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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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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

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

    PubMed Central

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

    2016-01-01

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

  7. 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

  8. 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-

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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

  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. 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.

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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,…

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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 area ratio Al : As). Wemore » 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

  2. 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.

  3. 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…

  4. 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.

  5. 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.

  6. 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.

  7. Multi-functional composite structures

    SciTech Connect

    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.

  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.

    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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. Discovering and Analyzing Network Function and Structure

    DTIC Science & Technology

    2015-07-08

    detecting spam web pages. It has also supported the development of faster algorithms for determining which edges are most critical to the structure of a...link structure to estimate the likelihood that other webpages are spam. This is possible because legitimate webpages are unlikely to link to spam web ...pages, so a link to a spam web page is evidence of spam. Similarly, a link from a legitimate webpage is evidence of legitimacy. Network interpolation

  7. 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.

  8. 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

  9. 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.

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

    PubMed

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

    2015-09-01

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

  11. 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.

  12. 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.

  13. Internal structure of nanoparticle dimers linked by DNA.

    PubMed

    Chi, Cheng; Vargas-Lara, Fernando; Tkachenko, Alexei V; Starr, Francis W; Gang, Oleg

    2012-08-28

    We construct nanoparticle dimers linked by DNA. These dimers are basic units in a possible multiscale, hierarchical assembly and serve as a model system to understand DNA-mediated interactions, especially in the nontrivial regime when the nanoparticle and DNA are comparable in their sizes. We examine the structure of nanoparticle dimers in detail by a combination of scattering experiments and molecular simulations. We find that, for a given DNA length, the interparticle separation within the dimer is controlled primarily by the number of linking DNA. We summarize our findings in a simple model that captures the interplay of the number of DNA bridges, their length, the particle's curvature, and the excluded volume effects. We demonstrate the applicability of the model to our results, without any free parameters. As a consequence, the increase of dimer separation with increasing temperature can be understood as a result of changing the number of connecting DNA.

  14. 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.

  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. 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.

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

    PubMed

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

    2015-07-01

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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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…

  5. 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

  6. [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.

  7. 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

  8. 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

  9. 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.

  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. 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.

  12. 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

  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. 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.

  15. 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.

  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. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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…

  16. 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

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

    PubMed

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

    2015-09-01

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

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

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

    PubMed Central

    Bertossa, Rinaldo C.

    2011-01-01

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

  8. 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.

  9. 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.

  10. 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

  11. 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…

  12. 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…

  13. 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

  14. 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 ...

  15. 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

  16. 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.

  17. 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…

  18. Functional keratin as structural platforms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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.

  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. 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

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

    DTIC Science & Technology

    2015-10-01

    the day-to-day operations and overseen the neuropsychological assessment procedures and database creation during the study start-up. She has worked...after the PI has explained the study), scheduling the cognitive and MRI visits, performing neuropsychological testing and confirming that all scheduled

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. Link prediction based on hyperbolic mapping with community structure for complex networks

    NASA Astrophysics Data System (ADS)

    Wang, Zuxi; Wu, Yao; Li, Qingguang; Jin, Fengdong; Xiong, Wei

    2016-05-01

    Link prediction is becoming a concerned topic in the complex network field in recent years. However, the existing link prediction methods are unsatisfactory for processing topological information and have high time complexity. This paper presents a novel method of Link Prediction with Community Structure (LPCS) based on hyperbolic mapping. Different from the existing link prediction methods, to utilize global structure information of the network, LPCS deals with the network from an overall perspective. LPCS takes full advantage of the community structure and its hierarchical organization to map networks into hyperbolic space, and obtains the hyperbolic coordinates which depict the global structure information of the network, then uses hyperbolic distance to describe the similarity between the nodes, finally predicts missing links according to the degree of the similarity between unconnected node pairs. The combination of the hyperbolic geometry framework and the community structure makes LPCS perform well in predicting missing links, and the time complexity of LPCS is linear, which makes LPCS can be applied to handle large scale networks in acceptable time. LPCS outperforms many state-of-the-art link prediction methods in the networks obeying power-law degree distribution.

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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

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

    PubMed

    Madl, Christopher M; Heilshorn, Sarah C

    2017-02-02

    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. 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

  12. 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

  13. 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.

  14. 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

  15. 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…

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

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

    PubMed

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

    2015-01-01

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

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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…

  8. 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

  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. 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

  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. 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

  15. 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.

  16. 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) .

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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. .

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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…

  2. 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…

  3. 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.…

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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…

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. (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.

  3. 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

  4. Soil microbial community structure and functionality during grassland restoration in the Texas High Plains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Links between adolescent sympathetic and parasympathetic nervous system functioning and interpersonal behavior over time.

    PubMed

    Diamond, Lisa M; Cribbet, Matthew R

    2013-06-01

    Extensive research has investigated links between individual differences in youths' autonomic nervous system (ANS) functioning and psychological outcomes related to emotion regulation, yet little of this research has examined developmental change. The study tested whether individual differences in youths' tonic and stress-induced ANS functioning, assessed at age 14, and changes in ANS functioning from age 14 to 16 predicted corresponding changes in youths' behavioral warmth, as displayed during videotaped mother-child conflict interactions conducted at age 14 and 16. Increased behavioral warmth was predicted by increased baseline respiratory sinus arrhythmia (RSA), increased SCL stress reactivity, decreased RSA stress reactivity (i.e., greater vagal suppression), and decreased baseline SCL. There was also an interaction between RSA stress reactivity at age 14 and changes in maternal warmth from age 14 to 16, such that increased maternal warmth was only associated with increased adolescent warmth for adolescents with lower RSA stress reactivity at age 14.

  2. 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 rich source of experimental knowledge. To this end, we review recent advances in generating whole-genome experimental datasets, where this data can be accessed, and how it can be used to drive prediction of gene function. PMID:21310501

  3. 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.

  4. 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.

  5. 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.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-08-01

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

  8. Adversity in childhood linked to elevated striatal dopamine function in adulthood.

    PubMed

    Egerton, Alice; Valmaggia, Lucia R; Howes, Oliver D; Day, Fern; Chaddock, Christopher A; Allen, Paul; Winton-Brown, Toby T; Bloomfield, Michael A P; Bhattacharyya, Sagnik; Chilcott, Jack; Lappin, Julia M; Murray, Robin M; McGuire, Philip

    2016-10-01

    Childhood adversity increases the risk of psychosis in adulthood. Theoretical and animal models suggest that this effect may be mediated by increased striatal dopamine neurotransmission. The primary objective of this study was to examine the relationship between adversity in childhood and striatal dopamine function in early adulthood. Secondary objectives were to compare exposure to childhood adversity and striatal dopamine function in young people at ultra high risk (UHR) of psychosis and healthy volunteers. Sixty-seven young adults, comprising 47 individuals at UHR for psychosis and 20 healthy volunteers were recruited from the same geographic area and were matched for age, gender and substance use. Presynaptic dopamine function in the associative striatum was assessed using 18F-DOPA positron emission tomography. Childhood adversity was assessed using the Childhood Experience of Care and Abuse questionnaire. Within the sample as a whole, both severe physical or sexual abuse (T63=2.92; P=0.005), and unstable family arrangements (T57=2.80; P=0.007) in childhood were associated with elevated dopamine function in the associative striatum in adulthood. Comparison of the UHR and volunteer subgroups revealed similar incidence of childhood adverse experiences, and there was no significant group difference in dopamine function. This study provides evidence that childhood adversity is linked to elevated striatal dopamine function in adulthood.

  9. Linked-cluster expansion for the Green's function of the infinite-U Hubbard model.

    PubMed

    Khatami, Ehsan; Perepelitsky, Edward; Rigol, Marcos; Shastry, B Sriram

    2014-06-01

    We implement a highly efficient strong-coupling expansion for the Green's function of the Hubbard model. In the limit of extreme correlations, where the onsite interaction is infinite, the evaluation of diagrams simplifies dramatically enabling us to carry out the expansion to the eighth order in powers of the hopping amplitude. We compute the finite-temperature Green's function analytically in the momentum and Matsubara frequency space as a function of the electron density. Employing Padé approximations, we study the equation of state, Kelvin thermopower, momentum distribution function, quasiparticle fraction, and quasiparticle lifetime of the system at temperatures lower than, or of the order of, the hopping amplitude. We also discuss several different approaches for obtaining the spectral functions through analytic continuation of the imaginary frequency Green's function, and show results for the system near half filling. We benchmark our results for the equation of state against those obtained from a numerical linked-cluster expansion carried out to the eleventh order.

  10. Linking Resting-State Networks in the Prefrontal Cortex to Executive Function: A Functional Near Infrared Spectroscopy Study

    PubMed Central

    Zhao, Jia; Liu, Jiangang; Jiang, Xin; Zhou, Guifei; Chen, Guowei; Ding, Xiao P.; Fu, Genyue; Lee, Kang

    2016-01-01

    Executive function (EF) plays vital roles in our everyday adaptation to the ever-changing environment. However, limited existing studies have linked EF to the resting-state brain activity. The functional connectivity in the resting state between the sub-regions of the brain can reveal the intrinsic neural mechanisms involved in cognitive processing of EF without disturbance from external stimuli. The present study investigated the relations between the behavioral executive function (EF) scores and the resting-state functional network topological properties in the Prefrontal Cortex (PFC). We constructed complex brain functional networks in the PFC from 90 healthy young adults using functional near infrared spectroscopy (fNIRS). We calculated the correlations between the typical network topological properties (regional topological properties and global topological properties) and the scores of both the Total EF and components of EF measured by computer-based Cambridge Neuropsychological Test Automated Battery (CANTAB). We found that the Total EF scores were positively correlated with regional properties in the right dorsal superior frontal gyrus (SFG), whereas the opposite pattern was found in the right triangular inferior frontal gyrus (IFG). Different EF components were related to different regional properties in various PFC areas, such as planning in the right middle frontal gyrus (MFG), working memory mainly in the right MFG and triangular IFG, short-term memory in the left dorsal SFG, and task switch in the right MFG. In contrast, there were no significant findings for global topological properties. Our findings suggested that the PFC plays an important role in individuals' behavioral performance in the executive function tasks. Further, the resting-state functional network can reveal the intrinsic neural mechanisms involved in behavioral EF abilities. PMID:27774047

  11. Persulfate initiated ultra-low cross-linked poly(N-isopropylacrylamide) microgels possess an unusual inverted cross-linking structure.

    PubMed

    Virtanen, O L J; Mourran, A; Pinard, P T; Richtering, W

    2016-05-07

    Cross-linking density and distribution are decisive for the mechanical and other properties of stimuli-sensitive poly(N-isopropylacrylamide) microgels. Here we investigate the structure of ultra-low cross-linked microgels by static light scattering and scanning force microscopy, and show that they have an inverted cross-linking structure with respect to conventional microgels, contrary to what has been assumed previously. The conventional microgels have the largest polymer volume fraction in the core from where the particle density decays radially outwards, whereas ultra-low cross-linked particles have the highest polymer volume fraction close to the surface. On a solid substrate these particles form buckled shapes at high surface coverage, as shown by scanning force micrographs. The special structure of ultra-low cross-linked microgels is attributed to cross-linking of the particle surface, which is exposed to hydrogen abstraction by radicals generated from persulfate initiators during and after polymerization. The particle core, which is less accessible to the diffusion of radicals, has consequently a lower polymer volume fraction in the swollen state. By systematic variation of the cross-linker concentration it is shown that the cross-linking contribution from peroxide under typical synthesis conditions is weaker than that from the use of 1 mol% N,N'-methylenebisacrylamide. Soft deformable hydrogel particles are of interest because they emulate biological tissues, and understanding the underlying synthesis principle enables tailoring the microgel structure for biomimetic applications. Deformability of microgels is usually controlled by the amount of added cross-linker; here we however highlight an alternative approach through structural softness.

  12. 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.

  13. 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

  14. 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.

  15. Both α2,3- and α2,6-Linked Sialic Acids on O-Linked Glycoproteins Act as Functional Receptors for Porcine Sapovirus

    PubMed Central

    Alfajaro, Mia Madel; Kim, Ji-Yun; Park, Jun-Gyu; Son, Kyu-Yeol; Ryu, Eun-Hye; Sorgeloos, Frederic; Kwon, Hyung-Jun; Park, Su-Jin; Lee, Woo Song; Cho, Duck; Kwon, Joseph; Choi, Jong-Soon; Kang, Mun-Il; Goodfellow, Ian; Cho, Kyoung-Oh

    2014-01-01

    Sapovirus, a member of the Caliciviridae family, is an important cause of acute gastroenteritis in humans and pigs. Currently, the porcine sapovirus (PSaV) Cowden strain remains the only cultivable member of the Sapovirus genus. While some caliciviruses are known to utilize carbohydrate receptors for entry and infection, a functional receptor for sapovirus is unknown. To characterize the functional receptor of the Cowden strain of PSaV, we undertook a comprehensive series of protein-ligand biochemical assays in mock and PSaV-infected cell culture and/or piglet intestinal tissue sections. PSaV revealed neither hemagglutination activity with red blood cells from any species nor binding activity to synthetic histo-blood group antigens, indicating that PSaV does not use histo-blood group antigens as receptors. Attachment and infection of PSaV were markedly blocked by sialic acid and Vibrio cholerae neuraminidase (NA), suggesting a role for α2,3-linked, α2,6-linked or α2,8-linked sialic acid in virus attachment. However, viral attachment and infection were only partially inhibited by treatment of cells with sialidase S (SS) or Maackia amurensis lectin (MAL), both specific for α2,3-linked sialic acid, or Sambucus nigra lectin (SNL), specific for α2,6-linked sialic acid. These results indicated that PSaV recognizes both α2,3- and α2,6-linked sialic acids for viral attachment and infection. Treatment of cells with proteases or with benzyl 4-O-β-D-galactopyranosyl-β-D-glucopyranoside (benzylGalNAc), which inhibits O-linked glycosylation, also reduced virus binding and infection, whereas inhibition of glycolipd synthesis or N-linked glycosylation had no such effect on virus binding or infection. These data suggest PSaV binds to cellular receptors that consist of α2,3- and α2,6-linked sialic acids on glycoproteins attached via O-linked glycosylation. PMID:24901849

  16. Structural empowerment, Magnet hospital characteristics, and patient safety culture: making the link.

    PubMed

    Armstrong, Kevin J; Laschinger, Heather

    2006-01-01

    Nurse managers are seeking ways to improve patient safety in their organizations. At the same time, they struggle to address nurse recruitment and retention concerns by focusing on the quality of nurses' work environment. This exploratory study tested a theoretical model, linking the quality of the nursing practice environments to a culture of patient safety. Specific strategies to increase nurses' access to empowerment structures and thereby increase the culture of patient safety are suggested.

  17. A link between attentional function, effective eye movements, and driving ability.

    PubMed

    Mackenzie, Andrew K; Harris, Julie M

    2017-02-01

    The misallocation of driver visual attention has been suggested as a major contributing factor to vehicle accidents. One possible reason is that the relatively high cognitive demands of driving limit the ability to efficiently allocate gaze. We present an experiment that explores the relationship between attentional function and visual performance when driving. Drivers performed 2 variations of a multiple-object tracking task targeting aspects of cognition including sustained attention, dual-tasking, covert attention, and visuomotor skill. They also drove a number of courses in a driving simulator. Eye movements were recorded throughout. We found that individuals who performed better in the cognitive tasks exhibited more effective eye movement strategies when driving, such as scanning more of the road, and they also exhibited better driving performance. We discuss the potential link between an individual's attentional function, effective eye movements, and driving ability. We also discuss the use of a visuomotor task in assessing driving behavior. (PsycINFO Database Record

  18. A Link Between Attentional Function, Effective Eye Movements, and Driving Ability

    PubMed Central

    2016-01-01

    The misallocation of driver visual attention has been suggested as a major contributing factor to vehicle accidents. One possible reason is that the relatively high cognitive demands of driving limit the ability to efficiently allocate gaze. We present an experiment that explores the relationship between attentional function and visual performance when driving. Drivers performed 2 variations of a multiple-object tracking task targeting aspects of cognition including sustained attention, dual-tasking, covert attention, and visuomotor skill. They also drove a number of courses in a driving simulator. Eye movements were recorded throughout. We found that individuals who performed better in the cognitive tasks exhibited more effective eye movement strategies when driving, such as scanning more of the road, and they also exhibited better driving performance. We discuss the potential link between an individual’s attentional function, effective eye movements, and driving ability. We also discuss the use of a visuomotor task in assessing driving behavior. PMID:27893270

  19. BK channel activation: structural and functional insights

    PubMed Central

    Lee, Urvi S.; Cui, Jianmin

    2010-01-01

    The voltage and Ca2+ activated K+ (BK) channels are involved in the regulation of neurotransmitter release and neuronal excitability. Structurally, BK channels are homologous to voltage- and ligand-gated K+ channels, having a voltage sensor and pore as the membrane-spanning domain and a cytosolic domain containing metal binding sites. Recently published electron cryomicroscopy (cryo-EM) and X-ray crystallographic structures of the BK channel provided the first look into the assembly of these domains, corroborating the close interactions among these domains during channel gating that have been suggested by functional studies. This review discusses these latest findings and an emerging new understanding about BK channel gating and implications for diseases such as epilepsy, in which mutations in BK channel genes have been associated. PMID:20663573

  20. Picornaviral polymerase structure, function, and fidelity modulation.

    PubMed

    Peersen, Olve B

    2017-02-02

    Like all positive strand RNA viruses, the picornaviruses replicate their genomes using a virally encoded RNA-dependent RNA polymerase enzyme known as 3D(pol). Over the past decade we have made tremendous advances in our understanding of 3D(pol) structure and function, including the discovery of a novel mechanism for closing the active site that allows these viruses to easily fine tune replication fidelity and quasispecies distributions. This review summarizes current knowledge of picornaviral polymerase structure and how the enzyme interacts with RNA and other viral proteins to form stable and processive elongation complexes. The picornaviral RdRPs are among the smallest viral polymerases, but their fundamental molecular mechanism for catalysis appears to be generally applicable as a common feature of all positive strand RNA virus polymerases.

  1. Androgen Modulation of Hippocampal Structure and Function.

    PubMed

    Atwi, Sarah; McMahon, Dallan; Scharfman, Helen; MacLusky, Neil J

    2016-02-01

    Androgens have profound effects on hippocampal structure and function, including induction of spines and spine synapses on the dendrites of CA1 pyramidal neurons, as well as alterations in long-term synaptic plasticity (LTP) and hippocampally dependent cognitive behaviors. How these effects occur remains largely unknown. Emerging evidence, however, suggests that one of the key elements in the response mechanism may be modulation of brain-derived neurotrophic factor (BDNF) in the mossy fiber (MF) system. In male rats, orchidectomy increases synaptic transmission and excitability in the MF pathway. Testosterone reverses these effects, suggesting that testosterone exerts tonic suppression on MF BDNF levels. These findings suggest that changes in hippocampal function resulting from declining androgen levels may reflect the outcome of responses mediated through normally balanced, but opposing, mechanisms: loss of androgen effects on the hippocampal circuitry may be compensated, at least in part, by an increase in BDNF-dependent MF plasticity.

  2. Androgen Modulation of Hippocampal Structure and Function

    PubMed Central

    Atwi, Sarah; McMahon, Dallan; Scharfman, Helen; MacLusky, Neil J.

    2016-01-01

    Androgens have profound effects on hippocampal structure and function, including induction of spines and spine synapses on the dendrites of CA1 pyramidal neurons, as well as alterations in long-term synaptic plasticity (LTP) and hippocampally dependent cognitive behaviors. How these effects occur remains largely unknown. Emerging evidence, however, suggests that one of the key elements in the response mechanism may be modulation of brain-derived neurotrophic factor (BDNF) in the mossy fiber (MF) system. In male rats, orchidectomy increases synaptic transmission and excitability in the MF pathway. Testosterone reverses these effects, suggesting that testosterone exerts tonic suppression on MF BDNF levels. These findings suggest that changes in hippocampal function resulting from declining androgen levels may reflect the outcome of responses mediated through normally balanced, but opposing, mechanisms: loss of androgen effects on the hippocampal circuitry may be compensated, at least in part, by an increase in BDNF-dependent MF plasticity. PMID:25416742

  3. Electronic and structural properties of functional nanostructures

    NASA Astrophysics Data System (ADS)

    Yang, Teng

    In this Thesis, I present a study of electronic and structural properties of functional nanostructures such as MoSxIy nanowires, self-assembled monolayer on top of metallic surfaces and structural changes induced in graphite by photo excitations. MoSxI y nanowires, which can be easily synthesized in one step, show many advantages over conventional carbon nanotubes in molecular electronics and many other applications. But how to self-assemble them into desired pattern for practical electronic network? Self-assembled monolayers of polymers on metallic surfaces may help to guide pattern formation of some nanomaterials such as MoSxIy nanowires. I have investigated the physical properties of these nanoscale wires and microscopic self-assembly mechanisms of patterns by total energy calculations combined with molecular dynamics simulations and structure optimization. First, I studied the stability of novel Molybdenum chaicohalide nanowires, a candidate for molecular electronics applications. Next, I investigated the self-assembly of nanoparticles into ordered arrays with the aid of a template. Such templates, I showed, can be formed by polymer adsorption on surfaces such as highly ordered pyrolytic graphite and Ag(111). Finally, I studied the physical origin of of structural changes induced in graphite by light in form of a femtosecond laser pulse.

  4. Stable Isotope Probing: Linking Functional Activity to Specific Members of Microbial Communities

    SciTech Connect

    Kreuzer-Martin, Helen W.

    2007-03-12

    Abstract Linking organisms or groups of organisms to specific functions within natural environments is a fundamental challenge in microbial ecology. Advances in technology for manipulating and analyzing nucleic acids have made it possible to characterize the members of microbial communities without the intervention of laboratory culturing. Results from such studies have shown that the vast majority of soil organisms have never been cultured, highlighting the risks of culture-based approaches in community analysis. The development of culture-independent techniques for following the flow of substrates through microbial communities therefore represents an important advance. These techniques, collectively known as stable isotope probing (SIP), involve introducing a stable isotope-labeled substrate into a microbial community and following the fate of the substrate by detecting the appearance of the isotope in diagnostic molecules such as fatty acids and nucleic acids. The molecules in which the isotope label appears provide identifying information about the organism that incorporated the substrate. SIP allows direct observations of substrate assimilation in minimally disturbed communities, and thus represents an exciting new tool for linking microbial identity and function. The use of lipids or nucleic acids as the diagnostic molecule brings different strengths and weaknesses to the experimental approach, and necessitates the use of significantly different instrumentation and analytical techniques. This mini-review provides an overview of the lipid and nucleic acid approaches, discusses their strengths and weaknesses, gives examples of applications in various settings, and looks at prospects for the future of SIP technology.

