Science.gov

Sample records for functional link structure

  1. Linking community size structure and ecosystem functioning using metabolic theory.

    PubMed

    Yvon-Durocher, Gabriel; Allen, Andrew P

    2012-11-05

    Understanding how biogeochemical cycles relate to the structure of ecological communities is a central research question in ecology. Here we approach this problem by focusing on body size, which is an easily measured species trait that has a pervasive influence on multiple aspects of community structure and ecosystem functioning. We test the predictions of a model derived from metabolic theory using data on ecosystem metabolism and community size structure. These data were collected as part of an aquatic mesocosm experiment that was designed to simulate future environmental warming. Our analyses demonstrate significant linkages between community size structure and ecosystem functioning, and the effects of warming on these links. Specifically, we show that carbon fluxes were significantly influenced by seasonal variation in temperature, and yielded activation energies remarkably similar to those predicted based on the temperature dependencies of individual-level photosynthesis and respiration. We also show that community size structure significantly influenced fluxes of ecosystem respiration and gross primary production, particularly at the annual time-scale. Assessing size structure and the factors that control it, both empirically and theoretically, therefore promises to aid in understanding links between individual organisms and biogeochemical cycles, and in predicting the responses of key ecosystem functions to future environmental change.

  2. Linking structural dynamics and functional diversity in asymmetric catalysis.

    PubMed

    Nojiri, Akihiro; Kumagai, Naoya; Shibasaki, Masakatsu

    2009-03-18

    Proteins, the functional molecules in biological systems, are sophisticated chemical devices that have evolved over billions of years. Their function is intimately related to their three-dimensional structure and elegantly regulated by conformational changes through allosteric regulators and a number of reversible or unidirectional post-translational modifications. This functional diversification in response to external stimuli allows for an orderly and timely progression of intra- and extracellular events. In contrast, enantioselective catalysts generally exhibit limited conformational flexibility and thereby exert a single specific function. Exploiting the features of conformationally flexible asymmetric ligands and the variable coordination patterns of rare earth metals, we demonstrate dynamic structural and functional changes of a catalyst in asymmetric catalysis, leading to two distinct reaction outcomes in a single flask.

  3. Lung morphometry: the link between structure and function.

    PubMed

    Weibel, Ewald R

    2017-03-01

    The study of the structural basis of gas exchange function in the lung depends on the availability of quantitative information that concerns the structures establishing contact between the air in the alveoli and the blood in the alveolar capillaries, which can be entered into physiological equations for predicting oxygen uptake. This information is provided by morphometric studies involving stereological methods and allows estimates of the pulmonary diffusing capacity of the human lung that agree, in experimental studies, with the maximal oxygen consumption. The basis for this "machine lung" structure lies in the complex design of the cells building an extensive air-blood barrier with minimal cell mass.

  4. Linking stoichiometric homoeostasis with ecosystem structure, functioning and stability.

    PubMed

    Yu, Qiang; Chen, Quansheng; Elser, James J; He, Nianpeng; Wu, Honghui; Zhang, Guangming; Wu, Jianguo; Bai, Yongfei; Han, Xingguo

    2010-11-01

    Ecosystem structure, functioning and stability have been a focus of ecological and environmental sciences during the past two decades. The mechanisms underlying their relationship, however, are not well understood. Based on comprehensive studies in Inner Mongolia grassland, here we show that species-level stoichiometric homoeostasis was consistently positively correlated with dominance and stability on both 2-year and 27-year temporal scales and across a 1200-km spatial transect. At the community level, stoichiometric homoeostasis was also positively correlated with ecosystem function and stability in most cases. Thus, homoeostatic species tend to have high and stable biomass; and ecosystems dominated by more homoeostatic species have higher productivity and greater stability. By modulating organism responses to key environmental drivers, stoichiometric homoeostasis appears to be a major mechanism responsible for the structure, functioning and stability of grassland ecosystems. © 2010 Blackwell Publishing Ltd/CNRS.

  5. Linking structural features of protein complexes and biological function

    PubMed Central

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

    2015-01-01

    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

  6. 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.

  7. 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.

  8. Linking Microbial Community Structure to Function in Representative Simulated Systems

    PubMed Central

    Marcus, Ian M.; Wilder, Hailey A.; Quazi, Shanin J.

    2013-01-01

    Pathogenic bacteria are generally studied as a single strain under ideal growing conditions, although these conditions are not the norm in the environments in which pathogens typically proliferate. In this investigation, a representative microbial community along with Escherichia coli O157:H7, a model pathogen, was studied in three environments in which such a pathogen could be found: a human colon, a septic tank, and groundwater. Each of these systems was built in the lab in order to retain the physical/chemical and microbial complexity of the environments while maintaining control of the feed into the models. The microbial community in the colon was found to have a high percentage of bacteriodetes and firmicutes, while the septic tank and groundwater systems were composed mostly of proteobacteria. The introduction of E. coli O157:H7 into the simulated systems elicited a shift in the structures and phenotypic cell characteristics of the microbial communities. The fate and transport of the microbial community with E. coli O157:H7 were found to be significantly different from those of E. coli O157:H7 studied as a single isolate, suggesting that the behavior of the organism in the environment was different from that previously conceived. The findings in this study clearly suggest that to gain insight into the fate of pathogens, cells should be grown and analyzed under conditions simulating those of the environment in which the pathogens are present. PMID:23396331

  9. 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.

  10. Extending CATH: increasing coverage of the protein structure universe and linking structure with function.

    PubMed

    Cuff, Alison L; Sillitoe, Ian; Lewis, Tony; Clegg, Andrew B; Rentzsch, Robert; Furnham, Nicholas; Pellegrini-Calace, Marialuisa; Jones, David; Thornton, Janet; Orengo, Christine A

    2011-01-01

    CATH version 3.3 (class, architecture, topology, homology) contains 128,688 domains, 2386 homologous superfamilies and 1233 fold groups, and reflects a major focus on classifying structural genomics (SG) structures and transmembrane proteins, both of which are likely to add structural novelty to the database and therefore increase the coverage of protein fold space within CATH. For CATH version 3.4 we have significantly improved the presentation of sequence information and associated functional information for CATH superfamilies. The CATH superfamily pages now reflect both the functional and structural diversity within the superfamily and include structural alignments of close and distant relatives within the superfamily, annotated with functional information and details of conserved residues. A significantly more efficient search function for CATH has been established by implementing the search server Solr (http://lucene.apache.org/solr/). The CATH v3.4 webpages have been built using the Catalyst web framework.

  11. 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.

  12. Structural flexibility allows the functional diversity of potyvirus genome-linked protein VPg.

    PubMed

    Rantalainen, Kimmo I; Eskelin, Katri; Tompa, Peter; Mäkinen, Kristiina

    2011-03-01

    Several viral genome-linked proteins (VPgs) of plant viruses are intrinsically disordered and undergo folding transitions in the presence of partners. This property has been postulated to be one of the factors that enable the functional diversity of the protein. We created a homology model of Potato virus A VPg and positioned the known functions and structural properties of potyviral VPgs on the novel structural model. The model suggests an elongated structure with a hydrophobic core composed of antiparallel β-sheets surrounded by helices and a positively charged contact surface where most of the known activities are localized. The model most probably represents the fold induced immediately after binding of VPg to a negatively charged lipid surface or to SDS. When the charge of the positive surface was lowered by lysine mutations, the efficiencies of in vitro NTP binding, uridylylation reaction, and unspecific RNA binding were reduced and in vivo the infectivity was debilitated. The most likely uridylylation site, Tyr63, locates to the positively charged surface. Surprisingly, a Tyr63Ala mutation did not prevent replication completely but blocked spreading of the virus. Based on the localization of Tyr119 in the model, it was hypothesized to serve as an alternative uridylylation site. Evidence to support the role of Tyr119 in replication was obtained which gives a positive example of the prediction power of the model. Taken together, our experimental data support the features presented in the model and the idea that the functional diversity is attributable to structural flexibility.

  13. Structural Flexibility Allows the Functional Diversity of Potyvirus Genome-Linked Protein VPg▿ §

    PubMed Central

    Rantalainen, Kimmo I.; Eskelin, Katri; Tompa, Peter; Mäkinen, Kristiina

    2011-01-01

    Several viral genome-linked proteins (VPgs) of plant viruses are intrinsically disordered and undergo folding transitions in the presence of partners. This property has been postulated to be one of the factors that enable the functional diversity of the protein. We created a homology model of Potato virus A VPg and positioned the known functions and structural properties of potyviral VPgs on the novel structural model. The model suggests an elongated structure with a hydrophobic core composed of antiparallel β-sheets surrounded by helices and a positively charged contact surface where most of the known activities are localized. The model most probably represents the fold induced immediately after binding of VPg to a negatively charged lipid surface or to SDS. When the charge of the positive surface was lowered by lysine mutations, the efficiencies of in vitro NTP binding, uridylylation reaction, and unspecific RNA binding were reduced and in vivo the infectivity was debilitated. The most likely uridylylation site, Tyr63, locates to the positively charged surface. Surprisingly, a Tyr63Ala mutation did not prevent replication completely but blocked spreading of the virus. Based on the localization of Tyr119 in the model, it was hypothesized to serve as an alternative uridylylation site. Evidence to support the role of Tyr119 in replication was obtained which gives a positive example of the prediction power of the model. Taken together, our experimental data support the features presented in the model and the idea that the functional diversity is attributable to structural flexibility. PMID:21177813

  14. 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.

  15. A simple structure wavelet transform circuit employing function link neural networks and SI filters

    NASA Astrophysics Data System (ADS)

    Mu, Li; Yigang, He

    2016-12-01

    Signal processing by means of analog circuits offers advantages from a power consumption viewpoint. Implementing wavelet transform (WT) using analog circuits is of great interest when low-power consumption becomes an important issue. In this article, a novel simple structure WT circuit in analog domain is presented by employing functional link neural network (FLNN) and switched-current (SI) filters. First, the wavelet base is approximated using FLNN algorithms for giving a filter transfer function that is suitable for simple structure WT circuit implementation. Next, the WT circuit is constructed with the wavelet filter bank, whose impulse response is the approximated wavelet and its dilations. The filter design that follows is based on a follow-the-leader feedback (FLF) structure with multiple output bilinear SI integrators and current mirrors as the main building blocks. SI filter is well suited for this application since the dilation constant across different scales of the transform can be precisely implemented and controlled by the clock frequency of the circuit with the same system architecture. Finally, to illustrate the design procedure, a seventh-order FLNN-approximated Gaussian wavelet is implemented as an example. Simulations have successfully verified that the designed simple structure WT circuit has low sensitivity, low-power consumption and litter effect to the imperfections.

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

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

    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.

  17. 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

    2016-02-17

    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.

  18. 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

  19. 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

  20. Using joint ICA to link function and structure using MEG and DTI in schizophrenia.

    PubMed

    Stephen, J M; Coffman, B A; Jung, R E; Bustillo, J R; Aine, C J; Calhoun, V D

    2013-12-01

    In this study we employed joint independent component analysis (jICA) to perform a novel multivariate integration of magnetoencephalography (MEG) and diffusion tensor imaging (DTI) data to investigate the link between function and structure. This model-free approach allows one to identify covariation across modalities with different temporal and spatial scales [temporal variation in MEG and spatial variation in fractional anisotropy (FA) maps]. Healthy controls (HC) and patients with schizophrenia (SP) participated in an auditory/visual multisensory integration paradigm to probe cortical connectivity in schizophrenia. To allow direct comparisons across participants and groups, the MEG data were registered to an average head position and regional waveforms were obtained by calculating the local field power of the planar gradiometers. Diffusion tensor images obtained in the same individuals were preprocessed to provide FA maps for each participant. The MEG/FA data were then integrated using the jICA software (http://mialab.mrn.org/software/fit). We identified MEG/FA components that demonstrated significantly different (p<0.05) covariation in MEG/FA data between diagnostic groups (SP vs. HC) and three components that captured the predominant sensory responses in the MEG data. Lower FA values in bilateral posterior parietal regions, which include anterior/posterior association tracts, were associated with reduced MEG amplitude (120-170 ms) of the visual response in occipital sensors in SP relative to HC. Additionally, increased FA in a right medial frontal region was linked with larger amplitude late MEG activity (300-400 ms) in bilateral central channels for SP relative to HC. Step-wise linear regression provided evidence that right temporal, occipital and late central components were significant predictors of reaction time and cognitive performance based on the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) cognitive assessment

  1. Using joint ICA to link function and structure using MEG and DTI in schizophrenia

    PubMed Central

    Stephen, JM; Coffman, BA; Jung, RE; Bustillo, JR; Aine, CJ; Calhoun, VD

    2013-01-01

    In this study we employed joint independent component analysis (jICA) to perform a novel multivariate integration of magnetoencephalography (MEG) and diffusion tensor imaging (DTI) data to investigate the link between function and structure. This model-free approach allows one to identify covariation across modalities with different temporal and spatial scales [temporal variation in MEG and spatial variation in fractional anisotropy (FA) maps]. Healthy controls (HC) and patients with schizophrenia (SP) participated in an auditory/visual multisensory integration paradigm to probe cortical connectivity in schizophrenia. To allow direct comparisons across participants and groups, the MEG data were registered to an average head position and regional waveforms were obtained by calculating the local field power of the planar gradiometers. Diffusion tensor images obtained in the same individuals were preprocessed to provide FA maps for each participant. The MEG/FA data were then integrated using the jICA software (http://mialab.mrn.org/software/fit). We identified MEG/FA components that demonstrated significantly different (p < 0.05) covariation in MEG/FA data between diagnostic groups (SP vs. HC) and three components that captured the predominant sensory responses in the MEG data. Lower FA values in bilateral posterior parietal regions, which include anterior/posterior association tracts, were associated with reduced MEG amplitude (120-170 ms) of the visual response in occipital sensors in SP relative to HC. Additionally, increased FA in a right medial frontal region was linked with larger amplitude late MEG activity (300-400 ms) in bilateral central channels for SP relative to HC. Step-wise linear regression provided evidence that right temporal, occipital and late central components were significant predictors of reaction time and cognitive performance based on the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) cognitive assessment

  2. Modeling the link between soil microbial community structure and function in a bottom-up approach

    NASA Astrophysics Data System (ADS)

    Kaiser, C.; Richter, A.; Franklin, O.; Evans, S. E.; Dieckmann, U.

    2012-12-01

    Understanding mechanisms of soil carbon (C) turnover requires understanding the link between microbial community dynamics and soil decomposition processes. We present here an individual-based model that aims at elucidating this link by a bottom-up approach. Our approach differs from traditional soil C cycling models in that the overall dynamics of soil organic matter turnover emerges as the result of interactions between individual microbes at the soil microsite level, rather than being described by stock and flow rate equations at the bulk soil level. All soil microbes are modeled individually, each belonging to one of several functional groups defined by functional traits. Specifically, functional traits determine (1) growth and turnover rates, (2) production of extracellular enzymes and (3) microbial cell stoichiometry. Our model incorporates competition for space and nutrients (C and nitrogen, N) as well as synergistic interactions between individual microbes in a spatially structured environment represented by a two-dimensional grid. Due to different C and N limitations of different functional groups, community composition is sensitive to the availability of complex and labile C and N. Thus, altered resource availability changes microbial community composition, which in turn affects CO2 and N release from the soil. In our model, microbes constantly alter their own environment through the decomposition of different substrates, thereby exerting a feedback on community composition, which leads to a succession of microbial groups. We used the model's intrinsic link between resource availability, community dynamics and decomposition function to investigate the mechanism underlying the rhizosphere priming effect (i.e. increased decomposition of older soil C triggered by the input of labile C). In particular, we examined the spatial growth of a root releasing exudates of varying C:N ratios under the presence or absence of different functional groups. We find that a

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

    PubMed Central

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

    2013-01-01

    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

  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 neural network that links brain function, white-matter structure and risky behavior.

    PubMed

    Kohno, Milky; Morales, Angelica M; Guttman, Zoe; London, Edythe D

    2017-04-01

    The ability to evaluate the balance between risk and reward and to adjust behavior accordingly is fundamental to adaptive decision-making. Although brain-imaging studies consistently have shown involvement of the dorsolateral prefrontal cortex, anterior insula and striatum during risky decision-making, activation in a neural network formed by these regions has not been linked to structural connectivity. Therefore, in this study, white-matter connectivity was measured with diffusion-weighted imaging in 40 healthy research participants who performed the Balloon Analogue Risk Task, a test of risky decision-making, during fMRI. Fractional anisotropy within a network that includes white-matter pathways connecting four regions (the prefrontal cortex, insula and midbrain to the striatum) was positively correlated with the number of risky choices and total amount earned on the task, and with the parametric modulation of activation in regions within the network to the level of risk during choice selection. Furthermore, analysis using a mixed model demonstrated how relationships of the parametric modulation of activation in each of the four aforementioned regions are related to risk probabilities, and how previous trial outcomes and task progression influence the choice to take risk. The present findings provide the first direct evidence that white-matter integrity is linked to function within previously identified components of a network that is activated during risky decision-making, and demonstrate that the integrity of white-matter tracts is critical in consolidating and processing signals between cortical and striatal circuits during the decision-making process.

  6. Linking epigenetic function to electrostatics: The DNMT2 structural model example.

    PubMed

    Vieira, Gilberto Cavalheiro; Vieira, Gustavo Fioravanti; Sinigaglia, Marialva; Silva Valente, Vera Lúcia da

    2017-01-01

    The amino acid sequence of DNMT2 is very similar to the catalytic domains of bacterial and eukaryotic proteins. However, there is great variability in the region of recognition of the target sequence. While bacterial DNMT2 acts as a DNA methyltransferase, previous studies have indicated low DNA methylation activity in eukaryotic DNMT2, with preference by tRNA methylation. Drosophilids are known as DNMT2-only species and the DNA methylation phenomenon is a not elucidated case yet, as well as the ontogenetic and physiologic importance of DNMT2 for this species group. In addition, more recently study showed that methylation in the genome in Drosophila melanogaster is independent in relation to DNMT2. Despite these findings, Drosophilidae family has more than 4,200 species with great ecological diversity and historical evolution, thus we, therefore, aimed to examine the drosophilids DNMT2 in order to verify its conservation at the physicochemical and structural levels in a functional context. We examined the twenty-six DNMT2 models generated by molecular modelling and five crystallographic structures deposited in the Protein Data Bank (PDB) using different approaches. Our results showed that despite sequence and structural similarity between species close related, we found outstanding differences when they are analyzed in the context of surface distribution of electrostatic properties. The differences found in the electrostatic potentials may be linked with different affinities and processivity of DNMT2 for its different substrates (DNA, RNA or tRNA) and even for interactions with other proteins involved in the epigenetic mechanisms.

  7. The linked conservation of structure and function in a family of high diversity: the monomeric cupredoxins.

    PubMed

    Gough, Julian; Chothia, Cyrus

    2004-06-01

    The monomeric cupredoxins are a highly divergent family of copper binding electron transport proteins that function in photosynthesis and respiration. To determine how function and structure are conserved in the context of large sequence differences, we have carried out a detailed analysis of the cupredoxins of known structure and their sequence homologs. The common structure of the cupredoxins is formed by a sandwich of two beta sheets which support a copper binding site. The structure of the deeply buried core is intimately coupled to the binding site on the surface of the protein; in each protein the conserved regions form one continuous substructure that extends from the surface active site and through the center of the molecule. Residues around the active site are conserved for functional reasons, while those deeper in the structure will be conserved for structural reasons. Together the two sets support each other.

  8. Chronic cigarette smoking is linked with structural alterations in brain regions showing acute nicotinic drug-induced functional modulations.

    PubMed

    Sutherland, Matthew T; Riedel, Michael C; Flannery, Jessica S; Yanes, Julio A; Fox, Peter T; Stein, Elliot A; Laird, Angela R

    2016-06-02

    Whereas acute nicotine administration alters brain function which may, in turn, contribute to enhanced attention and performance, chronic cigarette smoking is linked with regional brain atrophy and poorer cognition. However, results from structural magnetic resonance imaging (MRI) studies comparing smokers versus nonsmokers have been inconsistent and measures of gray matter possess limited ability to inform functional relations or behavioral implications. The purpose of this study was to address these interpretational challenges through meta-analytic techniques in the service of clarifying the impact of chronic smoking on gray matter integrity and more fully contextualizing such structural alterations. We first conducted a coordinate-based meta-analysis of structural MRI studies to identify consistent structural alterations associated with chronic smoking. Subsequently, we conducted two additional meta-analytic assessments to enhance insight into potential functional and behavioral relations. Specifically, we performed a multimodal meta-analytic assessment to test the structural-functional hypothesis that smoking-related structural alterations overlapped those same regions showing acute nicotinic drug-induced functional modulations. Finally, we employed database driven tools to identify pairs of structurally impacted regions that were also functionally related via meta-analytic connectivity modeling, and then delineated behavioral phenomena associated with such functional interactions via behavioral decoding. Across studies, smoking was associated with convergent structural decreases in the left insula, right cerebellum, parahippocampus, multiple prefrontal cortex (PFC) regions, and the thalamus. Indicating a structural-functional relation, we observed that smoking-related gray matter decreases overlapped with the acute functional effects of nicotinic agonist administration in the left insula, ventromedial PFC, and mediodorsal thalamus. Suggesting structural

  9. 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

  10. 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

  11. N-linked glycosylation in Archaea: a structural, functional, and genetic analysis.

    PubMed

    Jarrell, Ken F; Ding, Yan; Meyer, Benjamin H; Albers, Sonja-Verena; Kaminski, Lina; Eichler, Jerry

    2014-06-01

    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.

  12. 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

  13. X-ray Structural and Functional Studies of the Three Tandemly Linked Domains of Non-structural Protein 3 (nsp3) from Murine Hepatitis Virus Reveal Conserved Functions*

    PubMed Central

    Chen, Yafang; Savinov, Sergey N.; Mielech, Anna M.; Cao, Thu; Baker, Susan C.; Mesecar, Andrew D.

    2015-01-01

    Murine hepatitis virus (MHV) has long served as a model system for the study of coronaviruses. Non-structural protein 3 (nsp3) is the largest nsp in the coronavirus genome, and it contains multiple functional domains that are required for coronavirus replication. Despite the numerous functional studies on MHV and its nsp3 domain, the structure of only one domain in nsp3, the small ubiquitin-like domain 1 (Ubl1), has been determined. We report here the x-ray structure of three tandemly linked domains of MHV nsp3, including the papain-like protease 2 (PLP2) catalytic domain, the ubiquitin-like domain 2 (Ubl2), and a third domain that we call the DPUP (domain preceding Ubl2 and PLP2) domain. DPUP has close structural similarity to the severe acute respiratory syndrome coronavirus unique domain C (SUD-C), suggesting that this domain may not be unique to the severe acute respiratory syndrome coronavirus. The PLP2 catalytic domain was found to have both deubiquitinating and deISGylating isopeptidase activities in addition to proteolytic activity. A computationally derived model of MHV PLP2 bound to ubiquitin was generated, and the potential interactions between ubiquitin and PLP2 were probed by site-directed mutagenesis. These studies extend substantially our structural knowledge of MHV nsp3, providing a platform for further investigation of the role of nsp3 domains in MHV viral replication. PMID:26296883

  14. Bottom up modeling of the connectome: linking structure and function in the resting brain and their changes in aging.

    PubMed

    Nakagawa, Tristan T; Jirsa, Viktor K; Spiegler, Andreas; McIntosh, Anthony R; Deco, Gustavo

    2013-10-15

    With the increasing availability of advanced imaging technologies, we are entering a new era of neuroscience. Detailed descriptions of the complex brain network enable us to map out a structural connectome, characterize it with graph theoretical methods, and compare it to the functional networks with increasing detail. To link these two aspects and understand how dynamics and structure interact to form functional brain networks in task and in the resting state, we use theoretical models. The advantage of using theoretical models is that by recreating functional connectivity and time series explicitly from structure and pre-defined dynamics, we can extract critical mechanisms by linking structure and function in ways not directly accessible in the real brain. Recently, resting-state models with varying local dynamics have reproduced empirical functional connectivity patterns, and given support to the view that the brain works at a critical point at the edge of a bifurcation of the system. Here, we present an overview of a modeling approach of the resting brain network and give an application of a neural mass model in the study of complexity changes in aging. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. 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

  16. How do SMA-linked mutations of SMN1 lead to structural/functional deficiency of the SMA protein?

    PubMed

    Li, Wei

    2017-01-01

    Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease with dysfunctional α-motor neurons in the anterior horn of the spinal cord. SMA is caused by loss (∼95% of SMA cases) or mutation (∼5% of SMA cases) of the survival motor neuron 1 gene SMN1. As the product of SMN1, SMN is a component of the SMN complex, and is also involved in the biosynthesis of the small nuclear ribonucleoproteins (snRNPs), which play critical roles in pre-mRNA splicing in the pathogenesis of SMA. To investigate how SMA-linked mutations of SMN1 lead to structural/functional deficiency of SMN, a set of computational analysis of SMN-related structures were conducted and are described in this article. Of extraordinary interest, the structural analysis highlights three SMN residues (Asp44, Glu134 and Gln136) with SMA-linked missense mutations, which cause disruptions of electrostatic interactions for Asp44, Glu134 and Gln136, and result in three functionally deficient SMA-linked SMN mutants, Asp44Val, Glu134Lys and Gln136Glu. From the computational analysis, it is also possible that SMN's Lys45 and Asp36 act as two electrostatic clips at the SMN-Gemin2 complex structure interface.

  17. Neisseria gonorrhoeae O-linked pilin glycosylation: functional analyses define both the biosynthetic pathway and glycan structure

    PubMed Central

    Aas, Finn Erik; Vik, Åshild; Vedde, John; Koomey, Michael; Egge-Jacobsen, Wolfgang

    2007-01-01

    Neisseria gonorrhoeae expresses an O-linked protein glycosylation pathway that targets PilE, the major pilin subunit protein of the Type IV pilus colonization factor. Efforts to define glycan structure and thus the functions of pilin glycosylation (Pgl) components at the molecular level have been hindered by the lack of sensitive methodologies. Here, we utilized a ‘top-down’ mass spectrometric approach to characterize glycan status using intact pilin protein from isogenic mutants. These structural data enabled us to directly infer the function of six components required for pilin glycosylation and to define the glycan repertoire of strain N400. Additionally, we found that the N. gonorrhoeae pilin glycan is O-acetylated, and identified an enzyme essential for this unique modification. We also identified the N. gonorrhoeae pilin oligosaccharyltransferase using bioinformatics and confirmed its role in pilin glycosylation by directed mutagenesis. Finally, we examined the effects of expressing the PglA glycosyltransferase from the Campylobacter jejuni N-linked glycosylation system that adds N-acetylgalactosamine onto undecaprenylpyrophosphate-linked bacillosamine. The results indicate that the C. jejuni and N. gonorrhoeae pathways can interact in the synthesis of O-linked di- and trisaccharides, and therefore provide the first experimental evidence that biosynthesis of the N. gonorrhoeae pilin glycan involves a lipid-linked oligosaccharide precursor. Together, these findings underpin more detailed studies of pilin glycosylation biology in both N. gonorrhoeae and N. meningitidis, and demonstrate how components of bacterial O- and N-linked pathways can be combined in novel glycoengineering strategies. PMID:17608667

  18. LINKING LUNG AIRWAY STRUCTURE TO PULMONARY FUNCTION VIA COMPOSITE BRIDGE REGRESSION

    PubMed Central

    Chen, Kun; Hoffman, Eric A.; Seetharaman, Indu; Jiao, Feiran; Lin, Ching-Long; Chan, Kung-Sik

    2017-01-01

    The human lung airway is a complex inverted tree-like structure. Detailed airway measurements can be extracted from MDCT-scanned lung images, such as segmental wall thickness, airway diameter, parent-child branch angles, etc. The wealth of lung airway data provides a unique opportunity for advancing our understanding of the fundamental structure-function relationships within the lung. An important problem is to construct and identify important lung airway features in normal subjects and connect these to standardized pulmonary function test results such as FEV1%. Among other things, the problem is complicated by the fact that a particular airway feature may be an important (relevant) predictor only when it pertains to segments of certain generations. Thus, the key is an efficient, consistent method for simultaneously conducting group selection (lung airway feature types) and within-group variable selection (airway generations), i.e., bi-level selection. Here we streamline a comprehensive procedure to process the lung airway data via imputation, normalization, transformation and groupwise principal component analysis, and then adopt a new composite penalized regression approach for conducting bi-level feature selection. As a prototype of composite penalization, the proposed composite bridge regression method is shown to admit an efficient algorithm, enjoy bi-level oracle properties, and outperform several existing methods. We analyze the MDCT lung image data from a cohort of 132 subjects with normal lung function. Our results show that, lung function in terms of FEV1% is promoted by having a less dense and more homogeneous lung comprising an airway whose segments enjoy more heterogeneity in wall thicknesses, larger mean diameters, lumen areas and branch angles. These data hold the potential of defining more accurately the “normal” subject population with borderline atypical lung functions that are clearly influenced by many genetic and environmental factors. PMID

  19. 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

  20. The Structural and Functional Implications of Linked SNARE Motifs in SNAP25

    PubMed Central

    Wang, Li; Bittner, Mary A.; Axelrod, Daniel

    2008-01-01

    We investigated the functional and structural implications of SNAP25 having two SNARE motifs (SN1 and SN2). A membrane-bound, intramolecular FRET probe was constructed to report on the folding of N-terminal SN1 and C-terminal SN2 in living cells. Membrane-bound constructs containing either or both SNARE motifs were also singly labeled with donor or acceptor fluorophores. Interaction of probes with other SNAREs was monitored by the formation of SDS-resistant complexes and by changes in FRET measured in vitro using spectroscopy and in the plasma membrane of living cells using TIRF microscopy. The probes formed the predicted SDS-resistant SNARE complexes. FRET measurements revealed that syntaxin induced a close association of the N-termini of SN1 and SN2. This association required that the SNARE motifs reside in the same molecule. Unexpectedly, the syntaxin-induced FRET was prevented by VAMP. Both full-length SNAP25 constructs and the combination of its separated, membrane-bound constituent chains supported secretion in permeabilized chromaffin cells that had been allowed to rundown. However, only full-length SNAP25 constructs enabled robust secretion from intact cells or permeabilized cells before rundown. The experiments suggest that the bidentate structure permits specific conformations in complexes with syntaxin and VAMP and facilitates the function of SN1 and SN2 in exocytosis. PMID:18596234

  1. A functional link between rhythmic changes in chromatin structure and the Arabidopsis biological clock.

    PubMed

    Perales, Mariano; Más, Paloma

    2007-07-01

    Circadian clocks rhythmically coordinate biological processes in resonance with the environmental cycle. The clock function relies on negative feedback loops that generate 24-h rhythms in multiple outputs. In Arabidopsis thaliana, the clock component TIMING OF CAB EXPRESSION1 (TOC1) integrates the environmental information to coordinate circadian responses. Here, we use chromatin immunoprecipitation as well as physiological and luminescence assays to demonstrate that proper photoperiodic phase of TOC1 expression is important for clock synchronization of plant development with the environment. Our studies show that TOC1 circadian induction is accompanied by clock-controlled cycles of histone acetylation that favor transcriptionally permissive chromatin structures at the TOC1 locus. At dawn, TOC1 repression relies on the in vivo circadian binding of the clock component CIRCADIAN CLOCK ASSOCIATED1 (CCA1), while histone deacetylase activities facilitate the switch to repressive chromatin structures and contribute to the declining phase of TOC1 waveform around dusk. The use of cca1 late elongated hypocotyl double mutant and CCA1-overexpressing plants suggests a highly repressing function of CCA1, antagonizing H3 acetylation to regulate TOC1 mRNA abundance. The chromatin remodeling activities relevant at the TOC1 locus are distinctively modulated by photoperiod, suggesting a mechanism by which the clock sets the phase of physiological and developmental outputs.

  2. Accelerating Nanoscale Research with Neutron Total Scattering: Linking Structure and Function in Finite Materials

    NASA Astrophysics Data System (ADS)

    Page, Katharine

    2012-10-01

    h -abstract-pard In contrast to bulk materials, nanomaterials and nanoparticles, comprised of a few hundred to tens of thousands of atoms, require every atom's position to be located in order to understand their structure-property relationships. New behavior can arise with a constricted, expanded, or distorted lattice, variation in surface termination structure, ligand capping or stabilization, or with the increasingly diverse set of shapes and architectures appearing in nanoscience literature today: tubes, pyramids, stars, core-shell and matrix-confined particles, multilayer films, etc. Pair distribution function (PDF) analysis, based on spallation neutron or synchrotron x-ray total scattering data, has emerged as a very promising characterization method for nanomaterials in recent years. Total scattering methods provide information about every pair of atoms probed in a diffraction experiment and thus contain an unexploited wealth of information for finite systems. In this contribution we will present our work establishing the influence of particle size and shape on the nature and correlation of local atomic dipoles in finite ferroelectric systems. We also review current data-driven modeling capabilities and outline the need for evolution of robust computational tools to follow other complex nanoscale phenomena with scattering data. pard-/abstract-

  3. A Three-way Parallel ICA Approach to Analyze Links among Genetics, Brain Structure and Brain Function

    PubMed Central

    Vergara, Victor M.; Ulloa, Alvaro; Calhoun, Vince D.; Boutte, David; Chen, Jiayu; Liu, Jingyu

    2014-01-01

    Multi-modal data analysis techniques, such as the Parallel Independent Component Analysis (pICA), are essential in neuroscience, medical imaging and genetic studies. The pICA algorithm allows the simultaneous decomposition of up to two data modalities achieving better performance than separate ICA decompositions and enabling the discovery of links between modalities. However, advances in data acquisition techniques facilitate the collection of more than two data modalities from each subject. Examples of commonly measured modalities include genetic information, structural magnetic resonance imaging (MRI) and functional MRI. In order to take full advantage of the available data, this work extends the pICA approach to incorporate three modalities in one comprehensive analysis. Simulations demonstrate the three-way pICA performance in identifying pairwise links between modalities and estimating independent components which more closely resemble the true sources than components found by pICA or separate ICA analyses. In addition, the three-way pICA algorithm is applied to real experimental data obtained from a study that investigate genetic effects on alcohol dependence. Considered data modalities include functional MRI (contrast images during alcohol exposure paradigm), gray matter concentration images from structural MRI and genetic single nucleotide polymorphism (SNP). The three-way pICA approach identified links between a SNP component (pointing to brain function and mental disorder associated genes, including BDNF, GRIN2B and NRG1), a functional component related to increased activation in the precuneus area, and a gray matter component comprising part of the default mode network and the caudate. Although such findings need further verification, the simulation and in-vivo results validate the three-way pICA algorithm presented here as a useful tool in biomedical data fusion applications. PMID:24795156

  4. A three-way parallel ICA approach to analyze links among genetics, brain structure and brain function.

    PubMed

    Vergara, Victor M; Ulloa, Alvaro; Calhoun, Vince D; Boutte, David; Chen, Jiayu; Liu, Jingyu

    2014-09-01

    Multi-modal data analysis techniques, such as the Parallel Independent Component Analysis (pICA), are essential in neuroscience, medical imaging and genetic studies. The pICA algorithm allows the simultaneous decomposition of up to two data modalities achieving better performance than separate ICA decompositions and enabling the discovery of links between modalities. However, advances in data acquisition techniques facilitate the collection of more than two data modalities from each subject. Examples of commonly measured modalities include genetic information, structural magnetic resonance imaging (MRI) and functional MRI. In order to take full advantage of the available data, this work extends the pICA approach to incorporate three modalities in one comprehensive analysis. Simulations demonstrate the three-way pICA performance in identifying pairwise links between modalities and estimating independent components which more closely resemble the true sources than components found by pICA or separate ICA analyses. In addition, the three-way pICA algorithm is applied to real experimental data obtained from a study that investigate genetic effects on alcohol dependence. Considered data modalities include functional MRI (contrast images during alcohol exposure paradigm), gray matter concentration images from structural MRI and genetic single nucleotide polymorphism (SNP). The three-way pICA approach identified links between a SNP component (pointing to brain function and mental disorder associated genes, including BDNF, GRIN2B and NRG1), a functional component related to increased activation in the precuneus area, and a gray matter component comprising part of the default mode network and the caudate. Although such findings need further verification, the simulation and in-vivo results validate the three-way pICA algorithm presented here as a useful tool in biomedical data fusion applications.

  5. Linking phloem function to structure: analysis with a coupled xylem-phloem transport model.

    PubMed

    Hölttä, T; Mencuccini, M; Nikinmaa, E

    2009-07-21

    We carried out a theoretical analysis of phloem transport based on Münch hypothesis by developing a coupled xylem-phloem transport model. Results showed that the maximum sugar transport rate of the phloem was limited by solution viscosity and that transport requirements were strongly affected by prevailing xylem water potential. The minimum number of xylem and phloem conduits required to sustain transpiration and assimilation, respectively, were calculated. At its maximum sugar transport rate, the phloem functioned with a high turgor pressure difference between the sugar sources and sinks but the turgor pressure difference was reduced if additional parallel conduits were added or solute relays were introduced. Solute relays were shown to decrease the number of parallel sieve tubes needed for phloem transport, leading to a more uniform turgor pressure and allowing faster information transmission within the phloem. Because xylem water potential affected both xylem and phloem transport, the conductance of the two systems was found to be coupled such that large structural investments in the xylem reduced the need for investment in the phloem and vice versa.

  6. CNA web server: rigidity theory-based thermal unfolding simulations of proteins for linking structure, (thermo-)stability, and function

    PubMed Central

    Krüger, Dennis M.; Rathi, Prakash Chandra; Pfleger, Christopher; Gohlke, Holger

    2013-01-01

    The Constraint Network Analysis (CNA) web server provides a user-friendly interface to the CNA approach developed in our laboratory for linking results from rigidity analyses to biologically relevant characteristics of a biomolecular structure. The CNA web server provides a refined modeling of thermal unfolding simulations that considers the temperature dependence of hydrophobic tethers and computes a set of global and local indices for quantifying biomacromolecular stability. From the global indices, phase transition points are identified where the structure switches from a rigid to a floppy state; these phase transition points can be related to a protein’s (thermo-)stability. Structural weak spots (unfolding nuclei) are automatically identified, too; this knowledge can be exploited in data-driven protein engineering. The local indices are useful in linking flexibility and function and to understand the impact of ligand binding on protein flexibility. The CNA web server robustly handles small-molecule ligands in general. To overcome issues of sensitivity with respect to the input structure, the CNA web server allows performing two ensemble-based variants of thermal unfolding simulations. The web server output is provided as raw data, plots and/or Jmol representations. The CNA web server, accessible at http://cpclab.uni-duesseldorf.de/cna or http://www.cnanalysis.de, is free and open to all users with no login requirement. PMID:23609541

  7. Constraint Network Analysis (CNA): a Python software package for efficiently linking biomacromolecular structure, flexibility, (thermo-)stability, and function.

    PubMed

    Pfleger, Christopher; Rathi, Prakash Chandra; Klein, Doris L; Radestock, Sebastian; Gohlke, Holger

    2013-04-22

    For deriving maximal advantage from information on biomacromolecular flexibility and rigidity, results from rigidity analyses must be linked to biologically relevant characteristics of a structure. Here, we describe the Python-based software package Constraint Network Analysis (CNA) developed for this task. CNA functions as a front- and backend to the graph-based rigidity analysis software FIRST. CNA goes beyond the mere identification of flexible and rigid regions in a biomacromolecule in that it (I) provides a refined modeling of thermal unfolding simulations that also considers the temperature-dependence of hydrophobic tethers, (II) allows performing rigidity analyses on ensembles of network topologies, either generated from structural ensembles or by using the concept of fuzzy noncovalent constraints, and (III) computes a set of global and local indices for quantifying biomacromolecular stability. This leads to more robust results from rigidity analyses and extends the application domain of rigidity analyses in that phase transition points ("melting points") and unfolding nuclei ("structural weak spots") are determined automatically. Furthermore, CNA robustly handles small-molecule ligands in general. Such advancements are important for applying rigidity analysis to data-driven protein engineering and for estimating the influence of ligand molecules on biomacromolecular stability. CNA maintains the efficiency of FIRST such that the analysis of a single protein structure takes a few seconds for systems of several hundred residues on a single core. These features make CNA an interesting tool for linking biomacromolecular structure, flexibility, (thermo-)stability, and function. CNA is available from http://cpclab.uni-duesseldorf.de/software for nonprofit organizations.

  8. The structural and functional effects of the familial hypertrophic cardiomyopathy-linked cardiac troponin C mutation, L29Q.

    PubMed

    Robertson, Ian M; Sevrieva, Ivanka; Li, Monica X; Irving, Malcolm; Sun, Yin-Biao; Sykes, Brian D

    2015-10-01

    Familial hypertrophic cardiomyopathy (FHC) is characterized by severe abnormal cardiac muscle growth. The traditional view of disease progression in FHC is that an increase in the Ca(2+)-sensitivity of cardiac muscle contraction ultimately leads to pathogenic myocardial remodeling, though recent studies suggest this may be an oversimplification. For example, FHC may be developed through altered signaling that prevents downstream regulation of contraction. The mutation L29Q, found in the Ca(2+)-binding regulatory protein in heart muscle, cardiac troponin C (cTnC), has been linked to cardiac hypertrophy. However, reports on the functional effects of this mutation are conflicting, and our goal was to combine in vitro and in situ structural and functional data to elucidate its mechanism of action. We used nuclear magnetic resonance and circular dichroism to solve the structure and characterize the backbone dynamics and stability of the regulatory domain of cTnC with the L29Q mutation. The overall structure and dynamics of cTnC were unperturbed, although a slight rearrangement of site 1, an increase in backbone flexibility, and a small decrease in protein stability were observed. The structure and function of cTnC was also assessed in demembranated ventricular trabeculae using fluorescence for in situ structure. L29Q reduced the cooperativity of the Ca(2+)-dependent structural change in cTnC in trabeculae under basal conditions and abolished the effect of force-generating myosin cross-bridges on this structural change. These effects could contribute to the pathogenesis of this mutation.

  9. Test–Retest Intervisit Variability of Functional and Structural Parameters in X-Linked Retinoschisis

    PubMed Central

    Jeffrey, Brett G.; Cukras, Catherine A.; Vitale, Susan; Turriff, Amy; Bowles, Kristin; Sieving, Paul A.

    2014-01-01

    Purpose To examine the variability of four outcome measures that could be used to address safety and efficacy in therapeutic trials with X-linked juvenile retinoschisis. Methods Seven men with confirmed mutations in the RS1 gene were evaluated over four visits spanning 6 months. Assessments included visual acuity, full-field electroretinograms (ERG), microperimetric macular sensitivity, and retinal thickness measured by optical coherence tomography (OCT). Eyes were separated into Better or Worse Eye groups based on acuity at baseline. Repeatability coefficients were calculated for each parameter and jackknife resampling used to derive 95% confidence intervals (CIs). Results The threshold for statistically significant change in visual acuity ranged from three to eight letters. For ERG a-wave, an amplitude reduction greater than 56% would be considered significant. For other parameters, variabilities were lower in the Worse Eye group, likely a result of floor effects due to collapse of the schisis pockets and/or retinal atrophy. The criteria for significant change (Better/Worse Eye) for three important parameters were: ERG b/a-wave ratio (0.44/0.23), point wise sensitivity (10.4/7.0 dB), and central retinal thickness (31%/18%). Conclusions The 95% CI range for visual acuity, ERG, retinal sensitivity, and central retinal thickness relative to baseline are described for this cohort of participants with X-linked juvenile retinoschisis (XLRS). Translational Relevance A quantitative understanding of the variability of outcome measures is vital to establishing the safety and efficacy limits for therapeutic trials of XLRS patients. PMID:25346871

  10. 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

  11. Crystal Structure of Human Senescence Marker Protein 30; Insights Linking Structural, Enzymatic and Physiological Functions †,‡

    PubMed Central

    Chakraborti, Subhendu; Bahnson, Brian J.

    2010-01-01

    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 non-primate 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 Å. The protein has a 6-bladed β-propeller fold and it contains a single metal ion. Crystal structures have been solved with the metal site bound with either a Ca2+ or a Zn2+ 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 kcat preference of divalent cations in the order Zn2+ > Mn2+ > Ca2+ > Mg2+. Notably, the Ca2+ had a significantly higher value of Kd compared to the other metal ions tested (566, 82, 7 and 0.6 µm for Ca2+, Mg2+, Zn2+ and Mn2+, respectively), suggesting the Ca2+-bound form may be physiologically relevant for stressed cells with an elevated free calcium level. PMID:20329768

  12. Functional and structural characterization of the mammalian TREX-2 complex that links transcription with nuclear messenger RNA export

    PubMed Central

    Jani, Divyang; Lutz, Sheila; Hurt, Ed; Laskey, Ronald A.; Stewart, Murray; Wickramasinghe, Vihandha O.

    2012-01-01

    Export of messenger RNA (mRNA) from the nucleus to the cytoplasm is a critical step in the gene expression pathway of eukaryotic cells. Here, we report the functional and structural characterization of the mammalian TREX-2 complex and show how it links transcription/processing with nuclear mRNA export. Mammalian TREX-2 is based on a germinal-centre associated nuclear protein (GANP) scaffold to which ENY2, PCID2 and centrins bind and depletion of any of these components inhibits mRNA export. The crystal structure of the GANP:ENY2 complex shows that two ENY2 chains interact directly with GANP, but they have different orientations from those observed on yeast Sac3. GANP is required to recruit ENY2 to nuclear pore complexes (NPCs), but ENY2 is not necessary to recruit GANP, which requires both its CID and MCM3AP domains, together with nucleoporin Nup153. GANP and ENY2 associate with RNA polymerase II and inhibition of mRNA processing redistributes GANP from NPCs into nuclear foci indicating that mammalian TREX-2 is associated with transcription. Thus, we implicate TREX-2 as an integral component of the mammalian mRNA export machinery where it links transcription and nuclear export by facilitating the transfer of mature mRNPs from the nuclear interior to NPCs. PMID:22307388

  13. 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…

  14. 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…

  15. Corticolimbic structural alterations linked to health status and trait anxiety in functional neurological disorder.

    PubMed

    Perez, David L; Williams, Benjamin; Matin, Nassim; LaFrance, W Curt; Costumero-Ramos, Victor; Fricchione, Gregory L; Sepulcre, Jorge; Keshavan, Matcheri S; Dickerson, Bradford C

    2017-08-26

    Affective symptoms influence health status (health-related quality of life) in functional neurological disorder (FND), and the salience network is implicated in the pathophysiology of FND and mood/anxiety disorders. We hypothesised that self-reported health status and affective symptoms would map onto salience network regions and that patients with FND would show decreased insular volumes compared with controls. This voxel-based morphometry study investigated volumetric differences in 26 patients with FND (21 women, 5 men; mean age=40.3±11.5) compared with 27 healthy controls (22 women, 5 men; mean age=40.5±10.8). Post hoc analyses stratified patients with FND by mental and physical health scores (Short Form Health Survey-36). Within-group analyses investigated associations with mental health, physical health, trait anxiety and depression in patients with FND. There were no volumetric differences between the complete FND cohort and controls. In stratified analyses, however, patients with FND reporting the most severe physical health impairments showed reduced left anterior insular volume compared with controls. In within-group analyses, impaired mental health and elevated trait anxiety were associated with increased right amygdalar volumes in patients with FND. The relationship between amygdalar volume and mental health, driven by emotional well-being deficits and role limitations due to emotional problems, was independent of sensorimotor functional neurological symptom severity and motor FND subtype. In secondary within-group analyses, increased periaqueductal grey volume was associated with role limitations due to emotional problems. Impaired physical functioning correlated with decreased left anterior insular volumes. These findings support roles for several regions of the salience network in the pathophysiology of FND. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is

  16. Linking DNA polymerase theta structure and function in health and disease

    PubMed Central

    Beagan, Kelly; McVey, Mitch

    2015-01-01

    DNA Polymerase theta (Pol θ) is an error-prone A-family polymerase that is highly conserved among multicellular eukaryotes and plays multiple roles in DNA repair and the regulation of genome integrity. Studies conducted in several model organisms have shown that Pol θ can be utilized during DNA interstrand crosslink repair and during alternative end-joining repair of double-strand breaks. Recent genetic and biochemical studies have begun to elucidate the unique structural features of Pol θ that promote alternative end-joining repair. Importantly, Pol θ-dependent end joining appears to be important for overall genome stability, as it affects chromosome translocation formation in murine and human cell lines. Pol θ has also been suggested to act as a modifier of replication timing in human cells, though the mechanism of action remains unknown. Pol θ is highly upregulated in a number of human cancer types, which could indicate that mutagenic Pol θ-dependent end joining is used during cancer cell proliferation. Here we review the various roles of Pol θ across species and discuss how these roles may be relevant to cancer therapy. PMID:26514729

  17. Linking ocean biogeochemical cycles and ecosystem structure and function: results of the complex SWAMCO-4 model

    NASA Astrophysics Data System (ADS)

    Pasquer, Bénédicte; Laruelle, Goulven; Becquevort, Sylvie; Schoemann, Véronique; Goosse, Hugues; Lancelot, Christiane

    2005-01-01

    We present results obtained with SWAMCO-4, a complex model of the marine planktonic system calculating C, N, P, Si, Fe cycling within the upper ocean, the export production and the exchange of CO 2 between the ocean and atmosphere. The model, constrained by physical, chemical and biological (grazing, lysis) controls, explicitly details the dynamics of four relevant phytoplankton functional groups with respect to C, N, P, Si, Fe cycling and climate change. Those are diatoms, pico/nano phytoplankton, coccolithophorids, and Phaeocystis spp. whose growth regulation by light, temperature and nutrients has been obtained based on a comprehensive analysis of literature reviews on these taxonomic groups. The performance of SWAMCO-4 is first evaluated in a 1D physical frame throughout its cross application in provinces with contrasted key species dominance, export production, CO 2 air-sea fluxes and where biogeochemical time-series data are available for model initialisation and comparison of results. These are: (i) the ice-free Southern Ocean Time Series station KERFIX (50°40S, 68°E) for the period 1993-1994 (diatom-dominated); (ii) the sea-ice associated Ross Sea domain (Station S; 76°S, 180°W) of the Antarctic Environment and Southern Ocean Process Study AESOPS in 1996-1997 ( Phaeocystis-dominated); and (iii) the North Atlantic Bloom Experiment NABE (60°N, 20°W) in 1991 (coccolithophorids). We then explore and compare the ocean response to increased atmospheric CO 2 by running SWAMCO-4 at the different locations over the last decade. Results show that at all tested latitudes the prescribed increase of atmospheric CO 2 enhances the carbon uptake by the ocean. However, the amplitude of the predicted atmospheric CO 2 sinks displays large regional and interannual variations due to the actual meteorological forcing that drives the local hydrodynamics. This is particularly true in the marginal ice zone of the Ross Sea (AESOPS) where the magnitude of the predicted annual

  18. A functional-structural model of rice linking quantitative genetic information with morphological development and physiological processes.

    PubMed

    Xu, Lifeng; Henke, Michael; Zhu, Jun; Kurth, Winfried; Buck-Sorlin, Gerhard

    2011-04-01

    Although quantitative trait loci (QTL) analysis of yield-related traits for rice has developed rapidly, crop models using genotype information have been proposed only relatively recently. As a first step towards a generic genotype-phenotype model, we present here a three-dimensional functional-structural plant model (FSPM) of rice, in which some model parameters are controlled by functions describing the effect of main-effect and epistatic QTLs. The model simulates the growth and development of rice based on selected ecophysiological processes, such as photosynthesis (source process) and organ formation, growth and extension (sink processes). It was devised using GroIMP, an interactive modelling platform based on the Relational Growth Grammar formalism (RGG). RGG rules describe the course of organ initiation and extension resulting in final morphology. The link between the phenotype (as represented by the simulated rice plant) and the QTL genotype was implemented via a data interface between the rice FSPM and the QTLNetwork software, which computes predictions of QTLs from map data and measured trait data. Using plant height and grain yield, it is shown how QTL information for a given trait can be used in an FSPM, computing and visualizing the phenotypes of different lines of a mapping population. Furthermore, we demonstrate how modification of a particular trait feeds back on the entire plant phenotype via the physiological processes considered. We linked a rice FSPM to a quantitative genetic model, thereby employing QTL information to refine model parameters and visualizing the dynamics of development of the entire phenotype as a result of ecophysiological processes, including the trait(s) for which genetic information is available. Possibilities for further extension of the model, for example for the purposes of ideotype breeding, are discussed.

  19. Structure-Function Studies Link Class II Viral Fusogens with the Ancestral Gamete Fusion Protein HAP2.

    PubMed

    Pinello, Jennifer Fricke; Lai, Alex L; Millet, Jean K; Cassidy-Hanley, Donna; Freed, Jack H; Clark, Theodore G

    2017-03-06

    The conserved transmembrane protein, HAP2/GCS1, has been linked to fertility in a wide range of taxa and is hypothesized to be an ancient gamete fusogen. Using template-based structural homology modeling, we now show that the ectodomain of HAP2 orthologs from Tetrahymena thermophila and other species adopt a protein fold remarkably similar to the dengue virus E glycoprotein and related class II viral fusogens. To test the functional significance of this predicted structure, we developed a flow-cytometry-based assay that measures cytosolic exchange across the conjugation junction to rapidly probe the effects of HAP2 mutations in the Tetrahymena system. Using this assay, alterations to a region in and around a predicted "fusion loop" in T. thermophila HAP2 were found to abrogate membrane pore formation in mating cells. Consistent with this, a synthetic peptide corresponding to the HAP2 fusion loop was found to interact directly with model membranes in a variety of biophysical assays. These results raise interesting questions regarding the evolutionary relationships of class II membrane fusogens and harken back to a long-held argument that eukaryotic sex arose as the byproduct of selection for the horizontal transfer of a "selfish" genetic element from cell to cell via membrane fusion.

  20. Function and structure in social brain regions can link oxytocin-receptor genes with autistic social behavior.

    PubMed

    Yamasue, Hidenori

    2013-02-01

    Difficulties in appropriate social and communicative behaviors are the most prevalent and core symptoms of autism spectrum disorders (ASDs). Although recent intensive research has focused on the neurobiological background of these difficulties, many aspects of them were not yet elucidated. Recent studies have employed multimodal magnetic resonance imaging (MRI) indices as intermediate phenotypes of this behavioral phenotype to link candidate genes with the autistic social difficulty. As MRI indices, functional MRI (fMRI), structural MRI, and MR-spectroscopy have been examined in subjects with autism spectrum disorders. As candidate genes, this mini-review has much interest in oxytocin-receptor genes (OXTR), since recent studies have repeatedly reported their associations with normal variations in social cognition and behavior as well as with their extremes, autistic social dysfunction. Through previous increasing studies, medial prefrontal cortex, hypothalamus and amygdala have repeatedly been revealed as neural correlates of autistic social behavior by MRI multimodalities and their relationship to OXTR. For further development of this research area, this mini-review integrates recent accumulating evidence about human behavioral and neural correlates of OXTR.

  1. Tapping linked to function and structure in premanifest and symptomatic Huntington disease(e–Pub ahead of print)

    PubMed Central

    Bechtel, N.; Scahill, R.I.; Rosas, H.D.; Acharya, T.; van den Bogaard, S.J.A.; Jauffret, C.; Say, M.J.; Sturrock, A.; Johnson, H.; Onorato, C.E.; Salat, D.H.; Durr, A.; Leavitt, B.R.; Roos, R.A.C.; Landwehrmeyer, G.B.; Langbehn, D.R.; Stout, J.C.; Tabrizi, S.J.; Reilmann, R.

    2010-01-01

    Objective: Motor signs are functionally disabling features of Huntington disease. Characteristic motor signs define disease manifestation. Their severity and onset are assessed by the Total Motor Score of the Unified Huntington's Disease Rating Scale, a categorical scale limited by interrater variability and insensitivity in premanifest subjects. More objective, reliable, and precise measures are needed which permit clinical trials in premanifest populations. We hypothesized that motor deficits can be objectively quantified by force-transducer-based tapping and correlate with disease burden and brain atrophy. Methods: A total of 123 controls, 120 premanifest, and 123 early symptomatic gene carriers performed a speeded and a metronome tapping task in the multicenter study TRACK-HD. Total Motor Score, CAG repeat length, and MRIs were obtained. The premanifest group was subdivided into A and B, based on the proximity to estimated disease onset, the manifest group into stages 1 and 2, according to their Total Functional Capacity scores. Analyses were performed centrally and blinded. Results: Tapping variability distinguished between all groups and subgroups in both tasks and correlated with 1) disease burden, 2) clinical motor phenotype, 3) gray and white matter atrophy, and 4) cortical thinning. Speeded tapping was more sensitive to the detection of early changes. Conclusion: Tapping deficits are evident throughout manifest and premanifest stages. Deficits are more pronounced in later stages and correlate with clinical scores as well as regional brain atrophy, which implies a link between structure and function. The ability to track motor phenotype progression with force-transducer-based tapping measures will be tested prospectively in the TRACK-HD study. GLOSSARY CoV = coefficient of variation; DBS = disease burden score; Freq = frequency; HD = Huntington disease; ICV = intracranial volume; IOI = interonset interval; ΔIOI = deviation from interonset interval; IPI

  2. Linking catchment structure to hydrologic function: Implications of catchment topography for patterns of landscape hydrologic connectivity and stream flow dynamics

    NASA Astrophysics Data System (ADS)

    Jencso, K. G.; McGlynn, B. L.; Marshall, L. A.

