singh, A.; Couture, J. J.; Shiklomanov, A. N.; Rogers, A.; Desai, A. R.; Kruger, E. L.; Townsend, P. A.

    2015-12-01

    Terrestrial ecosystem process models require detailed information on ecosystem states and canopy properties to properly simulate the fluxes of carbon (C), water and energy from the land to the atmosphere and assess the vulnerability of ecosystems to perturbations. Current models fail to adequately capture the magnitude, spatial variation, and seasonality of terrestrial C uptake and storage, leading to significant uncertainties in the size and fate of the terrestrial C sink. By and large, these parameter and process uncertainties arise from inadequate spatial and temporal representation of plant traits, vegetation structure, and functioning. With increases in computational power and changes to model architecture and approaches, it is now possible for models to leverage detailed, data rich and spatially explicit descriptions of ecosystems to inform parameter distributions and trait tradeoffs. In this regard, spectroscopy and imaging spectroscopy data have been shown to be invaluable observational datasets to capture broad-scale spatial and, eventually, temporal dynamics in important vegetation properties. We illustrate the linkage of plant traits and spectral observations to supply key data constraints for model parameterization. These constraints can come either in the form of the raw spectroscopic data (reflectance, absorbtance) or physiological traits derived from spectroscopy. In this presentation we highlight our ongoing work to build ecological scaling relationships between critical vegetation characteristics and optical properties across diverse and complex canopies, including temperate broadleaf and conifer forests, Mediterranean vegetation, Arctic systems, and agriculture. We focus on work at the leaf, stand, and landscape scales, illustrating the importance of capturing the underlying variability in a range of parameters (including vertical variation within canopies) to enable more efficient scaling of traits related to functional diversity of ecosystems.

  13. Glutamatergic Neurotransmission Links Sensitivity to Volatile Anesthetics with Mitochondrial Function.

    PubMed

    Zimin, Pavel I; Woods, Christian B; Quintana, Albert; Ramirez, Jan-Marino; Morgan, Philip G; Sedensky, Margaret M

    2016-08-22

    An enigma of modern medicine has persisted for over 150 years. The mechanisms by which volatile anesthetics (VAs) produce their effects (loss of consciousness, analgesia, amnesia, and immobility) remain an unsolved mystery. Many attractive putative molecular targets have failed to produce a significant effect when genetically tested in whole-animal models [1-3]. However, mitochondrial defects increase VA sensitivity in diverse organisms from nematodes to humans [4-6]. Ndufs4 knockout (KO) mice lack a subunit of mitochondrial complex I and are strikingly hypersensitive to VAs yet resistant to the intravenous anesthetic ketamine [7]. The change in VA sensitivity is the largest reported for a mammal. Limiting NDUFS4 loss to a subset of glutamatergic neurons recapitulates the VA hypersensitivity of Ndufs4(KO) mice, while loss in GABAergic or cholinergic neurons does not. Baseline electrophysiologic function of CA1 pyramidal neurons does not differ between Ndufs4(KO) and control mice. Isoflurane concentrations that anesthetize only Ndufs4(KO) mice (0.6%) decreased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) only in Ndufs4(KO) CA1 neurons, while concentrations effective in control mice (1.2%) decreased sEPSC frequencies in both control and Ndufs4(KO) CA1 pyramidal cells. Spontaneous inhibitory postsynaptic currents (sIPSCs) were not differentially affected between genotypes. The effects of isoflurane were similar on evoked field excitatory postsynaptic potentials (fEPSPs) and paired pulse facilitation (PPF) in KO and control hippocampal slices. We propose that CA1 presynaptic excitatory neurotransmission is hypersensitive to isoflurane in Ndufs4(KO) mice due to the inhibition of pre-existing reduced complex I function, reaching a critical reduction that can no longer meet metabolic demands. PMID:27498564

  14. Practical Application of a Synthetic Linking Function on Small-Sample Equating

    ERIC Educational Resources Information Center

    Kim, Sooyeon; von Davier, Alina A.; Haberman, Shelby

    2011-01-01

    The synthetic function is a weighted average of the identity (the linking function for forms that are known to be completely parallel) and a traditional equating method. The purpose of the present study was to investigate the benefits of the synthetic function on small-sample equating using various real data sets gathered from different…

  15. Growth Points in Linking Representations of Function: A Research-Based Framework

    ERIC Educational Resources Information Center

    Ronda, Erlina

    2015-01-01

    This paper describes five growth points in linking representations of function developed from a study of secondary school learners. Framed within the cognitivist perspective and process-object conception of function, the growth points were identified and described based on linear and quadratic function tasks learners can do and their strategies…

  16. Flexible link functions in nonparametric binary regression with Gaussian process priors.

    PubMed

    Li, Dan; Wang, Xia; Lin, Lizhen; Dey, Dipak K

    2016-09-01

    In many scientific fields, it is a common practice to collect a sequence of 0-1 binary responses from a subject across time, space, or a collection of covariates. Researchers are interested in finding out how the expected binary outcome is related to covariates, and aim at better prediction in the future 0-1 outcomes. Gaussian processes have been widely used to model nonlinear systems; in particular to model the latent structure in a binary regression model allowing nonlinear functional relationship between covariates and the expectation of binary outcomes. A critical issue in modeling binary response data is the appropriate choice of link functions. Commonly adopted link functions such as probit or logit links have fixed skewness and lack the flexibility to allow the data to determine the degree of the skewness. To address this limitation, we propose a flexible binary regression model which combines a generalized extreme value link function with a Gaussian process prior on the latent structure. Bayesian computation is employed in model estimation. Posterior consistency of the resulting posterior distribution is demonstrated. The flexibility and gains of the proposed model are illustrated through detailed simulation studies and two real data examples. Empirical results show that the proposed model outperforms a set of alternative models, which only have either a Gaussian process prior on the latent regression function or a Dirichlet prior on the link function. PMID:26686333

  17. Chemoselective cross-linking and functionalization of alginate via Staudinger ligation

    PubMed Central

    Gattás-Asfura, Kerim M.; Stabler, Cherie L.

    2010-01-01

    In this study, we demonstrate the applicability of functionalized alginate to serve as a platform for the covalent cross-linking or immobilization of complimentary phosphine functionalized groups via the chemoselective Staudinger ligation scheme. Azide groups were covalently linked to alginate through a heterobifunctional polyethylene glycol (PEG) linker and carbodiimide. Degree of azide functionalization was varied as a function of carbodiimide concentration and determined by proton nuclear magnetic resonance (1H NMR) and infrared spectroscopy. Spontaneous and covalently cross-linked alginate-PEG gels were generated via the Staudinger ligation scheme upon incubation of the azide functionalized alginate with PEG chains having 1-methyl-2-diphenylphosphino-terephthalate (MDT) as end groups. Modulation of the MDT to N3 ratio resulted in variability of gel characteristics. In addition, azide functionalized alginate retained its capacity to instantaneously form hydrogels via electrostatic interaction with multivalent cations such as Ca2+ and Ba2+. Subsequently, covalent linkage of phosphine functionalized agents post-gelation of the alginate was feasible, as illustrated via linkage of MDT-PEG-carboxyfluorescein. Capitalization of the chemoselective and cell compatible Staudinger ligation scheme for covalent cross-linking of alginate hydrogels may enhance the utility of this polymer for the stable encapsulation of various cell types, in addition to their use in the immobilization of labeling agents, proteins, and other bioactive molecules. PMID:19848408

  18. Socioeconomic risk moderates the link between household chaos and maternal executive function.

    PubMed

    Deater-Deckard, Kirby; Chen, Nan; Wang, Zhe; Bell, Martha Ann

    2012-06-01

    We examined the link between household chaos (i.e., noise, clutter, disarray, lack of routines) and maternal executive function (i.e., effortful regulation of attention and memory), and whether it varied as a function of socioeconomic risk (i.e., single parenthood, lower mother and father educational attainment, housing situation, and father unemployment). We hypothesized that: 1) higher levels of household chaos would be linked with poorer maternal executive function, even when controlling for other measures of cognitive functioning (e.g., verbal ability), and 2) this link would be strongest in the most socioeconomically distressed or lowest-socioeconomic status households. The diverse sample included 153 mothers from urban and rural areas who completed a questionnaire and a battery of cognitive executive function tasks and a verbal ability task in the laboratory. Results were mixed for Hypothesis 1, and consistent with Hypothesis 2. Two-thirds of the variance overlapped between household chaos and maternal executive function, but only in families with high levels of socioeconomic risk. This pattern was not found for chaos and maternal verbal ability, suggesting that the potentially deleterious effects of household chaos may be specific to maternal executive function. The findings implicate household chaos as a powerful statistical predictor of maternal executive function in socioeconomically distressed contexts. PMID:22563703

  19. Functional analysis of the Campylobacter jejuni N-linked protein glycosylation pathway.

    PubMed

    Linton, Dennis; Dorrell, Nick; Hitchen, Paul G; Amber, Saba; Karlyshev, Andrey V; Morris, Howard R; Dell, Anne; Valvano, Miguel A; Aebi, Markus; Wren, Brendan W

    2005-03-01

    We describe in this report the characterization of the recently discovered N-linked glycosylation locus of the human bacterial pathogen Campylobacter jejuni, the first such system found in a species from the domain Bacteria. We exploited the ability of this locus to function in Escherichia coli to demonstrate through mutational and structural analyses that variant glycan structures can be transferred onto protein indicating the relaxed specificity of the putative oligosaccharyltransferase PglB. Structural data derived from these variant glycans allowed us to infer the role of five individual glycosyltransferases in the biosynthesis of the N-linked heptasaccharide. Furthermore, we show that C. jejuni- and E. coli-derived pathways can interact in the biosynthesis of N-linked glycoproteins. In particular, the E. coli encoded WecA protein, a UDP-GlcNAc: undecaprenylphosphate GlcNAc-1-phosphate transferase involved in glycolipid biosynthesis, provides for an alternative N-linked heptasaccharide biosynthetic pathway bypassing the requirement for the C. jejuni-derived glycosyltransferase PglC. This is the first experimental evidence that biosynthesis of the N-linked glycan occurs on a lipid-linked precursor prior to transfer onto protein. These findings provide a framework for understanding the process of N-linked protein glycosylation in Bacteria and for devising strategies to exploit this system for glycoengineering. PMID:15752194

  20. Cross-Linked Conjugated Polymer Fibrils: Robust Nanowires from Functional Polythiophene Diblock Copolymers

    SciTech Connect

    Hammer, Brenton A. G.; Bokel, Felicia A.; Hayward, Ryan C.; Emrick, Todd

    2011-09-27

    A series of poly(3-hexyl thiophene) (P3HT)-based diblock copolymers were prepared and examined in solution for their assembly into fibrils, and post-assembly cross-linking into robust nanowire structures. P3HT-b-poly(3-methanol thiophene) (P3MT), and P3HT-b-poly(3-aminopropyloxymethyl thiophene) (P3AmT) diblock copolymers were synthesized using Grignard metathesis (GRIM) polymerization. Fibrils formed from solution assembly of these copolymers are thus decorated with hydroxyl and amine functionality, and cross-linking is achieved by reaction of diisocyanates with the hydroxyl and amine groups. A variety of cross-linked structures, characterized by transmission electron microscopy (TEM), were produced by this method, including dense fibrillar sheets, fibril bundles, or predominately individual fibrils, depending on the chosen reaction conditions. In solution, the cross-linked fibrils maintained their characteristic vibronic structure in solvents that would normally disrupt (dissolve) the structures.

  1. Ecosystem functions across trophic levels are linked to functional and phylogenetic diversity.

    PubMed

    Thompson, Patrick L; Davies, T Jonathan; Gonzalez, Andrew

    2015-01-01

    In experimental systems, it has been shown that biodiversity indices based on traits or phylogeny can outperform species richness as predictors of plant ecosystem function. However, it is unclear whether this pattern extends to the function of food webs in natural ecosystems. Here we tested whether zooplankton functional and phylogenetic diversity explains the functioning of 23 natural pond communities. We used two measures of ecosystem function: (1) zooplankton community biomass and (2) phytoplankton abundance (Chl a). We tested for diversity-ecosystem function relationships within and across trophic levels. We found a strong correlation between zooplankton diversity and ecosystem function, whereas local environmental conditions were less important. Further, the positive diversity-ecosystem function relationships were more pronounced for measures of functional and phylogenetic diversity than for species richness. Zooplankton and phytoplankton biomass were best predicted by different indices, suggesting that the two functions are dependent upon different aspects of diversity. Zooplankton community biomass was best predicted by zooplankton trait-based functional richness, while phytoplankton abundance was best predicted by zooplankton phylogenetic diversity. Our results suggest that the positive relationship between diversity and ecosystem function can extend across trophic levels in natural environments, and that greater insight into variation in ecosystem function can be gained by combining functional and phylogenetic diversity measures. PMID:25693188

  2. Measuring changes in functional status among patients with schizophrenia: the link with cognitive impairment.

    PubMed

    Matza, Louis S; Buchanan, Robert; Purdon, Scot; Brewster-Jordan, Jessica; Zhao, Yang; Revicki, Dennis A

    2006-10-01

    Cognitive impairment associated with schizophrenia (CIAS) includes neuropsychological deficits in attention, working memory, verbal learning, and problem solving. These deficits have been shown to be linked to impairment in functional status (eg, social behavior, work performance, and activities of daily living) among patients with schizophrenia in cross-sectional studies. Less is known about the relationship between cognitive and functional change over time, such as potential functional implications of treatment-related improvement in CIAS. The purpose of this review is to summarize research on the association between change in CIAS and change in functional status, to discuss responsiveness of functional outcomes measures, and to provide recommendations for future research and measure development. Nine longitudinal studies were located on the link between CIAS and functional status, and 8 functional outcomes measures were used across these studies. The 9 studies offer initial support for a link between change in cognitive function and change in functional status. However, inconsistent findings across studies indicate that available research is preliminary, and substantial questions remain unanswered. Shortcomings of functional status measures are noted: most instruments were not developed for the target population, and none have demonstrated responsiveness to cognitive change among schizophrenic patients. It is recommended that new functional outcome measures be developed that are specifically designed to be responsive to change in cognition, with domains previously shown to be related to cognitive ability. When creating new functional outcomes measures for assessment of patients with schizophrenia, responsiveness to change in CIAS should be evaluated as part of the development and validation process. PMID:16829550

  3. Exploring Population Sensitivity of Linking Functions across Three Law School Admission Test Administrations

    ERIC Educational Resources Information Center

    Liu, Mei; Holland, Paul W.

    2008-01-01

    The simplified version of the Dorans and Holland (2000) measure of population invariance, the root mean square difference (RMSD), is used to explore the degree of dependence of linking functions on the Law School Admission Test (LSAT) subpopulations defined by examinees' gender, ethnic background, geographic region, law school application status,…

  4. The Link between Emotion Regulation, Social Functioning, and Depression in Boys with ASD

    ERIC Educational Resources Information Center

    Pouw, Lucinda B. C.; Rieffe, Carolien; Stockmann, Lex; Gadow, Kenneth D.

    2013-01-01

    Purpose: Symptoms of depression are common in children and adolescents with an autism spectrum disorder (ASD), but information about underlying developmental factors is limited. Depression is often linked to aspects of emotional functioning such as coping strategies, but in children with ASD difficulties with social interactions are also a likely…

  5. Direct Patterning of Organic Functional Polymers through Conventional Photolithography and Noninvasive Cross-Link Agents.

    PubMed

    Squillaci, Marco A; Qiu, Feng; Aliprandi, Alessandro; Zhang, Fan; Feng, Xinliang; Samorì, Paolo

    2016-07-01

    A new technique for direct patterning of functional organic polymers using commercial photolithography setups with a minimal loss of the materials' performances is reported. This result is achieved through novel cross-link agents made by boron- and fluorine-containing heterocycles that can react between themselves upon UV- and white-light exposure. PMID:27153351

  6. Remission of Depression in Parents: Links to Healthy Functioning in Their Children

    ERIC Educational Resources Information Center

    Garber, Judy; Ciesla, Jeff A.; McCauley, Elizabeth; Diamond, Guy; Schloredt, Kelly A.

    2011-01-01

    This study examined whether improvement in parents' depression was linked with changes in their children's depressive symptoms and functioning. Participants were 223 parents and children ranging in age from 7 to 17 years old (M = 12.13, SD = 2.31); 126 parents were in treatment for depression and 97 parents were nondepressed. Children were…

  7. Geochip: A high throughput genomic tool for linking community structure to functions

    SciTech Connect

    Van Nostrand, Joy D.; Liang, Yuting; He, Zhili; Li, Guanghe; Zhou, Jizhong

    2009-01-30

    GeoChip is a comprehensive functional gene array that targets key functional genes involved in the geochemical cycling of N, C, and P, sulfate reduction, metal resistance and reduction, and contaminant degradation. Studies have shown the GeoChip to be a sensitive, specific, and high-throughput tool for microbial community analysis that has the power to link geochemical processes with microbial community structure. However, several challenges remain regarding the development and applications of microarrays for microbial community analysis.

  8. Functional analysis of N-linking oligosaccharyl transferase enzymes encoded by deep-sea vent proteobacteria.

    PubMed

    Mills, Dominic C; Jervis, Adrian J; Abouelhadid, Sherif; Yates, Laura E; Cuccui, Jon; Linton, Dennis; Wren, Brendan W

    2016-04-01

    Bacterial N-linking oligosaccharyl transferases (OTase enzymes) transfer lipid-linked glycans to selected proteins in the periplasm and were first described in the intestinal pathogen Campylobacter jejuni, a member of the ε-proteobacteria-subdivision of bacteria. More recently, orthologues from other ε-proteobacterial Campylobacter and Helicobacter species and a δ-proteobacterium, Desulfovibrio desulfuricans, have been described, suggesting that these two subdivisions of bacteria may be a source of further N-linked protein glycosylation systems. Whole-genome sequencing of both ε- and δ-proteobacteria from deep-sea vent habitats, a rich source of species from these subdivisions, revealed putative ORFs encoding OTase enzymes and associated adjacent glycosyltransferases similar to the C. jejuni N-linked glycosylation locus. We expressed putative OTase ORFs from the deep-sea vent species Nitratiruptor tergarcus, Sulfurovum lithotrophicum and Deferribacter desulfuricans in Escherichia coli and showed that they were able to functionally complement the C. jejuni OTase, CjPglB. The enzymes were shown to possess relaxed glycan specificity, transferring diverse glycan structures and demonstrated different glycosylation sequon specificities. Additionally, a permissive D. desulfuricans acceptor protein was identified, and we provide evidence that the N-linked glycan synthesized by N. tergarcus and S. lithotrophicum contains an acetylated sugar at the reducing end. This work demonstrates that deep-sea vent bacteria encode functional N-glycosylation machineries and are a potential source of biotechnologically important OTase enzymes. PMID:26610891

  9. Functional analysis of N-linking oligosaccharyl transferase enzymes encoded by deep-sea vent proteobacteria

    PubMed Central

    Mills, Dominic C.; Jervis, Adrian J.; Abouelhadid, Sherif; Yates, Laura E.; Cuccui, Jon; Linton, Dennis; Wren, Brendan W.

    2016-01-01

    Bacterial N-linking oligosaccharyl transferases (OTase enzymes) transfer lipid-linked glycans to selected proteins in the periplasm and were first described in the intestinal pathogen Campylobacter jejuni, a member of the ε-proteobacteria-subdivision of bacteria. More recently, orthologues from other ε-proteobacterial Campylobacter and Helicobacter species and a δ-proteobacterium, Desulfovibrio desulfuricans, have been described, suggesting that these two subdivisions of bacteria may be a source of further N-linked protein glycosylation systems. Whole-genome sequencing of both ε- and δ-proteobacteria from deep-sea vent habitats, a rich source of species from these subdivisions, revealed putative ORFs encoding OTase enzymes and associated adjacent glycosyltransferases similar to the C. jejuni N-linked glycosylation locus. We expressed putative OTase ORFs from the deep-sea vent species Nitratiruptor tergarcus, Sulfurovum lithotrophicum and Deferribacter desulfuricans in Escherichia coli and showed they were able to functionally complement the C. jejuni OTase, CjPglB . The enzymes were shown to possess relaxed glycan specificity, transferring diverse glycan structures and demonstrated different glycosylation sequon specificities. Additionally a permissive D. desulfuricans acceptor protein was identified, and we provide evidence that the N-linked glycan synthesised by N. tergarcus and S. lithotrophicum contains an acetylated sugar at the reducing end. This work demonstrates that deep-sea vent bacteria encode functional N-glycosylation machineries and are a potential source of biotechnologically important OTase enzymes. PMID:26610891

  10. Identification of nonlinear dynamic systems using functional link artificial neural networks.

    PubMed

    Patra, J C; Pal, R N; Chatterji, B N; Panda, G

    1999-01-01

    We have presented an alternate ANN structure called functional link ANN (FLANN) for nonlinear dynamic system identification using the popular backpropagation algorithm. In contrast to a feedforward ANN structure, i.e., a multilayer perceptron (MLP), the FLANN is basically a single layer structure in which nonlinearity is introduced by enhancing the input pattern with nonlinear functional expansion. With proper choice of functional expansion in a FLANN, this network performs as good as and in some cases even better than the MLP structure for the problem of nonlinear system identification. PMID:18252296

  11. Trophic links between functional groups of arable plants and beetles are stable at a national scale.

    PubMed

    Brooks, David R; Storkey, Jonathan; Clark, Suzanne J; Firbank, Les G; Petit, Sandrine; Woiwod, Ian P

    2012-01-01

    1. There is an urgent need to accurately model how environmental change affects the wide-scale functioning of ecosystems, but advances are hindered by a lack of knowledge of how trophic levels are linked across space. It is unclear which theoretical approach to take to improve modelling of such interactions, but evidence is gathering that linking species responses to their functional traits can increase understanding of ecosystem dynamics. Currently, there are no quantitative studies testing how this approach might improve models of multiple, trophically interacting species, at wide spatial scales. 2. Arable weeds play a foundational role in linking food webs, providing resources for many taxa, including carabid beetles that feed on their seeds and weed-associated invertebrate prey. Here, we model associations between weeds and carabids across farmland in Great Britain (GB), to test the hypothesis that wide-scale trophic links between these groups are structured by their species functional traits. 3. A network of c. 250 arable fields, covering four crops and most lowland areas of GB, was sampled for weed, carabid and invertebrate taxa over 3 years. Data sets of these groups were closely matched in time and space, and each contained numerous species with a range of eco-physiological traits. The consistency of trophic linkages between multiple taxa sharing functional traits was tested within multivariate and log-linear models. 4. Robust links were established between the functional traits of taxa and their trophic interactions. Autumn-germinating, small-seeded weeds were associated with smaller, spring-breeding carabids, more specialised in seed feeding, whereas spring-germinating, large-seeded weeds were associated with a range of larger, autumn-breeding omnivorous carabids. These relationships were strong and dynamic, being independent of changes in invertebrate food resources and consistent across sample dates, crops and regions of GB. 5. We conclude that, in at

  12. Grammar learning in older adults is linked to white matter microstructure and functional connectivity.

    PubMed

    Antonenko, Daria; Meinzer, Marcus; Lindenberg, Robert; Witte, A Veronica; Flöel, Agnes

    2012-09-01

    Age-related decline in cognitive function has been linked to alterations of white matter and functional brain connectivity. With regard to language, aging has been shown to be associated with impaired syntax processing, but the underlying structural and functional correlates are poorly understood. In the present study, we used an artificial grammar learning (AGL) task to determine the ability to extract grammatical rules from new material in healthy older adults. White matter microstructure and resting-state functional connectivity (FC) of task-relevant brain regions were assessed using multimodal magnetic resonance imaging (MRI). AGL performance correlated positively with fractional anisotropy (FA) underlying left and right Brodmann areas (BA) 44/45 and in tracts originating from left BA 44/45. An inverse relationship was found between task performance and FC of left and right BA 44/45, linking lower performance to stronger inter-hemispheric functional coupling. Our results suggest that white matter microstructure underlying specific prefrontal regions and their functional coupling affect acquisition of syntactic knowledge in the aging brain, offering further insight into mechanisms of functional decline in older adults. PMID:22659480

  13. Single proteins that serve linked functions in intracellular and extracellular microenvironments

    SciTech Connect

    Radisky, Derek C.; Stallings-Mann, Melody; Hirai, Yohei; Bissell, Mina J.

    2009-06-03

    Maintenance of organ homeostasis and control of appropriate response to environmental alterations requires intimate coordination of cellular function and tissue organization. An important component of this coordination may be provided by proteins that can serve distinct, but linked, functions on both sides of the plasma membrane. Here we present a novel hypothesis in which non-classical secretion can provide a mechanism through which single proteins can integrate complex tissue functions. Single genes can exert a complex, dynamic influence through a number of different processes that act to multiply the function of the gene product(s). Alternative splicing can create many different transcripts that encode proteins of diverse, even antagonistic, function from a single gene. Posttranslational modifications can alter the stability, activity, localization, and even basic function of proteins. A protein can exist in different subcellular localizations. More recently, it has become clear that single proteins can function both inside and outside the cell. These proteins often lack defined secretory signal sequences, and transit the plasma membrane by mechanisms separate from the classical ER/Golgi secretory process. When examples of such proteins are examined individually, the multifunctionality and lack of a signal sequence are puzzling - why should a protein with a well known function in one context function in such a distinct fashion in another? We propose that one reason for a single protein to perform intracellular and extracellular roles is to coordinate organization and maintenance of a global tissue function. Here, we describe in detail three specific examples of proteins that act in this fashion, outlining their specific functions in the extracellular space and in the intracellular space, and we discuss how these functions may be linked. We present epimorphin/syntaxin-2, which may coordinate morphogenesis of secretory organs (as epimorphin) with control of

  14. Distributed intrusion monitoring system with fiber link backup and on-line fault diagnosis functions

    NASA Astrophysics Data System (ADS)

    Xu, Jiwei; Wu, Huijuan; Xiao, Shunkun

    2014-12-01

    A novel multi-channel distributed optical fiber intrusion monitoring system with smart fiber link backup and on-line fault diagnosis functions was proposed. A 1× N optical switch was intelligently controlled by a peripheral interface controller (PIC) to expand the fiber link from one channel to several ones to lower the cost of the long or ultra-long distance intrusion monitoring system and also to strengthen the intelligent monitoring link backup function. At the same time, a sliding window auto-correlation method was presented to identify and locate the broken or fault point of the cable. The experimental results showed that the proposed multi-channel system performed well especially whenever any a broken cable was detected. It could locate the broken or fault point by itself accurately and switch to its backup sensing link immediately to ensure the security system to operate stably without a minute idling. And it was successfully applied in a field test for security monitoring of the 220-km-length national borderline in China.

  15. Numerous Genes in Loci Associated With Body Fat Distribution Are Linked to Adipose Function.

    PubMed

    Dahlman, Ingrid; Rydén, Mikael; Brodin, David; Grallert, Harald; Strawbridge, Rona J; Arner, Peter

    2016-02-01

    Central fat accumulation is a strong risk factor for type 2 diabetes. Genome-wide association studies have identified numerous loci associated with body fat distribution. The objectives of the current study are to examine whether genes in genetic loci linked to fat distribution can be linked to fat cell size and number (morphology) and/or adipose tissue function. We show, in a cohort of 114 women, that almost half of the 96 genes in these loci are indeed associated with abdominal subcutaneous adipose tissue parameters. Thus, adipose mRNA expression of the genes is strongly related to adipose morphology, catecholamine-induced lipid mobilization (lipolysis), or insulin-stimulated lipid synthesis in adipocytes (lipogenesis). In conclusion, the genetic influence on body fat distribution could be mediated via several specific alterations in adipose tissue morphology and function, which in turn may influence the development of type 2 diabetes. PMID:26798124

  16. CRISPR/Cas9 Promotes Functional Study of Testis Specific X-Linked Gene In Vivo

    PubMed Central

    Jiang, Xue; Chen, Yuxi; Zhang, Zhen; Zhang, Xiya; Liang, Puping; Zhan, Shaoquan; Cao, Shanbo; Songyang, Zhou; Huang, Junjiu

    2015-01-01

    Mammalian spermatogenesis is a highly regulated multistage process of sperm generation. It is hard to uncover the real function of a testis specific gene in vitro since the in vitro model is not yet mature. With the development of the CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated 9) system, we can now rapidly generate knockout mouse models of testis specific genes to study the process of spermatogenesis in vivo. SYCP3-like X-linked 2 (SLX2) is a germ cell specific component, which contains a Cor1 domain and belongs to the XLR (X-linked, lymphocyte regulated) family. Previous studies suggested that SLX2 might play an important role in mouse spermatogenesis based on its subcellular localization and interacting proteins. However, the function of SLX2 in vivo is still elusive. Here, to investigate the functions of SLX2 in spermatogenesis, we disrupted the Slx2 gene by using the CRISPR/Cas9 system. Since Slx2 is a testis specific X-linked gene, we obtained knockout male mice in the first generation and accelerated the study process. Compared with wild-type mice, Slx2 knockout mice have normal testis and epididymis. Histological observation of testes sections showed that Slx2 knockout affected none of the three main stages of spermatogenesis: mitosis, meiosis and spermiogenesis. In addition, we further confirmed that disruption of Slx2 did not affect the number of spermatogonial stem cells, meiosis progression or XY body formation by immunofluorescence analysis. As spermatogenesis was normal in Slx2 knockout mice, these mice were fertile. Taken together, we showed that Slx2 itself is not an essential gene for mouse spermatogenesis and CRISPR/Cas9 technique could speed up the functional study of testis specific X-linked gene in vivo. PMID:26599493

  17. Linking structure and function in food webs: maximization of different ecological functions generates distinct food web structures.

    PubMed

    Yen, Jian D L; Cabral, Reniel B; Cantor, Mauricio; Hatton, Ian; Kortsch, Susanne; Patrício, Joana; Yamamichi, Masato

    2016-03-01

    Trophic interactions are central to ecosystem functioning, but the link between food web structure and ecosystem functioning remains obscure. Regularities (i.e. consistent patterns) in food web structure suggest the possibility of regularities in ecosystem functioning, which might be used to relate structure to function. We introduce a novel, genetic algorithm approach to simulate food webs with maximized throughput (a proxy for ecosystem functioning) and compare the structure of these simulated food webs to real empirical food webs using common metrics of food web structure. We repeat this analysis using robustness to secondary extinctions (a proxy for ecosystem resilience) instead of throughput to determine the relative contributions of ecosystem functioning and ecosystem resilience to food web structure. Simulated food webs that maximized robustness were similar to real food webs when connectance (i.e. levels of interaction across the food web) was high, but this result did not extend to food webs with low connectance. Simulated food webs that maximized throughput or a combination of throughput and robustness were not similar to any real food webs. Simulated maximum-throughput food webs differed markedly from maximum-robustness food webs, which suggests that maximizing different ecological functions can generate distinct food web structures. Based on our results, food web structure would appear to have a stronger relationship with ecosystem resilience than with ecosystem throughput. Our genetic algorithm approach is general and is well suited to large, realistically complex food webs. Genetic algorithms can incorporate constraints on structure and can generate outputs that can be compared directly to empirical data. Our method can be used to explore a range of maximization or minimization hypotheses, providing new perspectives on the links between structure and function in ecological systems. PMID:26749320

  18. Link functions in multi-locus genetic models: implications for testing, prediction, and interpretation.

    PubMed

    Clayton, David

    2012-05-01

    "Complex" diseases are, by definition, influenced by multiple causes, both genetic and environmental, and statistical work on the joint action of multiple risk factors has, for more than 40 years, been dominated by the generalized linear model (GLM). In genetics, models for dichotomous traits have traditionally been approached via the model of an underlying, normally distributed, liability. This corresponds to the GLM with binomial errors and a probit link function. Elsewhere in epidemiology, however, the logistic regression model, a GLM with logit link function, has been the tool of choice, largely because of its convenient properties in case-control studies. The choice of link function has usually been dictated by mathematical convenience, but it has some important implications in (a) the choice of association test statistic in the presence of existing strong risk factors, (b) the ability to predict disease from genotype given its heritability, and (c) the definition, and interpretation of epistasis (or epistacy). These issues are reviewed, and a new association test proposed. PMID:22508388

  19. Oxidative stress modulates mitochondrial failure and cyclophilin D function in X-linked adrenoleukodystrophy

    PubMed Central

    López-Erauskin, Jone; Galino, Jorge; Bianchi, Patrizia; Fourcade, Stéphane; Andreu, Antoni L.; Ferrer, Isidre; Muñoz-Pinedo, Cristina

    2012-01-01

    A common process associated with oxidative stress and severe mitochondrial impairment is the opening of the mitochondrial permeability transition pore, as described in many neurodegenerative diseases. Thus, inhibition of mitochondrial permeability transition pore opening represents a potential target for inhibiting mitochondrial-driven cell death. Among the mitochondrial permeability transition pore components, cyclophilin D is the most studied and has been found increased under pathological conditions. Here, we have used in vitro and in vivo models of X-linked adrenoleukodystrophy to investigate the relationship between the mitochondrial permeability transition pore opening and redox homeostasis. X-linked adrenoleukodystrophy is a neurodegenerative condition caused by loss of function of the peroxisomal ABCD1 transporter, in which oxidative stress plays a pivotal role. In this study, we provide evidence of impaired mitochondrial metabolism in a peroxisomal disease, as fibroblasts in patients with X-linked adrenoleukodystrophy cannot survive when forced to rely on mitochondrial energy production, i.e. on incubation in galactose. Oxidative stress induced under galactose conditions leads to mitochondrial damage in the form of mitochondrial inner membrane potential dissipation, ATP drop and necrotic cell death, together with increased levels of oxidative modifications in cyclophilin D protein. Moreover, we show increased expression levels of cyclophilin D in the affected zones of brains in patients with adrenomyeloneuropathy, in spinal cord of a mouse model of X-linked adrenoleukodystrophy (Abcd1-null mice) and in fibroblasts from patients with X-linked adrenoleukodystrophy. Notably, treatment with antioxidants rescues mitochondrial damage markers in fibroblasts from patients with X-linked adrenoleukodystrophy, including cyclophilin D oxidative modifications, and reverses cyclophilin D induction in vitro and in vivo. These findings provide mechanistic insight into the

  20. Fluorescent structural DNA nanoballs functionalized with phosphate-linked nucleotide triphosphates.

    PubMed

    Anderson, Jon P; Reynolds, Bambi L; Baum, Kristin; Williams, John G

    2010-03-10

    Highly labeled DNA nanoballs functionalized with phosphate-linked nucleotide triphosphates (dNTPs) were developed as a source of dNTPs for DNA polymerase. The particles were prepared by strand-displacement polymerization from a self-complementary circular template. Imaged by atomic force microscopy, these functionalized particles appear as condensed fuzzy balls with diameters between 50 and 150 nm. They emit a bright fluorescent signal, detected in 2 ms exposures with a signal-to-noise ratio of 25 when imaged using a TIR fluorescence microscope. PMID:20158249

  1. Fluorescent Structural DNA Nanoballs Functionalized With Phosphate-Linked Nucleotide Triphosphates

    PubMed Central

    Anderson, Jon P.; Reynolds, Bambi L.; Baum, Kristin; Williams, John G.

    2010-01-01

    Highly labeled DNA nanoballs functionalized with phosphate-linked nucleotide triphosphates (dNTPs) were developed as a source of dNTPs for DNA polymerase. The particles were prepared by strand-displacement polymerization from a self-complementary circular template. Imaged by atomic force microscopy, these functionalized particles appear as condensed fuzzy balls with diameters between 50–150 nm. They emit a bright fluorescent signal, detected in 2 msec exposures with a signal-to-noise of 25 when imaged using a TIR fluorescence microscope. PMID:20158249

  2. Linking social anxiety and adolescent romantic relationship functioning: indirect effects and the importance of peers.

