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Sample records for biotic ligand model

  1. Challenges for the development of a biotic ligand model predicting copper toxicity in estuaries and seas

    OpenAIRE

    de Polo, A; Scrimshaw, MD

    2012-01-01

    This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2011 SETAC. An effort is ongoing to develop a biotic ligand model (BLM) that predicts copper (Cu) toxicity in estuarine and marine environments. At present, the BLM accounts for the effects of water chemistry on Cu speciation, but it does not consider the influence of water chemistry on the physiology of the organisms. We discuss how chemistry affects Cu toxicity not only by ...

  2. Challenges for the development of a biotic ligand model predicting copper toxicity in estuaries and seas.

    Science.gov (United States)

    de Polo, Anna; Scrimshaw, Mark D

    2012-02-01

    An effort is ongoing to develop a biotic ligand model (BLM) that predicts copper (Cu) toxicity in estuarine and marine environments. At present, the BLM accounts for the effects of water chemistry on Cu speciation, but it does not consider the influence of water chemistry on the physiology of the organisms. We discuss how chemistry affects Cu toxicity not only by controlling its speciation, but also by affecting the osmoregulatory physiology of the organism, which varies according to salinity. In an attempt to understand the mechanisms of Cu toxicity and predict its impacts, we explore the hypothesis that the common factor linking the main toxic effects of Cu is the enzyme carbonic anhydrase (CA), because it is a Cu target with multiple functions and salinity-dependent expression and activity. According to this hypothesis, the site of action of Cu in marine fish may be not only the gill, but also the intestine, because in this tissue CA plays an important role in ion transport and water adsorption. Therefore, the BLM of Cu toxicity to marine fish should also consider the intestine as a biotic ligand. Finally, we underline the need to incorporate the osmotic gradient into the BLM calculations to account for the influence of physiology on Cu toxicity. Copyright © 2011 SETAC.

  3. Development and validation of a chronic copper biotic ligand model for Ceriodaphnia dubia

    International Nuclear Information System (INIS)

    Schwartz, Melissa L.; Vigneault, Bernard

    2007-01-01

    A biotic ligand model (BLM) to predict chronic Cu toxicity to Ceriodaphnia dubia was developed and tested. The effect of cationic competition, pH and natural organic matter complexation of Cu was examined to develop the model. There was no effect of cationic competition using increasing Ca and Na concentrations in our exposures. However, we did see a significant regression of decreasing toxicity (measured as the IC25; concentration at which there was a 25% inhibition of reproduction) as Mg concentration increased. However, taking into account the actual variability of the IC25 and since the relative increase in IC25 due to additional Mg was small (1.5-fold) Mg competition was not included in the model. Changes in pH had a significant effect on Cu IC25, which is consistent with proton competition as often suggested for acute BLMs. Finally, natural organic matter (NOM) was added to exposures resulting in significant decreases in toxicity. Therefore, our predictive model for chronic Cu toxicity to C. dubia includes the effect of pH and NOM complexation. The model was validated with Cu IC25 data generated in six natural surface waters collected from across Canada. Using WHAM VI, we calculated Cu speciation in each natural water and using our model, we generated 'predicted' IC25 data. We successfully predicted all Cu IC25 within a factor of 3 for the six waters used for validation

  4. Coupled metal partitioning dynamics and toxicodynamics at biointerfaces: a theory beyond the biotic ligand model framework.

    Science.gov (United States)

    Duval, Jérôme F L

    2016-04-14

    A mechanistic understanding of the processes governing metal toxicity to microorganisms (bacteria, algae) calls for an adequate formulation of metal partitioning at biointerfaces during cell exposure. This includes the account of metal transport dynamics from bulk solution to biomembrane and the kinetics of metal internalisation, both potentially controlling the intracellular and surface metal fractions that originate cell growth inhibition. A theoretical rationale is developed here for such coupled toxicodynamics and interfacial metal partitioning dynamics under non-complexing medium conditions with integration of the defining cell electrostatic properties. The formalism explicitly considers intertwined metal adsorption at the biointerface, intracellular metal excretion, cell growth and metal depletion from bulk solution. The theory is derived under relevant steady-state metal transport conditions on the basis of coupled Nernst-Planck equation and continuous logistic equation modified to include metal-induced cell growth inhibition and cell size changes. Computational examples are discussed to identify limitations of the classical Biotic Ligand Model (BLM) in evaluating metal toxicity over time. In particular, BLM is shown to severely underestimate metal toxicity depending on cell exposure time, metal internalisation kinetics, cell surface electrostatics and initial cell density. Analytical expressions are provided for the interfacial metal concentration profiles in the limit where cell-growth is completely inhibited. A rigorous relationship between time-dependent cell density and metal concentrations at the biosurface and in bulk solution is further provided, which unifies previous equations formulated by Best and Duval under constant cell density and cell size conditions. The theory is sufficiently flexible to adapt to toxicity scenarios with involved cell survival-death processes.

  5. Framework for Derivation of Water Quality Criteria Using the Biotic Ligand Model: Copper as a Case Study.

    Science.gov (United States)

    Gondek, John C; Gensemer, Robert W; Claytor, Carrie A; Canton, Steven P; Gorsuch, Joseph W

    2018-06-01

    Acceptance of the Biotic Ligand Model (BLM) to derive aquatic life criteria, for metals in general and copper in particular, is growing amongst regulatory agencies worldwide. Thus, it is important to ensure that water quality data are used appropriately and consistently in deriving such criteria. Here we present a suggested BLM implementation framework (hereafter referred to as "the Framework") to help guide the decision-making process when designing sampling and analysis programs for use of the BLM to derive water quality criteria applied on a site-specific basis. Such a framework will help inform stakeholders on the requirements needed to derive BLM-based criteria, and thus, ensure the appropriate types and amount of data are being collected and interpreted. The Framework was developed for calculating BLM-based criteria when data are available from multiple sampling locations on a stream. The Framework aspires to promote consistency when applying the BLM across datasets of disparate water quality, data quantity, and spatial and temporal representativeness, and is meant to be flexible to maximize applicability over a wide range of scenarios. Therefore, the Framework allows for a certain level of interpretation and adjustment to address the issues unique to each dataset. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  6. Dissolved and labile concentrations of Cd, Cu, Pb, and Zn in the South Fork Coeur d'Alene River, Idaho: Comparisons among chemical equilibrium models and implications for biotic ligand models

    Science.gov (United States)

    Balistrieri, L.S.; Blank, R.G.

    2008-01-01

    In order to evaluate thermodynamic speciation calculations inherent in biotic ligand models, the speciation of dissolved Cd, Cu, Pb, and Zn in aquatic systems influenced by historical mining activities is examined using equilibrium computer models and the diffusive gradients in thin films (DGT) technique. Several metal/organic-matter complexation models, including WHAM VI, NICA-Donnan, and Stockholm Humic model (SHM), are used in combination with inorganic speciation models to calculate the thermodynamic speciation of dissolved metals and concentrations of metal associated with biotic ligands (e.g., fish gills). Maximum dynamic metal concentrations, determined from total dissolved metal concentrations and thermodynamic speciation calculations, are compared with labile metal concentrations measured by DGT to assess which metal/organic-matter complexation model best describes metal speciation and, thereby, biotic ligand speciation, in the studied systems. Results indicate that the choice of model that defines metal/organic-matter interactions does not affect calculated concentrations of Cd and Zn associated with biotic ligands for geochemical conditions in the study area, whereas concentrations of Cu and Pb associated with biotic ligands depend on whether the speciation calculations use WHAM VI, NICA-Donnan, or SHM. Agreement between labile metal concentrations and dynamic metal concentrations occurs when WHAM VI is used to calculate Cu speciation and SHM is used to calculate Pb speciation. Additional work in systems that contain wide ranges in concentrations of multiple metals should incorporate analytical speciation methods, such as DGT, to constrain the speciation component of biotic ligand models. ?? 2008 Elsevier Ltd.

  7. Validation of a biotic ligand model on site-specific copper toxicity to Daphnia magna in the Yeongsan River, Korea.

    Science.gov (United States)

    Park, Jinhee; Ra, Jin-Sung; Rho, Hojung; Cho, Jaeweon; Kim, Sang Don

    2018-03-01

    The objective of this study was to determine whether the water effect ratio (WER) or biotic ligand model (BLM) could be applied to efficiently develop water quality criteria (WQC) in Korea. Samples were collected from 12 specific sites along the Yeongsan River (YSR), Korea, including two sewage treatment plants and one estuary lake. A copper toxicity test using Daphnia magna was performed to determine the WER and to compare to the BLM prediction. The results of the WER from YSR samples also indicated significantly different copper toxicities in all sites. The model-based predictions showed that effluent and estuary waters had significantly different properties in regard to their ability to be used to investigate water characteristics and copper toxicity. It was supposed that the slight water characteristics changes, such as pH, DOC, hardness, conductivity, among others, influence copper toxicity, and these variable effects on copper toxicity interacted with the water composition. The 38% prediction was outside of the validation range by a factor of two in all sites, showing a poor predictive ability, especially in STPs and streams adjacent to the estuary, while the measured toxicity was more stable. The samples that ranged from pH 7.3-7.7 generated stable predictions, while other samples, including those with lower and the higher pH values, led to more unstable predictions. The results also showed that the toxicity of Cu in sample waters to D. magna was closely proportional to the amounts of acidity, including the carboxylic and phenolic groups, as well as the DOC concentrations. Consequently, the acceptable prediction of metal toxicity in various water samples needs the site-specific results considering the water characteristics such as pH and DOC properties particularly in STPs and estuary regions. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Development of biotic ligand models for chronic manganese toxicity to fish, invertebrates, and algae.

    Science.gov (United States)

    Peters, Adam; Lofts, Stephen; Merrington, Graham; Brown, Bruce; Stubblefield, William; Harlow, Keven

    2011-11-01

    Ecotoxicity tests were performed with fish, invertebrates, and algae to investigate the effect of water quality parameters on Mn toxicity. Models were developed to describe the effects of Mn as a function of water quality. Calcium (Ca) has a protective effect on Mn toxicity for both fish and invertebrates, and magnesium (Mg) also provides a protective effect for invertebrates. Protons have a protective effect on Mn toxicity to algae. The models derived are consistent with models of the toxicity of other metals to aquatic organisms in that divalent cations can act as competitors to Mn toxicity in fish and invertebrates, and protons act as competitors to Mn toxicity in algae. The selected models are able to predict Mn toxicity to the test organisms to within a factor of 2 in most cases. Under low-pH conditions invertebrates are the most sensitive taxa, and under high-pH conditions algae are most sensitive. The point at which algae become more sensitive than invertebrates depends on the Ca concentration and occurs at higher pH when Ca concentrations are low, because of the sensitivity of invertebrates under these conditions. Dissolved organic carbon concentrations have very little effect on the toxicity of Mn to aquatic organisms. Copyright © 2011 SETAC.

  9. Development and validation of a terrestrial biotic ligand model predicting the effect of cobalt on root growth of barley (Hordeum vulgare)

    International Nuclear Information System (INIS)

    Lock, K.; De Schamphelaere, K.A.C.; Becaus, S.; Criel, P.; Van Eeckhout, H.; Janssen, C.R.

    2007-01-01

    A Biotic Ligand Model was developed predicting the effect of cobalt on root growth of barley (Hordeum vulgare) in nutrient solutions. The extent to which Ca 2+ , Mg 2+ , Na + , K + ions and pH independently affect cobalt toxicity to barley was studied. With increasing activities of Mg 2+ , and to a lesser extent also K + , the 4-d EC50 Co2+ increased linearly, while Ca 2+ , Na + and H + activities did not affect Co 2+ toxicity. Stability constants for the binding of Co 2+ , Mg 2+ and K + to the biotic ligand were obtained: log K CoBL = 5.14, log K MgBL = 3.86 and log K KBL = 2.50. Limited validation of the model with one standard artificial soil and one standard field soil showed that the 4-d EC50 Co2+ could only be predicted within a factor of four from the observed values, indicating further refinement of the BLM is needed. - Biotic Ligand Models are not only a useful tool to assess metal toxicity in aquatic systems but can also be used for terrestrial plants

  10. Applying biotic ligand models and Bayesian techniques: ecological risk assessment of copper and nickel in Tokyo rivers.

    Science.gov (United States)

    Hayashi, Takehiko I

    2013-01-01

    Biotic ligand models (BLMs) have been broadly accepted and used in ecological risk assessment of heavy metals for toxicity normalization with respect to water chemistry. However, the importance of assessing bioavailability by using BLMs has not been widely recognized among Japanese stakeholders. Failing to consider bioavailability may result in less effective risk management than would be possible if currently available state-of-the-art methods were used to relate bioavailable concentrations to toxic effects. In this study, an ecological risk assessment was conducted using BLMs for 6 rivers in Tokyo to stimulate discussion about bioavailability of heavy metals and the use of BLMs in ecological risk management in Japan. In the risk analysis, a Bayesian approach was used to take advantage of information from previous analyses and to calculate uncertainties in the estimation of risk. Risks were judged to be a concern if the predicted environmental concentration exceeded the 5th percentile concentration (HC5) of the species sensitivity distribution. Based on this criterion, risks to stream biota from exposure to Cu were judged not to be very severe, but it would be desirable to conduct further monitoring and field surveys to determine whether temporary exposure to concentrations exceeding the HC5 causes any irreversible effects on the river ecosystem. The risk of exposure to Ni was a concern at only 1 of the 6 sites. BLM corrections affected these conclusions in the case of Cu but were moot in the case of Ni. The use of BLMs in risk assessment calculations for Japanese rivers requires water quality information that is, unfortunately, not always available. Copyright © 2012 SETAC.

  11. An in vitro biotic ligand model (BLM) for silver binding to cultured gill epithelia of freshwater rainbow trout (Oncorhynchus mykiss)

    International Nuclear Information System (INIS)

    Zhou Bingsheng; Nichols, Joel; Playle, Richard C.; Wood, Chris M.

    2005-01-01

    'Reconstructed' gill epithelia on filter supports were grown in primary culture from dispersed gill cells of freshwater rainbow trout (Oncorhynchus mykiss). This preparation contains both pavement cells and chloride cells, and after 7-9 days in culture, permits exposure of the apical surface to true freshwater while maintaining blood-like culture media on the basolateral surface, and exhibits a stable transepithelial resistance (TER) and transepithelial potential (TEP) under these conditions. These epithelia were used to develop a possible in vitro version of the biotic ligand model (BLM) for silver; the in vivo BLM uses short-term gill binding of the metal to predict acute silver toxicity as a function of freshwater chemistry. Radio-labeled silver ( 110m Ag as AgNO 3 ) was placed on the apical side (freshwater), and the appearance of 110m Ag in the epithelia (binding) and in the basolateral media (flux) over 3 h were monitored. Silver binding (greater than the approximate range 0-100 μg l -1 ) and silver flux were concentration-dependent with a 50% saturation point (apparent K d ) value of about 10 μg l -1 or 10 -7 M, very close to the 96-h LC50 in vivo in the same water chemistry. There were no adverse effects of silver on TER, TEP, or Na + , K + -ATPase activity, though the latter declined over longer exposures, as in vivo. Silver flux over 3 h was small ( + and dissolved organic carbon (humic acid) concentrations, increased by elevations in freshwater Cl - and reductions in pH, and insensitive to elevations in Ca 2+ . With the exception of the pH response, these effects were qualitatively and quantitatively similar to in vivo BLM responses. The results suggest that an in vitro BLM approach may provide a simple and cost-effective way for evaluating the protective effects of site-specific waters

  12. Comparison of the capacity of two biotic ligand models to predict chronic copper toxicity to two Daphnia magna clones and formulation of a generalized bioavailability model.

    Science.gov (United States)

    Van Regenmortel, Tina; Janssen, Colin R; De Schamphelaere, Karel A C

    2015-07-01

    Although it is increasingly recognized that biotic ligand models (BLMs) are valuable in the risk assessment of metals in aquatic systems, the use of 2 differently structured and parameterized BLMs (1 in the United States and another in the European Union) to obtain bioavailability-based chronic water quality criteria for copper is worthy of further investigation. In the present study, the authors evaluated the predictive capacity of these 2 BLMs for a large dataset of chronic copper toxicity data with 2 Daphnia magna clones, termed K6 and ARO. One BLM performed best with clone K6 data, whereas the other performed best with clone ARO data. In addition, there was an important difference between the 2 BLMs in how they predicted the bioavailability of copper as a function of pH. These modeling results suggested that the effect of pH on chronic copper toxicity is different between the 2 clones considered, which was confirmed with additional chronic toxicity experiments. Finally, because fundamental differences in model structure between the 2 BLMs made it impossible to create an average BLM, a generalized bioavailability model (gBAM) was developed. Of the 3 gBAMs developed, the authors recommend the use of model gBAM-C(uni), which combines a log-linear relation between the 21-d median effective concentration (expressed as free Cu(2+) ion activity) and pH, with more conventional BLM-type competition constants for sodium, calcium, and magnesium. This model can be considered a first step in further improving the accuracy of chronic toxicity predictions of copper as a function of water chemistry (for a variety of Daphnia magna clones), even beyond the robustness of the current BLMs used in regulatory applications. © 2015 SETAC.

  13. Consideration of the bioavailability of metal/metalloid species in freshwaters: experiences regarding the implementation of biotic ligand model-based approaches in risk assessment frameworks.

    Science.gov (United States)

    Rüdel, Heinz; Díaz Muñiz, Cristina; Garelick, Hemda; Kandile, Nadia G; Miller, Bradley W; Pantoja Munoz, Leonardo; Peijnenburg, Willie J G M; Purchase, Diane; Shevah, Yehuda; van Sprang, Patrick; Vijver, Martina; Vink, Jos P M

    2015-05-01

    After the scientific development of biotic ligand models (BLMs) in recent decades, these models are now considered suitable for implementation in regulatory risk assessment of metals in freshwater bodies. The BLM approach has been described in many peer-reviewed publications, and the original complex BLMs have been applied in prospective risk assessment reports for metals and metal compounds. BLMs are now also recommended as suitable concepts for the site-specific evaluation of monitoring data in the context of the European Water Framework Directive. However, the use is hampered by the data requirements for the original BLMs (about 10 water parameters). Recently, several user-friendly BLM-based bioavailability software tools for assessing the aquatic toxicity of relevant metals (mainly copper, nickel, and zinc) became available. These tools only need a basic set of commonly determined water parameters as input (i.e., pH, hardness, dissolved organic matter, and dissolved metal concentration). Such tools seem appropriate to foster the implementation of routine site-specific water quality assessments. This work aims to review the existing bioavailability-based regulatory approaches and the application of available BLM-based bioavailability tools for this purpose. Advantages and possible drawbacks of these tools (e.g., feasibility, boundaries of validity) are discussed, and recommendations for further implementation are given.

  14. Testing the Underlying Chemical Principles of the Biotic Ligand Model (BLM) to Marine Copper Systems: Measuring Copper Speciation Using Fluorescence Quenching.

    Science.gov (United States)

    Tait, Tara N; McGeer, James C; Smith, D Scott

    2018-01-01

    Speciation of copper in marine systems strongly influences the ability of copper to cause toxicity. Natural organic matter (NOM) contains many binding sites which provides a protective effect on copper toxicity. The purpose of this study was to characterize copper binding with NOM using fluorescence quenching techniques. Fluorescence quenching of NOM with copper was performed on nine sea water samples. The resulting stability constants and binding capacities were consistent with literature values of marine NOM, showing strong binding with [Formula: see text] values from 7.64 to 10.2 and binding capacities ranging from 15 to 3110 nmol mg [Formula: see text] Free copper concentrations estimated at total dissolved copper concentrations corresponding to previously published rotifer effect concentrations, in the same nine samples, were statistically the same as the range of free copper calculated for the effect concentration in NOM-free artificial seawater. These data confirms the applicability of fluorescence spectroscopy techniques for NOM and copper speciation characterization in sea water and demonstrates that such measured speciation is consistent with the chemical principles underlying the biotic ligand model approach for bioavailability-based metals risk assessment.

  15. Measured Copper Toxicity to Cnesterodon decemmaculatus (Pisces: Poeciliidae and Predicted by Biotic Ligand Model in Pilcomayo River Water: A Step for a Cross-Fish-Species Extrapolation

    Directory of Open Access Journals (Sweden)

    María Victoria Casares

    2012-01-01

    Full Text Available In order to determine copper toxicity (LC50 to a local species (Cnesterodon decemmaculatus in the South American Pilcomayo River water and evaluate a cross-fish-species extrapolation of Biotic Ligand Model, a 96 h acute copper toxicity test was performed. The dissolved copper concentrations tested were 0.05, 0.19, 0.39, 0.61, 0.73, 1.01, and 1.42 mg Cu L-1. The 96 h Cu LC50 calculated was 0.655 mg L-1 (0.823-0.488. 96-h Cu LC50 predicted by BLM for Pimephales promelas was 0.722 mg L-1. Analysis of the inter-seasonal variation of the main water quality parameters indicates that a higher protective effect of calcium, magnesium, sodium, sulphate, and chloride is expected during the dry season. The very high load of total suspended solids in this river might be a key factor in determining copper distribution between solid and solution phases. A cross-fish-species extrapolation of copper BLM is valid within the water quality parameters and experimental conditions of this toxicity test.

  16. Use of Multiple Linear Regression Models for Setting Water Quality Criteria for Copper: A Complementary Approach to the Biotic Ligand Model.

    Science.gov (United States)

    Brix, Kevin V; DeForest, David K; Tear, Lucinda; Grosell, Martin; Adams, William J

    2017-05-02

    Biotic Ligand Models (BLMs) for metals are widely applied in ecological risk assessments and in the development of regulatory water quality guidelines in Europe, and in 2007 the United States Environmental Protection Agency (USEPA) recommended BLM-based water quality criteria (WQC) for Cu in freshwater. However, to-date, few states have adopted BLM-based Cu criteria into their water quality standards on a state-wide basis, which appears to be due to the perception that the BLM is too complicated or requires too many input variables. Using the mechanistic BLM framework to first identify key water chemistry parameters that influence Cu bioavailability, namely dissolved organic carbon (DOC), pH, and hardness, we developed Cu criteria using the same basic methodology used by the USEPA to derive hardness-based criteria but with the addition of DOC and pH. As an initial proof of concept, we developed stepwise multiple linear regression (MLR) models for species that have been tested over wide ranges of DOC, pH, and hardness conditions. These models predicted acute Cu toxicity values that were within a factor of ±2 in 77% to 97% of tests (5 species had adequate data) and chronic Cu toxicity values that were within a factor of ±2 in 92% of tests (1 species had adequate data). This level of accuracy is comparable to the BLM. Following USEPA guidelines for WQC development, the species data were then combined to develop a linear model with pooled slopes for each independent parameter (i.e., DOC, pH, and hardness) and species-specific intercepts using Analysis of Covariance. The pooled MLR and BLM models predicted species-specific toxicity with similar precision; adjusted R 2 and R 2 values ranged from 0.56 to 0.86 and 0.66-0.85, respectively. Graphical exploration of relationships between predicted and observed toxicity, residuals and observed toxicity, and residuals and concentrations of key input parameters revealed many similarities and a few key distinctions between the

  17. The relationship between metal toxicity and biotic ligand binding affinities in aquatic and soil organisms: a review.

    Science.gov (United States)

    Ardestani, Masoud M; van Straalen, Nico M; van Gestel, Cornelis A M

    2014-12-01

    The biotic ligand model (BLM) is a theoretical, potentially mechanistic approach to assess metal bioavailability in soil and aquatic systems. In a BLM, toxicity is linked to the fraction of biotic ligand occupied, which in turn, depends on the various components of the solution, including activity of the metal. Bioavailability is a key factor in determining toxicity and uptake of metals in organisms. In this study, the present status of BLM development for soil and aquatic organisms is summarized. For all species and all metals, toxicity was correlated with the conditional biotic ligand binding constants. For almost all organisms, values for Ag, Cu, and Cd were higher than those for Zn and Ni. The constants derived for aquatic systems seem to be equally valid for soil organisms, but in the case of soils, bioavailability from the soil solution is greatly influenced by the presence of the soil solid phase. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Temporal assessment of copper speciation, bioavailability and toxicity in UK freshwaters using chemical equilibrium and biotic ligand models: Implications for compliance with copper environmental quality standards.

    Science.gov (United States)

    Lathouri, Maria; Korre, Anna

    2015-12-15

    Although significant progress has been made in understanding how environmental factors modify the speciation, bioavailability and toxicity of metals such as copper in aquatic environments, the current methods used to establish water quality standards do not necessarily consider the different geological and geochemical characteristics of a given site and the factors that affect copper fate, bioavailability potential and toxicity. In addition, the temporal variation in the concentration and bioavailable metal fraction is also important in freshwater systems. The work presented in this paper illustrates the temporal and seasonal variability of a range of water quality parameters, and Cu speciation, bioavailability and toxicity at four freshwaters sites in the UK. Rivers Coquet, Cree, Lower Clyde and Eden (Kent) were selected to cover a broad range of different geochemical environments and site characteristics. The monitoring data used covered a period of around six years at almost monthly intervals. Chemical equilibrium modelling was used to study temporal variations in Cu speciation and was combined with acute toxicity modelling to assess Cu bioavailability for two aquatic species, Daphnia magna and Daphnia pulex. The estimated copper bioavailability, toxicity levels and the corresponding ecosystem risks were analysed in relation to key water quality parameters (alkalinity, pH and DOC). Although copper concentrations did not vary much during the sampling period or between the seasons at the different sites; copper bioavailability varied markedly. In addition, through the chronic-Cu BLM-based on the voluntary risk assessment approach, the potential environmental risk in terms of the chronic toxicity was assessed. A much higher likelihood of toxicity effects was found during the cold period at all sites. It is suggested that besides the metal (copper) concentration in the surface water environment, the variability and seasonality of other important water quality

  19. Ligand modeling and design

    Energy Technology Data Exchange (ETDEWEB)

    Hay, B.P. [Pacific Northwest National Lab., Richland, WA (United States)

    1997-10-01

    The purpose of this work is to develop and implement a molecular design basis for selecting organic ligands that would be used in the cost-effective removal of specific radionuclides from nuclear waste streams. Organic ligands with metal ion specificity are critical components in the development of solvent extraction and ion exchange processes that are highly selective for targeted radionuclides. The traditional approach to the development of such ligands involves lengthy programs of organic synthesis and testing, which in the absence of reliable methods for screening compounds before synthesis, results in wasted research effort. The author`s approach breaks down and simplifies this costly process with the aid of computer-based molecular modeling techniques. Commercial software for organic molecular modeling is being configured to examine the interactions between organic ligands and metal ions, yielding an inexpensive, commercially or readily available computational tool that can be used to predict the structures and energies of ligand-metal complexes. Users will be able to correlate the large body of existing experimental data on structure, solution binding affinity, and metal ion selectivity to develop structural design criteria. These criteria will provide a basis for selecting ligands that can be implemented in separations technologies through collaboration with other DOE national laboratories and private industry. The initial focus will be to select ether-based ligands that can be applied to the recovery and concentration of the alkali and alkaline earth metal ions including cesium, strontium, and radium.

  20. Acute dysprosium toxicity to Daphnia pulex and Hyalella azteca and development of the biotic ligand approach

    Energy Technology Data Exchange (ETDEWEB)

    Vukov, Oliver, E-mail: vuko3930@mylaurier.ca [Biology Department, Wilfrid Laurier University, Waterloo, Ontario N2L 3C5 (Canada); Smith, D. Scott [Chemistry Department, Wilfrid Laurier University, Waterloo, Ontario N2L 3C5 (Canada); McGeer, James C. [Biology Department, Wilfrid Laurier University, Waterloo, Ontario N2L 3C5 (Canada)

    2016-01-15

    The toxicological understanding of rare earth elements (REEs) in the aquatic environment is very limited but of increasing concern. The objective of this research is to compare the toxicological effect of the REE dysprosium to the freshwater invertebrates Daphnia pulex and Hyalella azteca and in the more sensitive organism, understand the toxicity modifying influence of Ca, Na, Mg, pH and dissolved organic matter (DOM). Standard methods (Environment Canada) were followed for testing and culture in media of intermediate hardness (60 mg CaCO{sub 3} mg/L) at pH 7.8 with Ca at 0.5, Na 0.5, Mg 0.125 (mM) and 23 °C. Acute toxicity tests were done with <24 h old neonates for 48 h in the case of D. pulex and with 2–9 days old offspring for 96 h tests with Hyalella. The potential protective effect of cationic competition was tested with Ca (0.5–2.0 mM), Na (0.5–2.0 mM) and Mg (0.125–0.5 mM). The effect of pH (6.5–8.0) and Suwannee River DOM complexation (at dissolved organic carbon (DOC) concentrations of 9 and 13 mg C/L) were evaluated. Dissolved Dy concentrations were lower than total (unfiltered) indicating precipitation, particularly at higher concentrations. Acute toxicity of Dy to H. azteca and D. pulex revealed Hyalella to be 1.4 times more sensitive than Daphnia. Additions of Ca and Na but not Mg provided significant protection against Dy toxicity to Hyalella. Similarly, low pH was associated with reduction in toxicity. Exposures which were pH buffered with and without MOPS were significantly different and indicated that MOPS enhanced Dy toxicity. DOM also mitigated Dy toxicity. Biotic ligand based parameters (Log K values) were calculated based on free ion relationships as determined by geochemical equilibrium modeling software (WHAM ver. 7.02). The log K value for Dy{sup 3+} toxicity to Hyalella was 7.75 while the protective influence of Ca and Na were 3.95 and 4.10, respectively. This study contributes data towards the development of site specific

  1. Acute dysprosium toxicity to Daphnia pulex and Hyalella azteca and development of the biotic ligand approach

    International Nuclear Information System (INIS)

    Vukov, Oliver; Smith, D. Scott; McGeer, James C.

    2016-01-01

    The toxicological understanding of rare earth elements (REEs) in the aquatic environment is very limited but of increasing concern. The objective of this research is to compare the toxicological effect of the REE dysprosium to the freshwater invertebrates Daphnia pulex and Hyalella azteca and in the more sensitive organism, understand the toxicity modifying influence of Ca, Na, Mg, pH and dissolved organic matter (DOM). Standard methods (Environment Canada) were followed for testing and culture in media of intermediate hardness (60 mg CaCO 3 mg/L) at pH 7.8 with Ca at 0.5, Na 0.5, Mg 0.125 (mM) and 23 °C. Acute toxicity tests were done with <24 h old neonates for 48 h in the case of D. pulex and with 2–9 days old offspring for 96 h tests with Hyalella. The potential protective effect of cationic competition was tested with Ca (0.5–2.0 mM), Na (0.5–2.0 mM) and Mg (0.125–0.5 mM). The effect of pH (6.5–8.0) and Suwannee River DOM complexation (at dissolved organic carbon (DOC) concentrations of 9 and 13 mg C/L) were evaluated. Dissolved Dy concentrations were lower than total (unfiltered) indicating precipitation, particularly at higher concentrations. Acute toxicity of Dy to H. azteca and D. pulex revealed Hyalella to be 1.4 times more sensitive than Daphnia. Additions of Ca and Na but not Mg provided significant protection against Dy toxicity to Hyalella. Similarly, low pH was associated with reduction in toxicity. Exposures which were pH buffered with and without MOPS were significantly different and indicated that MOPS enhanced Dy toxicity. DOM also mitigated Dy toxicity. Biotic ligand based parameters (Log K values) were calculated based on free ion relationships as determined by geochemical equilibrium modeling software (WHAM ver. 7.02). The log K value for Dy 3+ toxicity to Hyalella was 7.75 while the protective influence of Ca and Na were 3.95 and 4.10, respectively. This study contributes data towards the development of site specific water quality

  2. Hydrolysis and biotic transformation in water in the pesticide model

    NARCIS (Netherlands)

    Horst, ter M.M.S.; Beltman, W.H.J.; Adriaanse, P.I.; Mulder, H.M.

    2017-01-01

    The TOXSWA model has been extended with the functionality to simulate hydrolysis and biotic transformation in water. TOXSWA simulates the fate of pesticides in water bodies to calculate exposure calculations for aquatic organisms or sediment-dwelling organisms as part of the aquatic risk assessment

  3. Toxicity of Silver Nanoparticles to Green Algae – Towards a Biotic Ligand Understanding

    DEFF Research Database (Denmark)

    Laruelle, Sacha; Sørensen, Sara Nørgaard; Cupi, Denisa

    with the freshwater green algae Pseudokirschneriella subcapitata were carried out to falsify the hypothesis: “The toxicity of silver nanoparticles towards algae is solely caused by the monovalent silver ion”. These experiments were based on PHREEQC modeling of silver ion behavior (added as AgNO3) in 72h OECD algal...

  4. Potential role of biotic transport models in low-level-waste management

    International Nuclear Information System (INIS)

    Kennedy, W.E. Jr.; Soldat, J.K.; Cadwell, L.L.; McKenzie, D.H.

    1982-01-01

    This paper is a summary of the initial results of a study being conducted for the US Nuclear Regulatory Commission (NRC) to determine the relevance of biotic pathways to the regulation of nuclear waste disposal. Biotic transport is defined as the actions of plants and animals that result in the transport of radioactive materials from a LLW burial ground to a location where they can enter exposure pathways to man. A critical review of the role of modeling in evaluating biotic transport is given. Both current applications and the need for future modeling development are discussed

  5. Natural biotic resources in LCA: Towards an impact assessment model for sustainable supply chain management.

    Science.gov (United States)

    Crenna, Eleonora; Sozzo, Sara; Sala, Serenella

    2018-01-20

    Natural resources, biotic and abiotic, are fundamental from both the ecological and socio-economic point of view, being at the basis of life-support. However, since the demand for finite resources continues to increase, the sustainability of current production and consumption patterns is questioned both in developed and developing countries. A transition towards an economy based on biotic renewable resources (bio-economy) is considered necessary in order to support a steady provision of resources, representing an alternative to an economy based on fossil and abiotic resources. However, to ensure a sustainable use of biotic resources, there is the need of properly accounting for their use along supply chains as well as defining a robust and comprehensive impact assessment model. Since so far naturally occurring biotic resources have gained little attention in impact assessment methods, such as life cycle assessment, the aim of this study is to enable the inclusion of biotic resources in the assessment of products and supply chains. This paper puts forward a framework for biotic resources assessment, including: i) the definition of system boundaries between ecosphere and technosphere, namely between naturally occurring and man-made biotic resources; ii) a list of naturally occurring biotic resources which have a commercial value, as basis for building life cycle inventories (NOBR, e.g. wild animals, plants etc); iii) an impact pathway to identify potential impacts on both resource provision and ecosystem quality; iv) a renewability-based indicator (NOBRri) for the impact assessment of naturally occurring biotic resources, including a list of associated characterization factors. The study, building on a solid review of literature and of available statistical data, highlights and discusses the critical aspects and paradoxes related to biotic resource inclusion in LCA: from the system boundaries definition up to the resource characterization.

  6. Biotic interactions in the face of climate change: a comparison of three modelling approaches.

    Directory of Open Access Journals (Sweden)

    Anja Jaeschke

    Full Text Available Climate change is expected to alter biotic interactions, and may lead to temporal and spatial mismatches of interacting species. Although the importance of interactions for climate change risk assessments is increasingly acknowledged in observational and experimental studies, biotic interactions are still rarely incorporated in species distribution models. We assessed the potential impacts of climate change on the obligate interaction between Aeshna viridis and its egg-laying plant Stratiotes aloides in Europe, based on an ensemble modelling technique. We compared three different approaches for incorporating biotic interactions in distribution models: (1 We separately modelled each species based on climatic information, and intersected the future range overlap ('overlap approach'. (2 We modelled the potential future distribution of A. viridis with the projected occurrence probability of S. aloides as further predictor in addition to climate ('explanatory variable approach'. (3 We calibrated the model of A. viridis in the current range of S. aloides and multiplied the future occurrence probabilities of both species ('reference area approach'. Subsequently, all approaches were compared to a single species model of A. viridis without interactions. All approaches projected a range expansion for A. viridis. Model performance on test data and amount of range gain differed depending on the biotic interaction approach. All interaction approaches yielded lower range gains (up to 667% lower than the model without interaction. Regarding the contribution of algorithm and approach to the overall uncertainty, the main part of explained variation stems from the modelling algorithm, and only a small part is attributed to the modelling approach. The comparison of the no-interaction model with the three interaction approaches emphasizes the importance of including obligate biotic interactions in projective species distribution modelling. We recommend the use of

  7. The lake foodweb: modelling predation and abiotic/biotic interactions

    National Research Council Canada - National Science Library

    Hakanson, L; Boulion, V.V

    2002-01-01

    .... The model is based on many new approaches of structuring lake foodweb interactions. It uses ordinary differential equations and gives weekly variations in production and biomass for its nine groups of organisms...

  8. Asymmetric biotic interactions and abiotic niche differences revealed by a dynamic joint species distribution model.

    Science.gov (United States)

    Lany, Nina K; Zarnetske, Phoebe L; Schliep, Erin M; Schaeffer, Robert N; Orians, Colin M; Orwig, David A; Preisser, Evan L

    2018-05-01

    A species' distribution and abundance are determined by abiotic conditions and biotic interactions with other species in the community. Most species distribution models correlate the occurrence of a single species with environmental variables only, and leave out biotic interactions. To test the importance of biotic interactions on occurrence and abundance, we compared a multivariate spatiotemporal model of the joint abundance of two invasive insects that share a host plant, hemlock woolly adelgid (HWA; Adelges tsugae) and elongate hemlock scale (EHS; Fiorina externa), to independent models that do not account for dependence among co-occurring species. The joint model revealed that HWA responded more strongly to abiotic conditions than EHS. Additionally, HWA appeared to predispose stands to subsequent increase of EHS, but HWA abundance was not strongly dependent on EHS abundance. This study demonstrates how incorporating spatial and temporal dependence into a species distribution model can reveal the dependence of a species' abundance on other species in the community. Accounting for dependence among co-occurring species with a joint distribution model can also improve estimation of the abiotic niche for species affected by interspecific interactions. © 2018 by the Ecological Society of America.

  9. Sigma-2 receptor ligands QSAR model dataset

    Directory of Open Access Journals (Sweden)

    Antonio Rescifina

    2017-08-01

    Full Text Available The data have been obtained from the Sigma-2 Receptor Selective Ligands Database (S2RSLDB and refined according to the QSAR requirements. These data provide information about a set of 548 Sigma-2 (σ2 receptor ligands selective over Sigma-1 (σ1 receptor. The development of the QSAR model has been undertaken with the use of CORAL software using SMILES, molecular graphs and hybrid descriptors (SMILES and graph together. Data here reported include the regression for σ2 receptor pKi QSAR models. The QSAR model was also employed to predict the σ2 receptor pKi values of the FDA approved drugs that are herewith included.

  10. Dynamic ligand-based pharmacophore modeling and virtual ...

    Indian Academy of Sciences (India)

    Five ligand-based pharmacophore models were generated from 40 different .... the Phase module of the Schrodinger program.35 Each model consisted of six types of ... ligand preparation included the OPLS_2005 force field and to retain the ...

  11. Variability in connectivity patterns of fish with ontogenetic migrations: Modelling effects of abiotic and biotic factors

    Directory of Open Access Journals (Sweden)

    Susanne Eva Tanner

    2015-10-01

    Full Text Available Connectivity is a critical property of marine fish populations as it drives population replenishment, determines colonization patterns and the resilience of populations to harvest. Understanding connectivity patterns is particularly important in species that present ontogenetic migrations and segregated habitat use during their life history, such as marine species with estuarine nursery areas. Albeit challenging, fish movement can be estimated and quantified using different methodologies depending on the life history stages of interest (e.g. biophysical modelling, otolith chemistry, genetic markers. Relative contributions from estuarine nursery areas to the adult coastal populations were determined using otolith elemental composition and maximum likelihood estimation for four commercially important species (Dicentrarchus labrax, Plathichtys flesus, Solea senegalensis and Solea solea and showed high interannual variability. Here, the effects of abiotic and biotic factors on the observed variability in connectivity rates and extent between estuarine juvenile and coastal adult subpopulations are investigated using generalized linear models (GLM and generalized mixed models (GMM. Abiotic factors impacting both larval and juvenile life history stages are included in the models (e.g. wind force and direction, NAO, water temperature while biotic factors relative to the estuarine residency of juvenile fish are evaluated (e.g. juvenile density, food availability. Factors contributing most to the observed variability in connectivity rates are singled out and compared among species. General trends are identified and results area discussed in the general context of identifying potential management frameworks applicable to different life stages and which may prove useful for ontogenetically migrating species.

  12. Abiotic/biotic coupling in the rhizosphere: a reactive transport modeling analysis

    Science.gov (United States)

    Lawrence, Corey R.; Steefel, Carl; Maher, Kate

    2014-01-01

    A new generation of models is needed to adequately simulate patterns of soil biogeochemical cycling in response changing global environmental drivers. For example, predicting the influence of climate change on soil organic matter storage and stability requires models capable of addressing complex biotic/abiotic interactions of rhizosphere and weathering processes. Reactive transport modeling provides a powerful framework simulating these interactions and the resulting influence on soil physical and chemical characteristics. Incorporation of organic reactions in an existing reactive transport model framework has yielded novel insights into soil weathering and development but much more work is required to adequately capture root and microbial dynamics in the rhizosphere. This endeavor provides many advantages over traditional soil biogeochemical models but also many challenges.

  13. A Model of Continental Growth and Mantle Degassing Comparing Biotic and Abiotic Worlds

    Science.gov (United States)

    Höning, D.; Hansen-Goos, H.; Spohn, T.

    2012-12-01

    the phase area where the net degassing and continental growth rates are zero. Many of the parameter combinations result in one stable fixed point with a completely dry mantle that lacks continents altogether and a second stable fixed point with a continent coverage and mantle water concentration close to that of the present Earth. In addition, there is an unstable fixed point situated between the two. In general, the abiotic world has a larger zone of attraction for the fixed point with a dry mantle and no continents than the biotic world. Thus a biotic world is found to be more likely to develop continents and a have wet mantle. Furthermore, the biotic model is generally found to have a wetter mantle than an abiotic model with the same continent coverage. Through the effect of water on the mantle rheology, the biotic world would thus tend to be tectonically more active and have a more rapid long-term carbon silicate cycle. References: J. Kim, H. Dong, J. Seabaugh, S. W. Newell, D. D. Eberl, Science 303, 830-832, 2004 N. H. Sleep, D. K. Bird, E. Pope, Annu. Rev. Earth Planet. Sci. 40, 277-300, 2012 M. T. Rosing, D. K. Bird, N. H. Sleep, W. Glassley, F. Albarede, Paleo3 232, 90-113, 2006

  14. The role of biotic interactions in shaping distributions and realised assemblages of species: implications for species distribution modelling.

    Science.gov (United States)

    Wisz, Mary Susanne; Pottier, Julien; Kissling, W Daniel; Pellissier, Loïc; Lenoir, Jonathan; Damgaard, Christian F; Dormann, Carsten F; Forchhammer, Mads C; Grytnes, John-Arvid; Guisan, Antoine; Heikkinen, Risto K; Høye, Toke T; Kühn, Ingolf; Luoto, Miska; Maiorano, Luigi; Nilsson, Marie-Charlotte; Normand, Signe; Öckinger, Erik; Schmidt, Niels M; Termansen, Mette; Timmermann, Allan; Wardle, David A; Aastrup, Peter; Svenning, Jens-Christian

    2013-02-01

    Predicting which species will occur together in the future, and where, remains one of the greatest challenges in ecology, and requires a sound understanding of how the abiotic and biotic environments interact with dispersal processes and history across scales. Biotic interactions and their dynamics influence species' relationships to climate, and this also has important implications for predicting future distributions of species. It is already well accepted that biotic interactions shape species' spatial distributions at local spatial extents, but the role of these interactions beyond local extents (e.g. 10 km(2) to global extents) are usually dismissed as unimportant. In this review we consolidate evidence for how biotic interactions shape species distributions beyond local extents and review methods for integrating biotic interactions into species distribution modelling tools. Drawing upon evidence from contemporary and palaeoecological studies of individual species ranges, functional groups, and species richness patterns, we show that biotic interactions have clearly left their mark on species distributions and realised assemblages of species across all spatial extents. We demonstrate this with examples from within and across trophic groups. A range of species distribution modelling tools is available to quantify species environmental relationships and predict species occurrence, such as: (i) integrating pairwise dependencies, (ii) using integrative predictors, and (iii) hybridising species distribution models (SDMs) with dynamic models. These methods have typically only been applied to interacting pairs of species at a single time, require a priori ecological knowledge about which species interact, and due to data paucity must assume that biotic interactions are constant in space and time. To better inform the future development of these models across spatial scales, we call for accelerated collection of spatially and temporally explicit species data. Ideally

  15. Models of protein-ligand crystal structures: trust, but verify.

    Science.gov (United States)

    Deller, Marc C; Rupp, Bernhard

    2015-09-01

    X-ray crystallography provides the most accurate models of protein-ligand structures. These models serve as the foundation of many computational methods including structure prediction, molecular modelling, and structure-based drug design. The success of these computational methods ultimately depends on the quality of the underlying protein-ligand models. X-ray crystallography offers the unparalleled advantage of a clear mathematical formalism relating the experimental data to the protein-ligand model. In the case of X-ray crystallography, the primary experimental evidence is the electron density of the molecules forming the crystal. The first step in the generation of an accurate and precise crystallographic model is the interpretation of the electron density of the crystal, typically carried out by construction of an atomic model. The atomic model must then be validated for fit to the experimental electron density and also for agreement with prior expectations of stereochemistry. Stringent validation of protein-ligand models has become possible as a result of the mandatory deposition of primary diffraction data, and many computational tools are now available to aid in the validation process. Validation of protein-ligand complexes has revealed some instances of overenthusiastic interpretation of ligand density. Fundamental concepts and metrics of protein-ligand quality validation are discussed and we highlight software tools to assist in this process. It is essential that end users select high quality protein-ligand models for their computational and biological studies, and we provide an overview of how this can be achieved.

  16. Ligand based pharmacophore modelling of anticancer histone ...

    African Journals Online (AJOL)

    USER

    2010-06-21

    Jun 21, 2010 ... The study was carried out using the software Ligand Scout (version .... Computer Science, for his great help and support. We are also grateful to Faculty of Engineering and applied. Sciences, Mohammad .... Aided Mol. Design ...

  17. Adding Biotic Interactions into Paleodistribution Models: A Host-Cleptoparasite Complex of Neotropical Orchid Bees.

    Directory of Open Access Journals (Sweden)

    Daniel Paiva Silva

    Full Text Available Orchid bees compose an exclusive Neotropical pollinators group, with bright body coloration. Several of those species build their own nests, while others are reported as nest cleptoparasites. Here, the objective was to evaluate whether the inclusion of a strong biotic interaction, such as the presence of a host species, improved the ability of species distribution models (SDMs to predict the geographic range of the cleptoparasite species. The target species were Aglae caerulea and its host species Eulaema nigrita. Additionally, since A. caerulea is more frequently found in the Amazon rather than the Cerrado areas, a secondary objective was to evaluate whether this species is increasing or decreasing its distribution given South American past and current climatic conditions. SDMs methods (Maxent and Bioclim, in addition with current and past South American climatic conditions, as well as the occurrences for A. caerulea and E. nigrita were used to generate the distribution models. The distribution of A. caerulea was generated with and without the inclusion of the distribution of E. nigrita as a predictor variable. The results indicate A. caerulea was barely affected by past climatic conditions and the populations from the Cerrado savanna could be at least 21,000 years old (the last glacial maximum, as well as the Amazonian ones. On the other hand, in this study, the inclusion of the host-cleptoparasite interaction complex did not statistically improve the quality of the produced models, which means that the geographic range of this cleptoparasite species is mainly constrained by climate and not by the presence of the host species. Nonetheless, this could also be caused by unknown complexes of other Euglossini hosts with A. caerulea, which still are still needed to be described by science.

  18. Models of protein–ligand crystal structures: trust, but verify

    Science.gov (United States)

    Deller, Marc C.

    2015-01-01

    X-ray crystallography provides the most accurate models of protein–ligand structures. These models serve as the foundation of many computational methods including structure prediction, molecular modelling, and structure-based drug design. The success of these computational methods ultimately depends on the quality of the underlying protein–ligand models. X-ray crystallography offers the unparalleled advantage of a clear mathematical formalism relating the experimental data to the protein–ligand model. In the case of X-ray crystallography, the primary experimental evidence is the electron density of the molecules forming the crystal. The first step in the generation of an accurate and precise crystallographic model is the interpretation of the electron density of the crystal, typically carried out by construction of an atomic model. The atomic model must then be validated for fit to the experimental electron density and also for agreement with prior expectations of stereochemistry. Stringent validation of protein–ligand models has become possible as a result of the mandatory deposition of primary diffraction data, and many computational tools are now available to aid in the validation process. Validation of protein–ligand complexes has revealed some instances of overenthusiastic interpretation of ligand density. Fundamental concepts and metrics of protein–ligand quality validation are discussed and we highlight software tools to assist in this process. It is essential that end users select high quality protein–ligand models for their computational and biological studies, and we provide an overview of how this can be achieved. PMID:25665575

  19. An unified framework to integrate biotic, abiotic processes and human activities in spatially explicit models of agricultural landscapes

    Directory of Open Access Journals (Sweden)

    Fabrice eVinatier

    2016-02-01

    Full Text Available Recent concern over possible ways to sustain ecosystem services has triggered important research worldwide on ecosystem processes at the landscape scale. Understanding this complexity of landscape functioning calls for coupled and spatially-explicit modelling approaches. However, disciplinary boundaries have limited the number of multi-process studies at the landscape scale, and current progress in coupling processes at this scale often reveals strong imbalance between biotic and abiotic processes, depending on the core discipline of the modellers. We propose a spatially-explicit, unified conceptual framework that allows researchers from different fields to develop a shared view of agricultural landscapes. In particular,we distinguish landscape elements that are mobile in space and represent biotic or abiotic objects (for example water, fauna or flora populations, and elements that are immobile and represent fixed landscape elements with a given geometry (for example ditch section or plot. The shared representation of these elements allows setting common objects and spatio-temporal process boundaries that may otherwise differ between disciplines. We present guidelines and an assessment of the applicability of this framework to a virtual landscape system with realistic properties. This framework allows the complex system to be represented with a limited set of concepts but leaves the possibility to include current modelling strategies specific to biotic or abiotic disciplines. Future operational challenges include model design, space and time discretization, and the availability of both landscape modelling platforms and data.

  20. A grand unified model for liganded gold clusters

    Science.gov (United States)

    Xu, Wen Wu; Zhu, Beien; Zeng, Xiao Cheng; Gao, Yi

    2016-12-01

    A grand unified model (GUM) is developed to achieve fundamental understanding of rich structures of all 71 liganded gold clusters reported to date. Inspired by the quark model by which composite particles (for example, protons and neutrons) are formed by combining three quarks (or flavours), here gold atoms are assigned three `flavours' (namely, bottom, middle and top) to represent three possible valence states. The `composite particles' in GUM are categorized into two groups: variants of triangular elementary block Au3(2e) and tetrahedral elementary block Au4(2e), all satisfying the duet rule (2e) of the valence shell, akin to the octet rule in general chemistry. The elementary blocks, when packed together, form the cores of liganded gold clusters. With the GUM, structures of 71 liganded gold clusters and their growth mechanism can be deciphered altogether. Although GUM is a predictive heuristic and may not be necessarily reflective of the actual electronic structure, several highly stable liganded gold clusters are predicted, thereby offering GUM-guided synthesis of liganded gold clusters by design.

  1. Ligand based pharmacophore modelling of anticancer histone ...

    African Journals Online (AJOL)

    USER

    2010-06-21

    Jun 21, 2010 ... are useful in predicting the biological activity of the compound or compound library by screening it ... with high affinity of binding toward a given protein ..... High- throughput structure-based pharmacophore modelling as a basis for successful parallel virtual screening. J. Comp. Aided Mol. Design, 20:.

  2. Linking Spatial Structure and Community-Level Biotic Interactions through Cooccurrence and Time Series Modeling of the Human Intestinal Microbiota.

    Science.gov (United States)

    de Muinck, Eric J; Lundin, Knut E A; Trosvik, Pål

    2017-01-01

    The gastrointestinal (GI) microbiome is a densely populated ecosystem where dynamics are determined by interactions between microbial community members, as well as host factors. The spatial organization of this system is thought to be important in human health, yet this aspect of our resident microbiome is still poorly understood. In this study, we report significant spatial structure of the GI microbiota, and we identify general categories of spatial patterning in the distribution of microbial taxa along a healthy human GI tract. We further estimate the biotic interaction structure in the GI microbiota, both through time series and cooccurrence modeling of microbial community data derived from a large number of sequentially collected fecal samples. Comparison of these two approaches showed that species pairs involved in significant negative interactions had strong positive contemporaneous correlations and vice versa, while for species pairs without significant interactions, contemporaneous correlations were distributed around zero. We observed similar patterns when comparing these models to the spatial correlations between taxa identified in the adherent microbiota. This suggests that colocalization of microbial taxon pairs, and thus the spatial organization of the GI microbiota, is driven, at least in part, by direct or indirect biotic interactions. Thus, our study can provide a basis for an ecological interpretation of the biogeography of the human gut. IMPORTANCE The human gut microbiome is the subject of intense study due to its importance in health and disease. The majority of these studies have been based on the analysis of feces. However, little is known about how the microbial composition in fecal samples relates to the spatial distribution of microbial taxa along the gastrointestinal tract. By characterizing the microbial content both in intestinal tissue samples and in fecal samples obtained daily, we provide a conceptual framework for how the spatial

  3. Quantitative chemogenomics: machine-learning models of protein-ligand interaction.

    Science.gov (United States)

    Andersson, Claes R; Gustafsson, Mats G; Strömbergsson, Helena

    2011-01-01

    Chemogenomics is an emerging interdisciplinary field that lies in the interface of biology, chemistry, and informatics. Most of the currently used drugs are small molecules that interact with proteins. Understanding protein-ligand interaction is therefore central to drug discovery and design. In the subfield of chemogenomics known as proteochemometrics, protein-ligand-interaction models are induced from data matrices that consist of both protein and ligand information along with some experimentally measured variable. The two general aims of this quantitative multi-structure-property-relationship modeling (QMSPR) approach are to exploit sparse/incomplete information sources and to obtain more general models covering larger parts of the protein-ligand space, than traditional approaches that focuses mainly on specific targets or ligands. The data matrices, usually obtained from multiple sparse/incomplete sources, typically contain series of proteins and ligands together with quantitative information about their interactions. A useful model should ideally be easy to interpret and generalize well to new unseen protein-ligand combinations. Resolving this requires sophisticated machine-learning methods for model induction, combined with adequate validation. This review is intended to provide a guide to methods and data sources suitable for this kind of protein-ligand-interaction modeling. An overview of the modeling process is presented including data collection, protein and ligand descriptor computation, data preprocessing, machine-learning-model induction and validation. Concerns and issues specific for each step in this kind of data-driven modeling will be discussed. © 2011 Bentham Science Publishers

  4. Belowground biotic complexity drives aboveground dynamics: a test of the soil community feedback model.

    Science.gov (United States)

    Pendergast, Thomas H; Burke, David J; Carson, Walter P

    2013-03-01

    Feedbacks between soil communities and plants may determine abundance and diversity in plant communities by influencing fitness and competitive outcomes. We tested the core hypotheses of soil community feedback theory: plant species culture distinct soil communities that alter plant performance and the outcome of interspecific competition. We applied this framework to inform the repeated dominance of Solidago canadensis in old-field communities. In glasshouse experiments, we examined the effects of soil communities on four plant species' performance in monoculture and outcomes of interspecific competition. We used terminal restriction fragment length polymorphism (TRFLP) analysis to infer differences in the soil communities associated with these plant species. Soil community origin had strong effects on plant performance, changed the intensity of interspecific competition and even reversed whether plant species were limited by conspecifics or heterospecifics. These plant-soil feedbacks are strong enough to upend winners and losers in classic competition models. Plant species cultured significantly different mycorrhizal fungal and bacterial soil communities, indicating that these feedbacks are likely microbiotic in nature. In old-fields and other plant communities, these soil feedbacks appear common, fundamentally alter the intensity and nature of plant competition and potentially maintain diversity while facilitating the dominance of So. canadensis. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  5. Explicit all-atom modeling of realistically sized ligand-capped nanocrystals

    KAUST Repository

    Kaushik, Ananth P.

    2012-01-01

    We present a study of an explicit all-atom representation of nanocrystals of experimentally relevant sizes (up to 6 nm), capped with alkyl chain ligands, in vacuum. We employ all-atom molecular dynamics simulation methods in concert with a well-tested intermolecular potential model, MM3 (molecular mechanics 3), for the studies presented here. These studies include determining the preferred conformation of an isolated single nanocrystal (NC), pairs of isolated NCs, and (presaging studies of superlattice arrays) unit cells of NC superlattices. We observe that very small NCs (3 nm) behave differently in a superlattice as compared to larger NCs (6 nm and above) due to the conformations adopted by the capping ligands on the NC surface. Short ligands adopt a uniform distribution of orientational preferences, including some that lie against the face of the nanocrystal. In contrast, longer ligands prefer to interdigitate. We also study the effect of changing ligand length and ligand coverage on the NCs on the preferred ligand configurations. Since explicit all-atom modeling constrains the maximum system size that can be studied, we discuss issues related to coarse-graining the representation of the ligands, including a comparison of two commonly used coarse-grained models. We find that care has to be exercised in the choice of coarse-grained model. The data provided by these realistically sized ligand-capped NCs, determined using explicit all-atom models, should serve as a reference standard for future models of coarse-graining ligands using united atom models, especially for self-assembly processes. © 2012 American Institute of Physics.

  6. Assessment and Challenges of Ligand Docking into Comparative Models of G-Protein Coupled Receptors

    DEFF Research Database (Denmark)

    Nguyen, E.D.; Meiler, J.; Norn, C.

    2013-01-01

    screening and to design and optimize drug candidates. However, low sequence identity between receptors, conformational flexibility, and chemical diversity of ligands present an enormous challenge to molecular modeling approaches. It is our hypothesis that rapid Monte-Carlo sampling of protein backbone...... extracellular loop. Furthermore, these models are consistently correlated with low Rosetta energy score. To predict their binding modes, ligand conformers of the 14 ligands co-crystalized with the GPCRs were docked against the top ranked comparative models. In contrast to the comparative models themselves...

  7. QSAR ligand dataset for modelling mutagenicity, genotoxicity, and rodent carcinogenicity

    Directory of Open Access Journals (Sweden)

    Davy Guan

    2018-04-01

    Full Text Available Five datasets were constructed from ligand and bioassay result data from the literature. These datasets include bioassay results from the Ames mutagenicity assay, Greenscreen GADD-45a-GFP assay, Syrian Hamster Embryo (SHE assay, and 2 year rat carcinogenicity assay results. These datasets provide information about chemical mutagenicity, genotoxicity and carcinogenicity.

  8. Classification of Beta-lactamases and penicillin binding proteins using ligand-centric network models.

    Directory of Open Access Journals (Sweden)

    Hakime Öztürk

    Full Text Available β-lactamase mediated antibiotic resistance is an important health issue and the discovery of new β-lactam type antibiotics or β-lactamase inhibitors is an area of intense research. Today, there are about a thousand β-lactamases due to the evolutionary pressure exerted by these ligands. While β-lactamases hydrolyse the β-lactam ring of antibiotics, rendering them ineffective, Penicillin-Binding Proteins (PBPs, which share high structural similarity with β-lactamases, also confer antibiotic resistance to their host organism by acquiring mutations that allow them to continue their participation in cell wall biosynthesis. In this paper, we propose a novel approach to include ligand sharing information for classifying and clustering β-lactamases and PBPs in an effort to elucidate the ligand induced evolution of these β-lactam binding proteins. We first present a detailed summary of the β-lactamase and PBP families in the Protein Data Bank, as well as the compounds they bind to. Then, we build two different types of networks in which the proteins are represented as nodes, and two proteins are connected by an edge with a weight that depends on the number of shared identical or similar ligands. These models are analyzed under three different edge weight settings, namely unweighted, weighted, and normalized weighted. A detailed comparison of these six networks showed that the use of ligand sharing information to cluster proteins resulted in modules comprising proteins with not only sequence similarity but also functional similarity. Consideration of ligand similarity highlighted some interactions that were not detected in the identical ligand network. Analysing the β-lactamases and PBPs using ligand-centric network models enabled the identification of novel relationships, suggesting that these models can be used to examine other protein families to obtain information on their ligand induced evolutionary paths.

  9. 5D-QSAR for spirocyclic sigma1 receptor ligands by Quasar receptor surface modeling.

    Science.gov (United States)

    Oberdorf, Christoph; Schmidt, Thomas J; Wünsch, Bernhard

    2010-07-01

    Based on a contiguous and structurally as well as biologically diverse set of 87 sigma(1) ligands, a 5D-QSAR study was conducted in which a quasi-atomistic receptor surface modeling approach (program package Quasar) was applied. The superposition of the ligands was performed with the tool Pharmacophore Elucidation (MOE-package), which takes all conformations of the ligands into account. This procedure led to four pharmacophoric structural elements with aromatic, hydrophobic, cationic and H-bond acceptor properties. Using the aligned structures a 3D-model of the ligand binding site of the sigma(1) receptor was obtained, whose general features are in good agreement with previous assumptions on the receptor structure, but revealed some novel insights since it represents the receptor surface in more detail. Thus, e.g., our model indicates the presence of an H-bond acceptor moiety in the binding site as counterpart to the ligands' cationic ammonium center, rather than a negatively charged carboxylate group. The presented QSAR model is statistically valid and represents the biological data of all tested compounds, including a test set of 21 ligands not used in the modeling process, with very good to excellent accuracy [q(2) (training set, n=66; leave 1/3 out) = 0.84, p(2) (test set, n=21)=0.64]. Moreover, the binding affinities of 13 further spirocyclic sigma(1) ligands were predicted with reasonable accuracy (mean deviation in pK(i) approximately 0.8). Thus, in addition to novel insights into the requirements for binding of spirocyclic piperidines to the sigma(1) receptor, the presented model can be used successfully in the rational design of new sigma(1) ligands. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

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

    Science.gov (United States)

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

    2009-01-01

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

  11. Cavity-ligand binding in a simple two-dimensional water model

    Directory of Open Access Journals (Sweden)

    G. Mazovec

    2016-02-01

    Full Text Available By means of Monte Carlo computer simulations in the isothermal-isobaric ensemble, we investigated the interaction of a hydrophobic ligand with the hydrophobic surfaces of various curvatures (planar, convex and concave. A simple two-dimensional model of water, hydrophobic ligand and surface was used. Hydration/dehidration phenomena concerning water molecules confined close to the molecular surface were investigated. A notable dewetting of the hydrophobic surfaces was observed together with the reorientation of the water molecules close to the surface. The hydrogen bonding network was formed to accommodate cavities next to the surfaces as well as beyond the first hydration shell. The effects were most strongly pronounced in the case of concave surfaces having large curvature. This simplified model can be further used to evaluate the thermodynamic fingerprint of the docking of hydrophobic ligands.

  12. LiCABEDS II. Modeling of ligand selectivity for G-protein-coupled cannabinoid receptors.

    Science.gov (United States)

    Ma, Chao; Wang, Lirong; Yang, Peng; Myint, Kyaw Z; Xie, Xiang-Qun

    2013-01-28

    The cannabinoid receptor subtype 2 (CB2) is a promising therapeutic target for blood cancer, pain relief, osteoporosis, and immune system disease. The recent withdrawal of Rimonabant, which targets another closely related cannabinoid receptor (CB1), accentuates the importance of selectivity for the development of CB2 ligands in order to minimize their effects on the CB1 receptor. In our previous study, LiCABEDS (Ligand Classifier of Adaptively Boosting Ensemble Decision Stumps) was reported as a generic ligand classification algorithm for the prediction of categorical molecular properties. Here, we report extension of the application of LiCABEDS to the modeling of cannabinoid ligand selectivity with molecular fingerprints as descriptors. The performance of LiCABEDS was systematically compared with another popular classification algorithm, support vector machine (SVM), according to prediction precision and recall rate. In addition, the examination of LiCABEDS models revealed the difference in structure diversity of CB1 and CB2 selective ligands. The structure determination from data mining could be useful for the design of novel cannabinoid lead compounds. More importantly, the potential of LiCABEDS was demonstrated through successful identification of newly synthesized CB2 selective compounds.

  13. Assessing potential peptide targeting ligands by quantification of cellular adhesion of model nanoparticles under flow conditions.

    Science.gov (United States)

    Broda, Ellen; Mickler, Frauke Martina; Lächelt, Ulrich; Morys, Stephan; Wagner, Ernst; Bräuchle, Christoph

    2015-09-10

    Sophisticated drug delivery systems are coated with targeting ligands to improve the specific adhesion to surface receptors on diseased cells. In our study, we developed a method with which we assessed the potential of peptide ligands to specifically bind to receptor overexpressing target cells. Therefore, a microfluidic setup was used where the cellular adhesion of nanoparticles with ligand and of control nanoparticles was observed in parallel under the same experimental conditions. The effect of the ligand on cellular binding was quantified by counting the number of adhered nanoparticles with ligand and differently labeled control nanoparticles on single cells after incubation under flow conditions. To provide easy-to-synthesize, stable and reproducible nanoparticles which mimic the surface characteristics of drug delivery systems and meet the requirements for quantitative analysis, latex beads based on amine-modified polystyrene were used as model nanoparticles. Two short peptides were tested to serve as targeting ligand on the beads by increasing the specific binding to HuH7 cells. The c-Met binding peptide cMBP2 was used for hepatocyte growth factor receptor (c-Met) targeting and the peptide B6 for transferrin receptor (TfR) targeting. The impact of the targeting peptide on binding was investigated by comparing the beads with ligand to different internal control beads: 1) without ligand and tailored surface charge (electrostatic control) and 2) with scrambled peptide and similar surface charge, but a different amino acid sequence (specificity control). Our results demonstrate that the method is very useful to select suitable targeting ligands for specific nanoparticle binding to receptor overexpressing tumor cells. We show that the cMBP2 ligand specifically enhances nanoparticle adhesion to target cells, whereas the B6 peptide mediates binding to tumor cells mainly by nonspecific interactions. All together, we suggest that cMBP2 is a suitable choice for

  14. Comparison of the kinetics of different Markov models for ligand binding under varying conditions

    International Nuclear Information System (INIS)

    Martini, Johannes W. R.; Habeck, Michael

    2015-01-01

    We recently derived a Markov model for macromolecular ligand binding dynamics from few physical assumptions and showed that its stationary distribution is the grand canonical ensemble [J. W. R. Martini, M. Habeck, and M. Schlather, J. Math. Chem. 52, 665 (2014)]. The transition probabilities of the proposed Markov process define a particular Glauber dynamics and have some similarity to the Metropolis-Hastings algorithm. Here, we illustrate that this model is the stochastic analog of (pseudo) rate equations and the corresponding system of differential equations. Moreover, it can be viewed as a limiting case of general stochastic simulations of chemical kinetics. Thus, the model links stochastic and deterministic approaches as well as kinetics and equilibrium described by the grand canonical ensemble. We demonstrate that the family of transition matrices of our model, parameterized by temperature and ligand activity, generates ligand binding kinetics that respond to changes in these parameters in a qualitatively similar way as experimentally observed kinetics. In contrast, neither the Metropolis-Hastings algorithm nor the Glauber heat bath reflects changes in the external conditions correctly. Both converge rapidly to the stationary distribution, which is advantageous when the major interest is in the equilibrium state, but fail to describe the kinetics of ligand binding realistically. To simulate cellular processes that involve the reversible stochastic binding of multiple factors, our pseudo rate equation model should therefore be preferred to the Metropolis-Hastings algorithm and the Glauber heat bath, if the stationary distribution is not of only interest

  15. Comparison of the kinetics of different Markov models for ligand binding under varying conditions

    Energy Technology Data Exchange (ETDEWEB)

    Martini, Johannes W. R., E-mail: jmartin2@gwdg.de [Max Planck Institute for Developmental Biology, Tübingen (Germany); Felix Bernstein Institute for Mathematical Statistics in the Biosciences, University of Göttingen, Göttingen (Germany); Habeck, Michael, E-mail: mhabeck@gwdg.de [Felix Bernstein Institute for Mathematical Statistics in the Biosciences, University of Göttingen, Göttingen (Germany); Max Planck Institute for Biophysical Chemistry, Göttingen (Germany)

    2015-03-07

    We recently derived a Markov model for macromolecular ligand binding dynamics from few physical assumptions and showed that its stationary distribution is the grand canonical ensemble [J. W. R. Martini, M. Habeck, and M. Schlather, J. Math. Chem. 52, 665 (2014)]. The transition probabilities of the proposed Markov process define a particular Glauber dynamics and have some similarity to the Metropolis-Hastings algorithm. Here, we illustrate that this model is the stochastic analog of (pseudo) rate equations and the corresponding system of differential equations. Moreover, it can be viewed as a limiting case of general stochastic simulations of chemical kinetics. Thus, the model links stochastic and deterministic approaches as well as kinetics and equilibrium described by the grand canonical ensemble. We demonstrate that the family of transition matrices of our model, parameterized by temperature and ligand activity, generates ligand binding kinetics that respond to changes in these parameters in a qualitatively similar way as experimentally observed kinetics. In contrast, neither the Metropolis-Hastings algorithm nor the Glauber heat bath reflects changes in the external conditions correctly. Both converge rapidly to the stationary distribution, which is advantageous when the major interest is in the equilibrium state, but fail to describe the kinetics of ligand binding realistically. To simulate cellular processes that involve the reversible stochastic binding of multiple factors, our pseudo rate equation model should therefore be preferred to the Metropolis-Hastings algorithm and the Glauber heat bath, if the stationary distribution is not of only interest.

  16. Can ligand addition to soil enhance Cd phytoextraction? A mechanistic model study.

    Science.gov (United States)

    Lin, Zhongbing; Schneider, André; Nguyen, Christophe; Sterckeman, Thibault

    2014-11-01

    Phytoextraction is a potential method for cleaning Cd-polluted soils. Ligand addition to soil is expected to enhance Cd phytoextraction. However, experimental results show that this addition has contradictory effects on plant Cd uptake. A mechanistic model simulating the reaction kinetics (adsorption on solid phase, complexation in solution), transport (convection, diffusion) and root absorption (symplastic, apoplastic) of Cd and its complexes in soil was developed. This was used to calculate plant Cd uptake with and without ligand addition in a great number of combinations of soil, ligand and plant characteristics, varying the parameters within defined domains. Ligand addition generally strongly reduced hydrated Cd (Cd(2+)) concentration in soil solution through Cd complexation. Dissociation of Cd complex ([Formula: see text]) could not compensate for this reduction, which greatly lowered Cd(2+) symplastic uptake by roots. The apoplastic uptake of [Formula: see text] was not sufficient to compensate for the decrease in symplastic uptake. This explained why in the majority of the cases, ligand addition resulted in the reduction of the simulated Cd phytoextraction. A few results showed an enhanced phytoextraction in very particular conditions (strong plant transpiration with high apoplastic Cd uptake capacity), but this enhancement was very limited, making chelant-enhanced phytoextraction poorly efficient for Cd.

  17. Injury Profile SIMulator, a qualitative aggregative modelling framework to predict crop injury profile as a function of cropping practices, and the abiotic and biotic environment. I. Conceptual bases.

    Directory of Open Access Journals (Sweden)

    Jean-Noël Aubertot

    Full Text Available The limitation of damage caused by pests (plant pathogens, weeds, and animal pests in any agricultural crop requires integrated management strategies. Although significant efforts have been made to i develop, and to a lesser extent ii combine genetic, biological, cultural, physical and chemical control methods in Integrated Pest Management (IPM strategies (vertical integration, there is a need for tools to help manage Injury Profiles (horizontal integration. Farmers design cropping systems according to their goals, knowledge, cognition and perception of socio-economic and technological drivers as well as their physical, biological, and chemical environment. In return, a given cropping system, in a given production situation will exhibit a unique injury profile, defined as a dynamic vector of the main injuries affecting the crop. This simple description of agroecosystems has been used to develop IPSIM (Injury Profile SIMulator, a modelling framework to predict injury profiles as a function of cropping practices, abiotic and biotic environment. Due to the tremendous complexity of agroecosystems, a simple holistic aggregative approach was chosen instead of attempting to couple detailed models. This paper describes the conceptual bases of IPSIM, an aggregative hierarchical framework and a method to help specify IPSIM for a given crop. A companion paper presents a proof of concept of the proposed approach for a single disease of a major crop (eyespot on wheat. In the future, IPSIM could be used as a tool to help design ex-ante IPM strategies at the field scale if coupled with a damage sub-model, and a multicriteria sub-model that assesses the social, environmental, and economic performances of simulated agroecosystems. In addition, IPSIM could also be used to help make diagnoses on commercial fields. It is important to point out that the presented concepts are not crop- or pest-specific and that IPSIM can be used on any crop.

  18. Injury Profile SIMulator, a qualitative aggregative modelling framework to predict crop injury profile as a function of cropping practices, and the abiotic and biotic environment. I. Conceptual bases.

    Science.gov (United States)

    Aubertot, Jean-Noël; Robin, Marie-Hélène

    2013-01-01

    The limitation of damage caused by pests (plant pathogens, weeds, and animal pests) in any agricultural crop requires integrated management strategies. Although significant efforts have been made to i) develop, and to a lesser extent ii) combine genetic, biological, cultural, physical and chemical control methods in Integrated Pest Management (IPM) strategies (vertical integration), there is a need for tools to help manage Injury Profiles (horizontal integration). Farmers design cropping systems according to their goals, knowledge, cognition and perception of socio-economic and technological drivers as well as their physical, biological, and chemical environment. In return, a given cropping system, in a given production situation will exhibit a unique injury profile, defined as a dynamic vector of the main injuries affecting the crop. This simple description of agroecosystems has been used to develop IPSIM (Injury Profile SIMulator), a modelling framework to predict injury profiles as a function of cropping practices, abiotic and biotic environment. Due to the tremendous complexity of agroecosystems, a simple holistic aggregative approach was chosen instead of attempting to couple detailed models. This paper describes the conceptual bases of IPSIM, an aggregative hierarchical framework and a method to help specify IPSIM for a given crop. A companion paper presents a proof of concept of the proposed approach for a single disease of a major crop (eyespot on wheat). In the future, IPSIM could be used as a tool to help design ex-ante IPM strategies at the field scale if coupled with a damage sub-model, and a multicriteria sub-model that assesses the social, environmental, and economic performances of simulated agroecosystems. In addition, IPSIM could also be used to help make diagnoses on commercial fields. It is important to point out that the presented concepts are not crop- or pest-specific and that IPSIM can be used on any crop.