    2010-12-01

    The relationship between catchment structure (topography and topology), stream network hydrologic connectivity, and runoff response remains poorly understood. Hillslope-riparian-stream (HRS) water table connectivity serves as the hydrologic linkage between a catchment’s uplands and the channel network and facilitates the transmission of water and solutes to streams. While there has been tremendous interest in the concept of hydrological connectivity to characterize catchments, there are relatively few studies that have quantified hydrologic connectivity at the stream network and catchment scales. Here, we examine how catchment topography influenced patterns of stream network HRS connectivity and resultant runoff dynamics across 11 nested headwater catchments in the Tenderfoot Creek Experimental Forest (TCEF), MT. This study extends the empirical findings of Jencso et al. (2009) who found a strong linear relationship (r2 = 0.92) between the upslope accumulated area (UAA) and annual duration of shallow ground water table connectivity observed across 24 HRS transects (146 groundwater recording wells) within the TCEF. We applied this relationship to the entire stream network to quantify the frequency distribution of stream network connectivity through time (as a function of UAA) and ascertain its relationship to catchment-scale runoff dynamics. Each catchment’s estimated connectivity duration curve (CDC) was highly related to its flow duration curve (FDC); albeit the rate of change of runoff with respect to stream network connectedness varied significantly across catchments. To ascertain potential reasons for these differences we compared the slope of each catchment’s CDC-FDC relationship (annual, peak, transition and baseflow periods) in multiple linear models against median values of common terrain indices and land cover-vegetation characteristics. Significant predictors (p<0.05) included the flow path distance to the creek (DFC), the flow path gradient to the

  3. Linking structural and functional connectivity in a simple runoff-runon model over soils with heterogeneous infiltrability

    NASA Astrophysics Data System (ADS)

    Harel, M.; Mouche, E.

    2012-12-01

    Runoff production on a hillslope during a rainfall event may be simplified as follows. Given a soil of constant infiltrability I, which is the maximum amount of water that the soil can infiltrate, and a constant rainfall intensity R, runoff is observed wherever R is greater than I. The infiltration rate equals the infiltrability where runoff is produced, R otherwise. When ponding time, topography, and overall spatial and temporal variations of physical parameters, such as R and I, are neglected, the runoff equation remains simple. In this study, we consider soils of spatially variable infiltrability. As runoff can re-infiltrate on down-slope areas of higher infiltrabilities (runon process), the resulting process is highly non-linear. The stationary runoff equation is: Qn+1 = max (Qn + (R - In)*Δx , 0) where Qn is the runoff arriving on pixel n of size Δx [L2/T], R and In the rainfall intensity and infiltrability on that same pixel [L/T]. The non-linearity is due to the dependence of infiltration on R and Qn, that is runon. This re-infiltration process generates patterns of runoff along the slope, patterns that organise and connect differently to each other depending on the rainfall intensity and the nature of the soil heterogeneity. In order to characterize the runoff patterns and their connectivity, we use the connectivity function defined by Allard (1993) in Geostatistics. Our aim is to assess, in a stochastic framework, the runoff organization on 1D and 2D slopes with random infiltrabilities (log-normal, exponential and bimodal distributions) by means of numerical simulations. Firstly, we show how runoff is produced and organized in patterns along a 2D slope according to the infiltrability distribution. We specifically illustrate and discuss the link between the statistical nature of the infiltrability and that of the flow-rate, with a special focus on the relations between the connectivities of both fields: the structural connectivity (infiltrability patterns

  4. In situ infrared spectroscopic and density-functional studies of the cross-linked structure of one-dimensional C{sub 60} polymer

    SciTech Connect

    Takashima, A.; Onoe, J.; Nishii, T.

    2010-08-15

    We have examined the infrared (IR) spectra of electron-beam (EB) irradiated C{sub 60} films, using in situ IR spectroscopy in the temperature range of 60-300 K. The irradiation-time evolution of the IR spectra shows that two highly intense new peaks finally appear around 565 and 1340 cm{sup -1} when the EB-induced C{sub 60} polymerization was saturated. To determine the cross-linked structure of the polymer explicitly, we have compared the IR spectra with theoretical spectra obtained from the cross-linked structure of all C{sub 120} stable isomers derived from the general Stone-Wales (GSW) rearrangement, using first-principles density-functional calculations. Since each C{sub 120} isomer has the same cross-linked structure as that of its corresponding one-dimensional (1D) C{sub 60} polymer, the IR modes obtained from the cross-linked structure of C{sub 120} are close to those obtained from the corresponding 1D polymer. Comparison between the experimental and theoretical IR spectra suggests that the 1D peanut-shaped C{sub 60} polymer has a cross-linked structure roughly similar to that of the P08 peanut-shaped C{sub 120} isomer.

  5. Linking microbial community structure and function to seasonal differences in soil moisture and temperature in a Chihuahuan desert grassland.

    PubMed

    Bell, Colin W; Acosta-Martinez, Veronica; McIntyre, Nancy E; Cox, Stephen; Tissue, David T; Zak, John C

    2009-11-01

    Global and regional climate models predict higher air temperature and less frequent, but larger precipitation events in arid regions within the next century. While many studies have addressed the impact of variable climate in arid ecosystems on plant growth and physiological responses, fewer studies have addressed soil microbial community responses to seasonal shifts in precipitation and temperature in arid ecosystems. This study examined the impact of a wet (2004), average (2005), and dry (2006) year on subsequent responses of soil microbial community structure, function, and linkages, as well as soil edaphic and nutrient characteristics in a mid-elevation desert grassland in the Chihuahuan Desert. Microbial community structure was classified as bacterial (Gram-negative, Gram-positive, and actinomycetes) and fungal (saprophytic fungi and arbuscular mycorrhiza) categories using (fatty acid methyl ester) techniques. Carbon substrate use and enzymic activity was used to characterize microbial community function annually and seasonally (summer and winter). The relationship between saprophytic fungal community structure and function remained consistent across season independent of the magnitude or frequency of precipitation within any given year. Carbon utilization by fungi in the cooler winter exceeded use in the warmer summer each year suggesting that soil temperature, rather than soil moisture, strongly influenced fungal carbon use and structure and function dynamics. The structure/function relationship for AM fungi and soil bacteria notably changed across season. Moreover, the abundance of Gram-positive bacteria was lower in the winter compared to Gram-negative bacteria. Bacterial carbon use, however, was highest in the summer and lower during the winter. Enzyme activities did not respond to either annual or seasonal differences in the magnitude or timing of precipitation. Specific structural components of the soil microbiota community became uncoupled from total

  6. 2D-RNA-coupling numbers: a new computational chemistry approach to link secondary structure topology with biological function.

    PubMed

    González-Díaz, Humberto; Agüero-Chapin, Guillermín; Varona, Javier; Molina, Reinaldo; Delogu, Giovanna; Santana, Lourdes; Uriarte, Eugenio; Podda, Gianni

    2007-04-30

    Methods for prediction of proteins, DNA, or RNA function and mapping it onto sequence often rely on bioinformatics alignment approach instead of chemical structure. Consequently, it is interesting to develop computational chemistry approaches based on molecular descriptors. In this sense, many researchers used sequence-coupling numbers and our group extended them to 2D proteins representations. However, no coupling numbers have been reported for 2D-RNA topology graphs, which are highly branched and contain useful information. Here, we use a computational chemistry scheme: (a) transforming sequences into RNA secondary structures, (b) defining and calculating new 2D-RNA-coupling numbers, (c) seek a structure-function model, and (d) map biological function onto the folded RNA. We studied as example 1-aminocyclopropane-1-carboxylic acid (ACC) oxidases known as ACO, which control fruit ripening having importance for biotechnology industry. First, we calculated tau(k)(2D-RNA) values to a set of 90-folded RNAs, including 28 transcripts of ACO and control sequences. Afterwards, we compared the classification performance of 10 different classifiers implemented in the software WEKA. In particular, the logistic equation ACO = 23.8 . tau(1)(2D-RNA) + 41.4 predicts ACOs with 98.9%, 98.0%, and 97.8% of accuracy in training, leave-one-out and 10-fold cross-validation, respectively. Afterwards, with this equation we predict ACO function to a sequence isolated in this work from Coffea arabica (GenBank accession DQ218452). The tau(1)(2D-RNA) also favorably compare with other descriptors. This equation allows us to map the codification of ACO activity on different mRNA topology features. The present computational-chemistry approach is general and could be extended to connect RNA secondary structure topology to other functions.

  7. The architecture of cross-hemispheric communication in the aging brain: linking behavior to functional and structural connectivity.

    PubMed

    Davis, Simon W; Kragel, James E; Madden, David J; Cabeza, Roberto

    2012-01-01

    Contralateral recruitment remains a controversial phenomenon in both the clinical and normative populations. To investigate the neural correlates of this phenomenon, we explored the tendency for older adults to recruit prefrontal cortex (PFC) regions contralateral to those most active in younger adults. Participants were scanned with diffusion tensor imaging and functional magnetic rresonance imaging during a lateralized word matching task (unilateral vs. bilateral). Cross-hemispheric communication was measured behaviorally as greater accuracy for bilateral than unilateral trials (bilateral processing advantage [BPA]) and at the neural level by functional and structural connectivity between contralateral PFC. Compared with the young, older adults exhibited 1) greater BPAs in the behavioral task, 2) greater compensatory activity in contralateral PFC during the bilateral condition, 3) greater functional connectivity between contralateral PFC during bilateral trials, and 4) a positive correlation between fractional anisotropy in the corpus callosum and both the BPA and the functional connectivity between contralateral PFC, indicating that older adults' ability to distribute processing across hemispheres is constrained by white matter integrity. These results clarify how older adults' ability to recruit extra regions in response to the demands of aging is mediated by existing structural architecture, and how this architecture engenders corresponding functional changes that allow subjects to meet those task demands.

  8. Linking Tropical Forest Function to Hydraulic Traits in a Size-Structured and Trait-Based Model

    NASA Astrophysics Data System (ADS)

    Christoffersen, B. O.; Gloor, E. U.; Fauset, S.; Fyllas, N.; Galbraith, D.; Baker, T. R.; Rowland, L.; Fisher, R.; Binks, O.; Mencuccini, M.; Malhi, Y.; Stahl, C.; Wagner, F. H.; Bonal, D.; da Costa, A. C. L.; Ferreira, L.; Meir, P.

    2014-12-01

    A major weakness of forest ecosystem models applied to Amazonia is their inability to capture the diversity of responses to changes in water availability commonly observed within and across forest communities, severely hampering efforts to predict the fate of Amazon forests under climate change. Such models often prescribe moisture sensitivity using heuristic response functions which are uniform across all individuals and lack important knowledge about trade-offs in hydraulic traits. We address this weakness by implementing a process representation of plant hydraulics into an individual- and trait-based model (Trait Forest Simulator; TFS) intended for application at discrete sites across Amazonia. The model represents a trade-off in the safety and efficiency of water conduction in xylem tissue through hydraulic traits, which then lead to variation in plant water use and growth dynamics. The model accounts for the buffering effects of leaf and stem capacitance on leaf water potential at short time scales, and cavitation-induced reductions in whole-plant conductance over longer periods of water stress. We explore multiple possible links between this hydraulic trait spectrum and other whole-plant traits, such as maximum photosynthetic capacity and wood density. The model is shown to greatly improve the diversity of tree response to seasonal changes in water availability as well as response to drought, as determined by comparison with sap flux and stem dendrometry measurements. Importantly, this individual- and trait-based framework provides a testbed for identifying both critical processes and functional traits needed for inclusion in coarse-scale Dynamic Global Vegetation Models, which will lead to reduced uncertainty in the future state of Amazon tropical forests.

  9. Equilibrium conformational ensemble of the intrinsically disordered peptide n16N: linking subdomain structures and function in nacre.

    PubMed

    Brown, Aaron H; Rodger, P Mark; Evans, John Spencer; Walsh, Tiffany R

    2014-12-08

    n16 is a framework protein family associated with biogenic mineral stabilization, thought to operate at three key interfaces in nacre: protein/β-chitin, protein/protein, and protein/CaCO3. The N-terminal half of this protein, n16N, is known to be active in conferring this mineral stabilization and organization. While some details relating to the stabilization and organization of the mineral are known, the molecular mechanisms that underpin these processes are not yet established. To provide these molecular-scale details, here we explore current hypotheses regarding the possible subdomain organization of n16N, as related to these three interfaces in nacre, by combining outcomes of Replica Exchange with Solute Tempering molecular dynamics simulations with NMR experiments, to investigate the conformational ensemble of n16N in solution. We verify that n16N lacks a well-defined secondary structure, both with and without the presence of Ca(2+) ions, as identified from previous experiments. Our data support the presence of three different, functional subdomains within n16N. Our results reveal that tyrosine, chiefly located in the center of the peptide, plays a multifunctional role in stabilizing conformations of n16N, for intrapeptide and possibly interpeptide interactions. Complementary NMR spectroscopy data confirm the participation of tyrosine in this stabilization. The C-terminal half of n16N, lacking in tyrosine and highly charged, shows substantive conformational diversity and is proposed as a likely site for nucleation of calcium carbonate. Finally, dominant structures from our predicted conformational ensemble suggest the presentation of key residues thought to be critical to the selective binding to β-chitin surfaces.

  10. New wrapped distribution via Richard link function

    NASA Astrophysics Data System (ADS)

    Demirelli, Arzu Ekinci; Gürcan, Mehmet

    2017-07-01

    In this paper, we investigate a new wrapped distribution obtained from Richard link function. In the literature, many probability distributions are used wrapped form via normal, Cauchy, etc.. In this point, the most important characteristic of the Richard link function is that the flexible. Because of this feature Richard link function is useful. But, the Richard link function does not have a distribution form and analytical solution of parameter estimation. In this study we examined properties of wrapped Richard distribution and we have sampled for ant data.

  11. Analysis of bacterial core communities in the central Baltic by comparative RNA-DNA-based fingerprinting provides links to structure-function relationships.

    PubMed

    Brettar, Ingrid; Christen, Richard; Höfle, Manfred G

    2012-01-01

    Understanding structure-function links of microbial communities is a central theme of microbial ecology since its beginning. To this end, we studied the spatial variability of the bacterioplankton community structure and composition across the central Baltic Sea at four stations, which were up to 450 km apart and at a depth profile representative for the central part (Gotland Deep, 235 m). Bacterial community structure was followed by 16S ribosomal RNA (rRNA)- and 16S rRNA gene-based fingerprints using single-strand conformation polymorphism (SSCP) electrophoresis. Species composition was determined by sequence analysis of SSCP bands. High similarities of the bacterioplankton communities across several hundred kilometers were observed in the surface water using RNA- and DNA-based fingerprints. In these surface communities, the RNA- and DNA-based fingerprints resulted in very different pattern, presumably indicating large difference between the active members of the community as represented by RNA-based fingerprints and the present members represented by the DNA-based fingerprints. This large discrepancy changed gradually over depth, resulting in highly similar RNA- and DNA-based fingerprints in the anoxic part of the water column below 130 m depth. A conceivable mechanism explaining this high similarity could be the reduced oxidative stress in the anoxic zone. The stable communities on the surface and in the anoxic zone indicate the strong influence of the hydrography on the bacterioplankton community structure. Comparative analysis of RNA- and DNA-based community structure provided criteria for the identification of the core community, its key members and their links to biogeochemical functions.

  12. Linking sediment structure, hydrological functioning and biogeochemical cycling in disturbed coastal saltmarshes and implications for vegetation development

    NASA Astrophysics Data System (ADS)

    Spencer, Kate; Harvey, Gemma; James, Tempest; Simon, Carr; Michelle, Morris

    2014-05-01

    Saltmarsh restoration undoubtedly provides environmental enhancement, with vegetation quickly re-establishing following the breach of sea walls and subsequent tidal inundation of previously defended areas. Yet evidence increasingly suggests that the restored saltmarshes do not have the same biological characteristics as their natural counterparts (Mossman et al. 2012) and this may be in part be due to physicochemical parameters at the site including anoxia and poor drainage. Hence, restored saltmarshes may not offer the range and quality of ecosystem services anticipated. These environments will have been 'disturbed' by previous land use and there is little understanding of the impacts of this disturbance on the wider hydrogeomorphic and biogeochemical functioning in restored saltmarshes and the implications for saltmarsh vegetation development. This study examines linkages between physical sediment characteristics, sediment structure (using X-ray microtomography), sub-surface hydrology (using pressure transducers and time series analysis), and sediment and porewater geochemistry (major and trace elements, major anions) in sediment cores collected from undisturbed saltmarshes and those restored by de-embankment. Sub-surface sediments in restored saltmarshes have lower organic matter content, lower moisture content and higher bulk density than undisturbed sites. Using X-ray tomography a clear horizon can be observed which separates relict agricultural soils at depth with less dense and structureless sediments deposited since de-embankment. Ratios of open to closed pore space suggest that while undisturbed saltmarshes have the highest porosity, restored saltmarshes have larger void spaces, but limited pore connectivity. Sub-surface hydrological response to tidal flooding was subdued in the restored compared to the undisturbed site, suggesting that porewater flow may be impeded. Time series analysis indicated that flow pathways differ in restored saltmarsh sediments

  13. 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

  14. Linking structure to function: The search for active sites in non-platinum group metal oxygen reduction reaction catalysts

    SciTech Connect

    Holby, Edward F.; Zelenay, Piotr

    2016-05-17

    Atomic-scale structures of oxygen reduction reaction (ORR) active sites in non-platinum group metal (non-PGM) catalysts, made from pyrolysis of carbon, nitrogen, and transition-metal (TM) precursors have been the subject of continuing discussion in the fuel cell electrocatalysis research community. We found that quantum chemical modeling is a path forward for understanding of these materials and how they catalyze the ORR. Here, we demonstrate through literature examples of how such modeling can be used to better understand non-PGM ORR active site relative stability and activity and how such efforts can also aid in the interpretation of experimental signatures produced by these materials.

  15. Linking structure to function: The search for active sites in non-platinum group metal oxygen reduction reaction catalysts

    SciTech Connect

    Holby, Edward F.; Zelenay, Piotr

    2016-05-17

    Atomic-scale structures of oxygen reduction reaction (ORR) active sites in non-platinum group metal (non-PGM) catalysts, made from pyrolysis of carbon, nitrogen, and transition-metal (TM) precursors have been the subject of continuing discussion in the fuel cell electrocatalysis research community. We found that quantum chemical modeling is a path forward for understanding of these materials and how they catalyze the ORR. Here, we demonstrate through literature examples of how such modeling can be used to better understand non-PGM ORR active site relative stability and activity and how such efforts can also aid in the interpretation of experimental signatures produced by these materials.

  16. Linking Tropical Forest Function to Hydraulic Traits in a Size-Structured and Trait-Based Model

    NASA Astrophysics Data System (ADS)

    Christoffersen, B. O.; Gloor, M.; Fauset, S.; Fyllas, N.; Galbraith, D.; Baker, T. R.; Rowland, L.; Fisher, R.; Binks, O.; Sevanto, S.; Xu, C.; Jansen, S.; Choat, B.; Mencuccini, M.; McDowell, N. G.; Meir, P.

    2015-12-01

    A major weakness of forest ecosystem models is their inability to capture the diversity of responses to changes in water availability, severely hampering efforts to predict the fate of tropical forests under climate change. Such models often prescribe moisture sensitivity using heuristic response functions that are uniform across all individuals and lack important knowledge about trade-offs in hydraulic traits. We address this weakness by implementing a process representation of plant hydraulics into an individual- and trait-based model (Trait Forest Simulator; TFS) intended for application at discrete sites where community-level distributions of stem and leaf trait spectra (wood density, leaf mass per area, leaf nitrogen and phosphorus content) are known. The model represents a trade-off in the safety and efficiency of water conduction in xylem tissue through hydraulic traits, while accounting for the counteracting effects of increasing hydraulic path length and xylem conduit taper on whole-plant hydraulic resistance with increasing tree size. Using existing trait databases and additional meta-analyses from the rich literature on tropical tree ecophysiology, we obtained all necessary hydraulic parameters associated with xylem conductivity, vulnerability curves, pressure-volume curves, and hydraulic architecture (e.g., leaf-to-sapwood area ratios) as a function of the aforementioned traits and tree size. Incorporating these relationships in the model greatly improved the diversity of tree response to seasonal changes in water availability as well as in response to drought, as determined by comparison with field observations and experiments. Importantly, this individual- and trait-based framework provides a testbed for identifying both critical processes and functional traits needed for inclusion in coarse-scale Dynamic Global Vegetation Models, which will lead to reduced uncertainty in the future state of tropical forests.

  17. Linking structure to function: The search for active sites in non-platinum group metal oxygen reduction reaction catalysts

    DOE PAGES

    Holby, Edward F.; Zelenay, Piotr

    2016-05-17

    Atomic-scale structures of oxygen reduction reaction (ORR) active sites in non-platinum group metal (non-PGM) catalysts, made from pyrolysis of carbon, nitrogen, and transition-metal (TM) precursors have been the subject of continuing discussion in the fuel cell electrocatalysis research community. We found that quantum chemical modeling is a path forward for understanding of these materials and how they catalyze the ORR. Here, we demonstrate through literature examples of how such modeling can be used to better understand non-PGM ORR active site relative stability and activity and how such efforts can also aid in the interpretation of experimental signatures produced by thesemore » materials.« less

  18. Patterns in benthic biodiversity link lake trophic status to structure and potential function of three large, deep lakes.

    PubMed

    Hayford, Barbara L; Caires, Andrea M; Chandra, Sudeep; Girdner, Scott F

    2015-01-01

    Relative to their scarcity, large, deep lakes support a large proportion of the world's freshwater species. This biodiversity is threatened by human development and is in need of conservation. Direct comparison of biodiversity is the basis of biological monitoring for conservation but is difficult to conduct between large, insular ecosystems. The objective of our study was to conduct such a comparison of benthic biodiversity between three of the world's largest lakes: Lake Tahoe, USA; Lake Hövsgöl, Mongolia; and Crater Lake, USA. We examined biodiversity of common benthic organism, the non-biting midges (Chironomidae) and determined lake trophic status using chironomid-based lake typology, tested whether community structure was similar between the three lakes despite geographic distance; and tested whether chironomid diversity would show significant variation within and between lakes. Typology analysis indicated that Lake Hövsgöl was ultra-oligotrophic, Crater Lake was oligotrophic, and Lake Tahoe was borderline oligotrophic/mesotrophic. These results were similar to traditional pelagic measures of lake trophic status for Lake Hövsgöl and Crater Lake but differed for Lake Tahoe, which has been designated as ultra-oligotrophic by traditional pelagic measures such as transparency found in the literature. Analysis of similarity showed that Lake Tahoe and Lake Hövsgöl chironomid communities were more similar to each other than either was to Crater Lake communities. Diversity varied between the three lakes and spatially within each lake. This research shows that chironomid communities from these large lakes were sensitive to trophic conditions. Chironomid communities were similar between the deep environments of Lake Hövsgöl and Lake Tahoe, indicating that chironomid communities from these lakes may be useful in comparing trophic state changes in large lakes. Spatial variation in Lake Tahoe's diversity is indicative of differential response of chironomid

  19. Patterns in Benthic Biodiversity Link Lake Trophic Status to Structure and Potential Function of Three Large, Deep Lakes

    PubMed Central

    Hayford, Barbara L.; Caires, Andrea M.; Chandra, Sudeep; Girdner, Scott F.

    2015-01-01

    Relative to their scarcity, large, deep lakes support a large proportion of the world’s freshwater species. This biodiversity is threatened by human development and is in need of conservation. Direct comparison of biodiversity is the basis of biological monitoring for conservation but is difficult to conduct between large, insular ecosystems. The objective of our study was to conduct such a comparison of benthic biodiversity between three of the world’s largest lakes: Lake Tahoe, USA; Lake Hövsgöl, Mongolia; and Crater Lake, USA. We examined biodiversity of common benthic organism, the non-biting midges (Chironomidae) and determined lake trophic status using chironomid-based lake typology, tested whether community structure was similar between the three lakes despite geographic distance; and tested whether chironomid diversity would show significant variation within and between lakes. Typology analysis indicated that Lake Hövsgöl was ultra-oligotrophic, Crater Lake was oligotrophic, and Lake Tahoe was borderline oligotrophic/mesotrophic. These results were similar to traditional pelagic measures of lake trophic status for Lake Hövsgöl and Crater Lake but differed for Lake Tahoe, which has been designated as ultra-oligotrophic by traditional pelagic measures such as transparency found in the literature. Analysis of similarity showed that Lake Tahoe and Lake Hövsgöl chironomid communities were more similar to each other than either was to Crater Lake communities. Diversity varied between the three lakes and spatially within each lake. This research shows that chironomid communities from these large lakes were sensitive to trophic conditions. Chironomid communities were similar between the deep environments of Lake Hövsgöl and Lake Tahoe, indicating that chironomid communities from these lakes may be useful in comparing trophic state changes in large lakes. Spatial variation in Lake Tahoe’s diversity is indicative of differential response of chironomid

  20. Glycosylation-deficient mutations in tissue-nonspecific alkaline phosphatase impair its structure and function and are linked to infantile hypophosphatasia.

    PubMed

    Komaru, Keiichi; Satou, Yasuhito; Al-Shawafi, Hiba A; Numa-Kinjoh, Natsuko; Sohda, Miwa; Oda, Kimimitsu

    2016-03-01

    Tissue-nonspecific alkaline phosphatase (TNSALP) is a membrane glycoprotein with a proposed role in bone mineralization. Indeed, mutations in TNSALP have been identified in patients with hypophosphatasia (HPP), a genetic disease characterized by hypomineralization of bone and teeth and a deficiency in serum ALP activity. TNSALP has five potential N-glycosylation sites at N140, N230, N271, N303 and N430 by standard nomenclature. A mutation at one of these sites, N430, was recently detected in a patient with infantile HPP. Using site-directed mutagenesis, we demonstrated that TNSALP has five N-glycans in transfected COS-1 cells and that individual single N-glycan deletion mutants of TNSALP retain the dimeric structure required for ALP activity, excluding the possibility that any single N-glycan plays a vital role in the structure and function of TNSALP. However, we found that TNSALP (N430Q) and TNSALP (N430E) mutants, but not a TNSALP (N430D) mutant, failed to form dimers. The TNSALP (N430S) mutant linked to infantile HPP was glycosylation-defective and unable to dimerise, similar to TNSALP (N430Q) and TNSALP (N430E) mutants; therefore, TNSALP (N430S) was established as a severe allele without strong ALP activity. By contrast to individual single N-glycan deletion mutants, TNSALP devoid of all five N-glycans was present to a much lesser extent than wild-type TNSALP in transfected cells, possibly reflecting its instability. A comprehensive analysis of a series of multiple N-glycan depletion mutants in TNSALP revealed that three N-glycans on N230, N271 and N303 were the minimal requirement for the structure and function of TNSALP and a prerequisite for its stable expression in a cell.

  1. Formation of higher-order nuclear Rad51 structures is functionally linked to p21 expression and protection from DNA damage-induced apoptosis.

    PubMed

    Raderschall, Elke; Bazarov, Alex; Cao, Jiangping; Lurz, Rudi; Smith, Avril; Mann, Wolfgang; Ropers, Hans-Hilger; Sedivy, John M; Golub, Efim I; Fritz, Eberhard; Haaf, Thomas

    2002-01-01

    After exposure of mammalian cells to DNA damage, the endogenous Rad51 recombination protein is concentrated in multiple discrete foci, which are thought to represent nuclear domains for recombinational DNA repair. Overexpressed Rad51 protein forms foci and higher-order nuclear structures, even in the absence of DNA damage, in cells that do not undergo DNA replication synthesis. This correlates with increased expression of the cyclin-dependent kinase (Cdk) inhibitor p21. Following DNA damage, constitutively Rad51-overexpressing cells show reduced numbers of DNA breaks and chromatid-type chromosome aberrations and a greater resistance to apoptosis. In contrast, Rad51 antisense inhibition reduces p21 protein levels and sensitizes cells to etoposide treatment. Downregulation of p21 inhibits Rad51 foci formation in both normal and Rad51-overexpressing cells. Collectively, our results show that Rad51 expression, Rad51 foci formation and p21 expression are interrelated, suggesting a functional link between mammalian Rad51 protein and p21-mediated cell cycle regulation. This mechanism may contribute to a highly effective recombinational DNA repair in cell cycle-arrested cells and protection against DNA damage-induced apoptosis.

  2. Structure-Property Relationships in Porous 3-D Nanostructures as a Function of Preparation Conditions: Isocyanate Cross-Linked Silica Aerogels

    NASA Technical Reports Server (NTRS)

    Meador, Mary Ann B.; Capadona, Lynn A.; McCorkle, Linda; Padadopoulos, Demetrios S.; Leventis, Nicholas

    2007-01-01

    Sol-gel derived silica aerogels are attractive candidates for many unique thermal, optical, catalytic, and chemical applications because of their low density and high mesoporosity. However, their inherent fragility has restricted use of aerogel monoliths to applications where they are not subject to any load. We have previously reported cross-linking the mesoporous silica structure of aerogels with di-isocyanates, styrenes or epoxies reacting with amine decorated silica surfaces. These approaches have been shown to significantly increase the strength of aerogels with only a small effect on density or porosity. Though density is a prime predictor of properties such as strength and thermal conductivity for aerogels, it is becoming clear from previous studies that varying the silica backbone and size of the polymer cross-link independently can give rise to combinations of properties which cannot be predicted from density alone. Herein, we examine the effects of four processing parameters for producing this type of polymer cross-linked aerogel on properties of the resulting monoliths. We focus on the results of C-13 CP-MAS NMR which gives insight to the size and structure of polymer cross-link present in the monoliths, and relates the size of the cross-links to microstructure, mechanical properties and other characteristics of the materials obtained.

  3. Structure-Property Relationships in Porous 3-D Nanostructures as a Function of Preparation Conditions: Isocyanate Cross-Linked Silica Aerogels

    NASA Technical Reports Server (NTRS)

    Meador, Mary Ann B.; Capadona, Lynn A.; McCorkle, Linda; Papadopoulos, Demetrios S.; Leventis, Nicholas

    2007-01-01

    Sol-gel derived silica aerogels are attractive candidates for many unique thermal, optical, catalytic, and chemical applications because of their low density and high mesoporosity. However, their inherent fragility has restricted use of aerogel monoliths to applications where they are not subject to any load. We have previously reported cross-linking the mesoporous silica structure of aerogels with di-isocyanates, styrenes or epoxies reacting with amine decorated silica surfaces. These approaches have been shown to significantly increase the strength of aerogels with only a small effect on density or porosity. Though density is a prime predictor of properties such as strength and thermal conductivity for aerogels, it is becoming clear from previous studies that varying the silica backbone and size of the polymer cross-link independently can give rise to combinations of properties which cannot be predicted from density alone. Herein, we examine the effects of four processing parameters for producing this type of polymer cross-linked aerogel on properties of the resulting monoliths. We focus on the results of 13C CP-MAS NMR which gives insight to the size and structure of polymer cross-link present in the monoliths, and relates the size of the cross-links to microstructure, mechanical properties and other characteristics of the materials obtained.

  4. Structure-Function Analysis of a Broad Specificity Populus trichocarpa Endo-β-glucanase Reveals an Evolutionary Link between Bacterial Licheninases and Plant XTH Gene Products*

    PubMed Central

    Eklöf, Jens M.; Shojania, Shaheen; Okon, Mark; McIntosh, Lawrence P.; Brumer, Harry

    2013-01-01

    The large xyloglucan endotransglycosylase/hydrolase (XTH) gene family continues to be the focus of much attention in studies of plant cell wall morphogenesis due to the unique catalytic functions of the enzymes it encodes. The XTH gene products compose a subfamily of glycoside hydrolase family 16 (GH16), which also comprises a broad range of microbial endoglucanases and endogalactanases, as well as yeast cell wall chitin/β-glucan transglycosylases. Previous whole-family phylogenetic analyses have suggested that the closest relatives to the XTH gene products are the bacterial licheninases (EC 3.2.1.73), which specifically hydrolyze linear mixed linkage β(1→3)/β(1→4)-glucans. In addition to their specificity for the highly branched xyloglucan polysaccharide, XTH gene products are distinguished from the licheninases and other GH16 enzyme subfamilies by significant active site loop alterations and a large C-terminal extension. Given these differences, the molecular evolution of the XTH gene products in GH16 has remained enigmatic. Here, we present the biochemical and structural analysis of a unique, mixed function endoglucanase from black cottonwood (Populus trichocarpa), which reveals a small, newly recognized subfamily of GH16 members intermediate between the bacterial licheninases and plant XTH gene products. We postulate that this clade comprises an important link in the evolution of the large plant XTH gene families from a putative microbial ancestor. As such, this analysis provides new insights into the diversification of GH16 and further unites the apparently disparate members of this important family of proteins. PMID:23572521

  5. Linking N2O emissions from biochar-amended soil to the structure and function of the N-cycling microbial community.

    PubMed

    Harter, Johannes; Krause, Hans-Martin; Schuettler, Stefanie; Ruser, Reiner; Fromme, Markus; Scholten, Thomas; Kappler, Andreas; Behrens, Sebastian

    2014-03-01

    Nitrous oxide (N2O) contributes 8% to global greenhouse gas emissions. Agricultural sources represent about 60% of anthropogenic N2O emissions. Most agricultural N2O emissions are due to increased fertilizer application. A considerable fraction of nitrogen fertilizers are converted to N2O by microbiological processes (that is, nitrification and denitrification). Soil amended with biochar (charcoal created by pyrolysis of biomass) has been demonstrated to increase crop yield, improve soil quality and affect greenhouse gas emissions, for example, reduce N2O emissions. Despite several studies on variations in the general microbial community structure due to soil biochar amendment, hitherto the specific role of the nitrogen cycling microbial community in mitigating soil N2O emissions has not been subject of systematic investigation. We performed a microcosm study with a water-saturated soil amended with different amounts (0%, 2% and 10% (w/w)) of high-temperature biochar. By quantifying the abundance and activity of functional marker genes of microbial nitrogen fixation (nifH), nitrification (amoA) and denitrification (nirK, nirS and nosZ) using quantitative PCR we found that biochar addition enhanced microbial nitrous oxide reduction and increased the abundance of microorganisms capable of N2-fixation. Soil biochar amendment increased the relative gene and transcript copy numbers of the nosZ-encoded bacterial N2O reductase, suggesting a mechanistic link to the observed reduction in N2O emissions. Our findings contribute to a better understanding of the impact of biochar on the nitrogen cycling microbial community and the consequences of soil biochar amendment for microbial nitrogen transformation processes and N2O emissions from soil.

  6. Linking N2O emissions from biochar-amended soil to the structure and function of the N-cycling microbial community

    PubMed Central

    Harter, Johannes; Krause, Hans-Martin; Schuettler, Stefanie; Ruser, Reiner; Fromme, Markus; Scholten, Thomas; Kappler, Andreas; Behrens, Sebastian

    2014-01-01

    Nitrous oxide (N2O) contributes 8% to global greenhouse gas emissions. Agricultural sources represent about 60% of anthropogenic N2O emissions. Most agricultural N2O emissions are due to increased fertilizer application. A considerable fraction of nitrogen fertilizers are converted to N2O by microbiological processes (that is, nitrification and denitrification). Soil amended with biochar (charcoal created by pyrolysis of biomass) has been demonstrated to increase crop yield, improve soil quality and affect greenhouse gas emissions, for example, reduce N2O emissions. Despite several studies on variations in the general microbial community structure due to soil biochar amendment, hitherto the specific role of the nitrogen cycling microbial community in mitigating soil N2O emissions has not been subject of systematic investigation. We performed a microcosm study with a water-saturated soil amended with different amounts (0%, 2% and 10% (w/w)) of high-temperature biochar. By quantifying the abundance and activity of functional marker genes of microbial nitrogen fixation (nifH), nitrification (amoA) and denitrification (nirK, nirS and nosZ) using quantitative PCR we found that biochar addition enhanced microbial nitrous oxide reduction and increased the abundance of microorganisms capable of N2-fixation. Soil biochar amendment increased the relative gene and transcript copy numbers of the nosZ-encoded bacterial N2O reductase, suggesting a mechanistic link to the observed reduction in N2O emissions. Our findings contribute to a better understanding of the impact of biochar on the nitrogen cycling microbial community and the consequences of soil biochar amendment for microbial nitrogen transformation processes and N2O emissions from soil. PMID:24067258

  7. Transfer functions for a single flexible link

    SciTech Connect

    Wang, D. ); Vidyasagar, M. )

    1991-10-01

    This article examines some issues in the transfer function modeling of a single flexible link. Using the assumed-modes approach to represent the elastic deformation, one can find the transfer function between the torque input and the net tip deflection. It is shown here that when the number of modes is increased for more accurate modeling, the relative degree of the transfer function becomes ill defined. This can greatly affect the performance of a controller designed using this model. It is then shown that this problem occurs regardless of the method used to represent the elastic deformation. An alternate modeling approach is proposed that used the rigid body deformations minus the elastic deformations as the output. This solves this problem and results in a transfer function with a well-defined relative degree of two. Simulation results are presented that illustrate the advantages of using the proposed alternate transfer function.

  8. Cross-linked structure of network evolution

    SciTech Connect

    Bassett, Danielle S.; Wymbs, Nicholas F.; Grafton, Scott T.; Porter, Mason A.; Mucha, Peter J.

    2014-03-15

    We study the temporal co-variation of network co-evolution via the cross-link structure of networks, for which we take advantage of the formalism of hypergraphs to map cross-link structures back to network nodes. We investigate two sets of temporal network data in detail. In a network of coupled nonlinear oscillators, hyperedges that consist of network edges with temporally co-varying weights uncover the driving co-evolution patterns of edge weight dynamics both within and between oscillator communities. In the human brain, networks that represent temporal changes in brain activity during learning exhibit early co-evolution that then settles down with practice. Subsequent decreases in hyperedge size are consistent with emergence of an autonomous subgraph whose dynamics no longer depends on other parts of the network. Our results on real and synthetic networks give a poignant demonstration of the ability of cross-link structure to uncover unexpected co-evolution attributes in both real and synthetic dynamical systems. This, in turn, illustrates the utility of analyzing cross-links for investigating the structure of temporal networks.

  9. Cross-linked structure of network evolution

    NASA Astrophysics Data System (ADS)

    Bassett, Danielle S.; Wymbs, Nicholas F.; Porter, Mason A.; Mucha, Peter J.; Grafton, Scott T.

    2014-03-01

    We study the temporal co-variation of network co-evolution via the cross-link structure of networks, for which we take advantage of the formalism of hypergraphs to map cross-link structures back to network nodes. We investigate two sets of temporal network data in detail. In a network of coupled nonlinear oscillators, hyperedges that consist of network edges with temporally co-varying weights uncover the driving co-evolution patterns of edge weight dynamics both within and between oscillator communities. In the human brain, networks that represent temporal changes in brain activity during learning exhibit early co-evolution that then settles down with practice. Subsequent decreases in hyperedge size are consistent with emergence of an autonomous subgraph whose dynamics no longer depends on other parts of the network. Our results on real and synthetic networks give a poignant demonstration of the ability of cross-link structure to uncover unexpected co-evolution attributes in both real and synthetic dynamical systems. This, in turn, illustrates the utility of analyzing cross-links for investigating the structure of temporal networks.

  10. Photon structure function - theory

    SciTech Connect

    Bardeen, W.A.

    1984-12-01

    The theoretical status of the photon structure function is reviewed. Particular attention is paid to the hadronic mixing problem and the ability of perturbative QCD to make definitive predictions for the photon structure function. 11 references.

  11. Linking the solution viscosity of an IgG2 monoclonal antibody to its structure as a function of pH and temperature.

    PubMed

    Cheng, Weiqiang; Joshi, Sangeeta B; Jain, Nishant Kumar; He, Feng; Kerwin, Bruce A; Volkin, David B; Middaugh, C Russell

    2013-12-01

    Although the viscosity of concentrated antibody solutions has been the focus of many recent studies, less attention has been concentrated on how changes in protein structure impact viscosity. This study examines viscosity profiles of an immunoglobulin G (IgG) 2 monoclonal antibody at 150 mg/mL as a function of temperature and pH. Although the structure of the antibody at pH 4.0-7.0 was comparable at lower temperatures as measured by second derivative UV absorbance and Fourier transform infrared spectroscopy, differences in 8-anilino-1-naphthalene sulfonate (ANS) fluorescence intensity indicated small structural alterations as a function of pH. Below the structural transition onset temperature, the viscosity profiles were pH dependent and linearly correlated with fluorescence intensity, and followed semilogarithmic behavior as a function of temperature. The transitions of the viscosity profiles correlated well with the major structure transitions at a protein concentration of 150 mg/mL. The viscosity correlated particularly well with ANS fluorescence intensity at 0.2 mg/mL below and above the structural transition temperatures. These results suggest: (1) ANS can be an important measure of the overall structure and (2) hydrophobic interactions and charge-charge interactions are the two major physical factors that contribute collectively to the high viscosity of concentrated IgG solutions.

  12. A refined model for the TSG-6 link module in complex with hyaluronan: use of defined oligosaccharides to probe structure and function.

    PubMed

    Higman, Victoria A; Briggs, David C; Mahoney, David J; Blundell, Charles D; Sattelle, Benedict M; Dyer, Douglas P; Green, Dixy E; DeAngelis, Paul L; Almond, Andrew; Milner, Caroline M; Day, Anthony J

    2014-02-28

    Tumor necrosis factor-stimulated gene-6 (TSG-6) is an inflammation-associated hyaluronan (HA)-binding protein that contributes to remodeling of HA-rich extracellular matrices during inflammatory processes and ovulation. The HA-binding domain of TSG-6 consists solely of a Link module, making it a prototypical member of the superfamily of proteins that interacts with this high molecular weight polysaccharide composed of repeating disaccharides of D-glucuronic acid and N-acetyl-D-glucosamine (GlcNAc). Previously we modeled a complex of the TSG-6 Link module in association with an HA octasaccharide based on the structure of the domain in its HA-bound conformation. Here we have generated a refined model for a HA/Link module complex using novel restraints identified from NMR spectroscopy of the protein in the presence of 10 distinct HA oligosaccharides (from 4- to 8-mers); the model was then tested using unique sugar reagents, i.e. chondroitin/HA hybrid oligomers and an octasaccharide in which a single sugar ring was (13)C-labeled. The HA chain was found to make more extensive contacts with the TSG-6 surface than thought previously, such that a D-glucuronic acid ring makes stacking and ionic interactions with a histidine and lysine, respectively. Importantly, this causes the HA to bend around two faces of the Link module (resembling the way that HA binds to CD44), potentially providing a mechanism for how TSG-6 can reorganize HA during inflammation. However, the HA-binding site defined here may not play a role in TSG-6-mediated transfer of heavy chains from inter-α-inhibitor onto HA, a process known to be essential for ovulation.

  13. Formaldehyde cross-linking and structural proteomics: Bridging the gap.

    PubMed

    Srinivasa, Savita; Ding, Xuan; Kast, Juergen

    2015-11-01

    Proteins are dynamic entities constantly moving and altering their structures based on their functions and interactions inside and outside the cell. Formaldehyde cross-linking combined with mass spectrometry can accurately capture interactions of these rapidly changing biomolecules while maintaining their physiological surroundings. Even with its numerous established uses in biology and compatibility with mass spectrometry, formaldehyde has not yet been applied in structural proteomics. However, formaldehyde cross-linking is moving toward analyzing tertiary structure, which conventional cross-linkers have already accomplished. The purpose of this review is to describe the potential of formaldehyde cross-linking in structural proteomics by highlighting its applications, characteristics and current status in the field. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Automatic Restructuring of Linked Data Structures

    NASA Astrophysics Data System (ADS)

    van der Spek, Harmen L. A.; Holm, C. W. Mattias; Wijshoff, Harry A. G.

    The memory subsystem is one of the major performance bottlenecks in modern computer systems. While much effort is spent on the optimization of codes which access data regularly, not all codes will do so. Programs using pointer linked data structures are notorious for producing such so called irregular memory access patterns. In this paper, we present a compilation and run-time framework that enables fully automatic restructuring of pointer-linked data structures for type-unsafe languages, such as C. The restructuring framework is based on run-time restructuring using run-time trace information. The compiler transformation chain first identifies disjoint data structures that are stored in type-homogeneous memory pools. Access to these pools is traced and from these run-time traces, a permutation vector is derived. The memory pool is restructured at run-time using this permutation, after which all pointers (both stack and heap) that refer to the restructured pool must be updated. While the run-time tracing incurs a considerable overhead, we show that restructuring pointer-linked data structures can yield substantial speedups and that in general, the incurred overhead is compensated for by the performance improvements.

  15. Dynamic Links between Memory and Functional Limitations in Old Age: Longitudinal Evidence for Age-Based Structural Dynamics from the AHEAD Study

    PubMed Central

    Infurna, Frank J.; Gerstorf, Denis; Ryan, Lindsay H.; Smith, Jacqui

    2012-01-01

    This study examined competing substantive hypotheses about dynamic (i.e., time-ordered) links between memory and functional limitations in old age. We applied the Bivariate Dual Change Score Model to 13-year longitudinal data from the Asset and Health Dynamics Among the Oldest Old Study (AHEAD; N = 6,990; ages 70 – 95). Results revealed that better memory predicted shallower increases in functional limitations. Little evidence was found for the opposite direction that functional limitations predict ensuing changes in memory. Spline models indicated that dynamic associations between memory and functional limitations were substantively similar between participants aged 70–79 and those aged 80–95. Potential covariates (gender, education, health conditions, and depressive symptoms) did not account for these differential lead–lag associations. Applying a multivariate approach, our results suggest that late-life developments in two key components of successful aging are intrinsically interrelated. Our discussion focuses on possible mechanisms why cognitive functioning may serve as a source of age-related changes in health both among the young-old and the old-old. PMID:21480716

  16. Polyimide Aerogels with Three-Dimensional Cross-Linked Structure

    NASA Technical Reports Server (NTRS)

    Panek, John

    2010-01-01

    Polyimide aerogels with three-dimensional cross-linked structure are made using linear oligomeric segments of polyimide, and linked with one of the following into a 3D structure: trifunctional aliphatic or aromatic amines, latent reactive end caps such as nadic anhydride or phenylethynylphenyl amine, and silica or silsesquioxane cage structures decorated with amine. Drying the gels supercritically maintains the solid structure of the gel, creating a polyimide aerogel with improved mechanical properties over linear polyimide aerogels. Lightweight, low-density structures are desired for acoustic and thermal insulation for aerospace structures, habitats, astronaut equipment, and aeronautic applications. Aerogels are a unique material for providing such properties because of their extremely low density and small pore sizes. However, plain silica aerogels are brittle. Reinforcing the aerogel structure with a polymer (X-Aerogel) provides vast improvements in strength while maintaining low density and pore structure. However, degradation of polymers used in cross-linking tends to limit use temperatures to below 150 C. Organic aerogels made from linear polyimide have been demonstrated, but gels shrink substantially during supercritical fluid extraction and may have lower use temperature due to lower glass transition temperatures. The purpose of this innovation is to raise the glass transition temperature of all organic polyimide aerogel by use of tri-, tetra-, or poly-functional units in the structure to create a 3D covalently bonded network. Such cross-linked polyimides typically have higher glass transition temperatures in excess of 300 400 C. In addition, the reinforcement provided by a 3D network should improve mechanical stability, and prevent shrinkage on supercritical fluid extraction. The use of tri-functional aromatic or aliphatic amine groups in the polyimide backbone will provide such a 3D structure.

  17. Using ecological production functions to link ecological ...

    EPA Pesticide Factsheets

    Ecological production functions (EPFs) link ecosystems, stressors, and management actions to ecosystem services (ES) production. Although EPFs are acknowledged as being essential to improve environmental management, their use in ecological risk assessment has received relatively little attention. Ecological production functions may be defined as usable expressions (i.e., models) of the processes by which ecosystems produce ES, often including external influences on those processes. We identify key attributes of EPFs and discuss both actual and idealized examples of their use to inform decision making. Whenever possible, EPFs should estimate final, rather than intermediate, ES. Although various types of EPFs have been developed, we suggest that EPFs are more useful for decision making if they quantify ES outcomes, respond to ecosystem condition, respond to stressor levels or management scenarios, reflect ecological complexity, rely on data with broad coverage, have performed well previously, are practical to use, and are open and transparent. In an example using pesticides, we illustrate how EPFs with these attributes could enable the inclusion of ES in ecological risk assessment. The biggest challenges to ES inclusion are limited data sets that are easily adapted for use in modeling EPFs and generally poor understanding of linkages among ecological components and the processes that ultimately deliver the ES. We conclude by advocating for the incorporation into E

  18. Using ecological production functions to link ecological ...

    EPA Pesticide Factsheets

    Ecological production functions (EPFs) link ecosystems, stressors, and management actions to ecosystem services (ES) production. Although EPFs are acknowledged as being essential to improve environmental management, their use in ecological risk assessment has received relatively little attention. Ecological production functions may be defined as usable expressions (i.e., models) of the processes by which ecosystems produce ES, often including external influences on those processes. We identify key attributes of EPFs and discuss both actual and idealized examples of their use to inform decision making. Whenever possible, EPFs should estimate final, rather than intermediate, ES. Although various types of EPFs have been developed, we suggest that EPFs are more useful for decision making if they quantify ES outcomes, respond to ecosystem condition, respond to stressor levels or management scenarios, reflect ecological complexity, rely on data with broad coverage, have performed well previously, are practical to use, and are open and transparent. In an example using pesticides, we illustrate how EPFs with these attributes could enable the inclusion of ES in ecological risk assessment. The biggest challenges to ES inclusion are limited data sets that are easily adapted for use in modeling EPFs and generally poor understanding of linkages among ecological components and the processes that ultimately deliver the ES. We conclude by advocating for the incorporation into E

  19. APP Function and Lipids: A Bidirectional Link.

    PubMed

    Grimm, Marcus O W; Mett, Janine; Grimm, Heike S; Hartmann, Tobias

    2017-01-01

    Extracellular neuritic plaques, composed of aggregated amyloid-β (Aβ) peptides, are one of the major histopathological hallmarks of Alzheimer's disease (AD), a progressive, irreversible neurodegenerative disorder and the most common cause of dementia in the elderly. One of the most prominent risk factor for sporadic AD, carrying one or two aberrant copies of the apolipoprotein E (ApoE) ε4 alleles, closely links AD to lipids. Further, several lipid classes and fatty acids have been reported to be changed in the brain of AD-affected individuals. Interestingly, the observed lipid changes in the brain seem not only to be a consequence of the disease but also modulate Aβ generation. In line with these observations, protective lipids being able to decrease Aβ generation and also potential negative lipids in respect to AD were identified. Mechanistically, Aβ peptides are generated by sequential proteolytic processing of the amyloid precursor protein (APP) by β- and γ-secretase. The α-secretase appears to compete with β-secretase for the initial cleavage of APP, preventing Aβ production. All APP-cleaving secretases as well as APP are transmembrane proteins, further illustrating the impact of lipids on Aβ generation. Beside the pathological impact of Aβ, accumulating evidence suggests that Aβ and the APP intracellular domain (AICD) play an important role in regulating lipid homeostasis, either by direct effects or by affecting gene expression or protein stability of enzymes involved in the de novo synthesis of different lipid classes. This review summarizes the current literature addressing the complex bidirectional link between lipids and AD and APP processing including lipid alterations found in AD post mortem brains, lipids that alter APP processing and the physiological functions of Aβ and AICD in the regulation of several lipid metabolism pathways.

  20. APP Function and Lipids: A Bidirectional Link

    PubMed Central

    Grimm, Marcus O. W.; Mett, Janine; Grimm, Heike S.; Hartmann, Tobias

    2017-01-01

    Extracellular neuritic plaques, composed of aggregated amyloid-β (Aβ) peptides, are one of the major histopathological hallmarks of Alzheimer’s disease (AD), a progressive, irreversible neurodegenerative disorder and the most common cause of dementia in the elderly. One of the most prominent risk factor for sporadic AD, carrying one or two aberrant copies of the apolipoprotein E (ApoE) ε4 alleles, closely links AD to lipids. Further, several lipid classes and fatty acids have been reported to be changed in the brain of AD-affected individuals. Interestingly, the observed lipid changes in the brain seem not only to be a consequence of the disease but also modulate Aβ generation. In line with these observations, protective lipids being able to decrease Aβ generation and also potential negative lipids in respect to AD were identified. Mechanistically, Aβ peptides are generated by sequential proteolytic processing of the amyloid precursor protein (APP) by β- and γ-secretase. The α-secretase appears to compete with β-secretase for the initial cleavage of APP, preventing Aβ production. All APP-cleaving secretases as well as APP are transmembrane proteins, further illustrating the impact of lipids on Aβ generation. Beside the pathological impact of Aβ, accumulating evidence suggests that Aβ and the APP intracellular domain (AICD) play an important role in regulating lipid homeostasis, either by direct effects or by affecting gene expression or protein stability of enzymes involved in the de novo synthesis of different lipid classes. This review summarizes the current literature addressing the complex bidirectional link between lipids and AD and APP processing including lipid alterations found in AD post mortem brains, lipids that alter APP processing and the physiological functions of Aβ and AICD in the regulation of several lipid metabolism pathways. PMID:28344547

  1. Functional and Structural Analyses of CYP1B1 Variants Linked to Congenital and Adult-Onset Glaucoma to Investigate the Molecular Basis of These Diseases

    PubMed Central

    Chakrabarti, Saikat; Ray, Kunal

    2016-01-01

    Glaucoma, the leading cause of irreversible blindness, appears in various forms. Mutations in CYP1B1 result in primary congenital glaucoma (PCG) by an autosomal recessive mode of inheritance while it acts as a modifier locus for primary open angle glaucoma (POAG). We investigated the molecular basis of the variable phenotypes resulting from the defects in CYP1B1 by using subclones of 23 CYP1B1 mutants reported in glaucoma patients, in a cell based system by measuring the dual activity of the enzyme to metabolize both retinol and 17β-estradiol. Most variants linked to POAG showed low steroid metabolism while null or very high retinol metabolism was observed in variants identified in PCG. We examined the translational turnover rates of mutant proteins after the addition of cycloheximide and observed that the levels of enzyme activity mostly corroborated the translational turnover rate. We performed extensive normal mode analysis and molecular-dynamics-simulations-based structural analyses and observed significant variation of fluctuation in certain segmental parts of the mutant proteins, especially at the B-C and F-G loops, which were previously shown to affect the dynamic behavior and ligand entry/exit properties of the cytochrome P450 family of proteins. Our molecular study corroborates the structural analysis, and suggests that the pathologic state of the carrier of CYP1B1 mutations is determined by the allelic state of the gene. To our knowledge, this is the first attempt to dissect biological activities of CYP1B1 for correlation with congenital and adult onset glaucomas. PMID:27243976

  2. Chip-SIP: Stable Isotope Probing of RNA combining phylogenetic microarrays and Secondary Ion Mass Spectrometry (NanoSIMS) to link structure and function in microbial systems (Invited)

    NASA Astrophysics Data System (ADS)

    Mayali, X.; Weber, P. K.; Mabery, S.; Dekas, A.; Pett-Ridge, J.

    2013-12-01

    A primary goal of microbial ecology is to understand the biogeochemical role of individual microbial taxa in the environment. Our approach to tackle this challenge (Chip-SIP) involves the combination of high-density phylogenetic microarrays ('chips') and Stable Isotope Probing (SIP) to directly link identity and function. Microbial communities are incubated in the presence of substrate(s) enriched in 13C or 15N, RNA is extracted and hybridized onto a microarray synthesized on a conductive surface, and the array is analyzed with a NanoSIMS imaging mass spectrometer to quantify isotopic enrichment of individual probes. After testing the method with mixtures of stable isotope labeled laboratory isolates, we have investigated organic and inorganic carbon and nitrogen incorporation by microbial taxa in various ecosystems including San Francisco Bay, the coastal Pacific Ocean, California soils, and the hindguts of wood-eating beetles. We will summarize the methodology, describe the types of questions it has allowed us to investigate, and discuss some testable hypotheses about biogeochemical cycling in various environments that can benefit from this approach.