    PubMed

    Hebert, Karen R; Fales, Jessica; Nangle, Douglas W; Papadakis, Alison A; Grover, Rachel L

    2013-11-01

    Peer relationships undergo dramatic shifts in form and function during adolescence, at the same time the incidence of socially evaluative fears sharply rises. Despite well-established links between social anxiety and broader interpersonal functioning, there is a dearth of research evaluating the impact of social anxiety on functioning in close relationships during this developmental stage. The present study examines the impact of social anxiety on functioning in close friendships and romantic relationships during adolescence. From a developmental psychopathology perspective, it was expected that social anxiety would influence functioning (quality, length, satisfaction) in romantic relationships through its influence on functioning in same- and other-sex friendships. Participants included 314 adolescents (60.5% female, 14-19 years of age) with a prior or current history of romantic relationship involvement. Structural equation modeling was used to test a mediation model positing an indirect pathway from social anxiety to romantic relationship functioning through functioning in close same- and other-sex friendships. Given known gender differences in social anxiety and relationship functioning, gender also was explored as a potential moderator. Results supported the hypothesized indirect pathway whereby social anxiety was associated with impairment in same-sex friendships; functioning in same-sex friendships was associated with functioning in other-sex friendships, which was associated, in turn, with functioning in romantic relationships. While the hypothesized indirect pathway was significant among both boys and girls, there was greater continuity of functioning between same- and other-sex friendships for girls. These findings highlight the importance of examining the multiple downstream effects of social anxiety on perceived social functioning in adolescence, and suggest that continuity may exist for maladaptive patterns of socialization, particularly across

  3. Massively parallel sequencing of single cells by epicPCR links functional genes with phylogenetic markers

    PubMed Central

    Spencer, Sarah J; Tamminen, Manu V; Preheim, Sarah P; Guo, Mira T; Briggs, Adrian W; Brito, Ilana L; A Weitz, David; Pitkänen, Leena K; Vigneault, Francois; Virta, Marko PJuhani; Alm, Eric J

    2016-01-01

    Many microbial communities are characterized by high genetic diversity. 16S ribosomal RNA sequencing can determine community members, and metagenomics can determine the functional diversity, but resolving the functional role of individual cells in high throughput remains an unsolved challenge. Here, we describe epicPCR (Emulsion, Paired Isolation and Concatenation PCR), a new technique that links functional genes and phylogenetic markers in uncultured single cells, providing a throughput of hundreds of thousands of cells with costs comparable to one genomic library preparation. We demonstrate the utility of our technique in a natural environment by profiling a sulfate-reducing community in a freshwater lake, revealing both known sulfate reducers and discovering new putative sulfate reducers. Our method is adaptable to any conserved genetic trait and translates genetic associations from diverse microbial samples into a sequencing library that answers targeted ecological questions. Potential applications include identifying functional community members, tracing horizontal gene transfer networks and mapping ecological interactions between microbial cells. PMID:26394010

  4. Massively parallel sequencing of single cells by epicPCR links functional genes with phylogenetic markers.

    PubMed

    Spencer, Sarah J; Tamminen, Manu V; Preheim, Sarah P; Guo, Mira T; Briggs, Adrian W; Brito, Ilana L; A Weitz, David; Pitkänen, Leena K; Vigneault, Francois; Juhani Virta, Marko P; Alm, Eric J

    2016-02-01

    Many microbial communities are characterized by high genetic diversity. 16S ribosomal RNA sequencing can determine community members, and metagenomics can determine the functional diversity, but resolving the functional role of individual cells in high throughput remains an unsolved challenge. Here, we describe epicPCR (Emulsion, Paired Isolation and Concatenation PCR), a new technique that links functional genes and phylogenetic markers in uncultured single cells, providing a throughput of hundreds of thousands of cells with costs comparable to one genomic library preparation. We demonstrate the utility of our technique in a natural environment by profiling a sulfate-reducing community in a freshwater lake, revealing both known sulfate reducers and discovering new putative sulfate reducers. Our method is adaptable to any conserved genetic trait and translates genetic associations from diverse microbial samples into a sequencing library that answers targeted ecological questions. Potential applications include identifying functional community members, tracing horizontal gene transfer networks and mapping ecological interactions between microbial cells. PMID:26394010

  5. Linking Functional Connectivity and Structural Connectivity Quantitatively: A Comparison of Methods.

    PubMed

    Huang, Haiqing; Ding, Mingzhou

    2016-03-01

    Structural connectivity in the brain is the basis of functional connectivity. Quantitatively linking the two, however, remains a challenge. For a pair of regions of interest (ROIs), anatomical connections derived from diffusion-weighted imaging are often quantified by fractional anisotropy (FA) or edge weight, whereas functional connections, derived from resting-state functional magnetic resonance imaging, can be characterized by non-time-series measures such as zero-lag cross correlation and partial correlation, as well as by time-series measures such as coherence and Granger causality. In this study, we addressed the question of linking structural connectivity and functional connectivity quantitatively by considering two pairs of ROIs, one from the default mode network (DMN) and the other from the central executive network (CEN), using two different data sets. Selecting (1) posterior cingulate cortex and medial prefrontal cortex of the DMN as the first pair of ROIs and (2) left dorsal lateral prefrontal cortex and left inferior parietal lobule of the CEN as the second pair of ROIs, we show that (1) zero-lag cross correlation, partial correlation, and pairwise Granger causality were not significantly correlated with either mean FA or edge weight and (2) conditional Granger causality (CGC) was significantly correlated with edge weight but not with mean FA. These results suggest that (1) edge weight may be a more appropriate measure to quantify the strength of the anatomical connection between ROIs and (2) CGC, which statistically removes common input and the indirect influences between a given ROI pair, may be a more appropriate measure to quantify the strength of the functional interaction enabled by the fibers linking the two ROIs. PMID:26598788

  6. Comparative interactomes of SIRT6 and SIRT7: Implication of functional links to aging.

    PubMed

    Lee, Namgyu; Kim, Dae-Kyum; Kim, Eung-Sam; Park, Sung Jin; Kwon, Jung-Hee; Shin, Jihye; Park, Seon-Min; Moon, Young Ho; Wang, Hee Jung; Gho, Yong Song; Choi, Kwan Yong

    2014-07-01

    Sirtuins are NAD(+) -dependent deacetylases that regulate a range of cellular processes. Although diverse functions of sirtuins have been proposed, those functions of SIRT6 and SIRT7 that are mediated by their interacting proteins remain elusive. In the present study, we identified SIRT6- and SIRT7-interacting proteins, and compared their interactomes to investigate functional links. Our interactomes revealed 136 interacting proteins for SIRT6 and 233 for SIRT7 while confirming seven and 111 proteins identified previously for SIRT6 and SIRT7, respectively. Comparison of SIRT6 and SIRT7 interactomes under the same experimental conditions disclosed 111 shared proteins, implying related functional links. The interaction networks of interactomes indicated biological processes associated with DNA repair, chromatin assembly, and aging. Interactions of two highly acetylated proteins, nucleophosmin (NPM1) and nucleolin, with SIRT6 and SIRT7 were confirmed by co-immunoprecipitation. NPM1 was found to be deacetylated by both SIRT6 and SIRT7. In senescent cells, the acetylation level of NPM1 was increased in conjunction with decreased levels of SIRT6 and SIRT7, suggesting that the acetylation of NPM1 could be regulated by SIRT6 and SIRT7 in the aging process. Our comparative interactomic study of SIRT6 and SIRT7 implies important functional links to aging by their associations with interacting proteins. All MS data have been deposited in the ProteomeXchange with identifiers PXD000159 and PXD000850 (http://proteomecentral.proteomexchange.org/dataset/PXD000159, http://proteomecentral.proteomexchange.org/dataset/PXD000850). PMID:24782448

  7. Crucial role of detailed function, task, timeline, link and human vulnerability analyses in HRA

    SciTech Connect

    Ryan, T.G.; Haney, L.N.; Ostrom, L.T.

    1992-10-01

    This paper addresses one major cause for large uncertainties in human reliability analysis (HRA) results, that is, an absence of detailed function, task, timeline, link and human vulnerability analyses. All too often this crucial step in the HRA process is done in a cursory fashion using word of mouth or written procedures which themselves may incompletely or inaccurately represent the human action sequences and human error vulnerabilities being analyzed. The paper examines the potential contributions these detailed analyses can make in achieving quantitative and qualitative HRA results which are: (1) creditable, that is, minimize uncertainty, (2) auditable, that is, systematically linking quantitative results and qualitative information from which the results are derived, (3) capable of supporting root cause analyses on human reliability factors determined to be major contributors to risk, and (4) capable of repeated measures and being combined with similar results from other analyses to examine HRA issues transcending individual systems and facilities. Based on experience analyzing test and commercial nuclear reactors, and medical applications of nuclear technology, an iterative process is suggested for doing detailed function, task, timeline, link and human vulnerability analyses using documentation reviews, open-ended and structured interviews, direct observations, and group techniques. Finally, the paper concludes that detailed analyses done in this manner by knowledgeable human factors practitioners, can contribute significantly to the credibility, auditability, causal factor analysis, and combining goals of the HRA.

  8. Identification of gene ontologies linked to prefrontal–hippocampal functional coupling in the human brain

    PubMed Central

    Dixson, Luanna; Walter, Henrik; Schneider, Michael; Erk, Susanne; Schäfer, Axel; Haddad, Leila; Grimm, Oliver; Mattheisen, Manuel; Nöthen, Markus M.; Cichon, Sven; Witt, Stephanie H.; Rietschel, Marcella; Mohnke, Sebastian; Seiferth, Nina; Heinz, Andreas; Tost, Heike; Meyer-Lindenberg, Andreas

    2014-01-01

    Functional interactions between the dorsolateral prefrontal cortex and hippocampus during working memory have been studied extensively as an intermediate phenotype for schizophrenia. Coupling abnormalities have been found in patients, their unaffected siblings, and carriers of common genetic variants associated with schizophrenia, but the global genetic architecture of this imaging phenotype is unclear. To achieve genome-wide hypothesis-free identification of genes and pathways associated with prefrontal–hippocampal interactions, we combined gene set enrichment analysis with whole-genome genotyping and functional magnetic resonance imaging data from 269 healthy German volunteers. We found significant enrichment of the synapse organization and biogenesis gene set. This gene set included known schizophrenia risk genes, such as neural cell adhesion molecule (NRCAM) and calcium channel, voltage-dependent, beta 2 subunit (CACNB2), as well as genes with well-defined roles in neurodevelopmental and plasticity processes that are dysfunctional in schizophrenia and have mechanistic links to prefrontal–hippocampal functional interactions. Our results demonstrate a readily generalizable approach that can be used to identify the neurogenetic basis of systems-level phenotypes. Moreover, our findings identify gene sets in which genetic variation may contribute to disease risk through altered prefrontal–hippocampal functional interactions and suggest a link to both ongoing and developmental synaptic plasticity. PMID:24979789

  9. The Structurally Plastic CH2 Domain Is Linked to Distinct Functions of Fimbrins/Plastins.

    PubMed

    Zhang, Ruihui; Chang, Ming; Zhang, Meng; Wu, Youjun; Qu, Xiaolu; Huang, Shanjin

    2016-08-19

    Fimbrins/plastins have been implicated in the generation of distinct actin structures, which are linked to different cellular processes. Historically, fimbrins/plastins were mainly considered as generating tight actin bundles. Here, we demonstrate that different members of the fimbrin/plastin family have diverged biochemically during evolution to generate either tight actin bundles or loose networks with distinct biochemical and biophysical properties. Using the phylogenetically and functionally distinct Arabidopsis fimbrins FIM4 and FIM5 we found that FIM4 generates both actin bundles and cross-linked actin filaments, whereas FIM5 only generates actin bundles. The distinct functions of FIM4 and FIM5 are clearly observed at single-filament resolution. Domain swapping experiments showed that cooperation between the conformationally plastic calponin-homology domain 2 (CH2) and the N-terminal headpiece determines the function of the full-length protein. Our study suggests that the structural plasticity of fimbrins/plastins has biologically meaningful consequences, and provides novel insights into the structure-function relationship of fimbrins/plastins as well as shedding light on how cells generate distinct actin structures. PMID:27261463

  10. Epigenetic Function of Activation-Induced Cytidine Deaminase and Its Link to Lymphomagenesis

    PubMed Central

    Dominguez, Pilar M.; Shaknovich, Rita

    2014-01-01

    Activation-induced cytidine deaminase (AID) is essential for somatic hypermutation and class switch recombination of immunoglobulin (Ig) genes during B cell maturation and immune response. Expression of AID is tightly regulated due to its mutagenic and recombinogenic potential, which is known to target not only Ig genes, but also non-Ig genes, contributing to lymphomagenesis. In recent years, a new epigenetic function of AID and its link to DNA demethylation came to light in several developmental systems. In this review, we summarize existing evidence linking deamination of unmodified and modified cytidine by AID to base-excision repair and mismatch repair machinery resulting in passive or active removal of DNA methylation mark, with the focus on B cell biology. We also discuss potential contribution of AID-dependent DNA hypomethylation to lymphomagenesis. PMID:25566255

  11. Longitudinal links between childhood peer victimization, internalizing and externalizing problems, and academic functioning: developmental cascades.

    PubMed

    Vaillancourt, Tracy; Brittain, Heather L; McDougall, Patricia; Duku, Eric

    2013-11-01

    Developmental cascade models linking childhood peer victimization, internalizing and externalizing problems, and academic functioning were examined in a sample of 695 children assessed in Grade 3 (academic only) and Grades 5, 6, 7, and 8. Results revealed several complex patterns of associations in which poorer functioning in one domain influenced poorer outcomes in other areas. For example, a symptom driven pathway was consistently found with internalizing problems predicting future peer victimization. Support for an academic incompetence model was also found-- lower GPA in Grade 5, 6, and 7 was associated with more externalizing issues in the following year, and poor writing performance in Grade 3 predicted lower grades in Grade 5, which in turn predicted more externalizing problems in Grade 6. Results highlight the need to examine bidirectional influences and multifarious transactions that exist between peer victimization, mental health, and academic functioning over time. PMID:23907699

  12. Non-dipolar gauge links for transverse-momentum-dependent pion wave functions

    NASA Astrophysics Data System (ADS)

    Wang, Yu-Ming

    2016-03-01

    I discuss the factorization-compatible definitions of transverse-momentumdependent (TMD) pion wave functions which are fundamental theory inputs entering QCD factorization formulae for many hard exclusive processes. I will first demonstrate that the soft subtraction factor introduced to remove both rapidity and pinch singularities can be greatly reduced by making the maximal use of the freedom to construct the Wilson-line paths when defining the TMD wave functions. I will then turn to show that the newly proposed TMD definition with non-dipolarWilson lines is equivalent to the one with dipolar gauge links and with a complicated soft function, to all orders of the perturbative expansion in the strong coupling, as far as the infrared behavior is concerned.

  13. Unconventional N-Linked Glycosylation Promotes Trimeric Autotransporter Function in Kingella kingae and Aggregatibacter aphrophilus

    PubMed Central

    Rempe, Katherine A.; Spruce, Lynn A.; Porsch, Eric A.; Seeholzer, Steven H.; Nørskov-Lauritsen, Niels

    2015-01-01

    ABSTRACT Glycosylation is a widespread mechanism employed by both eukaryotes and bacteria to increase the functional diversity of their proteomes. The nontypeable Haemophilus influenzae glycosyltransferase HMW1C mediates unconventional N-linked glycosylation of the adhesive protein HMW1, which is encoded in a two-partner secretion system gene cluster that also encodes HMW1C. In this system, HMW1 is modified in the cytoplasm by sequential transfer of hexose residues. In the present study, we examined Kingella kingae and Aggregatibacter aphrophilus homologues of HMW1C that are not encoded near a gene encoding an obvious acceptor protein. We found both homologues to be functional glycosyltransferases and identified their substrates as the K. kingae Knh and the A. aphrophilus EmaA trimeric autotransporter proteins. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed multiple sites of N-linked glycosylation on Knh and EmaA. Without glycosylation, Knh and EmaA failed to facilitate wild-type levels of bacterial autoaggregation or adherence to human epithelial cells, establishing that glycosylation is essential for proper protein function. PMID:26307167

  14. Sex differences in resting state brain function of cigarette smokers and links to nicotine dependence.

    PubMed

    Beltz, Adriene M; Berenbaum, Sheri A; Wilson, Stephen J

    2015-08-01

    Sex--a marker of biological and social individual differences--matters for drug use, particularly for cigarette smoking, which is the leading cause of preventable death in the United States. More men than women smoke, but women are less likely than men to quit. Resting state brain function, or intrinsic brain activity that occurs in the absence of a goal-directed task, is important for understanding cigarette smoking, as it has been shown to differentiate between smokers and nonsmokers. But, it is unclear whether and how sex influences the link between resting state brain function and smoking behavior. In this study, the authors demonstrate that sex is indeed associated with resting state connectivity in cigarette smokers, and that sex moderates the link between resting state connectivity and self-reported nicotine dependence. Using functional MRI and behavioral data from 50 adult daily smokers (23 women), the authors found that women had greater connectivity than men within the default mode network, and that increased connectivity within the reward network was related to increased nicotine tolerance in women but to decreased nicotine tolerance in men. Findings highlight the importance of sex-related individual differences reflected in resting state connectivity for understanding the etiology and treatment of substance use problems. PMID:26237322

  15. [Cognitive Function and Calcium. The link between dementia and bone and calcium metabolism disorders].

    PubMed

    Yamaguchi, Kiyoshi

    2015-02-01

    Bone and calcium metabolism disorders are closely linked with dementia. Screening for dementia is important since chronic hypercalcemia and hypocalcemia resulting from parathyroid function abnormalities can become a cause of dementia onset. In recent years, it has become clear that vitamin D deficiencies inducing cardiovascular disease and other factors are involved in the pathogenesis of various diseases that in turn become risk factors in dementia, especially Alzheimer's disease. Moreover, osteoporosis and dementia both commonly occur among the elderly. Treating dementia patients for osteoporosis is important since fragility fractures, especially femoral neck fractures, resulting from osteoporosis greatly affect the prognosis of patients with dementia. PMID:25634043

  16. Linking Executive Function and Peer Problems from Early Childhood Through Middle Adolescence.

    PubMed

    Holmes, Christopher J; Kim-Spoon, Jungmeen; Deater-Deckard, Kirby

    2016-01-01

    Peer interactions and executive function play central roles in the development of healthy children, as peer problems have been indicative of lower cognitive competencies such as self-regulatory behavior and poor executive function has been indicative of problem behaviors and social dysfunction. However, few studies have focused on the relation between peer interactions and executive function and the underlying mechanisms that may create this link. Using a national sample (n = 1164, 48.6% female) from the Study of Early Child Care and Youth Development (SECCYD), we analyzed executive function and peer problems (including victimization and rejection) across three waves within each domain (executive function or peer problems), beginning in early childhood and ending in middle adolescence. Executive function was measured as a multi-method, multi-informant composite including reports from parents on the Children's Behavior Questionnaire and Child Behavior Checklist and child's performance on behavioral tasks including the Continuous Performance Task, Woodcock-Johnson, Tower of Hanoi, Operation Span Task, Stroop, and Tower of London. Peer problems were measured as a multi-informant composite including self, teacher, and afterschool caregiver reports on multiple peer-relationship scales. Using a cross-lagged design, our Structural Equation Modeling findings suggested that experiencing peer problems contributed to lower executive function later in childhood and better executive function reduced the likelihood of experiencing peer problems later in childhood and middle adolescence, although these relations weakened as a child moves into adolescence. The results highlight that peer relationships are involved in the development of strengths and deficits in executive function and vice versa. PMID:26096194

  17. Linking EEG signals, brain functions and mental operations: Advantages of the Laplacian transformation.

    PubMed

    Vidal, Franck; Burle, Boris; Spieser, Laure; Carbonnell, Laurence; Meckler, Cédric; Casini, Laurence; Hasbroucq, Thierry

    2015-09-01

    Electroencephalography (EEG) is a very popular technique for investigating brain functions and/or mental processes. To this aim, EEG activities must be interpreted in terms of brain and/or mental processes. EEG signals being a direct manifestation of neuronal activity it is often assumed that such interpretations are quite obvious or, at least, straightforward. However, they often rely on (explicit or even implicit) assumptions regarding the structures supposed to generate the EEG activities of interest. For these assumptions to be used appropriately, reliable links between EEG activities and the underlying brain structures must be established. Because of volume conduction effects and the mixture of activities they induce, these links are difficult to establish with scalp potential recordings. We present different examples showing how the Laplacian transformation, acting as an efficient source separation method, allowed to establish more reliable links between EEG activities and brain generators and, ultimately, with mental operations. The nature of those links depends on the depth of inferences that can vary from weak to strong. Along this continuum, we show that 1) while the effects of experimental manipulation can appear widely distributed with scalp potentials, Laplacian transformation allows to reveal several generators contributing (in different manners) to these modulations, 2) amplitude variations within the same set of generators can generate spurious differences in scalp potential topographies, often interpreted as reflecting different source configurations. In such a case, Laplacian transformation provides much more similar topographies, evidencing the same generator(s) set, and 3) using the LRP as an index of response activation most often produces ambiguous results, Laplacian-transformed response-locked ERPs obtained over motor areas allow resolving these ambiguities. PMID:25958789

  18. Bayesian inference in an item response theory model with a generalized student t link function

    NASA Astrophysics Data System (ADS)

    Azevedo, Caio L. N.; Migon, Helio S.

    2012-10-01

    In this paper we introduce a new item response theory (IRT) model with a generalized Student t-link function with unknown degrees of freedom (df), named generalized t-link (GtL) IRT model. In this model we consider only the difficulty parameter in the item response function. GtL is an alternative to the two parameter logit and probit models, since the degrees of freedom (df) play a similar role to the discrimination parameter. However, the behavior of the curves of the GtL is different from those of the two parameter models and the usual Student t link, since in GtL the curve obtained from different df's can cross the probit curves in more than one latent trait level. The GtL model has similar proprieties to the generalized linear mixed models, such as the existence of sufficient statistics and easy parameter interpretation. Also, many techniques of parameter estimation, model fit assessment and residual analysis developed for that models can be used for the GtL model. We develop fully Bayesian estimation and model fit assessment tools through a Metropolis-Hastings step within Gibbs sampling algorithm. We consider a prior sensitivity choice concerning the degrees of freedom. The simulation study indicates that the algorithm recovers all parameters properly. In addition, some Bayesian model fit assessment tools are considered. Finally, a real data set is analyzed using our approach and other usual models. The results indicate that our model fits the data better than the two parameter models.

  19. Efficient estimation and prediction for the Bayesian binary spatial model with flexible link functions.

    PubMed

    Roy, Vivekananda; Evangelou, Evangelos; Zhu, Zhengyuan

    2016-03-01

    Spatial generalized linear mixed models (SGLMMs) are popular models for spatial data with a non-Gaussian response. Binomial SGLMMs with logit or probit link functions are often used to model spatially dependent binomial random variables. It is known that for independent binomial data, the robit regression model provides a more robust (against extreme observations) alternative to the more popular logistic and probit models. In this article, we introduce a Bayesian spatial robit model for spatially dependent binomial data. Since constructing a meaningful prior on the link function parameter as well as the spatial correlation parameters in SGLMMs is difficult, we propose an empirical Bayes (EB) approach for the estimation of these parameters as well as for the prediction of the random effects. The EB methodology is implemented by efficient importance sampling methods based on Markov chain Monte Carlo (MCMC) algorithms. Our simulation study shows that the robit model is robust against model misspecification, and our EB method results in estimates with less bias than full Bayesian (FB) analysis. The methodology is applied to a Celastrus Orbiculatus data, and a Rhizoctonia root data. For the former, which is known to contain outlying observations, the robit model is shown to do better for predicting the spatial distribution of an invasive species. For the latter, our approach is doing as well as the classical models for predicting the disease severity for a root disease, as the probit link is shown to be appropriate. Though this article is written for Binomial SGLMMs for brevity, the EB methodology is more general and can be applied to other types of SGLMMs. In the accompanying R package geoBayes, implementations for other SGLMMs such as Poisson and Gamma SGLMMs are provided. PMID:26331903

  20. Functional Divergence in the Role of N-Linked Glycosylation in Smoothened Signaling

    PubMed Central

    Marada, Suresh; Navarro, Gemma; Truong, Ashley; Stewart, Daniel P.; Arensdorf, Angela M.; Nachtergaele, Sigrid; Angelats, Edgar; Opferman, Joseph T.; Rohatgi, Rajat; McCormick, Peter J.; Ogden, Stacey K.

    2015-01-01

    The G protein-coupled receptor (GPCR) Smoothened (Smo) is the requisite signal transducer of the evolutionarily conserved Hedgehog (Hh) pathway. Although aspects of Smo signaling are conserved from Drosophila to vertebrates, significant differences have evolved. These include changes in its active sub-cellular localization, and the ability of vertebrate Smo to induce distinct G protein-dependent and independent signals in response to ligand. Whereas the canonical Smo signal to Gli transcriptional effectors occurs in a G protein-independent manner, its non-canonical signal employs Gαi. Whether vertebrate Smo can selectively bias its signal between these routes is not yet known. N-linked glycosylation is a post-translational modification that can influence GPCR trafficking, ligand responsiveness and signal output. Smo proteins in Drosophila and vertebrate systems harbor N-linked glycans, but their role in Smo signaling has not been established. Herein, we present a comprehensive analysis of Drosophila and murine Smo glycosylation that supports a functional divergence in the contribution of N-linked glycans to signaling. Of the seven predicted glycan acceptor sites in Drosophila Smo, one is essential. Loss of N-glycosylation at this site disrupted Smo trafficking and attenuated its signaling capability. In stark contrast, we found that all four predicted N-glycosylation sites on murine Smo were dispensable for proper trafficking, agonist binding and canonical signal induction. However, the under-glycosylated protein was compromised in its ability to induce a non-canonical signal through Gαi, providing for the first time evidence that Smo can bias its signal and that a post-translational modification can impact this process. As such, we postulate a profound shift in N-glycan function from affecting Smo ER exit in flies to influencing its signal output in mice. PMID:26291458

  1. Dopamine D2 receptor availability is linked to hippocampal-caudate functional connectivity and episodic memory.

    PubMed

    Nyberg, Lars; Karalija, Nina; Salami, Alireza; Andersson, Micael; Wåhlin, Anders; Kaboovand, Neda; Köhncke, Ylva; Axelsson, Jan; Rieckmann, Anna; Papenberg, Goran; Garrett, Douglas D; Riklund, Katrine; Lövdén, Martin; Lindenberger, Ulman; Bäckman, Lars

    2016-07-12

    D1 and D2 dopamine receptors (D1DRs and D2DRs) may contribute differently to various aspects of memory and cognition. The D1DR system has been linked to functions supported by the prefrontal cortex. By contrast, the role of the D2DR system is less clear, although it has been hypothesized that D2DRs make a specific contribution to hippocampus-based cognitive functions. Here we present results from 181 healthy adults between 64 and 68 y of age who underwent comprehensive assessment of episodic memory, working memory, and processing speed, along with MRI and D2DR assessment with [(11)C]raclopride and PET. Caudate D2DR availability was positively associated with episodic memory but not with working memory or speed. Whole-brain analyses further revealed a relation between hippocampal D2DR availability and episodic memory. Hippocampal and caudate D2DR availability were interrelated, and functional MRI-based resting-state functional connectivity between the ventral caudate and medial temporal cortex increased as a function of caudate D2DR availability. Collectively, these findings indicate that D2DRs make a specific contribution to hippocampus-based cognition by influencing striatal and hippocampal regions, and their interactions. PMID:27339132

  2. Regressive evolution of the arthropod tritocerebral segment linked to functional divergence of the Hox gene labial

    PubMed Central

    Pechmann, Matthias; Schwager, Evelyn E.; Turetzek, Natascha; Prpic, Nikola-Michael

    2015-01-01

    The intercalary segment is a limbless version of the tritocerebral segment and is present in the head of all insects, whereas other extant arthropods have retained limbs on their tritocerebral segment (e.g. the pedipalp limbs in spiders). The evolutionary origin of limb loss on the intercalary segment has puzzled zoologists for over a century. Here we show that an intercalary segment-like phenotype can be created in spiders by interfering with the function of the Hox gene labial. This links the origin of the intercalary segment to a functional change in labial. We show that in the spider Parasteatoda tepidariorum the labial gene has two functions: one function in head tissue maintenance that is conserved between spiders and insects, and a second function in pedipalp limb promotion and specification, which is only present in spiders. These results imply that labial was originally crucial for limb formation on the tritocerebral segment, but that it has lost this particular subfunction in the insect ancestor, resulting in limb loss on the intercalary segment. Such loss of a subfunction is a way to avoid adverse pleiotropic effects normally associated with mutations in developmental genes, and may thus be a common mechanism to accelerate regressive evolution. PMID:26311666

  3. Linking the patterns of change in composition and function in bacterioplankton successions along environmental gradients.

    PubMed

    Comte, Jérôme; del Giorgio, Paul A

    2010-05-01

    The connections that exist between the composition of bacterial communities and their functional attributes are still a matter of intense debate, despite over a decade of intense studies. Here we explored three different facets of the links that may exist between bacterioplankton compositional and functional successions that occurred along the water flow path in a complex watershed in southern Quebec. We analyzed the correlation between composition and function in terms of their absolute patterns, and in terms of their rates of change relative to transit time in environmental transitions, and relative to shifts in resources along the same transitions. Our results showed that the absolute patterns in bacterial community composition (BCC, using DGGE [denaturing gradient gel electrophoresis] profiles) and functional capacities (FC, using BIOLOG profiles) were not correlated, but that the rates of change in BCC and FC along the transitions were strongly correlated to each other. Further, we observed that the strength and shape of the relationship between the changes in BCC and FC varied relative to the type and intensity of gradient considered. Collectively, these results showed that BCC and FC are strongly related but in a very dynamic manner, such that their absolute patterns do not appear to be connected. This in turn suggests a high level of functional redundancy that occurs both within the existing community and in the meta-community from which phylotypes are selected to occupy the new niches that are created along the transitions. PMID:20503878

  4. Dopamine D2 receptor availability is linked to hippocampal–caudate functional connectivity and episodic memory

    PubMed Central

    Nyberg, Lars; Karalija, Nina; Salami, Alireza; Andersson, Micael; Wåhlin, Anders; Kaboovand, Neda; Köhncke, Ylva; Axelsson, Jan; Rieckmann, Anna; Papenberg, Goran; Garrett, Douglas D.; Riklund, Katrine; Lövdén, Martin; Bäckman, Lars

    2016-01-01

    D1 and D2 dopamine receptors (D1DRs and D2DRs) may contribute differently to various aspects of memory and cognition. The D1DR system has been linked to functions supported by the prefrontal cortex. By contrast, the role of the D2DR system is less clear, although it has been hypothesized that D2DRs make a specific contribution to hippocampus-based cognitive functions. Here we present results from 181 healthy adults between 64 and 68 y of age who underwent comprehensive assessment of episodic memory, working memory, and processing speed, along with MRI and D2DR assessment with [11C]raclopride and PET. Caudate D2DR availability was positively associated with episodic memory but not with working memory or speed. Whole-brain analyses further revealed a relation between hippocampal D2DR availability and episodic memory. Hippocampal and caudate D2DR availability were interrelated, and functional MRI-based resting-state functional connectivity between the ventral caudate and medial temporal cortex increased as a function of caudate D2DR availability. Collectively, these findings indicate that D2DRs make a specific contribution to hippocampus-based cognition by influencing striatal and hippocampal regions, and their interactions. PMID:27339132

  5. Using plant functional traits as a link between land use and bee foraging abundance

    NASA Astrophysics Data System (ADS)

    Pakeman, R. J.; Stockan, J.

    2013-07-01

    Many recent studies have shown that plant functional traits can be used to predict the response of plant assemblages to management or other environmental change. A further challenge is to use them to predict changes in the assemblages of other groups. Using data from a study of the impact of land use on biodiversity, the linkages between management drivers, a range of plant functional traits and the overall foraging numbers and assemblage of bees was assessed. Bee foraging numbers were only weakly predicted by plant traits, though bee foraging assemblage was closely related to a number of different groups of plant traits (flower colour and Forage Index, as well as taxonomic group). In turn, the selected traits were significantly correlated to some of the response traits that linked the plant assemblage to management, indicating that there was a predictive pathway from management to bee abundance and assemblage structure. However, models developed with just the environmental drivers proved superior at predicting both bee numbers and assemblage. Plant traits proved to be a moderately effective predictor of bee assemblage structure. However, the use of plant traits as a link between the bees and management did not offer any improvement on models directly developed from management variables. This suggests that the bee assemblage is responding to traits that have not been quantified and that developing these trophic linkage models may have to take a different approach.

  6. C2 Link Security for UAS: Technical Literature Study and Preliminary Functional Requirements. Version 0.9 (Working Draft)

    NASA Technical Reports Server (NTRS)

    2005-01-01

    This document provides a study of the technical literature related to Command and Control (C2) link security for Unmanned Aircraft Systems (UAS) for operation in the National Airspace System (NAS). Included is a preliminary set of functional requirements for C2 link security.

  7. Allocating structure to function: the strong links between neuroplasticity and natural selection

    PubMed Central

    Anderson, Michael L.; Finlay, Barbara L.

    2014-01-01

    A central question in brain evolution is how species-typical behaviors, and the neural function-structure mappings supporting them, can be acquired and inherited. Advocates of brain modularity, in its different incarnations across scientific subfields, argue that natural selection must target domain-dedicated, separately modifiable neural subsystems, resulting in genetically-specified functional modules. In such modular systems, specification of neuron number and functional connectivity are necessarily linked. Mounting evidence, however, from allometric, developmental, comparative, systems-physiological, neuroimaging and neurological studies suggests that brain elements are used and reused in multiple functional systems. This variable allocation can be seen in short-term neuromodulation, in neuroplasticity over the lifespan and in response to damage. We argue that the same processes are evident in brain evolution. Natural selection must preserve behavioral functions that may co-locate in variable amounts with other functions. In genetics, the uses and problems of pleiotropy, the re-use of genes in multiple networks have been much discussed, but this issue has been sidestepped in neural systems by the invocation of modules. Here we highlight the interaction between evolutionary and developmental mechanisms to produce distributed and overlapping functional architectures in the brain. These adaptive mechanisms must be robust to perturbations that might disrupt critical information processing and action selection, but must also recognize useful new sources of information arising from internal genetic or environmental variability, when those appear. These contrasting properties of “robustness” and “evolvability” have been discussed for the basic organization of body plan and fundamental cell physiology. Here we extend them to the evolution and development, “evo-devo,” of brain structure. PMID:24431995

  8. p62 Links β-adrenergic input to mitochondrial function and thermogenesis

    PubMed Central

    Müller, Timo D.; Lee, Sang Jun; Jastroch, Martin; Kabra, Dhiraj; Stemmer, Kerstin; Aichler, Michaela; Abplanalp, Bill; Ananthakrishnan, Gayathri; Bhardwaj, Nakul; Collins, Sheila; Divanovic, Senad; Endele, Max; Finan, Brian; Gao, Yuanqing; Habegger, Kirk M.; Hembree, Jazzmin; Heppner, Kristy M.; Hofmann, Susanna; Holland, Jenna; Küchler, Daniela; Kutschke, Maria; Krishna, Radha; Lehti, Maarit; Oelkrug, Rebecca; Ottaway, Nickki; Perez-Tilve, Diego; Raver, Christine; Walch, Axel K.; Schriever, Sonja C.; Speakman, John; Tseng, Yu-Hua; Diaz-Meco, Maria; Pfluger, Paul T.; Moscat, Jorge; Tschöp, Matthias H.

