WorldWideScience

Sample records for biotic ligand model

  1. Toxicity of copper and cadmium in combinations to Duckweed analyzed by the biotic ligand model.

    Science.gov (United States)

    Hatano, Ayumi; Shoji, Ryo

    2008-06-01

    The biotic ligand model (BLM) of acute toxicity to aquatic organisms is based on the concept that metals binding onto biotic ligand may cause toxic effect on the organism. The BLM can take into incorporation between metal speciation and the protective effects of competing cations account. The demonstrated BLM can provide a good estimation of the amount of single metal effect under various conditions such as pH, coexistence of other non toxic cations. However, toxic metals are often found as mixture in nature. This study estimated combined toxicity of Cu and Cd examined by growth inhibition of Duckweed (Lemna paucicostata) by using single toxicity data as toxic unit (TU) derived by three types of model, BLM and two conventional models, free ion activity model (FIAM), and total metal concentration model. According to our results, single toxicity data derived by the BLM can estimate combined toxicity described as a function of TU. Particularly under the high level of heavy metals stress, BLM clearly predicted toxicity of heavy metals compared with other two models. According to numeric correlation (R(2), root mean square error), the order is BLM (R=0.83, RMSE=13.5)> total metal concentration model (R=0.41, RMSE=24.9)> FIAM (R=0.36, RMSE=26.1).

  2. Using biotic ligand models to predict metal toxicity in mineralized systems

    Science.gov (United States)

    Smith, Kathleen S.; Balistrieri, Laurie S.; Todd, Andrew S.

    2015-01-01

    The biotic ligand model (BLM) is a numerical approach that couples chemical speciation calculations with toxicological information to predict the toxicity of aquatic metals. This approach was proposed as an alternative to expensive toxicological testing, and the U.S. Environmental Protection Agency incorporated the BLM into the 2007 revised aquatic life ambient freshwater quality criteria for Cu. Research BLMs for Ag, Ni, Pb, and Zn are also available, and many other BLMs are under development. Current BLMs are limited to ‘one metal, one organism’ considerations. Although the BLM generally is an improvement over previous approaches to determining water quality criteria, there are several challenges in implementing the BLM, particularly at mined and mineralized sites. These challenges include: (1) historically incomplete datasets for BLM input parameters, especially dissolved organic carbon (DOC), (2) several concerns about DOC, such as DOC fractionation in Fe- and Al-rich systems and differences in DOC quality that result in variations in metal-binding affinities, (3) water-quality parameters and resulting metal-toxicity predictions that are temporally and spatially dependent, (4) additional influences on metal bioavailability, such as multiple metal toxicity, dietary metal toxicity, and competition among organisms or metals, (5) potential importance of metal interactions with solid or gas phases and/or kinetically controlled reactions, and (6) tolerance to metal toxicity observed for aquatic organisms living in areas with elevated metal concentrations.

  3. Bioavailability and Environmental Regulation - Integrating a Fate & Effects Model with a Biotic Ligand Model for Copper in Seawater

    Science.gov (United States)

    Rivera, I.; Chadwick, B.; Rosen, G.; Wang, P. F.; Paquin, P.; Santore, R.; Ryan, A.