  3. Chromosome structure and function

    SciTech Connect

    Risley, M.S.

    1986-01-01

    This book presents topics in chromosome structure and function. Topics covered include: the structure of interphase chromatin; chromatin structure, gene expression and differentiation; organization of mitotic chromosomes; organization of meiotic chromosomes and synaptonimal complexes; the lampbrush chromsome of animal oocytes; dosage compensation in mammals: x chromosome inactivation; and polytene chromosomes.

  4. Surface-Based fMRI-Driven Diffusion Tractography in the Presence of Significant Brain Pathology: A Study Linking Structure and Function in Cerebral Palsy

    PubMed Central

    Cunnington, Ross; Boyd, Roslyn N.; Rose, Stephen E.

    2016-01-01

    Diffusion MRI (dMRI) tractography analyses are difficult to perform in the presence of brain pathology. Automated methods that rely on cortical parcellation for structural connectivity studies often fail, while manually defining regions is extremely time consuming and can introduce human error. Both methods also make assumptions about structure-function relationships that may not hold after cortical reorganisation. Seeding tractography with functional-MRI (fMRI) activation is an emerging method that reduces these confounds, but inherent smoothing of fMRI signal may result in the inclusion of irrelevant pathways. This paper describes a novel fMRI-seeded dMRI-analysis pipeline based on surface-meshes that reduces these issues and utilises machine-learning to generate task specific white matter pathways, minimising the requirement for manually-drawn ROIs. We directly compared this new strategy to a standard voxelwise fMRI-dMRI approach, by investigating correlations between clinical scores and dMRI metrics of thalamocortical and corticomotor tracts in 31 children with unilateral cerebral palsy. The surface-based approach successfully processed more participants (87%) than the voxel-based approach (65%), and provided significantly more-coherent tractography. Significant correlations between dMRI metrics and five clinical scores of function were found for the more superior regions of these tracts. These significant correlations were stronger and more frequently found with the surface-based method (15/20 investigated were significant; R2 = 0.43–0.73) than the voxelwise analysis (2 sig. correlations; 0.38 & 0.49). More restricted fMRI signal, better-constrained tractography, and the novel track-classification method all appeared to contribute toward these differences. PMID:27487011

  5. Linking N2O emissions from biochar-amended soil to the structure and function of the N-cycling microbial community

    NASA Astrophysics Data System (ADS)

    Harter, Johannes; Krause, Hans-Martin; Schuettler, Stefanie; Ruser, Reiner; Fromme, Markus; Scholten, Thomas; Kappler, Andreas; Behrens, Sebastian

    2014-05-01

    Nitrous oxide (N2O) contributes 8% to global greenhouse gas emissions. Agricultural sources represent about 60% of anthropogenic N2O emissions. Most agricultural N2O emissions are due to increased fertilizer application. A considerable fraction of nitrogen fertilizers are converted to N2O by microbially-mediated processes. Soil amended with biochar has been demonstrated to reduce N2O emissions in the field and in laboratory experiments. Although N2O emission mitigation following soil biochar amendment has been reported frequently the underlying processes and specific role of the nitrogen cycling microbial community in decreasing soil N2O emissions has not been subject of systematic investigation. To investigate the impact of biochar on the microbial community of nitrogen-transforming microorganisms we performed a microcosm study with arable soil amended with different amounts (0%, 2% and 10% (w/w)) of high-temperature wood derived biochar. By quantifying the abundance and activity of functional marker genes of microbial nitrogen fixation (nifH), nitrification (amoA) and denitrification (nirK, nirS and nosZ) using quantitative real-time PCR we found that biochar addition enhanced microbial nitrous oxide reduction and increased the abundance of microorganisms capable of N2-fixation. Soil biochar amendment increased the relative gene and transcript copy numbers of the nosZ-encoded bacterial N2O reductase, suggesting a mechanistic link to the observed reduction in N2O emissions. Our findings contribute to a better understanding of the impact of biochar on the nitrogen cycling microbial community and the consequences of soil biochar amendment for microbial nitrogen transformation processes and N2O emissions from soil.

  6. 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,…

  7. Molecular Structures of Isolevuglandin-Protein Cross-Links.

    PubMed

    Bi, Wenzhao; Jang, Geeng-Fu; Zhang, Lei; Crabb, John W; Laird, James; Linetsky, Mikhail; Salomon, Robert G

    2016-10-17

    Isolevuglandins (isoLGs) are stereo and structurally isomeric γ-ketoaldehydes produced through free radical-induced oxidation of arachidonates. Some isoLG isomers are also generated through enzymatic cyclooxygenation. Post-translational modification of proteins by isoLGs is associated with loss-of-function, cross-linking and aggregation. We now report that a low level of modification by one or two molecules of isoLG has a profound effect on the activity of a multi subunit protease, calpain-1. Modification of one or two key lysyl residues apparently suffices to abolish catalytic activity. Covalent modification of calpain-1 led to intersubunit cross-linking. Hetero- and homo-oligomers of the catalytic and regulatory subunits of calpain-1 were detected by SDS-PAGE with Western blotting. N-Acetyl-glycyl-lysine methyl ester and β-amyloid(11-17) peptide EVHHQKL were used as models for characterizing the cross-linking of protein lysyl residues resulting from adduction of iso[4]LGE2. Aminal, bispyrrole, and trispyrrole cross-links of these two peptides were identified and fully characterized by mass spectrometry. Aminal and bispyrrole dimers were both detected. Furthermore, a complex mixture of derivatives of the bispyrrole cross-link containing one or more additional atoms of oxygen was found. Interesting differences are evident in the predominant cross-link type generated in the reaction of iso[4]LGE2 with these peptides. More aminal cross-links versus bispyrrole are formed during the reaction of the dipeptide with iso[4]LGE2. In contrast, more bispyrrole versus aminal cross-links are formed during the reaction of EVHHQKL with iso[4]LGE2. It is tempting to speculate that the EVHHQKL peptide-pyrrole modification forms noncovalent aggregates that favor the production of covalent bispyrrole cross-links because β-amyloid(11-17) tends to spontaneously oligomerize.

  8. The Neutron Structure Function

    NASA Astrophysics Data System (ADS)

    Holt, Roy

    2013-10-01

    Knowledge of the neutron structure function is important for testing models of the nucleon, for a complete understanding of deep inelastic scattering (DIS) from nuclei, and for high energy experiments. As there exist no free neutron targets, neutron structure functions have been determined from deep inelastic scattering from the deuteron. Unfortunately, the short-range part of the deuteron wave function becomes important in extracting the neutron structure function at very high Bjorken x. New methods have been devised for Jefferson Lab experiments to mitigate this problem. The BONUS experiment involves tagging spectator neutrons in the deuteron, while the MARATHON experiment minimizes nuclear structure effects by a comparison of DIS from 3H and 3He. A summary of the status and future plans will be presented. This work supported by the U. S. Department of Energy, Office of Nuclear Physics, under contract DE-AC02-06CH11357.

  9. Structure function monitor

    DOEpatents

    McGraw, John T [Placitas, NM; Zimmer, Peter C [Albuquerque, NM; Ackermann, Mark R [Albuquerque, NM

    2012-01-24

    Methods and apparatus for a structure function monitor provide for generation of parameters characterizing a refractive medium. In an embodiment, a structure function monitor acquires images of a pupil plane and an image plane and, from these images, retrieves the phase over an aperture, unwraps the retrieved phase, and analyzes the unwrapped retrieved phase. In an embodiment, analysis yields atmospheric parameters measured at spatial scales from zero to the diameter of a telescope used to collect light from a source.

  10. A highly conserved gene island of three genes on chromosome 3B of hexaploid wheat: diverse gene function and genomic structure maintained in a tightly linked block

    PubMed Central

    2010-01-01

    Background The complexity of the wheat genome has resulted from waves of retrotransposable element insertions. Gene deletions and disruptions generated by the fast replacement of repetitive elements in wheat have resulted in disruption of colinearity at a micro (sub-megabase) level among the cereals. In view of genomic changes that are possible within a given time span, conservation of genes between species tends to imply an important functional or regional constraint that does not permit a change in genomic structure. The ctg1034 contig completed in this paper was initially studied because it was assigned to the Sr2 resistance locus region, but detailed mapping studies subsequently assigned it to the long arm of 3B and revealed its unusual features. Results BAC shotgun sequencing of the hexaploid wheat (Triticum aestivum cv. Chinese Spring) genome has been used to assemble a group of 15 wheat BACs from the chromosome 3B physical map FPC contig ctg1034 into a 783,553 bp genomic sequence. This ctg1034 sequence was annotated for biological features such as genes and transposable elements. A three-gene island was identified among >80% repetitive DNA sequence. Using bioinformatics analysis there were no observable similarity in their gene functions. The ctg1034 gene island also displayed complete conservation of gene order and orientation with syntenic gene islands found in publicly available genome sequences of Brachypodium distachyon, Oryza sativa, Sorghum bicolor and Zea mays, even though the intergenic space and introns were divergent. Conclusion We propose that ctg1034 is located within the heterochromatic C-band region of deletion bin 3BL7 based on the identification of heterochromatic tandem repeats and presence of significant matches to chromodomain-containing gypsy LTR retrotransposable elements. We also speculate that this location, among other highly repetitive sequences, may account for the relative stability in gene order and orientation within the gene

  11. Predicting missing links via structural similarity

    NASA Astrophysics Data System (ADS)

    Lyu, Guo-Dong; Fan, Chang-Jun; Yu, Lian-Fei; Xiu, Bao-Xin; Zhang, Wei-Ming

    2015-04-01

    Predicting missing links in networks plays a significant role in modern science. On the basis of structural similarity, our paper proposes a new node-similarity-based measure called biased resource allocation (BRA), which is motivated by the resource allocation (RA) measure. Comparisons between BRA and nine well-known node-similarity-based measures on five real networks indicate that BRA performs no worse than RA, which was the best node-similarity-based index in previous researches. Afterwards, based on localPath (LP) and Katz measure, we propose another two improved measures, named Im-LocalPath and Im-Katz respectively. Numerical results show that the prediction accuracy of both Im-LP and Im-Katz measure improve compared with the original LP and Katz measure. Finally, a new path-similarity-based measure and its improved measure, called LYU and Im-LYU measure, are proposed and especially, Im-LYU measure is shown to perform more remarkably than other mentioned measures.

  12. Linking network topology to function. Comment on "Drivers of structural features in gene regulatory networks: From biophysical constraints to biological function" by O.C. Martin, A. Krzywicki and M. Zagorski

    NASA Astrophysics Data System (ADS)

    di Bernardo, Diego

    2016-07-01

    The review by Martin et al. deals with a long standing problem at the interface of complex systems and molecular biology, that is the relationship between the topology of a complex network and its function. In biological terms the problem translates to relating the topology of gene regulatory networks (GRNs) to specific cellular functions. GRNs control the spatial and temporal activity of the genes encoded in the cell's genome by means of specialised proteins called Transcription Factors (TFs). A TF is able to recognise and bind specifically to a sequence (TF biding site) of variable length (order of magnitude of 10) found upstream of the sequence encoding one or more genes (at least in prokaryotes) and thus activating or repressing their transcription. TFs can thus be distinguished in activator and repressor. The picture can become more complex since some classes of TFs can form hetero-dimers consisting of a protein complex whose subunits are the individual TFs. Heterodimers can have completely different binding sites and activity compared to their individual parts. In this review the authors limit their attention to prokaryotes where the complexity of GRNs is somewhat reduced. Moreover they exploit a unique feature of living systems, i.e. evolution, to understand whether function can shape network topology. Indeed, prokaryotes such as bacteria are among the oldest living systems that have become perfectly adapted to their environment over geological scales and thus have reached an evolutionary steady-state where the fitness of the population has reached a plateau. By integrating in silico analysis and comparative evolution, the authors show that indeed function does tend to shape the structure of a GRN, however this trend is not always present and depends on the properties of the network being examined. Interestingly, the trend is more apparent for sparse networks, i.e. where the density of edges is very low. Sparsity is indeed one of the most prominent features

  13. Caveolae structure and function

    PubMed Central

    Thomas, Candice M; Smart, Eric J

    2008-01-01

    Abstract Studies on the structure and function of caveolae have revealed how this versatile subcellular organelle can influence numerous signalling pathways. This brief review will discuss a few of the key features of caveolae as it relates to signalling and disease processes. PMID:18315571

  14. Evolutionary link community structure discovery in dynamic weighted networks

    NASA Astrophysics Data System (ADS)

    Liu, Qiang; Liu, Caihong; Wang, Jiajia; Wang, Xiang; Zhou, Bin; Zou, Peng

    2017-01-01

    Traditional community detection methods are often restricted in static network analysis. In fact, most of networks in real world obviously show dynamic characteristics with time passing. In this paper, we design a link community structure discovery algorithm in dynamic weighted networks, which can not only reveal the evolutionary link community structure, but also detect overlapping communities by mapping link communities to node communities. Meanwhile, our algorithm can also get the hierarchical structure of link communities by tuning a parameter. The proposed algorithm is based on weighted edge fitness and weighted partition density so as to determine whether to add a link to a community and whether to merge two communities to form a new link community. Experiments on both synthetic and real world networks demonstrate the proposed algorithm can detect evolutionary link community structure in dynamic weighted networks effectively.

  15. Linking hydraulic traits to tropical forest function in a size-structured and trait-driven model (TFS v.1-Hydro)

    NASA Astrophysics Data System (ADS)

    Christoffersen, Bradley O.; Gloor, Manuel; Fauset, Sophie; Fyllas, Nikolaos M.; Galbraith, David R.; Baker, Timothy R.; Kruijt, Bart; Rowland, Lucy; Fisher, Rosie A.; Binks, Oliver J.; Sevanto, Sanna; Xu, Chonggang; Jansen, Steven; Choat, Brendan; Mencuccini, Maurizio; McDowell, Nate G.; Meir, Patrick

    2016-11-01

    Forest ecosystem models based on heuristic water stress functions poorly predict tropical forest response to drought partly because they do not capture the diversity of hydraulic traits (including variation in tree size) observed in tropical forests. We developed a continuous porous media approach to modeling plant hydraulics in which all parameters of the constitutive equations are biologically interpretable and measurable plant hydraulic traits (e.g., turgor loss point πtlp, bulk elastic modulus ɛ, hydraulic capacitance Cft, xylem hydraulic conductivity ks,max, water potential at 50 % loss of conductivity for both xylem (P50,x) and stomata (P50,gs), and the leaf : sapwood area ratio Al : As). We embedded this plant hydraulics model within a trait forest simulator (TFS) that models light environments of individual trees and their upper boundary conditions (transpiration), as well as providing a means for parameterizing variation in hydraulic traits among individuals. We synthesized literature and existing databases to parameterize all hydraulic traits as a function of stem and leaf traits, including wood density (WD), leaf mass per area (LMA), and photosynthetic capacity (Amax), and evaluated the coupled model (called TFS v.1-Hydro) predictions, against observed diurnal and seasonal variability in stem and leaf water potential as well as stand-scaled sap flux. Our hydraulic trait synthesis revealed coordination among leaf and xylem hydraulic traits and statistically significant relationships of most hydraulic traits with more easily measured plant traits. Using the most informative empirical trait-trait relationships derived from this synthesis, TFS v.1-Hydro successfully captured individual variation in leaf and stem water potential due to increasing tree size and light environment, with model representation of hydraulic architecture and plant traits exerting primary and secondary controls, respectively, on the fidelity of model predictions. The plant

  16. 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

  17. Linking hydraulic traits to tropical forest function in a size-structured and trait-driven model (TFS v.1-Hydro)

    DOE PAGES

    Christoffersen, Bradley O.; Gloor, Manuel; Fauset, Sophie; ...

    2016-11-24

    Forest ecosystem models based on heuristic water stress functions poorly predict tropical forest response to drought partly because they do not capture the diversity of hydraulic traits (including variation in tree size) observed in tropical forests. We developed a continuous porous media approach to modeling plant hydraulics in which all parameters of the constitutive equations are biologically interpretable and measurable plant hydraulic traits (e.g., turgor loss point πtlp, bulk elastic modulus ε, hydraulic capacitance Cft, xylem hydraulic conductivity ks,max, water potential at 50 % loss of conductivity for both xylem (P50,x) and stomata (P50,gs), and the leaf : sapwood areamore » ratio Al:As). We embedded this plant hydraulics model within a trait forest simulator (TFS) that models light environments of individual trees and their upper boundary conditions (transpiration), as well as providing a means for parameterizing variation in hydraulic traits among individuals. We synthesized literature and existing databases to parameterize all hydraulic traits as a function of stem and leaf traits, including wood density (WD), leaf mass per area (LMA), and photosynthetic capacity (Amax), and evaluated the coupled model (called TFS v.1-Hydro) predictions, against observed diurnal and seasonal variability in stem and leaf water potential as well as stand-scaled sap flux. Our hydraulic trait synthesis revealed coordination among leaf and xylem hydraulic traits and statistically significant relationships of most hydraulic traits with more easily measured plant traits. Using the most informative empirical trait–trait relationships derived from this synthesis, TFS v.1-Hydro successfully captured individual variation in leaf and stem water potential due to increasing tree size and light environment, with model representation of hydraulic architecture and plant traits exerting primary and secondary controls, respectively, on the fidelity of model predictions. The plant

  18. Parkin structure and function.

    PubMed

    Seirafi, Marjan; Kozlov, Guennadi; Gehring, Kalle

    2015-06-01

    Mutations in the parkin or PINK1 genes are the leading cause of the autosomal recessive form of Parkinson's disease. The gene products, the E3 ubiquitin ligase parkin and the serine/threonine kinase PINK1, are neuroprotective proteins, which act together in a mitochondrial quality control pathway. Here, we review the structure of parkin and mechanisms of its autoinhibition and function as a ubiquitin ligase. We present a model for the recruitment and activation of parkin as a key regulatory step in the clearance of depolarized or damaged mitochondria by autophagy (mitophagy). We conclude with a brief overview of other functions of parkin and considerations for drug discovery in the mitochondrial quality control pathway. © 2015 The Authors. FEBS Journal published by John Wiley & Sons Ltd on behalf of FEBS.

  19. 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.

  20. DNA structure and function.

    PubMed

    Travers, Andrew; Muskhelishvili, Georgi

    2015-06-01

    The proposal of a double-helical structure for DNA over 60 years ago provided an eminently satisfying explanation for the heritability of genetic information. But why is DNA, and not RNA, now the dominant biological information store? We argue that, in addition to its coding function, the ability of DNA, unlike RNA, to adopt a B-DNA structure confers advantages both for information accessibility and for packaging. The information encoded by DNA is both digital - the precise base specifying, for example, amino acid sequences - and analogue. The latter determines the sequence-dependent physicochemical properties of DNA, for example, its stiffness and susceptibility to strand separation. Most importantly, DNA chirality enables the formation of supercoiling under torsional stress. We review recent evidence suggesting that DNA supercoiling, particularly that generated by DNA translocases, is a major driver of gene regulation and patterns of chromosomal gene organization, and in its guise as a promoter of DNA packaging enables DNA to act as an energy store to facilitate the passage of translocating enzymes such as RNA polymerase.

  1. 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…

  2. 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…

  3. Correlations between Community Structure and Link Formation in Complex Networks

    PubMed Central

    Liu, Zhen; He, Jia-Lin; Kapoor, Komal; Srivastava, Jaideep

    2013-01-01

    Background Links in complex networks commonly represent specific ties between pairs of nodes, such as protein-protein interactions in biological networks or friendships in social networks. However, understanding the mechanism of link formation in complex networks is a long standing challenge for network analysis and data mining. Methodology/Principal Findings Links in complex networks have a tendency to cluster locally and form so-called communities. This widely existed phenomenon reflects some underlying mechanism of link formation. To study the correlations between community structure and link formation, we present a general computational framework including a theory for network partitioning and link probability estimation. Our approach enables us to accurately identify missing links in partially observed networks in an efficient way. The links having high connection likelihoods in the communities reveal that links are formed preferentially to create cliques and accordingly promote the clustering level of the communities. The experimental results verify that such a mechanism can be well captured by our approach. Conclusions/Significance Our findings provide a new insight into understanding how links are created in the communities. The computational framework opens a wide range of possibilities to develop new approaches and applications, such as community detection and missing link prediction. PMID:24039818

  4. Revealing how network structure affects accuracy of link prediction

    NASA Astrophysics Data System (ADS)

    Yang, Jin-Xuan; Zhang, Xiao-Dong

    2017-08-01

    Link prediction plays an important role in network reconstruction and network evolution. The network structure affects the accuracy of link prediction, which is an interesting problem. In this paper we use common neighbors and the Gini coefficient to reveal the relation between them, which can provide a good reference for the choice of a suitable link prediction algorithm according to the network structure. Moreover, the statistical analysis reveals correlation between the common neighbors index, Gini coefficient index and other indices to describe the network structure, such as Laplacian eigenvalues, clustering coefficient, degree heterogeneity, and assortativity of network. Furthermore, a new method to predict missing links is proposed. The experimental results show that the proposed algorithm yields better prediction accuracy and robustness to the network structure than existing currently used methods for a variety of real-world networks.

  5. Functional synergy of actin filament cross-linking proteins.

    PubMed

    Tseng, Yiider; Schafer, Benjamin W; Almo, Steven C; Wirtz, Denis

    2002-07-12

    The organization of filamentous actin (F-actin) in resilient networks is coordinated by various F-actin cross-linking proteins. The relative tolerance of cells to null mutations of genes that code for a single actin cross-linking protein suggests that the functions of those proteins are highly redundant. This apparent functional redundancy may, however, reflect the limited resolution of available assays in assessing the mechanical role of F-actin cross-linking/bundling proteins. Using reconstituted F-actin networks and rheological methods, we demonstrate how alpha-actinin and fascin, two F-actin cross-linking/bundling proteins that co-localize along stress fibers and in lamellipodia, could synergistically enhance the resilience of F-actin networks in vitro. These two proteins can generate microfilament arrays that "yield" at a strain amplitude that is much larger than each one of the proteins separately. F-actin/alpha-actinin/fascin networks display strain-induced hardening, whereby the network "stiffens" under shear deformations, a phenomenon that is non-existent in F-actin/fascin networks and much weaker in F-actin/alpha-actinin networks. Strain-hardening is further enhanced at high rates of deformation and high concentrations of actin cross-linking proteins. A simplified model suggests that the optimum results of the competition between the increased stiffness of bundles and their decreased density of cross-links. Our studies support a re-evaluation of the notion of functional redundancy among cytoskeletal regulatory proteins.

  6. From structure to function, via dynamics

    NASA Astrophysics Data System (ADS)

    Stetter, O.; Soriano, J.; Geisel, T.; Battaglia, D.

    2013-01-01

    Neurons in the brain are wired into a synaptic network that spans multiple scales, from local circuits within cortical columns to fiber tracts interconnecting distant areas. However, brain function require the dynamic control of inter-circuit interactions on time-scales faster than synaptic changes. In particular, strength and direction of causal influences between neural populations (described by the so-called directed functional connectivity) must be reconfigurable even when the underlying structural connectivity is fixed. Such directed functional influences can be quantified resorting to causal analysis of time-series based on tools like Granger Causality or Transfer Entropy. The ability to quickly reorganize inter-areal interactions is a chief requirement for performance in a changing natural environment. But how can manifold functional networks stem "on demand" from an essentially fixed structure? We explore the hypothesis that the self-organization of neuronal synchronous activity underlies the control of brain functional connectivity. Based on simulated and real recordings of critical neuronal cultures in vitro, as well as on mean-field and spiking network models of interacting brain areas, we have found that "function follows dynamics", rather than structure. Different dynamic states of a same structural network, characterized by different synchronization properties, are indeed associated to different functional digraphs (functional multiplicity). We also highlight the crucial role of dynamics in establishing a structure-to-function link, by showing that whenever different structural topologies lead to similar dynamical states, than the associated functional connectivities are also very similar (structural degeneracy).

  7. Multi-functional composite structures

    DOEpatents

    Mulligan, Anthony C.; Halloran, John; Popovich, Dragan; Rigali, Mark J.; Sutaria, Manish P.; Vaidyanathan, K. Ranji; Fulcher, Michael L.; Knittel, Kenneth L.

    2010-04-27

    Fibrous monolith processing techniques to fabricate multifunctional structures capable of performing more than one discrete function such as structures capable of bearing structural loads and mechanical stresses in service and also capable of performing at least one additional non-structural function.

  8. Multi-functional composite structures

    DOEpatents

    Mulligan, Anthony C.; Halloran, John; Popovich, Dragan; Rigali, Mark J.; Sutaria, Manish P.; Vaidyanathan, K. Ranji; Fulcher, Michael L.; Knittel, Kenneth L.

    2004-10-19

    Fibrous monolith processing techniques to fabricate multifunctional structures capable of performing more than one discrete function such as structures capable of bearing structural loads and mechanical stresses in service and also capable of performing at least one additional non-structural function.

  9. Optimal optical communication terminal structure for maximizing the link budget

    NASA Astrophysics Data System (ADS)

    Huang, Jian; Jiang, Dagang; Deng, Ke; Zhang, Peng

    2015-02-01

    Ordinary inter-satellite optical includes at least three optical paths for acquisition, tracking and communication, the three optical paths work simultaneously and share the received power. An optimal structure of inter-satellite optical communication terminal with single working optical path at each of working stages of acquisition and communication is introduced. A space optical switch based on frustrated total internal reflection effect is applied to switch the received laser power between the acquisition sensor and the communication sensor between the stages of acquisition and communication, this is named as power fusion which means power is transferred for shutting down unused optical path. For the stages of tracking and communication, a multiple cells sensor is used to accomplish the operation of tracking while communication, this is named as function fusion which means accomplishing multiple functions by one device to reduce the redundant optical paths. For optical communication terminal with single working path structure, the total received laser power would be detected by one sensor for each different stages of acquisition, tracking and communication, the link budget would be maximized, and this design would help to enlarge the system tolerance and reduce the acquisition time.

  10. Brain structure links loneliness to social perception.

    PubMed

    Kanai, Ryota; Bahrami, Bahador; Duchaine, Brad; Janik, Agnieszka; Banissy, Michael J; Rees, Geraint

    2012-10-23

    Loneliness is the distressing feeling associated with the perceived absence of satisfying social relationships. Loneliness is increasingly prevalent in modern societies and has detrimental effects on health and happiness. Although situational threats to social relationships can transiently induce the emotion of loneliness, susceptibility to loneliness is a stable trait that varies across individuals [6-8] and is to some extent heritable. However, little is known about the neural processes associated with loneliness (but see [12-14]). Here, we hypothesized that individual differences in loneliness might be reflected in the structure of the brain regions associated with social processes. To test this hypothesis, we used voxel-based morphometry and showed that lonely individuals have less gray matter in the left posterior superior temporal sulcus (pSTS)--an area implicated in basic social perception. As this finding predicted, we further confirmed that loneliness was associated with difficulty in processing social cues. Although other sociopsychological factors such as social network size, anxiety, and empathy independently contributed to loneliness, only basic social perception skills mediated the association between the pSTS volume and loneliness. Taken together, our results suggest that basic social perceptual abilities play an important role in shaping an individual's loneliness. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Linking structure and activity in nonlinear spiking networks

    PubMed Central

    Josić, Krešimir; Shea-Brown, Eric

    2017-01-01

    Recent experimental advances are producing an avalanche of data on both neural connectivity and neural activity. To take full advantage of these two emerging datasets we need a framework that links them, revealing how collective neural activity arises from the structure of neural connectivity and intrinsic neural dynamics. This problem of structure-driven activity has drawn major interest in computational neuroscience. Existing methods for relating activity and architecture in spiking networks rely on linearizing activity around a central operating point and thus fail to capture the nonlinear responses of individual neurons that are the hallmark of neural information processing. Here, we overcome this limitation and present a new relationship between connectivity and activity in networks of nonlinear spiking neurons by developing a diagrammatic fluctuation expansion based on statistical field theory. We explicitly show how recurrent network structure produces pairwise and higher-order correlated activity, and how nonlinearities impact the networks’ spiking activity. Our findings open new avenues to investigating how single-neuron nonlinearities—including those of different cell types—combine with connectivity to shape population activity and function. PMID:28644840

  12. OPTIMIZING LINKED PERCEPTUAL CLASS FORMATION AND TRANSFER OF FUNCTION

    PubMed Central

    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 woman's voice would occasion the selection of any picture of the woman and vice versa. In addition, after learning to name the woman in the presence of one picture, that name would be uttered when presented with all of the images of the woman's face and all of the sounds of her voice. This study involved 15 participants and sought to (a) maximize the percentage of participants who formed linked perceptual classes, and (b) determine whether those classes acted as transfer networks, that is, whether the discriminative function of one class member would generalize to other members of the class and not to members of a different class. The rate of emergence of each linked perceptual class was maximized by establishing a single class-linking conditional relation between the clearest member of one class used as a sample stimulus and the most ambiguous member of the other class used as a comparison stimulus. Class formation was demonstrated using the serial and programmed presentation of A′–B′ probes that consisted of untrained pairs of stimuli drawn from the A′ and B′ classes. Most participants showed immediate emergence of the two linked perceptual classes. The remaining participants showed delayed emergence following a second exposure to each originally error-producing probes. Once the linked perceptual classes had emerged, a differential response to a specific member of one perceptual class generalized mostly or completely to the other members of that linked class and rarely, if ever, to members of the other linked class. Thus, generalization did not depend on the specific class members that had been used for

  13. Functional polymer laminates from hyperthermal hydrogen induced cross-linking.

    PubMed

    Thompson, David B; Trebicky, Tomas; Crewdson, Patrick; McEachran, Matthew J; Stojcevic, Goran; Arsenault, Gilles; Lau, Woon M; Gillies, Elizabeth R

    2011-12-20

    The use of a hyperthermal hydrogen induced cross-linking process to prepare laminates comprising polypropylene, poly(isobutylene-co-isoprene), and poly(vinyl acetate) is described. In this new, milder alternative to conventional plasma techniques, neutral molecular hydrogen projectiles were used to create carbon radicals on impacted surfaces by collision-induced dissociation of C-H bonds, and this process was used to cross-link polymers on a polypropylene surface. It was demonstrated that multiple layers of cross-linked materials could be added, creating polymer laminates with each layer introducing new functionalities and properties. In particular, the present work shows that the process is largely nondestructive toward ester functionalities. First, the esters were grafted to become nonleachable. Then, the esters were subsequently hydrolyzed to convert the surface from hydrophobic to hydrophilic. Afterward, the esters could be recovered by simple esterification demonstrating that further chemical transformations were possible.

  14. Improving link prediction in complex networks by adaptively exploiting multiple structural features of networks

    NASA Astrophysics Data System (ADS)

    Ma, Chuang; Bao, Zhong-Kui; Zhang, Hai-Feng

    2017-10-01

    So far, many network-structure-based link prediction methods have been proposed. However, these methods only highlight one or two structural features of networks, and then use the methods to predict missing links in different networks. The performances of these existing methods are not always satisfied in all cases since each network has its unique underlying structural features. In this paper, by analyzing different real networks, we find that the structural features of different networks are remarkably different. In particular, even in the same network, their inner structural features are utterly different. Therefore, more structural features should be considered. However, owing to the remarkably different structural features, the contributions of different features are hard to be given in advance. Inspired by these facts, an adaptive fusion model regarding link prediction is proposed to incorporate multiple structural features. In the model, a logistic function combing multiple structural features is defined, then the weight of each feature in the logistic function is adaptively determined by exploiting the known structure information. Last, we use the "learnt" logistic function to predict the connection probabilities of missing links. According to our experimental results, we find that the performance of our adaptive fusion model is better than many similarity indices.

  15. DNA-linked nanoparticle materials: optical, electrical, and structural properties

    NASA Astrophysics Data System (ADS)

    Lazarides, A.; Park, S.-J.; Mirkin, C.; Storhoff, J.; Schatz, G.; Brazis, P.; Kannewurf, C.

    2001-03-01

    Novel bioinorganic materials composed of Au nanoparticles linked with DNA have been developed as colorimetric DNA sensors. In the presence of complimentary DNA, particles dressed with one of two oligonucleotide sequences are linked to form binary nanoparticle aggregates. Assemblies linked at 298K have plasmon frequency shifts that decrease with increasing linker length; annealing, however, eliminates the length dependence of the shift. Neither sedimentation rate measurements nor theoretical studies of the optical properties provide unambiguous explanation. However, small-angle X-ray scattering (SAXS) measurements indicate that separations between nanoparticles with or without annealing are proportional to the number of base pairs in the oligonucleotide linkers. DNA is thus shown to offer a means for tuning separations in nanoparticle materials. We have also investigated the electrical and structural properties of dry Au nanoparticle films linked by DNA. The assemblies are semiconducting, which suggests that DNA can be used as a chemically specific scaffolding material for assembly of conductive structures.

  16. Flexible Link Functions in Nonparametric Binary Regression with Gaussian Process Priors

    PubMed Central

    Li, Dan; Lin, Lizhen; Dey, Dipak K.

    2015-01-01

    Summary 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. 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. © 2015, The International Biometric Society.

  18. Mentalizing functions provide a conceptual link of brain function and social cognition in major mental disorders.

    PubMed

    Schnell, Knut

    2014-01-01

    The review presents a research perspective that defines mentalizing functions as a very promising topic to bridge psychopathology and neurobiological foundations of mental disorders. However, the high diversity of existing observations in mentalizing research calls for a structured assessment of functional mentalizing subdomains. A notable problem is the overlap of functional systems involved in mentalizing and emotion processing. A proposed solution is to conceptualize mentalizing functions due to their content (visuospatial vs. emotional) perspective and substrates (cognitive or explicit signals). This conceptual organization is mirrored in functional imaging experiments dissociating anteromedial and posterolateral brain regions, especially the involvement of the medial prefrontal cortex in mentalizing emotions and the temporoparietal cortex in visuospatial perspective taking. The present state and perspectives of mentalizing research are demonstrated in two major fields of mental disorders, depression and schizophrenia. In depression the existent contradictory findings demand a control of cognitive impairments, which are frequently associated with depressive disorders. In schizophrenia there is already consistent evidence that defines mentalizing functions as promising endophenotype, which can possibly link psychopathology to its neurobiological foundations.

  19. Deployment of a multi-link flexible structure

    NASA Astrophysics Data System (ADS)

    Na, Kyung-Su; Kim, Ji-Hwan

    2006-06-01

    Deployment of a multi-link beam structure undergoing locking is analyzed in the Timoshenko beam theory. In the modeling of the system, dynamic forces are assumed to be torques and restoring forces due to the torsion spring at each joint. Hamilton's principle is used to determine the equations of motion and the finite element method is adopted to analyze the system. Newmark time integration and Newton-Raphson iteration methods are used to solve for the non-linear equations of motion at each time step. The locking at the joints of the multi-link flexible structure is analyzed by the momentum balance method. Numerical results are compared with the previous experimental data. The angles and angular velocities of each joint, tip displacement, and velocity of each link are investigated to study the motions of the links at each time step. To analyze the effect of thickness on the motion of the link, the angle and the tip displacement of each link are compared according to the various slenderness ratios. Additionally, in order to investigate the effect of shear, the tip displacements of a Timoshenko beam are compared with those of an Euler-Bernoulli beam.

  20. High-resolution structure of hair-cell tip links

    PubMed Central

    Kachar, Bechara; Parakkal, Marianne; Kurc, Mauricio; Zhao, Yi-dong; Gillespie, Peter G.

    2000-01-01

    Transduction-channel gating by hair cells apparently requires a gating spring, an elastic element that transmits force to the channels. To determine whether the gating spring is the tip link, a filament interconnecting two stereocilia along the axis of mechanical sensitivity, we examined the tip link's structure at high resolution by using rapid-freeze, deep-etch electron microscopy. We found that the tip link is a right-handed, coiled double filament that usually forks into two branches before contacting a taller stereocilium; at the other end, several short filaments extend to the tip link from the shorter stereocilium. The structure of the tip link suggests that it is either a helical polymer or a braided pair of filamentous macromolecules and is thus likely to be relatively stiff and inextensible. Such behavior is incompatible with the measured elasticity of the gating spring, suggesting that the gating spring instead lies in series with the helical segment of the tip link. PMID:11087873

  1. Spliceosome structure and function.

    PubMed

    Will, Cindy L; Lührmann, Reinhard

    2011-07-01

    Pre-mRNA splicing is catalyzed by the spliceosome, a multimegadalton ribonucleoprotein (RNP) complex comprised of five snRNPs and numerous proteins. Intricate RNA-RNA and RNP networks, which serve to align the reactive groups of the pre-mRNA for catalysis, are formed and repeatedly rearranged during spliceosome assembly and catalysis. Both the conformation and composition of the spliceosome are highly dynamic, affording the splicing machinery its accuracy and flexibility, and these remarkable dynamics are largely conserved between yeast and metazoans. Because of its dynamic and complex nature, obtaining structural information about the spliceosome represents a major challenge. Electron microscopy has revealed the general morphology of several spliceosomal complexes and their snRNP subunits, and also the spatial arrangement of some of their components. X-ray and NMR studies have provided high resolution structure information about spliceosomal proteins alone or complexed with one or more binding partners. The extensive interplay of RNA and proteins in aligning the pre-mRNA's reactive groups, and the presence of both RNA and protein at the core of the splicing machinery, suggest that the spliceosome is an RNP enzyme. However, elucidation of the precise nature of the spliceosome's active site, awaits the generation of a high-resolution structure of its RNP core.

  2. Spliceosome Structure and Function

    PubMed Central

    Will, Cindy L.; Lührmann, Reinhard

    2011-01-01

    SUMMARY Pre-mRNA splicing is catalyzed by the spliceosome, a multimegadalton ribonucleoprotein (RNP) complex comprised of five snRNPs and numerous proteins. Intricate RNA-RNA and RNP networks, which serve to align the reactive groups of the pre-mRNA for catalysis, are formed and repeatedly rearranged during spliceosome assembly and catalysis. Both the conformation and composition of the spliceosome are highly dynamic, affording the splicing machinery its accuracy and flexibility, and these remarkable dynamics are largely conserved between yeast and metazoans. Because of its dynamic and complex nature, obtaining structural information about the spliceosome represents a major challenge. Electron microscopy has revealed the general morphology of several spliceosomal complexes and their snRNP subunits, and also the spatial arrangement of some of their components. X-ray and NMR studies have provided high resolution structure information about spliceosomal proteins alone or complexed with one or more binding partners. The extensive interplay of RNA and proteins in aligning the pre-mRNA's reactive groups, and the presence of both RNA and protein at the core of the splicing machinery, suggest that the spliceosome is an RNP enzyme. However, elucidation of the precise nature of the spliceosome's active site, awaits the generation of a high-resolution structure of its RNP core. PMID:21441581

  3. Proton structure functions at HERA

    NASA Astrophysics Data System (ADS)

    Abt, Iris

    2014-05-01

    The "proton structure" is a wide field. Discussed are predominantly the precision measurements of the proton structure functions at HERA and some of their implications for the LHC measurements. In addition, a discussion of what a proton structure function represents is provided. Finally, a connection to nuclear physics is attempted. This contribution is an updated reprint of a contribution to "Deep Inelastic Scattering 2012".1

  4. Polyimide Aerogels with Three-Dimensional Cross-Linked Structure

    NASA Technical Reports Server (NTRS)

    Meador, Mary Ann B. (Inventor)

    2016-01-01

    A method for creating a three dimensional cross-linked polyimide structure includes dissolving a diamine, a dianhydride, and a triamine in a solvent, imidizing a polyamic acid gel by heating the gel, extracting the gel in a second solvent, supercritically drying the gel, and removing the solvent to create a polyimide aerogel.

  5. Integrative data-mining tools to link gene and function.

    PubMed

    El Yacoubi, Basma; de Crécy-Lagard, Valérie

    2014-01-01

    Information derived from genomic and post-genomic data can be efficiently used to link gene and function. Several web-based platforms have been developed to mine these types of data by integrating different tools. This method paper is designed to allow the user to navigate these platforms in order to make functional predictions. The main focus is on phylogenetic distribution and physical clustering tools, but other tools such as pathway reconstruction, gene fusions, and analysis of high-throughput experimental data are also surveyed.

  6. Design, synthesis and characterization of novel binary V(V)-Schiff base materials linked with insulin-mimetic vanadium-induced differentiation of 3T3-L1 fibroblasts to adipocytes. Structure-function correlations at the molecular level.

    PubMed

    Halevas, E; Tsave, O; Yavropoulou, M P; Hatzidimitriou, A; Yovos, J G; Psycharis, V; Gabriel, C; Salifoglou, A

    2015-06-01

    Among the various roles of vanadium in the regulation of intracellular signaling, energy metabolism and insulin mimesis, its exogenous activity stands as a contemporary challenge currently under investigation and a goal to pursue as a metallodrug against Diabetes mellitus II. In this regard, the lipogenic activity of vanadium linked to the development of well-defined anti-diabetic vanadodrugs has been investigated through: a) specifically designing and synthesizing Schiff base organic ligands L, bearing a variable number of terminal alcohols, b) a series of well-defined soluble binary V(V)-L compounds synthesized and physicochemically characterized, c) a study of their cytotoxic effect and establishment of adipogenic activity in 3T3-L1 fibroblasts toward mature adipocytes, and d) biomarker examination of a closely-linked molecular target involving or influenced by the specific V(V) forms, cumulatively delineating factors involved in potential pathways linked to V(V)-induced insulin-like activity. Collectively, the results a) project the importance of specific structural features in Schiff ligands bound to V(V), thereby influencing the emergence of its (a)toxicity and for the first time its insulin-like activity in pre-adipocyte differentiation, b) contribute to the discovery of molecular targets influenced by the specific vanadoforms seeking to induce glucose uptake, and c) indicate an interplay of V(V) structural speciation and cell-differentiation biological activity, thereby gaining insight into vanadium's potential as a future metallodrug in Diabetes mellitus.

  7. Linking biodiversity to ecosystem function: Implications for conservation ecology

    USGS Publications Warehouse

    Schwartz, M.W.; Brigham, C.A.; Hoeksema, J.D.; Lyons, K.G.; Mills, M.H.; van Mantgem, P.

    2000-01-01

    We evaluate the empirical and theoretical support for the hypothesis that a large proportion of native species richness is required to maximize ecosystem stability and sustain function. This assessment is important for conservation strategies because sustenance of ecosystem functions has been used as an argument for the conservation of species. If ecosystem functions are sustained at relatively low species richness, then arguing for the conservation of ecosystem function, no matter how important in its own right, does not strongly argue for the conservation of species. Additionally, for this to be a strong conservation argument the link between species diversity and ecosystem functions of value to the human community must be clear. We review the empirical literature to quantify the support for two hypotheses: (1) species richness is positively correlated with ecosystem function, and (2) ecosystem functions do not saturate at low species richness relative to the observed or experimental diversity. Few empirical studies demonstrate improved function at high levels of species richness. Second, we analyze recent theoretical models in order to estimate the level of species richness required to maintain ecosystem function. Again we find that, within a single trophic level, most mathematical models predict saturation of ecosystem function at a low proportion of local species richness. We also analyze a theoretical model linking species number to ecosystem stability. This model predicts that species richness beyond the first few species does not typically increase ecosystem stability. One reason that high species richness may not contribute significantly to function or stability is that most communities are characterized by strong dominance such that a few species provide the vast majority of the community biomass. Rapid turnover of species may rescue the concept that diversity leads to maximum function and stability. The role of turnover in ecosystem function and

  8. Linking biodiversity to ecosystem function: implications for conservation ecology.

    PubMed

    Schwartz, M W; Brigham, C A; Hoeksema, J D; Lyons, K G; Mills, M H; van Mantgem, P J

    2000-02-01

    We evaluate the empirical and theoretical support for the hypothesis that a large proportion of native species richness is required to maximize ecosystem stability and sustain function. This assessment is important for conservation strategies because sustenance of ecosystem functions has been used as an argument for the conservation of species. If ecosystem functions are sustained at relatively low species richness, then arguing for the conservation of ecosystem function, no matter how important in its own right, does not strongly argue for the conservation of species. Additionally, for this to be a strong conservation argument the link between species diversity and ecosystem functions of value to the human community must be clear. We review the empirical literature to quantify the support for two hypotheses: (1) species richness is positively correlated with ecosystem function, and (2) ecosystem functions do not saturate at low species richness relative to the observed or experimental diversity. Few empirical studies demonstrate improved function at high levels of species richness. Second, we analyze recent theoretical models in order to estimate the level of species richness required to maintain ecosystem function. Again we find that, within a single trophic level, most mathematical models predict saturation of ecosystem function at a low proportion of local species richness. We also analyze a theoretical model linking species number to ecosystem stability. This model predicts that species richness beyond the first few species does not typically increase ecosystem stability. One reason that high species richness may not contribute significantly to function or stability is that most communities are characterized by strong dominance such that a few species provide the vast majority of the community biomass. Rapid turnover of species may rescue the concept that diversity leads to maximum function and stability. The role of turnover in ecosystem function and

  9. Structural Preferential Attachment: Network Organization beyond the Link

    NASA Astrophysics Data System (ADS)

    Hébert-Dufresne, Laurent; Allard, Antoine; Marceau, Vincent; Noël, Pierre-André; Dubé, Louis J.

    2011-10-01

    We introduce a mechanism which models the emergence of the universal properties of complex networks, such as scale independence, modularity and self-similarity, and unifies them under a scale-free organization beyond the link. This brings a new perspective on network organization where communities, instead of links, are the fundamental building blocks of complex systems. We show how our simple model can reproduce social and information networks by predicting their community structure and more importantly, how their nodes or communities are interconnected, often in a self-similar manner.

  10. Leveraging enzyme structure-function relationships for functional inference and experimental design: the structure-function linkage database.

    PubMed

    Pegg, Scott C-H; Brown, Shoshana D; Ojha, Sunil; Seffernick, Jennifer; Meng, Elaine C; Morris, John H; Chang, Patricia J; Huang, Conrad C; Ferrin, Thomas E; Babbitt, Patricia C

    2006-02-28

    The study of mechanistically diverse enzyme superfamilies-collections of enzymes that perform different overall reactions but share both a common fold and a distinct mechanistic step performed by key conserved residues-helps elucidate the structure-function relationships of enzymes. We have developed a resource, the structure-function linkage database (SFLD), to analyze these structure-function relationships. Unique to the SFLD is its hierarchical classification scheme based on linking the specific partial reactions (or other chemical capabilities) that are conserved at the superfamily, subgroup, and family levels with the conserved structural elements that mediate them. We present the results of analyses using the SFLD in correcting misannotations, guiding protein engineering experiments, and elucidating the function of recently solved enzyme structures from the structural genomics initiative. The SFLD is freely accessible at http://sfld.rbvi.ucsf.edu.

  11. The Internal Structure of Nanoparticle Dimers Linked by DNA

    NASA Astrophysics Data System (ADS)

    Vargas Lara, Fernando; Cheng, Ching-Jung; Gang, Oleg; Starr, Francis W.

    2012-02-01

    The self-assembly of inorganic units controlled by the interactions of biological molecules, like DNA, has received attention for the possibility to specify higher-order structure, with potential biological, optical and electronic applications. In biology, self-assembly of complex materials (eg. bone, spider silk) frequently occurs in a stepwise, hierarchical fashion. Here, we consider a first step towards a hierarchical approach for synthetic nanostructures of nanoparticles (NPs) linked by DNA. The most basic unit in this multiscale approach is a dimer of NPs linked by DNA. We use a coarse-grained molecular model to explain experimental measurements of the separation of two DNA-coated NPs connected by linking single-stranded DNA (ssDNA). We show that the dimer separation is primarily controlled by the number of DNA links between NPs. If these links are not constrained to lie along the axis between NPs, the separation is limited by off-axis connections that force the NPs to be closer. We also determine how the number of connections alters the effective persistence length of the ssDNA that connects the dimer. We discuss how these dimers might be used for subsequent assembly at larger scales.

  12. Fluxomics links cellular functional analyses to whole-plant phenotyping.

    PubMed

    Salon, Christophe; Avice, Jean-Christophe; Colombié, Sophie; Dieuaide-Noubhani, Martine; Gallardo, Karine; Jeudy, Christian; Ourry, Alain; Prudent, Marion; Voisin, Anne-Sophie; Rolin, Dominique

    2017-04-01

    Fluxes through metabolic pathways reflect the integration of genetic and metabolic regulations. While it is attractive to measure all the mRNAs (transcriptome), all the proteins (proteome), and a large number of the metabolites (metabolome) in a given cellular system, linking and integrating this information remains difficult. Measurement of metabolome-wide fluxes (termed the fluxome) provides an integrated functional output of the cell machinery and a better tool to link functional analyses to plant phenotyping. This review presents and discusses sets of methodologies that have been developed to measure the fluxome. First, the principles of metabolic flux analysis (MFA), its 'short time interval' version Inst-MFA, and of constraints-based methods, such as flux balance analysis and kinetic analysis, are briefly described. The use of these powerful methods for flux characterization at the cellular scale up to the organ (fruits, seeds) and whole-plant level is illustrated. The added value given by fluxomics methods for unravelling how the abiotic environment affects flux, the process, and key metabolic steps are also described. Challenges associated with the development of fluxomics and its integration with 'omics' for thorough plant and organ functional phenotyping are discussed. Taken together, these will ultimately provide crucial clues for identifying appropriate target plant phenotypes for breeding. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  13. GRASPs in Golgi Structure and Function

    PubMed Central

    Zhang, Xiaoyan; Wang, Yanzhuang

    2016-01-01

    The Golgi apparatus is a central intracellular membrane organelle for trafficking and modification of proteins and lipids. Its basic structure is a stack of tightly aligned flat cisternae. In mammalian cells, dozens of stacks are concentrated in the pericentriolar region and laterally connected to form a ribbon. Despite extensive research in the last decades, how this unique structure is formed and why its formation is important for proper Golgi functioning remain largely unknown. The Golgi ReAssembly Stacking Proteins, GRASP65, and GRASP55, are so far the only proteins shown to function in Golgi stacking. They are peripheral membrane proteins on the cytoplasmic face of the Golgi cisternae that form trans-oligomers through their N-terminal GRASP domain, and thereby function as the “glue” to stick adjacent cisternae together into a stack and to link Golgi stacks into a ribbon. Depletion of GRASPs in cells disrupts the Golgi structure and results in accelerated protein trafficking and defective glycosylation. In this minireview we summarize our current knowledge on how GRASPs function in Golgi structure formation and discuss why Golgi structure formation is important for its function. PMID:26779480

  14. Fragment and conquer: from structure to complexes to function.

    PubMed

    Guichou, Jean-François; Labesse, Gilles

    2012-10-10

    In this issue of Structure, Shumilin and colleagues show the power of metabolite screening by means of X-ray crystallography to link an orphan protein domain with an orphan biochemical function. This result paves the way for large-scale functional annotation and sets new objectives for structural genomics. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Structural determinants of TRIM protein function.

    PubMed

    Esposito, Diego; Koliopoulos, Marios G; Rittinger, Katrin

    2017-02-08

    Tripartite motif (TRIM) proteins constitute one of the largest subfamilies of Really Interesting New Gene (RING) E3 ubiquitin ligases and contribute to the regulation of numerous cellular activities, including innate immune responses. The conserved TRIM harbours a RING domain that imparts E3 ligase activity to TRIM family proteins, whilst a variable C-terminal region can mediate recognition of substrate proteins. The knowledge of the structure of these multidomain proteins and the functional interplay between their constituent domains is paramount to understanding their cellular roles. To date, available structural information on TRIM proteins is still largely restricted to subdomains of many TRIMs in isolation. Nevertheless, applying a combination of structural, biophysical and biochemical approaches has recently allowed important progress to be made towards providing a better understanding of the molecular features that underlie the function of TRIM family proteins and has uncovered an unexpected diversity in the link between self-association and catalytic activity.

  16. Structure and function of complex brain networks.

    PubMed

    Sporns, Olaf

    2013-09-01

    An increasing number of theoretical and empirical studies approach the function of the human brain from a network perspective. The analysis of brain networks is made feasible by the development of new imaging acquisition methods as well as new tools from graph theory and dynamical systems. This review surveys some of these methodological advances and summarizes recent findings on the architecture of structural and functional brain networks. Studies of the structural connectome reveal several modules or network communities that are interlinked by hub regions mediating communication processes between modules. Recent network analyses have shown that network hubs form a densely linked collective called a "rich club," centrally positioned for attracting and dispersing signal traffic. In parallel, recordings of resting and task-evoked neural activity have revealed distinct resting-state networks that contribute to functions in distinct cognitive domains. Network methods are increasingly applied in a clinical context, and their promise for elucidating neural substrates of brain and mental disorders is discussed.

  17. Structured Functional Principal Component Analysis

    PubMed Central

    Shou, Haochang; Zipunnikov, Vadim; Crainiceanu, Ciprian M.; Greven, Sonja

    2015-01-01

    Summary Motivated by modern observational studies, we introduce a class of functional models that expand nested and crossed designs. These models account for the natural inheritance of the correlation structures from sampling designs in studies where the fundamental unit is a function or image. Inference is based on functional quadratics and their relationship with the underlying covariance structure of the latent processes. A computationally fast and scalable estimation procedure is developed for high-dimensional data. Methods are used in applications including high-frequency accelerometer data for daily activity, pitch linguistic data for phonetic analysis, and EEG data for studying electrical brain activity during sleep. PMID:25327216

  18. Structure of brain functional networks.

    PubMed

    Kuchaiev, Oleksii; Wang, Po T; Nenadic, Zoran; Przulj, Natasa

    2009-01-01

    Brain is a complex network optimized both for segregated and distributed information processing. To perform cognitive tasks, different areas of the brain must "cooperate," thereby forming complex networks of interactions also known as brain functional networks. Previous studies have shown that these networks exhibit "small-world" characteristics. Small-world topology, however, is a general property of all brain functional networks and does not capture structural changes in these networks in response to different stimuli or cognitive tasks. Here we show how novel graph theoretic techniques can be utilized for precise analysis of brain functional networks. These techniques allow us to detect structural changes in brain functional networks in response to different stimuli or cognitive tasks. For certain types of cognitive tasks we have found that these networks exhibit geometric structure in addition to the small-world topology. The method has been applied to the electrocorticographic signals of six epileptic patients.

  19. Time resolved structural dynamics of butadiyne-linked porphyrin dimers

    PubMed Central

    Camargo, Franco V. A.; Hall, Christopher R.; Anderson, Harry L.; Meech, Stephen R.; Heisler, Ismael A.

    2016-01-01

    In this work, the timescales and mechanisms associated with the structural dynamics of butadiyne-linked porphyrin dimers are investigated through time resolved narrowband pump/broadband probe transient absorption spectroscopy. Our results confirm previous findings that the broadening is partly due to a distribution of structures with different (dihedral) angular conformations. Comparison of measurements with excitations on the red and blue sides of the Q-band unravel the ground and excited state conformational re-equilibration timescales. Further comparison to a planarized dimer, through the addition of a ligand, provides conclusive evidence for the twisting motion performed by the porphyrin dimer in solution. PMID:26798839

  20. Sex-linked genes in age-structured populations.

    PubMed

    Cornette, J L

    1978-04-01

    We study the progress towards equilibrium of the frequencies of sex-linked genes in elementary discrete time models of age-structured, overlapping generation populations. It is found that, if a finite upper age limit is assumed, the difference in the frequencies of an allele in males and females will oscillate as in the familiar non-overlapping generation models, although the oscillations may be irregular. Monotonic convergence of that difference, as found by Nagylaki (1975) in continuous-time overlapping generation models without age-structure, occurs in the models considered here only when there is no upper age limit and when there is "sufficient" overlap of generations.