  5. Removal of anionic azo dyes from aqueous solution by functional ionic liquid cross-linked polymer.

    PubMed

    Gao, Hejun; Kan, Taotao; Zhao, Siyuan; Qian, Yixia; Cheng, Xiyuan; Wu, Wenli; Wang, Xiaodong; Zheng, Liqiang

    2013-10-15

    A novel functional ionic liquid based cross-linked polymer (PDVB-IL) was synthesized from 1-aminoethyl-3-vinylimidazolium chloride and divinylbenzene for use as an adsorbent. The physicochemical properties of PDVB-IL were investigated by Fourier transform infrared spectroscopy, scanning electron microscopy and thermogravimetric analysis. The adsorptive capacity was investigated using anionic azo dyes of orange II, sunset yellow FCF, and amaranth as adsorbates. The maximum adsorption capacity could reach 925.09, 734.62, and 547.17 mg/g for orange II, sunset yellow FCF and amaranth at 25°C, respectively, which are much better than most of the other adsorbents reported earlier. The effect of pH value was investigated in the range of 1-8. The result shows that a low pH value is found to favor the adsorption of those anionic azo dyes. The adsorption kinetics and isotherms are well fitted by a pseudo second-order model and Langmuir model, respectively. The adsorption process is found to be dominated by physisorption. The introduction of functional ionic liquid moieties into cross-linked poly(divinylbenzene) polymer constitutes a new and efficient kind of adsorbent.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  8. [Structure and biologic function of IFNgamma].

    PubMed

    Nammous, Abdul Halim; Pietruczuk, Małgorzata; Zubacki, Dymitr; Dobrzycki, Ignacy

    2005-01-01

    IFNgamma is a pro-inflammatory, pleiotropic cytokine mainly produced by the CD4+, CD8+ lymphocytes and NK cells, that play an important role in macrophage activation, antigen presentation enhance and induce innate, and acquired immune responses. IFNgamma by interaction with they cell-surface receptors (IFNgammaR) activates cellular effects including stimulation of antiviral and antimicrobial mechanisms, inhibition of cellular proliferation, regulates cells apoptosis and leukocyte trafficing to sites of inflammation. The purpose of this article is to present the current understending of structure and biological function of IFNgamma in the light of current opinions regarding this matter.

  9. Discovering and Analyzing Network Function and Structure

    DTIC Science & Technology

    2015-07-08

    experiments demonstrating their utility in detecting spam web pages. It has also supported the development of faster algorithms for determining which edges...utility in detecting spam web pages. It has also supported the development of faster algorithms for determining which edges are most critical to the...link to spam web pages, so a link to a spam web page is evidence of spam. Similarly, a link from a legitimate webpage is evidence of legitimacy. Network

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

    NASA Technical Reports Server (NTRS)

    2005-01-01

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

  11. 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.

  12. Structure and function of biotin-dependent carboxylases

    PubMed Central

    Tong, Liang

    2012-01-01

    Biotin-dependent carboxylases include acetyl-CoA carboxylase (ACC), propionyl-CoA carboxylase (PCC), 3-methylcrotonyl-CoA carboxylase (MCC), geranyl-CoA carboxylase (GCC), pyruvate carboxylase (PC), and urea carboxylase (UC). They contain biotin carboxylase (BC), carboxyltransferase (CT) and biotin-carboxyl carrier protein (BCCP) components. These enzymes are widely distributed in nature and have important functions in fatty acid metabolism, amino acid metabolism, carbohydrate metabolism, polyketide biosynthesis, urea utilization, and other cellular processes. ACCs are also attractive targets for drug discovery against type 2 diabetes, obesity, cancer, microbial infections, and other diseases, and the plastid ACC of grasses is the target of action of three classes of commercial herbicides. Deficiencies in the activities of PCC, MCC or PC are linked to serious diseases in humans. Our understanding of these enzymes has been greatly enhanced over the past few years by the crystal structures of the holoenzymes of PCC, MCC, PC, and UC. The structures reveal unanticipated features in the architectures of the holoenzymes, including the presence of previously unrecognized domains, and provide a molecular basis for understanding their catalytic mechanism as well as the large collection of disease-causing mutations in PCC, MCC and PC. This review will summarize the recent advances in our knowledge on the structure and function of these important metabolic enzymes. PMID:22869039

  13. Structural study of asparagine-linked oligosaccharide moiety of taste-modifying protein, miraculin.

    PubMed

    Takahashi, N; Hitotsuya, H; Hanzawa, H; Arata, Y; Kurihara, Y

    1990-05-15

    The structures of the N-linked oligosaccharides of miraculin, which is a taste modifying glycoprotein isolated from miracle fruits, berries of Richadella dulcifica, are reported. Asparagine-linked oligosaccharides were released from the protein by glycopeptidase (almond) digestion. The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by high performance liquid chromatography (HPLC) on an ODS-silica column. More than five kinds of oligosaccharide fractions were separated by the one chromatographic run. The structure of each oligosaccharide thus isolated was analyzed by a combination of sequential exoglycosidase digestion and another kind of HPLC with an amidesilica column. Furthermore, high resolution proton nuclear magnetic resonance (1H NMR) measurements were carried out. It was found that 1) five oligosaccharides obtained are a series of compounds with xylose-containing common structural core, Xyl beta 1----2 (Man alpha 1----6) Man beta 1----4-GlcNAc beta 1----4 (Fuca1----3)GlcNAc, 2) a variety of oligosaccharide structures are significant for two glycosylation sites, Asn-42 and Asn-186, and 3) two new oligosaccharides, B and D, with unusual structures containing monoantennary complex-type were characterized. (formula; see text)

  14. Cryo-imaging and modeling of the super molecular structure of cross-linked gelatin and its applications

    NASA Astrophysics Data System (ADS)

    Marmorat, Clement; Arinstein, Arkadi; Koifman, Naama; Talmon, Yeshayahu; Zussman, Eyal; Rafailovich, Miriam

    The need for naturally derived materials to synthetize bio-compatible scaffolds is growing. In its natural state, gelatin derives its properties from a network of structured, intertwined, triple helical chains. The mechanical properties can be further controlled by additional enzymatic cross-linking. But, in contrast to simple polymer systems, the response to an imposed deformation is then determined by two competing factors, the establishment of the cross-linked mesh vs. the self-assembly of the fibrils into larger and therefore stronger hierarchical structures. Properties deduced from the response functions to measurements; such as rheology or swelling, are then a combination of these two very different factors, hence impossible to model unless more precise knowledge is available regarding the internal structure. We applied cryogenic-temperature scanning electron microscopy (cryo-SEM) to image the networks. Based on these images, a theoretical model was developed, for which we obtained excellent agreement for the mesh size of both networks, and their mechanical properties. We then used these controlled scaffolds, embedding them with fluorescent beads, to image live cells traction forces at stake during cell migration.

  15. Link direction for link prediction

    NASA Astrophysics Data System (ADS)

    Shang, Ke-ke; Small, Michael; Yan, Wei-sheng

    2017-03-01

    Almost all previous studies on link prediction have focused on using the properties of the network to predict the existence of links between pairs of nodes. Unfortunately, previous methods rarely consider the role of link direction for link prediction. In fact, many real-world complex networks are directed and ignoring the link direction will mean overlooking important information. In this study, we propose a phase-dynamic algorithm of the directed network nodes to analyse the role of link directions and demonstrate that the bi-directional links and the one-directional links have different roles in link prediction and network structure formation. From this, we propose new directional prediction methods and use six real networks to test our algorithms. In real networks, we find that compared to a pair of nodes which are connected by a one-directional link, a pair of nodes which are connected by a bi-directional link always have higher probabilities to connect to the common neighbours with only bi-directional links (or conversely by one-directional links). We suggest that, in the real networks, the bi-directional links will generally be more informative for link prediction and network structure formation. In addition, we propose a new directional randomized algorithm to demonstrate that the direction of the links plays a significant role in link prediction and network structure formation.

  16. Structure, function, and plasticity of GABA transporters

    PubMed Central

    Scimemi, Annalisa

    2014-01-01

    GABA transporters belong to a large family of neurotransmitter:sodium symporters. They are widely expressed throughout the brain, with different levels of expression in different brain regions. GABA transporters are present in neurons and in astrocytes and their activity is crucial to regulate the extracellular concentration of GABA under basal conditions and during ongoing synaptic events. Numerous efforts have been devoted to determine the structural and functional properties of GABA transporters. There is also evidence that the expression of GABA transporters on the cell membrane and their lateral mobility can be modulated by different intracellular signaling cascades. The strength of individual synaptic contacts and the activity of entire neuronal networks may be finely tuned by altering the density, distribution and diffusion rate of GABA transporters within the cell membrane. These findings are intriguing because they suggest the existence of complex regulatory systems that control the plasticity of GABAergic transmission in the brain. Here we review the current knowledge on the structural and functional properties of GABA transporters and highlight the molecular mechanisms that alter the expression and mobility of GABA transporters at central synapses. PMID:24987330

  17. The lipocalin protein family: structure and function.

    PubMed Central

    Flower, D R

    1996-01-01

    The lipocalin protein family is a large group of small extracellular proteins. The family demonstrates great diversity at the sequence level; however, most lipocalins share three characteristic conserved sequence motifs, the kernel lipocalins, while a group of more divergent family members, the outlier lipocalins, share only one. Belying this sequence dissimilarity, lipocalin crystal structures are highly conserved and comprise a single eight-stranded continuously hydrogen-bonded antiparallel beta-barrel, which encloses an internal ligand-binding site. Together with two other families of ligand-binding proteins, the fatty-acid-binding proteins (FABPs) and the avidins, the lipocalins form part of an overall structural superfamily: the calycins. Members of the lipocalin family are characterized by several common molecular-recognition properties: the ability to bind a range of small hydrophobic molecules, binding to specific cell-surface receptors and the formation of complexes with soluble macromolecules. The varied biological functions of the lipocalins are mediated by one or more of these properties. In the past, the lipocalins have been classified as transport proteins; however, it is now clear that the lipocalins exhibit great functional diversity, with roles in retinol transport, invertebrate cryptic coloration, olfaction and pheromone transport, and prostaglandin synthesis. The lipocalins have also been implicated in the regulation of cell homoeostasis and the modulation of the immune response, and, as carrier proteins, to act in the general clearance of endogenous and exogenous compounds. PMID:8761444

  18. Models of protocellular structures, functions and evolution

    NASA Technical Reports Server (NTRS)

    Pohorille, Andrew; New, Michael H.; DeVincenzi, Donald L. (Technical Monitor)

    2000-01-01

    The central step in the origin of life was the emergence of organized structures from organic molecules available on the early earth. These predecessors to modern cells, called 'proto-cells,' were simple, membrane bounded structures able to maintain themselves, grow, divide, and evolve. Since there is no fossil record of these earliest of life forms, it is a scientific challenge to discover plausible mechanisms for how these entities formed and functioned. To meet this challenge, it is essential to create laboratory models of protocells that capture the main attributes associated with living systems, while remaining consistent with known, or inferred, protobiological conditions. This report provides an overview of a project which has focused on protocellular metabolism and the coupling of metabolism to energy transduction. We have assumed that the emergence of systems endowed with genomes and capable of Darwinian evolution was preceded by a pre-genomic phase, in which protocells functioned and evolved using mostly proteins, without self-replicating nucleic acids such as RNA.

  19. Red cell antigens: Structure and function

    PubMed Central

    Pourazar, Abbasali

    2007-01-01

    Landsteiner and his colleagues demonstrated that human beings could be classified into four groups depending on the presence of one (A) or another (B) or both (AB) or none (O) of the antigens on their red cells. The number of the blood group antigens up to 1984 was 410. In the next 20 years, there were 16 systems with 144 antigens and quite a collection of antigens waiting to be assigned to systems, pending the discovery of new information about their relationship to the established systems. The importance of most blood group antigens had been recognized by immunological complications of blood transfusion or pregnancies; their molecular structure and function however remained undefined for many decades. Recent advances in molecular genetics and cellular biochemistry resulted in an abundance of new information in this field of research. In this review, we try to give some examples of advances made in the field of ‘structure and function of the red cell surface molecules.’ PMID:21938229

  20. Structure, expression and functions of MTA genes.

    PubMed

    Kumar, Rakesh; Wang, Rui-An

    2016-05-15

    Metastatic associated proteins (MTA) are integrators of upstream regulatory signals with the ability to act as master coregulators for modifying gene transcriptional activity. The MTA family includes three genes and multiple alternatively spliced variants. The MTA proteins neither have their own enzymatic activity nor have been shown to directly interact with DNA. However, MTA proteins interact with a variety of chromatin remodeling factors and complexes with enzymatic activities for modulating the plasticity of nucleosomes, leading to the repression or derepression of target genes or other extra-nuclear and nucleosome remodeling and histone deacetylase (NuRD)-complex independent activities. The functions of MTA family members are driven by the steady state levels and subcellular localization of MTA proteins, the dynamic nature of modifying signals and enzymes, the structural features and post-translational modification of protein domains, interactions with binding proteins, and the nature of the engaged and resulting features of nucleosomes in the proximity of target genes. In general, MTA1 and MTA2 are the most upregulated genes in human cancer and correlate well with aggressive phenotypes, therapeutic resistance, poor prognosis and ultimately, unfavorable survival of cancer patients. Here we will discuss the structure, expression and functions of the MTA family of genes in the context of cancer cells.

  1. Krebs cycle metabolon: structural evidence of substrate channeling revealed by cross-linking and mass spectrometry.

    PubMed

    Wu, Fei; Minteer, Shelley

    2015-02-02

    It has been hypothesized that the high metabolic flux in the mitochondria is due to the self-assembly of enzyme supercomplexes (called metabolons) that channel substrates from one enzyme to another, but there has been no experimental confirmation of this structure or the channeling. A structural investigation of enzyme organization within the Krebs cycle metabolon was accomplished by in vivo cross-linking and mass spectrometry. Eight Krebs cycle enzyme components were isolated upon chemical fixation, and interfacial residues between mitochondrial malate dehydrogenase, citrate synthase, and aconitase were identified. Using constraint protein docking, a low-resolution structure for the three-enzyme complex was achieved, as well as the two-fold symmetric octamer. Surface analysis showed formation of electrostatic channeling upon protein-protein association, which is the first structural evidence of substrate channeling in the Krebs cycle metabolon.

  2. Linking plat traits at ecosystem scale to ecosystem functions as observed by eddy covariance measurements

    NASA Astrophysics Data System (ADS)

    Sadat Musavi, Talie; Kattge, Jens; Mahecha, Miguel; Reichstein, Markus; Van de Weg, Marjan; Van Bodegom, Peter; Bahn, Michael

    2013-04-01

    In this study we analyze the correlation structure among plant traits, ecosystem functional properties, characteristics of climate, soil and vegetation at 253 FLUXNET sites. This correlation structure may provide a basis for assessing vegetation functioning and its vulnerability under climate change. Until now, analyses of the FLUXNET dataset have shown that much of the observed spatial and temporal variation of ecosystem fluxes can be explained and scaled by information on soil, climate and vegetation structure, without considering the variation in the functional characteristics of the vegetation occurring at the FLUXNET sites. Instead, these studies have used plant functional types (PFT) as a parameter representing the vegetation influence on fluxes. However, provided the variability in traits that exists within an individual PFT at different sites, we analyze in this study how traits additionally influence ecosystem functional properties. We use community mean trait values to understand how vegetation characteristics relate to ecosystem functional properties, like maximum GPP at light saturation, or photosynthetic water use efficiency. These functional properties are derived from the combination of ecosystem level flux observation and information of spatial meteorology and vegetation remote sensing covariates. In addition, we investigate whether vegetation characteristics have an influence on ecosystem fluxes when combined with climate and soil information. So far analyses of this kind were impossible due to a lack of plant trait information. But the plant trait dataset TRY has been growing for years and in combination with novel methods in machine learning. We now have the opportunity to predict plant trait values for individual sites. We will present first results focusing on the relationship of ecosystem functional properties to leaf traits like specific leaf area and leaf carbon, nitrogen and phosphorus concentration scaled to canopy level.

  3. Structure elucidation of DNA interstrand cross-link by a combination of nuclease P1 digestion with mass spectrometry.

    PubMed

    Wang, Yuesong; Wang, Yinsheng

    2003-11-15

    DNA interstrand cross-link reagents are among the most powerful agents for cancer treatment. Here we report a combined nuclease P1 digestion/mass spectrometry method for the structure elucidation of duplex oligodeoxynucleotides (ODNs) containing an interstrand cross-link. Our results demonstrate that nuclease P1 digestion of a double-stranded ODN containing an interstrand cross-link (ICL) of 4,5',8-trimethylpsoralen or mitomycin C gives a tetranucleotide bearing the cross-linked nucleobase moiety. Product ion spectra of the deprotonated ions of the tetranucleotides provide information about the structure of the cross-link. Furthermore, product-ion spectra of tetranucleotides containing two orientation isomers of mitomycin C interstrand cross-link are distinctive. We believe that the method described in this paper can be generally applicable for investigating the structures of other DNA ICLs.

  4. Partition function and astronomical observation of interstellar isomers: Is there a link?

    NASA Astrophysics Data System (ADS)

    Etim, Emmanuel E.; Arunan, Elangannan

    2017-02-01

    The unsuccessful astronomical searches for some important astrophysical and astrobiological molecules have been linked to the large partition function of these molecules. This letter reports an extensive investigation of the relationship between partition function and astronomical observation of interstellar isomers using high level quantum chemical calculations. 120 molecules from 30 different isomeric groups have been considered. Partition function and thermodynamic stabilities are determined for each set of isomeric species. From the results, there is no direct correlation between partition function and astronomical observation of the same isomeric species. Though interstellar formations processes are generally controlled by factors like kinetics, thermodynamics, formation and destruction pathways. However, the observation of the isomers seems to correlate well with thermodynamics. For instance, in all the groups considered, the astronomically detected isomers are the thermodynamically most stable molecules in their respective isomeric groups. The implications of these results in accounting for the limited number of known cyclic interstellar molecules, unsuccessful searches for amino acid and the possible molecules for astronomical observations are discussed.

  5. Genomic islands link secondary metabolism to functional adaptation in marine Actinobacteria

    PubMed Central

    Penn, Kevin; Jenkins, Caroline; Nett, Markus; Udwary, Daniel W.; Gontang, Erin A.; McGlinchey, Ryan P.; Foster, Brian; Lapidus, Alla; Podell, Sheila; Allen, Eric E.; Moore, Bradley S.; Jensen, Paul R.

    2009-01-01

    Genomic islands have been shown to harbor functional traits that differentiate ecologically distinct populations of environmental bacteria. A comparative analysis of the complete genome sequences of the marine Actinobacteria Salinispora tropica and S. arenicola reveals that 75% of the species-specific genes are located in 21 genomic islands. These islands are enriched in genes associated with secondary metabolite biosynthesis providing evidence that secondary metabolism is linked to functional adaptation. Secondary metabolism accounts for 8.8% and 10.9% of the genes in the S. tropica and S. arenicola genomes, respectively, and represents the major functional category of annotated genes that differentiates the two species. Genomic islands harbor all 25 of the species-specific biosynthetic pathways, the majority of which occur in S. arenicola and may contribute to the cosmopolitan distribution of this species. Genome evolution is dominated by gene duplication and acquisition, which in the case of secondary metabolism provide immediate opportunities for the production of new bioactive products. Evidence that secondary metabolic pathways are exchanged horizontally, coupled with prior evidence for fixation among globally distributed populations, supports a functional role and suggests that the acquisition of natural product biosynthetic gene clusters represents a previously unrecognized force driving bacterial diversification. Species-specific differences observed in CRISPR (clustered regularly interspaced short palindromic repeat) sequences suggest that S. arenicola may possess a higher level of phage immunity, while a highly duplicated family of polymorphic membrane proteins provides evidence of a new mechanism of marine adaptation in Gram-positive bacteria. PMID:19474814

  6. An Annotated Bibliography of Resources on Educational Linking Agents: Roles, Functions, and Training Materials.

    ERIC Educational Resources Information Center

    Barth, Rodney J., Comp.

    The resources cited in this selected annotated bibliography are intended for linking agents, trainers of linking agents, managers of linking agents and their support systems, and educational policy makers. These resources, which date from 1975 to the present, variously refer to linking agents, change agents, extension agents, field agents, field…

  7. Structure and function of KH domains.

    PubMed

    Valverde, Roberto; Edwards, Laura; Regan, Lynne

    2008-06-01

    The hnRNP K homology (KH) domain was first identified in the protein human heterogeneous nuclear ribonucleoprotein K (hnRNP K) 14 years ago. Since then, KH domains have been identified as nucleic acid recognition motifs in proteins that perform a wide range of cellular functions. KH domains bind RNA or ssDNA, and are found in proteins associated with transcriptional and translational regulation, along with other cellular processes. Several diseases, e.g. fragile X mental retardation syndrome and paraneoplastic disease, are associated with the loss of function of a particular KH domain. Here we discuss the progress made towards understanding both general and specific features of the molecular recognition of nucleic acids by KH domains. The typical binding surface of KH domains is a cleft that is versatile but that can typically accommodate only four unpaired bases. Van der Waals forces and hydrophobic interactions and, to a lesser extent, electrostatic interactions, contribute to the nucleic acid binding affinity. 'Augmented' KH domains or multiple copies of KH domains within a protein are two strategies that are used to achieve greater affinity and specificity of nucleic acid binding. Isolated KH domains have been seen to crystallize as monomers, dimers and tetramers, but no published data support the formation of noncovalent higher-order oligomers by KH domains in solution. Much attention has been given in the literature to a conserved hydrophobic residue (typically Ile or Leu) that is present in most KH domains. The interest derives from the observation that an individual with this Ile mutated to Asn, in the KH2 domain of fragile X mental retardation protein, exhibits a particularly severe form of the syndrome. The structural effects of this mutation in the fragile X mental retardation protein KH2 domain have recently been reported. We discuss the use of analogous point mutations at this position in other KH domains to dissect both structure and function.

  8. Latent structures of female sexual functioning.

    PubMed

    Carvalho, Joana; Vieira, Armando Luís; Nobre, Pedro

    2012-08-01

    For the last three decades, male and female sexual responses have been conceptualized as similar, based on separated and sequential phases as proposed by the models of Masters and Johnson (1966) and Kaplan (1979) model. However, there is a growing debate around the need to conceptualize female sexual response and the classification of sexual dysfunction in women, in view of the upcoming editions of the DSM and ICD. The aim of this study was to test, using structural equation modeling, five conceptual, alternative models of female sexual function, using a sample of women with sexual difficulties and a sample of women without sexual problems. A total of 1993 Portuguese women participated in the study and completed a modified version of the Female Sexual Function Index. Findings suggested a four-factor solution as the model that best fit the data regarding women presenting sexual difficulties: (1) desire/arousal; (2) lubrication; (3) orgasm; (4) pain/vaginismus. In relation to sexually healthy women, the best model was a five-factor solution comprising of (1) desire; (2) arousal; (3) lubrication; (4) orgasm; and (5) pain/vaginismus. Discriminant validity between factors was supported, suggesting that these dimensions measure distinct phenomena. Model fit to the data significantly decreased in both samples, as models began to successively consider greater levels of overlap among phases of sexual function, towards a single-factor solution. By suggesting the overlap between pain and vaginismus, results partially support the new classification that is currently being discussed regarding DSM-5. Additionally, results on the relationship between sexual desire and arousal were inconclusive as sexually healthy women were better characterized by a five-factor model that considered the structural independence among these factors, whereas women with sexual difficulties better fit with a four-factor model merging sexual desire and subjective sexual arousal.