  19. Theoretical modeling of 'REE's - novel ligand interaction' for waste management

    International Nuclear Information System (INIS)

    Singha, M.; Hareendran, K.N.; Pal, Sangita

    2013-01-01

    Many industrial wastewaters, starting from mining, milling, washing, regeneration, fabrication, operation, reprocessing etc contain valuable metal ions which are mostly present in lean concentration (1 ppm-100 ppb). These metals, especially heavy metals above the permissible limit are toxic and pose a major environmental hazard but are potentially economic and demand a recovery. Thus, the removal/recovery of these lean valuables is important and a technological challenge with respect to cost and safe disposal. In the present study, a neutron absorber (during nuclear reactor shut down) lanthanides e.g., gadolinium sorption was studied with a specially anchored sequestering agent in an extremely hydrophilic three dimensionally cross-linked matrix. In this regard, validation of Langmuir and Freundlich model and intra-molecular diffusion regarding 'Weber Morris' enlightens novel aspects of formation of hydrated sheath and easy diffusion of hydrated metal ion through micro-pores of gel-breathed resin. (author)

  20. Combined modeling of cell aggregation and adhesion mediated by receptor–ligand interactions under shear flow

    Directory of Open Access Journals (Sweden)

    Yu Du

    2015-11-01

    Full Text Available Blood cell aggregation and adhesion to endothelial cells under shear flow are crucial to many biological processes such as thrombi formation, inflammatory cascade, and tumor metastasis, in which these cellular interactions are mainly mediated by the underlying receptor–ligand bindings. While theoretical modeling of aggregation dynamics and adhesion kinetics of interacting cells have been well studied separately, how to couple these two processes remains unclear. Here we develop a combined model that couples cellular aggregation dynamics and adhesion kinetics under shear flow. The impacts of shear rate (or shear stress and molecular binding affinity were elucidated. This study provides a unified model where the action of a fluid flow drives cell aggregation and adhesion under the modulations of the mechanical shear flow and receptor–ligand interaction kinetics. It offers an insight into understanding the relevant biological processes and functions.

  1. Application of ecohydraulic bank protection model to improve river bank stability and biotic community in Surabaya River

    Directory of Open Access Journals (Sweden)

    Daru Setyo Rini

    2017-10-01

    Full Text Available Ecohydraulic river bank protection design was developed as ECO-RIPRAP model and has been applied along 100 meter length to restore accelerated erosion sites in Surabaya River at Wringinanom and Klubuk. The model combined re-profiled and re-vegetated bank with rock toe reinforcement and addition of log groynes at 10 meter length interval. Various native plant species were planted on bank slopes, including water plants Ipomoea aquatica and Pistia stratiotes, grasses and shrubs Ipomoea carnea, Pluchea indica, Saccharum spontaneum, Arundo donax, and native tree species Ficus glomerata, Bambusa arundinacea, Dendrocalamus asper, Bambusa vulgaris, Ficus benjamina, Dillenia indica, Psidium guajava, Arthocarpus camansi, Arthocarpus elasticus, Hibiscus mutabilis, Nauclea sp., Inocarpus edulis, and Syzygium polyanthum. The river bank morphology after ECO-RIPRAP application showed alteration from erosion to sedimentation due to rock toe enforcement, log groynes protection, and increase of plant cover on littoral banks that decreased near bank velocity. The macro-invertebrate community shown increase of taxa richness, EPT richness, %EPT and %Atyidae, but decrease of %Chironomidae at restored sites. The fish community shown increase of taxa richness, increase of abundance by 54.2%, increase of Pangasius micronemus abundance by 25.6%, and increase of Hemibragus nemurus abundance by 6.3 % at restored reach. Rare fish species thrive back at restored area, namely Oxyeleotris marmorata, Mastacembelus unicolor and Hampala macrolepidota.

  2. @TOME-2: a new pipeline for comparative modeling of protein–ligand complexes

    Science.gov (United States)

    Pons, Jean-Luc; Labesse, Gilles

    2009-01-01

    @TOME 2.0 is new web pipeline dedicated to protein structure modeling and small ligand docking based on comparative analyses. @TOME 2.0 allows fold recognition, template selection, structural alignment editing, structure comparisons, 3D-model building and evaluation. These tasks are routinely used in sequence analyses for structure prediction. In our pipeline the necessary software is efficiently interconnected in an original manner to accelerate all the processes. Furthermore, we have also connected comparative docking of small ligands that is performed using protein–protein superposition. The input is a simple protein sequence in one-letter code with no comment. The resulting 3D model, protein–ligand complexes and structural alignments can be visualized through dedicated Web interfaces or can be downloaded for further studies. These original features will aid in the functional annotation of proteins and the selection of templates for molecular modeling and virtual screening. Several examples are described to highlight some of the new functionalities provided by this pipeline. The server and its documentation are freely available at http://abcis.cbs.cnrs.fr/AT2/ PMID:19443448

  3. @TOME-2: a new pipeline for comparative modeling of protein-ligand complexes.

    Science.gov (United States)

    Pons, Jean-Luc; Labesse, Gilles

    2009-07-01

    @TOME 2.0 is new web pipeline dedicated to protein structure modeling and small ligand docking based on comparative analyses. @TOME 2.0 allows fold recognition, template selection, structural alignment editing, structure comparisons, 3D-model building and evaluation. These tasks are routinely used in sequence analyses for structure prediction. In our pipeline the necessary software is efficiently interconnected in an original manner to accelerate all the processes. Furthermore, we have also connected comparative docking of small ligands that is performed using protein-protein superposition. The input is a simple protein sequence in one-letter code with no comment. The resulting 3D model, protein-ligand complexes and structural alignments can be visualized through dedicated Web interfaces or can be downloaded for further studies. These original features will aid in the functional annotation of proteins and the selection of templates for molecular modeling and virtual screening. Several examples are described to highlight some of the new functionalities provided by this pipeline. The server and its documentation are freely available at http://abcis.cbs.cnrs.fr/AT2/

  4. Molecular modeling of ligand-receptor interactions in the OR5 olfactory receptor.

    Science.gov (United States)

    Singer, M S; Shepherd, G M

    1994-06-02

    Olfactory receptors belong to the superfamily of seven transmembrane domain, G protein-coupled receptors. In order to begin analysis of mechanisms of receptor activation, a computer model of the OR5 olfactory receptor has been constructed and compared with other members of this superfamily. We have tested docking of the odor molecule lyral, which is known to activate the OR5 receptor. The results point to specific ligand-binding residues on helices III through VII that form a binding pocket in the receptor. Some of these residues occupy sequence positions identical to ligand-binding residues conserved among other superfamily members. The results provide new insights into possible molecular mechanisms of odor recognition and suggest hypotheses to guide future experimental studies using site-directed mutagenesis.

  5. Reduction of dinitrogen ligands

    International Nuclear Information System (INIS)

    Richards, R.L.

    1983-01-01

    Processes of dinitrogen ligand reduction in complexes of transition metals are considered. The basic character of the dinitrogen ligand is underlined. Data on X-ray photoelectronic spectroscopy and intensities of bands ν (N 2 ) in IR-spectra of nitrogen complexes are given. The mechanism of protonation of an edge dinitrogen ligand is discussed. Model systems and mechanism of nitrogenogenase are compared

  6. In Silico Modeling of Novel Drug Ligands for Treatment of Concussion Associated Tauopathy.

    Science.gov (United States)

    Zhao, Wei; Ho, Lap; Wang, Jun; Bi, Weina; Yemul, Shrishailam; Ward, Libby; Freire, Daniel; Mazzola, Paolo; Brathwaite, Justin; Mezei, Mihaly; Sanchez, Roberto; Elder, Gregory A; Pasinetti, Giulio Maria

    2016-10-01

    The objective of this study was to develop an in silico screening model for characterization of potential novel ligands from commercial drug libraries able to functionally activate certain olfactory receptors (ORs), which are members of the class A rhodopsin-like family of G protein couple receptors (GPCRs), in the brain of murine models of concussion. We previously found that concussions may significantly influence expression of certain ORs, for example, OR4M1 in subjects with a history of concussion/traumatic brain injury (TBI). In this study, we built a 3-D OR4M1 model and used it in in silico screening of potential novel ligands from commercial drug libraries. We report that in vitro activation of OR4M1 with the commercially available ZINC library compound 10915775 led to a significant attenuation of abnormal tau phosphorylation in embryonic cortico-hippocampal neuronal cultures derived from NSE-OR4M1 transgenic mice, possibly through modulation of the JNK signaling pathway. The attenuation of abnormal tau phosphorylation was rather selective since ZINC10915775 significantly decreased tau phosphorylation on tau Ser202/T205 (AT8 epitope) and tau Thr212/Ser214 (AT100 epitope), but not on tau Ser396/404 (PHF-1 epitope). Moreover, no response of ZINC10915775 was found in control hippocampal neuronal cultures derived from wild type littermates. Our in silico model provides novel means to pharmacologically modulate select ubiquitously expressed ORs in the brain through high affinity ligand activation to prevent and eventually to treat concussion induced down regulation of ORs and subsequent cascade of tau pathology. J. Cell. Biochem. 117: 2241-2248, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  7. Mutation analysis and molecular modeling for the investigation of ligand-binding modes of GPR84.

    Science.gov (United States)

    Nikaido, Yoshiaki; Koyama, Yuuta; Yoshikawa, Yasushi; Furuya, Toshio; Takeda, Shigeki

    2015-05-01

    GPR84 is a G protein-coupled receptor for medium-chain fatty acids. Capric acid and 3,3'-diindolylmethane are specific agonists for GPR84. We built a homology model of a GPR84-capric acid complex to investigate the ligand-binding mode using the crystal structure of human active-state β2-adrenergic receptor. We performed site-directed mutagenesis to subject ligand-binding sites to our model using GPR84-Giα fusion proteins and a [(35)S]GTPγS-binding assay. We compared the activity of the wild type and mutated forms of GPR84 by [(35)S]GTPγS binding to capric acid and diindolylmethane. The mutations L100D `Ballesteros-Weinstein numbering: 3.32), F101Y (3.33) and N104Q (3.36) in the transmembrane helix III and N357D (7.39) in the transmembrane helix VII resulted in reduced capric acid activity but maintained the diindolylmethane responses. Y186F (5.46) and Y186H (5.46) mutations had no characteristic effect on capric acid but with diindolylmethane they significantly affected the G protein activation efficiency. The L100D (3.32) mutant responded to decylamine, a fatty amine, instead of a natural agonist, the fatty acid capric acid, suggesting that we have identified a mutated G protein-coupled receptor-artificial ligand pairing. Our molecular model provides an explanation for these results and interactions between GPR84 and capric acid. Further, from the results of a double stimulation assay, we concluded that diindolylmethane was a positive allosteric modulator for GPR84. © The Authors 2014. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  8. A comparison of molecular dynamics results for two models of nanoparticles with fixed and mobile ligands in two-dimensions

    Energy Technology Data Exchange (ETDEWEB)

    Baran, Ł., E-mail: lukasz.baran95@gmail.com; Sokołowski, S.

    2017-02-28

    Highlights: • We evaluated phase diagrams, thermodynamics and structure of particles. • We proposed RAM approach for nanoparticle–nanoparticle pair correlation functions. • We applied mass dipoles to describe orientation of particles with movable ligands. - Abstract: We compare the results of simulations of models of nanoparticles in two dimensions. Nanoparticles are built of central, big circle (core) with 4 ligands attached to it. The models differ by the mobility of the ligands and by ligand–core interactions. We evaluated liquid–vapor phase diagrams, as well as structural and thermodynamic properties at supercritical temperatures. In order to characterize the orientational ordering in the systems with mobile ligands, we use the concept of mass dipole. Moreover, we propose the application of the theoretical approximation for evaluation of the core–core pair correlation functions.

  9. Functional characterization of neurotransmitter activation and modulation in a nematode model ligand-gated ion channel.

    Science.gov (United States)

    Heusser, Stephanie A; Yoluk, Özge; Klement, Göran; Riederer, Erika A; Lindahl, Erik; Howard, Rebecca J

    2016-07-01

    The superfamily of pentameric ligand-gated ion channels includes neurotransmitter receptors that mediate fast synaptic transmission in vertebrates, and are targets for drugs including alcohols, anesthetics, benzodiazepines, and anticonvulsants. However, the mechanisms of ion channel opening, gating, and modulation in these receptors leave many open questions, despite their pharmacological importance. Subtle conformational changes in both the extracellular and transmembrane domains are likely to influence channel opening, but have been difficult to characterize given the limited structural data available for human membrane proteins. Recent crystal structures of a modified Caenorhabditis elegans glutamate-gated chloride channel (GluCl) in multiple states offer an appealing model system for structure-function studies. However, the pharmacology of the crystallographic GluCl construct is not well established. To establish the functional relevance of this system, we used two-electrode voltage-clamp electrophysiology in Xenopus oocytes to characterize activation of crystallographic and native-like GluCl constructs by L-glutamate and ivermectin. We also tested modulation by ethanol and other anesthetic agents, and used site-directed mutagenesis to explore the role of a region of Loop F which was implicated in ligand gating by molecular dynamics simulations. Our findings indicate that the crystallographic construct functionally models concentration-dependent agonism and allosteric modulation of pharmacologically relevant receptors. Specific substitutions at residue Leu174 in loop F altered direct L-glutamate activation, consistent with computational evidence for this region's role in ligand binding. These insights demonstrate conservation of activation and modulation properties in this receptor family, and establish a framework for GluCl as a model system, including new possibilities for drug discovery. In this study, we elucidate the validity of a modified glutamate

  10. Descriptor Data Bank (DDB): A Cloud Platform for Multiperspective Modeling of Protein-Ligand Interactions.

    Science.gov (United States)

    Ashtawy, Hossam M; Mahapatra, Nihar R

    2018-01-22

    Protein-ligand (PL) interactions play a key role in many life processes such as molecular recognition, molecular binding, signal transmission, and cell metabolism. Examples of interaction forces include hydrogen bonding, hydrophobic effects, steric clashes, electrostatic contacts, and van der Waals attractions. Currently, a large number of hypotheses and perspectives to model these interaction forces are scattered throughout the literature and largely forgotten. Instead, had they been assembled and utilized collectively, they would have substantially improved the accuracy of predicting binding affinity of protein-ligand complexes. In this work, we present Descriptor Data Bank (DDB), a data-driven platform on the cloud for facilitating multiperspective modeling of PL interactions. DDB is an open-access hub for depositing, hosting, executing, and sharing descriptor extraction tools and data for a large number of interaction modeling hypotheses. The platform also implements a machine-learning (ML) toolbox for automatic descriptor filtering and analysis and scoring function (SF) fitting and prediction. The descriptor filtering module is used to filter out irrelevant and/or noisy descriptors and to produce a compact subset from all available features. We seed DDB with 16 diverse descriptor extraction tools developed in-house and collected from the literature. The tools altogether generate over 2700 descriptors that characterize (i) proteins, (ii) ligands, and (iii) protein-ligand complexes. The in-house descriptors we extract are protein-specific which are based on pairwise primary and tertiary alignment of protein structures followed by clustering and trilateration. We built and used DDB's ML library to fit SFs to the in-house descriptors and those collected from the literature. We then evaluated them on several data sets that were constructed to reflect real-world drug screening scenarios. We found that multiperspective SFs that were constructed using a large number

  11. Targeting Dengue Virus NS-3 Helicase by Ligand based Pharmacophore Modeling and Structure based Virtual Screening

    Science.gov (United States)

    Halim, Sobia A.; Khan, Shanza; Khan, Ajmal; Wadood, Abdul; Mabood, Fazal; Hussain, Javid; Al-Harrasi, Ahmed

    2017-10-01

    Dengue fever is an emerging public health concern, with several million viral infections occur annually, for which no effective therapy currently exist. Non-structural protein 3 (NS-3) Helicase encoded by the dengue virus (DENV) is considered as a potential drug target to design new and effective drugs against dengue. Helicase is involved in unwinding of dengue RNA. This study was conducted to design new NS-3 Helicase inhibitor by in silico ligand- and structure based approaches. Initially ligand-based pharmacophore model was generated that was used to screen a set of 1201474 compounds collected from ZINC Database. The compounds matched with the pharmacophore model were docked into the active site of NS-3 helicase. Based on docking scores and binding interactions, twenty five compounds are suggested to be potential inhibitors of NS3 Helicase. The pharmacokinetic properties of these hits were predicted. The selected hits revealed acceptable ADMET properties. This study identified potential inhibitors of NS-3 Helicase in silico, and can be helpful in the treatment of Dengue.

  12. Kinetic modeling of receptor-ligand binding applied to positron emission tomographic studies with neuroleptic tracers

    Energy Technology Data Exchange (ETDEWEB)

    Logan, J; Wolf, A P; Shiue, C Y; Fowler, J S

    1987-01-01

    Positron emission tomography (PET) with labeled neuroleptics has made possible the study of neurotransmitter-receptor systems in vivo. In this study we investigate the kinetics of the 3,4-dihydroxyphenylethylamine (dopamine) receptor-ligand binding using PET data from a series of experiments in the baboon with the /sup 18/F-labeled drugs spiperone, haloperidol, and benperidol. Models used to describe these systems are based on first-order kinetics which applies at high specific activity (low receptor occupancy). The parameters governing the uptake and loss of drug from the brain were found by fitting PET data from regions with little or no receptor concentration (cerebellum) and from experiments in which specific binding was blocked by pretreatment with the drug (+)-butaclamol. Receptor constants were determined by fitting data from receptor-containing structures. Correcting the arterial plasma activities (the model driving function) for the presence of drug metabolites was found to be important in the modeling of these systems.

  13. [Modeling of a three-dimensional structure of cytochrome P-450 1A2 and search for its new ligands].

    Science.gov (United States)

    Belkina, N V; Skvortsov, V S; Ivanov, A S; Archakov, A I

    1998-01-01

    The substances inhibiting cytochrome P450 1A2 (CYP1A2) represent a perspective class of new drugs, which application in clinical practice can become the important part in preventive maintenance in oncology. The present work is devoted to computer modelling of 3-D structure of CYP1A2 and searching of new inhibitors by database mining. The modelling of CYP1A2 was done based on homology with 4 bacterial cytochromes P450 with known 3-D structure. For optimization of CYP1A2 active site structure the models of its complexes with characteristic substrates (caffeine and 7-ethoxyresorufin) were designed. These complexes were optimized by molecular dynamics simulation in water. The models of 24 complexes of CYP1A2 with known ligands with known Kd were designed by means of DockSearch and LeapFrog programs. 3D-QSAR model with good predictive force was created based on these complexes. On a final stage the search of knew CYP1A2 ligands in testing database (more than 23.000 substances from database Maybridge and 112 known CYP1A2 ligands from database Metabolite, MDL) was executed. 680 potential ligands of CYP1A2 with Kd values, comparable with known ones were obtained. This number has included 73 compounds from 112 known ligands, introduced in tested database as the internal control.

  14. Surface ligand dependent toxicity of zinc oxide nanoparticles in HepG2 cell model

    International Nuclear Information System (INIS)

    Bartczak, D; Baradez, M-O; Merson, S; Goenaga-Infante, H; Marshall, D

    2013-01-01

    Physicochemical properties of nanoparticles (NP) strongly affect their influence on cell behaviour, but can be significantly distorted by interactions with the proteins present in biological solutions. In this study we show how different surface functionalities of zinc oxide (ZnO) NP lead to changes in the size distribution and dissolution of the NP in serum containing cell culture media and how this impacts on NP toxicity. NPs capped with weakly bound large proteins undergo substantial transformations due to the exchange of the original surface ligands to the components of the cell culture media. Conversely, NP capped with a tight monolayer of small organic molecules or with covalently conjugated proteins show significantly higher stability. These differences in ligand exchange also affect the toxicity of the NP to the HepG2 liver cell model, with the NP capped with small organic molecules being more toxic than those capped with large proteins. This study highlights the importance of characterising NPs in biological media and the effect the media has during in-vitro analysis.

  15. Large-scale ligand-based predictive modelling using support vector machines.

    Science.gov (United States)

    Alvarsson, Jonathan; Lampa, Samuel; Schaal, Wesley; Andersson, Claes; Wikberg, Jarl E S; Spjuth, Ola

    2016-01-01

    The increasing size of datasets in drug discovery makes it challenging to build robust and accurate predictive models within a reasonable amount of time. In order to investigate the effect of dataset sizes on predictive performance and modelling time, ligand-based regression models were trained on open datasets of varying sizes of up to 1.2 million chemical structures. For modelling, two implementations of support vector machines (SVM) were used. Chemical structures were described by the signatures molecular descriptor. Results showed that for the larger datasets, the LIBLINEAR SVM implementation performed on par with the well-established libsvm with a radial basis function kernel, but with dramatically less time for model building even on modest computer resources. Using a non-linear kernel proved to be infeasible for large data sizes, even with substantial computational resources on a computer cluster. To deploy the resulting models, we extended the Bioclipse decision support framework to support models from LIBLINEAR and made our models of logD and solubility available from within Bioclipse.

  16. Enhanced effects of biotic interactions on predicting multispecies spatial distribution of submerged macrophytes after eutrophication.

    Science.gov (United States)

    Song, Kun; Cui, Yichong; Zhang, Xijin; Pan, Yingji; Xu, Junli; Xu, Kaiqin; Da, Liangjun

    2017-10-01

    Water eutrophication creates unfavorable environmental conditions for submerged macrophytes. In these situations, biotic interactions may be particularly important for explaining and predicting the submerged macrophytes occurrence. Here, we evaluate the roles of biotic interactions in predicting spatial occurrence of submerged macrophytes in 1959 and 2009 for Dianshan Lake in eastern China, which became eutrophic since the 1980s. For the four common species occurred in 1959 and 2009, null species distribution models based on abiotic variables and full models based on both abiotic and biotic variables were developed using generalized linear model (GLM) and boosted regression trees (BRT) to determine whether the biotic variables improved the model performance. Hierarchical Bayesian-based joint species distribution models capable of detecting paired biotic interactions were established for each species in both periods to evaluate the changes in the biotic interactions. In most of the GLM and BRT models, the full models showed better performance than the null models in predicting the species presence/absence, and the relative importance of the biotic variables in the full models increased from less than 50% in 1959 to more than 50% in 2009 for each species. Moreover, co-occurrence correlation of each paired species interaction was higher in 2009 than that in 1959. The findings suggest biotic interactions that tend to be positive play more important roles in the spatial distribution of multispecies assemblages of macrophytes and should be included in prediction models to improve prediction accuracy when forecasting macrophytes' distribution under eutrophication stress.

  17. Theoretical Analysis of Fas Ligand-Induced Apoptosis with an Ordinary Differential Equation Model.

    Science.gov (United States)

    Shi, Zhimin; Li, Yan; Liu, Zhihai; Mi, Jun; Wang, Renxiao

    2012-12-01

    Upon the treatment of Fas ligand, different types of cells exhibit different apoptotic mechanisms, which are determined by a complex network of biological pathways. In order to derive a quantitative interpretation of the cell sensitivity and apoptosis pathways, we have developed an ordinary differential equation model. Our model is intended to include all of the known major components in apoptosis pathways mediated by Fas receptor. It is composed of 29 equations using a total of 49 rate constants and 13 protein concentrations. All parameters used in our model were derived through nonlinear fitting to experimentally measured concentrations of four selected proteins in Jurkat T-cells, including caspase-3, caspase-8, caspase-9, and Bid. Our model is able to correctly interpret the role of kinetic parameters and protein concentrations in cell sensitivity to FasL. It reveals the possible reasons for the transition between type-I and type-II pathways and also provides some interesting predictions, such as the more decisive role of Fas over Bax in apoptosis pathway and a possible feedback mechanism between type-I and type-II pathways. But our model failed in predicting FasL-induced apoptotic mechanism of NCI-60 cells from their gene-expression levels. Limitations in our model are also discussed. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Machine Learning Biogeographic Processes from Biotic Patterns: A New Trait-Dependent Dispersal and Diversification Model with Model Choice By Simulation-Trained Discriminant Analysis.

    Science.gov (United States)

    Sukumaran, Jeet; Economo, Evan P; Lacey Knowles, L

    2016-05-01

    Current statistical biogeographical analysis methods are limited in the ways ecology can be related to the processes of diversification and geographical range evolution, requiring conflation of geography and ecology, and/or assuming ecologies that are uniform across all lineages and invariant in time. This precludes the possibility of studying a broad class of macroevolutionary biogeographical theories that relate geographical and species histories through lineage-specific ecological and evolutionary dynamics, such as taxon cycle theory. Here we present a new model that generates phylogenies under a complex of superpositioned geographical range evolution, trait evolution, and diversification processes that can communicate with each other. We present a likelihood-free method of inference under our model using discriminant analysis of principal components of summary statistics calculated on phylogenies, with the discriminant functions trained on data generated by simulations under our model. This approach of model selection by classification of empirical data with respect to data generated under training models is shown to be efficient, robust, and performs well over a broad range of parameter space defined by the relative rates of dispersal, trait evolution, and diversification processes. We apply our method to a case study of the taxon cycle, that is testing for habitat and trophic level constraints in the dispersal regimes of the Wallacean avifaunal radiation. ©The Author(s) 2015. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. A literature review on biotic homogenization

    OpenAIRE

    Guangmei Wang; Jingcheng Yang; Chuangdao Jiang; Hongtao Zhao; Zhidong Zhang

    2009-01-01

    Biotic homogenization is the process whereby the genetic, taxonomic and functional similarity of two or more biotas increases over time. As a new research agenda for conservation biogeography, biotic homogenization has become a rapidly emerging topic of interest in ecology and evolution over the past decade. However, research on this topic is rare in China. Herein, we introduce the development of the concept of biotic homogenization, and then discuss methods to quantify its three components (...

  20. Biotic Interaction in Space and Time

    DEFF Research Database (Denmark)

    Schmidt, Andreas Kelager

    Myrmica host ants by using chemical and acoustic mimicry to coerce the ant workers to feed and nurture the caterpillar preferentially over their own brood. Maculinea alcon is thus an extreme dietary specialist as absence of just one of the hosts precludes presence of the butterfly and as a result...... further enhance the risk of extinction. Maculinea alcon is selected as an umbrella for conservation and numerous aspects of its biology has been studied extensively. This thesis explores the spatio-temporal impact of the tight biotic dependence in this tritrophic interaction system and integrates...... in host ant use as expected, and is an example of a genetic barrier operating on a temporal scale rather than spatial. In chapter II, we developed habitat suitability models for M. alcon and G. pneumonanthe potentially useful in locating undocumented populations and for improving management of them...

  1. Ligands, cell-based models, and readouts required for Toll-like receptor action.

    LENUS (Irish Health Repository)

    Dellacasagrande, Jerome

    2012-02-01

    This chapter details the tools that are available to study Toll-like receptor (TLR) biology in vitro. This includes ligands, host cells, and readouts. The use of modified TLRs to circumvent some technical problems is also discussed.

  2. Is the isolated ligand binding domain a good model of the domain in the native receptor?

    Science.gov (United States)

    Deming, Dustin; Cheng, Qing; Jayaraman, Vasanthi

    2003-05-16

    Numerous studies have used the atomic level structure of the isolated ligand binding domain of the glutamate receptor to elucidate the agonist-induced activation and desensitization processes in this group of proteins. However, no study has demonstrated the structural equivalence of the isolated ligand binding fragments and the protein in the native receptor. In this report, using visible absorption spectroscopy we show that the electronic environment of the antagonist 6-cyano-7-nitro-2,3-dihydroxyquinoxaline is identical for the isolated protein and the native glutamate receptors expressed in cells. Our results hence establish that the local structure of the ligand binding site is the same in the two proteins and validate the detailed structure-function relationships that have been developed based on a comparison of the structure of the isolated ligand binding domain and electrophysiological consequences in the native receptor.

  3. Biotic elements of NPP techno-ecosystem

    International Nuclear Information System (INIS)

    Protasov, A.A.; Silaeva, A.A.

    2013-01-01

    Specific features of biotic elements in the NPP techno-ecosystems were considered and compared with natural ecosystems. Relationships between biotic communities and environmental factors that are specific to the techno-ecosystems were discussed, and the problems of limitation of biological hindrances in operation of equipment, principles of hydrobiological and environmental monitoring were considered.

  4. Nerve Regenerative Effects of GABA-B Ligands in a Model of Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Valerio Magnaghi

    2014-01-01

    Full Text Available Neuropathic pain arises as a direct consequence of a lesion or disease affecting the peripheral somatosensory system. It may be associated with allodynia and increased pain sensitivity. Few studies correlated neuropathic pain with nerve morphology and myelin proteins expression. Our aim was to test if neuropathic pain is related to nerve degeneration, speculating whether the modulation of peripheral GABA-B receptors may promote nerve regeneration and decrease neuropathic pain. We used the partial sciatic ligation- (PSL- induced neuropathic model. The biochemical, morphological, and behavioural outcomes of sciatic nerve were analysed following GABA-B ligands treatments. Simultaneous 7-days coadministration of baclofen (10 mg/kg and CGP56433 (3 mg/kg alters tactile hypersensitivity. Concomitantly, specific changes of peripheral nerve morphology, nerve structure, and myelin proteins (P0 and PMP22 expression were observed. Nerve macrophage recruitment decreased and step coordination was improved. The PSL-induced changes in nociception correlate with altered nerve morphology and myelin protein expression. Peripheral synergic effects, via GABA-B receptor activation, promote nerve regeneration and likely ameliorate neuropathic pain.

  5. Synthesis, Molecular Modelling and Biological Evaluation of Novel Heterodimeric, Multiple Ligands Targeting Cholinesterases and Amyloid Beta

    Directory of Open Access Journals (Sweden)

    Michalina Hebda

    2016-03-01

    Full Text Available Cholinesterases and amyloid beta are one of the major biological targets in the search for a new and efficacious treatment of Alzheimer’s disease. The study describes synthesis and pharmacological evaluation of new compounds designed as dual binding site acetylcholinesterase inhibitors. Among the synthesized compounds, two deserve special attention—compounds 42 and 13. The former is a saccharin derivative and the most potent and selective acetylcholinesterase inhibitor (EeAChE IC50 = 70 nM. Isoindoline-1,3-dione derivative 13 displays balanced inhibitory potency against acetyl- and butyrylcholinesterase (BuChE (EeAChE IC50 = 0.76 μM, EqBuChE IC50 = 0.618 μM, and it inhibits amyloid beta aggregation (35.8% at 10 μM. Kinetic studies show that the developed compounds act as mixed or non-competitive acetylcholinesterase inhibitors. According to molecular modelling studies, they are able to interact with both catalytic and peripheral active sites of the acetylcholinesterase. Their ability to cross the blood-brain barrier (BBB was confirmed in vitro in the parallel artificial membrane permeability BBB assay. These compounds can be used as a solid starting point for further development of novel multifunctional ligands as potential anti-Alzheimer’s agents.

  6. Binding Mode Prediction of 5-Hydroxytryptamine 2C Receptor Ligands by Homology Modeling and Molecular Docking Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Ahmed, Asif; Nagarajan, Shanthi; Doddareddy, Munikumar Reddy; Cho, Yong Seo; Pae, Ae Nim [Korea Institute of Science and Technology, Seoul (Korea, Republic of)

    2011-06-15

    Serotonin or 5-hydroxytryptamine subtype 2C (5-HT{sub 2C}) receptor belongs to class A amine subfamily of Gprotein- coupled receptor (GPCR) super family and its ligands has therapeutic promise as anti-depressant and -obesity agents. So far, bovine rhodopsin from class A opsin subfamily was the mostly used X-ray crystal template to model this receptor. Here, we explained homology model using beta 2 adrenergic receptor (β2AR), the model was energetically minimized and validated by flexible ligand docking with known agonists and antagonists. In the active site Asp134, Ser138 of transmembrane 3 (TM3), Arg195 of extracellular loop 2 (ECL2) and Tyr358 of TM7 were found as important residues to interact with agonists. In addition to these, V208 of ECL2 and N351 of TM7 was found to interact with antagonists. Several conserved residues including Trp324, Phe327 and Phe328 were also found to contribute hydrophobic interaction. The predicted ligand binding mode is in good agreement with published mutagenesis and homology model data. This new template derived homology model can be useful for further virtual screening based lead identification.

  7. eMatchSite: sequence order-independent structure alignments of ligand binding pockets in protein models.

    Directory of Open Access Journals (Sweden)

    Michal Brylinski

    2014-09-01

    Full Text Available Detecting similarities between ligand binding sites in the absence of global homology between target proteins has been recognized as one of the critical components of modern drug discovery. Local binding site alignments can be constructed using sequence order-independent techniques, however, to achieve a high accuracy, many current algorithms for binding site comparison require high-quality experimental protein structures, preferably in the bound conformational state. This, in turn, complicates proteome scale applications, where only various quality structure models are available for the majority of gene products. To improve the state-of-the-art, we developed eMatchSite, a new method for constructing sequence order-independent alignments of ligand binding sites in protein models. Large-scale benchmarking calculations using adenine-binding pockets in crystal structures demonstrate that eMatchSite generates accurate alignments for almost three times more protein pairs than SOIPPA. More importantly, eMatchSite offers a high tolerance to structural distortions in ligand binding regions in protein models. For example, the percentage of correctly aligned pairs of adenine-binding sites in weakly homologous protein models is only 4-9% lower than those aligned using crystal structures. This represents a significant improvement over other algorithms, e.g. the performance of eMatchSite in recognizing similar binding sites is 6% and 13% higher than that of SiteEngine using high- and moderate-quality protein models, respectively. Constructing biologically correct alignments using predicted ligand binding sites in protein models opens up the possibility to investigate drug-protein interaction networks for complete proteomes with prospective systems-level applications in polypharmacology and rational drug repositioning. eMatchSite is freely available to the academic community as a web-server and a stand-alone software distribution at http://www.brylinski.org/ematchsite.

  8. Accuracy comparison of several common implicit solvent models and their implementations in the context of protein-ligand binding.

    Science.gov (United States)

    Katkova, E V; Onufriev, A V; Aguilar, B; Sulimov, V B

    2017-03-01

    In this study several commonly used implicit solvent models are compared with respect to their accuracy of estimating solvation energies of small molecules and proteins, as well as desolvation penalty in protein-ligand binding. The test set consists of 19 small proteins, 104 small molecules, and 15 protein-ligand complexes. We compared predicted hydration energies of small molecules with their experimental values; the results of the solvation and desolvation energy calculations for small molecules, proteins and protein-ligand complexes in water were also compared with Thermodynamic Integration calculations based on TIP3P water model and Amber12 force field. The following implicit solvent (water) models considered here are: PCM (Polarized Continuum Model implemented in DISOLV and MCBHSOLV programs), GB (Generalized Born method implemented in DISOLV program, S-GB, and GBNSR6 stand-alone version), COSMO (COnductor-like Screening Model implemented in the DISOLV program and the MOPAC package) and the Poisson-Boltzmann model (implemented in the APBS program). Different parameterizations of the molecules were examined: we compared MMFF94 force field, Amber12 force field and the quantum-chemical semi-empirical PM7 method implemented in the MOPAC package. For small molecules, all of the implicit solvent models tested here yield high correlation coefficients (0.87-0.93) between the calculated solvation energies and the experimental values of hydration energies. For small molecules high correlation (0.82-0.97) with the explicit solvent energies is seen as well. On the other hand, estimated protein solvation energies and protein-ligand binding desolvation energies show substantial discrepancy (up to 10kcal/mol) with the explicit solvent reference. The correlation of polar protein solvation energies and protein-ligand desolvation energies with the corresponding explicit solvent results is 0.65-0.99 and 0.76-0.96 respectively, though this difference in correlations is caused

  9. Mutual control of axial and equatorial ligands: model studies with [Ni]-bacteriochlorophyll-a.

    Science.gov (United States)

    Yerushalmi, Roie; Noy, Dror; Baldridge, Kim K; Scherz, Avigdor

    2002-07-17

    Modification of the metal's electronic environment by ligand association and dissociation in metalloenzymes is considered cardinal to their catalytic activity. We have recently presented a novel system that utilizes the bacteriochlorophyll (BChl) macrocycle as a ligand and reporter. This system allows for charge mobilization in the equatorial plane and experimental estimate of changes in the electronic charge density around the metal with no modification of the metal's chemical environment. The unique spectroscopy, electrochemistry and coordination chemistry of [Ni]-bacteriochlorophyll ([Ni]-BChl) enable us to follow directly fine details and steps involved in the function of the metal redox center. This approach is utilized here whereby electro-chemical reduction of [Ni]-BChl to the monoanion [Ni]-BChl(-) results in reversible dissociation of biologically relevant axial ligands. Similar ligand dissociation was previously detected upon photoexcitation of [Ni]-BChl (Musewald, C.; Hartwich, G.; Lossau, H.; Gilch, P.; Pollinger-Dammer, F.; Scheer, H.; Michel-Beyerle, M. E. J. Phys. Chem. B 1999, 103, 7055-7060 and Noy, D.; Yerushalmi, R.; Brumfeld, V.; Ashur, I.; Baldridge, K. K.; Scheer, H.; Scherz, A. J. Am. Chem. Soc. 2000, 122, 3937-3944). The electrochemical measurements and quantum mechanical (QM) calculations performed here for the neutral, singly reduced, monoligated, and singly reduced, monoligated [Ni]-BChl suggest the following: (a) Electroreduction, although resulting in a pi anion [Ni]-BChl(-) radical, causes electron density migration to the [Ni]-BChl core. (b) Reduction of nonligated [Ni]-BChl does not change the macrocycle conformation, whereas axial ligation results in a dramatic expansion of the metal core and a flattening of the highly ruffled macrocycle conformation. (c) In both the monoanion and singly excited [Ni]-BChl ([Ni]-BChl*), the frontier singly occupied molecular orbital (SOMO) has a small but nonnegligible metal character. Finally, (d

  10. Modelling the interdependence between the stoichiometry of receptor oligomerization and ligand binding for a coexisting dimer/tetramer receptor system.

    Science.gov (United States)

    Rovira, X; Vivó, M; Serra, J; Roche, D; Strange, P G; Giraldo, J

    2009-01-01

    Many G protein-coupled receptors have been shown to exist as oligomers, but the oligomerization state and the effects of this on receptor function are unclear. For some G protein-coupled receptors, in ligand binding assays, different radioligands provide different maximal binding capacities. Here we have developed mathematical models for co-expressed dimeric and tetrameric species of receptors. We have considered models where the dimers and tetramers are in equilibrium and where they do not interconvert and we have also considered the potential influence of the ligands on the degree of oligomerization. By analogy with agonist efficacy, we have considered ligands that promote, inhibit or have no effect on oligomerization. Cell surface receptor expression and the intrinsic capacity of receptors to oligomerize are quantitative parameters of the equations. The models can account for differences in the maximal binding capacities of radioligands in different preparations of receptors and provide a conceptual framework for simulation and data fitting in complex oligomeric receptor situations.

  11. A Statistical Thermodynamic Model for Ligands Interacting With Ion Channels: Theoretical Model and Experimental Validation of the KCNQ2 Channel

    Directory of Open Access Journals (Sweden)

    Fang Bai

    2018-03-01

    Full Text Available Ion channels are important therapeutic targets, and their pharmacology is becoming increasingly important. However, knowledge of the mechanism of interaction of the activators and ion channels is still limited due to the complexity of the mechanisms. A statistical thermodynamic model has been developed in this study to characterize the cooperative binding of activators to ion channels. By fitting experimental concentration-response data, the model gives eight parameters for revealing the mechanism of an activator potentiating an ion channel, i.e., the binding affinity (KA, the binding cooperative coefficients for two to four activator molecules interacting with one channel (γ, μ, and ν, and the channel conductance coefficients for four activator binding configurations of the channel (a, b, c, and d. Values for the model parameters and the mechanism underlying the interaction of ztz240, a proven KCNQ2 activator, with the wild-type channel have been obtained and revealed by fitting the concentration-response data of this activator potentiating the outward current amplitudes of KCNQ2. With these parameters, our model predicted an unexpected bi-sigmoid concentration-response curve of ztz240 activation of the WT-F137A mutant heteromeric channel that was in good agreement with the experimental data determined in parallel in this study, lending credence to the assumptions on which the model is based and to the model itself. Our model can provide a better fit to the measured data than the Hill equation and estimates the binding affinity, as well as the cooperative coefficients for the binding of activators and conductance coefficients for binding states, which validates its use in studying ligand-channel interaction mechanisms.

  12. Explicit all-atom modeling of realistically sized ligand-capped nanocrystals

    KAUST Repository

    Kaushik, Ananth P.; Clancy, Paulette

    2012-01-01

    We present a study of an explicit all-atom representation of nanocrystals of experimentally relevant sizes (up to 6 nm), capped with alkyl chain ligands, in vacuum. We employ all-atom molecular dynamics simulation methods in concert with a well

  13. Injury profile SIMulator, a Qualitative aggregative modelling framework to predict injury profile as a function of cropping practices, and abiotic and biotic environment. II. Proof of concept: design of IPSIM-wheat-eyespot.

    Science.gov (United States)

    Robin, Marie-Hélène; Colbach, Nathalie; Lucas, Philippe; Montfort, Françoise; Cholez, Célia; Debaeke, Philippe; Aubertot, Jean-Noël

    2013-01-01

    IPSIM (Injury Profile SIMulator) is a generic modelling framework presented in a companion paper. It aims at predicting a crop injury profile as a function of cropping practices and abiotic and biotic environment. IPSIM's modelling approach consists of designing a model with an aggregative hierarchical tree of attributes. In order to provide a proof of concept, a model, named IPSIM-Wheat-Eyespot, has been developed with the software DEXi according to the conceptual framework of IPSIM to represent final incidence of eyespot on wheat. This paper briefly presents the pathosystem, the method used to develop IPSIM-Wheat-Eyespot using IPSIM's modelling framework, simulation examples, an evaluation of the predictive quality of the model with a large dataset (526 observed site-years) and a discussion on the benefits and limitations of the approach. IPSIM-Wheat-Eyespot proved to successfully represent the annual variability of the disease, as well as the effects of cropping practices (Efficiency = 0.51, Root Mean Square Error of Prediction = 24%; bias = 5.0%). IPSIM-Wheat-Eyespot does not aim to precisely predict the incidence of eyespot on wheat. It rather aims to rank cropping systems with regard to the risk of eyespot on wheat in a given production situation through ex ante evaluations. IPSIM-Wheat-Eyespot can also help perform diagnoses of commercial fields. Its structure is simple and permits to combine available knowledge in the scientific literature (data, models) and expertise. IPSIM-Wheat-Eyespot is now available to help design cropping systems with a low risk of eyespot on wheat in a wide range of production situations, and can help perform diagnoses of commercial fields. In addition, it provides a proof of concept with regard to the modelling approach of IPSIM. IPSIM-Wheat-Eyespot will be a sub-model of IPSIM-Wheat, a model that will predict injury profile on wheat as a function of cropping practices and the production situation.

  14. Sequential application of ligand and structure based modeling approaches to index chemicals for their hH4R antagonism.

    Directory of Open Access Journals (Sweden)

    Matteo Pappalardo

    Full Text Available The human histamine H4 receptor (hH4R, a member of the G-protein coupled receptors (GPCR family, is an increasingly attractive drug target. It plays a key role in many cell pathways and many hH4R ligands are studied for the treatment of several inflammatory, allergic and autoimmune disorders, as well as for analgesic activity. Due to the challenging difficulties in the experimental elucidation of hH4R structure, virtual screening campaigns are normally run on homology based models. However, a wealth of information about the chemical properties of GPCR ligands has also accumulated over the last few years and an appropriate combination of these ligand-based knowledge with structure-based molecular modeling studies emerges as a promising strategy for computer-assisted drug design. Here, two chemoinformatics techniques, the Intelligent Learning Engine (ILE and Iterative Stochastic Elimination (ISE approach, were used to index chemicals for their hH4R bioactivity. An application of the prediction model on external test set composed of more than 160 hH4R antagonists picked from the chEMBL database gave enrichment factor of 16.4. A virtual high throughput screening on ZINC database was carried out, picking ∼ 4000 chemicals highly indexed as H4R antagonists' candidates. Next, a series of 3D models of hH4R were generated by molecular modeling and molecular dynamics simulations performed in fully atomistic lipid membranes. The efficacy of the hH4R 3D models in discrimination between actives and non-actives were checked and the 3D model with the best performance was chosen for further docking studies performed on the focused library. The output of these docking studies was a consensus library of 11 highly active scored drug candidates. Our findings suggest that a sequential combination of ligand-based chemoinformatics approaches with structure-based ones has the potential to improve the success rate in discovering new biologically active GPCR drugs and

  15. Sequential application of ligand and structure based modeling approaches to index chemicals for their hH4R antagonism.

    Science.gov (United States)

    Pappalardo, Matteo; Shachaf, Nir; Basile, Livia; Milardi, Danilo; Zeidan, Mouhammed; Raiyn, Jamal; Guccione, Salvatore; Rayan, Anwar

    2014-01-01

    The human histamine H4 receptor (hH4R), a member of the G-protein coupled receptors (GPCR) family, is an increasingly attractive drug target. It plays a key role in many cell pathways and many hH4R ligands are studied for the treatment of several inflammatory, allergic and autoimmune disorders, as well as for analgesic activity. Due to the challenging difficulties in the experimental elucidation of hH4R structure, virtual screening campaigns are normally run on homology based models. However, a wealth of information about the chemical properties of GPCR ligands has also accumulated over the last few years and an appropriate combination of these ligand-based knowledge with structure-based molecular modeling studies emerges as a promising strategy for computer-assisted drug design. Here, two chemoinformatics techniques, the Intelligent Learning Engine (ILE) and Iterative Stochastic Elimination (ISE) approach, were used to index chemicals for their hH4R bioactivity. An application of the prediction model on external test set composed of more than 160 hH4R antagonists picked from the chEMBL database gave enrichment factor of 16.4. A virtual high throughput screening on ZINC database was carried out, picking ∼ 4000 chemicals highly indexed as H4R antagonists' candidates. Next, a series of 3D models of hH4R were generated by molecular modeling and molecular dynamics simulations performed in fully atomistic lipid membranes. The efficacy of the hH4R 3D models in discrimination between actives and non-actives were checked and the 3D model with the best performance was chosen for further docking studies performed on the focused library. The output of these docking studies was a consensus library of 11 highly active scored drug candidates. Our findings suggest that a sequential combination of ligand-based chemoinformatics approaches with structure-based ones has the potential to improve the success rate in discovering new biologically active GPCR drugs and increase the

  16. NNAlign: a platform to construct and evaluate artificial neural network models of receptor-ligand interactions

    DEFF Research Database (Denmark)

    Nielsen, Morten; Andreatta, Massimo

    2017-01-01

    Peptides are extensively used to characterize functional or (linear) structural aspects of receptor-ligand interactions in biological systems, e.g. SH2, SH3, PDZ peptide-recognition domains, the MHC membrane receptors and enzymes such as kinases and phosphatases. NNAlign is a method for the ident...... with insertions and deletions, encoding of receptor pseudo-sequences, and custom alphabets for the training sequences. The server is available at http://www.cbs.dtu.dk/services/NNAlign-2.0....

  17. A ligand predication tool based on modeling and reasoning with imprecise probabilistic knowledge.

    Science.gov (United States)

    Liu, Weiru; Yue, Anbu; Timson, David J

    2010-04-01

    Ligand prediction has been driven by a fundamental desire to understand more about how biomolecules recognize their ligands and by the commercial imperative to develop new drugs. Most of the current available software systems are very complex and time-consuming to use. Therefore, developing simple and efficient tools to perform initial screening of interesting compounds is an appealing idea. In this paper, we introduce our tool for very rapid screening for likely ligands (either substrates or inhibitors) based on reasoning with imprecise probabilistic knowledge elicited from past experiments. Probabilistic knowledge is input to the system via a user-friendly interface showing a base compound structure. A prediction of whether a particular compound is a substrate is queried against the acquired probabilistic knowledge base and a probability is returned as an indication of the prediction. This tool will be particularly useful in situations where a number of similar compounds have been screened experimentally, but information is not available for all possible members of that group of compounds. We use two case studies to demonstrate how to use the tool. 2009 Elsevier Ireland Ltd. All rights reserved.

  18. Probing ligand binding modes of Mycobacterium tuberculosis MurC ligase by molecular modeling, dynamics simulation and docking.

    Science.gov (United States)

    Anuradha, C M; Mulakayala, Chaitanya; Babajan, Banaganapalli; Naveen, M; Rajasekhar, Chikati; Kumar, Chitta Suresh

    2010-01-01

    Multi drug resistance capacity for Mycobacterium tuberculosis (MDR-Mtb) demands the profound need for developing new anti-tuberculosis drugs. The present work is on Mtb-MurC ligase, which is an enzyme involved in biosynthesis of peptidoglycan, a component of Mtb cell wall. In this paper the 3-D structure of Mtb-MurC has been constructed using the templates 1GQQ and 1P31. Structural refinement and energy minimization of the predicted Mtb-MurC ligase model has been carried out by molecular dynamics. The streochemical check failures in the energy minimized model have been evaluated through Procheck, Whatif ProSA, and Verify 3D. Further torsion angles for the side chains of amino acid residues of the developed model were determined using Predictor. Docking analysis of Mtb-MurC model with ligands and natural substrates enabled us to identify specific residues viz. Gly125, Lys126, Arg331, and Arg332, within the Mtb-MurC binding pocket to play an important role in ligand and substrate binding affinity and selectivity. The availability of Mtb-MurC ligase built model, together with insights gained from docking analysis will promote the rational design of potent and selective Mtb-MurC ligase inhibitors as antituberculosis therapeutics.

  19. Coevolutionary aesthetics in human and biotic artworlds.

    Science.gov (United States)

    Prum, Richard O

    2013-01-01

    This work proposes a coevolutionary theory of aesthetics that encompasses both biotic and human arts. Anthropocentric perspectives in aesthetics prevent the recognition of the ontological complexity of the aesthetics of nature, and the aesthetic agency of many non-human organisms. The process of evaluative coevolution is shared by all biotic advertisements. I propose that art consists of a form of communication that coevolves with its own evaluation. Art and art history are population phenomena. I expand Arthur Danto's Artworld concept to any aesthetic population of producers and evaluators. Current concepts of art cannot exclusively circumscribe the human arts from many forms of non-human biotic art. Without assuming an arbitrarily anthropocentric perspective, any concept of art will need to engage with biodiversity, and either recognize many instances of biotic advertisements as art, or exclude some instances of human art. Coevolutionary aesthetic theory provides a heuristic account of aesthetic change in both human and biotic artworlds, including the coevolutionary origin of aesthetic properties and aesthetic value within artworlds. Restructuring aesthetics, art criticism, and art history without human beings at the organizing centers of these disciplines stimulate new progress in our understanding of art, and the unique human contributions to aesthetics and aesthetic diversity.

  20. Aromatic interactions impact ligand binding and function at serotonin 5-HT2C G protein-coupled receptors: receptor homology modelling, ligand docking, and molecular dynamics results validated by experimental studies

    Science.gov (United States)

    Córdova-Sintjago, Tania; Villa, Nancy; Fang, Lijuan; Booth, Raymond G.

    2014-02-01

    The serotonin (5-hydroxytryptamine, 5-HT) 5-HT2 G protein-coupled receptor (GPCR) family consists of types 2A, 2B, and 2C that share ∼75% transmembrane (TM) sequence identity. Agonists for 5-HT2C receptors are under development for psychoses; whereas, at 5-HT2A receptors, antipsychotic effects are associated with antagonists - in fact, 5-HT2A agonists can cause hallucinations and 5-HT2B agonists cause cardiotoxicity. It is known that 5-HT2A TM6 residues W6.48, F6.51, and F6.52 impact ligand binding and function; however, ligand interactions with these residues at the 5-HT2C receptor have not been reported. To predict and validate molecular determinants for 5-HT2C-specific activation, results from receptor homology modelling, ligand docking, and molecular dynamics simulation studies were compared with experimental results for ligand binding and function at wild type and W6.48A, F6.51A, and F6.52A point-mutated 5-HT2C receptors.

  1. Modelling a 3D structure for EgDf1 from shape Echinococcus granulosus: putative epitopes, phosphorylation motifs and ligand

    Science.gov (United States)

    Paulino, M.; Esteves, A.; Vega, M.; Tabares, G.; Ehrlich, R.; Tapia, O.

    1998-07-01

    EgDf1 is a developmentally regulated protein from the parasite Echinococcus granulosus related to a family of hydrophobic ligand binding proteins. This protein could play a crucial role during the parasite life cycle development since this organism is unable to synthetize most of their own lipids de novo. Furthermore, it has been shown that two related protein from other parasitic platyhelminths (Fh15 from Fasciola hepatica and Sm14 from Schistosoma mansoni) are able to confer protective inmunity against experimental infection in animal models. A three-dimensional structure would help establishing structure/function relationships on a knowledge based manner. 3D structures for EgDf1 protein were modelled by using myelin P2 (mP2) and intestine fatty acid binding protein (I-FABP) as templates. Molecular dynamics techniques were used to validate the models. Template mP2 yielded the best 3D structure for EgDf1. Palmitic and oleic acids were docked inside EgDf1. The present theoretical results suggest definite location in the secondary structure of the epitopic regions, consensus phosphorylation motifs and oleic acid as a good ligand candidate to EgDf1. This protein might well be involved in the process of supplying hydrophobic metabolites for membrane biosynthesis and for signaling pathways.

  2. Forced unbinding of GPR17 ligands from wild type and R255I mutant receptor models through a computational approach

    Directory of Open Access Journals (Sweden)

    Fantucci Piercarlo

    2010-03-01

    Full Text Available Abstract Background GPR17 is a hybrid G-protein-coupled receptor (GPCR activated by two unrelated ligand families, extracellular nucleotides and cysteinyl-leukotrienes (cysteinyl-LTs, and involved in brain damage and repair. Its exploitment as a target for novel neuro-reparative strategies depends on the elucidation of the molecular determinants driving binding of purinergic and leukotrienic ligands. Here, we applied docking and molecular dynamics simulations (MD to analyse the binding and the forced unbinding of two GPR17 ligands (the endogenous purinergic agonist UDP and the leukotriene receptor antagonist pranlukast from both the wild-type (WT receptor and a mutant model, where a basic residue hypothesized to be crucial for nucleotide binding had been mutated (R255I to Ile. Results MD suggested that GPR17 nucleotide binding pocket is enclosed between the helical bundle and extracellular loop (EL 2. The driving interaction involves R255 and the UDP phosphate moiety. To support this hypothesis, steered MD experiments showed that the energy required to unbind UDP is higher for the WT receptor than for R255I. Three potential binding sites for pranlukast where instead found and analysed. In one of its preferential docking conformations, pranlukast tetrazole group is close to R255 and phenyl rings are placed into a subpocket highly conserved among GPCRs. Pulling forces developed to break polar and aromatic interactions of pranlukast were comparable. No differences between the WT receptor and the R255I receptor were found for the unbinding of pranlukast. Conclusions These data thus suggest that, in contrast to which has been hypothesized for nucleotides, the lack of the R255 residue doesn't affect the binding of pranlukast a crucial role for R255 in binding of nucleotides to GPR17. Aromatic interactions are instead likely to play a predominant role in the recognition of pranlukast, suggesting that two different binding subsites are present on GPR17.

  3. Design, engineering and utility of biotic games.

    Science.gov (United States)

    Riedel-Kruse, Ingmar H; Chung, Alice M; Dura, Burak; Hamilton, Andrea L; Lee, Byung C

    2011-01-07

    Games are a significant and defining part of human culture, and their utility beyond pure entertainment has been demonstrated with so-called 'serious games'. Biotechnology--despite its recent advancements--has had no impact on gaming yet. Here we propose the concept of 'biotic games', i.e., games that operate on biological processes. Utilizing a variety of biological processes we designed and tested a collection of games: 'Enlightenment', 'Ciliaball', 'PAC-mecium', 'Microbash', 'Biotic Pinball', 'POND PONG', 'PolymerRace', and 'The Prisoner's Smellemma'. We found that biotic games exhibit unique features compared to existing game modalities, such as utilizing biological noise, providing a real-life experience rather than virtual reality, and integrating the chemical senses into play. Analogous to video games, biotic games could have significant conceptual and cost-reducing effects on biotechnology and eventually healthcare; enable volunteers to participate in crowd-sourcing to support medical research; and educate society at large to support personal medical decisions and the public discourse on bio-related issues.

  4. Biotic interactions reduce microbial carbon use efficiency

    Science.gov (United States)

    Bradford, M.; Maynard, D. S.

    2017-12-01

    The efficiency by which microbes decompose organic matter governs the amount of carbon that is retained in microbial biomass versus lost to the atmosphere as respiration. This carbon use efficiency (CUE) is affected by various abiotic conditions, such as temperature and nutrient availability. In biogeochemical model simulations, CUE is a key variable regulating how much soil carbon is stored or lost from ecosystems under simulated global changes, such as climate warming. Theoretically, the physiological costs of biotic interactions such as competition should likewise alter CUE, yet the direction and magnitude of these costs are untested. Here we conduct a microcosm experiment to quantify how competitive interactions among saprotrophic fungi alter growth, respiration, and CUE. Free-living decomposer fungi representing a broad range of traits and phylogenies were grown alone, in pairwise competition, and in multi-species (up to 15) communities. By combing culturing and stable carbon isotope approaches, we could resolve the amount of carbon substrate allocated to fungal biomass versus respiration, and so estimate CUE. By then comparing individual performance to community-level outcomes, we show that species interactions induce consistent declines in CUE, regardless of abiotic conditions. Pairwise competition lowers CUE by as much as 25%, with the magnitude of these costs equal to or greater than the observed variation across abiotic conditions. However, depending on the competitive network structure, increasing species richness led to consistent gains or declines in CUE. Our results suggest that the extent to which microbial-mediated carbon fluxes respond to environmental change may be influenced strongly by competitive interactions. As such, knowledge of abiotic conditions and community composition is necessary to confidently project CUE and hence ecosystem carbon dynamics.

  5. Development of 7TM receptor-ligand complex models using ligand-biased, semi-empirical helix-bundle repacking in torsion space: application to the agonist interaction of the human dopamine D2 receptor.

    Science.gov (United States)

    Malo, Marcus; Persson, Ronnie; Svensson, Peder; Luthman, Kristina; Brive, Lars

    2013-03-01

    Prediction of 3D structures of membrane proteins, and of G-protein coupled receptors (GPCRs) in particular, is motivated by their importance in biological systems and the difficulties associated with experimental structure determination. In the present study, a novel method for the prediction of 3D structures of the membrane-embedded region of helical membrane proteins is presented. A large pool of candidate models are produced by repacking of the helices of a homology model using Monte Carlo sampling in torsion space, followed by ranking based on their geometric and ligand-binding properties. The trajectory is directed by weak initial restraints to orient helices towards the original model to improve computation efficiency, and by a ligand to guide the receptor towards a chosen conformational state. The method was validated by construction of the β1 adrenergic receptor model in complex with (S)-cyanopindolol using bovine rhodopsin as template. In addition, models of the dopamine D2 receptor were produced with the selective and rigid agonist (R)-N-propylapomorphine ((R)-NPA) present. A second quality assessment was implemented by evaluating the results from docking of a library of 29 ligands with known activity, which further discriminated between receptor models. Agonist binding and recognition by the dopamine D2 receptor is interpreted using the 3D structure model resulting from the approach. This method has a potential for modeling of all types of helical transmembrane proteins for which a structural template with sequence homology sufficient for homology modeling is not available or is in an incorrect conformational state, but for which sufficient empirical information is accessible.

  6. Modeling and analysis of PET studies with norepinephrine transporter ligands: the search for a reference region

    Energy Technology Data Exchange (ETDEWEB)

    Logan, Jean [Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973 (United States)]. E-mail: logan@bnl.gov; Ding, Y.-S. [Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Lin, K.-S. [Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Pareto, Deborah [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Functional Imaging, Berkeley National Laboratory, Berkeley, CA 94720 (United States); Fowler, Joanna [Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Biegon, Anat [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States)

    2005-07-01

    The development of positron emission tomography (PET) ligands for the norepinephrine transporter (NET) has been slow compared to the development of radiotracers for others systems, such as the dopamine (DAT) or the serotonin transporters (SERT). The main reason for this appears to be the high nonspecific (non-NET) binding exhibited by many of these tracers, which makes the identification of a reference region difficult. With other PET ligands the use of a reference region increases the reproducibility of the outcome measure in test/retest studies. The focus of this work is to identify a suitable reference region or means of normalizing data for the NET ligands investigated. Methods: We have analyzed the results of PET studies in the baboon brain with labeled reboxetine derivatives (S,S)-[{sup 11}C]O-methyl reboxetine (SS-MRB), (S,S)-[{sup 18}F]fluororeboxetine (SS-FRB) as well as O-[{sup 11}C]nisoxetine and N-[{sup 11}C]nisoxetine (NIS), and, for comparison, the less active (R,R) enantiomers (RR-MRB, RR-FRB) in terms of the distribution volume (DV) using measured arterial input functions. Results: (1) For a given subject, a large variation in DV for successive baseline studies was observed in regions with both high and low NET density. (2) The occipital cortex and the basal ganglia were found to be the regions with the smallest change between baseline (SS-MRB) and pretreatment with cocaine, and were therefore used as a composite reference region for calculation of a distribution volume ratio (DVR). (3) The variability [as measured by the coefficient of variation (CV)=standard deviation/mean] in the distribution volume ratio (DVR) of thalamus (to reference region) was considerably reduced over that of the DV using this composite reference region. (4) Pretreatment with nisoxetine (1.0 mg/kg 10 min prior to tracer) in one study produced (in decreasing order) reductions in thalamus, cerebellum, cingulate and frontal cortex consistent with known NET densities. (5) [{sup

  7. Modeling and analysis of PET studies with norepinephrine transporter ligands: the search for a reference region.

    Science.gov (United States)

    Logan, Jean; Ding, Yu-Shin; Lin, Kuo-Shyan; Pareto, Deborah; Fowler, Joanna; Biegon, Anat

    2005-07-01

    The development of positron emission tomography (PET) ligands for the norepinephrine transporter (NET) has been slow compared to the development of radiotracers for others systems, such as the dopamine (DAT) or the serotonin transporters (SERT). The main reason for this appears to be the high nonspecific (non-NET) binding exhibited by many of these tracers, which makes the identification of a reference region difficult. With other PET ligands the use of a reference region increases the reproducibility of the outcome measure in test/retest studies. The focus of this work is to identify a suitable reference region or means of normalizing data for the NET ligands investigated. We have analyzed the results of PET studies in the baboon brain with labeled reboxetine derivatives (S,S)-[(11)C]O-methyl reboxetine (SS-MRB), (S,S)-[(18)F]fluororeboxetine (SS-FRB) as well as O-[(11)C]nisoxetine and N-[(11)C]nisoxetine (NIS), and, for comparison, the less active (R,R) enantiomers (RR-MRB, RR-FRB) in terms of the distribution volume (DV) using measured arterial input functions. (1) For a given subject, a large variation in DV for successive baseline studies was observed in regions with both high and low NET density. (2) The occipital cortex and the basal ganglia were found to be the regions with the smallest change between baseline (SS-MRB) and pretreatment with cocaine, and were therefore used as a composite reference region for calculation of a distribution volume ratio (DVR). (3) The variability [as measured by the coefficient of variation (CV) = standard deviation/mean] in the distribution volume ratio (DVR) of thalamus (to reference region) was considerably reduced over that of the DV using this composite reference region. (4) Pretreatment with nisoxetine (1.0 mg/kg 10 min prior to tracer) in one study produced (in decreasing order) reductions in thalamus, cerebellum, cingulate and frontal cortex consistent with known NET densities. (5) [(11)C]Nisoxetine had a higher

  8. Modeling and analysis of PET studies with norepinephrine transporter ligands: the search for a reference region

    International Nuclear Information System (INIS)

    Logan, Jean; Ding, Y.-S.; Lin, K.-S.; Pareto, Deborah; Fowler, Joanna; Biegon, Anat

    2005-01-01

    The development of positron emission tomography (PET) ligands for the norepinephrine transporter (NET) has been slow compared to the development of radiotracers for others systems, such as the dopamine (DAT) or the serotonin transporters (SERT). The main reason for this appears to be the high nonspecific (non-NET) binding exhibited by many of these tracers, which makes the identification of a reference region difficult. With other PET ligands the use of a reference region increases the reproducibility of the outcome measure in test/retest studies. The focus of this work is to identify a suitable reference region or means of normalizing data for the NET ligands investigated. Methods: We have analyzed the results of PET studies in the baboon brain with labeled reboxetine derivatives (S,S)-[ 11 C]O-methyl reboxetine (SS-MRB), (S,S)-[ 18 F]fluororeboxetine (SS-FRB) as well as O-[ 11 C]nisoxetine and N-[ 11 C]nisoxetine (NIS), and, for comparison, the less active (R,R) enantiomers (RR-MRB, RR-FRB) in terms of the distribution volume (DV) using measured arterial input functions. Results: (1) For a given subject, a large variation in DV for successive baseline studies was observed in regions with both high and low NET density. (2) The occipital cortex and the basal ganglia were found to be the regions with the smallest change between baseline (SS-MRB) and pretreatment with cocaine, and were therefore used as a composite reference region for calculation of a distribution volume ratio (DVR). (3) The variability [as measured by the coefficient of variation (CV)=standard deviation/mean] in the distribution volume ratio (DVR) of thalamus (to reference region) was considerably reduced over that of the DV using this composite reference region. (4) Pretreatment with nisoxetine (1.0 mg/kg 10 min prior to tracer) in one study produced (in decreasing order) reductions in thalamus, cerebellum, cingulate and frontal cortex consistent with known NET densities. (5) [ 11 C]Nisoxetine had

  9. Homology-modeled ligand-binding domains of medaka estrogen receptors and androgen receptors: A model system for the study of reproduction

    International Nuclear Information System (INIS)

    Cui Jianzhou; Shen Xueyan; Yan Zuowei; Zhao Haobin; Nagahama, Yoshitaka

    2009-01-01

    Estrogen and androgen and their receptors play critical roles in physiological processes such as sexual differentiation and development. Using the available structural models for the human estrogen receptors alpha and beta and androgen receptor as templates, we designed in silico agonist and antagonist models of medaka estrogen receptor (meER) alpha, beta-1, and beta-2, and androgen receptor (meAR) alpha and beta. Using these models, we studied (1) the structural relationship between the ligand-binding domains (LBDs) of ERs and ARs of human and medaka, and (2) whether medaka ER and AR can be potential models for studying the ligand-binding activities of various agonists and antagonists of these receptors by docking analysis. A high level of conservation was observed between the sequences of the ligand-binding domains of meERα and huERα, meERβ1 and huERβ, meERβ2, and huERβ with 62.8%, 66.4%, and 65.1% identity, respectively. The sequence conservation between meARα and huAR, meARβ, and huAR was found with 70.1% and 61.0% of identity, respectively. Thirty-three selected endocrine disrupting chemicals (EDCs), including both agonists and antagonists, were docked into the LBD of ER and AR, and the corresponding docking score for medaka models and human templates were calculated. In order to confirm the conservation of the overall geometry and the binding pocket, the backbone root mean square deviation (RMSD) for Cα atoms was derived from the structure superposition of all 10 medaka homology models to the six human templates. Our results suggested conformational conservation between the ERs and ARs of medaka and human, Thus, medaka could be highly useful as a model system for studies involving estrogen and androgen interaction with their receptors.

  10. Macrocyclic G-quadruplex ligands

    DEFF Research Database (Denmark)

    Nielsen, M C; Ulven, Trond

    2010-01-01

    are macrocyclic structures which have been modeled after the natural product telomestatin or from porphyrin-based ligands discovered in the late 1990s. These two structural classes of G-quadruplex ligands are reviewed here with special attention to selectivity and structure-activity relationships, and with focus...

  11. Effects of various cannabinoid ligands on choice behaviour in a rat model of gambling.

    Science.gov (United States)

    Gueye, Aliou B; Trigo, Jose M; Vemuri, Kiran V; Makriyannis, Alexandros; Le Foll, Bernard

    2016-04-01

    It is estimated that 0.6-1% of the population in the USA and Canada fulfil the Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5) criteria for gambling disorders (GD). To date, there are no approved pharmacological treatments for GD. The rat gambling task (rGT) is a recently developed rodent analogue of the Iowa gambling task in which rats are trained to associate four response holes with different magnitudes and probabilities of food pellet rewards and punishing time-out periods. Similar to healthy human volunteers, most rats adopt the optimal strategies (optimal group). However, a subset of animals show preference for the disadvantageous options (suboptimal group), mimicking the choice pattern of patients with GD. Here, we explored for the first time the effects of various cannabinoid ligands (WIN 55,212-2, AM 4113, AM 630 and URB 597) on the rGT. Administration of the cannabinoid agonist CB1/CB2 WIN 55,212-2 improved choice strategy and increased choice latency in the suboptimal group, but only increased perseverative behaviour, when punished, in the optimal group. Blockade of CB1 or CB2 receptors or inhibition of fatty-acid amide hydrolase did not affect rGT performance. These results suggest that stimulation of cannabinoid receptors could affect gambling choice behaviours differentially in some subgroups of subjects.

  12. Infobiotics information in biotic systems

    CERN Document Server

    Manca, Vincenzo

    2013-01-01

    The book presents topics in discrete biomathematics. Mathematics has been widely used in modeling biological phenomena. However, the molecular and discrete nature of basic life processes suggests that their logic follow principles that are intrinsically based on discrete and informational mechanisms. The ultimate reason of  polymers, as key element of life, is directly based on the computational power of strings, and the intrinsic necessity of metabolism is related to the mathematical notion of multiset.   The switch of the two roots of bioinformatics suggests a change of perspective. In bioinformatics, the biologists ask computer scientists to assist them in processing biological data. Conversely, in infobiotics mathematicians and computer scientists investigate principles and theories yielding new interpretation keys of biological phenomena. Life is too important to be investigated by biologists alone, and though computers are essential to process data from biological laboratories, many fundamental questi...

  13. Linking macroecology and community ecology: refining predictions of species distributions using biotic interaction networks.

    Science.gov (United States)

    Staniczenko, Phillip P A; Sivasubramaniam, Prabu; Suttle, K Blake; Pearson, Richard G

    2017-06-01

    Macroecological models for predicting species distributions usually only include abiotic environmental conditions as explanatory variables, despite knowledge from community ecology that all species are linked to other species through biotic interactions. This disconnect is largely due to the different spatial scales considered by the two sub-disciplines: macroecologists study patterns at large extents and coarse resolutions, while community ecologists focus on small extents and fine resolutions. A general framework for including biotic interactions in macroecological models would help bridge this divide, as it would allow for rigorous testing of the role that biotic interactions play in determining species ranges. Here, we present an approach that combines species distribution models with Bayesian networks, which enables the direct and indirect effects of biotic interactions to be modelled as propagating conditional dependencies among species' presences. We show that including biotic interactions in distribution models for species from a California grassland community results in better range predictions across the western USA. This new approach will be important for improving estimates of species distributions and their dynamics under environmental change. © 2017 The Authors. Ecology Letters published by CNRS and John Wiley & Sons Ltd.

  14. Biotic and Biogeochemical Feedbacks to Climate Change

    Science.gov (United States)

    Torn, M. S.; Harte, J.

    2002-12-01

    Feedbacks to paleoclimate change are evident in ice core records showing correlations of temperature with carbon dioxide, nitrous oxide, and methane. Such feedbacks may be explained by plant and microbial responses to climate change, and are likely to occur under impending climate warming, as evidenced by results of ecosystem climate manipulation experiments and biometeorological observations along ecological and climate gradients. Ecosystems exert considerable influence on climate, by controlling the energy and water balance of the land surface as well as being sinks and sources of greenhouse gases. This presentation will focus on biotic and biogeochemical climate feedbacks on decadal to century time scales, emphasizing carbon storage and energy exchange. In addition to the direct effects of climate on decomposition rates and of climate and CO2 on plant productivity, climate change can alter species composition; because plant species differ in their surface properties, productivity, phenology, and chemistry, climate-induced changes in plant species composition can exert a large influence on the magnitude and sign of climate feedbacks. We discuss the effects of plant species on ecosystem carbon storage that result from characteristic differences in plant biomass and lifetime, allocation to roots vs. leaves, litter quality, microclimate for decomposition and the ultimate stabilization of soil organic matter. We compare the effect of species transitions on transpiration, albedo, and other surface properties, with the effect of elevated CO2 and warming on single species' surface exchange. Global change models and experiments that investigate the effect of climate only on existing vegetation may miss the biggest impacts of climate change on biogeochemical cycling and feedbacks. Quantification of feedbacks will require understanding how species composition and long-term soil processes will change under global warming. Although no single approach, be it experimental

  15. Colloidal nanoparticle size control: experimental and kinetic modeling investigation of the ligand-metal binding role in controlling the nucleation and growth kinetics.

    Science.gov (United States)

    Mozaffari, Saeed; Li, Wenhui; Thompson, Coogan; Ivanov, Sergei; Seifert, Soenke; Lee, Byeongdu; Kovarik, Libor; Karim, Ayman M

    2017-09-21

    Despite the major advancements in colloidal metal nanoparticles synthesis, a quantitative mechanistic treatment of the ligand's role in controlling their size remains elusive. We report a methodology that combines in situ small angle X-ray scattering (SAXS) and kinetic modeling to quantitatively capture the role of ligand-metal binding (with the metal precursor and the nanoparticle surface) in controlling the synthesis kinetics. We demonstrate that accurate extraction of the kinetic rate constants requires using both, the size and number of particles obtained from in situ SAXS to decouple the contributions of particle nucleation and growth to the total metal reduction. Using Pd acetate and trioctylphosphine in different solvents, our results reveal that the binding of ligands with both the metal precursor and nanoparticle surface play a key role in controlling the rates of nucleation and growth and consequently the final size. We show that the solvent can affect the metal-ligand binding and consequently ligand coverage on the nanoparticles surface which has a strong effect on the growth rate and final size (1.4 nm in toluene and 4.3 nm in pyridine). The proposed kinetic model quantitatively predicts the effects of varying the metal concentration and ligand/metal ratio on nanoparticle size for our work and literature reports. More importantly, we demonstrate that the final size is exclusively determined by the nucleation and growth kinetics at early times and not how they change with time. Specifically, the nanoparticle size in this work and many literature reports can be predicted using a single, model independent kinetic descriptor, (growth-to-nucleation rate ratio) 1/3 , despite the different metals and synthetic conditions. The proposed model and kinetic descriptor could serve as powerful tools for the design of colloidal nanoparticles with specific sizes.