    2012-01-01

    The scaffold protein p62 (sequestosome 1; SQSTM1) is an emerging key molecular link among the metabolic, immune, and proliferative processes of the cell. Here, we report that adipocyte-specific, but not CNS-, liver-, muscle-, or myeloid-specific p62-deficient mice are obese and exhibit a decreased metabolic rate caused by impaired nonshivering thermogenesis. Our results show that p62 regulates energy metabolism via control of mitochondrial function in brown adipose tissue (BAT). Accordingly, adipocyte-specific p62 deficiency led to impaired mitochondrial function, causing BAT to become unresponsive to β-adrenergic stimuli. Ablation of p62 leads to decreased activation of p38 targets, affecting signaling molecules that control mitochondrial function, such as ATF2, CREB, PGC1α, DIO2, NRF1, CYTC, COX2, ATP5β, and UCP1. p62 ablation in HIB1B and BAT primary cells demonstrated that p62 controls thermogenesis in a cell-autonomous manner, independently of brown adipocyte development or differentiation. Together, our data identify p62 as a novel regulator of mitochondrial function and brown fat thermogenesis. PMID:23257354

  9. Ecological-network models link diversity, structure and function in the plankton food-web

    PubMed Central

    D’Alelio, Domenico; Libralato, Simone; Wyatt, Timothy; Ribera d’Alcalà, Maurizio

    2016-01-01

    A planktonic food-web model including sixty-three functional nodes (representing auto- mixo- and heterotrophs) was developed to integrate most trophic diversity present in the plankton. The model was implemented in two variants - which we named ‘green’ and ‘blue’ - characterized by opposite amounts of phytoplankton biomass and representing, respectively, bloom and non-bloom states of the system. Taxonomically disaggregated food-webs described herein allowed to shed light on how components of the plankton community changed their trophic behavior in the two different conditions, and modified the overall functioning of the plankton food web. The green and blue food-webs showed distinct organizations in terms of trophic roles of the nodes and carbon fluxes between them. Such re-organization stemmed from switches in selective grazing by both metazoan and protozoan consumers. Switches in food-web structure resulted in relatively small differences in the efficiency of material transfer towards higher trophic levels. For instance, from green to blue states, a seven-fold decrease in phytoplankton biomass translated into only a two-fold decrease in potential planktivorous fish biomass. By linking diversity, structure and function in the plankton food-web, we discuss the role of internal mechanisms, relying on species-specific functionalities, in driving the ‘adaptive’ responses of plankton communities to perturbations. PMID:26883643

  10. Ecological-network models link diversity, structure and function in the plankton food-web.

    PubMed

    D'Alelio, Domenico; Libralato, Simone; Wyatt, Timothy; Ribera d'Alcalà, Maurizio

    2016-01-01

    A planktonic food-web model including sixty-three functional nodes (representing auto- mixo- and heterotrophs) was developed to integrate most trophic diversity present in the plankton. The model was implemented in two variants - which we named 'green' and 'blue' - characterized by opposite amounts of phytoplankton biomass and representing, respectively, bloom and non-bloom states of the system. Taxonomically disaggregated food-webs described herein allowed to shed light on how components of the plankton community changed their trophic behavior in the two different conditions, and modified the overall functioning of the plankton food web. The green and blue food-webs showed distinct organizations in terms of trophic roles of the nodes and carbon fluxes between them. Such re-organization stemmed from switches in selective grazing by both metazoan and protozoan consumers. Switches in food-web structure resulted in relatively small differences in the efficiency of material transfer towards higher trophic levels. For instance, from green to blue states, a seven-fold decrease in phytoplankton biomass translated into only a two-fold decrease in potential planktivorous fish biomass. By linking diversity, structure and function in the plankton food-web, we discuss the role of internal mechanisms, relying on species-specific functionalities, in driving the 'adaptive' responses of plankton communities to perturbations. PMID:26883643

  11. Non-Invasive Brain-to-Brain Interface (BBI): Establishing Functional Links between Two Brains

    PubMed Central

    Yoo, Seung-Schik; Kim, Hyungmin; Filandrianos, Emmanuel; Taghados, Seyed Javid; Park, Shinsuk

    2013-01-01

    Transcranial focused ultrasound (FUS) is capable of modulating the neural activity of specific brain regions, with a potential role as a non-invasive computer-to-brain interface (CBI). In conjunction with the use of brain-to-computer interface (BCI) techniques that translate brain function to generate computer commands, we investigated the feasibility of using the FUS-based CBI to non-invasively establish a functional link between the brains of different species (i.e. human and Sprague-Dawley rat), thus creating a brain-to-brain interface (BBI). The implementation was aimed to non-invasively translate the human volunteer’s intention to stimulate a rat’s brain motor area that is responsible for the tail movement. The volunteer initiated the intention by looking at a strobe light flicker on a computer display, and the degree of synchronization in the electroencephalographic steady-state-visual-evoked-potentials (SSVEP) with respect to the strobe frequency was analyzed using a computer. Increased signal amplitude in the SSVEP, indicating the volunteer’s intention, triggered the delivery of a burst-mode FUS (350 kHz ultrasound frequency, tone burst duration of 0.5 ms, pulse repetition frequency of 1 kHz, given for 300 msec duration) to excite the motor area of an anesthetized rat transcranially. The successful excitation subsequently elicited the tail movement, which was detected by a motion sensor. The interface was achieved at 94.0±3.0% accuracy, with a time delay of 1.59±1.07 sec from the thought-initiation to the creation of the tail movement. Our results demonstrate the feasibility of a computer-mediated BBI that links central neural functions between two biological entities, which may confer unexplored opportunities in the study of neuroscience with potential implications for therapeutic applications. PMID:23573251

  12. Adolescent emotionality and effortful control: Core latent constructs and links to psychopathology and functioning

    PubMed Central

    Snyder, Hannah R.; Gulley, Lauren D.; Bijttebier, Patricia; Hartman, Catharina A.; Oldehinkel, Albertine J.; Mezulis, Amy; Young, Jami F.; Hankin, Benjamin L.

    2015-01-01

    Temperament is associated with important outcomes in adolescence, including academic and interpersonal functioning and psychopathology. Rothbart’s temperament model is among the most well-studied and supported approaches to adolescent temperament, and contains three main components: positive emotionality (PE), negative emotionality (NE), and effortful control (EC). However, the latent factor structure of Rothbart’s temperament measure for adolescents, the Early Adolescent Temperament Questionnaire Revised (EATQ-R, Ellis & Rothbart, 2001) has not been definitively established. To address this problem and investigate links between adolescent temperament and functioning, we used confirmatory factor analysis to examine the latent constructs of the EATQ-R in a large combined sample. For EC and NE, bifactor models consisting of a common factor plus specific factors for some sub-facets of each component fit best, providing a more nuanced understanding of these temperament dimensions. The nature of the PE construct in the EATQ-R is less clear. Models replicated in a hold-out dataset. The common components of high NE and low EC where broadly associated with increased psychopathology symptoms, and poor interpersonal and school functioning, while specific components of NE were further associated with corresponding specific components of psychopathology. Further questioning the construct validity of PE as measured by the EATQ-R, PE factors did not correlate with construct validity measures in a way consistent with theories of PE. Bringing consistency to the way the EATQ-R is modeled and using purer latent variables has the potential to advance the field in understanding links between dimensions of temperament and important outcomes of adolescent development. PMID:26011660

  13. Scorpion Potassium Channel-blocking Defensin Highlights a Functional Link with Neurotoxin.

    PubMed

    Meng, Lanxia; Xie, Zili; Zhang, Qian; Li, Yang; Yang, Fan; Chen, Zongyun; Li, Wenxin; Cao, Zhijian; Wu, Yingliang

    2016-03-25

    The structural similarity between defensins and scorpion neurotoxins suggests that they might have evolved from a common ancestor. However, there is no direct experimental evidence demonstrating a functional link between scorpion neurotoxins and defensins. The scorpion defensin BmKDfsin4 from Mesobuthus martensiiKarsch contains 37 amino acid residues and a conserved cystine-stabilized α/β structural fold. The recombinant BmKDfsin4, a classical defensin, has been found to have inhibitory activity against Gram-positive bacteria such as Staphylococcus aureus, Bacillus subtilis, and Micrococcus luteusas well as methicillin-resistant Staphylococcus aureus Interestingly, electrophysiological experiments showed that BmKDfsin4,like scorpion potassium channel neurotoxins, could effectively inhibit Kv1.1, Kv1.2, and Kv1.3 channel currents, and its IC50value for the Kv1.3 channel was 510.2 nm Similar to the structure-function relationships of classical scorpion potassium channel-blocking toxins, basic residues (Lys-13 and Arg-19) of BmKDfsin4 play critical roles in peptide-Kv1.3 channel interactions. Furthermore, mutagenesis and electrophysiological experiments demonstrated that the channel extracellular pore region is the binding site of BmKDfsin4, indicating that BmKDfsin4 adopts the same mechanism for blocking potassium channel currents as classical scorpion toxins. Taken together, our work identifies scorpion BmKDfsin4 as the first invertebrate defensin to block potassium channels. These findings not only demonstrate that defensins from invertebrate animals are a novel type of potassium channel blockers but also provide evidence of a functional link between defensins and neurotoxins. PMID:26817841

  14. Modelling the multidimensional niche by linking functional traits to competitive performance.

    PubMed

    Maynard, Daniel S; Leonard, Kenneth E; Drake, John M; Hall, David W; Crowther, Thomas W; Bradford, Mark A

    2015-07-22

    Linking competitive outcomes to environmental conditions is necessary for understanding species' distributions and responses to environmental change. Despite this importance, generalizable approaches for predicting competitive outcomes across abiotic gradients are lacking, driven largely by the highly complex and context-dependent nature of biotic interactions. Here, we present and empirically test a novel niche model that uses functional traits to model the niche space of organisms and predict competitive outcomes of co-occurring populations across multiple resource gradients. The model makes no assumptions about the underlying mode of competition and instead applies to those settings where relative competitive ability across environments correlates with a quantifiable performance metric. To test the model, a series of controlled microcosm experiments were conducted using genetically related strains of a widespread microbe. The model identified trait microevolution and performance differences among strains, with the predicted competitive ability of each organism mapped across a two-dimensional carbon and nitrogen resource space. Areas of coexistence and competitive dominance between strains were identified,and the predicted competitive outcomes were validated in approximately 95% of the pairings. By linking trait variation to competitive ability, our work demonstrates a generalizable approach for predicting and modelling competitive outcomes across changing environmental contexts. PMID:26136444

  15. Nonlinear dynamic system identification using Chebyshev functional link artificial neural networks.

    PubMed

    Patra, J C; Kot, A C

    2002-01-01

    A computationally efficient artificial neural network (ANN) for the purpose of dynamic nonlinear system identification is proposed. The major drawback of feedforward neural networks, such as multilayer perceptrons (MLPs) trained with the backpropagation (BP) algorithm, is that they require a large amount of computation for learning. We propose a single-layer functional-link ANN (FLANN) in which the need for a hidden layer is eliminated by expanding the input pattern by Chebyshev polynomials. The novelty of this network is that it requires much less computation than that of a MLP. We have shown its effectiveness in the problem of nonlinear dynamic system identification. In the presence of additive Gaussian noise, the performance of the proposed network is found to be similar or superior to that of a MLP. A performance comparison in terms of computational complexity has also been carried out. PMID:18238146

  16. Functional links between stability and reactivity of strontium ruthenate single crystals during oxygen evolution

    NASA Astrophysics Data System (ADS)

    Chang, Seo Hyoung; Danilovic, Nemanja; Chang, Kee-Chul; Subbaraman, Ram; Paulikas, Arvydas P.; Fong, Dillon D.; Highland, Matthew J.; Baldo, Peter M.; Stamenkovic, Vojislav R.; Freeland, John W.; Eastman, Jeffrey A.; Markovic, Nenad M.

    2014-06-01

    In developing cost-effective complex oxide materials for the oxygen evolution reaction, it is critical to establish the missing links between structure and function at the atomic level. The fundamental and practical implications of the relationship on any oxide surface are prerequisite to the design of new stable and active materials. Here we report an intimate relationship between the stability and reactivity of oxide catalysts in exploring the reaction on strontium ruthenate single-crystal thin films in alkaline environments. We determine that for strontium ruthenate films with the same conductance, the degree of stability, decreasing in the order (001)>(110)>(111), is inversely proportional to the activity. Both stability and reactivity are governed by the potential-induced transformation of stable Ru4+ to unstable Run>4+. This ordered(Ru4+)-to-disordered(Run>4+) transition and the development of active sites for the reaction are determined by a synergy between electronic and morphological effects.

  17. Single-input/single-output transfer functions for a flexible slewing link

    NASA Technical Reports Server (NTRS)

    Barbieri, Enrique

    1993-01-01

    Truncated linear models based on constrained and unconstrained mode expansions for a flexible link with torque actuation at its hub led us to examine the behavior of the open-loop-zeros of five commonly used SISO transfer functions. We arrive at new conclusions with regard to minimum- and non-minimum-phase zeros, and passivity of the transfer functions. The flexible-to-rigid inertia (FRI) ratio plays an important role in the determination of these characteristics. This paper illustrates how the zero locations of some of the transfer functions are dramatically affected by the FRI ratio. We also investigate the performance of a hub angle, hub rate, and relative tip position static feedback controller based on a reduced-order constrained mode model when applied to both unconstrained and constrained mode models of the same dimension. Simulations indicate that the constrained model can be stable while the unconstrained model is not for high FRI ratios. Our findings can provide useful information to designers in cases where the controller is sensitive to the 1ocation of the plant's zeros.

  18. The Link between Dietary Protein Intake, Skeletal Muscle Function and Health in Older Adults

    PubMed Central

    Baum, Jamie I.; Wolfe, Robert R.

    2015-01-01

    Skeletal muscle mass and function are progressively lost with age, a condition referred to as sarcopenia. By the age of 60, many older adults begin to be affected by muscle loss. There is a link between decreased muscle mass and strength and adverse health outcomes such as obesity, diabetes and cardiovascular disease. Data suggest that increasing dietary protein intake at meals may counterbalance muscle loss in older individuals due to the increased availability of amino acids, which stimulate muscle protein synthesis by activating the mammalian target of rapamycin (mTORC1). Increased muscle protein synthesis can lead to increased muscle mass, strength and function over time. This review aims to address the current recommended dietary allowance (RDA) for protein and whether or not this value meets the needs for older adults based upon current scientific evidence. The current RDA for protein is 0.8 g/kg body weight/day. However, literature suggests that consuming protein in amounts greater than the RDA can improve muscle mass, strength and function in older adults.

  19. Functional links between Drosophila Nipped-B and cohesin in somatic and meiotic cells

    PubMed Central

    Gause, Maria; Webber, Hayley A.; Misulovin, Ziva; Haller, Gabe; Rollins, Robert A.; Eissenberg, Joel C.; Bickel, Sharon E.

    2008-01-01

    Drosophila Nipped-B is an essential protein that has multiple functions. It facilitates expression of homeobox genes and is also required for sister chromatid cohesion. Nipped-B is conserved from yeast to man, and its orthologs also play roles in deoxyribonucleic acid repair and meiosis. Mutation of the human ortholog, Nipped-B-Like (NIPBL), causes Cornelia de Lange syndrome (CdLS), associated with multiple developmental defects. The Nipped-B protein family is required for the cohesin complex that mediates sister chromatid cohesion to bind to chromosomes. A key question, therefore, is whether the Nipped-B family regulates gene expression, meiosis, and development by controlling cohesin. To gain insights into Nipped-B's functions, we compared the effects of several Nipped-B mutations on gene expression, sister chromatid cohesion, and meiosis. We also examined association of Nipped-B and cohesin with somatic and meiotic chromosomes by immunostaining. Missense Nipped-B alleles affecting the same HEAT repeat motifs as CdLS-causing NIPBL mutations have intermediate effects on both gene expression and mitotic chromatid cohesion, linking these two functions and the role of NIPBL in human development. Nipped-B colocalizes extensively with cohesin on chromosomes in both somatic and meiotic cells and is present in soluble complexes with cohesin subunits in nuclear extracts. In meiosis, Nipped-B also colocalizes with the synaptonemal complex and contributes to maintenance of meiotic chromosome cores. These results support the idea that direct regulation of cohesin function underlies the diverse functions of Nipped-B and its orthologs. PMID:17909832

  20. Endothelial Markers May Link Kidney Function to Cardiovascular Events in Type 2 Diabetes

    PubMed Central

    Maier, Christina; Clodi, Martin; Neuhold, Stephanie; Resl, Michael; Elhenicky, Marie; Prager, Rudolf; Moertl, Deddo; Strunk, Guido; Luger, Anton; Struck, Joachim; Pacher, Richard; Hülsmann, Martin

    2009-01-01

    OBJECTIVE The increased cardiovascular risk in diabetes has been linked to endothelial and renal dysfunction. The aim of this study was to investigate the role of stable fragments of the precursors of adrenomedullin, endothelin-1, vasopressin, and atrial natriuretic peptide in progression of cardiovascular disease in patients with diabetes. RESEARCH DESIGN AND METHODS This was a prospective, observational study design with a composite end point (death or unexpected admission to hospital due to a cardiovascular event) on 781 patients with type 2 diabetes (54 events, median duration of observation 15 months). The four stable precursor peptides midregional adrenomedullin (MR-proADM), midregional proatrial natriuretic peptide (MR-proANP), COOH-terminal proendothelin-1 (CT-proET-1), and COOH-terminal provasopressin or copeptin (CT-proAVP) were determined at baseline, and their association to renal function and cardiovascular events was studied using stepwise linear and Cox logistic regression analysis and receiver operating characteristic analysis, respectively. RESULTS MR-proADM, CT-proET-1, CT-proAVP, and MR-proANP were all elevated in patients with future cardiovascular events and independently correlated to serum creatinine. MR-proADM and MR-proANP were significant predictors of a future cardiovascular event, with MR-proANP being the stronger (area under the curve 0.802 ± 0.034, sensitivity 0.833, specificity 0.576, positive predictive value 0.132, and negative predictive value 0.978 with a cutoff value of 75 pmol/l). CONCLUSIONS The four serum markers of vasoactive and natriuretic peptides are related to both kidney function and cardiovascular events, thus linking two major complications of diabetes, diabetic nephropathy and cardiovascular disease. PMID:19564455

  1. Ecosystem functional properties - useful links to organism and to global scale?

    NASA Astrophysics Data System (ADS)

    Reichstein, M.

    2015-12-01

    Classical biogeographical observations tell us that ecosystems (vegetation and soils) strongly respond to climate variation in terms of their structure and function. On the other hand the influence of vegetation function on climate via exchange of matter and energy with the atmosphere has become evident in the last decades via observational and modeling studies. Recent continuous observations of this exchange of CO2, H2O and sensible heat within the global observation network FLUXNET have enabled us to quantify ecosystem function in response to large eco-climatological spatio-temporal variability of climate. We see that ecosystem function co-varies strongly with climate, but that climate alone does not suffice to explain the variation in total. Instead vegetation biophysical and structural parameters co-determine the exchange of carbon, water and energy between the ecosystem and the atmosphere. By combining ecosystem level observation and information of spatial meteorological and vegetation remote sensing covariates we can infer global patterns of ecosystem atmosphere fluxes and derive key ecosystem functional properties globally. While this approach is powerful and meteorological and vegetation structural predictors explain more than 70% of the spatial variation of monthly fluxes at FLUXNET sites, it ignores the effect of ecophysiological vegetation properties, which is expected from plant physiological leaf or whole-plant studies. Hence, future research has to more strongly link the organismic trait information with ecosystem functional properties. For this we propose a framework that involves 1) the correlation of community aggregated traits with flux-derived ecosystem properties across a range of ecosystems, 2) the up-scaling of vegetation traits using spatially distributed geo-ecological co-variates and the comparison with global ecosystem functional properties and their co-variation with climate, 3) the use of vegetation traits instead of vegetation classes

  2. Linking of sensor molecules with amino groups to amino-functionalized AFM tips.

    PubMed

    Wildling, Linda; Unterauer, Barbara; Zhu, Rong; Rupprecht, Anne; Haselgrübler, Thomas; Rankl, Christian; Ebner, Andreas; Vater, Doris; Pollheimer, Philipp; Pohl, Elena E; Hinterdorfer, Peter; Gruber, Hermann J

    2011-06-15

    The measuring tip of an atomic force microscope (AFM) can be upgraded to a specific biosensor by attaching one or a few biomolecules to the apex of the tip. The biofunctionalized tip is then used to map cognate target molecules on a sample surface or to study biophysical parameters of interaction with the target molecules. The functionality of tip-bound sensor molecules is greatly enhanced if they are linked via a thin, flexible polymer chain. In a typical scheme of tip functionalization, reactive groups are first generated on the tip surface, a bifunctional cross-linker is then attached with one of its two reactive ends, and finally the probe molecule of interest is coupled to the free end of the cross-linker. Unfortunately, the most popular functional group generated on the tip surface is the amino group, while at the same time, the only useful coupling functions of many biomolecules (such as antibodies) are also NH(2) groups. In the past, various tricks or detours were applied to minimize the undesired bivalent reaction of bifunctional linkers with adjacent NH(2) groups on the tip surface. In the present study, an uncompromising solution to this problem was found with the help of a new cross-linker ("acetal-PEG-NHS") which possesses one activated carboxyl group and one acetal-protected benzaldehyde function. The activated carboxyl ensures rapid unilateral attachment to the amino-functionalized tip, and only then is the terminal acetal group converted into the amino-reactive benzaldehyde function by mild treatment (1% citric acid, 1-10 min) which does not harm the AFM tip. As an exception, AFM tips with magnetic coating become demagnetized in 1% citric acid. This problem was solved by deprotecting the acetal group before coupling the PEG linker to the AFM tip. Bivalent binding of the corresponding linker ("aldehyde-PEG-NHS") to adjacent NH(2) groups on the tip was largely suppressed by high linker concentrations. In this way, magnetic AFM tips could be

  3. Linking suspended sediment transport metrics with fish functional traits in the Northwestern Great Plains (Invited)

    NASA Astrophysics Data System (ADS)

    Schwartz, J. S.; Simon, A.; Klimetz, L.

    2009-12-01

    Loss of ecological integrity due to excessive suspended sediment in rivers and streams is a major cause of water quality impairment in the United States. Although 32 states have developed numeric criteria for turbidity or suspended solids, or both according to the USEPA (2006), criteria is typically written as a percent exceedance above background and what constitutes background is not well defined. Defining a background level is problematic considering suspended sediments and related turbidity levels change with flow stage and season, and limited scientific data exists on relationships between sediment exposure and biotic response. Current assessment protocols for development of sediment total maximum daily loads (TMDLs) lack a means to link temporally-variable sediment transport rates with specific losses of ecological functions as loads increase. This study, within the in Northwestern Great Plains Ecoregion, co-located 58 USGS gauging stations with existing flow and suspended sediment data, and fish data from federal and state agencies. Suspended sediment concentration (SSC) transport metrics were quantified into exceedance frequencies of a given magnitude, duration as the number of consecutive days a given concentration was equaled or exceeded, dosage as concentration x duration, and mean annual suspended sediment yields. A functional traits-based approach was used to correlate SSC transport metrics with site occurrences of 20 fish traits organized into four main groups: preferred rearing mesohabitat, trophic structure, feeding habits, and spawning behavior. Negative correlations between SSC metrics and trait occurrences were assumed to represent potential conditions for impairment, specifically identifying an ecological loss by functional trait. Potential impairment conditions were linked with presence of the following traits: habitat preferences for stream pool and river shallow waters; feeding generalists, omnivores, piscivores; and several spawning

  4. Linking Microbial Community Structure to β-Glucosidic Function in Soil Aggregates

    SciTech Connect

    Bailey, Vanessa L.; Fansler, Sarah J.; Stegen, James C.; McCue, Lee Ann

    2013-10-01

    To link microbial community 16S structure to a measured function in a natural soil we have scaled both DNA and β-glucosidase assays down to a volume of soil that may approach a unique microbial community. β-glucosidase activity was assayed in 450 individual aggregates which were then sorted into classes of high or low activities, from which groups of 10 or 11 aggregates were identified and grouped for DNA extraction and pyrosequencing. Tandem assays of ATP were conducted for each aggregate in order to normalize these small groups of aggregates for biomass size. In spite of there being no significant differences in the richness or diversity of the microbial communities associated with high β-glucosidase activities compared with the communities associated with low β-glucosidase communities, several analyses of variance clearly show that the communities of these two groups differ. The separation of these groups is partially driven by the differential abundances of members of the Chitinophagaceae family. It may be that observed functional differences in otherwise similar soil aggregates can be largely attributed to differences in resource availability, rather than to presence or absence of particular taxonomic groups.

  5. A generalized linear mixed model for longitudinal binary data with a marginal logit link function

    PubMed Central

    Parzen, Michael; Ghosh, Souparno; Lipsitz, Stuart; Sinha, Debajyoti; Fitzmaurice, Garrett M.; Mallick, Bani K.; Ibrahim, Joseph G.

    2010-01-01

    Summary Longitudinal studies of a binary outcome are common in the health, social, and behavioral sciences. In general, a feature of random effects logistic regression models for longitudinal binary data is that the marginal functional form, when integrated over the distribution of the random effects, is no longer of logistic form. Recently, Wang and Louis (2003) proposed a random intercept model in the clustered binary data setting where the marginal model has a logistic form. An acknowledged limitation of their model is that it allows only a single random effect that varies from cluster to cluster. In this paper, we propose a modification of their model to handle longitudinal data, allowing separate, but correlated, random intercepts at each measurement occasion. The proposed model allows for a flexible correlation structure among the random intercepts, where the correlations can be interpreted in terms of Kendall’s τ. For example, the marginal correlations among the repeated binary outcomes can decline with increasing time separation, while the model retains the property of having matching conditional and marginal logit link functions. Finally, the proposed method is used to analyze data from a longitudinal study designed to monitor cardiac abnormalities in children born to HIV-infected women. PMID:21532998

  6. RTTN Mutations Link Primary Cilia Function to Organization of the Human Cerebral Cortex

    PubMed Central

    Kheradmand Kia, Sima; Verbeek, Elly; Engelen, Erik; Schot, Rachel; Poot, Raymond A.; de Coo, Irenaeus F.M.; Lequin, Maarten H.; Poulton, Cathryn J.; Pourfarzad, Farzin; Grosveld, Frank G.; Brehm, António; de Wit, Marie Claire Y.; Oegema, Renske; Dobyns, William B.; Verheijen, Frans W.; Mancini, Grazia M.S.

    2012-01-01

    Polymicrogyria is a malformation of the developing cerebral cortex caused by abnormal organization and characterized by many small gyri and fusion of the outer molecular layer. We have identified autosomal-recessive mutations in RTTN, encoding Rotatin, in individuals with bilateral diffuse polymicrogyria from two separate families. Rotatin determines early embryonic axial rotation, as well as anteroposterior and dorsoventral patterning in the mouse. Human Rotatin has recently been identified as a centrosome-associated protein. The Drosophila melanogaster homolog of Rotatin, Ana3, is needed for structural integrity of centrioles and basal bodies and maintenance of sensory neurons. We show that Rotatin colocalizes with the basal bodies at the primary cilium. Cultured fibroblasts from affected individuals have structural abnormalities of the cilia and exhibit downregulation of BMP4, WNT5A, and WNT2B, which are key regulators of cortical patterning and are expressed at the cortical hem, the cortex-organizing center that gives rise to Cajal-Retzius (CR) neurons. Interestingly, we have shown that in mouse embryos, Rotatin colocalizes with CR neurons at the subpial marginal zone. Knockdown experiments in human fibroblasts and neural stem cells confirm a role for RTTN in cilia structure and function. RTTN mutations therefore link aberrant ciliary function to abnormal development and organization of the cortex in human individuals. PMID:22939636

  7. Linking Functional Domains of the Human Insulin Receptor with the Bacterial Aspartate Receptor

    NASA Astrophysics Data System (ADS)

    Ellis, Leland; Morgan, David O.; Koshland, Daniel E.; Clauser, Eric; Moe, Gregory R.; Bollag, Gideon; Roth, Richard A.; Rutter, William J.

    1986-11-01

    A hybrid receptor has been constructed that is composed of the extracellular domain of the human insulin receptor fused to the transmembrane and cytoplasmic domains of the bacterial aspartate chemoreceptor. This hybrid protein can be expressed in rodent (CHO) cells and displays several functional features comparable to wild-type insulin receptor. It is localized to the cell surface, binds insulin with high affinity, forms oligomers, and is recognized by conformation-specific monoclonal antibodies. Although most of the expressed protein accumulates as a 180-kDa proreceptor, some processed 135-kDa receptor can be detected on the cell surface by covalent cross-linking. Expression of the hybrid receptor inhibits the insulin-activated uptake of 2-deoxyglucose by CHO cells. Thus, this hybrid is partially functional and can be processed; however, it is incapable of native transmembrane signaling. The results indicate that the intact domains of different types of receptors can retain some of the native features in a hybrid molecule but specific requirements will need to be satisfied for transmembrane signaling.

  8. Splice-correcting oligonucleotides restore BTK function in X-linked agammaglobulinemia model.

    PubMed

    Bestas, Burcu; Moreno, Pedro M D; Blomberg, K Emelie M; Mohammad, Dara K; Saleh, Amer F; Sutlu, Tolga; Nordin, Joel Z; Guterstam, Peter; Gustafsson, Manuela O; Kharazi, Shabnam; Piątosa, Barbara; Roberts, Thomas C; Behlke, Mark A; Wood, Matthew J A; Gait, Michael J; Lundin, Karin E; El Andaloussi, Samir; Månsson, Robert; Berglöf, Anna; Wengel, Jesper; Smith, C I Edvard

    2014-09-01

    X-linked agammaglobulinemia (XLA) is an inherited immunodeficiency that results from mutations within the gene encoding Bruton's tyrosine kinase (BTK). Many XLA-associated mutations affect splicing of BTK pre-mRNA and severely impair B cell development. Here, we assessed the potential of antisense, splice-correcting oligonucleotides (SCOs) targeting mutated BTK transcripts for treating XLA. Both the SCO structural design and chemical properties were optimized using 2'-O-methyl, locked nucleic acid, or phosphorodiamidate morpholino backbones. In order to have access to an animal model of XLA, we engineered a transgenic mouse that harbors a BAC with an authentic, mutated, splice-defective human BTK gene. BTK transgenic mice were bred onto a Btk knockout background to avoid interference of the orthologous mouse protein. Using this model, we determined that BTK-specific SCOs are able to correct aberrantly spliced BTK in B lymphocytes, including pro-B cells. Correction of BTK mRNA restored expression of functional protein, as shown both by enhanced lymphocyte survival and reestablished BTK activation upon B cell receptor stimulation. Furthermore, SCO treatment corrected splicing and restored BTK expression in primary cells from patients with XLA. Together, our data demonstrate that SCOs can restore BTK function and that BTK-targeting SCOs have potential as personalized medicine in patients with XLA. PMID:25105368

  9. PDGFRβ expression and function in fibroblasts derived from pluripotent cells is linked to DNA demethylation

    PubMed Central

    Hewitt, Kyle J.; Shamis, Yulia; Knight, Elana; Smith, Avi; Maione, Anna; Alt-Holland, Addy; Sheridan, Steven D.; Haggarty, Stephen J.; Garlick, Jonathan A.

    2012-01-01

    Platelet-derived growth factor receptor-beta (PDGFRβ) is required for the development of mesenchymal cell types, and plays a diverse role in the function of fibroblasts in tissue homeostasis and regeneration. In this study, we characterized the expression of PDGFRβ in fibroblasts derived from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), and showed that this expression is important for cellular functions such as migration, extracellular matrix production and assembly in 3D self-assembled tissues. To determine potential regulatory regions predictive of expression of PDGFRβ following differentiation from ESCs and iPSCs, we analyzed the DNA methylation status of a region of the PDGFRB promoter that contains multiple CpG sites, before and after differentiation. We demonstrated that this promoter region is extensively demethylated following differentiation, and represents a developmentally regulated, differentially methylated region linked to PDGFRβ expression. Understanding the epigenetic regulation of genes such as PDGFRB, and identifying sites of active DNA demethylation, is essential for future applications of iPSC-derived fibroblasts for regenerative medicine. PMID:22344267

  10. An exploration of links between early parenting experiences and personality disorder type and disordered personality functioning.

    PubMed

    Parker, G; Roy, K; Wilhelm, K; Mitchell, P; Austin, M P; Hadzi-Pavlovic, D

    1999-01-01

    Reports of early parenting were assessed using two measures, the Parental Bonding Index (PBI) and the Measure of Parenting Style (MOPS), in a sample of 265 patients with DSM-defined major depressive disorder. Psychiatrists then rated the extent to which sample members evidenced the personality "styles" underpinning 15 separate personality disorders, returning personality vignette scores. The extent of disordered functioning was also assessed across "parameters" and "domains" by psychiatrists, referrers, and family members, using a range of measures. Those with higher scores on vignettes measuring borderline, anxious, depressive, and self-defeating personality style rated parents as uncaring, overcontrolling, and abusive. When vignettes were consolidated into scores akin to the DSM clusters, the most consistent links between perceived dysfunctional parenting were with the Cluster C (anxious), and Cluster B (dramatic) styles and were nonsignificant for Cluster A (eccentric) style. Meeting criteria for an increasing number of personality disorder clusters was associated with increasing levels of adverse parenting. Multiple regression analyses indicated that disordered functioning (as assessed by the three independent rater groups) was most distinctly associated with paternal indifference and maternal overcontrol. PMID:10633316

  11. Integrin-Linked Kinase Is Indispensable for Keratinocyte Differentiation and Epidermal Barrier Function.

    PubMed

    Sayedyahossein, Samar; Rudkouskaya, Alena; Leclerc, Valerie; Dagnino, Lina

    2016-02-01

    A functional permeability barrier is essential to prevent the passage of water and electrolytes, macromolecules, and pathogens through the epidermis. This is accomplished in terminally differentiated keratinocytes through formation of a cornified envelope and the assembly of tight intercellular junctions. Integrin-linked kinase (ILK) is a scaffold protein essential for hair follicle morphogenesis and epidermal attachment to the basement membrane. However, the biological functions of ILK in differentiated keratinocytes remain poorly understood. Furthermore, whether ILK is implicated in keratinocyte differentiation and intercellular junction formation has remained an unresolved issue. Here we describe a pivotal role for ILK in keratinocyte differentiation responses to increased extracellular Ca(2+), regulation of adherens and tight junction assembly, and the formation of an outside-in permeability barrier toward macromolecules. In the absence of ILK, the calcium sensing receptor, E-cadherin, and ZO-1 fail to translocate to the cell membrane, through mechanisms that involve abnormalities in microtubules and in RhoA activation. In situ, ILK-deficient epidermis exhibits reduced tight junction formation and increased outside-in permeability to a dextran tracer, indicating reduced barrier properties toward macromolecules. Therefore, ILK is an essential component of keratinocyte differentiation programs that contribute to epidermal integrity and the establishment of its barrier properties. PMID:26967476

  12. Links between Theory of Mind and Executive Function in Young Children with Autism: Clues to Developmental Primacy

    ERIC Educational Resources Information Center

    Pellicano, Elizabeth

    2007-01-01

    There has been much theoretical discussion of a functional link between theory of mind (ToM) and executive function (EF) in autism. This study sought to establish the relationship between ToM and EF in young children with autism (M = 5 years, 6 months) and to examine issues of developmental primacy. Thirty children with autism and 40 typically…

  13. Metabolically Driven Self-Restoration of Energy-Linked Functions by Avocado Mitochondria

    PubMed Central

    Huang, Li-Shar; Romani, Roger J.