  9. Structure and Function of KH Domains

    SciTech Connect

    Valverde, R.; Regan, E

    2008-01-01

    The hnRNP K homology (KH) domain was first identified in the protein human heterogeneous nuclear ribonucleoprotein K (hnRNP K) 14 years ago. Since then, KH domains have been identified as nucleic acid recognition motifs in proteins that perform a wide range of cellular functions. KH domains bind RNA or ssDNA, and are found in proteins associated with transcriptional and translational regulation, along with other cellular processes. Several diseases, e.g. fragile X mental retardation syndrome and paraneoplastic disease, are associated with the loss of function of a particular KH domain. Here we discuss the progress made towards understanding both general and specific features of the molecular recognition of nucleic acids by KH domains. The typical binding surface of KH domains is a cleft that is versatile but that can typically accommodate only four unpaired bases. Van der Waals forces and hydrophobic interactions and, to a lesser extent, electrostatic interactions, contribute to the nucleic acid binding affinity. 'Augmented' KH domains or multiple copies of KH domains within a protein are two strategies that are used to achieve greater affinity and specificity of nucleic acid binding. Isolated KH domains have been seen to crystallize as monomers, dimers and tetramers, but no published data support the formation of noncovalent higher-order oligomers by KH domains in solution. Much attention has been given in the literature to a conserved hydrophobic residue (typically Ile or Leu) that is present in most KH domains. The interest derives from the observation that an individual with this Ile mutated to Asn, in the KH2 domain of fragile X mental retardation protein, exhibits a particularly severe form of the syndrome. The structural effects of this mutation in the fragile X mental retardation protein KH2 domain have recently been reported. We discuss the use of analogous point mutations at this position in other KH domains to dissect both structure and function.

  10. Structure to function: Spider silk and human collagen

    NASA Astrophysics Data System (ADS)

    Rabotyagova, Olena S.

    Nature has the ability to assemble a variety of simple molecules into complex functional structures with diverse properties. Collagens, silks and muscles fibers are some examples of fibrous proteins with self-assembling properties. One of the great challenges facing Science is to mimic these designs in Nature to find a way to construct molecules that are capable of organizing into functional supra-structures by self-assembly. In order to do so, a construction kit consisting of molecular building blocks along with a complete understanding on how to form functional materials is required. In this current research, the focus is on spider silk and collagen as fibrous protein-based biopolymers that can shed light on how to generate nanostructures through the complex process of self-assembly. Spider silk in fiber form offers a unique combination of high elasticity, toughness, and mechanical strength, along with biological compatibility and biodegrability. Spider silk is an example of a natural block copolymer, in which hydrophobic and hydrophilic blocks are linked together generating polymers that organize into functional materials with extraordinary properties. Since silks resemble synthetic block copolymer systems, we adopted the principles of block copolymer design from the synthetic polymer literature to build block copolymers based on spider silk sequences. Moreover, we consider spider silk to be an important model with which to study the relationships between structure and properties in our system. Thus, the first part of this work was dedicated to a novel family of spider silk block copolymers, where we generated a new family of functional spider silk-like block copolymers through recombinant DNA technology. To provide fundamental insight into relationships between peptide primary sequence, block composition, and block length and observed morphological and structural features, we used these bioengineered spider silk block copolymers to study secondary structure

  11. Structure and function of milk allergens.

    PubMed

    Wal, J M

    2001-01-01

    Proteins (CMP) involved in milk allergy are numerous and heterogeneous, with very few structural or functional common features. This heterogeneity is complicated by their genetic polymorphism, resulting in several variants for each protein. These variants are characterized by point substitutions of amino acids or by deletions of peptide fragments of varying size or by post-translational modifications such as phosphorylation or glycosylation. All of these modifications may affect allergenicity. No common molecular structure can be associated with allergenicity, although some homologous regions such as casein phospho-peptides can explain an IgE cross-reactivity. Three-dimensional structure is an important feature in CMP allergenicity but denatured and linear epitopes are also involved. Epitopes are numerous and widely spread along the CMP molecule. They may be located in hydrophobic parts of the molecule where they are inaccessible for IgE antibodies in the native conformation of the protein but become bioavailable after digestive processes. Peptides as short as ca. 12-14 amino acid residues may account for a significant part of the allergenicity of the whole molecule, which justifies the need to be careful before proposing any CMP hydrolysate for highly allergenic children.

  12. Structure, dynamics, and function of biomolecules

    SciTech Connect

    Frauenfelder, H.; Berendzen, J.R.; Garcia, A.; Gupta, G.; Olah, G.A.; Terwilliger, T.C.; Trewhella, J.; Wood, C.C.; Woodruff, W.H.

    1998-11-01

    This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The authors enhanced Los Alamos' core competency in Bioscience and Biotechnology by building on present strengths in experimental techniques, theory, high-performance computing, modeling, and simulation applied to biomolecular structure, dynamics, and function. Specifically, the authors strengthened their capabilities in neutron/x-ray scattering, x-ray crystallography, NMR, laser, and optical spectroscopies. Initially they focused on supporting the Los alamos Neutron Science Center (LANSCE) in the design and implementation of new neutron scattering instrumentation, they developed new methods for analysis of scattering data, and they developed new projects to study the structures of biomolecular complexes. The authors have also worked to strengthen interactions between theory and experiment, and between the biological and physical sciences. They sponsored regular meetings of members from all interested LANL technical divisions, and supported two lecture series: ''Biology for Physicists'' and ''Issues in Modern Biology''. They also supported the formation of interdisciplinary/inter-divisional teams to develop projects in science-based bioremediation and an integrated structural biology resource. Finally, they successfully worked with a multidisciplinary team to put forward the Laboratory's Genome and Beyond tactical goal.

  13. Sialylation regulates brain structure and function

    PubMed Central

    Yoo, Seung-Wan; Motari, Mary G.; Susuki, Keiichiro; Prendergast, Jillian; Mountney, Andrea; Hurtado, Andres; Schnaar, Ronald L.

    2015-01-01

    Every cell expresses a molecularly diverse surface glycan coat (glycocalyx) comprising its interface with its cellular environment. In vertebrates, the terminal sugars of the glycocalyx are often sialic acids, 9-carbon backbone anionic sugars implicated in intermolecular and intercellular interactions. The vertebrate brain is particularly enriched in sialic acid-containing glycolipids termed gangliosides. Human congenital disorders of ganglioside biosynthesis result in paraplegia, epilepsy, and intellectual disability. To better understand sialoglycan functions in the nervous system, we studied brain anatomy, histology, biochemistry, and behavior in mice with engineered mutations in St3gal2 and St3gal3, sialyltransferase genes responsible for terminal sialylation of gangliosides and some glycoproteins. St3gal2/3 double-null mice displayed dysmyelination marked by a 40% reduction in major myelin proteins, 30% fewer myelinated axons, a 33% decrease in myelin thickness, and molecular disruptions at nodes of Ranvier. In part, these changes may be due to dysregulation of ganglioside-mediated oligodendroglial precursor cell proliferation. Neuronal markers were also reduced up to 40%, and hippocampal neurons had smaller dendritic arbors. Young adult St3gal2/3 double-null mice displayed impaired motor coordination, disturbed gait, and profound cognitive disability. Comparisons among sialyltransferase mutant mice provide insights into the functional roles of brain gangliosides and sialoglycoproteins consistent with related human congenital disorders.—Yoo, S.-W., Motari, M. G., Susuki, K., Prendergast, J., Mountney, A., Hurtado, A., Schnaar, R. L. Sialylation regulates brain structure and function. PMID:25846372

  14. Melanocortin 1 Receptor: Structure, Function, and Regulation

    PubMed Central

    Wolf Horrell, Erin M.; Boulanger, Mary C.; D’Orazio, John A.

    2016-01-01

    The melanocortin 1 receptor (MC1R) is a melanocytic Gs protein coupled receptor that regulates skin pigmentation, UV responses, and melanoma risk. It is a highly polymorphic gene, and loss of function correlates with a fair, UV-sensitive, and melanoma-prone phenotype due to defective epidermal melanization and sub-optimal DNA repair. MC1R signaling, achieved through adenylyl cyclase activation and generation of the second messenger cAMP, is hormonally controlled by the positive agonist melanocortin, the negative agonist agouti signaling protein, and the neutral antagonist β-defensin 3. Activation of cAMP signaling up-regulates melanin production and deposition in the epidermis which functions to limit UV penetration into the skin and enhances nucleotide excision repair (NER), the genomic stability pathway responsible for clearing UV photolesions from DNA to avoid mutagenesis. Herein we review MC1R structure and function and summarize our laboratory’s findings on the molecular mechanisms by which MC1R signaling impacts NER. PMID:27303435

  15. Tuning heterogeneous poly(dopamine) structures and mechanics: in silico covalent cross-linking and thin film nanoindentation.

    PubMed

    Lin, Shangchao; Chen, Chun-Teh; Bdikin, Igor; Ball, Vincent; Grácio, José; Buehler, Markus J

    2014-01-21

    Mussel-inspired synthetic poly(dopamine) thin films from dihydroxyphenylalanine (DOPA) and lysine, structurally similar to natural melanin, have drawn extensive interest as a versatile surface functionalization and coating material for use in a broad range of applications. In order to gain a better understanding of its complex and heterogeneous polymeric structure and mechanical properties, we report a computational model of poly(dopamine) by mimicking the polymerization process of the intermediate oxidized product of dopamine, 5,6-dihydroxyindole (DHI), via controlled in silico covalent cross-linking under the two most possible reaction schemes proposed in experiments. To validate our results using experiment, we synthesize poly(dopamine) thin films and perform experimental nanoindentations on the film. We observe an overall linear behavior for Young's modulus as a function of the degree of cross-linking, demonstrating the possibility of enhancing the mechanical robustness of poly(dopamine) materials by increasing the extent of polymerization. At the highest degree of polymerization considered (70%), the model mimics the linear tetrameric model for poly(dopamine) and melanin. At this degree of polymerization, we find a Young's modulus of 4.1-4.4 GPa, in agreement with our nanoindentation results of 4.3-10.5 GPa, previous experiments for natural melanin, as well as simulation results for the cyclic tetrameric melanin model (Chen et al., ACS Nano, 2013). Our results suggest that the non-covalent DHI aggregate model might not be appropriate to represent the structure of poly(dopamine) and melanin-like materials, since it gives a much smaller Young's modulus than the experimental lower bound. Our model not only nicely complements the previous computational work, but also provides new computational tools to study the heterogeneous structural and physicochemical properties of poly(dopamine) and melanin, as well as their formation pathways.

  16. Effect of colicin K on a membrane-associated, energy-linked function.

    PubMed Central

    Sabet, S F

    1976-01-01

    The purpose of this work was in investigate the capability of cell extracts of Escherichia coli and E. coli treated with colicin K to catalyze the following energy-dependent reverse transhydrogenase reaction: NADP + NADH + ATP in equilibrium NADPH + NAD +ADP + Pi. Under anaerobic conditions this reaction requires the presence of a specific portion of the electron transport chain, a functional energy coupling system, including an adenosine triphosphatase, enzyme, and ATP as energy source. The ATP-linked reaction was partially inhibited in French press extracts of E. coli K-12 C600 cells that had been pretreated with colicin K but not in extracts from similarly treated cells of a colicin-tolerant mutant. Ultracentrifugation of extracts yielded particulate fractions competent in catalyzing the reaction; this reaction is substantially inhibited in fractions from colicin-treated cells. The extent of inhibition increased with increasing concentration of colicin. Supernatants also supported ATP-linked formation of NADPH, but this reaction was insensitive to the colicin effect. A comparison between the requirement of the reaction in supernatant and particulate fractions suggests that the reaction in the supernatant is different from the one inhibited by colicin. The ATP-hydrolyzing ability of particulate fractions from the control or treated bacteria was identical. Likewise, the electron transport chain was not affected by colicin treatment, as evidenced from lack of effect on NADH oxidase, succinic dehydrogenase, and NADPH-NAD transhydrogenase. It is concluded that colicin K interferes with the coupling of ATP the utilization of the intermediate for the ATP-linked transdehydrogenase reaction. PMID:4429

  17. Consumer trophic diversity as a fundamental mechanism linking predation and ecosystem functioning.

    PubMed

    Hines, Jes; Gessner, Mark O

    2012-11-01

    1. Primary production and decomposition, two fundamental processes determining the functioning of ecosystems, may be sensitive to changes in biodiversity and food web interactions. 2. The impacts of food web interactions on ecosystem functioning are generally quantified by experimentally decoupling these linked processes and examining either primary production-based (green) or decomposition-based (brown) food webs in isolation. This decoupling may strongly limit our ability to assess the importance of food web interactions on ecosystem processes. 3. To evaluate how consumer trophic diversity mediates predator effects on ecosystem functioning, we conducted a mesocosm experiment and a field study using an assemblage of invertebrates that naturally co-occur on North Atlantic coastal saltmarshes. We measured the indirect impact of predation on primary production and leaf decomposition as a result of prey communities composed of herbivores alone, detritivores alone or both prey in combination. 4. We find that primary consumers can influence ecosystem process rates not only within, but also across green and brown sub-webs. Moreover, by feeding on a functionally diverse consumer assemblage comprised of both herbivores and detritivores, generalist predators can diffuse consumer effects on decomposition, primary production and feedbacks between the two processes. 5. These results indicate that maintaining functional diversity among primary consumers can alter the consequences of traditional trophic cascades, and they emphasize the role of the detritus-based sub-web when seeking key biotic drivers of plant production. Clearly, traditional compartmentalization of empirical food webs can limit our ability to predict the influence of food web interactions on ecosystem functioning.

  18. Familial Alzheimer disease–linked mutations specifically disrupt Ca2+ leak function of presenilin 1

    PubMed Central

    Nelson, Omar; Tu, Huiping; Lei, Tianhua; Bentahir, Mostafa; de Strooper, Bart; Bezprozvanny, Ilya

    2007-01-01

    Mutations in presenilins are responsible for approximately 40% of all early-onset familial Alzheimer disease (FAD) cases in which a genetic cause has been identified. In addition, a number of mutations in presenilin-1 (PS1) have been suggested to be associated with the occurrence of frontal temporal dementia (FTD). Presenilins are highly conserved transmembrane proteins that support cleavage of the amyloid precursor protein by γ-secretase. Recently, we discovered that presenilins also function as passive ER Ca2+ leak channels. Here we used planar lipid bilayer reconstitution assays and Ca2+ imaging experiments with presenilin-null mouse embryonic fibroblasts to analyze ER Ca2+ leak function of 6 FAD-linked PS1 mutants and 3 known FTD-associated PS1 mutants. We discovered that L166P, A246E, E273A, G384A, and P436Q FAD mutations in PS1 abolished ER Ca2+ leak function of PS1. In contrast, A79V FAD mutation or FTD-associated mutations (L113P, G183V, and Rins352) did not appear to affect ER Ca2+ leak function of PS1 in our experiments. We validated our findings in Ca2+ imaging experiments with primary fibroblasts obtained from an FAD patient possessing mutant PS1-A246E. Our results indicate that many FAD mutations in presenilins are loss-of-function mutations affecting ER Ca2+ leak activity. In contrast, none of the FTD-associated mutations affected ER Ca2+ leak function of PS1, indicating that the observed effects are disease specific. Our observations are consistent with the potential role of disturbed Ca2+ homeostasis in Alzheimer disease pathogenesis. PMID:17431506

  19. TMEM16 proteins: unknown structure and confusing functions

    PubMed Central

    Picollo, Alessandra; Malvezzi, Mattia; Accardi, Alessio

    2014-01-01

    The TMEM16 family of membrane proteins, also known as anoctamins, play key roles in a variety of physiological functions that range from ion transport, to phospholipid scrambling and to regulating other ion channels. The first two family members to be functionally characterized, TMEM16A (ANO1) and TMEM16B (ANO2), form Ca2+-activated Cl− channels (CaCCs) and are important for transepithelial ion transport, olfaction, phototransduction, smooth muscle contraction, nociception, cell proliferation and control of neuronal excitability. The role(s) of other family members, such as TMEM16C (ANO3), TMEM16D (ANO4), TMEM16F (ANO6), TMEM16G (ANO7), and TMEM16J (ANO9), remain poorly understood and controversial. These homologues were reported to be phospholipid scramblases, ion channels, to have both functions or to be regulatory subunits of other channels. Mutations in TMEM16F cause Scott syndrome, a bleeding disorder caused by impaired Ca2+-dependent externalization of phosphatidylserine in activated platelets, suggesting that this homologue might be a scramblase. However, overexpression of TMEM16F has also been associated with a remarkable number of different ion channel types, raising the possibility that this protein might be involved in both ion and lipid transport. The recent identification of an ancestral TMEM16 homologue with intrinsic channel and scramblase activities supports this hypothesis. Thus, the TMEM16 family might have diverged in two or three different subclasses, channels, scramblases and dual function channel/scramblases. The structural bases and functional implication of such a functional diversity within a single protein family remain to be elucidated and the links between TMEM16 functions and human physiology and pathologies need to be investigated. PMID:25451786

  20. Nitric oxide synthases: structure, function and inhibition.

    PubMed Central

    Alderton, W K; Cooper, C E; Knowles, R G

    2001-01-01

    This review concentrates on advances in nitric oxide synthase (NOS) structure, function and inhibition made in the last seven years, during which time substantial advances have been made in our understanding of this enzyme family. There is now information on the enzyme structure at all levels from primary (amino acid sequence) to quaternary (dimerization, association with other proteins) structure. The crystal structures of the oxygenase domains of inducible NOS (iNOS) and vascular endothelial NOS (eNOS) allow us to interpret other information in the context of this important part of the enzyme, with its binding sites for iron protoporphyrin IX (haem), biopterin, L-arginine, and the many inhibitors which interact with them. The exact nature of the NOS reaction, its mechanism and its products continue to be sources of controversy. The role of the biopterin cofactor is now becoming clearer, with emerging data implicating one-electron redox cycling as well as the multiple allosteric effects on enzyme activity. Regulation of the NOSs has been described at all levels from gene transcription to covalent modification and allosteric regulation of the enzyme itself. A wide range of NOS inhibitors have been discussed, interacting with the enzyme in diverse ways in terms of site and mechanism of inhibition, time-dependence and selectivity for individual isoforms, although there are many pitfalls and misunderstandings of these aspects. Highly selective inhibitors of iNOS versus eNOS and neuronal NOS have been identified and some of these have potential in the treatment of a range of inflammatory and other conditions in which iNOS has been implicated. PMID:11463332

  1. Modular structure of functional networks in olfactory memory.

    PubMed

    Meunier, David; Fonlupt, Pierre; Saive, Anne-Lise; Plailly, Jane; Ravel, Nadine; Royet, Jean-Pierre

    2014-07-15

    Graph theory enables the study of systems by describing those systems as a set of nodes and edges. Graph theory has been widely applied to characterize the overall structure of data sets in the social, technological, and biological sciences, including neuroscience. Modular structure decomposition enables the definition of sub-networks whose components are gathered in the same module and work together closely, while working weakly with components from other modules. This processing is of interest for studying memory, a cognitive process that is widely distributed. We propose a new method to identify modular structure in task-related functional magnetic resonance imaging (fMRI) networks. The modular structure was obtained directly from correlation coefficients and thus retained information about both signs and weights. The method was applied to functional data acquired during a yes-no odor recognition memory task performed by young and elderly adults. Four response categories were explored: correct (Hit) and incorrect (False alarm, FA) recognition and correct and incorrect rejection. We extracted time series data for 36 areas as a function of response categories and age groups and calculated condition-based weighted correlation matrices. Overall, condition-based modular partitions were more homogeneous in young than elderly subjects. Using partition similarity-based statistics and a posteriori statistical analyses, we demonstrated that several areas, including the hippocampus, caudate nucleus, and anterior cingulate gyrus, belonged to the same module more frequently during Hit than during all other conditions. Modularity values were negatively correlated with memory scores in the Hit condition and positively correlated with bias scores (liberal/conservative attitude) in the Hit and FA conditions. We further demonstrated that the proportion of positive and negative links between areas of different modules (i.e., the proportion of correlated and anti-correlated areas

  2. OTUB1 co-opts Lys48-linked ubiquitin recognition to suppress E2 enzyme function

    PubMed Central

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

    2012-01-01

    SUMMARY Ubiquitylation entails the concerted action of E1, E2 and E3 enzymes. We recently reported that OTUB1, a deubiquitylase, inhibits the DNA damage response independently of its isopeptidase activity. OTUB1 does so by blocking ubiquitin transfer by UBC13, the cognate E2 enzyme for RNF168. OTUB1 also inhibits E2s of the UBE2D and UBE2E families. Here we elucidate the structural mechanism by which OTUB1 binds E2s to inhibit ubiquitin transfer. OTUB1 recognizes ubiquitin-charged E2s through contacts with both donor ubiquitin and the E2 enzyme. Surprisingly, free ubiquitin associates with the canonical distal ubiquitin-binding site on OTUB1 to promote formation of the inhibited E2 complex. Lys48 of donor ubiquitin lies near the OTUB1 catalytic site and the C-terminus of free ubiquitin, a configuration that mimics the products of Lys48-linked ubiquitin chain cleavage. OTUB1 therefore co-opts Lys48-linked ubiquitin chain recognition to suppress ubiquitin conjugation and the DNA damage response. PMID:22325355

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

    SciTech Connect

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

    2012-03-26

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

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

    PubMed Central

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

    2015-01-01

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

  5. Verrucomicrobial community structure and abundance as indicators for changes in chemical factors linked to soil fertility.