  16. The signaling pathway of dopamine D2 receptor (D2R) activation using normal mode analysis (NMA) and the construction of pharmacophore models for D2R ligands.

    Science.gov (United States)

    Salmas, Ramin Ekhteiari; Stein, Matthias; Yurtsever, Mine; Seeman, Philip; Erol, Ismail; Mestanoglu, Mert; Durdagi, Serdar

    2017-07-01

    G-protein-coupled receptors (GPCRs) are targets of more than 30% of marketed drugs. Investigation on the GPCRs may shed light on upcoming drug design studies. In the present study, we performed a combination of receptor- and ligand-based analysis targeting the dopamine D2 receptor (D2R). The signaling pathway of D2R activation and the construction of universal pharmacophore models for D2R ligands were also studied. The key amino acids, which contributed to the regular activation of the D2R, were in detail investigated by means of normal mode analysis (NMA). A derived cross-correlation matrix provided us an understanding of the degree of pair residue correlations. Although negative correlations were not observed in the case of the inactive D2R state, a high degree of correlation appeared between the residues in the active state. NMA results showed that the cytoplasmic side of the TM5 plays a significant role in promoting of residue-residue correlations in the active state of D2R. Tracing motions of the amino acids Arg219, Arg220, Val223, Asn224, Lys226, and Ser228 in the position of the TM5 are found to be critical in signal transduction. Complementing the receptor-based modeling, ligand-based modeling was also performed using known D2R ligands. The top-scored pharmacophore models were found as 5-sited (AADPR.671, AADRR.1398, AAPRR.3900, and ADHRR.2864) hypotheses from PHASE modeling from a pool consisting of more than 100 initial candidates. The constructed models using 38 D2R ligands (in the training set) were validated with 15 additional test set compounds. The resulting model correctly predicted the pIC 50 values of an additional test set compounds as true unknowns.

  17. Silver(I)-promoted conversion of thioamides to amidines: divergent synthesis of a key series of vancomycin aglycon residue 4 amidines that clarify binding behavior to model ligands.

    Science.gov (United States)

    Okano, Akinori; James, Robert C; Pierce, Joshua G; Xie, Jian; Boger, Dale L

    2012-05-30

    Development of a general Ag(I)-promoted reaction for the conversion of thioamides to amidines is disclosed. This reaction was employed to prepare a key series of vancomycin aglycon residue 4 substituted amidines that were used to clarify their interaction with model ligands of peptidoglycan precursors and explore their resulting impact on antimicrobial properties.

  18. PET imaging of neuroinflammation in a rat traumatic brain injury model with radiolabeled TSPO ligand DPA-714

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yu [Medical School of Southeast University, Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Nanjing (China); National Institutes of Health - NIH, Laboratory of Molecular Imaging and Nanomedicine - LOMIN, National Institute of Biomedical Imaging and Bioengineering - NIBIB, Bethesda, MD (United States); Yue, Xuyi; Kiesewetter, Dale O.; Niu, Gang; Chen, Xiaoyuan [National Institutes of Health - NIH, Laboratory of Molecular Imaging and Nanomedicine - LOMIN, National Institute of Biomedical Imaging and Bioengineering - NIBIB, Bethesda, MD (United States); Teng, Gaojun [Medical School of Southeast University, Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Nanjing (China)

    2014-07-15

    The inflammatory response in injured brain parenchyma after traumatic brain injury (TBI) is crucial in the pathological process. In order to follow microglia activation and neuroinflammation after TBI, we performed PET imaging in a rat model of TBI using {sup 18}F-labeled DPA-714, a ligand of the 18-kDa translocator protein (TSPO). TBI was induced in male SD rats by a controlled cortical impact. The success of the TBI model was confirmed by MRI. [{sup 18}F]DPA-714 was synthesized using a slightly modified TRACERLab FX-FN module and an automated procedure. In vivo PET imaging was performed at different time points after surgery using an Inveon small-animal PET scanner. The specificity of [{sup 18}F]DPA-714 was confirmed by a displacement study with an unlabeled competitive TSPO ligand, PK11195. Ex vivo autoradiography as well as immunofluorescence staining was carried out to confirm the in vivo PET results. Both in vivo T{sub 2}-weighted MR images and ex vivo TTC staining results revealed successful establishment of the TBI model. Compared with the sham-treated group, [{sup 18}F]DPA-714 uptake was significantly higher in the injured brain area on PET images. Increased lesion-to-normal ratios of [{sup 18}F]DPA-714 were observed in the brain of TBI rats on day 2 after surgery. Ratios peaked around day 6 (2.65 ± 0.36) and then decreased gradually to nearly normal levels on day 28. The displacement study using PK11195 confirmed the specific binding of [{sup 18}F]DPA-714 to TSPO. The results of ex vivo autoradiography were consistent with in vivo PET results. Immunofluorescence staining showed the time course of TSPO expression after TBI and the temporal and the spatial distribution of microglia in the damaged brain area. TSPO-targeted PET using [{sup 18}F]DPA-714 as the imaging probe can be used to dynamically monitor the inflammatory response after TBI in a noninvasive manner. This method will not only facilitate a better understanding of the inflammatory process

  19. Analgesic efficacy of CR4056, a novel imidazoline-2 receptor ligand, in rat models of inflammatory and neuropathic pain

    Directory of Open Access Journals (Sweden)

    Ferrari F

    2011-04-01

    Full Text Available Flora Ferrari1, Simonetta Fiorentino1, Laura Mennuni1, Paolo Garofalo1, Ornella Letari1, Stefano Mandelli2, Antonio Giordani3, Marco Lanza1, Gianfranco Caselli11Department of Pharmacology and Toxicology; 2Department of Medicinal Chemistry; 3R&D Chemistry Drug Development and OS, Rottapharm S.p.A., Monza (MB, ItalyAbstract: Two decades of investigations have failed to unequivocally clarify the functions and the molecular nature of imidazoline-2 receptors (I2R. However, there is robust pharmacological evidence for the functional modulation of monoamino oxidase (MAO and other important enzyme activities by I2 site ligands. Some compounds of this class proved to be active experimental tools in preventing both experimental pain and opioid tolerance and dependence. Unfortunately, even though these compounds bind with high potency to central I2 sites, they fail to represent a valid clinical opportunity due to their pharmacokinetic, selectivity or side-effects profile. This paper presents the preclinical profile of a novel I2 ligand (2-phenyl-6-(1H-imidazol-1ylquinazoline; [CR4056] that selectively inhibits the activity of human recombinant MAO-A in a concentration-dependent manner. A sub-chronic four day oral treatment of CR4056 increased norepinephrine (NE tissue levels both in the rat cerebral cortex (63.1% ± 4.2%; P<0.05 and lumbar spinal cord (51.3% ± 6.7%; P < 0.05. In the complete Freund's adjuvant (CFA rat model of inflammatory pain, CR4056 was found to be orally active (ED50 = 5.8 mg/kg, by mouth [p.o.]. In the acute capsaicin model, CR4056 completely blocked mechanical hyperalgesia in the injured hind paw (ED50 = 4.1 mg/kg, p.o.; ED100 = 17.9 mg/kg, p.o.. This effect was dose-dependently antagonized by the non-selective imidazoline I2/α2 antagonist idazoxan. In rat models of neuropathic pain, oral administration of CR4056 significantly attenuated mechanical hyperalgesia and allodynia. In summary, the present study suggests a novel

  20. Effect of abiotic and biotic stress factors analysis using machine learning methods in zebrafish.

    Science.gov (United States)

    Gutha, Rajasekar; Yarrappagaari, Suresh; Thopireddy, Lavanya; Reddy, Kesireddy Sathyavelu; Saddala, Rajeswara Reddy

    2018-03-01

    In order to understand the mechanisms underlying stress responses, meta-analysis of transcriptome is made to identify differentially expressed genes (DEGs) and their biological, molecular and cellular mechanisms in response to stressors. The present study is aimed at identifying the effect of abiotic and biotic stress factors, and it is found that several stress responsive genes are common for both abiotic and biotic stress factors in zebrafish. The meta-analysis of micro-array studies revealed that almost 4.7% i.e., 108 common DEGs are differentially regulated between abiotic and biotic stresses. This shows that there is a global coordination and fine-tuning of gene regulation in response to these two types of challenges. We also performed dimension reduction methods, principal component analysis, and partial least squares discriminant analysis which are able to segregate abiotic and biotic stresses into separate entities. The supervised machine learning model, recursive-support vector machine, could classify abiotic and biotic stresses with 100% accuracy using a subset of DEGs. Beside these methods, the random forests decision tree model classified five out of 8 stress conditions with high accuracy. Finally, Functional enrichment analysis revealed the different gene ontology terms, transcription factors and miRNAs factors in the regulation of stress responses. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. A model for the calculation of lanthanide induced shifts of bidentate ligands - 1,3-diols

    International Nuclear Information System (INIS)

    Hofer, O.; Griengl, H.; Nowak, P.

    1978-01-01

    The NMR-LIS data of the four diastereomeric 2-(hydroxyphenylmethyl) cyclohexanols 1-4 are used to test two possible computational models for bidentate Eu(dpm)B 3 complexes. A model taking into account the presence of two equivalent coordinaton centers by averaging the corresponding dipolar fields of both centers proved to be superior to the simpler one assuming only one dipolar field with a fictive coordination center at a point equidistant between the two actual coordination sites. (author)

  2. Ligand binding modes from low resolution GPCR models and mutagenesis: chicken bitter taste receptor as a test-case.

    Science.gov (United States)

    Di Pizio, Antonella; Kruetzfeldt, Louisa-Marie; Cheled-Shoval, Shira; Meyerhof, Wolfgang; Behrens, Maik; Niv, Masha Y

    2017-08-15

    Bitter taste is one of the basic taste modalities, warning against consuming potential poisons. Bitter compounds activate members of the bitter taste receptor (Tas2r) subfamily of G protein-coupled receptors (GPCRs). The number of functional Tas2rs is species-dependent. Chickens represent an intriguing minimalistic model, because they detect the bitter taste of structurally different molecules with merely three bitter taste receptor subtypes. We investigated the binding modes of several known agonists of a representative chicken bitter taste receptor, ggTas2r1. Because of low sequence similarity between ggTas2r1 and crystallized GPCRs (~10% identity, ~30% similarity at most), the combination of computational approaches with site-directed mutagenesis was used to characterize the agonist-bound conformation of ggTas2r1 binding site between TMs 3, 5, 6 and 7. We found that the ligand interactions with N93 in TM3 and/or N247 in TM5, combined with hydrophobic contacts, are typically involved in agonist recognition. Next, the ggTas2r1 structural model was successfully used to identify three quinine analogues (epiquinidine, ethylhydrocupreine, quinidine) as new ggTas2r1 agonists. The integrated approach validated here may be applicable to additional cases where the sequence identity of the GPCR of interest and the existing experimental structures is low.

  3. Ligand-based modeling of Akt3 lead to potent dual Akt1/Akt3 inhibitor.

    Science.gov (United States)

    Al-Sha'er, Mahmoud A; Taha, Mutasem O

    2018-02-13

    Akt1 and Akt3 are important serine/threonine-specific protein kinases involved in G2 phase required by cancer cells to maintain cell cycle and to prevent cell death. Accordingly, inhibitors of these kinases should have potent anti-cancer properties. This prompted us to use pharmacophore/QSAR modeling to identify optimal binding models and physicochemical descriptors that explain bioactivity variation within a set of 74 diverse Akt3 inhibitors. Two successful orthogonal pharmacophores were identified and further validated using receiver operating characteristic (ROC) curve analyses. The pharmacophoric models and associated QSAR equation were applied to screen the national cancer institute (NCI) list of compounds for new Akt3 inhibitors. Six hits showed significant experimental anti-Akt3 IC 50 values, out of which one compound exhibited dual low micromolar anti-Akt1 and anti-Akt3 inhibitory profiles. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Impact on the Fe redox cycling of organic ligands released by Synechococcus PCC 7002, under different iron fertilization scenarios. Modeling approach

    Science.gov (United States)

    Samperio-Ramos, Guillermo; González-Dávila, Melchor; Santana-Casiano, J. Magdalena

    2018-06-01

    The kinetics of Fe redox transformations are of crucial importance in determining the bioavailability of iron, due to inorganic Fe(II) and Fe weakly organic complexes being the most easily assimilated species by phytoplankton. The role played by the natural organic ligands excreted by the cyanobacteria Synecococcus PCC 7002 on the iron redox chemistry was studied at different stages of growth, considering changes in the organic exudation of the cyanobacteria, associated with growth under two different scenarios of iron availability. The oxidation/reduction processes of iron were studied at nanomolar levels and under different physicochemical conditions of pH (7.2- 8.2), temperature (5- 35 °C) and salinity (10- 37). The presence of natural organic exudates of Synechococcus affected the redox behavior of iron. A pH-dependent and photo-induced Fe(III) reduction process was detected in the presence of exudates produced under Fe-Low conditions. Photolytic reactions also modified the reactivity of those exudates with respect to Fe(II), increasing its lifetime in seawater. Without light mediated processes, organic ligands excreted under iron deficient conditions intensified the Fe(II) oxidation at pH redox constants between iron and the major ligands present in solution. Two organic type ligands for the exudates of Synechococcus PCC 7002, with different iron-chelation properties were included in the model. The Fe(II) speciation was radically affected when organic ligands were considered. The individual contributions to the overall Fe(II) oxidation rate demonstrated that these organic ligands played a key role in the oxidation process, although their contributions were dependent on the prescribed iron conditions. The study, therefore, suggests that the variability in the composition and nature of organic exudates released, due to iron availability conditions, might determine the redox behaviour of iron in seawater.

  5. Design of potentially active ligands for SH2 domains by molecular modeling methods

    Directory of Open Access Journals (Sweden)

    Hurmach V. V.

    2014-07-01

    Full Text Available Search for new chemical structures possessing specific biological activity is a complex problem that needs the use of the latest achievements of molecular modeling technologies. It is well known that SH2 domains play a major role in ontogenesis as intermediaries of specific protein-protein interactions. Aim. Developing an algorithm to investigate the properties of SH2 domain binding, search for new potential active compounds for the whole SH2 domains class. Methods. In this paper, we utilize a complex of computer modeling methods to create a generic set of potentially active compounds targeting universally at the whole class of SH2 domains. A cluster analysis of all available three-dimensional structures of SH2 domains was performed and general pharmacophore models were formulated. The models were used for virtual screening of collection of drug-like compounds provided by Enamine Ltd. Results. The design technique for library of potentially active compounds for SH2 domains class was proposed. Conclusions. The original algorithm of SH2 domains research with molecular docking method was developed. Using our algorithm, the active compounds for SH2 domains were found.

  6. A predictive ligand-based Bayesian model for human drug-induced liver injury.

    Science.gov (United States)

    Ekins, Sean; Williams, Antony J; Xu, Jinghai J

    2010-12-01

    Drug-induced liver injury (DILI) is one of the most important reasons for drug development failure at both preapproval and postapproval stages. There has been increased interest in developing predictive in vivo, in vitro, and in silico models to identify compounds that cause idiosyncratic hepatotoxicity. In the current study, we applied machine learning, a Bayesian modeling method with extended connectivity fingerprints and other interpretable descriptors. The model that was developed and internally validated (using a training set of 295 compounds) was then applied to a large test set relative to the training set (237 compounds) for external validation. The resulting concordance of 60%, sensitivity of 56%, and specificity of 67% were comparable to results for internal validation. The Bayesian model with extended connectivity functional class fingerprints of maximum diameter 6 (ECFC_6) and interpretable descriptors suggested several substructures that are chemically reactive and may also be important for DILI-causing compounds, e.g., ketones, diols, and α-methyl styrene type structures. Using Smiles Arbitrary Target Specification (SMARTS) filters published by several pharmaceutical companies, we evaluated whether such reactive substructures could be readily detected by any of the published filters. It was apparent that the most stringent filters used in this study, such as the Abbott alerts, which captures thiol traps and other compounds, may be of use in identifying DILI-causing compounds (sensitivity 67%). A significant outcome of the present study is that we provide predictions for many compounds that cause DILI by using the knowledge we have available from previous studies. These computational models may represent cost-effective selection criteria before in vitro or in vivo experimental studies.

  7. Interpretation of complexometric titration data: An intercomparison of methods for estimating models of trace metal complexation by natural organic ligands

    NARCIS (Netherlands)

    Pižeta, I.; Sander, S.G.; Hudson, R.J.M.; Omanovic, D.; Baars, O.; Barbeau, K.A.; Buck, K.N.; Bundy, R.M.; Carrasco, G.; Croot, P.L.; Garnier, C.; Gerringa, L.J.A.; Gledhill, M.; Hirose, K.; Kondo, Y.; Laglera, L.M.; Nuester, J.; Rijkenberg, M.J.A.; Takeda, S.; Twining, B.S.; Wells, M.

    2015-01-01

    With the common goal of more accurately and consistently quantifying ambient concentrations of free metal ions and natural organic ligands in aquatic ecosystems, researchers from 15 laboratories that routinely analyze trace metal speciation participated in an intercomparison of statistical methods

  8. Modelling of Octahedral Manganese II Complexes with Inorganic Ligands: A Problem with Spin-States

    Directory of Open Access Journals (Sweden)

    Ludwik Adamowicz

    2003-08-01

    Full Text Available Abstract: Quantum mechanical ab initio UHF, MP2, MC-SCF and DFT calculations with moderate Gaussian basis sets were performed for MnX6, X = H2O, F-, CN-, manganese octahedral complexes. The correct spin-state of the complexes was obtained only when the counter ions neutralizing the entire complexes were used in the modelling at the B3LYP level of theory.

  9. COMPARATIVE MODELLING AND LIGAND BINDING SITE PREDICTION OF A FAMILY 43 GLYCOSIDE HYDROLASE FROM Clostridium thermocellum

    Directory of Open Access Journals (Sweden)

    Shadab Ahmed

    2012-06-01

    Full Text Available The phylogenetic analysis of Clostridium thermocellum family 43 glycoside hydrolase (CtGH43 showed close evolutionary relation with carbohydrate binding family 6 proteins from C. cellulolyticum, C. papyrosolvens, C. cellulyticum, and A. cellulyticum. Comparative modeling of CtGH43 was performed based on crystal structures with PDB IDs 3C7F, 1YIF, 1YRZ, 2EXH and 1WL7. The structure having lowest MODELLER objective function was selected. The three-dimensional structure revealed typical 5-fold beta–propeller architecture. Energy minimization and validation of predicted model with VERIFY 3D indicated acceptability of the proposed atomic structure. The Ramachandran plot analysis by RAMPAGE confirmed that family 43 glycoside hydrolase (CtGH43 contains little or negligible segments of helices. It also showed that out of 301 residues, 267 (89.3% were in most favoured region, 23 (7.7% were in allowed region and 9 (3.0% were in outlier region. IUPred analysis of CtGH43 showed no disordered region. Active site analysis showed presence of two Asp and one Glu, assumed to form a catalytic triad. This study gives us information about three-dimensional structure and reaffirms the fact that it has the similar core 5-fold beta–propeller architecture and so probably has the same inverting mechanism of action with the formation of above mentioned catalytic triad for catalysis of polysaccharides.

  10. Expression and function of Delta-like ligand 4 in a rat model of retinopathy of prematurity

    Institute of Scientific and Technical Information of China (English)

    Shaoyang Shi; Xun Li; You Li; Cunwen Pei; Hongwei Yang; Xiaolong Chen

    2013-01-01

    The Delta-like ligand 4/Notch signaling pathway was shown to participate in the process of retinal development and angiogenesis. However, the function of the Delta-like ligand 4/Notch signaling pathway in retinopathy of prematurity requires further study. Retinopathy of prematurity was induced in 5-day-old Sprague-Dawley rats exposed to hyperoxia for 7 days, and then returned to room air. Reverse transcription-PCR and western blot revealed that Delta-like ligand 4 levels decreased at postnatal day 12 and increased at postnatal day 17 in retinopathy of prematurity rats. Flat-mounted adenosine diphosphatase stained retina and hematoxylin-eosin stained retinal tissue slices showed that the clock hour scores and the nuclei counts in retinopathy of prematurity rats were significantly different compared to normal control rats. After retinopathy of prematurity rats were intravitreally injected with Delta-like ligand 4 monoclonal antibody to inhibit the Delta-like ligand 4/Notch signaling pathway, there was a significant increase in the severity of retinal neovascularization (clock hours) in the intravitreally injected eyes. The nuclei count was highly correlated with the clock hour score. These results suggest that Delta-like ligand 4/Notch signaling plays an essential role in the process of physiological and pathological angiogenesis in the retina.

  11. Spinal NF-κB and chemokine ligand 5 expression during spinal glial cell activation in a neuropathic pain model.

    Directory of Open Access Journals (Sweden)

    Qin Yin

    Full Text Available BACKGROUND: The NF-κB pathway and chemokine (C-C motif ligand 5 (CCL5 are involved in pain modulation; however, the precise mechanisms of their interactions in chronic neuropathic pain have yet to be established. METHODS: The present study examined the roles of spinal NF-κB and CCL5 in a neuropathic pain model after chronic constriction injury (CCI surgery. CCI-induced pain facilitation was evaluated using the Plantar and von Frey tests. The changes in NF-κB and CCL5 expression were analyzed by immunohistochemistry and Western blot analyses. RESULTS: Spinal NF-κB and CCL5 expression increased after CCI surgery. Repeated intrathecal infusions of pyrrolidine dithiocarbamate (PDTC, a NF-κB inhibitor decreased CCL5 expression, inhibited the activation of microglia and astrocytes, and attenuated CCI-induced allodynia and hyperalgesia. Intrathecal injection of a CCL5-neutralizing antibody attenuated CCI-induced pain facilitation and also suppressed spinal glial cell activation after CCI surgery. However, the CCL5-neutralizing antibody did not affect NF-κB expression. Furthermore, selective glial inhibitors, minocycline and fluorocitrate, attenuated the hyperalgesia induced by intrathecal CCL5. CONCLUSIONS: The inhibition of spinal CCL5 expression may provide a new method to prevent and treat nerve injury-induced neuropathic pain.

  12. Calcium Signalling in Plant Biotic Interactions

    Directory of Open Access Journals (Sweden)

    Didier Aldon

    2018-02-01

    Full Text Available Calcium (Ca2+ is a universal second messenger involved in various cellular processes, leading to plant development and to biotic and abiotic stress responses. Intracellular variation in free Ca2+ concentration is among the earliest events following the plant perception of environmental change. These Ca2+ variations differ in their spatio-temporal properties according to the nature, strength and duration of the stimulus. However, their conversion into biological responses requires Ca2+ sensors for decoding and relaying. The occurrence in plants of calmodulin (CaM but also of other sets of plant-specific Ca2+ sensors such as calmodulin-like proteins (CMLs, Ca2+-dependent protein kinases (CDPKs and calcineurin B-like proteins (CBLs indicate that plants possess specific tools and machineries to convert Ca2+ signals into appropriate responses. Here, we focus on recent progress made in monitoring the generation of Ca2+ signals at the whole plant or cell level and their long distance propagation during biotic interactions. The contribution of CaM/CMLs and CDPKs in plant immune responses mounted against bacteria, fungi, viruses and insects are also presented.

  13. Generation of a homology model of the human histamine H3 receptor for ligand docking and pharmacophore-based screening

    Science.gov (United States)

    Schlegel, Birgit; Laggner, Christian; Meier, Rene; Langer, Thierry; Schnell, David; Seifert, Roland; Stark, Holger; Höltje, Hans-Dieter; Sippl, Wolfgang

    2007-08-01

    The human histamine H3 receptor (hH3R) is a G-protein coupled receptor (GPCR), which modulates the release of various neurotransmitters in the central and peripheral nervous system and therefore is a potential target in the therapy of numerous diseases. Although ligands addressing this receptor are already known, the discovery of alternative lead structures represents an important goal in drug design. The goal of this work was to study the hH3R and its antagonists by means of molecular modelling tools. For this purpose, a strategy was pursued in which a homology model of the hH3R based on the crystal structure of bovine rhodopsin was generated and refined by molecular dynamics simulations in a dipalmitoylphosphatidylcholine (DPPC)/water membrane mimic before the resulting binding pocket was used for high-throughput docking using the program GOLD. Alternatively, a pharmacophore-based procedure was carried out where the alleged bioactive conformations of three different potent hH3R antagonists were used as templates for the generation of pharmacophore models. A pharmacophore-based screening was then carried out using the program Catalyst. Based upon a database of 418 validated hH3R antagonists both strategies could be validated in respect of their performance. Seven hits obtained during this screening procedure were commercially purchased, and experimentally tested in a [3H]Nα-methylhistamine binding assay. The compounds tested showed affinities at hH3R with K i values ranging from 0.079 to 6.3 μM.

  14. Modeling the preferred shapes of polyamine transporter ligands and dihydromotuporamine-C mimics: shovel versus hoe.

    Science.gov (United States)

    Breitbeil, Fred; Kaur, Navneet; Delcros, Jean-Guy; Martin, Bénédicte; Abboud, Khalil A; Phanstiel, Otto

    2006-04-20

    Preferred conformers generated from motuporamine and anthracene-polyamine derivatives provided insight into the shapes associated with polyamine transporter (PAT) recognition and potentially dihydromotuporamine C (4a) bioactivity. Molecular modeling revealed that N(1)-(anthracen-9-ylmethyl)-3,3-triamine (6a), N(1)-(anthracen-9-ylmethyl)-4,4-triamine (6b), N(1)-(anthracen-9-ylmethyl)-N(1)-ethyl-3,3-triamine (7a), N(1)-(anthracen-9-ylmethyl)-N(1)-ethyl-4,4-triamine (7b), and 4a all preferred a hoe motif. This hoe shape was defined by the all-anti polyamine shaft extending above the relatively flat, appended ring system. The hoe geometry was also inferred by the (1)H NMR spectrum of the free amine of 7a (CDCl(3)), which showed a strong shielding effect of the anthracene ring on the chemical shifts associated with the appended polyamine chain. This shielding effect was found to be independent over a broad concentration range of 7a, which also supported an intramolecular phenomenon. The degree of substitution at the N(1)-position seems to be an important determinant of both the molecular shape preferences and biological activity of anthracenylmethyl-polyamine conjugates.

  15. Biotic and abiotic variables show little redundancy in explaining tree species distributions

    DEFF Research Database (Denmark)

    Meier, Elaine S.; Kienast, Felix; Pearman, Peter B.

    2010-01-01

    Abiotic factors such as climate and soil determine the species fundamental niche, which is further constrained by biotic interactions such as interspecific competition. To parameterize this realized niche, species distribution models (SDMs) most often relate species occurrence data to abiotic var...

  16. Climate, trees, pests, and weeds: Change, uncertainty, and biotic stressors in eastern US national park forests

    Science.gov (United States)

    Nicholas A. Fisichelli; Scott R. Abella; Matthew Peters; Frank J. Krist

    2014-01-01

    The US National Park Service (NPS) manages over 8900 km2 of forest area in the eastern United States where climate change and nonnative species are altering forest structure, composition, and processes. Understanding potential forest change in response to climate, differences in habitat projections among models (uncertainty), and nonnative biotic...

  17. Rapid biotic homogenization of marine fish assemblages

    Science.gov (United States)

    Magurran, Anne E.; Dornelas, Maria; Moyes, Faye; Gotelli, Nicholas J.; McGill, Brian

    2015-01-01

    The role human activities play in reshaping biodiversity is increasingly apparent in terrestrial ecosystems. However, the responses of entire marine assemblages are not well-understood, in part, because few monitoring programs incorporate both spatial and temporal replication. Here, we analyse an exceptionally comprehensive 29-year time series of North Atlantic groundfish assemblages monitored over 5° latitude to the west of Scotland. These fish assemblages show no systematic change in species richness through time, but steady change in species composition, leading to an increase in spatial homogenization: the species identity of colder northern localities increasingly resembles that of warmer southern localities. This biotic homogenization mirrors the spatial pattern of unevenly rising ocean temperatures over the same time period suggesting that climate change is primarily responsible for the spatial homogenization we observe. In this and other ecosystems, apparent constancy in species richness may mask major changes in species composition driven by anthropogenic change. PMID:26400102

  18. GPR17: Molecular modeling and dynamics studies of the 3-D structure and purinergic ligand binding features in comparison with P2Y receptors

    Directory of Open Access Journals (Sweden)

    Ranghino Graziella

    2008-06-01

    Full Text Available Abstract Background GPR17 is a G-protein-coupled receptor located at intermediate phylogenetic position between two distinct receptor families: the P2Y and CysLT receptors for extracellular nucleotides and cysteinyl-LTs, respectively. We previously showed that GPR17 can indeed respond to both classes of endogenous ligands and to synthetic compounds active at the above receptor families, thus representing the first fully characterized non-peptide "hybrid" GPCR. In a rat brain focal ischemia model, the selective in vivo knock down of GPR17 by anti-sense technology or P2Y/CysLT antagonists reduced progression of ischemic damage, thus highlighting GPR17 as a novel therapeutic target for stroke. Elucidation of the structure of GPR17 and of ligand binding mechanisms are the necessary steps to obtain selective and potent drugs for this new potential target. On this basis, a 3-D molecular model of GPR17 embedded in a solvated phospholipid bilayer and refined by molecular dynamics simulations has been the first aim of this study. To explore the binding mode of the "purinergic" component of the receptor, the endogenous agonist UDP and two P2Y receptor antagonists demonstrated to be active on GPR17 (MRS2179 and cangrelor were then modeled on the receptor. Results Molecular dynamics simulations suggest that GPR17 nucleotide binding pocket is similar to that described for the other P2Y receptors, although only one of the three basic residues that have been typically involved in ligand recognition is conserved (Arg255. The binding pocket is enclosed between the helical bundle and covered at the top by EL2. Driving interactions are H-bonds and salt bridges between the 6.55 and 6.52 residues and the phosphate moieties of the ligands. An "accessory" binding site in a region formed by the EL2, EL3 and the Nt was also found. Conclusion Nucleotide binding to GPR17 occurs on the same receptor regions identified for already known P2Y receptors. Agonist

  19. Efficacy of the semiempirical sparkle model as compared to ECP ab-initio calculations for the prediction of ligand field parameters of europium (III) complexes

    International Nuclear Information System (INIS)

    Freire, Ricardo O.; Rocha, Gerd B.; Albuquerque, Rodrigo Q.; Simas, Alfredo M.

    2005-01-01

    The second version of the sparkle model for the calculation of lanthanide complexes (SMLC II) as well as ab-initio calculations (HF/STO-3G and HF/3-21G) have been used to calculate the geometries of a series of europium (III) complexes with different coordination numbers (CN=7, 8 and 9), ligating atoms (O and N) and ligands (mono, bi and polydentate). The so-called ligand field parameters, Bqk's, have been calculated from both SMLC II and ab-initio optimized structures and compared to the ones calculated from crystallographic data. The results show that the SMLC II model represents a significant improvement over the previous version (SMLC) and has given good results when compared to ab-initio methods, which demand a much higher computational effort. Indeed, ab-initio methods take around a hundred times more computing time than SMLC. As such, our results indicate that our sparkle model can be a very useful and a fast tool when applied to the prediction of both ground state geometries and ligand field parameters of europium (III) complexes

  20. An equilibrium model for ligand-modified micellar-enhanced ultrafiltration. Selective separation of metal ions using iminoacetic substituted polyamines and a theoretical model for the titration behavior of polyamines

    Energy Technology Data Exchange (ETDEWEB)

    Dharmawardana, Udeni Rajaratna [Univ. of Oklahoma, Norman, OK (United States)

    1992-01-01

    This thesis consists of three chapters. Chapter 1, An equilibrium model for ligand-modified micellar-enhanced ultrafiltration, describes a theoretical model and experimental investigations which used the semi-equilibrium-dialysis method with N-n-dodecyl iminodiacetic acid as the ligand. In Chapter 2, Selective separation of metal ions using iminoacetic substituted polyamines, polyamines with a substituted ligand group are synthesized and used in investigating selective separation of copper ions from aqueous solution. In Chapter 3, A theoretical model for the titration behavior of polyamines, a novel approach to explain the titration behavior of polymeric amines based on the binding behavior of counterions is described. The application of this study is to the investigation of inexpensive and efficient methods of industrial waste water treatment.

  1. Insights into an original pocket-ligand pair classification: a promising tool for ligand profile prediction.

    Directory of Open Access Journals (Sweden)

    Stéphanie Pérot

    Full Text Available Pockets are today at the cornerstones of modern drug discovery projects and at the crossroad of several research fields, from structural biology to mathematical modeling. Being able to predict if a small molecule could bind to one or more protein targets or if a protein could bind to some given ligands is very useful for drug discovery endeavors, anticipation of binding to off- and anti-targets. To date, several studies explore such questions from chemogenomic approach to reverse docking methods. Most of these studies have been performed either from the viewpoint of ligands or targets. However it seems valuable to use information from both ligands and target binding pockets. Hence, we present a multivariate approach relating ligand properties with protein pocket properties from the analysis of known ligand-protein interactions. We explored and optimized the pocket-ligand pair space by combining pocket and ligand descriptors using Principal Component Analysis and developed a classification engine on this paired space, revealing five main clusters of pocket-ligand pairs sharing specific and similar structural or physico-chemical properties. These pocket-ligand pair clusters highlight correspondences between pocket and ligand topological and physico-chemical properties and capture relevant information with respect to protein-ligand interactions. Based on these pocket-ligand correspondences, a protocol of prediction of clusters sharing similarity in terms of recognition characteristics is developed for a given pocket-ligand complex and gives high performances. It is then extended to cluster prediction for a given pocket in order to acquire knowledge about its expected ligand profile or to cluster prediction for a given ligand in order to acquire knowledge about its expected pocket profile. This prediction approach shows promising results and could contribute to predict some ligand properties critical for binding to a given pocket, and conversely

  2. Insights into an original pocket-ligand pair classification: a promising tool for ligand profile prediction.

    Science.gov (United States)

    Pérot, Stéphanie; Regad, Leslie; Reynès, Christelle; Spérandio, Olivier; Miteva, Maria A; Villoutreix, Bruno O; Camproux, Anne-Claude

    2013-01-01

    Pockets are today at the cornerstones of modern drug discovery projects and at the crossroad of several research fields, from structural biology to mathematical modeling. Being able to predict if a small molecule could bind to one or more protein targets or if a protein could bind to some given ligands is very useful for drug discovery endeavors, anticipation of binding to off- and anti-targets. To date, several studies explore such questions from chemogenomic approach to reverse docking methods. Most of these studies have been performed either from the viewpoint of ligands or targets. However it seems valuable to use information from both ligands and target binding pockets. Hence, we present a multivariate approach relating ligand properties with protein pocket properties from the analysis of known ligand-protein interactions. We explored and optimized the pocket-ligand pair space by combining pocket and ligand descriptors using Principal Component Analysis and developed a classification engine on this paired space, revealing five main clusters of pocket-ligand pairs sharing specific and similar structural or physico-chemical properties. These pocket-ligand pair clusters highlight correspondences between pocket and ligand topological and physico-chemical properties and capture relevant information with respect to protein-ligand interactions. Based on these pocket-ligand correspondences, a protocol of prediction of clusters sharing similarity in terms of recognition characteristics is developed for a given pocket-ligand complex and gives high performances. It is then extended to cluster prediction for a given pocket in order to acquire knowledge about its expected ligand profile or to cluster prediction for a given ligand in order to acquire knowledge about its expected pocket profile. This prediction approach shows promising results and could contribute to predict some ligand properties critical for binding to a given pocket, and conversely, some key pocket

  3. Beware of ligand efficiency (LE): understanding LE data in modeling structure-activity and structure-economy relationships.

    Science.gov (United States)

    Polanski, Jaroslaw; Tkocz, Aleksandra; Kucia, Urszula

    2017-09-11

    On the one hand, ligand efficiency (LE) and the binding efficiency index (BEI), which are binding properties (B) averaged versus the heavy atom count (HAC: LE) or molecular weight (MW: BEI), have recently been declared a novel universal tool for drug design. On the other hand, questions have been raised about the mathematical validity of the LE approach. In fact, neither the critics nor the advocates are precise enough to provide a generally understandable and accepted chemistry of the LE metrics. In particular, this refers to the puzzle of the LE trends for small and large molecules. In this paper, we explain the chemistry and mathematics of the LE type of data. Because LE is a weight metrics related to binding per gram, its hyperbolic decrease with an increasing number of heavy atoms can be easily understood by its 1/MW dependency. Accordingly, we analyzed how this influences the LE trends for ligand-target binding, economic big data or molecular descriptor data. In particular, we compared the trends for the thermodynamic ∆G data of a series of ligands that interact with 14 different target classes, which were extracted from the BindingDB database with the market prices of a commercial compound library of ca. 2.5 mln synthetic building blocks. An interpretation of LE and BEI that clearly explains the observed trends for these parameters are presented here for the first time. Accordingly, we show that the main misunderstanding of the chemical meaning of the BEI and LE parameters is their interpretation as molecular descriptors that are connected with a single molecule, while binding is a statistical effect in which a population of ligands limits the formation of ligand-receptor complexes. Therefore, LE (BEI) should not be interpreted as a molecular (physicochemical) descriptor that is connected with a single molecule but as a property (binding per gram). Accordingly, the puzzle of the surprising behavior of LE is explained by the 1/MW dependency. This effect

  4. Predicting binding affinities of protein ligands from three-dimensional models: application to peptide binding to class I major histocompatibility proteins

    DEFF Research Database (Denmark)

    Rognan, D; Lauemoller, S L; Holm, A

    1999-01-01

    A simple and fast free energy scoring function (Fresno) has been developed to predict the binding free energy of peptides to class I major histocompatibility (MHC) proteins. It differs from existing scoring functions mainly by the explicit treatment of ligand desolvation and of unfavorable protein...... coordinates of the MHC-bound peptide have first been determined with an accuracy of about 1-1.5 A. Furthermore, it may be easily recalibrated for any protein-ligand complex.......) and of a series of 16 peptides to H-2K(k). Predictions were more accurate for HLA-A2-binding peptides as the training set had been built from experimentally determined structures. The average error in predicting the binding free energy of the test peptides was 3.1 kJ/mol. For the homology model-derived equation...

  5. Partitioning controls on Amazon forest photosynthesis between environmental and biotic factors at hourly to interannual timescales.

    Science.gov (United States)

    Wu, Jin; Guan, Kaiyu; Hayek, Matthew; Restrepo-Coupe, Natalia; Wiedemann, Kenia T; Xu, Xiangtao; Wehr, Richard; Christoffersen, Bradley O; Miao, Guofang; da Silva, Rodrigo; de Araujo, Alessandro C; Oliviera, Raimundo C; Camargo, Plinio B; Monson, Russell K; Huete, Alfredo R; Saleska, Scott R

    2017-03-01

    Gross ecosystem productivity (GEP) in tropical forests varies both with the environment and with biotic changes in photosynthetic infrastructure, but our understanding of the relative effects of these factors across timescales is limited. Here, we used a statistical model to partition the variability of seven years of eddy covariance-derived GEP in a central Amazon evergreen forest into two main causes: variation in environmental drivers (solar radiation, diffuse light fraction, and vapor pressure deficit) that interact with model parameters that govern photosynthesis and biotic variation in canopy photosynthetic light-use efficiency associated with changes in the parameters themselves. Our fitted model was able to explain most of the variability in GEP at hourly (R 2  = 0.77) to interannual (R 2  = 0.80) timescales. At hourly timescales, we found that 75% of observed GEP variability could be attributed to environmental variability. When aggregating GEP to the longer timescales (daily, monthly, and yearly), however, environmental variation explained progressively less GEP variability: At monthly timescales, it explained only 3%, much less than biotic variation in canopy photosynthetic light-use efficiency, which accounted for 63%. These results challenge modeling approaches that assume GEP is primarily controlled by the environment at both short and long timescales. Our approach distinguishing biotic from environmental variability can help to resolve debates about environmental limitations to tropical forest photosynthesis. For example, we found that biotically regulated canopy photosynthetic light-use efficiency (associated with leaf phenology) increased with sunlight during dry seasons (consistent with light but not water limitation of canopy development) but that realized GEP was nonetheless lower relative to its potential efficiency during dry than wet seasons (consistent with water limitation of photosynthesis in given assemblages of leaves). This work

  6. Effects of biotic interactions and dispersal on the presence-absence of multiple species

    International Nuclear Information System (INIS)

    Mohd, Mohd Hafiz; Murray, Rua; Plank, Michael J.; Godsoe, William

    2017-01-01

    One of the important issues in ecology is to predict which species will be present (or absent) across a geographical region. Dispersal is thought to have an important influence on the range limits of species, and understanding this problem in a multi-species community with priority effects (i.e. initial abundances determine species presence-absence) is a challenging task because dispersal also interacts with biotic and abiotic factors. Here, we propose a simple multi-species model to investigate the joint effects of biotic interactions and dispersal on species presence-absence. Our results show that dispersal can substantially expand species ranges when biotic and abiotic forces are present; consequently, coexistence of multiple species is possible. The model also exhibits ecologically interesting priority effects, mediated by intense biotic interactions. In the absence of dispersal, competitive exclusion of all but one species occurs. We find that dispersal reduces competitive exclusion effects that occur in no-dispersal case and promotes coexistence of multiple species. These results also show that priority effects are still prevalent in multi-species communities in the presence of dispersal process. We also illustrate the existence of threshold values of competitive strength (i.e. transcritical bifurcations), which results in different species presence-absence in multi-species communities with and without dispersal.

  7. Desertification, salinization, and biotic homogenization in a dryland river ecosystem.

    Science.gov (United States)

    Miyazono, Seiji; Patiño, Reynaldo; Taylor, Christopher M

    2015-04-01

    This study determined long-term changes in fish assemblages, river discharge, salinity, and local precipitation, and examined hydrological drivers of biotic homogenization in a dryland river ecosystem, the Trans-Pecos region of the Rio Grande/Rio Bravo del Norte (USA/Mexico). Historical (1977-1989) and current (2010-2011) fish assemblages were analyzed by rarefaction analysis (species richness), nonmetric multidimensional scaling (composition/variability), multiresponse permutation procedures (composition), and paired t-test (variability). Trends in hydrological conditions (1970s-2010s) were examined by Kendall tau and quantile regression, and associations between streamflow and specific conductance (salinity) by generalized linear models. Since the 1970s, species richness and variability of fish assemblages decreased in the Rio Grande below the confluence with the Rio Conchos (Mexico), a major tributary, but not above it. There was increased representation of lower-flow/higher-salinity tolerant species, thus making fish communities below the confluence taxonomically and functionally more homogeneous to those above it. Unlike findings elsewhere, this biotic homogenization was due primarily to changes in the relative abundances of native species. While Rio Conchos discharge was>2-fold higher than Rio Grande discharge above their confluence, Rio Conchos discharge decreased during the study period causing Rio Grande discharge below the confluence to also decrease. Rio Conchos salinity is lower than Rio Grande salinity above their confluence and, as Rio Conchos discharge decreased, it caused Rio Grande salinity below the confluence to increase (reduced dilution). Trends in discharge did not correspond to trends in precipitation except at extreme-high (90th quantile) levels. In conclusion, decreasing discharge from the Rio Conchos has led to decreasing flow and increasing salinity in the Rio Grande below the confluence. This spatially uneven desertification and

  8. Early Triassic marine biotic recovery: the predators' perspective.

    Science.gov (United States)

    Scheyer, Torsten M; Romano, Carlo; Jenks, Jim; Bucher, Hugo

    2014-01-01

    Examining the geological past of our planet allows us to study periods of severe climatic and biological crises and recoveries, biotic and abiotic ecosystem fluctuations, and faunal and floral turnovers through time. Furthermore, the recovery dynamics of large predators provide a key for evaluation of the pattern and tempo of ecosystem recovery because predators are interpreted to react most sensitively to environmental turbulences. The end-Permian mass extinction was the most severe crisis experienced by life on Earth, and the common paradigm persists that the biotic recovery from the extinction event was unusually slow and occurred in a step-wise manner, lasting up to eight to nine million years well into the early Middle Triassic (Anisian) in the oceans, and even longer in the terrestrial realm. Here we survey the global distribution and size spectra of Early Triassic and Anisian marine predatory vertebrates (fishes, amphibians and reptiles) to elucidate the height of trophic pyramids in the aftermath of the end-Permian event. The survey of body size was done by compiling maximum standard lengths for the bony fishes and some cartilaginous fishes, and total size (estimates) for the tetrapods. The distribution and size spectra of the latter are difficult to assess because of preservation artifacts and are thus mostly discussed qualitatively. The data nevertheless demonstrate that no significant size increase of predators is observable from the Early Triassic to the Anisian, as would be expected from the prolonged and stepwise trophic recovery model. The data further indicate that marine ecosystems characterized by multiple trophic levels existed from the earliest Early Triassic onwards. However, a major change in the taxonomic composition of predatory guilds occurred less than two million years after the end-Permian extinction event, in which a transition from fish/amphibian to fish/reptile-dominated higher trophic levels within ecosystems became apparent.

  9. Desertification, salinization, and biotic homogenization in a dryland river ecosystem

    Science.gov (United States)

    Miyazono, S.; Patino, Reynaldo; Taylor, C.M.

    2015-01-01

    This study determined long-term changes in fish assemblages, river discharge, salinity, and local precipitation, and examined hydrological drivers of biotic homogenization in a dryland river ecosystem, the Trans-Pecos region of the Rio Grande/Rio Bravo del Norte (USA/Mexico). Historical (1977-1989) and current (2010-2011) fish assemblages were analyzed by rarefaction analysis (species richness), nonmetric multidimensional scaling (composition/variability), multiresponse permutation procedures (composition), and paired t-test (variability). Trends in hydrological conditions (1970s-2010s) were examined by Kendall tau and quantile regression, and associations between streamfiow and specific conductance (salinity) by generalized linear models. Since the 1970s, species richness and variability of fish assemblages decreased in the Rio Grande below the confluence with the Rio Conchos (Mexico), a major tributary, but not above it. There was increased representation of lower-flow/higher-salinity tolerant species, thus making fish communities below the confluence taxonomically and functionally more homogeneous to those above it. Unlike findings elsewhere, this biotic homogenization was due primarily to changes in the relative abundances of native species. While Rio Conchos discharge was > 2-fold higher than Rio Grande discharge above their confluence, Rio Conchos discharge decreased during the study period causing Rio Grande discharge below the confluence to also decrease. Rio Conchos salinity is lower than Rio Grande salinity above their confluence and, as Rio Conchos discharge decreased, it caused Rio Grande salinity below the confluence to increase (reduced dilution). Trends in discharge did not correspond to trends in precipitation except at extreme-high (90th quantile) levels. In conclusion, decreasing discharge from the Rio Conchos has led to decreasing flow and increasing salinity in the Rio Grande below the confluence. This spatially uneven desertification and

  10. Early Triassic marine biotic recovery: the predators' perspective.

    Directory of Open Access Journals (Sweden)

    Torsten M Scheyer

    Full Text Available Examining the geological past of our planet allows us to study periods of severe climatic and biological crises and recoveries, biotic and abiotic ecosystem fluctuations, and faunal and floral turnovers through time. Furthermore, the recovery dynamics of large predators provide a key for evaluation of the pattern and tempo of ecosystem recovery because predators are interpreted to react most sensitively to environmental turbulences. The end-Permian mass extinction was the most severe crisis experienced by life on Earth, and the common paradigm persists that the biotic recovery from the extinction event was unusually slow and occurred in a step-wise manner, lasting up to eight to nine million years well into the early Middle Triassic (Anisian in the oceans, and even longer in the terrestrial realm. Here we survey the global distribution and size spectra of Early Triassic and Anisian marine predatory vertebrates (fishes, amphibians and reptiles to elucidate the height of trophic pyramids in the aftermath of the end-Permian event. The survey of body size was done by compiling maximum standard lengths for the bony fishes and some cartilaginous fishes, and total size (estimates for the tetrapods. The distribution and size spectra of the latter are difficult to assess because of preservation artifacts and are thus mostly discussed qualitatively. The data nevertheless demonstrate that no significant size increase of predators is observable from the Early Triassic to the Anisian, as would be expected from the prolonged and stepwise trophic recovery model. The data further indicate that marine ecosystems characterized by multiple trophic levels existed from the earliest Early Triassic onwards. However, a major change in the taxonomic composition of predatory guilds occurred less than two million years after the end-Permian extinction event, in which a transition from fish/amphibian to fish/reptile-dominated higher trophic levels within ecosystems became

  11. End-Triassic nonmarine biotic events

    Directory of Open Access Journals (Sweden)

    Spencer G. Lucas

    2015-10-01

    Full Text Available The Late Triassic was a prolonged interval of elevated extinction rates and low origination rates that manifested themselves in a series of extinctions during Carnian, Norian and Rhaetian time. Most of these extinctions took place in the marine realm, particularly affecting radiolarians, conodonts, bivalves, ammonoids and reef-building organisms. On land, the case for a Late Triassic mass extinction is much more tenuous and has largely focused on tetrapod vertebrates (amphibians and reptiles, though some workers advocate a sudden end-Triassic (TJB extinction of land plants. Nevertheless, an extensive literature does not identify a major extinction of land plants at the TJB, and a comprehensive review of palynological records concluded that TJB vegetation changes were non-uniform (different changes in different places, not synchronous and not indicative of a mass extinction of land plants. Claims of a substantial perturbation of plant ecology and diversity at the TJB in East Greenland are indicative of a local change in the paleoflora largely driven by lithofacies changes resulting in changing taphonomic filters. Plant extinctions at the TJB were palaeogeographically localized events, not global in extent. With new and more detailed stratigraphic data, the perceived TJB tetrapod extinction is mostly an artifact of coarse temporal resolution, the compiled correlation effect. The amphibian, archosaur and synapsid extinctions of the Late Triassic are not concentrated at the TJB, but instead occur stepwise, beginning in the Norian and extending into the Hettangian. There was a disruption of the terrestrial ecosystem across the TJB, but it was more modest than generally claimed. The ecological severity of the end-Triassic nonmarine biotic events are relatively low on the global scale. Biotic turnover at the end of the Triassic was likely driven by the CAMP (Central Atlantic Magmatic Province eruptions, which caused significant environmental

  12. Relevance of biotic pathways to the long-term regulation of nuclear waste disposal. Phase I. Final report. Vol. 4

    International Nuclear Information System (INIS)

    McKenzie, D.H.; Cadwell, L.L.; Eberhardt, L.E.; Kennedy, W.E. Jr.; Peloquin, R.A.; Simmons, M.A.

    1984-05-01

    Licensing and regulation of commercial low-level waste (CLLW) burial facilities require that anticipated risks associated with burial sites be evaluated for the life of the facility. This work reviewed the existing capability to evaluate dose to man resulting from the potential redistribution of buried radionuclides by plants and animals that we have termed biotic transport. Through biotic transport, radionuclides can be moved to locations where they can enter exposure pathways to man. We found that predictive models currently in use did not address the long-term risks resulting from the cumulative transport of radionuclides. Although reports in the literature confirm that biotic transport phenomena are common, assessments routinely ignore the associated risks or dismiss them as insignificant without quantitative evaluation. To determine the potential impacts of biotic transport, we made order-of-magnitude estimates of the dose to man for biotic transport processes at reference arid and humid CLLW disposal sites. Estimated doses to site residents after assumed loss of institutional control were comparable to dose estimates for the intruder-agricultural scenario defined in the DEIS for 10 CFR 61 (NRC). The reported lack of potential importance of biotic transport at low-level waste sites in earlier assessment studies is not confirmed by order of magnitude estimates presented in this study. 17 references, 10 figures, 8 tables

  13. CavityPlus: a web server for protein cavity detection with pharmacophore modelling, allosteric site identification and covalent ligand binding ability prediction.

    Science.gov (United States)

    Xu, Youjun; Wang, Shiwei; Hu, Qiwan; Gao, Shuaishi; Ma, Xiaomin; Zhang, Weilin; Shen, Yihang; Chen, Fangjin; Lai, Luhua; Pei, Jianfeng

    2018-05-10

    CavityPlus is a web server that offers protein cavity detection and various functional analyses. Using protein three-dimensional structural information as the input, CavityPlus applies CAVITY to detect potential binding sites on the surface of a given protein structure and rank them based on ligandability and druggability scores. These potential binding sites can be further analysed using three submodules, CavPharmer, CorrSite, and CovCys. CavPharmer uses a receptor-based pharmacophore modelling program, Pocket, to automatically extract pharmacophore features within cavities. CorrSite identifies potential allosteric ligand-binding sites based on motion correlation analyses between cavities. CovCys automatically detects druggable cysteine residues, which is especially useful to identify novel binding sites for designing covalent allosteric ligands. Overall, CavityPlus provides an integrated platform for analysing comprehensive properties of protein binding cavities. Such analyses are useful for many aspects of drug design and discovery, including target selection and identification, virtual screening, de novo drug design, and allosteric and covalent-binding drug design. The CavityPlus web server is freely available at http://repharma.pku.edu.cn/cavityplus or http://www.pkumdl.cn/cavityplus.

  14. Electrode impedance analysis of chronic tungsten microwire neural implants: understanding abiotic vs. biotic contributions

    Directory of Open Access Journals (Sweden)

    Viswanath eSankar

    2014-05-01

    Full Text Available Changes in biotic and abiotic factors can be reflected in the complex impedance spectrum of the microelectrodes chronically implanted into the neural tissue. The recording surface of the tungsten electrode in vivo undergoes abiotic changes due to recording site corrosion and insulation delamination as well as biotic changes due to tissue encapsulation as a result of the foreign body immune response. We reported earlier that large changes in electrode impedance measured at 1 kHz were correlated with poor electrode functional performance, quantified through electrophysiological recordings during the chronic lifetime of the electrode. There is a need to identity the factors that contribute to the chronic impedance variation. In this work, we use numerical simulation and regression to equivalent circuit models to evaluate both the abiotic and biotic contributions to the impedance response over chronic implant duration. COMSOL® simulation of abiotic electrode morphology changes provide a possible explanation for the decrease in the electrode impedance at long implant duration while biotic changes play an important role in the large increase in impedance observed initially.

  15. Macrocyclic ligand decorated ordered mesoporous silica with large-pore and short-channel characteristics for effective separation of lithium isotopes: synthesis, adsorptive behavior study and DFT modeling.

    Science.gov (United States)

    Liu, Yuekun; Liu, Fei; Ye, Gang; Pu, Ning; Wu, Fengcheng; Wang, Zhe; Huo, Xiaomei; Xu, Jian; Chen, Jing

    2016-10-18

    Effective separation of lithium isotopes is of strategic value which attracts growing attention worldwide. This study reports a new class of macrocyclic ligand decorated ordered mesoporous silica (OMS) with large-pore and short-channel characteristics, which holds the potential to effectively separate lithium isotopes in aqueous solutions. Initially, a series of benzo-15-crown-5 (B15C5) derivatives containing different electron-donating or -withdrawing substituents were synthesized. Extractive separation of lithium isotopes in a liquid-liquid system was comparatively studied, highlighting the effect of the substituent, solvent, counter anion and temperature. The optimal NH 2 -B15C5 ligands were then covalently anchored to a short-channel SBA-15 OMS precursor bearing alkyl halides via a post-modification protocol. Adsorptive separation of the lithium isotopes was fully investigated, combined with kinetics and thermodynamics analysis, and simulation by using classic adsorption isotherm models. The NH 2 -B15C5 ligand functionalized OMSs exhibited selectivity to lithium ions against other alkali metal ions including K(i). Additionally, a more efficient separation of lithium isotopes could be obtained at a lower temperature in systems with softer counter anions and solvents with a lower dielectric constant. The highest value separation factor (α = 1.049 ± 0.002) was obtained in CF 3 COOLi aqueous solution at 288.15 K. Moreover, theoretical computation based on the density functional theory (DFT) was performed to elucidate the complexation interactions between the macrocyclic ligands and lithium ions. A suggested mechanism involving an isotopic exchange equilibrium was proposed to describe the lithium isotope separation by the functionalized OMSs.

  16. Regulation of abiotic and biotic stress responses by plant hormones

    DEFF Research Database (Denmark)

    Grosskinsky, Dominik Kilian; van der Graaff, Eric; Roitsch, Thomas Georg

    2016-01-01

    Plant hormones (phytohormones) are signal molecules produced within the plant, and occur in very low concentrations. In the present chapter, the current knowledge on the regulation of biotic and biotic stress responses by plant hormones is summarized with special focus on the novel insights...... into the complex hormonal crosstalk of classical growth stimulating plant hormones within the naturally occurring biotic and abiotic multistress environment of higher plants. The MAPK- and phytohormone-cascades which comprise a multitude of single molecules on different signalling levels, as well as interactions...

  17. Biotic interactions overrule plant responses to climate, depending on the species' biogeography.

    Directory of Open Access Journals (Sweden)

    Astrid Welk

    Full Text Available This study presents an experimental approach to assess the relative importance of climatic and biotic factors as determinants of species' geographical distributions. We asked to what extent responses of grassland plant species to biotic interactions vary with climate, and to what degree this variation depends on the species' biogeography. Using a gradient from oceanic to continental climate represented by nine common garden transplant sites in Germany, we experimentally tested whether congeneric grassland species of different geographic distribution (oceanic vs. continental plant range type responded differently to combinations of climate, competition and mollusc herbivory. We found the relative importance of biotic interactions and climate to vary between the different components of plant performance. While survival and plant height increased with precipitation, temperature had no effect on plant performance. Additionally, species with continental plant range type increased their growth in more benign climatic conditions, while those with oceanic range type were largely unable to take a similar advantage of better climatic conditions. Competition generally caused strong reductions of aboveground biomass and growth. In contrast, herbivory had minor effects on survival and growth. Against expectation, these negative effects of competition and herbivory were not mitigated under more stressful continental climate conditions. In conclusion we suggest variation in relative importance of climate and biotic interactions on broader scales, mediated via species-specific sensitivities and factor-specific response patterns. Our results have important implications for species distribution models, as they emphasize the large-scale impact of biotic interactions on plant distribution patterns and the necessity to take plant range types into account.

  18. Physico-chemical and biotic factors influencing microalgal seed ...

    African Journals Online (AJOL)

    Physico-chemical and biotic factors influencing microalgal seed culture propagation for inoculation of a ... African Journal of Biotechnology ... used to inoculate an open raceway pond for large scale biomass production for biodiesel production.

  19. Biotic interactions mediate soil microbial feedbacks to climate change

    Czech Academy of Sciences Publication Activity Database

    Crowther, T. W.; Thomas, S.M.; Maynard, D.S.; Baldrian, Petr; Covey, K.; Frey, S. D.; van Diepen, L. T. A.; Bradford, M.A.

    2015-01-01

    Roč. 112, č. 22 (2015), s. 7033-7038 ISSN 0027-8424 Institutional support: RVO:61388971 Keywords : global change * soil feedback * biotic interaction Subject RIV: EE - Microbiology, Virology Impact factor: 9.423, year: 2015

  20. Relevance of biotic pathways to the long-term regulation of nuclear waste disposal. A report on Tasks 1 and 2 of Phase I

    International Nuclear Information System (INIS)

    McKenzie, D.H.; Cadwell, L.L.; Cushing, C.E. Jr.; Harty, R.; Kennedy, W.E. Jr.; Simmons, M.A.; Soldat, J.K.; Swartzman, B.

    1982-07-01

    The purpose of the work reported here was to evaluate the relevance of biotic transport to the assessment of impacts and licensing of low-level waste disposal sites. Available computer models and their recent applications at low-level waste disposal sites are considered. Biotic transport mechanisms and processes for both terrestrial and aquatic systems are presented with examples from existing waste disposal sites. Following a proposed system for ranking radionuclides by their potential for biotic transport, recommendations for completing Phase I research are presented. To evaluate the long-term importance of biotic transport at low-level waste sites, scenarios for biotic pathways and mechanisms need to be developed. Scenarios should begin with a description of the waste form and should include a description of biotic processes and mechanisms, approximations of the magnitude of materials transported, and a linkage to processes or mechanisms in existing models. Once these scenarios are in place, existing models could be used to evaluate impacts resulting from biotic transport and to assess the relevance to site selection and licensing of low-level waste disposal sites

  1. Ligands in PSI structures

    International Nuclear Information System (INIS)

    Kumar, Abhinav; Chiu, Hsiu-Ju; Axelrod, Herbert L.; Morse, Andrew; Elsliger, Marc-André; Wilson, Ian A.; Deacon, Ashley

    2010-01-01

    A survey of the types and frequency of ligands that are bound to PSI structures is analyzed as well as their utility in functional annotation of previously uncharacterized proteins. Approximately 65% of PSI structures report some type of ligand(s) that is bound in the crystal structure. Here, a description is given of how such ligands are handled and analyzed at the JCSG and a survey of the types, variety and frequency of ligands that are observed in the PSI structures is also compiled and analyzed, including illustrations of how these bound ligands have provided functional clues for annotation of proteins with little or no previous experimental characterization. Furthermore, a web server was developed as a tool to mine and analyze the PSI structures for bound ligands and other identifying features

  2. Discovery of novel urokinase plasminogen activator (uPA) inhibitors using ligand-based modeling and virtual screening followed by in vitro analysis.

    Science.gov (United States)

    Al-Sha'er, Mahmoud A; Khanfar, Mohammad A; Taha, Mutasem O

    2014-01-01

    Urokinase plasminogen activator (uPA)-a serine protease-is thought to play a central role in tumor metastasis and angiogenesis and, therefore, inhibition of this enzyme could be beneficial in treating cancer. Toward this end, we explored the pharmacophoric space of 202 uPA inhibitors using seven diverse sets of inhibitors to identify high-quality pharmacophores. Subsequently, we employed genetic algorithm-based quantitative structure-activity relationship (QSAR) analysis as a competition arena to select the best possible combination of pharmacophoric models and physicochemical descriptors that can explain bioactivity variation within the training inhibitors (r (2) 162 = 0.74, F-statistic = 64.30, r (2) LOO = 0.71, r (2) PRESS against 40 test inhibitors = 0.79). Three orthogonal pharmacophores emerged in the QSAR equation suggesting the existence of at least three binding modes accessible to ligands within the uPA binding pocket. This conclusion was supported by receiver operating characteristic (ROC) curve analyses of the QSAR-selected pharmacophores. Moreover, the three pharmacophores were comparable with binding interactions seen in crystallographic structures of bound ligands within the uPA binding pocket. We employed the resulting pharmacophoric models and associated QSAR equation to screen the national cancer institute (NCI) list of compounds. The captured hits were tested in vitro. Overall, our modeling workflow identified new low micromolar anti-uPA hits.

  3. Surface anisotropy of iron oxide nanoparticles and slabs from first principles: Influence of coatings and ligands as a test of the Heisenberg model

    Energy Technology Data Exchange (ETDEWEB)

    Brymora, Katarzyna; Calvayrac, Florent, E-mail: Florent.Calvayrac@univ-lemans.fr

    2017-07-15

    Highlights: • A new method is given to extract surface anisotropies from ab initio calculations. • Heisenberg model for magnetic clusters and surfaces is validated in simple cases. • Ligands, metallic clusters, or coatings degrade the validity of the Heisenberg model. • Values for surface anisotropies, volume anisotropies, exchange constants are computed. • Results are in agreement with experimental data, previous theoretical findings. - Abstract: We performed ab initio computations of the magnetic properties of simple iron oxide clusters and slabs. We considered an iron oxide cluster functionalized by a molecule or glued to a gold cluster of the same size. We also considered a magnetite slab coated by cobalt oxide or a mixture of iron oxide and cobalt oxide. The changes in magnetic behavior were explored using constrained magnetic calculations. A possible value for the surface anisotropy was estimated from the fit of a classical Heisenberg model on ab initio results. The value was found to be compatible with estimations obtained by other means, or inferred from experimental results. The addition of a ligand, coating, or of a metallic nanoparticle to the systems degraded the quality of the description by the Heisenberg Hamiltonian. Proposing a change in the anisotropies allowing for the proportion of each transition atom we could get a much better description of the magnetism of series of hybrid cobalt and iron oxide systems.

  4. Molecular modeling and docking studies of human 5-hydroxytryptamine 2A (5-HT2A) receptor for the identification of hotspots for ligand binding.

    Science.gov (United States)

    Kanagarajadurai, Karuppiah; Malini, Manoharan; Bhattacharya, Aditi; Panicker, Mitradas M; Sowdhamini, Ramanathan

    2009-12-01

    The serotonergic system has been implicated in emotional and cognitive function. In particular, 5-HT(2A) (5-hydroxytrytamine receptor 2A) is attributed to a number of disorders like schizophrenia, depression, eating disorders and anxiety. 5-HT(2A), being a GPCR (G-protein coupled receptor), is important in the pharmaceutical industry as a proven target for these disorders. Despite their extensive clinical importance, the structural studies of this protein is lacking due to difficulties in determining its crystal structure. We have performed sequence analysis and molecular modeling of 5-HT(2A) that has revealed a set of conserved residues and motifs considered to play an important role in maintaining structural integrity and function of the receptor. The analysis also revealed a set of residues specific to the receptor which distinguishes them from other members of the subclass and their orthologs. Further, starting from the model structure of human 5-HT(2A) receptor, docking studies were attempted to envisage how it might interact with eight of its ligands (such as serotonin, dopamine, DOI, LSD, haloperidol, ketanserin, risperidone and clozapine). The binding studies of dopamine to 5-HT(2A) receptor can bring up better understanding in the etiology of a number of neurological disorders involving both these two receptors. Our sequence analysis and study of interactions of this receptor with other ligands reveal additional residue hotspots such as Asn 363 and Tyr 370. The function of these residues can be further analyzed by rational design of site-directed mutagenesis. Two distinct binding sites are identified which could play important roles in ligand binding and signaling.

  5. Autocrine signal transmission with extracellular ligand degradation

    Science.gov (United States)

    Muratov, C B; Posta, F; Shvartsman, S Y

    2009-03-01

    Traveling waves of cell signaling in epithelial layers orchestrate a number of important processes in developing and adult tissues. These waves can be mediated by positive feedback autocrine loops, a mode of cell signaling where binding of a diffusible extracellular ligand to a cell surface receptor can lead to further ligand release. We formulate and analyze a biophysical model that accounts for ligand-induced ligand release, extracellular ligand diffusion and ligand-receptor interaction. We focus on the case when the main mode for ligand degradation is extracellular and analyze the problem with the sharp threshold positive feedback nonlinearity. We derive expressions that link the speed of propagation and other characteristics of traveling waves to the parameters of the biophysical processes, such as diffusion rates, receptor expression level, etc. Analyzing the derived expressions we found that traveling waves in such systems can exhibit a number of unusual properties, e.g. non-monotonic dependence of the speed of propagation on ligand diffusivity. Our results for the fully developed traveling fronts can be used to analyze wave initiation from localized perturbations, a scenario that frequently arises in the in vitro models of epithelial wound healing, and guide future modeling studies of cell communication in epithelial layers.

  6. Ligand identification using electron-density map correlations

    International Nuclear Information System (INIS)

    Terwilliger, Thomas C.; Adams, Paul D.; Moriarty, Nigel W.; Cohn, Judith D.

    2007-01-01

    An automated ligand-fitting procedure is applied to (F o − F c )exp(iϕ c ) difference density for 200 commonly found ligands from macromolecular structures in the Protein Data Bank to identify ligands from density maps. A procedure for the identification of ligands bound in crystal structures of macromolecules is described. Two characteristics of the density corresponding to a ligand are used in the identification procedure. One is the correlation of the ligand density with each of a set of test ligands after optimization of the fit of that ligand to the density. The other is the correlation of a fingerprint of the density with the fingerprint of model density for each possible ligand. The fingerprints consist of an ordered list of correlations of each the test ligands with the density. The two characteristics are scored using a Z-score approach in which the correlations are normalized to the mean and standard deviation of correlations found for a variety of mismatched ligand-density pairs, so that the Z scores are related to the probability of observing a particular value of the correlation by chance. The procedure was tested with a set of 200 of the most commonly found ligands in the Protein Data Bank, collectively representing 57% of all ligands in the Protein Data Bank. Using a combination of these two characteristics of ligand density, ranked lists of ligand identifications were made for representative (F o − F c )exp(iϕ c ) difference density from entries in the Protein Data Bank. In 48% of the 200 cases, the correct ligand was at the top of the ranked list of ligands. This approach may be useful in identification of unknown ligands in new macromolecular structures as well as in the identification of which ligands in a mixture have bound to a macromolecule

  7. Calculation of site affinity constants and cooperativity coefficients for binding of ligands and/or protons to macromolecules. II. Relationships between chemical model and partition function algorithm.

    Science.gov (United States)

    Fisicaro, E; Braibanti, A; Lamb, J D; Oscarson, J L

    1990-05-01

    The relationships between the chemical properties of a system and the partition function algorithm as applied to the description of multiple equilibria in solution are explained. The partition functions ZM, ZA, and ZH are obtained from powers of the binary generating functions Jj = (1 + kappa j gamma j,i[Y])i tau j, where i tau j = p tau j, q tau j, or r tau j represent the maximum number of sites in sites in class j, for Y = M, A, or H, respectively. Each term of the generating function can be considered an element (ij) of a vector Jj and each power of the cooperativity factor gamma ij,i can be considered an element of a diagonal cooperativity matrix gamma j. The vectors Jj are combined in tensor product matrices L tau = (J1) [J2]...[Jj]..., thus representing different receptor-ligand combinations. The partition functions are obtained by summing elements of the tensor matrices. The relationship of the partition functions with the total chemical amounts TM, TA, and TH has been found. The aim is to describe the total chemical amounts TM, TA, and TH as functions of the site affinity constants kappa j and cooperativity coefficients bj. The total amounts are calculated from the sum of elements of tensor matrices Ll. Each set of indices (pj..., qj..., rj...) represents one element of a tensor matrix L tau and defines each term of the summation. Each term corresponds to the concentration of a chemical microspecies. The distinction between microspecies MpjAqjHrj with ligands bound on specific sites and macrospecies MpAqHR corresponding to a chemical stoichiometric composition is shown. The translation of the properties of chemical model schemes into the algorithms for the generation of partition functions is illustrated with reference to a series of examples of gradually increasing complexity. The equilibria examined concern: (1) a unique class of sites; (2) the protonation of a base with two classes of sites; (3) the simultaneous binding of ligand A and proton H to a

  8. Identification of putative agouti-related protein(87-132)-melanocortin-4 receptor interactions by homology molecular modeling and validation using chimeric peptide ligands.

    Science.gov (United States)

    Wilczynski, Andrzej; Wang, Xiang S; Joseph, Christine G; Xiang, Zhimin; Bauzo, Rayna M; Scott, Joseph W; Sorensen, Nicholas B; Shaw, Amanda M; Millard, William J; Richards, Nigel G; Haskell-Luevano, Carrie

    2004-04-22

    Agouti-related protein (AGRP) is one of only two naturally known antagonists of G-protein-coupled receptors (GPCRs) identified to date. Specifically, AGRP antagonizes the brain melanocortin-3 and -4 receptors involved in energy homeostasis. Alpha-melanocyte stimulating hormone (alpha-MSH) is one of the known endogenous agonists for these melanocortin receptors. Insight into putative interactions between the antagonist AGRP amino acids with the melanocortin-4 receptor (MC4R) may be important for the design of unique ligands for the treatment of obesity related diseases and is currently lacking in the literature. A three-dimensional homology molecular model of the mouse MC4 receptor complex with the hAGRP(87-132) ligand docked into the receptor has been developed to identify putative antagonist ligand-receptor interactions. Key putative AGRP-MC4R interactions include the Arg111 of hAGRP(87-132) interacting in a negatively charged pocket located in a cavity formed by transmembrane spanning (TM) helices 1, 2, 3, and 7, capped by the acidic first extracellular loop (EL1) and specifically with the conserved melanocortin receptor residues mMC4R Glu92 (TM2), mMC4R Asp114 (TM3), and mMC4R Asp118 (TM3). Additionally, Phe112 and Phe113 of hAGRP(87-132) putatively interact with an aromatic hydrophobic pocket formed by the mMC4 receptor residues Phe176 (TM4), Phe193 (TM5), Phe253 (TM6), and Phe254 (TM6). To validate the AGRP-mMC4R model complex presented herein from a ligand perspective, we generated nine chimeric peptide ligands based on a modified antagonist template of the hAGRP(109-118) (Tyr-c[Asp-Arg-Phe-Phe-Asn-Ala-Phe-Dpr]-Tyr-NH(2)). In these chimeric ligands, the antagonist AGRP Arg-Phe-Phe residues were replaced by the melanocortin agonist His/D-Phe-Arg-Trp amino acids. These peptides resulted in agonist activity at the mouse melanocortin receptors (mMC1R and mMC3-5Rs). The most notable results include the identification of a novel subnanomolar melanocortin peptide

  9. ESI-MS studies of the reactions of novel platinum(II) complexes containing O,O'-chelated acetylacetonate and sulfur ligands with selected model proteins.

    Science.gov (United States)

    Marzo, Tiziano; De Pascali, Sandra A; Gabbiani, Chiara; Fanizzi, Francesco P; Messori, Luigi; Pratesi, Alessandro

    2017-08-01

    A group of mixed-ligand Pt(II) complexes bearing acetylacetonate and sulphur ligands were recently developed in the University of Lecce as a new class of prospective anticancer agents that manifested promising pharma-cological properties in preliminary in vitro and in vivo tests. Though modelled on the basis of cisplatin, these Pt(II) complexes turned out to exhibit a profoundly distinct mode of action as they were found to act mainly on non-genomic targets rather than on DNA. Accordingly, we have explored here their reactions with two representative model proteins through an established ESI-MS procedure with the aim to describe their general interaction mechanism with protein targets. A pronounced reactivity with the tested proteins was indeed documented; the nature of the resulting metallodrug-protein interactions could be characterised in depth in the various cases. Preferential binding to protein targets compared to DNA is supported by independent ICP-OES measurements. The implications of these findings are discussed.