    2015-12-01

    Understanding the bioavailability of metals in the aquatic environment is important for defining appropriate regulatory constraints. A failure to recognize the importance of bioavailability factors on metal toxicity can result in criteria that are over- or under-protective. USEPA addresses the tendency of the national Water Quality Criterion (WQC) for regulation of copper in marine waters to underestimate the natural attenuation of copper toxicity in harbors by the application of site-specific Water Quality Standards (WQS). Which provides the level of protection intended by the WQC, and establishes realistic regulatory objectives. However, development of site-specific WQS involves a long-term effort, and does not account for temporal variation. The toxicity model seawater-Biotic Ligand Model (BLM) was developed and integrated with the existing Curvilinear Hydrodynamics in 3 Dimensions (CH3D) transport & fate model to create an efficient tool for development of site-specific WQS in harbors. The integrated model was demonstrated at a harbor-wide scale in San Diego Bay and Pearl Harbor, and accounted for the natural physical, chemical, biological and toxicological characteristics of the harbor to achieve more scientifically based compliance. In both harbors the spatial and temporal distributions of copper species, toxic effects, and Water Effect Ratio predicted by the integrated model are comparable to previous data. The model was further demonstrated in Shelter Island Yacht Basin (SIYB) marina in San Diego Bay. The integrated model agreed with toxicological and chemical approaches by indicating negligible bioavailability as well as no toxicity; but for a single event, even though an increasing gradient in Cu was observed both horizontally and vertically, with concentrations that reached levels well above current regulatory thresholds. These results support the incorporation by USEPA of the seawater-BLM in a full-strength seawater criterion.

  4. Re-evaluation of metal bioaccumulation and chronic toxicity in Hyalella azteca using saturation curves and the biotic ligand model

    Energy Technology Data Exchange (ETDEWEB)

    Borgmann, U.; Norwood, W.P.; Dixon, D.G

    2004-10-01

    Bioaccumulation by Hyalella of all metals studied so far in our laboratory was re-evaluated to determine if the data could be explained satisfactorily using saturation models. Saturation kinetics are predicted by the biotic ligand model (BLM), now widely used in modelling acute toxicity, and are a pre-requisite if the BLM is to be applied to chronic toxicity. Saturation models provided a good fit to all the data. Since these are mechanistically based, they provide additional insights into metal accumulation mechanisms not immediately apparent when using allometric models. For example, maximum Cd accumulation is dependent on the hardness of the water to which Hyalella are acclimated. The BLM may need to be modified when applied to chronic toxicity. Use of saturation models for bioaccumulation, however, also necessitates the need for using saturation models for dose-response relationships in order to produce unambiguous estimates of LC50 values based on water and body concentrations. This affects predictions of toxicity at very low metal concentrations and results in lower predicted toxicity of mixtures when many metals are present at low concentrations.

  5. Biotic ligand modeling approach: Synthesis of the effect of major cations on the toxicity of metals to soil and aquatic organisms.

    Science.gov (United States)

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

    2015-10-01

    The biotic ligand model (BLM) approach is used to assess metal toxicity, taking into account the competition of other cations with the free metal ions for binding to the biotic ligand sites of aquatic and soil organisms. The bioavailable fraction of metals, represented by the free metal ion, is a better measure than the total concentration for assessing their potential risk to the environment. Because BLMs are relating toxicity to the fraction of biotic ligands occupied by the metal, they can be useful for investigating factors affecting metal bioaccumulation and toxicity. In the present review, the effects of major cations on the toxicity of metals to soil and aquatic organisms were comprehensively studied by performing a meta-analysis of BLM literature data. Interactions at the binding sites were shown to be species- and metal-specific. The main factors affecting the relationships between toxicity and conditional binding constants for metal binding at the biotic ligand appeared to be Ca(2+) , Mg(2+) , and protons. Other important characteristics of the exposure medium, such as levels of dissolved organic carbon and concentrations of other cations, should also be considered to obtain a proper assessment of metal toxicity to soil and aquatic organisms.

  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. Use of the Biotic Ligand Model to predict metal toxicity to aquatic biota in areas of differing geology

    Science.gov (United States)

    Smith, Kathleen S.