    PubMed

    Navarrete, Acacio Aparecido; Soares, Tielle; Rossetto, Raffaella; van Veen, Johannes Antonie; Tsai, Siu Mui; Kuramae, Eiko Eurya

    2015-09-01

    Here we show that verrucomicrobial community structure and abundance are extremely sensitive to changes in chemical factors linked to soil fertility. Terminal restriction fragment length polymorphism fingerprint and real-time quantitative PCR assay were used to analyze changes in verrucomicrobial communities associated with contrasting soil nutrient conditions in tropical regions. In case study Model I ("Slash-and-burn deforestation") the verrucomicrobial community structures revealed disparate patterns in nutrient-enriched soils after slash-and-burn deforestation and natural nutrient-poor soils under an adjacent primary forest in the Amazonia (R = 0.819, P = 0.002). The relative proportion of Verrucomicrobia declined in response to increased soil fertility after slash-and-burn deforestation, accounting on average, for 4 and 2 % of the total bacterial signal, in natural nutrient-poor forest soils and nutrient-enriched deforested soils, respectively. In case study Model II ("Management practices for sugarcane") disparate patterns were revealed in sugarcane rhizosphere sampled on optimal and deficient soil fertility for sugarcane (R = 0.786, P = 0.002). Verrucomicrobial community abundance in sugarcane rhizosphere was negatively correlated with soil fertility, accounting for 2 and 5 % of the total bacterial signal, under optimal and deficient soil fertility conditions for sugarcane, respectively. In nutrient-enriched soils, verrucomicrobial community structures were related to soil factors linked to soil fertility, such as total nitrogen, phosphorus, potassium and sum of bases, i.e., the sum of calcium, magnesium and potassium contents. We conclude that community structure and abundance represent important ecological aspects in soil verrucomicrobial communities for tracking the changes in chemical factors linked to soil fertility under tropical environmental conditions.

  6. N-linked glycans of the human insulin receptor and their distribution over the crystal structure.

    PubMed

    Sparrow, Lindsay G; Lawrence, Michael C; Gorman, Jeffrey J; Strike, Phillip M; Robinson, Christine P; McKern, Neil M; Ward, Colin W

    2008-04-01

    The human insulin receptor (IR) homodimer is heavily glycosylated and contains a total of 19 predicted N-linked glycosylation sites in each monomer. The recent crystal structure of the IR ectodomain shows electron density consistent with N-linked glycosylation at the majority of sites present in the construct. Here, we describe a refined structure of the IR ectodomain that incorporates all of the N-linked glycans and reveals the extent to which the attached glycans mask the surface of the IR dimer from interaction with antibodies or other potential therapeutic binding proteins. The usefulness of Fab complexation in the crystallization of heavily glycosylated proteins is also discussed. The compositions of the glycans on IR expressed in CHO-K1 cells and the glycosylation deficient Lec8 cell line were determined by protease digestion, glycopeptide purification, amino acid sequence analysis, and mass spectrometry. Collectively the data reveal: multiple species of complex glycan at residues 25, 255, 295, 418, 606, 624, 742, 755, and 893 (IR-B numbering); multiple species of high-mannose glycan at residues 111 and 514; a single species of complex glycan at residue 671; and a single species of high-mannose glycan at residue 215. Residue 16 exhibited a mixture of complex, hybrid, and high-mannose glycan species. Of the remaining five predicted N-linked sites, those at residues 397 and 906 were confirmed by amino acid sequencing to be glycosylated, while that at residue 78 and the atypical (NKC) site at residue 282 were not glycosylated. The peptide containing the final site at residue 337 was not recovered but is seen to be glycosylated in the electron density maps of the IR ectodomain. The model of the fully glycosylated IR reveals that the sites carrying high-mannose glycans lie at positions of relatively low steric accessibility.

  7. The abundant symmetry structure of hierarchies of nonlinear equations obtained by reciprocal links

    NASA Astrophysics Data System (ADS)

    Carillo, Sandra; Fuchssteiner, Benno

    1989-07-01

    Explicit computation for a Kawamoto-type equation shows that there is a rich associated symmetry structure for four separate hierarchies of nonlinear integrodifferential equations. Contrary to the general belief that symmetry groups for nonlinear evolution equations in 1+1 dimensions have to be Abelian, it is shown that, in this case, the symmetry group is noncommutative. Its semisimple part is isomorphic to the affine Lie algebra A(1)1 associated to sl(2,C). In two of the additional hierarchies that were found, an explicit dependence of the independent variable occurs. Surprisingly, the generic invariance for the Kawamoto-type equation obtained in Rogers and Carillo [Phys. Scr. 36, 865 (1987)] via a reciprocal link to the Möbius invariance of the singularity equation of the Kaup-Kupershmidt (KK) equation only holds for one of the additional hierarchies of symmetry groups. Thus the generic invariance is not a universal property for the complete symmetry group of equations obtained by reciprocal links. In addition to these results, the bi-Hamiltonian formulation of the hierarchy is given. A direct Bäcklund transformation between the (KK) hierarchy and the hierarchy of singularity equation for the Caudrey-Dodd-Gibbon-Sawada-Kotera equation is exhibited: This shows that the abundant symmetry structure found for the Kawamoto equation must exist for all fifth-order equations, which are known to be completely integrable since these equations are connected either by Bäcklund transformations or reciprocal links. It is shown that similar results must hold for all hierarchies emerging out of singularity hierarchies via reciprocal links. Furthermore, general aspects of the results are discussed.

  8. Remission of Depression in Parents: Links to Healthy Functioning in their Children

    PubMed Central

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

    2010-01-01

    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 7–17 years old (Mean=12.13, SD=2.31); 126 parents were in treatment for depression and 97 parents were nondepressed. Children were evaluated six times over two years. Changes in parents’ depressive symptoms predicted changes in children’s depressive symptoms over and above the effect of time; children’s symptoms significantly predicted parents’ symptoms. Trajectories of children’s depressive symptoms differed significantly for children of remitted versus nonremitted depressed parents, and these differences were significantly predicted by their parents’ level of depression. The relation between parents’ and children’s depressive symptoms was partially mediated by parental acceptance. PMID:21291439

  9. Linking Cultural Competence to Functional Life Outcomes in Mental Health Care Settings.

    PubMed

    Michalopoulou, Georgia; Falzarano, Pamela; Butkus, Michael; Zeman, Lori; Vershave, Judy; Arfken, Cynthia

    2014-01-01

    Minorities in the United States have well-documented health disparities. Cultural barriers and biases by health care providers may contribute to lower quality of services which may contribute to these disparities. However, evidence linking cultural competency and health outcomes is lacking. This study, part of an ongoing quality improvement effort, tested the mediation hypothesis that patients' perception of provider cultural competency indirectly influences patients' health outcomes through process of care. Data were from patient satisfaction surveys collected in seven mental health clinics (n=94 minority patients). Consistent with our hypothesis, patients' perception of clinicians' cultural competency was indirectly associated with patients' self-reported improvements in social interactions, improvements in performance at work or school, and improvements in managing life problems through the patients' experience of respect, trust, and communication with the clinician. These findings indicate that process of care characteristics during the clinical encounter influence patients' perceptions of clinicians' cultural competency and affect functional outcomes.

  10. Aegerolysins: Structure, function, and putative biological role

    PubMed Central

    Berne, Sabina; Lah, Ljerka; Sepčić, Kristina

    2009-01-01

    Aegerolysins, discovered in fungi, bacteria and plants, are highly similar proteins with interesting biological properties. Certain aegerolysins possess antitumoral, antiproliferative, and antibacterial activities. Further possible medicinal applications include their use in the prevention of atherosclerosis, or as vaccines. Additional biotechnological value of fungal aegerolysins lies in their involvement in development, which could improve cultivation of commercially important edible mushrooms. Besides, new insights on microheterogeneity of raft-like membrane domains could be gained by using aegerolysins as specific markers in cell and molecular biology. Although the exact function of aegerolysins in their producing organisms remains to be explained, they are biochemically well characterized all-β structured proteins sharing the following common features: low isoelectric points, similar molecular weights (15–17 kDa), and stability in a wide pH range. PMID:19309687

  11. 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.; DeVincenzi, Donald L. (Technical Monitor)

    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.

  12. Structure and function of eukaryotic chromosomes

    SciTech Connect

    Hennig, W.

    1987-01-01

    Contents: Introduction; Polytene Chromosomel Giant Chromosomes in Ciliates; The sp-I Genes in the Balbiani Rings of Chironomus Salivary Glands; The White Locus of Drosophila Melanogaster; The Genetic and Molecular Organization of the Dense Cluster of Functionally Related Vital Genes in the DOPA Decarboxylase Region of the Drosophila melanogaster Genome; Heat Shock Puffs and Response to Environmental Stress; The Y Chromosomal Lampbrush Loops of Drosophila; Contributions of Electron Microscopic Spreading Preparations (''Miller Spreads'') to the Analysis of Chromosome Structure; Replication of DNA in Eukaryotic Chromosomes; Gene Amplification in Dipteran Chromosomes; The Significance of Plant Transposable Elements in Biologically Relevant Processes; Arrangement of Chromosomes in Interphase Cell Nuclei; Heterochromatin and the Phenomenon of Chromosome Banding; Multiple Nonhistone Protein-DNA Complexes in Chromatin Regulate the Cell- and Stage-Specific Activity of an Eukaryotic Gene; Genetics of Sex Determination in Eukaryotes; Application of Basic Chromosome Research in Biotechnology and Medicine. This book presents an overview of various aspects of chromosome research.

  13. Guanylyl cyclase structure, function and regulation.

    PubMed

    Potter, Lincoln R

    2011-12-01

    Nitric oxide, bicarbonate, natriuretic peptides (ANP, BNP and CNP), guanylins, uroguanylins and guanylyl cyclase activating proteins (GCAPs) activate a family of enzymes variously called guanyl, guanylyl or guanylate cyclases that catalyze the conversion of guanosine triphosphate to cyclic guanosine monophosphate (cGMP) and pyrophosphate. Intracellular cyclic GMP is a second messenger that modulates: platelet aggregation, neurotransmission, sexual arousal, gut peristalsis, blood pressure, long bone growth, intestinal fluid secretion, lipolysis, phototransduction, cardiac hypertrophy and oocyte maturation. This review briefly discusses the discovery of cGMP and guanylyl cyclases, then nitric oxide, nitric oxide synthase and soluble guanylyl cyclase are described in slightly greater detail. Finally, the structure, function, and regulation of the individual mammalian single membrane-spanning guanylyl cyclases GC-A, GC-B, GC-C, GC-D, GC-E, GC-F and GC-G are described in greatest detail as determined by biochemical, cell biological and gene-deletion studies.

  14. The Spin Structure Function g2

    SciTech Connect

    Rock, Stephen E.

    2003-02-27

    We have measured the spin structure functions g{sub 2}{sup p} and g{sub 2}{sup d} over the kinematic range 0.02 {le} x {le} 0.8 and 0.7 {le} Q{sup 2} {le} 20 GeV{sup 2} by scattering 29.1 and 32.3 GeV longitudinally polarized electrons from transversely polarized NH{sub 3} and {sup 6}LiD targets. Our measured g{sub 2} approximately follows the twist-2 Wandzura-Wilczek calculation. The twist-3 reduced matrix elements d{sub 2}{sup p} and d{sub 2}{sup n} are less than two standard deviations from zero. The data are inconsistent with the Burkhardt-Cottingham sum rule. The Efremov-Leader-Teryaev integral is consistent with zero within our measured kinematic range.

  15. Relationships Between Watershed Emergy Flow and Coastal New England Salt Marsh Structure, Function, and Condition

    EPA Science Inventory

    This study evaluated the link between watershed activities and salt marsh structure, function, and condition using spatial emergy flow density (areal empower density) in the watershed and field data from 10 tidal salt marshes in Narragansett Bay, RI. The field-collected data wer...

  16. Structural changes in soil communities after triclopyr application in soils invaded by Acacia dealbata Link.

    PubMed

    Souza-Alonso, Pablo; Guisande, Alejandra; González, Luís

    2015-01-01

    Triclopyr is a commonly used herbicide in the control of woody plants and can exhibit toxic effects to soil microorganisms. However, the impact on soils invaded by plant exotics has not yet been addressed. Here, we present the results of an 18-month field study conducted to evaluate the impact of triclopyr on the structure of fungal and bacterial communities in soils invaded by Acacia dealbata Link, through the use of denature gradient gel electrophoresis. After triclopyr application, analyses of bacterial fingerprints suggested a change in the structure of the soil bacterial community, whereas the structure of the soil fungal community remained unaltered. Bacterial density and F:B ratio values changed across the year but were not altered due to herbicide spraying. On the contrary, fungal diversity was increased in plots sprayed with triclopyr 5 months after the first application. Richness and diversity (H') of both bacteria and fungi were not modified after triclopyr application.

  17. An apomixis-linked ORC3-like pseudogene is associated with silencing of its functional homolog in apomictic Paspalum simplex.

    PubMed

    Siena, Lorena A; Ortiz, Juan Pablo A; Calderini, Ornella; Paolocci, Francesco; Cáceres, Maria E; Kaushal, Pankaj; Grisan, Simone; Pessino, Silvina C; Pupilli, Fulvio

    2016-03-01

    Apomixis in plants consists of asexual reproduction by seeds. Here we characterized at structural and functional levels an apomixis-linked sequence of Paspalum simplex homologous to subunit 3 of the ORIGIN RECOGNITION COMPLEX (ORC3). ORC is a multiprotein complex which controls DNA replication and cell differentiation in eukaryotes. Three PsORC3 copies were identified, each one characterized by a specific expression profile. Of these, PsORC3a, specific for apomictic genotypes, is a pseudogene that was poorly and constitutively expressed in all developmental stages of apomictic flowers, whereas PsORC3b, the putative functional gene in sexual flowers, showed a precise time-related regulation. Sense transcripts of PsORC3 were expressed in the female cell lineage of both apomictic and sexual reproductive phenotypes, and in aposporous initials. Although strong expression was detected in sexual early endosperm, no expression was present in the apomictic endosperm. Antisense PsORC3 transcripts were revealed exclusively in apomictic germ cell lineages. Defective orc3 mutants of rice and Arabidopsis showed normal female gametophytes although the embryo and endosperm were arrested at early phases of development. We hypothesize that PsORC3a is associated with the down-regulation of its functional homolog and with the development of apomictic endosperm which deviates from the canonical 2(maternal):1(paternal) genome ratio.

  18. Functional deregulation of KIT: link to mast cell proliferative diseases and other neoplasms.

    PubMed

    Cruse, Glenn; Metcalfe, Dean D; Olivera, Ana

    2014-05-01

    In this review, the authors discuss common gain-of-function mutations in the stem cell factor receptor KIT found in mast cell proliferation disorders and summarize the current understanding of the molecular mechanisms by which these transforming mutations may affect KIT structure and function leading to altered downstream signaling and cellular transformation. Drugs targeting KIT have shown mixed success in the treatment of mastocytosis and other hyperproliferative diseases. A brief overview of the most common KIT inhibitors currently used, the reasons for the varied clinical results of such inhibitors and a discussion of potential new strategies are provided.

  19. Bromodomains: Structure, function and pharmacology of inhibition.

    PubMed

    Ferri, Elena; Petosa, Carlo; McKenna, Charles E

    2016-04-15

    Bromodomains are epigenetic readers of histone acetylation involved in chromatin remodeling and transcriptional regulation. The human proteome comprises 46 bromodomain-containing proteins with a total of 61 bromodomains, which, despite highly conserved structural features, recognize a wide array of natural peptide ligands. Over the past five years, bromodomains have attracted great interest as promising new epigenetic targets for diverse human diseases, including inflammation, cancer, and cardiovascular disease. The demonstration in 2010 that two small molecule compounds, JQ1 and I-BET762, potently inhibit proteins of the bromodomain and extra-terminal (BET) family with translational potential for cancer and inflammatory disease sparked intense efforts in academia and pharmaceutical industry to develop novel bromodomain antagonists for therapeutic applications. Several BET inhibitors are already in clinical trials for hematological malignancies, solid tumors and cardiovascular disease. Currently, the field faces the challenge of single-target selectivity, especially within the BET family, and of overcoming problems related to the development of drug resistance. At the same time, new trends in bromodomain inhibitor research are emerging, including an increased interest in non-BET bromodomains and a focus on drug synergy with established antitumor agents to improve chemotherapeutic efficacy. This review presents an updated view of the structure and function of bromodomains, traces the development of bromodomain inhibitors and their potential therapeutic applications, and surveys the current challenges and future directions of this vibrant new field in drug discovery.

  20. Structure and functionality of bromine doped graphite.

    PubMed

    Hamdan, Rashid; Kemper, A F; Cao, Chao; Cheng, H P

    2013-04-28

    First-principles calculations are used to study the enhanced in-plane conductivity observed experimentally in Br-doped graphite, and to study the effect of external stress on the structure and functionality of such systems. The model used in the numerical calculations is that of stage two doped graphite. The band structure near the Fermi surface of the doped systems with different bromine concentrations is compared to that of pure graphite, and the charge transfer between carbon and bromine atoms is analyzed to understand the conductivity change along different high symmetry directions. Our calculations show that, for large interlayer separation between doped graphite layers, bromine is stable in the molecular form (Br2). However, with increased compression (decreased layer-layer separation) Br2 molecules tend to dissociate. While in both forms, bromine is an electron acceptor. The charge exchange between the graphite layers and Br atoms is higher than that with Br2 molecules. Electron transfer to the Br atoms increases the number of hole carriers in the graphite sheets, resulting in an increase of conductivity.

  1. Structure and functionality of bromine doped graphite

    SciTech Connect

    Hamdan, Rashid; Kemper, A. F.; Cao Chao; Cheng, H. P.

    2013-04-28

    First-principles calculations are used to study the enhanced in-plane conductivity observed experimentally in Br-doped graphite, and to study the effect of external stress on the structure and functionality of such systems. The model used in the numerical calculations is that of stage two doped graphite. The band structure near the Fermi surface of the doped systems with different bromine concentrations is compared to that of pure graphite, and the charge transfer between carbon and bromine atoms is analyzed to understand the conductivity change along different high symmetry directions. Our calculations show that, for large interlayer separation between doped graphite layers, bromine is stable in the molecular form (Br{sub 2}). However, with increased compression (decreased layer-layer separation) Br{sub 2} molecules tend to dissociate. While in both forms, bromine is an electron acceptor. The charge exchange between the graphite layers and Br atoms is higher than that with Br{sub 2} molecules. Electron transfer to the Br atoms increases the number of hole carriers in the graphite sheets, resulting in an increase of conductivity.

  2. Extraction of neutron structure from tagged structure functions

    NASA Astrophysics Data System (ADS)

    Cosyn, W.; Sargsian, M.

    2011-09-01

    We present work in a model used to describe semi-inclusive deep inelastic scattering off the deuteron. The model uses the virtual nucleon approximation to describe the interaction of the photon with the bound neutron and the generalized eikonal approximation is applied to calculate the final-state interaction diagram. Comparison with data taken at Jefferson Lab shows good agreement in the covered range of kinematics and points at a largely suppressed off-shell rescattering amplitude. The W and Q2 dependences of the total cross section and slope factor of the interaction of DIS products, X, off the spectator nucleon are extracted. Starting from the JLab data and our model calculations, we outline and apply an extrapolation method to obtain the neutron structure function F2N at high Bjorken x.

  3. Structure, Function, and Evolution of Rice Centromeres

    SciTech Connect

    Jiang, Jiming

    2010-02-04

    The centromere is the most characteristic landmark of eukaryotic chromosomes. Centromeres function as the site for kinetochore assembly and spindle attachment, allowing for the faithful pairing and segregation of sister chromatids during cell division. Characterization of centromeric DNA is not only essential to understand the structure and organization of plant genomes, but it is also a critical step in the development of plant artificial chromosomes. The centromeres of most model eukaryotic species, consist predominantly of long arrays of satellite DNA. Determining the precise DNA boundary of a centromere has proven to be a difficult task in multicellular eukaryotes. We have successfully cloned and sequenced the centromere of rice chromosome 8 (Cen8), representing the first fully sequenced centromere from any multicellular eukaryotes. The functional core of Cen8 spans ~800 kb of DNA, which was determined by chromatin immunoprecipitation (ChIP) using an antibody against the rice centromere-specific H3 histone. We discovered 16 actively transcribed genes distributed throughout the Cen8 region. In addition to Cen8, we have characterized eight additional rice centromeres using the next generation sequencing technology. We discovered four subfamilies of the CRR retrotransposon that is highly enriched in rice centromeres. CRR elements are constitutively transcribed and different CRR subfamilies are differentially processed by RNAi. These results suggest that different CRR subfamilies may play different roles in the RNAi-mediated pathway for formation and maintenance of centromeric chromatin.

  4. Pentraxins: Structure, Function, and Role in Inflammation

    PubMed Central

    Du Clos, Terry W.

    2013-01-01

    The pentraxins are an ancient family of proteins with a unique architecture found as far back in evolution as the Horseshoe crab. In humans the two members of this family are C-reactive protein and serum amyloid P. Pentraxins are defined by their sequence homology, their pentameric structure and their calcium-dependent binding to their ligands. Pentraxins function as soluble pattern recognition molecules and one of the earliest and most important roles for these proteins is host defense primarily against pathogenic bacteria. They function as opsonins for pathogens through activation of the complement pathway and through binding to Fc gamma receptors. Pentraxins also recognize membrane phospholipids and nuclear components exposed on or released by damaged cells. CRP has a specific interaction with small nuclear ribonucleoproteins whereas SAP is a major recognition molecule for DNA, two nuclear autoantigens. Studies in autoimmune and inflammatory disease models suggest that pentraxins interact with macrophage Fc receptors to regulate the inflammatory response. Because CRP is a strong acute phase reactant it is widely used as a marker of inflammation and infection. PMID:24167754

  5. The Structural and Functional Organization of Cognition.

    PubMed

    Snow, Peter J

    2016-01-01

    This article proposes that what have been historically and contemporarily defined as different domains of human cognition are served by one of four functionally- and structurally-distinct areas of the prefrontal cortex (PFC). Their contributions to human intelligence are as follows: (a) BA9, enables our emotional intelligence, engaging the psychosocial domain; (b) BA47, enables our practical intelligence, engaging the material domain; (c) BA46 (or BA46-9/46), enables our abstract intelligence, engaging the hypothetical domain; and (d) BA10, enables our temporal intelligence, engaging in planning within any of the other three domains. Given their unique contribution to human cognition, it is proposed that these areas be called the, social (BA9), material (BA47), abstract (BA46-9/46) and temporal (BA10) mind. The evidence that BA47 participates strongly in verbal and gestural communication suggests that language evolved primarily as a consequence of the extreme selective pressure for practicality; an observation supported by the functional connectivity between BA47 and orbital areas that negatively reinforce lying. It is further proposed that the abstract mind (BA46-9/46) is the primary seat of metacognition charged with creating adaptive behavioral strategies by generating higher-order concepts (hypotheses) from lower-order concepts originating from the other three domains of cognition.

  6. The Structural and Functional Organization of Cognition

    PubMed Central

    Snow, Peter J.