  1. Using the Structure-Function Linkage Database to Characterize Functional Domains in Enzymes

    PubMed Central

    Brown, Shoshana; Babbitt, Patricia

    2015-01-01

    The Structure-Function Linkage Database (SFLD; http://sfld.rbvi.ucsf.edu/) is a web-accessible database designed to link enzyme sequence, structure and functional information. This unit describes the protocol by which a user may query the database to predict the function of uncharacterized enzymes and to correct misannotated functional assignments. It is especially useful in helping a user discriminate functional capabilities of a sequence that is only distantly related to characterized sequences in publicly available databases. PMID:25501940

  2. Functional Generalized Structured Component Analysis.

    PubMed

    Suk, Hye Won; Hwang, Heungsun

    2016-12-01

    An extension of Generalized Structured Component Analysis (GSCA), called Functional GSCA, is proposed to analyze functional data that are considered to arise from an underlying smooth curve varying over time or other continua. GSCA has been geared for the analysis of multivariate data. Accordingly, it cannot deal with functional data that often involve different measurement occasions across participants and a large number of measurement occasions that exceed the number of participants. Functional GSCA addresses these issues by integrating GSCA with spline basis function expansions that represent infinite-dimensional curves onto a finite-dimensional space. For parameter estimation, functional GSCA minimizes a penalized least squares criterion by using an alternating penalized least squares estimation algorithm. The usefulness of functional GSCA is illustrated with gait data.

  3. HMG Nuclear Proteins: Linking Chromatin Structure to Cellular Phenotype

    PubMed Central

    Reeves, Raymond

    2009-01-01

    I. Summary Although the three families of mammalian HMG proteins (HMGA, HMGB and HMGN) participate in many of the same nuclear processes, each family plays its own unique role in modulating chromatin structure and regulating genomic function. This review focuses on the similarities and differences in the mechanisms by which the different HMG families impact chromatin structure and influence cellular phenotype. The biological implications of having three architectural transcription factor families with complementary, but partially overlapping, nuclear functions are discussed. PMID:19748605

  4. Ecosystem structure and function modeling

    USGS Publications Warehouse

    Humphries, H.C.; Baron, J.S.; Jensen, M.E.; Bourgeron, P.

    2001-01-01

    An important component of ecological assessments is the ability to predict and display changes in ecosystem structure and function over a variety of spatial and temporal scales. These changes can occur over short (less than 1 year) or long time frames (over 100 years). Models may emphasize structural responses (changes in species composition, growth forms, canopy height, amount of old growth, etc.) or functional responses (cycling of carbon, nutrients, and water). Both are needed to display changes in ecosystem components for use in robust ecological assessments. Structure and function models vary in the ecosystem components included, algorithms employed, level of detail, and spatial and temporal scales incorporated. They range from models that track individual organisms to models of broad-scale landscape changes. This chapter describes models appropriate for ecological assessments. The models selected for inclusion can be implemented in a spatial framework and for the most part have been run in more than one system.

  5. The structure of rigid functions

    NASA Astrophysics Data System (ADS)

    Balka, Richárd; Elekes, Márton

    2008-09-01

    A function is called vertically rigid if graph(cf) is isometric to graph(f) for all c[not equal to]0. We prove Jankovic's conjecture by showing that a continuous function is vertically rigid if and only if it is of the form a+bx or a+bekx (). We answer the question of Cain, Clark and Rose by showing that there exists a Borel measurable vertically rigid function which is not of the above form. We discuss the Lebesgue and Baire measurable case, consider functions bounded on some interval and functions with at least one point of continuity. We also introduce horizontally rigid functions, and show that a certain structure theorem can be proved without assuming any regularity.

  6. Structure functions and parton distributions

    SciTech Connect

    Martin, A.D.; Stirling, W.J.; Roberts, R.G.

    1995-07-01

    The MRS parton distribution analysis is described. The latest sets are shown to give an excellent description of a wide range of deep-inelastic and other hard scattering data. Two important theoretical issues-the behavior of the distributions at small x and the flavor structure of the quark sea-are discussed in detail. A comparison with the new structure function data from HERA is made, and the outlook for the future is discussed.

  7. 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.

  8. Link prediction boosted psychiatry disorder classification for functional connectivity network

    NASA Astrophysics Data System (ADS)

    Li, Weiwei; Mei, Xue; Wang, Hao; Zhou, Yu; Huang, Jiashuang

    2017-02-01

    Functional connectivity network (FCN) is an effective tool in psychiatry disorders classification, and represents cross-correlation of the regional blood oxygenation level dependent signal. However, FCN is often incomplete for suffering from missing and spurious edges. To accurate classify psychiatry disorders and health control with the incomplete FCN, we first `repair' the FCN with link prediction, and then exact the clustering coefficients as features to build a weak classifier for every FCN. Finally, we apply a boosting algorithm to combine these weak classifiers for improving classification accuracy. Our method tested by three datasets of psychiatry disorder, including Alzheimer's Disease, Schizophrenia and Attention Deficit Hyperactivity Disorder. The experimental results show our method not only significantly improves the classification accuracy, but also efficiently reconstructs the incomplete FCN.

  9. 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.

  10. Nrf2 links epidermal barrier function with antioxidant defense

    PubMed Central

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

    2012-01-01

    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

  11. Structural Plasticity and Hippocampal Function

    PubMed Central

    Leuner, Benedetta; Gould, Elizabeth

    2010-01-01

    The hippocampus is a region of the mammalian brain that shows an impressive capacity for structural reorganization. Preexisting neural circuits undergo modifications in dendritic complexity and synapse number, and entirely novel neural connections are formed through the process of neurogenesis. These types of structural change were once thought to be restricted to development. However, it is now generally accepted that the hippocampus remains structurally plastic throughout life. This article reviews structural plasticity in the hippocampus over the lifespan, including how it is investigated experimentally. The modulation of structural plasticity by various experiential factors as well as the possible role it may have in hippocampal functions such as learning and memory, anxiety, and stress regulation are also considered. Although significant progress has been made in many of these areas, we highlight some of the outstanding issues that remain. PMID:19575621

  12. Effect of O-Linked Glycosylation on the Equilibrium Structural Ensemble of Intrinsically Disordered Polypeptides.

    PubMed

    Zerze, Gül H; Mittal, Jeetain

    2015-12-24

    Glycosylation is one of the most common post-translational modifications (PTMs), which provides a large proteome diversity. Previous work on glycosylation of globular proteins has revealed remarkable effects of glycosylation on protein function, altering the folding stability and structure and/or altering the protein surface which affects their binding characteristics. Intrinsically disordered proteins (IDPs) or intrinsically disordered regions (IDRs) of large proteins are also frequently glycosylated, yet how glycosylation affects their function remains to be elucidated. An important open question is, does glycosylation affect IDP structure or binding characteristics or both? In this work, we particularly address the structural effects of O-linked glycosylation by investigating glycosylated and unglycosylated forms of two different IDPs, tau174-183 and human islet amyloid polypeptide (hIAPP), by all-atom explicit solvent simulations. We simulate these IDPs in aqueous solution for O-linked glycosylated and unglycosylated forms by employing two modern all-atom force fields for which glycan parameters are also available. We find that O-linked glycosylation only has a modest effect on equilibrium structural ensembles of IDPs, for the cases studied here, which suggests that the functional role of glycosylation may be primarily exerted by modulation of the protein binding characteristics rather than structure.

  13. Structure and Function of Wood

    Treesearch

    Alex C. Wiedenhoeft

    2012-01-01

    Wood is a complex biological structure, a composite of many cell types and chemistries acting together to serve the needs of living plant. Attempting to understand wood inthe context of wood technology, we have often overlooked the basic fact that wood evolved over the course of millions of years to serve three main functions in plants-conduction of water from the...

  14. Supersaturated lysozyme solution structure studied by chemical cross-linking.

    PubMed

    Hall, Clayton L; Clemens, John R; Brown, Amanda M; Wilson, Lori J

    2005-06-01

    Glutaraldehyde cross-linking followed by separation has been used to detect aggregates of chicken egg-white lysozyme (CEWL) in supersaturated solutions. In solutions of varying NaCl content, the number of aggregates was found to be related to the ionic strength of the solution. Separation by SDS-PAGE showed that percentage of dimer in solution ranged from 25.3% for no NaCl to 27.1% at 15% NaCl, and the aggregates larger than dimer increased from 1.9% for no NaCl to 36.8% at 15% NaCl. Conversely, the percentage of monomers decreased from 72.8% without NaCl to 36.1% at 15% NaCl. Molecular weights by capillary electrophoresis (SDS-CE) were found to be multiples of the monomer molecular weights, with the exception of trimer, which indicates a very compact structure. Native separation was accomplished using size-exclusion chromatography (SEC) and gave a lower monomer concentration and higher aggregate concentration than SDS-CE, which is a denaturing separation method. Most noticeably, trimers were absent in the SEC separation. The number of aggregates did not change with increased time between addition of NaCl and addition of cross-linking agent when separated by gel electrophoresis (SDS-PAGE). The results suggest that high ionic strength CEWL solutions are highly aggregated and that denaturing separation methods disrupt cross-linked products.

  15. 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

  16. Exploring the link between character, personality disorder, and neuropsychological function.

    PubMed

    Bergvall, A H; Nilsson, T; Hansen, S

    2003-11-01

    Personality deviations and deficits in cognitive executive function are common among forensic populations. The present study on incarcerated offenders explored whether there are links between the two domains. Personality was assessed using the Temperament and Character Inventory (TCI). Neuropsychological performance, including visual working memory, attentional set-shifting and planning, were tested with the Cambridge Neuropsychological Test Automated Battery (CANTAB). Subjects with personality disorders scored high on harm avoidance, and low on self-directedness and cooperativeness. Personality disordered offenders did not differ from the comparison groups (offenders without personality disorder, and non-criminal controls) with regard to CANTAB measures of visual working memory (delayed matching to sample, spatial working memory) and planning (Stockings of Cambridge), but they made a larger number of errors on the attentional set-shifting task. Dimensional analysis of the personality and neuropsychological variables revealed significant associations between self-directedness and cooperativeness on the one hand, and attentional set-shifting on the other. Intellectually disabled, non-criminal individuals (marginal mental retardation) who performed poorly on attentional set-shifting also scored low on self-directedness and cooperativeness. The results indicate that poor development of certain personality traits may be associated with deficits in neuropsychological functioning.

  17. The Structure and Conformation of Lys63-Linked Tetraubiquitin

    SciTech Connect

    Datta, Ajit B.; Hura, Greg L.; Wolberger, Cynthia

    2009-10-07

    Ubiquitination involves the covalent attachment of the ubiquitin (Ub) C-terminus to the lysine side chain of a substrate protein by an isopeptide bond. The modification can comprise a single Ub moiety or a chain of Ub molecules joined by isopeptide bonds between the C-terminus of one Ub with one of the seven lysine residues in the next Ub. Modification of substrate proteins with Lys63-linked poly-Ub plays a key nondegradative signaling role in many biological processes, including DNA repair and nuclear factor-{kappa}B activation, whereas substrates modified by Lys48-linked chains are targeted to the proteasome for degradation. The distinct signaling properties of alternatively linked Ub chains presumably stem from structural differences that can be distinguished by effector proteins. We have determined the crystal structure of Lys63 tetra-Ub at a resolution of 1.96 {angstrom} and performed small-angle X-ray scattering experiments and molecular dynamics simulations to probe the conformation of Lys63 tetra-Ub in solution. The chain adopts a highly extended conformation in the crystal, in contrast with the compact globular fold of Lys48 tetra-Ub. Small-angle X-ray scattering experiments show that the Lys63 tetra-Ub chain is dynamic in solution, adopting an ensemble of conformations that are more compact than the extended form in the crystal. The results of these studies provide a basis for understanding the differences in the behavior and recognition of Lys63 poly-Ub chains.

  18. Hypoxia and Brittlestars: Linking Physiology and Behaviour to Ecosystem Function.

    NASA Astrophysics Data System (ADS)

    Calder-Potts, R.; Spicer, J. I.; Calosi, P.; Findlay, H. S.; Widdicombe, S.

    2016-02-01

    Hypoxic events are increasing in frequency and duration, particularly in areas susceptible to eutrophication. Such events pose a growing threat to the health and function of marine ecosystems by altering large-scale biological and ecological processes. Linking how hypoxia impacts upon key benthic invertebrates, both in terms of their physiology and behaviour, to the disruption of ecosystem function and services is of primary importance. Station L4 forms part of the Western Channel Observatory, a long-standing oceanic time-series and marine biodiversity reference site. Recent observations indicate that L4 has experienced unusually large and long-lived spring blooms and seasonally driven periods of reduced O2 levels altering benthic community composition. Using a mesocosm experiment, we investigated the effects of short-term moderate hypoxia (14 d, 3.59 mg O2 L-1) and organism density (5, 9, 13, 17, and 21 ind. per aquarium) on the aerobic metabolism and reproductive biology of a key infaunal species, the brittlestar Amphiura filiformis. In addition, bioturbation parameters were recorded as a measure of organism activity, alongside nutrient flux measurements as a proxy for ecosystem function effects. Exposure to hypoxia resulted in reduced metabolism, and caused a delay in metabolic recovery rates once normoxic (8.09 mg O2 L-1) conditions were re-established. Additionally, hypoxia also caused a delay in females' reproductive cell development, smaller oocyte diameters, and a greater number of pre-vitellogenic oocytes present within the ovaries. Interestingly, while organism density had no significant effect on the physiological or histological traits examined, it did have a positive effect on bioturbation activity, an effect which was reduced by hypoxia. The observed disruptions to metabolic rates, reproductive biology and organisms' activity will be further discussed in terms of their ecological implications and possible long-term effects if repeated hypoxic events

  19. Structure and Function of AApeptides

    PubMed Central

    Bolarinwa, Olapeju; Nimmagadda, Alekhya; Su, Ma; Cai, Jianfeng

    2017-01-01

    The intrinsic drawbacks encountered in bioactive peptides in chemical biology and biomedical sciences have diverted research efforts to the development of sequence-specific peptidomimetics that are capable of mimicking the structure and function of peptides and proteins. Modifications in the backbone and/or the side chain of peptides have been explored to develop biomimetic molecular probes or drug leads for biologically important targets. To expand the family of oligomeric peptidomimetics to facilitate their further application, we recently developed a new class of peptidomimetics, AApeptides based on a chiral peptide nucleic acid backbone. AApeptides are resistant to proteolytic degradation and amenable to enormous chemical diversification. Moreover, they could mimic the primary structure of peptides and also fold into discrete secondary structure such as helices and turn-like structures. Furthermore, they have started to show promise in applications in material and biomedical sciences. Herein, we highlight the structural design and some function of AApeptides and present our perspective on their future development. PMID:28029249

  20. Linking Neural and Symbolic Representation and Processing of Conceptual Structures

    PubMed Central

    van der Velde, Frank; Forth, Jamie; Nazareth, Deniece S.; Wiggins, Geraint A.

    2017-01-01

    We compare and discuss representations in two cognitive architectures aimed at representing and processing complex conceptual (sentence-like) structures. First is the Neural Blackboard Architecture (NBA), which aims to account for representation and processing of complex and combinatorial conceptual structures in the brain. Second is IDyOT (Information Dynamics of Thinking), which derives sentence-like structures by learning statistical sequential regularities over a suitable corpus. Although IDyOT is designed at a level more abstract than the neural, so it is a model of cognitive function, rather than neural processing, there are strong similarities between the composite structures developed in IDyOT and the NBA. We hypothesize that these similarities form the basis of a combined architecture in which the individual strengths of each architecture are integrated. We outline and discuss the characteristics of this combined architecture, emphasizing the representation and processing of conceptual structures. PMID:28848460

  1. Linking Neural and Symbolic Representation and Processing of Conceptual Structures.

    PubMed

    van der Velde, Frank; Forth, Jamie; Nazareth, Deniece S; Wiggins, Geraint A

    2017-01-01

    We compare and discuss representations in two cognitive architectures aimed at representing and processing complex conceptual (sentence-like) structures. First is the Neural Blackboard Architecture (NBA), which aims to account for representation and processing of complex and combinatorial conceptual structures in the brain. Second is IDyOT (Information Dynamics of Thinking), which derives sentence-like structures by learning statistical sequential regularities over a suitable corpus. Although IDyOT is designed at a level more abstract than the neural, so it is a model of cognitive function, rather than neural processing, there are strong similarities between the composite structures developed in IDyOT and the NBA. We hypothesize that these similarities form the basis of a combined architecture in which the individual strengths of each architecture are integrated. We outline and discuss the characteristics of this combined architecture, emphasizing the representation and processing of conceptual structures.

  2. Developmental imaging genetics: linking dopamine function to adolescent behavior

    PubMed Central

    Padmanabhan, Aarthi; Luna, Beatriz

    2014-01-01

    Adolescence is a period of development characterized by numerous neurobiological changes that significantly influence behavior and brain function. Adolescence is of particular interest due to the alarming statistics indicating that mortality rates increase two to three-fold during this time compared to childhood, due largely to a peak in risk-taking behaviors resulting from increased impulsivity and sensation seeking. Furthermore, there exists large unexplained variability in these behaviors that are in part mediated by biological factors. Recent advances in molecular genetics and functional neuroimaging have provided a unique and exciting opportunity to noninvasively study the influence of genetic factors on brain function in humans. While genes do not code for specific behaviors, they do determine the structure and function of proteins that are essential to the neuronal processes that underlie behavior. Therefore, studying the interaction of genotype with measures of brain function over development could shed light on critical time points when biologically mediated individual differences in complex behaviors emerge. Here we review animal and human literature examining the neurobiological basis of adolescent development related to dopamine neurotransmission. Dopamine is of critical importance because of (1) its role in cognitive and affective behaviors, (2) its role in the pathogenesis of major psychopathology, and (3) the protracted development of dopamine signaling pathways over adolescence. We will then focus on current research examining the role of dopamine-related genes on brain function. We propose the use of imaging genetics to examine the influence of genetically mediated dopamine variability on brain function during adolescence, keeping in mind the limitations of this approach. PMID:24139694

  3. Developmental imaging genetics: linking dopamine function to adolescent behavior.

    PubMed

    Padmanabhan, Aarthi; Luna, Beatriz

    2014-08-01

    Adolescence is a period of development characterized by numerous neurobiological changes that significantly influence behavior and brain function. Adolescence is of particular interest due to the alarming statistics indicating that mortality rates increase two to three-fold during this time compared to childhood, due largely to a peak in risk-taking behaviors resulting from increased impulsivity and sensation seeking. Furthermore, there exists large unexplained variability in these behaviors that are in part mediated by biological factors. Recent advances in molecular genetics and functional neuroimaging have provided a unique and exciting opportunity to non-invasively study the influence of genetic factors on brain function in humans. While genes do not code for specific behaviors, they do determine the structure and function of proteins that are essential to the neuronal processes that underlie behavior. Therefore, studying the interaction of genotype with measures of brain function over development could shed light on critical time points when biologically mediated individual differences in complex behaviors emerge. Here we review animal and human literature examining the neurobiological basis of adolescent development related to dopamine neurotransmission. Dopamine is of critical importance because of (1) its role in cognitive and affective behaviors, (2) its role in the pathogenesis of major psychopathology, and (3) the protracted development of dopamine signaling pathways over adolescence. We will then focus on current research examining the role of dopamine-related genes on brain function. We propose the use of imaging genetics to examine the influence of genetically mediated dopamine variability on brain function during adolescence, keeping in mind the limitations of this approach. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. [Protein phosphatases: structure and function].

    PubMed

    Bulanova, E G; Budagian, V M

    1994-01-01

    The process of protein and enzyme systems phosphorylation is necessary for cell growth, differentiation and preparation for division and mitosis. The conformation changes of protein as a result of phosphorylation lead to increased enzyme activity and enhanced affinity to substrates. A large group of enzymes--protein kinases--is responsible for phosphorylation process in cell, which are divided into tyrosine- and serine-threonine-kinases depending on their ability to phosphorylate appropriate amino acid residues. In this review has been considered the functional importance and structure of protein phosphatases--enzymes, which are functional antagonists of protein kinases.

  5. 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

  6. The structure of human cleavage factor I(m) hints at functions beyond UGUA-specific RNA binding: a role in alternative polyadenylation and a potential link to 5' capping and splicing.

    PubMed

    Yang, Qin; Gilmartin, Gregory M; Doublié, Sylvie

    2011-01-01

    3'-end cleavage and subsequent polyadenylation are critical steps in mRNA maturation. The precise location where cleavage occurs (referred to as poly(A) site) is determined by a tripartite mechanism in which a A(A/U)UAAA hexamer, GU rich downstream element and UGUA upstream element are recognized by the cleavage and polyadenylation factor (CPSF), cleavage stimulation factor (CstF) and cleavage factor I(m) (CFI(m)), respectively. CFI(m) is composed of a smaller 25 kDa subunit (CFI(m)25) and a larger 59, 68 or 72 kDa subunit. CFI(m)68 interacts with CFI(m)25 through its N-terminal RNA recognition motif (RRM). We recently solved the crystal structures of CFI(m)25 bound to RNA and of a complex of CFI(m)25, the RRM domain of CFI(m)68 and RNA. Our study illustrated the molecular basis for UGUA recognition by the CFI(m) complex, suggested a possible mechanism for CFI(m) mediated alternative polyadenylation, and revealed potential links between CFI(m) and other mRNA processing factors, such as the 20 kDa subunit of the cap binding protein (CBP20), and the splicing regulator U2AF65.

  7. Structure and functions of angiotensinogen

    PubMed Central

    Lu, Hong; Cassis, Lisa A; Kooi, Craig W Vander; Daugherty, Alan

    2016-01-01

    Angiotensinogen (AGT) is the sole precursor of all angiotensin peptides. Although AGT is generally considered as a passive substrate of the renin–angiotensin system, there is accumulating evidence that the regulation and functions of AGT are intricate. Understanding the diversity of AGT properties has been enhanced by protein structural analysis and animal studies. In addition to whole-body genetic deletion, AGT can be regulated in vivo by cell-specific procedures, adeno-associated viral approaches and antisense oligonucleotides. Indeed, the availability of these multiple manipulations of AGT in vivo has provided new insights into the multifaceted roles of AGT. In this review, the combination of structural and functional studies is highlighted to focus on the increasing recognition that AGT exerts effects beyond being a sole provider of angiotensin peptides. PMID:26888118

  8. Structural insights into Elongator function.

    PubMed

    Glatt, Sebastian; Müller, Christoph W

    2013-04-01

    The eukaryotic Elongator complex was initially identified in yeast as a RNA polymerase II (Pol II) associated transcription elongation factor, although there is accumulating evidence that its main cellular function is the specific modification of uridines at the wobble base position of tRNAs. Elongator complex is built up by six highly conserved subunits and was shown to be involved in a variety of different cellular activities. Here, we summarize structural and functional information on individual Elongator subunits or subcomplexes. On the basis of homology models of the Elp1, Elp2 and Elp3 subunits and the crystal structure of the Elp456 subcomplex, the role of each subunit in Elongator complex assembly and catalytic activity is discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Structure and function of wood

    Treesearch

    Alex Wiedenhoeft

    2010-01-01

    Wood is a complex biological structure, a composite of many chemistries and cell types acting together to serve the needs of a living plant. Attempting to understand wood in the context of wood technology, we have often overlooked the key and basic fact that wood evolved over the course of millions of years to serve three main functions in plants― conduction of water...

  10. Structure and Function of Glucansucrases

    NASA Astrophysics Data System (ADS)

    Dijkstra, B. W.; Vujičić-Žagar, A.

    2008-03-01

    Glucansucrases are relatively large (~160 kDa) extracellular enzymes produced by lactic acid bacteria. Using sucrose as a substrate they synthesize high molecular mass glucose polymers, called α-glucans, which allow the bacteria to adhere to surfaces and create a biofilm. The glucan polymers are of importance for the food and dairy industry as thickening and jellying agents. An overview is given of the current insights into the structure and functioning of these and related enzymes.

  11. Neural Circuit Inference from Function to Structure.

    PubMed

    Real, Esteban; Asari, Hiroki; Gollisch, Tim; Meister, Markus

    2017-01-23

    Advances in technology are opening new windows on the structural connectivity and functional dynamics of brain circuits. Quantitative frameworks are needed that integrate these data from anatomy and physiology. Here, we present a modeling approach that creates such a link. The goal is to infer the structure of a neural circuit from sparse neural recordings, using partial knowledge of its anatomy as a regularizing constraint. We recorded visual responses from the output neurons of the retina, the ganglion cells. We then generated a systematic sequence of circuit models that represents retinal neurons and connections and fitted them to the experimental data. The optimal models faithfully recapitulated the ganglion cell outputs. More importantly, they made predictions about dynamics and connectivity among unobserved neurons internal to the circuit, and these were subsequently confirmed by experiment. This circuit inference framework promises to facilitate the integration and understanding of big data in neuroscience.

  12. Connectivity and functional profiling of abnormal brain structures in pedophilia

    PubMed Central

    Poeppl, Timm B.; Eickhoff, Simon B.; Fox, Peter T.; Laird, Angela R.; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo

    2015-01-01

    Despite its 0.5–1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multi-modal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia. PMID:25733379

  13. Connectivity and functional profiling of abnormal brain structures in pedophilia.

    PubMed

    Poeppl, Timm B; Eickhoff, Simon B; Fox, Peter T; Laird, Angela R; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo

    2015-06-01

    Despite its 0.5-1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multimodal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia. © 2015 Wiley Periodicals, Inc.

  14. Visual Function in Carriers of X-Linked Retinitis Pigmentosa.

    PubMed

    Comander, Jason; Weigel-DiFranco, Carol; Sandberg, Michael A; Berson, Eliot L

    2015-09-01

    To determine the frequency and severity of visual function loss in female carriers of X-linked retinitis pigmentosa (XLRP). Case series. Two hundred seventy-six XLRP carriers with cross-sectional data (n = 242) and longitudinal data (n = 34; median follow-up, 16 years; follow-up range, 3-37 years). Half of the carriers were from RPGR- or RP2-genotyped families. Retrospective medical records review. Visual acuities, visual field areas, final dark adaptation thresholds, and full-field electroretinography (ERG) responses to 0.5-Hz and 30-Hz flashes. In genotyped families, 40% of carriers showed a baseline abnormality on at least 1 of 3 psychophysical tests. There was a wide range of function among carriers. For example, 3 of 121 (2%) genotyped carriers were legally blind because of poor visual acuity, some as young as 35 years. Visual fields were less affected than visual acuity. In all carriers, the average ERG amplitude to 30-Hz flashes was approximately 50% of normal, and the average exponential rate of amplitude loss over time was half that of XLRP males (3.7%/year vs. 7.4%/year, respectively). Among obligate carriers with affected fathers, sons, or both, 53 of 55 (96%) had abnormal baseline ERG results. Some carriers who initially had completely normal fundi in both eyes went on to experience moderately decreased vision, although not legal blindness. Among carriers with RPGR mutations, those with mutations in ORF15, compared with those in exons 1-14, had worse final dark adaptation thresholds and lower 0.5-Hz and 30-Hz ERG amplitudes. Most carriers of XLRP had mildly or moderately reduced visual function but rarely became legally blind. In most cases, obligate carriers could be identified by ERG testing. Carriers of RPGR ORF15 mutations tended to have worse visual function than carriers of RPGR exon 1 through 14 mutations. Because XLRP carrier ERG amplitudes and decay rates over time were on average half of those of affected men, these observations were

  15. 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

  16. Mechanical behavior of highly cross-linked polymer networks and its links to microscopic structure.

    PubMed

    Mukherji, Debashish; Abrams, Cameron F

    2009-06-01

    Highly cross-linked polymer (HCP) networks are becoming increasingly important as high-performance adhesives and multifunctional composite materials. Because of their cross-linked molecular architectures, HCPs can be strong but brittle. One key goal in improving the performance of an HCP is to increase toughness without sacrificing strength. Using large scale molecular-dynamics simulation, we compare and characterize the mechanical behavior of two model HCPs under tensile deformation. In the first case, bond angles among any three connected monomers are unconstrained and in the second case we impose harmonic tetrahedral bond angle constraints. We perform a detailed microstructural analysis that establishes a unique correlation between macroscopic mechanical behavior and the microscopic structure of an HCP. While, in the unconstrained system, strain-hardening behavior is observed that is attributed to the formation of microvoids, the void growth is completely arrested in the constrained system and no strain hardening is observed. Moreover, after the initial strain-hardening phase, the unconstrained system displays the same stress-strain behavior as that of a constrained network. Strain hardening makes the unconstrained system ductile while it retains the same tensile strength as the constrained system. We suggest that bond angle flexibility of cross-linkers might be a possible means to control ductility in an HCP network at a constant cross-linker density. We have also studied the effect of temperature, strain rate, and intermonomer nonbonded interaction strength on the stress-strain behavior. Interestingly at a strong intermonomer nonbonded interaction strength, no strain hardening is observed even in the unconstrained system and fracture sets in at around 1% strain, similar to what is observed in an experimental system such as epoxy and vinyl-ester based thermosets. This indicates that strong nonbonded interactions play a key role in making an HCP strong but

  17. Linking symbiont community structures in a model arbuscular mycorrhizal system.

    PubMed

    Meadow, James F; Zabinski, Catherine A

    2012-05-01

    • The influence of plant communities on symbiotic arbuscular mycorrhizal fungal (AMF) communities is difficult to study in situ as both symbionts are strongly influenced by some of the same soil and environmental conditions, and thus we have a poor understanding of the potential links in community composition and structure between host and fungal communities. • AMF were characterized in colonized roots of thermal soil Mimulus guttatus in both isolated plants supporting AMF for only a few months of the growing season and plants growing in mixed plant communities composed of annual and perennial hosts. Cluster and discriminant analysis were used to compare competing models based on either communities or soil conditions. • Mimulus guttatus in adjacent contrasting plant community situations harbored distinct AMF communities with few fungal taxa occurring in both community types. Isolated plants harbored communities of fewer fungal taxa with lower diversity than plants in mixed communities. Host community type was more indicative than pH of AMF community structure. • Our results support an inherent relationship between host plant and AMF community structures, although pH-based models were also statistically supported. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

  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. Mitochondria: isolation, structure and function.

    PubMed

    Picard, Martin; Taivassalo, Tanja; Gouspillou, Gilles; Hepple, Russell T

    2011-09-15

    Mitochondria are complex organelles constantly undergoing processes of fusion and fission, processes that not only modulate their morphology, but also their function. Yet the assessment of mitochondrial function in skeletal muscle often involves mechanical isolation of the mitochondria, a process which disrupts their normally heterogeneous branching structure and yields relatively homogeneous spherical organelles. Alternatively, methods have been used where the sarcolemma is permeabilized and mitochondrial morphology is preserved, but both methods face the downside that they remove potential influences of the intracellular milieu on mitochondrial function. Importantly, recent evidence shows that the fragmented mitochondrial morphology resulting from routine mitochondrial isolation procedures used with skeletal muscle alters key indices of function in a manner qualitatively similar to mitochondria undergoing fission in vivo. Although these results warrant caution when interpreting data obtained with mitochondria isolated from skeletal muscle, they also suggest that isolated mitochondrial preparations might present a useful way of interrogating the stress resistance of mitochondria. More importantly, these new findings underscore the empirical value of studying mitochondrial function in minimally disruptive experimental preparations. In this review, we briefly discuss several considerations and hypotheses emerging from this work.

  20. Mitochondria: isolation, structure and function

    PubMed Central

    Picard, Martin; Taivassalo, Tanja; Gouspillou, Gilles; Hepple, Russell T

    2011-01-01

    Abstract Mitochondria are complex organelles constantly undergoing processes of fusion and fission, processes that not only modulate their morphology, but also their function. Yet the assessment of mitochondrial function in skeletal muscle often involves mechanical isolation of the mitochondria, a process which disrupts their normally heterogeneous branching structure and yields relatively homogeneous spherical organelles. Alternatively, methods have been used where the sarcolemma is permeabilized and mitochondrial morphology is preserved, but both methods face the downside that they remove potential influences of the intracellular milieu on mitochondrial function. Importantly, recent evidence shows that the fragmented mitochondrial morphology resulting from routine mitochondrial isolation procedures used with skeletal muscle alters key indices of function in a manner qualitatively similar to mitochondria undergoing fission in vivo. Although these results warrant caution when interpreting data obtained with mitochondria isolated from skeletal muscle, they also suggest that isolated mitochondrial preparations might present a useful way of interrogating the stress resistance of mitochondria. More importantly, these new findings underscore the empirical value of studying mitochondrial function in minimally disruptive experimental preparations. In this review, we briefly discuss several considerations and hypotheses emerging from this work. PMID:21708903

  1. The structure and function of fungal cells

    NASA Technical Reports Server (NTRS)

    Nozawa, Y.

    1984-01-01

    The structure and function of fungal cell walls were studied with particular emphasis on dermatophytes. Extraction, isolation, analysis, and observation of the cell wall structure and function were performed. The structure is described microscopically and chemically.

  2. Desmosome structure, composition and function.

    PubMed

    Garrod, David; Chidgey, Martyn

    2008-03-01

    Desmosomes are intercellular junctions of epithelia and cardiac muscle. They resist mechanical stress because they adopt a strongly adhesive state in which they are said to be hyper-adhesive and which distinguishes them from other intercellular junctions; desmosomes are specialised for strong adhesion and their failure can result in diseases of the skin and heart. They are also dynamic structures whose adhesiveness can switch between high and low affinity adhesive states during processes such as embryonic development and wound healing, the switching being signalled by protein kinase C. Desmosomes may also act as signalling centres, regulating the availability of signalling molecules and thereby participating in fundamental processes such as cell proliferation, differentiation and morphogenesis. Here we consider the structure, composition and function of desmosomes, and their role in embryonic development and disease.

  3. Structure and functions of arrestins.

    PubMed Central

    Palczewski, K.

    1994-01-01

    Transmembrane signal transductions in a variety of cell types that mediate signals as diverse as those carried by neurotransmitters, hormones, and sensory signals share basic biochemical mechanisms that include: (1) an extracellular perturbation (neurotransmitter, hormone, odor, light); (2) specific receptors; (3) coupling proteins, such as G proteins; and (4) effector enzymes or ion channels. Parallel to these amplification reactions, receptors are precisely inactivated by mechanisms that involve protein kinases and regulatory proteins called arrestins. The structure and functions of arrestins are the focus of this review. PMID:7833798

  4. The g2 Structure Function

    SciTech Connect

    Matthias Burkardt

    2009-07-01

    Polarized structure functions at low $Q^2$ have the physical interpretation of (generalized) spin polarizabilities. At high $Q^2$, the polarized parton distribution $g_2(x)$ provides access to quark-gluon correlations in the nucleon. We discuss the interpretation of the $x^2$ moment of $\\bar{g}_2(x)$ as an average transverse force on quarks in deep-inelastic scattering from a transversely polarized target. Qualitative connections with generalized parton distributions are emphasized. The $x^2$ moment of the chirally-odd twist-3 parton distribution $e(x)$ provides information on the dependence of the average transverse force on the transversity of the quark.

  5. Linking Frailty Instruments to the International Classification of Functioning, Disability, and Health: A Systematic Review.

    PubMed

    Azzopardi, Roberta Vella; Vermeiren, Sofie; Gorus, Ellen; Habbig, Ann-Katrin; Petrovic, Mirko; Van Den Noortgate, Nele; De Vriendt, Patricia; Bautmans, Ivan; Beyer, Ingo

    2016-11-01

    To date, the major dilemma concerning frailty is the lack of a standardized language regarding its operationalization. Considering the demographic challenge that the world is facing, standardization of frailty identification is indeed the first step in tackling the burdensome consequences of frailty. To demonstrate this diversity in frailty assessment, the available frailty instruments have been linked to the International Classification of Functioning, Disability, and Health (ICF): a standardized and hierarchically coded language developed by World Health Organization regarding health conditions and their positive (functioning) and negative (disability) consequences. A systematic review on frailty instruments was carried out in PubMed, Web of Knowledge, and PsycINFO. The items of the identified frailty instruments were then linked to the ICF codes. 79 original or adapted frailty instruments were identified and categorized into single (n = 25) and multidomain (n = 54) groups. Only 5 frailty instruments (indexes) were linked to all 5 ICF components. Whereas the ICF components Body Functions and Activities and Participation were frequently linked to the frailty instruments, Body Structures, Environmental and Personal factors were sparingly represented mainly in the multidomain frailty instruments. This review highlights the heterogeneity in frailty operationalization. Environmental and personal factors should be given more thought in future frailty assessments. Being unambiguous, structured, and neutral, the ICF language allows comparing observations made with different frailty instruments. In conclusion, this systematic overview and ICF translation can be a cornerstone for future standardization of frailty assessment. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  6. 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

  7. Functional nanometer-scale structures

    NASA Astrophysics Data System (ADS)

    Chan, Tsz On Mario

    Nanometer-scale structures have properties that are fundamentally different from their bulk counterparts. Much research effort has been devoted in the past decades to explore new fabrication techniques, model the physical properties of these structures, and construct functional devices. The ability to manipulate and control the structure of matter at the nanoscale has made many new classes of materials available for the study of fundamental physical processes and potential applications. The interplay between fabrication techniques and physical understanding of the nanostructures and processes has revolutionized the physical and material sciences, providing far superior properties in materials for novel applications that benefit society. This thesis consists of two major aspects of my graduate research in nano-scale materials. In the first part (Chapters 3--6), a comprehensive study on the nanostructures based on electrospinning and thermal treatment is presented. Electrospinning is a well-established method for producing high-aspect-ratio fibrous structures, with fiber diameter ranging from 1 nm--1 microm. A polymeric solution is typically used as a precursor in electrospinning. In our study, the functionality of the nanostructure relies on both the nanostructure and material constituents. Metallic ions containing precursors were added to the polymeric precursor following a sol-gel process to prepare the solution suitable for electrospinning. A typical electrospinning process produces as-spun fibers containing both polymer and metallic salt precursors. Subsequent thermal treatments of the as-spun fibers were carried out in various conditions to produce desired structures. In most cases, polymer in the solution and the as-spun fibers acted as a backbone for the structure formation during the subsequent heat treatment, and were thermally removed in the final stage. Polymers were also designed to react with the metallic ion precursors during heat treatment in some

  8. Brain structure links everyday creativity to creative achievement.

    PubMed

    Zhu, Wenfeng; Chen, Qunlin; Tang, Chaoying; Cao, Guikang; Hou, Yuling; Qiu, Jiang

    2016-03-01

    Although creativity is commonly considered to be a cornerstone of human progress and vital to all realms of our lives, its neural basis remains elusive, partly due to the different tasks and measurement methods applied in research. In particular, the neural correlates of everyday creativity that can be experienced by everyone, to some extent, are still unexplored. The present study was designed to investigate the brain structure underlying individual differences in everyday creativity, as measured by the Creative Behavioral Inventory (CBI) (N=163). The results revealed that more creative activities were significantly and positively associated with larger gray matter volume (GMV) in the regional premotor cortex (PMC), which is a motor planning area involved in the creation and selection of novel actions and inhibition. In addition, the gray volume of the PMC had a significant positive relationship with creative achievement and Art scores, which supports the notion that training and practice may induce changes in brain structures. These results indicate that everyday creativity is linked to the PMC and that PMC volume can predict creative achievement, supporting the view that motor planning may play a crucial role in creative behavior.

  9. MPOD: A Material Property Open Database linked to structural information

    NASA Astrophysics Data System (ADS)

    Pepponi, Giancarlo; Gražulis, Saulius; Chateigner, Daniel

    2012-08-01

    Inspired by the Crystallography Open Database (COD), the Material Properties Open Database (MPOD) was given birth. MPOD aims at collecting and making publicly available at no charge tensorial properties (including scalar properties) of phases and linking such properties to structural information of the COD when available. MPOD files are written with the STAR file syntax, used and developed for the Crystallographic Information Files. A dictionary containing new definitions has been written according to the Dictionary Definition Language 1, although some tricks were adopted to allow for multiple entries still avoiding ambiguousness. The initial set includes mechanical properties, elastic stiffness and compliance, internal friction; electrical properties, resistivity, dielectric permittivity and stiffness, thermodynamic properties, heat capacity, thermal conductivity, diffusivity and expansion; electromechanical properties, piezoelectricity, electrostriction, electromechanical coupling; optical properties; piezooptic and photoelastic properties; superconducting properties, critical fields, penetration and coherence lengths. Properties are reported in MPOD files where the original published paper containing the data is cited and structural and experimental information is also given. One MPOD file contains information relative to only one publication and one phase. The files and the information contained therein can also be consulted on-line at http://www.materialproperties.org.

  10. Brain Structure Linking Delay Discounting and Academic Performance.

    PubMed

    Wang, Song; Kong, Feng; Zhou, Ming; Chen, Taolin; Yang, Xun; Chen, Guangxiang; Gong, Qiyong

    2017-08-01

    As a component of self-discipline, delay discounting refers to the ability to wait longer for preferred rewards and plays a pivotal role in shaping students' academic performance. However, the neural basis of the association between delay discounting and academic performance remains largely unknown. Here, we examined the neuroanatomical substrates underlying delay discounting and academic performance in 214 adolescents via voxel-based morphometry (VBM) by performing structural magnetic resonance imaging (S-MRI). Behaviorally, we confirmed the significant correlation between delay discounting and academic performance. Neurally, whole-brain regression analyses indicated that regional gray matter volume (rGMV) of the left dorsolateral prefrontal cortex (DLPFC) was associated with both delay discounting and academic performance. Furthermore, delay discounting partly accounted for the association between academic performance and brain structure. Differences in the rGMV of the left DLPFC related to academic performance explained over one-third of the impact of delay discounting on academic performance. Overall, these results provide the first evidence for the common neural basis linking delay discounting and academic performance. Hum Brain Mapp 38:3917-3926, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. Structure and function of complex brain networks

    PubMed Central

    Sporns, Olaf

    2013-01-01

    An increasing number of theoretical and empirical studies approach the function of the human brain from a network perspective. The analysis of brain networks is made feasible by the development of new imaging acquisition methods as well as new tools from graph theory and dynamical systems. This review surveys some of these methodological advances and summarizes recent findings on the architecture of structural and functional brain networks. Studies of the structural connectome reveal several modules or network communities that are interlinked by hub regions mediating communication processes between modules. Recent network analyses have shown that network hubs form a densely linked collective called a “rich club,” centrally positioned for attracting and dispersing signal traffic. In parallel, recordings of resting and task-evoked neural activity have revealed distinct resting-state networks that contribute to functions in distinct cognitive domains. Network methods are increasingly applied in a clinical context, and their promise for elucidating neural substrates of brain and mental disorders is discussed. PMID:24174898

  12. Structure and function of tuna tail tendons.

    PubMed

    Shadwick, Robert E; Rapoport, H Scott; Fenger, Joelle M

    2002-12-01

    The caudal tendons in tunas and other scombrid fish link myotomal muscle directly to the caudal fin rays, and thus serve to transfer muscle power to the hydrofoil-like tail during swimming. These robust collagenous tendons have structural and mechanical similarity to tendons found in other vertebrates, notably the leg tendons of terrestrial mammals. Biochemical studies indicate that tuna tendon collagen is composed of the (alpha1)(2),alpha2 heterotrimer that is typical of vertebrate Type I collagen, while tuna skin collagen has the unusual alpha1,alpha2,alpha3 trimer previously described in the skin of some other teleost species. Tuna collagen, like that of other fish, has high solubility due to the presence of an acid-labile intermolecular cross-link. Unlike collagen in mammalian tendons, no differences related to cross-link maturation were detected among tendons in tuna ranging from 0.05 to 72 kg (approx. 0.25-6 years). Tendons excised post-mortem were subjected to load cycling to determine the modulus of elasticity and resilience (mean of 1.3 GPa and 90%, respectively). These material properties compare closely to those of leg tendons from adult mammals that can function as effective biological springs in terrestrial locomotion, but the breaking strength is substantially lower. Peak tendon forces recorded during steady swimming appear to impose strains of much less than 1% of tendon length, and no more than 1.5% during bursts. Thus, the caudal tendons in tunas do not appear to function as elastic storage elements, even at maximal swimming effort.

  13. Desmin Cytoskeleton Linked to Muscle Mitochondrial Distribution and Respiratory Function

    PubMed Central

    Milner, Derek J.; Mavroidis, Manolis; Weisleder, Noah; Capetanaki, Yassemi

    2000-01-01

    Ultrastructural studies have previously suggested potential association of intermediate filaments (IFs) with mitochondria. Thus, we have investigated mitochondrial distribution and function in muscle lacking the IF protein desmin. Immunostaining of skeletal muscle tissue sections, as well as histochemical staining for the mitochondrial marker enzymes cytochrome C oxidase and succinate dehydrogenase, demonstrate abnormal accumulation of subsarcolemmal clumps of mitochondria in predominantly slow twitch skeletal muscle of desmin-null mice. Ultrastructural observation of desmin-null cardiac muscle demonstrates in addition to clumping, extensive mitochondrial proliferation in a significant fraction of the myocytes, particularly after work overload. These alterations are frequently associated with swelling and degeneration of the mitochondrial matrix. Mitochondrial abnormalities can be detected very early, before other structural defects become obvious. To investigate related changes in mitochondrial function, we have analyzed ADP-stimulated respiration of isolated muscle mitochondria, and ADP-stimulated mitochondrial respiration in situ using saponin skinned muscle fibers. The in vitro maximal rates of respiration in isolated cardiac mitochondria from desmin-null and wild-type mice were similar. However, mitochondrial respiration in situ is significantly altered in desmin-null muscle. Both the maximal rate of ADP-stimulated oxygen consumption and the dissociation constant (Km) for ADP are significantly reduced in desmin-null cardiac and soleus muscle compared with controls. Respiratory parameters for desmin-null fast twitch gastrocnemius muscle were unaffected. Additionally, respiratory measurements in the presence of creatine indicate that coupling of creatine kinase and the adenine translocator is lost in desmin-null soleus muscle. This coupling is unaffected in cardiac muscle from desmin-null animals. All of these studies indicate that desmin IFs play a significant

  14. Adjusting to change: linking family structure transitions with parenting and boys' adjustment.

    PubMed

    Martinez, Charles R; Forgatch, Marion S

    2002-06-01

    This study examined links between family structure transitions and children's academic, behavioral, and emotional outcomes in a sample of 238 divorcing mothers and their sons in Grades 1-3. Multiple methods and agents were used in assessing family process variables and child outcomes. Findings suggest that greater accumulations of family transitions were associated with poorer academic functioning, greater acting-out behavior, and worse emotional adjustment for boys. However, in all three cases, these relationships were mediated by parenting practices: Parental academic skill encouragement mediated the relationship between transitions and academic functioning, and a factor of more general effective parenting practices mediated the relationships between transitions and acting out and emotional adjustment.

  15. Structural and functional bases of inhibited temperament.

    PubMed

    Clauss, Jacqueline A; Seay, April L; VanDerKlok, Ross M; Avery, Suzanne N; Cao, Aize; Cowan, Ronald L; Benningfield, Margaret M; Blackford, Jennifer Urbano

    2014-12-01

    Children born with an inhibited temperament are at heightened risk for developing anxiety, depression and substance use. Inhibited temperament is believed to have a biological basis; however, little is known about the structural brain basis of this vulnerability trait. Structural MRI scans were obtained from 84 (44 inhibited, 40 uninhibited) young adults. Given previous findings of amygdala hyperactivity in inhibited individuals, groups were compared on three measures of amygdala structure. To identify novel substrates of inhibited temperament, a whole brain analysis was performed. Functional activation and connectivity were examined across both groups. Inhibited adults had larger amygdala and caudate volume and larger volume predicted greater activation to neutral faces. In addition, larger amygdala volume predicted greater connectivity with subcortical and higher order visual structures. Larger caudate volume predicted greater connectivity with the basal ganglia, and less connectivity with primary visual and auditory cortex. We propose that larger volume in these salience detection regions may result in increased activation and enhanced connectivity in response to social stimuli. Given the strong link between inhibited temperament and risk for psychiatric illness, novel therapeutics that target these brain regions and related neural circuits have the potential to reduce rates of illness in vulnerable individuals. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  16. Rhodopsin: the Functional Significance of Asn-Linked Glycosylation and Other Post-translational Modifications

    PubMed Central

    Murray, Anne R.; Fliesler, Steven J.; Al-Ubaidi, Muayyad R.

    2010-01-01

    Rhodopsin, the G-protein coupled receptor in retinal rod photoreceptors, is a highly conserved protein that undergoes several types of post-translational modifications. These modifications are essential to maintain the protein’s structure as well as its proper function in the visual transduction cycle. Rhodopsin is N-glycosylated at Asn-2 and Asn-15 in its extracellular N-terminal domain. Mutations within the glycosylation consensus sequences of rhodopsin cause autosomal dominant retinitis pigmentosa, a disease that leads to blindness. Several groups have studied the role of rhodopsin’s N-linked glycan chains in protein structure and function using a variety of approaches. These include the generation of a transgenic mouse model, study of a naturally occurring mutant animal model, in vivo pharmacological inhibition of glycosylation, and in vitro analyses using transfected COS-1 cells. These studies have provided insights into the possible role of rhodopsin glycosylation, but have yielded conflicting results. PMID:19941415

  17. Structural and functional diversity of desmosomes.

    PubMed

    Harmon, Robert M; Green, Kathleen J

    2013-12-01

    Desmosomes anchor intermediate filaments at sites of cell contact established by the interaction of cadherins extending from opposing cells. The incorporation of cadherins, catenin adaptors, and cytoskeletal elements resembles the closely related adherens junction. However, the recruitment of intermediate filaments distinguishes desmosomes and imparts a unique function. By linking the load-bearing intermediate filaments of neighboring cells, desmosomes create mechanically contiguous cell sheets and, in so doing, confer structural integrity to the tissues they populate. This trait and a well-established role in human disease have long captured the attention of cell biologists, as evidenced by a publication record dating back to the mid-1860s. Likewise, emerging data implicating the desmosome in signaling events pertinent to organismal development, carcinogenesis, and genetic disorders will secure a prominent role for desmosomes in future biological and biomedical investigations.

  18. 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. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Testing the link between functional diversity and ecosystem functioning in a Minnesota grassland experiment.

    PubMed

    Clark, Christopher M; Flynn, Dan F B; Butterfield, Bradley J; Reich, Peter B

    2012-01-01

    The functional diversity of a community can influence ecosystem functioning and reflects assembly processes. The large number of disparate metrics used to quantify functional diversity reflects the range of attributes underlying this concept, generally summarized as functional richness, functional evenness, and functional divergence. However, in practice, we know very little about which attributes drive which ecosystem functions, due to a lack of field-based tests. Here we test the association between eight leading functional diversity metrics (Rao's Q, FD, FDis, FEve, FDiv, convex hull volume, and species and functional group richness) that emphasize different attributes of functional diversity, plus 11 extensions of these existing metrics that incorporate heterogeneous species abundances and trait variation. We assess the relationships among these metrics and compare their performances for predicting three key ecosystem functions (above- and belowground biomass and light capture) within a long-term grassland biodiversity experiment. Many metrics were highly correlated, although unique information was captured in FEve, FDiv, and dendrogram-based measures (FD) that were adjusted by abundance. FD adjusted by abundance outperformed all other metrics in predicting both above- and belowground biomass, although several others also performed well (e.g. Rao's Q, FDis, FDiv). More generally, trait-based richness metrics and hybrid metrics incorporating multiple diversity attributes outperformed evenness metrics and single-attribute metrics, results that were not changed when combinations of metrics were explored. For light capture, species richness alone was the best predictor, suggesting that traits for canopy architecture would be necessary to improve predictions. Our study provides a comprehensive test linking different attributes of functional diversity with ecosystem function for a grassland system.

  20. Testing the Link between Functional Diversity and Ecosystem Functioning in a Minnesota Grassland Experiment

    PubMed Central

    Butterfield, Bradley J.; Reich, Peter B.

    2012-01-01

    The functional diversity of a community can influence ecosystem functioning and reflects assembly processes. The large number of disparate metrics used to quantify functional diversity reflects the range of attributes underlying this concept, generally summarized as functional richness, functional evenness, and functional divergence. However, in practice, we know very little about which attributes drive which ecosystem functions, due to a lack of field-based tests. Here we test the association between eight leading functional diversity metrics (Rao’s Q, FD, FDis, FEve, FDiv, convex hull volume, and species and functional group richness) that emphasize different attributes of functional diversity, plus 11 extensions of these existing metrics that incorporate heterogeneous species abundances and trait variation. We assess the relationships among these metrics and compare their performances for predicting three key ecosystem functions (above- and belowground biomass and light capture) within a long-term grassland biodiversity experiment. Many metrics were highly correlated, although unique information was captured in FEve, FDiv, and dendrogram-based measures (FD) that were adjusted by abundance. FD adjusted by abundance outperformed all other metrics in predicting both above- and belowground biomass, although several others also performed well (e.g. Rao’s Q, FDis, FDiv). More generally, trait-based richness metrics and hybrid metrics incorporating multiple diversity attributes outperformed evenness metrics and single-attribute metrics, results that were not changed when combinations of metrics were explored. For light capture, species richness alone was the best predictor, suggesting that traits for canopy architecture would be necessary to improve predictions. Our study provides a comprehensive test linking different attributes of functional diversity with ecosystem function for a grassland system. PMID:23300787

  1. Alteration of Golgi Structure by Stress: A Link to Neurodegeneration?

    PubMed Central

    Alvarez-Miranda, Eduardo A.; Sinnl, Markus; Farhan, Hesso

    2015-01-01

    The Golgi apparatus is well-known for its role as a sorting station in the secretory pathway as well as for its role in regulating post-translational protein modification. Another role for the Golgi is the regulation of cellular signaling by spatially regulating kinases, phosphatases, and GTPases. All these roles make it clear that the Golgi is a central regulator of cellular homeostasis. The response to stress and the initiation of adaptive responses to cope with it are fundamental abilities of all living cells. It was shown previously that the Golgi undergoes structural rearrangements under various stress conditions such as oxidative or osmotic stress. Neurodegenerative diseases are also frequently associated with alterations of Golgi morphology and many stress factors have been described to play an etiopathological role in neurodegeneration. It is however unclear whether the stress-Golgi connection plays a role in neurodegenerative diseases. Using a combination of bioinformatics modeling and literature mining, we will investigate evidence for such a tripartite link and we ask whether stress-induced Golgi arrangements are cause or consequence in neurodegeneration. PMID:26617486

  2. Structural asymmetry of the insula is linked to the lateralization of gesture and language

    PubMed Central

    Biduła, Szymon P; Króliczak, Gregory

    2015-01-01

    The control of gesture is one of the most left-lateralized functions, and the insular cortex is one of the most left-biased structures in the human brain. Therefore, we investigated whether structural asymmetries of the insula are linked to the organization of functional activity during gesture planning. We reconstructed and parcellated the insular cortex of 27 participants. First, we tested 15 strongly left-handed individuals because of a higher incidence of atypical organization of functions such as gesture and language in such a population. The inter-hemispheric structural asymmetries were compared with the lateralization of activity for gesture in the supramarginal gyrus (the hotspot of signal increase regardless of the gesturing hand) and Broca’s area (the hotspot of signal increase for language production). The more pronounced leftward structural asymmetries were accompanied by greater left-hemisphere dominance for both of the studied functions. Conversely, an atypical, bilateral or rightward functional shift of gesture and language was accompanied by an attenuated leftward asymmetry of the insula. These significant relationships were driven primarily by differences in surface area. Subsequently, by adding 12 right-handed individuals to these analyses we demonstrated that the observed significant associations are generalizable to the population. These results provide the first demonstration of the relationships between structural inter-hemispheric differences of the insula and the cerebral specialization for gesture. They also corroborate the link between insular asymmetries and language lateralization. As such, these outcomes are relevant to the common cerebral specialization for gesture and language. PMID:25858359

  3. Structures and Functions of Oligosaccharins

    SciTech Connect

    Albersheim, Peter

    1995-12-01

    We have made considerable progress during the 2.5 year funding period just ending in our studies of the structures and functions of oligosaccharide signal molecules (oligosaccharins). We have emphasized studies of the enzymes that solubilize, process, and degrade oligosaccharins and of the proteins that inhibit those enzymes. We have been especially interested in elucidating how oligosaccharins and their processing enzymes participate in determining the outcome of challenges to plants by pathogenic microbes. We have studied, to a lesser extent, the roles of oligosaccharins in plant growth and development. Abstracts of papers describing results acquired with support from this grant that have been published, submitted, or in preparation are presented to summarize the progress made during the last two and one half years. The report highlights the most important contributions made in our oiigosaccharin research during this time period, and the corresponding abstract is referenced. Results of work in progress are described primarily in conjunction with our application for continued support.

  4. Functional evolution of nuclear structure

    PubMed Central

    Dawson, Scott C.