    1991-01-01

    To assess the restorative capacity of isolated avocado (Persea americana) fruit mitochondria, the organelles were first aged in the absence of an energy source at 25°C for several hours until respiratory control and oxidative phosphorylation were greatly diminished or totally lost. Energy-linked functions were then gradually restored over a period of several hours after the addition of substrate. Restoration of respiratory control resulted from both an increase in state 3 and a decrease in state 4 respiratory rates. Either α-ketoglutarate or succinate served as restorants, each with distinctive rates of recovery in state 3 and state 4 respiration. ATP also served as a restorative agent but not as effectively as metabolizable substrate. ATP synthase activity was modulated by stress and restoration but neither the extent nor the rate of change was sufficient to constrain state 3 rates. Orthophosphate was released from the mitochondria during substrate-deprived stress. Restoration of phosphorylation preceded that of RC with phosphate uptake and phosphorylation being evident immediately upon the addition of substrate. During restoration [32P]orthophosphate was incorporated into several organic fractions: phospholipid, ATP, a trichloroacetic acid-precipitable mitochondrial fraction, and an organophosphate that accumulated in the medium in relatively large amounts. The organophosphate was tentatively identified as a hexosephosphate. Incorporation into ATP and the putative hexosephosphate continued unabated beyond the point of maximum restoration. Phosphate metabolism thus appears to be a necessary but not sufficient precondition for mitochondrial restoration and maintenance. Based on the recovery kinetics of the various phosphorylated components, the mitochondrial-bound fraction appears to be most directly linked with restoration. Results are discussed with reference to specific characteristics and components of self-restoration and to possible underlying mechanisms

  14. Spatial patterns and links between microbial community composition and function in cyanobacterial mats

    PubMed Central

    Al-Najjar, Mohammad A. A.; Ramette, Alban; Kühl, Michael; Hamza, Waleed; Klatt, Judith M.; Polerecky, Lubos

    2014-01-01

    We imaged reflectance and variable fluorescence in 25 cyanobacterial mats from four distant sites around the globe to assess, at different scales of resolution, spatial variabilities in the physiological parameters characterizing their photosynthetic capacity, including the absorptivity by chlorophyll a (Achl), maximum quantum yield of photosynthesis (Ymax), and light acclimation irradiance (Ik). Generally, these parameters significantly varied within individual mats on a sub-millimeter scale, with about 2-fold higher variability in the vertical than in the horizontal direction. The average vertical profiles of Ymax and Ik decreased with depth in the mat, while Achl exhibited a sub-surface maximum. The within-mat variability was comparable to, but often larger than, the between-sites variability, whereas the within-site variabilities (i.e., between samples from the same site) were generally lowest. When compared based on averaged values of their photosynthetic parameters, mats clustered according to their site of origin. Similar clustering was found when the community composition of the mats' cyanobacterial layers were compared by automated ribosomal intergenic spacer analysis (ARISA), indicating a significant link between the microbial community composition and function. Although this link is likely the result of community adaptation to the prevailing site-specific environmental conditions, our present data is insufficient to identify the main factors determining these patterns. Nevertheless, this study demonstrates that the spatial variability in the photosynthetic capacity and light acclimation of benthic phototrophic microbial communities is at least as large on a sub-millimeter scale as it is on a global scale, and suggests that this pattern of variability scaling is similar for the microbial community composition. PMID:25147548

  15. Microtubule-Actin Cross-Linking Factor 1: Domains, Interaction Partners, and Tissue-Specific Functions.

    PubMed

    Goryunov, Dmitry; Liem, Ronald K H

    2016-01-01

    The cytoskeleton of most eukaryotic cells is composed of three principal filamentous components: actin filaments, microtubules (MTs), and intermediate filaments. It is a highly dynamic system that plays crucial roles in a wide range of cellular processes, including migration, adhesion, cytokinesis, morphogenesis, intracellular traffic and signaling, and structural flexibility. Among the large number of cytoskeleton-associated proteins characterized to date, microtubule-actin cross-linking factor 1 (MACF1) is arguably the most versatile integrator and modulator of cytoskeleton-related processes. MACF1 belongs to the plakin family of proteins, and within it, to the spectraplakin subfamily. These proteins are characterized by the ability to bridge MT and actin cytoskeletal networks in a dynamic fashion, which underlies their involvement in the regulation of cell migration, axonal extension, and vesicular traffic. Studying MACF1 functions has provided insights not only into the regulation of the cytoskeleton but also into molecular mechanisms of both normal cellular physiology and cellular pathology. Multiple MACF1 isoforms exist, composed of a large variety of alternatively spliced domains. Each of these domains mediates a specific set of interactions and functions. These functions are manifested in tissue and cell-specific phenotypes observed in conditional MACF1 knockout mice. The conditional models described to date reveal critical roles of MACF1 in mammalian skin, nervous system, heart muscle, and intestinal epithelia. Complete elimination of MACF1 is early embryonic lethal, indicating an essential role for MACF1 in early development. Further studies of MACF1 domains and their interactions will likely reveal multiple new roles of this protein in various tissues. PMID:26778566

  16. Linking human brain local activity fluctuations to structural and functional network architectures.

    PubMed

    Baria, A T; Mansour, A; Huang, L; Baliki, M N; Cecchi, G A; Mesulam, M M; Apkarian, A V

    2013-06-01

    Activity of cortical local neuronal populations fluctuates continuously, and a large proportion of these fluctuations are shared across populations of neurons. Here we seek organizational rules that link these two phenomena. Using neuronal activity, as identified by functional MRI (fMRI) and for a given voxel or brain region, we derive a single measure of full bandwidth brain-oxygenation-level-dependent (BOLD) fluctuations by calculating the slope, α, for the log-linear power spectrum. For the same voxel or region, we also measure the temporal coherence of its fluctuations to other voxels or regions, based on exceeding a given threshold, Θ, for zero lag correlation, establishing functional connectivity between pairs of neuronal populations. From resting state fMRI, we calculated whole-brain group-averaged maps for α and for functional connectivity. Both maps showed similar spatial organization, with a correlation coefficient of 0.75 between the two parameters across all brain voxels, as well as variability with hodology. A computational model replicated the main results, suggesting that synaptic low-pass filtering can account for these interrelationships. We also investigated the relationship between α and structural connectivity, as determined by diffusion tensor imaging-based tractography. We observe that the correlation between α and connectivity depends on attentional state; specifically, α correlated more highly to structural connectivity during rest than while attending to a task. Overall, these results provide global rules for the dynamics between frequency characteristics of local brain activity and the architecture of underlying brain networks. PMID:23396160

  17. Linking Carbonic Anhydrase Abundance and Diversity in Soils to Ecological Function

    NASA Astrophysics Data System (ADS)

    Pang, E.; Meredith, L. K.; Welander, P. V.

    2015-12-01

    Carbonic anhydrase (CA) is an ancient enzyme widespread among bacteria, archaea, and eukarya that catalyzes the following reaction: CO2 + H2O ⇌ HCO3- + H+. Its functions are critical for key cellular processes such as concentrating CO2 for autotrophic growth, pH regulation, and pathogen survival in hosts. Currently, there are six known CA classes (α, β, γ, δ, η, ζ) arising from several distinct evolutionary lineages. CA are widespread in sequenced genomes, with many organisms containing multiple classes of CA or multiple CA of the same class. Soils host rich microbial communities with diverse and important ecological functions, but the diversity and abundance of CA in soils has not been explored. CA appears to play an important, but poorly understood, role in some biogeochemical cycles such as those of CO2 and its oxygen isotope composition and also carbonyl sulfide (COS), which are potential tracers in predictive carbon cycle models. Recognizing the prevalence and functional significance of CA in soils, we used a combined bioinformatics and molecular biology approach to address fundamental questions regarding the abundance, diversity, and function of CA in soils. To characterize the abundance and diversity of the different CA classes in soils, we analyzed existing soil metagenomic and metatranscriptomic data from the DOE Joint Genome Institute databases. Out of the six classes of CA, we only found the α, β, and γ classes to be present in soils, with the β class being the most abundant. We also looked at genomes of sequenced soil microorganisms to learn what combination of CA classes they contain, from which we can begin to predict the physiological role of CA. To characterize the functional roles of the different CA classes in soils, we collected soil samples from a variety of biomes with diverse chemical and physical properties and quantified the rate of two CA-mediated processes: soil uptake of COS and acceleration of the oxygen isotope exchange

  18. Application of Radial Basis Functional Link Networks to Exploration for Proterozoic Mineral Deposits in Central Iran

    SciTech Connect

    Behnia, Pouran

    2007-06-15

    The metallogeny of Central Iran is characterized mainly by the presence of several iron, apatite, and uranium deposits of Proterozoic age. Radial Basis Function Link Networks (RBFLN) were used as a data-driven method for GIS-based predictive mapping of Proterozoic mineralization in this area. To generate the input data for RBFLN, the evidential maps comprising stratigraphic, structural, geophysical, and geochemical data were used. Fifty-eight deposits and 58 'nondeposits' were used to train the network. The operations for the application of neural networks employed in this study involve both multiclass and binary representation of evidential maps. Running RBFLN on different input data showed that an increase in the number of evidential maps and classes leads to a larger classification sum of squared error (SSE). As a whole, an increase in the number of iterations resulted in the improvement of training SSE. The results of applying RBFLN showed that a successful classification depends on the existence of spatially well distributed deposits and nondeposits throughout the study area.

  19. Possible functional links among brain- and skull-related genes selected in modern humans.

    PubMed

    Benítez-Burraco, Antonio; Boeckx, Cedric

    2015-01-01

    The sequencing of the genomes from extinct hominins has revealed that changes in some brain-related genes have been selected after the split between anatomically-modern humans and Neanderthals/Denisovans. To date, no coherent view of these changes has been provided. Following a line of research we initiated in Boeckx and Benítez-Burraco (2014a), we hypothesize functional links among most of these genes and their products, based on the existing literature for each of the gene discussed. The genes we focus on are found mutated in different cognitive disorders affecting modern populations and their products are involved in skull and brain morphology, and neural connectivity. If our hypothesis turns out to be on the right track, it means that the changes affecting most of these proteins resulted in a more globular brain and ultimately brought about modern cognition, with its characteristic generativity and capacity to form and exploit cross-modular concepts, properties most clearly manifested in language. PMID:26136701

  20. Uncoupling of energy-linked functions of corn mitochondria by linoleic Acid and monomethyldecenylsuccinic Acid.

    PubMed

    Baddeley, M S; Hanson, J B

    1967-12-01

    Linoleic acid and monomethyldecenylsuccinic acid were tested as uncoupling agents for energy linked functions of corn mitochondria. 2,4-dinitrophenol was used as a standard for comparison. Both compounds uncoupled oxidative phosphorylation, released oligomycin-blocked respiration, and accelerated adenosine triphosphatase. Linoleic acid uncoupled calcium-activated phosphate accumulation and the increase in light scattering that accompanies the accumulation. Unlike dinitrophenol, linoleic acid at 0.1 mm had a destructive effect on membrane semipermeability. Kinetic studies indicated that dinitrophenol and linoleic acid compete with phosphate for active sites in oxidative phosphorylation.Some linoleic acid is taken up by respiring mitochondria and a major share of the uptake is incorporated into phospholipids. Calcium ion and oligomycin promote the uptake, but coenzyme A does not. It is deduced that fatty acid probably attacks the non-phosphorylated intermediate, I approximately X, producing X approximately acyl. Uncoupling results from breakdown of X approximately acyl, but sufficient X approximately acyl is maintained to serve as a source of activated fatty acid. PMID:16656708

  1. Functional Characterization of Bacterial Oligosaccharyltransferases Involved in O-Linked Protein Glycosylation▿

    PubMed Central

    Faridmoayer, Amirreza; Fentabil, Messele A.; Mills, Dominic C.; Klassen, John S.; Feldman, Mario F.

    2007-01-01

    Protein glycosylation is an important posttranslational modification that occurs in all domains of life. Pilins, the structural components of type IV pili, are O glycosylated in Neisseria meningitidis, Neisseria gonorrhoeae, and some strains of Pseudomonas aeruginosa. In this work, we characterized the P. aeruginosa 1244 and N. meningitidis MC58 O glycosylation systems in Escherichia coli. In both cases, sugars are transferred en bloc by an oligosaccharyltransferase (OTase) named PglL in N. meningitidis and PilO in P. aeruginosa. We show that, like PilO, PglL has relaxed glycan specificity. Both OTases are sufficient for glycosylation, but they require translocation of the undecaprenol-pyrophosphate-linked oligosaccharide substrates into the periplasm for activity. Whereas PilO activity is restricted to short oligosaccharides, PglL is able to transfer diverse oligo- and polysaccharides. This functional characterization supports the concept that despite their low sequence similarity, PilO and PglL belong to a new family of “O-OTases” that transfer oligosaccharides from lipid carriers to hydroxylated amino acids in proteins. To date, such activity has not been identified for eukaryotes. To our knowledge, this is the first report describing recombinant O glycoproteins synthesized in E. coli. PMID:17890310

  2. Linking Mother and Youth Parenting Attitudes: Indirect Effects via Maltreatment, Parent Involvement, and Youth Functioning

    PubMed Central

    Thompson, Richard; Jones, Deborah J.; Litrownik, Alan J.; English, Diana J.; Kotch, Jonathan B.; Lewis, Terri; Dubowitz, Howard

    2014-01-01

    Evidence suggests that parenting attitudes are transmitted within families. However, limited research has examined this prospectively. The current prospective study examined direct effects of early maternal attitudes toward parenting (as measured at child age 4 by the Adult-Adolescent Parenting Inventory [AAPI]) on later youth parenting attitudes (as measured by the AAPI at youth age 18). Indirect effects via child maltreatment (physical abuse, sexual abuse, neglect, and emotional maltreatment), parent involvement, and youth functioning (internalizing and externalizing problems) were also assessed. Analyses were conducted on data from 412 families enrolled in the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN). There were significant direct effects for three of the four classes of mother parenting attitudes (appropriate developmental expectations of children, empathy toward children, and appropriate family roles) on youth attitudes but not for rejection of punishment. In addition, the following indirect effects were obtained: Mother expectations influenced youth expectations via neglect; mother empathy influenced youth empathy via both parental involvement and youth externalizing problems; and mother rejection of punishment influenced youth rejection of punishment via youth internalizing problems. None of the child or family process variables, however, affected the link between mother and youth attitudes about roles. PMID:25113632

  3. Non-random distribution of homo-repeats: links with biological functions and human diseases.

    PubMed

    Lobanov, Michail Yu; Klus, Petr; Sokolovsky, Igor V; Tartaglia, Gian Gaetano; Galzitskaya, Oxana V

    2016-01-01

    The biological function of multiple repetitions of single amino acids, or homo-repeats, is largely unknown, but their occurrence in proteins has been associated with more than 20 hereditary diseases. Analysing 122 bacterial and eukaryotic genomes, we observed that the number of proteins containing homo-repeats is significantly larger than expected from theoretical estimates. Analysis of statistical significance indicates that the minimal size of homo-repeats varies with amino acid type and proteome. In an attempt to characterize proteins harbouring long homo-repeats, we found that those containing polar or small amino acids S, P, H, E, D, K, Q and N are enriched in structural disorder as well as protein- and RNA-interactions. We observed that E, S, Q, G, L, P, D, A and H homo-repeats are strongly linked with occurrence in human diseases. Moreover, S, E, P, A, Q, D and T homo-repeats are significantly enriched in neuronal proteins associated with autism and other disorders. We release a webserver for further exploration of homo-repeats occurrence in human pathology at http://bioinfo.protres.ru/hradis/. PMID:27256590

  4. Linking mother and youth parenting attitudes: indirect effects via maltreatment, parent involvement, and youth functioning.

    PubMed

    Thompson, Richard; Jones, Deborah J; Litrownik, Alan J; English, Diana J; Kotch, Jonathan B; Lewis, Terri; Dubowitz, Howard

    2014-01-01

    Evidence suggests that parenting attitudes are transmitted within families. However, limited research has examined this prospectively. The current prospective study examined direct effects of early maternal attitudes toward parenting (as measured at child age 4 by the Adult-Adolescent Parenting Inventory [AAPI]) on later youth parenting attitudes (as measured by the AAPI at youth age 18). Indirect effects via child maltreatment (physical abuse, sexual abuse, neglect, and emotional maltreatment), parent involvement, and youth functioning (internalizing and externalizing problems) were also assessed. Analyses were conducted on data from 412 families enrolled in the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN). There were significant direct effects for three of the four classes of mother parenting attitudes (appropriate developmental expectations of children, empathy toward children, and appropriate family roles) on youth attitudes but not for rejection of punishment. In addition, the following indirect effects were obtained: Mother expectations influenced youth expectations via neglect; mother empathy influenced youth empathy via both parental involvement and youth externalizing problems; and mother rejection of punishment influenced youth rejection of punishment via youth internalizing problems. None of the child or family process variables, however, affected the link between mother and youth attitudes about roles. PMID:25113632

  5. Possible functional links among brain- and skull-related genes selected in modern humans

    PubMed Central

    Benítez-Burraco, Antonio; Boeckx, Cedric

    2015-01-01

    The sequencing of the genomes from extinct hominins has revealed that changes in some brain-related genes have been selected after the split between anatomically-modern humans and Neanderthals/Denisovans. To date, no coherent view of these changes has been provided. Following a line of research we initiated in Boeckx and Benítez-Burraco (2014a), we hypothesize functional links among most of these genes and their products, based on the existing literature for each of the gene discussed. The genes we focus on are found mutated in different cognitive disorders affecting modern populations and their products are involved in skull and brain morphology, and neural connectivity. If our hypothesis turns out to be on the right track, it means that the changes affecting most of these proteins resulted in a more globular brain and ultimately brought about modern cognition, with its characteristic generativity and capacity to form and exploit cross-modular concepts, properties most clearly manifested in language. PMID:26136701

  6. Hubs of knowledge: using the functional link structure in Biozon to mine for biologically significant entities

    PubMed Central

    Shafer, Paul; Isganitis, Timothy; Yona, Golan

    2006-01-01

    Background Existing biological databases support a variety of queries such as keyword or definition search. However, they do not provide any measure of relevance for the instances reported, and result sets are usually sorted arbitrarily. Results We describe a system that builds upon the complex infrastructure of the Biozon database and applies methods similar to those of Google to rank documents that match queries. We explore different prominence models and study the spectral properties of the corresponding data graphs. We evaluate the information content of principal and non-principal eigenspaces, and test various scoring functions which combine contributions from multiple eigenspaces. We also test the effect of similarity data and other variations which are unique to the biological knowledge domain on the quality of the results. Query result sets are assessed using a probabilistic approach that measures the significance of coherence between directly connected nodes in the data graph. This model allows us, for the first time, to compare different prominence models quantitatively and effectively and to observe unique trends. Conclusion Our tests show that the ranked query results outperform unsorted results with respect to our significance measure and the top ranked entities are typically linked to many other biological entities. Our study resulted in a working ranking system of biological entities that was integrated into Biozon at . PMID:16480496

  7. Non-random distribution of homo-repeats: links with biological functions and human diseases

    PubMed Central

    Lobanov, Michail Yu.; Klus, Petr; Sokolovsky, Igor V.; Tartaglia, Gian Gaetano; Galzitskaya, Oxana V.

    2016-01-01

    The biological function of multiple repetitions of single amino acids, or homo-repeats, is largely unknown, but their occurrence in proteins has been associated with more than 20 hereditary diseases. Analysing 122 bacterial and eukaryotic genomes, we observed that the number of proteins containing homo-repeats is significantly larger than expected from theoretical estimates. Analysis of statistical significance indicates that the minimal size of homo-repeats varies with amino acid type and proteome. In an attempt to characterize proteins harbouring long homo-repeats, we found that those containing polar or small amino acids S, P, H, E, D, K, Q and N are enriched in structural disorder as well as protein- and RNA-interactions. We observed that E, S, Q, G, L, P, D, A and H homo-repeats are strongly linked with occurrence in human diseases. Moreover, S, E, P, A, Q, D and T homo-repeats are significantly enriched in neuronal proteins associated with autism and other disorders. We release a webserver for further exploration of homo-repeats occurrence in human pathology at http://bioinfo.protres.ru/hradis/. PMID:27256590

  8. Framework of Consciousness from Semblance of Activity at Functionally LINKed Postsynaptic Membranes

    PubMed Central

    Vadakkan, Kunjumon I.

    2010-01-01

    Consciousness is seen as a difficult “binding” problem. Binding, a process where different sensations evoked by an item are associated in the nervous system, can be viewed as a process similar to associative learning. Several reports that consciousness is associated with some form of memory imply that different forms of memories have a common feature contributing to consciousness. Based on a proposed synaptic mechanism capable of explaining different forms of memory, we developed a framework for consciousness. It is based on the formation of semblance of sensory stimulus from (1) synaptic semblances when excitatory postsynaptic potentials arrive at functionally LINKed postsynaptic membranes, and (2) network semblances when these potentials summate to elicit action potential initiating activity in a network of neurons. It is then possible to derive a framework for consciousness as a multi-dimensional semblance. According to this framework, a continuum of semblances formed from background sensory stimuli and oscillating neuronal activities serve to maintain consciousness. Feasibility of this framework to explain various physiological and pathological states of consciousness, its subjective nature and qualia is examined. PMID:21833231

  9. Anomalous kinetics in diffusion limited reactions linked to non-Gaussian concentration probability distribution function.

    PubMed

    de Anna, Pietro; Le Borgne, Tanguy; Dentz, Marco; Bolster, Diogo; Davy, Philippe

    2011-11-01

    We investigate anomalous reaction kinetics related to segregation in the one-dimensional reaction-diffusion system A + B → C. It is well known that spatial fluctuations in the species concentrations cause a breakdown of the mean-field behavior at low concentration values. The scaling of the average concentration with time changes from the mean-field t(-1) to the anomalous t(-1/4) behavior. Using a stochastic modeling approach, the reaction-diffusion system can be fully characterized by the multi-point probability distribution function (PDF) of the species concentrations. Its evolution is governed by a Fokker-Planck equation with moving boundaries, which are determined by the positivity of the species concentrations. The concentration PDF is in general non-Gaussian. As long as the concentration fluctuations are small compared to the mean, the PDF can be approximated by a Gaussian distribution. This behavior breaks down in the fluctuation dominated regime, for which anomalous reaction kinetics are observed. We show that the transition from mean field to anomalous reaction kinetics is intimately linked to the evolution of the concentration PDF from a Gaussian to non-Gaussian shape. This establishes a direct relationship between anomalous reaction kinetics, incomplete mixing and the non-Gaussian nature of the concentration PDF. PMID:22070289

  10. Functional Importance of Covalent Homodimer of Reelin Protein Linked via Its Central Region*

    PubMed Central

    Yasui, Norihisa; Kitago, Yu; Beppu, Ayako; Kohno, Takao; Morishita, Shunsuke; Gomi, Hiroki; Nagae, Masamichi; Hattori, Mitsuharu; Takagi, Junichi

    2011-01-01

    Reelin is a 3461-residue secreted glycoprotein that plays a critical role in brain development through its action on target neurons. Although it is known that functional reelin protein exists as multimer formed by interchain disulfide bond(s) as well as through non-covalent interactions, the chemical nature of the multimer assembly has been elusive. In the present study, we identified, among 122 cysteines present in full-length reelin, the single critical cysteine residue (Cys2101) responsible for the covalent multimerization. C2101A mutant reelin failed to assemble into disulfide-bonded multimers, whereas it still exhibited non-covalently associated high molecular weight oligomeric states in solution. Detailed analysis of tryptic fragments produced from the purified reelin proteins revealed that the minimum unit of the multimer is a homodimeric reelin linked via Cys2101 present in the central region and that this cysteine does not connect to the N-terminal region of reelin, which had been postulated as the primary oligomerization domain. A surface plasmon resonance binding assay confirmed that C2101A mutant reelin retained binding capability toward two neuronal receptors apolipoprotein E receptor 2 and very low density lipoprotein receptor. However, it failed to show signaling activity in the assay using the cultured neurons. These results indicate that an intact higher order architecture of reelin multimer maintained by both Cys2101-mediated homodimerization and other non-covalent association present elsewhere in the reelin primary structure are essential for exerting its full biological activity. PMID:21844191

  11. Role of complex asparagine-linked oligosaccharides in the expression of a functional thyrotropin receptor.

    PubMed Central

    Siffroi-Fernandez, S; Costagliola, S; Paumel, S; Giraud, A; Banga, J P; Franc, J L

    2001-01-01

    To evaluate the functional role of complex asparagine-linked oligosaccharides of the human thyrotropin receptor (TSHR), a Chinese hamster ovary cell line (JP09) and a K562 cell line (K562-TSHR) expressing this receptor were treated with deoxymannojirimycin (dMM), a mannosidase I inhibitor. dMM blocks the formation of complex-type structures and leads to the formation of high-mannose-type structures. Treatment of cells with dMM led to a decrease in the number of thyrotropin (TSH)-binding sites at the cell surface. Detection of the TSHR at the cell surface using a monoclonal antibody directed against the A subunit showed that this decrease was not due to a decrease in the number of TSHRs expressed at the cell surface. However the recognition of TSHR by a monoclonal antibody directed against the C peptide was greatly decreased. On immunoblotting, after deglycosylation using peptide N-glycanase F, the A subunit was visualized as a doublet (36 and 41 kDa). In control cells the species of higher molecular mass was more abundant whereas after dMM treatment the species of lower molecular mass became more abundant. This difference in molecular mass between the two peptides is compatible with the removal of the C peptide. In conclusion, the results show that inhibition of complex-type structure formation leads to (i) an incapacity for TSHR to bind TSH, without affecting its intracellular transport and (ii) an increase of TSHR susceptibility to proteases that remove the C peptide. We then hypothesized that removal of the C peptide could contribute to the formation of a non-functional TSHR. PMID:11171111

  12. Translational informatics approach for identifying the functional molecular communicators linking coronary artery disease, infection and inflammation.

    PubMed

    Sharma, Ankit; Ghatge, Madankumar; Mundkur, Lakshmi; Vangala, Rajani Kanth

    2016-05-01

    Translational informatics approaches are required for the integration of diverse and accumulating data to enable the administration of effective translational medicine specifically in complex diseases such as coronary artery disease (CAD). In the current study, a novel approach for elucidating the association between infection, inflammation and CAD was used. Genes for CAD were collected from the CAD‑gene database and those for infection and inflammation were collected from the UniProt database. The cytomegalovirus (CMV)‑induced genes were identified from the literature and the CAD‑associated clinical phenotypes were obtained from the Unified Medical Language System. A total of 55 gene ontologies (GO) termed functional communicator ontologies were identified in the gene sets linking clinical phenotypes in the diseasome network. The network topology analysis suggested that important functions including viral entry, cell adhesion, apoptosis, inflammatory and immune responses networked with clinical phenotypes. Microarray data was extracted from the Gene Expression Omnibus (dataset: GSE48060) for highly networked disease myocardial infarction. Further analysis of differentially expressed genes and their GO terms suggested that CMV infection may trigger a xenobiotic response, oxidative stress, inflammation and immune modulation. Notably, the current study identified γ‑glutamyl transferase (GGT)‑5 as a potential biomarker with an odds ratio of 1.947, which increased to 2.561 following the addition of CMV and CMV‑neutralizing antibody (CMV‑NA) titers. The C‑statistics increased from 0.530 for conventional risk factors (CRFs) to 0.711 for GGT in combination with the above mentioned infections and CRFs. Therefore, the translational informatics approach used in the current study identified a potential molecular mechanism for CMV infection in CAD, and a potential biomarker for risk prediction. PMID:27035874

  13. Translational informatics approach for identifying the functional molecular communicators linking coronary artery disease, infection and inflammation

    PubMed Central

    SHARMA, ANKIT; GHATGE, MADANKUMAR; MUNDKUR, LAKSHMI; VANGALA, RAJANI KANTH

    2016-01-01

    Translational informatics approaches are required for the integration of diverse and accumulating data to enable the administration of effective translational medicine specifically in complex diseases such as coronary artery disease (CAD). In the current study, a novel approach for elucidating the association between infection, inflammation and CAD was used. Genes for CAD were collected from the CAD-gene database and those for infection and inflammation were collected from the UniProt database. The cytomegalovirus (CMV)-induced genes were identified from the literature and the CAD-associated clinical phenotypes were obtained from the Unified Medical Language System. A total of 55 gene ontologies (GO) termed functional communicator ontologies were identifed in the gene sets linking clinical phenotypes in the diseasome network. The network topology analysis suggested that important functions including viral entry, cell adhesion, apoptosis, inflammatory and immune responses networked with clinical phenotypes. Microarray data was extracted from the Gene Expression Omnibus (dataset: GSE48060) for highly networked disease myocardial infarction. Further analysis of differentially expressed genes and their GO terms suggested that CMV infection may trigger a xenobiotic response, oxidative stress, inflammation and immune modulation. Notably, the current study identified γ-glutamyl transferase (GGT)-5 as a potential biomarker with an odds ratio of 1.947, which increased to 2.561 following the addition of CMV and CMV-neutralizing antibody (CMV-NA) titers. The C-statistics increased from 0.530 for conventional risk factors (CRFs) to 0.711 for GGT in combination with the above mentioned infections and CRFs. Therefore, the translational informatics approach used in the current study identified a potential molecular mechanism for CMV infection in CAD, and a potential biomarker for risk prediction. PMID:27035874

  14. FACILE CHEMICAL FUNCTIONALIZATION OF PROTEINS THROUGH INTEIN-LINKED YEAST DISPLAY

    PubMed Central

    Marshall, Carrie J.; Agarwal, Nitin; Kalia, Jeet; Grosskopf, Vanessa A.; McGrath, Nicholas A.; Abbott, Nicholas L.; Raines, Ronald T.; Shusta, Eric V.

    2013-01-01

    Intein-mediated expressed protein ligation (EPL) permits the site-specific chemical customization of proteins. While traditional techniques have used purified, soluble proteins, we have extended these methods to release and modify intein fusion proteins expressed on the yeast surface, thereby eliminating the need for soluble protein expression and purification. To this end, we sought to simultaneously release yeast surface-displayed proteins and selectively conjugate with chemical functionalities compatible with EPL and click chemistry. Single-chain antibodies (scFv) and green fluorescent protein (GFP) were displayed on the yeast surface as fusions to the N-terminus of the Mxe GyrA intein. ScFv and GFP were released from the yeast surface with either a sulfur nucleophile (MESNA) or a nitrogen nucleophile (hydrazine) linked to an azido group. The hydrazine azide permitted the simultaneous release and azido functionalization of displayed proteins, but nonspecific reactions with other yeast proteins were detected, and cleavage efficiency was limited. In contrast, MESNA released significantly more protein from the yeast surface while also generating a unique thioester at the carboxy-terminus of the released protein. These protein thioesters were subsequently reacted with a cysteine alkyne in an EPL reaction and then employed in an azide–alkyne cycloaddition to immobilize the scFv and GFP on an azide-decorated surface with >90% site-specificity. Importantly, the immobilized proteins retained their activity. Since yeast surface display is also a protein engineering platform, these approaches provide a particularly powerful tool for the rapid assessment of engineered proteins. PMID:23924245

  15. Normal birth weight variation and children's neuropsychological functioning: links between language, executive functioning, and theory of mind.

    PubMed

    Wade, M; Browne, D T; Madigan, S; Plamondon, A; Jenkins, J M

    2014-10-01

    The effect of low birth weight on children's development has been documented for a range of neurocognitive outcomes. However, few previous studies have examined the effect of birth weight variability within the normal range on children's neuropsychological development. The current study examined birth weight variation amongst children weighing ≥2500 g in relation to their language, executive functioning (EF), and theory of mind (ToM), and specified a developmental pathway in which birth weight was hypothesized to be associated with children's EF and ToM through their intermediary language skills. The current study used a prospective community birth cohort of 468 children. Families were recruited when children were newborns and followed up every 18 months until children were age 4.5. Language was assessed at age 3 using a standardized measure of receptive vocabulary (PPVT), and EF and ToM were measured at age 4.5 using previously validated and developmentally appropriate tasks. After controlling for potential confounding variables (family income, parent education, gestational age), birth weight within the normal range was associated with language ability at age 3 (β=.17; p=.012); and the effect of birth weight on both EF (z=2.09; p=.03) and ToM (z=2.07; p=.03) at age 4.5 operated indirectly through their language ability at age 3. Our findings indicate that the effects of birth weight on child neurocognition extend into the normal range of birth weight, and specific developmental mechanisms may link these skills over time. PMID:25171131

  16. Arabidopsis CROLIN1, a Novel Plant Actin-binding Protein, Functions in Cross-linking and Stabilizing Actin Filaments*

    PubMed Central

    Jia, Honglei; Li, Jisheng; Zhu, Jingen; Fan, Tingting; Qian, Dong; Zhou, Yuelong; Wang, Jiaojiao; Ren, Haiyun; Xiang, Yun; An, Lizhe

    2013-01-01

    Higher order actin filament structures are necessary for cytoplasmic streaming, organelle movement, and other physiological processes. However, the mechanism by which the higher order cytoskeleton is formed in plants remains unknown. In this study, we identified a novel actin-cross-linking protein family (named CROLIN) that is well conserved only in the plant kingdom. There are six isovariants of CROLIN in the Arabidopsis genome, with CROLIN1 specifically expressed in pollen. In vitro biochemical analyses showed that CROLIN1 is a novel actin-cross-linking protein with binding and stabilizing activities. Remarkably, CROLIN1 can cross-link actin bundles into actin networks. CROLIN1 loss of function induces pollen germination and pollen tube growth hypersensitive to latrunculin B. All of these results demonstrate that CROLIN1 may play an important role in stabilizing and remodeling actin filaments by binding to and cross-linking actin filaments. PMID:24072702

  17. Mechanistic links between gut microbial community dynamics, microbial functions and metabolic health.

    PubMed

    Ha, Connie W Y; Lam, Yan Y; Holmes, Andrew J

    2014-11-28

    Gut microbes comprise a high density, biologically active community that lies at the interface of an animal with its nutritional environment. Consequently their activity profoundly influences many aspects of the physiology and metabolism of the host animal. A range of microbial structural components and metabolites directly interact with host intestinal cells and tissues to influence nutrient uptake and epithelial health. Endocrine, neuronal and lymphoid cells in the gut also integrate signals from these microbial factors to influence systemic responses. Dysregulation of these host-microbe interactions is now recognised as a major risk factor in the development of metabolic dysfunction. This is a two-way process and understanding the factors that tip host-microbiome homeostasis over to dysbiosis requires greater appreciation of the host feedbacks that contribute to regulation of microbial community composition. To date, numerous studies have employed taxonomic profiling approaches to explore the links between microbial composition and host outcomes (especially obesity and its comorbidities), but inconsistent host-microbe associations have been reported. Available data indicates multiple factors have contributed to discrepancies between studies. These include the high level of functional redundancy in host-microbiome interactions combined with individual variation in microbiome composition; differences in study design, diet composition and host system between studies; and inherent limitations to the resolution of rRNA-based community profiling. Accounting for these factors allows for recognition of the common microbial and host factors driving community composition and development of dysbiosis on high fat diets. New therapeutic intervention options are now emerging. PMID:25469018

  18. Mechanistic links between gut microbial community dynamics, microbial functions and metabolic health

    PubMed Central

    Ha, Connie WY; Lam, Yan Y; Holmes, Andrew J

    2014-01-01

    Gut microbes comprise a high density, biologically active community that lies at the interface of an animal with its nutritional environment. Consequently their activity profoundly influences many aspects of the physiology and metabolism of the host animal. A range of microbial structural components and metabolites directly interact with host intestinal cells and tissues to influence nutrient uptake and epithelial health. Endocrine, neuronal and lymphoid cells in the gut also integrate signals from these microbial factors to influence systemic responses. Dysregulation of these host-microbe interactions is now recognised as a major risk factor in the development of metabolic dysfunction. This is a two-way process and understanding the factors that tip host-microbiome homeostasis over to dysbiosis requires greater appreciation of the host feedbacks that contribute to regulation of microbial community composition. To date, numerous studies have employed taxonomic profiling approaches to explore the links between microbial composition and host outcomes (especially obesity and its comorbidities), but inconsistent host-microbe associations have been reported. Available data indicates multiple factors have contributed to discrepancies between studies. These include the high level of functional redundancy in host-microbiome interactions combined with individual variation in microbiome composition; differences in study design, diet composition and host system between studies; and inherent limitations to the resolution of rRNA-based community profiling. Accounting for these factors allows for recognition of the common microbial and host factors driving community composition and development of dysbiosis on high fat diets. New therapeutic intervention options are now emerging. PMID:25469018

  19. The Swine Plasma Metabolome Chronicles "Many Days" Biological Timing and Functions Linked to Growth

    PubMed Central

    Bromage, Timothy G.; Idaghdour, Youssef; Lacruz, Rodrigo S.; Crenshaw, Thomas D.; Ovsiy, Olexandra; Rotter, Björn; Hoffmeier, Klaus; Schrenk, Friedemann

    2016-01-01

    The paradigm of chronobiology is based almost wholly upon the daily biological clock, or circadian rhythm, which has been the focus of intense molecular, cellular, pharmacological, and behavioral, research. However, the circadian rhythm does not explain biological timings related to fundamental aspects of life history such as rates of tissue/organ/body size development and control of the timing of life stages such as gestation length, age at maturity, and lifespan. This suggests that another biological timing mechanism is at work. Here we focus on a "many days" (multidien) chronobiological period first observed as enigmatic recurring growth lines in developing mammalian tooth enamel that is strongly associate with all adult tissue, organ, and body masses as well as life history attributes such as gestation length, age at maturity, weaning, and lifespan, particularly among the well studied primates. Yet, knowledge of the biological factors regulating the patterning of mammalian life, such as the development of body size and life history structure, does not exist. To identify underlying molecular mechanisms we performed metabolome and genome analyses from blood plasma in domestic pigs. We show that blood plasma metabolites and small non-coding RNA (sncRNA) drawn from 33 domestic pigs over a two-week period strongly oscillate on a 5-day multidien rhythm, as does the pig enamel rhythm. Metabolomics and genomics pathway analyses actually reveal two 5-day rhythms, one related to growth in which biological functions include cell proliferation, apoptosis, and transcription regulation/protein synthesis, and another 5-day rhythm related to degradative pathways that follows three days later. Our results provide experimental confirmation of a 5-day multidien rhythm in the domestic pig linking the periodic growth of enamel with oscillations of the metabolome and genome. This association reveals a new class of chronobiological rhythm and a snapshot of the biological bases that

  20. Occupational exposure to aluminum and its amyloidogenic link with cognitive functions.

    PubMed

    Zawilla, N H; Taha, F M; Kishk, N A; Farahat, S A; Farghaly, M; Hussein, M

    2014-10-01

    As many other metals, aluminum is a widely recognized neurotoxicant and its link with neurodegenerative disorders has been the subject of scientific debate. One proposal focuses on amyloid β deposition (amyloidogenesis) as the key player in triggering neuronal dysfunction the so-called amyloid cascade hypothesis. We undertook this study first to investigate the cognition status of workers exposed to Al dust in an Al factory in Southern Cairo, second, to evaluate serum amyloid precursor protein (APP) and cathepsin D (CD) enzyme activity to study the possible role of Al in amyloidogenesis, and finally to explore the relation between these potential biomarkers and cognitive functions. The study was conducted on 54 exposed workers and 51 matched controls. They were subjected to questionnaire, neurological examination and a cognitive test battery, Addenbrooke's Cognitive Examination - Revised (ACE-R). Serum Al, APP and CD enzyme activity were measured. A significant increase of serum Al was found in the exposed workers with an associated increase in serum APP and decrement in CD activity. The exposed workers displayed poor performance on the ACE-R test. No significant correlation was detected between ACE-R test total score and either APP or CD activity. We concluded that occupational exposure to Al is associated with cognitive impairment. The effect of occupational Al exposure on the serum levels of APP and CD activity may be regarded as a possible mechanism of Al in amyloidogenesis. However, our findings do not support the utility of serum APP and CD activity as screening markers for early or preclinical cognitive impairment. PMID:24973993

  1. Specifying Links between Executive Functioning and Theory of Mind during Middle Childhood: Cognitive Flexibility Predicts Social Understanding

    ERIC Educational Resources Information Center

    Bock, Allison M.; Gallaway, Kristin C.; Hund, Alycia M.