    2005-01-01

    This work evaluates the use of the biotic ligand model (BLM), an aquatic toxicity model, to predict toxic effects of metals on aquatic biota in areas underlain by different rock types. The chemical composition of water, soil, and sediment is largely derived from the composition of the underlying rock. Geologic source materials control key attributes of water chemistry that affect metal toxicity to aquatic biota, including: 1) potentially toxic elements, 2) alkalinity, 3) total dissolved solids, and 4) soluble major elements, such as Ca and Mg, which contribute to water hardness. Miller (2002) compiled chemical data for water samples collected in watersheds underlain by ten different rock types, and in a mineralized area in western Colorado. He found that each rock type has a unique range of water chemistry. In this study, the ten rock types were grouped into two general categories, igneous and sedimentary. Water collected in watersheds underlain by sedimentary rock has higher mean pH, alkalinity, and calcium concentrations than water collected in watersheds underlain by igneous rock. Water collected in the mineralized area had elevated concentrations of calcium and sulfate in addition to other chemical constituents. Miller's water-chemistry data were used in the BLM (computer program) to determine copper and zinc toxicity to Daphnia magna. Modeling results show that waters from watersheds underlain by different rock types have characteristic ranges of predicted LC 50 values (a measurement of aquatic toxicity) for copper and zinc, with watersheds underlain by igneous rock having lower predicted LC 50 values than watersheds underlain by sedimentary rock. Lower predicted LC 50 values suggest that aquatic biota in watersheds underlain by igneous rock may be more vulnerable to copper and zinc inputs than aquatic biota in watersheds underlain by sedimentary rock. For both copper and zinc, there is a trend of increasing predicted LC 50 values with increasing dissolved

  8. Evaluation of the Biotic Ligand Model relative to other site-specific criteria derivation methods for copper in surface waters with elevated hardness.

    Science.gov (United States)

    Van Genderen, Eric; Gensemer, Robert; Smith, Carrie; Santore, Robert; Ryan, Adam

    2007-08-30

    The goal of this study was to evaluate the reliability of the Biotic Ligand Model to predict Cu toxicity in very hard surface water (>200 mg/L as CaCO(3)), relative to current copper criteria methodologies (hardness-based equation and the water-effect ratio; WER). To test these methods, we conducted acute Cu toxicity tests with three aquatic test species (Ceriodaphnia dubia, Daphnia pulex and Pimephales promelas) in seven surface waters. The sites were representative of effluent-dependent or effluent-dominated streams common to the arid western United States of America (arid West) and a wide range of water quality variables were tested. In addition, concurrent Cu toxicity tests were conducted in laboratory waters that were matched to hardness and alkalinity of the sites to facilitate calculation of WER values. Results were used to characterize empirical relationships between water quality characteristics and Cu toxicity, and to compare measured Cu toxicity with Biotic Ligand Model (BLM) predictions. Acute toxicity tests were also conducted with C. dubia and P. promelas in a range of Ca or Mg-dominated hardness concentrations to determine the independent effects of Ca or Mg on Cu toxicity at high hardness levels. Conclusions from this study suggest that the BLM generates appropriate criteria for the waters tested in this study when compared to the hardness-based equation or WER approach. Although the historical site-specific methods are useful for surface waters with hardness alkalinity, Ca, Mg and Na). Therefore, the BLM offers an improved alternative to the hardness-based and WER approaches, particularly for situations where the current methods would be under-protective of sensitive aquatic life.

  9. Copper(II) binding by dissolved organic matter: importance of the copper-to-dissolved organic matter ratio and implications for the biotic ligand model.

    Science.gov (United States)

    Craven, Alison M; Aiken, George R; Ryan, Joseph N

    2012-09-18

    The ratio of copper to dissolved organic matter (DOM) is known to affect the strength of copper binding by DOM, but previous methods to determine the Cu(2+)-DOM binding strength have generally not measured binding constants over the same Cu:DOM ratios. In this study, we used a competitive ligand exchange-solid-phase extraction (CLE-SPE) method to determine conditional stability constants for Cu(2+)-DOM binding at pH 6.6 and 0.01 M ionic strength over a range of Cu:DOM ratios that bridge the detection windows of copper-ion-selective electrode and voltammetry measurements. As the Cu:DOM ratio increased from 0.0005 to 0.1 mg of Cu/mg of DOM, the measured conditional binding constant ((c)K(CuDOM)) decreased from 10(11.5) to 10(5.6) M(-1). A comparison of the binding constants measured by CLE-SPE with those measured by copper-ion-selective electrode and voltammetry demonstrates that the Cu:DOM ratio is an important factor controlling Cu(2+)-DOM binding strength even for DOM isolates of different types and different sources and for whole water samples. The results were modeled with Visual MINTEQ and compared to results from the biotic ligand model (BLM). The BLM was found to over-estimate Cu(2+) at low total copper concentrations and under-estimate Cu(2+) at high total copper concentrations.