  10. How do Humans interact with the Biotic Pump of South America?

    Science.gov (United States)

    Sharma, Ajar; Pande, Saket; Renata Cordeiro Ortigara, Angela; Uhlenbrook, Stefan

    2017-04-01

    The negative effects of the deforestation have been both advertised and down played. However, the effects are far more tangible than what they seem to be. It has been shown that the change in forest cover causes the rainfall patterns to change as the forests work as so-called Biotic Pumps. This changes the water availability in the area by modifying the water balance. Local water balances affect the changes that may take longer to be visible on the larger scales. The Amazon rain forest, one of the most bio-diverse areas worldwide, is an essential part of the biosphere of South America. However, there are clear links between deforestation carried out for agricultural purposes, specifically, Soybean and Sugarcane and the variability in global food prices. Here we analyse the anthropogenic actions that may influence the biotic pump. Variables such as volatility in commodity prices, risk taking capacities, land availability, government subsidies are used to drive the decision making of farmers. These variables are embedded in a lumped biotic pump model made for Brazil, utilizing data from different sources including MODIS, Centro de Previsão do Tempo e Estudos Climáticos (CPTEC), European Centre for Medium-Range Weather Forecasts (ECMWF). The biotic pump model essentially transports atmospheric moisture downwind, part of which falls as rain. The atmospheric moisture 'upwind' accounts for evaporation, incorporating land cover changes in response to land use decisions made by farmers and rainfall. The model is run for scenarios to demonstrate how rain downwind is affected by upwind land cover and provides first insights in to how much rain and productivity (agriculture) downwind is caused by the Amazonian rain forest upwind We then discuss the value of environmental conservation based on marginal productivity analysis, i.e., finding harmony between the conservation of rainforest and the economic growth of the country.

  11. Synthesis, Spectral, Thermogravimetric, XRD, Molecular Modelling and Potential Antibacterial Studies of Dimeric Complexes with Bis Bidentate ON–NO Donor Azo Dye Ligands

    Directory of Open Access Journals (Sweden)

    Bipin Bihari Mahapatra

    2013-01-01

    Full Text Available The dimeric complexes of Co(II, Ni(II, Cu(II, Zn(II, Cd(II, and Hg(II with two new symmetrical ON–NO donor bis bidentate (tetradentate azo dye ligands, LH2 = 4,4′-bis(4′-hydroxyquinolinolinylazodiphenylsulphone, and L′H2 = 4,4′-bis(acetoacetanilideazodiphenylsulphone have been synthesized. The metal complexes have been characterised by elemental analytical, conductance, magnetic susceptibility, IR, electronic spectra, ESR, NMR, thermogravimetry, X-ray diffraction (powder pattern spectra, and molecular modelling studies. The Co(II and Ni(II complexes are found to be octahedral, Cu(II complexes are distorted octahedral, and a tetrahedral stereochemistry has been assigned to Zn(II, Cd(II, and Hg(II complexes. The thermogravimetric study indicates that compounds are quite stable. The energy optimized structures are proposed using the semiempirical ZINDO/1 quantum mechanical calculations. The potential antibacterial study of the ligands and some metal complexes has been made with one gram positive bacteria Staphylococcus aureus and one gram negative bacteria E. coli which gives encouraging results. Both the Co(II complexes are found to possess monoclinic crystal system.

  12. A response calculus for immobilized T cell receptor ligands

    DEFF Research Database (Denmark)

    Andersen, P S; Menné, C; Mariuzza, R A

    2001-01-01

    determine the level of T cell activation. When fitted to T cell responses against purified ligands immobilized on plastic surfaces, the 2D-affinity model adequately simulated changes in cellular activation as a result of varying ligand affinity and ligand density. These observations further demonstrated...

  13. Effect of Organic Fe-Ligands, Released by Emiliania huxleyi, on Fe(II Oxidation Rate in Seawater Under Simulated Ocean Acidification Conditions: A Modeling Approach

    Directory of Open Access Journals (Sweden)

    Guillermo Samperio-Ramos

    2018-06-01

    Full Text Available The potential effect of ocean acidification on the exudation of organic matter by phytoplankton and, consequently, on the iron redox chemistry is largely unknown. In this study, the coccolithophorid Emiliania huxleyi was exposed to different pCO2 conditions (225–900 μatm, in order to determine the role of natural organic ligands on the Fe(II oxidation rate. Oxidation kinetics of Fe(II were studied as a function of pH (7.75–8.25 and dissolved organic carbon levels produced (0–141.11 μmol C L−1 during the different growth stages. The Fe(II oxidation rate always decreased in the presence of exudates as compared to that in the exudates-free seawater. The organic ligands present in the coccolithophorid exudates were responsible for this decrease. The oxidation of Fe(II in artificial seawater was also investigated at nanomolar levels over a range of pH (7.75–8.25 at 25°C in the presence of different glucuronic acid concentrations. Dissolved uronic acids (DUA slightly increased the experimental rate compared to control artificial seawater (ASW which can be ascribed to the stabilization of the oxidized form by chelation. This behavior was a function of the Fe(II:DUA ratio and was a pH dependent process. A kinetic model in ASW, with a single organic ligand, was applied for computing the equilibrium constant (log KFeCHO+ = 3.68 ± 0.81 M−1 and the oxidation rate (log kFeCHO+ = 3.28 ± 0.41 M−1 min−1 for the Fe(II-DUA complex (FeCHO+, providing an excellent description of data obtained over a wide range of DUA concentrations and pH conditions. Considering the Marcus theory the Fe(III complexing constant with DUA was limited to between 1013 and 1016. For the seawater enriched with exudates of E. huxleyi a second kinetic modeling approach was carried out for fitting the Fe(II speciation, and the contribution of each Fe(II species to the overall oxidation rate as a function of the pH/pCO2 conditions. The influence of organic ligands in the

  14. Ligand-receptor Interactions by NMR Spectroscopy

    Directory of Open Access Journals (Sweden)

    Novak. P.

    2008-04-01

    Full Text Available Today NMR spectroscopy is a method of choice for elucidation of interactions between biomolecules and the potential ligands. Knowledge on these interactions is an essential prerequisite for the rational drug design. The most important contribution of NMR to drug design a few years ago was the 3D structure determination of proteins. Besides delivering the 3D structures of the free proteins as a raw material for the modeling studies on ligand binding, NMR can directly yield valuable experimental data on the biologically important protein-ligand complexes. In addition to X-ray diffraction, NMR spectroscopy can provide information on the internal protein dynamics ordynamics of intermolecular interactions. Changes in NMR parameters allow us to detect ("SAR by NMR" and quantitatively determine binding affinities (titration, diffusion NMR experiments, etc. of potential ligands. Also, it is possible to determine the binding site and conformations of ligands, receptors and receptor-ligand complexes with the help of NMR methods such as tr-NOESY. Epitopes or functional groups responsible for binding of ligands to the receptor can be identified by employing STD or WaterLOGSY experiments. In this review are described some of the most frequent NMR methods for the characterization of the interactions between biomolecules and ligands, together with their advantages and disadvantages.

  15. The Role of Silicon under Biotic and Abiotic Stress Conditions

    Directory of Open Access Journals (Sweden)

    İlkay YAVAŞ

    2017-06-01

    Full Text Available Biotic and abiotic stress factors can adversely affect the agricultural productivity leading to physiological and biochemical damage to crops. Therefore, the most effective way is to increase the resistance to stresses. Silicon plays a ro le in reducing the effects of abiotic and biotic stresses (drought, salt stress, disease and insect stress etc. on plants. Silicon is accumulated in the cell walls and intercellular spaces and thus it has beneficial effects on disease infestations in especially small grains. The application of silicon may reduce the effects of environmental stresses on plants while making effective use of plant nutrients such as nitrogen and phosphorous. Also, silicon may reduce the toxic effects of heavy metals in soil. I t may protect the foliage and increase light uptake and reduce respiration. Therefore, in this review, we discussed the effects of silicon on abiotic and biotic stresses in especially field crops.

  16. A compartment model of VEGF distribution in humans in the presence of soluble VEGF receptor-1 acting as a ligand trap.

    Directory of Open Access Journals (Sweden)

    Florence T H Wu

    Full Text Available Vascular endothelial growth factor (VEGF, through its activation of cell surface receptor tyrosine kinases including VEGFR1 and VEGFR2, is a vital regulator of stimulatory and inhibitory processes that keep angiogenesis--new capillary growth from existing microvasculature--at a dynamic balance in normal physiology. Soluble VEGF receptor-1 (sVEGFR1--a naturally-occurring truncated version of VEGFR1 lacking the transmembrane and intracellular signaling domains--has been postulated to exert inhibitory effects on angiogenic signaling via two mechanisms: direct sequestration of angiogenic ligands such as VEGF; or dominant-negative heterodimerization with surface VEGFRs. In pre-clinical studies, sVEGFR1 gene and protein therapy have demonstrated efficacy in inhibiting tumor angiogenesis; while in clinical studies, sVEGFR1 has shown utility as a diagnostic or prognostic marker in a widening array of angiogenesis-dependent diseases. Here we developed a novel computational multi-tissue model for recapitulating the dynamic systemic distributions of VEGF and sVEGFR1. Model features included: physiologically-based multi-scale compartmentalization of the human body; inter-compartmental macromolecular biotransport processes (vascular permeability, lymphatic drainage; and molecularly-detailed binding interactions between the ligand isoforms VEGF(121 and VEGF(165, signaling receptors VEGFR1 and VEGFR2, non-signaling co-receptor neuropilin-1 (NRP1, as well as sVEGFR1. The model was parameterized to represent a healthy human subject, whereupon we investigated the effects of sVEGFR1 on the distribution and activation of VEGF ligands and receptors. We assessed the healthy baseline stability of circulating VEGF and sVEGFR1 levels in plasma, as well as their reliability in indicating tissue-level angiogenic signaling potential. Unexpectedly, simulated results showed that sVEGFR1 - acting as a diffusible VEGF sink alone, i.e., without sVEGFR1-VEGFR heterodimerization

  17. Schiff base ligand

    Indian Academy of Sciences (India)

    Unknown

    Low-temperature stoichiometric Schiff base reaction in air in 3 : 1 mole ratio between benz- aldehyde and triethylenetetramine (trien) in methanol yields a novel tetraaza µ-bis(bidentate) acyclic ligand L. It was .... electrochemical work was performed as reported in ..... change in ligand shape through change in oxidation.

  18. Autocrine signal transmission with extracellular ligand degradation

    International Nuclear Information System (INIS)

    Muratov, C B; Posta, F; Shvartsman, S Y

    2009-01-01

    Traveling waves of cell signaling in epithelial layers orchestrate a number of important processes in developing and adult tissues. These waves can be mediated by positive feedback autocrine loops, a mode of cell signaling where binding of a diffusible extracellular ligand to a cell surface receptor can lead to further ligand release. We formulate and analyze a biophysical model that accounts for ligand-induced ligand release, extracellular ligand diffusion and ligand–receptor interaction. We focus on the case when the main mode for ligand degradation is extracellular and analyze the problem with the sharp threshold positive feedback nonlinearity. We derive expressions that link the speed of propagation and other characteristics of traveling waves to the parameters of the biophysical processes, such as diffusion rates, receptor expression level, etc. Analyzing the derived expressions we found that traveling waves in such systems can exhibit a number of unusual properties, e.g. non-monotonic dependence of the speed of propagation on ligand diffusivity. Our results for the fully developed traveling fronts can be used to analyze wave initiation from localized perturbations, a scenario that frequently arises in the in vitro models of epithelial wound healing, and guide future modeling studies of cell communication in epithelial layers

  19. Effect of Temperature on the Biotic Potential of Honeybee Microsporidia▿

    Science.gov (United States)

    Martín-Hernández, Raquel; Meana, Aránzazu; García-Palencia, Pilar; Marín, Pilar; Botías, Cristina; Garrido-Bailón, Encarna; Barrios, Laura; Higes, Mariano

    2009-01-01

    The biological cycle of Nosema spp. in honeybees depends on temperature. When expressed as total spore counts per day after infection, the biotic potentials of Nosema apis and N. ceranae at 33°C were similar, but a higher proportion of immature stages of N. ceranae than of N. apis were seen. At 25 and 37°C, the biotic potential of N. ceranae was higher than that of N. apis. The better adaptation of N. ceranae to complete its endogenous cycle at different temperatures clearly supports the observation of the different epidemiological patterns. PMID:19233948

  20. Developing a Phytoplankton Biotic Index as an Indicator of Freshwater Inflow within a Subtropical Estuary

    Science.gov (United States)

    Steichen, J. L.; Quigg, A.; Lucchese, A.; Preischel, H.

    2016-02-01

    Freshwater inflows drive the water and sediment quality in coastal bays and estuaries influencing the ecosystem and health of the biological community. Phytoplankton accessory pigments (used as a proxy for major taxonomic groups) have been utilized to develop a biotic index of physical, chemical and biotic disturbances in Chesapeake Bay (USA) and other estuarine systems. In this study we have used the Chesapeake Bay - Phytoplankton Index of Biotic Integrity model as a guide in developing an index for Galveston Bay, TX (USA) as an indicator of sufficient freshwater inflow to a subtropical estuary. Multivariate statistical analyses were run using PRIMER-E+PERMANOVA to determine the correlations between phytoplankton accessory pigment concentrations and a suite of abiotic factors associated with freshwater inflow (salinity, DIN, PO4, secchi). Phytoplankton pigment concentrations and water quality parameters were collected across Galveston Bay on a monthly basis from 2008-2013. In the upper region of the bay nearest the river source Dinophyceae, Cryptophyceae (winter (Dec-Feb)) and Chlorophyceae (winter and spring (Mar-May)) were significantly correlated to freshwater inflow and nutrient concentrations PO4 (p<0.05). Increased concentrations of Bacillariophyceae and Cyanophyceae (summer (Jun-Aug)) were significantly correlated to lower concentrations of DIN (p<0.05). Near the mouth of the estuary there was a significant correlation between the increase in Bacillariophyceae, Cyanophyceae, Cryptophyceae and Dinophyceae with decreasing PO4 (p<0.05). Within the dynamic system of Galveston Bay we are working to apply a Phytoplankton Index of Biotic Integrity as a means of monitoring the biological health of this ecologically and economically important estuarine ecosystem.

  1. Relevance of biotic pathways to the long-term regulation of nuclear waste disposal: Phase 2, Final report

    International Nuclear Information System (INIS)

    McKenzie, D.H.; Cadwell, L.L.; Kennedy, W.E. Jr.; Prohammer, L.A.; Simmons, M.A.

    1986-11-01

    The results reported here establish the relevance and propose a method for including biotic transport in the assessment and licensing process for commercial low-level waste disposal sites. Earlier work identified the biotic transport mechanisms and process scenarios linking biotic transport with dose to man, and developed models for assessment of impacts. Model modification and improvement efforts in enhancing the ability to represent soil erosion and soil transport within the trench cover. Two alternative hypotheses on plant root uptake were incorporated into the model to represent transport of radionuclides by roots that penetrate the buried waste. Enhancements were also made to the scenario for future site intruder activities. Representation of waste package decomposition in the model was confirmed as the best available alternative. Results from sensitivity analyses indicate that additional information is needed to evaluate the alternative hypotheses for plant root uptake of buried wastes. Site-specific evaluations of the contribution from biotic transport to the potential dose to man establish the relevance in the assessment process. The BIOPORT/MAXI1 computer software package is proposed for dose assessments of commercial low-level waste disposal sites

  2. Relevance of biotic pathways to the long-term regulation of nuclear waste disposal: Phase 2, Final report

    Energy Technology Data Exchange (ETDEWEB)

    McKenzie, D.H.; Cadwell, L.L.; Kennedy, W.E. Jr.; Prohammer, L.A.; Simmons, M.A.

    1986-11-01

    The results reported here establish the relevance and propose a method for including biotic transport in the assessment and licensing process for commercial low-level waste disposal sites. Earlier work identified the biotic transport mechanisms and process scenarios linking biotic transport with dose to man, and developed models for assessment of impacts. Model modification and improvement efforts in enhancing the ability to represent soil erosion and soil transport within the trench cover. Two alternative hypotheses on plant root uptake were incorporated into the model to represent transport of radionuclides by roots that penetrate the buried waste. Enhancements were also made to the scenario for future site intruder activities. Representation of waste package decomposition in the model was confirmed as the best available alternative. Results from sensitivity analyses indicate that additional information is needed to evaluate the alternative hypotheses for plant root uptake of buried wastes. Site-specific evaluations of the contribution from biotic transport to the potential dose to man establish the relevance in the assessment process. The BIOPORT/MAXI1 computer software package is proposed for dose assessments of commercial low-level waste disposal sites.

  3. Invasion by nonnative brook trout in Panther Creek, Idaho: Roles of habitat quality, connectivity, and biotic resistance

    Science.gov (United States)

    Joseph R. Benjamin

    2006-01-01

    Theoretical models suggest the invasion of nonnative freshwater species is facilitated through the interaction of three factors: biotic resistance, habitat quality, and connectivity. We measured variables that represented each component to determine which were associated with small (150 mm) brook trout occurrence in Panther Creek, a tributary...

  4. A Versatile Dinucleating Ligand Containing Sulfonamide Groups

    DEFF Research Database (Denmark)

    Sundberg, Jonas; Witt, Hannes; Cameron, Lisa

    2014-01-01

    ligand can be prepared in aqueous solutions using only divalent metal ions. Two of the copper(II) complexes, [Cu2(psmp)(OH)] and [Cu2(psmp)(OAc)2]-, demonstrate the anticipated 1:2 ligand/metal stoichiometry and show that the dimetallic binding site created for exogenous ligands possesses high inherent...... of antiferromagnetic coupling. This is corroborated computationally by broken-symmetry density functional theory, which for isotropic modeling of the coupling predicts an antiferromagnetic coupling strength of J = 70.5 cm-1....

  5. Scaled biotic disruption during early Eocene global warming events

    Directory of Open Access Journals (Sweden)

    S. J. Gibbs

    2012-11-01

    Full Text Available Late Paleocene and early Eocene hyperthermals are transient warming events associated with massive perturbations of the global carbon cycle, and are considered partial analogues for current anthropogenic climate change. Because the magnitude of carbon release varied between the events, they are natural experiments ideal for exploring the relationship between carbon cycle perturbations, climate change and biotic response. Here we quantify marine biotic variability through three million years of the early Eocene that include five hyperthermals, utilizing a method that allows us to integrate the records of different plankton groups through scenarios ranging from background to major extinction events. Our long time-series calcareous nannoplankton record indicates a scaling of biotic disruption to climate change associated with the amount of carbon released during the various hyperthermals. Critically, only the three largest hyperthermals, the Paleocene–Eocene Thermal Maximum (PETM, Eocene Thermal Maximum 2 (ETM2 and the I1 event, show above-background variance, suggesting that the magnitude of carbon input and associated climate change needs to surpass a threshold value to cause significant biotic disruption.

  6. Plant Hormesis Management with Biostimulants of Biotic Origin in Agriculture.

    Science.gov (United States)

    Vargas-Hernandez, Marcela; Macias-Bobadilla, Israel; Guevara-Gonzalez, Ramon G; Romero-Gomez, Sergio de J; Rico-Garcia, Enrique; Ocampo-Velazquez, Rosalia V; Alvarez-Arquieta, Luz de L; Torres-Pacheco, Irineo

    2017-01-01

    Over time plants developed complex mechanisms in order to adapt themselves to the environment. Plant innate immunity is one of the most important mechanisms for the environmental adaptation. A myriad of secondary metabolites with nutraceutical features are produced by the plant immune system in order to get adaptation to new environments that provoke stress (stressors). Hormesis is a phenomenon by which a stressor (i.e., toxins, herbicides, etc.) stimulates the cellular stress response, including secondary metabolites production, in order to help organisms to establish adaptive responses. Hormetins of biotic origin (i.e., biostimulants or biological control compounds), in certain doses might enhance plant performance, however, in excessive doses they are commonly deleterious. Biostimulants or biological control compounds of biotic origin are called "elicitors" that have widely been studied as inducers of plant tolerance to biotic and abiotic stresses. The plant response toward elicitors is reminiscent of hormetic responses toward toxins in several organisms. Thus, controlled management of hormetic responses in plants using these types of compounds is expected to be an important tool to increase nutraceutical quality of plant food and trying to minimize negative effects on yields. The aim of this review is to analyze the potential for agriculture that the use of biostimulants and biological control compounds of biotic origin could have in the management of the plant hormesis. The use of homolog DNA as biostimulant or biological control compound in crop production is also discussed.

  7. Compartment specific importance of glutathione during abiotic and biotic stress

    Directory of Open Access Journals (Sweden)

    Bernd eZechmann

    2014-10-01

    Full Text Available The tripeptide thiol glutathione (γ-L-glutamyl-L-cysteinyl-glycine is the most important sulfur containing antioxidant in plants and essential for plant defense against abiotic and biotic stress conditions. It is involved in the detoxification of reactive oxygen species, redox signaling, the modulation of defense gene expression and important for the regulation of enzymatic activities. Even though changes in glutathione contents are well documented in plants and its roles in plant defense are well established, still too little is known about its compartment specific importance during abiotic and biotic stress conditions. Due to technical advances in the visualization of glutathione and the redox state of plants through microscopical methods some progress was made in the last few years in studying the importance of subcellular glutathione contents during stress conditions in plants. This review summarizes the data available on compartment specific importance of glutathione in the protection against abiotic and biotic stress conditions such as high light stress, exposure to cadmium, drought, and pathogen attack (Pseudomonas, Botrytis, Tobacco Mosaic Virus. The data will be discussed in connection with the subcellular accumulation of ROS during these conditions and glutathione synthesis which are both highly compartment specific (e.g. glutathione synthesis takes place in chloroplasts and the cytosol. Thus this review will reveal the compartment specific importance of glutathione during abiotic and biotic stress conditions.

  8. River Quality Investigations, Part 1: Some Diversity and Biotic Indices.

    Science.gov (United States)

    Hewitt, G.

    1991-01-01

    The following indices for assessing river water quality are described: Shannon-Weiner Diversity Index, Sorenson Quotient of Similarity, Czekanowski's Index of Similarity, Trent Biotic Index, Chandler Score, and Biological Monitoring Working Party Score. Their advantages and disadvantages are outlined. (Author)

  9. Development and Validation of an Aquatic Fine Sediment Biotic Index

    Science.gov (United States)

    Relyea, Christina D.; Minshall, G. Wayne; Danehy, Robert J.

    2012-01-01

    The Fine Sediment Biotic Index (FSBI) is a regional, stressor-specific biomonitoring index to assess fine sediment (Plecoptera (5), Trichoptera (3), and Ephemeroptera (2) contained all but one of the species or species groups classified as extremely sensitive. Index validation with an independent data set of 255 streams found FSBI scores to accurately predict both high and low levels of measured fine sediment.

  10. Biotic diversity interfaces with urbanization in the Lake Tahoe basin

    Science.gov (United States)

    Patricia N. Manley; Dennis D. Murphy; Lori A. Campbell; Kirsten E. Heckmann; Susan Merideth; Sean A. Parks; Monte P. Sanford; Matthew D. Schlesinger

    2006-01-01

    In the Lake Tahoe Basin, the retention of native ecosystems within urban areas may greatly enhance the landscape’s ability to maintain biotic diversity. Our study of plant, invertebrate and vertebrate species showed that many native species were present in remnant forest stands in developed areas; however, their richness and abundance declined in association with...

  11. The interactions of ants with their biotic environment.

    Science.gov (United States)

    Chomicki, Guillaume; Renner, Susanne S

    2017-03-15

    This s pecial feature results from the symposium 'Ants 2016: ant interactions with their biotic environments' held in Munich in May 2016 and deals with the interactions between ants and other insects, plants, microbes and fungi, studied at micro- and macroevolutionary levels with a wide range of approaches, from field ecology to next-generation sequencing, chemical ecology and molecular genetics. In this paper, we review key aspects of these biotic interactions to provide background information for the papers of this s pecial feature After listing the major types of biotic interactions that ants engage in, we present a brief overview of ant/ant communication, ant/plant interactions, ant/fungus symbioses, and recent insights about ants and their endosymbionts. Using a large molecular clock-dated Formicidae phylogeny, we map the evolutionary origins of different ant clades' interactions with plants, fungi and hemiptera. Ants' biotic interactions provide ideal systems to address fundamental ecological and evolutionary questions about mutualism, coevolution, adaptation and animal communication. © 2017 The Author(s).

  12. STRESS ECOLOGY IN FUCUS : ABIOTIC, BIOTIC AND GENETIC INTERACTIONS

    NARCIS (Netherlands)

    Wahl, Martin; Jormalainen, Veijo; Eriksson, Britas Klemens; Coyer, James A.; Molis, Markus; Schubert, Hendrik; Dethier, Megan; Karez, Rolf; Kruse, Inken; Lenz, Mark; Pearson, Gareth; Rohde, Sven; Wikstrom, Sofia A.; Olsen, Jeanine L.; Lesser, M

    2011-01-01

    Stress regimes defined as the synchronous or sequential action of abiotic and biotic stresses determine the performance and distribution of species. The natural patterns of stress to which species are more or less well adapted have recently started to shift and alter under the influence of global

  13. Legumes affect alpine tundra community composition via multiple biotic interactions

    NARCIS (Netherlands)

    Soudzilovskaia, N.A.; Aksenova, A.A.; Makarov, M.I.; Onipchenko, V.G.; Logvinenko, O.A.; Braak, ter C.J.F.; Cornelissen, J.H.C.

    2012-01-01

    The soil engineering function of legumes in natural ecosystems is paramount but associated solely with soil nitrogen (N) subsidies, ignoring concomitant biotic interactions such as competitive or inhibitory effects and exchange between mycorrhizas and rhizobia. We aim to (1) disentangle legume

  14. Experimental reduction in interaction intensity strongly affects biotic selection.

    Science.gov (United States)

    Sletvold, Nina; Ågren, Jon

    2016-11-01

    The link between biotic interaction intensity and strength of selection is of fundamental interest for understanding biotically driven diversification and predicting the consequences of environmental change. The strength of selection resulting from biotic interactions is determined by the strength of the interaction and by the covariance between fitness and the trait under selection. When the relationship between trait and absolute fitness is constant, selection strength should be a direct function of mean population interaction intensity. To test this prediction, we excluded pollinators for intervals of different length to induce five levels of pollination intensity within a single plant population. Pollen limitation (PL) increased from 0 to 0.77 across treatments, accompanied by a fivefold increase in the opportunity for selection. Trait-fitness covariance declined with PL for number of flowers, but varied little for other traits. Pollinator-mediated selection on plant height, corolla size, and spur length increased by 91%, 34%, and 330%, respectively, in the most severely pollen-limited treatment compared to open-pollinated plants. The results indicate that realized biotic selection can be predicted from mean population interaction intensity when variation in trait-fitness covariance is limited, and that declines in pollination intensity will strongly increase selection on traits involved in the interaction. © 2016 by the Ecological Society of America.

  15. Does prescribed burning result in biotic homogenization of coastal heathlands?

    Science.gov (United States)

    Velle, Liv Guri; Nilsen, Liv Sigrid; Norderhaug, Ann; Vandvik, Vigdis

    2014-05-01

    Biotic homogenization due to replacement of native biodiversity by widespread generalist species has been demonstrated in a number of ecosystems and taxonomic groups worldwide, causing growing conservation concern. Human disturbance is a key driver of biotic homogenization, suggesting potential conservation challenges in seminatural ecosystems, where anthropogenic disturbances such as grazing and burning are necessary for maintaining ecological dynamics and functioning. We test whether prescribed burning results in biotic homogenization in the coastal heathlands of north-western Europe, a seminatural landscape where extensive grazing and burning has constituted the traditional land-use practice over the past 6000 years. We compare the beta-diversity before and after fire at three ecological scales: within local vegetation patches, between wet and dry heathland patches within landscapes, and along a 470 km bioclimatic gradient. Within local patches, we found no evidence of homogenization after fire; species richness increased, and the species that entered the burnt Calluna stands were not widespread specialists but native grasses and herbs characteristic of the heathland system. At the landscapes scale, we saw a weak homogenization as wet and dry heathland patches become more compositionally similar after fire. This was because of a decrease in habitat-specific species unique to either wet or dry habitats and postfire colonization by a set of heathland specialists that established in both habitat types. Along the bioclimatic gradient, species that increased after fire generally had more specific environmental requirements and narrower geographical distributions than the prefire flora, resulting in a biotic 'heterogenisation' after fire. Our study demonstrates that human disturbance does not necessarily cause biotic homogenization, but that continuation of traditional land-use practices can instead be crucial for the maintenance of the diversity and ecological

  16. A direct-gradient multivariate index of biotic condition

    Science.gov (United States)

    Miranda, Leandro E.; Aycock, J.N.; Killgore, K. J.

    2012-01-01

    Multimetric indexes constructed by summing metric scores have been criticized despite many of their merits. A leading criticism is the potential for investigator bias involved in metric selection and scoring. Often there is a large number of competing metrics equally well correlated with environmental stressors, requiring a judgment call by the investigator to select the most suitable metrics to include in the index and how to score them. Data-driven procedures for multimetric index formulation published during the last decade have reduced this limitation, yet apprehension remains. Multivariate approaches that select metrics with statistical algorithms may reduce the level of investigator bias and alleviate a weakness of multimetric indexes. We investigated the suitability of a direct-gradient multivariate procedure to derive an index of biotic condition for fish assemblages in oxbow lakes in the Lower Mississippi Alluvial Valley. Although this multivariate procedure also requires that the investigator identify a set of suitable metrics potentially associated with a set of environmental stressors, it is different from multimetric procedures because it limits investigator judgment in selecting a subset of biotic metrics to include in the index and because it produces metric weights suitable for computation of index scores. The procedure, applied to a sample of 35 competing biotic metrics measured at 50 oxbow lakes distributed over a wide geographical region in the Lower Mississippi Alluvial Valley, selected 11 metrics that adequately indexed the biotic condition of five test lakes. Because the multivariate index includes only metrics that explain the maximum variability in the stressor variables rather than a balanced set of metrics chosen to reflect various fish assemblage attributes, it is fundamentally different from multimetric indexes of biotic integrity with advantages and disadvantages. As such, it provides an alternative to multimetric procedures.

  17. Biotic prognostications: Global warming and biological diversity

    Energy Technology Data Exchange (ETDEWEB)

    Peters, R.L.; Lovejoy, T.E. [eds.

    1992-12-31

    This book focuses on the impacts of the greenhouse effect on biological diversity and on natural ecosystems. Included are chapters which include the following topics: government attitudes to climate change problems; general conclusions and deficiencies of general circulation models; impacts of past climate changes on global biota; effects of climate on vegetation, soils, wildlife diversity, animal physiology, ecology, behavior, migration, and parasites and diseases; arctic mariene ecosystems and coasta marine zones; tropical forests; arctic tundra; western North American forests, etc.; indirect linkages and snyergisms among climate change, biodiversity, geosphere, and anthropogenic stresses.

  18. In silico molecular modeling of neuraminidase enzyme H1N1 avian influenza virus and docking with zanamivir ligands

    Directory of Open Access Journals (Sweden)

    Muthiyan Ramachandran

    2012-12-01

    Full Text Available Objective: Neuraminidase is an enzyme aspartic protease that is essential for the life cycle of H1N1. Methods: Constructed a model of Neuraminidase enzyme the 3D structure as template using with Modeller software. The Neuraminidase enzyme model was predicted and validated by Procheck, What check, Errat, Verify-3D and AutoDock web server for reliability. Results: The Modeller homology-modeling algorithm was demonstrated excellent accuracy in blind predictions. The Neuraminidase enzyme model built with little, 35% identity could be accurate enough to be successfully used in receptor based rational drug design. The closest homologue with the highest sequence identity 100% was selected. Zanamivir drug and analogues were retrieved from PubChem database, as well as subjected to docking interaction with Neuraminidase enzyme used AutoDock programme. Based on the root mean square deviation and lowest binding energy values the best docking orientation was selected. The better lowest binding energy value -6.91 was selected of CID_25209232. Conclusions: This study will be used in broad screening of inhibitors of the protein. However, further implemented experimental and clinical verification is needed to establishment these analogues as drug.

  19. Knowledge-based modeling of a legume lectin and docking of the carbohydrate ligand: the Ulex europaeus lectin I and its interaction with fucose.

    Science.gov (United States)

    Gohier, A; Espinosa, J F; Jimenez-Barbero, J; Carrupt, P A; Pérez, S; Imberty, A

    1996-12-01

    Ulex europaeus isolectin I is specific for fucose-containing oligosaccharide such as H type 2 trisaccharide alpha-L-Fuc (1-->2) beta-D-Gal (1-->4) beta-D-GlcNAc. Several legume lectins have been crystallized and modeled, but no structural data are available concerning such fucose-binding lectin. The three-dimensional structure of Ulex europaeus isolectin I has been constructed using seven legume lectins for which high-resolution crystal structures were available. Some conserved water molecules, as well as the structural cations, were taken into account for building the model. In the predicted binding site, the most probable locations of the secondary hydroxyl groups were determined using the GRID method. Several possible orientations could be determined for a fucose residue. All of the four possible conformations compatible with energy calculations display several hydrogen bonds with Asp-87 and Ser-132 and a stacking interaction with Tyr-220 and Phe-136. In two orientations, the O-3 and O-4 hydroxyl groups of fucose are the most buried ones, whereas two other, the O-2 and O-3 hydroxyl groups are at the bottom of the site. Possible docking modes are also studied by analysis of the hydrophobic and hydrophilic surfaces for both the ligand and the protein. The SCORE method allows for a quantitative evaluation of the complementarity of these surfaces, on the basis of molecular lipophilicity calculations. The predictions presented here are compared with known biochemical data.

  20. The IntFOLD server: an integrated web resource for protein fold recognition, 3D model quality assessment, intrinsic disorder prediction, domain prediction and ligand binding site prediction.

    Science.gov (United States)

    Roche, Daniel B; Buenavista, Maria T; Tetchner, Stuart J; McGuffin, Liam J

    2011-07-01

    The IntFOLD server is a novel independent server that integrates several cutting edge methods for the prediction of structure and function from sequence. Our guiding principles behind the server development were as follows: (i) to provide a simple unified resource that makes our prediction software accessible to all and (ii) to produce integrated output for predictions that can be easily interpreted. The output for predictions is presented as a simple table that summarizes all results graphically via plots and annotated 3D models. The raw machine readable data files for each set of predictions are also provided for developers, which comply with the Critical Assessment of Methods for Protein Structure Prediction (CASP) data standards. The server comprises an integrated suite of five novel methods: nFOLD4, for tertiary structure prediction; ModFOLD 3.0, for model quality assessment; DISOclust 2.0, for disorder prediction; DomFOLD 2.0 for domain prediction; and FunFOLD 1.0, for ligand binding site prediction. Predictions from the IntFOLD server were found to be competitive in several categories in the recent CASP9 experiment. The IntFOLD server is available at the following web site: http://www.reading.ac.uk/bioinf/IntFOLD/.

  1. Predicting binding poses and affinities for protein - ligand complexes in the 2015 D3R Grand Challenge using a physical model with a statistical parameter estimation

    Science.gov (United States)

    Grudinin, Sergei; Kadukova, Maria; Eisenbarth, Andreas; Marillet, Simon; Cazals, Frédéric

    2016-09-01

    The 2015 D3R Grand Challenge provided an opportunity to test our new model for the binding free energy of small molecules, as well as to assess our protocol to predict binding poses for protein-ligand complexes. Our pose predictions were ranked 3-9 for the HSP90 dataset, depending on the assessment metric. For the MAP4K dataset the ranks are very dispersed and equal to 2-35, depending on the assessment metric, which does not provide any insight into the accuracy of the method. The main success of our pose prediction protocol was the re-scoring stage using the recently developed Convex-PL potential. We make a thorough analysis of our docking predictions made with AutoDock Vina and discuss the effect of the choice of rigid receptor templates, the number of flexible residues in the binding pocket, the binding pocket size, and the benefits of re-scoring. However, the main challenge was to predict experimentally determined binding affinities for two blind test sets. Our affinity prediction model consisted of two terms, a pairwise-additive enthalpy, and a non pairwise-additive entropy. We trained the free parameters of the model with a regularized regression using affinity and structural data from the PDBBind database. Our model performed very well on the training set, however, failed on the two test sets. We explain the drawback and pitfalls of our model, in particular in terms of relative coverage of the test set by the training set and missed dynamical properties from crystal structures, and discuss different routes to improve it.

  2. The application of molecular modelling in the safety assessment of chemicals: A case study on ligand-dependent PPARγ dysregulation.

    Science.gov (United States)

    Al Sharif, Merilin; Tsakovska, Ivanka; Pajeva, Ilza; Alov, Petko; Fioravanzo, Elena; Bassan, Arianna; Kovarich, Simona; Yang, Chihae; Mostrag-Szlichtyng, Aleksandra; Vitcheva, Vessela; Worth, Andrew P; Richarz, Andrea-N; Cronin, Mark T D

    2017-12-01

    The aim of this paper was to provide a proof of concept demonstrating that molecular modelling methodologies can be employed as a part of an integrated strategy to support toxicity prediction consistent with the mode of action/adverse outcome pathway (MoA/AOP) framework. To illustrate the role of molecular modelling in predictive toxicology, a case study was undertaken in which molecular modelling methodologies were employed to predict the activation of the peroxisome proliferator-activated nuclear receptor γ (PPARγ) as a potential molecular initiating event (MIE) for liver steatosis. A stepwise procedure combining different in silico approaches (virtual screening based on docking and pharmacophore filtering, and molecular field analysis) was developed to screen for PPARγ full agonists and to predict their transactivation activity (EC 50 ). The performance metrics of the classification model to predict PPARγ full agonists were balanced accuracy=81%, sensitivity=85% and specificity=76%. The 3D QSAR model developed to predict EC 50 of PPARγ full agonists had the following statistical parameters: q 2 cv =0.610, N opt =7, SEP cv =0.505, r 2 pr =0.552. To support the linkage of PPARγ agonism predictions to prosteatotic potential, molecular modelling was combined with independently performed mechanistic mining of available in vivo toxicity data followed by ToxPrint chemotypes analysis. The approaches investigated demonstrated a potential to predict the MIE, to facilitate the process of MoA/AOP elaboration, to increase the scientific confidence in AOP, and to become a basis for 3D chemotype development. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Biotic turnover rates during the Pleistocene-Holocene transition

    Science.gov (United States)

    Stivrins, Normunds; Soininen, Janne; Amon, Leeli; Fontana, Sonia L.; Gryguc, Gražyna; Heikkilä, Maija; Heiri, Oliver; Kisielienė, Dalia; Reitalu, Triin; Stančikaitė, Miglė; Veski, Siim; Seppä, Heikki

    2016-11-01

    The Northern Hemisphere is currently warming at the rate which is unprecedented during the Holocene. Quantitative palaeoclimatic records show that the most recent time in the geological history with comparable warming rates was during the Pleistocene-Holocene transition (PHT) about 14,000 to 11,000 years ago. To better understand the biotic response to rapid temperature change, we explore the community turnover rates during the PHT by focusing on the Baltic region in the southeastern sector of the Scandinavian Ice Sheet, where an exceptionally dense network on microfossil and macrofossil data that reflect the biotic community history are available. We further use a composite chironomid-based summer temperature reconstruction compiled specifically for our study region to calculate the rate of temperature change during the PHT. The fastest biotic turnover in the terrestrial and aquatic communities occurred during the Younger Dryas-Holocene shift at 11,700 years ago. This general shift in species composition was accompanied by regional extinctions, including disappearance of mammoth (Mammuthus primigenius) and reindeer (Rangifer tarandus) and many arctic-alpine plant taxa, such as Dryas octopetala, Salix polaris and Saxifraga aizoides, from the region. This rapid biotic turnover rate occurred when the rate of warming was 0.17 °C/decade, thus slightly lower than the current Northern Hemisphere warming of 0.2 °C/decade. We therefore conclude that the Younger Dryas-Holocene shift with its rapid turnover rates and associated regional extinctions represents an important palaeoanalogue to the current high latitude warming and gives insights about the probable future turnover rates and patterns of the terrestrial and aquatic ecosystem change.

  4. Changes in biotic and abiotic processes following mangrove clearing

    Science.gov (United States)

    Granek, Elise; Ruttenberg, Benjamin I.

    2008-12-01

    Mangrove forests, important tropical coastal habitats, are in decline worldwide primarily due to removal by humans. Changes to mangrove systems can alter ecosystem properties through direct effects on abiotic factors such as temperature, light and nutrient supply or through changes in biotic factors such as primary productivity or species composition. Despite the importance of mangroves as transitional habitats between land and sea, little research has examined changes that occur when they are cleared. We examined changes in a number of biotic and abiotic factors following the anthropogenic removal of red mangroves ( Rhizophora mangle) in the Panamanian Caribbean, including algal biomass, algal diversity, algal grazing rates, light penetration, temperature, sedimentation rates and sediment organic content. In this first study examining multiple ecosystem-level effects of mangrove disturbance, we found that areas cleared of mangroves had higher algal biomass and richness than intact mangrove areas. This increase in algal biomass and richness was likely due to changes in abiotic factors (e.g. light intensity, temperature), but not biotic factors (fish herbivory). Additionally the algal and cyanobacterial genera dominating mangrove-cleared areas were rare in intact mangroves and included a number of genera that compete with coral for space on reefs. Interestingly, sedimentation rates did not differ between intact and cleared areas, but the sediments that accumulated in intact mangroves had higher organic content. These findings are the first to demonstrate that anthropogenic clearing of mangroves changes multiple biotic and abiotic processes in mangrove forests and that some of these changes may influence adjacent habitats such as coral reefs and seagrass beds. Additional research is needed to further explore the community and ecosystem-level effects of mangrove clearing and their influence on adjacent habitats, but it is clear that mangrove conservation is an

  5. Assessment of derelict soil quality: Abiotic, biotic and functional approaches.

    Science.gov (United States)

    Vincent, Quentin; Auclerc, Apolline; Beguiristain, Thierry; Leyval, Corinne

    2018-02-01

    The intensification and subsequent closing down of industrial activities during the last century has left behind large surfaces of derelict lands. Derelict soils have low fertility, can be contaminated, and many of them remain unused. However, with the increasing demand of soil surfaces, they might be considered as a resource, for example for non-food biomass production. The study of their physico-chemical properties and of their biodiversity and biological activity may provide indications for their potential re-use. The objective of our study was to investigate the quality of six derelict soils, considering abiotic, biotic, and functional parameters. We studied (i) the soil bacteria, fungi, meso- and macro-fauna and plant communities of six different derelict soils (two from coking plants, one from a settling pond, two constructed ones made from different substrates and remediated soil, and an inert waste storage one), and (ii) their decomposition function based on the decomposer trophic network, enzyme activities, mineralization activity, and organic pollutant degradation. Biodiversity levels in these soils were high, but all biotic parameters, except the mycorrhizal colonization level, discriminated them. Multivariate analysis showed that biotic parameters co-varied more with fertility proxies than with soil contamination parameters. Similarly, functional parameters significantly co-varied with abiotic parameters. Among functional parameters, macro-decomposer proportion, enzyme activity, average mineralization capacity, and microbial polycyclic aromatic hydrocarbon degraders were useful to discriminate the soils. We assessed their quality by combining abiotic, biotic, and functional parameters: the compost-amended constructed soil displayed the highest quality, while the settling pond soil and the contaminated constructed soil displayed the lowest. Although differences among the soils were highlighted, this study shows that derelict soils may provide a

  6. Development of a new biotic index to assess freshwater pollution

    International Nuclear Information System (INIS)

    Jiang Jianguo

    2006-01-01

    We developed a new biotic index of species pollution value (SPV) and community pollution value (CPV) based on the correlation of protozoan communities with chemical water quality to assess freshwater pollution. Five hundred and twenty-three species of protozoa SPV were established based on the data of River Hangjiang and Lake Donghu. The present research was conducted in order to further consummate the biotic index. Protozoa of the water system in Changde City were collected from 16 stations using the PFU method and the water chemical parameters of the stations were analyzed. The results showed that CPV calculated from SPV had a close correlation with the degree of water pollution (p < 0.00001), which indicated that the method is reliable. By combining the data of River Hangjiang, Lake Donghu and Changde City, the final form of SPV was accomplished and the SPV list increased to 757. The ultimate water standard evaluated by CPV calculated from SPV was proposed. - A new biotic index of water quality based on protozoa is described

  7. Quantitative XRD analysis of {110} twin density in biotic aragonites.

    Science.gov (United States)

    Suzuki, Michio; Kim, Hyejin; Mukai, Hiroki; Nagasawa, Hiromichi; Kogure, Toshihiro

    2012-12-01

    {110} Twin densities in biotic aragonite have been estimated quantitatively from the peak widths of specific reflections in powder X-ray diffraction (XRD) patterns, as well as direct confirmation of the twins using transmission electron microscopy (TEM). Influence of the twin density on the peak widths in the XRD pattern was simulated using DIFFaX program, regarding (110) twin as interstratification of two types of aragonite unit layers with mirrored relationship. The simulation suggested that the twin density can be estimated from the difference of the peak widths between 111 and 021, or between 221 and 211 reflections. Biotic aragonite in the crossed-lamellar microstructure (three species) and nacreous microstructure (four species) of molluscan shells, fish otoliths (two species), and a coral were investigated. The XRD analyses indicated that aragonite crystals in the crossed-lamellar microstructure of the three species contain high density of the twins, which is consistent with the TEM examination. On the other hand, aragonite in the nacre of the four species showed almost no difference of the peak widths between the paired reflections, indicating low twin densities. The results for the fish otoliths were varied between the species. Such variation of the twin density in biotic aragonites may reflect different schemes of crystal growth in biomineralization. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Pattern and process of biotic homogenization in the New Pangaea.

    Science.gov (United States)

    Baiser, Benjamin; Olden, Julian D; Record, Sydne; Lockwood, Julie L; McKinney, Michael L

    2012-12-07

    Human activities have reorganized the earth's biota resulting in spatially disparate locales becoming more or less similar in species composition over time through the processes of biotic homogenization and biotic differentiation, respectively. Despite mounting evidence suggesting that this process may be widespread in both aquatic and terrestrial systems, past studies have predominantly focused on single taxonomic groups at a single spatial scale. Furthermore, change in pairwise similarity is itself dependent on two distinct processes, spatial turnover in species composition and changes in gradients of species richness. Most past research has failed to disentangle the effect of these two mechanisms on homogenization patterns. Here, we use recent statistical advances and collate a global database of homogenization studies (20 studies, 50 datasets) to provide the first global investigation of the homogenization process across major faunal and floral groups and elucidate the relative role of changes in species richness and turnover. We found evidence of homogenization (change in similarity ranging from -0.02 to 0.09) across nearly all taxonomic groups, spatial extent and grain sizes. Partitioning of change in pairwise similarity shows that overall change in community similarity is driven by changes in species richness. Our results show that biotic homogenization is truly a global phenomenon and put into question many of the ecological mechanisms invoked in previous studies to explain patterns of homogenization.

  9. Development of a new biotic index to assess freshwater pollution

    Energy Technology Data Exchange (ETDEWEB)

    Jiang Jianguo [College of Food and Bioengineering, South China University of Technology, Guangzhou 510640 (China)]. E-mail: jgjiang@scut.edu.cn

    2006-01-15

    We developed a new biotic index of species pollution value (SPV) and community pollution value (CPV) based on the correlation of protozoan communities with chemical water quality to assess freshwater pollution. Five hundred and twenty-three species of protozoa SPV were established based on the data of River Hangjiang and Lake Donghu. The present research was conducted in order to further consummate the biotic index. Protozoa of the water system in Changde City were collected from 16 stations using the PFU method and the water chemical parameters of the stations were analyzed. The results showed that CPV calculated from SPV had a close correlation with the degree of water pollution (p < 0.00001), which indicated that the method is reliable. By combining the data of River Hangjiang, Lake Donghu and Changde City, the final form of SPV was accomplished and the SPV list increased to 757. The ultimate water standard evaluated by CPV calculated from SPV was proposed. - A new biotic index of water quality based on protozoa is described.

  10. Ab initio and density functional theoretical design and screening of model crown ether based ligand (host) for extraction of lithium metal ion (guest): effect of donor and electronic induction.

    Science.gov (United States)

    Boda, Anil; Ali, Sk Musharaf; Rao, Hanmanth; Ghosh, Sandip K

    2012-08-01

    The structures, energetic and thermodynamic parameters of model crown ethers with different donor, cavity and electron donating/ withdrawing functional group have been determined with ab initio MP2 and density functional theory in gas and solvent phase. The calculated values of binding energy/ enthalpy for lithium ion complexation are marginally higher for hard donor based aza and oxa crown compared to soft donor based thia and phospha crown. The calculated values of binding enthalpy for lithium metal ion with 12C4 at MP2 level of theory is in good agreement with the available experimental result. The binding energy is altered due to the inductive effect imparted by the electron donating/ withdrawing group in crown ether, which is well correlated with the values of electron transfer. The role of entropy for extraction of hydrated lithium metal ion by different donor and functional group based ligand has been demonstrated. The HOMO-LUMO gap is decreased and dipole moment of the ligand is increased from gas phase to organic phase because of the dielectric constant of the solvent. The gas phase binding energy is reduced in solvent phase as the solvent molecules weaken the metal-ligand binding. The theoretical values of extraction energy for LiCl salt from aqueous solution in different organic solvent is validated by the experimental trend. The study presented here should contribute to the design of model host ligand and screening of solvent for metal ion recognition and thus can contribute in planning the experiments.

  11. Towards an animal model of ovarian cancer: cataloging chicken blood proteins using combinatorial peptide ligand libraries coupled with shotgun proteomic analysis for translational research.

    Science.gov (United States)

    Ma, Yingying; Sun, Zeyu; de Matos, Ricardo; Zhang, Jing; Odunsi, Kunle; Lin, Biaoyang

    2014-05-01

    Epithelial ovarian cancer is the most deadly gynecological cancer around the world, with high morbidity in industrialized countries. Early diagnosis is key in reducing its morbidity rate. Yet, robust biomarkers, diagnostics, and animal models are still limited for ovarian cancer. This calls for broader omics and systems science oriented diagnostics strategies. In this vein, the domestic chicken has been used as an ovarian cancer animal model, owing to its high rate of developing spontaneous epithelial ovarian tumors. Chicken blood has thus been considered a surrogate reservoir from which cancer biomarkers can be identified. However, the presence of highly abundant proteins in chicken blood has compromised the applicability of proteomics tools to study chicken blood owing to a lack of immunodepletion methods. Here, we demonstrate that a combinatorial peptide ligand library (CPLL) can efficiently remove highly abundant proteins from chicken blood samples, consequently doubling the number of identified proteins. Using an integrated CPLL-1DGE-LC-MSMS workflow, we identified a catalog of 264 unique proteins. Functional analyses further suggested that most proteins were coagulation and complement factors, blood transport and binding proteins, immune- and defense-related proteins, proteases, protease inhibitors, cellular enzymes, or cell structure and adhesion proteins. Semiquantitative spectral counting analysis identified 10 potential biomarkers from the present chicken ovarian cancer model. Additionally, many human homologs of chicken blood proteins we have identified have been independently suggested as diagnostic biomarkers for ovarian cancer, further triangulating our novel observations reported here. In conclusion, the CPLL-assisted proteomic workflow using the chicken ovarian cancer model provides a feasible platform for translational research to identify ovarian cancer biomarkers and understand ovarian cancer biology. To the best of our knowledge, we report here

  12. Cell-specific targeting by heterobivalent ligands.

    Science.gov (United States)

    Josan, Jatinder S; Handl, Heather L; Sankaranarayanan, Rajesh; Xu, Liping; Lynch, Ronald M; Vagner, Josef; Mash, Eugene A; Hruby, Victor J; Gillies, Robert J

    2011-07-20

    Current cancer therapies exploit either differential metabolism or targeting to specific individual gene products that are overexpressed in aberrant cells. The work described herein proposes an alternative approach--to specifically target combinations of cell-surface receptors using heteromultivalent ligands ("receptor combination approach"). As a proof-of-concept that functionally unrelated receptors can be noncovalently cross-linked with high avidity and specificity, a series of heterobivalent ligands (htBVLs) were constructed from analogues of the melanocortin peptide ligand ([Nle(4), dPhe(7)]-α-MSH) and the cholecystokinin peptide ligand (CCK-8). Binding of these ligands to cells expressing the human Melanocortin-4 receptor and the Cholecystokinin-2 receptor was analyzed. The MSH(7) and CCK(6) were tethered with linkers of varying rigidity and length, constructed from natural and/or synthetic building blocks. Modeling data suggest that a linker length of 20-50 Å is needed to simultaneously bind these two different G-protein coupled receptors (GPCRs). These ligands exhibited up to 24-fold enhancement in binding affinity to cells that expressed both (bivalent binding), compared to cells with only one (monovalent binding) of the cognate receptors. The htBVLs had up to 50-fold higher affinity than that of a monomeric CCK ligand, i.e., Ac-CCK(6)-NH(2). Cell-surface targeting of these two cell types with labeled heteromultivalent ligand demonstrated high avidity and specificity, thereby validating the receptor combination approach. This ability to noncovalently cross-link heterologous receptors and target individual cells using a receptor combination approach opens up new possibilities for specific cell targeting in vivo for therapy or imaging.

  13. Development of a Self-Consistent Model of Plutonium Sorption: Quantification of Sorption Enthalpy and Ligand-Promoted Dissolution

    Energy Technology Data Exchange (ETDEWEB)

    Powell, Brian [Clemson Univ., SC (United States); Kaplan, Daniel I [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Arai, Yuji [Univ. of Illinois, Urbana-Champaign, IL (United States); Becker, Udo [Univ. of Michigan, Ann Arbor, MI (United States); Ewing, Rod [Stanford Univ., CA (United States)

    2016-12-29

    This university lead SBR project is a collaboration lead by Dr. Brian Powell (Clemson University) with co-principal investigators Dan Kaplan (Savannah River National Laboratory), Yuji Arai (presently at the University of Illinois), Udo Becker (U of Michigan) and Rod Ewing (presently at Stanford University). Hypothesis: The underlying hypothesis of this work is that strong interactions of plutonium with mineral surfaces are due to formation of inner sphere complexes with a limited number of high-energy surface sites, which results in sorption hysteresis where Pu(IV) is the predominant sorbed oxidation state. The energetic favorability of the Pu(IV) surface complex is strongly influenced by positive sorption entropies, which are mechanistically driven by displacement of solvating water molecules from the actinide and mineral surface during sorption. Objectives: The overarching objective of this work is to examine Pu(IV) and Pu(V) sorption to pure metal (oxyhydr)oxide minerals and sediments using variable temperature batch sorption, X-ray absorption spectroscopy, electron microscopy, and quantum-mechanical and empirical-potential calculations. The data will be compiled into a self-consistent surface complexation model. The novelty of this effort lies largely in the manner the information from these measurements and calculations will be combined into a model that will be used to evaluate the thermodynamics of plutonium sorption reactions as well as predict sorption of plutonium to sediments from DOE sites using a component additivity approach.

  14. Methyl-orvinol-Dual activity opioid receptor ligand inhibits gastrointestinal transit and alleviates abdominal pain in the mouse models mimicking diarrhea-predominant irritable bowel syndrome.

    Science.gov (United States)

    Zielińska, Marta; Jarmuż, Agata; Wasilewski, Andrzej; Cami-Kobeci, Gerta; Husbands, Stephen; Fichna, Jakub

    2017-04-01

    Diarrhea-predominant irritable bowel syndrome (IBS-D) is a functional disorder of the gastrointestinal (GI) tract. The major IBS-D symptoms include diarrhea, abdominal pain and discomfort. High density of opioid receptors (ORs) in the GI tract and their participation in the maintenance of GI homeostasis make ORs ligands an attractive option for developing new anti-IBS-D treatments. The aim of this study was to characterize the effect of methyl-orvinol on the GI motility and secretion and in mouse models mimicking symptoms of IBS-D. In vitro, the effects of methyl-orvinol on electrical field stimulated smooth muscle contractility and epithelial ion transport were characterized in the mouse colon. In vivo, the following tests were used to determine methyl-orvinol effect on mouse GI motility: colonic bead expulsion, whole GI transit and fecal pellet output. An antinociceptive action of methyl-orvinol was assessed in the mouse model of visceral pain induced by mustard oil. Methyl-orvinol (10 -10 to 10 -6 M) inhibited colonic smooth muscle contractions in a concentration-dependent manner. This effect was reversed by naloxone (non-selective opioid antagonist) and β-funaltrexamine (selective MOP antagonist). Experiments with a selective KOP receptor agonist, U50488 revealed that methyl-orvinol is a KOP receptor antagonist in the GI tract. Methyl-orvinol enhanced epithelial ion transport. In vivo, methyl-orvinol inhibited colonic bead expulsion and prolonged GI transit. Methyl-orvinol improved hypermotility and reduced abdominal pain in the mouse models mimicking IBS-D symptoms. Methyl-orvinol could become a promising drug candidate in chronic therapy of functional GI diseases such as IBS-D. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  15. Suppression of immunodeficiency virus-associated neural damage by the p75 neurotrophin receptor ligand, LM11A-31, in an in vitro feline model.

    Science.gov (United States)

    Meeker, Rick B; Poulton, Winona; Feng, Wen-hai; Hudson, Lola; Longo, Frank M

    2012-06-01

    Feline immunodeficiency virus (FIV) infection like human immunodeficiency virus (HIV), produces systemic and central nervous system disease in its natural host, the domestic cat, that parallels the pathogenesis seen in HIV-infected humans. The ability to culture feline nervous system tissue affords the unique opportunity to directly examine interactions of infectious virus with CNS cells for the development of models and treatments that can then be translated to a natural infectious model. To explore the therapeutic potential of a new p75 neurotrophin receptor ligand, LM11A-31, we evaluated neuronal survival, neuronal damage and calcium homeostasis in cultured feline neurons following inoculation with FIV. FIV resulted in the gradual appearance of dendritic beading, pruning of processes and shrinkage of neuronal perikarya in the neurons. Astrocytes developed a more activated appearance and there was an enhanced accumulation of microglia, particularly at longer times post-inoculation. Addition of 10 nM LM11A-31, to the cultures greatly reduced or eliminated the neuronal pathology as well as the FIV effects on astrocytes and microglia. LM11A-31 also, prevented the development of delayed calcium deregulation in feline neurons exposed to conditioned medium from FIV treated macrophages. The suppression of calcium accumulation prevented the development of foci of calcium accumulation and beading in the dendrites. FIV replication was unaffected by LM11A-31. The strong neuroprotection afforded by LM11A-31 in an infectious in vitro model indicates that LM11A-31 may have excellent potential for the treatment of HIV-associated neurodegeneration.

  16. Glutamate receptor ligands

    DEFF Research Database (Denmark)

    Guldbrandt, Mette; Johansen, Tommy N; Frydenvang, Karla Andrea

    2002-01-01

    Homologation and substitution on the carbon backbone of (S)-glutamic acid [(S)-Glu, 1], as well as absolute stereochemistry, are structural parameters of key importance for the pharmacological profile of (S)-Glu receptor ligands. We describe a series of methyl-substituted 2-aminoadipic acid (AA...

  17. The lake foodweb: modelling predation and abiotic/biotic interactions

    National Research Council Canada - National Science Library

    Hakanson, L; Boulion, V.V

    2002-01-01

    .... LakeWeb includes the following key functional groups of organisms: phytoplankton, bacterioplankton, benthic algae, macrophytes, zoobenthos, herbivorous and predatory zooplankton, prey fish and predatory fish...

  18. LIBRA: LIgand Binding site Recognition Application.

    Science.gov (United States)

    Hung, Le Viet; Caprari, Silvia; Bizai, Massimiliano; Toti, Daniele; Polticelli, Fabio

    2015-12-15

    In recent years, structural genomics and ab initio molecular modeling activities are leading to the availability of a large number of structural models of proteins whose biochemical function is not known. The aim of this study was the development of a novel software tool that, given a protein's structural model, predicts the presence and identity of active sites and/or ligand binding sites. The algorithm implemented by ligand binding site recognition application (LIBRA) is based on a graph theory approach to find the largest subset of similar residues between an input protein and a collection of known functional sites. The algorithm makes use of two predefined databases for active sites and ligand binding sites, respectively, derived from the Catalytic Site Atlas and the Protein Data Bank. Tests indicate that LIBRA is able to identify the correct binding/active site in 90% of the cases analyzed, 90% of which feature the identified site as ranking first. As far as ligand binding site recognition is concerned, LIBRA outperforms other structure-based ligand binding sites detection tools with which it has been compared. The application, developed in Java SE 7 with a Swing GUI embedding a JMol applet, can be run on any OS equipped with a suitable Java Virtual Machine (JVM), and is available at the following URL: http://www.computationalbiology.it/software/LIBRAv1.zip. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Biotic and a-biotic Mn and Fe cycling in deep sediments across a gradient of sulfate reduction rates along the California margin

    Science.gov (United States)

    Schneider-Mor, A.; Steefel, C.; Maher, K.

    2011-12-01

    The coupling between the biological and a-biotic processes controlling trace metals in deep marine sediments are not well understood, although the fluxes of elements and trace metals across the sediment-water interface can be a major contribution to ocean water. Four marine sediment profiles (ODP leg 167 sites 1011, 1017, 1018 and 1020)were examined to evaluate and quantify the biotic and abiotic reaction networks and fluxes that occur in deep marine sediments. We compared biogeochemical processes across a gradient of sulfate reduction (SR) rates with the objective of studying the processes that control these rates and how they affect major elements as well as trace metal redistribution. The rates of sulfate reduction, methanogenesis and anaerobic methane oxidation (AMO) were constrained using a multicomponent reactive transport model (CrunchFlow). Constraints for the model include: sediment and pore water concentrations, as well as %CaCO3, %biogenic silica, wt% carbon and δ13C of total organic carbon (TOC), particulate organic matter (POC) and mineral associated carbon (MAC). The sites are distinguished by the depth of AMO: a shallow zone is observed at sites 1018 (9 to 19 meters composite depth (mcd)) and 1017 (19 to 30 mcd), while deeper zones occur at sites 1011 (56 to 76 mcd) and 1020 (101 to 116 mcd). Sulfate reduction rates at the shallow AMO sites are on the order 1x10-16 mol/L/yr, much faster than rates in the deeper zone sulfate reduction (1-3x10-17 mol/L/yr), as expected. The dissolved metal ion concentrations varied between the sites, with Fe (0.01-7 μM) and Mn (0.01-57 μM) concentrations highest at Site 1020 and lowest at site 1017. The highest Fe and Mn concentrations occurred at various depths, and were not directly correlated with the rates of sulfate reduction and the maximum alkalinity values. The main processes that control cycling of Fe are the production of sulfide from sulfate reduction and the distribution of Fe-oxides. The Mn distribution

  20. Polymer complexes.. XXXX. Supramolecular assembly on coordination models of mixed-valence-ligand poly[1-acrylamido-2-(2-pyridyl)ethane] complexes

    Science.gov (United States)

    El-Sonbati, A. Z.; El-Bindary, A. A.; Diab, M. A.

    2003-02-01

    The build-up of polymer metallic supramolecules based on homopolymer (1-acrylamido-2-(2-pyridyl)ethane (AEPH)) and ruthenium, rhodium, palladium as well as platinum complexes has been pursued with great interest. The homopolymer shows three types of coordination behaviour. In the mixed valence paramagnetic trinuclear polymer complexes [( 11)+( 12)] in the paper and in mononuclear polymer complexes ( 1)-( 5) it acts as a neutral bidentate ligand coordinating through the N-pyridine and NH-imino atoms, while in the mixed ligand diamagnetic poly-chelates, which are obtained from the reaction of AEPH with PdX 2 and KPtCl 4 in the presence of N-heterocyclic base consisting of polymer complexes ( 9)+( 10), and in monouclear compounds ( 6)-( 8), it behaves as a monobasic bidentate ligand coordinating through the same donor atoms. In mononuclear compounds ( 13)+( 14) it acts as a monobasic and neutral bidentate ligand coordinating only through the same donor atoms. Monomeric distorted octahedral or trimeric chlorine-bridged, approximately octahedral structures are proposed for these polymer complexes. The poly-chelates are of 1:1, 1:2 and 3:2 (metal-homopolymer) stoichiometry and exhibit six coordination. The values of ligand field parameters were calculated. The homopolymer and their polymer complexes have been characterized physicochemically.

  1. Towards ligand docking including explicit interface water molecules.

    Directory of Open Access Journals (Sweden)

    Gordon Lemmon

    Full Text Available Small molecule docking predicts the interaction of a small molecule ligand with a protein at atomic-detail accuracy including position and conformation the ligand but also conformational changes of the protein upon ligand binding. While successful in the majority of cases, docking algorithms including RosettaLigand fail in some cases to predict the correct protein/ligand complex structure. In this study we show that simultaneous docking of explicit interface water molecules greatly improves Rosetta's ability to distinguish correct from incorrect ligand poses. This result holds true for both protein-centric water docking wherein waters are located relative to the protein binding site and ligand-centric water docking wherein waters move with the ligand during docking. Protein-centric docking is used to model 99 HIV-1 protease/protease inhibitor structures. We find protease inhibitor placement improving at a ratio of 9:1 when one critical interface water molecule is included in the docking simulation. Ligand-centric docking is applied to 341 structures from the CSAR benchmark of diverse protein/ligand complexes [1]. Across this diverse dataset we see up to 56% recovery of failed docking studies, when waters are included in the docking simulation.

  2. Local biotic adaptation of trees and shrubs to plant neighbors

    Science.gov (United States)

    Grady, Kevin C.; Wood, Troy E.; Kolb, Thomas E.; Hersch-Green, Erika; Shuster, Stephen M.; Gehring, Catherine A.; Hart, Stephen C.; Allan, Gerard J.; Whitham, Thomas G.

    2017-01-01

    Natural selection as a result of plant–plant interactions can lead to local biotic adaptation. This may occur where species frequently interact and compete intensely for resources limiting growth, survival, and reproduction. Selection is demonstrated by comparing a genotype interacting with con- or hetero-specific sympatric neighbor genotypes with a shared site-level history (derived from the same source location), to the same genotype interacting with foreign neighbor genotypes (from different sources). Better genotype performance in sympatric than allopatric neighborhoods provides evidence of local biotic adaptation. This pattern might be explained by selection to avoid competition by shifting resource niches (differentiation) or by interactions benefitting one or more members (facilitation). We tested for local biotic adaptation among two riparian trees, Populus fremontii and Salix gooddingii, and the shrub Salix exigua by transplanting replicated genotypes from multiple source locations to a 17 000 tree common garden with sympatric and allopatric treatments along the Colorado River in California. Three major patterns were observed: 1) across species, 62 of 88 genotypes grew faster with sympatric neighbors than allopatric neighbors; 2) these growth rates, on an individual tree basis, were 44, 15 and 33% higher in sympatric than allopatric treatments for P. fremontii, S. exigua and S. gooddingii, respectively, and; 3) survivorship was higher in sympatric treatments for P. fremontiiand S. exigua. These results support the view that fitness of foundation species supporting diverse communities and dominating ecosystem processes is determined by adaptive interactions among multiple plant species with the outcome that performance depends on the genetic identity of plant neighbors. The occurrence of evolution in a plant-community context for trees and shrubs builds on ecological evolutionary research that has demonstrated co-evolution among herbaceous taxa, and

  3. Citrus flush shoot ontogeny modulates biotic potential of Diaphorina citri.

    Science.gov (United States)

    Cifuentes-Arenas, Juan Camilo; de Goes, António; de Miranda, Marcelo Pedreira; Beattie, George Andrew Charles; Lopes, Silvio Aparecido

    2018-01-01

    The biology and behaviour of the psyllid Diaphorina citri Kuwayama (Hemiptera: Sternorrhyncha: Liviidae), the major insect vector of bacteria associated with huanglongbing, have been extensively studied with respect to host preferences, thermal requirements, and responses to visual and chemical volatile stimuli. However, development of the psyllid in relation to the ontogeny of immature citrus flush growth has not been clearly defined or illustrated. Such information is important for determining the timing and frequency of measures used to minimize populations of the psyllid in orchards and spread of HLB. Our objective was to study how flush ontogeny influences the biotic potential of the psyllid. We divided citrus flush growth into six stages within four developmental phases: emergence (V1), development (V2 and V3), maturation (V4 and V5), and dormancy (V6). Diaphorina citri oviposition and nymph development were assessed on all flush stages in a temperature controlled room, and in a screen-house in which ambient temperatures varied. Our results show that biotic potential of Diaphorina citri is not a matter of the size or the age of the flushes (days after budbreak), but the developmental stage within its ontogeny. Females laid eggs on flush V1 to V5 only, with the time needed to commence oviposition increasing with the increasing in flush age. Stages V1, V2 and V3 were most suitable for oviposition, nymph survival and development, and adult emergence, which showed evidence of protandry. Flush shoots at emerging and developmental phases should be the focus of any chemical or biological control strategy to reduce the biotic potential of D. citri, to protect citrus tree from Liberibacter infection and to minimize HLB dissemination.

  4. Dockomatic - automated ligand creation and docking.

    Science.gov (United States)

    Bullock, Casey W; Jacob, Reed B; McDougal, Owen M; Hampikian, Greg; Andersen, Tim

    2010-11-08

    The application of computational modeling to rationally design drugs and characterize macro biomolecular receptors has proven increasingly useful due to the accessibility of computing clusters and clouds. AutoDock is a well-known and powerful software program used to model ligand to receptor binding interactions. In its current version, AutoDock requires significant amounts of user time to setup and run jobs, and collect results. This paper presents DockoMatic, a user friendly Graphical User Interface (GUI) application that eases and automates the creation and management of AutoDock jobs for high throughput screening of ligand to receptor interactions. DockoMatic allows the user to invoke and manage AutoDock jobs on a single computer or cluster, including jobs for evaluating secondary ligand interactions. It also automates the process of collecting, summarizing, and viewing results. In addition, DockoMatic automates creation of peptide ligand .pdb files from strings of single-letter amino acid abbreviations. DockoMatic significantly reduces the complexity of managing multiple AutoDock jobs by facilitating ligand and AutoDock job creation and management.

  5. Dockomatic - automated ligand creation and docking

    Directory of Open Access Journals (Sweden)

    Hampikian Greg

    2010-11-01

    Full Text Available Abstract Background The application of computational modeling to rationally design drugs and characterize macro biomolecular receptors has proven increasingly useful due to the accessibility of computing clusters and clouds. AutoDock is a well-known and powerful software program used to model ligand to receptor binding interactions. In its current version, AutoDock requires significant amounts of user time to setup and run jobs, and collect results. This paper presents DockoMatic, a user friendly Graphical User Interface (GUI application that eases and automates the creation and management of AutoDock jobs for high throughput screening of ligand to receptor interactions. Results DockoMatic allows the user to invoke and manage AutoDock jobs on a single computer or cluster, including jobs for evaluating secondary ligand interactions. It also automates the process of collecting, summarizing, and viewing results. In addition, DockoMatic automates creation of peptide ligand .pdb files from strings of single-letter amino acid abbreviations. Conclusions DockoMatic significantly reduces the complexity of managing multiple AutoDock jobs by facilitating ligand and AutoDock job creation and management.

  6. PRO_LIGAND: an approach to de novo molecular design. 2. Design of novel molecules from molecular field analysis (MFA) models and pharmacophores.

    Science.gov (United States)

    Waszkowycz, B; Clark, D E; Frenkel, D; Li, J; Murray, C W; Robson, B; Westhead, D R

    1994-11-11

    A computational approach for molecular design, PRO_LIGAND, has been developed within the PROMETHEUS molecular design and simulation system in order to provide a unified framework for the de novo generation of diverse molecules which are either similar or complementary to a specified target. In this instance, the target is a pharmacophore derived from a series of active structures either by a novel interpretation of molecular field analysis data or by a pharmacophore-mapping procedure based on clique detection. After a brief introduction to PRO_LIGAND, a detailed description is given of the two pharmacophore generation procedures and their abilities are demonstrated by the elucidation of pharmacophores for steroid binding and ACE inhibition, respectively. As a further indication of its efficacy in aiding the rational drug design process, PRO_LIGAND is then employed to build novel organic molecules to satisfy the physicochemical constraints implied by the pharmacophores.

  7. Binding equilibrium and kinetics of membrane-anchored receptors and ligands in cell adhesion: Insights from computational model systems and theory

    Science.gov (United States)

    Weikl, Thomas R.; Hu, Jinglei; Xu, Guang-Kui; Lipowsky, Reinhard

    2016-01-01

    ABSTRACT The adhesion of cell membranes is mediated by the binding of membrane-anchored receptor and ligand proteins. In this article, we review recent results from simulations and theory that lead to novel insights on how the binding equilibrium and kinetics of these proteins is affected by the membranes and by the membrane anchoring and molecular properties of the proteins. Simulations and theory both indicate that the binding equilibrium constant K2D and the on- and off-rate constants of anchored receptors and ligands in their 2-dimensional (2D) membrane environment strongly depend on the membrane roughness from thermally excited shape fluctuations on nanoscales. Recent theory corroborated by simulations provides a general relation between K2D and the binding constant K3D of soluble variants of the receptors and ligands that lack the membrane anchors and are free to diffuse in 3 dimensions (3D). PMID:27294442

  8. Slowing global warming biotically - Options for the United States

    International Nuclear Information System (INIS)

    Anon.

    1991-01-01

    Each of the five biotic approaches introduced in Chapter 2 is applicable to some extent in the US. Taking US land-use characteristics into account, a menu of policy options tailored to US carbon storage opportunities is presented. Several of the options are capable of significantly reducing net US carbon emissions; several offer corollary benefits in areas other than global warming mitigation. The time frame and costs of the different options vary widely, although in most cases some level of implementation appears economically justified even without considering global warming. The approach, projected costs, and advantages of seven different policy options are profiled

  9. Correlation between intravoxel incoherent motion magnetic resonance imaging derived metrics and serum soluble CD40 ligand level in an embolic canine stroke model

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Xiao Quan; Wu, Chen Jiang; Lu, Shan Shan; Gao, Qian Qian; Zu, Qing Quan; Liu, Xing Long; Shi, Hai Bin; Liu, Sheng [Dept. of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing (China)

    2017-09-15

    To determine the relationship between intravoxel incoherent motion (IVIM) imaging derived quantitative metrics and serum soluble CD40 ligand (sCD40L) level in an embolic canine stroke model. A middle cerebral artery occlusion model was established in 24 beagle dogs. Experimental dogs were divided into low- and high-sCD40L group according to serum sCD40L level at 4.5 hours after establishing the model. IVIM imaging was scanned at 4.5 hours after model establishment using 10 b values ranging from 0 to 900 s/mm{sup 2}. Quantitative metrics diffusion coefficient (D), pseudodiffusion coefficient (D{sup *}), and perfusion fraction (f) of ischemic lesions were calculated. Quantitative metrics of ischemic lesions were normalized by contralateral hemisphere using the following formula: normalized D = D{sub stroke} / D{sub contralateral}. Differences in IVIM metrics between the low- and high-sCD40L groups were compared using t test. Pearson's correlation analyses were performed to determine the relationship between IVIM metrics and serum sCD40L level. The high-sCD40L group showed significantly lower f and normalized f values than the low-sCD40L group (f, p < 0.001; normalized f, p < 0.001). There was no significant difference in D{sup *}, normalized D{sup *}, D, or normalized D value between the two groups (All p > 0.05). Both f and normalized f values were negatively correlated with serum sCD40L level (f, r = −0.789, p < 0.001; normalized f, r = −0.823, p < 0.001). However, serum sCD40L level had no significant correlation with D{sup *}, normalized D{sup *}, D, or normalized D (All p > 0.05). The f value derived from IVIM imaging was negatively correlated with serum sCD40L level. f value might serve as a potential imaging biomarker to assess the formation of microvascular thrombosis in hyperacute period of ischemic stroke.