    2015-01-01

    The purpose of this study was to specify the development of and links between executive functioning and theory of mind during middle childhood. One hundred four 7- to 12-year-old children completed a battery of age-appropriate tasks measuring working memory, inhibition, flexibility, theory of mind, and vocabulary. As expected, spatial working…

  2. Executive Function as a Mediator in the Link between Attention-Deficit/Hyperactivity Disorder and Social Problems

    ERIC Educational Resources Information Center

    Tseng, Wan-Ling; Gau, Susan Shur-Fen

    2013-01-01

    Background: Cognitive processes and mechanisms underlying the strong link between attention-deficit/hyperactivity disorder (ADHD) and social problems remain unclear. Limited knowledge also exists regarding a subgroup of youth with ADHD who do not have social problems. This study investigated the extent to which executive function (EF) mediated the…

  3. The Broader Context of Relational Aggression in Adolescent Romantic Relationships: Predictions from Peer Pressure and Links to Psychosocial Functioning

    ERIC Educational Resources Information Center

    Schad, Megan M.; Szwedo, David E.; Antonishak, Jill; Hare, Amanda; Allen, Joseph P.

    2008-01-01

    The broader context of relational aggression in adolescent romantic relationships was assessed by considering the ways such aggression emerged from prior experiences of peer pressure and was linked to concurrent difficulties in psychosocial functioning. Longitudinal, multi-reporter data were obtained from 97 adolescents and their best friends at…

  4. Exogenous collagen cross-linking recovers tendon functional integrity in an experimental model of partial tear.

    PubMed

    Fessel, Gion; Wernli, Jeremy; Li, Yufei; Gerber, Christian; Snedeker, Jess G

    2012-06-01

    We investigated the hypothesis that exogenous collagen cross-linking can augment intact regions of tendon to mitigate mechanical propagation of partial tears. We first screened the low toxicity collagen cross-linkers genipin, methylglyoxal and ultra-violet (UV) light for their ability to augment tendon stiffness and failure load in rat tail tendon fascicles (RTTF). We then investigated cross-linking effects in load bearing equine superficial digital flexor tendons (SDFT). Data indicated that all three cross-linking agents augmented RTTF mechanical properties but reduced native viscoelasticity. In contrast to effects observed in fascicles, methylglyoxal treatment of SDFT detrimentally affected tendon mechanical integrity, and in the case of UV did not alter tendon mechanics. As in the RTTF experiments, genipin cross-linking of SDFT resulted in increased stiffness, higher failure loads and reduced viscoelasticity. Based on this result we assessed the efficacy of genipin in arresting tendon tear propagation in cyclic loading to failure. Genipin cross-linking secondary to a mid-substance biopsy-punch significantly reduced tissue strains, increased elastic modulus and increased resistance to fatigue failure. We conclude that genipin cross-linking of injured tendons holds potential for arresting tendon tear progression, and that implications of the treatment on matrix remodeling in living tendons should now be investigated. PMID:22102295

  5. Assembly, cross-linking and encapsulation using functionalized nanoparticles at liquid interfaces

    NASA Astrophysics Data System (ADS)

    Tangirala, Ravisubhash

    The assembly of nanoparticles at the interface of immiscible fluids holds promise for the preparation of new materials that benefit from both the physical properties of the nanoparticles and the chemistry associated with the ligands. Shaking nanoparticle solutions in organic solvents with water, results in the formation of nanoparticle-coated droplets that range in size from 10 microm to 200 microm. A strategy to control the size of these emulsions is described, by passing the droplets through commercial track-etch membranes with known pore sizes. Extrusion reduces the droplet size by breaking the droplets while passing theough the membrane pores, and reforming in the presence of excess nanoparticles in solution to form droplets as small as 1-5 microm. Crosslinking of nanoparticles at a liquid interface lends greater stability to the interfacial assembly, leading to ultrathin nanoparticle-based capsules, which possess mechanical integrity even after removal of the interface. Two approaches towards crosslinking are used in this thesis. Norbornene-functionalized CdSe/ZnS are used to afford facile capsule visualization by fluorescence confocal microscopy, as well as ease of crosslinking in mild conditions by means of ring-opening metathesis polymerization (ROMP). The crosslinked capsules can be used to encapsulate materials, and display size-selective retention capability, governed by the interstitial spaces between the nanoparticles. In a second approach to making hybrid capsules and sheets, horse spleen ferritin bionanoparticles and aldehyde-functionalized CdSe quantum dots are co-assembled at an oil-water interface. The cross-linked materials formed by reaction of the aldehyde functionality on the quantum dots with the surface-available amines on the ferritin bionanoparticles can be disrupted by addition of acid, thus leading to pH-degradable capsules and sheets. The driving force for assembly of nanoparticles at liquid interfaces is the reduction of the

  6. Linking the Disabilities of Arm, Shoulder, and Hand to the International Classification of Functioning, Disability, and Health.

    PubMed

    Silva Drummond, Adriana; Ferreira Sampaio, Rosana; Cotta Mancini, Marisa; Noce Kirkwood, Renata; Stamm, Tanja A

    2007-01-01

    The objective of this study was to explore whether the items from a specific outcome measure, that is, Disabilities of the Arm, Shoulder, and Hand (DASH), for quantifying limb symptoms and functions in musculoskeletal disorders fit into the framework of the International Classification of Functioning, Disability and Health (ICF). All DASH items were compared to the ICF according to eight linking rules. Two groups of researchers performed the linking independently, and the results were compared by correlation. The 30 DASH items and four items from the optional modules were linked to 63 ICF categories and 11 chapters: 15 categories belong to the ICF body functions component and 48 to the activities and participation component. There were no items coded under the components body structure or environmental factors. Kappa index showed an agreement of 0.73 (p<0.001). The results showed that the content of the DASH does link well with the ICF framework. Clinicians and researchers must attend to the fact that certain domains and categories from the ICF are not covered by the DASH. Limitations of the instrument may be overcome by simultaneously using other instruments that address the intended content. PMID:17954354

  7. Using natural salmon colonization as a guide to identify functional links between physical and biological processes (Invited)

    NASA Astrophysics Data System (ADS)

    Pess, G. R.

    2009-12-01

    Establishing clear functional links between physical and biological processes in aquatic systems has been difficult to accomplish because many of the aquatic ecosystems we attempt to quantify have been significantly degraded from both perspectives. However there are freshwater ecosystems along the Western Pacific Rim where these functional relationships between physical and biological processes remain intact. I present three examples from Alaska, British Columbia, and Washington State where natural salmon colonization in functioning aquatic ecosystems has allowed for the quantification of functional links between habitat characteristics and the occurrence, persistence, and abundance of salmon populations in newly opened habitats. Habitat metrics such as habitat area, residual depth, and substrate size, combined with biological factors such as individual salmon condition (e.g., length, weight), population dynamics (e.g., population growth rate), and exogenous variables (e.g. ocean conditions) determine many of the functional links that are important to aquatic ecosystems. The relationships between these physical and biological variables can help better define what is needed in aquatic ecosystems that have been simplified and where aquatic biota have significantly declined.

  8. Bridging Multiple Lines Of Evidence To Quantify Plant Phenology And Assess Links To Dryland Ecosystem Function

    NASA Astrophysics Data System (ADS)

    Browning, D. M.; Tweedie, C. E.; Vivoni, E. R.; Maynard, J. J.; Karl, J.

    2015-12-01

    The clear and pressing need to reliably identify and predict shifts in plant phenology at landscape scales requires a critical link between mechanistic understanding of climate drivers and broad scale forecasts of plant responses to climate change. A multi-scale phenology study co-located with two eddy covariance towers was initiated on the Jornada Basin LTER in New Mexico in 2010 to bridge phenology patterns at the plant level with those representing aggregated signals at the landscape level. The study integrates phenology observations collected in the field along with those collected via remotely using imagery from phenocams, unmanned aerial vehicles (UAVs), and satellite sensors along with estimates of carbon flux. We applied the Breaks for Additive Seasonal and Trend (BFAST) time series algorithm to MODIS 250-m NDVI greenness index values to partition the NDVI signal into components representing the long-term trend, seasonal periodicity, and residuals and identified significant shifts in the NDVI signal (i.e., "breaks"). Previous work verified breaks representing significant deviations from the BFAST seasonal and trend models using field-estimated plant biomass collected between 2000 and 2014. We subsequently examine estimates of fractional cover by functional group derived from UAV images acquired 2010 through 2015. At a mixed grassland site, the BFAST algorithm detected four breaks in the trend model denoting significant increases in NDVI in May 2004, July 2006, and March 2010 and a significant decrease in May 2012. The 2004 and 2006 breaks corresponded to herbaceous vegetation responses to rainfall following prolonged periods of drought. The 2012 decrease in NDVI corresponded to the marked reduction of herbaceous biomass following an exceptionally dry period in late 2010-2011. Seasonal breaks representing changes in the timing and magnitude of NDVI identified in July 2006 and September 2008 coincide with rapid increases in production of annual species in

  9. Linking Remotely Sensed Functional Diversity of Structural Traits to the Radiative Regime of a Temperate Mixed Forest

    NASA Astrophysics Data System (ADS)

    Schneider, F. D.; Morsdorf, F.; Furrer, R.; Schmid, B.; Schaepman, M. E.

    2015-12-01

    Patterns of functional diversity reflect the inter- and intraspecific variability of plant traits and are linked to other aspects of biodiversity, environmental factors and ecosystem function. To study the patterns at plot and stand level, spatially continuous trait measurements are required. Remote sensing methods based on airborne observations can offer such continuous high-resolution measurements, resolving individual trees of a forest at a regional extent. The study was performed at the Laegern forest, a temperate mixed forest dominated by deciduous and coniferous trees (Fagus sylvatica, Picea abies; 47°28'42.0" N, 8°21'51.8" E, 682 m asl; Switzerland). Canopy height, plant area index and foliage height diversity were derived from full-waveform airborne laser scanning data. These structural traits were used to calculate functional richness, functional evenness and functional divergence at a range of scales. A Bayesian multiresolution scale analysis was used to infer the scales at which functional diversity patterns occur. The radiative regime of the forest was simulated using the 3D radiative transfer model DART. Using a voxel-based forest reconstruction allowed us to derive top of canopy, bottom of canopy and absorbed photosynthetically active radiation. The results of this study will provide new insights on linking forest canopy structure to the radiative regime of the forest. Light availability is a critical factor determining plant growth and competition. Within canopy light scattering is mainly driven by the arrangement of leaves and their leaf optical properties. Therefore, we expect a link between the structural complexity of the forest as encompassed by functional diversity and the light availability within and below the canopy. Ultimately, this information can be used in dynamic ecosystem models such as ED2, allowing us to predict the influence of functional diversity and radiative properties on ecosystem functioning under current conditions and

  10. Functional cross-linked hemoglobin bis-tetramers: geometry and cooperativity.

    PubMed

    Hu, Dongxin; Kluger, Ronald

    2008-11-25

    Hemoglobin-based oxygen carriers have been sought as stable, sterile alternatives to red cells in transfusions. Problems in clinical trials using cross-linked tetramers have led to proposals that larger assemblies of tetramers may alleviate some of the problems. A study of such assemblies requires materials with defined structures and physical properties. Evaluation of cross-linked bis-tetramers with inflexible linear links between the tetramers revealed that these have very low cooperativity in oxygen binding and would thus be inefficient as oxygen carriers. New, more flexible reagents were designed to cross-link and connect tetramers in two modes: with angular connectors that permit torsional movement (1-3) and with linear connectors that resemble previously studied systems (4-6). The resulting cross-linked bis-tetramers were produced in high yield and were isolated and characterized. Digest mapping showed that modifications were specifically introduced as expected at amino groups in the 2,3-bisphosphoglycerate binding sites within beta subunits. Circular dichroism showed that the secondary structure of the globin chains is maintained while the microenvironment of the hemes is altered. The bis-tetramers derived from 1-3 have oxygen affinity (P(50) = 3.6-4.7) and cooperativity (n(50) = 2.2-2.7) that appear to be suitable for efficient oxygen delivery to hypoxic regions along with increased mass that is expected to minimize extravasation. PMID:18956893

  11. Linking self-determined functional problems of patients with neck pain to the International Classification of Functioning, Disability, and Health (ICF)

    PubMed Central

    Andelic, Nada; Johansen, Jan Borre; Bautz-Holter, Erik; Mengshoel, Anne Marit; Bakke, Eva; Roe, Cecilie

    2012-01-01

    Objective To describe commonly reported self-determined functional problems in patients with neck pain and to evaluate their fit to the components of the International Classification of Functioning, Disability, and Health (ICF). Methods Overall, 249 patients were included in this cross-sectional study that comprised patients with neck pain referred to the outpatient clinic at Oslo University Hospital (2007–2009). Patients were asked to report their three most significant functional problems on the Patient-Specific Functional Scale, a self-determined measure of function. The ICF was used as a tool for analysis. Meaningful concepts within the functional problems were identified, coded, and linked to second-level categories within the components of “body functions,” and “activities and participation.” Two researchers performed coding and linking independently. The ICF categories were presented by percentage of the total number of functional problems linked to the ICF. Results Of 628 reported functional problems, 13 meaningful ICF domains were identified: four domains belonging to the body functions component (b) and nine domains belonging to activities and participation components (d). Within the 88 second-level ICF classification categories of body functions, the most frequently reported items were sleep function (b134; 27%) and mobility of joint functions (b710; 26%). Within the 538 second-level categories of activities and participation, remunerative employment was reported as the most frequent item (d850; 15%), closely followed by doing housework (d640; 14%), and recreation and leisure activities (d920; 13%). Only two meaningful concepts, described as “be active” and “to function after activities,” were not assigned to a specific ICF category. Conclusion The majority of the specific functional problems presented by patients in this study showed a good fit with the ICF model. The substantial number of links to the activities and participation

  12. The Extent to Which Collaborative Teams of Educators Link the Results of Functional Assessment to Function-Based Interventions

    ERIC Educational Resources Information Center

    de Courcy-Bower, Laurie

    2010-01-01

    A promising approach to addressing challenging behavior in schools is to develop and implement "function-based interventions" (Dunlap et al., 2006; Hanley, Iwata, & McCord, 2003). Function-based interventions are individualized interventions in which five key outcomes of functional assessment (i.e., identification of challenging behavior,…

  13. Sleep and Cognition in Preschool Years: Specific Links to Executive Functioning

    ERIC Educational Resources Information Center

    Bernier, Annie; Beauchamp, Miriam H.; Bouvette-Turcot, Andrée-Anne; Carlson, Stephanie M.; Carrier, Julie

    2013-01-01

    This study investigated the prospective links between sleep in infancy and preschoolers' cognitive performance. Mothers of 65 infants completed a sleep diary when infants were aged 1 year, and children completed two subscales of the Wechsler Preschool and Primary Scale of Intelligence at 4 years, indexing general cognitive ability and complex…

  14. Molecular Cloning and Functional Characterization of Two Brachypodium distachyon UBC13 Genes Whose Products Promote K63-Linked Polyubiquitination

    PubMed Central

    Guo, Huiping; Wen, Rui; Liu, Zhi; Datla, Raju; Xiao, Wei

    2016-01-01

    Living organisms are constantly subject to DNA damage from environmental sources. Due to the sessile nature of plants, UV irradiation is a major genotoxic agent and imposes a significant threat on plant survival, genome stability and crop yield. In addition, other environmental chemicals can also influence the stability of the plant genome. Eukaryotic organisms have evolved a mechanism to cope with replication-blocking lesions and stabilize the genome. This mechanism is known as error-free DNA damage tolerance, and is mediated by K63-linked PCNA polyubiquitination. Genes related to K63-linked polyubiquitination have been isolated recently from model plants like Arabidopsis and rice, but we are unaware of such reports on the crop model Brachypodium distachyon. Here, we report the identification and functional characterization of two B. distachyon UBC13 genes. Both Ubc13s form heterodimers with Uevs from other species, which are capable of catalyzing K63 polyubiquitination in vitro. Both genes can functionally rescue the yeast ubc13 null mutant from killing by DNA-damaging agents. These results suggest that Ubc13-Uev-promoted K63-linked polyubiquitination is highly conserved in eukaryotes including B. distachyon. Consistent with recent findings that K63-linked polyubiquitination is involved in several developmental and stress-responsive pathways, the expression of BdUbc13s appears to be constitutive and is regulated by abnormal temperatures. PMID:26779244

  15. Developing functional musculoskeletal tissues through hypoxia and lysyl oxidase-induced collagen cross-linking

    PubMed Central

    Makris, Eleftherios A.; Responte, Donald J.; Hu, Jerry C.; Athanasiou, Kyriacos A.

    2014-01-01

    The inability to recapitulate native tissue biomechanics, especially tensile properties, hinders progress in regenerative medicine. To address this problem, strategies have focused on enhancing collagen production. However, manipulating collagen cross-links, ubiquitous throughout all tissues and conferring mechanical integrity, has been underinvestigated. A series of studies examined the effects of lysyl oxidase (LOX), the enzyme responsible for the formation of collagen cross-links. Hypoxia-induced endogenous LOX was applied in multiple musculoskeletal tissues (i.e., cartilage, meniscus, tendons, ligaments). Results of these studies showed that both native and engineered tissues are enhanced by invoking a mechanism of hypoxia-induced pyridinoline (PYR) cross-links via intermediaries like LOX. Hypoxia was shown to enhance PYR cross-linking 1.4- to 6.4-fold and, concomitantly, to increase the tensile properties of collagen-rich tissues 1.3- to 2.2-fold. Direct administration of exogenous LOX was applied in native cartilage and neocartilage generated using a scaffold-free, self-assembling process of primary chondrocytes. Exogenous LOX was found to enhance native tissue tensile properties 1.9-fold. LOX concentration- and time-dependent increases in PYR content (∼16-fold compared with controls) and tensile properties (approximately fivefold compared with controls) of neocartilage were also detected, resulting in properties on par with native tissue. Finally, in vivo subcutaneous implantation of LOX-treated neocartilage in nude mice promoted further maturation of the neotissue, enhancing tensile and PYR content approximately threefold and 14-fold, respectively, compared with in vitro controls. Collectively, these results provide the first report, to our knowledge, of endogenous (hypoxia-induced) and exogenous LOX applications for promoting collagen cross-linking and improving the tensile properties of a spectrum of native and engineered tissues both in vitro and in

  16. The Role of Representations in Executive Function: Investigating a Developmental Link between Flexibility and Abstraction

    PubMed Central

    Kharitonova, Maria; Munakata, Yuko

    2011-01-01

    Young children often perseverate, engaging in previously correct, but no longer appropriate behaviors. One account posits that such perseveration results from the use of stimulus-specific representations of a situation, which are distinct from abstract, generalizable representations that support flexible behavior. Previous findings supported this account, demonstrating that only children who flexibly switch between rules could generalize their behavior to novel stimuli. However, this link between flexibility and generalization might reflect general cognitive abilities, or depend upon similarities across the measures or their temporal order. The current work examined these issues by testing the specificity and generality of this link. In two experiments with 3-year-old children, flexibility was measured in terms of switching between rules in a card-sorting task, while abstraction was measured in terms of selecting which stimulus did not belong in an odd-one-out task. The link between flexibility and abstraction was general across (1) abstraction dimensions similar to or different from those in the card-sorting task and (2) abstraction tasks that preceded or followed the switching task. Good performance on abstraction and flexibility measures did not extend to all cognitive tasks, including an IQ measure, and dissociated from children’s ability to gaze at the correct stimulus in the odd-one-out task, suggesting that the link between flexibility and abstraction is specific to such measures, rather than reflecting general abilities that affect all tasks. We interpret these results in terms of the role that developing prefrontal cortical regions play in processes such as working memory, which can support both flexibility and abstraction. PMID:22144971

  17. Nitrocinnamate-functionalized gelatin: synthesis and "smart"hydrogel formation via photo-cross-linking.

    PubMed

    Gattás-Asfura, Kerim M; Weisman, Eric; Andreopoulos, Fotios M; Micic, Miodrag; Muller, Bill; Sirpal, Sanjeev; Pham, Si M; Leblanc, Roger M

    2005-01-01

    Gelatin having p-nitrocinnamate pendant groups (Gel-NC) was prepared via an efficient one-pot synthesis, yield >87%. (1)H NMR data indicated that 1 mol of gelatin was modified with 18 +/- 6 mol of the photosensitive group. Upon exposure to low-intensity 365 nm UV light and in the absence of photoinitiators or catalysts, Gel-NC cross-linked within minutes into a gelatin-based hydrogel as monitored by UV-vis spectroscopy. The degree of swelling of this biodegradable hydrogel in aqueous solutions responded to changes in Gel-NC concentration levels, the ionic strength of the aqueous solutions, and photo-cross-linking time. Topography changes associated with phase transition resulting from "photocleavage" of the hydrogel network with 254 nm UV light were studied with AFM. Both Gel-NC and its hydrogel expressed low toxicity to human neonatal fibroblast cells. In addition, gelatin-based microgels were prepared via the photo-cross-linking of Gel-NC within inverse micelles. PMID:15877371

  18. The use of controlled microbial cenoses in producers' link to increase steady functioning of artificial ecosystems

    NASA Astrophysics Data System (ADS)

    Somova, Lydia; Mikheeva, Galina; Somova, Lydia

    The life support systems (LSS) for long-term missions are to use cycling-recycling systems, including biological recycling. Simple ecosystems include 3 links: producers (plants), consumers (man, animals) and reducers (microorganisms). Microorganisms are substantial component of every link of LSS. Higher plants are the traditional regenerator of air and producer of food. They should be used in many successive generations of their reproduction in LSS. Controlled microbiocenoses can increase productivity of producer's link and protect plants from infections. The goal of this work was development of methodological bases of formation of stable, controlled microbiocenoses, intended for increase of productivity of plants and for obtaining ecologically pure production of plants. Main results of our investigations: 1. Experimental microbiocenoses, has been produced in view of the developed methodology on the basis of natural association of microorganisms by long cultivation on specially developed medium. Dominating groups are bacteria of genera: Lactobacillus, Streptococcus, Leuconostoc, Bifidobacterium, Rhodopseudomonas and yeast of genera: Kluyveromyces, Saccharomyces, Torulopsis. 2. Optimal parameters of microbiocenosis cultivation (t, pH, light exposure, biogenic elements concentrations) were experimentally established. Conditions of cultivation on which domination of different groups of microbiocenosis have been found. 3. It was shown, that processing of seeds of wheat, oats, bulbs and plants Allium cepa L. (an onions) with microbial association raised energy of germination of seeds and bulbs and promoted the increase (on 20-30 %) of growth green biomass and root system of plants in comparison with the control. This work is supported by grant, Yenissey , 07-04-96806

  19. Neutron strength functions: the link between resolved resonances and the optical model

    SciTech Connect

    Moldauer, P.A.

    1980-01-01

    Neutron strength functions and scattering radii are useful as energy and channel radius independent parameters that characterize neutron scattering resonances and provide a connection between R-matrix resonance analysis and the optical model. The choice of R-matrix channel radii is discussed, as are limitations on the accuracies of strength functions. New definitions of the p-wave strength function and scattering radius are proposed. For light nuclei, where strength functions display optical model energy variations over the resolved resonances, a doubly reduced partial neutron width is introduced for more meaningful statistical analyses of widths. The systematic behavior of strength functions and scattering radii is discussed.

  20. Crucial role of detailed function, task, timeline, link and human vulnerability analyses in HRA. [Human Reliability Analysis (HRA)

    SciTech Connect

    Ryan, T.G.; Haney, L.N.; Ostrom, L.T.

    1992-01-01

    This paper addresses one major cause for large uncertainties in human reliability analysis (HRA) results, that is, an absence of detailed function, task, timeline, link and human vulnerability analyses. All too often this crucial step in the HRA process is done in a cursory fashion using word of mouth or written procedures which themselves may incompletely or inaccurately represent the human action sequences and human error vulnerabilities being analyzed. The paper examines the potential contributions these detailed analyses can make in achieving quantitative and qualitative HRA results which are: (1) creditable, that is, minimize uncertainty, (2) auditable, that is, systematically linking quantitative results and qualitative information from which the results are derived, (3) capable of supporting root cause analyses on human reliability factors determined to be major contributors to risk, and (4) capable of repeated measures and being combined with similar results from other analyses to examine HRA issues transcending individual systems and facilities. Based on experience analyzing test and commercial nuclear reactors, and medical applications of nuclear technology, an iterative process is suggested for doing detailed function, task, timeline, link and human vulnerability analyses using documentation reviews, open-ended and structured interviews, direct observations, and group techniques. Finally, the paper concludes that detailed analyses done in this manner by knowledgeable human factors practitioners, can contribute significantly to the credibility, auditability, causal factor analysis, and combining goals of the HRA.

  1. Linking Soil Microbial Ecology to Ecosystem Functioning in Integrated Crop-Livestock Systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Enhanced soil stability, nutrient cycling and C sequestration potential are important ecosystem functions driven by soil microbial processes and are directly influenced by agricultural management. Integrated crop-livestock agroecosystems (ICL) can enhance these functions via high-residue returning c...

  2. School Functioning in Early Adolescence: Gender-Linked Responses to Peer Victimization

    ERIC Educational Resources Information Center

    Hoglund, Wendy L. G.

    2007-01-01

    Research indicates that peer victimization contributes to poor school functioning in childhood and adolescence, yet the processes by which victimization interferes with school functioning are unclear. This study examined internalizing and externalizing problems as domain-specific mediators of the association between subtypes of peer victimization…

  3. Application of systems engineering techniques to component design - Capturing functionality and linking part 'critical to quality' features to requirements

    SciTech Connect

    Patel, C. M.; Moorby, J. S.; Sulley, J. L.

    2012-07-01

    A systems engineering approach - focusing upon functionality - has predominantly been applied in industry to the design of complex systems with many functional interactions, inputs and outputs, eg the design of a decay heat removal system. This paper presents how systems engineering techniques can be applied to component design, i.e. treating the component as a system in its own right, and using functionality as the 'bridge' between the customer requirements and accepted performance. A pressure relief valve is used as an example to present the techniques of: Functional Modelling to establish the functional requirements and Functional Failure Modes and Effects Analysis to establish any emergent functionality to reduce the risk of adverse behaviour. A key aspect of component design is capturing the design intent and establishing the 'Critical to Quality 'features that can critically affect quality and performance. This paper details 'Quality Function Deployment' being applied to a component to capture such features and to establish a clear link to the overarching performance requirements. This approach is particularly useful in ensuring continuity of design understanding throughout the component life cycle, assessing the effects of any proposed changes to the design and the effects of changes in system or customer requirements, or for using the design in a different application. (authors)

  4. Executive function moderates the intention-behavior link for physical activity and dietary behavior.

    PubMed

    Hall, Peter A; Fong, Geoffrey T; Epp, Lynette J; Elias, Lorin J

    2008-01-01

    Dominant theories of health behavior posit that social-cognitive and conative variables are sufficient to explain health behavior tendencies. The current studies challenge this assumption in two ways: (1) by demonstrating that unique variance in health protective behavior is predictable by knowing about individual differences in executive functioning, and (2) by demonstrating that executive function moderates the association between intention and behavior. In Studies 1 and 2, participants completed a computer-based task of executive function (Go/NoGo task) and articulated 1-week behavioral intentions for physical activity (Study 1) and dietary behavior (Study 2). Hierarchical regression analyses revealed that executive function predicts unique variance in both behaviors, and strongly moderates the association between behavioral intention and behavioral performance. Together behavioral intention and executive function explain more variance in health protective behavior than 'rational actor' models that have been widely adopted and disseminated. PMID:25160480

  5. BRCA1 functions independently of homologous recombination in DNA interstrand cross-link repair

    PubMed Central

    Bunting, Samuel F; Callen, Elsa; Kozak, Marina L; Kim, Jung-Min; Wong, Nancy; Lopez-Contreras, Andres J; Ludwig, Thomas; Baer, Richard; Faryabi, Robert B; Malhowski, Amy; Chen, Hua-Tang; Fernandez-Capetillo, Oscar; D’Andrea, Alan; Nussenzweig, Andre

    2012-01-01

    Brca1 is required for DNA repair by homologous recombination (HR) and normal embryonic development. Here we report that deletion of the DNA damage response factor 53BP1 overcomes embryonic lethality in Brca1-nullizygous mice, and rescues HR deficiency, as measured by hypersensitivity to PARP (polyADP-ribose polymerase) inhibition. However, Brca1,53BP1 double-deficient cells are hypersensitive to DNA interstrand cross-links (ICLs), indicating that BRCA1 has an additional role in DNA cross-link repair that is distinct from HR. Disruption of the non-homologous end-joining (NHEJ) factor, Ku, promotes DNA repair in Brca1-deficient cells; however deletion of either Ku or 53BP1 exacerbates genomic instability in cells lacking FANCD2, a mediator of the Fanconi Anemia pathway for ICL repair. BRCA1 therefore has two separate roles in ICL repair, whereas FANCD2 provides a key activity that can not be bypassed by ablation of 53BP1 or Ku. PMID:22445484

  6. OTUB1 Co-opts Lys48-Linked Ubiquitin Recognition to Suppress E2 Enzyme Function

    SciTech Connect

    Juang, Yu-Chi; Landry, Marie-Claude; Sanches, Mario; Vittal, Vinayak; Leung, Charles C.Y.; Ceccarelli, Derek F.; Mateo, Abigail-Rachele F.; Pruneda, Jonathan N.; Mao, Daniel Y.L.; Szilard, Rachel K.; Orlicky, Stephen; Munro, Meagan; Brzovic, Peter S.; Klevit, Rachel E.; Sicheri, Frank; Durocher, Daniel

    2012-03-26

    Ubiquitylation entails the concerted action of E1, E2, and E3 enzymes. We recently reported that OTUB1, a deubiquitylase, inhibits the DNA damage response independently of its isopeptidase activity. OTUB1 does so by blocking ubiquitin transfer by UBC13, the cognate E2 enzyme for RNF168. OTUB1 also inhibits E2s of the UBE2D and UBE2E families. Here we elucidate the structural mechanism by which OTUB1 binds E2s to inhibit ubiquitin transfer. OTUB1 recognizes ubiquitin-charged E2s through contacts with both donor ubiquitin and the E2 enzyme. Surprisingly, free ubiquitin associates with the canonical distal ubiquitin-binding site on OTUB1 to promote formation of the inhibited E2 complex. Lys48 of donor ubiquitin lies near the OTUB1 catalytic site and the C terminus of free ubiquitin, a configuration that mimics the products of Lys48-linked ubiquitin chain cleavage. OTUB1 therefore co-opts Lys48-linked ubiquitin chain recognition to suppress ubiquitin conjugation and the DNA damage response.

  7. N-Linked Glycosylation in Archaea: a Structural, Functional, and Genetic Analysis

    PubMed Central

    Ding, Yan; Meyer, Benjamin H.; Albers, Sonja-Verena; Kaminski, Lina; Eichler, Jerry

    2014-01-01

    SUMMARY N-glycosylation of proteins is one of the most prevalent posttranslational modifications in nature. Accordingly, a pathway with shared commonalities is found in all three domains of life. While excellent model systems have been developed for studying N-glycosylation in both Eukarya and Bacteria, an understanding of this process in Archaea was hampered until recently by a lack of effective molecular tools. However, within the last decade, impressive advances in the study of the archaeal version of this important pathway have been made for halophiles, methanogens, and thermoacidophiles, combining glycan structural information obtained by mass spectrometry with bioinformatic, genetic, biochemical, and enzymatic data. These studies reveal both features shared with the eukaryal and bacterial domains and novel archaeon-specific aspects. Unique features of N-glycosylation in Archaea include the presence of unusual dolichol lipid carriers, the use of a variety of linking sugars that connect the glycan to proteins, the presence of novel sugars as glycan constituents, the presence of two very different N-linked glycans attached to the same protein, and the ability to vary the N-glycan composition under different growth conditions. These advances are the focus of this review, with an emphasis on N-glycosylation pathways in Haloferax, Methanococcus, and Sulfolobus. PMID:24847024

  8. Converging genetic and functional brain imaging evidence links neuronal excitability to working memory, psychiatric disease, and brain activity

    PubMed Central

    Heck, A.; Fastenrath, M.; Ackermann, S.; Auschra, B.; Bickel, H.; Coynel, D.; Gschwind, L.; Jessen, F.; Kaduszkiewicz, H.; Maier, W.; Milnik, A.; Pentzek, M.; Riedel-Heller, S.G.; Ripke, S.; Spalek, K.; Sullivan, P.; Vogler, C.; Wagner, M.; Weyerer, S.; Wolfsgruber, S.; de Quervain, D.; Papassotiropoulos, A.

    2014-01-01

    Summary Working memory, the capacity of actively maintaining task-relevant information during a cognitive task, is a heritable trait. Working memory deficits are characteristic for many psychiatric disorders. We performed genome-wide gene-set enrichment analyses in multiple independent data sets of young and aged cognitively healthy subjects (n = 2’824), and in a large schizophrenia case-control sample (n = 32’143). The voltage-gated cation channel activity gene-set, consisting of genes related to neuronal excitability, was robustly linked to performance in working memory-related tasks across ages, and to schizophrenia. Functional brain imaging in 707 healthy participants linked this gene-set also to working memory-related activity in the parietal cortex and the cerebellum. Gene-set analyses may help to dissect the molecular underpinnings of cognitive dimensions, brain activity and psychopathology. PMID:24529980

  9. Converging genetic and functional brain imaging evidence links neuronal excitability to working memory, psychiatric disease, and brain activity.