    2016-01-01

    This article proposes that what have been historically and contemporarily defined as different domains of human cognition are served by one of four functionally- and structurally-distinct areas of the prefrontal cortex (PFC). Their contributions to human intelligence are as follows: (a) BA9, enables our emotional intelligence, engaging the psychosocial domain; (b) BA47, enables our practical intelligence, engaging the material domain; (c) BA46 (or BA46-9/46), enables our abstract intelligence, engaging the hypothetical domain; and (d) BA10, enables our temporal intelligence, engaging in planning within any of the other three domains. Given their unique contribution to human cognition, it is proposed that these areas be called the, social (BA9), material (BA47), abstract (BA46-9/46) and temporal (BA10) mind. The evidence that BA47 participates strongly in verbal and gestural communication suggests that language evolved primarily as a consequence of the extreme selective pressure for practicality; an observation supported by the functional connectivity between BA47 and orbital areas that negatively reinforce lying. It is further proposed that the abstract mind (BA46-9/46) is the primary seat of metacognition charged with creating adaptive behavioral strategies by generating higher-order concepts (hypotheses) from lower-order concepts originating from the other three domains of cognition. PMID:27799901

  7. Physicochemical properties and micro-structural characteristics in starch from kudzu root as affected by cross-linking.

    PubMed

    Chen, Boru; Dang, Leping; Zhang, Xiao; Fang, Wenzhi; Hou, Mengna; Liu, Tiankuo; Wang, Zhanzhong

    2017-03-15

    Kudzu starch was cross-linked with sodium trimetaphosphate (STMP) at different temperatures, time and of STMP concentrations in this work. The cross-linked starches (CLSs) were fractionated further into cross-linked amylose and amylopectin in order to compare the effect of cross-linking on the microstructure. According to scanning electron microscope (SEM), CLSs displayed the resemble appearance of spherical and polygonal shapes like NS. X-ray diffraction (XRD) revealed that amylose of native starch (A), NS and CLS displayed a combination of A-type and B-type structure, while that was not found in amylose of cross-linked starch (CLA). The deconvoluted fourier transform infrared (FT-IR) indicated that crystal structure of kudzu starch was losing with the proceeding of cross-linking reaction. The CLSs exhibited a higher retrogradation and freeze-thaw stability than NS. This was accompanied by a significant decrease in sedimentation, transparency, swelling power and solubility.

  8. Structure-function relationships of human meniscus.

    PubMed

    Danso, Elvis K; Oinas, Joonas M T; Saarakkala, Simo; Mikkonen, Santtu; Töyräs, Juha; Korhonen, Rami K

    2017-03-01

    Biomechanical properties of human meniscus have been shown to be site-specific. However, it is not known which meniscus constituents at different depths and locations contribute to biomechanical properties obtained from indentation testing. Therefore, we investigated the composition and structure of human meniscus in a site- and depth-dependent manner and their relationships with tissue site-specific biomechanical properties. Elastic and poroelastic properties were analyzed from experimental stress-relaxation and sinusoidal indentation measurements with fibril reinforced poroelastic finite element modeling. Proteoglycan (PG) and collagen contents, as well as the collagen orientation angle, were determined as a function of tissue depth using microscopic and spectroscopic methods, and they were compared with biomechanical properties. For all the measurement sites (anterior, middle and posterior) of lateral and medial menisci (n=26), PG content and collagen orientation angle increased as a function of tissue depth while the collagen content had an initial sharp increase followed by a decrease across tissue depth. The highest values (p<0.05) of elastic parameters (equilibrium and instantaneous moduli) and strain-dependent biomechanical parameters (strain-dependent fibril network modulus and permeability) were observed in the anterior horn of the medial meniscus. This location had also higher (p<0.05) PG content in the deep meniscus, higher (p<0.05) collagen content in the entire tissue depth, and lower (p<0.05) collagen orientation angle at the superficial tissue, as compared to many other locations. On the other hand, in certain comparisons (such as anterior vs. middle sites of the medial meniscus) significantly higher (p<0.05) collagen content and lower orientation angle, without any difference in the PG content, were consistent with increased meniscus modulus and/or nonlinear permeability. This study suggests that nonlinear biomechanical properties of meniscus

  9. Structure of the sirtuin-linked macrodomain SAV0325 from Staphylococcus aureus.

    PubMed

    Appel, C Denise; Feld, Geoffrey K; Wallace, Bret D; Williams, R Scott

    2016-09-01

    Cells use the post-translational modification ADP-ribosylation to control a host of biological activities. In some pathogenic bacteria, an operon-encoded mono-ADP-ribosylation cycle mediates response to host-induced oxidative stress. In this system, reversible mono ADP-ribosylation of a lipoylated target protein represses oxidative stress response. An NAD(+) -dependent sirtuin catalyzes the single ADP-ribose (ADPr) addition, while a linked macrodomain-containing protein removes the ADPr. Here we report the crystal structure of the sitruin-linked macrodomain protein from Staphylococcus aureus, SauMacro (also known as SAV0325) to 1.75-Å resolution. The monomeric SauMacro bears a previously unidentified Zn(2+) -binding site that putatively aids in substrate recognition and catalysis. An amino-terminal three-helix bundle motif unique to this class of macrodomain proteins provides a structural scaffold for the Zn(2+) site. Structural features of the enzyme further indicate a cleft proximal to the Zn(2+) binding site appears well suited for ADPr binding, while a deep hydrophobic channel in the protein core is suitable for binding the lipoate of the lipoylated protein target.

  10. Photosynthetic pathway alters hydraulic structure and function in woody plants.

    PubMed

    Kocacinar, Ferit; Sage, Rowan F

    2004-04-01

    Xylem structure and function is proposed to reflect an evolutionary balance between demands for efficient movement of water to the leaf canopy and resistance to cavitation during high xylem tension. Water use efficiency (WUE) affects this balance by altering the water cost of photosynthesis. Therefore species of greater WUE, such as C(4) plants, should have altered xylem properties. To evaluate this hypothesis, we assessed the hydraulic and anatomical properties of 19 C(3) and C(4) woody species from arid regions of the American west and central Asia. Specific conductivity of stem xylem ( K(s) ) was 16%-98% lower in the C(4) than C(3) shrubs from the American west. In the Asian species, the C(3) Nitraria schoberi had similar and Halimodendron halodendron higher K(s) values compared with three C(4) species. Leaf specific conductivity ( K(L); hydraulic conductivity per leaf area) was 60%-98% lower in the C(4) than C(3) species, demonstrating that the presence of the C(4) pathway alters the relationship between leaf area and the ability of the xylem to transport water. C(4) species produced similar or smaller vessels than the C(3) shrubs except in Calligonum, and most C(4) shrubs exhibited higher wood densities than the C(3) species. Together, smaller conduit size and higher wood density indicate that in most cases, the C(4) shrubs exploited higher WUE by altering xylem structure to enhance safety from cavitation. In a minority of cases, the C(4) shrubs maintained similar xylem properties but enhanced the canopy area per branch. By establishing a link between C(4) photosynthesis and xylem structure, this study indicates that other phenomena that affect WUE, such as atmospheric CO(2) variation, may also affect the evolution of wood structure and function.

  11. Structures, structural hierarchy, and function in sea urchin spines

    NASA Astrophysics Data System (ADS)

    Stock, S. R.; Ebert, T. A.; Ignatiev, K.; De Carlo, F.

    2006-08-01

    Sea urchin spines protect the animal's body from predators and from the effect of high energy environments. The spines of urchins from different orders, families and genera have very different sizes, morphologies and microarchitectures, and the different designs of sea urchin spines reveal much about the design space available for functional biogenic calcite-based structures. The 3D microarchitecture of primary spines of a number of sea urchins was studied with synchrotron microCT and reconstructed with 5 μm or smaller voxels (volume elements), and similarities and differences were determined in order to better understand the design space. Hollow spines from different genera of the family Diadematidae, order Diadematoida, are one type of solution, but significant differences were observed within this phylogenic subset. Spines from members of order Echinoidea, family Toxopneustidae, employ a very different strategy, one that emphasizes interconnected trabeculae to a greater degree than do the diadematids. Numerical data for some 3D structural characteristics are presented, data that would be impractical to obtain by methods other than microCT.

  12. Structural basis for recognition of 2',5'-linked oligoadenylates by human ribonuclease L.

    PubMed

    Tanaka, Nobutada; Nakanishi, Masayuki; Kusakabe, Yoshio; Goto, Yoshikuni; Kitade, Yukio; Nakamura, Kazuo T

    2004-10-13

    An interferon-induced endoribonuclease, ribonuclease L (RNase L), is implicated in both the molecular mechanism of action of interferon and the fundamental control of RNA stability in mammalian cells. RNase L is catalytically active only after binding to an unusual activator molecule containing a 5'-phosphorylated 2',5'-linked oligoadenylate (2-5A), in the N-terminal half. Here, we report the crystal structure of the N-terminal ankyrin repeat domain (ANK) of human RNase L complexed with the activator 2-5A. This is the first structural view of an ankyrin repeat structure directly interacting with a nucleic acid, rather than with a protein. The ANK domain folds into eight ankyrin repeat elements and forms an extended curved structure with a concave surface. The 2-5A molecule is accommodated at a concave site and directly interacts with ankyrin repeats 2-4. Interestingly, two structurally equivalent 2-5A binding motifs are found at repeats 2 and 4. The structural basis for 2-5A recognition by ANK is essential for designing stable 2-5As with a high likelihood of activating RNase L.

  13. Bacterial structures and ecosystem functions in glaciated floodplains: contemporary states and potential future shifts.

    PubMed

    Freimann, Remo; Bürgmann, Helmut; Findlay, Stuart E G; Robinson, Christopher T

    2013-12-01

    Glaciated alpine floodplains are responding quickly to climate change through shrinking ice masses. Given the expected future changes in their physicochemical environment, we anticipated variable shifts in structure and ecosystem functioning of hyporheic microbial communities in proglacial alpine streams, depending on present community characteristics and landscape structures. We examined microbial structure and functioning during different hydrologic periods in glacial (kryal) streams and, as contrasting systems, groundwater-fed (krenal) streams. Three catchments were chosen to cover an array of landscape features, including interconnected lakes, differences in local geology and degree of deglaciation. Community structure was assessed by automated ribosomal intergenic spacer analysis and microbial function by potential enzyme activities. We found each catchment to contain a distinct bacterial community structure and different degrees of separation in structure and functioning that were linked to the physicochemical properties of the waters within each catchment. Bacterial communities showed high functional plasticity, although achieved by different strategies in each system. Typical kryal communities showed a strong linkage of structure and function that indicated a major prevalence of specialists, whereas krenal sediments were dominated by generalists. With the rapid retreat of glaciers and therefore altered ecohydrological characteristics, lotic microbial structure and functioning are likely to change substantially in proglacial floodplains in the future. The trajectory of these changes will vary depending on contemporary bacterial community characteristics and landscape structures that ultimately determine the sustainability of ecosystem functioning.

  14. Bacterial structures and ecosystem functions in glaciated floodplains: contemporary states and potential future shifts

    PubMed Central

    Freimann, Remo; Bürgmann, Helmut; Findlay, Stuart EG; Robinson, Christopher T

    2013-01-01

    Glaciated alpine floodplains are responding quickly to climate change through shrinking ice masses. Given the expected future changes in their physicochemical environment, we anticipated variable shifts in structure and ecosystem functioning of hyporheic microbial communities in proglacial alpine streams, depending on present community characteristics and landscape structures. We examined microbial structure and functioning during different hydrologic periods in glacial (kryal) streams and, as contrasting systems, groundwater-fed (krenal) streams. Three catchments were chosen to cover an array of landscape features, including interconnected lakes, differences in local geology and degree of deglaciation. Community structure was assessed by automated ribosomal intergenic spacer analysis and microbial function by potential enzyme activities. We found each catchment to contain a distinct bacterial community structure and different degrees of separation in structure and functioning that were linked to the physicochemical properties of the waters within each catchment. Bacterial communities showed high functional plasticity, although achieved by different strategies in each system. Typical kryal communities showed a strong linkage of structure and function that indicated a major prevalence of specialists, whereas krenal sediments were dominated by generalists. With the rapid retreat of glaciers and therefore altered ecohydrological characteristics, lotic microbial structure and functioning are likely to change substantially in proglacial floodplains in the future. The trajectory of these changes will vary depending on contemporary bacterial community characteristics and landscape structures that ultimately determine the sustainability of ecosystem functioning. PMID:23842653

  15. Structural Analysis and Mechanical Characterization of Hyaluronic Acid-Based Doubly Cross-Linked Networks

    PubMed Central

    Jha, Amit K.; Hule, Rohan A.; Jiao, Tong; Teller, Sean S.; Clifton, Rodney J.; Duncan, Randall L.; Pochan, Darrin J.; Jia, Xinqiao

    2009-01-01

    We have created a new class of hyaluronic acid (HA)-based hydrogel materials with HA hydrogel particles (HGPs) embedded in and covalently cross-linked to a secondary network. HA HGPs with an average diameter of ∼900 nm and narrow particle size distribution were synthesized using a refined reverse micelle polymerization technique. The average mesh size of the HGPs was estimated to be approximately 5.5 to 7.0 nm by a protein uptake experiment. Sodium periodate oxidation not only introduced aldehyde groups to the particles but also reduced the average particle size. The aldehyde groups generated were used as reactive handles for subsequent cross-linking with an HA derivative containing hydrazide groups. The resulting macroscopic gels contain two distinct hierarchical networks (doubly cross-linked networks, DXNs): one within individual particles and another among different particles. Bulk gels (BGs) formed by direct mixing of HA derivatives with mutually reactive groups were included for comparison. The hydrogel microstructures were collectively characterized by microscopy and neutron scattering techniques. Their viscoelasticity was quantified at low frequencies (0.1−10 Hz) using a controlled stress rheometer and at high frequencies (up to 200 Hz) with a home-built torsional wave apparatus. Both BGs and DXNs are stable elastic gels that become stiffer at higher frequencies. The HA-based DXN offers unique structural hierarchy and mechanical properties that are suitable for soft tissue regeneration. PMID:20046226

  16. An Improved Ensemble of Random Vector Functional Link Networks Based on Particle Swarm Optimization with Double Optimization Strategy.

    PubMed

    Ling, Qing-Hua; Song, Yu-Qing; Han, Fei; Yang, Dan; Huang, De-Shuang

    2016-01-01

    For ensemble learning, how to select and combine the candidate classifiers are two key issues which influence the performance of the ensemble system dramatically. Random vector functional link networks (RVFL) without direct input-to-output links is one of suitable base-classifiers for ensemble systems because of its fast learning speed, simple structure and good generalization performance. In this paper, to obtain a more compact ensemble system with improved convergence performance, an improved ensemble of RVFL based on attractive and repulsive particle swarm optimization (ARPSO) with double optimization strategy is proposed. In the proposed method, ARPSO is applied to select and combine the candidate RVFL. As for using ARPSO to select the optimal base RVFL, ARPSO considers both the convergence accuracy on the validation data and the diversity of the candidate ensemble system to build the RVFL ensembles. In the process of combining RVFL, the ensemble weights corresponding to the base RVFL are initialized by the minimum norm least-square method and then further optimized by ARPSO. Finally, a few redundant RVFL is pruned, and thus the more compact ensemble of RVFL is obtained. Moreover, in this paper, theoretical analysis and justification on how to prune the base classifiers on classification problem is presented, and a simple and practically feasible strategy for pruning redundant base classifiers on both classification and regression problems is proposed. Since the double optimization is performed on the basis of the single optimization, the ensemble of RVFL built by the proposed method outperforms that built by some single optimization methods. Experiment results on function approximation and classification problems verify that the proposed method could improve its convergence accuracy as well as reduce the complexity of the ensemble system.

  17. An Improved Ensemble of Random Vector Functional Link Networks Based on Particle Swarm Optimization with Double Optimization Strategy

    PubMed Central

    Ling, Qing-Hua; Song, Yu-Qing; Han, Fei; Yang, Dan; Huang, De-Shuang

    2016-01-01

    For ensemble learning, how to select and combine the candidate classifiers are two key issues which influence the performance of the ensemble system dramatically. Random vector functional link networks (RVFL) without direct input-to-output links is one of suitable base-classifiers for ensemble systems because of its fast learning speed, simple structure and good generalization performance. In this paper, to obtain a more compact ensemble system with improved convergence performance, an improved ensemble of RVFL based on attractive and repulsive particle swarm optimization (ARPSO) with double optimization strategy is proposed. In the proposed method, ARPSO is applied to select and combine the candidate RVFL. As for using ARPSO to select the optimal base RVFL, ARPSO considers both the convergence accuracy on the validation data and the diversity of the candidate ensemble system to build the RVFL ensembles. In the process of combining RVFL, the ensemble weights corresponding to the base RVFL are initialized by the minimum norm least-square method and then further optimized by ARPSO. Finally, a few redundant RVFL is pruned, and thus the more compact ensemble of RVFL is obtained. Moreover, in this paper, theoretical analysis and justification on how to prune the base classifiers on classification problem is presented, and a simple and practically feasible strategy for pruning redundant base classifiers on both classification and regression problems is proposed. Since the double optimization is performed on the basis of the single optimization, the ensemble of RVFL built by the proposed method outperforms that built by some single optimization methods. Experiment results on function approximation and classification problems verify that the proposed method could improve its convergence accuracy as well as reduce the complexity of the ensemble system. PMID:27835638

  18. Assessing intervention efficacy on high-risk drinkers using generalized linear mixed models with a new class of link functions.

    PubMed

    Prates, Marcos O; Aseltine, Robert H; Dey, Dipak K; Yan, Jun

    2013-11-01

    Unhealthy alcohol use is one of the leading causes of morbidity and mortality in the United States. Brief interventions with high-risk drinkers during an emergency department (ED) visit are of great interest due to their possible efficacy and low cost. In a collaborative study with patients recruited at 14 academic ED across the United States, we examined the self-reported number of drinks per week by each patient following the exposure to a brief intervention. Count data with overdispersion have been mostly analyzed with generalized linear mixed models (GLMMs), of which only a limited number of link functions are available. Different choices of link function provide different fit and predictive power for a particular dataset. We propose a class of link functions from an alternative way to incorporate random effects in a GLMM, which encompasses many existing link functions as special cases. The methodology is naturally implemented in a Bayesian framework, with competing links selected with Bayesian model selection criteria such as the conditional predictive ordinate (CPO). In application to the ED intervention study, all models suggest that the intervention was effective in reducing the number of drinks, but some new models are found to significantly outperform the traditional model as measured by CPO. The validity of CPO in link selection is confirmed in a simulation study that shared the same characteristics as the count data from high-risk drinkers. The dataset and the source code for the best fitting model are available in Supporting Information.

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

    PubMed

    Sridharan, Devarajan; Knudsen, Eric I

    2015-04-01

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

  20. Callosal Function in Pediatric Traumatic Brain Injury Linked to Disrupted White Matter Integrity

    PubMed Central

    Dennis, Emily L.; Ellis, Monica U.; Marion, Sarah D.; Jin, Yan; Moran, Lisa; Olsen, Alexander; Kernan, Claudia; Babikian, Talin; Mink, Richard; Babbitt, Christopher; Johnson, Jeffrey; Giza, Christopher C.; Asarnow, Robert F.

    2015-01-01

    Traumatic brain injury (TBI) often results in traumatic axonal injury and white matter (WM) damage, particularly to the corpus callosum (CC). Damage to the CC can lead to impaired performance on neurocognitive tasks, but there is a high degree of heterogeneity in impairment following TBI. Here we examined the relation between CC microstructure and function in pediatric TBI. We used high angular resolution diffusion-weighted imaging (DWI) to evaluate the structural integrity of the CC in humans following brain injury in a sample of 32 children (23 males and 9 females) with moderate-to-severe TBI (msTBI) at 1–5 months postinjury, compared with well matched healthy control children. We assessed CC function through interhemispheric transfer time (IHTT) as measured using event-related potentials (ERPs), and related this to DWI measures of WM integrity. Finally, the relation between DWI and IHTT results was supported by additional results of neurocognitive performance assessed using a single composite performance scale. Half of the msTBI participants (16 participants) had significantly slower IHTTs than the control group. This slow IHTT group demonstrated lower CC integrity (lower fractional anisotropy and higher mean diffusivity) and poorer neurocognitive functioning than both the control group and the msTBI group with normal IHTTs. Lower fractional anisotropy—a common sign of impaired WM—and slower IHTTs also predicted poor neurocognitive function. This study reveals that there is a subset of pediatric msTBI patients during the post-acute phase of injury who have markedly impaired CC functioning and structural integrity that is associated with poor neurocognitive functioning. SIGNIFICANCE STATEMENT Traumatic brain injury (TBI) is the primary cause of death and disability in children and adolescents. There is considerable heterogeneity in postinjury outcome, which is only partially explained by injury severity. Imaging biomarkers may help explain some of this

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

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    1986-11-01

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

  4. Engineering of the function of diamond-like carbon binding peptides through structural design.

    PubMed

    Gabryelczyk, Bartosz; Szilvay, Géza R; Singh, Vivek K; Mikkilä, Joona; Kostiainen, Mauri A; Koskinen, Jari; Linder, Markus B

    2015-02-09

    The use of phage display to select material-specific peptides provides a general route towards modification and functionalization of surfaces and interfaces. However, a rational structural engineering of the peptides for optimal affinity is typically not feasible because of insufficient structure-function understanding. Here, we investigate the influence of multivalency of diamond-like carbon (DLC) binding peptides on binding characteristics. We show that facile linking of peptides together using different lengths of spacers and multivalency leads to a tuning of affinity and kinetics. Notably, increased length of spacers in divalent systems led to significantly increased affinities. Making multimers influenced also kinetic aspects of surface competition. Additionally, the multivalent peptides were applied as surface functionalization components for a colloidal form of DLC. The work suggests the use of a set of linking systems to screen parameters for functional optimization of selected material-specific peptides.

  5. Structural features of piperazinyl-linked ciprofloxacin dimers required for activity against drug-resistant strains of Staphylococcus aureus.

    PubMed

    Kerns, Robert J; Rybak, Michael J; Kaatz, Glenn W; Vaka, Flamur; Cha, Raymond; Grucz, Richard G; Diwadkar, Veena U

    2003-07-07

    We previously demonstrated that piperazinyl-linked fluoroquinolone dimers possess potent antibacterial activity against drug-resistant strains of Staphylococcus aureus. In this study, we report the preparation and evaluation of a series of incomplete dimers toward ascertaining structural features of piperazinyl-linked ciprofloxacin dimers that render these agents refractory to fluoroquinolone-resistance mechanisms in Staphylococcus aureus.

  6. Vibrational transfer functions for complex structures

    NASA Technical Reports Server (NTRS)

    Jones, P. A.; Berry, R. L.

    1972-01-01

    Evaluation of effects of vibrational multiple frequency forcing functions is discussed. Computer program for developing vibrational transfer functions is described. Possible applications of computer program are enumerated.