    2011-01-01

    The evolution of the nucleus, the defining feature of eukaryotic cells, was long shrouded in speculation and mystery. There is now strong evidence that nuclear pore complexes (NPCs) and nuclear membranes coevolved with the endomembrane system, and that the last eukaryotic common ancestor (LECA) had fully functional NPCs. Recent studies have identified many components of the nuclear envelope in living Opisthokonts, the eukaryotic supergroup that includes fungi and metazoan animals. These components include diverse chromatin-binding membrane proteins, and membrane proteins with adhesive lumenal domains that may have contributed to the evolution of nuclear membrane architecture. Further discoveries about the nucleoskeleton suggest that the evolution of nuclear structure was tightly coupled to genome partitioning during mitosis. PMID:22006947

  5. Rotavirus gene structure and function.

    PubMed Central

    Estes, M K; Cohen, J

    1989-01-01

    Knowledge of the structure and function of the genes and proteins of the rotaviruses has expanded rapidly. Information obtained in the last 5 years has revealed unexpected and unique molecular properties of rotavirus proteins of general interest to virologists, biochemists, and cell biologists. Rotaviruses share some features of replication with reoviruses, yet antigenic and molecular properties of the outer capsid proteins, VP4 (a protein whose cleavage is required for infectivity, possibly by mediating fusion with the cell membrane) and VP7 (a glycoprotein), show more similarities with those of other viruses such as the orthomyxoviruses, paramyxoviruses, and alphaviruses. Rotavirus morphogenesis is a unique process, during which immature subviral particles bud through the membrane of the endoplasmic reticulum (ER). During this process, transiently enveloped particles form, the outer capsid proteins are assembled onto particles, and mature particles accumulate in the lumen of the ER. Two ER-specific viral glycoproteins are involved in virus maturation, and these glycoproteins have been shown to be useful models for studying protein targeting and retention in the ER and for studying mechanisms of virus budding. New ideas and approaches to understanding how each gene functions to replicate and assemble the segmented viral genome have emerged from knowledge of the primary structure of rotavirus genes and their proteins and from knowledge of the properties of domains on individual proteins. Localization of type-specific and cross-reactive neutralizing epitopes on the outer capsid proteins is becoming increasingly useful in dissecting the protective immune response, including evaluation of vaccine trials, with the practical possibility of enhancing the production of new, more effective vaccines. Finally, future analyses with recently characterized immunologic and gene probes and new animal models can be expected to provide a basic understanding of what regulates the

  6. 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

  7. Novel Covalently Linked Insulin Dimer Engineered to Investigate the Function of Insulin Dimerization

    PubMed Central

    Vinther, Tine N.; Norrman, Mathias; Strauss, Holger M.; Huus, Kasper; Schlein, Morten; Pedersen, Thomas Å.; Kjeldsen, Thomas; Jensen, Knud J.; Hubálek, František

    2012-01-01

    An ingenious system evolved to facilitate insulin binding to the insulin receptor as a monomer and at the same time ensure sufficient stability of insulin during storage. Insulin dimer is the cornerstone of this system. Insulin dimer is relatively weak, which ensures dissociation into monomers in the circulation, and it is stabilized by hexamer formation in the presence of zinc ions during storage in the pancreatic β-cell. Due to the transient nature of insulin dimer, direct investigation of this important form is inherently difficult. To address the relationship between insulin oligomerization and insulin stability and function, we engineered a covalently linked insulin dimer in which two monomers were linked by a disulfide bond. The structure of this covalent dimer was identical to the self-association dimer of human insulin. Importantly, this covalent dimer was capable of further oligomerization to form the structural equivalent of the classical hexamer. The covalently linked dimer neither bound to the insulin receptor, nor induced a metabolic response in vitro. However, it was extremely thermodynamically stable and did not form amyloid fibrils when subjected to mechanical stress, underlining the importance of oligomerization for insulin stability. PMID:22363506

  8. Using the structure-function linkage database to characterize functional domains in enzymes.

    PubMed

    Brown, Shoshana; Babbitt, Patricia

    2014-12-12

    The Structure-Function Linkage Database (SFLD; http://sfld.rbvi.ucsf.edu/) is a Web-accessible database designed to link enzyme sequence, structure, and functional information. This unit describes the protocols by which a user may query the database to predict the function of uncharacterized enzymes and to correct misannotated functional assignments. The information in this unit is especially useful in helping a user discriminate functional capabilities of a sequence that is only distantly related to characterized sequences in publicly available databases.

  9. Using the Structure-function Linkage Database to characterize functional domains in enzymes.

    PubMed

    Brown, Shoshana; Babbitt, Patricia

    2006-03-01

    The Structure-Function Linkage Database (SFLD; http://sfld.rbvi.ucsf.edu/) is a Web-accessible database designed to link enzyme sequence, structure, and functional information. This unit describes the protocols by which a user may query the database to predict the function of newly sequenced enzymes and to correct misannotated functional assignments for enzymes currently in public databases. It is especially useful in helping a user discriminate functional capabilities of a sequence that is only distantly related to characterized sequences in publicly available databases.

  10. 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.

  11. Microbial functional diversity enhances predictive models linking environmental parameters to ecosystem properties.

    PubMed

    Powell, Jeff R; Welsh, Allana; Hallin, Sara

    2015-07-01

    Microorganisms drive biogeochemical processes, but linking these processes to real changes in microbial communities under field conditions is not trivial. Here, we present a model-based approach to estimate independent contributions of microbial community shifts to ecosystem properties. The approach was tested empirically, using denitrification potential as our model process, in a spatial survey of arable land encompassing a range of edaphic conditions and two agricultural production systems. Soil nitrate was the most important single predictor of denitrification potential (the change in Akaike's information criterion, corrected for sample size, ΔAIC(c) = 20.29); however, the inclusion of biotic variables (particularly the evenness and size of denitrifier communities [ΔAIC(c) = 12.02], and the abundance of one denitrifier genotype [ΔAIC(c) = 18.04]) had a substantial effect on model precision, comparable to the inclusion of abiotic variables (biotic R2 = 0.28, abiotic R2 = 0.50, biotic + abiotic R2 = 0.76). This approach provides a valuable tool for explicitly linking microbial communities to ecosystem functioning. By making this link, we have demonstrated that including aspects of microbial community structure and diversity in biogeochemical models can improve predictions of nutrient cycling in ecosystems and enhance our understanding of ecosystem functionality.

  12. Linking microbial community structure and microbial processes: An empirical and conceptual overview

    USGS Publications Warehouse

    Bier, R.L.; Bernhardt, E.S.;; Boot, C.M.; Graham, E.B.;; Hall, E.K.; Lennon, J.T.; Nemergut, D.R.; Osborne, B.B.; Ruiz-Gonzalez, C.; Schimel, J.P.; Waldrop, Mark P.; Wallenstein, M.D.

    2015-01-01

    A major goal of microbial ecology is to identify links between microbial community structure and microbial processes. Although this objective seems straightforward, there are conceptual and methodological challenges to designing studies that explicitly evaluate this link. Here, we analyzed literature documenting structure and process responses to manipulations to determine the frequency of structure-process links and whether experimental approaches and techniques influence link detection. We examined nine journals (published 2009–13) and retained 148 experimental studies measuring microbial community structure and processes. Many qualifying papers (112 of 148) documented structure and process responses, but few (38 of 112 papers) reported statistically testing for a link. Of these tested links, 75% were significant and typically used Spearman or Pearson's correlation analysis (68%). No particular approach for characterizing structure or processes was more likely to produce significant links. Process responses were detected earlier on average than responses in structure or both structure and process. Together, our findings suggest that few publications report statistically testing structure-process links. However, when links are tested for they often occur but share few commonalities in the processes or structures that were linked and the techniques used for measuring them.

  13. Linking microbial community structure and microbial processes: an empirical and conceptual overview.

    PubMed

    Bier, Raven L; Bernhardt, Emily S; Boot, Claudia M; Graham, Emily B; Hall, Edward K; Lennon, Jay T; Nemergut, Diana R; Osborne, Brooke B; Ruiz-González, Clara; Schimel, Joshua P; Waldrop, Mark P; Wallenstein, Matthew D

    2015-10-01

    A major goal of microbial ecology is to identify links between microbial community structure and microbial processes. Although this objective seems straightforward, there are conceptual and methodological challenges to designing studies that explicitly evaluate this link. Here, we analyzed literature documenting structure and process responses to manipulations to determine the frequency of structure-process links and whether experimental approaches and techniques influence link detection. We examined nine journals (published 2009-13) and retained 148 experimental studies measuring microbial community structure and processes. Many qualifying papers (112 of 148) documented structure and process responses, but few (38 of 112 papers) reported statistically testing for a link. Of these tested links, 75% were significant and typically used Spearman or Pearson's correlation analysis (68%). No particular approach for characterizing structure or processes was more likely to produce significant links. Process responses were detected earlier on average than responses in structure or both structure and process. Together, our findings suggest that few publications report statistically testing structure-process links. However, when links are tested for they often occur but share few commonalities in the processes or structures that were linked and the techniques used for measuring them.

  14. Chromatin structure analysis of single gene molecules by psoralen cross-linking and electron microscopy.

    PubMed

    Brown, Christopher R; Eskin, Julian A; Hamperl, Stephan; Griesenbeck, Joachim; Jurica, Melissa S; Boeger, Hinrich

    2015-01-01

    Nucleosomes occupy a central role in regulating eukaryotic gene expression by blocking access of transcription factors to their target sites on chromosomal DNA. Analysis of chromatin structure and function has mostly been performed by probing DNA accessibility with endonucleases. Such experiments average over large numbers of molecules of the same gene, and more recently, over entire genomes. However, both digestion and averaging erase the structural variation between molecules indicative of dynamic behavior, which must be reconstructed for any theory of regulation. Solution of this problem requires the structural analysis of single gene molecules. In this chapter, we describe a method by which single gene molecules are purified from the yeast Saccharomyces cerevisiae and cross-linked with psoralen, allowing the determination of nucleosome configurations by transmission electron microscopy. We also provide custom analysis software that semi-automates the analysis of micrograph data. This single-gene technique enables detailed examination of chromatin structure at any genomic locus in yeast.

  15. Structure and functions of fungal cell surfaces

    NASA Technical Reports Server (NTRS)

    Nozawa, Y.

    1984-01-01

    A review with 24 references on the biochemistry, molecular structure, and function of cell surfaces of fungi, especially dermatophytes: the chemistry and structure of the cell wall, the effect of polyene antibiotics on the morphology and function of cytoplasmic membranes, and the chemical structure and function of pigments produced by various fungi are discussed.

  16. 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.

  17. Linking and Psychological Functioning in a Chinese Sample: The Multiple Mediation of Response to Positive Affect

    ERIC Educational Resources Information Center

    Yang, Hongfei; Li, Juan

    2016-01-01

    The present study examined the associations between linking, response to positive affect, and psychological functioning in Chinese college students. The results of conducting multiple mediation analyses indicated that emotion- and self-focused positive rumination mediated the relationship between linking and psychological functioning, whereas…

  18. Linking and Psychological Functioning in a Chinese Sample: The Multiple Mediation of Response to Positive Affect

    ERIC Educational Resources Information Center

    Yang, Hongfei; Li, Juan

    2016-01-01

    The present study examined the associations between linking, response to positive affect, and psychological functioning in Chinese college students. The results of conducting multiple mediation analyses indicated that emotion- and self-focused positive rumination mediated the relationship between linking and psychological functioning, whereas…

  19. Variable and complex food web structures revealed by exploring missing trophic links between birds and biofilm.

    PubMed

    Kuwae, Tomohiro; Miyoshi, Eiichi; Hosokawa, Shinya; Ichimi, Kazuhiko; Hosoya, Jun; Amano, Tatsuya; Moriya, Toshifumi; Kondoh, Michio; Ydenberg, Ronald C; Elner, Robert W

    2012-04-01

    Food webs are comprised of a network of trophic interactions and are essential to elucidating ecosystem processes and functions. However, the presence of unknown, but critical networks hampers understanding of complex and dynamic food webs in nature. Here, we empirically demonstrate a missing link, both critical and variable, by revealing that direct predator-prey relationships between shorebirds and biofilm are widespread and mediated by multiple ecological and evolutionary determinants. Food source mixing models and energy budget estimates indicate that the strength of the missing linkage is dependent on predator traits (body mass and foraging action rate) and the environment that determines food density. Morphological analyses, showing that smaller bodied species possess more developed feeding apparatus to consume biofilm, suggest that the linkage is also phylogenetically dependent and affords a compelling re-interpretation of niche differentiation. We contend that exploring missing links is a necessity for revealing true network structure and dynamics.

  20. 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.

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

    PubMed Central

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

    2016-01-01

    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 martensii Karsch 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 luteus as 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 IC50 value 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 BmKDfsin4adopts 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

  2. Current topics of functional links between primary cilia and cell cycle.

    PubMed

    Izawa, Ichiro; Goto, Hidemasa; Kasahara, Kousuke; Inagaki, Masaki

    2015-01-01

    Primary cilia, microtubule-based sensory structures, orchestrate various critical signals during development and tissue homeostasis. In view of the rising interest into the reciprocal link between ciliogenesis and cell cycle, we discuss here several recent advances to understand the molecular link between the individual step of ciliogenesis and cell cycle control. At the onset of ciliogenesis (the transition from centrosome to basal body), distal appendage proteins have been established as components indispensable for the docking of vesicles at the mother centriole. In the initial step of axonemal extension, CP110, Ofd1, and trichoplein, key negative regulators of ciliogenesis, are found to be removed by a kinase-dependent mechanism, autophagy, and ubiquitin-proteasome system, respectively. Of note, their disposal functions as a restriction point to decide that the axonemal nucleation and extension begin. In the elongation step, Nde1, a negative regulator of ciliary length, is revealed to be ubiquitylated and degraded by CDK5-SCF(Fbw7) in a cell cycle-dependent manner. With regard to ciliary length control, it has been uncovered in flagellar shortening of Chlamydomonas that cilia itself transmit a ciliary length signal to cytoplasm. At the ciliary resorption step upon cell cycle re-entry, cilia are found to be disassembled not only by Aurora A-HDAC6 pathway but also by Nek2-Kif24 and Plk1-Kif2A pathways through their microtubule-depolymerizing activity. On the other hand, it is becoming evident that the presence of primary cilia itself functions as a structural checkpoint for cell cycle re-entry. These data suggest that ciliogenesis and cell cycle intimately link each other, and further elucidation of these mechanisms will contribute to understanding the pathology of cilia-related disease including cancer and discovering targets of therapeutic interventions.

  3. Direct link between RACK1 function and localization at the ribosome in vivo.

    PubMed

    Coyle, Scott M; Gilbert, Wendy V; Doudna, Jennifer A

    2009-03-01

    The receptor for activated C-kinase (RACK1), a conserved protein implicated in numerous signaling pathways, is a stoichiometric component of eukaryotic ribosomes located on the head of the 40S ribosomal subunit. To test the hypothesis that ribosome association is central to the function of RACK1 in vivo, we determined the 2.1-A crystal structure of RACK1 from Saccharomyces cerevisiae (Asc1p) and used it to design eight mutant versions of RACK1 to assess roles in ribosome binding and in vivo function. Conserved charged amino acids on one side of the beta-propeller structure were found to confer most of the 40S subunit binding affinity, whereas an adjacent conserved and structured loop had little effect on RACK1-ribosome association. Yeast mutations that confer moderate to strong defects in ribosome binding mimic some phenotypes of a RACK1 deletion strain, including increased sensitivity to drugs affecting cell wall biosynthesis and translation elongation. Furthermore, disruption of RACK1's position at the 40S ribosomal subunit results in the failure of the mRNA binding protein Scp160 to associate with actively translating ribosomes. These results provide the first direct evidence that RACK1 functions from the ribosome, implying a physical link between the eukaryotic ribosome and cell signaling pathways in vivo.

  4. Cell wall-related proteins of unknown function: missing links in plant cell wall development.

    PubMed

    Mewalal, Ritesh; Mizrachi, Eshchar; Mansfield, Shawn D; Myburg, Alexander A

    2014-06-01

    Lignocellulosic biomass is an important feedstock for the pulp and paper industry as well as emerging biofuel and biomaterial industries. However, the recalcitrance of the secondary cell wall to chemical or enzymatic degradation remains a major hurdle for efficient extraction of economically important biopolymers such as cellulose. It has been estimated that approximately 10-15% of about 27,000 protein-coding genes in the Arabidopsis genome are dedicated to cell wall development; however, only about 130 Arabidopsis genes thus far have experimental evidence validating cell wall function. While many genes have been implicated through co-expression analysis with known genes, a large number are broadly classified as proteins of unknown function (PUFs). Recently the functionality of some of these unknown proteins in cell wall development has been revealed using reverse genetic approaches. Given the large number of cell wall-related PUFs, how do we approach and subsequently prioritize the investigation of such unknown genes that may be essential to or influence plant cell wall development and structure? Here, we address the aforementioned question in two parts; we first identify the different kinds of PUFs based on known and predicted features such as protein domains. Knowledge of inherent features of PUFs may allow for functional inference and a concomitant link to biological context. Secondly, we discuss omics-based technologies and approaches that are helping identify and prioritize cell wall-related PUFs by functional association. In this way, hypothesis-driven experiments can be designed for functional elucidation of many proteins that remain missing links in our understanding of plant cell wall biosynthesis. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  5. Disgust: Evolved Function and Structure

    ERIC Educational Resources Information Center

    Tybur, Joshua M.; Lieberman, Debra; Kurzban, Robert; DeScioli, Peter

    2013-01-01

    Interest in and research on disgust has surged over the past few decades. The field, however, still lacks a coherent theoretical framework for understanding the evolved function or functions of disgust. Here we present such a framework, emphasizing 2 levels of analysis: that of evolved function and that of information processing. Although there is…

  6. Linking mutated primary structure of adrenoleukodystrophy protein with X-linked adrenoleukodystrophy.

    PubMed

    Yan, Shaomin; Wu, Guang

    2010-06-01

    The phenotype expression in X-linked adrenoleukodystrophy is one of the most intriguing issues of the disease, because there is no general correlation between the type of ABCD1 gene mutation and the clinical phenotype. In this study, we use the cross-impact analysis to build a descriptively quantitative relationship between mutant adrenoleukodystrophy protein and classification of adrenoleukodystrophy with the amino-acid distribution probability, which is a quantitative measure sensitive to mutation. Then we determine the probability that the adrenoleukodystrophy can be classified under mutations with the help of a Bayesian equation.

  7. 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.

  8. Linking Executive Function and Peer Problems from Early Childhood through Middle Adolescence

    PubMed Central

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

    2015-01-01

    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 = 1,164, 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 after school 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

  9. 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

  10. The origin and function of mirror neurons: the missing link.

    PubMed

    Lingnau, Angelika; Caramazza, Alfonso

    2014-04-01

    We argue, by analogy to the neural organization of the object recognition system, that demonstration of modulation of mirror neurons by associative learning does not imply absence of genetic adaptation. Innate connectivity defines the types of processes mirror neurons can participate in while allowing for extensive local plasticity. However, the proper function of these neurons remains to be worked out.

  11. Stories: The Function of Structure.

    ERIC Educational Resources Information Center

    Mandler, Jean M.

    The differences between story grammar and story schema are outlined and discussed based on research on story understanding by children and adults. The contention of all story grammars is that stories have a relatively invariant structure despite great differences in story content. The importance of structure within folk tales, and the ways in…

  12. Diisocyanate modified graphene oxide network structure: steric effect of diisocyanates on bimolecular cross-linking degree

    NASA Astrophysics Data System (ADS)

    Saha, Uttam; Jaiswal, Rimpa; Singh, Jyoti Prakash; Goswami, Thako Hari

    2014-05-01

    Relative reactivity and the extent of functionalization of graphene oxide (GO) during its bimolecular reaction with three different classes of diisocyanates, i.e., aliphatic (hexamethylene diisocyanate, HMDI), alicyclic (isophorone diisocyanates, IPDI), and aromatic (toluene diisocyanates, TDI), are correlated on the basis of steric and electronic effect of diisocyanate functionalizing agents. The bimolecular reaction produces cross-linked network structure and the steric nature of diisocyanates dominates over electronic factor in regulating the relative reactivity, extent of functionalization and disorder in final structure. Formation of carbamate and amide bonds on participation of GO's sp3-hydroxyl groups at top and bottom of basal plane and sp2-carboxyl groups at the edges are recognized from FTIR and XPS spectra. Extent of functionalization in different locations are predicted from relative ratio of hydroxyl and carboxyl groups participated in diisocyanate reaction and N1s XPS spectra show nearly 3:1, 2:1, 1.3:1 in HMDI, IPDI, and TDI respectively. The disorders in final structure are evaluated by comparing Raman, UV-Vis, and C1s XPS spectra of functionalized materials with GO. TDI, the most sterically hindered diisocyanate among the reported one, shows slowest reactivity and minimum disorder in the final structure compared to long chain aliphatic diisocyanate, HMDI. Depending on the relative participation of oxygenated functional groups at basal and/or edges of two adjacent GO nano sheets, the three possible reaction patterns, i.e., basal to basal, basal to edge, and edge to edge, are proposed. Different crystallographic orientations and out-of-plane arrangement of graphene layers arises from these reactions are correlated through XRD data.

  13. Functional keratin as structural platforms

    USDA-ARS?s Scientific Manuscript database

    Wool with up to 95% keratin by weight is a rich and pure source of proteinous biomaterial. As polymeric polyamide it exhibits high functionality through amide, carboxyl, sulfoxide, sulfide, and thiosulfide functions. Solubilized wool was transformed into keratin morphologies with the unique characte...

  14. Structural Properties of Prokaryotic Promoter Regions Correlate with Functional Features

    PubMed Central

    Meysman, Pieter; Collado-Vides, Julio; Morett, Enrique; Viola, Roberto

    2014-01-01

    The structural properties of the DNA molecule are known to play a critical role in transcription. In this paper, the structural profiles of promoter regions were studied within the context of their diversity and their function for eleven prokaryotic species; Escherichia coli, Klebsiella pneumoniae, Salmonella Typhimurium, Pseudomonas auroginosa, Geobacter sulfurreducens Helicobacter pylori, Chlamydophila pneumoniae, Synechocystis sp., Synechoccocus elongates, Bacillus anthracis, and the archaea Sulfolobus solfataricus. The main anchor point for these promoter regions were transcription start sites identified through high-throughput experiments or collected within large curated databases. Prokaryotic promoter regions were found to be less stable and less flexible than the genomic mean across all studied species. However, direct comparison between species revealed differences in their structural profiles that can not solely be explained by the difference in genomic GC content. In addition, comparison with functional data revealed that there are patterns in the promoter structural profiles that can be linked to specific functional loci, such as sigma factor regulation or transcription factor binding. Interestingly, a novel structural element clearly visible near the transcription start site was found in genes associated with essential cellular functions and growth in several species. Our analyses reveals the great diversity in promoter structural profiles both between and within prokaryotic species. We observed relationships between structural diversity and functional features that are interesting prospects for further research to yet uncharacterized functional loci defined by DNA structural properties. PMID:24516674

  15. Structural properties of prokaryotic promoter regions correlate with functional features.

    PubMed

    Meysman, Pieter; Collado-Vides, Julio; Morett, Enrique; Viola, Roberto; Engelen, Kristof; Laukens, Kris

    2014-01-01

    The structural properties of the DNA molecule are known to play a critical role in transcription. In this paper, the structural profiles of promoter regions were studied within the context of their diversity and their function for eleven prokaryotic species; Escherichia coli, Klebsiella pneumoniae, Salmonella Typhimurium, Pseudomonas auroginosa, Geobacter sulfurreducens Helicobacter pylori, Chlamydophila pneumoniae, Synechocystis sp., Synechoccocus elongates, Bacillus anthracis, and the archaea Sulfolobus solfataricus. The main anchor point for these promoter regions were transcription start sites identified through high-throughput experiments or collected within large curated databases. Prokaryotic promoter regions were found to be less stable and less flexible than the genomic mean across all studied species. However, direct comparison between species revealed differences in their structural profiles that can not solely be explained by the difference in genomic GC content. In addition, comparison with functional data revealed that there are patterns in the promoter structural profiles that can be linked to specific functional loci, such as sigma factor regulation or transcription factor binding. Interestingly, a novel structural element clearly visible near the transcription start site was found in genes associated with essential cellular functions and growth in several species. Our analyses reveals the great diversity in promoter structural profiles both between and within prokaryotic species. We observed relationships between structural diversity and functional features that are interesting prospects for further research to yet uncharacterized functional loci defined by DNA structural properties.

  16. Synthesis of chiral alpha-amino aldehydes linked by their amine function to solid support.

    PubMed

    Cantel, Sonia; Heitz, Annie; Martinez, Jean; Fehrentz, Jean-Alain

    2004-09-01

    The anchoring of an alpha-amino-acid derivative by its amine function on to a solid support allows some chemical reactions starting from the carboxylic acid function. This paper describes the preparation of alpha-amino aldehydes linked to the support by their amine function. This was performed by reduction with LiAlH4 of the corresponding Weinreb amide linked to the resin. The aldehydes obtained were then involved in Wittig or reductive amination reactions. In addition, the linked Weinreb amide was reacted with methylmagnesium bromide to yield the corresponding ketone. After cleavage from the support, the compounds were obtained in good to excellent yields and characterized.

  17. Multimodal analyses identify linked functional and white matter abnormalities within the working memory network in schizophrenia.

    PubMed

    Sugranyes, Gisela; Kyriakopoulos, Marinos; Dima, Danai; O'Muircheartaigh, Jonathan; Corrigall, Richard; Pendelbury, Gabrielle; Hayes, Daniel; Calhoun, Vince D; Frangou, Sophia

    2012-07-01

    Dysconnectivity between brain regions is thought to underlie the cognitive abnormalities that characterise schizophrenia (SZ). Consistent with this notion functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) studies in SZ have reliably provided evidence of abnormalities in functional integration and in white matter connectivity. Yet little is known about how alterations at the functional level related to abnormalities in anatomical connectivity. We obtained fMRI data during the 2-back working memory task from 25 patients with SZ and 19 healthy controls matched for age, sex and IQ. DTI data were also acquired in the same session. In addition to conventional unimodal analyses we extracted "features" [contrast maps for fMRI and fractional anisotropy (FA) for DTI] that were subjected to joint independent component analysis (JICA) in order to examine interactions between fMRI and DTI data sources. Conventional unimodal analyses revealed both functional and structural deficits in patients with SZ. The JICA identified regions of joint, multimodal brain sources that differed in patients and controls. The fMRI source implicated regions within the anterior cingulate and ventrolateral prefrontal cortex and in the cuneus where patients showed relative hypoactivation and within the frontopolar cortex where patients showed relative hyperactivation. The DTI source localised reduced FA in patients in the splenium and posterior cingulum. This study promotes our understanding of structure-function relationships in SZ by characterising linked functional and white matter changes that contribute to working memory dysfunction in this disorder. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Multimodal analyses identify linked functional and white matter abnormalities within the working memory network in schizophrenia

    PubMed Central

    Sugranyes, Gisela; Kyriakopoulos, Marinos; Dima, Danai; O’Muircheartaigh, Jonathan; Corrigall, Richard; Pendelbury, Gabrielle; Hayes, Daniel; Calhoun, Vince D.; Frangou, Sophia

    2015-01-01

    Background Dysconnectivity between brain regions is thought to underlie the cognitive abnormalities that characterise schizophrenia (SZ). Consistent with this notion functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) studies in SZ have reliably provided evidence of abnormalities in functional integration and in white matter connectivity. Yet little is known about how alterations at the functional level related to abnormalities in anatomical connectivity. Methods We obtained fMRI data during the 2-back working memory task from 25 patients with SZ and 19 healthy controls matched for age, sex and IQ. DTI data were also acquired in the same session. In addition to conventional unimodal analyses we extracted “features” [contrast maps for fMRI and fractional anisotropy (FA) for DTI] that were subjected to joint independent component analysis (JICA) in order to examine interactions between fMRI and DTI data sources. Results Conventional unimodal analyses revealed both functional and structural deficits in patients with SZ. The JICA identified regions of joint, multimodal brain sources that differed in patients and controls. The fMRI source implicated regions within the anterior cingulate and ventrolateral prefrontal cortex and in the cuneus where patients showed relative hypoactivation and within the frontopolar cortex where patients showed relative hyperactivation. The DTI source localised reduced FA in patients in the splenium and posterior cingulum. Conclusions This study promotes our understanding of structure-function relationships in SZ by characterising linked functional and white matter changes that contribute to working memory dysfunction in this disorder. PMID:22475381

  19. Dependence of Invadopodia Function on Collagen Fiber Spacing and Cross-Linking: Computational Modeling and Experimental Evidence

    PubMed Central

    Enderling, Heiko; Alexander, Nelson R.; Clark, Emily S.; Branch, Kevin M.; Estrada, Lourdes; Crooke, Cornelia; Jourquin, Jérôme; Lobdell, Nichole; Zaman, Muhammad H.; Guelcher, Scott A.; Anderson, Alexander R. A.; Weaver, Alissa M.

    2008-01-01

    Invadopodia are subcellular organelles thought to be critical for extracellular matrix (ECM) degradation and the movement of cells through tissues. Here we examine invadopodia generation, turnover, and function in relation to two structural aspects of the ECM substrates they degrade: cross-linking and fiber density. We set up a cellular automaton computational model that simulates ECM penetration and degradation by invadopodia. Experiments with denatured collagen (gelatin) were used to calibrate the model and demonstrate the inhibitory effect of ECM cross-linking on invadopodia degradation and penetration. Incorporation of dynamic invadopodia behavior into the model amplified the effect of cross-linking on ECM degradation, and was used to model feedback from the ECM. When the model was parameterized with spatial fibrillar dimensions that closely matched the organization, in real life, of native ECM collagen into triple-helical monomers, microfibrils, and macrofibrils, little or no inhibition of invadopodia penetration was observed in simulations of sparse collagen gels, no matter how high the degree of cross-linking. Experimental validation, using live-cell imaging of invadopodia in cells plated on cross-linked gelatin, was consistent with simulations in which ECM cross-linking led to higher rates of both invadopodia retraction and formation. Analyses of invadopodia function from cells plated on cross-linked gelatin and collagen gels under standard concentrations were consistent with simulation results in which sparse collagen gels provided a weak barrier to invadopodia. These results suggest that the organization of collagen, as it may occur in stroma or in vitro collagen gels, forms gaps large enough so as to have little impact on invadopodia penetration/degradation. By contrast, dense ECM, such as gelatin or possibly basement membranes, is an effective obstacle to invadopodia penetration and degradation, particularly when cross-linked. These results provide a

  20. New link between conceptual density functional theory and electron delocalization.

    PubMed

    Matito, Eduard; Putz, Mihai V

    2011-11-17

    In this paper we give a new definition of the softness kernel based on the exchange-correlation density. This new kernel is shown to correspond to the change of electron fluctuation upon external perturbation, thus helping to bridge the gap between conceptual density functional theory and some tools describing electron localization in molecules. With the aid of a few computational calculations on diatomics we illustrate the performance of this new computational tool.

  1. Polarized DIS Structure Functions from Neural Networks

    SciTech Connect

    Del Debbio, L.; Guffanti, A.; Piccione, A.

    2007-06-13

    We present a parametrization of polarized Deep-Inelastic-Scattering (DIS) structure functions based on Neural Networks. The parametrization provides a bias-free determination of the probability measure in the space of structure functions, which retains information on experimental errors and correlations. As an example we discuss the application of this method to the study of the structure function g{sub 1}{sup p}(x,Q{sup 2})

  2. Structure and Function of Your Skin

    MedlinePlus

    ... Name: Category: Share: Yes No, Keep Private Structure & Function of Your Skin Share | What It Looks Like . . . ... in the dermis. What It Does . . . The major function of skin is to provide a barrier between ...

  3. 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…

  4. 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…

  5. Infrared Structural Biology: Detect Functionally Important Structural Motions of Proteins

    NASA Astrophysics Data System (ADS)

    Xie, Aihua

    Proteins are dynamic. Lack of dynamic structures of proteins hampers our understanding of protein functions. Infrared structural biology (IRSB) is an emerging technology. There are several advantages of IRSB for mechanistic studies of proteins: (1) its excellent dynamic range (detecting structural motions from picoseconds to >= seconds); (2) its high structural sensitivity (detect tiny but functionally important structural motions such as proton transfer and changes in hydrogen bonding interaction); (3) its ability to detect different structural motions simultaneously. Successful development of infrared structural biology demands not only new experimental techniques (from infrared technologies to chemical synthesis and cell biology), but also new data processing (how to translate infrared signals into quantitative structural information of proteins). These topics will be discussed as well as examples of how to use IRSB to study structure-function relationship of proteins. This work was supported by NSF DBI1338097 and OCAST HR10-078.

  6. Models of Protocellular Structure, Function and Evolution

    NASA Technical Reports Server (NTRS)

    New, Michael H.; Pohorille, Andrew; Szostak, Jack W.; Keefe, Tony; Lanyi, Janos K.

    2001-01-01

    In the absence of any record of protocells, the most direct way to test our understanding of the origin of cellular life is to construct laboratory models that capture important features of protocellular systems. Such efforts are currently underway in a collaborative project between NASA-Ames, Harvard Medical School and University of California. They are accompanied by computational studies aimed at explaining self-organization of simple molecules into ordered structures. The centerpiece of this project is a method for the in vitro evolution of protein enzymes toward arbitrary catalytic targets. A similar approach has already been developed for nucleic acids in which a small number of functional molecules are selected from a large, random population of candidates. The selected molecules are next vastly multiplied using the polymerase chain reaction. A mutagenic approach, in which the sequences of selected molecules are randomly altered, can yield further improvements in performance or alterations of specificities. Unfortunately, the catalytic potential of nucleic acids is rather limited. Proteins are more catalytically capable but cannot be directly amplified. In the new technique, this problem is circumvented by covalently linking each protein of the initial, diverse, pool to the RNA sequence that codes for it. Then, selection is performed on the proteins, but the nucleic acids are replicated. Additional information is contained in the original extended abstract.

  7. Models of Protocellular Structure, Function and Evolution

    NASA Technical Reports Server (NTRS)

    New, Michael H.; Pohorille, Andrew; Szostak, Jack W.; Keefe, Tony; Lanyi, Janos K.

    2001-01-01

    In the absence of any record of protocells, the most direct way to test our understanding of the origin of cellular life is to construct laboratory models that capture important features of protocellular systems. Such efforts are currently underway in a collaborative project between NASA-Ames, Harvard Medical School and University of California. They are accompanied by computational studies aimed at explaining self-organization of simple molecules into ordered structures. The centerpiece of this project is a method for the in vitro evolution of protein enzymes toward arbitrary catalytic targets. A similar approach has already been developed for nucleic acids in which a small number of functional molecules are selected from a large, random population of candidates. The selected molecules are next vastly multiplied using the polymerase chain reaction. A mutagenic approach, in which the sequences of selected molecules are randomly altered, can yield further improvements in performance or alterations of specificities. Unfortunately, the catalytic potential of nucleic acids is rather limited. Proteins are more catalytically capable but cannot be directly amplified. In the new technique, this problem is circumvented by covalently linking each protein of the initial, diverse, pool to the RNA sequence that codes for it. Then, selection is performed on the proteins, but the nucleic acids are replicated. Additional information is contained in the original extended abstract.

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

    PubMed Central

    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.

    2015-01-01

    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

  9. 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. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Joining the dots: neurobiological links in a functional analysis of depression

    PubMed Central

    2010-01-01

    Depression is one of the major contributors to the Total Disease Burden and afflicts about one-sixth of Western populations. One of the most effective treatments for depression focuses upon analysis of causal chains in overt behaviour, but does not include brain-related phenomena as steps along these causal pathways. Recent research findings regarding the neurobiological concomitants of depressive behaviour suggest a sequence of structural and functional alterations to the brain which may also produce a beneficial outcome for the depressed individual--that of adaptive withdrawal from uncontrollable aversive stressors. Linking these brain-based explanations to models of observable contingencies for depressive behaviour can provide a comprehensive explanation of how depressive behaviour occurs and why it persists in many patients. PMID:21143991

  11. X-linked mental retardation: focus on synaptic function and plasticity.

    PubMed

    Humeau, Yann; Gambino, Frédéric; Chelly, Jamel; Vitale, Nicolas

    2009-04-01

    Among mental disorders, mental retardation has been shown to be caused by various factors including a large array of genetic mutations. On the basis of remarkable progress, the emerging view is that defects in the regulation of synaptic activity and morphogenesis of dendritic spines are apparently common features associated with mutations in several genes implicated in mental retardation. In this review, we will discuss X-linked MR-related gene products that are potentially involved in the normal structure and function of the synapses, with a particular focus on pre- and/or post-synaptic plasticity mechanisms. Progress in understanding the underlying conditions leading to mental retardation will undoubtedly be gained from a closer collaboration of geneticists, physiologists and cognitive neuroscientists, which should enable the establishment of standardized approaches.

  12. Cryo-EM structure of respiratory complex I reveals a link to mitochondrial sulfur metabolism.

    PubMed

    D'Imprima, Edoardo; Mills, Deryck J; Parey, Kristian; Brandt, Ulrich; Kühlbrandt, Werner; Zickermann, Volker; Vonck, Janet

    2016-12-01

    Mitochondrial complex I is a 1MDa membrane protein complex with a central role in aerobic energy metabolism. The bioenergetic core functions are executed by 14 central subunits that are conserved from bacteria to man. Despite recent progress in structure determination, our understanding of the function of the ~30 accessory subunits associated with the mitochondrial complex is still limited. We have investigated the structure of complex I from the aerobic yeast Yarrowia lipolytica by cryo-electron microscopy. Our density map at 7.9Å resolution closely matches the 3.6-3.9Å X-ray structure of the Yarrowia lipolytica complex. However, the cryo-EM map indicated an additional subunit on the side of the matrix arm above the membrane surface, pointing away from the membrane arm. The density, which is not present in any previously described complex I structure and occurs in about 20 % of the particles, was identified as the accessory sulfur transferase subunit ST1. The Yarrowia lipolytica complex I preparation is active in generating H2S from the cysteine derivative 3-mercaptopyruvate, catalyzed by ST1. We thus provide evidence for a link between respiratory complex I and mitochondrial sulfur metabolism. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Functional analysis of RYR1 variants linked to malignant hyperthermia

    PubMed Central

    Stephens, Jeremy; Schiemann, Anja H.; Roesl, Cornelia; Miller, Dorota; Massey, Sean; Pollock, Neil; Bulger, Terasa; Stowell, Kathryn

    2016-01-01

    ABSTRACT Malignant hyperthermia manifests as a rapid and sustained rise in temperature in response to pharmacological triggering agents, e.g. inhalational anesthetics and the muscle relaxant suxamethonium. Other clinical signs include an increase in end-tidal CO2, increased O2 consumption, as well as tachycardia, and if untreated a malignant hyperthermia episode can result in death. The metabolic changes are caused by dysregulation of skeletal muscle Ca2+ homeostasis, resulting from a defective ryanodine receptor Ca2+ channel, which resides in the sarcoplasmic reticulum and controls the flux of Ca2+ ions from intracellular stores to the cytoplasm. Most genetic variants associated with susceptibility to malignant hyperthermia occur in the RYR1 gene encoding the ryanodine receptor type 1. While malignant hyperthermia susceptibility can be diagnosed by in vitro contracture testing of skeletal muscle biopsy tissue, it is advantageous to use DNA testing. Currently only 35 of over 400 potential variants in RYR1 have been classed as functionally causative of malignant hyperthermia and thus can be used for DNA diagnostic tests. Here we describe functional analysis of 2 RYR1 variants (c. 7042_7044delCAG, p.ΔGlu2348 and c.641C>T, p.Thr214Met) that occur in the same malignant hyperthermia susceptible family. The p.Glu2348 deletion, causes hypersensitivity to ryanodine receptor agonists using in vitro analysis of cloned human RYR1 cDNA expressed in HEK293T cells, while the Thr214Met substitution, does not appear to significantly alter sensitivity to agonist in the same system. We suggest that the c. 7042_7044delCAG, p.ΔGlu2348 RYR1 variant could be added to the list of diagnostic mutations for susceptibility to malignant hyperthermia. PMID:27857962

  14. Functional analysis of RYR1 variants linked to malignant hyperthermia.

    PubMed

    Stephens, Jeremy; Schiemann, Anja H; Roesl, Cornelia; Miller, Dorota; Massey, Sean; Pollock, Neil; Bulger, Terasa; Stowell, Kathryn

    2016-01-01

    Malignant hyperthermia manifests as a rapid and sustained rise in temperature in response to pharmacological triggering agents, e.g. inhalational anesthetics and the muscle relaxant suxamethonium. Other clinical signs include an increase in end-tidal CO2, increased O2 consumption, as well as tachycardia, and if untreated a malignant hyperthermia episode can result in death. The metabolic changes are caused by dysregulation of skeletal muscle Ca(2+) homeostasis, resulting from a defective ryanodine receptor Ca(2+) channel, which resides in the sarcoplasmic reticulum and controls the flux of Ca(2+) ions from intracellular stores to the cytoplasm. Most genetic variants associated with susceptibility to malignant hyperthermia occur in the RYR1 gene encoding the ryanodine receptor type 1. While malignant hyperthermia susceptibility can be diagnosed by in vitro contracture testing of skeletal muscle biopsy tissue, it is advantageous to use DNA testing. Currently only 35 of over 400 potential variants in RYR1 have been classed as functionally causative of malignant hyperthermia and thus can be used for DNA diagnostic tests. Here we describe functional analysis of 2 RYR1 variants (c. 7042_7044delCAG, p.ΔGlu2348 and c.641C>T, p.Thr214Met) that occur in the same malignant hyperthermia susceptible family. The p.Glu2348 deletion, causes hypersensitivity to ryanodine receptor agonists using in vitro analysis of cloned human RYR1 cDNA expressed in HEK293T cells, while the Thr214Met substitution, does not appear to significantly alter sensitivity to agonist in the same system. We suggest that the c. 7042_7044delCAG, p.ΔGlu2348 RYR1 variant could be added to the list of diagnostic mutations for susceptibility to malignant hyperthermia.

  15. 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.

  16. Using ecological production functions to link ecological processes to ecosystem services.

    EPA Science Inventory

    Ecological production functions (EPFs) link ecosystems, stressors, and management actions to ecosystem services (ES) production. Although EPFs are acknowledged as being essential to improve environmental management, their use in ecological risk assessment has received relatively ...

  17. Using ecological production functions to link ecological processes to ecosystem services.

    EPA Science Inventory

    Ecological production functions (EPFs) link ecosystems, stressors, and management actions to ecosystem services (ES) production. Although EPFs are acknowledged as being essential to improve environmental management, their use in ecological risk assessment has received relatively ...

  18. 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…

  19. 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…

  20. Structure and function of wood

    Treesearch

    Alex C. Wiedenhoeft; Regis B. Miller

    2005-01-01

    Despite the many human uses to which various woods are suited, at a fundamental level wood is a complex biological structure, itself a composite of many chemistries and cell types acting together to serve the needs of the plant. Although humans have striven to understand wood in the context of wood technology, we have often overlooked the key and basic fact that wood...

  1. Transceptors as a functional link of transporters and receptors

    PubMed Central

    Diallinas, George

    2017-01-01

    Cells need to communicate with their environment in order to obtain nutrients, grow, divide and respond to signals related to adaptation in changing physiological conditions or stress. A very basic question in biology is how cells, especially of those organisms living in rapidly changing habitats, sense their environment. Apparently, this question is of particular importance to all free-living microorganisms. The critical role of receptors, transporters and channels, transmembrane proteins located in the plasma membrane of all types of cells, in signaling environmental changes is well established. A relative newcomer in environment sensing are the so called transceptors, membrane proteins that possess both solute transport and receptor-like signaling activities. Now, the transceptor concept is further enlarged to include micronutrient sensing via the iron and zinc high-affinity transporters of Saccharomyces cerevisiae. Interestingly, what seems to underline the transport and/or sensing function of receptors, transporters and transceptors is ligand-induced conformational alterations recognized by downstream intracellular effectors. PMID:28357392

  2. 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

  3. Assessment of protein function following cross-linking by alpha-dicarbonyls.

    PubMed

    Miller, Antonia G; Gerrard, Juliet A

    2005-06-01

    Protein cross-linking via the Maillard reaction with alpha-dicarbonyl compounds has been the subject of intense scrutiny in the literature. We report here a study of the impact of this cross-linking on enzyme function. Protein function following glycation was examined by treating ribonuclease A with methylglyoxal, glyoxal, and diacetyl, which cross-linked the enzyme and impaired its activity. The effects of two reported Maillard reaction inhibitors, aminoguanidine and 3,5-dimethylpyrazole-1-carboxamidine, on the cross-linking reaction were assessed, with a parallel measurement of the effect on enzyme activity. The results demonstrate that preventing protein cross-linking does not necessarily preserve enzyme activity. These results cast doubt on the likely efficacy of some purported antiaging compounds in vivo.

  4. Nopp140 Functions as a Molecular Link Between the Nucleolus and the Coiled Bodies

    PubMed Central

    Isaac, Cynthia; Yang, Yunfeng; Thomas Meier, U.

    1998-01-01

    Coiled bodies are small nuclear organelles that are highly enriched in small nuclear RNAs, and that have long been thought to be associated with the nucleolus. Here we use mutational analysis, transient transfections, and the yeast two-hybrid system to show that the nucleolar phosphoprotein Nopp140 functions as a molecular link between the two prominent nuclear organelles. Exogenous Nopp140 accumulated in the nucleolus rapidly, but only after a lag phase in coiled bodies, suggesting a pathway between the two organelles. The expression of partial Nopp140 constructs exerted dominant negative effects on the endogenous Nopp140 by chasing it and other antigens that were common to both organelles out of the nucleolus. The alternating positively and negatively charged repeat domain of Nopp140 was required for targeting to both organelles. In addition, partial Nopp140 constructs caused formation of novel structures in the nucleoplasm and, in the case of the conserved carboxy terminus, led to the dispersal of coiled bodies. As a final link, we identified the coiled body–specific protein p80 coilin in a yeast two-hybrid screen with Nopp140. The interaction of the two proteins was confirmed by coimmunoprecipitation. Taken together, Nopp140 appeared to shuttle between the nucleolus and the coiled bodies, and to chaperone the transport of other molecules. PMID:9679133

  5. Structure and Function of Immunoglobulins

    PubMed Central

    Schroeder, Harry W; Cavacini, Lisa

    2013-01-01

    Immunoglobulins are heterodimeric proteins composed of two heavy (H) and two light (L) chains. They can be separated functionally into variable (V) domains that binds antigens and constant (C) domains that specify effector functions such as activation of complement or binding to Fc receptors. The variable domains are created by means of a complex series of gene rearrangement events, and can then be subjected to somatic hypermutation after exposure to antigen to allow affinity maturation. Each V domain can be split into three regions of sequence variability, termed the complementarity determining regions, or CDRs, and four regions of relatively constant sequence termed the framework regions, or FRs. The three CDRs of the H chain are paired with the three CDRs of the L chain to form the antigen binding site, as classically defined. There are five main classes of heavy chain C domains. Each class defines the IgM, IgG, IgA, IgD, and IgE isotypes. IgG can be split into four subclasses, IgG1, IgG2, IgG3, and IgG4, each with its own biologic properties; and IgA can similarly be split into IgA1 and IgA2. The constant domains of the H chain can be switched to allow altered effector function while maintaining antigen specificity. PMID:20176268

  6. Structure and function of immunoglobulins.

    PubMed

    Schroeder, Harry W; Cavacini, Lisa

    2010-02-01

    Immunoglobulins are heterodimeric proteins composed of 2 heavy and 2 light chains. They can be separated functionally into variable domains that bind antigens and constant domains that specify effector functions, such as activation of complement or binding to Fc receptors. The variable domains are created by means of a complex series of gene rearrangement events and can then be subjected to somatic hypermutation after exposure to antigen to allow affinity maturation. Each variable domain can be split into 3 regions of sequence variability termed the complementarity-determining regions (CDRs) and 4 regions of relatively constant sequence termed the framework regions. The 3 CDRs of the heavy chain are paired with the 3 CDRs of the light chain to form the antigen-binding site, as classically defined. The constant domains of the heavy chain can be switched to allow altered effector function while maintaining antigen specificity. There are 5 main classes of heavy chain constant domains. Each class defines the IgM, IgG, IgA, IgD, and IgE isotypes. IgG can be split into 4 subclasses, IgG1, IgG2, IgG3, and IgG4, each with its own biologic properties, and IgA can similarly be split into IgA1 and IgA2.

  7. Pulmonary function and adverse cardiovascular outcomes: Can cardiac function explain the link?

    PubMed

    Burroughs Peña, Melissa S; Dunning, Allison; Schulte, Phillip J; Durheim, Michael T; Kussin, Peter; Checkley, William; Velazquez, Eric J

    2016-12-01

    The complex interaction between pulmonary function, cardiac function and adverse cardiovascular events has only been partially described. We sought to describe the association between pulmonary function with left heart structure and function, all-cause mortality and incident cardiovascular hospitalization. This study is a retrospective analysis of patients evaluated in a single tertiary care medical center. We used multivariable linear regression analyses to examine the relationship between FVC and FEV1 with left ventricular ejection fraction (LVEF), left ventricular internal dimension in systole and diastole (LVIDS, LVIDD) and left atrial diameter, adjusting for baseline characteristics, right ventricular function and lung hyperinflation. We also used Cox proportional hazards models to examine the relationship between FVC and FEV1 with all-cause mortality and cardiac hospitalization. A total of 1807 patients were included in this analysis with a median age of 61 years and 50% were female. Decreased FVC and FEV1 were both associated with decreased LVEF. In individuals with FVC less than 2.75 L, decreased FVC was associated with increased all-cause mortality after adjusting for left and right heart echocardiographic variables (hazard ratio [HR] 0.49, 95% CI 0.29, 0.82, respectively). Decreased FVC was associated with increased cardiac hospitalization after adjusting for left heart size (HR 0.80, 95% CI 0.67, 0.96), even in patients with normal LVEF (HR 0.75, 95% CI 0.57, 0.97). In a tertiary care center reduced pulmonary function was associated with adverse cardiovascular events, a relationship that is not fully explained by left heart remodeling or right heart dysfunction. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Conserved properties of Drosophila Insomniac link sleep regulation and synaptic function.

    PubMed

    Li, Qiuling; Kellner, David A; Hatch, Hayden A M; Yumita, Tomohiro; Sanchez, Sandrine; Machold, Robert P; Frank, C Andrew; Stavropoulos, Nicholas

    2017-05-01

    Sleep is an ancient animal behavior that is regulated similarly in species ranging from flies to humans. Various genes that regulate sleep have been identified in invertebrates, but whether the functions of these genes are conserved in mammals remains poorly explored. Drosophila insomniac (inc) mutants exhibit severely shortened and fragmented sleep. Inc protein physically associates with the Cullin-3 (Cul3) ubiquitin ligase, and neuronal depletion of Inc or Cul3 strongly curtails sleep, suggesting that Inc is a Cul3 adaptor that directs the ubiquitination of neuronal substrates that impact sleep. Three proteins similar to Inc exist in vertebrates-KCTD2, KCTD5, and KCTD17-but are uncharacterized within the nervous system and their functional conservation with Inc has not been addressed. Here we show that Inc and its mouse orthologs exhibit striking biochemical and functional interchangeability within Cul3 complexes. Remarkably, KCTD2 and KCTD5 restore sleep to inc mutants, indicating that they can substitute for Inc in vivo and engage its neuronal targets relevant to sleep. Inc and its orthologs localize similarly within fly and mammalian neurons and can traffic to synapses, suggesting that their substrates may include synaptic proteins. Consistent with such a mechanism, inc mutants exhibit defects in synaptic structure and physiology, indicating that Inc is essential for both sleep and synaptic function. Our findings reveal that molecular functions of Inc are conserved through ~600 million years of evolution and support the hypothesis that Inc and its orthologs participate in an evolutionarily conserved ubiquitination pathway that links synaptic function and sleep regulation.

  9. Structural analysis of key gap junction domains--Lessons from genome data and disease-linked mutants.

    PubMed

    Bai, Donglin

    2016-02-01

    A gap junction (GJ) channel is formed by docking of two GJ hemichannels and each of these hemichannels is a hexamer of connexins. All connexin genes have been identified in human, mouse, and rat genomes and their homologous genes in many other vertebrates are available in public databases. The protein sequences of these connexins align well with high sequence identity in the same connexin across different species. Domains in closely related connexins and several residues in all known connexins are also well-conserved. These conserved residues form signatures (also known as sequence logos) in these domains and are likely to play important biological functions. In this review, the sequence logos of individual connexins, groups of connexins with common ancestors, and all connexins are analyzed to visualize natural evolutionary variations and the hot spots for human disease-linked mutations. Several gap junction domains are homologous, likely forming similar structures essential for their function. The availability of a high resolution Cx26 GJ structure and the subsequently-derived homology structure models for other connexin GJ channels elevated our understanding of sequence logos at the three-dimensional GJ structure level, thus facilitating the understanding of how disease-linked connexin mutants might impair GJ structure and function. This knowledge will enable the design of complementary variants to rescue disease-linked mutants.

  10. Functionalized Nano and Micro Structured Composite Coatings

    DTIC Science & Technology

    2011-06-01

    AFRL-RX-TY-TR-2011-0069 FUNCTIONALIZED NANO AND MICRO STRUCTURED COMPOSITE COATINGS (FINAL REPORT) Igor Luzinov and Konstantin Kornev...Technical Report 21-MAY-2009 -- 31-MAY-2011 Functional Polymeric Materials - from Research Labs to Field Applications: Functionalized Nano and Micro ...work was to conduct research on development of effective nano and micro structured composite coatings capable to collect and decontaminate the

  11. Structural Health Monitoring Using Transmittance Functions

    NASA Astrophysics Data System (ADS)

    Zhang, H.; Schulz, M. J.; Naser, A.; Ferguson, F.; Pai, P. F.

    1999-09-01

    A technique for structural health monitoring that can detect damage away from a sensor location and during operation of a structure is presented. The technique, Transmittance Function Monitoring, uses vibration measurements to detect damage, but without measuring the excitation force or using a model of the structure. Accelerometers or piezoceramic patches are attached to the structure for sensing, and piezoceramic patches or inertial actuators are used for exciting the structure. The sensor-actuator system actively interrogates the structure using broadband excitation, and transmittance functions between consecutive sensors from the healthy structure are stored as historical data. Changes in the functions are then used to detect, locate and assess damage to the structure. Transmittance functions can be computed from different types of measured structural responses. Here, structural translations and curvatures are used to detect damage on a composite beam. The sensitivity of the two different methods is compared, and the optimal frequency range to detect damage is experimentally determined. In addition, the wavelengths of the structural mode shapes are computed to estimate the highest frequency at which the structural response can be measured by a given length piezoceramic sensor.

  12. Structure and function of desmosomes.

    PubMed

    Holthöfer, Bastian; Windoffer, Reinhard; Troyanovsky, Sergey; Leube, Rudolf E

    2007-01-01

    Desmosomes are prominent adhesion sites that are tightly associated with the cytoplasmic intermediate filament cytoskeleton providing mechanical stability in epithelia and also in several nonepithelial tissues such as cardiac muscle and meninges. They are unique in terms of ultrastructural appearance and molecular composition with cell type-specific variations. The dynamic assembly properties of desmosomes are important prerequisites for the acquisition and maintenance of tissue homeostasis. Disturbance of this equilibrium therefore not only compromises mechanical resilience but also affects many other tissue functions as becomes evident in various experimental scenarios and multiple diseases.

  13. District nurses' prescribing practice and its link to structural conditions.

    PubMed

    Blanck, Susanne; Engström, Maria

    2015-10-01

    To describe district nurses' (DNs') prescribing practice and examine associations between DNs' self-reported prescribing frequency, opinions about prescribing, and structural conditions/empowerment. A cross-sectional and correlational design was employed. Data were collected during 2012 using questionnaires and a prescribing register. A random sample of 150 DNs from 32 primary care centers in Sweden was invited. DNs' ability to prescribe is used to a relatively small extent and access to "opportunities" and "informal power" seems to be the most important structural empowerment conditions for increased prescribing frequency and positive opinions about prescribing. The results support Kanter's theory of structural empowerment. This article regarding restricted prescribing shows how important structural conditions/empowerment is to DNs' prescribing and employers have to enhance nurses' access to especially the structures "opportunities" and "informal power" to increase nurse prescribing. More targeted support and training are needed in different prescribing areas to make use of DNs' prescription qualification to a greater extent. ©2015 American Association of Nurse Practitioners.

  14. Tear Lipocalin: Structure and Function

    PubMed Central

    Dartt, Darlene A.