    PubMed

    Heck, Angela; Fastenrath, Matthias; Ackermann, Sandra; Auschra, Bianca; Bickel, Horst; Coynel, David; Gschwind, Leo; Jessen, Frank; Kaduszkiewicz, Hanna; Maier, Wolfgang; Milnik, Annette; Pentzek, Michael; Riedel-Heller, Steffi G; Ripke, Stephan; Spalek, Klara; Sullivan, Patrick; Vogler, Christian; Wagner, Michael; Weyerer, Siegfried; Wolfsgruber, Steffen; de Quervain, Dominique J-F; Papassotiropoulos, Andreas

    2014-03-01

    Working memory, the capacity of actively maintaining task-relevant information during a cognitive task, is a heritable trait. Working memory deficits are characteristic for many psychiatric disorders. We performed genome-wide gene set enrichment analyses in multiple independent data sets of young and aged cognitively healthy subjects (n = 2,824) and in a large schizophrenia case-control sample (n = 32,143). The voltage-gated cation channel activity gene set, consisting of genes related to neuronal excitability, was robustly linked to performance in working memory-related tasks across ages and to schizophrenia. Functional brain imaging in 707 healthy participants linked this gene set also to working memory-related activity in the parietal cortex and the cerebellum. Gene set analyses may help to dissect the molecular underpinnings of cognitive dimensions, brain activity, and psychopathology. PMID:24529980

  10. Linking multidimensional functional diversity to quantitative methods: a graphical hypothesis--evaluation framework.

    PubMed

    Boersma, Kate S; Dee, Laura E; Miller, Steve J; Bogan, Michael T; Lytle, David A; Gitelman, Alix I

    2016-03-01

    Functional trait analysis is an appealing approach to study differences among biological communities because traits determine species' responses to the environment and their impacts on ecosystem functioning. Despite a rapidly expanding quantitative literature, it remains challenging to conceptualize concurrent changes in multiple trait dimensions ("trait space") and select quantitative functional diversity methods to test hypotheses prior to analysis. To address this need, we present a widely applicable framework for visualizing ecological phenomena in trait space to guide the selection, application, and interpretation of quantitative functional diversity methods. We describe five hypotheses that represent general patterns of responses to disturbance in functional community ecology and then apply a formal decision process to determine appropriate quantitative methods to test ecological hypotheses. As a part of this process, we devise a new statistical approach to test for functional turnover among communities. Our combination of hypotheses and metrics can be applied broadly to address ecological questions across a range of systems and study designs. We illustrate the framework with a case study of disturbance in freshwater communities. This hypothesis-driven approach will increase the rigor and transparency of applied functional trait studies. PMID:27197386

  11. Ferroportin diseases: functional studies, a link between genetic and clinical phenotype.

    PubMed

    Détivaud, Lénaïck; Island, Marie-Laure; Jouanolle, Anne-Marie; Ropert, Martine; Bardou-Jacquet, Edouard; Le Lan, Caroline; Mosser, Annick; Leroyer, Patricia; Deugnier, Yves; David, Véronique; Brissot, Pierre; Loréal, Olivier

    2013-11-01

    Ferroportin (FPN) mediates iron export from cells and this function is modulated by serum hepcidin. Mutations in the FPN gene (SLC40A1) lead to autosomal dominant iron overload diseases related either to loss or to gain of function, and usually characterized by normal or low transferrin saturation versus elevated transferrin saturation, respectively. However, for the same mutation, the phenotypic expression may vary from one patient to another. Using in vitro overexpression of wild-type or mutant FPN proteins, we characterized the functional impact of five recently identified FPN gene mutations regarding FPN localization, cell iron status, and hepcidin sensitivity. Our aim was to integrate functional results and biological findings in probands and relatives. We show that while the p.Arg371Gln (R371Q) mutation had no impact on studied parameters, the p.Trp158Leu (W158L), p.Arg88Gly (R88G), and p.Asn185Asp (N185D) mutations caused an iron export defect and were classified as loss-of-function mutations. The p.Gly204Ser (G204S) mutation induced a gain of FPN function. Functional studies are useful to determine whether or not a FPN gene mutation found in an iron overloaded patient is deleterious and to characterize its biological impact, especially when family studies are not fully informative and/or additional confounding factors may affect bio-clinical expression. PMID:23943237

  12. The application of a mathematical model linking structural and functional connectomes in severe brain injury

    PubMed Central

    Kuceyeski, A.; Shah, S.; Dyke, J.P.; Bickel, S.; Abdelnour, F.; Schiff, N.D.; Voss, H.U.; Raj, A.

    2016-01-01

    Following severe injuries that result in disorders of consciousness, recovery can occur over many months or years post-injury. While post-injury synaptogenesis, axonal sprouting and functional reorganization are known to occur, the network-level processes underlying recovery are poorly understood. Here, we test a network-level functional rerouting hypothesis in recovery of patients with disorders of consciousness following severe brain injury. This hypothesis states that the brain recovers from injury by restoring normal functional connections via alternate structural pathways that circumvent impaired white matter connections. The so-called network diffusion model, which relates an individual's structural and functional connectomes by assuming that functional activation diffuses along structural pathways, is used here to capture this functional rerouting. We jointly examined functional and structural connectomes extracted from MRIs of 12 healthy and 16 brain-injured subjects. Connectome properties were quantified via graph theoretic measures and network diffusion model parameters. While a few graph metrics showed groupwise differences, they did not correlate with patients' level of consciousness as measured by the Coma Recovery Scale — Revised. There was, however, a strong and significant partial Pearson's correlation (accounting for age and years post-injury) between level of consciousness and network diffusion model propagation time (r = 0.76, p < 0.05, corrected), i.e. the time functional activation spends traversing the structural network. We concluded that functional rerouting via alternate (and less efficient) pathways leads to increases in network diffusion model propagation time. Simulations of injury and recovery in healthy connectomes confirmed these results. This work establishes the feasibility for using the network diffusion model to capture network-level mechanisms in recovery of consciousness after severe brain injury. PMID:27200264

  13. Linking T-cell receptor sequence to functional phenotype at the single-cell level

    PubMed Central

    Han, Arnold; Glanville, Jacob; Hansmann, Leo; Davis, Mark M

    2015-01-01

    Although each T lymphocyte expresses a T-cell receptor (TCR) that recognizes cognate antigen and controls T-cell activation, different T cells bearing the same TCR can be functionally distinct. Each TCR is a heterodimer, and both α- and β-chains contribute to determining TCR antigen specificity. Here we present a methodology enabling integration of information about TCR specificity with information about T cell function. This method involves sequencing of TCRα and TCRβ genes, and amplifying functional genes characteristic of different T cell subsets, in single T cells. Because this approach retains information about individual TCRα-TCRβ pairs, TCRs of interest can be expressed and used in functional studies, for antigen discovery, or in therapeutic applications. We apply this approach to study the clonal ancestry and differentiation of T lymphocytes infiltrating a human colorectal carcinoma. PMID:24952902

  14. Single cell-derived clonal analysis of human glioblastoma links functional and genomic heterogeneity

    PubMed Central

    Meyer, Mona; Reimand, Jüri; Lan, Xiaoyang; Head, Renee; Zhu, Xueming; Kushida, Michelle; Bayani, Jane; Pressey, Jessica C.; Lionel, Anath C.; Clarke, Ian D.; Cusimano, Michael; Squire, Jeremy A.; Scherer, Stephen W.; Bernstein, Mark; Woodin, Melanie A.; Bader, Gary D.; Dirks, Peter B.

    2015-01-01

    Glioblastoma (GBM) is a cancer comprised of morphologically, genetically, and phenotypically diverse cells. However, an understanding of the functional significance of intratumoral heterogeneity is lacking. We devised a method to isolate and functionally profile tumorigenic clones from patient glioblastoma samples. Individual clones demonstrated unique proliferation and differentiation abilities. Importantly, naïve patient tumors included clones that were temozolomide resistant, indicating that resistance to conventional GBM therapy can preexist in untreated tumors at a clonal level. Further, candidate therapies for resistant clones were detected with clone-specific drug screening. Genomic analyses revealed genes and pathways that associate with specific functional behavior of single clones. Our results suggest that functional clonal profiling used to identify tumorigenic and drug-resistant tumor clones will lead to the discovery of new GBM clone-specific treatment strategies. PMID:25561528

  15. Linking Changes in Management and Riparian Physical Functionality to Water Quality and Aquatic Habitat

    EPA Science Inventory

    Wildlife and aquatic habitats are dependent on the development of riparian area management strategies. Land management strategies consider certain basic ecological and economic relationships. These relationships are functions of riparian and te rrestrial ecosystems, which include...

  16. LINKING COMMUNITY STRUCTURE AND ECOSYSTEM FUNCTION IN AQUATIC ECOSYSTEMS DEGRADED BY MOUNTAINTOP MINING

    EPA Science Inventory

    The Clean Water Act and its subsequent amendments recognize the importance of protecting biological integrity, a concept synonymous with preserving structure and function within lotic ecosystems. This research will improve current taxonomically based risk assessment models,...

  17. Possible pathways linking ploidy level to cell elongation and cuticular function in hypocotyls of dark-grown Arabidopsis seedlings

    PubMed Central

    Narukawa, Hideki; Yokoyama, Ryusuke; Nishitani, Kazuhiko

    2016-01-01

    abstract The mechanisms underlying correlations between ploidy level and cell size in eukaryotes remain unclear. Recently, we showed that cell length was higher in tetraploid than in diploid dark-grown Arabidopsis hypocotyls. Cuticular function was aberrant, and expression of genes of cuticle formation was reduced. Here, the links between cell elongation, cuticular function, and ploidy level in the etiolated hypocotyl were examined. Seedlings defective in cuticle formation exhibited shorter hypocotyls. This was due to inhibition of cell elongation rather than cell proliferation, indicating that the reduced cuticular function was a consequence of tetraploidy-induced cell elongation rather than its cause. Inhibition of hypocotyl elongation by impaired cuticles was lower in tetraploid than diploid, indicating that tetraploid hypocotyls were less sensitive to cuticular damage. PMID:26618780

  18. Structure and function of phosphonoacetaldehyde dehydrogenase: the missing link in phosphonoacetate formation

    PubMed Central

    Agarwal, Vinayak; Peck, Spencer C.; Chen, Jui-Hui; Borisova, Svetlana A.; Chekan, Jonathan R.; van der Donk, Wilfred A.; Nair, Satish K.

    2015-01-01

    Summary Phosphonates (C-PO32−) have application as antibiotics, herbicides and detergents. In some environments, these molecules represent the predominant source for phosphorus, and several microbes have evolved dedicated enzymatic machineries for phosphonate degradation. For example, most common naturally occurring phosphonates can be catabolized to either phosphonoacetaldehyde or phosphonoacetate, which can then be hydrolyzed to generate inorganic phosphate and acetaldehyde or acetate, respectively. The phosphonoacetaldehyde oxidase gene (phnY) links these two hydrolytic processes and provides a previously unknown catabolic mechanism for phosphonoacetate production in the microbial metabolome. Here, we present biochemical characterization of PhnY and high-resolution crystal structures of the apo state, as well as complexes with substrate, cofactor and product. Kinetic analysis of active site mutants demonstrates how a highly conserved aldehyde dehydrogenase active site has been modified in nature to generate activity with a phosphonate substrate. PMID:24361046

  19. Radiation cross-linking of ethylene vinyl alcohol copolymer functionalized with m-isopropenyl-[alpha],[alpha]-dimethyl benzyl isocyanate

    SciTech Connect

    Ekman, K.B.; Naesman, J.H. . Lab. of Polymer Technology)

    1993-10-10

    An ethylene vinyl alcohol copolymer was functionalized with m-isopropenyl-[alpha],[alpha]-dimethyl benzyl isocyanate using reactive processing in a mixer. The functionalization introduces pendant unsaturation to the polymer, which allows radiation cross-linked to gel contents >70% at radiation doses below 100 kGy. Unfunctionalized ethylene vinyl alcohol copolymer, on the other hand, forms no gel upon irradiation. The functionalization was completed within a few minutes of reactive mixing, which was confirmed with both FTIR and [sup 13]C-NMR measurements. The oxygen permeability of ethylene vinyl alcohol copolymer increased with increasing degree of functionalization, and irradiation of the samples formed trapped radicals, which act as oxygen scavengers. Consequently no oxygen permeability was detected. However, radical activity was inhibited by annealing the samples at 110 C resulting in a 24% higher oxygen permeability value for the irradiated unfunctionalized copolymer. The oxygen permeability values of the irradiated functionalized samples were approximately 13% lower. Laminates of m-isopropenyl-[alpha],[alpha]-dimethyl benzyl isocyanate functionalized ethylene vinyl alcohol copolymer and m-isopropenyl-[alpha],[alpha]-dimethyl benzyl isocyanate functionalized ethylene hydroxyethyl methacrylate copolymer acquired improved adhesive strength both at dry and wet conditions as well as at elevated temperature upon exposure to radiation.

  20. Rice DB: an Oryza Information Portal linking annotation, subcellular location, function, expression, regulation, and evolutionary information for rice and Arabidopsis

    PubMed Central

    Narsai, Reena; Devenish, James; Castleden, Ian; Narsai, Kabir; Xu, Lin; Shou, Huixia; Whelan, James

    2013-01-01

    Omics research in Oryza sativa (rice) relies on the use of multiple databases to obtain different types of information to define gene function. We present Rice DB, an Oryza information portal that is a functional genomics database, linking gene loci to comprehensive annotations, expression data and the subcellular location of encoded proteins. Rice DB has been designed to integrate the direct comparison of rice with Arabidopsis (Arabidopsis thaliana), based on orthology or ‘expressology’, thus using and combining available information from two pre-eminent plant models. To establish Rice DB, gene identifiers (more than 40 types) and annotations from a variety of sources were compiled, functional information based on large-scale and individual studies was manually collated, hundreds of microarrays were analysed to generate expression annotations, and the occurrences of potential functional regulatory motifs in promoter regions were calculated. A range of computational subcellular localization predictions were also run for all putative proteins encoded in the rice genome, and experimentally confirmed protein localizations have been collated, curated and linked to functional studies in rice. A single search box allows anything from gene identifiers (for rice and/or Arabidopsis), motif sequences, subcellular location, to keyword searches to be entered, with the capability of Boolean searches (such as AND/OR). To demonstrate the utility of Rice DB, several examples are presented including a rice mitochondrial proteome, which draws on a variety of sources for subcellular location data within Rice DB. Comparisons of subcellular location, functional annotations, as well as transcript expression in parallel with Arabidopsis reveals examples of conservation between rice and Arabidopsis, using Rice DB (http://ricedb.plantenergy.uwa.edu.au). PMID:24147765

  1. Serotonin Transporter Promoter Gain-of-Function Genotypes Are Linked to Obsessive-Compulsive Disorder

    PubMed Central

    Hu, Xian-Zhang; Lipsky, Robert H.; Zhu, Guanshan; Akhtar, Longina A.; Taubman, Julie; Greenberg, Benjamin D.; Xu, Ke; Arnold, Paul D.; Richter, Margaret A.; Kennedy, James L.; Murphy, Dennis L.; Goldman, David

    2006-01-01

    A functional serotonin transporter promoter polymorphism, HTTLPR, alters the risk of disease as well as brain morphometry and function. Here, we show that HTTLPR is functionally triallelic. The LG allele, which is the L allele with a common G substitution, creates a functional AP2 transcription-factor binding site. Expression assays in 62 lymphoblastoid cell lines representing the six genotypes and in transfected raphe-derived cells showed codominant allele action and low, nearly equivalent expression for the S and LG alleles, accounting for more variation in HTT expression than previously recognized. The gain-of-function LALA genotype was approximately twice as common in 169 whites with obsessive-compulsive disorder (OCD) than in 253 ethnically matched controls. We performed a replication study in 175 trios consisting of probands with OCD and their parents. The LA allele was twofold overtransmitted to the patients with OCD. The HTTLPR LALA genotype exerts a moderate (1.8-fold) effect on risk of OCD, which crystallizes the evidence that the HTT gene has a role in OCD. PMID:16642437

  2. The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation.

    PubMed Central

    Halestrap, A P; Price, N T

    1999-01-01

    Monocarboxylates such as lactate and pyruvate play a central role in cellular metabolism and metabolic communication between tissues. Essential to these roles is their rapid transport across the plasma membrane, which is catalysed by a recently identified family of proton-linked monocarboxylate transporters (MCTs). Nine MCT-related sequences have so far been identified in mammals, each having a different tissue distribution, whereas six related proteins can be recognized in Caenorhabditis elegans and 4 in Saccharomyces cerevisiae. Direct demonstration of proton-linked lactate and pyruvate transport has been demonstrated for mammalian MCT1-MCT4, but only for MCT1 and MCT2 have detailed analyses of substrate and inhibitor kinetics been described following heterologous expression in Xenopus oocytes. MCT1 is ubiquitously expressed, but is especially prominent in heart and red muscle, where it is up-regulated in response to increased work, suggesting a special role in lactic acid oxidation. By contrast, MCT4 is most evident in white muscle and other cells with a high glycolytic rate, such as tumour cells and white blood cells, suggesting it is expressed where lactic acid efflux predominates. MCT2 has a ten-fold higher affinity for substrates than MCT1 and MCT4 and is found in cells where rapid uptake at low substrate concentrations may be required, including the proximal kidney tubules, neurons and sperm tails. MCT3 is uniquely expressed in the retinal pigment epithelium. The mechanisms involved in regulating the expression of different MCT isoforms remain to be established. However, there is evidence for alternative splicing of the 5'- and 3'-untranslated regions and the use of alternative promoters for some isoforms. In addition, MCT1 and MCT4 have been shown to interact specifically with OX-47 (CD147), a member of the immunoglobulin superfamily with a single transmembrane helix. This interaction appears to assist MCT expression at the cell surface. There is still

  3. Polysiloxane Functionalized Carbon Dots and Their Cross-Linked Flexible Silicone Rubbers for Color Conversion and Encapsulation of White LEDs.

    PubMed

    Wang, Yunfeng; Yin, Zhengmao; Xie, Zheng; Zhao, Xinxin; Zhou, Chuanjian; Zhou, Shuyun; Chen, Ping

    2016-04-20

    In this work, aminopropylmethylpolysiloxane (AMS) functionalized luminescent carbon dots (AMS-CDs) were prepared via a one-step solvothermal method. AMS-CDs could be self- or co-cross-linking with AMS to form 3D flexible transparent silicone rubbers (SRs) where CDs acted as cross-linking points, so the loading fraction of AMS-CDs could be adjusted from 10 to 100 wt %, thus modulating fluorescence properties and flexibility of silicone rubbers. Because of the self-curing property and high thermal stability, AMS-CDs were also studied in white LEDs (WLEDs), serving as a color conversion and encapsulation layer of GaN based blue LEDs simultaneously that would avoid the traditional problem of poor compatibility between emitting and packaging materials. And the color coordinate of AMS-CDs based WLEDs (0.33, 0.28) was very close to the pure white light. In addition, the obtained CDs cross-linked SRs had good transparency (T > 80%) at 510-1400 nm and high refractive indexes (1.33-1.54) that could meet the need of commercial packaging materials and optical application. AMS-CDs were also promising to be used in the UV LEDs based WLEDs according to their wide wavelength emission and flexible optoelectronic device. PMID:27035213

  4. Linking Ecosystem Services Benefit Transfer Databases and Ecosystem Services Production Function Libraries

    EPA Science Inventory

    The quantification or estimation of the economic and non-economic values of ecosystem services can be done from a number of distinct approaches. For example, practitioners may use ecosystem services production function models (ESPFMs) for a particular location, or alternatively, ...

  5. The Link between Functional Behavioral Assessments (FBAs) and Behavioral Intervention Plans (BIPs). ERIC Digest E592.

    ERIC Educational Resources Information Center

    Jolivette, Kristine; Scott, Terrance M.; Nelson, C. Michael

    This Digest discusses provisions in the Individuals with Disabilities Education Act (IDEA) that require functional behavioral assessments (FBAs) and behavioral intervention plans (BIPs) to be conducted prior to a change in placement or suspension for more than 10 days, based on inappropriate behaviors for students with disabilities. It presents…

  6. Stability and Change in Kindergartners' Friendships: Examination of Links with Social Functioning

    ERIC Educational Resources Information Center

    Proulx, Marie-France; Poulin, Francois

    2013-01-01

    Stability and change in kindergartners' friendships were examined based on a typology of profiles (stable, fluid, loss, gain, friendless). Our purpose was to determine whether children belonging to the five profiles differed in their social functioning. The sample was composed of 2353 kindergartners. Reciprocal friendships and social functioning…

  7. "Bad Romance": Links between Psychological and Physical Aggression and Relationship Functioning in Adolescent Couples.

    PubMed

    Seiffge-Krenke, Inge; Burk, William J

    2015-01-01

    Assortative mating is an important issue in explaining antisocial, aggressive behavior. It is yet unclear, whether the similarity paradigm fully explains frequent displays of aggression in adolescents' romantic relationships. In a sample of 194 romantic partner dyads, differences between female and male partners' reports of aggression (psychological and physical) and different measures of relationship functioning (e.g., jealousy, conflicts, and the affiliative and romantic quality of the relationship) were assessed. A hierarchical cluster analysis identified five distinct subgroups of dyads based on male and female reports of psychological and physical aggression: nonaggressive couples, couples with higher perceived aggressiveness (both physical and psychological) by females, couples with higher aggressiveness perceived by males and mutually aggressive couples. A substantial number of non-aggressive dyads emerged. Of note was the high number of females showing one-sided aggression, which was, however, not countered by their partner. The mutually aggressive couples showed the least adaptive relationship functioning, with a lack of supportive, trusting relationship qualities, high conflict rates and high jealousy. The discussion focuses on the different functions of aggression in these early romantic relations, and the aggravating impact of mutual aggression on relationship functioning and its potential antisocial outcomes. PMID:26067515

  8. From Early Childhood to Adolescence: Linking Family Functioning and School Behavior

    ERIC Educational Resources Information Center

    Johnson, Vanessa K.

    2010-01-01

    The present study uses observational assessment of 66 two-parent families working and playing together when their eldest child is in kindergarten and again in ninth grade to identify distinct patterns of family functioning derived from structural family systems theory. Whereas concurrent assessment of the relationship between family type and…

  9. Sex Differences in Mental Ability: A Proposed Means to Link Them to Brain Structure and Function

    ERIC Educational Resources Information Center

    Johnson, Wendy; Bouchard, Thomas J., Jr.

    2007-01-01

    Recent work with the 42 mental ability tests administered to participants of the Minnesota Study of Twins Reared Apart (MISTRA) has suggested that there are important dimensions of mental ability that function independently of "g". Two of these dimensions, rotation-verbal and focus-diffusion, appear to involve trade-offs: greater residual rotation…

  10. Nonoccupational environmental exposure to manganese is linked to deficits in peripheral and central olfactory function.

    PubMed

    Guarneros, Marco; Ortiz-Romo, Nahum; Alcaraz-Zubeldia, Mireya; Drucker-Colín, René; Hudson, Robyn

    2013-11-01

    Manganese is of growing concern as a toxic air pollutant. It is readily transported from the olfactory epithelium to the olfactory bulb, and unlike other metals, it is transported transynaptically to structures deep within the brain. However, little is known regarding the possible effect of nonoccupational exposure to manganese on olfactory function. Using the Sniffin' Sticks test battery, we compared the olfactory performance of subjects from a manganese mining district living <1 km from a manganese processing plant, with nonexposed subjects living 50 km from the closest source of exposure (N = 30/group). Groups were matched for age, sex, and schooling, and none had ever worked in mining-related activities. Concentrations of manganese in hair were measured as a biomarker of exposure; exposed subjects had significantly higher concentrations than nonexposed subjects. They were also significantly outperformed by the nonexposed subjects on all olfactory measures (threshold, discrimination, and identification), indicating adverse effects of manganese exposure on a range of olfactory functions, including those involving higher order cognitive processes. This contrasts with previous findings showing adverse peripheral but not central effects on olfactory function of big city air pollution, which mostly consists of toxicants known to affect the olfactory epithelium but with lower transynaptic transport capacity compared with manganese. We conclude that nonoccupational exposure to airborne manganese is associated with decrements in both peripheral and central olfactory function. PMID:24097266

  11. Linking avian communities and avian influenza ecology in southern Africa using epidemiological functional groups

    PubMed Central

    2012-01-01

    The ecology of pathogens, and particularly their emergence in multi-host systems, is complex. New approaches are needed to reduce superficial complexities to a level that still allows scientists to analyse underlying and more fundamental processes. One promising approach for simplification is to use an epidemiological-function classification to describe ecological diversity in a way that relates directly to pathogen dynamics. In this article, we develop and apply the epidemiological functional group (EFG) concept to explore the relationships between wild bird communities and avian influenza virus (AIV) in three ecosystems in southern Africa. Using a two year dataset that combined bird counts and bimonthly sampling for AIV, we allocated each bird species to a set of EFGs that captured two overarching epidemiological functions: the capacity of species to maintain AIV in the system, and their potential to introduce the virus. Comparing AIV prevalence between EFGs suggested that the hypothesis that anseriforms (ducks) and charadriiforms (waders) drive AIV epidemiology cannot entirely explain the high prevalence observed in some EFGs. If anseriforms do play an important role in AIV dynamics in each of the three ecosystems, the role of other species in the local maintenance of AIV cannot be ruled out. The EFG concept thus helped us to identify gaps in knowledge and to highlight understudied bird groups that might play a role in AIV epidemiology. In general, the use of EFGs has potential for generating a range of valuable insights in epidemiology, just as functional group approaches have done in ecology. PMID:23101696

  12. The Link between Preschoolers' Executive Function and Theory of Mind and the Role of Epistemic States

    ERIC Educational Resources Information Center

    Henning, Anne; Spinath, Frank M.; Aschersleben, Gisa

    2011-01-01

    The aim of this study was to assess the specific relation between 3- to 6-year-olds' performance on a task measuring executive function (EF), the Dimensional Change Card Sort task (DCCS), and different developmental attainments in their theory of mind (ToM) by employing a battery of scaled ToM tasks that were comparable in task format and task…

  13. “Bad Romance”: Links between Psychological and Physical Aggression and Relationship Functioning in Adolescent Couples

    PubMed Central

    Seiffge-Krenke, Inge; Burk, William J.

    2015-01-01

    Assortative mating is an important issue in explaining antisocial, aggressive behavior. It is yet unclear, whether the similarity paradigm fully explains frequent displays of aggression in adolescents’ romantic relationships. In a sample of 194 romantic partner dyads, differences between female and male partners’ reports of aggression (psychological and physical) and different measures of relationship functioning (e.g., jealousy, conflicts, and the affiliative and romantic quality of the relationship) were assessed. A hierarchical cluster analysis identified five distinct subgroups of dyads based on male and female reports of psychological and physical aggression: nonaggressive couples, couples with higher perceived aggressiveness (both physical and psychological) by females, couples with higher aggressiveness perceived by males and mutually aggressive couples. A substantial number of non-aggressive dyads emerged. Of note was the high number of females showing one-sided aggression, which was, however, not countered by their partner. The mutually aggressive couples showed the least adaptive relationship functioning, with a lack of supportive, trusting relationship qualities, high conflict rates and high jealousy. The discussion focuses on the different functions of aggression in these early romantic relations, and the aggravating impact of mutual aggression on relationship functioning and its potential antisocial outcomes. PMID:26067515

  14. Linking hydrology, ecosystem function, and livelihood sustainability in African papyrus wetlands using a Bayesian Network Model

    NASA Astrophysics Data System (ADS)

    van Dam, A.; Gettel, G. M.; Kipkemboi, J.; Rahman, M. M.

    2011-12-01

    Papyrus wetlands in East Africa provide ecosystem services supporting the livelihoods of millions but are rapidly degrading due to economic development. For ecosystem conservation, an integrated understanding of the natural and social processes driving ecosystem change is needed. This research focuses on integrating the causal relationships between hydrology, ecosystem function, and livelihood sustainability in Nyando wetland, western Kenya. Livelihood sustainability is based on ecosystem services that include plant and animal harvest for building material and food, conversion of wetlands to crop and grazing land, water supply, and water quality regulation. Specific objectives were: to integrate studies of hydrology, ecology, and livelihood activities using a Bayesian Network (BN) model and include stakeholder involvement in model development. The BN model (Netica 4.16) had 35 nodes with seven decision nodes describing demography, economy, papyrus market, and rainfall, and two target nodes describing ecosystem function (defined by groundwater recharge, nutrient and sediment retention, and biodiversity) and livelihood sustainability (drinking water supply, crop production, livestock production, and papyrus yield). The conditional probability tables were populated using results of ecohydrological and socio-economic field work and consultations with stakeholders. The model was evaluated for an average year with decision node probabilities set according to data from research, expert opinion, and stakeholders' views. Then, scenarios for dry and wet seasons and for economic development (low population growth and unemployment) and policy development (more awareness of wetland value) were evaluated. In an average year, the probability for maintaining a "good" level of sediment and nutrient retention functions, groundwater recharge, and biodiversity was about 60%. ("Good" is defined by expert opinion based on ongoing field research.) In the dry season, the probability was

  15. Hypothesizing Darkness Induced Alcohol Intake Linked to Dopaminergic Regulation of Brain Function

    PubMed Central

    Blum, Kenneth; Oscar-Berman, Marlene; Badgaiyan, Rajendra; Braverman, Eric R.; Gold, Mark S.

    2014-01-01

    Understanding the role of neurotransmission in the prefrontal cortex and mesolimbic brain regions has become the subject of intensive neuroscience research worldwide. In the 1970s, our group provided evidence that rats exposed to darkness significantly augmented their alcohol intake. At that time, we proposed that melatonin was the culprit. At around the same time, our laboratory, amongst a few others, proposed that dopamine-adducts with acetaldehyde to induce alcohol intake both in rodents and in humans. While the work in these areas has declined considerably over the years, more recent scientifically sound studies continue to show the importance of these earlier controversial ideas involving alcohol abuse and alcoholism. A review of the literature has provided impetus to systematically access the newer genetic and molecular neurobiological findings relevant to the physiological and psychological motives for high alcohol consumption in animals and humans alike. Thus, we hypothesize that darkness-induced alcohol intake is linked not only to serotonergic-melatonin mechanisms, but also to dopaminergic regulation of brain mesolimbic pathways involving neuronal expression switching in response to long photoperiods affecting gene expression. PMID:25009759

  16. Decoding the conformation-linked functional properties of nucleic acids by the use of computational tools.

    PubMed

    Iacovelli, Federico; Falconi, Mattia

    2015-09-01

    DNA and RNA are large and flexible polymers selected by nature to transmit information. The most common DNA three-dimensional structure is represented by the double helix, but this biopolymer is extremely flexible and polymorphic, and can easily change its conformation to adapt to different interactions and purposes. DNA can also adopt singular topologies, giving rise, for instance, to supercoils, formed because of the limited free rotation of the DNA domain flanking a replication or transcription complex. Our understanding of the importance of these unusual or transient structures is growing, as recent studies of DNA topology, supercoiling, knotting and linking have shown that the geometric changes can drive, or strongly influence, the interactions between protein and DNA, so altering its own metabolism. On the other hand, the unique self-recognition properties of DNA, determined by the strict Watson-Crick rules of base pairing, make this material ideal for the creation of self-assembling, predesigned nanostructures. The construction of such structures is one of the main focuses of the thriving area of DNA nanotechnology, where several assembly strategies have been employed to build increasingly complex DNA nanostructures. DNA nanodevices can have direct applications in biomedicine, but also in the materials science field, requiring the immersion of DNA in an environment far from the physiological one. Crucial help in the understanding and planning of natural and artificial nanostructures is given by modern computer simulation techniques, which are able to provide a reliable structural and dynamic description of nucleic acids. PMID:25940731

  17. Linking the functions of unrelated proteins using a novel directed evolution domain insertion method

    PubMed Central

    Edwards, Wayne R.; Busse, Kathy; Allemann, Rudolf K.; Jones, D. Dafydd

    2008-01-01

    We have successfully developed a new directed evolution method for generating integral protein fusions comprising of one domain inserted within another. Creating two connections between the insert and accepting parent domain can result in the inter-dependence of the separate protein activities, thus providing a general strategy for constructing molecular switches. Using an engineered transposon termed MuDel, contiguous trinucleotide sequences were removed at random positions from the bla gene encoding TEM-1 β-lactamase. The deleted trinucleotide sequence was then replaced by a DNA cassette encoding cytochrome b562 with differing linking sequences at each terminus and sampling all three reading frames. The result was a variety of chimeric genes encoding novel integral fusion proteins that retained TEM-1 activity. While most of the tolerated insertions were observed in loops, several also occurred close to the termini of α-helices and β-strands. Several variants conferred a switching phenotype on Escherichia coli, with bacterial tolerance to ampicillin being dependent on the presence of haem in the growth medium. The magnitude of the switching phenotype ranged from 4- to 128-fold depending on the insertion position within TEM-1 and the linker sequences that join the two domains. PMID:18559359

  18. Physical soil architectural traits are functionally linked to carbon decomposition and bacterial diversity.

    PubMed

    Rabbi, S M F; Daniel, H; Lockwood, P V; Macdonald, C; Pereg, L; Tighe, M; Wilson, B R; Young, I M

    2016-01-01

    Aggregates play a key role in protecting soil organic carbon (SOC) from microbial decomposition. The objectives of this study were to investigate the influence of pore geometry on the organic carbon decomposition rate and bacterial diversity in both macro- (250-2000 μm) and micro-aggregates (53-250 μm) using field samples. Four sites of contrasting land use on Alfisols (i.e. native pasture, crop/pasture rotation, woodland) were investigated. 3D Pore geometry of the micro-aggregates and macro-aggregates were examined by X-ray computed tomography (μCT). The occluded particulate organic carbon (oPOC) of aggregates was measured by size and density fractionation methods. Micro-aggregates had 54% less μCT observed porosity but 64% more oPOC compared with macro-aggregates. In addition, the pore connectivity in micro-aggregates was lower than macro-aggregates. Despite both lower μCT observed porosity and pore connectivity in micro-aggregates, the organic carbon decomposition rate constant (Ksoc) was similar in both aggregate size ranges. Structural equation modelling showed a strong positive relationship of the concentration of oPOC with bacterial diversity in aggregates. We use these findings to propose a conceptual model that illustrates the dynamic links between substrate, bacterial diversity, and pore geometry that suggests a structural explanation for differences in bacterial diversity across aggregate sizes. PMID:27615807

  19. Identification of functions linking quorum sensing with biofilm formation in Burkholderia cenocepacia H111

    PubMed Central

    Inhülsen, Silja; Aguilar, Claudio; Schmid, Nadine; Suppiger, Angela; Riedel, Kathrin; Eberl, Leo

    2012-01-01

    Burkholderia cenocepacia has emerged as an important pathogen for patients suffering from cystic fibrosis (CF). Previous work has shown that this organism employs the CepIR quorum-sensing (QS) system to control the expression of virulence factors as well as the formation of biofilms. To date, however, very little is known about the QS-regulated virulence factors and virtually nothing about the factors that link QS and biofilm formation. Here, we have employed a combined transcriptomic and proteomic approach to precisely define the QS regulon in our model strain B. cenocepacia H111, a CF isolate. Among the identified CepR-activated loci, three were analyzed in better detail for their roles in biofilm development: (i) a gene cluster coding for the BclACB lectins, (ii) the large surface protein BapA, and (iii) a type I pilus. The analysis of defined mutants revealed that BapA plays a major role in biofilm formation on abiotic surfaces while inactivation of the type I pilus showed little effect both in a static microtitre dish-based biofilm assay and in flow-through cells. Inactivation of the bclACB lectin genes resulted in biofilms containing hollow microcolonies, suggesting that the lectins are important for biofilm structural development. PMID:22950027

  20. Linking functional decline of telomeres, mitochondria and stem cells during ageing

    PubMed Central

    Sahin, Ergün; DePinho, Ronald A.