  10. Modelling the magnetic behaviour of square-pyramidal Co(II)5 aggregates: tuning SMM behaviour through variations in the ligand shell.

    Science.gov (United States)

    Klöwer, Frederik; Lan, Yanhua; Nehrkorn, Joscha; Waldmann, Oliver; Anson, Christopher E; Powell, Annie K

    2009-07-27

    Three new mu4-bridged Co(II)5 clusters with similar core motifs have been synthesised with the use of N-tert-butyldiethanolamine (tbdeaH2) and pivalic acid (piv): [Co(II)5(mu4-N3)(tbdea)2(mu-piv)4(piv)(CH3CN)2].CH3CN (1), [Co(II)5(mu4-Cl)(Cl)(tbdea)2(mu-piv)4(pivH)2] (2) and [Co(II)5(mu4-N3)(Cl)(tbdea)2(mu-piv)4(pivH)2] (3). Magnetic measurements were performed for all three compounds. It was found that while the chloride-bridged cluster 2 does not show an out-of-phase signal, which excludes single-molecule magnet (SMM) behaviour, the azide-bridged compounds 1 and 3 show out-of-phase signals as well as frequency dependence of the ac susceptibility, as expected for SMMs. We confirmed that 1 is a SMM with zero-field quantum tunnelling of the magnetisation at 1.8 K. Compound 3 is likely a SMM with a blocking temperature well below 1.8 K. We established a physical model to fit the chiT versus T and M versus B curves of the three compounds to reproduce the observed SMM trend. The analysis showed that small changes in the ligand shell modify not only the magnitude of exchange constants, but also affect the J and g matrices in a non-trivial way.

  11. Biotic Stress Shifted Structure and Abundance of Enterobacteriaceae in the Lettuce Microbiome

    Science.gov (United States)

    Erlacher, Armin; Cardinale, Massimiliano; Grube, Martin; Berg, Gabriele

    2015-01-01

    Lettuce cultivars are not only amongst the most popular vegetables eaten raw, they are also involved in severe pathogen outbreaks world-wide. While outbreaks caused by Enterobacteriaceae species are well-studied, less is known about their occurrence in natural environments as well as the impact of biotic stress. Here, we studied the ecology of the human health-relevant bacterial family Enterobacteriaceae and assessed the impact of biotic disturbances by a soil-borne phytopathogenic fungus and Gastropoda on their structure and abundance in mesocosm and pot experiments. Using a polyphasic approach including network analyses of 16S rRNA gene amplicon libraries, quantitative PCR and complementary fluorescence in situ hybridization (FISH) microscopy we found substantial yet divergent Enterobacteriaceae communities. A similar spectrum of 14 genera was identified from rhizo- and phyllospheres but the abundance of Enterobacteriaceae was on average 3fold higher in phyllosphere samples. Both stress factors shifted the bacterial community of the leaf habitat, characterized by increases of species abundance and diversity. For the rhizosphere, we observed significant structural shifts of Enterobacteriaceae communities but also a high degree of resilience. These results could be confirmed by FISH microscopy but it was difficult to visualize phyllosphere communities. Additional inoculation experiments with Escherichia coli as model revealed their presence below the wax layer as well as in the endosphere of leaves. The observed presence influenced by stress factors and the endophytic life style of Enterobacteriaceae on lettuce can be an important aspect in relation to human health. PMID:25714833

  12. Biotic stress shifted structure and abundance of Enterobacteriaceae in the lettuce microbiome.

    Science.gov (United States)

    Erlacher, Armin; Cardinale, Massimiliano; Grube, Martin; Berg, Gabriele

    2015-01-01

    Lettuce cultivars are not only amongst the most popular vegetables eaten raw, they are also involved in severe pathogen outbreaks world-wide. While outbreaks caused by Enterobacteriaceae species are well-studied, less is known about their occurrence in natural environments as well as the impact of biotic stress. Here, we studied the ecology of the human health-relevant bacterial family Enterobacteriaceae and assessed the impact of biotic disturbances by a soil-borne phytopathogenic fungus and Gastropoda on their structure and abundance in mesocosm and pot experiments. Using a polyphasic approach including network analyses of 16S rRNA gene amplicon libraries, quantitative PCR and complementary fluorescence in situ hybridization (FISH) microscopy we found substantial yet divergent Enterobacteriaceae communities. A similar spectrum of 14 genera was identified from rhizo- and phyllospheres but the abundance of Enterobacteriaceae was on average 3fold higher in phyllosphere samples. Both stress factors shifted the bacterial community of the leaf habitat, characterized by increases of species abundance and diversity. For the rhizosphere, we observed significant structural shifts of Enterobacteriaceae communities but also a high degree of resilience. These results could be confirmed by FISH microscopy but it was difficult to visualize phyllosphere communities. Additional inoculation experiments with Escherichia coli as model revealed their presence below the wax layer as well as in the endosphere of leaves. The observed presence influenced by stress factors and the endophytic life style of Enterobacteriaceae on lettuce can be an important aspect in relation to human health.

  13. Biotic stress shifted structure and abundance of Enterobacteriaceae in the lettuce microbiome.

    Directory of Open Access Journals (Sweden)

    Armin Erlacher

    Full Text Available Lettuce cultivars are not only amongst the most popular vegetables eaten raw, they are also involved in severe pathogen outbreaks world-wide. While outbreaks caused by Enterobacteriaceae species are well-studied, less is known about their occurrence in natural environments as well as the impact of biotic stress. Here, we studied the ecology of the human health-relevant bacterial family Enterobacteriaceae and assessed the impact of biotic disturbances by a soil-borne phytopathogenic fungus and Gastropoda on their structure and abundance in mesocosm and pot experiments. Using a polyphasic approach including network analyses of 16S rRNA gene amplicon libraries, quantitative PCR and complementary fluorescence in situ hybridization (FISH microscopy we found substantial yet divergent Enterobacteriaceae communities. A similar spectrum of 14 genera was identified from rhizo- and phyllospheres but the abundance of Enterobacteriaceae was on average 3fold higher in phyllosphere samples. Both stress factors shifted the bacterial community of the leaf habitat, characterized by increases of species abundance and diversity. For the rhizosphere, we observed significant structural shifts of Enterobacteriaceae communities but also a high degree of resilience. These results could be confirmed by FISH microscopy but it was difficult to visualize phyllosphere communities. Additional inoculation experiments with Escherichia coli as model revealed their presence below the wax layer as well as in the endosphere of leaves. The observed presence influenced by stress factors and the endophytic life style of Enterobacteriaceae on lettuce can be an important aspect in relation to human health.

  14. Biotic games and cloud experimentation as novel media for biophysics education

    Science.gov (United States)

    Riedel-Kruse, Ingmar; Blikstein, Paulo

    2014-03-01

    First-hand, open-ended experimentation is key for effective formal and informal biophysics education. We developed, tested and assessed multiple new platforms that enable students and children to directly interact with and learn about microscopic biophysical processes: (1) Biotic games that enable local and online play using galvano- and photo-tactic stimulation of micro-swimmers, illustrating concepts such as biased random walks, Low Reynolds number hydrodynamics, and Brownian motion; (2) an undergraduate course where students learn optics, electronics, micro-fluidics, real time image analysis, and instrument control by building biotic games; and (3) a graduate class on the biophysics of multi-cellular systems that contains a cloud experimentation lab enabling students to execute open-ended chemotaxis experiments on slimemolds online, analyze their data, and build biophysical models. Our work aims to generate the equivalent excitement and educational impact for biophysics as robotics and video games have had for mechatronics and computer science, respectively. We also discuss how scaled-up cloud experimentation systems can support MOOCs with true lab components and life-science research in general.

  15. AMPA receptor ligands

    DEFF Research Database (Denmark)

    Strømgaard, Kristian; Mellor, Ian

    2004-01-01

    Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player in the f......Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player...... in the formation of memory. Hence, ligands affecting AMPARs are highly important for the study of the structure and function of this receptor, and in this regard polyamine-based ligands, particularly polyamine toxins, are unique as they selectively block Ca2+ -permeable AMPARs. Indeed, endogenous intracellular...

  16. Radiobiology with DNA ligands

    International Nuclear Information System (INIS)

    Weinreich, R.; Argentini, M.; Guenther, I.; Koziorowski, J.; Larsson, B.; Nievergelt-Egido, M.C.; Salt, C.; Wyer, L.; Dos Santos, D.F.; Hansen, H.J.

    1997-01-01

    The paper deals with the following topics: labelling of DNA ligands and other tumour-affinic compounds with 4.15-d 124 I, radiotoxicity of Hoechst 33258 and 33342 and of iodinated Hoechst 33258 in cell cultures, preparation of 76 Br-, 123 I-, and 221 At-labelled 5-halo-2'-deoxyuridine, chemical syntheses of boron derivatives of Hoechst 33258.III., Gadolinium neutron capture therapy

  17. Decision-tree model for health economic comparison of two long-acting somatostatin receptor ligand devices in France, Germany, and the UK.

    Science.gov (United States)

    Marty, Rémi; Roze, Stéphane; Kurth, Hannah

    2012-01-01

    Long-acting somatostatin receptor ligands (SRL) with product-specific formulation and means of administration are injected periodically in patients with acromegaly and neuroendocrine tumors. A simple decision-tree model aimed at comparing cost savings with ready-to-use Somatuline Autogel(®) (lanreotide) and Sandostatin LAR(®) (octreotide) for the UK, France, and Germany. The drivers of cost savings studied were the reduction of time to administer as well as a reduced baseline risk of clogging during product administration reported for Somatuline Autogel(®). The decision-tree model assumed two settings for SRL administration, ie, by either hospital-based or community-based nurses. In the case of clogging, the first dose was assumed to be lost and a second injection performed. Successful injection depended on the probability of clogging. Direct medical costs were included. A set of scenarios were run, varying the cost drivers, such as the baseline risk of clogging, SRL administration time, and percentage of patients injected during a hospital stay. Costs per successful injection were less for Somatuline Autogel(®)/Depot, ranging from Euros (EUR) 13-45, EUR 52-108, and EUR 127-151, respectively, for France, Germany, and the UK. The prices for both long-acting SRL were the same in France, and cost savings came to 100% from differences other than drug prices. For Germany and the UK, the proportion of savings due to less clogging and shorter administration time was estimated to be around 32% and 20%, respectively. Based on low and high country-specific patient cohort size estimations of individuals eligible for SRL treatment among the patient population with acromegaly and neuroendocrine tumors, annual savings were estimated to be up to EUR 2,000,000 for France, EUR 6,000,000 for Germany, and EUR 7,000,000 for the UK. This model suggests that increasing usage of the Somatuline device for injection of SRL might lead to substantial savings for health care providers

  18. Spectroscopic investigations on the complexation of Cm(III) and Eu(III) with organic model ligands and their binding mode in human urine (in vitro)

    International Nuclear Information System (INIS)

    Heller, Anne

    2011-01-01

    In case of incorporation, trivalent actinides (An(III)) and lanthanides (Ln(III)) pose a serious health risk to humans. An(III) are artificial, highly radioactive elements which are mainly produced during the nuclear fuel cycle in nuclear power plants. Via hazardous accidents or nonprofessional storage of radioactive waste, they can be released in the environment and enter the human food chain. In contrast, Ln(III) are nonradioactive, naturally occurring elements with multiple applications in technique and medicine. Consequently it is possible that humans get in contact and incorporate both, An(III) and Ln(III). Therefore, it is of particular importance to elucidate the behaviour of these elements in the human body. While macroscopic processes such as distribution, accumulation and excretion are studied quite well, knowledge about the chemical binding form (speciation) of An(III) and Ln(III) in various body fluids is still sparse. In the present work, for the first time, the speciation of Cm(III) and Eu(III) in natural human urine (in vitro) has been investigated spectroscopically and the formed complex identified. For this purpose, also basic investigations on the complex formation of Cm(III) and Eu(III) in synthetic model urine as well as with the urinary relevant, organic model ligands urea, alanine, phenylalanine, threonine and citrate have been performed and the previously unknown complex stability constants determined. Finally, all experimental results were compared to literature data and predictions calculated by thermodynamic modelling. Since both, Cm(III) and Eu(III), exhibit unique luminescence properties, particularly the suitability of time-resolved laser-induced fluorescence spectroscopy (TRLFS) could be demonstrated as a method to investigate these metal ions in untreated, complex biofluids. The results of this work provide new scientific findings on the biochemical reactions of An(III) and Ln(III) in human body fluids on a molecular scale and

  19. Understanding the roles of ligand promoted dissolution, water column saturation and hydrological properties on intense basalt weathering using reactive transport and watershed-scale hydrologic modeling

    Science.gov (United States)

    Perez Fodich, A.; Walter, M. T.; Derry, L. A.

    2016-12-01

    The interaction of rocks with rainwater generates physical and chemical changes, which ultimately culminates in soil development. The addition of catalyzers such as plants, atmospheric gases and hydrological properties will result in more intense and/or faster weathering transformations. The intensity of weathering across the Island of Hawaii is strongly correlated with exposure age and time-integrated precipitation. Intense weathering has resulted from interaction between a thermodynamically unstable lithology, high water/rock ratios, atmospheric gases (O2, CO2) and biota as an organic acid and CO2 producer. To further investigate the role of different weathering agents we have developed 1-D reactive transport models (RTM) to understand mineralogical and fluid chemistry changes in the initially basaltic porous media. The initial meso-scale heterogeneity of porosity makes it difficult for RTMs to capture changes in runoff/groundwater partitioning. Therefore, hydraulic properties (hydraulic conductivity and aquifer depth) are modeled as a watershed parameter appropriate for this system where sub-surface hydraulic data is scarce(1). Initial results agree with field data in a broad sense: different rainfall regimes and timescales show depletion of mobile cations, increasingly low pH, congruent dissolution of olivine and pyroxene, incongruent dissolution of plagioclase and basaltic glass, precipitation of non-crystalline allophane and ferrihydrite, and porosity changes due to dissolution and precipitation of minerals; ultimately Al and Fe are also exported from the system. RTM is used to examine the roles of unsaturation in the soil profile, ligand promoted dissolution of Al- and Fe-bearing phases, and Fe-oxide precipitation at the outcrop scale. Also, we aim to test the use of recession flow analysis to model watershed-scale hydrological properties to extrapolate changes in the runoff/groundwater partitioning. The coupling between weathering processes and hydrologic

  20. Regulation of Translation Initiation under Biotic and Abiotic Stresses

    Directory of Open Access Journals (Sweden)

    Ana B. Castro-Sanz

    2013-02-01

    Full Text Available Plants have developed versatile strategies to deal with the great variety of challenging conditions they are exposed to. Among them, the regulation of translation is a common target to finely modulate gene expression both under biotic and abiotic stress situations. Upon environmental challenges, translation is regulated to reduce the consumption of energy and to selectively synthesize proteins involved in the proper establishment of the tolerance response. In the case of viral infections, the situation is more complex, as viruses have evolved unconventional mechanisms to regulate translation in order to ensure the production of the viral encoded proteins using the plant machinery. Although the final purpose is different, in some cases, both plants and viruses share common mechanisms to modulate translation. In others, the mechanisms leading to the control of translation are viral- or stress-specific. In this paper, we review the different mechanisms involved in the regulation of translation initiation under virus infection and under environmental stress in plants. In addition, we describe the main features within the viral RNAs and the cellular mRNAs that promote their selective translation in plants undergoing biotic and abiotic stress situations.

  1. PLASS: Protein-ligand affinity statistical score a knowledge-based force-field model of interaction derived from the PDB

    Science.gov (United States)

    Ozrin, V. D.; Subbotin, M. V.; Nikitin, S. M.

    2004-04-01

    We have developed PLASS (Protein-Ligand Affinity Statistical Score), a pair-wise potential of mean-force for rapid estimation of the binding affinity of a ligand molecule to a protein active site. This scoring function is derived from the frequency of occurrence of atom-type pairs in crystallographic complexes taken from the Protein Data Bank (PDB). Statistical distributions are converted into distance-dependent contributions to the Gibbs free interaction energy for 10 atomic types using the Boltzmann hypothesis, with only one adjustable parameter. For a representative set of 72 protein-ligand structures, PLASS scores correlate well with the experimentally measured dissociation constants: a correlation coefficient R of 0.82 and RMS error of 2.0 kcal/mol. Such high accuracy results from our novel treatment of the volume correction term, which takes into account the inhomogeneous properties of the protein-ligand complexes. PLASS is able to rank reliably the affinity of complexes which have as much diversity as in the PDB.

  2. Model studies of the Cu(B) site of cytochrome c oxidase utilizing a Zn(II) complex containing an imidazole-phenol cross-linked ligand.

    Science.gov (United States)

    Pesavento, Russell P; Pratt, Derek A; Jeffers, Jerry; van der Donk, Wilfred A

    2006-07-21

    Cytochrome c oxidase, the enzyme complex responsible for the four-electron reduction of O2 to H2O, contains an unusual histidine-tyrosine cross-link in its bimetallic heme a3-CuB active site. We have synthesised an unhindered, tripodal chelating ligand, BPAIP, containing the unusual ortho-imidazole-phenol linkage, which mimics the coordination environment of the CuB center. The ligand was used to investigate the physicochemical (pKa, oxidation potential) and coordination properties of the imidazole-phenol linkage when bound to a dication. Zn(II) coordination lowers the pKa of the phenol by 0.6 log units, and increases the potential of the phenolate/phenoxyl radical couple by approximately 50 mV. These results are consistent with inductive withdrawal of electron density from the phenolic ring. Spectroscopic data and theoretical calculations (DFT) were used to establish that the cationic complex [Zn(BPAIP)Br]+ has an axially distorted trigonal bipyramidal structure, with three coordinating nitrogen ligands (two pyridine and one imidazole) occupying the equatorial plane and the bromide and the tertiary amine nitrogen of the tripod in the axial positions. Interestingly, the Zn-Namine bonding interaction is weak or absent in [Zn(BPAIP)Br]+ and the complex gains stability in basic solutions, as indicated by 1H NMR spectroscopy. These observations are supported by theoretical calculations (DFT), which suggest that the electron-donating capacity of the equatorial imidazole ligand can be varied by modulation of the protonation and/or redox state of the cross-linked phenol. Deprotonation of the phenol makes the equatorial imidazole a stronger sigma-donor, resulting in an increased Zn-Nimd interaction and thereby leading to distortion of the axial ligand axis toward a more tetrahedral geometry.

  3. Differentiating biotic from abiotic methane genesis in hydrothermally active planetary surfaces.

    Science.gov (United States)

    Oze, Christopher; Jones, L Camille; Goldsmith, Jonas I; Rosenbauer, Robert J

    2012-06-19

    Molecular hydrogen (H(2)) is derived from the hydrothermal alteration of olivine-rich planetary crust. Abiotic and biotic processes consume H(2) to produce methane (CH(4)); however, the extent of either process is unknown. Here, we assess the temporal dependence and limit of abiotic CH(4) related to the presence and formation of mineral catalysts during olivine hydrolysis (i.e., serpentinization) at 200 °C and 0.03 gigapascal. Results indicate that the rate of CH(4) production increases to a maximum value related to magnetite catalyzation. By identifying the dynamics of CH(4) production, we kinetically model how the H(2) to CH(4) ratio may be used to assess the origin of CH(4) in deep subsurface serpentinization systems on Earth and Mars. Based on our model and available field data, low H(2)/CH(4) ratios (less than approximately 40) indicate that life is likely present and active.

  4. Considerations in forecasting the demand for carbon sequestration and biotic storage technologies

    Energy Technology Data Exchange (ETDEWEB)

    Trexler, M.C. [Trexler and Associates, Inc., Portland, OR (United States)

    1997-12-31

    The Intergovernmental Panel on Climate Change (IPCC) has identified forestry and other land-use based mitigation measures as possible sources and sinks of greenhouse gases. An overview of sequestration and biotic storage is presented, and the potential impacts of the use of carbon sequestration as a mitigation technology are briefly noted. Carbon sequestration is also compare to other mitigation technologies. Biotic mitigation technologies are concluded to be a legitimate and potentially important part of greenhouse gas mitigation due to their relatively low costs, ancillary benefits, and climate impact. However, not all biotic mitigation techniques perfectly match the idealized definition of a mitigation measure, and policies are becoming increasingly biased against biotic technologies.

  5. Superior serum half life of albumin tagged TNF ligands

    International Nuclear Information System (INIS)

    Mueller, Nicole; Schneider, Britta; Pfizenmaier, Klaus; Wajant, Harald

    2010-01-01

    Due to their immune stimulating and apoptosis inducing properties, ligands of the TNF family attract increasing interest as therapeutic proteins. A general limitation of in vivo applications of recombinant soluble TNF ligands is their notoriously rapid clearance from circulation. To improve the serum half life of the TNF family members TNF, TWEAK and TRAIL, we genetically fused soluble variants of these molecules to human serum albumin (HSA). The serum albumin-TNF ligand fusion proteins were found to be of similar bioactivity as the corresponding HSA-less counterparts. Upon intravenous injection (i.v.), serum half life of HSA-TNF ligand fusion proteins, as determined by ELISA, was around 15 h as compared to approximately 1 h for all of the recombinant control TNF ligands without HSA domain. Moreover, serum samples collected 6 or 24 h after i.v. injection still contained high TNF ligand bioactivity, demonstrating that there is only limited degradation/inactivation of circulating HSA-TNF ligand fusion proteins in vivo. In a xenotransplantation model, significantly less of the HSA-TRAIL fusion protein compared to the respective control TRAIL protein was required to achieve inhibition of tumor growth indicating that the increased half life of HSA-TNF ligand fusion proteins translates into better therapeutic action in vivo. In conclusion, our data suggest that genetic fusion to serum albumin is a powerful and generally applicable mean to improve bioavailability and in vivo activity of TNF ligands.

  6. Bexarotene ligand pharmaceuticals.

    Science.gov (United States)

    Hurst, R E

    2000-12-01

    Bexarotene (LGD-1069), from Ligand, was the first retinoid X receptor (RXR)-selective, antitumor retinoid to enter clinical trials. The company launched the drug for the treatment of cutaneous T-cell lymphoma (CTCL), as Targretin capsules, in the US in January 2000 [359023]. The company filed an NDA for Targretin capsules in June 1999, and for topical gel in December 1999 [329011], [349982] specifically for once-daily oral administration for the treatment of patients with early-stage CTCL who have not tolerated other therapies, patients with refractory or persistent early stage CTCL and patients with refractory advanced stage CTCL. The FDA approved Targretin capsules at the end of December 1999 for once-daily oral treatment of all stages of CTCL in patients refractory to at least one prior systemic therapy, at an initial dose of 300 mg/m2/day. After an NDA was submitted in December 1999 for Targretin gel, the drug received Priority Review status for use as a treatment of cutaneous lesions in patients with stage IA, IB or IIA CTCL [354836]. The FDA issued an approvable letter in June 2000, and granted marketing clearance for CTCL in the same month [370687], [372768], [372769], [373279]. Ligand had received Orphan Drug designation for this indication [329011]. At the request of the FDA, Ligand agreed to carry out certain post-approval phase IV and pharmacokinetic studies [351604]. The company filed an MAA with the EMEA for Targretin Capsules to treat lymphoma in November 1999 [348944]. The NDA for Targretin gel is based on a multicenter phase III trial that was conducted in the US, Canada, Europe and Australia involving 50 patients and a multicenter phase I/II clinical program involving 67 patients. Targretin gel was evaluated for the treatment of patients with early stage CTCL (IA-IIA) who were refractory to, intolerant to, or reached a response plateau for at least 6 months on at least two prior therapies. Efficacy results exceeded the protocol-defined response

  7. Invasion by non-native brook trout in Panther Creek, Idaho: Roles of habitat quality, biotic resistance, and connectivity to source habitats

    Science.gov (United States)

    Joseph R. Benjamin; Jason B. Dunham; Matthew R. Dare

    2007-01-01

    Theoretical models and empirical evidence suggest that the invasion of nonnative species in freshwaters is facilitated through the interaction of three factors: habitat quality, biotic resistance, and connectivity. We measured variables that represented each factor to determine which were associated with the occurrence of nonnative brook trout Salvelinus...

  8. Views on Biotic Nature and the Idea of Sustainable Development

    Science.gov (United States)

    Łepko, Zbigniew

    2017-12-01

    The search for balance between humankind's civilisational aspirations and the durable protection of nature is conditioned by contemporaneous views of biotic nature. Of particular importance in this regard are physiocentric and physiological views that may be set against one another. The first of these was presented by Hans Jonas, the second by Lothar Schäfer. This paper does not confine itself to setting one view against the other, but rather sets minimum conditions for cooperation between their promoters in the interests of balance between the aspirations of the present generation and those of future generations. Both views of nature are in their own way conducive to a break with the illusion present in some areas of the modern natural sciences - that nature is a boundless area of are inexhaustible resources.

  9. Hydro-chemical study of the evolution of interstellar pre-biotic molecules during the collapse of molecular clouds

    International Nuclear Information System (INIS)

    Majumdar, Liton; Das, Ankan; Chakrabarti, Sandip K.; Chakrabarti, Sonali

    2012-01-01

    One of the stumbling blocks for studying the evolution of interstellar molecules is the lack of adequate knowledge about the rate coefficients of various reactions which take place in the interstellar medium and molecular clouds. Some theoretical models of rate coefficients do exist in the literature for computing abundances of complex pre-biotic molecules. So far these have been used to study the abundances of these molecules in space. However, in order to obtain more accurate final compositions in these media, we have calculated the rate coefficients for the formation of some of the most important interstellar pre-biotic molecules by using quantum chemical theory. We use these rates inside our hydro-chemical model to examine the chemical evolution and final abundances of pre-biotic species during the collapsing phase of a proto-star. We find that a significant amount of various pre-biotic molecules could be produced during the collapse phase of a proto-star. We thoroughly study the formation of these molecules via successive neutral-neutral and radical-radical/radical-molecular reactions. We present the time evolution of the chemical species with an emphasis on how the production of these molecules varies with the depth of a cloud. We compare the formation of adenine in interstellar space using our rate-coefficients and using those obtained from existing theoretical models. Formation routes of the pre-biotic molecules are found to be highly dependent on the abundances of the reactive species and the rate coefficients involved in the reactions. The presence of grains strongly affects the abundances of the gas phase species. We also carry out a comparative study between different pathways available for the synthesis of adenine, alanine, glycine and other molecules considered in our network. Despite the huge abundances of the neutral reactive species, production of adenine is found to be strongly dominated by the radical-radical/radical-molecular reaction pathways

  10. Biotic homogenization of three insect groups due to urbanization.

    Science.gov (United States)

    Knop, Eva

    2016-01-01

    Cities are growing rapidly, thereby expected to cause a large-scale global biotic homogenization. Evidence for the homogenization hypothesis is mostly derived from plants and birds, whereas arthropods have so far been neglected. Here, I tested the homogenization hypothesis with three insect indicator groups, namely true bugs, leafhoppers, and beetles. In particular, I was interested whether insect species community composition differs between urban and rural areas, whether they are more similar between cities than between rural areas, and whether the found pattern is explained by true species turnover, species diversity gradients and geographic distance, by non-native or specialist species, respectively. I analyzed insect species communities sampled on birch trees in a total of six Swiss cities and six rural areas nearby. In all indicator groups, urban and rural community composition was significantly dissimilar due to native species turnover. Further, for bug and leafhopper communities, I found evidence for large-scale homogenization due to urbanization, which was driven by reduced species turnover of specialist species in cities. Species turnover of beetle communities was similar between cities and rural areas. Interestingly, when specialist species of beetles were excluded from the analyses, cities were more dissimilar than rural areas, suggesting biotic differentiation of beetle communities in cities. Non-native species did not affect species turnover of the insect groups. However, given non-native arthropod species are increasing rapidly, their homogenizing effect might be detected more often in future. Overall, the results show that urbanization has a negative large-scale impact on the diversity specialist species of the investigated insect groups. Specific measures in cities targeted at increasing the persistence of specialist species typical for the respective biogeographic region could help to stop the loss of biodiversity. © 2015 John Wiley & Sons Ltd.

  11. The Genetics Underlying Natural Variation in the Biotic Interactions of Arabidopsis thaliana: The Challenges of Linking Evolutionary Genetics and Community Ecology.

    Science.gov (United States)

    Roux, F; Bergelson, J

    2016-01-01

    In the context of global change, predicting the responses of plant communities in an ever-changing biotic environment calls for a multipronged approach at the interface of evolutionary genetics and community ecology. However, our understanding of the genetic basis of natural variation involved in mediating biotic interactions, and associated adaptive dynamics of focal plants in their natural communities, is still in its infancy. Here, we review the genetic and molecular bases of natural variation in the response to biotic interactions (viruses, bacteria, fungi, oomycetes, herbivores, and plants) in the model plant Arabidopsis thaliana as well as the adaptive value of these bases. Among the 60 identified genes are a number that encode nucleotide-binding site leucine-rich repeat (NBS-LRR)-type proteins, consistent with early examples of plant defense genes. However, recent studies have revealed an extensive diversity in the molecular mechanisms of defense. Many types of genetic variants associate with phenotypic variation in biotic interactions, even among the genes of large effect that tend to be identified. In general, we found that (i) balancing selection rather than directional selection explains the observed patterns of genetic diversity within A. thaliana and (ii) the cost/benefit tradeoffs of adaptive alleles can be strongly dependent on both genomic and environmental contexts. Finally, because A. thaliana rarely interacts with only one biotic partner in nature, we highlight the benefit of exploring diffuse biotic interactions rather than tightly associated host-enemy pairs. This challenge would help to improve our understanding of coevolutionary quantitative genetics within the context of realistic community complexity. © 2016 Elsevier Inc. All rights reserved.

  12. Comparison of in vivo binding properties of the 18-kDa translocator protein (TSPO) ligands [18F]PBR102 and [18F]PBR111 in a model of excitotoxin-induced neuroinflammation

    International Nuclear Information System (INIS)

    Callaghan, P.D.; Gregoire, M.C.; Wimberley, C.A.; Rahardjo, G.L.; Berghofer, P.J.; Zahra, D.; Pham, T.Q.; Jackson, T.; Wyatt, N.; Greguric, I.; Howell, N.R.; Loc'h, C.; Bourdier, T.; Mattner, F.; Katsifis, A.; Siegele, R.; Pastuovic, Z.

    2015-01-01

    The in vivo binding parameters of the novel imidazopyridine TSPO ligand [ 18 F]PBR102 were assessed and compared with those of [ 18 F]PBR111 in a rodent model of neuroinflammation. The validity of the key assumptions of the simplified reference tissue model (SRTM) for estimation of binding potential (BP) was determined, with validation against a two-tissue compartment model (2TC). Acute neuroinflammation was assessed 7 days after unilateral stereotaxic administration of (R,S)-α-amino-3-hydroxy-5-methyl-4-isoxazolopropionique (AMPA) in anaesthetized adult Wistar rats. Anaesthetized rats were implanted with a femoral arterial cannula then injected with a low mass of [ 18 F]PBR102 or [ 18 F]PBR111 and dynamic images were acquired over 60 min using an INVEON PET/CT camera. Another population of rats underwent the same PET protocol after pretreatment with a presaturating mass of the same unlabelled tracer (1 mg/kg) to assess the validity of the reference region for SRTM analysis. Arterial blood was sampled during imaging, allowing pharmacokinetic determination of radiotracer concentrations. Plasma activity concentration-time curves were corrected for unchanged tracer based on metabolic characterization experiments in a separate cohort of Wistar rats. The stability of neuroinflammation in both imaging cohorts was assessed by [ 125 I] CLINDE TSPO quantitative autoradiography, OX42/GFAP immunohistochemistry, Fluoro-Jade C histology, and elemental mapping using microparticle-induced x-ray emission spectroscopy. The BP of each ligand were assessed in the two cohorts of lesioned animals using both SRTM and a 2TC with arterial parent compound concentration, coupled with the results from the presaturation cohort for comparison and validation of the SRTM. The BPs of [ 18 F]PBR102 [ 18 F]PBR111 were equivalent, with improved signal-to-noise ratio and sensitivity compared with [ 11 C]PK11195. The presaturation study showed differences in the volume of distribution between the

  13. Modelling thermodynamic properties of lanthanide (LnL)3+ and actinide (AnL)3+ complexes with tridentate planar nitrogen ligands (L)

    International Nuclear Information System (INIS)

    Ionova, G.; Rabbe, C.; Charbonnel, M.C.; Hill, C.; Guillaumont, D.; Guillaumont, R.; Ionov, S.; Madic, C.

    2004-01-01

    We report here the results obtained from a systematic theoretical study on the thermodynamic properties of trivalent lanthanide (Ln) and actinide (An) complexes with chelating nitrogen tridentate ligands. The mechanism of chelation has been investigated and the role of cation dissolution is investigated through a comparison of the thermodynamic properties of solvated cations and complexes. The difference in thermodynamic properties of LnL and AnL complexes is analyzed. (authors)

  14. Determination of ligand binding modes in weak protein–ligand complexes using sparse NMR data

    Energy Technology Data Exchange (ETDEWEB)

    Mohanty, Biswaranjan; Williams, Martin L.; Doak, Bradley C.; Vazirani, Mansha; Ilyichova, Olga [Monash University, Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences (Australia); Wang, Geqing [La Trobe University, La Trobe Institute for Molecular Bioscience (Australia); Bermel, Wolfgang [Bruker Biospin GmbH (Germany); Simpson, Jamie S.; Chalmers, David K. [Monash University, Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences (Australia); King, Glenn F. [The University of Queensland, Institute for Molecular Bioscience (Australia); Mobli, Mehdi, E-mail: m.mobli@uq.edu.au [The University of Queensland, Centre for Advanced Imaging (Australia); Scanlon, Martin J., E-mail: martin.scanlon@monash.edu [Monash University, Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences (Australia)

    2016-11-15

    We describe a general approach to determine the binding pose of small molecules in weakly bound protein–ligand complexes by deriving distance constraints between the ligand and methyl groups from all methyl-containing residues of the protein. We demonstrate that using a single sample, which can be prepared without the use of expensive precursors, it is possible to generate high-resolution data rapidly and obtain the resonance assignments of Ile, Leu, Val, Ala and Thr methyl groups using triple resonance scalar correlation data. The same sample may be used to obtain Met {sup ε}CH{sub 3} assignments using NOESY-based methods, although the superior sensitivity of NOESY using [U-{sup 13}C,{sup 15}N]-labeled protein makes the use of this second sample more efficient. We describe a structural model for a weakly binding ligand bound to its target protein, DsbA, derived from intermolecular methyl-to-ligand nuclear Overhauser enhancements, and demonstrate that the ability to assign all methyl resonances in the spectrum is essential to derive an accurate model of the structure. Once the methyl assignments have been obtained, this approach provides a rapid means to generate structural models for weakly bound protein–ligand complexes. Such weak complexes are often found at the beginning of programs of fragment based drug design and can be challenging to characterize using X-ray crystallography.

  15. Zinc Bioavailability from Phytate-Rich Foods and Zinc Supplements. Modeling the Effects of Food Components with Oxygen, Nitrogen, and Sulfur Donor Ligands.

    Science.gov (United States)

    Tang, Ning; Skibsted, Leif H

    2017-10-04

    Aqueous solubility of zinc phytate (K sp = (2.6 ± 0.2) × 10 -47 mol 7 /L 7 ), essential for zinc bioavailability from plant foods, was found to decrease with increasing temperature corresponding to ΔH dis of -301 ± 22 kJ/mol and ΔS dis of -1901 ± 72 J/(mol K). Binding of zinc to phytate was found to be exothermic for the stronger binding site and endothermic for the weaker binding site. The solubility of the slightly soluble zinc citrate and insoluble zinc phytate was found to be considerably enhanced by the food components with oxygen donor, nitrogen donor, and sulfur donor ligands. The driving force for the enhanced solubility is mainly due to the complex formation between zinc and the investigated food components rather than ligand exchange and ternary complex formation as revealed by quantum mechanical calculations and isothermal titration calorimetry. Histidine and citrate are promising ligands for improving zinc absorption from phytate-rich foods.

  16. Early biotic stress detection in tomato ( Solanum lycopersicum ) by BVOC emissions

    NARCIS (Netherlands)

    Kasal-Slavik, Tina; Eschweiler, Julia; Kleist, Einhard; Mumm, Roland; Goldbach, Heiner E.; Schouten, Sander; Wildt, Jürgen

    2017-01-01

    We investigated impacts of early and mild biotic stress on Biogenic Volatile Organic Compounds (BVOC) emissions from tomato in order to test their potential for early (biotic) stress detection. Tomato plants were exposed to two common fungal pathogens, Botrytis cinerea and Oidium neolycopesici and

  17. Potential for biotic resistance from herbivores to tropical and subtropical plant invasions in aquatic ecosystems

    NARCIS (Netherlands)

    Petruzella, A.; Grutters, B.M.C.; Thomaz, S.M.; Bakker, E.S.

    2017-01-01

    Invasions of tropical and subtropical aquatic plants threaten biodiversity and cause ecological and economic impacts worldwide. An urgent question is whether native herbivores are able to inhibit the spread of these alien species thus providing biotic resistance. The potential for biotic resistance

  18. Identification of VDR Antagonists among Nuclear Receptor Ligands Using Virtual Screening

    Directory of Open Access Journals (Sweden)

    Kelly Teske

    2014-04-01

    Full Text Available Herein, we described the development of two virtual screens to identify new vitamin D receptor (VDR antagonists among nuclear receptor (NR ligands. Therefore, a database of 14330 nuclear receptor ligands and their NR affinities was assembled using the online available “Binding Database.” Two different virtual screens were carried out in conjunction with a reported VDR crystal structure applying a stringent and less stringent pharmacophore model to filter docked NR ligand conformations. The pharmacophore models were based on the spatial orientation of the hydroxyl functionalities of VDR's natural ligands 1,25(OH2D3 and 25(OH2D3. The first virtual screen identified 32 NR ligands with a calculated free energy of VDR binding of more than -6.0 kJ/mol. All but nordihydroguaiaretic acid (NDGA are VDR ligands, which inhibited the interaction between VDR and coactivator peptide SRC2-3 with an IC50 value of 15.8 μM. The second screen identified 162 NR ligands with a calculated free energy of VDR binding of more than -6.0 kJ/mol. More than half of these ligands were developed to bind VDR followed by ERα/β ligands (26%, TRα/β ligands (7%, and LxRα/β ligands (7%. The binding between VDR and ERα ligand H6036 as well as TRα/β ligand triiodothyronine and a homoserine analog thereof was confirmed by fluorescence polarization.

  19. Can we trace biotic dispersals back in time? Introducing backward flow connectivity

    Directory of Open Access Journals (Sweden)

    Alessandro Ferrarini

    2014-06-01

    Full Text Available Connectivity in ecology deals with the problem of how species dispersal will happen given actual landscape and species presence/absence over such landscape. Hence it can be considered a forward (ahead in time scientific problem. I observe here that a backward theory of connectivity could be of deep interest as well: given the actual species presence/absence on the landscape, where with the highest probability such species is coming from? In other words, can we trace biotic dispersals back in time? Recently I have introduced a modelling and theoretical approach to ecological connectivity that is alternative to circuit theory and is able to fix the weak point of the "from-to" connectivity approach. The proposed approach holds also for mountain and hilly landscapes. In addition, it doesn't assume any intention for a species to go from source points to sink ones, because the expected path for the species is determined locally (pixel by pixel by landscape features. In this paper, I introduce a new theoretical and modelling approach called "backward flow connectivity". While flow connectivity predicts future species dispersal by minimizing at each step the potential energy due to fictional gravity over a frictional landscape, backward flow connectivity does exactly the opposite, i.e. maximizes potential energy at each step sending back the species to higher levels of potential energy due to fictional gravity on the frictional landscape. Using backward flow connectivity, one has at hand a new tool to revert timeline of species dispersal, hence being able to trace backward biotic dispersals. With few modifications, the applications of backward flow connectivity can be countless, for instance tracing back-in-time not only plants and animals but also ancient human migrations and viral paths.

  20. Forest calcium depletion and biotic retention along a soil nitrogen gradient

    Science.gov (United States)

    Perakis, Steven S.; Sinkhorn, Emily R.; Catricala, Christina; Bullen, Thomas D.; Fitzpatrick, John A.; Hynicka, Justin D.; Cromack, Kermit

    2013-01-01

    High nitrogen (N) accumulation in terrestrial ecosystems can shift patterns of nutrient limitation and deficiency beyond N toward other nutrients, most notably phosphorus (P) and base cations (calcium [Ca], magnesium [Mg], and potassium [K]). We examined how naturally high N accumulation from a legacy of symbiotic N fixation shaped P and base cation cycling across a gradient of nine temperate conifer forests in the Oregon Coast Range. We were particularly interested in whether long-term legacies of symbiotic N fixation promoted coupled N and organic P accumulation in soils, and whether biotic demands by non-fixing vegetation could conserve ecosystem base cations as N accumulated. Total soil N (0–100 cm) pools increased nearly threefold across the N gradient, leading to increased nitrate leaching, declines in soil pH from 5.8 to 4.2, 10-fold declines in soil exchangeable Ca, Mg, and K, and increased mobilization of aluminum. These results suggest that long-term N enrichment had acidified soils and depleted much of the readily weatherable base cation pool. Soil organic P increased with both soil N and C across the gradient, but soil inorganic P, biomass P, and P leaching loss did not vary with N, implying that historic symbiotic N fixation promoted soil organic P accumulation and P sufficiency for non-fixers. Even though soil pools of Ca, Mg, and K all declined as soil N increased, only Ca declined in biomass pools, suggesting the emergence of Ca deficiency at high N. Biotic conservation and tight recycling of Ca increased in response to whole-ecosystem Ca depletion, as indicated by preferential accumulation of Ca in biomass and surface soil. Our findings support a hierarchical model of coupled N–Ca cycling under long-term soil N enrichment, whereby ecosystem-level N saturation and nitrate leaching deplete readily available soil Ca, stimulating biotic Ca conservation as overall supply diminishes. We conclude that a legacy of biological N fixation can increase N

  1. Screening of ligands for the Ullmann synthesis of electron-rich diaryl ethers.

    Science.gov (United States)

    Otto, Nicola; Opatz, Till

    2012-01-01

    In the search for new ligands for the Ullmann diaryl ether synthesis, permitting the coupling of electron-rich aryl bromides at relatively low temperatures, 56 structurally diverse multidentate ligands were screened in a model system that uses copper iodide in acetonitrile with potassium phosphate as the base. The ligands differed largely in their performance, but no privileged structural class could be identified.

  2. Ligand Depot: a data warehouse for ligands bound to macromolecules.

    Science.gov (United States)

    Feng, Zukang; Chen, Li; Maddula, Himabindu; Akcan, Ozgur; Oughtred, Rose; Berman, Helen M; Westbrook, John

    2004-09-01

    Ligand Depot is an integrated data resource for finding information about small molecules bound to proteins and nucleic acids. The initial release (version 1.0, November, 2003) focuses on providing chemical and structural information for small molecules found as part of the structures deposited in the Protein Data Bank. Ligand Depot accepts keyword-based queries and also provides a graphical interface for performing chemical substructure searches. A wide variety of web resources that contain information on small molecules may also be accessed through Ligand Depot. Ligand Depot is available at http://ligand-depot.rutgers.edu/. Version 1.0 supports multiple operating systems including Windows, Unix, Linux and the Macintosh operating system. The current drawing tool works in Internet Explorer, Netscape and Mozilla on Windows, Unix and Linux.

  3. Automated identification of crystallographic ligands using sparse-density representations

    International Nuclear Information System (INIS)

    Carolan, C. G.; Lamzin, V. S.

    2014-01-01

    A novel procedure for identifying ligands in macromolecular crystallographic electron-density maps is introduced. Density clusters in such maps can be rapidly attributed to one of 82 different ligands in an automated manner. A novel procedure for the automatic identification of ligands in macromolecular crystallographic electron-density maps is introduced. It is based on the sparse parameterization of density clusters and the matching of the pseudo-atomic grids thus created to conformationally variant ligands using mathematical descriptors of molecular shape, size and topology. In large-scale tests on experimental data derived from the Protein Data Bank, the procedure could quickly identify the deposited ligand within the top-ranked compounds from a database of candidates. This indicates the suitability of the method for the identification of binding entities in fragment-based drug screening and in model completion in macromolecular structure determination

  4. Pro biotic as Alternative to Antibiotic for Broiler Chicken fed Food Industrial Residual Oil

    International Nuclear Information System (INIS)

    EL-Faramawy, A.A.; El-Maghraby, A.F.; El-Danasoury, M.M.; Hussien, H.A.; Hegazy, E.S.

    2016-01-01

    This study aimed to evaluate the effect of pro biotic (some lactic acid bacteria) with different levels of food industrial residual oil in broiler commercial diets on growth performance, meat yield, internal organs, economical efficiency and performance index. One hundred and eighty one day old Cobb chicks (45 ± 0.4 g) were equally and randomly divided into 6 groups namely; the antibiotic with fresh oil (FO), the antibiotic with mixed oil (MO) [FO+RO ( 1:1 w/w)], the antibiotic with food industrial residual oil (RO), the pro biotic with FO, the pro biotic with MO and the pro biotic with RO. Virginiamycin, Phibro, USA (15 ppm), was the antibiotic, while a mixture of lactic acid bacteria is chosen as pro biotic. Both were added to the water. During the experiment which lasted for 42 days, the body weight, the feed intake and the mortality rate were recorded at 2, 4 and 6 weeks of age then the body weight gain, feed conversion ratio, economical efficiency and performance index were calculated. The results revealed that the average body weight, body weight gain and feed consumption significantly (P 0.05) while liver increased significantly (P<0.05) in pro biotic FO and gizzard in all pro biotic group and antibiotic MO. The highest performance index was observed in groups of birds treated with pro biotic with MO followed by birds treated with pro biotic FO without significant difference. It could be concluded that supplementation of pro biotic in broiler diet containing different levels of RO was economically more beneficial than antibiotic

  5. Metal-ligand interactions

    Science.gov (United States)

    Ervin, Kent M.

    Experimental studies of the interactions of small transition-metal cluster anions with carbonyl ligands are reviewed and compared with neutral and cationic clusters. Under thermal conditions, the reaction rates of transition-metal clusters with carbon monoxide are measured as a function of cluster size. Saturation limits for carbon monoxide addition can be related to the geometric structures of the clusters. Both energy-resolved threshold collision-induced dissociation experiments and time-resolved photodissociation experiments are used to measure metal-carbonyl binding energies. For platinum and palladium trimer anions, the carbonyl binding energies are assigned to different geometric binding sites. Platinum and palladium cluster anions catalyse the oxidation of carbon monoxide to carbon dioxide in a full catalytic cycle at thermal energies.

  6. Melatonin: functions and ligands.

    Science.gov (United States)

    Singh, Mahaveer; Jadhav, Hemant R

    2014-09-01

    Melatonin is a chronobiotic substance that acts as synchronizer by stabilizing bodily rhythms. Its synthesis occurs in various locations throughout the body, including the pineal gland, skin, lymphocytes and gastrointestinal tract (GIT). Its synthesis and secretion is controlled by light and dark conditions, whereby light decreases and darkness increases its production. Thus, melatonin is also known as the 'hormone of darkness'. Melatonin and analogs that bind to the melatonin receptors are important because of their role in the management of depression, insomnia, epilepsy, Alzheimer's disease (AD), diabetes, obesity, alopecia, migraine, cancer, and immune and cardiac disorders. In this review, we discuss the mechanism of action of melatonin in these disorders, which could aid in the design of novel melatonin receptor ligands. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Regulation mechanisms of the FLT3-ligand after irradiation

    International Nuclear Information System (INIS)

    Prat-Lepesant, M.

    2005-06-01

    The hematopoietic compartment is one of the most severely damaged after chemotherapy, radiotherapy or accidental irradiations. Whatever its origin, the resulting damage to the bone marrow remains difficult to evaluate. Thus, it would be of great interest to get a biological indicator of residual hematopoiesis in order to adapt the treatment to each clinical situation. Recent results indicated that the plasma Flt3 ligand concentration was increased in patients suffering from either acquired or induced aplasia, suggesting that Flt3 ligand might be useful as a biological indicator of bone marrow status. We thus followed in a mouse model as well as in several clinical situations the variations in plasma Flt3 ligand concentration, after either homogeneous or heterogeneous irradiations. These variations were correlated to the number of hematopoietic progenitors and to other parameters such as duration and depth of pancytopenia. The results indicated that the concentration of Flt3 ligand in the blood reflects the bone marrow status, and that the follow-up of plasma Flt3 ligand concentration could give predictive information about the bone marrow function and the duration and severity of pancytopenia and thrombocytopenia. Nevertheless, the clinical use of Flt3 ligand as a biological indicator of bone marrow damage require the knowledge of the mechanisms regulating the variations in plasma Flt3 ligand concentration. We thus developed a study in the mouse model. The results indicated that the variations in plasma Flt3 ligand variations were not solely due to a balance between its production by lymphoid cells and its consumption by hematopoietic cells. Moreover, we showed that T lymphocytes are not the main regulator of plasma Flt3 ligand concentration as previously suggested, and that other cell types, possibly including bone marrow stromal cells, might be strongly implicated. These results also suggest that the Flt3 ligand is a main systemic regulator of hematopoiesis

  8. Murine CMV Expressing the High Affinity NKG2D Ligand MULT-1: A Model for the Development of Cytomegalovirus-Based Vaccines

    Directory of Open Access Journals (Sweden)

    Lea Hiršl

    2018-05-01

    Full Text Available The development of a vaccine against human cytomegalovirus (CMV has been a subject of long-term medical interest. The research during recent years identified CMV as an attractive vaccine vector against infectious diseases and tumors. The immune response to CMV persists over a lifetime and its unique feature is the inflationary T cell response to certain viral epitopes. CMV encodes numerous genes involved in immunoevasion, which are non-essential for virus growth in vitro. The deletion of those genes results in virus attenuation in vivo, which enables us to dramatically manipulate its virulence and the immune response. We have previously shown that the murine CMV (MCMV expressing RAE-1γ, one of the cellular ligands for the NKG2D receptor, is highly attenuated in vivo but retains the ability to induce a strong CD8+ T cell response. Here, we demonstrate that recombinant MCMV expressing high affinity NKG2D ligand murine UL16 binding protein-like transcript (MULT-1 (MULT-1MCMV inserted in the place of its viral inhibitor is dramatically attenuated in vivo in a NK cell-dependent manner, both in immunocompetent adult mice and in immunologically immature newborns. MULT-1MCMV was more attenuated than the recombinant virus expressing RAE-1γ. Despite the drastic sensitivity to innate immune control, MULT-1MCMV induced an efficient CD8+ T cell response to viral and vectored antigens. By using in vitro assay, we showed that similar to RAE-1γMCMV, MULT-1 expressing virus provided strong priming of CD8+ T cells. Moreover, MULT-1MCMV was able to induce anti-viral antibodies, which after passing the transplacental barrier protect offspring of immunized mothers from challenge infection. Altogether, this study further supports the concept that CMV expressing NKG2D ligand possesses excellent characteristics to serve as a vaccine or vaccine vector.

  9. Ecosystem development in roadside grasslands: biotic control, plant–soil interactions and dispersal limitations

    Science.gov (United States)

    García-Palacios, Pablo; Bowker, Matthew A.; Maestre, Fernando T.; Soliveres, Santiago; Valladares, Fernando; Papadopoulos, Jorge; Escudero, Adrián

    2015-01-01

    Roadside grasslands undergoing secondary succession are abundant, and represent ecologically meaningful examples of novel, human-created ecosystems. Interactions between plant and soil communities (hereafter plant–soil interactions) are of major importance in understanding the role of biotic control in ecosystem functioning, but little is known about these links in the context of ecosystem restoration and succession. The assessment of the key biotic communities and interactions driving ecosystem development will help practitioners to better allocate the limited resources devoted to roadside grassland restoration. We surveyed roadside grasslands from three successional stages (0–2, 7–9 and > 20 years) in two Mediterranean regions of Spain. Structural equation modeling was used to evaluate how interactions between plants, biological soil crusts [BSCs], and soil microbial functional diversity [soil microorganisms] affect indicators of ecosystem development and restoration: plant similarity to the reference ecosystem, erosion control and soil C storage and N accumulation. Changes in plant community composition along the successional gradient exerted the strongest influence on these indicators. High BSC cover was associated with high soil stability, and high soil microbial functional diversity from late-successional stages was associated with high soil fertility. Contrary to our expectations, the indirect effects of plants, mediated by either BSCs or soil microorganisms, were very weak in both regions, suggesting a minor role for plant–soil interactions upon ecosystem development indicators over long periods. Our results suggest that natural vegetation dynamics effectively improved ecosystem development within a time frame of 20 years in the grasslands evaluated. They also indicate that this time could be shortened if management actions focus on: 1) maintain well-conserved natural areas close to roadsides to enhance plant compositional changes towards late

  10. Ecosystem development in roadside grasslands: Biotic control, plant-soil interactions, and dispersal limitations

    Science.gov (United States)

    Garcia-Palacios, P.; Bowker, M.A.; Maestre, F.T.; Soliveres, S.; Valladares, F.; Papadopoulos, J.; Escudero, A.

    2011-01-01

    Roadside grasslands undergoing secondary succession are abundant, and represent ecologically meaningful examples of novel, human-created ecosystems. Interactions between plant and soil communities (hereafter plant-soil interactions) are of major importance in understanding the role of biotic control in ecosystem functioning, but little is known about these links in the context of ecosystem restoration and succession. The assessment of the key biotic communities and interactions driving ecosystem development will help practitioners to better allocate the limited resources devoted to roadside grassland restoration. We surveyed roadside grasslands from three successional stages (0-2, 7-9, and > 20 years) in two Mediterranean regions of Spain. Structural equation modeling was used to evaluate how interactions between plants, biological soil crusts (BSCs), and soil microbial functional diversity (soil microorganisms) affect indicators of ecosystem development and restoration: plant similarity to the reference ecosystem, erosion control, and soil C storage and N accumulation. Changes in plant community composition along the successional gradient exerted the strongest influence on these indicators. High BSC cover was associated with high soil stability, and high soil microbial functional diversity from late-successional stages was associated with high soil fertility. Contrary to our expectations, the indirect effects of plants, mediated by either BSCs or soil microorganisms, were very weak in both regions, suggesting a minor role for plant-soil interactions upon ecosystem development indicators over long periods. Our results suggest that natural vegetation dynamics effectively improved ecosystem development within a time frame of 20 years in the grasslands evaluated. They also indicate that this time could be shortened if management actions focus on: (1) maintaining wellconserved natural areas close to roadsides to enhance plant compositional changes towards late

  11. Abiotic and biotic controls on local spatial distribution and performance of Boechera stricta

    Directory of Open Access Journals (Sweden)

    KUSUM J NAITHANI

    2014-07-01

    Full Text Available This study investigates the relative influence of biotic and abiotic factors on community dynamics using an integrated approach and highlights the influence of space on genotypic and phenotypic traits in plant community structure. We examined the relative influence of topography, environment, spatial distance, and intra- and interspecific interactions on spatial distribution and performance of Boechera stricta (rockcress, a close perennial relative of model plant Arabidopsis. First, using Bayesian kriging, we mapped the topography and environmental gradients and explored the spatial distribution of naturally occurring rockcress plants and two neighbors, Taraxacum officinale (dandelion and Solidago missouriensis (goldenrod found in close proximity within a typical diverse meadow community across topographic and environmental gradients. We then evaluated direct and indirect relationships among variables using Mantel path analysis and developed a network displaying abiotic and biotic interactions in this community. We found significant spatial autocorrelation among rockcress individuals, either because of common microhabitats as displayed by high density of individuals at lower elevation and high soil moisture area, or limited dispersal as shown by significant spatial autocorrelation of naturally occurring inbred lines, or a combination of both. Goldenrod and dandelion density around rockcress does not show any direct relationship with rockcress fecundity, possibly due to spatial segregation of resources. However, dandelion density around rockcress shows an indirect negative influence on rockcress fecundity via herbivory, indicating interspecific competition. Overall, we suggest that common microhabitat preference and limited dispersal are the main drivers for spatial distribution. However, intra-specific interactions and insect herbivory are the main drivers of rockcress performance in the meadow community.

  12. Biotic Interactions Shape the Ecological Distributions of Staphylococcus Species.

    Science.gov (United States)

    Kastman, Erik K; Kamelamela, Noelani; Norville, Josh W; Cosetta, Casey M; Dutton, Rachel J; Wolfe, Benjamin E

    2016-10-18

    Many metagenomic sequencing studies have observed the presence of closely related bacterial species or genotypes in the same microbiome. Previous attempts to explain these patterns of microdiversity have focused on the abiotic environment, but few have considered how biotic interactions could drive patterns of microbiome diversity. We dissected the patterns, processes, and mechanisms shaping the ecological distributions of three closely related Staphylococcus species in cheese rind biofilms. Paradoxically, the most abundant species (S. equorum) is the slowest colonizer and weakest competitor based on growth and competition assays in the laboratory. Through in vitro community reconstructions, we determined that biotic interactions with neighboring fungi help resolve this paradox. Species-specific stimulation of the poor competitor by fungi of the genus Scopulariopsis allows S. equorum to dominate communities in vitro as it does in situ Results of comparative genomic and transcriptomic experiments indicate that iron utilization pathways, including a homolog of the S. aureus staphyloferrin B siderophore operon pathway, are potential molecular mechanisms underlying Staphylococcus-Scopulariopsis interactions. Our integrated approach demonstrates that fungi can structure the ecological distributions of closely related bacterial species, and the data highlight the importance of bacterium-fungus interactions in attempts to design and manipulate microbiomes. Decades of culture-based studies and more recent metagenomic studies have demonstrated that bacterial species in agriculture, medicine, industry, and nature are unevenly distributed across time and space. The ecological processes and molecular mechanisms that shape these distributions are not well understood because it is challenging to connect in situ patterns of diversity with mechanistic in vitro studies in the laboratory. Using tractable cheese rind biofilms and a focus on coagulase-negative staphylococcus (CNS

  13. Regulation mechanisms of the FLT3-ligand after irradiation; Mecanismes de regulation du FLT3-ligand apres irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Prat-Lepesant, M

    2005-06-15

    The hematopoietic compartment is one of the most severely damaged after chemotherapy, radiotherapy or accidental irradiations. Whatever its origin, the resulting damage to the bone marrow remains difficult to evaluate. Thus, it would be of great interest to get a biological indicator of residual hematopoiesis in order to adapt the treatment to each clinical situation. Recent results indicated that the plasma Flt3 ligand concentration was increased in patients suffering from either acquired or induced aplasia, suggesting that Flt3 ligand might be useful as a biological indicator of bone marrow status. We thus followed in a mouse model as well as in several clinical situations the variations in plasma Flt3 ligand concentration, after either homogeneous or heterogeneous irradiations. These variations were correlated to the number of hematopoietic progenitors and to other parameters such as duration and depth of pancytopenia. The results indicated that the concentration of Flt3 ligand in the blood reflects the bone marrow status, and that the follow-up of plasma Flt3 ligand concentration could give predictive information about the bone marrow function and the duration and severity of pancytopenia and thrombocytopenia. Nevertheless, the clinical use of Flt3 ligand as a biological indicator of bone marrow damage require the knowledge of the mechanisms regulating the variations in plasma Flt3 ligand concentration. We thus developed a study in the mouse model. The results indicated that the variations in plasma Flt3 ligand variations were not solely due to a balance between its production by lymphoid cells and its consumption by hematopoietic cells. Moreover, we showed that T lymphocytes are not the main regulator of plasma Flt3 ligand concentration as previously suggested, and that other cell types, possibly including bone marrow stromal cells, might be strongly implicated. These results also suggest that the Flt3 ligand is a main systemic regulator of hematopoiesis

  14. H2-rich fluids from serpentinization: geochemical and biotic implications.

    Science.gov (United States)

    Sleep, N H; Meibom, A; Fridriksson, Th; Coleman, R G; Bird, D K

    2004-08-31

    Metamorphic hydration and oxidation of ultramafic rocks produces serpentinites, composed of serpentine group minerals and varying amounts of brucite, magnetite, and/or FeNi alloys. These minerals buffer metamorphic fluids to extremely reducing conditions that are capable of producing hydrogen gas. Awaruite, FeNi3, forms early in this process when the serpentinite minerals are Fe-rich. Olivine with the current mantle Fe/Mg ratio was oxidized during serpentinization after the Moon-forming impact. This process formed some of the ferric iron in the Earth's mantle. For the rest of Earth's history, serpentinites covered only a small fraction of the Earth's surface but were an important prebiotic and biotic environment. Extant methanogens react H2 with CO2 to form methane. This is a likely habitable environment on large silicate planets. The catalytic properties of FeNi3 allow complex organic compounds to form within serpentinite and, when mixed with atmospherically produced complex organic matter and waters that circulated through basalts, constitutes an attractive prebiotic substrate. Conversely, inorganic catalysis of methane by FeNi3 competes with nascent and extant life. Copyright 2004 The National Academy of Sciencs of the USA

  15. The Importance of Biotic vs. Abiotic Drivers of Local Plant Community Composition Along Regional Bioclimatic Gradients.

    Directory of Open Access Journals (Sweden)

    Kari Klanderud

    Full Text Available We assessed if the relative importance of biotic and abiotic factors for plant community composition differs along environmental gradients and between functional groups, and asked which implications this may have in a warmer and wetter future. The study location is a unique grid of sites spanning regional-scale temperature and precipitation gradients in boreal and alpine grasslands in southern Norway. Within each site we sampled vegetation and associated biotic and abiotic factors, and combined broad- and fine-scale ordination analyses to assess the relative explanatory power of these factors for species composition. Although the community responses to biotic and abiotic factors did not consistently change as predicted along the bioclimatic gradients, abiotic variables tended to explain a larger proportion of the variation in species composition towards colder sites, whereas biotic variables explained more towards warmer sites, supporting the stress gradient hypothesis. Significant interactions with precipitation suggest that biotic variables explained more towards wetter climates in the sub alpine and boreal sites, but more towards drier climates in the colder alpine. Thus, we predict that biotic interactions may become more important in alpine and boreal grasslands in a warmer future, although more winter precipitation may counteract this trend in oceanic alpine climates. Our results show that both local and regional scales analyses are needed to disentangle the local vegetation-environment relationships and their regional-scale drivers, and biotic interactions and precipitation must be included when predicting future species assemblages.

  16. Relevance of biotic pathways to the long-term regulation of nuclear waste disposal. Estimation of radiation dose to man resulting from biotic transport: the BIOPORT/MAXI1 software package. Volume 5

    Energy Technology Data Exchange (ETDEWEB)

    McKenzie, D.H.; Cadwell, L.L.; Gano, K.A.; Kennedy, W.E. Jr.; Napier, B.A.; Peloquin, R.A.; Prohammer, L.A.; Simmons, M.A.

    1985-10-01

    BIOPORT/MAXI1 is a collection of five computer codes designed to estimate the potential magnitude of the radiation dose to man resulting from biotic transport processes. Dose to man is calculated for ingestion of agricultural crops grown in contaminated soil, inhalation of resuspended radionuclides, and direct exposure to penetrating radiation resulting from the radionuclide concentrations established in the available soil surface by the biotic transport model. This document is designed as both an instructional and reference document for the BIOPORT/MAXI1 computer software package and has been written for two major audiences. The first audience includes persons concerned with the mathematical models of biological transport of commercial low-level radioactive wastes and the computer algorithms used to implement those models. The second audience includes persons concerned with exercising the computer program and exposure scenarios to obtain results for specific applications. The report contains sections describing the mathematical models, user operation of the computer programs, and program structure. Input and output for five sample problems are included. In addition, listings of the computer programs, data libraries, and dose conversion factors are provided in appendices.

  17. Relevance of biotic pathways to the long-term regulation of nuclear waste disposal. Estimation of radiation dose to man resulting from biotic transport: the BIOPORT/MAXI1 software package. Volume 5

    International Nuclear Information System (INIS)

    McKenzie, D.H.; Cadwell, L.L.; Gano, K.A.; Kennedy, W.E. Jr.; Napier, B.A.; Peloquin, R.A.; Prohammer, L.A.; Simmons, M.A.

    1985-10-01

    BIOPORT/MAXI1 is a collection of five computer codes designed to estimate the potential magnitude of the radiation dose to man resulting from biotic transport processes. Dose to man is calculated for ingestion of agricultural crops grown in contaminated soil, inhalation of resuspended radionuclides, and direct exposure to penetrating radiation resulting from the radionuclide concentrations established in the available soil surface by the biotic transport model. This document is designed as both an instructional and reference document for the BIOPORT/MAXI1 computer software package and has been written for two major audiences. The first audience includes persons concerned with the mathematical models of biological transport of commercial low-level radioactive wastes and the computer algorithms used to implement those models. The second audience includes persons concerned with exercising the computer program and exposure scenarios to obtain results for specific applications. The report contains sections describing the mathematical models, user operation of the computer programs, and program structure. Input and output for five sample problems are included. In addition, listings of the computer programs, data libraries, and dose conversion factors are provided in appendices

  18. Inhibition of signaling between human CXCR4 and zebrafish ligands by the small molecule IT1t impairs the formation of triple-negative breast cancer early metastases in a zebrafish xenograft model

    Directory of Open Access Journals (Sweden)

    Claudia Tulotta

    2016-02-01

    Full Text Available Triple-negative breast cancer (TNBC is a highly aggressive and recurrent type of breast carcinoma that is associated with poor patient prognosis. Because of the limited efficacy of current treatments, new therapeutic strategies need to be developed. The CXCR4-CXCL12 chemokine signaling axis guides cell migration in physiological and pathological processes, including breast cancer metastasis. Although targeted therapies to inhibit the CXCR4-CXCL12 axis are under clinical experimentation, still no effective therapeutic approaches have been established to block CXCR4 in TNBC. To unravel the role of the CXCR4-CXCL12 axis in the formation of TNBC early metastases, we used the zebrafish xenograft model. Importantly, we demonstrate that cross-communication between the zebrafish and human ligands and receptors takes place and human tumor cells expressing CXCR4 initiate early metastatic events by sensing zebrafish cognate ligands at the metastatic site. Taking advantage of the conserved intercommunication between human tumor cells and the zebrafish host, we blocked TNBC early metastatic events by chemical and genetic inhibition of CXCR4 signaling. We used IT1t, a potent CXCR4 antagonist, and show for the first time its promising anti-tumor effects. In conclusion, we confirm the validity of the zebrafish as a xenotransplantation model and propose a pharmacological approach to target CXCR4 in TNBC.

  19. Two novel mixed-ligand complexes containing organosulfonate ligands.

    Science.gov (United States)

    Li, Mingtian; Huang, Jun; Zhou, Xuan; Fang, Hua; Ding, Liyun

    2008-07-01

    The structures reported herein, viz. bis(4-aminonaphthalene-1-sulfonato-kappaO)bis(4,5-diazafluoren-9-one-kappa(2)N,N')copper(II), [Cu(C(10)H(8)NO(3)S)(2)(C(11)H(6)N(2)O)(2)], (I), and poly[[[diaquacadmium(II)]-bis(mu-4-aminonaphthalene-1-sulfonato)-kappa(2)O:N;kappa(2)N:O] dihydrate], {[Cd(C(10)H(8)NO(3)S)(2)(H(2)O)(2)].2H(2)O}(n), (II), are rare examples of sulfonate-containing complexes where the anion does not fulfill a passive charge-balancing role, but takes an active part in coordination as a monodentate and/or bridging ligand. Monomeric complex (I) possesses a crystallographic inversion center at the Cu(II) atom, and the asymmetric unit contains one-half of a Cu atom, one complete 4-aminonaphthalene-1-sulfonate (ans) ligand and one 4,5-diazafluoren-9-one (DAFO) ligand. The Cu(II) atom has an elongated distorted octahedral coordination geometry formed by two O atoms from two monodentate ans ligands and by four N atoms from two DAFO molecules. Complex (II) is polymeric and its crystal structure is built up by one-dimensional chains and solvent water molecules. Here also the cation (a Cd(II) atom) lies on a crystallographic inversion center and adopts a slightly distorted octahedral geometry. Each ans anion serves as a bridging ligand linking two Cd(II) atoms into one-dimensional infinite chains along the [010] direction, with each Cd(II) center coordinated by four ans ligands via O and N atoms and by two aqua ligands. In both structures, there are significant pi-pi stacking interactions between adjacent ligands and hydrogen bonds contribute to the formation of two- and three-dimensional networks.

  20. Modeling the Syn-Disposition of Nitrogen Donors in Non-Heme Diiron Enzymes. Synthesis, Characterization, and Hydrogen Peroxide Reactivity of Diiron(III) Complexes with the Syn N-Donor Ligand H2BPG2DEV

    Science.gov (United States)

    Friedle, Simone; Kodanko, Jeremy J.; Morys, Anna J.; Hayashi, Takahiro; Moënne-Loccoz, Pierre; Lippard, Stephen J.

    2009-01-01

    In order to model the syn disposition of histidine residues in carboxylate-bridged non-heme diiron enzymes, we prepared a new dinucleating ligand, H2BPG2DEV, that provides this geometric feature. The ligand incorporates biologically relevant carboxylate functionalities, which have not been explored as extensively as nitrogen-only analogs. Three novel oxo-bridged diiron(III) complexes [Fe2(μ-O)(H2O)2-(BPG2DEV)](ClO4)2 (6), [Fe2(μ-O)(μ-O CAriPrO)(BPG2DEV)](ClO4) (7), and [Fe2(μ-O)(μ-CO3)(BPG2DEV)] (8) were prepared. Single crystal X-ray structural characterization confirms that two pyridines are bound syn with respect to the Fe–Fe vector in these compounds. The carbonato-bridged complex 8 forms quantitatively from 6 in a rapid reaction with gaseous CO2 in organic solvents. A common maroon-colored intermediate (λmax = 490 nm; ε = 1500 M−1 cm−1) forms in reactions of 6, 7, or 8 with H2O2 and NEt3 in CH3CN/H2O solutions. Mass spectrometric analyses of this species, formed using 18O-labeled H2O2, indicate the presence of a peroxide ligand bound to the oxo-bridged diiron(III) center. The Mössbauer spectrum at 90 K of the EPR-silent intermediate exhibits a quadrupole doublet with δ. = 0.58 mm/s and ΔEQ = 0.58 mm/s. The isomer shift is typical for a peroxodiiron(III) species, but the quadrupole splitting parameter is unusually small compared to related complexes. These Mössbauer parameters are comparable to those observed for a peroxo intermediate formed in the reaction of reduced toluene/o-xylene monooxygenase hydroxylase (ToMOH) with dioxygen. Resonance Raman studies reveal an unusually low-energy O–O stretching mode in the peroxo intermediate that is consistent with a short diiron distance. Although peroxodiiron(III) intermediates generated from 6, 7, and 8 are poor O-atom transfer catalysts, they display highly efficient catalase activity, with turnover numbers up to 10,000. In contrast to hydrogen peroxide reactions of diiron(III) complexes that lack

  1. Correcting ligands, metabolites, and pathways

    NARCIS (Netherlands)

    Ott, M.A.; Vriend, G.

    2006-01-01

    BACKGROUND: A wide range of research areas in bioinformatics, molecular biology and medicinal chemistry require precise chemical structure information about molecules and reactions, e.g. drug design, ligand docking, metabolic network reconstruction, and systems biology. Most available databases,

  2. Effects of electrostatic interactions on ligand dissociation kinetics

    Science.gov (United States)

    Erbaş, Aykut; de la Cruz, Monica Olvera; Marko, John F.

    2018-02-01

    We study unbinding of multivalent cationic ligands from oppositely charged polymeric binding sites sparsely grafted on a flat neutral substrate. Our molecular dynamics simulations are suggested by single-molecule studies of protein-DNA interactions. We consider univalent salt concentrations spanning roughly a 1000-fold range, together with various concentrations of excess ligands in solution. To reveal the ionic effects on unbinding kinetics of spontaneous and facilitated dissociation mechanisms, we treat electrostatic interactions both at a Debye-Hückel (DH) (or implicit ions, i.e., use of an electrostatic potential with a prescribed decay length) level and by the more precise approach of considering all ionic species explicitly in the simulations. We find that the DH approach systematically overestimates unbinding rates, relative to the calculations where all ion pairs are present explicitly in solution, although many aspects of the two types of calculation are qualitatively similar. For facilitated dissociation (FD) (acceleration of unbinding by free ligands in solution) explicit-ion simulations lead to unbinding at lower free-ligand concentrations. Our simulations predict a variety of FD regimes as a function of free-ligand and ion concentrations; a particularly interesting regime is at intermediate concentrations of ligands where nonelectrostatic binding strength controls FD. We conclude that explicit-ion electrostatic modeling is an essential component to quantitatively tackle problems in molecular ligand dissociation, including nucleic-acid-binding proteins.

  3. The thermodynamic principles of ligand binding in chromatography and biology

    DEFF Research Database (Denmark)

    Mollerup, Jørgen

    2007-01-01

    the general thermodynamic principles of ligand binding. Models of the multi-component adsorption in ion-exchange and hydrophobic chromatography, HIC and RPLC, are developed. The parameters in the models have a well-defined physical significance. The models are compared to the Langmuir model...

  4. The Role of Tomato WRKY Genes in Plant Responses to Combined Abiotic and Biotic Stresses

    Directory of Open Access Journals (Sweden)

    Yuling Bai

    2018-06-01

    Full Text Available In the field, plants constantly face a plethora of abiotic and biotic stresses that can impart detrimental effects on plants. In response to multiple stresses, plants can rapidly reprogram their transcriptome through a tightly regulated and highly dynamic regulatory network where WRKY transcription factors can act as activators or repressors. WRKY transcription factors have diverse biological functions in plants, but most notably are key players in plant responses to biotic and abiotic stresses. In tomato there are 83 WRKY genes identified. Here we review recent progress on functions of these tomato WRKY genes and their homologs in other plant species, such as Arabidopsis and rice, with a special focus on their involvement in responses to abiotic and biotic stresses. In particular, we highlight WRKY genes that play a role in plant responses to a combination of abiotic and biotic stresses.