    2014-01-01

    Lipocalins are a family of diverse low molecular weight proteins that act extracellularly. They use multiple recognition properties that include: 1) ligand binding to small hydrophobic molecules, 2) macromolecular complexation with other soluble macromolecules, and 3) binding to specific cell surface receptors to deliver cargo. Tear lipocalin (TLC) is a major protein in tears and has a large ligand binding cavity that allows the lipocalin to bind an extensive and diverse set of lipophilic molecules. TLC can also bind to macromolecules including the tear proteins lactoferin and lysozyme. The receptor to which TLC binds is termed tear lipocalin interacting membrane receptor (LIMR). LIMR appears to work by endocytosis. TLC has a variety of suggested functions in tears including regulation of tear viscosity, binding and release of lipids, endonuclease inactivation of viral DNA, binding of microbial siderophores (iron chelators used to deliver essential iron to bacteria), use as a biomarker for dry eye, and possession of anti-inflammatory activity. Additional research is warranted to determine the actual functions of TLC in tears and the presence of its receptor on the ocular surface. PMID:21791187

  15. Structural elucidation of an asparagine-linked oligosaccharide from the hyperthermophilic archaeon, Archaeoglobus fulgidus.

    PubMed

    Fujinami, Daisuke; Nyirenda, James; Matsumoto, Shunsuke; Kohda, Daisuke

    2015-09-02

    The genome of the hyperthermophilic archaeon, Archaeoglobus fulgidus, contains three paralogous AglB genes that encode oligosaccharyltransferase (OST) proteins. The OST enzymes catalyze the transfer of an oligosaccharide chain from lipid-linked oligosaccharides (LLO) to asparagine residues in proteins. The detergent-solubilized membrane fractions prepared from cultured A. fulgidus cells contain both OST and LLO. The addition of a peptide containing the glycosylation sequon produced oligosaccharide chains attached to a structurally defined peptide. To facilitate the NMR analysis, the cells were grown in rich medium supplemented with (13)C-glucose, to label the LLOs metabolically. The MS analysis of the glycopeptide revealed that the glucose and galactose residues were nearly fully (13)C-labeled, but the mannose residues were fractionally labeled with about 20% efficiency. An immunodetection experiment revealed that the longest AglB paralog (AfAglB-L) was expressed in the membrane fractions under our cell culture conditions, while the other two shorter AglB paralogs (AfAglB-S1 and AfAglB-S2) were not. Thus, the oligosaccharide chain analyzed in this study was the product of AfAglB-L. The N-glycan consists of eight hexose residues, as follows: The α1,3-linked glucose is an optional residue branching from the distal mannose residue. The MS analysis of the minor HPLC peak of the in vitro oligosaccharyl transfer products also revealed an optional sulfate modification on the glucose residue directly linked to the Asn residue. The present data will be useful for structural and functional studies of the N-glycosylation system of A. fulgidus.

  16. [Interferons: between structure and function].

    PubMed

    Bandurska, Katarzyna; Król, Izabela; Myga-Nowak, Magdalena

    2014-05-06

    Interferons are a family of proteins that are released by a variety of cells in response to infections caused by viruses. Currently, we distinguish three types of interferons. They are classified based on the nucleotide sequence, interaction with specific receptors, chromosomal location, structure and physicochemical properties. The following interferons are classified as type I: α, β, ω, κ, ε, ζ, τ, δ, ν. They are recognized and bound by a receptor formed by two peptides, IFN-αR1 and IFN-αR2. Representative of type II interferons is interferon-γ. It binds to a receptor composed of chains IFNGR-1 and IFNGR-2. The recently classified type III interferons comprise IFN-λ1, IFN-λ2, and IFN-λ3. They act on receptors formed by λR1 IFN-and IL-10R2 subunits. A high level of antiviral protection is achieved by IFN-α, IFN-β and IFN-λ. Antiviral activity of interferons is based on the induction and regulation of innate and acquired immune mechanisms. By binding to transmembrane receptors, IFN interacts with target cells mainly by activating the JAK/STAT, but also other signaling pathways. This leads to induction and activation of many antiviral agents, such as protein kinase RNA-activated (PKR), ribonuclease 2-5A pathway, and Mx proteins, as well as numerous apoptotic pathways. As a result of the protective effect of interferons, the virus binding to cells and viral particles penetration into cells is stopped, and the release of the nucleocapsid from an envelope is suppressed. Disruption of transcription and translation processes of the structural proteins prevents the formation of virions or budding of viruses, and as a result degradation of the viral mRNA; the started processes inhibit the chain synthesis of viral proteins and therefore further stimulate the immune system cells.

  17. Cognitive Impairment in MS Linked to Structural and Functional Connectivity

    DTIC Science & Technology

    2015-10-01

    mediated inflammation and neurodegeneration within the central nervous system (CNS). Cognitive impairment is estimated to occur in up to 70% of all...neurologic disorder to occur in adults of working-age. Pathologically, MS is characterized by demyelination, immune- mediated inflammation and...sMRI) is sensitive to the neuro -axonal loss and demyelination that occurs in MS 1. A recent meta-analysis of 18 studies of regional grey matter

  18. Cognitive Impairment in MS Linked to Structural and Functional Connectivity

    DTIC Science & Technology

    2016-10-01

    inflammation and neurodegeneration within the central nervous system (CNS). Cognitive impairment is estimated to occur in up to 70% of all patients...disorder to occur in adults of working-age. Pathologically, MS is characterized by demyelination, immune- mediated inflammation and neurodegeneration... neuro -axonal loss and demyelination that occurs in MS 1. A recent meta-analysis of 18 studies of regional grey matter loss in RRMS found that, in

  19. Structural analysis of the asparagine-linked oligosaccharides of cholinesterases. N-linked carbohydrates of cholinesterases

    SciTech Connect

    Saxena, A.; Doctor, B.P.

    1995-12-31

    Cholinesterases are serine esterases that hydrolyse choline esters faster than other substrates. They are highly glycosylated proteins with up to 24% of their molecular weight constituted of carbohydrates. Here we report the results of our studies on the glycosylation of fetal bovine serum acetylcholinesterase (FBS AChE) and horse serum butyrylcholinesterase (Eq BChE). Analysis of the monosaccharide content of the two enzymes indicated that Eq BChE contained 520 nmoles of monosaccharide/mg protein, as compared to 1290 nmoles/mg protein for Eq BChE. Both enzymes contained mannose, galactose, N-acetylglucosamine and sialic acid. Fucose was present in Eq BChE only. The structures of the two major oligosaccharides from FBS AChE and one major oligosaccharide from Eq BChE were determined and found to be very similar except that one of the oligosaccharides from FBS AChE contained a galactose alphal-3 galactose betal-4-determinant which has been identified as a potentially immunogenic determinant.

  20. Nitrogenase structure and function relationships by density functional theory.

    PubMed

    Harris, Travis V; Szilagyi, Robert K

    2011-01-01

    Modern density functional theory has tremendous potential with matching popularity in metalloenzymology to reveal the unseen atomic and molecular details of structural data, spectroscopic measurements, and biochemical experiments by providing insights into unobservable structures and states, while also offering theoretical justifications for observed trends and differences. An often untapped potential of this theoretical approach is to bring together diverse experimental structural and reactivity information and allow for these to be critically evaluated at the same level. This is particularly applicable for the tantalizingly complex problem of the structure and molecular mechanism of biological nitrogen fixation. In this chapter we provide a review with extensive practical details of the compilation and evaluation of experimental data for an unbiased and systematic density functional theory analysis that can lead to remarkable new insights about the structure-function relationships of the iron-sulfur clusters of nitrogenase.

  1. Water linked 3D coordination polymers: Syntheses, structures and applications

    NASA Astrophysics Data System (ADS)

    Singh, Suryabhan; Bhim, Anupam

    2016-12-01

    Three new coordination polymers (CPs) based on Cd and Pb, [Cd(OBA)(μ-H2O)(H2O)]n1, [Pb(OBA)(μ-H2O)]n2 [where OBA=4,4'-Oxybis(benzoate)] and [Pb(SDBA)(H2O)]n.1/4DMF 3 (SDBA=4,4'-Sulfonyldibenzoate), have been synthesized and characterized. The single crystal structural studies reveal that CPs 1 and 2 have three dimensional structure. A water molecule bridges two metal centres which appears to the responsible for the dimensionality increase from 2D to 3D. Compound 3 has a supramolecular 3D structure involving water molecule and hydrogen bonds. A structural transformation is observed when 3 was heated at 100 °C or kept in methanol, forming [Pb(SDBA)]n4. Compound 4 is used as supporting matrix for palladium nanoparticles, PdNPs@4. The PdNPs@4 exhibits good catalytic activity toward the reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) in the presence of NaBH4 at room temperature. Luminescence studies revealed that all CPs could be an effective sensor for nitroaromatic explosives.

  2. Mammalian protein glycosylation--structure versus function.

    PubMed

    Defaus, S; Gupta, P; Andreu, D; Gutiérrez-Gallego, R

    2014-06-21

    Carbohydrates fulfil many common as well as extremely important functions in nature. They show a variety of molecular displays--e.g., free mono-, oligo-, and polysaccharides, glycolipids, proteoglycans, glycoproteins, etc.--with particular roles and localizations in living organisms. Structure-specific peculiarities are so many and diverse that it becomes virtually impossible to cover them all from an analytical perspective. Hence this manuscript, focused on mammalian glycosylation, rather than a complete list of analytical descriptors or recognized functions for carbohydrate structures, comprehensively reviews three central issues in current glycoscience, namely (i) structural analysis of glycoprotein glycans, covering both classical and novel approaches for teasing out the structural puzzle as well as potential pitfalls of these processes; (ii) an overview of functions attributed to carbohydrates, covering from monosaccharide to complex, well-defined epitopes and full glycans, including post-glycosylational modifications, and (iii) recent technical advances allowing structural identification of glycoprotein glycans with simultaneous assignation of biological functions.

  3. Functional materials discovery using energy-structure-function maps.

    PubMed

    Pulido, Angeles; Chen, Linjiang; Kaczorowski, Tomasz; Holden, Daniel; Little, Marc A; Chong, Samantha Y; Slater, Benjamin J; McMahon, David P; Bonillo, Baltasar; Stackhouse, Chloe J; Stephenson, Andrew; Kane, Christopher M; Clowes, Rob; Hasell, Tom; Cooper, Andrew I; Day, Graeme M

    2017-03-30

    Molecular crystals cannot be designed in the same manner as macroscopic objects, because they do not assemble according to simple, intuitive rules. Their structures result from the balance of many weak interactions, rather than from the strong and predictable bonding patterns found in metal-organic frameworks and covalent organic frameworks. Hence, design strategies that assume a topology or other structural blueprint will often fail. Here we combine computational crystal structure prediction and property prediction to build energy-structure-function maps that describe the possible structures and properties that are available to a candidate molecule. Using these maps, we identify a highly porous solid, which has the lowest density reported for a molecular crystal so far. Both the structure of the crystal and its physical properties, such as methane storage capacity and guest-molecule selectivity, are predicted using the molecular structure as the only input. More generally, energy-structure-function maps could be used to guide the experimental discovery of materials with any target function that can be calculated from predicted crystal structures, such as electronic structure or mechanical properties.

  4. Functional materials discovery using energy-structure-function maps

    NASA Astrophysics Data System (ADS)

    Pulido, Angeles; Chen, Linjiang; Kaczorowski, Tomasz; Holden, Daniel; Little, Marc A.; Chong, Samantha Y.; Slater, Benjamin J.; McMahon, David P.; Bonillo, Baltasar; Stackhouse, Chloe J.; Stephenson, Andrew; Kane, Christopher M.; Clowes, Rob; Hasell, Tom; Cooper, Andrew I.; Day, Graeme M.

    2017-03-01

    Molecular crystals cannot be designed in the same manner as macroscopic objects, because they do not assemble according to simple, intuitive rules. Their structures result from the balance of many weak interactions, rather than from the strong and predictable bonding patterns found in metal-organic frameworks and covalent organic frameworks. Hence, design strategies that assume a topology or other structural blueprint will often fail. Here we combine computational crystal structure prediction and property prediction to build energy-structure-function maps that describe the possible structures and properties that are available to a candidate molecule. Using these maps, we identify a highly porous solid, which has the lowest density reported for a molecular crystal so far. Both the structure of the crystal and its physical properties, such as methane storage capacity and guest-molecule selectivity, are predicted using the molecular structure as the only input. More generally, energy-structure-function maps could be used to guide the experimental discovery of materials with any target function that can be calculated from predicted crystal structures, such as electronic structure or mechanical properties.

  5. Linking magma transport structures at Kīlauea volcano

    NASA Astrophysics Data System (ADS)

    Wech, Aaron G.; Thelen, Weston A.

    2015-09-01

    Identifying magma pathways is important for understanding and interpreting volcanic signals. At Kīlauea volcano, seismicity illuminates subsurface plumbing, but the broad spectrum of seismic phenomena hampers event identification. Discrete, long-period (LP) events dominate the shallow (5-10 km) plumbing, and deep (40+ km) tremor has been observed offshore. However, our inability to routinely identify these events limits their utility in tracking ascending magma. Using envelope cross-correlation, we systematically catalog non-earthquake seismicity between 2008 and 2014. We find that the LPs and deep tremor are spatially distinct, separated by the 15-25 km deep, horizontal mantle fault zone (MFZ). Our search corroborates previous observations, but we find broader band (0.5-20 Hz) tremor comprising collocated earthquakes and reinterpret the deep tremor as earthquake swarms in a volume surrounding and responding to magma intruding from the mantle plume beneath the MFZ. We propose that the overlying MFZ promotes lateral magma transport, linking this deep intrusion with Kīlauea's shallow magma plumbing.

  6. Linking magma transport structures at Kīlauea volcano

    USGS Publications Warehouse

    Wech, Aaron G.; Thelen, Weston A.

    2015-01-01

    Identifying magma pathways is important for understanding and interpreting volcanic signals. At Kīlauea volcano, seismicity illuminates subsurface plumbing, but the broad spectrum of seismic phenomena hampers event identification. Discrete, long-period events (LPs) dominate the shallow (5-10 km) plumbing, and deep (40+ km) tremor has been observed offshore. However, our inability to routinely identify these events limits their utility in tracking ascending magma. Using envelope cross-correlation, we systematically catalog non-earthquake seismicity between 2008-2014. We find the LPs and deep tremor are spatially distinct, separated by the 15-25 km deep, horizontal mantle fault zone (MFZ). Our search corroborates previous observations, but we find broader-band (0.5-20 Hz) tremor comprising collocated earthquakes and reinterpret the deep tremor as earthquake swarms in a volume surrounding and responding to magma intruding from the mantle plume beneath the MFZ. We propose the overlying MFZ promotes lateral magma transport, linking this deep intrusion with Kīlauea’s shallow magma plumbing.

  7. Cilia in the nervous system: linking cilia function and neurodevelopmental disorders

    PubMed Central

    Lee, Ji E.; Gleeson, Joseph G.

    2014-01-01

    Purpose of review Ciliopathies are genetic disorders caused by defects of primary ciliary structure and/or function and are characterized by pleiotropic clinical features. The ciliopathies include several partially overlapping syndromes such as Joubert syndrome, Bardet–Biedl syndrome and Meckel–Gruber syndrome, all of which have pronounced neurodevelopmental features. Here we focus on potential roles of cilia in central nervous system function, to explore how impairments may cause brain malformation and neurodevelopmental disease. Recent findings Cilia have long been considered as ‘sensory cellular antennae’, responding as chemo-sensors, mechano-sensors and thermo-sensors, although their roles in development were not well understood until recently. The surprising finding that disparate syndromes are all due to defects of the primary cilia, along with the recent advances in genetics, has helped elucidate further roles of primary cilia beyond sensory functions. Several molecules that are associated with key signaling pathways have been discovered in primary cilia. These include sonic hedgehog, wingless, planar cell polarity and fibroblast growth factor, which are essential for many cellular processes. Additionally, mutations in ‘ciliome’ genes have largely shown developmental defects such as abnormal body axis and brain malformation, implying disrupted cilia-related signaling pathways. Accordingly, the emerging theme is that primary cilia may play roles as modulators of signal transduction to help shape cellular responses within the environmental context during both development and homeostasis. Summary The link between cilia and signal pathways has become a framework for understanding the pathogenesis of ciliopathies. Despite recent progress in ciliary biology, fundamental questions remain about how cilia regulate neuronal function in the central nervous system. Therefore, investigation of ciliary function in the nervous system may reveal cilia

  8. Cilia in the nervous system: linking cilia function and neurodevelopmental disorders.

    PubMed

    Lee, Ji E; Gleeson, Joseph G

    2011-04-01

    Ciliopathies are genetic disorders caused by defects of primary ciliary structure and/or function and are characterized by pleiotropic clinical features. The ciliopathies include several partially overlapping syndromes such as Joubert syndrome, Bardet-Biedl syndrome and Meckel-Gruber syndrome, all of which have pronounced neurodevelopmental features. Here we focus on potential roles of cilia in central nervous system function, to explore how impairments may cause brain malformation and neurodevelopmental disease. Cilia have long been considered as 'sensory cellular antennae', responding as chemo-sensors, mechano-sensors and thermo-sensors, although their roles in development were not well understood until recently. The surprising finding that disparate syndromes are all due to defects of the primary cilia, along with the recent advances in genetics, has helped elucidate further roles of primary cilia beyond sensory functions. Several molecules that are associated with key signaling pathways have been discovered in primary cilia. These include sonic hedgehog, wingless, planar cell polarity and fibroblast growth factor, which are essential for many cellular processes. Additionally, mutations in 'ciliome' genes have largely shown developmental defects such as abnormal body axis and brain malformation, implying disrupted cilia-related signaling pathways. Accordingly, the emerging theme is that primary cilia may play roles as modulators of signal transduction to help shape cellular responses within the environmental context during both development and homeostasis. The link between cilia and signal pathways has become a framework for understanding the pathogenesis of ciliopathies. Despite recent progress in ciliary biology, fundamental questions remain about how cilia regulate neuronal function in the central nervous system. Therefore, investigation of ciliary function in the nervous system may reveal cilia-modulating mechanisms in neurodevelopmental processes, as well

  9. Biological spectra analysis: Linking biological activity profiles to molecular structure

    PubMed Central

    Fliri, Anton F.; Loging, William T.; Thadeio, Peter F.; Volkmann, Robert A.

    2005-01-01

    Establishing quantitative relationships between molecular structure and broad biological effects has been a longstanding challenge in science. Currently, no method exists for forecasting broad biological activity profiles of medicinal agents even within narrow boundaries of structurally similar molecules. Starting from the premise that biological activity results from the capacity of small organic molecules to modulate the activity of the proteome, we set out to investigate whether descriptor sets could be developed for measuring and quantifying this molecular property. Using a 1,567-compound database, we show that percent inhibition values, determined at single high drug concentration in a battery of in vitro assays representing a cross section of the proteome, provide precise molecular property descriptors that identify the structure of molecules. When broad biological activity of molecules is represented in spectra form, organic molecules can be sorted by quantifying differences between biological spectra. Unlike traditional structure–activity relationship methods, sorting of molecules by using biospectra comparisons does not require knowledge of a molecule's putative drug targets. To illustrate this finding, we selected as starting point the biological activity spectra of clotrimazole and tioconazole because their putative target, lanosterol demethylase (CYP51), was not included in the bioassay array. Spectra similarity obtained through profile similarity measurements and hierarchical clustering provided an unbiased means for establishing quantitative relationships between chemical structures and biological activity spectra. This methodology, which we have termed biological spectra analysis, provides the capability not only of sorting molecules on the basis of biospectra similarity but also of predicting simultaneous interactions of new molecules with multiple proteins. PMID:15625110

  10. A Link between Protein Structure and Enzyme Catalyzed Hydrogen Tunneling

    NASA Astrophysics Data System (ADS)

    Bahnson, Brian J.; Colby, Thomas D.; Chin, Jodie K.; Goldstein, Barry M.; Klinman, Judith P.

    1997-11-01

    We present evidence that the size of an active site side chain may modulate the degree of hydrogen tunneling in an enzyme-catalyzed reaction. Primary and secondary kH/kT and kD/kT kinetic isotope effects have been measured for the oxidation of benzyl alcohol catalyzed by horse liver alcohol dehydrogenase at 25 degrees C. As reported in earlier studies, the relationship between secondary kH/kT and kD/kT isotope effects provides a sensitive probe for deviations from classical behavior. In the present work, catalytic efficiency and the extent of hydrogen tunneling have been correlated for the alcohol dehydrogenase-catalyzed hydride transfer among a group of site-directed mutants at position 203. Val-203 interacts with the opposite face of the cofactor NAD+ from the alcohol substrate. The reduction in size of this residue is correlated with diminished tunneling and a two orders of magnitude decrease in catalytic efficiency. Comparison of the x-ray crystal structures of a ternary complex of a high-tunneling (Phe-93 --> Trp) and a low-tunneling (Val-203 --> Ala) mutant provides a structural basis for the observed effects, demonstrating an increase in the hydrogen transfer distance for the low-tunneling mutant. The Val-203 --> Ala ternary complex crystal structure also shows a hyperclosed interdomain geometry relative to the wild-type and the Phe-93 --> Trp mutant ternary complex structures. This demonstrates a flexibility in interdomain movement that could potentially narrow the distance between the donor and acceptor carbons in the native enzyme and may enhance the role of tunneling in the hydride transfer reaction.

  11. Structural and functional assessment of APOBEC3G macromolecular complexes.

    PubMed

    Polevoda, Bogdan; McDougall, William M; Bennett, Ryan P; Salter, Jason D; Smith, Harold C

    2016-09-01

    There are eleven members in the human APOBEC family of proteins that are evolutionarily related through their zinc-dependent cytidine deaminase domains. The human APOBEC gene clusters arose on chromosome 6 and 22 through gene duplication and divergence to where current day APOBEC proteins are functionally diverse and broadly expressed in tissues. APOBEC serve enzymatic and non enzymatic functions in cells. In both cases, formation of higher-order structures driven by APOBEC protein-protein interactions and binding to RNA and/or single stranded DNA are integral to their function. In some circumstances, these interactions are regulatory and modulate APOBEC activities. We are just beginning to understand how macromolecular interactions drive processes such as APOBEC subcellular compartmentalization, formation of holoenzyme complexes, gene targeting, foreign DNA restriction, anti-retroviral activity, formation of ribonucleoprotein particles and APOBEC degradation. Protein-protein and protein-nucleic acid cross-linking methods coupled with mass spectrometry, electrophoretic mobility shift assays, glycerol gradient sedimentation, fluorescence anisotropy and APOBEC deaminase assays are enabling mapping of interacting surfaces that are essential for these functions. The goal of this methods review is through example of our research on APOBEC3G, describe the application of cross-linking methods to characterize and quantify macromolecular interactions and their functional implications. Given the homology in structure and function, it is proposed that these methods will be generally applicable to the discovery process for other APOBEC and RNA and DNA editing and modifying proteins.

  12. Sevoflurane Alters Spatiotemporal Functional Connectivity Motifs That Link Resting-State Networks during Wakefulness

    PubMed Central

    Kafashan, MohammadMehdi; Ching, ShiNung; Palanca, Ben J. A.

    2016-01-01

    Background: The spatiotemporal patterns of correlated neural activity during the transition from wakefulness to general anesthesia have not been fully characterized. Correlation analysis of blood-oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI) allows segmentation of the brain into resting-state networks (RSNs), with functional connectivity referring to the covarying activity that suggests shared functional specialization. We quantified the persistence of these correlations following the induction of general anesthesia in healthy volunteers and assessed for a dynamic nature over time. Methods: We analyzed human fMRI data acquired at 0 and 1.2% vol sevoflurane. The covariance in the correlated activity among different brain regions was calculated over time using bounded Kalman filtering. These time series were then clustered into eight orthogonal motifs using a K-means algorithm, where the structure of correlated activity throughout the brain at any time is the weighted sum of all motifs. Results: Across time scales and under anesthesia, the reorganization of interactions between RSNs is related to the strength of dynamic connections between member pairs. The covariance of correlated activity between RSNs persists compared to that linking individual member pairs of different RSNs. Conclusions: Accounting for the spatiotemporal structure of correlated BOLD signals, anesthetic-induced loss of consciousness is mainly associated with the disruption of motifs with intermediate strength within and between members of different RSNs. In contrast, motifs with higher strength of connections, predominantly with regions-pairs from within-RSN interactions, are conserved among states of wakefulness and sevoflurane general anesthesia. PMID:28082871

  13. Encoding Hydrogel Mechanics via Network Cross-Linking Structure

    PubMed Central

    2015-01-01

    The effects of mechanical cues on cell behaviors in 3D remain difficult to characterize as the ability to tune hydrogel mechanics often requires changes in the polymer density, potentially altering the material’s biochemical and physical characteristics. Additionally, with most PEG diacrylate (PEGDA) hydrogels, forming materials with compressive moduli less than ∼10 kPa has been virtually impossible. Here, we present a new method of controlling the mechanical properties of PEGDA hydrogels independent of polymer chain density through the incorporation of additional vinyl group moieties that interfere with the cross-linking of the network. This modification can tune hydrogel mechanics in a concentration dependent manner from <1 to 17 kPa, a more physiologically relevant range than previously possible with PEG-based hydrogels, without altering the hydrogel’s degradation and permeability. Across this range of mechanical properties, endothelial cells (ECs) encapsulated within MMP-2/MMP-9 degradable hydrogels with RGDS adhesive peptides revealed increased cell spreading as hydrogel stiffness decreased in contrast to behavior typically observed for cells on 2D surfaces. EC-pericyte cocultures exhibited vessel-like networks within 3 days in highly compliant hydrogels as compared to a week in stiffer hydrogels. These vessel networks persisted for at least 4 weeks and deposited laminin and collagen IV perivascularly. These results indicate that EC morphogenesis can be regulated using mechanical cues in 3D. Furthermore, controlling hydrogel compliance independent of density allows for the attainment of highly compliant mechanical regimes in materials that can act as customizable cell microenvironments. PMID:26082943

  14. Establishing a link between sex-related differences in the structural connectome and behaviour.

    PubMed

    Tunç, Birkan; Solmaz, Berkan; Parker, Drew; Satterthwaite, Theodore D; Elliott, Mark A; Calkins, Monica E; Ruparel, Kosha; Gur, Raquel E; Gur, Ruben C; Verma, Ragini

    2016-02-19

    Recent years have witnessed an increased attention to studies of sex differences, partly because such differences offer important considerations for personalized medicine. While the presence of sex differences in human behaviour is well documented, our knowledge of their anatomical foundations in the brain is still relatively limited. As a natural gateway to fathom the human mind and behaviour, studies concentrating on the human brain network constitute an important segment of the research effort to investigate sex differences. Using a large sample of healthy young individuals, each assessed with diffusion MRI and a computerized neurocognitive battery, we conducted a comprehensive set of experiments examining sex-related differences in the meso-scale structures of the human connectome and elucidated how these differences may relate to sex differences at the level of behaviour. Our results suggest that behavioural sex differences, which indicate complementarity of males and females, are accompanied by related differences in brain structure across development. When using subnetworks that are defined over functional and behavioural domains, we observed increased structural connectivity related to the motor, sensory and executive function subnetworks in males. In females, subnetworks associated with social motivation, attention and memory tasks had higher connectivity. Males showed higher modularity compared to females, with females having higher inter-modular connectivity. Applying multivariate analysis, we showed an increasing separation between males and females in the course of development, not only in behavioural patterns but also in brain structure. We also showed that these behavioural and structural patterns correlate with each other, establishing a reliable link between brain and behaviour.

  15. DNA-Protein Cross-links: Formation, Structural Identities, and Biological Outcomes

    PubMed Central

    Tretyakova, Natalia Y.; Groehler, Arnold; Ji, Shaofei

    2015-01-01

    CONSPECTUS Non-covalent DNA-protein interactions are at the heart of normal cell function. In eukaryotic cells, genomic DNA is wrapped around histone octamers to allow for chromosomal packaging in the nucleus. Binding of regulatory protein factors to DNA directs replication, controls transcription, and mediates cellular responses to DNA damage. Because of their fundamental significance in all cellular processes involving DNA, dynamic DNA-protein interactions are required for cell survival, and their disruption is likely to have serious biological consequences. DNA-protein cross-links (DPCs) form when cellular proteins become covalently trapped on DNA strands upon exposure to various endogenous, environmental and chemotherapeutic agents. DPCs progressively accumulate in the brain and heart tissues as a result of endogenous exposure to reactive oxygen species and lipid peroxidation products, as well as normal cellular metabolism. A range of structurally diverse DPCs are found following treatment with chemotherapeutic drugs, transition metal ions, and metabolically activated carcinogens. Because of their considerable size and their helix-distorting nature, DPCs interfere with the progression of replication and transcription machineries and hence hamper the faithful expression of genetic information, potentially contributing to mutagenesis and carcinogenesis. Mass spectrometry-based studies have identified hundreds of proteins that can become cross-linked to nuclear DNA in the presence of reactive oxygen species, carcinogen metabolites, and antitumor drugs. While many of these proteins including histones, transcription factors, and repair proteins are known DNA binding partners, other gene products with no documented affinity for DNA also participate in DPC formation. Furthermore, multiple sites within DNA can be targeted for cross-linking including the N7 of guanine, the C-5 methyl group of thymine, and the exocyclic amino groups of guanine, cytosine, and adenine

  16. Structure and function analysis of protein-nucleic acid complexes

    NASA Astrophysics Data System (ADS)

    Kuznetsova, S. A.; Oretskaya, T. S.

    2016-05-01

    The review summarizes published data on the results and achievements in the field of structure and function analysis of protein-nucleic acid complexes by means of main physical and biochemical methods, including X-ray diffraction, nuclear magnetic resonance spectroscopy, electron and atomic force microscopy, small-angle X-ray and neutron scattering, footprinting and cross-linking. Special attention is given to combined approaches. The advantages and limitations of each method are considered, and the prospects of their application for wide-scale structural studies in vivo are discussed. The bibliography includes 145 references.

  17. Micro-review of structure functions and parton distribution functions

    SciTech Connect

    Morfin, J.G.

    1989-01-01

    There has recently been a great deal of discussion concerning the surprising differences in the measurements of the nucleon structure function F/sub 2/(x,Q/sup 2/), off of a hydrogen target, by the high statistics muoproduction experiments EMC and BCDMS. In this short review I will attempt to summarize the status of the experimental measurements of the structure functions and highlight any significant disagreements. At the conclusion I will comment on the status of the extraction of the parton distribution functions from these measurements. 17 refs., 16 figs., 2 tabs.

  18. What are the links between maternal social status, hippocampal function, and HPA axis function in children?

    PubMed

    Sheridan, Margaret A; How, Joan; Araujo, Melanie; Schamberg, Michelle A; Nelson, Charles A

    2013-09-01

    The association of parental social status with multiple health and achievement indicators in adulthood has driven researchers to attempt to identify mechanisms by which social experience in childhood could shift developmental trajectories. Some accounts for observed linkages between parental social status in childhood and health have hypothesized that early stress exposure could result in chronic disruptions in hypothalamic-pituitary-adrenal (HPA) axis activation, and that this activation could lead to long-term changes. A robust literature in adult animals has demonstrated that chronic HPA axis activation leads to changes in hippocampal structure and function. In the current study, consistent with studies in animals, we observe an association between both maternal self-rated social status and hippocampal activation in children and between maternal self-rated social status and salivary cortisol in children.

  19. Four RNA families with functional transient structures.

    PubMed

    Zhu, Jing Yun A; Meyer, Irmtraud M

    2015-01-01

    Protein-coding and non-coding RNA transcripts perform a wide variety of cellular functions in diverse organisms. Several of their functional roles are expressed and modulated via RNA structure. A given transcript, however, can have more than a single functional RNA structure throughout its life, a fact which has been previously overlooked. Transient RNA structures, for example, are only present during specific time intervals and cellular conditions. We here introduce four RNA families with transient RNA structures that play distinct and diverse functional roles. Moreover, we show that these transient RNA structures are structurally well-defined and evolutionarily conserved. Since Rfam annotates one structure for each family, there is either no annotation for these transient structures or no such family. Thus, our alignments either significantly update and extend the existing Rfam families or introduce a new RNA family to Rfam. For each of the four RNA families, we compile a multiple-sequence alignment based on experimentally verified transient and dominant (dominant in terms of either the thermodynamic stability and/or attention received so far) RNA secondary structures using a combination of automated search via covariance model and manual curation. The first alignment is the Trp operon leader which regulates the operon transcription in response to tryptophan abundance through alternative structures. The second alignment is the HDV ribozyme which we extend to the 5' flanking sequence. This flanking sequence is involved in the regulation of the transcript's self-cleavage activity. The third alignment is the 5' UTR of the maturation protein from Levivirus which contains a transient structure that temporarily postpones the formation of the final inhibitory structure to allow translation of maturation protein. The fourth and last alignment is the SAM riboswitch which regulates the downstream gene expression by assuming alternative structures upon binding of SAM. All

  20. Four RNA families with functional transient structures

    PubMed Central

    Zhu, Jing Yun A; Meyer, Irmtraud M

    2015-01-01

    Protein-coding and non-coding RNA transcripts perform a wide variety of cellular functions in diverse organisms. Several of their functional roles are expressed and modulated via RNA structure. A given transcript, however, can have more than a single functional RNA structure throughout its life, a fact which has been previously overlooked. Transient RNA structures, for example, are only present during specific time intervals and cellular conditions. We here introduce four RNA families with transient RNA structures that play distinct and diverse functional roles. Moreover, we show that these transient RNA structures are structurally well-defined and evolutionarily conserved. Since Rfam annotates one structure for each family, there is either no annotation for these transient structures or no such family. Thus, our alignments either significantly update and extend the existing Rfam families or introduce a new RNA family to Rfam. For each of the four RNA families, we compile a multiple-sequence alignment based on experimentally verified transient and dominant (dominant in terms of either the thermodynamic stability and/or attention received so far) RNA secondary structures using a combination of automated search via covariance model and manual curation. The first alignment is the Trp operon leader which regulates the operon transcription in response to tryptophan abundance through alternative structures. The second alignment is the HDV ribozyme which we extend to the 5′ flanking sequence. This flanking sequence is involved in the regulation of the transcript's self-cleavage activity. The third alignment is the 5′ UTR of the maturation protein from Levivirus which contains a transient structure that temporarily postpones the formation of the final inhibitory structure to allow translation of maturation protein. The fourth and last alignment is the SAM riboswitch which regulates the downstream gene expression by assuming alternative structures upon binding of SAM

  1. Probing structural elements in RNA using engineered disulfide cross-links.

    PubMed Central

    Maglott, E J; Glick, G D

    1998-01-01

    Three analogs of unmodified yeast tRNAPhe, each possessing a single disulfide cross-link, have been designed and synthesized. One cross-link is between G1 and C72 in the amino acid acceptor stem, a second cross-link is in the central D region of yeast tRNAPhe between C11 and C25 and the third cross-link bridges U16 and C60 at the D loop/T loop interface. Air oxidation to form the cross-links is quantitative and analysis of the cross-linked products by native and denaturing PAGE, RNase T1 mapping, Pb(II) cleavage, UV cross-linking and thermal denaturation demonstrates that the disulfide bridges do not alter folding of the modified tRNAs relative to the parent sequence. The finding that cross-link formation between thiol-derivatized residues correlates with the position of these groups in the crystal structure of native yeast tRNAPhe and that the modifications do not significantly perturb native structure suggests that this methodology should be applicable to the study of RNA structure, conformational dynamics and folding pathways. PMID:9469841

  2. 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

  3. Dipole rescattering and the nuclear structure function

    SciTech Connect

    Carvalho, F.; Goncalves, V. P.; Navarra, F. S.; Oliveira, E. G.

    2013-03-25

    In the framework of the dipole model, we study the effects of the dipole multiple scatterings in a nuclear target and compute the nuclear structure function. We compare different unitarization schemes and confront our results with the E665 data.

  4. Understanding Microbial Communities: Function, Structure and Dynamics

    DTIC Science & Technology

    2015-02-11

    microbial communities: Function, structure and dynamics’, at the Isaac Newton Institute, University of Cambridge, United Kingdom, from August to...dynamics’, at the Isaac Newton Institute, University of Cambridge, United Kingdom, from August to December 2014. The programme involved over 150...Communities: Function, Structure and Dynamics’, at the Isaac Newton Institute, Cambridge University, UK, from 19th August 2014 – 19th December 2014

  5. Structure functions of electroweak boson and leptons

    SciTech Connect

    Slominski, W; Szwed, J. |

    1996-04-02

    The QCD structure of the electroweak bosons is reviewed and the lepton structure function is defined and calculated. The leading order splitting functions of electron into quarks are extracted, showing an important contribution from {gamma}-Z interference. Leading logarithmic QCD evolution equations are constructed and solved in the asymptotic region where log{sup 2} behavior of the Parton densities is observed. Possible applications with clear manifestation of ``resolved`` photon and weak bosons are discussed. 8 refs., 3 figs.

  6. Molecular tools for investigating ANME community structure and function

    SciTech Connect

    Hallam, Steven J.; Page, Antoine P.; Constan, Lea; Song, Young C.; Norbeck, Angela D.; Brewer, Heather M.; Pasa-Tolic, Ljiljana

    2011-05-20

    Methane production and consumption in anaerobic marine sediments 1 is catalyzed by a series of reversible tetramethanopterin (H4MPT)-linked C1 transfer reactions. Although many of these reactions are conserved between one-carbon compound utilizing microorganisms, two remain diagnostic for archaeal methane metabolism. These include reactions catalyzed by N5-methyltetrahydromethanopterin: coenzyme M methyltransferase and methyl coenzyme M reductase. The latter enzyme is central to C-H bond formation and cleavage underlying methanogenic and reverse methanogenic phenotypes. Here we describe a set of novel tools for the detection and functional analysis of H4MPT-linked C1 transfer reactions mediated by uncultivated anaerobic methane oxidizing archaea (ANME). These tools include polymerase chain reaction primers targeting ANME methyl coenzyme M reductase subunit A subgroups and protein extraction methods from marine sediments compatible with high-resolution mass spectrometry for profiling population structure and functional dynamics. [910, 1,043

  7. 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

  8. Proton structure functions at small x

    DOE PAGES

    Hentschinski, Martin

    2015-11-03

    Proton structure functions are measured in electron-proton collision through inelastic scattering of virtual photons with virtuality Q on protons; x denotes the momentum fraction carried by the struck parton. Proton structure functions are currently described with excellent accuracy in terms of scale dependent parton distribution functions, defined in terms of collinear factorization and DGLAP evolution in Q. With decreasing x however, parton densities increase and are ultimately expected to saturate. In this regime DGLAP evolution will finally break down and non-linear evolution equations w.r.t x are expected to take over. In the first part of the talk we present recentmore » result on an implementation of physical DGLAP evolution. Unlike the conventional description in terms of parton distribution functions, the former describes directly the Q dependence of the measured structure functions. It is therefore physical insensitive to factorization scheme and scale ambiguities. It therefore provides a more stringent test of DGLAP evolution and eases the manifestation of (non-linear) small x effects. It however requires a precise measurement of both structure functions F2 and FL, which will be only possible at future facilities, such as an Electron Ion Collider. In the second part we present a recent analysis of the small x region of the combined HERA data on the structure function F2. We demonstrate that (linear) next-to-leading order BFKL evolution describes the effective Pomeron intercept, determined from the combined HERA data, once a resummation of collinear enhanced terms is included and the renormalization scale is fixed using the BLM optimal scale setting procedure. We also provide a detailed description of the Q and x dependence of the full structure functions F2 in the small x region, as measured at HERA. As a result, predictions for the structure function FL are found to be in agreement with the existing HERA data.« less

  9. Proton structure functions at small x

    SciTech Connect

    Hentschinski, Martin

    2015-11-03

    Proton structure functions are measured in electron-proton collision through inelastic scattering of virtual photons with virtuality Q on protons; x denotes the momentum fraction carried by the struck parton. Proton structure functions are currently described with excellent accuracy in terms of scale dependent parton distribution functions, defined in terms of collinear factorization and DGLAP evolution in Q. With decreasing x however, parton densities increase and are ultimately expected to saturate. In this regime DGLAP evolution will finally break down and non-linear evolution equations w.r.t x are expected to take over. In the first part of the talk we present recent result on an implementation of physical DGLAP evolution. Unlike the conventional description in terms of parton distribution functions, the former describes directly the Q dependence of the measured structure functions. It is therefore physical insensitive to factorization scheme and scale ambiguities. It therefore provides a more stringent test of DGLAP evolution and eases the manifestation of (non-linear) small x effects. It however requires a precise measurement of both structure functions F2 and FL, which will be only possible at future facilities, such as an Electron Ion Collider. In the second part we present a recent analysis of the small x region of the combined HERA data on the structure function F2. We demonstrate that (linear) next-to-leading order BFKL evolution describes the effective Pomeron intercept, determined from the combined HERA data, once a resummation of collinear enhanced terms is included and the renormalization scale is fixed using the BLM optimal scale setting procedure. We also provide a detailed description of the Q and x dependence of the full structure functions F2 in the small x region, as measured at HERA. As a result, predictions for the structure function FL are found to be in agreement with the existing HERA

  10. Next-order structure-function equations

    NASA Astrophysics Data System (ADS)

    Hill, Reginald J.; Boratav, Olus N.

    2001-01-01

    Kolmogorov's equation [Dokl. Akad. Nauk SSSR 32, 16 (1941)] relates the two-point second- and third-order velocity structure functions and the energy dissipation rate. The analogous next higher-order two-point equation relates the third- and fourth-order velocity structure functions and the structure function of the product of pressure-gradient difference and two factors of velocity difference, denoted Tijk. The equation is simplified on the basis of local isotropy. Laboratory and numerical simulation data are used to evaluate and compare terms in the equation, examine the balance of the equation, and evaluate components of Tijk. Atmospheric surface-layer data are used to evaluate Tijk in the inertial range. Combined with the random sweeping hypothesis, the equation relates components of the fourth-order velocity structure function. Data show the resultant error of this application of random sweeping. The next-order equation constrains the relationships that have been suggested among components of the fourth-order velocity structure function. The pressure structure function, pressure-gradient correlation, and mean-squared pressure gradient are related to Tijk. Inertial range formulas are discussed.

  11. [Snake venom metalloproteinases: structure, biosynthesis and function(s)].

    PubMed

    Limam, I; El Ayeb, M; Marrakchi, N

    2010-01-01

    The biochemical and the pharmacological characterization of snake venoms revealed an important structural and functional polymorphism of proteins which they contain. Among them, snake venom metalloproteases (SVMPs) constitute approximatively 20 to 60% of the whole venom proteins. During the last decades, a significant progress was performed against structure studies and the biosynthesis of the SVMPs. Indeed, several metalloproteases were isolated and characterized against their structural and pharmacological properties. In this review, we report the most important properties concerning the classification, the structure of the various domains of the SVMPs as well as their biosynthesis and their activities as potential therapeutic agents.

  12. Phosphatidylethanolamine is the donor of the phosphorylethanolamine linked to the alpha1,4-linked mannose of yeast GPI structures.

    PubMed

    Imhof, I; Canivenc-Gansel, E; Meyer, U; Conzelmann, A

    2000-12-01

    Glycosylphosphatidylinositol (GPI) anchors of all species contain the core structure protein-CO-NH-(CH(2))(2)-PO(4)-Manalpha1-2Manalpha1-6Manalpha1-4GlcNalpha1-6inositol-PO(4)-lipid. In recent studies in yeast it was found that gpi10-1 mutants accumulate M2, an abnormal intermediate having the structure Manalpha1-6[NH(2)-(CH(2))(2)-PO(4)-->]Manalpha1-4GlcNalpha1-6(acyl-->)inositol-PO(4)-lipid. It thus was realized that yeast GPI lipids, as their mammalian counterparts, contain an additional phosphorylethanolamine side chain on the alpha1,4-linked mannose. The biosynthetic origin of this phosphorylethanolamine group was investigated using gpi10-1 Deltaept1 Deltacpt1, a strain which is unable to synthesize phosphatidylethanolamine by transferring phosphorylethanolamine from CDP-ethanolamine onto diacylglycerol, but which still can make phosphatidylethanolamine by decarboxylation of phosphatidylserine. Gpi10-1 Deltaept1 Deltacpt1 triple mutants are unable to incorporate [(3)H]ethanolamine into M2 although metabolic labeling with [(3)H]inositol demonstrates that they make as much M2 as gpi10-1. In contrast, when labeled with [(3)H]serine, the triple mutant incorporates more label into M2 than gpi10-1. This result establishes that the phosphorylethanolamine group on the alpha1,4-linked mannose is derived from phosphatidylethanolamine and not from CDP-ethanolamine.

  13. Feminine Faces of Leadership: Beyond Structural- Functionalism?

    ERIC Educational Resources Information Center

    Fennell, Hope-Arlene

    1999-01-01

    Reviews four philosophical leadership perspectives: structural-functionalism, constructivism, critical theory, and feminism. Explores the leadership phenomenon through the eyes of six women principals. Although the behaviors of all six fall within a structural-functionalist perspective, each is attempting to construct inclusive, positive, and…

  14. Functional structure of the human X chromosome

    SciTech Connect

    1993-12-31

    Chapter 23, describes the functional structure of the human X chromosome. It provides a functional map of the human X chromosome, discussing in depth the inactivation center, always-active regions, and critical region. Finally, it provides a summary of X inactivation. 34 refs., 4 figs.

  15. Brain Structure-function Couplings (FY11)

    DTIC Science & Technology

    2012-01-01

    influence time-evolving models of global brain function and dynamic changes in cognitive performance. Both structural and functional connections change on...Artifact Resistant Measure to Detect Cognitive EEG Activity During Locomotion. Journal of NeuroEngineering and Rehabilitation, submitted. 10...Specifically, identifying the communication between brain regions that occurs during tasks may provide information regarding the cognitive processes involved in

  16. 2004 Structural, Function and Evolutionary Genomics

    SciTech Connect

    Douglas L. Brutlag Nancy Ryan Gray

    2005-03-23

    This Gordon conference will cover the areas of structural, functional and evolutionary genomics. It will take a systematic approach to genomics, examining the evolution of proteins, protein functional sites, protein-protein interactions, regulatory networks, and metabolic networks. Emphasis will be placed on what we can learn from comparative genomics and entire genomes and proteomes.

  17. Bacteriophage HK97 structure: wholesale covalent cross-linking between the major head shell subunits.

    PubMed Central

    Popa, M P; McKelvey, T A; Hempel, J; Hendrix, R W

    1991-01-01

    We describe initial genetic and structural characterizations of HK97, a temperate bacteriophage of Escherichia coli. We isolated 28 amber mutants, characterized them with respect to what phage-related structures they make, and mapped many of them to restriction fragments of genomic DNA. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of HK97 virions revealed nine different protein species plus a substantial amount of material that failed to enter the gel, apparently because it is too large. Five proteins are tail components and are assigned functions as tail fiber subunit, tail length template, and major shaft subunit (two and possibly three species). The four remaining proteins and the material that did not enter the gel are head components. One of these proteins is assigned as the portal subunit, and the remaining three head proteins in the gel and the material that did not enter the gel are components of the head shell. All of the head shell protein species have apparent molecular masses well in excess of 100 kDa; they share amino acid sequence with each other and also with a 42-kDa protein that is found in infected lysates and as the major component of prohead structures that accumulate in infections by one of the amber mutants. We propose that all of the head shell species found in mature heads are covalently cross-linked oligomers derived from the 42-kDa precursor during head shell maturation. Images PMID:1709700

  18. Maintenance of Functionality during Earthquakes: Structural and Non Structural Aspects

    SciTech Connect

    Di Donato, Enrico

    2008-07-08

    The necessity to maintain functionality during and after an earthquake, means that we have to protect not only structures but also functional elements that are inside each building, in particular for strategic constructions, like hospitals, schools. Fortunately, modern solutions to prevent the possibility of failure exist and, very important, are available.

  19. Forging the link between nuclear reactions and nuclear structure.

    PubMed

    Mahzoon, M H; Charity, R J; Dickhoff, W H; Dussan, H; Waldecker, S J

    2014-04-25

    A comprehensive description of all single-particle properties associated with the nucleus Ca40 is generated by employing a nonlocal dispersive optical potential capable of simultaneously reproducing all relevant data above and below the Fermi energy. The introduction of nonlocality in the absorptive potentials yields equivalent elastic differential cross sections as compared to local versions but changes the absorption profile as a function of angular momentum suggesting important consequences for the analysis of nuclear reactions. Below the Fermi energy, nonlocality is essential to allow for an accurate representation of particle number and the nuclear charge density. Spectral properties implied by (e, e'p) and (p, 2p) reactions are correctly incorporated, including the energy distribution of about 10% high-momentum nucleons, as experimentally determined by data from Jefferson Lab. These high-momentum nucleons provide a substantial contribution to the energy of the ground state, indicating a residual attractive contribution from higher-body interactions for Ca40 of about 0.64  MeV/A.

  20. Positive selection in octopus haemocyanin indicates functional links to temperature adaptation.

    PubMed

    Oellermann, Michael; Strugnell, Jan M; Lieb, Bernhard; Mark, Felix C

    2015-07-05

    Octopods have successfully colonised the world's oceans from the tropics to the poles. Yet, successful persistence in these habitats has required adaptations of their advanced physiological apparatus to compensate impaired oxygen supply. Their oxygen transporter haemocyanin plays a major role in cold tolerance and accordingly has undergone functional modifications to sustain oxygen release at sub-zero temperatures. However, it remains unknown how molecular properties evolved to explain the observed functional adaptations. We thus aimed to assess whether natural selection affected molecular and structural properties of haemocyanin that explains temperature adaptation in octopods. Analysis of 239 partial sequences of the haemocyanin functional units (FU) f and g of 28 octopod species of polar, temperate, subtropical and tropical origin revealed natural selection was acting primarily on charge properties of surface residues. Polar octopods contained haemocyanins with higher net surface charge due to decreased glutamic acid content and higher numbers of basic amino acids. Within the analysed partial sequences, positive selection was present at site 2545, positioned between the active copper binding centre and the FU g surface. At this site, methionine was the dominant amino acid in polar octopods and leucine was dominant in tropical octopods. Sites directly involved in oxygen binding or quaternary interactions were highly conserved within the analysed sequence. This study has provided the first insight into molecular and structural mechanisms that have enabled octopods to sustain oxygen supply from polar to tropical conditions. Our findings imply modulation of oxygen binding via charge-charge interaction at the protein surface, which stabilize quaternary interactions among functional units to reduce detrimental effects of high pH on venous oxygen release. Of the observed partial haemocyanin sequence, residue 2545 formed a close link between the FU g surface and the

  1. Morphological and functional correlations in riboflavin UV A corneal collagen cross-linking for keratoconus.

    PubMed

    Mazzotta, Cosimo; Caporossi, Tomaso; Denaro, Rosario; Bovone, Cristina; Sparano, Caterina; Paradiso, Anna; Baiocchi, Stefano; Caporossi, Aldo

    2012-05-01

    To investigate the correlations between corneal structural modifications assessed by in vivo corneal confocal microscopy with visual function [uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA)] and morphological data (corneal topography, pachymetry, elevation analysis) after riboflavin UV A corneal collagen cross-linking (CXL) for the stabilization of progressive keratoconus. Forty-four eyes with progressive keratoconus were enrolled in the Siena Eye Cross Study (prospective nonrandomized phase II open trial). All eyes underwent Riboflavin UV A CXL. Preoperative and postoperative evaluation comprised: UCVA, BSCVA, optical pachymetry (Visante OCT, Zeiss, Germany), corneal topography (CSO, Florence, Italy) and tomography (Orbscan IIz; B&L, Rochester, NY, USA) and in vivo confocal microscopy (Heidelberg Retina Tomograph II; Rostock, Heidelberg Gmbh, Germany). Examinations were performed preoperatively 6 months and one day before treatment and at 1, 3, 6 and 12 months of follow-up. In vivo corneal confocal microscopy showed time-dependent postoperative epithelial and stromal modifications after cross-linking. Epithelial thinning associated with stromal oedema and keratocytes apoptosis explained initial tendency towards slightly reduced VA and more glare one month postoperatively in 70% of eyes. Furthermore, a statistically not significant early worsening of topographic mean K values was observed. Orbscan II analysis significantly underestimated pachymetric values after treatment. Pachymetric underestimation was rectified by high-resolution optical pachymetry provided by the Visante OCT system. After the third post-CXL month, epithelial thickening, disappearance of oedema and new collagen compaction recorded by in vivo corneal confocal microscopy explained the improvements in visual performance during the follow-up. Changes in stromal reflectivity and collagen compaction observed by in vivo confocal microscopy were associated with corneal

  2. Forging the link between nuclear reactions and nuclear structure

    NASA Astrophysics Data System (ADS)

    Dickhoff, W. H.

    2016-06-01

    A review of the recent applications of the dispersive optical model (DOM) is presented. Emphasis is on the nonlocal implementation of the DOM that is capable of describing ground-state properties accurately when data like the nuclear charge density are available. The present understanding of the role of short- and long-range physics in determining proton properties near the Fermi energy for stable closed-shell nuclei has relied mostly on data from the (e, e' p) reaction. Hadronic tools to extract such spectroscopic information have been hampered by the lack of a consistent reaction description that provides unambiguous and undisputed results. The DOM, conceived by Claude Mahaux, provides a unified description of both elastic nucleon scattering and structure information related to single-particle properties below the Fermi energy. We have recently introduced a nonlocal dispersive optical potential for both the real and imaginary part. Nonlocal absorptive potentials yield equivalent elastic differential cross sections for 40Ca as compared to local ones but change the l-dependent absorption profile suggesting important consequences for the analysis of nuclear reactions. Below the Fermi energy, nonlocality is essential for an accurate representation of particle number and the nuclear charge density. Spectral properties implied by (e, e' p) and (p, 2p) reactions are correctly described, including the energy distribution of about 10% high-momentum protons obtained at Jefferson Lab. The nonlocal DOM allows a complete description of experimental data both above (up to 200 MeV) and below the Fermi energy in 40Ca. It is further demonstrated that elastic nucleon-nucleus scattering data constrain the spectral strength in the continuum of orbits that are nominally bound in the independent-particle model. Extension of this analysis to 48Ca allows a prediction of the neutron skin of this nucleus that is larger than most predictions made so far.

  3. Coseismic Slip Variation and the Intimate Link with Fault Structure

    NASA Astrophysics Data System (ADS)

    Milliner, C. W. D.; Sammis, C. G.; Allam, A. A.; Dolan, J. F.; Hollingsworth, J.; Leprince, S.; Ayoub, F.

    2015-12-01

    Co-seismic along-strike slip heterogeneity is widely observed for many surface-rupturing earthquakes as revealed by field and high-resolution geodetic methods. However, this co-seismic slip variability is currently a poorly understood phenomenon. Key unanswered questions include: What are the characteristics and underlying causes of along-strike slip variability? Do the properties of slip variability change from fault-to-fault, along-strike or at different scales? We cross-correlate optical, pre- and post-event air photos using the program COSI-Corr to measure the near-field, surface deformation pattern of the 1992 Mw = 7.3 Landers and 1999 Mw = 7.1 Hector Mine earthquakes in high-resolution. We produce the co-seismic slip profiles of both events from over 1,500 displacement measurements and observe consistent along-strike slip variability. Although the observed slip heterogeneity seems apparently complex and disordered, a spectral analysis reveals that the slip distributions are self-affine fractal and variations of slip are not random. We find a fractal dimension of 1.68 + 0.25 and 1.58 + 0.30 for the Landers and Hector Mine earthquakes, respectively, indicating the slip distribution is rougher for the former. We show deterministically that the wavelength and amplitude of slip fluctuations of both earthquakes can be directly correlated to points of geometrical fault complexities (such as stepovers, kinks or bends) of similar size. We find the correlation of the wavelength of slip fluctuations to the size of geometrical fault complexities at all observable length scales, can explain why the complex surface rupture of the Landers earthquake has a rougher slip distribution than the geometrically simpler surface rupture of the Hector Mine event. Our results address longstanding questions concerning co-seismic slip variability, resulting in a more complete understanding of the relationship between slip distributions and fault structure.