  7. Discovery of a Missing Link: Detection and Structure of the Elusive Disilicon Carbide Cluster.

    PubMed

    McCarthy, Michael C; Baraban, Joshua H; Changala, P Bryan; Stanton, John F; Martin-Drumel, Marie-Aline; Thorwirth, Sven; Gottlieb, Carl A; Reilly, Neil J

    2015-06-04

    The rotational spectrum of the elusive but fundamentally important silicon carbide SiCSi has been detected using sensitive microwave techniques aided by high-level ab initio methods. Its equilibrium structure has been determined to very high precision using isotopic substitution and vibrational corrections calculated quantum-chemically: it is an isosceles triangle with a Si-C bond length of 1.693(1) Å, and an apex angle of 114.87(5)°. Now that all four Si(m)C(n) clusters with m + n = 3 have been observed experimentally, their structure and chemical bonding can be rigorously compared. Because Si2C is so closely linked to other Si-bearing molecules that have been detected in the evolved carbon star IRC+10216, it is an extremely promising candidate for detection with radio telescopes.

  8. Social carry-over effects underpin trans-seasonally linked structure in a wild bird population.

    PubMed

    Firth, Josh A; Sheldon, Ben C

    2016-11-01

    Spatial structure underpins numerous population processes by determining the environment individuals' experience and which other individuals they encounter. Yet, how the social landscape influences individuals' spatial decisions remains largely unexplored. Wild great tits (Parus major) form freely moving winter flocks, but choose a single location to establish a breeding territory over the spring. We demonstrate that individuals' winter social associations carry-over into their subsequent spatial decisions, as individuals breed nearer to those they were most associated with during winter. Further, they also form territory boundaries with their closest winter associates, irrespective of breeding distance. These findings were consistent across years, and among all demographic classes, suggesting that such social carry-over effects may be general. Thus, prior social structure can shape the spatial proximity, and fine-scale arrangement, of breeding individuals. In this way, social networks can influence a wide range of processes linked to individuals' breeding locations, including other social interactions themselves.

  9. GlycoMinestruct: a new bioinformatics tool for highly accurate mapping of the human N-linked and O-linked glycoproteomes by incorporating structural features

    PubMed Central

    Li, Fuyi; Li, Chen; Revote, Jerico; Zhang, Yang; Webb, Geoffrey I.; Li, Jian; Song, Jiangning; Lithgow, Trevor

    2016-01-01

    Glycosylation plays an important role in cell-cell adhesion, ligand-binding and subcellular recognition. Current approaches for predicting protein glycosylation are primarily based on sequence-derived features, while little work has been done to systematically assess the importance of structural features to glycosylation prediction. Here, we propose a novel bioinformatics method called GlycoMinestruct(http://glycomine.erc.monash.edu/Lab/GlycoMine_Struct/) for improved prediction of human N- and O-linked glycosylation sites by combining sequence and structural features in an integrated computational framework with a two-step feature-selection strategy. Experiments indicated that GlycoMinestruct outperformed NGlycPred, the only predictor that incorporated both sequence and structure features, achieving AUC values of 0.941 and 0.922 for N- and O-linked glycosylation, respectively, on an independent test dataset. We applied GlycoMinestruct to screen the human structural proteome and obtained high-confidence predictions for N- and O-linked glycosylation sites. GlycoMinestruct can be used as a powerful tool to expedite the discovery of glycosylation events and substrates to facilitate hypothesis-driven experimental studies. PMID:27708373

  10. Structure Determination of Ornithine-Linked Cisplatin by Infrared Multiple Photon Dissociation Action Spectroscopy

    NASA Astrophysics Data System (ADS)

    He, Chenchen; Kimutai, Bett; Hamlow, Lucas; Roy, Harrison; Nei, Y.-W.; Bao, Xun; Gao, Juehan; Martens, Jonathan K.; Berden, Giel; Oomens, Jos; Maitre, Philippe; Steinmetz, Vincent; McNary, Christopher P.; Armentrout, Peter B.; Chow, C. S.; Rodgers, M. T.

    2016-06-01

    Cisplatin [(NH_3)_2PtCl_2], the first FDA-approved platinum-based anticancer drug, has been widely used in cancer chemotherapy. Its pharmacological mechanism has been identified as its ability to coordinate to genomic DNA with guanine as its major target. Amino acid-linked cisplatin derivatives are being investigated as alternatives for cisplatin that may exhibit altered binding selectivity such as that found for ornithine-linked cisplatin (Ornplatin, [(Orn)PtCl_2]), which exhibits a preference for adenine over guanine in RNA. Infrared multiple photon dissociation (IRMPD) action spectroscopy experiments and complementary electronic structure calculations are performed on a series of Ornplatin complexes to elucidate the nature of binding of the Orn amino acid to the Pt center and how that binding is influenced by the local environment. The complexes examined in the work include: [(Orn-H)PtCl_2]-, [(Orn)PtCl]+, [(Orn)Pt(H_2O)Cl]+, and [(Orn)PtCl_2+Na]+. In contrast to that found previously for the glycine-linked cisplatin complex (Glyplatin), which binds via the backbone amino and carboxylate groups, binding of Orn in these complexes is found to involve both the backbone and sidechain amino groups. Extensive broadening of the IRMPD spectrum for the [(Orn)Pt(H_2O)Cl]+ complex suggests that either multiple structures are contributing to the measured spectrum or strong intra-molecular hydrogen-binding interactions are present. The results for Ornplatin lead to an interesting discussion about the differences in selectivity and reactivity versus cisplatin.

  11. Structure-based inference of molecular functions of proteins of unknown function from Berkeley Structural Genomics Center

    SciTech Connect

    Kim, Sung-Hou; Shin, Dong Hae; Hou, Jingtong; Chandonia, John-Marc; Das, Debanu; Choi, In-Geol; Kim, Rosalind; Kim, Sung-Hou

    2007-09-02

    Advances in sequence genomics have resulted in an accumulation of a huge number of protein sequences derived from genome sequences. However, the functions of a large portion of them cannot be inferred based on the current methods of sequence homology detection to proteins of known functions. Three-dimensional structure can have an important impact in providing inference of molecular function (physical and chemical function) of a protein of unknown function. Structural genomics centers worldwide have been determining many 3-D structures of the proteins of unknown functions, and possible molecular functions of them have been inferred based on their structures. Combined with bioinformatics and enzymatic assay tools, the successful acceleration of the process of protein structure determination through high throughput pipelines enables the rapid functional annotation of a large fraction of hypothetical proteins. We present a brief summary of the process we used at the Berkeley Structural Genomics Center to infer molecular functions of proteins of unknown function.

  12. Structure-based inference of molecular functions of proteins of unknown function from Berkeley Structural Genomics Center.

    PubMed

    Shin, Dong Hae; Hou, Jingtong; Chandonia, John-Marc; Das, Debanu; Choi, In-Geol; Kim, Rosalind; Kim, Sung-Hou

    2007-09-01

    Advances in sequence genomics have resulted in an accumulation of a huge number of protein sequences derived from genome sequences. However, the functions of a large portion of them cannot be inferred based on the current methods of sequence homology detection to proteins of known functions. Three-dimensional structure can have an important impact in providing inference of molecular function (physical and chemical function) of a protein of unknown function. Structural genomics centers worldwide have been determining many 3-D structures of the proteins of unknown functions, and possible molecular functions of them have been inferred based on their structures. Combined with bioinformatics and enzymatic assay tools, the successful acceleration of the process of protein structure determination through high throughput pipelines enables the rapid functional annotation of a large fraction of hypothetical proteins. We present a brief summary of the process we used at the Berkeley Structural Genomics Center to infer molecular functions of proteins of unknown function.

  13. A Potential Link Between the Cosmological Constant and the Fine-structure Constant

    NASA Astrophysics Data System (ADS)

    Goradia, Shantilal

    2008-04-01

    The age of the universe, about 10^60 Planck times, makes the spherical radius (R) of its space 10^60 Planck lengths, as the light moves one Planck length per one Planck time. The fine-structure constant (α) closely equals the natural logarithm of the square root of the reciprocal of the cosmological constant (λ), making α ln (1/λ), where λ = 1/ R^2 as originally introduced by Einstein in equation number (14) in his 1917 paper: Cosmological Considerations on the General Theory of Relativity. This confirms the time-dependent variation of fine-structure constant in [1], but does not address the issue of dark energy. While [1] invokes negative entropy (-Q/T), so it also invokes dark energy simply. The problem still remains that no theory, as yet, combines the probabilistic aspect of quantum mechanics with gravity. In the meanwhile, we can link [1] with the quantum information theory as information links to entropy. [1] Goradia S. Preprint at (http://www.arxiv.org/physics/0210040 v3 (Jan 2007).

  14. Psychological symptoms linking exposure to community violence and academic functioning in African American adolescents.

    PubMed

    Busby, Danielle R; Lambert, Sharon F; Ialongo, Nicholas S

    2013-02-01

    African American adolescents are exposed disproportionately to community violence, increasing their risk for emotional and behavioral symptoms that can detract from learning and undermine academic outcomes. The present study examined whether aggressive behavior and depressive and anxious symptoms mediated the association between exposure to community violence and academic functioning, and if the indirect effects of community violence on academic functioning differed for boys and girls, in a community sample of urban African American adolescents (N = 491; 46.6 % female). Structural equation modeling was used to examine the indirect effect of exposure to community violence in grade 6 on grade 8 academic functioning. Results revealed that aggression in grade 7 mediated the association between grade 6 exposure to community violence and grade 8 academic functioning. There were no indirect effects through depressive and anxious symptoms, and gender did not moderate the indirect effect. Findings highlight the importance of targeting aggressive behavior for youth exposed to community violence to not only improve their behavioral adjustment but also their academic functioning. Implications for future research are discussed.

  15. Anisotropic nanomaterials: structure, growth, assembly, and functions

    PubMed Central

    Sajanlal, Panikkanvalappil R.; Sreeprasad, Theruvakkattil S.; Samal, Akshaya K.; Pradeep, Thalappil

    2011-01-01

    Comprehensive knowledge over the shape of nanomaterials is a critical factor in designing devices with desired functions. Due to this reason, systematic efforts have been made to synthesize materials of diverse shape in the nanoscale regime. Anisotropic nanomaterials are a class of materials in which their properties are direction-dependent and more than one structural parameter is needed to describe them. Their unique and fine-tuned physical and chemical properties make them ideal candidates for devising new applications. In addition, the assembly of ordered one-dimensional (1D), two-dimensional (2D), and three-dimensional (3D) arrays of anisotropic nanoparticles brings novel properties into the resulting system, which would be entirely different from the properties of individual nanoparticles. This review presents an overview of current research in the area of anisotropic nanomaterials in general and noble metal nanoparticles in particular. We begin with an introduction to the advancements in this area followed by general aspects of the growth of anisotropic nanoparticles. Then we describe several important synthetic protocols for making anisotropic nanomaterials, followed by a summary of their assemblies, and conclude with major applications. PMID:22110867

  16. Muscle structural assembly and functional consequences.

    PubMed

    Narici, Marco; Franchi, Martino; Maganaris, Constantinos

    2016-01-01

    The relationship between muscle structure and function has been a matter of investigation since the Renaissance period. Extensive use of anatomical dissections and the introduction of the scientific method enabled early scholars to lay the foundations of muscle physiology and biomechanics. Progression of knowledge in these disciplines led to the current understanding that muscle architecture, together with muscle fibre contractile properties, has a major influence on muscle mechanical properties. Recently, advances in laser diffraction, optical microendoscopy and ultrasonography have enabled in vivo investigations into the behaviour of human muscle fascicles and sarcomeres with varying joint angle and muscle contraction intensity. With these technologies it has become possible to identify the length region over which fascicles and sarcomeres develop maximum isometric force in vivo as well as the operating ranges of fascicles and sarcomeres during real-life activities such as walking. Also, greater insights into the remodelling of muscle architecture in response to overloading and unloading, and in ageing, have been obtained by the use of ultrasonography; these have led to the identification of clinical biomarkers of disuse atrophy and sarcopenia. Recent evidence also shows that the pattern of muscle hypertrophy in response to chronic loading is contraction-mode dependent (eccentric versus concentric), as similar gains in muscle mass, but through differing addition of sarcomeres in series and in parallel (as indirectly inferred from changes in fascicle length and pennation angle), have been found. These innovative observations prompted a new set of investigations into the molecular mechanisms regulating this contraction-specific muscle growth.

  17. Crustal Structure beneath Mexico from Receiver Functions

    NASA Astrophysics Data System (ADS)

    Espindola, V.; Quintanar, L.; Espindola, J.

    2011-12-01

    The Servicio Sismológico Nacional (SSN) is Mexico's official organism in charge of the observation of seismicity in the country. Operated by the Universidad Nacional Autonoma de Mexico, it counts with 32 broadband stations deployed throughout the country. The coverage includes most of the geologic provinces of the territory, which vary widely in their geologic characteristics. The availability of records from teleseisms at those stations makes feasible to obtain sound and homogeneous estimates of the structure of the crust in the Mexican territory through the analysis of receiver functions (RF). In this work we present the results of the analysis of RF obtained from events registered from 1998 to 2009 in the 32 stations of the SSN. The RF technique, which uses converted phases at major velocity discontinuities, is a well established technique to infer the velocity contrasts and thickness of the underlying crust. Using this method we were able to infer the depth of the Moho, a major intracrustal discontinuity and in some cases the depth to the base of the subducting plate. We present maps of crustal thickness in Mexico, which varies between about 29 km in the Yucatan peninsula to more than 40 km in central Mexico. Poisson's coefficient varies between 0.19 and 0.30. The position of the descending slab shows a large variation in the subduction angle (from about 6° in the SE margin of the Pacific coast to about 60° in the NW ) as has been found from other techniques.

  18. Hyperinsulinemia adversely affects lung structure and function.

    PubMed

    Singh, Suchita; Bodas, Manish; Bhatraju, Naveen K; Pattnaik, Bijay; Gheware, Atish; Parameswaran, Praveen Kolumam; Thompson, Michael; Freeman, Michelle; Mabalirajan, Ulaganathan; Gosens, Reinoud; Ghosh, Balaram; Pabelick, Christina; Linneberg, Allan; Prakash, Y S; Agrawal, Anurag

    2016-05-01

    There is limited knowledge regarding the consequences of hyperinsulinemia on the lung. Given the increasing prevalence of obesity, insulin resistance, and epidemiological associations with asthma, this is a critical lacuna, more so with inhaled insulin on the horizon. Here, we demonstrate that insulin can adversely affect respiratory health. Insulin treatment (1 μg/ml) significantly (P < 0.05) increased the proliferation of primary human airway smooth muscle (ASM) cells and induced collagen release. Additionally, ASM cells showed a significant increase in calcium response and mitochondrial respiration upon insulin exposure. Mice administered intranasal insulin showed increased collagen deposition in the lungs as well as a significant increase in airway hyperresponsiveness. PI3K/Akt mediated activation of β-catenin, a positive regulator of epithelial-mesenchymal transition and fibrosis, was observed in the lungs of insulin-treated mice and lung cells. Our data suggests that hyperinsulinemia may have adverse effects on airway structure and function. Insulin-induced activation of β-catenin in lung tissue and the contractile effects on ASM cells may be causally related to the development of asthma-like phenotype.

  19. Anisotropic nanomaterials: structure, growth, assembly, and functions.

    PubMed

    Sajanlal, Panikkanvalappil R; Sreeprasad, Theruvakkattil S; Samal, Akshaya K; Pradeep, Thalappil

    2011-01-01

    Comprehensive knowledge over the shape of nanomaterials is a critical factor in designing devices with desired functions. Due to this reason, systematic efforts have been made to synthesize materials of diverse shape in the nanoscale regime. Anisotropic nanomaterials are a class of materials in which their properties are direction-dependent and more than one structural parameter is needed to describe them. Their unique and fine-tuned physical and chemical properties make them ideal candidates for devising new applications. In addition, the assembly of ordered one-dimensional (1D), two-dimensional (2D), and three-dimensional (3D) arrays of anisotropic nanoparticles brings novel properties into the resulting system, which would be entirely different from the properties of individual nanoparticles. This review presents an overview of current research in the area of anisotropic nanomaterials in general and noble metal nanoparticles in particular. We begin with an introduction to the advancements in this area followed by general aspects of the growth of anisotropic nanoparticles. Then we describe several important synthetic protocols for making anisotropic nanomaterials, followed by a summary of their assemblies, and conclude with major applications.

  20. Molecular Evolution, Structure, and Function of Peroxidasins

    PubMed Central

    Soudi, Monika; Zamocky, Marcel; Jakopitsch, Christa; Furtmüller, Paul G; Obinger, Christian

    2012-01-01

    Peroxidasins represent the subfamily 2 of the peroxidase-cyclooxygenase superfamily and are closely related to chordata peroxidases (subfamily 1) and peroxinectins (subfamily 3). They are multidomain proteins containing a heme peroxidase domain with high homology to human lactoperoxidase that mediates one- and two-electron oxidation reactions. Additional domains of the secreted and glycosylated metalloproteins are type C-like immunoglobulin domains, typical leucine-rich repeats, as well as a von Willebrand factor C module. These are typical motifs of extracellular proteins that mediate protein–protein interactions. We have reconstructed the phylogeny of this new family of oxidoreductases and show the presence of four invertebrate clades as well as one vertebrate clade that includes also two different human representatives. The variability of domain assembly in the various clades was analyzed, as was the occurrence of relevant catalytic residues in the peroxidase domain based on the knowledge of catalysis of the mammalian homologues. Finally, the few reports on expression, localization, enzymatic activity, and physiological roles in the model organisms Drosophila melanogaster, Caenorhabditis elegans, and Homo sapiens are critically reviewed. Roles attributed to peroxidasins include antimicrobial defense, extracellular matrix formation, and consolidation at various developmental stages. Many research questions need to be solved in future, including detailed biochemical/physical studies and elucidation of the three dimensional structure of a model peroxidasin as well as the relation and interplay of the domains and the in vivo functions in various organisms including man. PMID:22976969

  1. Crustacean neuropeptides: structures, functions and comparative aspects.

    PubMed

    Keller, R

    1992-05-15

    In this article, an attempt is made to review the presently known, completely identified crustacean neuropeptides with regard to structure, function and distribution. Probably the most important progress has been made in the elucidation of a novel family of large peptides from the X-organ-sinus gland system which includes crustacean hyperglycemic hormone (CHH), putative molt-inhibiting hormone (MIH) and vitellogenesis (= gonad)-inhibiting hormone (VIH). These peptides have so far only been found in crustaceans. Renewed interest in the neurohemal pericardial organs has led to the identification of a number of cardioactive/myotropic neuropeptides, some of them unique to crustaceans. Important contributions have been made by immunocytochemical mapping of peptidergic neurons in the nervous system, which has provided evidence for a multiple role of several neuropeptides as neurohormones on the one hand and as local transmitters or modulators on the other. This has been corroborated by physiological studies. The long-known chromatophore-regulating hormones, red pigment concentrating hormone (RPCH) and pigment-dispending hormone (PDH), have been placed in a broader perspective by the demonstration of an additional role as local neuromodulators. The scope of crustacean neuropeptide research has thus been broadened considerably during the last years.

  2. Yeast peroxisomes: structure, functions and biotechnological opportunities.

    PubMed

    Sibirny, Andriy A

    2016-06-01

    Peroxisomes are ubiquitous organelles found in most eukaryotic cells. In yeasts, peroxisomes play important roles in cell metabolism, especially in different catabolic processes including fatty acid β-oxidation, the glyoxylic shunt and methanol metabolism, as well as some biosynthetic processes. In addition, peroxisomes are the compartment in which oxidases and catalase are localized. New peroxisomes mainly arise by fission of pre-existing ones, although they can also be formed from the endoplasmic reticulum (ER). Peroxisomes consist of matrix-soluble proteins and membrane proteins known as peroxins. A total of 34 PEX peroxin genes and proteins have been identified to date. and their functions have been elucidated. Protein import into peroxisomes depends on peroxins and requires specific signals in the structure of transported proteins: PTS1, PTS2 and mPTS. The mechanisms of metabolite penetration into peroxisomes are still poorly understood. Peroxisome number and the volume occupied by these organelles are tightly regulated. Methanol, fatty acids and methylamine act as efficient peroxisome proliferators, whereas glucose and ethanol induce peroxisome autophagic degradation (pexophagy). To date, 42 Atg proteins involved in pexophagy are known. Catabolism and alcoholic fermentation of the major pentose sugar, xylose, depend on peroxisomal enzymes. Overexpression of peroxisomal transketolase and transaldolase activates xylose fermentation. Peroxisomes could be useful as target organelles for overexpression of foreign toxic proteins.

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

  4. Identification of new surfaces of cofilin that link mitochondrial function to the control of multi-drug resistance

    PubMed Central

    Kotiadis, Vassilios N.; Leadsham, Jane E.; Bastow, Emma L.; Gheeraert, Aline; Whybrew, Jennafer M.; Bard, Martin; Lappalainen, Pekka; Gourlay, Campbell W.

    2012-01-01

    ADF/cofilin family proteins are essential regulators of actin cytoskeletal dynamics. Recent evidence also implicates cofilin in the regulation of mitochondrial function. Here, we identify new functional surfaces of cofilin that are linked with mitochondrial function and stress responses in the budding yeast Saccharomyces cerevisiae. Our data link surfaces of cofilin that are involved in separable activities of actin filament disassembly or stabilisation, to the regulation of mitochondrial morphology and the activation status of Ras, respectively. Importantly, charge alterations to conserved surfaces of cofilin that do not interfere with its actin regulatory activity lead to a dramatic increase in respiratory function that triggers a retrograde signal to upregulate a battery of ABC transporters and concurrent metabolic changes that support multi-drug resistance. We hypothesise that cofilin functions within a bio-sensing system that connects the cytoskeleton and mitochondrial function to environmental challenge. PMID:22344251

  5. Identification of new surfaces of cofilin that link mitochondrial function to the control of multi-drug resistance.

    PubMed

    Kotiadis, Vassilios N; Leadsham, Jane E; Bastow, Emma L; Gheeraert, Aline; Whybrew, Jennafer M; Bard, Martin; Lappalainen, Pekka; Gourlay, Campbell W

    2012-05-01

    ADF/cofilin family proteins are essential regulators of actin cytoskeletal dynamics. Recent evidence also implicates cofilin in the regulation of mitochondrial function. Here, we identify new functional surfaces of cofilin that are linked with mitochondrial function and stress responses in the budding yeast Saccharomyces cerevisiae. Our data link surfaces of cofilin that are involved in separable activities of actin filament disassembly or stabilisation, to the regulation of mitochondrial morphology and the activation status of Ras, respectively. Importantly, charge alterations to conserved surfaces of cofilin that do not interfere with its actin regulatory activity lead to a dramatic increase in respiratory function that triggers a retrograde signal to upregulate a battery of ABC transporters and concurrent metabolic changes that support multi-drug resistance. We hypothesise that cofilin functions within a bio-sensing system that connects the cytoskeleton and mitochondrial function to environmental challenge.