  5. Ligand-promoted protein folding by biased kinetic partitioning.

    Science.gov (United States)

    Hingorani, Karan S; Metcalf, Matthew C; Deming, Derrick T; Garman, Scott C; Powers, Evan T; Gierasch, Lila M

    2017-04-01

    Protein folding in cells occurs in the presence of high concentrations of endogenous binding partners, and exogenous binding partners have been exploited as pharmacological chaperones. A combined mathematical modeling and experimental approach shows that a ligand improves the folding of a destabilized protein by biasing the kinetic partitioning between folding and alternative fates (aggregation or degradation). Computationally predicted inhibition of test protein aggregation and degradation as a function of ligand concentration are validated by experiments in two disparate cellular systems.

  6. Simulated 21st century's increase in oceanic suboxia by CO2-enhanced biotic carbon export

    Science.gov (United States)

    Oschlies, Andreas; Schulz, Kai G.; Riebesell, Ulf; Schmittner, Andreas

    2008-12-01

    The primary impacts of anthropogenic CO2 emissions on marine biogeochemical cycles predicted so far include ocean acidification, global warming induced shifts in biogeographical provinces, and a possible negative feedback on atmospheric CO2 levels by CO2-fertilized biological production. Here we report a new potentially significant impact on the oxygen-minimum zones of the tropical oceans. Using a model of global climate, ocean circulation, and biogeochemical cycling, we extrapolate mesocosm-derived experimental findings of a pCO2-sensitive increase in biotic carbon-to-nitrogen drawdown to the global ocean. For a simulation run from the onset of the industrial revolution until A.D. 2100 under a "business-as-usual" scenario for anthropogenic CO2 emissions, our model predicts a negative feedback on atmospheric CO2 levels, which amounts to 34 Gt C by the end of this century. While this represents a small alteration of the anthropogenic perturbation of the carbon cycle, the model results reveal a dramatic 50% increase in the suboxic water volume by the end of this century in response to the respiration of excess organic carbon formed at higher CO2 levels. This is a significant expansion of the marine "dead zones" with severe implications not only for all higher life forms but also for oxygen-sensitive nutrient recycling and, hence, for oceanic nutrient inventories.

  7. Environmental conditions and biotic communities in Foz de Almargem and Salgados coastal lagoons, Algarve (South Portugal)

    OpenAIRE

    Coelho, Susana Isabel Eusébio

    2013-01-01

    The present study intended to compare environmental conditions and biotic communities of two choked coastal lagoons located in the Algarve region, Foz de Almargem and Salgados, with the purpose of evaluating the effects of organic pollution from wastewater discharges in water quality and biotic communities from different levels of the food chain, namely phytoplankton and benthic macroinvertebrates. Both lagoons were seasonally connected to the sea, but most of the year they were isolated r...

  8. Quantitative patterns between plant volatile emissions induced by biotic stresses and the degree of damage

    Directory of Open Access Journals (Sweden)

    Ülo eNiinemets

    2013-07-01

    Full Text Available Plants have to cope with a plethora of biotic stresses such as herbivory and pathogen attacks throughout their life cycle. The biotic stresses typically trigger rapid emissions of volatile products of lipoxygenase pathway (LOX products, various C6 aldehydes, alcohols and derivatives, also called green leaf volatiles associated with oxidative burst. Further a variety of defense pathways is activated, leading to induction of synthesis and emission of a complex blend of volatiles, often including methyl salicylate, indole, mono-, homo- and sesquiterpenes. The airborne volatiles are involved in systemic responses leading to elicitation of emissions from non-damaged plant parts. For several abiotic stresses, it has been demonstrated that volatile emissions are quantitatively related to the stress dose. The biotic impacts under natural conditions vary in severity from mild to severe, but it is unclear whether volatile emissions also scale with the severity of biotic stresses in a dose-dependent manner. Furthermore, biotic impacts are typically recurrent, but it is poorly understood how direct stress-triggered and systemic emission responses are silenced during periods intervening sequential stress events. Here we review the information on induced emissions elicited in response to biotic attacks, and argue that biotic stress severity vs. emission rate relationships should follow principally the same dose-response relationships as previously demonstrated for several abiotic stresses. Analysis of several case studies investigating the elicitation of emissions in response to chewing herbivores, aphids, rust fungi, powdery mildew and Botrytis, suggests that induced emissions do respond to stress severity in dose-dependent manner. Bi-phasic emission kinetics of several induced volatiles have been demonstrated in these experiments, suggesting that next to immediate stress-triggered emissions, biotic stress elicited emissions typically have a secondary

  9. Labeled receptor ligands for spect

    International Nuclear Information System (INIS)

    Kung, H.F.

    1989-01-01

    Receptor specific imaging agents for single photon emission computed tomography (SPECT) can potentially be useful in the understanding of basic biochemistry and pharmacology of receptors. SPECT images may also provide tools for evaluation of density and binding kinetics of a specific receptor, information important for diagnosis and patient management. Basic requirements for receptor imaging agents are: (a) they are labeled with short-lived isotopes, (b) they show high selectivity and specific uptake, (c) they exhibit high target/background ratio, and (d) they can be modeled to obtain quantitative information. Several good examples of CNS receptor specific ligands labeled with I-123 have been developed, including iodoQNB, iodoestrogen iodobenzadiazepine, iodobenazepine, iodobenzamides for muscarinic, estrogen benzadiazepine, D-1 and D-2 dopamine receptors. With the advent of newer and faster SPECT imaging devices, it may be feasible to quantitate the receptor density by in vivo imaging techniques. These new brain imaging agents can provide unique diagnostic information, which may not be available through other imaging modalities, such as CT and MRI

  10. Comparison of in vivo binding properties of the 18-kDa translocator protein (TSPO) ligands [{sup 18}F]PBR102 and [{sup 18}F]PBR111 in a model of excitotoxin-induced neuroinflammation

    Energy Technology Data Exchange (ETDEWEB)

    Callaghan, P.D.; Gregoire, M.C. [Australian Nuclear Science and Technology Organisation, ANSTO LifeSciences, Kirrawee DC, NSW (Australia); University of Sydney, Brain and Mind Research Institute, Sydney (Australia); University of Sydney, Discipline of Medical Radiation Sciences, Sydney (Australia); Wimberley, C.A.; Rahardjo, G.L.; Berghofer, P.J.; Zahra, D. [Australian Nuclear Science and Technology Organisation, ANSTO LifeSciences, Kirrawee DC, NSW (Australia); University of Sydney, Brain and Mind Research Institute, Sydney (Australia); Pham, T.Q.; Jackson, T.; Wyatt, N.; Greguric, I.; Howell, N.R.; Loc' h, C. [Australian Nuclear Science and Technology Organisation, ANSTO LifeSciences, Kirrawee DC, NSW (Australia); Bourdier, T.; Mattner, F.; Katsifis, A. [Australian Nuclear Science and Technology Organisation, ANSTO LifeSciences, Kirrawee DC, NSW (Australia); Royal Prince Alfred Hospital, Department of Molecular Imaging, Sydney (Australia); Siegele, R.; Pastuovic, Z. [Institute for Environmental Research, Centre for Accelerator Science, ANSTO, Sydney (Australia)

    2015-01-15

    The in vivo binding parameters of the novel imidazopyridine TSPO ligand [{sup 18}F]PBR102 were assessed and compared with those of [{sup 18}F]PBR111 in a rodent model of neuroinflammation. The validity of the key assumptions of the simplified reference tissue model (SRTM) for estimation of binding potential (BP) was determined, with validation against a two-tissue compartment model (2TC). Acute neuroinflammation was assessed 7 days after unilateral stereotaxic administration of (R,S)-α-amino-3-hydroxy-5-methyl-4-isoxazolopropionique (AMPA) in anaesthetized adult Wistar rats. Anaesthetized rats were implanted with a femoral arterial cannula then injected with a low mass of [{sup 18}F]PBR102 or [{sup 18}F]PBR111 and dynamic images were acquired over 60 min using an INVEON PET/CT camera. Another population of rats underwent the same PET protocol after pretreatment with a presaturating mass of the same unlabelled tracer (1 mg/kg) to assess the validity of the reference region for SRTM analysis. Arterial blood was sampled during imaging, allowing pharmacokinetic determination of radiotracer concentrations. Plasma activity concentration-time curves were corrected for unchanged tracer based on metabolic characterization experiments in a separate cohort of Wistar rats. The stability of neuroinflammation in both imaging cohorts was assessed by [{sup 125}I] CLINDE TSPO quantitative autoradiography, OX42/GFAP immunohistochemistry, Fluoro-Jade C histology, and elemental mapping using microparticle-induced x-ray emission spectroscopy. The BP of each ligand were assessed in the two cohorts of lesioned animals using both SRTM and a 2TC with arterial parent compound concentration, coupled with the results from the presaturation cohort for comparison and validation of the SRTM. The BPs of [{sup 18}F]PBR102 [{sup 18}F]PBR111 were equivalent, with improved signal-to-noise ratio and sensitivity compared with [{sup 11}C]PK11195. The presaturation study showed differences in the volume

  11. Role of Biotic and Abiotic Processes on Soil CO2 Dynamics in the McMurdo Dry Valleys, Antarctica

    Science.gov (United States)

    Risk, D. A.; Macintyre, C. M.; Lee, C.; Cary, C.; Shanhun, F.; Almond, P. C.

    2016-12-01

    In the harsh conditions of the Antarctic Dry Valleys, microbial activity has been recorded via measurements of soil carbon dioxide (CO2) concentration and surface efflux. However, high temporal resolution studies in the Dry Valleys have also shown that abiotic solubility-driven processes can strongly influence (and perhaps even dominate) the CO2 dynamics in these low flux environments and suggests that biological activity may be lower than previously thought. In this study, we aim to improve our understanding of CO2 dynamics (biotic and abiotic) in Antarctic Dry Valley soils using long-term automated measurements of soil CO2 surface flux and soil profile concentration at several sites, often at sub-diel frequency. We hypothesize that soil CO2 variations are driven primarily by environmental factors affecting CO2 solubility in soil solution, mainly temperature, and that these processes may even overprint biologic production in representative Dry Valley soils. Monitoring of all sites revealed only one likely biotic CO2 production event, lasting three weeks during the Austral summer and reaching fluxes of 0.4 µmol/m2/s. Under more typical low flux conditions (sampling campaigns. Subsurface CO2 monitoring and a lab-controlled Antarctic soil simulation experiment confirmed that abiotic processes are capable of dominating soil CO2 variability. Diel temperature cycles crossing the freezing boundary revealed a dual abiotic cycle of solubility cycling and gas exclusion from ice formation observed only by high temporal frequency measurements (30 min). This work demonstrates a need for a numerical model to partition the dynamic abiotic processes underlying any biotic CO2 production in order to understand potential climate-change induced increases in microbial productivity in terrestrial Antarctica.

  12. Reversible Size Control of Silver Nanoclusters via Ligand-exchange

    KAUST Repository

    Bootharaju, Megalamane Siddaramappa

    2015-05-21

    The properties of atomically monodisperse noble metal nanoclusters (NCs) are intricately intertwined with their precise molecular formula. The vast majority of size-specific NC syntheses start from the reduction of the metal salt and thiol ligand mixture. Only in gold was it recently shown that ligand-exchange could induce the growth of NCs from one atomically precise species to another; a process of yet unknown reversibility. Here, we present a process for the ligand-exchange-induced growth of atomically precise silver NCs, in a biphasic liquid-liquid system, which is particularly of interest because of its complete reversibility and ability to occur at room temperature. We explore this phenomenon in-depth using Ag35(SG)18 [SG= glutathionate] and Ag44(4-FTP)30 [4-FTP= 4-fluorothiophenol] as model systems. We show that the ligand-exchange conversion of Ag35(SG)18 into Ag44(4-FTP)30 is rapid (< 5 min) and direct, while the reverse process proceeds slowly through intermediate cluster sizes. We adapt a recently developed theory of reverse Ostwald ripening to model the NCs’ interconvertibility. The model’s predictions are in good agreement with the experimental observations, and they highlight the importance of small changes in the ligand-metal binding energy in determining the final equilibrium NC size. Based on the insight provided by this model, we demonstrated experimentally that by varying the choice of ligands, ligand-exchange can be used to obtain different sized NCs. The findings in this work establish ligand-exchange as a versatile tool for tuning cluster sizes.

  13. Reversible Size Control of Silver Nanoclusters via Ligand-exchange

    KAUST Repository

    Bootharaju, Megalamane Siddaramappa; Burlakov, Victor M.; Besong, Tabot M.D.; Joshi, Chakra Prasad; AbdulHalim, L; Black, David; Whetten, Robert; Goriely, Alain; Bakr, Osman

    2015-01-01

    The properties of atomically monodisperse noble metal nanoclusters (NCs) are intricately intertwined with their precise molecular formula. The vast majority of size-specific NC syntheses start from the reduction of the metal salt and thiol ligand mixture. Only in gold was it recently shown that ligand-exchange could induce the growth of NCs from one atomically precise species to another; a process of yet unknown reversibility. Here, we present a process for the ligand-exchange-induced growth of atomically precise silver NCs, in a biphasic liquid-liquid system, which is particularly of interest because of its complete reversibility and ability to occur at room temperature. We explore this phenomenon in-depth using Ag35(SG)18 [SG= glutathionate] and Ag44(4-FTP)30 [4-FTP= 4-fluorothiophenol] as model systems. We show that the ligand-exchange conversion of Ag35(SG)18 into Ag44(4-FTP)30 is rapid (< 5 min) and direct, while the reverse process proceeds slowly through intermediate cluster sizes. We adapt a recently developed theory of reverse Ostwald ripening to model the NCs’ interconvertibility. The model’s predictions are in good agreement with the experimental observations, and they highlight the importance of small changes in the ligand-metal binding energy in determining the final equilibrium NC size. Based on the insight provided by this model, we demonstrated experimentally that by varying the choice of ligands, ligand-exchange can be used to obtain different sized NCs. The findings in this work establish ligand-exchange as a versatile tool for tuning cluster sizes.

  14. Abiotic and Biotic Formation of Amino Acids in the Enceladus Ocean.

    Science.gov (United States)

    Steel, Elliot L; Davila, Alfonso; McKay, Christopher P

    2017-09-01

    The active plume at Enceladus' south pole makes the indirect sampling of its global ocean possible. The partially resolved chemistry of the plume, which points to conditions that are seemingly compatible with life, has made orbital sampling missions a priority. We present a conceptual model of energy flux, hydrothermal H 2 production, and both abiotic and biotic production of amino acids. Based on the energy flux observed at the south pole and the inferred internal hydrothermal activity, we estimate an H 2 production of 0.6-34 mol/s from serpentinization, sufficient to sustain abiotic and biotic amino acid synthesis of 1.6-87 and 1-44 g/s, respectively. Two-dimensional (2D) numerical simulations of the hydrothermal vent suggest that the vent fluids could reach the ice-water boundary in less than 11-55 days for a 50 km deep ocean diluted by ambient ocean water 10 to 1. Concentrations of glycine, alanine, α-amino isobutyric acid, and glutamic acid in the plume and in the ambient ocean could all be above 0.01 μM just due to abiotic production. Biological synthesis, if occurring, could produce a maximum of 90 μM concentrations of amino acids based on a methanogenic ecosystem consuming H 2 and CO 2 . Racemization timescales in the ocean are short compared with production timescales. Thus, no enantiomeric excess is expected in the ambient ocean, and if biology is present, enantiomeric excess at the vent fluids is expected to be less than 10% in the plume. From vent H 2 concentrations of 7.8 mM (e.g., Lost City) and assuming complete H 2 use and conversion to chemical energy by methanogens, cell production is estimated. Annual biomass production in the methanogenic-based biology model is 4 × 10 4 -2 × 10 6 kg/year. This corresponds to cell concentrations ∼10 9 cells/cm 3 in the vents and ∼10 8 cells/cm 3 in the plume, and when diluted into the ambient ocean, we predict cell concentrations of 80-4250 cells/cm 3 . Key Words: Abiotic organic

  15. Abiotic and biotic determinants of leaf carbon exchange capacity from tropical to high boreal biomes

    Science.gov (United States)

    Smith, N. G.; Dukes, J. S.

    2016-12-01

    Photosynthesis and respiration on land represent the two largest fluxes of carbon dioxide between the atmosphere and the Earth's surface. As such, the Earth System Models that are used to project climate change are high sensitive to these processes. Studies have found that much of this uncertainty is due to the formulation and parameterization of plant photosynthetic and respiratory capacity. Here, we quantified the abiotic and biotic factors that determine photosynthetic and respiratory capacity at large spatial scales. Specifically, we measured the maximum rate of Rubisco carboxylation (Vcmax), the maximum rate of Ribulose-1,5-bisphosphate regeneration (Jmax), and leaf dark respiration (Rd) in >600 individuals of 98 plant species from the tropical to high boreal biomes of Northern and Central America. We also measured a bevy of covariates including plant functional type, leaf nitrogen content, short- and long-term climate, leaf water potential, plant size, and leaf mass per area. We found that plant functional type and leaf nitrogen content were the primary determinants of Vcmax, Jmax, and Rd. Mean annual temperature and mean annual precipitation were not significant predictors of these rates. However, short-term climatic variables, specifically soil moisture and air temperature over the previous 25 days, were significant predictors and indicated that heat and soil moisture deficits combine to reduce photosynthetic capacity and increase respiratory capacity. Finally, these data were used as a model benchmarking tool for the Community Land Model version 4.5 (CLM 4.5). The benchmarking analyses determined errors in the leaf nitrogen allocation scheme of CLM 4.5. Under high leaf nitrogen levels within a plant type the model overestimated Vcmax and Jmax. This result suggested that plants were altering their nitrogen allocation patterns when leaf nitrogen levels were high, an effect that was not being captured by the model. These data, taken with models in mind

  16. Scale Expansion of Community Investigations and Integration of the Effects of Abiotic and Biotic Processes on Maintenance of Species Diversity

    Directory of Open Access Journals (Sweden)

    Zhenhong Wang

    2011-01-01

    Full Text Available Information on the maintenance of diversity patterns from regional to local scales is dispersed among academic fields due to the local focus of community ecology. To better understand these patterns, the study of ecological communities needs to be expanded to larger scales and the various processes affecting them need to be integrated using a suitable quantitative method. We determined a range of communities on a flora-subregional scale in Yunnan province, China (383210.02 km2. A series of species pools were delimited from the regional to plot scales. Plant diversity was evaluated and abiotic and biotic processes identified at each pool level. The species pool effect was calculated using an innovative model, and the contribution of these processes to the maintenance of plant species diversity was determined and integrated: climate had the greatest effect at the flora-subregional scale, with historical and evolutionary processes contributing ∼11%; climate and human disturbance had the greatest effect at the local site pool scale; competition exclusion and stress limitation explained strong filtering at the successional stage pool scale; biotic processes contributed more on the local community scale than on the regional scale. Scale expansion combined with the filtering model approach solves the local problem in community ecology.

  17. The biochar effect: plant resistance to biotic stresses

    Directory of Open Access Journals (Sweden)

    YIGAL ELAD

    2012-01-01

    Full Text Available Biochar (charcoal is the solid co-product of pyrolysis, the thermal degradation of biomass in the absence of oxygen. Pyrolysis also yields gaseous and liquid biofuel products. There is a growing interest worldwide in the pyrolysis platform, for at least four reasons: (i pyrolysis can be a source of renewable biofuels; (ii many biomass waste materials can be treated by pyrolysis and thus converted into a fuel resource; (iii long-term sequestration of carbon dioxide which originated in the atmosphere may result from adding biochar to soil; and (iv biochar soil amendment contributes to improved soil fertility and crop productivity. Currently, however, very little biochar is utilized in agriculture, in part because its agronomic value in terms of crop response and soil health benefits have yet to be quantified, and because the mechanisms by which it improves soil fertility are poorly understood. The positive effects of biochar on crop productivity under conditions of extensive agriculture are frequently attributed to direct effects of biochar-supplied nutrients and to several other indirect effects, including increased water and nutrient retention, improvements in soil pH, increased soil cation exchange capacity, effects on P and S transformations and turnover, neutralization of phytotoxic compounds in the soil, improved soil physical properties, promotion of mycorrhizal fungi, and alteration of soil microbial populations and functions. Yet, the biochar effect is also evident under conditions of intensive production where many of these parameters are not limited. Biochar addition to soil alters microbial populations in the rhizosphere, albeit via mechanisms not yet understood, and may cause a shift towards beneficial microorganism populations that promote plant growth and resistance to biotic stresses. In addition to some scant evidence for biochar-induced plant protection against soilborne diseases, the induction of systemic resistance towards

  18. 4-[[sup 123]I]iodospiperone as a ligand for dopamine DA receptors: in vitro and in vivo experiments in a rat model

    Energy Technology Data Exchange (ETDEWEB)

    Krogt, J.A. van der; Valkenburg, C F.M. van; Pauwels, E K.J.; Buruma, O J.S. [Rijksuniversiteit Leiden (Netherlands); Reiffers, S [Hospital De Weezenlanden, Zwolle (Netherlands); Doremalen, P.A.P.M. van; Wijnhoven, G [Cygne, Eindhoven (Netherlands)

    1992-10-01

    Radioiodinated spiperone is of interest for dopamine (DA) receptor studies in the living human brain by single photon emission computed tomography (SPECT). Simulated by data obtained with [[sup 11]C]-N-methyl-spiperone, we synthesized 4-[[sup 123]I]iodospiperone and investigated the in vitro binding characteristics of this ligand to the striatal membrane of the rat and the in vivo distribution over various rat brain regions. The in vitro binding experiments showed that this radioligand displays about 10 times less affinity for the DA receptor than spiperone and specific binding, as shown with [[sup 3]H]spiperone, was not observed. Displacement by butaclamol was not observed. The in vivo studies demonstrated that both 4-[[sup 123]I]iodospiperone and [[sup 3]H]spiperone concentrate in striatal tissue, respectively, 1.9 and 3.5 times as high as in cerebellar tissue. Haloperidol pretreatment largely prevented this accumulation. In view of the obtained target-to-non-target ratios we believe, however, that this accumulation in brain areas rich DA-receptors does not offer prospects for clinical receptor imaging with SPECT. (Author).

  19. Prediction of ligand effects in platinum-amyloid-β coordination.

    Science.gov (United States)

    Turner, Matthew; Deeth, Robert J; Platts, James A

    2017-08-01

    Ligand field molecular mechanics (LFMM) and semi-empirical Parametric Model 7 (PM7) methods are applied to a series of six Pt II -Ligand systems binding to the N-terminal domain of the amyloid-β (Aβ) peptide. Molecular dynamics using a combined LFMM/Assisted Model Building with Energy Refinement (AMBER) approach is used to explore the conformational freedom of the peptide fragment, and identifies favourable platinum binding modes and peptide conformations for each ligand investigated. Platinum coordination is found to depend on the nature of the ligand, providing evidence that binding mode may be controlled by suitable ligand design. Boltzmann populations at 310K indicate that each Pt-Aβ complex has a small number of thermodynamically accessible states. Ramachandran maps are constructed for the sampled Pt-Aβ conformations and secondary structural analysis of the obtained complex structures is performed and contrasted with the free peptide; coordination of these platinum complexes disrupts existing secondary structure in the Aβ peptide and promotes formation of ligand-specific turn-type secondary structure. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Modeling Equilibrium Fe Isotope Fractionation in Fe-Organic Complexes: Implications for the use of Fe Isotopes as a Biomarker and Trends Based on the Properties of Bound Ligands

    Science.gov (United States)

    Domagal-Goldman, S.; Kubicki, J. D.

    2006-05-01

    Fe Isotopes have been proposed as a useful tracer of biological and geochemical processes. Key to understanding the effects these various processes have on Fe isotopes is accurate modeling of the reactions responsible for the isotope fractionations. In this study, we examined the theoretical basis for the claims that Fe isotopes can be used as a biomarker. This was done by using molecular orbital/density functional theory (MO/DFT) calculations to predict the equilibrium fractionation of Fe isotopes due to changes in the redox state and the bonding environment of Fe. Specifically, we predicted vibrational frequencies for iron desferrioxamine (Fe-DFOB), iron triscatechol (Fe(cat)3), iron trisoxalate (Fe(ox)3), and hexaaquo iron (Fe(H2O)6) for complexes containing both ferrous (Fe2+) and ferric (Fe3+) iron. Using these vibrational frequencies, we then predicted fractionation factors between these six complexes. The predicted fractionation factors resulting from changes in the redox state of Fe fell in the range 2.5- 3.5‰. The fractionation factors resulting from changes in the bonding environment of Fe ranged from 0.2 to 1.4‰. These results indicate that changes in the bonding strength of Fe ligands are less important to Fe isotope fractionation processes than are changes to the redox state of Fe. The implications for use of Fe as a tracer of biological processes is clear: abiological redox changes must be ruled out in a sample before Fe isotopes are considered as a potential biomarker. Furthermore, the use of Fe isotopes to measure the redox state of the Earths surface environment through time is supported by this work, since changes in the redox state of Fe appear to be the more important driver of isotopic fractionations. In addition to the large differences between redox-driven fractionations and ligand-driven fractionations, we will also show general trends in the demand for heavy Fe isotopes as a function of properties of the bound ligand. This will help the

  1. Interactions among biotic and abiotic factors affect the reliability of tungsten microneedles puncturing in vitro and in vivo peripheral nerves: A hybrid computational approach

    Energy Technology Data Exchange (ETDEWEB)

    Sergi, Pier Nicola, E-mail: p.sergi@sssup.it [Translational Neural Engineering Laboratory, The Biorobotics Institute, Scuola Superiore Sant' Anna, Viale Rinaldo Piaggio 34, Pontedera, 56025 (Italy); Jensen, Winnie [Department of Health Science and Technology, Fredrik Bajers Vej 7, 9220 Aalborg (Denmark); Yoshida, Ken [Department of Biomedical Engineering, Indiana University - Purdue University Indianapolis, 723 W. Michigan St., SL220, Indianapolis, IN 46202 (United States)

    2016-02-01

    Tungsten is an elective material to produce slender and stiff microneedles able to enter soft tissues and minimize puncture wounds. In particular, tungsten microneedles are used to puncture peripheral nerves and insert neural interfaces, bridging the gap between the nervous system and robotic devices (e.g., hand prostheses). Unfortunately, microneedles fail during the puncture process and this failure is not dependent on stiffness or fracture toughness of the constituent material. In addition, the microneedles' performances decrease during in vivo trials with respect to the in vitro ones. This further effect is independent on internal biotic effects, while it seems to be related to external biotic causes. Since the exact synergy of phenomena decreasing the in vivo reliability is still not known, this work explored the connection between in vitro and in vivo behavior of tungsten microneedles through the study of interactions between biotic and abiotic factors. A hybrid computational approach, simultaneously using theoretical relationships and in silico models of nerves, was implemented to model the change of reliability varying the microneedle diameter, and to predict in vivo performances by using in vitro reliability and local differences between in vivo and in vitro mechanical response of nerves. - Highlights: • We provide phenomenological Finite Element (FE) models of peripheral nerves to study the interactions with W microneedles • We provide a general interaction-based approach to model the reliability of slender microneedles • We evaluate the reliability of W microneedels to puncture in vivo nerves • We provide a novel synergistic hybrid approach (theory + simulations) involving interactions among biotic and abiotic factors • We validate the hybrid approach by using experimental data from literature.

  2. Interactions among biotic and abiotic factors affect the reliability of tungsten microneedles puncturing in vitro and in vivo peripheral nerves: A hybrid computational approach

    International Nuclear Information System (INIS)

    Sergi, Pier Nicola; Jensen, Winnie; Yoshida, Ken

    2016-01-01

    Tungsten is an elective material to produce slender and stiff microneedles able to enter soft tissues and minimize puncture wounds. In particular, tungsten microneedles are used to puncture peripheral nerves and insert neural interfaces, bridging the gap between the nervous system and robotic devices (e.g., hand prostheses). Unfortunately, microneedles fail during the puncture process and this failure is not dependent on stiffness or fracture toughness of the constituent material. In addition, the microneedles' performances decrease during in vivo trials with respect to the in vitro ones. This further effect is independent on internal biotic effects, while it seems to be related to external biotic causes. Since the exact synergy of phenomena decreasing the in vivo reliability is still not known, this work explored the connection between in vitro and in vivo behavior of tungsten microneedles through the study of interactions between biotic and abiotic factors. A hybrid computational approach, simultaneously using theoretical relationships and in silico models of nerves, was implemented to model the change of reliability varying the microneedle diameter, and to predict in vivo performances by using in vitro reliability and local differences between in vivo and in vitro mechanical response of nerves. - Highlights: • We provide phenomenological Finite Element (FE) models of peripheral nerves to study the interactions with W microneedles • We provide a general interaction-based approach to model the reliability of slender microneedles • We evaluate the reliability of W microneedels to puncture in vivo nerves • We provide a novel synergistic hybrid approach (theory + simulations) involving interactions among biotic and abiotic factors • We validate the hybrid approach by using experimental data from literature

  3. [Supercomputer investigation of the protein-ligand system low-energy minima].

    Science.gov (United States)

    Oferkin, I V; Sulimov, A V; Katkova, E V; Kutov, D K; Grigoriev, F V; Kondakova, O A; Sulimov, V B

    2015-01-01

    The accuracy of the protein-ligand binding energy calculations and ligand positioning is strongly influenced by the choice of the docking target function. This work demonstrates the evaluation of the five different target functions used in docking: functions based on MMFF94 force field and functions based on PM7 quantum-chemical method accounting or without accounting the implicit solvent model (PCM, COSMO or SGB). For these purposes the ligand positions corresponding to the minima of the target function and the experimentally known ligand positions in the protein active site (crystal ligand positions) were compared. Each function was examined on the same test-set of 16 protein-ligand complexes. The new parallelized docking program FLM based on Monte Carlo search algorithm was developed to perform the comprehensive low-energy minima search and to calculate the protein-ligand binding energy. This study demonstrates that the docking target function based on the MMFF94 force field can be used to detect the crystal or near crystal positions of the ligand by the finding the low-energy local minima spectrum of the target function. The importance of solvent accounting in the docking process for the accurate ligand positioning is also shown. The accuracy of the ligand positioning as well as the correlation between the calculated and experimentally determined protein-ligand binding energies are improved when the MMFF94 force field is substituted by the new PM7 method with implicit solvent accounting.

  4. LigandRFs: random forest ensemble to identify ligand-binding residues from sequence information alone

    KAUST Repository

    Chen, Peng; Huang, Jianhua Z; Gao, Xin

    2014-01-01

    Protein-ligand binding is important for some proteins to perform their functions. Protein-ligand binding sites are the residues of proteins that physically bind to ligands. Despite of the recent advances in computational prediction

  5. Quantitative analysis of protein-ligand interactions by NMR.

    Science.gov (United States)

    Furukawa, Ayako; Konuma, Tsuyoshi; Yanaka, Saeko; Sugase, Kenji

    2016-08-01

    Protein-ligand interactions have been commonly studied through static structures of the protein-ligand complex. Recently, however, there has been increasing interest in investigating the dynamics of protein-ligand interactions both for fundamental understanding of the underlying mechanisms and for drug development. NMR is a versatile and powerful tool, especially because it provides site-specific quantitative information. NMR has widely been used to determine the dissociation constant (KD), in particular, for relatively weak interactions. The simplest NMR method is a chemical-shift titration experiment, in which the chemical-shift changes of a protein in response to ligand titration are measured. There are other quantitative NMR methods, but they mostly apply only to interactions in the fast-exchange regime. These methods derive the dissociation constant from population-averaged NMR quantities of the free and bound states of a protein or ligand. In contrast, the recent advent of new relaxation-based experiments, including R2 relaxation dispersion and ZZ-exchange, has enabled us to obtain kinetic information on protein-ligand interactions in the intermediate- and slow-exchange regimes. Based on R2 dispersion or ZZ-exchange, methods that can determine the association rate, kon, dissociation rate, koff, and KD have been developed. In these approaches, R2 dispersion or ZZ-exchange curves are measured for multiple samples with different protein and/or ligand concentration ratios, and the relaxation data are fitted to theoretical kinetic models. It is critical to choose an appropriate kinetic model, such as the two- or three-state exchange model, to derive the correct kinetic information. The R2 dispersion and ZZ-exchange methods are suitable for the analysis of protein-ligand interactions with a micromolar or sub-micromolar dissociation constant but not for very weak interactions, which are typical in very fast exchange. This contrasts with the NMR methods that are used

  6. Process-Based Species Pools Reveal the Hidden Signature of Biotic Interactions Amid the Influence of Temperature Filtering.

    Science.gov (United States)

    Lessard, Jean-Philippe; Weinstein, Ben G; Borregaard, Michael K; Marske, Katharine A; Martin, Danny R; McGuire, Jimmy A; Parra, Juan L; Rahbek, Carsten; Graham, Catherine H

    2016-01-01

    A persistent challenge in ecology is to tease apart the influence of multiple processes acting simultaneously and interacting in complex ways to shape the structure of species assemblages. We implement a heuristic approach that relies on explicitly defining species pools and permits assessment of the relative influence of the main processes thought to shape assemblage structure: environmental filtering, dispersal limitations, and biotic interactions. We illustrate our approach using data on the assemblage composition and geographic distribution of hummingbirds, a comprehensive phylogeny and morphological traits. The implementation of several process-based species pool definitions in null models suggests that temperature-but not precipitation or dispersal limitation-acts as the main regional filter of assemblage structure. Incorporating this environmental filter directly into the definition of assemblage-specific species pools revealed an otherwise hidden pattern of phylogenetic evenness, indicating that biotic interactions might further influence hummingbird assemblage structure. Such hidden patterns of assemblage structure call for a reexamination of a multitude of phylogenetic- and trait-based studies that did not explicitly consider potentially important processes in their definition of the species pool. Our heuristic approach provides a transparent way to explore patterns and refine interpretations of the underlying causes of assemblage structure.

  7. Identifying Watershed, Landscape, and Engineering Design Factors that Influence the Biotic Condition of Restored Streams

    Directory of Open Access Journals (Sweden)

    Barbara Doll

    2016-04-01

    Full Text Available Restored stream reaches at 79 sites across North Carolina were sampled for aquatic macroinvertebrates using a rapid bioassessment protocol. Morphological design parameters and geographic factors, including watershed and landscape parameters (e.g., valley slope, substrate, were also compiled for these streams. Principal component regression analyses revealed correlations between design and landscape variables with macroinvertebrate metrics. The correlations were strengthened by adding watershed variables. Ridge regression was used to find the best-fit model for predicting dominant taxa from the “pollution sensitive” orders of Ephemeroptera (mayflies, Plecoptera (stoneflies, and Trichoptera (caddisflies, or EPT taxa, resulting in coefficient weights that were most interpretable relative to site selection and design parameters. Results indicate that larger (wider streams located in the mountains and foothills where there are steeper valleys, larger substrate, and undeveloped watersheds are expected to have higher numbers of dominant EPT taxa. In addition, EPT taxa numbers are positively correlated with accessible floodplain width and negatively correlated with width-to-depth ratio and sinuosity. This study indicates that both site selection and design should be carefully considered in order to maximize the resulting biotic condition and associated potential ecological uplift of the stream.

  8. From the Cover: Environmental and biotic controls on the evolutionary history of insect body size

    Science.gov (United States)

    Clapham, Matthew E.; Karr, Jered A.

    2012-07-01

    Giant insects, with wingspans as large as 70 cm, ruled the Carboniferous and Permian skies. Gigantism has been linked to hyperoxic conditions because oxygen concentration is a key physiological control on body size, particularly in groups like flying insects that have high metabolic oxygen demands. Here we show, using a dataset of more than 10,500 fossil insect wing lengths, that size tracked atmospheric oxygen concentrations only for the first 150 Myr of insect evolution. The data are best explained by a model relating maximum size to atmospheric environmental oxygen concentration (pO2) until the end of the Jurassic, and then at constant sizes, independent of oxygen fluctuations, during the Cretaceous and, at a smaller size, the Cenozoic. Maximum insect size decreased even as atmospheric pO2 rose in the Early Cretaceous following the evolution and radiation of early birds, particularly as birds acquired adaptations that allowed more agile flight. A further decrease in maximum size during the Cenozoic may relate to the evolution of bats, the Cretaceous mass extinction, or further specialization of flying birds. The decoupling of insect size and atmospheric pO2 coincident with the radiation of birds suggests that biotic interactions, such as predation and competition, superseded oxygen as the most important constraint on maximum body size of the largest insects.

  9. The interactive biotic and abiotic processes of DDT transformation under dissimilatory iron-reducing conditions.

    Science.gov (United States)

    Jin, Xin; Wang, Fang; Gu, Chenggang; Yang, Xinglun; Kengara, Fredrick O; Bian, Yongrong; Song, Yang; Jiang, Xin

    2015-11-01

    The objective of the study was to elucidate the biotic and abiotic processes under dissimilatory iron reducing conditions involved in reductive dechlorination and iron reduction. DDT transformation was investigated in cultures of Shewanella putrefaciens 200 with/without α-FeOOH. A modified first-order kinetics model was developed and described DDT transformation well. Both the α-FeOOH reduction rate and the dechlorination rate of DDT were positively correlated to the biomass. Addition of α-FeOOH enhanced reductive dechlorination of DDT by favoring the cell survival and generating Fe(II) which was absorbed on the surface of bacteria and iron oxide. 92% of the absorbed Fe(II) was Na-acetate (1M) extractable. However, α-FeOOH also played a negative role of competing for electrons as reflected by the dechlorination rate of DDT was inhibited when increasing the α-FeOOH from 1 g L(-1) to 5 g L(-1). DDT was measured to be toxic to S. putrefaciens 200. The metabolites DDD, DDE and DDMU were recalcitrant to S. putrefaciens 200. The results suggested that iron oxide was not the key factor to promote the dissipation of DDX (DDT and the metabolites), whereas the one-electron reduction potential (E1) of certain organochlorines is the main factor and that the E1 higher than the threshold of the reductive driving forces of DIRB probably ensures the occur of reductive dechlorination. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Biotic and abiotic variables influencing plant litter breakdown in streams: a global study

    Science.gov (United States)

    Pearson, Richard G.; Hui, Cang; Gessner, Mark O.; Pérez, Javier; Alexandrou, Markos A.; Graça, Manuel A. S.; Cardinale, Bradley J.; Albariño, Ricardo J.; Arunachalam, Muthukumarasamy; Barmuta, Leon A.; Boulton, Andrew J.; Bruder, Andreas; Callisto, Marcos; Chauvet, Eric; Death, Russell G.; Dudgeon, David; Encalada, Andrea C.; Ferreira, Verónica; Figueroa, Ricardo; Flecker, Alexander S.; Gonçalves, José F.; Helson, Julie; Iwata, Tomoya; Jinggut, Tajang; Mathooko, Jude; Mathuriau, Catherine; M'Erimba, Charles; Moretti, Marcelo S.; Pringle, Catherine M.; Ramírez, Alonso; Ratnarajah, Lavenia; Rincon, José; Yule, Catherine M.

    2016-01-01

    Plant litter breakdown is a key ecological process in terrestrial and freshwater ecosystems. Streams and rivers, in particular, contribute substantially to global carbon fluxes. However, there is little information available on the relative roles of different drivers of plant litter breakdown in fresh waters, particularly at large scales. We present a global-scale study of litter breakdown in streams to compare the roles of biotic, climatic and other environmental factors on breakdown rates. We conducted an experiment in 24 streams encompassing latitudes from 47.8° N to 42.8° S, using litter mixtures of local species differing in quality and phylogenetic diversity (PD), and alder (Alnus glutinosa) to control for variation in litter traits. Our models revealed that breakdown of alder was driven by climate, with some influence of pH, whereas variation in breakdown of litter mixtures was explained mainly by litter quality and PD. Effects of litter quality and PD and stream pH were more positive at higher temperatures, indicating that different mechanisms may operate at different latitudes. These results reflect global variability caused by multiple factors, but unexplained variance points to the need for expanded global-scale comparisons. PMID:27122551

  11. Predicting Efficient Antenna Ligands for Tb(III) Emission

    Energy Technology Data Exchange (ETDEWEB)

    Samuel, Amanda P.S.; Xu, Jide; Raymond, Kenneth

    2008-10-06

    A series of highly luminescent Tb(III) complexes of para-substituted 2-hydroxyisophthalamide ligands (5LI-IAM-X) has been prepared (X = H, CH{sub 3}, (C=O)NHCH{sub 3}, SO{sub 3}{sup -}, NO{sub 2}, OCH{sub 3}, F, Cl, Br) to probe the effect of substituting the isophthalamide ring on ligand and Tb(III) emission in order to establish a method for predicting the effects of chromophore modification on Tb(III) luminescence. The energies of the ligand singlet and triplet excited states are found to increase linearly with the {pi}-withdrawing ability of the substituent. The experimental results are supported by time-dependent density functional theory (TD-DFT) calculations performed on model systems, which predict ligand singlet and triplet energies within {approx}5% of the experimental values. The quantum yield ({Phi}) values of the Tb(III) complex increases with the triplet energy of the ligand, which is in part due to the decreased non-radiative deactivation caused by thermal repopulation of the triplet. Together, the experimental and theoretical results serve as a predictive tool that can be used to guide the synthesis of ligands used to sensitize lanthanide luminescence.

  12. Transgenic crops with an improved resistance to biotic stresses. A review

    Directory of Open Access Journals (Sweden)

    Tohidfar, M.

    2015-01-01

    Full Text Available Introduction. Pests, diseases and weeds (biotic stresses are significant limiting factors for crop yield and production. However, the limitations associated with conventional breeding methods necessitated the development of alternative methods for improving new varieties with higher resistance to biotic stresses. Molecular techniques have developed applicable methods for genetic transformation of a wide range of plants. Genetic engineering approach has been demonstrated to provide enormous options for the selection of the resistance genes from different sources to introduce them into plants to provide resistance against different biotic stresses. Literature. In this review, we focus on strategies to achieve the above mentioned objectives including expression of insecticidal, antifungal, antibacterial, antiviral resistance and herbicide detoxification for herbicide resistance. Conclusion. Regardless of the concerns about commercialization of products from genetically modified (GM crops resistant to biotic stresses, it is observed that the cultivation area of these crops is growing fast each year. Considering this trend, it is expected that production and commercialization of GM crops resistant to biotic stresses will continue to increase but will also extend to production of crops resistant to abiotic stresses (e.g. drought, salinity, etc. in a near future.

  13. Rosetta Ligand docking with flexible XML protocols.

    Science.gov (United States)

    Lemmon, Gordon; Meiler, Jens

    2012-01-01

    RosettaLigand is premiere software for predicting how a protein and a small molecule interact. Benchmark studies demonstrate that 70% of the top scoring RosettaLigand predicted interfaces are within 2Å RMSD from the crystal structure [1]. The latest release of Rosetta ligand software includes many new features, such as (1) docking of multiple ligands simultaneously, (2) representing ligands as fragments for greater flexibility, (3) redesign of the interface during docking, and (4) an XML script based interface that gives the user full control of the ligand docking protocol.

  14. Effect of 2-chloro-substitution of adenine moiety in mixed-ligand gold(I triphenylphosphine complexes on anti-inflammatory activity: the discrepancy between the in vivo and in vitro models.

    Directory of Open Access Journals (Sweden)

    Jan Hošek

    Full Text Available A series of gold(I triphenylphosphine (PPh3 complexes (1-9 involving 2-chloro-N6-(substituted-benzyladenine derivatives as N-donor ligands was synthesized and thoroughly characterized by relevant methods, including electrospray-ionization (ESI mass spectrometry and multinuclear NMR spectroscopy. The anti-inflammatory and antiedematous effects of three representatives 1, 5 and 9 were evaluated by means of in vitro model based on the expression of pro- and anti-inflammatory cytokines and influence of the complexes on selected forms of matrix metalloproteinases secreted by LPS-activated THP-1 monocytes and in vivo model evaluating the antiedematous effect of the complexes in the carrageenan-induced rat hind-paw edema model. In addition to the pharmacological observations, the affected hind paws were post mortem subjected to histological and immunohistochemical evaluations. The results of both in vivo and ex vivo methods revealed low antiedematous and anti-inflammatory effects of the complexes, even though the in vitro model identified them as promising anti-inflammatory acting compounds. The reason for this discrepancy lies probably in low stability of the studied complexes in biological environment, as demonstrated by the solution interaction studies with sulfur-containing biomolecules (cysteine and reduced glutathione using the ESI mass spectrometry.

  15. Modeling the interactions of a peptide-major histocompatibility class I ligand with its receptors. I. Recognition by two alpha beta T cell receptors

    DEFF Research Database (Denmark)

    Rognan, D; Stryhn, A; Fugger, L

    2000-01-01

    dynamics. Next, three-dimensional models of two different T cell receptors (TCRs) both specific for the Ha255-262/Kk complex were generated based on previously published TCR X-ray structures. Finally, guided by the recently published X-ray structures of ternary TCR/peptide/MHC-I complexes, the TCR models...... the models. They were found to account well for the experimentally obtained data, lending considerable support to the proposed models and suggesting a universal docking mode for alpha beta TCRs to MHC-peptide complexes. Such models may also be useful in guiding future rational experimentation....

  16. Do Karst Rivers “deserve” their own biotic index? A ten years study on macrozoobenthos in Croatia

    Directory of Open Access Journals (Sweden)

    Rađa Biljana

    2010-07-01

    Full Text Available In this study we present the results of a ten year survey of the aquatic macroinvertebrate fauna along four karst rivers: Jadro, Žrnovnica, Grab and Ruda, all of them situated in the Middle Dalmatia region of Croatia, in an attempt to construct the Iliric Biotic Index, which will be more applicable for the water quality analysis than the most frequently applied biotic index in Croatia, the Italian Modification of Extended Biotic Index. The rivers geologically belong to the Dinaric karst, unique geological phenomena in Europe. Benthic macroinvertebrates were collected along each river at 15 sites by standard methods of sampling along with several physicochemical parameters, including: temperature, dissolved oxygen, carbon dioxide, alkalinity, hardness and pH. Univariate and multivariate techniques revealed differences in the macroinvertebrate community structure as well as in physicochemical parameters between the Karst rivers and continental rivers. Based on those differences, the Iliric Biotic Index was proposed as the standard of karst river water quality in Croatia in accordance with the EU Water Framework Directive. Differences between the Iliric Biotic Index and the most commonly used biotic indices in the European Community and the USA (The Biological Monitoring Working Party (B.M.W.P. scores, i.e. Extended Biotic Index, Indice Biotique, Family Biotic Index suggest that karst rivers need a new biotic index.

  17. Utilizing Genetic Resources and Precision Agriculture to Enhance Resistance to Biotic and Abiotic Stress in Watermelon

    Directory of Open Access Journals (Sweden)

    Mihail KANTOR

    2018-03-01

    Full Text Available Originally from Africa, watermelon is a staple crop in South Carolina and rich source of important phytochemicals that promote human health. As a result of many years of domestication and selection for desired fruit quality, modern watermelon cultivars are susceptible to biotic and abiotic stress. The present review discusses how genetic selection and breeding combined with geospatial technologies (precision agriculture may help enhance watermelon varieties for resistance to biotic and abiotic stress. Gene loci identified and selected in undomesticated watermelon accessions are responsible for resistance to diseases, pests and abiotic stress. Vegetable breeding programs use traditional breeding methodologies and genomic tools to introduce gene loci conferring biotic or abiotic resistance into the genome background of elite watermelon cultivars. This continuous approach of collecting, evaluating and identifying useful genetic material is valuable for enhancing genetic diversity and tolerance and combined with precision agriculture could increase food security in the Southeast.

  18. Climate change and the past, present, and future of biotic interactions.

    Science.gov (United States)

    Blois, Jessica L; Zarnetske, Phoebe L; Fitzpatrick, Matthew C; Finnegan, Seth

    2013-08-02

    Biotic interactions drive key ecological and evolutionary processes and mediate ecosystem responses to climate change. The direction, frequency, and intensity of biotic interactions can in turn be altered by climate change. Understanding the complex interplay between climate and biotic interactions is thus essential for fully anticipating how ecosystems will respond to the fast rates of current warming, which are unprecedented since the end of the last glacial period. We highlight episodes of climate change that have disrupted ecosystems and trophic interactions over time scales ranging from years to millennia by changing species' relative abundances and geographic ranges, causing extinctions, and creating transient and novel communities dominated by generalist species and interactions. These patterns emerge repeatedly across disparate temporal and spatial scales, suggesting the possibility of similar underlying processes. Based on these findings, we identify knowledge gaps and fruitful areas for research that will further our understanding of the effects of climate change on ecosystems.

  19. Screening of ligands for the Ullmann synthesis of electron-rich diaryl ethers

    Directory of Open Access Journals (Sweden)

    Nicola Otto

    2012-07-01

    Full Text Available In the search for new ligands for the Ullmann diaryl ether synthesis, permitting the coupling of electron-rich aryl bromides at relatively low temperatures, 56 structurally diverse multidentate ligands were screened in a model system that uses copper iodide in acetonitrile with potassium phosphate as the base. The ligands differed largely in their performance, but no privileged structural class could be identified.

  20. Application of Irradiated Pro biotic Microorganism in Black Tiger Shrimp (Penaeus monodon Fabricius) Culture

    International Nuclear Information System (INIS)

    Areechon, Nontawith; Purivrojkul, Watchariya; Srisapoome, Prapansak; Piadiang, Nattaya

    2006-09-01

    Marine shrimp culture in Thailand has been developed continuously for the past two decades. This development will ensure the highest level of shrimp quality that will be suitable for the consumption of the people in the country and also aboard. The trend of culture system emphasizes on disease prevention more than treatment which will consequently limit the application of drug and chemicals. Application of pro biotic has been one means of this prevention that are commonly practiced by shrimp farmers. This research was conducted to compare the efficacy of normal Bacillus subtilis isolate from shrimp intestine and an irradiated B. subtilis as a pro biotic in shrimp feed. It was found that overall results were quite the same. These included the broth Co-culture assay. Effects on immune functions were conducted with Penaeus monodon with initial average weight of 17 gms by feeding with 3 gms/kg feed of spore of these two pro biotic for two mouths. The results indicated that both pro biotic caused significant improvement on percent phagocytosis only at the forth week of feeding trial and the overall enhancement of bactericidal activity. However, total haemocyte count and phenoloxidase activity were not altered. Total bacterial count in shrimp intestine was also conducted during the two month trial. the results indicated significant reduction of Vibrio spp. of both pro biotic groups when compared with the control. Number of Bacillus spp. in intestine were continuously high even after pro biotic treatment had been stopped Growth rate of experiment and control shrimp was not significantly different.

  1. Long ligands reinforce biological adhesion under shear flow

    Science.gov (United States)

    Belyaev, Aleksey V.

    2018-04-01

    In this work, computer modeling has been used to show that longer ligands allow biological cells (e.g., blood platelets) to withstand stronger flows after their adhesion to solid walls. A mechanistic model of polymer-mediated ligand-receptor adhesion between a microparticle (cell) and a flat wall has been developed. The theoretical threshold between adherent and non-adherent regimes has been derived analytically and confirmed by simulations. These results lead to a deeper understanding of numerous biophysical processes, e.g., arterial thrombosis, and to the design of new biomimetic colloid-polymer systems.

  2. Crystallization of protein–ligand complexes

    International Nuclear Information System (INIS)

    Hassell, Anne M.; An, Gang; Bledsoe, Randy K.; Bynum, Jane M.; Carter, H. Luke III; Deng, Su-Jun J.; Gampe, Robert T.; Grisard, Tamara E.; Madauss, Kevin P.; Nolte, Robert T.; Rocque, Warren J.; Wang, Liping; Weaver, Kurt L.; Williams, Shawn P.; Wisely, G. Bruce; Xu, Robert; Shewchuk, Lisa M.

    2007-01-01

    Methods presented for growing protein–ligand complexes fall into the categories of co-expression of the protein with the ligands of interest, use of the ligands during protein purification, cocrystallization and soaking the ligands into existing crystals. Obtaining diffraction-quality crystals has long been a bottleneck in solving the three-dimensional structures of proteins. Often proteins may be stabilized when they are complexed with a substrate, nucleic acid, cofactor or small molecule. These ligands, on the other hand, have the potential to induce significant conformational changes to the protein and ab initio screening may be required to find a new crystal form. This paper presents an overview of strategies in the following areas for obtaining crystals of protein–ligand complexes: (i) co-expression of the protein with the ligands of interest, (ii) use of the ligands during protein purification, (iii) cocrystallization and (iv) soaks

  3. Distinct Iron-binding Ligands in the Upper Water Column at Station ALOHA

    Science.gov (United States)

    Bundy, R.; Boiteau, R.; Repeta, D.

    2016-02-01

    The distribution and chemical properties of iron-binding organic ligands at station ALOHA were examined using a combination of solid phase extraction (SPE) followed by high pressure liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICPMS). HPLC-ICPMS ligand measurements were complemented by competitive ligand exchange adsorptive cathodic stripping voltammetry (CLE-ACSV) analysis using salicylaldoxime as the added ligand. By HPLC-ICPMS, we find enhanced concentrations of distinct naturally-occurring polar iron-binding ligands present at the surface and in the chlorophyll maximum. Lower concentrations were found in the subsurface, where a suite of non-polar ligands was detected. Siderophores were present at the deepest depths sampled at station ALOHA, down to 400m. Incubation studies provided evidence for the production of iron-binding ligands associated with nutrient amended phytoplankton growth in surface waters, and as a result of microbial particle remineralization in the subsurface water column. Ligands classes identified via SPE were then compared to CLE-ACSV ligand measurements, as well as the conditional stability constants measured from model polar and non-polar siderophores, yielding insight to the sources of iron-binding ligands throughout the water column at station ALOHA.

  4. Iron and Zinc Complexes of Bulky Bis-Imidazole Ligands : Enzyme Mimicry and Ligand-Centered Redox Activity

    NARCIS (Netherlands)

    Folkertsma, E.

    2016-01-01

    The research described in this thesis is directed to the development of cheap and non-toxic iron-based homogeneous catalysts, using enzyme models and redox non-innocent ligands. Inspired by nature, the first approach focuses on the synthesis of structural models of the active site of non-heme iron

  5. Characterization and comparison of iron oxyhydroxide precipitates from biotic and abiotic groundwater treatments

    DEFF Research Database (Denmark)

    Arturi, Katarzyna R.; Bender Koch, Christian; Søgaard, Erik G.

    2017-01-01

    Removal of iron is an important step in groundwater treatment for drinking water production. It is performed to prevent organoleptic issues and clogging in water supply systems. Iron can be eliminated with a purely physico-chemical (abiotic) method or biotically with the help of iron......-oxidizing bacteria (FeOB). Each of the purification methods requires different operating conditions and results in formation of iron oxyhydroxide (FeOOH) precipitates. Knowledge about the differences in composition and properties of the biotic and abiotic precipitates is desirable from a technical, but also...

  6. WATER QUALITY ANALYSIS OF LOTIC ECOSYSTEMS FROM UPPER MUREŞ RIVER CATCHMENT AREA USING DIFFERENT BIOTIC INDICES

    Directory of Open Access Journals (Sweden)

    Milca PETROVICI

    2012-01-01

    Full Text Available Present paper approach the issue of assessing the water quality of tributaries located in the upper basin of the river Mureş, taking into account changes in the value of biotic indices. In this sense, have been selected the next five biotic indices: Ephemeroptera Plecoptera Trichoptera index (EPT, Total Invertebrates index (T, Chironomidae index (Ch, EPT / Total invertebrates index (EPT / T, EPT / Chironomidae index (EPT / Ch and % Chironomidae index (% Chironomidae. Considering all these indices, it was found existence of a medium to best quality water in Mureş tributaries from Harghita Mountains and a good quality water which comes from the Maramureş Mountains and Transylvania Plateau.

  7. Adsorption of hairy particles with mobile ligands: Molecular dynamics and density functional study

    Science.gov (United States)

    Borówko, M.; Sokołowski, S.; Staszewski, T.; Pizio, O.

    2018-01-01

    We study models of hairy nanoparticles in contact with a hard wall. Each particle is built of a spherical core with a number of ligands attached to it and each ligand is composed of several spherical, tangentially jointed segments. The number of segments is the same for all ligands. Particular models differ by the numbers of ligands and of segments per ligand, but the total number of segments is constant. Moreover, our model assumes that the ligands are tethered to the core in such a manner that they can "slide" over the core surface. Using molecular dynamics simulations we investigate the differences in the structure of a system close to the wall. In order to characterize the distribution of the ligands around the core, we have calculated the end-to-end distances of the ligands and the lengths and orientation of the mass dipoles. Additionally, we also employed a density functional approach to obtain the density profiles. We have found that if the number of ligands is not too high, the proposed version of the theory is capable to predict the structure of the system with a reasonable accuracy.

  8. -Pincer Ligand Family through Ligand Post-Modification

    KAUST Repository

    Huang, Mei-Hui; Hu, Jinsong; Huang, Kuo-Wei

    2017-01-01

    A series of air-stable nickel complexes containing triazine-based PN3P-pincer ligands were synthesized and fully characterized. Complex 3 contains a de-aromatized central triazine ring from the deprotonation of one of the N–H arms. With a post-modification strategy, the Me-PN3P*NiCl complex (3) could be converted into a new class of diimine–traizine PN3P-pincer nickel complexes.

  9. -Pincer Ligand Family through Ligand Post-Modification

    KAUST Repository

    Huang, Mei-Hui

    2017-10-02

    A series of air-stable nickel complexes containing triazine-based PN3P-pincer ligands were synthesized and fully characterized. Complex 3 contains a de-aromatized central triazine ring from the deprotonation of one of the N–H arms. With a post-modification strategy, the Me-PN3P*NiCl complex (3) could be converted into a new class of diimine–traizine PN3P-pincer nickel complexes.

  10. Reactivity of halide and pseudohalide ligands

    International Nuclear Information System (INIS)

    Kukushkin, Yu.N.

    1987-01-01

    Reactivity of halide and pseudohalide (cyanide, azide, thiocyanate, cyanate) ligands tending to form bridge bonds in transition metal (Re, Mo, W) complexes is considered. Complexes where transition metal salts are ligands of other, complex-forming ion, are described. Transformation of innerspheric pseudohalide ligands is an important way of directed synthesis of these metal coordination compounds

  11. Contamination of short-chain chlorinated paraffins to the biotic and abiotic environments in the Bohai Sea.

    Science.gov (United States)

    Jiang, Wanyanhan; Huang, Tao; Chen, Han; Lian, Lulu; Liang, Xiaoxue; Jia, Chenhui; Gao, Hong; Mao, Xiaoxuan; Zhao, Yuan; Ma, Jianmin

    2018-02-01

    Short-chain chlorinated paraffins (SCCPs) have been produced and emitted intensively around the Bohai Sea, potentially causing risks to this unique ecosystem and one of primary fishery resources in China and busiest seaways in the world. Little is known about fate, cycling, and sources of SCCPs in the Bohai Sea biotic and abiotic environment. In this study, we combined a marine food web model with a comprehensive atmospheric transport-multiple phase exchange model to quantify SCCPs in the biotic and abiotic environment in the Bohai Sea. We performed multiple modeling scenario investigations to examine SCCP levels in water, sediment, and phytoplankton. We assessed numerically dry and wet depositions, biomagnification and bioaccumulation of SCCPs in the Bohai Sea marine food web. Results showed declining SCCP levels in water and sediment with increasing distance from the coastline, and so do dry and wet depositions. The net deposition overwhelmed the water-air exchange of SCCPs due to their current use in China, though the diffusive gas deposition fluctuated monthly subject to mean wind speed and temperature. A risk assessment manifests that SCCPs levels in the Bohai Sea fish species are at present not posing risks to the residents in the Bohai Sea Rim region. We identified that the SCCP emission sources in the south of the Bohai Sea made a primary contribution to its loadings to the seawater and fish contamination associated with the East Asian summer monsoon. In contrast, the SCCP emissions from the north and northwest regions of the Bohai Sea were major sources contributing to their loading and contamination to Bohai Sea food web during the wintertime, potentially driven by the East Asian winter monsoon. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. In vitro evaluation of biodegradable microspheres with surface-bound ligands.

    Science.gov (United States)

    Keegan, Mark E; Royce, Sara M; Fahmy, Tarek; Saltzman, W Mark

    2006-02-21

    Protein ligands were conjugated to the surface of biodegradable microspheres. These microsphere-ligand conjugates were then used in two in vitro model systems to evaluate the effect of conjugated ligands on microsphere behavior. Microsphere retention in agarose columns was increased by ligands on the microsphere surface specific for receptors on the agarose matrix. In another experiment, conjugating the lectin Ulex europaeus agglutinin 1 to the microsphere surface increased microsphere adhesion to Caco-2 monolayers compared to control microspheres. This increase in microsphere adhesion was negated by co-administration of l-fucose, indicating that the increase in adhesion is due to specific interaction of the ligand with carbohydrate receptors on the cell surface. These results demonstrate that the ligands conjugated to the microspheres maintain their receptor binding activity and are present on the microsphere surface at a density sufficient to target the microspheres to both monolayers and three-dimensional matrices bearing complementary receptors.

  13. Modeling the interactions of a peptide-major histocompatibility class I ligand with its receptors. II. Cross-reaction between a monoclonal antibody and two alpha beta T cell receptors

    DEFF Research Database (Denmark)

    Rognan, D; Engberg, J; Stryhn, A

    2000-01-01

    -peptide pair into the Fab combining site. Interestingly, the most energetically favored binding mode shows numerous analogies to the recently determined recognition of class I MHC-peptide complexes by alpha beta T cell receptors (TCRs). The pSAN13.4.1 also binds diagonally across the MHC binding groove......The recombinant antibody, pSAN13.4.1, has a unique T cell like specificity; it binds an Influenza Hemagglutinin octapeptide (Ha255-262) in an MHC (H-2Kk)-restricted manner, and a detailed comparison of the fine specificity of pSAN13.4.1 with the fine specificity of two Ha255-262-specific, H-2Kk......-restricted T cell hybridomas has supported this contention. A three-dimensional model of pSAN13.4.1 has been derived by homology modeling techniques. Subsequently, the structure of the pSAN13.4.1 antibody in complex with the antigenic Ha-Kk ligand was derived after a flexible and automated docking of the MHC...

  14. Parallel screening of drug-like natural compounds using Caco-2 cell permeability QSAR model with applicability domain, lipophilic ligand efficiency index and shape property: A case study of HIV-1 reverse transcriptase inhibitors

    Science.gov (United States)

    Patel, Rikin D.; Kumar, Sivakumar Prasanth; Patel, Chirag N.; Shankar, Shetty Shilpa; Pandya, Himanshu A.; Solanki, Hitesh A.

    2017-10-01

    The traditional drug design strategy centrally focuses on optimizing binding affinity with the receptor target and evaluates pharmacokinetic properties at a later stage which causes high rate of attrition in clinical trials. Alternatively, parallel screening allows evaluation of these properties and affinity simultaneously. In a case study to identify leads from natural compounds with experimental HIV-1 reverse transcriptase (RT) inhibition, we integrated various computational approaches including Caco-2 cell permeability QSAR model with applicability domain (AD) to recognize drug-like natural compounds, molecular docking to study HIV-1 RT interactions and shape similarity analysis with known crystal inhibitors having characteristic butterfly-like model. Further, the lipophilic properties of the compounds refined from the process with best scores were examined using lipophilic ligand efficiency (LLE) index. Seven natural compound hits viz. baicalien, (+)-calanolide A, mniopetal F, fagaronine chloride, 3,5,8-trihydroxy-4-quinolone methyl ether derivative, nitidine chloride and palmatine, were prioritized based on LLE score which demonstrated Caco-2 well absorption labeling, encompassment in AD structural coverage, better receptor affinity, shape adaptation and permissible AlogP value. We showed that this integrative approach is successful in lead exploration of natural compounds targeted against HIV-1 RT enzyme.

  15. Theory of advection-driven long range biotic transport

    Science.gov (United States)

    We propose a simple mechanistic model to examine the effects of advective flow on the spread of fungal diseases spread by wind-blown spores. The model is defined by a set of two coupled non-linear partial differential equations for spore densities. One equation describes the long-distance advectiv...

  16. Ligand-regulated peptide aptamers.

    Science.gov (United States)

    Miller, Russell A

    2009-01-01

    The peptide aptamer approach employs high-throughput selection to identify members of a randomized peptide library displayed from a scaffold protein by virtue of their interaction with a target molecule. Extending this approach, we have developed a peptide aptamer scaffold protein that can impart small-molecule control over the aptamer-target interaction. This ligand-regulated peptide (LiRP) scaffold, consisting of the protein domains FKBP12, FRB, and GST, binds to the cell-permeable small-molecule rapamycin and the binding of this molecule can prevent the interaction of the randomizable linker region connecting FKBP12 with FRB. Here we present a detailed protocol for the creation of a peptide aptamer plasmid library, selection of peptide aptamers using the LiRP scaffold in a yeast two-hybrid system, and the screening of those peptide aptamers for a ligand-regulated interaction.

  17. Ligand binding by PDZ domains

    DEFF Research Database (Denmark)

    Chi, Celestine N.; Bach, Anders; Strømgaard, Kristian

    2012-01-01

    , for example, are particularly rich in these domains. The general function of PDZ domains is to bring proteins together within the appropriate cellular compartment, thereby facilitating scaffolding, signaling, and trafficking events. The many functions of PDZ domains under normal physiological as well...... as pathological conditions have been reviewed recently. In this review, we focus on the molecular details of how PDZ domains bind their protein ligands and their potential as drug targets in this context....

  18. Bitopic Ligands and Metastable Binding Sites

    DEFF Research Database (Denmark)

    Fronik, Philipp; Gaiser, Birgit I; Sejer Pedersen, Daniel

    2017-01-01

    of orthosteric binding sites. Bitopic ligands have been employed to address the selectivity problem by combining (linking) an orthosteric ligand with an allosteric modulator, theoretically leading to high-affinity subtype selective ligands. However, it remains a challenge to identify suitable allosteric binding...... that have been reported to date, this type of bitopic ligands would be composed of two identical pharmacophores. Herein, we outline the concept of bitopic ligands, review metastable binding sites, and discuss their potential as a new source of allosteric binding sites....

  19. Radioiodinated ligands for dopamine receptors

    International Nuclear Information System (INIS)

    Kung, H.F.

    1994-01-01

    The dopamine receptor system is important for normal brain function; it is also the apparent action site for various neuroleptic drugs for the treatment of schizophrenia and other metal disorders. In the past few years radioiodinated ligands for single photon emission tomography (SPECT) have been successfully developed and tested in humans: [ 123 I]TISCH for D1 dopamine receptors; [ 123 I]IBZM, epidepride, IBF and FIDA2, four iodobenzamide derivatives, for D2/D3 dopamine receptors. In addition, [ 123 I]β-CIT (RTI-55) and IPT, cocaine derivatives, for the dopamine reuptake site are potentially useful for diagnosis of loss of dopamine neurons. The first iodinated ligand, (R)trans-7-OH-PIPAT, for D3 dopamine receptors, was synthesized and characterized with cloned cell lines (Spodoptera frugiperda, Sf9) expressing the D2 and D3 dopamine receptors and with rat basal forebrain membrane preparations. Most of the known iodobenzamides displayed similar potency in binding to both D2 and D3 dopamine receptors expressed in the cell lines. Initial studies appear to suggest that by fine tuning the structures it may be possible to develop agents specific for D2 and D3 dopamine receptors. It is important to investigate D2/D3 selectivity for this series of potent ligands

  20. Linking biotic homogenization to habitat type, invasiveness and growth form of naturalized alien plants in North America

    Science.gov (United States)

    Hong Qian; Qinfeng. Guo

    2010-01-01

    Aim Biotic homogenization is a growing phenomenon and has recently attracted much attention. Here, we analyse a large dataset of native and alien plants in North America to examine whether biotic homogenization is related to several ecological and biological attributes. Location North America (north of Mexico). Methods We assembled...

  1. Stable carbon isotope analysis to distinguish biotic and abiotic degradation of 1,1,1-trichloroethane in groundwater sediments

    DEFF Research Database (Denmark)

    Broholm, Mette Martina; Hunkeler, Daniel; Tuxen, Nina

    2014-01-01

    not appear to be reductive dechlorination via 1,1-DCA. In the biotic microcosms, the degradation of 1,1,1-TCA occurred under iron and sulfate reducing conditions. Biotic reduction of iron and sulfate likely resulted in formation of FeS, which can abiotically degrade 1,1,1-TCA. Hence, abiotic degradation of 1...

  2. Hydrologic, abiotic and biotic interactions: plant density, windspeed, leaf size and groundwater all affect oak water use efficiency

    Science.gov (United States)

    Darin J. Law; Deborah M. Finch

    2011-01-01

    Plant water use in drylands can be complex due to variation in hydrologic, abiotic and biotic factors, particularly near ephemeral or intermittent streams. Plant use of groundwater may be important but is usually uncertain. Disturbances like fire contribute to complex spatiotemporal heterogeneity. Improved understanding of how such hydrologic, abiotic, and biotic...

  3. The role of biotic interactions in plant community assembly: What is the community species pool?

    Czech Academy of Sciences Publication Activity Database

    Švamberková, E.; Vítová, A.; Lepš, Jan

    2017-01-01

    Roč. 85, NOV 01 (2017), s. 150-156 ISSN 1146-609X Institutional support: RVO:60077344 Keywords : abiotic filter * biotic filter * competitive exclusion Subject RIV: EH - Ecology, Behaviour OBOR OECD: Ecology Impact factor: 1.652, year: 2016 http://www.sciencedirect.com/science/article/pii/S1146609X16303757

  4. Pivoting from Arabidopsis to wheat to understand how agricultural plants integrate responses to biotic stress

    Science.gov (United States)

    Here we argue for a research initiative on gene-for-gene (g-f-g) interactions between wheat and its parasites. One aim is to begin a conversation between the disparate communities of plant pathology and entomology. Another is to understand how responses to biotic stress are integrated in an import...

  5. Abiotic and biotic drivers of biomass change in a Neotropical forest

    NARCIS (Netherlands)

    Sande, van der M.T.; Pena Claros, M.; Ascarrunz, Nataly; Arets, E.J.M.M.; Licona, J.C.; Toledo, Marisol; Poorter, L.

    2017-01-01

    Summary
    1. Tropical fores ts play an important role in the global carbon cycle, but the drivers of net forest biomass change (i.e. net carbon sequestration) are poorly understood. Here, we evaluate how abiotic factors (soil co nditions and disturbance) and biotic factors (forest structure,

  6. Biotic soil crusts in relation to topography, cheatgrass, and fire in the Columbia Basin, Washington

    Science.gov (United States)

    Ponzetti, Jeanne; McCune, B.; Pyke, David A.

    2007-01-01

    We studied lichen and bryophyte soil crust communities in a large public grazing allotment within a sagebrush steppe ecosystem in which the biotic soil crusts are largely intact. The allotment had been rested from grazing for 12 years, but experienced an extensive series of wildfires. In the 350, 4 ?? 0.5 m plots, stratified by topographic position, we found 60 species or species groups that can be distinguished in the field with a hand lens, averaging 11.5 species groups per plot. Lichen and bryophyte soil crust communities differed among topographic positions. Draws were the most disturbed, apparently from water erosion in a narrow channel and mass wasting from the steepened sides. Presumably because of this disturbance, draws had the lowest average species richness of all the topographic strata we examined. Biotic crust species richness and cover were inversely related to cover of the invasive annual, cheatgrass (Bromus tectorum), and positively related to cover of native bunchgrasses. Integrity of the biotic crust was more strongly related to cheatgrass than to fire. In general, we observed good recovery of crusts following fire, but only in those areas dominated by perennial bunchgrasses. We interpret the resilience of the biotic crust, in this case, to the low abundance of cheatgrass, low amounts of soil disturbance and high moss cover. These fires have not resulted in an explosion of the cheatgrass population, perhaps because of the historically low levels of livestock grazing.

  7. Environmental and biotic controls over aboveground biomass throughout a tropical rainforest

    Science.gov (United States)

    G.P. Asner; R.F. Hughes; T.A. Varga; D.E. Knapp; T. Kennedy-Bowdoin

    2009-01-01

    The environmental and biotic factors affecting spatial variation in canopy three-dimensional (3-D) structure and aboveground tree biomass (AGB) are poorly understood in tropical rain forests. We combined field measurements and airborne light detection and ranging (lidar) to quantify 3-D structure and AGB across a 5,016 ha rain forest reserve on the...

  8. White-tailed deer are a biotic filter during community assembly, reducing species and phylogenetic diversity.

    Science.gov (United States)

    Begley-Miller, Danielle R; Hipp, Andrew L; Brown, Bethany H; Hahn, Marlene; Rooney, Thomas P

    2014-06-09

    Community assembly entails a filtering process, where species found in a local community are those that can pass through environmental (abiotic) and biotic filters and successfully compete. Previous research has demonstrated the ability of white-tailed deer (Odocoileus virginianus) to reduce species diversity and favour browse-tolerant plant communities. In this study, we expand on our previous work by investigating deer as a possible biotic filter altering local plant community assembly. We used replicated 23-year-old deer exclosures to experimentally assess the effects of deer on species diversity (H'), richness (SR), phylogenetic community structure and phylogenetic diversity in paired browsed (control) and unbrowsed (exclosed) plots. Additionally, we developed a deer-browsing susceptibility index (DBSI) to assess the vulnerability of local species to deer. Deer browsing caused a 12 % reduction in H' and 17 % reduction in SR, consistent with previous studies. Furthermore, browsing reduced phylogenetic diversity by 63 %, causing significant phylogenetic clustering. Overall, graminoids were the least vulnerable to deer browsing based on DBSI calculations. These findings demonstrate that deer are a significant driver of plant community assembly due to their role as a selective browser, or more generally, as a biotic filter. This study highlights the importance of knowledge about the plant tree of life in assessing the effects of biotic filters on plant communities. Application of such knowledge has considerable potential to advance our understanding of plant community assembly. Published by Oxford University Press on behalf of the Annals of Botany Company.

  9. Using biotechnology and genomics to improve biotic and abiotic stress in apple

    Science.gov (United States)

    Genomic sequencing, molecular biology, and transformation technologies are providing valuable tools to better understand the complexity of how plants develop, function, and respond to biotic and abiotic stress. These approaches should complement but not replace a solid understanding of whole plant ...

  10. Invasion by native tree species prevents biotic homogenization in novel forests of Puerto Rico

    Science.gov (United States)

    Oscar J. Abelleira Martinez

    2010-01-01

    There is concern that secondary forests dominated by introduced species, known as novel forests, increase taxonomical similarity between localities and lead to biotic homogenization in human dominated landscapes. In Puerto Rico, agricultural abandonment has given way to novel forests dominated by the introduced African tulip tree Spathodea campanulata Beauv. (...