    2013-01-01

    The study of human genetic disorders and mutant mouse models has provided evidence that genome maintenance mechanisms, DNA damage signalling and metabolic regulation cooperate to drive the ageing process. In particular, age-associated telomere damage, diminution of telomere ‘capping’ function and associated p53 activation have emerged as prime instigators of a functional decline of tissue stem cells and of mitochondrial dysfunction that adversely affect renewal and bioenergetic support in diverse tissues. Constructing a model of how telomeres, stem cells and mitochondria interact with key molecules governing genome integrity, ‘stemness’ and metabolism provides a framework for how diverse factors contribute to ageing and age-related disorders. PMID:20336134

  1. Physical activity and memory functions: are neurotrophins and cerebral gray matter volume the missing link?

    PubMed

    Flöel, A; Ruscheweyh, R; Krüger, K; Willemer, C; Winter, B; Völker, K; Lohmann, H; Zitzmann, M; Mooren, F; Breitenstein, C; Knecht, S

    2010-02-01

    Epidemiological studies reveal better cognitive function in physically active individuals. Possible mediators for this effect are neurotrophins, which are up-regulated through physical exercise and induce neuronal growth and synaptogenesis in the animal model. Here we cross-sectionally assessed 75 healthy older individuals for levels of physical activity, aerobic fitness, and memory encoding, as well as neurotrophin levels and cerebral gray matter volume. We found that physical activity, but not cardiovascular fitness, was associated with better memory encoding after controlling for age, sex, education, depression, alcohol consumption, and smoking. Higher levels of physical activity were associated with higher levels of the neurotrophin granulocyte colony stimulating factor (G-CSF) and increased cerebral gray matter volume in prefrontal and cingulate cortex as assessed by magnetic resonance voxel-based morphometry. While mediating factors will need to be further elucidated, these findings indicate that even low-level physical activity exerts beneficial effects on memory functions in older individuals. PMID:19853041

  2. Longitudinal and concurrent links between memory span, anxiety symptoms, and subsequent executive functioning in young children

    PubMed Central

    Visu-Petra, Laura; Stanciu, Oana; Benga, Oana; Miclea, Mircea; Cheie, Lavinia

    2014-01-01

    It has been conjectured that basic individual differences in attentional control influence higher-level executive functioning and subsequent academic performance in children. The current study sets out to complement the limited body of research on early precursors of executive functions (EFs). It provides both a cross-sectional, as well as a longitudinal exploration of the relationship between EF and more basic attentional control mechanisms, assessed via children's performance on memory storage tasks, and influenced by individual differences in anxiety. Multiple measures of verbal and visuospatial short-term memory (STM) were administered to children between 3 and 6 years old, alongside a non-verbal measure of intelligence, and a parental report of anxiety symptoms. After 9 months, children were re-tested on the same STM measures, at which time we also administered multiple measures of executive functioning: verbal and visuospatial working memory (WM), inhibition, and shifting. A cross-sectional view of STM development indicated that between 3 and 6 years the trajectory of visuospatial STM and EF underwent a gradual linear improvement. However, between 5 and 6 years progress in verbal STM performance stagnated. Hierarchical regression models revealed that trait anxiety was negatively associated with WM and shifting, while non-verbal intelligence was positively related to WM span. When age, gender, non-verbal intelligence, and anxiety were controlled for, STM (measured at the first assessment) was a very good predictor of overall executive performance. The models were most successful in predicting WM, followed by shifting, yet poorly predicted inhibition measures. Further longitudinal research is needed to directly address the contribution of attentional control mechanisms to emerging executive functioning and to the development of problematic behavior during early development. PMID:24904462

  3. Trans-ethnic Fine Mapping Highlights Kidney-Function Genes Linked to Salt Sensitivity.

    PubMed

    Mahajan, Anubha; Rodan, Aylin R; Le, Thu H; Gaulton, Kyle J; Haessler, Jeffrey; Stilp, Adrienne M; Kamatani, Yoichiro; Zhu, Gu; Sofer, Tamar; Puri, Sanjana; Schellinger, Jeffrey N; Chu, Pei-Lun; Cechova, Sylvia; van Zuydam, Natalie; Arnlov, Johan; Flessner, Michael F; Giedraitis, Vilmantas; Heath, Andrew C; Kubo, Michiaki; Larsson, Anders; Lindgren, Cecilia M; Madden, Pamela A F; Montgomery, Grant W; Papanicolaou, George J; Reiner, Alex P; Sundström, Johan; Thornton, Timothy A; Lind, Lars; Ingelsson, Erik; Cai, Jianwen; Martin, Nicholas G; Kooperberg, Charles; Matsuda, Koichi; Whitfield, John B; Okada, Yukinori; Laurie, Cathy C; Morris, Andrew P; Franceschini, Nora

    2016-09-01

    We analyzed genome-wide association studies (GWASs), including data from 71,638 individuals from four ancestries, for estimated glomerular filtration rate (eGFR), a measure of kidney function used to define chronic kidney disease (CKD). We identified 20 loci attaining genome-wide-significant evidence of association (p < 5 × 10(-8)) with kidney function and highlighted that allelic effects on eGFR at lead SNPs are homogeneous across ancestries. We leveraged differences in the pattern of linkage disequilibrium between diverse populations to fine-map the 20 loci through construction of "credible sets" of variants driving eGFR association signals. Credible variants at the 20 eGFR loci were enriched for DNase I hypersensitivity sites (DHSs) in human kidney cells. DHS credible variants were expression quantitative trait loci for NFATC1 and RGS14 (at the SLC34A1 locus) in multiple tissues. Loss-of-function mutations in ancestral orthologs of both genes in Drosophila melanogaster were associated with altered sensitivity to salt stress. Renal mRNA expression of Nfatc1 and Rgs14 in a salt-sensitive mouse model was also reduced after exposure to a high-salt diet or induced CKD. Our study (1) demonstrates the utility of trans-ethnic fine mapping through integration of GWASs involving diverse populations with genomic annotation from relevant tissues to define molecular mechanisms by which association signals exert their effect and (2) suggests that salt sensitivity might be an important marker for biological processes that affect kidney function and CKD in humans. PMID:27588450

  4. Exploring Protein Dynamics Space: The Dynasome as the Missing Link between Protein Structure and Function

    PubMed Central

    Hensen, Ulf; Meyer, Tim; Haas, Jürgen; Rex, René; Vriend, Gert; Grubmüller, Helmut

    2012-01-01

    Proteins are usually described and classified according to amino acid sequence, structure or function. Here, we develop a minimally biased scheme to compare and classify proteins according to their internal mobility patterns. This approach is based on the notion that proteins not only fold into recurring structural motifs but might also be carrying out only a limited set of recurring mobility motifs. The complete set of these patterns, which we tentatively call the dynasome, spans a multi-dimensional space with axes, the dynasome descriptors, characterizing different aspects of protein dynamics. The unique dynamic fingerprint of each protein is represented as a vector in the dynasome space. The difference between any two vectors, consequently, gives a reliable measure of the difference between the corresponding protein dynamics. We characterize the properties of the dynasome by comparing the dynamics fingerprints obtained from molecular dynamics simulations of 112 proteins but our approach is, in principle, not restricted to any specific source of data of protein dynamics. We conclude that: 1. the dynasome consists of a continuum of proteins, rather than well separated classes. 2. For the majority of proteins we observe strong correlations between structure and dynamics. 3. Proteins with similar function carry out similar dynamics, which suggests a new method to improve protein function annotation based on protein dynamics. PMID:22606222

  5. Soil restoration with organic amendments: linking cellular functionality and ecosystem processes

    PubMed Central

    Bastida, F.; Selevsek, N.; Torres, I. F.; Hernández, T.; García, C.

    2015-01-01

    A hot topic in recent decades, the application of organic amendments to arid-degraded soils has been shown to benefit microbially-mediated processes. However, despite the importance of soils for global sustainability, a gap has not been addressed yet in soil science: is there any connection between ecosystem-community processes, cellular functionality, and microbial lifestyles (i.e. oligotrophy-copiotrophy) in restored soils? Together with classical ecosystem indicators (fatty-acids, extracellular-enzyme activities, basal respiration), state-of-the-art metaproteomics was applied to fill this gap in a model-restoration experiment initiated 10-years ago by the addition of sewage-sludge and compost. Organic amendment strongly impacted ecosystem processes. Furthermore, the type of material used induced differences in the cellular functionalities through variations in the percentages of proteins involved in translation, transcription, energy production and C-fixation. We conclude that the long-term impact of organic restoration goes beyond ecosystem processes and affects cellular functionalities and phyla-lifestyles coupled with differences in microbial-community structures. PMID:26503516

  6. Soil restoration with organic amendments: linking cellular functionality and ecosystem processes

    NASA Astrophysics Data System (ADS)

    Bastida, F.; Selevsek, N.; Torres, I. F.; Hernández, T.; García, C.

    2015-10-01

    A hot topic in recent decades, the application of organic amendments to arid-degraded soils has been shown to benefit microbially-mediated processes. However, despite the importance of soils for global sustainability, a gap has not been addressed yet in soil science: is there any connection between ecosystem-community processes, cellular functionality, and microbial lifestyles (i.e. oligotrophy-copiotrophy) in restored soils? Together with classical ecosystem indicators (fatty-acids, extracellular-enzyme activities, basal respiration), state-of-the-art metaproteomics was applied to fill this gap in a model-restoration experiment initiated 10-years ago by the addition of sewage-sludge and compost. Organic amendment strongly impacted ecosystem processes. Furthermore, the type of material used induced differences in the cellular functionalities through variations in the percentages of proteins involved in translation, transcription, energy production and C-fixation. We conclude that the long-term impact of organic restoration goes beyond ecosystem processes and affects cellular functionalities and phyla-lifestyles coupled with differences in microbial-community structures.

  7. Soil restoration with organic amendments: linking cellular functionality and ecosystem processes.

    PubMed

    Bastida, F; Selevsek, N; Torres, I F; Hernández, T; García, C

    2015-01-01

    A hot topic in recent decades, the application of organic amendments to arid-degraded soils has been shown to benefit microbially-mediated processes. However, despite the importance of soils for global sustainability, a gap has not been addressed yet in soil science: is there any connection between ecosystem-community processes, cellular functionality, and microbial lifestyles (i.e. oligotrophy-copiotrophy) in restored soils? Together with classical ecosystem indicators (fatty-acids, extracellular-enzyme activities, basal respiration), state-of-the-art metaproteomics was applied to fill this gap in a model-restoration experiment initiated 10-years ago by the addition of sewage-sludge and compost. Organic amendment strongly impacted ecosystem processes. Furthermore, the type of material used induced differences in the cellular functionalities through variations in the percentages of proteins involved in translation, transcription, energy production and C-fixation. We conclude that the long-term impact of organic restoration goes beyond ecosystem processes and affects cellular functionalities and phyla-lifestyles coupled with differences in microbial-community structures. PMID:26503516

  8. Rab6-interacting protein 1 links Rab6 and Rab11 function.

    PubMed

    Miserey-Lenkei, Stéphanie; Waharte, François; Boulet, Annick; Cuif, Marie-Hélène; Tenza, Danielle; El Marjou, Amed; Raposo, Graça; Salamero, Jean; Héliot, Laurent; Goud, Bruno; Monier, Solange

    2007-10-01

    Rab11 and Rab6 guanosine triphosphatases are associated with membranes of the recycling endosomes (REs) and Golgi complex, respectively. Evidence indicates that they sequentially regulate a retrograde transport pathway between these two compartments, suggesting the existence of proteins that must co-ordinate their functions. Here, we report the characterization of two isoforms of a protein, Rab6-interacting protein 1 (R6IP1), originally identified as a Rab6-binding protein. R6IP1 also binds to Rab11A in its GTP-bound conformation. In interphase cells, R6IP1 is targeted to the Golgi in a Rab6-dependent manner but can associate with Rab11-positive compartments when the level of Rab11A is increased within the cells. Fluorescence resonance energy transfer analysis using fluorescence lifetime imaging shows that the overexpression of R6IP1 promotes an interaction between Rab11A and Rab6 in living cells. Accordingly, the REs marked by Rab11 and transferrin receptor are depleted from the cell periphery and accumulate in the pericentriolar area. However, endosomal and Golgi membranes do not appear to fuse with each other. We also show that R6IP1 function is required during metaphase and cytokinesis, two mitotic steps in which a role of Rab6 and Rab11 has been previously documented. We propose that R6IP1 may couple Rab6 and Rab11 function throughout the cell cycle. PMID:17725553

  9. A conditional system to specifically link disruption of protein coding function with reporter expression in mice

    PubMed Central

    Chiou, Shin-Heng; Kim-Kiselak, Caroline; Risca, Viviana I.; Heimann, Megan K.; Chuang, Chen-Hua; Burds, Aurora A.; Greenleaf, William J.; Jacks, Tyler E.; Feldser, David M.; Winslow, Monte M.

    2014-01-01

    Summary Conditional gene deletion in mice has contributed immensely to our understanding of many biological and biomedical processes. Despite an increasing awareness of non-protein coding functional elements within protein coding transcripts, current gene-targeting approaches typically involve simultaneous ablation of non-coding elements within targeted protein-coding genes. The potential for protein-coding genes to have additional non-coding functions necessitates the development of novel genetic tools capable of precisely interrogating individual functional elements. We present a strategy coupling Cre/loxP-mediated conditional gene disruption with faithful GFP-reporter expression in mice in which Cre-mediated stable inversion of a splice acceptor-GFP-splice donor cassette concurrently disrupts protein production and creates a GFP fusion product. Importantly, cassette inversion maintains physiologic transcript structure, thereby ensuring proper microRNA-mediated regulation of the GFP-reporter, as well as maintaining expression of non-protein coding elements. To test this potentially generalizable strategy, we generated and analyzed mice with this conditional knock-in reporter targeted to the Hmga2 locus. PMID:24931605

  10. Linking functional and relational service quality to customer satisfaction and loyalty: differences between men and women.

    PubMed

    Sánchez-Hernández, Rosa M; Martínez-Tur, Vicente; Peiró, José M; Moliner, Carolina

    2010-04-01

    This study assessed differences between men and women in the association of perceptions of service quality with customer evaluations. Functional (efficiency with which the service is delivered) and relational (customers' emotional benefits, beyond the core performance, related to the social interaction of customers with employees) dimensions of service quality were measured as well as customer satisfaction and loyalty. The sample of 277 customers (191 men, 86 women), surveyed in 29 Mexican hotels, had a mean age of 38.1 yr. (SD=9.7) for men and 34.5 yr. (SD=11.0) for women. To be eligible for survey, customers had to have spent at least one night in the hotel in question. Analysis indicated that the women and men differed in the association of functional and relational dimensions of service quality with their satisfaction and loyalty. Functional service quality was higher for the men than the women, while relational service quality showed greater predictive power for women than for men, although these accounted for only 4% of the customers' satisfaction variance and 6% of the loyalty variance. PMID:20524565

  11. Linking carbon storage with functional diversity in tropical rainforest in the central Congo Basin

    NASA Astrophysics Data System (ADS)

    Verbeeck, Hans; Kearsley, Elizabeth; Bauters, Marijn; Beeckman, Hans; Huygens, Dries; Steppe, Kathy; Boeckx, Pascal

    2015-04-01

    This presentation will show an overview of results of the COBIMFO project (Congo basin integrated monitoring for forest carbon mitigation and biodiversity). In the framework of this project we have established 21 permanent 1 ha sampling plots in different forest types in the Yangambi reserve. This UNESCO Man and Biosphere reserve has an area of more than 6000 km² and is located in the heart of the Congo Basin near the Yangambi research station (DR Congo). Analysis of the inventory data of these plots revealed that carbon stocks in mature forests in this area of the Congo Basin are significantly lower (24%) than stocks recorded in the outer regions of the basin. These lower stocks are attributed to a lower maximal tree height (Kearsley et al. 2013). In addition to the carbon inventories we collected leaf and wood samples on all species within 95% basal area of each of the Yangambi plots. A total of 995 individuals were sampled, covering 123 tree species. On the samples we measured 15 traits related to leaf and wood morphology and functioning. In the presented study, relationships between the observed functional diversity and biomass are analysed. One of the remarkable results of our analysis is that species with a high functional distinctiveness have a low contribution to the basal area and the carbon stocks. In contrast, species with a high contribution to the carbon stock have a low contribution to the functional diversity. Similar patterns have been observed elsewhere (e.g. Amazon basin), but are now for the first time confirmed for central African rainforest. Finally, we also present the first results of an analysis of carbons stocks and functional diversity in tropical plantations from a unique 70-years old tree diversity experiment that was established during the colonial period at the Yangambi research station. Kearsley, E., de Haulleville, T., Hufkens, K., Kidimbu, A., Toirambe, B., Baert, G., Huygens, D., Kebede, Y., Defourny, P., Bogaert, J., Beeckman, H

  12. Aliphatic polycarbonates based on carbon dioxide, furfuryl glycidyl ether, and glycidyl methyl ether: reversible functionalization and cross-linking.

    PubMed

    Hilf, Jeannette; Scharfenberg, Markus; Poon, Jeffrey; Moers, Christian; Frey, Holger

    2015-01-01

    Well-defined poly((furfuryl glycidyl ether)-co-(glycidyl methyl ether) carbonate) (P((FGE-co-GME)C)) copolymers with varying furfuryl glycidyl ether (FGE) content in the range of 26% to 100% are prepared directly from CO2 and the respective epoxides in a solvent-free synthesis. All materials are characterized by size-exclusion chromatography (SEC), (1)H NMR spectroscopy, and differential scanning calorimetry (DSC). The furfuryl-functional samples exhibit monomodal molecular weight distributions with Mw/Mn in the range of 1.16 to 1.43 and molecular weights (Mn) between 2300 and 4300 g mol(-1). Thermal properties reflect the amorphous structure of the polymers. Both post-functionalization and cross-linking are performed via Diels-Alder chemistry using maleimide derivatives, leading to reversible network formation. This transformation is shown to be thermally reversible at 110 °C. PMID:25407342

  13. Raf-1 Physically Interacts with Rb and Regulates Its Function: a Link between Mitogenic Signaling and Cell Cycle Regulation

    PubMed Central

    Wang, Sheng; Ghosh, Richik N.; Chellappan, Srikumar P.

    1998-01-01

    Cells initiate proliferation in response to growth factor stimulation, but the biochemical mechanisms linking signals received at the cell surface receptors to the cell cycle regulatory molecules are not yet clear. In this study, we show that the signaling molecule Raf-1 can physically interact with Rb and p130 proteins in vitro and in vivo and that this interaction can be detected in mammalian cells without overexpressing any component. The binding of Raf-1 to Rb occurs subsequent to mitogen stimulation, and this interaction can be detected only in proliferating cells. Raf-1 can inactivate Rb function and can reverse Rb-mediated repression of E2F1 transcription and cell proliferation efficiently. The region of Raf-1 involved in Rb binding spanned residues 1 to 28 at the N terminus, and functional inactivation of Rb required a direct interaction. Serum stimulation of quiescent human fibroblast HSF8 cells led to a partial translocation of Raf-1 into the nucleus, where it colocalized with Rb. Further, Raf-1 was able to phosphorylate Rb in vitro quite efficiently. We believe that the physical interaction of Raf-1 with Rb is a vital step in the growth factor-mediated induction of cell proliferation and that Raf-1 acts as a direct link between cell surface signaling cascades and the cell cycle machinery. PMID:9819434

  14. Highly efficient copper(II) ion sorbents obtained by calcium carbonate mineralization on functionalized cross-linked copolymers.

    PubMed

    Mihai, Marcela; Bunia, Ion; Doroftei, Florica; Varganici, Cristian-Dragos; Simionescu, Bogdan C

    2015-03-23

    A new type of Cu(II) ion sorbents is presented. These are obtained by CaCO3 mineralization from supersaturated solutions on gel-like cross-linked polymeric beads as insoluble templates. A divinylbenzene-ethylacrylate-acrylonitrile cross-linked copolymer functionalized with weakly acidic, basic, or amphoteric functional groups has been used, as well as different initial inorganic concentrations and addition procedures for CaCO3 crystal growth. The morphology of the new composites was investigated by SEM and compared to that of the unmodified beads, and the polymorph content was established by X-ray diffraction. The beads, before and after CaCO3 mineralization, were tested as sorbents for Cu(II) ions. The newly formed patterns on the bead surface after Cu(II) sorption were observed by SEM, and the elemental distribution on the composites and the chemical structure of crystals after interaction with Cu(II) were investigated by EDAX elemental mapping and by FTIR-ATR spectroscopy, respectively. The sorption capacity increased significantly after CaCO3 crystals growth on the weak anionic bead surface (up to 1041.5 mg Cu(II) /g sample) compared to that of unmodified beads (491.5 mg Cu(II) /g sample). PMID:25675892

  15. Linking Microbial Enzymatic Activities and Functional Diversity of Soil around Earthworm Burrows and Casts

    PubMed Central

    Lipiec, Jerzy; Frąc, Magdalena; Brzezińska, Małgorzata; Turski, Marcin; Oszust, Karolina

    2016-01-01

    The aim of this work was to evaluate the effect of earthworms (Lumbricidae) on the enzymatic activity and microbial functional diversity in the burrow system [burrow wall (BW) 0–3 mm, transitional zone (TZ) 3–7 mm, bulk soil (BS) > 20 mm from the BW] and cast aggregates of a loess soil under a pear orchard. The dehydrogenase, β-glucosidase, protease, alkaline phosphomonoesterase, and acid phosphomonoesterase enzymes were assessed using standard methods. The functional diversity (catabolic potential) was assessed using the Average Well Color Development and Richness Index following the community level physiological profiling from Biolog Eco Plates. All measurements were done using soil from each compartment immediately after in situ sampling in spring. The enzymatic activites including dehydrogenase, protease, β-glucosidase and alkaline phosphomonoesterase were appreciably greater in the BW or casts than in BS and TZ. Conversely, acid phosphomonoesterase had the largest value in the BS. Average Well Color Development in both the TZ and the BS (0.98–0.94 A590 nm) were more than eight times higher than in the BWs and casts. The lowest richness index in the BS (15 utilized substrates) increased by 86–113% in all the other compartments. The PC1 in principal component analysis mainly differentiated the BWs and the TZ. Utilization of all substrate categories was the lowest in the BS. The PC2 differentiated the casts from the other compartments. The enhanced activity of a majority of the enzymes and increased microbial functional diversity in most earthworm-influenced compartments make the soils less vulnerable to degradation and thus increases the stability of ecologically relevant processes in the orchard ecosystem. PMID:27625645

  16. Linking Microbial Enzymatic Activities and Functional Diversity of Soil around Earthworm Burrows and Casts.

    PubMed

    Lipiec, Jerzy; Frąc, Magdalena; Brzezińska, Małgorzata; Turski, Marcin; Oszust, Karolina

    2016-01-01

    The aim of this work was to evaluate the effect of earthworms (Lumbricidae) on the enzymatic activity and microbial functional diversity in the burrow system [burrow wall (BW) 0-3 mm, transitional zone (TZ) 3-7 mm, bulk soil (BS) > 20 mm from the BW] and cast aggregates of a loess soil under a pear orchard. The dehydrogenase, β-glucosidase, protease, alkaline phosphomonoesterase, and acid phosphomonoesterase enzymes were assessed using standard methods. The functional diversity (catabolic potential) was assessed using the Average Well Color Development and Richness Index following the community level physiological profiling from Biolog Eco Plates. All measurements were done using soil from each compartment immediately after in situ sampling in spring. The enzymatic activites including dehydrogenase, protease, β-glucosidase and alkaline phosphomonoesterase were appreciably greater in the BW or casts than in BS and TZ. Conversely, acid phosphomonoesterase had the largest value in the BS. Average Well Color Development in both the TZ and the BS (0.98-0.94 A590 nm) were more than eight times higher than in the BWs and casts. The lowest richness index in the BS (15 utilized substrates) increased by 86-113% in all the other compartments. The PC1 in principal component analysis mainly differentiated the BWs and the TZ. Utilization of all substrate categories was the lowest in the BS. The PC2 differentiated the casts from the other compartments. The enhanced activity of a majority of the enzymes and increased microbial functional diversity in most earthworm-influenced compartments make the soils less vulnerable to degradation and thus increases the stability of ecologically relevant processes in the orchard ecosystem. PMID:27625645

  17. Alanine scan of core positions in ubiquitin reveals links between dynamics, stability, and function.

    PubMed

    Lee, Shirley Y; Pullen, Lester; Virgil, Daniel J; Castañeda, Carlos A; Abeykoon, Dulith; Bolon, Daniel N A; Fushman, David

    2014-04-01

    Mutations at solvent-inaccessible core positions in proteins can impact function through many biophysical mechanisms including alterations to thermodynamic stability and protein dynamics. As these properties of proteins are difficult to investigate, the impacts of core mutations on protein function are poorly understood for most systems. Here, we determined the effects of alanine mutations at all 15 core positions in ubiquitin on function in yeast. The majority (13 of 15) of alanine substitutions supported yeast growth as the sole ubiquitin. Both the two null mutants (I30A and L43A) were less stable to temperature-induced unfolding in vitro than wild type (WT) but were well folded at physiological temperatures. Heteronuclear NMR studies indicated that the L43A mutation reduces temperature stability while retaining a ground-state structure similar to WT. This structure enables L43A to bind to common ubiquitin receptors in vitro. Many of the core alanine ubiquitin mutants, including one of the null variants (I30A), exhibited an increased accumulation of high-molecular-weight species, suggesting that these mutants caused a defect in the processing of ubiquitin-substrate conjugates. In contrast, L43A exhibited a unique accumulation pattern with reduced levels of high-molecular-weight species and undetectable levels of free ubiquitin. When conjugation to other proteins was blocked, L43A ubiquitin accumulated as free ubiquitin in yeast. Based on these findings, we speculate that ubiquitin's stability to unfolding may be required for efficient recycling during proteasome-mediated substrate degradation. PMID:24361330

  18. TOPICAL ANTIHISTAMINES DISPLAY POTENT ANTI-INFLAMMATORY ACTIVITY LINKED IN PART TO ENHANCED PERMEABILITY BARRIER FUNCTION

    PubMed Central

    Lin, Tzu-Kai; Man, Mao-Qiang; Santiago, Juan-Luis; Park, Kyungho; Roelandt, Truus; Oda, Yuko; Hupe, Melanie; Crumrine, Debra; Lee, Hae-Jin; Gschwandtner, Maria; Thyssen, Jacob P.; Trullas, Carles; Tschachler, Erwin; Feingold, Kenneth R.; Elias, Peter M.

    2012-01-01

    Systemic antagonists of the histamine type 1 and 2 receptors (H1/2r) are widely used as anti-pruritics and central sedatives, but demonstrate only modest anti-inflammatory activity. Because many inflammatory dermatoses result from defects in cutaneous barrier function, and because keratinocytes express both Hr1 and Hr2, we hypothesized that H1/2r antagonists might be more effective, if they were used topically to treat inflammatory dermatoses. Topical H1/2r antagonists additively enhanced permeability barrier homeostasis in normal mouse skin by: i) stimulation of epidermal differentiation, leading to thickened cornified envelopes; and ii) enhanced epidermal lipid synthesis and secretion. Since barrier homeostasis was enhanced to a comparable extent in mast cell-deficient mice, with no further improvement following application of topical H1/2r antagonists, H1/2r antagonists likely oppose mast cell-derived histamine. In four immunologically-diverse, murine disease models, characterized by either inflammation alone (acute irritant contact dermatitis, acute allergic contact dermatitis), or by prominent barrier abnormalities (subacute allergic contact dermatitis, atopic dermatitis), topical H1/2r agonists aggravated, while H1/2r antagonists improved inflammation and/or barrier function. The apparent ability of topical H1r/2r antagonists to target epidermal H1/2r could translate into increased efficacy in the treatment of inflammatory dermatoses, likely due to decreased inflammation and enhanced barrier function. These results could shift current paradigms of antihistamine utilization from a predominantly-systemic to a topical approach. PMID:23014339

  19. A methodological framework for linking bioreactor function to microbial communities and environmental conditions.

    PubMed

    de los Reyes, Francis L; Weaver, Joseph E; Wang, Ling

    2015-06-01

    In the continuing quest to relate microbial communities in bioreactors to function and environmental and operational conditions, engineers and biotechnologists have adopted the latest molecular and 'omic methods. Despite the large amounts of data generated, gaining mechanistic insights and using the data for predictive and practical purposes is still a huge challenge. We present a methodological framework that can guide experimental design, and discuss specific issues that can affect how researchers generate and use data to elucidate the relationships. We also identify, in general terms, bioreactor research opportunities that appear promising. PMID:25710123

  20. Functional design of tentacles in squid: linking sarcomere ultrastructure to gross morphological dynamics

    PubMed Central

    Leeuwen, J. L. van; Kier, W. M.

    1997-01-01

    This paper offers a quantitative analysis of tentacle extension in squid that integrates several levels of structural organization. The muscular stalks of the two tentacles of squid are rapidly elongated by 70 per cent of resting length during prey capture. A typical duration of the extension is 30 ms in Loligo pealei (with a contracted tentacle length of 93 mm and a strike distance of about 37 mm). In a successful strike, the terminal clubs hit the prey and attach to it via arrays of suckers. A forward dynamics model is proposed for the extension of the tentacular stalk and the forward motion of the terminal club. The stalk is modelled as a longitudinal array of thin muscular discs with extensor muscle fibres oriented parallel to the disc planes. As a disc contracts radially, it lengthens because its volume is constant. The equations of motion for the linked system of discs were formulated and solved numerically. The inputs of the model are the dimensions of the tentacle, passive and active muscle properties such as Hill's force–velocity relationship, myofilament lengths and activation of the muscle fibres. The model predicts the changing geometry of the tentacle, the pressure and stress distribution inside the tentacle and the velocity and kinetic energy distribution of the stalk and club. These predictions are in agreement with kinematic observations from high-speed films of prey capture. The model demonstrates also that the unusually short myosin filaments (reported range 0.5–0.9 micrometre) that characterize the extensor muscles are necessary for the observed extension performance. Myosin filament lengths typical for vertebrate sarcomeres (1.58 micrometre) would lead to a significant reduction in performance. In addition, the model predicts that, to maximize peak velocity of the terminal club, the myosin filaments should be longer at the base and shorter at the tip of the stalk (0.97 micrometre at the base and 0.50 micrometre at the tip for the tentacle

  1. SIRT7 is a histone desuccinylase that functionally links to chromatin compaction and genome stability.

    PubMed

    Li, Lei; Shi, Lan; Yang, Shangda; Yan, Ruorong; Zhang, Di; Yang, Jianguo; He, Lin; Li, Wanjin; Yi, Xia; Sun, Luyang; Liang, Jing; Cheng, Zhongyi; Shi, Lei; Shang, Yongfeng; Yu, Wenhua

    2016-01-01

    Although SIRT7 is a member of sirtuin family proteins that are described as NAD(+)-dependent class III histone deacetylases, the intrinsic enzymatic activity of this sirtuin protein remains to be investigated and the cellular function of SIRT7 remains to be explored. Here we report that SIRT7 is an NAD(+)-dependent histone desuccinylase. We show that SIRT7 is recruited to DNA double-strand breaks (DSBs) in a PARP1-dependent manner and catalyses desuccinylation of H3K122 therein, thereby promoting chromatin condensation and DSB repair. We demonstrate that depletion of SIRT7 impairs chromatin compaction during DNA-damage response and sensitizes cells to genotoxic stresses. Our study indicates SIRT7 is a histone desuccinylase, providing a molecular basis for the understanding of epigenetic regulation by this sirtuin protein. Our experiments reveal that SIRT7-catalysed H3K122 desuccinylation is critically implemented in DNA-damage response and cell survival, providing a mechanistic insight into the cellular function of SIRT7. PMID:27436229

  2. Coxiella burnetii glycomics and proteomics--tools for linking structure to function.

    PubMed

    Toman, Rudolf; Skultety, Ludovit; Ihnatko, Robert

    2009-05-01

    Coxiella burnetii, the causative agent of Q fever, is an obligate intracellular bacterium and a highly infectious pathogen. The disease is a widespread zoonosis and is endemic throughout the world. An easy aerosol dissemination, environmental persistence, and high infectivity make the bacterium a serious threat for humans and animals. Lipopolysaccharide is considered one of the major factors of virulence expression and infection of the bacterium. Detailed glycomic studies enabled to better understand structural and functional peculiarities of this biopolymer and its role in pathogenesis and immunity of Q fever. Recent proteomic studies of C. burnetii have brought new approaches in accurate detection of the infectious agent and offered new insights into the inter- or intra-species relatedness. Thus, structure/function relationship studies are currently of utmost importance in the field. This paper will focus on glycomic and proteomic approaches providing information on unique glycan and protein species of the microorganism as the candidate molecules for the use in detection/diagnosis, therapy, and prophylaxis. PMID:19538265

  3. Isolation of N-linked glycopeptides by hydrazine-functionalized magnetic particles.

    PubMed

    Sun, Shisheng; Yang, Ganglong; Wang, Ting; Wang, Qinzhe; Chen, Chao; Li, Zheng

    2010-04-01

    We introduce a novel combination of magnetic particles with hydrazine chemistry, dubbed as hydrazine-functionalized magnetic particles (HFMP) for isolation of glycopeptides. Four methods have been developed and compared for the production of HFMP by hydrazine modification of the surface of the carboxyl and epoxy-silanized magnetic particles, respectively. The evaluation of the capability and specificity of HFMP as well as the optimization of the coupling condition for capturing of glycoproteins were systematically investigated. The results showed that HFMP prepared by adipic dihydrazide functionalization from carboxyl-silanized magnetic particles (HFCA) displayed the maximum capture capacity and isolated efficiency for glycoprotein. When measured with glycoproteins, the capacity of the HFCA (1 g) for coupling bovine fetuin was 130 +/- 5.3 mg. The capability of this method was also confirmed by successful isolation of all formerly glycosylated peptides from standard glycoproteins and identification of their glycosylation sites, which demonstrated the feasibility of the HFCA as an alternative solid support for isolation of glycoproteins/glycopeptides. PMID:20169334

  4. Functionalized layered double hydroxide nanoparticles conjugated with disulfide-linked polycation brushes for advanced gene delivery.