  6. Structural and Functional Dissection of the Abp1 ADFH Actin-binding Domain Reveals Versatile In Vivo Adapter Functions

    SciTech Connect

    Quintero-Monzon,O.; Rodal, A.; Strokopytov, B.; Almo, S.; Goode, B.

    2005-01-01

    Abp1 is a multidomain protein that regulates the Arp2/3 complex and links proteins involved in endocytosis to the actin cytoskeleton. All of the proposed cellular functions of Abp1 involve actin filament binding, yet the actin binding site(s) on Abp1 have not been identified, nor has the importance of actin binding for Abp1 localization and function in vivo been tested. Here, we report the crystal structure of the Saccharomyces cerevisiae Abp1 actin-binding actin depolymerizing factor homology (ADFH) domain and dissect its activities by mutagenesis. Abp1-ADFH domain and ADF/cofilin structures are similar, and they use conserved surfaces to bind actin; however, there are also key differences that help explain their differential effects on actin dynamics. Using point mutations, we demonstrate that actin binding is required for localization of Abp1 in vivo, the lethality caused by Abp1 overexpression, and the ability of Abp1 to activate Arp2/3 complex. Furthermore, we genetically uncouple ABP1 functions that overlap with SAC6, SLA1, and SLA2, showing they require distinct combinations of activities and interactions. Together, our data provide the first structural and functional view of the Abp1-actin interaction and show that Abp1 has distinct cellular roles as an adapter, linking different sets of ligands for each function.

  7. Glutamate Receptor Ion Channels: Structure, Regulation, and Function

    PubMed Central

    Wollmuth, Lonnie P.; McBain, Chris J.; Menniti, Frank S.; Vance, Katie M.; Ogden, Kevin K.; Hansen, Kasper B.; Yuan, Hongjie; Myers, Scott J.; Dingledine, Ray

    2010-01-01

    The mammalian ionotropic glutamate receptor family encodes 18 gene products that coassemble to form ligand-gated ion channels containing an agonist recognition site, a transmembrane ion permeation pathway, and gating elements that couple agonist-induced conformational changes to the opening or closing of the permeation pore. Glutamate receptors mediate fast excitatory synaptic transmission in the central nervous system and are localized on neuronal and non-neuronal cells. These receptors regulate a broad spectrum of processes in the brain, spinal cord, retina, and peripheral nervous system. Glutamate receptors are postulated to play important roles in numerous neurological diseases and have attracted intense scrutiny. The description of glutamate receptor structure, including its transmembrane elements, reveals a complex assembly of multiple semiautonomous extracellular domains linked to a pore-forming element with striking resemblance to an inverted potassium channel. In this review we discuss International Union of Basic and Clinical Pharmacology glutamate receptor nomenclature, structure, assembly, accessory subunits, interacting proteins, gene expression and translation, post-translational modifications, agonist and antagonist pharmacology, allosteric modulation, mechanisms of gating and permeation, roles in normal physiological function, as well as the potential therapeutic use of pharmacological agents acting at glutamate receptors. PMID:20716669

  8. Structural remodeling and mechanical function in heart failure.

    PubMed

    Leonard, Bridget Louise; Smaill, Bruce Henry; LeGrice, Ian John

    2012-02-01

    The cardiac extracellular matrix (ECM) is the three-dimensional scaffold that defines the geometry and muscular architecture of the cardiac chambers and transmits forces produced during the cardiac cycle throughout the heart wall. The cardiac ECM is an active system that responds to the stresses to which it is exposed and in the normal heart is adapted to facilitate efficient mechanical function. There are marked differences in the short- and medium-term changes in ventricular geometry and cardiac ECM that occur as a result of volume overload, hypertension, and ischemic cardiomyopathy. Despite this, there is a widespread view that a common remodeling "phenotype" governs the final progression to end-stage heart failure in different forms of heart disease. In this review article, we make the case that this interpretation is not consistent with the clinical and experimental data on the topic. We argue that there is a need for new theoretical and experimental models that will enable stresses acting on the ECM and resultant deformations to be estimated more accurately and provide better spatial resolution of local signaling mechanisms that are activated as a result. These developments are necessary to link the effects of structural remodeling with altered cardiac mechanical function.

  9. Functional connectivity of the striatum links motivation to action control in humans.

    PubMed

    Harsay, Helga A; Cohen, Michael X; Oosterhof, Nikolaas N; Forstmann, Birte U; Mars, Rogier B; Ridderinkhof, K Richard

    2011-07-20

    Motivation improves the efficiency of intentional behavior, but how this performance modulation is instantiated in the human brain remains unclear. We used a reward-cued antisaccade paradigm to investigate how motivational goals (the expectation of a reward for good performance) modulate patterns of neural activation and functional connectivity to improve preparation for antisaccade performance. Behaviorally, subjects performed better (faster and more accurate antisaccades) when they knew they would be rewarded for good performance. Reward anticipation was associated with increased activation in the ventral and dorsal striatum, and cortical oculomotor regions. Functional connectivity between the caudate nucleus and cortical oculomotor control structures predicted individual differences in the behavioral benefit of reward anticipation. We conclude that although both dorsal and ventral striatal circuitry are involved in the anticipation of reward, only the dorsal striatum and its connected cortical network is involved in the direct modulation of oculomotor behavior by motivational incentive.

  10. Exploring the precursors of outcome evaluation in Australia: linking structure, process and outcome by peer review.

    PubMed

    Middleton, S; Lumby, J

    1998-09-01

    Reviews of the structure of the health system and the processes that contributed to them were the main forms of evaluation within nursing in Australia during the 1970s and 1980s. The documentation of the end result of care, or outcome evaluation, was rarely undertaken until more recent times. The development and implementation of formal assessment tools such as Qualpacs, the Phaneuf Nursing Audit, the Rush Medicus Nursing Process Methodology, Monitor, and Senior Monitor indicated the focus on structure and process evaluation. This paper examines how nursing care delivered to patients during the l970s and 1980s was evaluated, and explores why structure and process review were necessary precursors to outcome evaluation in the nineties. The necessity of linking structure and process analysis is discussed, in order to perform effective outcome evaluation to close the feedback loop between quality assessment and quality improvement. Peer review is one mechanism that can be used to achieve this. How this may also be a form of evidence-based practice which results in health gains for patients is also explored.

  11. Biomechanical variation of silk links spinning plasticity to spider web function.

    PubMed

    Boutry, Cecilia; Blackledge, Todd A

    2009-01-01

    Spider silk is renowned for its high tensile strength, extensibility and toughness. However, the variability of these material properties has largely been ignored, especially at the intra-specific level. Yet, this variation could help us understand the function of spider webs. It may also point to the mechanisms used by spiders to control their silk production, which could be exploited to expand the potential range of applications for silk. In this study, we focus on variation of silk properties within different regions of cobwebs spun by the common house spider, Achaearanea tepidariorum. The cobweb is composed of supporting threads that function to maintain the web shape and hold spiders and prey, and of sticky gumfooted threads that adhere to insects during prey capture. Overall, structural properties, especially thread diameter, are more variable than intrinsic material properties, which may reflect past directional selection on certain silk performance. Supporting threads are thicker and able to bear higher loads, both before deforming permanently and before breaking, compared with sticky gumfooted threads. This may facilitate the function of supporting threads through sustained periods of time. In contrast, sticky gumfooted threads are more elastic, which may reduce the forces that prey apply to webs and allow them to contact multiple sticky capture threads. Therefore, our study suggests that spiders actively modify silk material properties during spinning in ways that enhance web function.

  12. Structures linking the myonemes, endoplasmic reticulum, and surface membranes in the contractile ciliate Vorticella.

    PubMed

    Allen, R D

    1973-02-01

    An electron microscope investigation of the interface between the myonemes of Vorticella convallaria and their associated endoplasmic reticulum (ER) has revealed structures of a complex morphology linking these two organelles. These structures are named "linkage complexes". Each complex contains a spindle-shaped midpiece which lies in a groove of the ER membrane. Microfilaments splay out from the tips of the midpiece and may come in contact with the inner alveolar sac membrane. Three to six raillike structures lie on each side of the midpiece and parallel it. The ER membrane appears to pass through the sides of the rails. In the lumen of the ER these rails are associated with a meshwork of filaments. A cradle of five rods lies within the groove under the midpiece. The ER membrane also passes through these rods which contact the same meshwork. In the scopular region and in the stalk the microfilaments from the midpiece form a bundle which passes into the lumen of modified basal bodies. These basal bodies are connected to the alveolar sac which, in the stalk, passes as a flattened tube along its length. The parts of the dissociated linkage complex are scattered throughout the spasmoneme of the stalk along membranes of the intraspasmonemal tubules. Thus, both stalk and body contractile bundles have linkage complexes that link their associated membrane systems to the microfibrils and, in turn, connect this membrane-microfibrillar interface to the pellicular membranes. The arrangement of the linkage complex suggests an involvement in the control of the transport of calcium ions between ER and microfibrils, and possibly the transfer of a message from the surface membranes to the sites of calcium release to trigger myonemal contraction.

  13. a Novel Approach to Link the Structure and the Metabolic Rate of Biofilms

    NASA Astrophysics Data System (ADS)

    Freixa, A.; Rubol, S.; Romaní, A.; Sanchez-Vila, X.

    2013-12-01

    Biofilms are complex natural system and exhibits heterogeneity both in space and time. In this study, we aim to 1) investigate the effect of this spatially behavior of oxygen metabolic activity (measured as the rate of O2 consumption) for different temperatures (10°C and 20°C) and light conditions (dark and light) in biofilms and 2) link the oxygen consumption rate to the biofilm structure. To meet this objective, we used a novel optical sensor plus imaging technology called VisiSens (PreSens Precision Sensing) that gave us a unique opportunity to obtain percentage air saturation of biofilm in time and space using the images of the surface of the developing biofilm at a set interval (every 20 seconds for 40 minutes). Biofilm oxygen consumption was measured after glucose and humic acid addition in order to study metabolic differences depending on organic matter source. Each of these series of images (each consisting of 120 images) were analyzed for spatial statistical analysis (e.g. histogram) and kinetic rates of consumption were determined for one-week and two-week-old biofilms. In addition, the one week old biofilm structures were determined for both dark and light condition and for both temperatures by using a confocal microscope .The 2D and 3D images obtained were then used to determine the variogram of each treatment. Information obtained by the two approaches was then coupled. To the best of our knowledge this is the first work which attempt to link the biofilm spatial structure to its metabolism at this fine scale.

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

    PubMed Central

    Vadakkan, Kunjumon I.

    2010-01-01

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

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

    PubMed Central

    Benítez-Burraco, Antonio; Boeckx, Cedric

    2015-01-01

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

  16. Purification of a vesicle-vacuole fraction functionally linked to aflatoxin synthesis in Aspergillus parasiticus

    PubMed Central

    CHANDA, Anindya; ROZE, Ludmila; PASTOR, Alicia; FRAME, Melinda; LINZ, John E.

    2009-01-01

    Current studies in our laboratory demonstrate a functional link between vesicles, vacuoles and aflatoxin biosynthesis in the filamentous fungus, Aspergillus parasiticus. Under aflatoxin inducing conditions in liquid yeast-extract sucrose medium, A. parasiticus undergoes a shift from vacuole biogenesis to accumulation of an enhanced number of vesicles which exhibit significant heterogeneity in size and density. As a first step in conducting a detailed analysis of the role of these organelles in aflatoxin synthesis, we developed a novel method to purify the vesicle and vacuole fraction using protoplasts prepared from cells harvested during aflatoxin synthesis. The method includes the following steps: 1] preparation of protoplasts from mycelia grown for 36h under aflatoxin inducing conditions; 2] release of vesicles and vacuoles from purified protoplasts in the presence of Triton X-100; and 3] fractionation of the vesicles and vacuoles using a “one-step high density cushion”. The vesicle-vacuole fraction showed a 35 fold enrichment in alpha-mannosidase activity (vacuole marker) and non-detectable succinate dehydrogenase and lactate dehydrogenase activities (mitochondrial and cytoplasmic markers, respectively). Confocal laser scanning microscopy with the vacuole dyes MDY-64 and CMAC demonstrated that the fraction contained pure vesicles and vacuoles and was devoid of membranous debris. Transmission electron microscopy (TEM) confirmed that no mitochondria or unbroken protoplasts contaminated the purified fraction. The purified organelles exhibited significant size heterogeneity with a range of sizes similar to that observed in whole cells and protoplasts. PMID:19358865

  17. Chromium functionalized diglyme plasma polymer coating enhances enzyme-linked immunosorbent assay performance.

    PubMed

    Welch, Nicholas G; Madiona, Robert M T; Easton, Christopher D; Scoble, Judith A; Jones, Robert T; Muir, Benjamin W; Pigram, Paul J

    2016-11-10

    Ensuring the optimum orientation, conformation, and density of substrate-bound antibodies is critical for the success of sandwich enzyme-linked immunosorbent assays (ELISAs). In this work, the authors utilize a diethylene glycol dimethyl ether plasma polymer (DGpp) coating, functionalized with chromium within a 96 well plate for the enhanced immobilization of a capture antibody. For an equivalent amount of bound antibody, a tenfold improvement in the ELISA signal intensity is obtained on the DGpp after incubation with chromium, indicative of improved orientation on this surface. Time-of-flight secondary-ion-mass-spectrometry (ToF-SIMS) and principal component analysis were used to probe the molecular species at the surface and showed ion fragments related to lysine, methionine, histidine, and arginine coupled to chromium indicating candidate antibody binding sites. A combined x-ray photoelectron spectroscopy and ToF-SIMS analysis provided a surface molecular characterization that demonstrates antibody binding via the chromium complex. The DGpp+Cr surface treatment holds great promise for improving the efficacy of ELISAs.

  18. Uncoupling of Energy-Linked Functions of Corn Mitochondria by Linoleic Acid and Monomethyldecenylsuccinic Acid 1

    PubMed Central

    Baddeley, M. Susan; Hanson, J. B.

    1967-01-01

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

  19. Linking lung function and inflammatory responses in ventilator-induced lung injury.

    PubMed

    Cannizzaro, Vincenzo; Hantos, Zoltan; Sly, Peter D; Zosky, Graeme R

    2011-01-01

    Despite decades of research, the mechanisms of ventilator-induced lung injury are poorly understood. We used strain-dependent responses to mechanical ventilation in mice to identify associations between mechanical and inflammatory responses in the lung. BALB/c, C57BL/6, and 129/Sv mice were ventilated using a protective [low tidal volume and moderate positive end-expiratory pressure (PEEP) and recruitment maneuvers] or injurious (high tidal volume and zero PEEP) ventilation strategy. Lung mechanics and lung volume were monitored using the forced oscillation technique and plethysmography, respectively. Inflammation was assessed by measuring numbers of inflammatory cells, cytokine (IL-6, IL-1β, and TNF-α) levels, and protein content of the BAL. Principal components factor analysis was used to identify independent associations between lung function and inflammation. Mechanical and inflammatory responses in the lung were dependent on ventilation strategy and mouse strain. Three factors were identified linking 1) pulmonary edema, protein leak, and macrophages, 2) atelectasis, IL-6, and TNF-α, and 3) IL-1β and neutrophils, which were independent of responses in lung mechanics. This approach has allowed us to identify specific inflammatory responses that are independently associated with overstretch of the lung parenchyma and loss of lung volume. These data provide critical insight into the mechanical responses in the lung that drive local inflammation in ventilator-induced lung injury and the basis for future mechanistic studies in this field.

  20. Linking magnetite in the abdomen of honey bees to a magnetoreceptive function.

    PubMed

    Lambinet, Veronika; Hayden, Michael E; Reigl, Katharina; Gomis, Surath; Gries, Gerhard

    2017-03-29

    Previous studies of magnetoreception in honey bees, Apis mellifera, focused on the identification of magnetic material, its formation, the location of the receptor and potential underlying sensory mechanisms, but never directly linked magnetic material to a magnetoreceptive function. In our study, we demonstrate that ferromagnetic material consistent with magnetite plays an integral role in the bees' magnetoreceptor. Subjecting lyophilized and pelletized bee tagmata to analyses by a superconducting quantum interference device generated a distinct hysteresis loop for the abdomen but not for the thorax or the head of bees, indicating the presence of ferromagnetic material in the bee abdomen. Magnetic remanence of abdomen pellets produced from bees that were, or were not, exposed to the 2.2-kOe field of a magnet while alive differed, indicating that magnet exposure altered the magnetization of this magnetite in live bees. In behavioural two-choice field experiments, bees briefly exposed to the same magnet, but not sham-treated control bees, failed to sense a custom-generated magnetic anomaly, indicating that magnet exposure had rendered the bees' magnetoreceptor dysfunctional. Our data support the conclusion that honey bees possess a magnetite-based magnetoreceptor located in the abdomen.

  1. Linking magnetite in the abdomen of honey bees to a magnetoreceptive function

    PubMed Central

    Lambinet, Veronika; Hayden, Michael E.; Reigl, Katharina; Gomis, Surath

    2017-01-01

    Previous studies of magnetoreception in honey bees, Apis mellifera, focused on the identification of magnetic material, its formation, the location of the receptor and potential underlying sensory mechanisms, but never directly linked magnetic material to a magnetoreceptive function. In our study, we demonstrate that ferromagnetic material consistent with magnetite plays an integral role in the bees' magnetoreceptor. Subjecting lyophilized and pelletized bee tagmata to analyses by a superconducting quantum interference device generated a distinct hysteresis loop for the abdomen but not for the thorax or the head of bees, indicating the presence of ferromagnetic material in the bee abdomen. Magnetic remanence of abdomen pellets produced from bees that were, or were not, exposed to the 2.2-kOe field of a magnet while alive differed, indicating that magnet exposure altered the magnetization of this magnetite in live bees. In behavioural two-choice field experiments, bees briefly exposed to the same magnet, but not sham-treated control bees, failed to sense a custom-generated magnetic anomaly, indicating that magnet exposure had rendered the bees' magnetoreceptor dysfunctional. Our data support the conclusion that honey bees possess a magnetite-based magnetoreceptor located in the abdomen. PMID:28330921

  2. Gluon structure function of a color dipole in the light-cone limit of lattice QCD

    SciTech Connect

    Gruenewald, D.; Ilgenfritz, E.-M.; Pirner, H. J.

    2009-10-01

    We calculate the gluon structure function of a color dipole in near-light-cone SU(2) lattice QCD as a function of x{sub B}. The quark and antiquark are external nondynamical degrees of freedom which act as sources of the gluon string configuration defining the dipole. We compute the color dipole matrix element of transversal chromo-electric and chromo-magnetic field operators separated along a direction close to the light cone, the Fourier transform of which is the gluon structure function. As vacuum state in the pure glue sector, we use a variational ground state of the near-light-cone Hamiltonian. We derive a recursion relation for the gluon structure function on the lattice similar to the perturbative Dokshitzer-Gribov-Lipatov-Altarelli-Parisi equation. It depends on the number of transversal links assembling the Schwinger string of the dipole. Fixing the mean momentum fraction of the gluons to the 'experimental value' in a proton, we compare our gluon structure function for a dipole state with four links with the next-to-leading-order MRST 2002 and the CTEQ AB-0 parametrizations at Q{sup 2}=1.5 GeV{sup 2}. Within the systematic uncertainty we find rather good agreement. We also discuss the low x{sub B} behavior of the gluon structure function in our model calculation.

  3. Natural photonic crystals: formation, structure, function

    NASA Astrophysics Data System (ADS)

    Bartl, Michael H.; Dahlby, Michael R.; Barrows, Frank P.; Richens, Zachary J.; Terooatea, Tommy; Jorgensen, Matthew R.

    2012-03-01

    The structure and properties of natural photonic crystals are discussed using the colored scales of the beetle Lamprocyphus augustus as an example. While the exact mechanism behind the formation of these biopolymeric photonic structures has yet to be fully explored, similarities of these structures to intracellular cubic membrane architectures are introduced. Some crucial parameters behind the formation of cubic membranes are discussed. Using these insights, intracellular cubic membrane structures are transformed into an extracellular environment.

  4. Facile chemical functionalization of proteins through intein-linked yeast display.

    PubMed

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

    2013-09-18

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

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

    PubMed

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

    2016-05-01

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

  6. Structural foundations of resting-state and task-based functional connectivity in the human brain.

    PubMed

    Hermundstad, Ann M; Bassett, Danielle S; Brown, Kevin S; Aminoff, Elissa M; Clewett, David; Freeman, Scott; Frithsen, Amy; Johnson, Arianne; Tipper, Christine M; Miller, Michael B; Grafton, Scott T; Carlson, Jean M

    2013-04-09

    Magnetic resonance imaging enables the noninvasive mapping of both anatomical white matter connectivity and dynamic patterns of neural activity in the human brain. We examine the relationship between the structural properties of white matter streamlines (structural connectivity) and the functional properties of correlations in neural activity (functional connectivity) within 84 healthy human subjects both at rest and during the performance of attention- and memory-demanding tasks. We show that structural properties, including the length, number, and spatial location of white matter streamlines, are indicative of and can be inferred from the strength of resting-state and task-based functional correlations between brain regions. These results, which are both representative of the entire set of subjects and consistently observed within individual subjects, uncover robust links between structural and functional connectivity in the human brain.

  7. Structure and function of the archaeal exosome.

    PubMed

    Evguenieva-Hackenberg, Elena; Hou, Linlin; Glaeser, Stefanie; Klug, Gabriele

    2014-01-01

    The RNA-degrading exosome in archaea is structurally very similar to the nine-subunit core of the essential eukaryotic exosome and to bacterial polynucleotide phosphorylase (PNPase). In contrast to the eukaryotic exosome, PNPase and the archaeal exosome exhibit metal ion-dependent, phosphorolytic activities and synthesize heteropolymeric RNA tails in addition to the exoribonucleolytic RNA degradation in 3' → 5' direction. The archaeal nine-subunit exosome consists of four orthologs of eukaryotic exosomal subunits: the RNase PH-domain-containing subunits Rrp41 and Rrp42 form a hexameric ring with three active sites, whereas the S1-domain-containing subunits Rrp4 and Csl4 form an RNA-binding trimeric cap on the top of the ring. In vivo, this cap contains Rrp4 and Csl4 in variable amounts. Rrp4 confers poly(A) specificity to the exosome, whereas Csl4 is involved in the interaction with the archaea-specific subunit of the complex, the homolog of the bacterial primase DnaG. The archaeal DnaG is a highly conserved protein and its gene is present in all sequenced archaeal genomes, although the exosome was lost in halophilic archaea and some methanogens. In exosome-containing archaea, DnaG is tightly associated with the exosome. It functions as an additional RNA-binding subunit with poly(A) specificity in the reconstituted exosome of Sulfolobus solfataricus and enhances the degradation of adenine-rich transcripts in vitro. Not only the RNA-binding cap but also the hexameric Rrp41-Rrp42 ring alone shows substrate selectivity and prefers purines over pyrimidines. This implies a coevolution of the exosome and its RNA substrates resulting in 3'-ends with different affinities to the exosome.