  11. Rodent seed predation as a biotic filter influencing exotic plant abundance and distribution

    Science.gov (United States)

    D. E. Pearson; J. L. Hierro; M. Chiuffo; D. Villarreal

    2014-01-01

    Biotic resistance is commonly invoked to explain why many exotic plants fail to thrive in introduced ranges, but the role of seed predation as an invasion filter is understudied. Abiotic conditions may also influence plant populations and can interact with consumers to determine plant distributions, but how these factors jointly influence invasions is poorly understood...

  12. Temperature, precipitation and biotic interactions as determinants of tree seedling recruitment across the tree line ecotone.

    Science.gov (United States)

    Tingstad, Lise; Olsen, Siri Lie; Klanderud, Kari; Vandvik, Vigdis; Ohlson, Mikael

    2015-10-01

    Seedling recruitment is a critical life history stage for trees, and successful recruitment is tightly linked to both abiotic factors and biotic interactions. In order to better understand how tree species' distributions may change in response to anticipated climate change, more knowledge of the effects of complex climate and biotic interactions is needed. We conducted a seed-sowing experiment to investigate how temperature, precipitation and biotic interactions impact recruitment of Scots pine (Pinus sylvestris) and Norway spruce (Picea abies) seedlings in southern Norway. Seeds were sown into intact vegetation and experimentally created gaps. To study the combined effects of temperature and precipitation, the experiment was replicated across 12 sites, spanning a natural climate gradient from boreal to alpine and from sub-continental to oceanic. Seedling emergence and survival were assessed 12 and 16 months after sowing, respectively, and above-ground biomass and height were determined at the end of the experiment. Interestingly, very few seedlings were detected in the boreal sites, and the highest number of seedlings emerged and established in the alpine sites, indicating that low temperature did not limit seedling recruitment. Site precipitation had an overall positive effect on seedling recruitment, especially at intermediate precipitation levels. Seedling emergence, establishment and biomass were higher in gap plots compared to intact vegetation at all temperature levels. These results suggest that biotic interactions in the form of competition may be more important than temperature as a limiting factor for tree seedling recruitment in the sub- and low-alpine zone of southern Norway.

  13. Biotic resistance: Exclusion of native rodent consumers releases populations of a weak invader

    Science.gov (United States)

    Dean E. Pearson; Teal Potter; John L. Maron

    2012-01-01

    Biotic resistance is a commonly invoked hypothesis to explain why most exotic plant species naturalize at low abundance. Although numerous studies have documented negative impacts of native consumers on exotic plant performance, longer-term multi-generation studies are needed to understand how native consumer damage to exotics translates to their population-level...

  14. Genetics and regulation of combined abiotic and biotic stress tolerance in tomato

    NARCIS (Netherlands)

    Kissoudis, C.

    2016-01-01

    Projections on the impact of climate change on agricultural productivity foresee prolonged and/or increased stress intensities and enlargement of a significant number of pathogens habitats. This significantly raises the occurrence probability of (new) abiotic and biotic stress combinations. With

  15. Early biotic stress detection in tomato (Solanum lycopersicum) by BVOC emissions.

    Science.gov (United States)

    Kasal-Slavik, Tina; Eschweiler, Julia; Kleist, Einhard; Mumm, Roland; Goldbach, Heiner E; Schouten, Alexander; Wildt, Jürgen

    2017-12-01

    We investigated impacts of early and mild biotic stress on Biogenic Volatile Organic Compounds (BVOC) emissions from tomato in order to test their potential for early (biotic) stress detection. Tomato plants were exposed to two common fungal pathogens, Botrytis cinerea and Oidium neolycopesici and the sap-sucking aphid Myzus persicae. Furthermore, plants were exposed to methyl jasmonate (MeJA) in order to identify BVOC emissions related to activation of jasmonic acid (JA) signalling pathway. These emissions where then used as a reference for identifying active JA signalling pathway in plants at early stages of biotic stress. After infection by the necrotrophic fungus B. cinerea, changes in BVOC emissions indicated that tomato plants had predominantly activated the jasmonic acid (JA) signalling pathway. The plants were able to modify their defence pathways in order to overcome fungal infection. When tomato plants were infected with the biotrophic fungus O. neolycopersici, only minor changes in BVOC emissions were observed with additional emissions of the sesquiterpene α-copaene. α-copaene emissions allowed the identification of general biotic stress in the plants, without pinpointing the actual triggered defence pathway. BVOC emissions during M. persicae attack had changed before the occurrence of visual symptoms. Despite low infestation rates, plants emitted methyl salicylate indicating activation of the SA-mediated defence pathway. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Ecosystem services in grassland associated with biotic and abiotic soil parameters

    NARCIS (Netherlands)

    Eekeren, van N.J.M.; Boer, de Herman; Hanegraaf, M.C.; Bokhorst, J.; Nierop, D.; Bloem, J.; Schouten, T.; Goede, de R.G.M.; Brussaard, L.

    2010-01-01

    Biotic soil parameters have so far seldom played a role in practical soil assessment and management of grasslands. However, the ongoing reduction of external inputs in agriculture would imply an increasing reliance on ecosystem self-regulating processes. Since soil biota play an important role in

  17. Using the index of biotic integrity (IBI) to measure environmental quality in warmwater streams of Wisconsin.

    Science.gov (United States)

    John Lyons

    1992-01-01

    Describes an index based on attributes of fish assemblages that has proven effective in assessing biotic integrity and environmental health in intermediate-sized, warmwater (i.e., too warm for salmonids) streams and rivers of Wisconsin. Provides detailed guidelines for applying this index.

  18. Utilizing genetic resources and precision agriculture to enhance resistance to biotic and abiotic stress in watermelon

    Science.gov (United States)

    Originally from Africa, watermelon is a staple crop in South Carolina and rich source of important phytochemicals that promote human health. As a result of many years of domestication and selection for desired fruit quality, modern watermelon cultivars are susceptible to biotic and abiotic stress. T...

  19. Effects of biotic and abiotic factors on resistance versus resilience of Douglas fir to drought.

    Directory of Open Access Journals (Sweden)

    Gunnar Carnwath

    Full Text Available Significant increases in tree mortality due to drought-induced physiological stress have been documented worldwide. This trend is likely to continue with increased frequency and severity of extreme drought events in the future. Therefore, understanding the factors that influence variability in drought responses among trees will be critical to predicting ecosystem responses to climate change and developing effective management actions. In this study, we used hierarchical mixed-effects models to analyze drought responses of Pseudotsuga menziesii in 20 unmanaged forests stands across a broad range of environmental conditions in northeastern Washington, USA. We aimed to 1 identify the biotic and abiotic attributes most closely associated with the responses of individual trees to drought and 2 quantify the variability in drought responses at different spatial scales. We found that growth rates and competition for resources significantly affected resistance to a severe drought event in 2001: slow-growing trees and trees growing in subordinate canopy positions and/or with more neighbors suffered greater declines in radial growth during the drought event. In contrast, the ability of a tree to return to normal growth when climatic conditions improved (resilience was unaffected by competition or relative growth rates. Drought responses were significantly influenced by tree age: older trees were more resistant but less resilient than younger trees. Finally, we found differences between resistance and resilience in spatial scale: a significant proportion (approximately 50% of the variability in drought resistance across the study area was at broad spatial scales (i.e. among different forest types, most likely due to differences in the total amount of precipitation received at different elevations; in contrast, variation in resilience was overwhelmingly (82% at the level of individual trees within stands and there was no difference in drought resilience

  20. Speciation of Pu(4) complexes with weak ligands from visible spectra

    International Nuclear Information System (INIS)

    Berg, J.M.; Veirs, D.K.

    2001-01-01

    Stoichiometries of early actinide metal ion complexes in solution equilibrium can sometimes be determined by modelling the dependence of a species-sensitive measurement on ligand concentration. Weak ligands present the additional problem that these measurements cannot be made in the simplifying limiting case of low ligand concentration relative to the background electrolyte. At high ligand concentrations, constant ionic strength no longer implies constant activity coefficients. Additional parameters must be included in the equilibrium model to account for the variation of activity coefficients with ligand concentration as well as with overall ionic strength. We present the formalism of such a model based on SIT theory and its implementation for simultaneous fitting of spectra over a wide range of ionic strengths. As a test case, we analyse a subset of the spectra we have collected on complexation of Pu(IV) by nitrate in aqueous acid solutions. (authors)

  1. Effects of organic ligands on fractionation of rare earth elements (REEs) in hydroponic plants: an application to the determination of binding capacities by humic acid for modeling.

    Science.gov (United States)

    Ding, ShiMing; Liang, Tao; Zhang, ChaoSheng; Yan, JunCai; Zhang, ZiLi

    2006-12-01

    Previous studies have revealed the fractionation processes of rare earth elements (REEs) in hydroponic plants, with a heavy REE (HREE, the elements from Gd to Lu) enrichment in leaves. In this study, effects on the HREE enrichment in soybean leaves with additions of carboxylic acids (acetate, malate, citrate, NTA, EDTA and DTPA) and two soil humic acids (HAs) were investigated. REE speciation in carboxylic acid and HA solutions was simulated using Visual MINTEQ and Model V, respectively. The results showed that the effects caused by carboxylic acids were strongly dependent on the differences between their binding strengths for light REEs (LREEs, the elements from La to Eu) and those for HREEs. A good correlation existed between these effects and the changes of free REE ions in solutions. This relationship was also observed for the HA treatments, provided that the intrinsic equilibrium constants of REEs for cation-proton exchange with HA (i.e., pK(MHA)) in Model V were estimated using a free-energy relationship with the stability constants for REE complexation with lactic acid. It is suggested that this set of pK(MHA) values is more suitable for use in Model V for the simulation of REE complexation with HA.

  2. Designer ligands: The search for metal ion selectivity

    Directory of Open Access Journals (Sweden)

    Perry T. Kaye

    2011-03-01

    Full Text Available The paper reviews research conducted at Rhodes University towards the development of metal-selective ligands. The research has focused on the rational design, synthesis and evaluation of novel ligands for use in the formation of copper complexes as biomimetic models of the metalloenzyme, tyrosinase, and for the selective extraction of silver, nickel and platinum group metal ions in the presence of contaminating metal ions. Attention has also been given to the development of efficient, metal-selective molecular imprinted polymers.

  3. Elucidating the Role of Carbon Sources on Abiotic and Biotic Release of Arsenic into Cambodian Aquifers

    Science.gov (United States)

    Koeneke, M.

    2017-12-01

    Arsenic (As) is a naturally occurring contaminant in Cambodia that has been contaminating well-water sources of millions of people. Commonly, studies look into the biotic factors that cause the arsenic to be released from aquifer sediments to groundwater. However, abiotic release of As from sediments, though little studied, may also play key roles in As contamination of well water. The goal of this research is to quantitatively compare organic-carbon mediated abiotic and biotic release of arsenic from sediments to groundwater. Batch anaerobic incubation experiments under abiotic (sodium azide used to immobilize microbes) and biotic conditions were conducted using Cambodian aquifer sediments, four different organic carbon sources (sodium lactate, sodium citrate, sodium oxalate, and humic acid), and six different carbon concentrations (0, 1, 2.5, 5, 10, 25mg C/L). Dissolved arsenic, iron(Fe), and manganese(Mn) concentrations in the treatments were measured 112 days . In addition, sediment and solution carbon solution was measured . Collectively, these show how different carbon sources, different carbon concentrations, and how abiotic and biotic factors impact the release of arsenic from Cambodian sediments into aquifers. Overall, an introduction of organic carbon to the soil increases the amount of As released from the sediment. The biotic + abiotic and abiotic conditions seemed to play a minimal role in the amount of As released. Dissolved species analysis showed us that 100% of the As was As(V), Our ICP-MS results vary due to the heterogeneity of samples, but when high levels are Fe are seen in solution, we also see high levels of As. We also see higher As concentrations when there is a smaller amount of Mn in solution.

  4. Identification of Arabidopsis candidate genes in response to biotic and abiotic stresses using comparative microarrays.

    Directory of Open Access Journals (Sweden)

    Arjun Sham

    Full Text Available Plants have evolved with intricate mechanisms to cope with multiple environmental stresses. To adapt with biotic and abiotic stresses, plant responses involve changes at the cellular and molecular levels. The current study was designed to investigate the effects of combinations of different environmental stresses on the transcriptome level of Arabidopsis genome using public microarray databases. We investigated the role of cyclopentenones in mediating plant responses to environmental stress through TGA (TGACG motif-binding factor transcription factor, independently from jasmonic acid. Candidate genes were identified by comparing plants inoculated with Botrytis cinerea or treated with heat, salt or osmotic stress with non-inoculated or non-treated tissues. About 2.5% heat-, 19% salinity- and 41% osmotic stress-induced genes were commonly upregulated by B. cinerea-treatment; and 7.6%, 19% and 48% of genes were commonly downregulated by B. cinerea-treatment, respectively. Our results indicate that plant responses to biotic and abiotic stresses are mediated by several common regulatory genes. Comparisons between transcriptome data from Arabidopsis stressed-plants support our hypothesis that some molecular and biological processes involved in biotic and abiotic stress response are conserved. Thirteen of the common regulated genes to abiotic and biotic stresses were studied in detail to determine their role in plant resistance to B. cinerea. Moreover, a T-DNA insertion mutant of the Responsive to Dehydration gene (rd20, encoding for a member of the caleosin (lipid surface protein family, showed an enhanced sensitivity to B. cinerea infection and drought. Overall, the overlapping of plant responses to abiotic and biotic stresses, coupled with the sensitivity of the rd20 mutant, may provide new interesting programs for increased plant resistance to multiple environmental stresses, and ultimately increases its chances to survive. Future research

  5. Singular Value Decomposition and Ligand Binding Analysis

    Directory of Open Access Journals (Sweden)

    André Luiz Galo

    2013-01-01

    Full Text Available Singular values decomposition (SVD is one of the most important computations in linear algebra because of its vast application for data analysis. It is particularly useful for resolving problems involving least-squares minimization, the determination of matrix rank, and the solution of certain problems involving Euclidean norms. Such problems arise in the spectral analysis of ligand binding to macromolecule. Here, we present a spectral data analysis method using SVD (SVD analysis and nonlinear fitting to determine the binding characteristics of intercalating drugs to DNA. This methodology reduces noise and identifies distinct spectral species similar to traditional principal component analysis as well as fitting nonlinear binding parameters. We applied SVD analysis to investigate the interaction of actinomycin D and daunomycin with native DNA. This methodology does not require prior knowledge of ligand molar extinction coefficients (free and bound, which potentially limits binding analysis. Data are acquired simply by reconstructing the experimental data and by adjusting the product of deconvoluted matrices and the matrix of model coefficients determined by the Scatchard and McGee and von Hippel equation.

  6. Xanthene and Xanthone Derivatives as G-Quadruplex Stabilizing Ligands

    Directory of Open Access Journals (Sweden)

    Alessandro Altieri

    2013-10-01

    Full Text Available Following previous studies on anthraquinone and acridine-based G-quadruplex ligands, here we present a study of similar aromatic cores, with the specific aim of increasing G-quadruplex binding and selectivity with respect to duplex DNA. Synthesized compounds include two and three-side chain xanthone and xanthene derivatives, as well as a dimeric “bridged” form. ESI and FRET measurements suggest that all the studied molecules are good G-quadruplex ligands, both at telomeres and on G-quadruplex forming sequences of oncogene promoters. The dimeric compound and the three-side chain xanthone derivative have been shown to represent the best compounds emerging from the different series of ligands presented here, having also high selectivity for G-quadruplex structures with respect to duplex DNA. Molecular modeling simulations are in broad agreement with the experimental data.

  7. Speciation of Zinc Mixed Ligand Complexes in Salt Water Systems ...

    African Journals Online (AJOL)

    Speciation of Zinc Mixed Ligand Complexes in Salt Water Systems. ... method has been used to study heavy metal interaction in model lake water in KNO3 ... is of no consequential effect because in its normal state, the [OH-] of the lake water is ...

  8. Molecular modeling of human MT2 melatonin receptor: the role of Val204, Leu272 and Tyr298 in ligand binding

    Czech Academy of Sciences Publication Activity Database

    Mazna, Petr; Obšilová, Veronika; Jelínková, Irena; Balík, Aleš; Berka, K.; Sovová, Žofie; Ettrich, Rüdiger; Svoboda, Petr; Obšil, T.; Teisinger, Jan

    2004-01-01

    Roč. 91, č. 4 (2004), s. 836-842 ISSN 0022-3042 R&D Projects: GA ČR GA309/02/1479; GA ČR GA309/04/0496; GA ČR GA204/03/0714; GA AV ČR IAA5011103; GA AV ČR IAA5011408; GA AV ČR KJB5011308; GA MŠk LN00A141 Institutional research plan: CEZ:AV0Z5011922; CEZ:MSM 113100001 Keywords : homology modeling * MT2 melatonin receptor * site-directed mutagenesis Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 4.824, year: 2004

  9. Systems-level modeling the effects of arsenic exposure with sequential pulsed and fluctuating patterns for tilapia and freshwater clam

    International Nuclear Information System (INIS)

    Chen, W.-Y.; Tsai, J.-W.; Ju, Y.-R.; Liao, C.-M.

    2010-01-01

    The purpose of this paper was to use quantitative systems-level approach employing biotic ligand model based threshold damage model to examine physiological responses of tilapia and freshwater clam to sequential pulsed and fluctuating arsenic concentrations. We tested present model and triggering mechanisms by carrying out a series of modeling experiments where we used periodic pulses and sine-wave as featured exposures. Our results indicate that changes in the dominant frequencies and pulse timing can shift the safe rate distributions for tilapia, but not for that of freshwater clam. We found that tilapia increase bioenergetic costs to maintain the acclimation during pulsed and sine-wave exposures. Our ability to predict the consequences of physiological variation under time-varying exposure patterns has also implications for optimizing species growing, cultivation strategies, and risk assessment in realistic situations. - Systems-level modeling the pulsed and fluctuating arsenic exposures.

  10. Systems-level modeling the effects of arsenic exposure with sequential pulsed and fluctuating patterns for tilapia and freshwater clam

    Energy Technology Data Exchange (ETDEWEB)

    Chen, W.-Y. [Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei 10617, Taiwan (China); Tsai, J.-W. [Institute of Ecology and Evolutionary Ecology, China Medical University, Taichung 40402, Taiwan (China); Ju, Y.-R. [Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei 10617, Taiwan (China); Liao, C.-M., E-mail: cmliao@ntu.edu.t [Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei 10617, Taiwan (China)

    2010-05-15

    The purpose of this paper was to use quantitative systems-level approach employing biotic ligand model based threshold damage model to examine physiological responses of tilapia and freshwater clam to sequential pulsed and fluctuating arsenic concentrations. We tested present model and triggering mechanisms by carrying out a series of modeling experiments where we used periodic pulses and sine-wave as featured exposures. Our results indicate that changes in the dominant frequencies and pulse timing can shift the safe rate distributions for tilapia, but not for that of freshwater clam. We found that tilapia increase bioenergetic costs to maintain the acclimation during pulsed and sine-wave exposures. Our ability to predict the consequences of physiological variation under time-varying exposure patterns has also implications for optimizing species growing, cultivation strategies, and risk assessment in realistic situations. - Systems-level modeling the pulsed and fluctuating arsenic exposures.

  11. Abiotic and biotic controls of spatial pattern at alpine treeline

    Science.gov (United States)

    Malanson, George P.; Xiao, Ningchuan; Alftine, K.J.; Bekker, Mathew; Butler, David R.; Brown, Daniel G.; Cairns, David M.; Fagre, Daniel; Walsh, Stephen J.

    2000-01-01

    At alpine treeline, trees and krummholz forms affect the environment in ways that increase their growth and reproduction. We assess the way in which these positive feedbacks combine in spatial patterns to alter the environment in the neighborhood of existing plants. The research is significant because areas of alpine tundra are susceptible to encroachment by woody species as climate changes. Moreover, understanding the general processes of plant invasion is important. The importance of spatial pattern has been recognized, but the spatial pattern of positive feedbacks per se has not been explored in depth. We present a linked set of models of vegetation change at an alpine forest-tundra ecotone. Our aim is to create models that are as simple as possible in order to test specific hypotheses. We present results from a model of the resource averaging hypothesis and the positive feedback switch hypothesis of treelines. We compare the patterns generated by the models to patterns observed in fine scale remotely sensed data.

  12. Outcome of the first wwPDB/CCDC/D3R Ligand Validation Workshop

    Science.gov (United States)

    Adams, Paul D.; Aertgeerts, Kathleen; Bauer, Cary; Bell, Jeffrey A.; Berman, Helen M.; Bhat, Talapady N.; Blaney, Jeff; Bolton, Evan; Bricogne, Gerard; Brown, David; Burley, Stephen K.; Case, David A.; Clark, Kirk L.; Darden, Tom; Emsley, Paul; Feher, Victoria A.; Feng, Zukang; Groom, Colin R.; Harris, Seth F.; Hendle, Jorg; Holder, Thomas; Joachimiak, Andrzej; Kleywegt, Gerard J.; Krojer, Tobias; Marcotrigiano, Joseph; Mark, Alan E.; Markley, John L.; Miller, Matthew; Minor, Wladek; Montelione, Gaetano T.; Murshudov, Garib; Nakagawa, Atsushi; Nakamura, Haruki; Nicholls, Anthony; Nicklaus, Marc; Nolte, Robert T.; Padyana, Anil K.; Peishoff, Catherine E.; Pieniazek, Susan; Read, Randy J.; Shao, Chenghua; Sheriff, Steven; Smart, Oliver; Soisson, Stephen; Spurlino, John; Stouch, Terry; Svobodova, Radka; Tempel, Wolfram; Terwilliger, Thomas C.; Tronrud, Dale; Velankar, Sameer; Ward, Suzanna; Warren, Gregory L.; Westbrook, John D.; Williams, Pamela; Yang, Huanwang; Young, Jasmine

    2016-01-01

    Summary Crystallographic studies of ligands bound to biological macromolecules (proteins and nucleic acids) represent an important source of information concerning drug-target interactions, providing atomic level insights into the physical chemistry of complex formation between macromolecules and ligands. Of the more than 115,000 entries extant in the Protein Data Bank archive, ~75% include at least one non-polymeric ligand. Ligand geometrical and stereochemical quality, the suitability of ligand models for in silico drug discovery/design, and the goodness-of-fit of ligand models to electron density maps vary widely across the archive. We describe the proceedings and conclusions from the first Worldwide Protein Data Bank/Cambridge Crystallographic Data Centre/Drug Design Data Resource (wwPDB/CCDC/D3R) Ligand Validation Workshop held at the Research Collaboratory for Structural Bioinformatics at Rutgers University on July 30–31, 2015. Experts in protein crystallography from academe and industry came together with non-profit and for-profit software providers for crystallography and with experts in computational chemistry and data archiving to discuss and make recommendations on best practices, as framed by a series of questions central to structural studies of macromolecule-ligand complexes. What data concerning bound ligands should be archived in the Protein Data Bank? How should the ligands be best represented? How should structural models of macromolecule-ligand complexes be validated? What supplementary information should accompany publications of structural studies of biological macromolecules? Consensus recommendations on best practices developed in response to each of these questions are provided, together with some details regarding implementation. Important issues addressed but not resolved at the workshop are also enumerated. PMID:27050687

  13. ADN-1184, a monoaminergic ligand with 5-HT6/7 receptor antagonist action, exhibits activity in animal models of anxiety.

    Science.gov (United States)

    Partyka, Anna; Wasik, Anna; Jastrzębska-Więsek, Magdalena; Mierzejewski, Paweł; Bieńkowski, Przemysław; Kołaczkowski, Marcin; Wesołowska, Anna

    2016-06-01

    Behavioral and psychological symptoms of dementia (BPSD) include apathy, sleep problems, irritability, wandering, elation, agitation/aggression, and mood disorders such as depression and/or anxiety. Elderly patients are usually treated with second-generation antipsychotics; however, they present not enough efficacy against all symptoms observed. Hence, there still is an unmet need for novel pharmacotherapeutic agents targeted BPSD. A novel arylsulfonamide derivative ADN-1184 has been developed that possesses a preclinical profile of activity corresponding to criteria required for treatment of both psychosis and depressive symptoms of BPSD without exacerbating cognitive impairment or inducing motor disturbances. To broaden its pharmacological efficacy toward anxiety symptoms, its anxiolytic properties have been examined in common animal preclinical models in rats and mice. ADN-1184 significantly increased the number of entries into open arms measured in the elevated plus-maze test; however, it simultaneously increased parameters of exploratory activity. In the Vogel conflict drinking test, ADN-1184 dose-dependently and significantly increased the number of shocks accepted and the number of licks. Moreover, in mice, it also had specific anxiolytic-like activity in the four-plate test, and only negligible one at a specific mid-range dose measured in the spontaneous marble burying test. The obtained findings reveal that ADN-1184 displays anxiolytic-like activity in animal models of anxiety which employed punished stimuli. In its unusual combination of some anxiolytic action with already proven antipsychotic and antidepressant properties, and lack of any disruptive impact on learning and memory processes and motor coordination, ADN-1184 displays a profile that would be desired for a novel therapeutic for BPSD.

  14. Alterations in the α2 δ ligand, thrombospondin-1, in a rat model of spontaneous absence epilepsy and in patients with idiopathic/genetic generalized epilepsies.

    Science.gov (United States)

    Santolini, Ines; Celli, Roberta; Cannella, Milena; Imbriglio, Tiziana; Guiducci, Michela; Parisi, Pasquale; Schubert, Julian; Iacomino, Michele; Zara, Federico; Lerche, Holger; Moyanova, Slavianka; Ngomba, Richard Teke; van Luijtelaar, Gilles; Battaglia, Giuseppe; Bruno, Valeria; Striano, Pasquale; Nicoletti, Ferdinando

    2017-11-01

    Thrombospondins, which are known to interact with the α 2 δ subunit of voltage-sensitive calcium channels to stimulate the formation of excitatory synapses, have recently been implicated in the process of epileptogenesis. No studies have been so far performed on thrombospondins in models of absence epilepsy. We examined whether expression of the gene encoding for thrombospondin-1 was altered in the brain of WAG/Rij rats, which model absence epilepsy in humans. In addition, we examined the frequency of genetic variants of THBS1 in a large cohort of children affected by idiopathic/genetic generalized epilepsies (IGE/GGEs). We measured the transcripts of thrombospondin-1 and α 2 δ subunit, and protein levels of α 2 δ, Rab3A, and the vesicular glutamate transporter, VGLUT1, in the somatosensory cortex and ventrobasal thalamus of presymptomatic and symptomatic WAG/Rij rats and in two control strains by real-time polymerase chain reaction (PCR) and immunoblotting. We examined the genetic variants of THBS1 and CACNA2D1 in two independent cohorts of patients affected by IGE/GGE recruited through the Genetic Commission of the Italian League Against Epilepsy (LICE) and the EuroEPINOMICS-CoGIE Consortium. Thrombospondin-1 messenger RNA (mRNA) levels were largely reduced in the ventrobasal thalamus of both presymptomatic and symptomatic WAG/Rij rats, whereas levels in the somatosensory cortex were unchanged. VGLUT1 protein levels were also reduced in the ventrobasal thalamus of WAG/Rij rats. Genetic variants of THBS1 were significantly more frequent in patients affected by IGE/GGE than in nonepileptic controls, whereas the frequency of CACNA2D1 was unchanged. These findings suggest that thrombospondin-1 may have a role in the pathogenesis of IGE/GGEs. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  15. Interactive biotic and abiotic regulators of soil carbon cycling: evidence from controlled climate experiments on peatland and boreal soils.

    Science.gov (United States)

    Briones, María Jesús I; McNamara, Niall P; Poskitt, Jan; Crow, Susan E; Ostle, Nicholas J

    2014-09-01

    Partially decomposed plant and animal remains have been accumulating in organic soils (i.e. >40% C content) for millennia, making them the largest terrestrial carbon store. There is growing concern that, in a warming world, soil biotic processing will accelerate and release greenhouse gases that further exacerbate climate change. However, the magnitude of this response remains uncertain as the constraints are abiotic, biotic and interactive. Here, we examined the influence of resource quality and biological activity on the temperature sensitivity of soil respiration under different soil moisture regimes. Organic soils were sampled from 13 boreal and peatland ecosystems located in the United Kingdom, Ireland, Spain, Finland and Sweden, representing a natural resource quality range of C, N and P. They were incubated at four temperatures (4, 10, 15 and 20 °C) at either 60% or 100% water holding capacity (WHC). Our results showed that chemical and biological properties play an important role in determining soil respiration responses to temperature and moisture changes. High soil C : P and C : N ratios were symptomatic of slow C turnover and long-term C accumulation. In boreal soils, low bacterial to fungal ratios were related to greater temperature sensitivity of respiration, which was amplified in drier conditions. This contrasted with peatland soils which were dominated by bacterial communities and enchytraeid grazing, resulting in a more rapid C turnover under warmer and wetter conditions. The unexpected acceleration of C mineralization under high moisture contents was possibly linked to the primarily role of fermented organic matter, instead of oxygen, in mediating microbial decomposition. We conclude that to improve C model simulations of soil respiration, a better resolution of the interactions occurring between climate, resource quality and the decomposer community will be required. © 2014 John Wiley & Sons Ltd.

  16. Expression of an engineered heterologous antimicrobial peptide in potato alters plant development and mitigates normal abiotic and biotic responses.

    Directory of Open Access Journals (Sweden)

    Ravinder K Goyal

    Full Text Available Antimicrobial cationic peptides (AMPs are ubiquitous small proteins used by living cells to defend against a wide spectrum of pathogens. Their amphipathic property helps their interaction with negatively charged cellular membrane of the pathogen causing cell lysis and death. AMPs also modulate signaling pathway(s and cellular processes in animal models; however, little is known of cellular processes other than the pathogen-lysis phenomenon modulated by AMPs in plants. An engineered heterologous AMP, msrA3, expressed in potato was previously shown to cause resistance of the transgenic plants against selected fungal and bacterial pathogens. These lines together with the wild type were studied for growth habits, and for inducible defense responses during challenge with biotic (necrotroph Fusarium solani and abiotic stressors (dark-induced senescence, wounding and temperature stress. msrA3-expression not only conferred protection against F. solani but also delayed development of floral buds and prolonged vegetative phase. Analysis of select gene transcript profiles showed that the transgenic potato plants were suppressed in the hypersensitive (HR and reactive oxygen species (ROS responses to both biotic and abiotic stressors. Also, the transgenic leaves accumulated lesser amounts of the defense hormone jasmonic acid upon wounding with only a slight change in salicylic acid as compared to the wild type. Thus, normal host defense responses to the pathogen and abiotic stressors were mitigated by msrA3 expression suggesting MSRA3 regulates a common step(s of these response pathways. The stemming of the pathogen growth and mitigating stress response pathways likely contributes to resource reallocation for higher tuber yield.

  17. Organometallic model complexes elucidate the active gallium species in alkane dehydrogenation catalysts based on ligand effects in Ga K-edge XANES

    Energy Technology Data Exchange (ETDEWEB)

    Getsoian, Andrew “Bean”; Das, Ujjal; Camacho-Bunquin, Jeffrey; Zhang, Guanghui; Gallagher, James R.; Hu, Bo; Cheah, Singfoong; Schaidle, Joshua A.; Ruddy, Daniel A.; Hensley, Jesse E.; Krause, Theodore R.; Curtiss, Larry A.; Miller, Jeffrey T.; Hock, Adam S.

    2016-01-01

    Gallium-modified zeolites are known catalysts for the dehydrogenation of alkanes, reactivity that finds industrial application in the aromatization of light alkanes by Ga-ZSM5. While the role of gallium cations in alkane activation is well known, the oxidation state and coordination environment of gallium under reaction conditions has been the subject of debate. Edge shifts in Ga K-edge XANES spectra acquired under reaction conditions have long been interpreted as evidence for reduction of Ga(III) to Ga(I). However, a change in oxidation state is not the only factor that can give rise to a change in the XANES spectrum. In order to better understand the XANES spectra of working catalysts, we have synthesized a series of molecular model compounds and grafted surface organometallic Ga species and compared their XANES spectra to those of gallium-based catalysts acquired under reducing conditions. We demonstrate that changes in the identity and number of gallium nearest neighbors can give rise to changes in XANES spectra similar to those attributed in literature to changes in oxidation state. Specifically, spectral features previously attributed to Ga(I) may be equally well interpreted as evidence for low-coordinate Ga(III) alkyl or hydride species. These findings apply both to gallium-impregnated zeolite catalysts and to silica-supported single site gallium catalysts, the latter of which is found to be active and selective for dehydrogenation of propane and hydrogenation of propylene.

  18. Cloud computing approaches for prediction of ligand binding poses and pathways.

    Science.gov (United States)

    Lawrenz, Morgan; Shukla, Diwakar; Pande, Vijay S

    2015-01-22

    We describe an innovative protocol for ab initio prediction of ligand crystallographic binding poses and highly effective analysis of large datasets generated for protein-ligand dynamics. We include a procedure for setup and performance of distributed molecular dynamics simulations on cloud computing architectures, a model for efficient analysis of simulation data, and a metric for evaluation of model convergence. We give accurate binding pose predictions for five ligands ranging in affinity from 7 nM to > 200 μM for the immunophilin protein FKBP12, for expedited results in cases where experimental structures are difficult to produce. Our approach goes beyond single, low energy ligand poses to give quantitative kinetic information that can inform protein engineering and ligand design.

  19. Disturbance metrics predict a wetland Vegetation Index of Biotic Integrity

    Science.gov (United States)

    Stapanian, Martin A.; Mack, John; Adams, Jean V.; Gara, Brian; Micacchion, Mick

    2013-01-01

    Indices of biological integrity of wetlands based on vascular plants (VIBIs) have been developed in many areas in the USA. Knowledge of the best predictors of VIBIs would enable management agencies to make better decisions regarding mitigation site selection and performance monitoring criteria. We use a novel statistical technique to develop predictive models for an established index of wetland vegetation integrity (Ohio VIBI), using as independent variables 20 indices and metrics of habitat quality, wetland disturbance, and buffer area land use from 149 wetlands in Ohio, USA. For emergent and forest wetlands, predictive models explained 61% and 54% of the variability, respectively, in Ohio VIBI scores. In both cases the most important predictor of Ohio VIBI score was a metric that assessed habitat alteration and development in the wetland. Of secondary importance as a predictor was a metric that assessed microtopography, interspersion, and quality of vegetation communities in the wetland. Metrics and indices assessing disturbance and land use of the buffer area were generally poor predictors of Ohio VIBI scores. Our results suggest that vegetation integrity of emergent and forest wetlands could be most directly enhanced by minimizing substrate and habitat disturbance within the wetland. Such efforts could include reducing or eliminating any practices that disturb the soil profile, such as nutrient enrichment from adjacent farm land, mowing, grazing, or cutting or removing woody plants.

  20. Free-energy relationships in ion channels activated by voltage and ligand

    Science.gov (United States)

    Chowdhury, Sandipan

    2013-01-01

    Many ion channels are modulated by multiple stimuli, which allow them to integrate a variety of cellular signals and precisely respond to physiological needs. Understanding how these different signaling pathways interact has been a challenge in part because of the complexity of underlying models. In this study, we analyzed the energetic relationships in polymodal ion channels using linkage principles. We first show that in proteins dually modulated by voltage and ligand, the net free-energy change can be obtained by measuring the charge-voltage (Q-V) relationship in zero ligand condition and the ligand binding curve at highly depolarizing membrane voltages. Next, we show that the voltage-dependent changes in ligand occupancy of the protein can be directly obtained by measuring the Q-V curves at multiple ligand concentrations. When a single reference ligand binding curve is available, this relationship allows us to reconstruct ligand binding curves at different voltages. More significantly, we establish that the shift of the Q-V curve between zero and saturating ligand concentration is a direct estimate of the interaction energy between the ligand- and voltage-dependent pathway. These free-energy relationships were tested by numerical simulations of a detailed gating model of the BK channel. Furthermore, as a proof of principle, we estimate the interaction energy between the ligand binding and voltage-dependent pathways for HCN2 channels whose ligand binding curves at various voltages are available. These emerging principles will be useful for high-throughput mutagenesis studies aimed at identifying interaction pathways between various regulatory domains in a polymodal ion channel. PMID:23250866

  1. Ligand induced change of β2 adrenergic receptor from active to inactive conformation and its implication for the closed/open state of the water channel: insight from molecular dynamics simulation, free energy calculation and Markov state model analysis.

    Science.gov (United States)

    Bai, Qifeng; Pérez-Sánchez, Horacio; Zhang, Yang; Shao, Yonghua; Shi, Danfeng; Liu, Huanxiang; Yao, Xiaojun

    2014-08-14

    The reported crystal structures of β2 adrenergic receptor (β2AR) reveal that the open and closed states of the water channel are correlated with the inactive and active conformations of β2AR. However, more details about the process by which the water channel states are affected by the active to inactive conformational change of β2AR remain illusive. In this work, molecular dynamics simulations are performed to study the dynamical inactive and active conformational change of β2AR induced by inverse agonist ICI 118,551. Markov state model analysis and free energy calculation are employed to explore the open and close states of the water channel. The simulation results show that inverse agonist ICI 118,551 can induce water channel opening during the conformational transition of β2AR. Markov state model (MSM) analysis proves that the energy contour can be divided into seven states. States S1, S2 and S5, which represent the active conformation of β2AR, show that the water channel is in the closed state, while states S4 and S6, which correspond to the intermediate state conformation of β2AR, indicate the water channel opens gradually. State S7, which represents the inactive structure of β2AR, corresponds to the full open state of the water channel. The opening mechanism of the water channel is involved in the ligand-induced conformational change of β2AR. These results can provide useful information for understanding the opening mechanism of the water channel and will be useful for the rational design of potent inverse agonists of β2AR.

  2. Biotic and Climatic Velocity Identify Contrasting Areas of Vulnerability to Climate Change

    Science.gov (United States)

    Carroll, Carlos; Lawler, Joshua J.; Roberts, David R.; Hamann, Andreas

    2015-01-01

    Metrics that synthesize the complex effects of climate change are essential tools for mapping future threats to biodiversity and predicting which species are likely to adapt in place to new climatic conditions, disperse and establish in areas with newly suitable climate, or face the prospect of extirpation. The most commonly used of such metrics is the velocity of climate change, which estimates the speed at which species must migrate over the earth’s surface to maintain constant climatic conditions. However, “analog-based” velocities, which represent the actual distance to where analogous climates will be found in the future, may provide contrasting results to the more common form of velocity based on local climate gradients. Additionally, whereas climatic velocity reflects the exposure of organisms to climate change, resultant biotic effects are dependent on the sensitivity of individual species as reflected in part by their climatic niche width. This has motivated development of biotic velocity, a metric which uses data on projected species range shifts to estimate the velocity at which species must move to track their climatic niche. We calculated climatic and biotic velocity for the Western Hemisphere for 1961–2100, and applied the results to example ecological and conservation planning questions, to demonstrate the potential of such analog-based metrics to provide information on broad-scale patterns of exposure and sensitivity. Geographic patterns of biotic velocity for 2954 species of birds, mammals, and amphibians differed from climatic velocity in north temperate and boreal regions. However, both biotic and climatic velocities were greatest at low latitudes, implying that threats to equatorial species arise from both the future magnitude of climatic velocities and the narrow climatic tolerances of species in these regions, which currently experience low seasonal and interannual climatic variability. Biotic and climatic velocity, by approximating

  3. Force loading explains spatial sensing of ligands by cells

    Science.gov (United States)

    Oria, Roger; Wiegand, Tina; Escribano, Jorge; Elosegui-Artola, Alberto; Uriarte, Juan Jose; Moreno-Pulido, Cristian; Platzman, Ilia; Delcanale, Pietro; Albertazzi, Lorenzo; Navajas, Daniel; Trepat, Xavier; García-Aznar, José Manuel; Cavalcanti-Adam, Elisabetta Ada; Roca-Cusachs, Pere

    2017-12-01

    Cells can sense the density and distribution of extracellular matrix (ECM) molecules by means of individual integrin proteins and larger, integrin-containing adhesion complexes within the cell membrane. This spatial sensing drives cellular activity in a variety of normal and pathological contexts. Previous studies of cells on rigid glass surfaces have shown that spatial sensing of ECM ligands takes place at the nanometre scale, with integrin clustering and subsequent formation of focal adhesions impaired when single integrin-ligand bonds are separated by more than a few tens of nanometres. It has thus been suggested that a crosslinking ‘adaptor’ protein of this size might connect integrins to the actin cytoskeleton, acting as a molecular ruler that senses ligand spacing directly. Here, we develop gels whose rigidity and nanometre-scale distribution of ECM ligands can be controlled and altered. We find that increasing the spacing between ligands promotes the growth of focal adhesions on low-rigidity substrates, but leads to adhesion collapse on more-rigid substrates. Furthermore, disordering the ligand distribution drastically increases adhesion growth, but reduces the rigidity threshold for adhesion collapse. The growth and collapse of focal adhesions are mirrored by, respectively, the nuclear or cytosolic localization of the transcriptional regulator protein YAP. We explain these findings not through direct sensing of ligand spacing, but by using an expanded computational molecular-clutch model, in which individual integrin-ECM bonds—the molecular clutches—respond to force loading by recruiting extra integrins, up to a maximum value. This generates more clutches, redistributing the overall force among them, and reducing the force loading per clutch. At high rigidity and high ligand spacing, maximum recruitment is reached, preventing further force redistribution and leading to adhesion collapse. Measurements of cellular traction forces and actin flow speeds

  4. Ligand photo-isomerization triggers conformational changes in iGluR2 ligand binding domain.

    Directory of Open Access Journals (Sweden)

    Tino Wolter

    Full Text Available Neurological glutamate receptors bind a variety of artificial ligands, both agonistic and antagonistic, in addition to glutamate. Studying their small molecule binding properties increases our understanding of the central nervous system and a variety of associated pathologies. The large, oligomeric multidomain membrane protein contains a large and flexible ligand binding domains which undergoes large conformational changes upon binding different ligands. A recent application of glutamate receptors is their activation or inhibition via photo-switchable ligands, making them key systems in the emerging field of optochemical genetics. In this work, we present a theoretical study on the binding mode and complex stability of a novel photo-switchable ligand, ATA-3, which reversibly binds to glutamate receptors ligand binding domains (LBDs. We propose two possible binding modes for this ligand based on flexible ligand docking calculations and show one of them to be analogues to the binding mode of a similar ligand, 2-BnTetAMPA. In long MD simulations, it was observed that transitions between both binding poses involve breaking and reforming the T686-E402 protein hydrogen bond. Simulating the ligand photo-isomerization process shows that the two possible configurations of the ligand azo-group have markedly different complex stabilities and equilibrium binding modes. A strong but slow protein response is observed after ligand configuration changes. This provides a microscopic foundation for the observed difference in ligand activity upon light-switching.

  5. Above- and Belowground Trophic Interactions on Creeping Thistle (Cirsium arvense) in High- and Low-Diversity Plant Communities: Potential for Biotic Resistance?

    NARCIS (Netherlands)

    Bezemer, T.M.; Graça, O.; Rousseau, P.; Putten, van der W.H.

    2004-01-01

    The capacity of local communities to control introduced plants is called biotic resistance. Biotic resistance has been almost exclusively tested for plant competition and above-ground herbivores and pathogens, while neglecting root herbivores and soil pathogens. Here, we present biotic resistance by

  6. Above- and Belowground Trophic Interactions on Creeping Thistle (Cirsium arvense) in High- and Low-Diversity Plant Communities: Potential for Biotic Resistance?

    NARCIS (Netherlands)

    Bezemer, T.M.; Graça, O.; Rousseau, P.; Van der Putten, W.H.

    2004-01-01

    The capacity of local communities to control introduced plants is called biotic resistance. Biotic resistance has been almost exclusively tested for plant competition and aboveground herbivores and pathogens, while neglecting root herbivores and soil pathogens. Here, we present biotic resistance by

  7. Biotic Drivers of Spatial Heterogeneity and Implications for River Ecosystems

    Science.gov (United States)

    Wohl, Ellen

    2017-04-01

    Rivers throughout the northern hemisphere have been simplified and homogenized by the removal of beavers and instream wood, along with numerous forms of channel engineering and flow regulation. Loss of spatial heterogeneity in river corridors - channels and floodplains - affects downstream fluxes of water, sediment, organic matter, and nutrients, as well as stream metabolism, biomass, and biodiversity. Recent work in streams of the Colorado Rocky Mountains illustrates how the presence of beavers and instream wood can facilitate spatial heterogeneity by creating stable, persistent, multithread channel planform and high channel-floodplain and channel-hyporheic zone connectivity. This spatial heterogeneity facilitates retention of water in pools, floodplain wetlands, and hyporheic storage. Suspended sediment, particulate organic matter (POM), and solutes are also more likely to be retained in these stream segments than in more uniform stream segments with greater downstream conveyance. Retention of POM and solutes equates to greater volumes of organic carbon storage per unit valley length and greater rates of nitrogen uptake. Spatially heterogeneous stream segments also exhibit greater biomass and biodiversity of aquatic macroinvertebrates, salmonid fish, and riparian spiders than do more uniform stream segments. These significant differences in stream form and function are unlikely to be unique to this field area and can provide a conceptual model for understanding and restoring ecosystem functions in other rivers.

  8. Development of immobilized ligands for actinide separations

    International Nuclear Information System (INIS)

    Paine, R.T.

    1994-01-01

    Primary goals during this grant period were to (1) synthesize new bifunctional chelating ligands, (2) characterize the structural features of the Ln and An coordination complexes formed by these ligands, (3) use structural data to iteratively design new classes of multifunctional ligands, and (4) explore additional routes for attachment of key ligands to solid supports that could be useful for chromatographic separations. Some highlights of recently published work as well as a summary of submitted, unpublished and/or still in progress research are outlined

  9. Ligand-mediated adhesive mechanics of two static, deformed spheres.

    Science.gov (United States)

    Sircar, Sarthok; Nguyen, Giang; Kotousov, Andrei; Roberts, Anthony J

    2016-10-01

    A self-consistent model is developed to investigate attachment/detachment kinetics of two static, deformable microspheres with irregular surface and coated with flexible binding ligands. The model highlights how the microscale binding kinetics of these ligands as well as the attractive/repulsive potential of the charged surface affects the macroscale static deformed configuration of the spheres. It is shown that in the limit of smooth, neutrally charged surface (i.e., the dimensionless inverse Debye length, [Formula: see text]), interacting via elastic binders (i.e., the dimensionless stiffness coefficient, [Formula: see text]) the adhesion mechanics approaches the regime of application of the JKR theory, and in this particular limit, the contact radius, R c , scales with the particle radius, R, according to the scaling law, [Formula: see text]. We show that static, deformed, highly charged, ligand-coated surface of micro-spheres exhibit strong adhesion. Normal stress distribution within the contact area adjusts with the binder stiffness coefficient, from a maximum at the center to a maximum at the periphery of the region. Although reported in some in vitro experiments involving particle adhesion, until now a physical interpretation for this variation of the stress distribution for deformable, charged, ligand-coated microspheres is missing. Surface roughness results in a diminished adhesion with a distinct reduction in the pull-off force, larger separation gap, weaker normal stress and limited area of adhesion. These results are in agreement with the published experimental findings.

  10. A biotic game design project for integrated life science and engineering education.

    Directory of Open Access Journals (Sweden)

    Nate J Cira

    2015-03-01

    Full Text Available Engaging, hands-on design experiences are key for formal and informal Science, Technology, Engineering, and Mathematics (STEM education. Robotic and video game design challenges have been particularly effective in stimulating student interest, but equivalent experiences for the life sciences are not as developed. Here we present the concept of a "biotic game design project" to motivate student learning at the interface of life sciences and device engineering (as part of a cornerstone bioengineering devices course. We provide all course material and also present efforts in adapting the project's complexity to serve other time frames, age groups, learning focuses, and budgets. Students self-reported that they found the biotic game project fun and motivating, resulting in increased effort. Hence this type of design project could generate excitement and educational impact similar to robotics and video games.

  11. Land Use in LCIA: an absolute scale proposal for Biotic Production Potential

    DEFF Research Database (Denmark)

    Saez de Bikuna Salinas, Koldo; Ibrom, Andreas; Hauschild, Michael Zwicky

    , the present study proposes a single absolute scale for the midpoint impact category (MIC) of Biotic Production Potential (BPP). It is hypothesized that, for an ecosystem in equilibrium (where NPP equals decay), such an ecosystem has reached the maximum biotic throughput subject to site-specific conditions...... and no externally added inputs. The original ecosystem (or Potential Natural Vegetation) of a certain land gives then the maximum BPP with no additional, downstream or upstream, impacts. This Natural BPP is proposed as the maximum BPP in a hypothetical Absolute Scale for LCA’s Land Use framework. It is argued...... that this maximum BPP is Nature’s optimal solution through evolution-adaptation mechanisms, which provides the maximum matter throughput subject to the rest of environmental constraints (without further impacts). As a consequence, this scale rises a Land Use Optimality Point that suggests the existence of a limit...

  12. A biotic game design project for integrated life science and engineering education.

    Science.gov (United States)

    Cira, Nate J; Chung, Alice M; Denisin, Aleksandra K; Rensi, Stefano; Sanchez, Gabriel N; Quake, Stephen R; Riedel-Kruse, Ingmar H

    2015-03-01

    Engaging, hands-on design experiences are key for formal and informal Science, Technology, Engineering, and Mathematics (STEM) education. Robotic and video game design challenges have been particularly effective in stimulating student interest, but equivalent experiences for the life sciences are not as developed. Here we present the concept of a "biotic game design project" to motivate student learning at the interface of life sciences and device engineering (as part of a cornerstone bioengineering devices course). We provide all course material and also present efforts in adapting the project's complexity to serve other time frames, age groups, learning focuses, and budgets. Students self-reported that they found the biotic game project fun and motivating, resulting in increased effort. Hence this type of design project could generate excitement and educational impact similar to robotics and video games.

  13. Evolution and Adaptation of Wild Emmer Wheat Populations to Biotic and Abiotic Stresses.

    Science.gov (United States)

    Huang, Lin; Raats, Dina; Sela, Hanan; Klymiuk, Valentina; Lidzbarsky, Gabriel; Feng, Lihua; Krugman, Tamar; Fahima, Tzion

    2016-08-04

    The genetic bottlenecks associated with plant domestication and subsequent selection in man-made agroecosystems have limited the genetic diversity of modern crops and increased their vulnerability to environmental stresses. Wild emmer wheat, the tetraploid progenitor of domesticated wheat, distributed along a wide range of ecogeographical conditions in the Fertile Crescent, has valuable "left behind" adaptive diversity to multiple diseases and environmental stresses. The biotic and abiotic stress responses are conferred by series of genes and quantitative trait loci (QTLs) that control complex resistance pathways. The study of genetic diversity, genomic organization, expression profiles, protein structure and function of biotic and abiotic stress-resistance genes, and QTLs could shed light on the evolutionary history and adaptation mechanisms of wild emmer populations for their natural habitats. The continuous evolution and adaptation of wild emmer to the changing environment provide novel solutions that can contribute to safeguarding food for the rapidly growing human population.

  14. Wetland habitat disturbance best predicts metrics of an amphibian index of biotic integrity

    Science.gov (United States)

    Stapanian, Martin A.; Micacchion, Mick; Adams, Jean V.

    2015-01-01

    Regression and classification trees were used to identify the best predictors of the five component metrics of the Ohio Amphibian Index of Biotic Integrity (AmphIBI) in 54 wetlands in Ohio, USA. Of the 17 wetland- and surrounding landscape-scale variables considered, the best predictor for all AmphIBI metrics was habitat alteration and development within the wetland. The results were qualitatively similar to the best predictors for a wetland vegetation index of biotic integrity, suggesting that similar management practices (e.g., reducing or eliminating nutrient enrichment from agriculture, mowing, grazing, logging, and removing down woody debris) within the boundaries of the wetland can be applied to effectively increase the quality of wetland vegetation and amphibian communities.

  15. Understanding the Molecular Determinant of Reversible Human Monoamine Oxidase B Inhibitors Containing 2H-Chromen-2-One Core: Structure-Based and Ligand-Based Derived Three-Dimensional Quantitative Structure-Activity Relationships Predictive Models.

    Science.gov (United States)

    Mladenović, Milan; Patsilinakos, Alexandros; Pirolli, Adele; Sabatino, Manuela; Ragno, Rino

    2017-04-24

    Monoamine oxidase B (MAO B) catalyzes the oxidative deamination of aryalkylamines neurotransmitters with concomitant reduction of oxygen to hydrogen peroxide. Consequently, the enzyme's malfunction can induce oxidative damage to mitochondrial DNA and mediates development of Parkinson's disease. Thus, MAO B emerges as a promising target for developing pharmaceuticals potentially useful to treat this vicious neurodegenerative condition. Aiming to contribute to the development of drugs with the reversible mechanism of MAO B inhibition only, herein, an extended in silico-in vitro procedure for the selection of novel MAO B inhibitors is demonstrated, including the following: (1) definition of optimized and validated structure-based three-dimensional (3-D) quantitative structure-activity relationships (QSAR) models derived from available cocrystallized inhibitor-MAO B complexes; (2) elaboration of SAR features for either irreversible or reversible MAO B inhibitors to characterize and improve coumarin-based inhibitor activity (Protein Data Bank ID: 2V61 ) as the most potent reversible lead compound; (3) definition of structure-based (SB) and ligand-based (LB) alignment rule assessments by which virtually any untested potential MAO B inhibitor might be evaluated; (4) predictive ability validation of the best 3-D QSAR model through SB/LB modeling of four coumarin-based external test sets (267 compounds); (5) design and SB/LB alignment of novel coumarin-based scaffolds experimentally validated through synthesis and biological evaluation in vitro. Due to the wide range of molecular diversity within the 3-D QSAR training set and derived features, the selected N probe-derived 3-D QSAR model proves to be a valuable tool for virtual screening (VS) of novel MAO B inhibitors and a platform for design, synthesis and evaluation of novel active structures. Accordingly, six highly active and selective MAO B inhibitors (picomolar to low nanomolar range of activity) were disclosed as a

  16. Transcriptomic responses to biotic stresses in Malus x domestica: a meta-analysis study

    OpenAIRE

    Balan, Bipin; Marra, Francesco Paolo; Caruso, Tiziano; Martinelli, Federico

    2018-01-01

    RNA-Seq analysis is a strong tool to gain insight into the molecular responses to biotic stresses in plants. The objective of this work is to identify specific and common molecular responses between different transcriptomic data related to fungi, virus and bacteria attacks in Malus x domestica. We analyzed seven transcriptomic datasets in Malus x domestica divided in responses to fungal pathogens, virus (Apple Stem Grooving Virus) and bacteria (Erwinia amylovora). Data were dissected using an...

  17. Metabolomics reveals biotic and abiotic elicitor effects on the soft coral Sarcophyton ehrenbergi terpenoid content

    OpenAIRE

    Farag, Mohamed A.; Al-Mahdy, Dalia A.; Meyer, Achim; Westphal, Hildegard; Wessjohann, Ludger A.

    2017-01-01

    The effects of six biotic and abiotic elicitors, i.e. MeJA (methyl jasmonate), SA (salicylic acid), ZnCl2, glutathione and ?-glucan BG (fungal elicitor), and wounding, on the secondary metabolite accumulation in the soft coral Sarcophyton ehrenbergi were assessed. Upon elicitation, metabolites were extracted and analysed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Except for MeJA, no differences in photosynthetic efficiency were observed after treatments, suggestin...

  18. Presence of riparian vegetation increases biotic condition of fish assemblages in two Brazilian reservoirs

    OpenAIRE

    Ferreira, Fabio Cop; Souza, Ursulla Pereira; Petrere Junior2, Miguel

    2015-01-01

    Abstract The riparian vegetation in lakes and reservoirs is source of course wood structures such as trunks and branches and is used as sheltering, spawning and foraging habitats for fishes. The reduction of these submerged structures can thus, affect the composition and structure of fish assemblages in reservoirs. Aim To evaluate the influence of riparian vegetation on the biotic condition of fish assemblage by adapting the Reservoir Fish Assemblage Index (RFAI) to two reservoirs in the Upp...

  19. Effects of native biodiversity on grape loss of four castes: testing the biotic resistance hypothesis

    Directory of Open Access Journals (Sweden)

    M. Nereu

    2018-02-01

    Full Text Available Management of agricultural landscapes can influence the biodiversity and the ecological services provided by these ecosystems, such as natural biological pest control. Viticulture is a very important economic activity in most countries with Mediterranean climate, often shaping their landscapes and culture. Grape production is affected by a number of pests and diseases, and farmers use prophylactic and response-driven pesticides to control these pests. Here we quantified the main biotic causes of crop losses in four grape castes, two red (Touriga Nacional and Baga and two white (Arinto and Chardonnay, and evaluated the potential effect of native biodiversity to provide biotic resistance to pest outbreaks and grape losses. Specifically, the diversity and abundance of bird and insect communities in these vineyards were quantified and divided into functional guilds (pest, neutral or auxiliary, to test whether these natural communities hold the potential to naturally control grape pests (biotic resistance hypothesis under normal vineyard management (including pesticide application regimes. A potential association between distance to the vineyard edge and grape losses was also evaluated. We recorded a very small proportion of grape losses (mean  =  0.6 %; max  =  7.5 %, with insect pests showing a preference for the castes Baga (red and Chardonnay (white, while bird pests avoided the caste Arinto (white. Grape color did not influence losses caused by insect pests, but birds showed a preference for red castes. The caste Baga was also more vulnerable to losses caused by fungi. Despite their low impact on grape production, most insects and birds detected in the six vineyards were pests, which entails a potentially low level of biotic resistance in this highly managed agricultural ecosystem. Further research is necessary to fully evaluate the role of functional biodiversity in vineyards, particularly if alternative production processes

  20. Importance of biotic and abiotic components in feedback between plants and soil

    OpenAIRE

    Hanzelková, Věra

    2017-01-01

    The plant-soil feedback affects the forming of a plant community. Plants affect their own species as well as other species. The plant-soil feedback can be both positive and negative. Plants affect soil, change its properties, and the soil affects the plants reciprocally. Soil components can be divided into biotic and abiotic ones. The abiotic component is represented by physical and chemical properties of the soil. The main properties are the soil structure, the soil moisture, the soil temper...

  1. CD40 Ligand Deficient C57BL/6 Mouse Is a Potential Surrogate Model of Human X-Linked Hyper IgM (X-HIGM Syndrome for Characterizing Immune Responses against Pathogens

    Directory of Open Access Journals (Sweden)

    Catalina Lopez-Saucedo

    2015-01-01

    Full Text Available Individuals with X-HIGM syndrome fail to express functional CD40 ligand; consequently they cannot mount effective protective antibody responses against pathogenic bacteria. We evaluated, compared, and characterized the humoral immune response of wild type (WT and C57-CD40L deficient (C57-CD40L−/− mice infected with Citrobacter rodentium. Basal serum isotype levels were similar for IgM and IgG3 among mice, while total IgG and IgG2b concentrations were significantly lower in C57-CD40L−/− mice compared with WT. Essentially IgG1 and IgG2c levels were detectable only in WT mice. C57-CD40L−/− animals, orally inoculated with 2×109 CFU, presented several clinical manifestations since the second week of infection and eventually died. In contrast at this time point no clinical manifestations were observed among C57-CD40L−/− mice infected with 1×107 CFU. Infection was subclinical in WT mice inoculated with either bacterial dose. The serum samples from infected mice (1×107 CFU, collected at day 14 after infection, had similar C. rodentium-specific IgM titres. Although C57-CD40L−/− animals had lower IgG and IgG2b titres than WT mice, C57-CD40L−/− mice sera displayed complement-mediated bactericidal activity against C. rodentium. C. rodentium-infected C57-CD40L−/− mice are capable of producing antibodies that are protective. C57-CD40L−/− mouse is a useful surrogate model of X-HIGM syndrome for studying immune responses elicited against pathogens.

  2. Transcriptomic responses to biotic stresses in Malus x domestica: a meta-analysis study.

    Science.gov (United States)

    Balan, Bipin; Marra, Francesco Paolo; Caruso, Tiziano; Martinelli, Federico

    2018-01-31

    RNA-Seq analysis is a strong tool to gain insight into the molecular responses to biotic stresses in plants. The objective of this work is to identify specific and common molecular responses between different transcriptomic data related to fungi, virus and bacteria attacks in Malus x domestica. We analyzed seven transcriptomic datasets in Malus x domestica divided in responses to fungal pathogens, virus (Apple Stem Grooving Virus) and bacteria (Erwinia amylovora). Data were dissected using an integrated approach of pathway- and gene- set enrichment analysis, Mapman visualization tool, gene ontology analysis and inferred protein-protein interaction network. Our meta-analysis revealed that the bacterial infection enhanced specifically genes involved in sugar alcohol metabolism. Brassinosteroids were upregulated by fungal pathogens while ethylene was highly affected by Erwinia amylovora. Gibberellins and jasmonates were strongly repressed by fungal and viral infections. The protein-protein interaction network highlighted the role of WRKYs in responses to the studied pathogens. In summary, our meta-analysis provides a better understanding of the Malus X domestica transcriptome responses to different biotic stress conditions; we anticipate that these insights will assist in the development of genetic resistance and acute therapeutic strategies. This work would be an example for next meta-analysis works aiming at identifying specific common molecular features linked with biotic stress responses in other specialty crops.

  3. The application of biotic elicitor on Artemisia annua L. to increase artemisinin content

    Science.gov (United States)

    Darwati, I.; Manohara, D.; Rohimatun; Nurhayati, H.

    2018-01-01

    Artemisinin-based Combination Therapy (ACT) has been recommended by WHO as an alternative to treat malaria overcoming drug resistance. The secondary metabolic products in plants, including artemisinin, can be increased by utilizing biotic elicitor from fungi. The research was conducted in Gunung Putri Research Installation, Cipanas, West Java from 2010 to 2011. Phytophthora sp. from eggplant and Colletotrichum sp. from Artemisia annua were applied as biotic elicitor. The types of biotic elicitor applied to the plants were 1) the medium of potato dextrose broth were inoculated with fungi and harvested after 10 days (filtrate), 2) powdery mycelium of both fungi. There were 16 treatments: control negative, control positive (uninoculated medium) 1%, 2%, 3% (v/v)], Phytophthora sp. filtrate [1, 2% and 3% (v/v)], Colletotrichum sp. filtrate [1, 2% and 3% (v/v)], Phytophthora sp. mycelium [1%, 2% and 3% (w/v)], Colletotrichum sp mycelium [1%, 2% and 3% (w/v)]. The elicitor application increased plant production by 26.21% and artemisinin yield by 72% compared to control. Furthermore, the artemisinin production of the plants treated with medium inoculated with 2% filtrate of Phytophthora sp (FP2) (25.19 kg/ha) and 1% powdery mycelium of Colletotrichum sp (MC1) (26.42 kg/ha) were higher than control (K) (11.17 kg/ha).

  4. Diagnosis of abiotic and biotic stress factors using the visible symptoms in foliage

    International Nuclear Information System (INIS)

    Vollenweider, P.; Guenthardt-Goerg, Madeleine S.

    2005-01-01

    Visible symptoms in the foliage of trees are recorded to monitor the effects of abiotic and biotic stress. Difficulties are reported in diagnosing the origin of stress. The present paper discusses several diagnostic criteria which are usable in different species for a better determination of the stress factor type. A new diagnosis scheme to differentiate between classes of abiotic and biotic stress factors is supplied. Abiotic stress generates gradients of symptoms. The symptom specificity is determined by the degree of interaction between the stress factor and plant defense system. Symptoms caused by abiotic stress and natural autumnal senescence can be morphologically different or undistinguishable according to the stress and plant species. With biotic stress, the class of parasitic is generally recognizable on the basis of the visible symptoms. Structurally and physiologically based explanations of the symptom morphology are still missing for many stress factors. - The morphology and distribution of visible stress symptoms in tree foliage provides diagnostic tools to identify plant defense responses and differentiate stress from natural senescence symptoms

  5. Application of radiation processing to produce biotic elicitor for sugarcane in Vietnam

    International Nuclear Information System (INIS)

    Nguyen, Quoc Hien; Tran, Tich Canh; Truong, Thi Hanh; Vo, Thi Kim Lang; Dang, Van Phu; Cao, Anh Duong

    2007-01-01

    Sugarcane is the main raw material for production of sugar and ethanol. In Vietnam, it was reported in 1998 that the area for sugarcane growth was about 257,000ha. Up to now, the biotic elicitor, oligosaccharide has not been used for sugarcane yet. This study has been carried out to investigate the elicitation and the growth promotion effect of irradiated chitosan (oligochitosan) for sugarcane. The field test results indicated that alpha chitosan (shrimp shell) and beta chitosan (squid pen) samples with the content of water soluble oligomer of about 70% were the most effective. The disease ratio of sugarcane tree-trunk treated with irradiated chitosan before harvesting time decreased to 30-40% compared to non-treated one (100%). In addition, the productivity of sugarcane increased to about 20%. The combination of metal ion (Zn ++ , Cu ++ ) with oligochitosan did not show the synergic elicitation effect. The results revealed that biotic elicitor made from chitosan by radiation degradation method is very promising for field application not only for protection of disease infection but also for growth promotion of plants. It is believed that this biotic elicitor could be largely used for safe and sustainable development of agriculture. (author)

  6. Environmental Maternal Effects Mediate the Resistance of Maritime Pine to Biotic Stress

    Science.gov (United States)

    Vivas, María; Zas, Rafael; Sampedro, Luis; Solla, Alejandro

    2013-01-01

    The resistance to abiotic stress is increasingly recognised as being impacted by maternal effects, given that environmental conditions experienced by parent (mother) trees affect stress tolerance in offspring. We hypothesised that abiotic environmental maternal effects may also mediate the resistance of trees to biotic stress. The influence of maternal environment and maternal genotype and the interaction of these two factors on early resistance of Pinus pinaster half-sibs to the Fusarium circinatum pathogen was studied using 10 mother genotypes clonally replicated in two contrasting environments. Necrosis length of infected seedlings was 16% shorter in seedlings grown from favourable maternal environment seeds than in seedlings grown from unfavourable maternal environment seeds. Damage caused by F. circinatum was mediated by maternal environment and maternal genotype, but not by seed mass. Mechanisms unrelated to seed provisioning, perhaps of epigenetic nature, were probably involved in the transgenerational plasticity of P. pinaster, mediating its resistance to biotic stress. Our findings suggest that the transgenerational resistance of pines due to an abiotic stress may interact with the defensive response of pines to a biotic stress. PMID:23922944

  7. Environmental maternal effects mediate the resistance of maritime pine to biotic stress.

    Directory of Open Access Journals (Sweden)

    María Vivas

    Full Text Available The resistance to abiotic stress is increasingly recognised as being impacted by maternal effects, given that environmental conditions experienced by parent (mother trees affect stress tolerance in offspring. We hypothesised that abiotic environmental maternal effects may also mediate the resistance of trees to biotic stress. The influence of maternal environment and maternal genotype and the interaction of these two factors on early resistance of Pinus pinaster half-sibs to the Fusarium circinatum pathogen was studied using 10 mother genotypes clonally replicated in two contrasting environments. Necrosis length of infected seedlings was 16% shorter in seedlings grown from favourable maternal environment seeds than in seedlings grown from unfavourable maternal environment seeds. Damage caused by F. circinatum was mediated by maternal environment and maternal genotype, but not by seed mass. Mechanisms unrelated to seed provisioning, perhaps of epigenetic nature, were probably involved in the transgenerational plasticity of P. pinaster, mediating its resistance to biotic stress. Our findings suggest that the transgenerational resistance of pines due to an abiotic stress may interact with the defensive response of pines to a biotic stress.

  8. Pollinator-independent orchid attracts biotic pollinators due the production of lipoidal substances.

    Science.gov (United States)

    Pansarin, E R; Bergamo, P J; Ferreira-Caliman, M J

    2018-03-01

    Flowering plants often depend on the attraction of biotic pollinators for sexual reproduction. Consequently, the emergence and maintenance of selected floral attributes related to pollinator attraction and rewarding are driven by pollinator pressure. In this paper we explore the effect of pollinators, rainfall, temperature and air humidity on the reproduction of a Brazilian terrestrial orchid, Cranichis candida based on data of phenology, flower resources, olfactory and visual attraction cues, pollinators and breeding system. The flowers of C. candida are strongly protandrous and pollinated by workers of the social native bee Tetragonisca angustula. The bees collect labellar lipoidal substances (wax scales), which are transported to the nest. The lipoidal substance is composed of sterols, hydrocarbons and terpenes. The last presumably protects the bees and their nests against pathogens and other arthropods. C. candida sets fruits through biotic self- and cross-pollination, and spontaneously due the action of raindrops on flowers. Our results indicate that in C. candida, although rain-mediated spontaneous self-pollination happens, fructification mediated by biotic pollinations also occurs, which may result in fruit set by cross-pollination. A mixed pollination system must result in higher genetic variability when compared to species whose fruits are produced entirely by self-pollination. On the other hand, autogamy is a form of reproductive assurance, and has commonly evolved where pollination services are rare or absent. © 2017 German Society for Plant Sciences and The Royal Botanical Society of the Netherlands.

  9. Can plant-natural enemy communication withstand disruption by biotic and abiotic factors?

    Science.gov (United States)

    Clavijo McCormick, Andrea

    2016-12-01

    The attraction of natural enemies towards herbivore-induced plant volatiles is a well-documented phenomenon. However, the majority of published studies are carried under optimal water and nutrient regimes and with just one herbivore. But what happens when additional levels of ecological complexity are added? Does the presence of a second herbivore, microorganisms, and abiotic stress interfere with plant-natural enemy communication? or is communication stable enough to withstand disruption by additional biotic and abiotic factors?Investigating the effects of these additional levels of ecological complexity is key to understanding the stability of tritrophic interactions in natural ecosystems and may aid to forecast the impact of environmental disturbances on these, especially in climate change scenarios, which are often associated with modifications in plant and arthropod species distribution and increased levels of abiotic stress.This review explores the literature on natural enemy attraction to herbivore-induced volatiles when, besides herbivory, plants are challenged by additional biotic and abiotic factors.The aim of this review was to establish the impact of different biotic and abiotic factors on plant-natural enemy communication and to highlight critical aspects to guide future research efforts.

  10. Induced Systemic Tolerance to Multiple Stresses Including Biotic and Abiotic Factors by Rhizobacteria

    Directory of Open Access Journals (Sweden)

    Sung-Je Yoo

    2017-06-01

    Full Text Available Recently, global warming and drastic climate change are the greatest threat to the world. The climate change can affect plant productivity by reducing plant adaptation to diverse environments including frequent high temperature; worsen drought condition and increased pathogen transmission and infection. Plants have to survive in this condition with a variety of biotic (pathogen/pest attack and abiotic stress (salt, high/low temperature, drought. Plants can interact with beneficial microbes including plant growth-promoting rhizobacteria, which help plant mitigate biotic and abiotic stress. This overview presents that rhizobacteria plays an important role in induced systemic resistance (ISR to biotic stress or induced systemic tolerance (IST to abiotic stress condition; bacterial determinants related to ISR and/or IST. In addition, we describe effects of rhizobacteria on defense/tolerance related signal pathway in plants. We also review recent information including plant resistance or tolerance against multiple stresses (bioticabiotic. We desire that this review contribute to expand understanding and knowledge on the microbial application in a constantly varying agroecosystem, and suggest beneficial microbes as one of alternative environment-friendly application to alleviate multiple stresses.

  11. Benefits of Biotic Pollination for Non-Timber Forest Products and Cultivated Plants

    Directory of Open Access Journals (Sweden)

    Rehel Shiny

    2009-01-01

    Full Text Available Biodiversity supplies multiple goods and services to society and is critical for the support of livelihoods across the globe. Many indigenous people depend upon non-timber forest products (NTFP and crops for a range of goods including food, medicine, fibre and construction materials. However, the dependency of these products on biotic pollination services is poorly understood. We used the biologically and culturally diverse Nilgiri Biosphere Reserve in India to characterise the types of NTFP and crop products of 213 plant species and asses their degree of dependency on animal pollination. We found that 80 per cent of all species benefited from animal pollination in their reproduction, and that 62 per cent of crop products and 40 per cent of NTFP benefited from biotic pollination in their production. Further we identified the likely pollinating taxa documented as responsible for the production of these products, mainly bees and other insects. A lower proportion of indigenous plant products (39 per cent benefited from biotic pollination than products from introduced plants (61 per cent. We conclude that pollinators play an important role in the livelihoods of people in this region.

  12. Dynamic Ligand Based Pharmacophore Modeling and Virtual ...

    Indian Academy of Sciences (India)

    user

    QPlogS Predicted aqueous solubility, log S. S in mol dm–3 is the ... QPPCaco Predicted apparent Caco-2 cell permeability in nm/sec. ... HumanOralAbsorption Predicted qualitative human oral absorption: 1, 2, or 3 for low, medium, or high.

  13. Unravelling abiotic and biotic controls on the seasonal water balance using data-driven dimensionless diagnostics

    Directory of Open Access Journals (Sweden)

    S. P. Seibert

    2017-06-01

    Full Text Available The baffling diversity of runoff generation processes, alongside our sketchy understanding of how physiographic characteristics control fundamental hydrological functions of water collection, storage, and release, continue to pose major research challenges in catchment hydrology. Here, we propose innovative data-driven diagnostic signatures for overcoming the prevailing status quo in catchment inter-comparison. More specifically, we present dimensionless double mass curves (dDMC which allow inference of information on runoff generation and the water balance at the seasonal and annual timescales. By separating the vegetation and winter periods, dDMC furthermore provide information on the role of biotic and abiotic controls in seasonal runoff formation. A key aspect we address in this paper is the derivation of dimensionless expressions of fluxes which ensure the comparability of the signatures in space and time. We achieve this by using the limiting factors of a hydrological process as a scaling reference. We show that different references result in different diagnostics. As such we define two kinds of dDMC which allow us to derive seasonal runoff coefficients and to characterize dimensionless streamflow release as a function of the potential renewal rate of the soil storage. We expect these signatures for storage controlled seasonal runoff formation to remain invariant, as long as the ratios of release over supply and supply over storage capacity develop similarly in different catchments. We test the proposed methods by applying them to an operational data set comprising 22 catchments (12–166 km2 from different environments in southern Germany and hydrometeorological data from 4 hydrological years. The diagnostics are used to compare the sites and to reveal the dominant controls on runoff formation. The key findings are that dDMC are meaningful signatures for catchment runoff formation at the seasonal to annual scale and that the type of

  14. Potential ligand-binding residues in rat olfactory receptors identified by correlated mutation analysis

    Science.gov (United States)

    Singer, M. S.; Oliveira, L.; Vriend, G.; Shepherd, G. M.