  4. The proteome: structure, function and evolution

    PubMed Central

    Fleming, Keiran; Kelley, Lawrence A; Islam, Suhail A; MacCallum, Robert M; Muller, Arne; Pazos, Florencio; Sternberg, Michael J.E

    2006-01-01

    This paper reports two studies to model the inter-relationships between protein sequence, structure and function. First, an automated pipeline to provide a structural annotation of proteomes in the major genomes is described. The results are stored in a database at Imperial College, London (3D-GENOMICS) that can be accessed at www.sbg.bio.ic.ac.uk. Analysis of the assignments to structural superfamilies provides evolutionary insights. 3D-GENOMICS is being integrated with related proteome annotation data at University College London and the European Bioinformatics Institute in a project known as e-protein (http://www.e-protein.org/). The second topic is motivated by the developments in structural genomics projects in which the structure of a protein is determined prior to knowledge of its function. We have developed a new approach PHUNCTIONER that uses the gene ontology (GO) classification to supervise the extraction of the sequence signal responsible for protein function from a structure-based sequence alignment. Using GO we can obtain profiles for a range of specificities described in the ontology. In the region of low sequence similarity (around 15%), our method is more accurate than assignment from the closest structural homologue. The method is also able to identify the specific residues associated with the function of the protein family. PMID:16524832

  5. Socioeconomic Risk Moderates the Link between Household Chaos and Maternal Executive Function

    PubMed Central

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

    2012-01-01

    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

  6. The effect of cross linking density on the mechanical properties and structure of the epoxy polymers: molecular dynamics simulation.

    PubMed

    Shokuhfar, Ali; Arab, Behrouz

    2013-09-01

    Recently, great attention has been focused on using epoxy polymers in different fields such as aerospace, automotive, biotechnology, and electronics, owing to their superior properties. In this study, the classical molecular dynamics (MD) was used to simulate the cross linking of diglycidyl ether of bisphenol-A (DGEBA) with diethylenetriamine (DETA) curing agent, and to study the behavior of resulted epoxy polymer with different conversion rates. The constant-strain (static) approach was then applied to calculate the mechanical properties (Bulk, shear and Young's moduli, elastic stiffness constants, and Poisson's ratio) of the uncured and cross-linked systems. Estimated material properties were found to be in good agreement with experimental observations. Moreover, the dependency of mechanical properties on the cross linking density was investigated and revealed improvements in the mechanical properties with increasing the cross linking density. The radial distribution function (RDF) was also used to study the evolution of local structures of the simulated systems as a function of cross linking density.

  7. Intra-molecular cross-linking of acidic residues for protein structure studies.

    SciTech Connect

    Kruppa, Gary Hermann; Young, Malin M.; Novak, Petr; Schoeniger, Joseph S.

    2005-03-01

    Intra-molecular cross-linking has been suggested as a method of obtaining distance constraints that would be useful in developing structural models of proteins. Recent work published on intra-molecular cross-linking for protein structural studies has employed commercially available primary amine selective reagents that can cross-link lysine residues to other lysine residues or the amino terminus. Previous work using these cross-linkers has shown that for several proteins of known structure, the number of cross-links that can be obtained experimentally may be small compared to what would be expected from the known structure, due to the relative reactivity, distribution, and solvent accessibility of the lysines in the protein sequence. To overcome these limitations we have investigated the use of cross-linking reagents that can react with other reactive sidechains in proteins. We used 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) to activate the carboxylic acid containing residues, aspartic acid (D), glutamic acid (E), and the carboxy terminus (O), for cross-linking reactions. Once activated, the DEO sidechains can react to form 'zero-length' cross-links with nearby primary amine containing resides, lysines (K) and the amino terminus (X), via the formation of a new amide bond. We also show that the EDC-activated DEO sidechains can be cross-linked to each other using dihydrazides, two hydrazide moieties connected by an alkyl cross-linker ann of variable length. Using these reagents, we have found three new 'zero-length' cross-links in ubiquitin consistent with its known structure (M1-E16, M1-E18, and K63-E64). Using the dihydrazide cross-linkers, we have identified 2 new cross-links (D21-D32 and E24-D32) unambiguously. Using a library of dihydrazide cross-linkers with varying arm length, we have shown that there is a minimum arm length required for the DEO-DEO cross-links of 5.8 angstroms. These results show that additional structural information

  8. Linking morphology to ecosystem structure using satellite for monitoring Wetlands

    NASA Astrophysics Data System (ADS)

    Filipponi, F.; Valentini, E.; Taramelli, A.; Giulio, S.; Persichillo, M.; D'Alpaos, A.

    2013-12-01

    Modern views on the behavior of complex systems, like the low lying coastal areas, allow the interpretation of phenomenological coastal landscape as a steady state that corresponds to a dynamic equilibrium, and to a self-organized exogenic order of the edge of the chaos. Space-borne data, coupled with field spectral measurements and observations, are quantitative tools for the research on feedbacks between the biological influences and physical forming processes steering landscape changes, allowing the identification of critical thresholds beyond which the ecosystem reach a new steady state. This research deals with a multi-temporal change analysis of halophytic vegetation and morphology of two analogous accumulation sites along the northern Adriatic adjoining coast: the 'Bacan island' (Venice Lagoon) and the Spit of Goro Lagoon (Po Delta). These two sites represent delicate ecosystems and are susceptible to different drivers being located close to the lagoon's inlet. The two tests sites support a great biodiversity and supply important resources, so the conservation of their habitats is necessary to maintain the ecosystem services provision. Evidence from previous studies highlights the role of climate, mostly winds and hydrology acting on sediment transport, but only few accounts for the role of vegetation in landform shaping and sediment stabilizing. In this study spatial trends of both vegetation cover/typology and sediment/soil distribution are implemented to obtain detailed classification from EO. By means of sub-pixel processing techniques (Spectral Mixing Analysis), classifications are analyzed in terms of spatial (Power law) and temporal (Empirical Orthogonal Functions) patterns, in order to find the fingerprint of spatial patterns of vegetation, sediments and very shallow waters and their variation over time. The application of a double step analysis from coarse to finer spatial resolution lead first to a biophysical cover map in term of vegetation

  9. Structure and Functions of Linker Histones.

    PubMed

    Lyubitelev, A V; Nikitin, D V; Shaytan, A K; Studitsky, V M; Kirpichnikov, M P

    2016-03-01

    Linker histones such as variants H1, H5, and other similar proteins play an important role in regulation of chromatin structure and dynamics. However, interactions of linker histones with DNA and proteins, as well as specific functions of their different variants, are poorly studied. This is because they acquire tertiary structure only when interacting with a nucleosome, and because of limitations of currently available methods. However, deeper investigation of linker histones and their interactions with other proteins will address a number of important questions - from structure of compacted chromatin to regulation of early embryogenesis. In this review, structures of histone H1 variants and its interaction with chromatin DNA are considered. A possible functional significance of different H1 variants, a role of these proteins in maintaining interphase chromatin structure, and interactions of linker histones with other cellular proteins are also discussed.

  10. Tyrosine-Selective Functionalization for Bio-Orthogonal Cross-Linking of Engineered Protein Hydrogels.

    PubMed

    Madl, Christopher M; Heilshorn, Sarah C

    2017-03-15

    Engineered protein hydrogels have shown promise as artificial extracellular matrix materials for the 3D culture of stem cells due to the ability to decouple hydrogel biochemistry and mechanics. The modular design of these proteins allows for incorporation of various bioactive sequences to regulate cellular behavior. However, the chemistry used to cross-link the proteins into hydrogels can limit what bioactive sequences can be incorporated, in order to prevent nonspecific cross-linking within the bioactive region. Bio-orthogonal cross-linking chemistries may allow for the incorporation of any arbitrary bioactive sequence, but site-selective and scalable incorporation of bio-orthogonal reactive groups such as azides that do not rely on commonly used amine-reactive chemistry is often challenging. In response, we have optimized the reaction of an azide-bearing 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) with engineered elastin-like proteins (ELPs) to selectively azide-functionalize tyrosine residues within the proteins. The PTAD-azide functionalized ELPs cross-link with bicyclononyne (BCN) functionalized ELPs via the strain-promoted azide-alkyne cycloaddition (SPAAC) reaction to form hydrogels. Human mesenchymal stem cells and murine neural progenitor cells encapsulated within these hydrogels remain highly viable and maintain their phenotypes in culture. Tyrosine-specific modification may expand the number of bioactive sequences that can be designed into protein-engineered materials by permitting incorporation of lysine-containing sequences without concern for nonspecific cross-linking.

  11. The use of linked lists in the simulation of controller-structure interaction

    NASA Technical Reports Server (NTRS)

    Quan, Ralph

    1993-01-01

    An algorithm for the computer simulation of large space structures under active control is considered. Linked lists are used in a matrix data structure to implement the trapezoidal rule on the system differential equations. The use of the trapezoidal rule ensures that the numerical stability is equivalent to the system stability, which is essential for this type of simulation. The sparsity of the system matrices is exploited by the linked lists, and the algorithm efficiently steps through the lists in an orderly fashion. Results of simulations on a NASA large space structure experiment are reported.

  12. The use of linked lists in the simulation of controller-structure interaction

    NASA Technical Reports Server (NTRS)

    Quan, R.

    1993-01-01

    An algorithm for the computer simulation of large space structures under active control is considered. Linked lists are used in a matrix data structure to implement the trapezoidal rule on system differential equations. The use of the trapezoidal rule ensures that the numerical stability is equivalent to the system stability, which is essential for this type of simulation. The sparsity of the system matrices is exploited by the linked lists, and the algorithm efficiently steps through the lists in an orderly fashion. Results of simulations on a NASA large space structure experiment are reported.

  13. Family Structure History: Links to Relationship Formation Behaviors in Young Adulthood

    ERIC Educational Resources Information Center

    Ryan, Suzanne; Franzetta, Kerry; Schelar, Erin; Manlove, Jennifer

    2009-01-01

    Using data from three waves of the National Longitudinal Study of Adolescent Health (N = 4,667), we examined the intergenerational link between parental family structure history and relationship formation in young adulthood. We investigated (a) whether parental family structure history is associated with young adults' own relationship formation…

  14. Family Structure History: Links to Relationship Formation Behaviors in Young Adulthood

    ERIC Educational Resources Information Center

    Ryan, Suzanne; Franzetta, Kerry; Schelar, Erin; Manlove, Jennifer

    2009-01-01

    Using data from three waves of the National Longitudinal Study of Adolescent Health (N = 4,667), we examined the intergenerational link between parental family structure history and relationship formation in young adulthood. We investigated (a) whether parental family structure history is associated with young adults' own relationship formation…

  15. Function and structure of inherently disordered proteins.

    PubMed

    Dunker, A Keith; Silman, Israel; Uversky, Vladimir N; Sussman, Joel L

    2008-12-01

    The application of bioinformatics methodologies to proteins inherently lacking 3D structure has brought increased attention to these macromolecules. Here topics concerning these proteins are discussed, including their prediction from amino acid sequence, their enrichment in eukaryotes compared to prokaryotes, their more rapid evolution compared to structured proteins, their organization into specific groups, their structural preferences, their half-lives in cells, their contributions to signaling diversity (via high contents of multiple-partner binding sites, post-translational modifications, and alternative splicing), their distinct functional repertoire compared to that of structured proteins, and their involvement in diseases.

  16. Isoforms, structures, and functions of versatile spectraplakin MACF1

    PubMed Central

    Hu, Lifang; Su, Peihong; Li, Runzhi; Yin, Chong; Zhang, Yan; Shang, Peng; Yang, Tuanmin; Qian, Airong

    2016-01-01

    Spectraplakins are crucially important communicators, linking cytoskeletal components to each other and cellular junctions. Microtubule actin crosslinking factor 1 (MACF1), also known as actin crosslinking family 7 (ACF7), is a member of the spectraplakin family. It is expressed in numerous tissues and cells as one extensively studied spectraplakin. MACF1 has several isoforms with unique structures and well-known function to be able to crosslink F-actin and microtubules. MACF1 is one versatile spectraplakin with various functions in cell processes, embryo development, tissue-specific functions, and human diseases. The importance of MACF1 has become more apparent in recent years. Here, we summarize the current knowledge on the presence and function of MACF1 and provide perspectives on future research of MACF1 based on our studies and others. [BMB Reports 2016; 49(1): 37-44] PMID:26521939

  17. Soil-borne microbial functional structure across different land uses.

    PubMed

    Kuramae, Eiko E; Zhou, Jizhong Z; Kowalchuk, George A; van Veen, Johannes A

    2014-01-01

    Land use change alters the structure and composition of microbial communities. However, the links between environmental factors and microbial functions are not well understood. Here we interrogated the functional structure of soil microbial communities across different land uses. In a multivariate regression tree analysis of soil physicochemical properties and genes detected by functional microarrays, the main factor that explained the different microbial community functional structures was C : N ratio. C : N ratio showed a significant positive correlation with clay and soil pH. Fields with low C : N ratio had an overrepresentation of genes for carbon degradation, carbon fixation, metal reductase, and organic remediation categories, while fields with high C : N ratio had an overrepresentation of genes encoding dissimilatory sulfate reductase, methane oxidation, nitrification, and nitrogen fixation. The most abundant genes related to carbon degradation comprised bacterial and fungal cellulases; bacterial and fungal chitinases; fungal laccases; and bacterial, fungal, and oomycete polygalacturonases. The high number of genes related to organic remediation was probably driven by high phosphate content, while the high number of genes for nitrification was probably explained by high total nitrogen content. The functional gene diversity found in different soils did not group the sites accordingly to land management. Rather, the soil factors, C : N ratio, phosphate, and total N, were the main factors driving the differences in functional genes across the fields examined.

  18. Identifying the Critical Links in Road Transportation Networks: Centrality-based approach utilizing structural properties

    SciTech Connect

    Chinthavali, Supriya

    2016-04-01

    Surface transportation road networks share structural properties similar to other complex networks (e.g., social networks, information networks, biological networks, and so on). This research investigates the structural properties of road networks for any possible correlation with the traffic characteristics such as link flows those determined independently. Additionally, we define a criticality index for the links of the road network that identifies the relative importance in the network. We tested our hypotheses with two sample road networks. Results show that, correlation exists between the link flows and centrality measures of a link of the road (dual graph approach is followed) and the criticality index is found to be effective for one test network to identify the vulnerable nodes.

  19. 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.

  20. 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

  1. Adaptively combined FIR and functional link artificial neural network equalizer for nonlinear communication channel.

    PubMed

    Zhao, Haiquan; Zhang, Jiashu

    2009-04-01

    This paper proposes a novel computational efficient adaptive nonlinear equalizer based on combination of finite impulse response (FIR) filter and functional link artificial neural network (CFFLANN) to compensate linear and nonlinear distortions in nonlinear communication channel. This convex nonlinear combination results in improving the speed while retaining the lower steady-state error. In addition, since the CFFLANN needs not the hidden layers, which exist in conventional neural-network-based equalizers, it exhibits a simpler structure than the traditional neural networks (NNs) and can require less computational burden during the training mode. Moreover, appropriate adaptation algorithm for the proposed equalizer is derived by the modified least mean square (MLMS). Results obtained from the simulations clearly show that the proposed equalizer using the MLMS algorithm can availably eliminate various intensity linear and nonlinear distortions, and be provided with better anti-jamming performance. Furthermore, comparisons of the mean squared error (MSE), the bit error rate (BER), and the effect of eigenvalue ratio (EVR) of input correlation matrix are presented.

  2. 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

  3. 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.

  4. Ecosystem Functions across Trophic Levels Are Linked to Functional and Phylogenetic Diversity

    PubMed Central

    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

  5. The Structure-Function Linkage Database.

    PubMed

    Akiva, Eyal; Brown, Shoshana; Almonacid, Daniel E; Barber, Alan E; Custer, Ashley F; Hicks, Michael A; Huang, Conrad C; Lauck, Florian; Mashiyama, Susan T; Meng, Elaine C; Mischel, David; Morris, John H; Ojha, Sunil; Schnoes, Alexandra M; Stryke, Doug; Yunes, Jeffrey M; Ferrin, Thomas E; Holliday, Gemma L; Babbitt, Patricia C

    2014-01-01

    The Structure-Function Linkage Database (SFLD, http://sfld.rbvi.ucsf.edu/) is a manually curated classification resource describing structure-function relationships for functionally diverse enzyme superfamilies. Members of such superfamilies are diverse in their overall reactions yet share a common ancestor and some conserved active site features associated with conserved functional attributes such as a partial reaction. Thus, despite their different functions, members of these superfamilies 'look alike', making them easy to misannotate. To address this complexity and enable rational transfer of functional features to unknowns only for those members for which we have sufficient functional information, we subdivide superfamily members into subgroups using sequence information, and lastly into families, sets of enzymes known to catalyze the same reaction using the same mechanistic strategy. Browsing and searching options in the SFLD provide access to all of these levels. The SFLD offers manually curated as well as automatically classified superfamily sets, both accompanied by search and download options for all hierarchical levels. Additional information includes multiple sequence alignments, tab-separated files of functional and other attributes, and sequence similarity networks. The latter provide a new and intuitively powerful way to visualize functional trends mapped to the context of sequence similarity.

  6. Protein functional links in Trypanosoma brucei, identified by gene fusion analysis

    PubMed Central

    2011-01-01

    Background Domain or gene fusion analysis is a bioinformatics method for detecting gene fusions in one organism by comparing its genome to that of other organisms. The occurrence of gene fusions suggests that the two original genes that participated in the fusion are functionally linked, i.e. their gene products interact either as part of a multi-subunit protein complex, or in a metabolic pathway. Gene fusion analysis has been used to identify protein functional links in prokaryotes as well as in eukaryotic model organisms, such as yeast and Drosophila. Results In this study we have extended this approach to include a number of recently sequenced protists, four of which are pathogenic, to identify fusion linked proteins in Trypanosoma brucei, the causative agent of African sleeping sickness. We have also examined the evolution of the gene fusion events identified, to determine whether they can be attributed to fusion or fission, by looking at the conservation of the fused genes and of the individual component genes across the major eukaryotic and prokaryotic lineages. We find relatively limited occurrence of gene fusions/fissions within the protist lineages examined. Our results point to two trypanosome-specific gene fissions, which have recently been experimentally confirmed, one fusion involving proteins involved in the same metabolic pathway, as well as two novel putative functional links between fusion-linked protein pairs. Conclusions This is the first study of protein functional links in T. brucei identified by gene fusion analysis. We have used strict thresholds and only discuss results which are highly likely to be genuine and which either have already been or can be experimentally verified. We discuss the possible impact of the identification of these novel putative protein-protein interactions, to the development of new trypanosome therapeutic drugs. PMID:21729286

  7. Probing structures of large protein complexes using zero-length cross-linking.

    PubMed

    Rivera-Santiago, Roland F; Sriswasdi, Sira; Harper, Sandra L; Speicher, David W

    2015-11-01

    Structural mass spectrometry (MS) is a field with growing applicability for addressing complex biophysical questions regarding proteins and protein complexes. One of the major structural MS approaches involves the use of chemical cross-linking coupled with MS analysis (CX-MS) to identify proximal sites within macromolecules. Identified cross-linked sites can be used to probe novel protein-protein interactions or the derived distance constraints can be used to verify and refine molecular models. This review focuses on recent advances of "zero-length" cross-linking. Zero-length cross-linking reagents do not add any atoms to the cross-linked species due to the lack of a spacer arm. This provides a major advantage in the form of providing more precise distance constraints as the cross-linkable groups must be within salt bridge distances in order to react. However, identification of cross-linked peptides using these reagents presents unique challenges. We discuss recent efforts by our group to minimize these challenges by using multiple cycles of LC-MS/MS analysis and software specifically developed and optimized for identification of zero-length cross-linked peptides. Representative data utilizing our current protocol are presented and discussed.

  8. Probing structures of large protein complexes using zero-length cross-linking

    PubMed Central

    Rivera-Santiago, Roland F.; Sriswasdi, Sira; Harper, Sandra L.; Speicher, David W.

    2015-01-01

    Structural mass spectrometry (MS) is a field with growing applicability for addressing complex biophysical questions regarding proteins and protein complexes. One of the major structural MS approaches involves the use of chemical cross-linking coupled with MS analysis (CX-MS) to identify proximal sites within macromolecules. Identified cross-linked sites can be used to probe novel protein–protein interactions or the derived distance constraints can be used to verify and refine molecular models. This review focuses on recent advances of “zero-length” cross-linking. Zero-length cross-linking reagents do not add any atoms to the cross-linked species due to the lack of a spacer arm. This provides a major advantage in the form of providing more precise distance constraints as the cross-linkable groups must be within salt bridge distances in order to react. However, identification of cross-linked peptides using these reagents presents unique challenges. We discuss recent efforts by our group to minimize these challenges by using multiple cycles of LC–MS/MS analysis and software specifically developed and optimized for identification of zero-length cross-linked peptides. Representative data utilizing our current protocol are presented and discussed. PMID:25937394

  9. 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…

  10. 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…

  11. 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…

  12. 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…

  13. Imbalanced Functional Link between Valuation Networks in Abstinent Heroin-Dependent Subjects

    PubMed Central

    Xie, Chunming; Shao, Yongcong; Ma, Lin; Zhai, Tianye; Ye, Enmao; Fu, Liping; Bi, Guohua; Chen, Gang; Cohen, Alex; Li, Wenjun; Chen, Guangyu; Yang, Zheng; Li, Shi-Jiang

    2015-01-01

    Using neuroeconomic approaches, our findings demonstrate that the underlying duality of the β-δ discounting networks that jointly influence valuation is impaired to a pathogenic state in abstinent heroin dependents. The imbalanced functional link between the β-δ networks for valuation may orchestrate the irrational choice in drug addiction. PMID:23207652

  14. Effective Hyperfine-structure Functions of Ammonia

    NASA Astrophysics Data System (ADS)

    Augustovičová, L.; Soldán, P.; Špirko, V.

    2016-06-01

    The hyperfine structure of the rotation-inversion (v 2 = 0+, 0-, 1+, 1-) states of the 14NH3 and 15NH3 ammonia isotopomers is rationalized in terms of effective (ro-inversional) hyperfine-structure (hfs) functions. These are determined by fitting to available experimental data using the Hougen’s effective hyperfine-structure Hamiltonian within the framework of the non-rigid inverter theory. Involving only a moderate number of mass independent fitting parameters, the fitted hfs functions provide a fairly close reproduction of a large majority of available experimental data, thus evidencing adequacy of these functions for reliable prediction. In future experiments, this may help us derive spectroscopic constants of observed inversion and rotation-inversion transitions deperturbed from hyperfine effects. The deperturbed band centers of ammonia come to the forefront of fundamental physics especially as the probes of a variable proton-to-electron mass ratio.

  15. Survey of Quantification and Distance Functions Used for Internet-based Weak-link Sociological Phenomena

    DTIC Science & Technology

    2016-03-01

    Distribution Unlimited Final Report on "Survey of Quantification and Distance Functions Used for Internet -based Weak-link Sociological Phenomena...journals: Number of Papers published in non peer-reviewed journals: Final Report on "Survey of Quantification and Distance Functions Used for Internet ...improve the efficiency of the computation in hoping to speed up the search. Due to the explosive increase of the webpages and the Internet surfers

  16. Atomic structure of a rhinovirus C, a virus species linked to severe childhood asthma.

    PubMed

    Liu, Yue; Hill, Marchel G; Klose, Thomas; Chen, Zhenguo; Watters, Kelly; Bochkov, Yury A; Jiang, Wen; Palmenberg, Ann C; Rossmann, Michael G

    2016-08-09

    Isolates of rhinovirus C (RV-C), a recently identified Enterovirus (EV) species, are the causative agents of severe respiratory infections among children and are linked to childhood asthma exacerbations. The RV-C have been refractory to structure determination because they are difficult to propagate in vitro. Here, we report the cryo-EM atomic structures of the full virion and native empty particle (NEP) of RV-C15a. The virus has 60 "fingers" on the virus outer surface that probably function as dominant immunogens. Because the NEPs also display these fingers, they may have utility as vaccine candidates. A sequence-conserved surface depression adjacent to each finger forms a likely binding site for the sialic acid on its receptor. The RV-C, unlike other EVs, are resistant to capsid-binding antiviral compounds because the hydrophobic pocket in VP1 is filled with multiple bulky residues. These results define potential molecular determinants for designing antiviral therapeutics and vaccines.

  17. Quark-hadron duality in structure functions

    SciTech Connect

    Wally Melnitchouk

    2011-09-01

    We review recent progress in the study of quark-hadron duality in electron–nucleon structure functions. New developments include insights into the local aspects of duality obtained using truncated moments of structure functions, which allow duality-violating higher-twist contributions to be identified in individual resonance regions. Preliminary studies of pion electropro-duction have also showed the first glimpses of duality in semi-inclusive cross sections, which if confirmed would greatly expand the scope of constraining the flavor and spin dependence of parton distributions.

  18. Cross-linking cellulose nanofibrils for potential elastic cryo-structured gels

    NASA Astrophysics Data System (ADS)

    Syverud, Kristin; Kirsebom, Harald; Hajizadeh, Solmaz; Chinga-Carrasco, Gary

    2011-12-01

    Cellulose nanofibrils were produced from P. radiata kraft pulp fibers. The nanofibrillation was facilitated by applying 2,2,6,6-tetramethylpiperidinyl-1-oxyl-mediated oxidation as pretreatment. The oxidized nanofibrils were cross-linked with polyethyleneimine and poly N-isopropylacrylamide- co-allylamine- co-methylenebisacrylamide particles and were frozen to form cryo-structured gels. Samples of the gels were critical-point dried, and the corresponding structures were assessed with scanning electron microscopy. It appears that the aldehyde groups in the oxidized nanofibrils are suitable reaction sites for cross-linking. The cryo-structured materials were spongy, elastic, and thus capable of regaining their shape after a given pressure was released, indicating a successful cross-linking. These novel types of gels are considered potential candidates in biomedical and biotechnological applications.

  19. Energy transmission in a mechanically-linked double-wall structure coupled to an acoustic enclosure

    NASA Astrophysics Data System (ADS)

    Cheng, L.; Li, Y. Y.; Gao, J. X.

    2005-05-01

    The energy transmission in a mechanically linked double-wall structure into an acoustic enclosure is studied in this paper. Based on a fully coupled vibro-acoustic formulation, focus is put on investigating the effect of the air gap and mechanical links between the two panels on the energy transmission and noise insulation properties of such structures. An approximate formula reflecting the gap effect on the lower-order coupled frequencies of the system is proposed. A criterion, based on the ratio between the aerostatic stiffness of the gap cavity and the stiffness of the link, is proposed to predict the dominant transmitting path, with a view to provide guidelines for the design of appropriate control strategies. Numerical results reveal the existence of three distinct zones, within which energy transmission takes place following different mechanisms and transmitting paths. Corresponding effects on noise insulation properties of the double-wall structure are also investigated. .

  20. Energy transmission in a mechanically-linked double-wall structure coupled to an acoustic enclosure.

    PubMed

    Cheng, L; Li, Y Y; Gao, J X

    2005-05-01

    The energy transmission in a mechanically linked double-wall structure into an acoustic enclosure is studied in this paper. Based on a fully coupled vibro-acoustic formulation, focus is put on investigating the effect of the air gap and mechanical links between the two panels on the energy transmission and noise insulation properties of such structures. An approximate formula reflecting the gap effect on the lower-order coupled frequencies of the system is proposed. A criterion, based on the ratio between the aerostatic stiffness of the gap cavity and the stiffness of the link, is proposed to predict the dominant transmitting path, with a view to provide guidelines for the design of appropriate control strategies. Numerical results reveal the existence of three distinct zones, within which energy transmission takes place following different mechanisms and transmitting paths. Corresponding effects on noise insulation properties of the double-wall structure are also investigated.

  1. Structural and Functional Coordination of DNA and Histone Methylation

    PubMed Central

    Cheng, Xiaodong

    2014-01-01

    One of the most fundamental questions in the control of gene expression in mammals is how epigenetic methylation patterns of DNA and histones are established, erased, and recognized. This central process in controlling gene expression includes coordinated covalent modifications of DNA and its associated histones. This article focuses on structural aspects of enzymatic activities of histone (arginine and lysine) methylation and demethylation and functional links between the methylation status of the DNA and histones. An interconnected network of methyltransferases, demethylases, and accessory proteins is responsible for changing or maintaining the modification status of specific regions of chromatin. PMID:25085914

  2. Summary goodness-of-fit statistics for binary generalized linear models with noncanonical link functions.

    PubMed

    Canary, Jana D; Blizzard, Leigh; Barry, Ronald P; Hosmer, David W; Quinn, Stephen J

    2016-05-01

    Generalized linear models (GLM) with a canonical logit link function are the primary modeling technique used to relate a binary outcome to predictor variables. However, noncanonical links can offer more flexibility, producing convenient analytical quantities (e.g., probit GLMs in toxicology) and desired measures of effect (e.g., relative risk from log GLMs). Many summary goodness-of-fit (GOF) statistics exist for logistic GLM. Their properties make the development of GOF statistics relatively straightforward, but it can be more difficult under noncanonical links. Although GOF tests for logistic GLM with continuous covariates (GLMCC) have been applied to GLMCCs with log links, we know of no GOF tests in the literature specifically developed for GLMCCs that can be applied regardless of link function chosen. We generalize the Tsiatis GOF statistic originally developed for logistic GLMCCs, (TG), so that it can be applied under any link function. Further, we show that the algebraically related Hosmer-Lemeshow (HL) and Pigeon-Heyse (J(2) ) statistics can be applied directly. In a simulation study, TG, HL, and J(2) were used to evaluate the fit of probit, log-log, complementary log-log, and log models, all calculated with a common grouping method. The TG statistic consistently maintained Type I error rates, while those of HL and J(2) were often lower than expected if terms with little influence were included. Generally, the statistics had similar power to detect an incorrect model. An exception occurred when a log GLMCC was incorrectly fit to data generated from a logistic GLMCC. In this case, TG had more power than HL or J(2) .

  3. Structural and functional insights into Mimivirus ORFans

    PubMed Central

    Saini, Harpreet Kaur; Fischer, Daniel

    2007-01-01

    Background Mimivirus isolated from A. polyphaga is the largest virus discovered so far. It is unique among all the viruses in having genes related to translation, DNA repair and replication which bear close homology to eukaryotic genes. Nevertheless, only a small fraction of the proteins (33%) encoded in this genome has been assigned a function. Furthermore, a large fraction of the unassigned protein sequences bear no sequence similarity to proteins from other genomes. These sequences are referred to as ORFans. Because of their lack of sequence similarity to other proteins, they can not be assigned putative functions using standard sequence comparison methods. As part of our genome-wide computational efforts aimed at characterizing Mimivirus ORFans, we have applied fold-recognition methods to predict the structure of these ORFans and further functions were derived based on conservation of functionally important residues in sequence-template alignments. Results Using fold recognition, we have identified highly confident computational 3D structural assignments for 21 Mimivirus ORFans. In addition, highly confident functional predictions for 6 of these ORFans were derived by analyzing the conservation of functional motifs between the predicted structures and proteins of known function. This analysis allowed us to classify these 6 previously unannotated ORFans into their specific protein families: carboxylesterase/thioesterase, metal-dependent deacetylase, P-loop kinases, 3-methyladenine DNA glycosylase, BTB domain and eukaryotic translation initiation factor eIF4E. Conclusion Using stringent fold recognition criteria we have assigned three-dimensional structures for 21 of the ORFans encoded in the Mimivirus genome. Further, based on the 3D models and an analysis of the conservation of functionally important residues and motifs, we were able to derive functional attributes for 6 of the ORFans. Our computational identification of important functional sites in these

  4. A Structure-Function Mechanism for Schizophrenia

    PubMed Central

    Vadakkan, Kunjumon I.

    2012-01-01

    The multiple etiologies of schizophrenia prompt us to raise the question: what final common pathway can induce a convincing sense of the reality of the hallucinations in this disease? The observation that artificial stimulation of an intermediate order of neurons of a normal nervous system induces hallucinations indicates that the lateral entry of activity (not resulting from canonical synaptic transmission) at intermediate neuronal orders may provide a mechanism for hallucinations. Meaningful hallucinations can be de-constructed into an organized temporal sequence of internal sensations of associatively learned items that occur in the absence of any external stimuli. We hypothesize that these hallucinations are autonomously generated by the re-activation of pathological non-specific functional LINKs formed between the postsynaptic membranes at certain neuronal orders and are examined as a final common mechanism capable of explaining most of the features of the disease. Reversible and stabilizable hemi-fusion between simultaneously activated adjacent postsynaptic membranes is viewed as one of the normal mechanisms for functional LINK formation and is dependent on lipid membrane composition. Methods of removing the proteins that may traverse the non-specifically hemi-fused membrane segments and attempts to replace the phospholipid side chains to convert the membrane composition to a near-normal state may offer therapeutic opportunities. PMID:23293606

  5. Structure-function relationship of gonadotropins

    SciTech Connect

    Bellet, D.; Bidart, J.M.

    1989-01-01

    In this book, investigators highlight progress recently made in research on the structure-function relationship of gonadotropins. The contributors provide coverage of major breakthroughs such as the cloning of the ovarian receptor for lutropin and choriogonadotropin, the elucidation of the structure of this receptor, and the first crystallographic studies of human chorionic gonadotropin. The book also describes significant advances in the epitope mapping of gonadotropins, the immunochemical and biochemical study of their structure, the examination of regulatory processes involved in subunit association, and the elucidation of the complex mechanisms responsible for regulation and expression of gonadotropin genes.

  6. Using a trait-based approach to link microbial community composition and functioning to soil salinity

    NASA Astrophysics Data System (ADS)

    Rath, Kristin; Fierer, Noah; Rousk, Johannes

    2017-04-01

    Our knowledge of the dynamics structuring microbial communities and the consequences this has for soil functions is rudimentary. In particular, predictions of the response of microbial communities to environmental change and the implications for associated ecosystem processes remain elusive. Understanding how environmental factors structure microbial communities and regulate the functions they perform is key to a mechanistic understanding of how biogeochemical cycles respond to environmental change. Soil salinization is an agricultural problem in many parts of the world. The activity of soil microorganisms is reduced in saline soils compared to non-saline soil. However, soil salinity often co-varies with other factors, making it difficult to assign responses of microbial communities to direct effects of salinity. A trait-based approach allows us to connect the environmental factor salinity with the responses of microbial community composition and functioning. Salinity along a salinity gradient serves as a filter for the community trait distribution of salt tolerance, selecting for higher salt tolerance at more saline sites. This trait-environment relationship can be used to predict responses of microbial communities to environmental change. Our aims were to (i) use salinity along natural salinity gradients as an environmental filter, and (ii) link the resulting filtered trait-distributions of the communities (the trait being salt tolerance) to the community composition. Soil samples were obtained from two replicated salinity gradients along an Australian salt lake, spanning a wide range of soil salinities (0.1 dS m-1 to >50 dS m-1). In one of the two gradients salinity was correlated with pH. Community trait distributions for salt tolerance were assessed by establishing dose-dependences for extracted bacterial communities using growth rate assays. In addition, functional parameters were measured along the salt gradients. Community composition of sites was compared

  7. Linking morphological and functional variability in hand movement and silent reading.

    PubMed

    Sun, Z Y; Pinel, P; Rivière, D; Moreno, A; Dehaene, S; Mangin, J-F

    2016-09-01

    It is generally accepted in neuroscience that anatomy and function go hand in hand. Accordingly, a local morphological variability could lead to a corresponding functional variability. In this study, we tested this hypothesis by linking the variability of the cortical folding pattern of 252 right-handed subjects to the localization or the pattern of functional activations induced by hand motion or silent reading. Three regions are selected: the central sulcus, the precentral sulcus and the superior temporal sulcus (STS). "Essential morphological variability traits" are identified using a method building upon multidimensional scaling. The link between variability in anatomy and function is confirmed by the perfect match between the central sulcus morphological "hand knob" and the corresponding motor activation: as the location of the hand knob moves more or less dorsally along the central sulcus, the motor hand activation moves accordingly. Furthermore, the size of the left hand activation in the right hemisphere is correlated with the knob location in the central sulcus. A new link between functional and morphological variability is discovered relative to the location of a premotor activation induced by silent reading. While this reading activation is located next to the wall of the central sulcus when the hand knob has a ventral positioning, it is pushed into a deep gyrus interrupting the precentral sulcus when the knob is more dorsal. Finally, it is shown that the size of the reading activation along the STS is larger when the posterior branches are less developed.

  8. Linking functional group richness and ecosystem functions of dung beetles: an experimental quantification.

    PubMed

    Milotić, Tanja; Quidé, Stijn; Van Loo, Thomas; Hoffmann, Maurice

    2017-01-01

    Dung beetles form an insect group that fulfils important functions in terrestrial ecosystems throughout the world. These include nutrient cycling through dung removal, soil bioturbation, plant growth, secondary seed dispersal and parasite control. We conducted field experiments at two sites in the northern hemisphere temperate region in which dung removal and secondary seed dispersal were assessed. Dung beetles were classified in three functional groups, depending on their size and dung manipulation method: dwellers, large and small tunnelers. Other soil inhabiting fauna were included as a fourth functional group. Dung removal and seed dispersal by each individual functional group and combinations thereof were estimated in exclusion experiments using different dung types. Dwellers were the most diverse and abundant group, but tunnelers were dominant in terms of biomass. All dung beetle functional groups had a clear preference for fresh dung. The ecosystem services in dung removal and secondary seed dispersal provided by dung beetles were significant and differed between functional groups. Although in absolute numbers more dwellers were found, large tunnelers were disproportionally important for dung burial and seed removal. In the absence of dung beetles, other soil inhabiting fauna, such as earthworms, partly took over the dung decomposing role of dung beetles while most dung was processed when all native functional groups were present. Our results, therefore, emphasize the need to conserve functionally complete dung ecosystems to maintain full ecosystem functioning.

  9. Giving meaning to measure: linking self-reported fatigue and function to performance of everyday activities.

    PubMed

    Mallinson, Trudy; Cella, David; Cashy, John; Holzner, Bernhard

    2006-03-01

    Fatigue, a common symptom of cancer patients, particularly those on active treatment, is generally evaluated using self-report methods, yet it remains unclear how self-reported fatigue scores relate to performance of daily activities. This study examines the relationships among self-reported and performance-based measures of function in patients receiving chemotherapy (CT) to link self-reported fatigue measures to self-report and performance-based measures of function. Self-reported fatigue using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and self-reported physical function using the physical function 10 subscale of the Short Form 36 (SF-36) (PF-10) were measured in 64 patients within 2 weeks of beginning CT (n=64) and after three cycles of CT (n=48). Motor and cognitive functions were captured using five self-reported and seven observed-performance measures at each time point. Significant correlations between self-reported and observed measures ranged from 0.30 to 0.71. Self-reported fatigue correlated (0.30-0.45) with performance-based function. FACIT-F scores in the range of 30 and below and PF-10 scores in the range of 50 and below were related to an increased difficulty performing everyday activities. Observed measures of physical performance correlate moderately with self-reported fatigue and self-reported physical function. These relationships enable one to begin linking fatigue scores directly to a person's ability to perform everyday activities.

  10. Sequence, structure, function, immunity: structural genomics of costimulation

    PubMed Central

    Chattopadhyay, Kausik; Lazar-Molnar, Eszter; Yan, Qingrong; Rubinstein, Rotem; Zhan, Chenyang; Vigdorovich, Vladimir; Ramagopal, Udupi A.; Bonanno, Jeffrey; Nathenson, Stanley G.; Almo, Steven C.

    2010-01-01

    Summary Costimulatory receptors and ligands trigger the signaling pathways that are responsible for modulating the strength, course and duration of an immune response. High-resolution structures have provided invaluable mechanistic insights by defining the chemical and physical features underlying costimulatory receptor/ligand specificity, affinity, oligomeric state, and valency. Furthermore, these structures revealed general architectural features that are important for the integration of these interactions and their associated signaling pathways into overall cellular physiology. Recent technological advances in structural biology promise unprecedented opportunities for furthering our understanding of the structural features and mechanisms that govern costimulation. In this review we highlight unique insights that have been revealed by structures of costimulatory molecules from the immunoglobulin and tumor necrosis factor superfamilies, and describe a vision for future structural and mechanistic analysis of costimulation. This vision includes simple strategies for the selection of candidate molecules for structure determination and highlights the critical role of structure in the design of mutant costimulatory molecules for the generation of in vivo structure-function correlations in a mammalian model system. This integrated ‘atoms-to-animals’ paradigm provides a comprehensive approach for defining atomic and molecular mechanisms. PMID:19426233

  11. Surface Appendages of Archaea: Structure, Function, Genetics and Assembly

    PubMed Central

    Jarrell, Ken F.; Ding, Yan; Nair, Divya B.; Siu, Sarah

    2013-01-01

    Organisms representing diverse subgroupings of the Domain Archaea are known to possess unusual surface structures. These can include ones unique to Archaea such as cannulae and hami as well as archaella (archaeal flagella) and various types of pili that superficially resemble their namesakes in Bacteria, although with significant differences. Major advances have occurred particularly in the study of archaella and pili using model organisms with recently developed advanced genetic tools. There is common use of a type IV pili-model of assembly for several archaeal surface structures including archaella, certain pili and sugar binding structures termed bindosomes. In addition, there are widespread posttranslational modifications of archaellins and pilins with N-linked glycans, with some containing novel sugars. Archaeal surface structures are involved in such diverse functions as swimming, attachment to surfaces, cell to cell contact resulting in genetic transfer, biofilm formation, and possible intercellular communication. Sometimes functions are co-dependent on other surface structures. These structures and the regulation of their assembly are important features that allow various Archaea, including thermoacidophilic, hyperthermophilic, halophilic, and anaerobic ones, to survive and thrive in the extreme environments that are commonly inhabited by members of this domain. PMID:25371333

  12. Structures and Functions of Selective Attention.

    ERIC Educational Resources Information Center

    Posner, Michael I.

    While neuropsychology relates the neural structures damaged in traumatic brain injury with their cognitive functions in daily life, this report reviews evidence that elementary operations of cognition as defined by cognitive studies are the level at which the brain localizes its computations. Orienting of visual attention is used as a model task.…

  13. Body Structure and Function. Teacher Edition.

    ERIC Educational Resources Information Center

    Oklahoma State Dept. of Vocational and Technical Education, Stillwater. Curriculum and Instructional Materials Center.

    This curriculum guide contains the materials required to teach a course in body structure and function. The following topics are covered in the course's 17 instructional units: basic concepts of physical and life sciences; microbiology and bacteriology; the integumentary, skeletal, muscular, digestive, circulatory, respiratory, urinary, central…

  14. Cockroach allergens: function, structure and allergenicity.

    PubMed

    Pomés, A; Wünschmann, S; Hindley, J; Vailes, L D; Chapman, M D

    2007-01-01

    Cockroach allergy is a widespread health problem in the world, associated with the development of asthma. The German and American cockroach species are important producers of a wide variety of allergens. Knowledge of their structure and function contributes to understand their role in allergy and to design tools for diagnosis and immunotherapy.

  15. Structural Functionalism as a Heuristic Device.

    ERIC Educational Resources Information Center

    Chilcott, John H.

    1998-01-01

    Argues that structural functionalism as a method for conducting fieldwork and as a format for the analysis of ethnographic data remains a powerful model, one that is easily understood by professional educators. As a heuristic device, functionalist theory can help in the solution of a problem that is otherwise incapable of theoretical…

  16. Body Structure and Function. Teacher Edition.

    ERIC Educational Resources Information Center

    Oklahoma State Dept. of Vocational and Technical Education, Stillwater. Curriculum and Instructional Materials Center.

    This curriculum guide contains the materials required to teach a course in body structure and function. The following topics are covered in the course's 17 instructional units: basic concepts of physical and life sciences; microbiology and bacteriology; the integumentary, skeletal, muscular, digestive, circulatory, respiratory, urinary, central…

  17. Developing the group mind through functional subgrouping: linking systems-centered training (SCT) and interpersonal neurobiology.

    PubMed

    Gantt, Susan P; Agazarian, Yvonne M

    2010-10-01

    This article introduces the systems-centered concept of the "group mind" by linking systems-centered thinking and interpersonal neurobiology, building on Siegel's definition of mind as the process of regulating the flow of energy and information. Functional subgrouping, the systems-centered group method for resolving conflicts, discriminates and integrates the flow of energy and information within and between group members, subgroups, and the group-as-a-whole, thus potentiating survival, development, and transformation. This article uses the interpersonal neurobiological framework to discuss functional subgrouping as a tool for developing the group mind: considering how functional subgrouping facilitates emotional regulation, creates a secure relational context, and potentiates neural integration.

  18. Molecular Structure of a Functional Drosophila Centromere

    PubMed Central

    Sun, Xiaoping; Wahlstrom, Janice

    2011-01-01

    Summary Centromeres play a critical role in chromosome inheritance but are among the most difficult genomic components to analyze in multicellular eukaryotes. Here, we present a highly detailed molecular structure of a functional centromere in a multicellular organism. The centromere of the Drosophila minichromosome Dp1187 is contained within a 420 kb region of centric heterochromatin. We have used a new approach to characterize the detailed structure of this centromere and found that it is primarily composed of satellites and single, complete transposable elements. In the rest of the Drosophila genome, these satellites and transposable elements are neither unique to the centromeres nor present at all centromeres. We discuss the impact of these results on our understanding of heterochromatin structure and on the determinants of centromere identity and function. PMID:9428523

  19. Assembly and structure of Lys33-linked polyubiquitin reveals distinct conformations

    PubMed Central

    Kristariyanto, Yosua Adi; Choi, Soo-Youn; Rehman, Syed Arif Abdul; Ritorto, Maria Stella; Campbell, David G; Morrice, Nicholas A; Toth, Rachel; Kulathu, Yogesh

    2015-01-01

    Ubiquitylation regulates a multitude of biological processes and this versatility stems from the ability of ubiquitin (Ub) to form topologically different polymers of eight different linkage types. Whereas some linkages have been studied in detail, other linkage types including Lys33-linked polyUb are poorly understood. In the present study, we identify an enzymatic system for the large-scale assembly of Lys33 chains by combining the HECT (homologous to the E6–AP C-terminus) E3 ligase AREL1 (apoptosis-resistant E3 Ub protein ligase 1) with linkage selective deubiquitinases (DUBs). Moreover, this first characterization of the chain selectivity of AREL1 indicates its preference for assembling Lys33- and Lys11-linked Ub chains. Intriguingly, the crystal structure of Lys33-linked diUb reveals that it adopts a compact conformation very similar to that observed for Lys11-linked diUb. In contrast, crystallographic analysis of Lys33-linked triUb reveals a more extended conformation. These two distinct conformational states of Lys33-linked polyUb may be selectively recognized by Ub-binding domains (UBD) and enzymes of the Ub system. Importantly, our work provides a method to assemble Lys33-linked polyUb that will allow further characterization of this atypical chain type. PMID:25723849

  20. Expanding the Range of Protein Function at the Far End of the Order-Structure Continuum*

    PubMed Central

    Burger, Virginia M.; Nolasco, Diego O.; Stultz, Collin M.

    2016-01-01

    The traditional view of the structure-function paradigm is that a protein's function is inextricably linked to a well defined, three-dimensional structure, which is determined by the protein's primary amino acid sequence. However, it is now accepted that a number of proteins do not adopt a unique tertiary structure in solution and that some degree of disorder is required for many proteins to perform their prescribed functions. In this review, we highlight how a number of protein functions are facilitated by intrinsic disorder and introduce a new protein structure taxonomy that is based on quantifiable metrics of a protein's disorder. PMID:26851282

  1. Collagen type IX from human cartilage: a structural profile of intermolecular cross-linking sites.

    PubMed Central

    Diab, M; Wu, J J; Eyre, D R

    1996-01-01

    Type IX collagen, a quantitatively minor collagenous component of cartilage, is known to be associated with and covalently cross-linked to type II collagen fibrils in chick and bovine cartilage. Type IX collagen molecules have also been shown to form covalent cross-links with each other in bovine cartilage. In the present study we demonstrate by structural analysis and location of cross-linking sites that, in human cartilage, type IX collagen is covalently cross-linked to type II collagen and to other molecules of type IX collagen. We also present evidence that, if the proteoglycan form of type IX collagen is present in human cartilage, it can only be a minor component of the matrix, similar to findings with bovine cartilage. PMID:8660302

  2. Structure and function of echinoderm telomerase RNA.

    PubMed

    Podlevsky, Joshua D; Li, Yang; Chen, Julian J-L

    2016-02-01

    Telomerase is a ribonucleoprotein (RNP) enzyme that requires an integral telomerase RNA (TR) subunit, in addition to the catalytic telomerase reverse transcriptase (TERT), for enzymatic function. The secondary structures of TRs from the three major groups of species, ciliates, fungi, and vertebrates, have been studied extensively and demonstrate dramatic diversity. Herein, we report the first comprehensive secondary structure of TR from echinoderms-marine invertebrates closely related to vertebrates-determined by phylogenetic comparative analysis of 16 TR sequences from three separate echinoderm classes. Similar to vertebrate TR, echinoderm TR contains the highly conserved template/pseudoknot and H/ACA domains. However, echinoderm TR lacks the ancestral CR4/5 structural domain found throughout vertebrate and fungal TRs. Instead, echinoderm TR contains a distinct simple helical region, termed eCR4/5, that is functionally equivalent to the CR4/5 domain. The urchin and brittle star eCR4/5 domains bind specifically to their respective TERT proteins and stimulate telomerase activity. Distinct from vertebrate telomerase, the echinoderm TR template/pseudoknot domain with the TERT protein is sufficient to reconstitute significant telomerase activity. This gain-of-function of the echinoderm template/pseudoknot domain for conferring telomerase activity presumably facilitated the rapid structural evolution of the eCR4/5 domain throughout the echinoderm lineage. Additionally, echinoderm TR utilizes the template-adjacent P1.1 helix as a physical template boundary element to prevent nontelomeric DNA synthesis, a mechanism used by ciliate and fungal TRs. Thus, the chimeric and eccentric structural features of echinoderm TR provide unparalleled insights into the rapid evolution of telomerase RNP structure and function. © 2016 Podlevsky et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  3. Structure and function of echinoderm telomerase RNA

    PubMed Central

    Podlevsky, Joshua D.; Li, Yang; Chen, Julian J.-L.

    2016-01-01

    Telomerase is a ribonucleoprotein (RNP) enzyme that requires an integral telomerase RNA (TR) subunit, in addition to the catalytic telomerase reverse transcriptase (TERT), for enzymatic function. The secondary structures of TRs from the three major groups of species, ciliates, fungi, and vertebrates, have been studied extensively and demonstrate dramatic diversity. Herein, we report the first comprehensive secondary structure of TR from echinoderms—marine invertebrates closely related to vertebrates—determined by phylogenetic comparative analysis of 16 TR sequences from three separate echinoderm classes. Similar to vertebrate TR, echinoderm TR contains the highly conserved template/pseudoknot and H/ACA domains. However, echinoderm TR lacks the ancestral CR4/5 structural domain found throughout vertebrate and fungal TRs. Instead, echinoderm TR contains a distinct simple helical region, termed eCR4/5, that is functionally equivalent to the CR4/5 domain. The urchin and brittle star eCR4/5 domains bind specifically to their respective TERT proteins and stimulate telomerase activity. Distinct from vertebrate telomerase, the echinoderm TR template/pseudoknot domain with the TERT protein is sufficient to reconstitute significant telomerase activity. This gain-of-function of the echinoderm template/pseudoknot domain for conferring telomerase activity presumably facilitated the rapid structural evolution of the eCR4/5 domain throughout the echinoderm lineage. Additionally, echinoderm TR utilizes the template-adjacent P1.1 helix as a physical template boundary element to prevent nontelomeric DNA synthesis, a mechanism used by ciliate and fungal TRs. Thus, the chimeric and eccentric structural features of echinoderm TR provide unparalleled insights into the rapid evolution of telomerase RNP structure and function. PMID:26598712

  4. Protein tyrosine phosphatases: structure-function relationships.

    PubMed

    Tabernero, Lydia; Aricescu, A Radu; Jones, E Yvonne; Szedlacsek, Stefan E

    2008-03-01

    Structural analysis of protein tyrosine phosphatases (PTPs) has expanded considerably in the last several years, producing more than 200 structures in this class of enzymes (from 35 different proteins and their complexes with ligands). The small-medium size of the catalytic domain of approximately 280 residues plus a very compact fold makes it amenable to cloning and overexpression in bacterial systems thus facilitating crystallographic analysis. The low molecular weight PTPs being even smaller, approximately 150 residues, are also perfect targets for NMR analysis. The availability of different structures and complexes of PTPs with substrates and inhibitors has provided a wealth of information with profound effects in the way we understand their biological functions. Developments in mammalian expression technology recently led to the first crystal structure of a receptor-like PTP extracellular region. Altogether, the PTP structural work significantly advanced our knowledge regarding the architecture, regulation and substrate specificity of these enzymes. In this review, we compile the most prominent structural traits that characterize PTPs and their complexes with ligands. We discuss how the data can be used to design further functional experiments and as a basis for drug design given that many PTPs are now considered strategic therapeutic targets for human diseases such as diabetes and cancer.

  5. The evolution of protein structures and structural ensembles under functional constraint.

    PubMed

    Siltberg-Liberles, Jessica; Grahnen, Johan A; Liberles, David A

    2011-10-28

    Protein sequence, structure, and function are inherently linked through evolution and population genetics. Our knowledge of protein structure comes from solved structures in the Protein Data Bank (PDB), our knowledge of sequence through sequences found in the NCBI sequence databases (http://www.ncbi.nlm.nih.gov/), and our knowledge of function through a limited set of in-vitro biochemical studies. How these intersect through evolution is described in the first part of the review. In the second part, our understanding of a series of questions is addressed. This includes how sequences evolve within structures, how evolutionary processes enable structural transitions, how the folding process can change through evolution and what the fitness impacts of this might be. Moving beyond static structures, the evolution of protein kinetics (including normal modes) is discussed, as is the evolution of conformational ensembles and structurally disordered proteins. This ties back to a question of the role of neostructuralization and how it relates to selection on sequences for functions. The relationship between metastability, the fitness landscape, sequence divergence, and organismal effective population size is explored. Lastly, a brief discussion of modeling the evolution of sequences of ordered and disordered proteins is entertained.

  6. 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.

  7. Relating methanogen community structure and anaerobic digester function.

    PubMed

    Bocher, B T W; Cherukuri, K; Maki, J S; Johnson, M; Zitomer, D H

    2015-03-01

    Much remains unknown about the relationships between microbial community structure and anaerobic digester function. However, knowledge of links between community structure and function, such as specific methanogenic activity (SMA) and COD removal rate, are valuable to improve anaerobic bioprocesses. In this work, quantitative structure-activity relationships (QSARs) were developed using multiple linear regression (MLR) to predict SMA using methanogen community structure descriptors for 49 cultures. Community descriptors were DGGE demeaned standardized band intensities for amplicons of a methanogen functional gene (mcrA). First, predictive accuracy of MLR QSARs was assessed using cross validation with training (n = 30) and test sets (n = 19) for glucose and propionate SMA data. MLR equations correlating band intensities and SMA demonstrated good predictability for glucose (q(2) = 0.54) and propionate (q(2) = 0.53). Subsequently, data from all 49 cultures were used to develop QSARs to predict SMA values. Higher intensities of two bands were correlated with higher SMA values; high abundance of methanogens associated with these two bands should be encouraged to attain high SMA values. QSARs are helpful tools to identify key microorganisms or to study and improve many bioprocesses. Development of new, more robust QSARs is encouraged for anaerobic digestion or other bioprocesses, including nitrification, nitritation, denitrification, anaerobic ammonium oxidation, and enhanced biological phosphorus removal.

  8. Thermodynamic, Kinetic, and Structural Factors in the Synthesis of Imine-Linked Dynamic Covalent Frameworks.

    SciTech Connect

    Duncan, Nathan C; Hay, Benjamin; Hagaman, Edward {Ed} W; Custelcean, Radu

    2012-01-01

    The formation of imine-linked dynamic covalent frameworks (DCFs) has been systematically studied to determine how different factors such as reaction solvent and composition, reaction kinetics and thermodynamics, and structure of the building units influence the yield, degree of condensation, and homogeneity of the resulting products. Using molecular tetraimine analogs, we first investigated the kinetics and thermodynamics of imine condensation reactions under a variety of conditions, as well as the structures of the basic tetraimine units by X-ray crystallography. These model systems allowed us to identify conditions that favored both high reversibility and fast reaction kinetics for the imine condensation, leading in the end to the development of effective synthetic routes toward imine-linked DCFs with high degrees of cross-linking and homogeneity.

  9. 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

  10. The Integral Membrane Protein Snl1p Is Genetically Linked to Yeast Nuclear Pore Complex Function

    PubMed Central

    Ho, Albert K.; Raczniak, Gregory A.; Ives, Eric B.; Wente, Susan R.