    PubMed

    Hu, H; Xiu, K M; Xu, S L; Yang, W T; Xu, F J

    2013-06-19

    Layered double hydroxides (LDHs) have aroused great attention as potential nanosized drug delivery carriers, but independent inorganic LDH wrapped with DNA shows very low transfection efficiency. To manipulate and control the surface properties of LDH nanoparticles is of crucial importance in the designing of LDH-based drug carriers. In this work, surface-initiated atom transfer radical polymerization (ATRP) of 2-(dimethylamino)ethyl methacrylate (DMAEMA) is employed to tailor the functionality of LDH surfaces in a well-controlled manner and produce a series of well-defined novel gene delivery vectors (termed as LDH-PDs), where a flexible three-step method was first developed to introduce the ATRP initiation sites containing disulfide bonds onto LDH surfaces. In comparison the pristine LDH particles, the resultant LDH-PDs exhibited better ability to condense plasmid DNA (pDNA) and much higher levels to delivery genes in different cell lines including COS7 and HepG2 cell lines. Moreover, the LDH-PDs also could largely enhance cellular uptake. This present study demonstrates that functionalization of bioinorganic LDH with flexible polycation brushes is an effective means to produce new LDH-based gene delivery systems. PMID:23682934

  5. Balanced translocation linked to psychiatric disorder, glutamate, and cortical structure/function.

    PubMed

    Thomson, Pippa A; Duff, Barbara; Blackwood, Douglas H R; Romaniuk, Liana; Watson, Andrew; Whalley, Heather C; Li, Xiang; Dauvermann, Maria R; Moorhead, T William J; Bois, Catherine; Ryan, Niamh M; Redpath, Holly; Hall, Lynsey; Morris, Stewart W; van Beek, Edwin J R; Roberts, Neil; Porteous, David J; St Clair, David; Whitcher, Brandon; Dunlop, John; Brandon, Nicholas J; Hughes, Zoë A; Hall, Jeremy; McIntosh, Andrew; Lawrie, Stephen M

    2016-01-01

    Rare genetic variants of large effect can help elucidate the pathophysiology of brain disorders. Here we expand the clinical and genetic analyses of a family with a (1;11)(q42;q14.3) translocation multiply affected by major psychiatric illness and test the effect of the translocation on the structure and function of prefrontal, and temporal brain regions. The translocation showed significant linkage (LOD score 6.1) with a clinical phenotype that included schizophrenia, schizoaffective disorder, bipolar disorder, and recurrent major depressive disorder. Translocation carriers showed reduced cortical thickness in the left temporal lobe, which correlated with general psychopathology and positive psychotic symptom severity. They showed reduced gyrification in prefrontal cortex, which correlated with general psychopathology severity. Translocation carriers also showed significantly increased activation in the caudate nucleus on increasing verbal working memory load, as well as statistically significant reductions in the right dorsolateral prefrontal cortex glutamate concentrations. These findings confirm that the t(1;11) translocation is associated with a significantly increased risk of major psychiatric disorder and suggest a general vulnerability to psychopathology through altered cortical structure and function, and decreased glutamate levels. PMID:27602385

  6. Balanced translocation linked to psychiatric disorder, glutamate, and cortical structure/function

    PubMed Central

    Thomson, Pippa A; Duff, Barbara; Blackwood, Douglas H R; Romaniuk, Liana; Watson, Andrew; Whalley, Heather C; Li, Xiang; Dauvermann, Maria R; Moorhead, T William J; Bois, Catherine; Ryan, Niamh M; Redpath, Holly; Hall, Lynsey; Morris, Stewart W; van Beek, Edwin J R; Roberts, Neil; Porteous, David J; St. Clair, David; Whitcher, Brandon; Dunlop, John; Brandon, Nicholas J; Hughes, Zoë A; Hall, Jeremy; McIntosh, Andrew; Lawrie, Stephen M

    2016-01-01

    Rare genetic variants of large effect can help elucidate the pathophysiology of brain disorders. Here we expand the clinical and genetic analyses of a family with a (1;11)(q42;q14.3) translocation multiply affected by major psychiatric illness and test the effect of the translocation on the structure and function of prefrontal, and temporal brain regions. The translocation showed significant linkage (LOD score 6.1) with a clinical phenotype that included schizophrenia, schizoaffective disorder, bipolar disorder, and recurrent major depressive disorder. Translocation carriers showed reduced cortical thickness in the left temporal lobe, which correlated with general psychopathology and positive psychotic symptom severity. They showed reduced gyrification in prefrontal cortex, which correlated with general psychopathology severity. Translocation carriers also showed significantly increased activation in the caudate nucleus on increasing verbal working memory load, as well as statistically significant reductions in the right dorsolateral prefrontal cortex glutamate concentrations. These findings confirm that the t(1;11) translocation is associated with a significantly increased risk of major psychiatric disorder and suggest a general vulnerability to psychopathology through altered cortical structure and function, and decreased glutamate levels. PMID:27602385

  7. MELAS syndrome and cardiomyopathy: linking mitochondrial function to heart failure pathogenesis.

    PubMed

    Hsu, Ying-Han R; Yogasundaram, Haran; Parajuli, Nirmal; Valtuille, Lucas; Sergi, Consolato; Oudit, Gavin Y

    2016-01-01

    Heart failure remains an important clinical burden, and mitochondrial dysfunction plays a key role in its pathogenesis. The heart has a high metabolic demand, and mitochondrial function is a key determinant of myocardial performance. In mitochondrial disorders, hypertrophic remodeling is the early pattern of cardiomyopathy with progression to dilated cardiomyopathy, conduction defects and ventricular pre-excitation occurring in a significant proportion of patients. Cardiac dysfunction occurs in approximately a third of patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome, a stereotypical example of a mitochondrial disorder leading to a cardiomyopathy. We performed unique comparative ultrastructural and gene expression in a MELAS heart compared with non-failing controls. Our results showed a remarkable increase in mitochondrial inclusions and increased abnormal mitochondria in MELAS cardiomyopathy coupled with variable sarcomere thickening, heterogeneous distribution of affected cardiomyocytes and a greater elevation in the expression of disease markers. Investigation and management of patients with mitochondrial cardiomyopathy should follow the well-described contemporary heart failure clinical practice guidelines and include an important role of medical and device therapies. Directed metabolic therapy is lacking, but current research strategies are dedicated toward improving mitochondrial function in patients with mitochondrial disorders. PMID:26712328

  8. The functional genetic link of NLGN4X knockdown and neurodevelopment in neural stem cells

    PubMed Central

    Shi, Lingling; Chang, Xiao; Zhang, Peilin; Coba, Marcelo P.; Lu, Wange; Wang, Kai

    2013-01-01

    Genetic mutations in NLGN4X (neuroligin 4), including point mutations and copy number variants (CNVs), have been associated with susceptibility to autism spectrum disorders (ASDs). However, it is unclear how mutations in NLGN4X result in neurodevelopmental defects. Here, we used neural stem cells (NSCs) as in vitro models to explore the impacts of NLGN4X knockdown on neurodevelopment. Using two shRNAmir-based vectors targeting NLGN4X and one control shRNAmir vector, we modulated NLGN4X expression and differentiated these NSCs into mature neurons. We monitored the neurodevelopmental process at Weeks 0, 0.5, 1, 2, 4 and 6, based on morphological analysis and whole-genome gene expression profiling. At the cellular level, in NSCs with NLGN4X knockdown, we observed increasingly delayed neuronal development and compromised neurite formation, starting from Week 2 through Week 6 post differentiation. At the molecular level, we identified multiple pathways, such as neurogenesis, neuron differentiation and muscle development, which are increasingly disturbed in cells with NLGN4X knockdown. Notably, several postsynaptic genes, including DLG4, NLGN1 and NLGN3, also have decreased expression. Based on in vitro models, NLGN4X knockdown directly impacts neurodevelopmental process during the formation of neurons and their connections. Our functional genomics study highlights the utility of NSCs models in understanding the functional roles of CNVs in affecting neurodevelopment and conferring susceptibility to neurodevelopmental diseases. PMID:23710042

  9. Circadian clock functioning is linked to acute stress reactivity in rats.

    PubMed

    Weibel, L; Maccari, S; Van Reeth, O

    2002-10-01

    At least two major physiological systems are involved in the adaptation of the organism to environmental challenges: the circadian system and the stress reaction. This study addressed the possibility that interindividual differences in stress sensitivity and in the functioning of the circadian system are related. At 2 months of age, corticosterone secretion in response to a 20-min restraint stress was assessed in 9 Sprague-Dawley rats for which running wheel activity was recorded as a rhythmic behavioral marker of the circadian clock. Two weeks later, the adaptive response of the circadian system to an abrupt shift in the light:dark (LD) cycle was assessed in those rats using a jet-lag paradigm. Finally, after resynchronization to the new LD cycle, rats were transferred to constant darkness to assess the free-running period of their circadian rhythm of running-wheel activity. Results indicate that stress-induced corticosterone secretion was (1) positively correlated with the number of days to resynchronize the circadian activity rhythm to the new LD cycle, and with the value of its free-running period, and (2) negatively correlated with the intensity of daily locomotor activity. Those data, emphasizing the interactions between the stress response of an organism and the functioning of its circadian system, could explain interindividual differences in humans' susceptibility to shift work or other circadian-related disorders. PMID:12375620

  10. Mechanisms Linking Energy Substrate Metabolism to the Function of the Heart

    PubMed Central

    Carley, Andrew N.; Taegtmeyer, Heinrich; Lewandowski, E. Douglas

    2015-01-01

    Metabolic signaling mechanisms are increasingly recognized to mediate the cellular response to alterations in workload demand, as a consequence of physiological and pathophysiological challenges. Thus, an understanding of the metabolic mechanisms coordinating activity in the cytosol with the energy-providing pathways in the mitochondrial matrix becomes critical for deepening our insights into the pathogenic changes that occur in the stressed cardiomyocyte. Processes that exchange both metabolic intermediates and cations between the cytosol and mitochondria enable transduction of dynamic changes in contractile state to the mitochondrial compartment of the cell. Disruption of such metabolic transduction pathways has severe consequences for the energetic support of contractile function in the heart and is implicated in the pathogenesis of heart failure. Deficiencies in metabolic reserve and impaired metabolic transduction in the cardiomyocyte can result from inherent deficiencies in metabolic phenotype or maladaptive changes in metabolic enzyme expression and regulation in the response to pathogenic stress. This review examines both current and emerging concepts of the functional linkage between the cytosol and the mitochondrial matrix with a specific focus on metabolic reserve and energetic efficiency. These principles of exchange and transport mechanisms across the mitochondrial membrane are reviewed for the failing heart from the perspectives of chronic pressure overload and diabetes mellitus. PMID:24526677

  11. SIRT7 is a histone desuccinylase that functionally links to chromatin compaction and genome stability

    PubMed Central

    Li, Lei; Shi, Lan; Yang, Shangda; Yan, Ruorong; Zhang, Di; Yang, Jianguo; He, Lin; Li, Wanjin; Yi, Xia; Sun, Luyang; Liang, Jing; Cheng, Zhongyi; Shi, Lei; Shang, Yongfeng; Yu, Wenhua

    2016-01-01

    Although SIRT7 is a member of sirtuin family proteins that are described as NAD+-dependent class III histone deacetylases, the intrinsic enzymatic activity of this sirtuin protein remains to be investigated and the cellular function of SIRT7 remains to be explored. Here we report that SIRT7 is an NAD+-dependent histone desuccinylase. We show that SIRT7 is recruited to DNA double-strand breaks (DSBs) in a PARP1-dependent manner and catalyses desuccinylation of H3K122 therein, thereby promoting chromatin condensation and DSB repair. We demonstrate that depletion of SIRT7 impairs chromatin compaction during DNA-damage response and sensitizes cells to genotoxic stresses. Our study indicates SIRT7 is a histone desuccinylase, providing a molecular basis for the understanding of epigenetic regulation by this sirtuin protein. Our experiments reveal that SIRT7-catalysed H3K122 desuccinylation is critically implemented in DNA-damage response and cell survival, providing a mechanistic insight into the cellular function of SIRT7. PMID:27436229

  12. The Fanconi Anaemia Components UBE2T and FANCM Are Functionally Linked to Nucleotide Excision Repair

    PubMed Central

    Kelsall, Ian R.; Langenick, Judith; MacKay, Craig; Patel, Ketan J.; Alpi, Arno F.

    2012-01-01

    The many proteins that function in the Fanconi anaemia (FA) monoubiquitylation pathway initiate replicative DNA crosslink repair. However, it is not clear whether individual FA genes participate in DNA repair pathways other than homologous recombination and translesion bypass. Here we show that avian DT40 cell knockouts of two integral FA genes – UBE2T and FANCM are unexpectedly sensitive to UV-induced DNA damage. Comprehensive genetic dissection experiments indicate that both of these FA genes collaborate to promote nucleotide excision repair rather than translesion bypass to protect cells form UV genotoxicity. Furthermore, UBE2T deficiency impacts on the efficient removal of the UV-induced photolesion cyclobutane pyrimidine dimer. Therefore, this work reveals that the FA pathway shares two components with nucleotide excision repair, intimating not only crosstalk between the two major repair pathways, but also potentially identifying a UBE2T-mediated ubiquitin-signalling response pathway that contributes to nucleotide excision repair. PMID:22615860

  13. Incorporating Data Link Messaging into a Multi-function Display for General Aviation Aircraft

    NASA Technical Reports Server (NTRS)

    Adams, Catherine A.; Murdoch, Jennifer L.

    2006-01-01

    One objective of the Small Aircraft Transportation System (SATS) Project is to increase the capacity and utilization of small non-towered, non-radar equipped airports by transferring traffic management activities to an automated system and separation responsibilities to general aviation (GA) pilots. This paper describes the development of a research multi-function display (MFD) to support the interaction between pilots and an automated Airport Management Module (AMM). Preliminary results of simulation and flight tests indicate that adding the responsibility of monitoring other traffic for self-separation does not increase pilots subjective workload levels. Pilots preferred using the enhanced MFD to execute flight procedures, reporting improved situation awareness over conventional instrument flight rules (IFR) procedures.

  14. Gamma oscillations in the midbrain spatial attention network: linking circuits to function

    PubMed Central

    Sridharan, Devarajan; Knudsen, Eric I

    2016-01-01

    Gamma-band (25–140 Hz) oscillations are ubiquitous in mammalian forebrain structures involved in sensory processing, attention, learning and memory. The optic tectum (OT) is the central structure in a midbrain network that participates critically in controlling spatial attention. In this review, we summarize recent advances in characterizing a neural circuit in this midbrain network that generates large amplitude, space-specific, gamma oscillations in the avian OT, both in vivo and in vitro. We describe key physiological and pharmacological mechanisms that produce and regulate the structure of these oscillations. The extensive similarities between midbrain gamma oscillations in birds and those in the neocortex and hippocampus of mammals, offer important insights into the functional significance of a midbrain gamma oscillatory code. PMID:25485519

  15. Molecular Mechanisms Underlying the Link between Nuclear Receptor Function and Cholesterol Gallstone Formation

    PubMed Central

    Vázquez, Mary Carmen; Rigotti, Attilio; Zanlungo, Silvana

    2012-01-01

    Cholesterol gallstone disease is highly prevalent in western countries, particularly in women and some specific ethnic groups. The formation of water-insoluble cholesterol crystals is due to a misbalance between the three major lipids present in the bile: cholesterol, bile salts, and phospholipids. Many proteins implicated in biliary lipid secretion in the liver are regulated by several transcription factors, including nuclear receptors LXR and FXR. Human and murine genetic, physiological, pathophysiological, and pharmacological evidence is consistent with the relevance of these nuclear receptors in gallstone formation. In addition, there is emerging data that also suggests a role for estrogen receptor ESR1 in abnormal cholesterol metabolism leading to gallstone disease. A better comprehension of the role of nuclear receptor function in gallstone formation may help to design new and more effective therapeutic strategies for this highly prevalent disease condition. PMID:22132343

  16. Gamma oscillations in the midbrain spatial attention network: linking circuits to function.

    PubMed

    Sridharan, Devarajan; Knudsen, Eric I

    2015-04-01

    Gamma-band (25-140Hz) oscillations are ubiquitous in mammalian forebrain structures involved in sensory processing, attention, learning and memory. The optic tectum (OT) is the central structure in a midbrain network that participates critically in controlling spatial attention. In this review, we summarize recent advances in characterizing a neural circuit in this midbrain network that generates large amplitude, space-specific, gamma oscillations in the avian OT, both in vivo and in vitro. We describe key physiological and pharmacological mechanisms that produce and regulate the structure of these oscillations. The extensive similarities between midbrain gamma oscillations in birds and those in the neocortex and hippocampus of mammals, offer important insights into the functional significance of a midbrain gamma oscillatory code. PMID:25485519

  17. Antimicrobial Protegrin-1 Forms Amyloid-Like Fibrils with Rapid Kinetics Suggesting a Functional Link

    PubMed Central

    Jang, Hyunbum; Arce, Fernando Teran; Mustata, Mirela; Ramachandran, Srinivasan; Capone, Ricardo; Nussinov, Ruth; Lal, Ratnesh

    2011-01-01

    Protegrin-1 (PG-1) is an 18 residues long, cysteine-rich β-sheet antimicrobial peptide (AMP). PG-1 induces strong cytotoxic activities on cell membrane and acts as a potent antibiotic agent. Earlier we reported that its cytotoxicity is mediated by its channel-forming ability. In this study, we have examined the amyloidogenic fibril formation properties of PG-1 in comparison with a well-defined amyloid, the amyloid-β (Aβ1–42) peptide. We have used atomic force microscopy (AFM) and thioflavin-T staining to investigate the kinetics of PG-1 fibrils growth and molecular dynamics simulations to elucidate the underlying mechanism. AFM images of PG-1 on a highly hydrophilic surface (mica) show fibrils with morphological similarities to Aβ1–42 fibrils. Real-time AFM imaging of fibril growth suggests that PG-1 fibril growth follows a relatively fast kinetics compared to the Aβ1–42 fibrils. The AFM results are in close agreement with results from thioflavin-T staining data. Furthermore, the results indicate that PG-1 forms fibrils in solution. Significantly, in contrast, we do not detect fibrillar structures of PG-1 on an anionic lipid bilayer 2-dioleoyl-sn-glycero-3-phospho-L-serine/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine; only small PG-1 oligomers can be observed. Molecular dynamics simulations are able to identify the presence of these small oligomers on the membrane bilayer. Thus, our current results show that cytotoxic AMP PG-1 is amyloidogenic and capable of forming fibrils. Overall, comparing β-rich AMPs and amyloids such as Aβ, in addition to cytotoxicity and amyloidogenicity, they share a common structural motif, and are channel forming. These combined properties support a functional relationship between amyloidogenic peptides and β-sheet-rich cytolytic AMPs, suggesting that amyloids channels may have an antimicrobial function. PMID:21463591

  18. Linking activity and function to ecosystem dynamics in a coastal bacterioplankton community

    PubMed Central

    Gifford, Scott M.; Sharma, Shalabh; Moran, Mary Ann

    2014-01-01

    For bacterial communities containing hundreds to thousands of distinct populations, connecting functional processes and environmental dynamics at high taxonomic resolution has remained challenging. Here we use the expression of ribosomal proteins (%RP) as a proxy for in situ activity of 200 taxa within 20 metatranscriptomic samples in a coastal ocean time series encompassing both seasonal variability and diel dynamics. %RP patterns grouped the taxa into seven activity clusters with distinct profiles in functional gene expression and correlations with environmental gradients. Clusters 1–3 had their highest potential activity in the winter and fall, and included some of the most active taxa, while Clusters 4–7 had their highest potential activity in the spring and summer. Cluster 1 taxa were characterized by gene expression for motility and complex carbohydrate degradation (dominated by Gammaproteobacteria and Bacteroidetes), and Cluster 2 taxa by transcription of genes for amino acid and aromatic compound metabolism and aerobic anoxygenic phototrophy (Roseobacter). Other activity clusters were enriched in transcripts for proteorhodopsin and methylotrophy (Cluster 4; SAR11 and methylotrophs), photosynthesis and attachment (Clusters 5 and 7; Synechococcus, picoeukaryotes, Verucomicrobia, and Planctomycetes), and sulfur oxidation (Cluster 7; Gammaproteobacteria). The seasonal patterns in activity were overlain, and sometimes obscured, by large differences in %RP over shorter day-night timescales. Seventy-eight taxa, many of them heterotrophs, had a higher %RP activity index during the day than night, indicating a strong diel activity rhythm at this coastal site. Emerging from these taxonomically- and time-resolved estimates of in situ microbial activity are predictions of specific ecological groupings of microbial taxa in a dynamic coastal environment. PMID:24795712

  19. Impacts of warming revealed by linking resource growth rates with consumer functional responses.

    PubMed

    West, Derek C; Post, David M

    2016-05-01

    Warming global temperatures are driving changes in species distributions, growth and timing, but much uncertainty remains regarding how climate change will alter species interactions. Consumer-Resource interactions in particular can be strongly impacted by changes to the relative performance of interacting species. While consumers generally gain an advantage over their resources with increasing temperatures, nonlinearities can change this relation near temperature extremes. We use an experimental approach to determine how temperature changes between 5 and 30 °C will alter the growth of the algae Scenedesmus obliquus and the functional responses of the small-bodied Daphnia ambigua and the larger Daphnia pulicaria. The impact of warming generally followed expectations, making both Daphnia species more effective grazers, with the increase in feeding rates outpacing the increases in algal growth rate. At the extremes of our temperature range, however, warming resulted in a decrease in Daphnia grazing effectiveness. Between 25 and 30 °C, both species of Daphnia experienced a precipitous drop in feeding rates, while algal growth rates remained high, increasing the likelihood of algal blooms in warming summer temperatures. Daphnia pulicaria performed significantly better at cold temperatures than D. ambigua, but by 20 °C, there was no significant difference between the two species, and at 25 °C, D. ambigua outperformed D. pulicaria. Warming summer temperatures will favour the smaller D. ambigua, but only over a narrow temperature range, and warming beyond 25 °C could open D. ambigua to invasion from tropical species. By fitting our results to temperature-dependent functions, we develop a temperature- and density-dependent model, which produces a metric of grazing effectiveness, quantifying the grazer density necessary to halt algal growth. This approach should prove useful for tracking the transient dynamics of other density-dependent consumer

  20. Crystal Structure of Human Senescence Marker Protein 30: Insights Linking Structural, Enzymatic, and Physiological Functions

    SciTech Connect

    Chakraborti, Subhendu; Bahnson, Brian J.

    2010-05-25

    Human senescence marker protein 30 (SMP30), which functions enzymatically as a lactonase, hydrolyzes various carbohydrate lactones. The penultimate step in vitamin-C biosynthesis is catalyzed by this enzyme in nonprimate mammals. It has also been implicated as an organophosphate hydrolase, with the ability to hydrolyze diisopropyl phosphofluoridate and other nerve agents. SMP30 was originally identified as an aging marker protein, whose expression decreased androgen independently in aging cells. SMP30 is also referred to as regucalcin and has been suggested to have functions in calcium homeostasis. The crystal structure of the human enzyme has been solved from X-ray diffraction data collected to a resolution of 1.4 {angstrom}. The protein has a 6-bladed {beta}-propeller fold, and it contains a single metal ion. Crystal structures have been solved with the metal site bound with either a Ca{sup 2+} or a Zn{sup 2+} atom. The catalytic role of the metal ion has been confirmed by mutagenesis of the metal coordinating residues. Kinetic studies using the substrate gluconolactone showed a k{sub cat} preference of divalent cations in the order Zn{sup 2+} > Mn{sup 2+} > Ca{sup 2+} > Mg{sup 2+}. Notably, the Ca{sup 2+} had a significantly higher value of K{sub d} compared to those of the other metal ions tested (566, 82, 7, and 0.6 {micro}m for Ca{sup 2+}, Mg{sup 2+}, Zn{sup 2+}, and Mn{sup 2+}, respectively), suggesting that the Ca{sup 2+}-bound form may be physiologically relevant for stressed cells with an elevated free calcium level.

  1. Rapid chain generation of interpostsynaptic functional LINKs can trigger seizure generation: Evidence for potential interconnections from pathology to behavior.

    PubMed

    Vadakkan, Kunjumon I

    2016-06-01

    The experimental finding that a paroxysmal depolarizing shift (PDS), an electrophysiological correlate of seizure activity, is a giant excitatory postsynaptic potential (EPSP) necessitates a mechanism for spatially summating several EPSPs at the level of the postsynaptic terminals (dendritic spines). In this context, we will examine reversible interpostsynaptic functional LINKs (IPLs), a proposed mechanism for inducing first-person virtual internal sensations of higher brain functions concurrent with triggering behavioral motor activity for possible pathological changes that may contribute to seizures. Pathological conditions can trigger a rapid chain generation and propagation of different forms of IPLs leading to seizure generation. A large number of observations made at different levels during both ictal and interictal periods are explained by this mechanism, including the tonic and clonic motor activity, different types of hallucinations, loss of consciousness, gradual worsening of cognitive abilities, a relationship with kindling (which uses an augmented stimulation protocol than that used for inducing long-term potentiation (LTP), which is an electrophysiological correlate of behavioral makers of internal sensation of memory), effect of a ketogenic diet on seizure prevention, dendritic spine loss in seizure disorders, neurodegenerative changes, and associated behavioral changes. The interconnectable nature of these findings is explained as loss of function states of a proposed normal functioning of the nervous system. PMID:27085478

  2. Functional link between Rab GTPase-mediated membrane trafficking and PI4,5P2 signaling.

    PubMed

    Li, Cuifang; Kita, Ayako; Hashimoto, Yuuka; Ihara, Misako; Kato, Ayaka; Ogura, Naoya; Doi, Akira; Oku, Masahide; Itoh, Toshiki; Sakai, Yasuyoshi; Sugiura, Reiko

    2014-03-01

    Fission yeast its3(+) encodes an essential phosphatidylinositol-4-phosphate 5-kinase (PI4P5K) that regulates cell integrity and cytokinesis. We performed a genetic screen to identify genes that function in PI4P5K-mediated signaling, and identified gyp10(+) encoding a Rab GTPase-activating protein (GAP), a negative regulator for Rab GTPase signaling. Its3 overproduction caused growth defects and abnormal cytoplasmic accumulation of the Its3 protein, which can be stained by calcofluor. Notably, Its3 overproducing cells displayed abnormal membranous structures, multilamella Golgi and fragmented vacuoles showed by Electron microscopy. Furthermore, the excess cytoplasmic Its3 structure partly colocalized with the fluorescence of FM4-64. Gyp10 rescued both growth defects and abnormal Its3 localization when it was over-expressed. Gyp10 functionally interacted with the Rab GTPases Ypt3 and Ryh1, both of which regulate Golgi membrane trafficking. Consistently, mutation or deletion of Ypt3 and Ryh1 suppressed phenotypes associated with Its3 overproduction. Importantly, the plasma membrane localization of Its3 was also affected by the impairment of the Ypt3/Ryh1 Rab membrane trafficking, thus suggesting that membrane trafficking events regulated by two Rab GTPases functionally interacts with PI4,5P2 signaling. These results suggest a mechanism whereby PI4P5K signaling/localization is affected by Golgi membrane trafficking, thus provide a functional link between the PI4,5P2 signaling and Rab-mediated trafficking. PMID:24350606

  3. The functional, oxygen-linked chloride binding sites of hemoglobin are contiguous within a channel in the central cavity.

    PubMed

    Ueno, H; Manning, J M

    1992-04-01

    Chloride ion is a major allosteric regulator for many hemoglobins and particularly for bovine hemoglobin. A site-directed reagent for amino groups, methyl acetyl phosphate, when used for global rather than selective modification of R (oxy) and T (deoxy) state bovine hemoglobin, can acetylate those functional amino groups involved in binding of chloride; the extensively acetylated hemoglobin tetramer retains nearly full cooperativity. The chloride-induced decrease in the oxygen affinity parallels the acetylation of bovine hemoglobin (i.e., their effects are mutually exclusive), suggesting that methyl acetyl phosphate is a good probe for the functional chloride binding sites in hemoglobins. Studies on the overall alkaline Bohr effect indicates that the part of the contribution dependent on chloride and reduced by 60% after acetylation is due to amino groups, Val-1(alpha) and Lys-81(beta); the remaining 40% is contributed by the imidazole side chain of His-146(beta), which is not acetylated by methyl acetyl phosphate, and is not dependent on chloride. The five amino groups--Val-1(alpha), Lys-99(alpha), Met-1(beta), Lys-81(beta), and Lys-103(beta)--of bovine hemoglobin that are acetylated in an oxygen-linked fashion are considered functional chloride binding sites. Molecular modeling indicates that these functional chloride binding sites are contiguous from one end of the central cavity of hemoglobin to the other; some of them are aligned within a chloride channel connecting each end of the dyad axis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1326985

  4. Cholera Toxin B Subunit Linked to Glutamic Acid Decarboxylase Suppresses Dendritic Cell Maturation and Function

    PubMed Central

    Odumosu, Oludare; Nicholas, Dequina; Payne, Kimberly; Langridge, William

    2012-01-01

    Dendritic cells are the largest population of antigen presenting cells in the body. One of their main functions is to regulate the delicate balance between immunity and tolerance responsible for maintenance of immunological homeostasis. Disruption of this delicate balance often results in chronic inflammation responsible for initiation of organ specific autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and type I diabetes. The cholera toxin B subunit (CTB) is a weak mucosal adjuvant known for its ability to stimulate immunity to antigenic proteins. However, conjugation of CTB to many autoantigens can induce immunological tolerance resulting in suppression of autoimmunity. In this study, we examined whether linkage of CTB to a 5 kDa C-terminal protein fragment of the major diabetes autoantigen glutamic acid decarboxylase (GAD35), can block dendritic cell (DC) functions such as biosynthesis of co-stimulatory factor proteins CD86, CD83, CD80 and CD40 and secretion of inflammatory cytokines. The results of human umbilical cord blood monocyte-derived DC - GAD35 autoantigen incubation experiments showed that inoculation of immature DCs (iDCs), with CTB-GAD35 protein dramatically suppressed levels of CD86, CD83, CD80 and CD40 co-stimulatory factor protein biosynthesis in comparison with GAD35 alone inoculated iDCs. Surprisingly, incubation of iDCs in the presence of the CTB-autoantigen and the strong immunostimulatory molecules PMA and Ionomycin revealed that CTB-GAD35 was capable of arresting PMA + Ionomycin induced DC maturation. Consistant with this finding, CTB-GAD35 mediated suppression of DC maturation was accompanied by a dramatic decrease in the secretion of the pro-inflammatory cytokines IL-12/23p40 and IL-6 and a significant increase in secretion of the immunosuppressive cytokine IL-10. Taken together, our experimental data suggest that linkage of the weak adjuvant CTB to the dominant type 1 diabetes autoantigen GAD strongly inhibits DC

  5. Microplastic moves pollutants and additives to worms, reducing functions linked to health and biodiversity.

    PubMed

    Browne, Mark Anthony; Niven, Stewart J; Galloway, Tamara S; Rowland, Steve J; Thompson, Richard C

    2013-12-01

    Inadequate products, waste management, and policy are struggling to prevent plastic waste from infiltrating ecosystems [1, 2]. Disintegration into smaller pieces means that the abundance of micrometer-sized plastic (microplastic) in habitats has increased [3] and outnumbers larger debris [2, 4]. When ingested by animals, plastic provides a feasible pathway to transfer attached pollutants and additive chemicals into their tissues [5-15]. Despite positive correlations between concentrations of ingested plastic and pollutants in tissues of animals, few, if any, controlled experiments have examined whether ingested plastic transfers pollutants and additives to animals. We exposed lugworms (Arenicola marina) to sand with 5% microplastic that was presorbed with pollutants (nonylphenol and phenanthrene) and additive chemicals (Triclosan and PBDE-47). Microplastic transferred pollutants and additive chemicals into gut tissues of lugworms, causing some biological effects, although clean sand transferred larger concentrations of pollutants into their tissues. Uptake of nonylphenol from PVC or sand reduced the ability of coelomocytes to remove pathogenic bacteria by >60%. Uptake of Triclosan from PVC diminished the ability of worms to engineer sediments and caused mortality, each by >55%, while PVC alone made worms >30% more susceptible to oxidative stress. As global microplastic contamination accelerates, our findings indicate that large concentrations of microplastic and additives can harm ecophysiological functions performed by organisms. PMID:24309271

  6. In Vivo Evaluation of Vena Caval Filters: Can Function Be Linked to Design Characteristics?

    SciTech Connect

    Proctor, Mary C.; Cho, Kyung J.; Greenfield, Lazar J.

    2000-11-15

    Purpose: To compare the five vena caval filters marketed in the United States and one investigational vena caval filter and to determine whether there is an association between their design and their in vivo function.Methods: Four of each type of filter-Simon Nitinol (SN), Bird's Nest (BN), Vena Tech (VT), Greenfield stainless steel (PSGF), Greenfield titanium (TGF), and the investigational stent cone filter (NGF)-were studied for 60 days in 12 sheep. Radiographic and pathologic outcomes to be assessed included clot capture and resolution, vena caval penetration, position of the filter, thrombogenicity, and vessel wall reaction.Results: Filters differed with respect to the number of clot-trapping levels and the interdependence of the legs. All devices were successfully placed. Intentionally embolized clot was captured. One VT and two SN filters migrated in response to clot capture. Resolution of thrombus was variable, and related to the design of the device. Fibrin webbing was widely present with the VT, BN, and SN filters but limited in the others. The VT and NGF filters demonstrated the most stable filter base diameter.Conclusions: The performance of vena caval filters differs with respect to clot resolution and mechanical stability. Interdependent filter limbs and single-stage conical capture sites appear to result in more favorable performance in in vivo studies.

  7. Daily parental knowledge of youth activities is linked to youth physical symptoms and HPA functioning.

    PubMed

    Lippold, Melissa A; Davis, Kelly D; McHale, Susan M; Almeida, David M

    2016-03-01

    Considerable evidence documents linkages between parental knowledge of youth activities and youth risky behavior. We extended this research to determine whether parental knowledge was associated with youth physical health, including reports of physical symptoms (e.g., headaches, stomachaches) and a biomarker of hypothalamic pituitary adrenocortical (HPA) axis functioning (i.e., salivary cortisol levels). Participants were children of employees in the Information Technology division of a Fortune 500 company (N = 132, mean age youth = 13.39 years, 55% female) who participated in a daily diary study. Data were collected via telephone calls on 8 consecutive evenings. On 4 study days, cortisol samples were collected at 4 time points (waking, 30 min after waking, before dinner, bedtime). Multilevel models revealed that, at the between-person level, youth whose parents had higher average knowledge about their activities, exhibited lower bedtime cortisol levels. Furthermore, at the within-person level, on days when parents displayed more knowledge than usual (relative to their own 8-day average), youth had lower before-dinner cortisol than usual. Linkages between average parental knowledge and physical health symptoms were moderated by youth age: Younger but not older adolescents whose parents were more knowledgeable had fewer physical health symptoms, on average. A next step is to identify the processes that underlie these associations. (PsycINFO Database Record PMID:26751757

  8. CARD9 deficiencies linked to impaired neutrophil functions against Phialophora verrucosa.

    PubMed

    Liang, Pin; Wang, Xiaowen; Wang, Runchao; Wan, Zhe; Han, Wenling; Li, Ruoyu

    2015-06-01

    Caspase recruitment domain-containing protein 9 (CARD9) is an adaptor molecule that is critical for NF-κB activation and forms a complex with B cell lymphoma 10 and mucosa-associated lymphoid tissue lymphoma translocation gene 1 that mediates C-type lectin receptors (CLRs)-triggered intracellular signaling during antifungal immunity. However, the role of CARD9 in the host defense against Phialophora verrucosa (P. verrucosa) infection remains to be elucidated. In the present study, we investigated the functions of polymorphonuclear neutrophils (PMNs) from patients with CARD9 deficiencies against P. verrucosa. By isolating PMNs from patients and healthy blood donors and subsequently challenging the cells with P. verrucosa, we demonstrated that, compared with healthy donors, CARD9-deficient PMNs exhibited defects in P. verrucosa killing and pro-inflammatory cytokine productions, which can be rescued in the presence of serum; however, the CARD9-deficient PMNs exhibited normal reactive oxygen species generation and phagocytotic ability. In conclusion, our results indicate that CARD9 is indispensable for P. verrucosa killing by PMNs, and serum opsonization acts as a CARD9-independent way, which could be a promising immunotherapy in the future. PMID:25790941

  9. Functional Characterization of IPSC-Derived Brain Cells as a Model for X-Linked Adrenoleukodystrophy

    PubMed Central

    Baarine, Mauhamad; Khan, Mushfiquddin; Singh, Avtar; Singh, Inderjit

    2015-01-01

    X-ALD is an inherited neurodegenerative disorder where mutations in the ABCD1 gene result in clinically diverse phenotypes: the fatal disorder of cerebral childhood ALD (cALD) or a milder disorder of adrenomyeloneuropathy (AMN). The various models used to study the pathobiology of X-ALD disease lack the appropriate presentation for different phenotypes of cALD vs AMN. This study demonstrates that induced pluripotent stem cells (IPSC) derived brain cells astrocytes (Ast), neurons and oligodendrocytes (OLs) express morphological and functional activities of the respective brain cell types. The excessive accumulation of saturated VLCFA, a “hallmark” of X-ALD, was observed in both AMN OLs and cALD OLs with higher levels observed in cALD OLs than AMN OLs. The levels of ELOVL1 (ELOVL Fatty Acid Elongase 1) mRNA parallel the VLCFA load in AMN and cALD OLs. Furthermore, cALD Ast expressed higher levels of proinflammatory cytokines than AMN Ast and control Ast with or without stimulation with lipopolysaccharide. These results document that IPSC-derived Ast and OLs from cALD and AMN fibroblasts mimic the respective biochemical disease phenotypes and thus provide an ideal platform to investigate the mechanism of VLCFA load in cALD OLs and VLCFA-induced inflammatory disease mechanisms of cALD Ast and thus for testing of new therapeutics for AMN and cALD disease of X-ALD. PMID:26581106

  10. Trip report: pilot studies of factors linking watershed function and coastal ecosystem health in American Samoa

    USGS Publications Warehouse

    Atkinson, Carter T.; Medeiros, Arthur C.

    2010-01-01

    Coral reef resources in the territory of American Samoa face significant problems from overfishing, non-point source pollution, global warming, and continuing population growth and development. The islands are still relatively isolated relative to other parts of the Pacific and have managed to avoid some of the more devastating invasive species that have reached other archipelagoes. As a result, there are opportunities for collaborative and integrative research and monitoring programs to help restore and maintain biodiversity and functioning natural ecosystem in the archipelago. We found that the 'Ridge to Reef' paradigm already exists in American Samoa, with a high degree of interagency cooperation and efficient use of limited resources already taking place in the Territory. USGS may be able to make contributions as a partner organization in the Coral Reef Advisory Group (CRAG) through deployment of sediment monitoring instrumentation to supplement stream monitoring by the American Samoa Environmental Protection Agency, by providing high resolution vegetation and land-use maps of main islands, by providing additional support to the American Samoa Department of Marine and Wildlife Resources and the National Park Service for monitoring of invasive species, by working with members of CRAG to initiate sediment transport studies on Samoan reefs, and by developing new projects on the effects of bacterial contamination and pollutants on coral reef physiology and demography.