    1995-01-01

    A family of G-protein-coupled receptors is believed to mediate the recognition of odor molecules. In order to identify potential ligand-binding residues, we have applied correlated mutation analysis to receptor sequences from the rat. This method identifies pairs of sequence positions where residues remain conserved or mutate in tandem, thereby suggesting structural or functional importance. The analysis supported molecular modeling studies in suggesting several residues in positions that were consistent with ligand-binding function. Two of these positions, dominated by histidine residues, may play important roles in ligand binding and could confer broad specificity to mammalian odor receptors. The presence of positive (overdominant) selection at some of the identified positions provides additional evidence for roles in ligand binding. Higher-order groups of correlated residues were also observed. Each group may interact with an individual ligand determinant, and combinations of these groups may provide a multi-dimensional mechanism for receptor diversity.

  15. Macrocyclic ligands for uranium complexation

    International Nuclear Information System (INIS)

    Potts, K.T.

    1991-04-01

    A highly preorganized 24-macrocycle containing biuret, thiobiuret and pyridine subunits has been prepared by high dilution ring-closure procedures. Intermediate products to this macrocycle have been utilized to extend this synthetic route to include further representatives where solubility and stability will be influenced by substituent variation. A 1:1 complex has been formed from uranyl acetate and a quinquepyridine derivative, this representing a new type of ligand for the uranyl ion. A very convenient synthetic procedure that will allow the incorporation of these macrocycles into polymeric systems has been developed for the introduction of a vinyl substituent into the 4-position of the pyridine ring. Using triflate, vinyltributyltin and Pd 0 chemistry, this procedure should make a variety of substituted 4-vinylpyridines available for the first time. 3 refs

  16. AFAL: a web service for profiling amino acids surrounding ligands in proteins

    Science.gov (United States)

    Arenas-Salinas, Mauricio; Ortega-Salazar, Samuel; Gonzales-Nilo, Fernando; Pohl, Ehmke; Holmes, David S.; Quatrini, Raquel

    2014-11-01

    With advancements in crystallographic technology and the increasing wealth of information populating structural databases, there is an increasing need for prediction tools based on spatial information that will support the characterization of proteins and protein-ligand interactions. Herein, a new web service is presented termed amino acid frequency around ligand (AFAL) for determining amino acids type and frequencies surrounding ligands within proteins deposited in the Protein Data Bank and for assessing the atoms and atom-ligand distances involved in each interaction (availability: http://structuralbio.utalca.cl/AFAL/index.html). AFAL allows the user to define a wide variety of filtering criteria (protein family, source organism, resolution, sequence redundancy and distance) in order to uncover trends and evolutionary differences in amino acid preferences that define interactions with particular ligands. Results obtained from AFAL provide valuable statistical information about amino acids that may be responsible for establishing particular ligand-protein interactions. The analysis will enable investigators to compare ligand-binding sites of different proteins and to uncover general as well as specific interaction patterns from existing data. Such patterns can be used subsequently to predict ligand binding in proteins that currently have no structural information and to refine the interpretation of existing protein models. The application of AFAL is illustrated by the analysis of proteins interacting with adenosine-5'-triphosphate.

  17. The role of ligands in the optical and electronic spectra of CdSe nanoclusters

    Energy Technology Data Exchange (ETDEWEB)

    Kilina, Svletana [Los Alamos National Laboratory; Sergei, Ivanov A [Los Alamos National Laboratory; Victor, Klimov I [Los Alamos National Laboratory; Sergei, Tretiak [Los Alamos National Laboratory

    2008-01-01

    We investigate the impact of ligands on morphology, electronic structure, and optical response of the Cd33Se33 cluster, which already overlapps in size with the smallest synthesized CdSe quantum dots (QDs). Our Density Functional Theory (DFT) calculations demonstrate significant surface reorganization both for the bare cluster and for the cluster capped by amine and phosphine oxide ligand models. We observe strong surface-ligand interactions leading to substantial charge redistribution and polarization effects on the surface. This effect results in the appearance of hybridized states, where the electronic density is spread over the cluster and the ligands. Neither the ligand's nor hybridized molecular orbitals appear as trap states inside or near the band gap of the QD. Instead, being optically dark, dense hybridized states from the edges of the valence and the conduction bands could open new relaxation channels for high energy photoexcitations. Comparing quantum dots passivated by different ligands, we found that hybridized states are denser in at the edge of the conduction band of the cluster ligated with phosphine oxide molecules than that with primary amines. Such a different manifestation of ligand binding may potentially lead to the faster electron relaxation in dots passivated by phosphine oxide than by amine ligands, which is in agreement with experimental data.

  18. Structural determinants for selective recognition of peptide ligands for endothelin receptor subtypes ETA and ETB.

    Science.gov (United States)

    Lättig, Jens; Oksche, Alexander; Beyermann, Michael; Rosenthal, Walter; Krause, Gerd

    2009-07-01

    The molecular basis for recognition of peptide ligands endothelin-1, -2 and -3 in endothelin receptors is poorly understood. Especially the origin of ligand selectivity for ET(A) or ET(B) is not clearly resolved. We derived sequence-structure-function relationships of peptides and receptors from mutational data and homology modeling. Our major findings are the dissection of peptide ligands into four epitopes and the delineation of four complementary structural portions on receptor side explaining ligand recognition in both endothelin receptor subtypes. In addition, structural determinants for ligand selectivity could be described. As a result, we could improve the selectivity of BQ3020 about 10-fold by a single amino acid substitution, validating our hypothesis for ligand selectivity caused by different entrances to the receptors' transmembrane binding sites. A narrow tunnel shape in ET(A) is restrictive for a selected group of peptide ligands' N-termini, whereas a broad funnel-shaped entrance in ET(B) accepts a variety of different shapes and properties of ligands.

  19. Exploring biotic vs. abiotic controls on syngenetic carbonate and clay mineral precipitation

    Science.gov (United States)

    Nascimento, Gabriela S.; McKenzie, Judith A.; Martinez Ruiz, Francisca; Bontognali, Tomaso R. R.; Vasconcelos, Crisogono

    2016-04-01

    A possible syngenetic relationship between carbonate and clay mineral precipitation has been reported for sedimentary rocks deposited in both lacustrine and marine sedimentary environments throughout the geological record. In particular, the mineral dolomite is often found associated with Mg-rich clays, such as stevensite. It is notable that this carbonate/clay association has been recorded in numerous samples taken from modern dolomite precipitating environments; for example, the Coorong lakes, South Australia, coastal sabkhas, Abu Dhabi, UAE and coastal hypersaline lagoons (Lagoa Vermelha and Brejo do Espinho) east of Rio de Janeiro, Brazil. An HRTEM study of samples from these three locations indicates a possible physical/chemical association between the Ca-dolomite and Mg-rich clays, demonstrating a probable co-precipitation. To test this hypothesis, we have conducted a series of biotic and abiotic laboratory experiments. If this syngenesis actually occurs in nature, what, if any, are the biogeochemical processes controlling these precipitation reactions? Our experiments were designed to determine the extent of the biotic versus abiotic component influencing the mineral precipitation and, in the case of a biotic influence, to understand the mechanism through which microorganisms might mediate the formation of clay minerals. The experiments were carried out in the Geomicrobiology Laboratory of ETH Zürich using cultures of living microbes and artificial organic compounds that simulate functional groups present in natural biofilms formed under both aerobic and anaerobic conditions. In addition, pure inorganic experiments were designed to understand possible physico-chemical conditions for diagenetic processes that could induce dissolution of Mg-carbonates and precipitation of Mg-rich clays. Our results show a remarkable biotic influence during the formation of clay minerals. Specifically, extracellular polymeric substances (EPS), released by microbes in their

  20. Recommended Reference Genes for Quantitative PCR Analysis in Soybean Have Variable Stabilities during Diverse Biotic Stresses.

    Directory of Open Access Journals (Sweden)

    Raman Bansal

    Full Text Available For real-time reverse transcription-PCR (qRT-PCR in soybean, reference genes in different tissues, developmental stages, various cultivars, and under stress conditions have been suggested but their usefulness for research on soybean under various biotic stresses occurring in North-Central U.S. is not known. Here, we investigated the expression stabilities of ten previously recommended reference genes (ABCT, CYP, EF1A, FBOX, GPDH, RPL30, TUA4, TUB4, TUA5, and UNK2 in soybean under biotic stress from Bean pod mottle virus (BPMV, powdery mildew (PMD, soybean aphid (SBA, and two-spotted spider mite (TSSM. BPMV, PMD, SBA, and TSSM are amongst the most common pest problems on soybean in North-Central U.S. and other regions. Reference gene stability was determined using three software algorithms (geNorm, NormFinder, BestKeeper and a web-based tool (RefFinder. Reference genes showed variability in their expression as well as stability across various stressors and the best reference genes were stress-dependent. ABCT and FBOX were found to be the most stable in soybean under both BPMV and SBA stress but these genes had only minimal to moderate stability during PMD and TSSM stress. Expression of TUA4 and CYP was found to be most stable during PMD stress; TUB4 and TUA4 were stable under TSSM stress. Under various biotic stresses on soybean analyzed, GPDH expression was found to be consistently unstable. For all biotic stressors on soybean, we obtained pairwise variation (V2/3 values less than 0.15 which suggested that combined use of the two most stable reference genes would be sufficient for normalization. Further, we demonstrated the utility of normalizing the qRT-PCR data for target genes using the most stable reference genes validated in current study. Following of the recommendations from our current study will enable an accurate and reliable normalization of qRT-PCR data in soybean under biotic stress.

  1. Biotic Iron Precipitation in Sand Filtration Systems by Gallionella ferruginea: Morphology and content of Exopolymers

    DEFF Research Database (Denmark)

    Søgaard, Erik Gydesen; Simonsen, Charlotte

    conditions for principally biotic or abiotic iron precipitation is not well defined. An rH2 greater than 14 e.g. corresponding to an Eh a little above zero at slightly acidic pH is stated to be the best condition for biotic iron precipitation (Degremont, 1991). Abiotic iron precipitation is performed at a p...... are built with the purpose of biotic iron precipitation in order to reduce frequency of backwashing filtration systems. This is possibly due to the fact that biologically precipitated iron has a much denser structure than the corresponding abiotic precipitates (Søgaard et al. 2000). Both kinds of iron......-Peskir J. (2000) Conditions and rates of biotic and abiotic iron precipitation in selected Danish freshwater plants and microscopic analysis of precipitate morphology. Water Research, 34, 10, 2675-2682 Søgaard E.G., Aruna R., Abraham-Peskir, J. and Bender Koch, C. (2001) Conditions for iron precipitation...

  2. Impact of phenolic compounds and related enzymes in Sorghum varieties for resistance and susceptibility to biotic and abiotic stresses

    NARCIS (Netherlands)

    Dicko, M.H.; Gruppen, H.; Barro, C.; Traore, A.S.; Berkel, van W.J.H.; Voragen, A.G.J.

    2005-01-01

    Contents of phenolic compounds and related enzymes before and after sorghum grain germination were compared between varieties either resistant or susceptible to biotic (sooty stripe, sorghum midge, leaf anthracnose, striga, and grain molds) and abiotic (lodging, drought resistance, and photoperiod

  3. CXCR4 Ligands : The Next Big Hit?

    NARCIS (Netherlands)

    Walenkamp, Annemiek M. E.; Lapa, Constantin; Herrmann, Ken; Wester, Hans-Juergen

    2017-01-01

    The G protein-coupled protein receptor C-X-C chemokine receptor 4 (CXCR4) is an attractive target for cancer diagnosis and treatment, as it is overexpressed in many solid and hematologic cancers. Binding of its ligand, C-X-C chemokine ligand 12 (CXCL12), results in receptor internalization and

  4. Organotellurium ligands – designing and complexation reactions

    Indian Academy of Sciences (India)

    Unknown

    membered rings it is negative and ~30 ppm only. Keywords. Organotellurium ligands; hybrid telluroether; platinum metal complexes; tellurium-125 NMR. 1. Introduction. Tellurium is the noblest metalloid which may act as a Lewis acid as well as Lewis base. The ligand chemistry of tellurium, which acts as a 'soft' donor, was ...

  5. Biotic survival in the cryobiosphere on geological scale: implication for astro/terrestrial biogeoscience

    Science.gov (United States)

    Gilichinsky, D.

    2003-04-01

    In current opinion the most fundamental aspect of any environment, the temperature regime, acts as a regulator of all of the physical-chemical reactions and forms the basis of all biological processes. Now hard data indicate the biotic survival over geological periods from subzero temperatures (down to -27oC in permafrost and to -50oC in ice) to positive one in amber and halite. All these very different environments have, nevertheless, common features: complete isolation, stability and waterproof. In such unique physical-chemical complexes, the dehydration of macromolecules and the reorganization of membrane components apparently lead to a considerable decrease or stop of metabolic activity independently of temperature. This allowed the prolonged survival of ancient microbial lineage that realize unknown possibilities of physiological and biochemical adaptation incomparably longer than any other known habitat. The ability of microorganisms to survive on geological scale within the broad limits of natural systems forces us to redefine the spatial and temporal limits of the terrestrial and extraterrestrial biospheres and suggested that universal mechanisms of such adaptation might operate for millions of years. Among new scientific directions formed on this base, the most general is the fundamental question: how long the life might be preserved and what mechanisms could ensure survival? Because the length of lifetime cannot be reproduced, this highlights the natural storages that make possible the observation of the results of biotic survival on geological scale. Of special interest is the interaction of knowledge to understanding of the limits of the deep cold biosphere as a depository of ancient active biosignatures (biogases, biominerals, pigments, lipids, enzymes, proteins, RNA/DNA fragments) and viable cells. The last are the only known a huge mass of organisms that have retained viability over geological periods and upon thawing, renew physiological activity

  6. Selective kainate receptor (GluK1) ligands structurally based upon1H-Cyclopentapyrimidin-2,4(1H,3H)-dione: synthesis, molecular modeling, and pharmacological and biostructural characterization

    DEFF Research Database (Denmark)

    Venskutonyte, Raminta; Butini, Stefania; Coccone, Salvatore Sanna

    2011-01-01

    The physiological function of kainate receptors (GluK1- GluK5) in the central nervous system is not fully understood yet. With the aim of developing potent and selective GluK1 ligands, we have synthesized a series of new thiophene-based GluK1 agonists (6a-c) and antagonists (7a-d). Pharmacologica...

  7. Biotic components

    International Nuclear Information System (INIS)

    Uresk, D.W.; Fitzner, R.E.; Rogers, L.E.; Rickard, W.H.

    1977-01-01

    Representative plant communities are described. The major community is dominated by sagebrush/cheatgrass-sandberg blue grass. Mammal, bird and insect species inhabiting the 200 Area plateau are representative of surrounding regions. Prairie falcons are the only species present possibly threatened with extinction. They do not nest on the plateau but probably forage over the area

  8. Quantitation of species differences in albumin–ligand interactions for bovine, human and rat serum albumins using fluorescence spectroscopy: A test case with some Sudlow's site I ligands

    International Nuclear Information System (INIS)

    Poór, Miklós; Li, Yin; Matisz, Gergely; Kiss, László; Kunsági-Máté, Sándor; Kőszegi, Tamás

    2014-01-01

    Albumin, the most abundant plasma protein is an approximately 67 kDa sized water-soluble macromolecule. Since several drugs and xenobiotics circulate in the blood at least partially in albumin-bound form, albumin plays a key role in the pharmacokinetics/toxicokinetics of these chemicals. Most of the drugs and xenobiotics are Sudlow's site I ligands. In numerous studies, bovine serum albumin (BSA) is used for modeling albumin–ligand interactions and the results are extrapolated to human serum albumin (HSA). Furthermore, only limited information is available related to albumin–ligand interactions of different albumin species. Therefore, in our study, we have focused on the quantification of differences between bovine, human and rat serum albumin (RSA) using four Sudlow's site I ligands (luteolin, ochratoxin A, phenylbutazone and warfarin). Interactions were analyzed by fluorescence spectroscopy. Stability constants as well as competing capacities of the ligands were determined, and thermodynamic study was also performed. Our results highlight that there could be major differences between BSA, HSA and RSA in their ligand binding properties. Based on our observations we emphasize that in molecular aspects BSA behaves considerably differently from HSA or from albumins of other species therefore, it is strongly recommended to apply at least some confirmatory measurements when data obtained from other species are attempted to be extrapolated to HSA. -- Highlights: • Albumin–ligand interactions of human, bovine and rat albumins were studied. • Four Sudlow's site I ligands were tested by fluorescence spectroscopy. • Substantial differences were found in stability constants among albumin complexes. • Competing capacity of ligands showed major differences in the studied species. • Data obtained for BSA cannot be directly extrapolated to human albumin

  9. Calculation of protein-ligand binding affinities.

    Science.gov (United States)

    Gilson, Michael K; Zhou, Huan-Xiang

    2007-01-01

    Accurate methods of computing the affinity of a small molecule with a protein are needed to speed the discovery of new medications and biological probes. This paper reviews physics-based models of binding, beginning with a summary of the changes in potential energy, solvation energy, and configurational entropy that influence affinity, and a theoretical overview to frame the discussion of specific computational approaches. Important advances are reported in modeling protein-ligand energetics, such as the incorporation of electronic polarization and the use of quantum mechanical methods. Recent calculations suggest that changes in configurational entropy strongly oppose binding and must be included if accurate affinities are to be obtained. The linear interaction energy (LIE) and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) methods are analyzed, as are free energy pathway methods, which show promise and may be ready for more extensive testing. Ultimately, major improvements in modeling accuracy will likely require advances on multiple fronts, as well as continued validation against experiment.

  10. Abiotic versus biotic drivers of ocean pH variation under fast sea ice in McMurdo Sound, Antarctica.

    Science.gov (United States)

    Matson, Paul G; Washburn, Libe; Martz, Todd R; Hofmann, Gretchen E

    2014-01-01

    Ocean acidification is expected to have a major effect on the marine carbonate system over the next century, particularly in high latitude seas. Less appreciated is natural environmental variation within these systems, particularly in terms of pH, and how this natural variation may inform laboratory experiments. In this study, we deployed sensor-equipped moorings at 20 m depths at three locations in McMurdo Sound, comprising deep (bottom depth>200 m: Hut Point Peninsula) and shallow environments (bottom depth ∼25 m: Cape Evans and New Harbor). Our sensors recorded high-frequency variation in pH (Hut Point and Cape Evans only), tide (Cape Evans and New Harbor), and water mass properties (temperature and salinity) during spring and early summer 2011. These collective observations showed that (1) pH differed spatially both in terms of mean pH (Cape Evans: 8.009±0.015; Hut Point: 8.020±0.007) and range of pH (Cape Evans: 0.090; Hut Point: 0.036), and (2) pH was not related to the mixing of two water masses, suggesting that the observed pH variation is likely not driven by this abiotic process. Given the large daily fluctuation in pH at Cape Evans, we developed a simple mechanistic model to explore the potential for biotic processes--in this case algal photosynthesis--to increase pH by fixing carbon from the water column. For this model, we incorporated published photosynthetic parameters for the three dominant algal functional groups found at Cape Evans (benthic fleshy red macroalgae, crustose coralline algae, and sea ice algal communities) to estimate oxygen produced/carbon fixed from the water column underneath fast sea ice and the resulting pH change. These results suggest that biotic processes may be a primary driver of pH variation observed under fast sea ice at Cape Evans and potentially at other shallow sites in McMurdo Sound.

  11. Abiotic versus biotic drivers of ocean pH variation under fast sea ice in McMurdo Sound, Antarctica.

    Directory of Open Access Journals (Sweden)

    Paul G Matson

    Full Text Available Ocean acidification is expected to have a major effect on the marine carbonate system over the next century, particularly in high latitude seas. Less appreciated is natural environmental variation within these systems, particularly in terms of pH, and how this natural variation may inform laboratory experiments. In this study, we deployed sensor-equipped moorings at 20 m depths at three locations in McMurdo Sound, comprising deep (bottom depth>200 m: Hut Point Peninsula and shallow environments (bottom depth ∼25 m: Cape Evans and New Harbor. Our sensors recorded high-frequency variation in pH (Hut Point and Cape Evans only, tide (Cape Evans and New Harbor, and water mass properties (temperature and salinity during spring and early summer 2011. These collective observations showed that (1 pH differed spatially both in terms of mean pH (Cape Evans: 8.009±0.015; Hut Point: 8.020±0.007 and range of pH (Cape Evans: 0.090; Hut Point: 0.036, and (2 pH was not related to the mixing of two water masses, suggesting that the observed pH variation is likely not driven by this abiotic process. Given the large daily fluctuation in pH at Cape Evans, we developed a simple mechanistic model to explore the potential for biotic processes--in this case algal photosynthesis--to increase pH by fixing carbon from the water column. For this model, we incorporated published photosynthetic parameters for the three dominant algal functional groups found at Cape Evans (benthic fleshy red macroalgae, crustose coralline algae, and sea ice algal communities to estimate oxygen produced/carbon fixed from the water column underneath fast sea ice and the resulting pH change. These results suggest that biotic processes may be a primary driver of pH variation observed under fast sea ice at Cape Evans and potentially at other shallow sites in McMurdo Sound.

  12. Correcting ligands, metabolites, and pathways

    Directory of Open Access Journals (Sweden)

    Vriend Gert

    2006-11-01

    Full Text Available Abstract Background A wide range of research areas in bioinformatics, molecular biology and medicinal chemistry require precise chemical structure information about molecules and reactions, e.g. drug design, ligand docking, metabolic network reconstruction, and systems biology. Most available databases, however, treat chemical structures more as illustrations than as a datafield in its own right. Lack of chemical accuracy impedes progress in the areas mentioned above. We present a database of metabolites called BioMeta that augments the existing pathway databases by explicitly assessing the validity, correctness, and completeness of chemical structure and reaction information. Description The main bulk of the data in BioMeta were obtained from the KEGG Ligand database. We developed a tool for chemical structure validation which assesses the chemical validity and stereochemical completeness of a molecule description. The validation tool was used to examine the compounds in BioMeta, showing that a relatively small number of compounds had an incorrect constitution (connectivity only, not considering stereochemistry and that a considerable number (about one third had incomplete or even incorrect stereochemistry. We made a large effort to correct the errors and to complete the structural descriptions. A total of 1468 structures were corrected and/or completed. We also established the reaction balance of the reactions in BioMeta and corrected 55% of the unbalanced (stoichiometrically incorrect reactions in an automatic procedure. The BioMeta database was implemented in PostgreSQL and provided with a web-based interface. Conclusion We demonstrate that the validation of metabolite structures and reactions is a feasible and worthwhile undertaking, and that the validation results can be used to trigger corrections and improvements to BioMeta, our metabolite database. BioMeta provides some tools for rational drug design, reaction searches, and

  13. Invasion by nonnative brook trout in Panther Creek, Idaho: Roles of local habitat quality, biotic resistance, and connectivity to source habitats

    Science.gov (United States)

    Benjamin, Joseph R.; Dunham, Jason B.; Dare, M.R.

    2007-01-01

    Theoretical models and empirical evidence suggest that the invasion of nonnative species in freshwaters is facilitated through the interaction of three factors: habitat quality, biotic resistance, and connectivity. We measured variables that represented each factor to determine which were associated with the occurrence of nonnative brook trout Salvelinus fontinalis in Panther Creek, a tributary to the Salmon River, Idaho. Habitat variables included measures of summer and winter temperature, instream cover, and channel size. The abundance of native rainbow trout Oncorhynchus mykiss within sampled sites was used as a measure of biotic resistance. We also considered the connectivity of sample sites to unconfined valley bottoms, which were considered habitats that may serve as sources for the spread of established populations of brook trout. We analyzed the occurrence of small (<150‐mm [fork length]) and large (≥150‐mm) brook trout separately, assuming that the former represents an established invasion while accounting for the higher potential mobility of the latter. The occurrence of small brook trout was strongly associated with the proximity of sites to large, unconstrained valley bottoms, providing evidence that such habitats may serve as sources for the spread of brook trout invasion. Within sites, winter degree‐days and maximum summer temperature were positively associated with the occurrence of small brook trout. The occurrence of large brook trout was not related to any of the variables considered, perhaps due to the difficulty of linking site‐specific habitat factors to larger and more mobile individuals. The abundance of rainbow trout was not conclusively associated with the occurrence of either small or large brook trout, providing little support for the role of biotic resistance. Overall, our results suggest that source connectivity and local habitat characteristics, but not biotic resistance, influence the establishment and spread of

  14. Radiation induced ligand loss from cobalt complexes

    International Nuclear Information System (INIS)

    Funston, A. M.; McFadyen, W.D.; Tregloan, P.A.

    2000-01-01

    Full text: Due to the rapid nature of ligand dissociation from cobalt(II) complexes the study of the rate of ligand dissociation necessitates the use of a technique such as pulse radiolysis. This allows the rapid reduction of the corresponding cobalt(III) complex by a reducing radical, such as the aquated electron, to form the cobalt(II) complex. However, to date, no systematic study of either the mechanism of reduction or the influence of the electronic structure on the rate of ligand dissociation has been carried out. In order to understand these processes more fully the mechanism of reduction of a range of related cobalt(III) complexes by the aquated electron and the subsequent rate of ligand dissociation from the resulting cobalt(II) complexes is being investigated. It has been found that a number of processes are observed following the initial rapid reaction of the cobalt(III) complex with the aquated electron. Ultimately ligand loss is observed. Depending upon the complex, the initial processes observed may include the formation of coordinated radicals and electron transfer within the complex. For complexes containing aromatic ligands such as 2,2'-bipyridine, 1,10-phenanthroline and dipyrido[3,2-a:2',3'-c]phenazine the formation of a coordinated radical is observed as the initial reduction step. The kinetics of ligand dissociation of these complexes has been determined. The loss of monodentate ligands is fast and has been indistinguishable from the reduction processes when aromatic ligands are also present in the complex. However, for diamine chelates and diimine chelates spectra of the transient species can be resolved

  15. Ligand design for riboswitches, an emerging target class for novel antibiotics.

    Science.gov (United States)

    Rekand, Illimar Hugo; Brenk, Ruth

    2017-09-01

    Riboswitches are cis-acting gene regulatory elements and constitute potential targets for new antibiotics. Recent studies in this field have started to explore these targets for drug discovery. New ligands found by fragment screening, design of analogs of the natural ligands or serendipitously by phenotypic screening have shown antibacterial effects in cell assays against a range of bacteria strains and in animal models. In this review, we highlight the most advanced drug design work of riboswitch ligands and discuss the challenges in the field with respect to the development of antibiotics with a new mechanism of action.

  16. Constitutive and ligand-induced TCR degradation

    DEFF Research Database (Denmark)

    von Essen, Marina; Bonefeld, Charlotte Menné; Siersma, Volkert

    2004-01-01

    Modulation of TCR expression levels is a central event during T cell development and activation, and it probably plays an important role in adjusting T cell responsiveness. Conflicting data have been published on down-regulation and degradation rates of the individual TCR subunits, and several di...... to the lysosomes. Similar results were obtained in studies of primary human Vbeta8+ T cells stimulated with superantigen. Based on these results, the simplest model for TCR internalization, sorting, and degradation is proposed.......Modulation of TCR expression levels is a central event during T cell development and activation, and it probably plays an important role in adjusting T cell responsiveness. Conflicting data have been published on down-regulation and degradation rates of the individual TCR subunits, and several...... divergent models for TCR down-regulation and degradation have been suggested. The aims of this study were to determine the rate constants for constitutive and ligand-induced TCR degradation and to determine whether the TCR subunits segregate or are processed as an intact unit during TCR down...

  17. Investigation of road salts and biotic stressors on freshwater wetland communities.

    Science.gov (United States)

    Jones, Devin K; Mattes, Brian M; Hintz, William D; Schuler, Matthew S; Stoler, Aaron B; Lind, Lovisa A; Cooper, Reilly O; Relyea, Rick A

    2017-02-01

    The application of road deicing salts has led to the salinization of freshwater ecosystems in northern regions worldwide. Increased chloride concentrations in lakes, streams, ponds, and wetlands may negatively affect freshwater biota, potentially threatening ecosystem services. In an effort to reduce the effects of road salt, operators have increased the use of salt alternatives, yet we lack an understanding of how these deicers affect aquatic communities. We examined the direct and indirect effects of the most commonly used road salt (NaCl) and a proprietary salt mixture (NaCl, KCl, MgCl 2 ), at three environmentally relevant concentrations (150, 470, and 780 mg Cl - /L) on freshwater wetland communities in combination with one of three biotic stressors (control, predator cues, and competitors). The communities contained periphyton, phytoplankton, zooplankton, and two tadpole species (American toads, Anaxyrus americanus; wood frogs, Lithobates sylvaticus). Overall, we found the two road salts did not interact with the natural stressors. Both salts decreased pH and reduced zooplankton abundance. The strong decrease in zooplankton abundance in the highest NaCl concentration caused a trophic cascade that resulted in increased phytoplankton abundance. The highest NaCl concentration also reduced toad activity. For the biotic stressors, predatory stress decreased whereas competitive stress increased the activity of both tadpole species. Wood frog survival, time to metamorphosis, and mass at metamorphosis all decreased under competitive stress whereas toad time to metamorphosis increased and mass at metamorphosis decreased. Road salts and biotic stressors can both affect freshwater communities, but their effects are not interactive. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Biotic potential and reproductive parameters of Spodoptera eridania (Stoll (Lepidoptera, Noctuidae in the laboratory

    Directory of Open Access Journals (Sweden)

    Débora Goulart Montezano

    2013-09-01

    Full Text Available Biotic potential and reprodutcive parameters of Spodoptera eridania (Stoll (Lepidoptera, Noctuidae in the laboratory: This study aimed to evaluate the biotic potential and reproductive parameters of Spodoptera eridania (Stoll, 1782 under controlled conditions (25 ± 1ºC, 70 ± 10% RH and 14 hour photophase. The longevity, pre-, post- and oviposition periods, fecundity and fertility of 15 couples was evaluated. The longevity of females (10.80 days was not significantly higher than those of males (9.27 days. The mean durations of the pre, post and oviposition periods were 2.067, 0.600 and 8.133 days, respectively. The mean fecundity per female was 1,398 eggs and the mean fertility was 1,367.50 larvae. On average, females copulated 1.133 times. A strong positive correlation was observed between the number of mating and fecundity (r = 0.881, P <0.001. However a strong negative correlation was observed between the number of copulations and the duration of the pre-oviposition period (r = -0.826, P = 0.002 and longevity (r = -0.823, P = 0.001. The biotic potential of S. eridania was estimated at 1.894 x 10(25 individuals/female/year. The net reproductive rate (Ro was 560.531 times per generation and the mean generation time (T was 35.807 days. The intrinsic rate of increase (rm was 0.177, with a finite rate of increase (l of 1.193, per week

  19. Protein-Ligand Empirical Interaction Components for Virtual Screening.

    Science.gov (United States)

    Yan, Yuna; Wang, Weijun; Sun, Zhaoxi; Zhang, John Z H; Ji, Changge

    2017-08-28

    A major shortcoming of empirical scoring functions is that they often fail to predict binding affinity properly. Removing false positives of docking results is one of the most challenging works in structure-based virtual screening. Postdocking filters, making use of all kinds of experimental structure and activity information, may help in solving the issue. We describe a new method based on detailed protein-ligand interaction decomposition and machine learning. Protein-ligand empirical interaction components (PLEIC) are used as descriptors for support vector machine learning to develop a classification model (PLEIC-SVM) to discriminate false positives from true positives. Experimentally derived activity information is used for model training. An extensive benchmark study on 36 diverse data sets from the DUD-E database has been performed to evaluate the performance of the new method. The results show that the new method performs much better than standard empirical scoring functions in structure-based virtual screening. The trained PLEIC-SVM model is able to capture important interaction patterns between ligand and protein residues for one specific target, which is helpful in discarding false positives in postdocking filtering.

  20. Spatially dependent biotic and abiotic factors drive survivorship and physical structure of green roof vegetation.

    Science.gov (United States)

    Aloisio, Jason M; Palmer, Matthew I; Giampieri, Mario A; Tuininga, Amy R; Lewis, James D

    2017-01-01

    Plant survivorship depends on biotic and abiotic factors that vary at local and regional scales. This survivorship, in turn, has cascading effects on community composition and the physical structure of vegetation. Survivorship of native plant species is variable among populations planted in environmentally stressful habitats like urban roofs, but the degree to which factors at different spatial scales affect survivorship in urban systems is not well understood. We evaluated the effects of biotic and abiotic factors on survivorship, composition, and physical structure of two native perennial species assemblages, one characterized by a mixture of C 4 grasses and forbs (Hempstead Plains, HP) and one characterized by a mixture of C 3 grasses and forbs (Rocky Summit, RS), that were initially sown at equal ratios of growth forms (5:1:4; grass, N-fixing forb and non-N-fixing forb) in replicate 2-m 2 plots planted on 10 roofs in New York City (New York, USA). Of 24 000 installed plants, 40% survived 23 months after planting. Within-roof factors explained 71% of variation in survivorship, with biotic (species identity and assemblage) factors accounting for 54% of the overall variation, and abiotic (growing medium depth and plot location) factors explaining 17% of the variation. Among-roof factors explained 29% of variation in survivorship and increased solar radiation correlated with decreased survivorship. While growing medium properties (pH, nutrients, metals) differed among roofs there was no correlation with survivorship. Percent cover and sward height increased with increasing survivorship. At low survivorship, cover of the HP assemblage was greater compared to the RS assemblage. Sward height of the HP assemblage was about two times greater compared to the RS assemblage. These results highlight the effects of local biotic and regional abiotic drivers on community composition and physical structure of green roof vegetation. As a result, initial green roof plant

  1. Carbon trading and carbon taxation: how to consider biotic sources and sinks

    International Nuclear Information System (INIS)

    Madlener, Reinhard; Schlamadinger, Bernhard

    1999-01-01

    The Kyoto Protocol (KP) to the UNFCCC includes land-use change and forestry in the carbon accounting process, limited to afforestation, reforestation and deforestation since 1990, and explicitly provides for the option of using a variety of flexibility mechanisms to meet the greenhouse gas (GHG) reduction targets stipulated in a more cost-efficient manner. Domestically, different countries might adopt different approaches to achieve their emission reduction objectives, such as carbon trading or carbon taxation, and it is not clear to date what the implications for bioenergy use, forestry, and land-use change can be expected to be. With respect to national GHG emissions trading, the main issues studied in this paper are: Should trading of fossil fuel emissions allowances be coupled with trading of biotic credits and debits? Should credits for carbon sequestration in forests be auctioned or grandfathered? Should there be a distinction between a carbon permit issued for an additional biotic sink and those issued for fossil fuel carbon emissions? Is there a difference for biotic carbon sinks and sources between one-time permits and permits that allow a continued release of GHG over some pre-specified time? Should permits be issued only for the carbon-stock changes that count under the KP? With respect to national carbon taxation schemes, two questions are investigated: Should a tax credit be given for afforestation/reforestation (and a tax debit for deforestation)? Should tax credits also be given for projects that sequester carbon but do not count under the KP (such as forest protection rather than forest management)? For both schemes a crucial point is that by the formulation chosen in the KP two different classes of forest are created (i.e. those counted and those not counted under the KP), so that the implications for land prices might be significant. From a conceptual point of view this paper addresses the above-mentioned questions and contrasts some of the major

  2. The role of biotic interactions in plant community assembly: What is the community species pool?

    Science.gov (United States)

    Švamberková, Eva; Vítová, Alena; Lepš, Jan

    2017-11-01

    Differences in plant species composition between a community and its species pool are considered to reflect the effect of community filters. If we define the species pool as a set of species able to reach a site and form a viable population in a given abiotic environment (i.e. to pass the dispersal and abiotic filter), the difference in species composition should correspond to the effect of biotic interactions. However, most of the operational definitions of the species pool are based on co-occurrence patterns and thus also reflect the effect of biotic relationships, including definitions based on functional plant traits, Ellenberg indicator values or Beals index. We conducted two seed introduction experiments in an oligotrophic wet meadow with the aim of demonstrating that many species excluded, according to the above definitions, from a species pool are in fact able to establish there successfully if competition is removed. In sowing experiments, we studied the establishment and survival of species after the removal of competition (i.e. in artificial gaps) and in intact vegetation. We also investigated inter-annual variability of seed germination and seedling establishment and competitive exclusion of sown species. The investigated species also included those from very different habitats (i.e. species with very low corresponding Beals index or Ellenberg indicator values that were different from the target community weighted mean). Many of these species were able to grow in the focal wet meadow if competition was removed, but they did not establish and survive in the intact community. These species are thus not limited by abiotic conditions, but by the biotic filter. We also recorded a great inter-annual variability in seed germination and seedling establishment. Competitive exclusion of species with different ecological requirements could be quite fast (one and half seasons) in some species, but some non-resident species were able to survive several seasons; the

  3. Sampling and energy evaluation challenges in ligand binding protein design.

    Science.gov (United States)

    Dou, Jiayi; Doyle, Lindsey; Jr Greisen, Per; Schena, Alberto; Park, Hahnbeom; Johnsson, Kai; Stoddard, Barry L; Baker, David

    2017-12-01

    The steroid hormone 17α-hydroxylprogesterone (17-OHP) is a biomarker for congenital adrenal hyperplasia and hence there is considerable interest in development of sensors for this compound. We used computational protein design to generate protein models with binding sites for 17-OHP containing an extended, nonpolar, shape-complementary binding pocket for the four-ring core of the compound, and hydrogen bonding residues at the base of the pocket to interact with carbonyl and hydroxyl groups at the more polar end of the ligand. Eight of 16 designed proteins experimentally tested bind 17-OHP with micromolar affinity. A co-crystal structure of one of the designs revealed that 17-OHP is rotated 180° around a pseudo-two-fold axis in the compound and displays multiple binding modes within the pocket, while still interacting with all of the designed residues in the engineered site. Subsequent rounds of mutagenesis and binding selection improved the ligand affinity to nanomolar range, while appearing to constrain the ligand to a single bound conformation that maintains the same "flipped" orientation relative to the original design. We trace the discrepancy in the design calculations to two sources: first, a failure to model subtle backbone changes which alter the distribution of sidechain rotameric states and second, an underestimation of the energetic cost of desolvating the carbonyl and hydroxyl groups of the ligand. The difference between design model and crystal structure thus arises from both sampling limitations and energy function inaccuracies that are exacerbated by the near two-fold symmetry of the molecule. © 2017 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.

  4. Multiscale simulations of ligand adsorption and exchange on gold nanoparticles.

    Science.gov (United States)

    Gao, Hui-Min; Liu, Hong; Qian, Hu-Jun; Jiao, Gui-Sheng; Lu, Zhong-Yuan

    2018-01-17

    We have developed a multiscale model that combines first-principles methods with atomistic and mesoscopic simulations to explore the molecular structures and packing density of the ligands present on the gold nanoparticle (AuNP) surface, as well as the adsorption/exchange reaction kinetics of cetyltrimethylammonium bromide (CTAB)/PEG-SH ligands on different facets of gold, namely, Au(111), Au(100), and Au(110). Our model predicts that on clean gold surfaces, CTAB adsorption is diffusion limited. Specifically, CTAB has the preferentially higher adsorption rate and coverage density on Au(100) and Au(110) surfaces, forming a more compact layer with respect to that on the Au(111) surface, which could result in greater growth of gold nanoparticles along the (111) direction. As opposed to CTAB adsorption, the exchange reaction between PEG-SH with CTAB shows no selectivity to different crystal faces, and the reaction process follows Langmuir diffusion kinetics. Kinetic analysis reveals that, in water, the exchange reaction is zeroth order with respect to the concentration of an incoming PEG-SH, indicative of a dissociative exchange mechanism. The observed rate constant decreases exponentially with the PEG-SH chain length, consistent with a diffusion process for the free PEG-SH in water. In particular, we show that the exchange efficiency increases as the chain rigidness and size of the incoming ligand and/or steric bulk of the initial protecting ligand shell are decreased. Our objectives are to provide a model to assess the kinetics and thermodynamics of the adsorption/exchange reaction process, and we expect that these findings will have important implications for routine surface characterization of AuNPs.

  5. Combined effects of Corexit EC 9500A with secondary abiotic and biotic factors in the rotifer Brachionus plicatilis.

    Science.gov (United States)

    Williams, Michael B; Powell, Mickie L; Watts, Stephen A

    2016-10-01

    We examined lethality and behavioral effects of Corexit EC 9500A (C-9500A) exposure on the model marine zooplankton Brachionus plicatilis singularly and in combination with abiotic and biotic factors. C-9500A exposure at standard husbandry conditions (17.5ppt, 24°C, 200 rotifer*mL(-1) density) identified the 24h median lethal concentration, by Probit analysis, to be 107ppm for cultured B. plicatilis. Rotifers surviving exposure to higher concentrations (100 and 150ppm) exhibited a decreased swimming velocity and a reduced net to gross movement ratio. Significant interaction between C-9500A exposure and temperature or salinity was observed. Upper thermal range was reduced and maximal salinity stress was seen as ca. 25ppt. Increased or decreased nutritional availability over the exposure period did not significantly alter mortality of B. plicatilis populations at the concentrations tested. Results from this study may be useful for predicting possible outcomes on marine zooplankton following dispersant application under diverse natural conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Synthesis and characterization β-ketoamine ligands

    Science.gov (United States)

    Zaid, Nurzati Amani Mohamed; Hassan, Nur Hasyareeda; Karim, Nurul Huda Abd

    2018-04-01

    β-ketoamine ligands are important members of heterodonor ligand because of their ease of preparation and modification of both steric and/or electronic effects. Complexes with β-ketoamine has received much less attention and there has been no study about this complex with β-ketoamine in ionic liquid reported. Two type of β-ketoamine ligands which are 4-amino-3-pentene-2-onato (A) and 3-amino-2-butenoic acid methyl ester (B) have been synthesized in this work. The resulting compound formed was characterized using standard spectroscopic and structural techniques which includes 1H and 13C, NMR spectroscopy and FTIR spectroscopy. The 1H and 13C NMR spectrum displayed all the expected signals with correct integration and multiplicity. And it is proved that there are some differences between two ligands as observed in NMR and FTIR spectrum.

  7. EGFR Activation by Spatially Restricted Ligands

    National Research Council Canada - National Science Library

    Clouse, Katherine N; Goodrich, Jennifer S

    2006-01-01

    ...) activity has been associated with an increased prognosis of breast cancer. During cogenesis in Drosophila melanogaster local Egfr activation by the spatially-restricted TGFalpha-like ligand Gurken (Grk...

  8. EGFR Activation by Spatially Restricted Ligands

    National Research Council Canada - National Science Library

    Goodrich, Jennifer S

    2005-01-01

    ...) activity has been associated with an increased prognosis of breast cancer. During oogenesis in Drosophila melanogaster, local EGFR activation by the spatially restricted TGF alpha-like ligand, Gurken (Grk...

  9. High-affinity multivalent wheat germ agglutinin ligands by one-pot click reaction

    Directory of Open Access Journals (Sweden)

    Henning S. G. Beckmann

    2012-06-01

    Full Text Available A series of six mono-, di-, and trivalent N,N’-diacetylchitobiose derivatives was conveniently prepared by employing a one-pot procedure for Cu(II-catalyzed diazo transfer and Cu(I-catalyzed azide–alkyne cycloaddition (CuAAC starting from commercially available amines. These glycoclusters were probed for their binding potencies to the plant lectin wheat germ agglutinin (WGA from Triticum vulgaris by an enzyme-linked lectin assay (ELLA employing covalently immobilized N-acetylglucosamine (GlcNAc as a reference ligand. IC50 values were in the low micromolar/high nanomolar range, depending on the linker between the two disaccharides. Binding enhancements β up to 1000 for the divalent ligands and 2800 for a trivalent WGA ligand, compared to N,N’-diacetylchitobiose as the corresponding monovalent ligand, were observed. Molecular modeling studies, in which the chitobiose moieties were fitted into crystallographically determined binding sites of WGA, correlate the binding enhancements of the multivalent ligands with their ability to bind to the protein in a chelating mode. The best WGA ligand is a trivalent cluster with an IC50 value of 220 nM. Calculated per mol of contained chitobiose, this is the best WGA ligand known so far.

  10. Automatic generation of bioinformatics tools for predicting protein-ligand binding sites.

    Science.gov (United States)

    Komiyama, Yusuke; Banno, Masaki; Ueki, Kokoro; Saad, Gul; Shimizu, Kentaro

    2016-03-15

    Predictive tools that model protein-ligand binding on demand are needed to promote ligand research in an innovative drug-design environment. However, it takes considerable time and effort to develop predictive tools that can be applied to individual ligands. An automated production pipeline that can rapidly and efficiently develop user-friendly protein-ligand binding predictive tools would be useful. We developed a system for automatically generating protein-ligand binding predictions. Implementation of this system in a pipeline of Semantic Web technique-based web tools will allow users to specify a ligand and receive the tool within 0.5-1 day. We demonstrated high prediction accuracy for three machine learning algorithms and eight ligands. The source code and web application are freely available for download at http://utprot.net They are implemented in Python and supported on Linux. shimizu@bi.a.u-tokyo.ac.jp Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

  11. Physics-based scoring of protein-ligand interactions: explicit polarizability, quantum mechanics and free energies.

    Science.gov (United States)

    Bryce, Richard A

    2011-04-01

    The ability to accurately predict the interaction of a ligand with its receptor is a key limitation in computer-aided drug design approaches such as virtual screening and de novo design. In this article, we examine current strategies for a physics-based approach to scoring of protein-ligand affinity, as well as outlining recent developments in force fields and quantum chemical techniques. We also consider advances in the development and application of simulation-based free energy methods to study protein-ligand interactions. Fuelled by recent advances in computational algorithms and hardware, there is the opportunity for increased integration of physics-based scoring approaches at earlier stages in computationally guided drug discovery. Specifically, we envisage increased use of implicit solvent models and simulation-based scoring methods as tools for computing the affinities of large virtual ligand libraries. Approaches based on end point simulations and reference potentials allow the application of more advanced potential energy functions to prediction of protein-ligand binding affinities. Comprehensive evaluation of polarizable force fields and quantum mechanical (QM)/molecular mechanical and QM methods in scoring of protein-ligand interactions is required, particularly in their ability to address challenging targets such as metalloproteins and other proteins that make highly polar interactions. Finally, we anticipate increasingly quantitative free energy perturbation and thermodynamic integration methods that are practical for optimization of hits obtained from screened ligand libraries.

  12. Single-molecule photobleaching reveals increased MET receptor dimerization upon ligand binding in intact cells

    International Nuclear Information System (INIS)

    Dietz, Marina S; Haße, Daniel; Ferraris, Davide M; Göhler, Antonia; Niemann, Hartmut H; Heilemann, Mike

    2013-01-01

    The human receptor tyrosine kinase MET and its ligand hepatocyte growth factor/scatter factor are essential during embryonic development and play an important role during cancer metastasis and tissue regeneration. In addition, it was found that MET is also relevant for infectious diseases and is the target of different bacteria, amongst them Listeria monocytogenes that induces bacterial uptake through the surface protein internalin B. Binding of ligand to the MET receptor is proposed to lead to receptor dimerization. However, it is also discussed whether preformed MET dimers exist on the cell membrane. To address these issues we used single-molecule fluorescence microscopy techniques. Our photobleaching experiments show that MET exists in dimers on the membrane of cells in the absence of ligand and that the proportion of MET dimers increases significantly upon ligand binding. Our results indicate that partially preformed MET dimers may play a role in ligand binding or MET signaling. The addition of the bacterial ligand internalin B leads to an increase of MET dimers which is in agreement with the model of ligand-induced dimerization of receptor tyrosine kinases.

  13. Evaluation of Docking Target Functions by the Comprehensive Investigation of Protein-Ligand Energy Minima.

    Science.gov (United States)

    Oferkin, Igor V; Katkova, Ekaterina V; Sulimov, Alexey V; Kutov, Danil C; Sobolev, Sergey I; Voevodin, Vladimir V; Sulimov, Vladimir B

    2015-01-01

    The adequate choice of the docking target function impacts the accuracy of the ligand positioning as well as the accuracy of the protein-ligand binding energy calculation. To evaluate a docking target function we compared positions of its minima with the experimentally known pose of the ligand in the protein active site. We evaluated five docking target functions based on either the MMFF94 force field or the PM7 quantum-chemical method with or without implicit solvent models: PCM, COSMO, and SGB. Each function was tested on the same set of 16 protein-ligand complexes. For exhaustive low-energy minima search the novel MPI parallelized docking program FLM and large supercomputer resources were used. Protein-ligand binding energies calculated using low-energy minima were compared with experimental values. It was demonstrated that the docking target function on the base of the MMFF94 force field in vacuo can be used for discovery of native or near native ligand positions by finding the low-energy local minima spectrum of the target function. The importance of solute-solvent interaction for the correct ligand positioning is demonstrated. It is shown that docking accuracy can be improved by replacement of the MMFF94 force field by the new semiempirical quantum-chemical PM7 method.

  14. Evaluation of Docking Target Functions by the Comprehensive Investigation of Protein-Ligand Energy Minima

    Directory of Open Access Journals (Sweden)

    Igor V. Oferkin

    2015-01-01

    Full Text Available The adequate choice of the docking target function impacts the accuracy of the ligand positioning as well as the accuracy of the protein-ligand binding energy calculation. To evaluate a docking target function we compared positions of its minima with the experimentally known pose of the ligand in the protein active site. We evaluated five docking target functions based on either the MMFF94 force field or the PM7 quantum-chemical method with or without implicit solvent models: PCM, COSMO, and SGB. Each function was tested on the same set of 16 protein-ligand complexes. For exhaustive low-energy minima search the novel MPI parallelized docking program FLM and large supercomputer resources were used. Protein-ligand binding energies calculated using low-energy minima were compared with experimental values. It was demonstrated that the docking target function on the base of the MMFF94 force field in vacuo can be used for discovery of native or near native ligand positions by finding the low-energy local minima spectrum of the target function. The importance of solute-solvent interaction for the correct ligand positioning is demonstrated. It is shown that docking accuracy can be improved by replacement of the MMFF94 force field by the new semiempirical quantum-chemical PM7 method.

  15. AMMOS2: a web server for protein-ligand-water complexes refinement via molecular mechanics.

    Science.gov (United States)

    Labbé, Céline M; Pencheva, Tania; Jereva, Dessislava; Desvillechabrol, Dimitri; Becot, Jérôme; Villoutreix, Bruno O; Pajeva, Ilza; Miteva, Maria A

    2017-07-03

    AMMOS2 is an interactive web server for efficient computational refinement of protein-small organic molecule complexes. The AMMOS2 protocol employs atomic-level energy minimization of a large number of experimental or modeled protein-ligand complexes. The web server is based on the previously developed standalone software AMMOS (Automatic Molecular Mechanics Optimization for in silico Screening). AMMOS utilizes the physics-based force field AMMP sp4 and performs optimization of protein-ligand interactions at five levels of flexibility of the protein receptor. The new version 2 of AMMOS implemented in the AMMOS2 web server allows the users to include explicit water molecules and individual metal ions in the protein-ligand complexes during minimization. The web server provides comprehensive analysis of computed energies and interactive visualization of refined protein-ligand complexes. The ligands are ranked by the minimized binding energies allowing the users to perform additional analysis for drug discovery or chemical biology projects. The web server has been extensively tested on 21 diverse protein-ligand complexes. AMMOS2 minimization shows consistent improvement over the initial complex structures in terms of minimized protein-ligand binding energies and water positions optimization. The AMMOS2 web server is freely available without any registration requirement at the URL: http://drugmod.rpbs.univ-paris-diderot.fr/ammosHome.php. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  16. Preclinical Testing of a Translocator Protein Ligand for the Treatment of Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    2017-03-01

    investigated the neuroprotective effect and therapeutic value of a drug : the translocator protein (TSPO) ligand PK11195 (PK), which we found to be...Translocator protein (TSPO) ligand Neuroprotective drugs In vitro models of neurodegeneration Axon preservation Neuromuscular junctions 5 3...pharmacokinetic data of the JNK study were showing that daily gavage (30 mg/kg/day) allowed an efficient delivery of the drugs in the brain and the spinal

  17. Evolution of ligand specificity in vertebrate corticosteroid receptors

    Directory of Open Access Journals (Sweden)

    Deitcher David L

    2011-01-01

    Full Text Available Abstract Background Corticosteroid receptors include mineralocorticoid (MR and glucocorticoid (GR receptors. Teleost fishes have a single MR and duplicate GRs that show variable sensitivities to mineralocorticoids and glucocorticoids. How these receptors compare functionally to tetrapod MR and GR, and the evolutionary significance of maintaining two GRs, remains unclear. Results We used up to seven steroids (including aldosterone, cortisol and 11-deoxycorticosterone [DOC] to compare the ligand specificity of the ligand binding domains of corticosteroid receptors between a mammal (Mus musculus and the midshipman fish (Porichthys notatus, a teleost model for steroid regulation of neural and behavioral plasticity. Variation in mineralocorticoid sensitivity was considered in a broader phylogenetic context by examining the aldosterone sensitivity of MR and GRs from the distantly related daffodil cichlid (Neolamprologus pulcher, another teleost model for neurobehavioral plasticity. Both teleost species had a single MR and duplicate GRs. All MRs were sensitive to DOC, consistent with the hypothesis that DOC was the initial ligand of the ancestral MR. Variation in GR steroid-specificity corresponds to nine identified amino acid residue substitutions rather than phylogenetic relationships based on receptor sequences. Conclusion The mineralocorticoid sensitivity of duplicate GRs in teleosts is highly labile in the context of their evolutionary phylogeny, a property that likely led to neo-functionalization and maintenance of two GRs.

  18. Semiconductor Quantum Dots with Photoresponsive Ligands.

    Science.gov (United States)

    Sansalone, Lorenzo; Tang, Sicheng; Zhang, Yang; Thapaliya, Ek Raj; Raymo, Françisco M; Garcia-Amorós, Jaume

    2016-10-01

    Photochromic or photocaged ligands can be anchored to the outer shell of semiconductor quantum dots in order to control the photophysical properties of these inorganic nanocrystals with optical stimulations. One of the two interconvertible states of the photoresponsive ligands can be designed to accept either an electron or energy from the excited quantum dots and quench their luminescence. Under these conditions, the reversible transformations of photochromic ligands or the irreversible cleavage of photocaged counterparts translates into the possibility to switch luminescence with external control. As an alternative to regulating the photophysics of a quantum dot via the photochemistry of its ligands, the photochemistry of the latter can be controlled by relying on the photophysics of the former. The transfer of excitation energy from a quantum dot to a photocaged ligand populates the excited state of the species adsorbed on the nanocrystal to induce a photochemical reaction. This mechanism, in conjunction with the large two-photon absorption cross section of quantum dots, can be exploited to release nitric oxide or to generate singlet oxygen under near-infrared irradiation. Thus, the combination of semiconductor quantum dots and photoresponsive ligands offers the opportunity to assemble nanostructured constructs with specific functions on the basis of electron or energy transfer processes. The photoswitchable luminescence and ability to photoinduce the release of reactive chemicals, associated with the resulting systems, can be particularly valuable in biomedical research and can, ultimately, lead to the realization of imaging probes for diagnostic applications as well as to therapeutic agents for the treatment of cancer.

  19. Designer TGFβ superfamily ligands with diversified functionality.

    Directory of Open Access Journals (Sweden)

    George P Allendorph

    Full Text Available Transforming Growth Factor--beta (TGFβ superfamily ligands, including Activins, Growth and Differentiation Factors (GDFs, and Bone Morphogenetic Proteins (BMPs, are excellent targets for protein-based therapeutics because of their pervasiveness in numerous developmental and cellular processes. We developed a strategy termed RASCH (Random Assembly of Segmental Chimera and Heteromer, to engineer chemically-refoldable TGFβ superfamily ligands with unique signaling properties. One of these engineered ligands, AB208, created from Activin-βA and BMP-2 sequences, exhibits the refolding characteristics of BMP-2 while possessing Activin-like signaling attributes. Further, we find several additional ligands, AB204, AB211, and AB215, which initiate the intracellular Smad1-mediated signaling pathways more strongly than BMP-2 but show no sensitivity to the natural BMP antagonist Noggin unlike natural BMP-2. In another design, incorporation of a short N-terminal segment from BMP-2 was sufficient to enable chemical refolding of BMP-9, without which was never produced nor refolded. Our studies show that the RASCH strategy enables us to expand the functional repertoire of TGFβ superfamily ligands through development of novel chimeric TGFβ ligands with diverse biological and clinical values.

  20. LigandRFs: random forest ensemble to identify ligand-binding residues from sequence information alone

    KAUST Repository

    Chen, Peng

    2014-12-03

    Background Protein-ligand binding is important for some proteins to perform their functions. Protein-ligand binding sites are the residues of proteins that physically bind to ligands. Despite of the recent advances in computational prediction for protein-ligand binding sites, the state-of-the-art methods search for similar, known structures of the query and predict the binding sites based on the solved structures. However, such structural information is not commonly available. Results In this paper, we propose a sequence-based approach to identify protein-ligand binding residues. We propose a combination technique to reduce the effects of different sliding residue windows in the process of encoding input feature vectors. Moreover, due to the highly imbalanced samples between the ligand-binding sites and non ligand-binding sites, we construct several balanced data sets, for each of which a random forest (RF)-based classifier is trained. The ensemble of these RF classifiers forms a sequence-based protein-ligand binding site predictor. Conclusions Experimental results on CASP9 and CASP8 data sets demonstrate that our method compares favorably with the state-of-the-art protein-ligand binding site prediction methods.

  1. A biotic video game smart phone kit for formal and informal biophysics education

    Science.gov (United States)

    Kim, Honesty; Lee, Seung Ah; Riedel-Kruse, Ingmar

    2015-03-01

    Novel ways for formal and informal biophysics education are important. We present a low-cost biotic game design kit that incorporates microbial organisms into an interactive gaming experience: A 3D-printable microscope containing four LEDs controlled by a joystick enable human players to provide directional light stimuli to the motile single-celled organism Euglena gracilis. These cellular behaviors are displayed on the integrated smart phone. Real time cell-tracking couples these cells into interactive biotic video game play, i.e., the human player steers Euglena to play soccer with virtual balls and goals. The player's learning curve in mastering this fun game is intrinsically coupled to develop a deeper knowledge about Euglena's cell morphology and the biophysics of its phototactic behavior. This kit is dual educational - via construction and via play - and it provides an engaging theme for a formal biophysics devices class as well as to be presented in informal outreach activities; its low cost and open soft- and hardware should enable wide adoption.

  2. Alcohol dehydrogenase 1 (ADH1) confers both abiotic and biotic stress resistance in Arabidopsis.

    Science.gov (United States)

    Shi, Haitao; Liu, Wen; Yao, Yue; Wei, Yunxie; Chan, Zhulong

    2017-09-01

    Although the transcriptional regulation and upstream transcription factors of AtADH1 in response to abiotic stress are widely revealed, the in vivo roles of AtADH1 remain unknown. In this study, we found that the expression of AtADH1 was largely induced after salt, drought, cold and pathogen infection. Further studies found that AtADH1 overexpressing plants were more sensitive to abscisic acid (ABA) in comparison to wide type (WT), while AtADH1 knockout mutants showed no significant difference compared with WT in ABA sensitivity. Consistently, AtADH1 overexpressing plants showed improved stress resistance to salt, drought, cold and pathogen infection than WT, but the AtADH1 knockout mutants had no significant difference in abiotic and biotic stress resistance. Moreover, overexpression of AtADH1 expression increased the transcript levels of multiple stress-related genes, accumulation of soluble sugars and callose depositions. All these results indicate that AtADH1 confers enhanced resistance to both abiotic and biotic stresses. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. A new full-field interferometry approach for counting and differentiating aquatic biotic nanoparticles (Conference Presentation)

    Science.gov (United States)

    Boccara, A. Claude; Fedala, Yasmina; Voronkoff, Justine; Paffoni, Nina; Boccara, Martine

    2017-03-01

    Due to the huge abundance and the major role that viruses and membrane vesicles play in the seas or rivers ecosystems it is necessary to develop simple, sensitive, compact and reliable methods for their detection and characterization. Our approach is based on the measurement of the weak light level scattered by the biotic nanoparticles. We describe a new full-field, incoherently illuminated, shot-noise limited, common-path interferometric detection method coupled with the analysis of Brownian motion to detect, quantify, and differentiate biotic nanoparticles. The last developments take advantage of a new fast (700 Hz) camera with 2 Me- full well capacity that improves the signal to noise ratio and increases the precision of the Brownian motion characterization. We validated the method with calibrated nanoparticles and homogeneous DNA or RNA.viruses. The smallest virus size that we characterized with a suitable signal-to-noise ratio was around 30 nm in diameter with a target towards the numerous 20 nm diameter viruses. We show for the first time anisotropic trajectories for myoviruses meaning that there is a memory of the initial direction of their Brownian motions. Significant improvements have been made in the handling of the sample as well as in the statistical analysis for differentiating the various families of vesicles and virus. We further applied the method for vesicles detection and for analysis of coastal and oligotrophic samples from Tara Oceans circumnavigation as well of various rivers.

  4. Trichoderma species mediated differential tolerance against biotic stress of phytopathogens in Cicer arietinum L.

    Science.gov (United States)

    Saxena, Amrita; Raghuwanshi, Richa; Singh, Harikesh Bahadur

    2015-02-01

    Trichoderma spp. have been reported to aid in imparting biotic as well as abiotic tolerance to plants. However, there are only few reports unfolding the differential ability of separate species of Trichoderma genera generally exploited for their biocontrol potential in this framework. A study was undertaken to evaluate the biocontrol potential of different Trichoderma species namely T. harzianum, T. asperellum, T. koningiopsis, T. longibrachiatum, and T. aureoviride as identified in the group of indigenous isolates from the agricultural soils of Eastern Uttar Pradesh, India. Their biocontrol potential against three major soilborne phytopathogens, i.e., Sclerotium rolfsii, Sclerotinia sclerotiorum, and Colletotrichum capsici was confirmed by dual culture plate technique. Efficient mycoparasitic ability was further assessed in all the isolates in relation to chitinase, β-1,3 glucanase, pectinase, lipase, amylase, and cellulase production while equally consistent results were obtained for their probable phosphate solubilization and indole acetic acid (IAA) production abilities. The selected isolates were further subjected to test their ability to promote plant growth, to reduce disease incidence and to tolerate biotic stress in terms of lignification pattern against S. rolfsii in chickpea plants. Among the identified Trichoderma species, excellent results were observed for T. harzianum and T. koningiopsis indicating better biocontrol potential of these species in the group and thus exhibiting perspective for their commercial exploitation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Using fish communities to assess streams in Romania: Initial development of an index of biotic integrity

    Science.gov (United States)

    Angermeier, P.L.; Davideanu, G.

    2004-01-01

    Multimetric biotic indices increasingly are used to complement physicochemical data in assessments of stream quality. We initiated development of multimetric indices, based on fish communities, to assess biotic integrity of streams in two physiographic regions of central Romania. Unlike previous efforts to develop such indices for European streams, our metrics and scoring criteria were selected largely on the basis of empirical relations in the regions of interest. We categorised 54 fish species with respect to ten natural-history attributes, then used this information to compute 32 candidate metrics of five types (taxonomic, tolerance, abundance, reproductive, and feeding) for each of 35 sites. We assessed the utility of candidate metrics for detecting anthropogenic impact based on three criteria: (a) range of values taken, (b) relation to a site-quality index (SQI), which incorporated information on hydrologic alteration, channel alteration, land-use intensity, and water chemistry, and (c) metric redundancy. We chose seven metrics from each region to include in preliminary multimetric indices (PMIs). Both PMIs included taxonomic, tolerance, and feeding metrics, but only two metrics were common to both PMIs. Although we could not validate our PMIs, their strong association with the SQI in each region suggests that such indices would be valuable tools for assessing stream quality and could provide more comprehensive assessments than the traditional approaches based solely on water chemistry.

  6. Interactive Biophysics with Microswimmers: Education, Cloud Experimentation, Programmed Swarms, and Biotic Games

    Science.gov (United States)

    Riedel-Kruse, Ingmar

    Modern biotechnology gets increasingly powerful to manipulate and measure microscopic biophysical processes. Nevertheless, no platform exists to truly interact with these processes, certainly not with the convenience that we are accustomed to from our electronic smart devices. In my talk I will provide the rational for such Interactive Biotechnology and conceptualize its core component, the BPU (biotic processing unit), which is then connected to an according user interface. The biophysical phenomena currently featured on these platforms utilize the phototactic response of motile microorganisms, e.g., Euglena gracilis, resulting in spatio-temporal dynamics from the single cell to the self-organized multi-cellular scale. I will demonstrate multiple platforms, such as scalable biology cloud experimentation labs, tangible museum exhibits, biotic video games, low-cost interactive DIY kits using smartphones, and programming languages for swarm robotics. I will discuss applications for education as well as for professional and citizen science. Hence, we turn traditionally observational microscopy into an interactive experience. I was told that presenting in the educational section does not count against the ''one author - one talk policy'' - so I submit two abstracts. In case of conflict - please contact me: ingmar@stanford.edu.

  7. Overexpression of a Pathogenesis-Related Protein 10 Enhances Biotic and Abiotic Stress Tolerance in Rice

    Directory of Open Access Journals (Sweden)

    Jingni Wu

    2016-12-01

    Full Text Available Pathogenesis-related proteins play multiple roles in plant development and biotic and abiotic stress tolerance. Here, we characterize a rice defense related gene named “jasmonic acid inducible pathogenesis-related class 10” (JIOsPR10 to gain an insight into its functional properties. Semi-quantitative RT-PCR analysis showed up-regulation of JIOsPR10 under salt and drought stress conditions. Constitutive over-expression JIOsPR10 in rice promoted shoot and root development in transgenic plants, however, their productivity was unaltered. Further experiments exhibited that the transgenic plants showed reduced susceptibility to rice blast fungus, and enhanced salt and drought stress tolerance as compared to the wild type. A comparative proteomic profiling of wild type and transgenic plants showed that overexpression of JIOsPR10 led to the differential modulation of several proteins mainly related with oxidative stresses, carbohydrate metabolism, and plant defense. Taken together, our findings suggest that JIOsPR10 plays important roles in biotic and abiotic stresses tolerance probably by activation of stress related proteins.

  8. Molecular Analysis of Rice CIPKs Involved in Both Biotic and Abiotic Stress Responses

    Institute of Scientific and Technical Information of China (English)

    CHEN Xi-feng; Gu Zhi-min; LIU Feng; MA Bo-jun; ZHANG Hong-sheng

    2011-01-01

    Plant calcineurin B-like (CBL) proteins have been proposed as important Ca2+ sensors and specifically interact with CBL-interacting protein kinases (CIPKs) in plant-specific calcium signaling.Here,we identified and isolated 15 CIPK genes in a japonica rice variety Nipponbare based on the predicted sequences of rice CIPK gene family.Gene structure analysis showed that these 15 genes were divided into intron-less and intron-rich groups,and OsCIPK3 and OsCIPK24 exhibited alternative splicing in their mature process.The phylogenetic analyses indicated that rice CIPKs shared an ancestor with Arabidopsis and poplar CIPKs.Analyses of gene expression showed that these OsCIPK genes were differentially induced by biotic stresses such as bacterial blight and abiotic stresses (heavy metal such as Hg2+,high salinity,cold and ABA).Interestingly,five OsCIPK genes,OsCIPK1,2,10,11 and 12,were transcriptionally up-regulated after bacterial blight infection whereas four OsCIPK genes,OsCIPK2,10,11 and 14,were induced by all treatments,indicating that some of OsCIPK genes are involved in multiple stress response pathways in plants.Our finding suggests that CIPKs play a key role in both biotic and abiotic stress responses.

  9. Temperature sensitivity indicates that chlorination of organic matter in forest soil is primarily biotic.

    Science.gov (United States)

    Bastviken, David; Svensson, Teresia; Karlsson, Susanne; Sandén, Per; Oberg, Gunilla

    2009-05-15

    Old assumptions that chloride is inert and that most chlorinated organic matter in soils is anthropogenic have been challenged by findings of naturally formed organochlorines. Such natural chlorination has been recognized for several decades, but there are still very few measurements of chlorination rates or estimates of the quantitative importance of terrestrial chlorine transformations. While much is known about the formation of specific compounds, bulk chlorination remains poorly understood in terms of mechanisms and effects of environmental factors. We quantified bulk chlorination rates in coniferous forest soil using 36Cl-chloride in tracer experiments at different temperatures and with and without molecular oxygen (O2). Chlorination was enhanced by the presence of O2 and had a temperature optimum at 20 degrees C. Minimum rates were found at high temperatures (50 degrees C) or under anoxic conditions. The results indicate (1) that most of the chlorination between 4 and 40 degrees C was biotic and driven by O2 dependent enzymes, and (2) that there is also slower background chlorination occurring under anoxic conditions at 20 degrees C and under oxic conditions at 50 degrees C. Hence, while oxic and biotic chlorination clearly dominated, chlorination by other processes including possible abiotic reactions was also detected.

  10. Seed dispersers, seed predators, and browsers act synergistically as biotic filters in a mosaic landscape.

    Directory of Open Access Journals (Sweden)

    Regino Zamora

    Full Text Available In this study, we analize the functional influence of animals on the plants they interact with in a mediterranean mountain. We hypothesise that seed dispersers, seed predators, and browsers can act as biotic filters for plant communities. We analyse the combined effects of mutualistic (seed dispersal and antagonistic (seed predation, herbivory animal interactions in a mosaic landscape of Mediterranean mountains, basing our results on observational and experimental field. Most of the dispersed seeds came from tree species, whereas the population of saplings was composed predominantly of zoochorous shrub species. Seed predators preferentially consumed seeds from tree species, whereas seeds from the dominant fleshy-fruited shrubs had a higher probability of escaping these predators. The same pattern was repeated among the different landscape units by browsers, since they browsed selectively and far more intensely on tree-species saplings than on the surrounding shrubs. In synthesis, our work identifies the major biotic processes that appear to be favoring a community dominated by shrubs versus trees because seed dispersers, predators, and herbivores together favored shrub dispersal and establishment versus trees.

  11. Biotic indices for assessing the status of coastal waters: a review of strengths and weaknesses.

    Science.gov (United States)

    Martínez-Crego, Begoña; Alcoverro, Teresa; Romero, Javier

    2010-05-01

    Biotic indices have become key assessment tools in most recent national and trans-national policies aimed at improving the quality of coastal waters and the integrity of their associated ecosystems. In this study we analyzed 90 published biotic indices, classified them into four types, and analyzed the strengths and weaknesses of each type in relation to the requirements of these policies. We identified three main type-specific weaknesses. First, the problems of applicability, due to practical and conceptual difficulties, which affect most indices related to ecosystem function. Second, the failure of many indices based on structural attributes of the community (e.g. taxonomic composition) to link deterioration with causative stressors, or to provide an early-detection capacity. Third, the poor relevance to the ecological integrity of indices based on attributes at the sub-individual level (e.g. multi-biomarkers). Additionally, most indices still fail on two further aspects: the broad-scale applicability and the definition of reference conditions. Nowadays, the most promising approach seems to be the aggregation of indices with complementary strengths, and obtained from different biological communities.

  12. Presence of riparian vegetation increases biotic condition of fish assemblages in two Brazilian reservoirs

    Directory of Open Access Journals (Sweden)

    Fabio Cop Ferreira

    2015-09-01

    Full Text Available Abstract The riparian vegetation in lakes and reservoirs is source of course wood structures such as trunks and branches and is used as sheltering, spawning and foraging habitats for fishes. The reduction of these submerged structures can thus, affect the composition and structure of fish assemblages in reservoirs. Aim To evaluate the influence of riparian vegetation on the biotic condition of fish assemblage by adapting the Reservoir Fish Assemblage Index (RFAI to two reservoirs in the Upper Paranapanema river basin, São Paulo State, Brazil. Methods The RFAI was adapted from metrics related to the functional characteristics and composition of fish assemblages through a protocol of metric selection and validation, and to its response to the presence of riparian vegetation. Results The final RFAI was composed by nine metrics, been lower in sites without riparian vegetation as consequence of the predominance of larger individuals and the percent of piscivorous and detritivorous fishes. Conclusions These results suggest that increasing shore habitat complexity in reservoirs by maintaining riparian vegetation increases fish biotic integrity.

  13. Separating the role of biotic interactions and climate in determining adaptive response of plants to climate change.

    Science.gov (United States)

    Tomiolo, Sara; Van der Putten, Wim H; Tielbörger, Katja

    2015-05-01

    Altered rainfall regimes will greatly affect the response of plant species to climate change. However, little is known about how direct effects of changing precipitation on plant performance may depend on other abiotic factors and biotic interactions. We used reciprocal transplants between climatically very different sites with simultaneous manipulation of soil, plant population origin, and neighbor conditions to evaluate local adaptation and possible adaptive response of four Eastern Mediterranean annual plant species to climate change. The effect of site on plant performance was negligible, but soil origin had a strong effect on fecundity, most likely due to differential water retaining ability. Competition by neighbors strongly reduced fitness. We separated the effects of the abiotic and biotic soil properties on plant performance by repeating the field experiment in a greenhouse under homogenous environmental conditions and including a soil biota manipulation treatment. As in the field, plant performance differed among soil origins and neighbor treatments. Moreover, we found plant species-specific responses to soil biota that may be best explained by the differential sensitivity to negative and positive soil biota effects. Overall, under the conditions of our experiment with two contrasting sites, biotic interactions had a strong effect on plant fitness that interacted with and eventually overrode climate. Because climate and biotic interactions covary, reciprocal transplants and climate gradient studies should consider soil biotic interactions and abiotic conditions when evaluating climate change effects on plant performance.

  14. Synthesis and characterization of mixed ligand chiral nanoclusters

    KAUST Repository

    Guven, Zekiye P.

    2016-06-22

    Chiral mixed ligand silver nanoclusters were synthesized in the presence of a chiral and an achiral ligand. While the chiral ligand led mostly to the formation of nanoparticles, the presence of the achiral ligand drastically increased the yield of nanoclusters with enhanced chiral properties. © 2016 The Royal Society of Chemistry.

  15. Synthesis and characterization of mixed ligand chiral nanoclusters

    KAUST Repository

    Guven, Zekiye P.; Ustbas, Burcin; Harkness, Kellen M.; Coskun, Hikmet; Joshi, Chakra Prasad; Besong, Tabot M.D.; Stellacci, Francesco; Bakr, Osman; Akbulut, Ozge

    2016-01-01

    Chiral mixed ligand silver nanoclusters were synthesized in the presence of a chiral and an achiral ligand. Wh