    1998-01-01

    Integral membrane proteins are predicted to play key roles in the biogenesis and function of nuclear pore complexes (NPCs). Revealing how the transport apparatus is assembled will be critical for understanding the mechanism of nucleocytoplasmic transport. We observed that expression of the carboxyl-terminal 200 amino acids of the nucleoporin Nup116p had no effect on wild-type yeast cells, but it rendered the nup116 null strain inviable at all temperatures and coincidentally resulted in the formation of nuclear membrane herniations at 23°C. To identify factors related to NPC function, a genetic screen for high-copy suppressors of this lethal nup116-C phenotype was conducted. One gene (designated SNL1 for suppressor of nup116-C lethal) was identified whose expression was necessary and sufficient for rescuing growth. Snl1p has a predicted molecular mass of 18.3 kDa, a putative transmembrane domain, and limited sequence similarity to Pom152p, the only previously identified yeast NPC-associated integral membrane protein. By both indirect immunofluorescence microscopy and subcellular fractionation studies, Snl1p was localized to both the nuclear envelope and the endoplasmic reticulum. Membrane extraction and topology assays suggested that Snl1p was an integral membrane protein, with its carboxyl-terminal region exposed to the cytosol. With regard to genetic specificity, the nup116-C lethality was also suppressed by high-copy GLE2 and NIC96. Moreover, high-copy SNL1 suppressed the temperature sensitivity of gle2–1 and nic96-G3 mutant cells. The nic96-G3 allele was identified in a synthetic lethal genetic screen with a null allele of the closely related nucleoporin nup100. Gle2p physically associated with Nup116p in vitro, and the interaction required the N-terminal region of Nup116p. Therefore, genetic links between the role of Snl1p and at least three NPC-associated proteins were established. We suggest that Snl1p plays a stabilizing role in NPC structure and function

  11. The histidine phosphatase superfamily: structure and function.

    PubMed

    Rigden, Daniel J

    2008-01-15

    The histidine phosphatase superfamily is a large functionally diverse group of proteins. They share a conserved catalytic core centred on a histidine which becomes phosphorylated during the course of the reaction. Although the superfamily is overwhelmingly composed of phosphatases, the earliest known and arguably best-studied member is dPGM (cofactor-dependent phosphoglycerate mutase). The superfamily contains two branches sharing very limited sequence similarity: the first containing dPGM, fructose-2,6-bisphosphatase, PhoE, SixA, TIGAR [TP53 (tumour protein 53)-induced glycolysis and apoptosis regulator], Sts-1 and many other activities, and the second, smaller, branch composed mainly of acid phosphatases and phytases. Human representatives of both branches are of considerable medical interest, and various parasites contain superfamily members whose inhibition might have therapeutic value. Additionally, several phosphatases, notably the phytases, have current or potential applications in agriculture. The present review aims to draw together what is known about structure and function in the superfamily. With the benefit of an expanding set of histidine phosphatase superfamily structures, a clearer picture of the conserved elements is obtained, along with, conversely, a view of the sometimes surprising variation in substrate-binding and proton donor residues across the superfamily. This analysis should contribute to correcting a history of over- and mis-annotation in the superfamily, but also suggests that structural knowledge, from models or experimental structures, in conjunction with experimental assays, will prove vital for the future description of function in the superfamily.

  12. Improved network community structure improves function prediction

    PubMed Central

    Lee, Juyong; Gross, Steven P.; Lee, Jooyoung

    2013-01-01

    We are overwhelmed by experimental data, and need better ways to understand large interaction datasets. While clustering related nodes in such networks—known as community detection—appears a promising approach, detecting such communities is computationally difficult. Further, how to best use such community information has not been determined. Here, within the context of protein function prediction, we address both issues. First, we apply a novel method that generates improved modularity solutions than the current state of the art. Second, we develop a better method to use this community information to predict proteins' functions. We discuss when and why this community information is important. Our results should be useful for two distinct scientific communities: first, those using various cost functions to detect community structure, where our new optimization approach will improve solutions, and second, those working to extract novel functional information about individual nodes from large interaction datasets. PMID:23852097

  13. Optimizing nondecomposable loss functions in structured prediction.

    PubMed

    Ranjbar, Mani; Lan, Tian; Wang, Yang; Robinovitch, Steven N; Li, Ze-Nian; Mori, Greg

    2013-04-01

    We develop an algorithm for structured prediction with nondecomposable performance measures. The algorithm learns parameters of Markov Random Fields (MRFs) and can be applied to multivariate performance measures. Examples include performance measures such as Fβ score (natural language processing), intersection over union (object category segmentation), Precision/Recall at k (search engines), and ROC area (binary classifiers). We attack this optimization problem by approximating the loss function with a piecewise linear function. The loss augmented inference forms a Quadratic Program (QP), which we solve using LP relaxation. We apply this approach to two tasks: object class-specific segmentation and human action retrieval from videos. We show significant improvement over baseline approaches that either use simple loss functions or simple scoring functions on the PASCAL VOC and H3D Segmentation datasets, and a nursing home action recognition dataset.

  14. Application of Functional Use Predictions to Aid in Structure ...

    EPA Pesticide Factsheets

    Humans are potentially exposed to thousands of anthropogenic chemicals in commerce. Recent work has shown that the bulk of this exposure may occur in near-field indoor environments (e.g., home, school, work, etc.). Advances in suspect screening analyses (SSA) now allow an improved understanding of the chemicals present in these environments. However, due to the nature of suspect screening techniques, investigators are often left with chemical formula predictions, with the possibility of many chemical structures matching to each formula. Here, newly developed quantitative structure-use relationship (QSUR) models are used to identify potential exposure sources for candidate structures. Previously, a suspect screening workflow was introduced and applied to house dust samples collected from the U.S. Department of Housing and Urban Development’s American Healthy Homes Survey (AHHS) [Rager, et al., Env. Int. 88 (2016)]. This workflow utilized the US EPA’s Distributed Structure-Searchable Toxicity (DSSTox) Database to link identified molecular features to molecular formulas, and ultimately chemical structures. Multiple QSUR models were applied to support the evaluation of candidate structures. These QSURs predict the likelihood of a chemical having a functional use commonly associated with consumer products having near-field use. For 3,228 structures identified as possible chemicals in AHHS house dust samples, we were able to obtain the required descriptors to appl

  15. (Neutron scatter studies of chromatin structure related to function)

    SciTech Connect

    Bradbury, E.M.

    1990-01-01

    This study is concerned with the application of neutron scatter techniques to the different structural states of nucleosomes and chromatin with the long term objective of understanding how the enormous lengths of DNA are folded into chromosomes. Micrococcal nuclease digestion kinetics have defined two subnucleosome particles; the chromatosome with 168 bp DNA, the histone octamer and one H1 and the nucleosome core particle with 146 bp DNA and the histone octamer. As will be discussed, the structure of the 146 bp DNA core particle is known in solution at low resolution from neutron scatter studies and in crystals. Based on this structure, the authors have a working model for the chromatosome and the mode of binding of H1. In order to define the structure of the nucleosome and also the different orders of chromatin structures they need to know the paths of DNA that link nucleosomes and the factors associated with chromosome functions that act on those DNA paths. The major region for this situation is the inherent variabilities in nucleosome DNA sequences, in the histone subtypes and their states of chemical modification and in the precise locations of nucleosomes. Such variabilities obscure the underlying principles that govern the packaging of DNA into the different structural states of nucleosomes and chromatin. The only way to elucidate these principles is to study the structures of nucleosomes and oligonucleosomes that are fully defined. They have largely achieved these objectives.

  16. Application of Functional Use Predictions to Aid in Structure ...

    EPA Pesticide Factsheets

    Humans are potentially exposed to thousands of anthropogenic chemicals in commerce. Recent work has shown that the bulk of this exposure may occur in near-field indoor environments (e.g., home, school, work, etc.). Advances in suspect screening analyses (SSA) now allow an improved understanding of the chemicals present in these environments. However, due to the nature of suspect screening techniques, investigators are often left with chemical formula predictions, with the possibility of many chemical structures matching to each formula. Here, newly developed quantitative structure-use relationship (QSUR) models are used to identify potential exposure sources for candidate structures. Previously, a suspect screening workflow was introduced and applied to house dust samples collected from the U.S. Department of Housing and Urban Development’s American Healthy Homes Survey (AHHS) [Rager, et al., Env. Int. 88 (2016)]. This workflow utilized the US EPA’s Distributed Structure-Searchable Toxicity (DSSTox) Database to link identified molecular features to molecular formulas, and ultimately chemical structures. Multiple QSUR models were applied to support the evaluation of candidate structures. These QSURs predict the likelihood of a chemical having a functional use commonly associated with consumer products having near-field use. For 3,228 structures identified as possible chemicals in AHHS house dust samples, we were able to obtain the required descriptors to appl

  17. Are Causal Structure and Intervention Judgments Inextricably Linked? A Developmental Study

    ERIC Educational Resources Information Center

    Frosch, Caren A.; McCormack, Teresa; Lagnado, David A.; Burns, Patrick

    2012-01-01

    The application of the formal framework of causal Bayesian Networks to children's causal learning provides the motivation to examine the link between judgments about the causal structure of a system, and the ability to make inferences about interventions on components of the system. Three experiments examined whether children are able to make…

  18. Are Causal Structure and Intervention Judgments Inextricably Linked? A Developmental Study

    ERIC Educational Resources Information Center

    Frosch, Caren A.; McCormack, Teresa; Lagnado, David A.; Burns, Patrick

    2012-01-01

    The application of the formal framework of causal Bayesian Networks to children's causal learning provides the motivation to examine the link between judgments about the causal structure of a system, and the ability to make inferences about interventions on components of the system. Three experiments examined whether children are able to make…

  19. The Structural Formation and Physical Behaviour of Cross-Linked Epoxy Resins

    DTIC Science & Technology

    1981-04-01

    and by dicyandiamide or by catalytic polymerization are discussed and compared with those obtained by amine or anhydride curing. The highest...system. (e) Dicyandiamide cross-linking Structure formation reactions with dicyandiamide follow a complex pattern. Not only is one concerned with the...investigation4s one must consider cleavage of the dicyandiamide with the production of 2-aminooxazoline derivatives, in accordance with Fig 5. The structural

  20. Mitochondria Are Linked to Calcium Stores in Striated Muscle by Developmentally Regulated Tethering Structures

    PubMed Central

    Boncompagni, Simona; Rossi, Ann E.; Micaroni, Massimo; Beznoussenko, Galina V.; Polishchuk, Roman S.; Dirksen, Robert T.

    2009-01-01

    Bi-directional calcium (Ca2+) signaling between mitochondria and intracellular stores (endoplasmic/sarcoplasmic reticulum) underlies important cellular functions, including oxidative ATP production. In striated muscle, this coupling is achieved by mitochondria being located adjacent to Ca2+ stores (sarcoplasmic reticulum [SR]) and in proximity of release sites (Ca2+ release units [CRUs]). However, limited information is available with regard to the mechanisms of mitochondrial-SR coupling. Using electron microscopy and electron tomography, we identified small bridges, or tethers, that link the outer mitochondrial membrane to the intracellular Ca2+ stores of muscle. This association is sufficiently strong that treatment with hypotonic solution results in stretching of the SR membrane in correspondence of tethers. We also show that the association of mitochondria to the SR is 1) developmentally regulated, 2) involves a progressive shift from a longitudinal clustering at birth to a specific CRU-coupled transversal orientation in adult, and 3) results in a change in the mitochondrial polarization state, as shown by confocal imaging after JC1 staining. Our results suggest that tethers 1) establish and maintain SR–mitochondrial association during postnatal maturation and in adult muscle and 2) likely provide a structural framework for bi-directional signaling between the two organelles in striated muscle. PMID:19037102

  1. Mitochondria are linked to calcium stores in striated muscle by developmentally regulated tethering structures.

    PubMed

    Boncompagni, Simona; Rossi, Ann E; Micaroni, Massimo; Beznoussenko, Galina V; Polishchuk, Roman S; Dirksen, Robert T; Protasi, Feliciano

    2009-02-01

    Bi-directional calcium (Ca(2+)) signaling between mitochondria and intracellular stores (endoplasmic/sarcoplasmic reticulum) underlies important cellular functions, including oxidative ATP production. In striated muscle, this coupling is achieved by mitochondria being located adjacent to Ca(2+) stores (sarcoplasmic reticulum [SR]) and in proximity of release sites (Ca(2+) release units [CRUs]). However, limited information is available with regard to the mechanisms of mitochondrial-SR coupling. Using electron microscopy and electron tomography, we identified small bridges, or tethers, that link the outer mitochondrial membrane to the intracellular Ca(2+) stores of muscle. This association is sufficiently strong that treatment with hypotonic solution results in stretching of the SR membrane in correspondence of tethers. We also show that the association of mitochondria to the SR is 1) developmentally regulated, 2) involves a progressive shift from a longitudinal clustering at birth to a specific CRU-coupled transversal orientation in adult, and 3) results in a change in the mitochondrial polarization state, as shown by confocal imaging after JC1 staining. Our results suggest that tethers 1) establish and maintain SR-mitochondrial association during postnatal maturation and in adult muscle and 2) likely provide a structural framework for bi-directional signaling between the two organelles in striated muscle.

  2. Sorbitol dehydrogenase: structure, function and ligand design.

    PubMed

    El-Kabbani, O; Darmanin, C; Chung, R P-T

    2004-02-01

    Sorbitol dehydrogenase (SDH), a member of the medium-chain dehydrogenase/reductase protein family and the second enzyme of the polyol pathway of glucose metabolism, converts sorbitol to fructose strictly using NAD(+) as coenzyme. SDH is expressed almost ubiquitously in all mammalian tissues. The enzyme has attracted considerable interest due to its implication in the development of diabetic complications and thus its tertiary structure may facilitate the development of drugs for the treatment of diabetes sufferers. Modelling studies suggest that SDH is structurally homologous to mammalian alcohol dehydrogenase with respect to conserved zinc binding motif and a hydrophobic substrate-binding pocket. Recently, the three-dimensional (3-D) structure of a mammalian SDH was solved, and it was found that while the overall 3-D structures of SDH and alcohol dehydrogenase are similar, the zinc coordination in the active sites of the two enzymes is different. The available structural and biochemical information of SDH are currently being utilized in a structure-based approach to develop drugs for the treatment or prevention of the complications of diabetes. This review provides an overview of the recent advances in the structure, function and drug development fields of sorbitol dehydrogenase.

  3. 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

  4. 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

  5. Docosahexaenoic acid and cognitive function: Is the link mediated by the autonomic nervous system?

    PubMed Central

    Gustafson, Kathleen M.; Colombo, John; Carlson, Susan E.

    2013-01-01

    Docosahexaenoic acid is a long-chain polyunsaturated fatty acid that is found in large quantity in the brain and which has repeatedly been observed to be related in positive ways to both cognitive function and cardiovascular health. The mechanisms through which docosahexaenoic acid affects cognition are not well understood, but in this article, we propose a hypothesis that integrates the positive effects of docosahexaenoic acid in the cognitive and cardiovascular realms through the autonomic nervous system. The autonomic nervous system is known to regulate vital functions such as heart rate and respiration, and has also been linked to basic cognitive components related to arousal and attention. We review the literature from this perspective, and delineate the predictions generated by the hypothesis. In addition, we provide new data showing a link between docosahexaenoic acid and fetal heart rate that is consistent with the hypothesis. PMID:18930644

  6. Pollen structure and function in caesalpinioid legumes.

    PubMed

    Banks, Hannah; Rudall, Paula J

    2016-03-01

    A diverse range of pollen morphologies occurs within the large, paraphyletic legume subfamily Caesalpinioideae, especially among early-branching lineages. Previous studies have hypothesized an association between surface ornamentation and pollination syndrome or other aspects of pollen function such as desiccation tolerance and adaptations to accommodate volume changes. We reviewed caesalpinioid pollen morphology using light microscopy, scanning and transmission electron microscopy, in combination with a literature survey of pollination vectors. Pollen structural diversity is greatest in the early-branching tribes Cercideae and Detarieae, whereas Cassieae and Caesalpinieae are relatively low in pollen diversity. Functional structures to counter desiccation include opercula (lids) covering apertures and reduced aperture size. Structures preventing wall rupture during dehydration and rehydration include different forms of colpi (syncolpi, parasyncolpi, pseudocolpi), striate supratectal ornamentation, and columellate or granular wall structures that resist tensile or compressive forces respectively. Specialized aperture structures (Zwischenkörper) may be advantageous for efficient germination of the pollen tube. In Detarieae and Cercideae in particular, there is potential to utilize pollen characters to estimate pollination systems where these are unknown. Supratectal verrucae and gemmae have apparently evolved iteratively in Cercideae and Detarieae. At the species level, there is a potential correlation between striate/verrucate patterns and vertebrate pollination. © 2016 Botanical Society of America.

  7. Fungal lectins: structure, function and potential applications.

    PubMed

    Varrot, Annabelle; Basheer, Soorej M; Imberty, Anne

    2013-10-01

    Lectins are a widespread class of proteins implicated in many essential cellular and molecular recognition processes. They recognize carbohydrates in a non-catalytic, specific and reversible manner. Fungi, which include mushrooms, microfungi and yeasts, have attracted wide interest in recent years. They are indeed a promising source for novel lectins with unique specificity and potential for biomedical and biotechnological applications. Information on fungal lectins, particularly structural insight, is scarce compared to that on their plant and animal counterparts. This review therefore focuses on the structure, function, and exploitable properties of fungal lectins. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Vision-based stress estimation model for steel frame structures with rigid links

    NASA Astrophysics Data System (ADS)

    Park, Hyo Seon; Park, Jun Su; Oh, Byung Kwan

    2017-07-01

    This paper presents a stress estimation model for the safety evaluation of steel frame structures with rigid links using a vision-based monitoring system. In this model, the deformed shape of a structure under external loads is estimated via displacements measured by a motion capture system (MCS), which is a non-contact displacement measurement device. During the estimation of the deformed shape, the effective lengths of the rigid link ranges in the frame structure are identified. The radius of the curvature of the structural member to be monitored is calculated using the estimated deformed shape and is employed to estimate stress. Using MCS in the presented model, the safety of a structure can be assessed gauge-freely. In addition, because the stress is directly extracted from the radius of the curvature obtained from the measured deformed shape, information on the loadings and boundary conditions of the structure are not required. Furthermore, the model, which includes the identification of the effective lengths of the rigid links, can consider the influences of the stiffness of the connection and support on the deformation in the stress estimation. To verify the applicability of the presented model, static loading tests for a steel frame specimen were conducted. By comparing the stress estimated by the model with the measured stress, the validity of the model was confirmed.

  9. 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

  10. A structural perspective of CTD function.

    PubMed

    Meinhart, Anton; Kamenski, Tomislav; Hoeppner, Sabine; Baumli, Sonja; Cramer, Patrick

    2005-06-15

    The C-terminal domain (CTD) of RNA polymerase II (Pol II) integrates nuclear events by binding proteins involved in mRNA biogenesis. CTD-binding proteins recognize a specific CTD phosphorylation pattern, which changes during the transcription cycle, due to the action of CTD-modifying enzymes. Structural and functional studies of CTD-binding and -modifying proteins now reveal some of the mechanisms underlying CTD function. Proteins recognize CTD phosphorylation patterns either directly, by contacting phosphorylated residues, or indirectly, without contact to the phosphate. The catalytic mechanisms of CTD kinases and phosphatases are known, but the basis for CTD specificity of these enzymes remains to be understood.

  11. Soil microbial community structure and functionality during grassland restoration in the Texas High Plains

    USDA-ARS?s Scientific Manuscript database

    Soil microbial communities are an indispensable part of restoration programs due to their significant role in ecosystem functioning and sensitivity to disturbance. We evaluated soil microbial community structure using ester-linked fatty acid (EL-FAME) profiling and metabolic functioning, by measurin...

  12. Proteins with Novel Structure, Function and Dynamics

    NASA Technical Reports Server (NTRS)

    Pohorille, Andrew

    2014-01-01

    Recently, a small enzyme that ligates two RNA fragments with the rate of 10(exp 6) above background was evolved in vitro (Seelig and Szostak, Nature 448:828-831, 2007). This enzyme does not resemble any contemporary protein (Chao et al., Nature Chem. Biol. 9:81-83, 2013). It consists of a dynamic, catalytic loop, a small, rigid core containing two zinc ions coordinated by neighboring amino acids, and two highly flexible tails that might be unimportant for protein function. In contrast to other proteins, this enzyme does not contain ordered secondary structure elements, such as alpha-helix or beta-sheet. The loop is kept together by just two interactions of a charged residue and a histidine with a zinc ion, which they coordinate on the opposite side of the loop. Such structure appears to be very fragile. Surprisingly, computer simulations indicate otherwise. As the coordinating, charged residue is mutated to alanine, another, nearby charged residue takes its place, thus keeping the structure nearly intact. If this residue is also substituted by alanine a salt bridge involving two other, charged residues on the opposite sides of the loop keeps the loop in place. These adjustments are facilitated by high flexibility of the protein. Computational predictions have been confirmed experimentally, as both mutants retain full activity and overall structure. These results challenge our notions about what is required for protein activity and about the relationship between protein dynamics, stability and robustness. We hypothesize that small, highly dynamic proteins could be both active and fault tolerant in ways that many other proteins are not, i.e. they can adjust to retain their structure and activity even if subjected to mutations in structurally critical regions. This opens the doors for designing proteins with novel functions, structures and dynamics that have not been yet considered.

  13. 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.

  14. Effects of partial hydrolysis and subsequent cross-linking on wheat gluten physicochemical properties and structure.

    PubMed

    Wang, Kaiqiang; Luo, Shuizhong; Cai, Jing; Sun, Qiaoqiao; Zhao, Yanyan; Zhong, Xiyang; Jiang, Shaotong; Zheng, Zhi

    2016-04-15

    The rheological behavior and thermal properties of wheat gluten following partial hydrolysis using Alcalase and subsequent microbial transglutaminase (MTGase) cross-linking were investigated. The wheat gluten storage modulus (G') and thermal denaturation temperature (Tg) were significantly increased from 2.26 kPa and 54.43°C to 7.76 kPa and 57.69°C, respectively, by the combined action of partial hydrolysis (DH 0.187%) and cross-linking. The free SH content, surface hydrophobicity, and secondary structure analysis suggested that an appropriate degree of Alcalase-based hydrolysis allowed the compact wheat gluten structure to unfold, increasing the β-sheet content and surface hydrophobicity. This improved its molecular flexibility and exposed additional glutamine sites for MTGase cross-linking. SEM images showed that a compact 3D network formed, while SDS-PAGE profiles revealed that excessive hydrolysis resulted in high-molecular-weight subunits degrading to smaller peptides, unsuitable for cross-linking. It was also demonstrated that the combination of Alcalase-based partial hydrolysis with MTGase cross-linking might be an effective method for modifying wheat gluten rheological behavior and thermal properties.

  15. Dynamic versus Static Hadronic Structure Functions

    SciTech Connect

    Brodsky, Stanley J.; /SLAC

    2009-01-09

    'Static' structure functions are the probabilistic distributions computed from the square of the light-front wavefunctions of the target hadron. In contrast, the 'dynamic' structure functions measured in deep inelastic lepton-hadron scattering include the effects of rescattering associated with the Wilson line. Initial- and final-state rescattering, neglected in the parton model, can have a profound effect in QCD hard-scattering reactions, producing single-spin asymmetries, diffractive deep inelastic scattering, diffractive hard hadronic reactions, the breakdown of the Lam-Tung relation in Drell-Yan reactions, nuclear shadowing, and non-universal nuclear antishadowing|novel leading-twist physics not incorporated in the light-front wavefunctions of the target computed in isolation. I also review how 'direct' higher-twist processes--where a proton is produced in the hard subprocess itself--can explain the anomalous proton-to-pion ratio seen in high centrality heavy ion collisions.

  16. Phosphatidylinositol 4-kinases: Function, structure, and inhibition

    SciTech Connect

    Boura, Evzen Nencka, Radim

    2015-10-01

    The phosphatidylinositol 4-kinases (PI4Ks) synthesize phosphatidylinositol 4-phosphate (PI4P), a key member of the phosphoinositide family. PI4P defines the membranes of Golgi and trans-Golgi network (TGN) and regulates trafficking to and from the Golgi. Humans have two type II PI4Ks (α and β) and two type III enzymes (α and β). Recently, the crystal structures were solved for both type II and type III kinase revealing atomic details of their function. Importantly, the type III PI4Ks are hijacked by +RNA viruses to create so-called membranous web, an extensively phosphorylated and modified membrane system dedicated to their replication. Therefore, selective and potent inhibitors of PI4Ks have been developed as potential antiviral agents. Here we focus on the structure and function of PI4Ks and their potential in human medicine.

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

    PubMed

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

    2012-12-01

    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

  18. 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

  19. Structure function calculations for Ostwald Ripening processes

    NASA Technical Reports Server (NTRS)

    Hassan, Razi A.

    1990-01-01

    A program for computing the structure function for configurations involved in Ostwald Ripening was written. The basic algorithms are derived from a mathematical analysis of a two-dimensional model system developed by Bortz, et. al. (1974). While it is expected that the values form the computer simulations will reflect Ostwald Ripening, at this point the program is still being tested. Some preliminary runs seem to justify the expectations.

  20. DEP domains: structurally similar but functionally different.

    PubMed

    Consonni, Sarah V; Maurice, Madelon M; Bos, Johannes L

    2014-05-01

    The Dishevelled, EGL-10 and pleckstrin (DEP) domain is a globular protein domain that is present in about ten human protein families with well-defined structural features. A picture is emerging that DEP domains mainly function in the spatial and temporal control of diverse signal transduction events by recruiting proteins to the plasma membrane. DEP domains can interact with various partners at the membrane, including phospholipids and membrane receptors, and their binding is subject to regulation.

  1. Structure and function of mammalian cilia.

    PubMed

    Satir, Peter; Christensen, Søren T

    2008-06-01

    In the past half century, beginning with electron microscopic studies of 9 + 2 motile and 9 + 0 primary cilia, novel insights have been obtained regarding the structure and function of mammalian cilia. All cilia can now be viewed as sensory cellular antennae that coordinate a large number of cellular signaling pathways, sometimes coupling the signaling to ciliary motility or alternatively to cell division and differentiation. This view has had unanticipated consequences for our understanding of developmental processes and human disease.

  2. Industrial entrepreneurial network: Structural and functional analysis

    NASA Astrophysics Data System (ADS)

    Medvedeva, M. A.; Davletbaev, R. H.; Berg, D. B.; Nazarova, J. J.; Parusheva, S. S.

    2016-12-01

    Structure and functioning of two model industrial entrepreneurial networks are investigated in the present paper. One of these networks is forming when implementing an integrated project and consists of eight agents, which interact with each other and external environment. The other one is obtained from the municipal economy and is based on the set of the 12 real business entities. Analysis of the networks is carried out on the basis of the matrix of mutual payments aggregated over the certain time period. The matrix is created by the methods of experimental economics. Social Network Analysis (SNA) methods and instruments were used in the present research. The set of basic structural characteristics was investigated: set of quantitative parameters such as density, diameter, clustering coefficient, different kinds of centrality, and etc. They were compared with the random Bernoulli graphs of the corresponding size and density. Discovered variations of random and entrepreneurial networks structure are explained by the peculiarities of agents functioning in production network. Separately, were identified the closed exchange circuits (cyclically closed contours of graph) forming an autopoietic (self-replicating) network pattern. The purpose of the functional analysis was to identify the contribution of the autopoietic network pattern in its gross product. It was found that the magnitude of this contribution is more than 20%. Such value allows using of the complementary currency in order to stimulate economic activity of network agents.

  3. Membrane-bound mucin modular domains: from structure to function.

    PubMed

    Jonckheere, Nicolas; Skrypek, Nicolas; Frénois, Frédéric; Van Seuningen, Isabelle

    2013-06-01

    Mucins belong to a heterogeneous family of large O-glycoproteins composed of a long peptidic chain called apomucin on which are linked hundreds of oligosaccharidic chains. Among mucins, membrane-bound mucins are modular proteins and have a structural organization usually containing Pro/Thr/Ser-rich O-glycosylated domains (PTS), EGF-like and SEA domains. Via these modular domains, the membrane-bound mucins participate in cell signalling and cell interaction with their environment in normal and pathological conditions. Moreover, the recent knowledge of these domains and their biological activities led to the development of new therapeutic approaches involving mucins. In this review, we show 3D structures of EGF and SEA domains. We also describe the functional features of the evolutionary conserved domains of membrane-bound mucins and discuss consequences of splice events.

  4. The Mass Function of Cosmic Structures

    NASA Astrophysics Data System (ADS)

    Audit, E.; Teyssier, R.; Alimi, J.-M.

    We investigate some modifications to the Press and Schechter (1974) (PS) prescription resulting from shear and tidal effects. These modifications rely on more realistic treatments of the collapse process than the standard approach based on the spherical model. First, we show that the mass function resulting from a new approximate Lagrangian dynamic (Audit and Alimi, A&A 1996), contains more objects at high mass, than the classical PS mass function and is well fitted by a PS-like function with a threshold density of deltac ≍ 1.4. However, such a Lagrangian description can underestimate the epoch of structure formation since it defines it as the collapse of the first principal axis. We therefore suggest some analytical prescriptions, for computing the collapse time along the second and third principal axes, and we deduce the corresponding mass functions. The collapse along the third axis is delayed by the shear and the number of objects of high mass then decreases. Finally, we show that the shear also strongly affects the formation of low-mass halos. This dynamical effect implies a modification of the low-mass slope of the mass function and allows the reproduction of the observed luminosity function of field galaxies.

  5. Control design variable linking for optimization of structural/control systems

    NASA Technical Reports Server (NTRS)

    Jin, Ik Min; Schmit, Lucien A.

    1993-01-01

    A method is presented to integrate the design space of structural/control system optimization problems in the case of linear state feedback control. Conventional structural sizing variables and elements of the feedback gain matrix are both treated as strictly independent design variables in optimization by extending design variable linking concepts to the control gains. Several approximation concepts including new control design variable linking schemes are used to formulate the integrated structural/control optimization problem as a sequence of explicit nonlinear mathematical programming problems. Examples which involve a variety of behavior constraints, including constraints on dynamic stability, damped frequencies, control effort, peak transient displacement, acceleration, and control force limits, are effectively solved by using the method presented.

  6. Structural and regulatory functions of keratins

    SciTech Connect

    Magin, Thomas M. . E-mail: t.magin@uni-bonn.de; Vijayaraj, Preethi; Leube, Rudolf E. . E-mail: leube@uni-mainz.de

    2007-06-10

    The diversity of epithelial functions is reflected by the expression of distinct keratin pairs that are responsible to protect epithelial cells against mechanical stress and to act as signaling platforms. The keratin cytoskeleton integrates these functions by forming a supracellular scaffold that connects at desmosomal cell-cell adhesions. Multiple human diseases and murine knockouts in which the integrity of this system is destroyed testify to its importance as a mechanical stabilizer in certain epithelia. Yet, surprisingly little is known about the precise mechanisms responsible for assembly and disease pathology. In addition to these structural aspects of keratin function, experimental evidence accumulating in recent years has led to a much more complex view of the keratin cytoskeleton. Distinct keratins emerge as highly dynamic scaffolds in different settings and contribute to cell size determination, translation control, proliferation, cell type-specific organelle transport, malignant transformation and various stress responses. All of these properties are controlled by highly complex patterns of phosphorylation and molecular associations.

  7. Small catalytic RNA: Structure, function and application

    SciTech Connect

    Monforte, J.A.

    1991-04-01

    We have utilized a combination of photochemical cross-linking techniques and site-directed mutagenesis to obtain secondary and tertiary structure information for the self-cleaving, self-ligating subsequence of RNA from the negative strand of Satellite Tobacco Ringspot Virus. We have found that the helical regions fold about a hinge to promoting four different possible tertiary interactions, creating a molecular of similar shape to a paperclip. A model suggesting that the paperclip'' and hammerhead'' RNAs share a similar three dimensional structure is proposed. We have used a self-cleaving RNA molecule related to a subsequence of plant viroids, a hammerhead,'' to study the length-dependent folding of RNA produced during transcription by RNA polymerase. We have used this method to determine the length of RNA sequestered within elongating E. coli and T7 RNA polymerase complexes. The data show that for E. coli RNA polymerase 12{plus minus}1 nucleotides are sequestered within the ternary complex, which is consistent with the presence of an RNA-DNA hybrid within the transcription bubble, as proposed by others. The result for T7 RNA polymerase differs from E. coli RNA polymerase, with only 10{plus minus}1 nucleotides sequestered within the ternary complex, setting a new upper limit for the minimum RNA-DNA required for a stable elongating complex. Comparisons between E. coli and T7 RNA polymerase are made. The relevance of the results to models or transcription termination, abortive initiation, and initiation to elongation mode transitions are discussed.

  8. Brain Functional and Structural Predictors of Language Performance.

    PubMed

    Skeide, Michael A; Brauer, Jens; Friederici, Angela D

    2016-05-01

    The relation between brain function and behavior on the one hand and the relation between structural changes and behavior on the other as well as the link between the 2 aspects are core issues in cognitive neuroscience. It is an open question, however, whether brain function or brain structure is the better predictor for age-specific cognitive performance. Here, in a comprehensive set of analyses, we investigated the direct relation between hemodynamic activity in 2 pairs of frontal and temporal cortical areas, 2 long-distance white matter fiber tracts connecting each pair and sentence comprehension performance of 4 age groups, including 3 groups of children between 3 and 10 years as well as young adults. We show that the increasing accuracy of processing complex sentences throughout development is correlated with the blood-oxygen-level-dependent activation of 2 core language processing regions in Broca's area and the posterior portion of the superior temporal gyrus. Moreover, both accuracy and speed of processing are correlated with the maturational status of the arcuate fasciculus, that is, the dorsal white matter fiber bundle connecting these 2 regions. The present data provide compelling evidence for the view that brain function and white matter structure together best predict developing cognitive performance. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. 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.

  10. Phylogenetic and functional potential links pH and N2O emissions in pasture soils

    PubMed Central

    Samad, M. d. Sainur; Biswas, Ambarish; Bakken, Lars R.; Clough, Timothy J.; de Klein, Cecile A. M.; Richards, Karl G.; Lanigan, Gary J.; Morales, Sergio E.

    2016-01-01

    Denitrification is mediated by microbial, and physicochemical, processes leading to nitrogen loss via N2O and N2 emissions. Soil pH regulates the reduction of N2O to N2, however, it can also affect microbial community composition and functional potential. Here we simultaneously test the link between pH, community composition, and the N2O emission ratio (N2O/(NO + N2O + N2)) in 13 temperate pasture soils. Physicochemical analysis, gas kinetics, 16S rRNA amplicon sequencing, metagenomic and quantitative PCR (of denitrifier genes: nirS, nirK, nosZI and nosZII) analysis were carried out to characterize each soil. We found strong evidence linking pH to both N2O emission ratio and community changes. Soil pH was negatively associated with N2O emission ratio, while being positively associated with both community diversity and total denitrification gene (nir & nos) abundance. Abundance of nosZII was positively linked to pH, and negatively linked to N2O emissions. Our results confirm that pH imposes a general selective pressure on the entire community and that this results in changes in emission potential. Our data also support the general model that with increased microbial diversity efficiency increases, demonstrated in this study with lowered N2O emission ratio through more efficient conversion of N2O to N2. PMID:27782174

  11. ChIP bias as a function of cross-linking time.

    PubMed

    Baranello, Laura; Kouzine, Fedor; Sanford, Suzanne; Levens, David

    2016-05-01

    The chromatin immunoprecipitation (ChIP) assay is widely used to capture interactions between chromatin and regulatory proteins in vivo. Formaldehyde cross-linking of DNA and proteins is a critical step required to trap their interactions inside the cells before immunoprecipitation and analysis. Yet insufficient attention has been given to variables that might give rise to artifacts in this procedure, such as the duration of cross-linking. We analyzed the dependence of the ChIP signal on the duration of formaldehyde cross-linking time for two proteins: DNA topoisomerase 1 (Top1) that is functionally associated with the double helix in vivo, especially with active chromatin, and green fluorescent protein (GFP) that has no known bona fide interactions with DNA. With short time of formaldehyde fixation, only Top1 immunoprecipation efficiently recovered DNA from active promoters, whereas prolonged fixation augmented non-specific recovery of GFP dramatizing the need to optimize ChIP protocols to minimize the time of cross-linking, especially for abundant nuclear proteins. Thus, ChIP is a powerful approach to study the localization of protein on the genome when care is taken to manage potential artifacts.

  12. Phylogenetic and functional potential links pH and N2O emissions in pasture soils

    NASA Astrophysics Data System (ADS)

    Samad, M. D. Sainur; Biswas, Ambarish; Bakken, Lars R.; Clough, Timothy J.; de Klein, Cecile A. M.; Richards, Karl G.; Lanigan, Gary J.; Morales, Sergio E.

    2016-10-01

    Denitrification is mediated by microbial, and physicochemical, processes leading to nitrogen loss via N2O and N2 emissions. Soil pH regulates the reduction of N2O to N2, however, it can also affect microbial community composition and functional potential. Here we simultaneously test the link between pH, community composition, and the N2O emission ratio (N2O/(NO + N2O + N2)) in 13 temperate pasture soils. Physicochemical analysis, gas kinetics, 16S rRNA amplicon sequencing, metagenomic and quantitative PCR (of denitrifier genes: nirS, nirK, nosZI and nosZII) analysis were carried out to characterize each soil. We found strong evidence linking pH to both N2O emission ratio and community changes. Soil pH was negatively associated with N2O emission ratio, while being positively associated with both community diversity and total denitrification gene (nir & nos) abundance. Abundance of nosZII was positively linked to pH, and negatively linked to N2O emissions. Our results confirm that pH imposes a general selective pressure on the entire community and that this results in changes in emission potential. Our data also support the general model that with increased microbial diversity efficiency increases, demonstrated in this study with lowered N2O emission ratio through more efficient conversion of N2O to N2.

  13. Assessment of safety effects for widening urban roadways in developing crash modification functions using nonlinearizing link functions.

    PubMed

    Park, Juneyoung; Abdel-Aty, Mohamed; Wang, Jung-Han; Lee, Chris

    2015-06-01

    Since a crash modification factor (CMF) represents the overall safety performance of specific treatments in a single fixed value, there is a need to explore the variation of CMFs with different roadway characteristics among treated sites over time. Therefore, in this study, we (1) evaluate the safety performance of a sample of urban four-lane roadway segments that have been widened with one through lane in each direction and (2) determine the relationship between the safety effects and different roadway characteristics over time. Observational before-after analysis with the empirical Bayes (EB) method was assessed in this study to evaluate the safety effects of widening urban four-lane roadways to six-lanes. Moreover, the nonlinearizing link functions were utilized to achieve better performance of crash modification functions (CMFunctions). The CMFunctions were developed using a Bayesian regression method including the estimated nonlinearizing link function to incorporate the changes in safety effects of the treatment over time. Data was collected for urban arterials in Florida, and the Florida-specific full SPFs were developed and used for EB estimation. The results indicated that the conversion of four-lane roadways to six-lane roadways resulted in a crash reduction of 15 percent for total crashes, and 24 percent for injury crashes on urban roadways. The results show that the safety effects vary across the sites with different roadway characteristics. In particular, LOS changes, time changes, and shoulder widths are significant parameters that affect the variation of CMFs. Moreover, it was found that narrowing shoulder and median widths to make space for an extra through lane shows a negative safety impact. It was also found that including the nonlinearizing link functions in developing CMFunctions shows more reliable estimates, if the variation of CMFs with specific parameters has a nonlinear relationship. The findings provide insights into the selection of

  14. Structure and Function of the Reproductive System of Aplysia kurodai

    PubMed Central

    Lee, Chi-Hoon; Kaang, Bong-Kiun; Lee, Young-Don

    2015-01-01

    This study investigated structure and function of the reproductive system in Aplysia kurodai by means of anatomical, histological, and histochemical observation. Reproductive system of this species is consisted of ovotestis, small hermaphroditic duct, ampulla, accessory genital mass and large hermaphroditic duct. The ovotestis is composed of a large number of follicles, and both oocytes and spermatocytes matured in the same follicle. The small hermaphroditic duct is a single tube and contains a swelling, the ampulla, which functions as a storage organ for endogenous sperm and an oviduct. The accessory genital mass is connected to both the small and large hermaphroditic duct, and consisted of three glands: albumen, membrane (winding) and mucus gland. The albumen gland is consisted of granular cells producing basophilic and neutral mucopolysaccharides. The membrane and mucus gland are consisted of granular cells producing acidophilc and sulfated mucopolysaccharides. The large hermaphroditic duct is a single tubular gonoduct linking the accessory genital mass to the common genital aperture but is consisted of two parallel compartments. Internally, these two compartments are incompletely divided by internal septum or fold, which are called as the red hemiduct and white hemiduct, respectively. The red hemiduct functions as an oviduct and the white hemiduct functions as a copulatory duct. The reproductive system of A. kurodai is externally comprised a single tube, i.e., monaulic type. However, internal structure of duct is incompletely divided into oviduct and copulatory duct, i.e., the oodiaulic type. PMID:26973971

  15. 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.

  16. Introduction: the structural basis of virus function.

    PubMed

    Mateu, Mauricio G

    2013-01-01

    Viruses may be regarded as dynamic nucleoprotein assemblies capable of assisted multiplication within cells, and of propagation between cells and organisms. Infectious virus particles (virions) assembled in a host cell are dynamic, generally metastable particles: They are robust enough to protect the viral genome outside the cell, but are also poised to undergo structural changes and execute mechanochemical actions required for infection of other cells. This chapter provides an introduction to the structural and physical biology of viruses by including: (i) an elementary overview on virions and the structural basis of virus function; (ii) a concise summary on basic techniques used in structural or physical virology; (iii) brief structure-based general descriptions of the different stages in the virus cycle, especially those in which virions and/or their components are involved. These contents may facilitate a better understanding of the specialized subjects treated in the rest of the book. This chapter is also intended as a "road map" to help interconnect and integrate in a single picture the different topics described in depth in the 21 monographic chapters in this book.

  17. Regulation of the protein glycosylation pathway in yeast: structural control of N-linked oligosaccharide elongation

    SciTech Connect

    Gopal, P.K.; Ballou, C.E.

    1987-12-01

    The yeast Saccharomyces cerevisiae X2180 strain with the mnn1 mnn2 mnn9 mutations, all of which affect mannoprotein glycosylation, synthesizes N-linked oligosaccharides. Membrane fractions from the mnn1 mnn2 and mnn1 mnn2 mnn9 mutants are equally effective in catalyzing transfer from GDP-(/sup 3/H)mannose to add mannose in both ..cap alpha..1 ..-->.. 2 and ..cap alpha..1 ..-->.. 6 linkages to an oligosaccharide. Neither membrane preparation can utilize the homologous mnn1 mnn2 mnn9 oligosaccharide as an acceptor. Thus, addition of the ..cap alpha..1 ..-->.. 2-linked mannose side chain to the terminal ..cap alpha..1 ..-->.. 6-linked mannose in oligosaccharides of the mnn9 mutant inhibits the elongation reaction and may serve as an important structural control of mannoprotein glycosylation. The mnn9 mutation also increases the transit time for invertase secretion, meaning that this mutation could affect the processing machinery in the Golgi apparatus.

  18. Structural and psychological empowerment and reflective thinking: is there a link?

    PubMed

    Lethbridge, Kristen; Andrusyszyn, Mary-Anne; Iwasiw, Carroll; Laschinger, Heather K S; Fernando, Rajulton

    2011-11-01

    Baccalaureate nursing education prepares students to become registered nurses in evolving health care systems. During their program, students' perceptions of empowerment in the nursing profession begin to form, and they are introduced to the process of reflective thinking. The purpose of this integrative literature review is unique in that three concepts are examined and linked-structural empowerment (as conceptualized by Kanter), psychological empowerment (as described by Spreitzer), and reflective thinking (as characterized by Mezirow)-and a theoretical model for testing is proposed. In examining the conceptual links, it is apparent that all three are required for learning and nursing practice. By preparing students to be empowered, reflective professionals, it is proposed that they will be more effective in their academic and future practice work. The conceptual links and proposed model described in this article provide the foundation for building a body of evidence to support or refute this contention.

  19. Molecular dynamics simulations of viral RNA polymerases link conserved and correlated motions of functional elements to fidelity

    PubMed Central

    Moustafa, Ibrahim M.; Shen, Hujun; Morton, Brandon; Colina, Coray M.; Cameron, Craig E.

    2011-01-01

    The viral RNA-dependent RNA polymerase (RdRp) is essential for multiplication of all RNA viruses. The sequence diversity of an RNA virus population contributes to its ability to infect the host. This diversity emanates from errors made by the RdRp during RNA synthesis. The physical basis for RdRp fidelity is unclear but is linked to conformational changes occurring during the nucleotide-addition cycle. To understand RdRp dynamics that might influence RdRp function, we have analyzed all-atom molecular dynamics (MD) simulations on the nanosecond timescale of four RdRps from the picornavirus family that exhibit 30–74% sequence identity. Principal component analysis showed that the major motions observed during the simulations derived from conserved structural motifs and regions of known function. Dynamics of residues participating in the same biochemical property, for example RNA binding, nucleotide binding or catalysis, were correlated even when spatially distant on the RdRp structure. The conserved and correlated dynamics of functional, structural elements suggest co-evolution of dynamics with structure and function of the RdRp. Crystal structures of all picornavirus RdRps exhibit a template-nascent RNA duplex channel too small to fully accommodate duplex RNA. Simulations revealed opening and closing motions of the RNA and NTP channels, which might be relevant to NTP entry, PPi exit and translocation. A role for nanosecond timescale dynamics in RdRp fidelity is supported by altered dynamics of the high-fidelity G64S derivative of PV RdRp relative to wild-type enzyme. PMID:21575642

  20. Pipelined chebyshev functional link artificial recurrent neural network for nonlinear adaptive filter.

    PubMed

    Zhao, Haiquan; Zhang, Jiashu

    2010-02-01

    A novel nonlinear adaptive filter with pipelined Chebyshev functional link artificial recurrent neural network (PCFLARNN) is presented in this paper, which uses a modification real-time recurrent learning algorithm. The PCFLARNN consists of a number of simple small-scale Chebyshev functional link artificial recurrent neural network (CFLARNN) modules. Compared to the standard recurrent neural network (RNN), those modules of PCFLARNN can simultaneously be performed in a pipelined parallelism fashion, and this would lead to a significant improvement in its total computational efficiency. Furthermore, contrasted with the architecture of a pipelined RNN (PRNN), each module of PCFLARNN is a CFLARNN whose nonlinearity is introduced by enhancing the input pattern with Chebyshev functional expansion, whereas the RNN of each module in PRNN utilizing linear input and first-order recurrent term only fails to utilize the high-order terms of inputs. Therefore, the performance of PCFLARNN can further be improved at the cost of a slightly increased computational complexity. In addition, due to the introduced nonlinear functional expansion of each module in PRNN, the number of input signals can be reduced. Computer simulations have demonstrated that the proposed filter performs better than PRNN and RNN for nonlinear colored signal prediction, nonstationary speech signal prediction, and chaotic time series prediction.

  1. Capitals and capabilities: linking structure and agency to reduce health inequalities.

    PubMed

    Abel, Thomas; Frohlich, Katherine L

    2012-01-01

    While empirical evidence continues to show that low socio-economic position is associated with less likely chances of being in good health, our understanding of why this is so remains less than clear. In this paper we examine the theoretical foundations for a structure-agency approach to the reduction of social inequalities in health. We use Max Weber's work on lifestyles to provide the explanation for the dualism between life chances (structure) and choice-based life conduct (agency). For explaining how the unequal distribution of material and non-material resources leads to the reproduction of unequal life chances and limitations of choice in contemporary societies, we apply Pierre Bourdieu's theory on capital interaction and habitus. We find, however, that Bourdieu's habitus concept is insufficient with regard to the role of agency for structural change and therefore does not readily provide for a theoretically supported move from sociological explanation to public health action. We therefore suggest Amartya Sen's capability approach as a useful link between capital interaction theory and action to reduce social inequalities in health. This link allows for the consideration of structural conditions as well as an active role for individuals as agents in reducing these inequalities. We suggest that people's capabilities to be active for their health be considered as a key concept in public health practice to reduce health inequalities. Examples provided from an ongoing health promotion project in Germany link our theoretical perspective to a practical experience. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. InTERTpreting telomerase structure and function

    PubMed Central

    Wyatt, Haley D. M.; West, Stephen C.; Beattie, Tara L.

    2010-01-01

    The Nobel Prize in Physiology or Medicine was recently awarded to Elizabeth Blackburn, Carol Greider and Jack Szostak for their pioneering studies on chromosome termini (telomeres) and their discovery of telomerase, the enzyme that synthesizes telomeres. Telomerase is a unique cellular reverse transcriptase that contains an integral RNA subunit, the telomerase RNA and a catalytic protein subunit, the telomerase reverse transcriptase (TERT), as well as several species-specific accessory proteins. Telomerase is essential for genome stability and is associated with a broad spectrum of human diseases including various forms of cancer, bone marrow failure and pulmonary fibrosis. A better understanding of telomerase structure and function will shed important insights into how this enzyme contributes to human disease. To this end, a series of high-resolution structural studies have provided critical information on TERT architecture and may ultimately elucidate novel targets for therapeutic intervention. In this review, we discuss the current knowledge of TERT structure and function, revealed through the detailed analysis of TERT from model organisms. To emphasize the physiological importance of telomeres and telomerase, we also present a general discussion of the human diseases associated with telomerase dysfunction. PMID:20460453

  3. Structural and functional brain imaging in schizophrenia.

    PubMed Central

    Cleghorn, J M; Zipursky, R B; List, S J

    1991-01-01

    We present an evaluation of the contribution of structural and functional brain imaging to our understanding of schizophrenia. Methodological influences on the validity of the data generated by these new technologies include problems with measurement and clinical and anatomic heterogeneity. These considerations greatly affect the interpretation of the data generated by these technologies. Work in these fields to date, however, has produced strong evidence which suggests that schizophrenia is a disease which involves abnormalities in the structure and function of many brain areas. Structural brain imaging studies of schizophrenia using computed tomography (CT) and magnetic resonance imaging (MRI) are reviewed and their contribution to current theories of the pathogenesis of schizophrenia are discussed. Positron emission tomography (PET) studies of brain metabolic activity and dopamine receptor binding in schizophrenia are summarized and the critical questions raised by these studies are outlined. Future studies in these fields have the potential to yield critical insights into the pathophysiology of schizophrenia; new directions for studies of schizophrenia using these technologies are identified. PMID:1911736

  4. Phenylalanine hydroxylase: function, structure, and regulation.

    PubMed

    Flydal, Marte I; Martinez, Aurora

    2013-04-01

    Mammalian phenylalanine hydroxylase (PAH) catalyzes the rate-limiting step in the phenylalanine catabolism, consuming about 75% of the phenylalanine input from the diet and protein catabolism under physiological conditions. In humans, mutations in the PAH gene lead to phenylketonuria (PKU), and most mutations are mainly associated with PAH misfolding and instability. The established treatment for PKU is a phenylalanine-restricted diet and, recently, supplementation with preparations of the natural tetrahydrobiopterin cofactor also shows effectiveness for some patients. Since 1997 there has been a significant increase in the understanding of the structure, catalytic mechanism, and regulation of PAH by its substrate and cofactor, in addition to improved correlations between genotype and phenotype in PKU. Importantly, there has also been an increased number of studies on the structure and function of PAH from bacteria and lower eukaryote organisms, revealing an additional anabolic role of the enzyme in the synthesis of melanin-like pigments. In this review, we discuss these recent studies, which contribute to define the evolutionary adaptation of the PAH structure and function leading to sophisticated regulation for effective catabolic processing of phenylalanine in mammalian organisms.

  5. The structure and function of presynaptic endosomes

    SciTech Connect

    Jähne, Sebastian; Rizzoli, Silvio O.; Helm, Martin S.

    2015-07-15

    The function of endosomes and of endosome-like structures in the presynaptic compartment is still controversial. This is in part due to the absence of a consensus on definitions and markers for these compartments. Synaptic endosomes are sometimes seen as stable organelles, permanently present in the synapse. Alternatively, they are seen as short-lived intermediates in synaptic vesicle recycling, arising from the endocytosis of large vesicles from the plasma membrane, or from homotypic fusion of small vesicles. In addition, the potential function of the endosome is largely unknown in the synapse. Some groups have proposed that the endosome is involved in the sorting of synaptic vesicle proteins, albeit others have produced data that deny this possibility. In this review, we present the existing evidence for synaptic endosomes, we discuss their potential functions, and we highlight frequent technical pitfalls in the analysis of this elusive compartment. We also sketch a roadmap to definitely determine the role of synaptic endosomes for the synaptic vesicle cycle. Finally, we propose a common definition of synaptic endosome-like structures.

  6. Catchment Classification: Connecting Climate, Structure and Function

    NASA Astrophysics Data System (ADS)

    Sawicz, K. A.; Wagener, T.; Sivapalan, M.; Troch, P. A.; Carrillo, G. A.

    2010-12-01

    Hydrology does not yet possess a generally accepted catchment classification framework. Such a classification framework needs to: [1] give names to things, i.e. the main classification step, [2] permit transfer of information, i.e. regionalization of information, [3] permit development of generalizations, i.e. to develop new theory, and [4] provide a first order environmental change impact assessment, i.e., the hydrologic implications of climate, land use and land cover change. One strategy is to create a catchment classification framework based on the notion of catchment functions (partitioning, storage, and release). Results of an empirical study presented here connects climate and structure to catchment function (in the form of select hydrologic signatures), based on analyzing over 300 US catchments. Initial results indicate a wide assortment of signature relationships with properties of climate, geology, and vegetation. The uncertainty in the different regionalized signatures varies widely, and therefore there is variability in the robustness of classifying ungauged basins. This research provides insight into the controls of hydrologic behavior of a catchment, and enables a classification framework applicable to gauged and ungauged across the study domain. This study sheds light on what we can expect to achieve in mapping climate, structure and function in a top-down manner. Results of this study complement work done using a bottom-up physically-based modeling framework to generalize this approach (Carrillo et al., this session).

  7. Functional link between ribosome formation and biogenesis of iron-sulfur proteins.

    PubMed

    Yarunin, Alexander; Panse, Vikram Govind; Petfalski, Elisabeth; Dez, Christophe; Tollervey, David; Hurt, Eduard C

    2005-02-09

    In genetic screens for ribosomal export mutants, we identified CFD1, NBP35 and NAR1 as factors involved in ribosome biogenesis. Notably, these components were recently reported to function in extramitochondrial iron-sulfur (Fe-S) cluster biosynthesis. In particular, Nar1 was implicated to generate the Fe-S clusters within Rli1, a potential substrate protein of unknown function. We tested whether the Fe-S protein Rli1 functions in ribosome formation. We report that rli1 mutants are impaired in pre-rRNA processing and defective in the export of both ribosomal subunits. In addition, Rli1p is associated with both pre-40S particles and mature 40S subunits, and with the eIF3 translation initiation factor complex. Our data reveal an unexpected link between ribosome biogenesis and the biosynthetic pathway of cytoplasmic Fe-S proteins.

  8. Functional link between ribosome formation and biogenesis of iron–sulfur proteins

    PubMed Central

    Yarunin, Alexander; Panse, Vikram Govind; Petfalski, Elisabeth; Dez, Christophe; Tollervey, David; Hurt, Ed

    2005-01-01

    In genetic screens for ribosomal export mutants, we identified CFD1, NBP35 and NAR1 as factors involved in ribosome biogenesis. Notably, these components were recently reported to function in extramitochondrial iron–sulfur (Fe–S) cluster biosynthesis. In particular, Nar1 was implicated to generate the Fe–S clusters within Rli1, a potential substrate protein of unknown function. We tested whether the Fe–S protein Rli1 functions in ribosome formation. We report that rli1 mutants are impaired in pre-rRNA processing and defective in the export of both ribosomal subunits. In addition, Rli1p is associated with both pre-40S particles and mature 40S subunits, and with the eIF3 translation initiation factor complex. Our data reveal an unexpected link between ribosome biogenesis and the biosynthetic pathway of cytoplasmic Fe–S proteins. PMID:15660135

  9. 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.

  10. Mining high-throughput experimental data to link gene and function

    PubMed Central

    Blaby-Haas, Crysten E.; de Crécy-Lagard, Valérie

    2011-01-01

    Nearly 2200 genomes encoding some 6 million proteins have now been sequenced. Around 40% of these proteins are of unknown function even when function is loosely and minimally defined as “belonging to a superfamily”. In addition to in silico methods, the swelling stream of high-throughput experimental data can give valuable clues for linking these “unknowns” with precise biological roles. The goal is to develop integrative data-mining platforms that allow the scientific community at large to access and utilize this