  8. CO2/light gas separation performance of cross-linked poly(vinylimidazolium) gel membranes as a function of ionic liquid loading and cross-linker content

    SciTech Connect

    Carlisle, TK; Nicodemus, GD; Gin, DL; Noble, RD

    2012-04-15

    A series of cross-linked poly(vinylimidazolium)-RTIL gel membranes was synthesized and evaluated for room-temperature, ideal CO2/N-2, CO2/CH4, and CO2/H-2 separation performance. The membranes were formed by photo-polymerization of oligo(ethylene glycol)-functionalized cross-linking (i.e., di-functional) and non-cross-linking (i.e., mono-functional) vinylimidazolium RTIL monomers with nonpolymerizable, "free RTIL." The effect of free RTIL ([emim][Tf2N]) loading on CO2 separation performance was evaluated by varying RTIL loading at three levels (45, 65, and 75 wt.%). The effect of cross-linker content on CO2 separation performance was also evaluated by varying the copolymer composition of cross-linked membranes from 5 to 100 mol% di-functional monomer. The substituent on the monofunctional RTIL monomer was also varied to investigate the effect of substituent structure and chemistry on CO2 separation performance. CO2 permeability was dramatically increased with higher loading of free RTIL. Increased RTIL loading had no effect on CO2/N-2 or CO2/CH4 permeability selectivity, but significantly improved CO2/H-2 permeability selectivity. Reducing the cross-linking monomer concentration generally improved CO2 permeability. However, anomalous permeability and selectivity behavior was observed below critical concentrations of cross-linker. The effect of the substituent on the monofunctional monomer on CO2 separation performance was minimal compared to the effects of RTIL loading and copolymer composition. (C) 2012 Elsevier B.V. All rights reserved.

  9. Honeycomb structural composite polymer network of gelatin and functional cellulose ester for controlled release of omeprazole.

    PubMed

    Zhuang, Chen; Shi, Chengmei; Tao, Furong; Cui, Yuezhi

    2017-01-05

    The functionalized cellulose ester MCN was firstly synthesized and used to cross-link gelatin by amidation between -NH2 in gelatin and active ester groups in MCN to form a composite polymer network Gel-MCN, which was confirmed by Van Slyke method, FTIR, XRD and TGA-DTG spectra. The model drug omeprazole was loaded in Gel-MCN composites mainly by electrostatic interaction and hydrogen bonds, which were certified by FTIR, XRD and TGA-DSC. Thermal stability, anti-biodegradability, mechanical property and surface hydrophobicity of the composites with different cross-linking extents and drug loading were systematically investigated. SEM images demonstrated the honeycomb structural cells of cross-linked gelatin networks and this ensured drug entrapment. The drug release mechanism was dominated by a combined effect of diffusion and degradation, and the release rate decreased with cross-linking degree increased. The developed drug delivery system had profound significance in improving pesticide effect and bioavailability of drugs.

  10. Design and construction of higher-order structure and function in proteinosome-based protocells.

    PubMed

    Huang, Xin; Patil, Avinash J; Li, Mei; Mann, Stephen

    2014-06-25

    The design and construction of higher-order structure and function in proteinosome microcompartments enclosed by a cross-linked membrane of amphiphilic bovine serum albumin/poly(N-isopropylacrylamide) (BSA-NH2/PNIPAAm) nanoconjugates is described. Three structure/function relationships are investigated: (i) differential chemical cross-linking for the control of membrane disassembly and regulated release of encapsulated genetic polymers; (ii) enzyme-mediated hydrogel structuring of the internal microenvironment to increase mechanical robustness and generate a molecularly crowded reaction environment; and (iii) self-production of a membrane-enclosing outer hydrogel wall for generating protease-resistant forms of the protein-polymer protocells. Our results highlight the potential of integrating aspects of supramolecular and polymer chemistry into the design and construction of novel bioinspired microcompartments as a step toward small-scale materials systems based on synthetic cellularity.

  11. Gut hormone GPCRs: structure, function, drug discovery.

    PubMed

    Cordomí, Arnau; Fourmy, Daniel; Tikhonova, Irina G

    2016-12-01

    Crystallization and determination of the high resolution three-dimensional structure of the β2-adrenergic receptor in 2007 was followed by structure elucidation of a number of other receptors, including those for neurotensin and glucagon. These major advances foster the understanding of structure-activity relationship of these receptors and structure-based rational design of new ligands having more predictable activity. At present, structure determination of gut hormone receptors in complex with their ligands (natural, synthetic) and interacting signalling proteins, for example, G-proteins, arrestins, represents a challenge which promises to revolutionize gut hormone endocrinonology.

  12. Pathway analysis supports association of nonsyndromic cryptorchidism with genetic loci linked to cytoskeleton-dependent functions

    PubMed Central

    Barthold, Julia Spencer; Wang, Yanping; Kolon, Thomas F.; Kollin, Claude; Nordenskjöld, Agneta; Olivant Fisher, Alicia; Figueroa, T. Ernesto; BaniHani, Ahmad H.; Hagerty, Jennifer A.; Gonzaléz, Ricardo; Noh, Paul H.; Chiavacci, Rosetta M.; Harden, Kisha R.; Abrams, Debra J.; Kim, Cecilia E.; Li, Jin; Hakonarson, Hakon; Devoto, Marcella

    2015-01-01

    STUDY QUESTION What are the genetic loci that increase susceptibility to nonsyndromic cryptorchidism, or undescended testis? SUMMARY ANSWER A genome-wide association study (GWAS) suggests that susceptibility to cryptorchidism is heterogeneous, with a subset of suggestive signals linked to cytoskeleton-dependent functions and syndromic forms of the disease. WHAT IS KNOWN ALREADY Population studies suggest moderate genetic risk of cryptorchidism and possible maternal and environmental contributions to risk. Previous candidate gene analyses have failed to identify a major associated locus, although variants in insulin-like 3 (INSL3), relaxin/insulin-like family peptide receptor 2 (RXFP2) and other hormonal pathway genes may increase risk in a small percentage of patients. STUDY DESIGN, SIZE, DURATION This is a case–control GWAS of 844 boys with nonsyndromic cryptorchidism and 2718 control subjects without syndromes or genital anomalies, all of European ancestry. PARTICIPANTS/MATERIALS, SETTING, METHODS All boys with cryptorchidism were diagnosed and treated by a pediatric specialist. In the discovery phase, DNA was extracted from tissue or blood samples and genotyping performed using the Illumina HumanHap550 and Human610-Quad (Group 1) or OmniExpress (Group 2) platform. We imputed genotypes genome-wide, and combined single marker association results in meta-analyses for all cases and for secondary subphenotype analyses based on testis position, laterality and age, and defined genome-wide significance as P = 7 × 10−9 to correct for multiple testing. Selected markers were genotyped in an independent replication group of European cases (n = 298) and controls (n = 324). We used several bioinformatics tools to analyze top (P < 10−5) and suggestive (P < 10−3) signals for significant enrichment of signaling pathways, cellular functions and custom gene lists after multiple testing correction. MAIN RESULTS AND THE ROLE OF CHANCE In the full analysis, we identified 20

  13. Weak links between fast mobility and local structure in molecular and atomic liquids

    SciTech Connect

    Bernini, S.; Puosi, F.; Leporini, D.

    2015-03-28

    We investigate by molecular-dynamics simulations, the fast mobility—the rattling amplitude of the particles temporarily trapped by the cage of the neighbors—in mildly supercooled states of dense molecular (linear trimers) and atomic (binary mixtures) liquids. The mixture particles interact by the Lennard-Jones potential. The non-bonded particles of the molecular system are coupled by the more general Mie potential with variable repulsive and attractive exponents in a range which is a characteristic of small n-alkanes and n-alcohols. Possible links between the fast mobility and the geometry of the cage (size and shape) are searched. The correlations on a per-particle basis are rather weak. Instead, if one groups either the particles in fast-mobility subsets or the cages in geometric subsets, the increase of the fast mobility with both the size and the asphericity of the cage is revealed. The observed correlations are weak and differ in states with equal relaxation time. Local forces between a tagged particle and the first-neighbour shell do not correlate with the fast mobility in the molecular liquid. It is concluded that the cage geometry alone is unable to provide a microscopic interpretation of the known, universal link between the fast mobility and the slow structural relaxation. We suggest that the particle fast dynamics is affected by regions beyond the first neighbours, thus supporting the presence of collective, extended fast modes.

  14. Decoupling of mechanical systems based on in-situ frequency response functions: The link-preserving, decoupling method

    NASA Astrophysics Data System (ADS)

    Keersmaekers, Laurent; Mertens, Luc; Penne, Rudi; Guillaume, Patrick; Steenackers, Gunther

    2015-06-01

    Mechanical structures often consist of active and passive parts, the former containing the sources, the latter the transfer paths and the targets. The active and passive parts are connected to each other by means of links. In this paper, an innovative theoretical model has been developed to achieve the mathematical decoupling of such structures without disassembling the substructures, when the links connecting the structures are resilient enough. This procedure is required to identify components causing a specific Noise, Vibration and Harsh-ness (NVH) problem. The links are regarded as a parallel connection of springs and dampers, ignoring some physical properties. However, the new procedure will provide a powerful construction in which different link models can be investigated. Therefore, this procedure will be called the Link-Preserving, Decoupling Method (LPD method). The absence of a time-consuming physical decoupling procedure distinguishes the LPD method from all known methods such as the classical TPA method. The LPD method is validated by two numerical simulations using linear and nonlinear lumped parameter models and by an experimental case study.

  15. Vibro-acoustic modelling of aircraft double-walls with structural links using Statistical Energy Analysis

    NASA Astrophysics Data System (ADS)

    Campolina, Bruno L.

    The prediction of aircraft interior noise involves the vibroacoustic modelling of the fuselage with noise control treatments. This structure is composed of a stiffened metallic or composite panel, lined with a thermal and acoustic insulation layer (glass wool), and structurally connected via vibration isolators to a commercial lining panel (trim). The goal of this work aims at tailoring the noise control treatments taking design constraints such as weight and space optimization into account. For this purpose, a representative aircraft double-wall is modelled using the Statistical Energy Analysis (SEA) method. Laboratory excitations such as diffuse acoustic field and point force are addressed and trends are derived for applications under in-flight conditions, considering turbulent boundary layer excitation. The effect of the porous layer compression is firstly addressed. In aeronautical applications, compression can result from the installation of equipment and cables. It is studied analytically and experimentally, using a single panel and a fibrous uniformly compressed over 100% of its surface. When compression increases, a degradation of the transmission loss up to 5 dB for a 50% compression of the porous thickness is observed mainly in the mid-frequency range (around 800 Hz). However, for realistic cases, the effect should be reduced since the compression rate is lower and compression occurs locally. Then the transmission through structural connections between panels is addressed using a four-pole approach that links the force-velocity pair at each side of the connection. The modelling integrates experimental dynamic stiffness of isolators, derived using an adapted test rig. The structural transmission is then experimentally validated and included in the double-wall SEA model as an equivalent coupling loss factor (CLF) between panels. The tested structures being flat, only axial transmission is addressed. Finally, the dominant sound transmission paths are

  16. Biocomposites from Natural Rubber: Synergistic Effects of Functionalized Cellulose Nanocrystals as Both Reinforcing and Cross-Linking Agents via Free-Radical Thiol-ene Chemistry.

    PubMed

    Parambath Kanoth, Bipinbal; Claudino, Mauro; Johansson, Mats; Berglund, Lars A; Zhou, Qi

    2015-08-05

    Natural rubber/cellulose nanocrystals (NR/CNCs) form true biocomposites from renewable resources and are demonstrated to show significantly improved thermo-mechanical properties and reduced stress-softening. The nanocomposites were prepared from chemically functionalized CNCs bearing thiols. CNCs served as both reinforcing and cross-linking agents in the NR matrix, and the study was designed to prove the cross-linking function of modified CNCs. CNCs were prepared from cotton, and the cross-linkable mercapto-groups were introduced onto the surface of CNCs by esterification. Nanocomposite films were prepared by dispersing the modified CNCs (m-CNCs) in NR matrix by solution casting. The cross-links at the filler-matrix (m-CNCs-NR) interface were generated by photochemically initiated thiol-ene reactions as monitored by real-time FTIR analysis. The synergistic effects of reinforcement and chemical cross-linking at the m-CNCs-NR interface on structure, thermo-mechanical, and stress-softening behavior were investigated. Methods included field emission scanning electron microscopy (FE-SEM), swelling tests, dynamic mechanical analysis, and tensile tests. Compared to biocomposites from NR with unmodified CNCs, the NR/m-CNCs nanocomposites showed 2.4-fold increase in tensile strength, 1.6-fold increase in strain-to-failure, and 2.9-fold increase in work-of-fracture at 10 wt % of m-CNCs in NR.

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

    PubMed

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

    2014-04-03

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

  18. Linking landscape structure and rainfall runoff behaviour in a thermodynamic optimality context

    NASA Astrophysics Data System (ADS)

    Zehe, Erwin; Ehret, Uwe; Blume, Theresa; Kleidon, Axel; Scherer, Ulrike; Westhoff, Martijn

    2015-04-01

    gradients, and thus a faster relaxation back towards local thermodynamic equilibrium. Thermodynamic optimality principles allow for a priory optimization of the resistance field at a given gradient, not in the sense how they exactly look like but in the sense how they function with respect to export and dissipation of free energy associated with rainfall runoff processes. Based on this framework we explored the possibility of independent predictions of rainfall runoff, in the sense that the a-priory optimum model structures should match independent observations. We found that spatially organized patterns of soils and macropores observed in two distinctly different landscapes are in close accordance with thermodynamic optima expressed either by minimized relaxation times towards local thermodynamic equilibrium in cohesive soils or as steady state in the potential energy of soil water in non-cohesive soils. Predicted rainfall runoff based on the two optimized model structures was in both catchments in acceptable accordance with independent discharge observations. However, the nature of these optima suggests there might be two distinctly different thermodynamically optimal regimes of rainfall runoff behaviour. In the capillary- or c--regime, free energy dynamics of soil water is dominated by changes in its capillary binding energy, which is the case for cohesive soils. Soil wetting during rainfall in the c-regime implies pushing the system back towards LTE, especially after long dry spells. Dead ended macropores (roots, worm burrows which end in the soil matrix) act as dissipative wetting structures by enlarging water flows against steep gradients in soil water potential after long dry spells. This implies accelerated depletion of these gradients and faster relaxation back towards LTE during rainfall runoff. In the c-regime several optimum macropore densities with respect to maximization of net reduction of free energy exist. This is because the governing equation is a second

  19. Non-parametric estimation of the odds ratios for continuous exposures using generalized additive models with an unknown link function.

    PubMed

    Cadarso-Suárez, Carmen; Roca-Pardiñas, Javier; Figueiras, Adolfo; González-Manteiga, Wenceslao

    2005-04-30

    The generalized additive, model (GAM) is a powerful and widely used tool that allows researchers to fit, non-parametrically, the effect of continuous predictors on a transformation of the mean response variable. Such a transformation is given by a so-called link function, and in GAMs this link function is assumed to be known. Nevertheless, if an incorrect choice is made for the link, the resulting GAM is misspecified and the results obtained may be misleading. In this paper, we propose a modified version of the local scoring algorithm that allows for the non-parametric estimation of the link function, by using local linear kernel smoothers. To better understand the effect that each covariate produces on the outcome, results are expressed in terms of the non-parametric odds ratio (OR) curves. Bootstrap techniques were used to correct the bias in the OR estimation and to construct point-wise confidence intervals. A simulation study was carried out to assess the behaviour of the resulting estimates. The proposed methodology was illustrated using data from the AIDS Register of Galicia (NW Spain), with a view to assessing the effect of the CD4 lymphocyte count on the probability of being AIDS-diagnosed via Tuberculosis (TB). This application shows how the link's flexibility makes it possible to obtain OR curve estimates that are less sensitive to the presence of outliers and unusual values that are often present in the extremes of the covariate distributions.

  20. Structure and stability of online chat networks built on emotion-carrying links

    NASA Astrophysics Data System (ADS)

    Gligorijević, Vladimir; Skowron, Marcin; Tadić, Bosiljka

    2013-02-01

    High-resolution data of online chats are studied as a physical system in the laboratory in order to quantify collective behavior of users. Our analysis reveals strong regularities characteristic of natural systems with additional features. In particular, we find self-organized dynamics with long-range correlations in user actions and persistent associations among users that have the properties of a social network. Furthermore, the evolution of the graph and its architecture with specific k-core structure are shown to be related with the type and the emotion arousal of exchanged messages. Partitioning of the graph by deletion of the links which carry high arousal messages exhibits critical fluctuations at the percolation threshold.

  1. Discovery of Potent, Selective, and Structurally Novel Dot1L Inhibitors by a Fragment Linking Approach.

    PubMed

    Möbitz, Henrik; Machauer, Rainer; Holzer, Philipp; Vaupel, Andrea; Stauffer, Frédéric; Ragot, Christian; Caravatti, Giorgio; Scheufler, Clemens; Fernandez, Cesar; Hommel, Ulrich; Tiedt, Ralph; Beyer, Kim S; Chen, Chao; Zhu, Hugh; Gaul, Christoph

    2017-03-09

    Misdirected catalytic activity of histone methyltransferase Dot1L is believed to be causative for a subset of highly aggressive acute leukemias. Targeting the catalytic domain of Dot1L represents a potential therapeutic approach for these leukemias. In the context of a comprehensive Dot1L hit finding strategy, a knowledge-based virtual screen of the Dot1L SAM binding pocket led to the discovery of 2, a non-nucleoside fragment mimicking key interactions of SAM bound to Dot1L. Fragment linking of 2 and 3, an induced back pocket binder identified in earlier studies, followed by careful ligand optimization led to the identification of 7, a highly potent, selective and structurally novel Dot1L inhibitor.

  2. Structural basis for complement factor H–linked age-related macular degeneration

    PubMed Central

    Prosser, Beverly E.; Johnson, Steven; Roversi, Pietro; Herbert, Andrew P.; Blaum, Bärbel S.; Tyrrell, Jess; Jowitt, Thomas A.; Clark, Simon J.; Tarelli, Edward; Uhrín, Dušan; Barlow, Paul N.; Sim, Robert B.; Day, Anthony J.; Lea, Susan M.

    2007-01-01

    Nearly 50 million people worldwide suffer from age-related macular degeneration (AMD), which causes severe loss of central vision. A single-nucleotide polymorphism in the gene for the complement regulator factor H (FH), which causes a Tyr-to-His substitution at position 402, is linked to ∼50% of attributable risks for AMD. We present the crystal structure of the region of FH containing the polymorphic amino acid His402 in complex with an analogue of the glycosaminoglycans (GAGs) that localize the complement regulator on the cell surface. The structure demonstrates direct coordination of ligand by the disease-associated polymorphic residue, providing a molecular explanation of the genetic observation. This glycan-binding site occupies the center of an extended interaction groove on the regulator's surface, implying multivalent binding of sulfated GAGs. This finding is confirmed by structure-based site-directed mutagenesis, nuclear magnetic resonance–monitored binding experiments performed for both H402 and Y402 variants with this and another model GAG, and analysis of an extended GAG–FH complex. PMID:17893204

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

    PubMed

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

    2015-10-27

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

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

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

  6. Inorganic pyrophosphatases: structural diversity serving the function

    NASA Astrophysics Data System (ADS)

    Samygina, V. R.

    2016-05-01

    The review is devoted to ubiquitous enzymes, inorganic pyrophosphatases, which are essential in all living organisms. Despite the long history of investigations, these enzymes continue to attract interest. The review focuses on the three-dimensional structures of various representatives of this class of proteins. The structural diversity, the relationship between the structure and some properties of pyrophosphatases and various mechanisms of enzyme action related to the structural diversity of these enzymes are discussed. Interactions of pyrophosphatase with other proteins and possible practical applications are considered. The bibliography includes 56 references.

  7. Fungal catalases: function, phylogenetic origin and structure.

    PubMed

    Hansberg, Wilhelm; Salas-Lizana, Rodolfo; Domínguez, Laura

    2012-09-15

    a peroxisomal catalase. Catalases have a deep buried active site and H(2)O(2) has to go through a long passage to reach it. In all known structures of catalases, the major channel has common features, particularly in the straight and narrow final section that is positioned perpendicular to the heme. Besides, other conserved channels are present in catalases whose function remains to be elucidated. One of these channels intercommunicates the major channels from the two R-related subunits. In three of the four known large-subunits catalase structures, the heme b is partially transformed into heme d. In Neurospora crassa, this occurs in vivo and is related to oxidative stress conditions in which singlet oxygen is produced. A pure source of singlet oxygen oxidizes catalases purified from different sources and singlet oxygen quenchers prevent oxidation. A second modification is observed in N. crassa catalase-1, in which the tyrosine that forms the fifth coordination bound to the heme iron makes a covalent bond with a vicinal cysteine, similarly to the tyrosine-histidine bonding found in Escherichia coli hydroperoxidase II. Molecular dynamics has been used to determine how H(2)O(2) reaches the enzyme active site and how products exit the protein. We found that the bottleneck of the major channel seems to disappear in water and is wide open in the presence of substrate. Amino acid residues exhibiting an increased residence time for H(2)O(2) are abundant at the protein surface and at the entrances to the major channel. The net effect of this is an increased H(2)O(2)/H(2)O ratio in the major channel. Once in the final section of this channel, H(2)O(2) is retained and tends to occupy specific sites while water molecules have a higher turnover rate and occupy different sites. Despite the intense study of catalases our knowledge of this enzyme is still limited and in need of new studies and different approaches.

  8. Structure of bovine lactoperoxidase with a partially linked heme moiety at 1.98Å resolution.

    PubMed

    Singh, Prashant K; Sirohi, Harsh V; Iqbal, Naseer; Tiwari, Pragya; Kaur, Punit; Sharma, Sujata; Singh, Tej P

    2017-03-01

    Lactoperoxidase (LPO) is a member of mammalian heme peroxidase superfamily whose other members are myeloperoxidase (MPO), eosinophil peroxidase (EPO) and thyroid peroxidase (TPO). In these enzymes, the heme moiety is linked to protein through two or three covalent bonds. In the mature LPO, the heme moiety is linked to protein through two ester bonds with highly conserved glutamate and aspartate residues. The previously reported structures of LPO have confirmed the formation of two covalent linkages involving Glu258 and Asp108 with 1-methyl and 5-methyl groups of pyrrole rings A and C respectively. We report here a new form of structure of LPO where the covalent bond between Glu258 and 1-methyl group of pyrrole ring A is present only in a fraction of protein molecules. In this case, the side chain of Glu258 occupies two distinct positions, each of which has a 0.5 occupancy. In one position, it forms a normal ester covalent linkage while in the second position, the side chain of Glu258 is located in the middle of the substrate binding site on the distal heme side. In t