  10. 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.

  11. Incorporating bioavailability into toxicity assessment of Cu-Ni, Cu-Cd, and Ni-Cd mixtures with the extended biotic ligand model and the WHAM-F(tox) approach.

    Science.gov (United States)

    Qiu, Hao; Vijver, Martina G; He, Erkai; Liu, Yang; Wang, Peng; Xia, Bing; Smolders, Erik; Versieren, Liske; Peijnenburg, Willie J G M

    2015-12-01

    There are only a limited number of studies that have developed appropriate models which incorporate bioavailability to estimate mixture toxicity. Here, we explored the applicability of the extended biotic ligand model (BLM) and the WHAM-F(tox) approach for predicting and interpreting mixture toxicity, with the assumption that interactions between metal ions obey the BLM theory. Seedlings of lettuce Lactuca sativa were exposed to metal mixtures (Cu-Ni, Cu-Cd, and Ni-Cd) contained in hydroponic solutions for 4 days. Inhibition to root elongation was the endpoint used to quantify the toxic response. Assuming that metal ions compete with each other for binding at a single biotic ligand, the extended BLM succeeded in predicting toxicity of three mixtures to lettuce, with more than 82% of toxicity variation explained. There were no significant differences in the values of f(mix50) (i.e., the overall amounts of metal ions bound to the biotic ligand inducing 50% effect) for the three mixture combinations, showing the possibility of extrapolating these values to other binary metal combinations. The WHAM-F(tox) approach showed a similar level of precision in estimating mixture toxicity while requiring fewer parameters than the BLM-f(mix) model. External validation of the WHAM-F(tox) approach using literature data showed its applicability for other species and other mixtures. The WHAM-F(tox) model is suitable for delineating mixture effects where the extended BLM also applies. Therefore, in case of lower data availability, we recommend the lower parameterized WHAM-F(tox) as an effective approach to incorporate bioavailability in quantifying mixture toxicity.

  12. 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.

  13. BLM预测水中重金属生物有效性研究进展%An Updated Review on Biotic Ligand Model in Predicing Metal Bioavailability in Surface Waters

    Institute of Scientific and Technical Information of China (English)

    王春艳; 陈浩; 安立会; 秦延文; 吴坤炳; 郑丙辉

    2011-01-01

    生物配体模型( BLM)是利用环境参数来预测重金属生物有效性的模型.它生物受体位点作为生物配体,考虑了影响生物毒性的水化学性质,并把生物有效性的概念引入到水质标准中,在较宽的模拟水质范围内取得较好的预测效果.生物配体模型是多学科共同发展的成果,综合了金属在水环境中的化学、生物学、生理学等以及计算机科学方面的成果,这学科的发展也为模型的实现提供了条件.它利用水环境中特定的水质参数,就可以得到重金属生物有效性的预测结果,而水质参数通常可由水环境监测结果得到,数据来源方便简单.生物配体模型适用于多种金属和生物.文章详细介绍了生物配体模型的提出、理论基础及其国内外地表水中的应用现状,并对模型的不足和亟需改进的地方进行了探讨.%Biotic ligand model (BLM) is a model that predicts the metal bioavailability based on environmental parameters. Biological sites that interact with metal ions are considered as biotic ligands. Aquatic chemistry is taken into accoun by BLM model to predict the bioavailability, an important concept that is tightly associated with toxicity and has been used η water quality standard. Benefited from advancement of various sciences including environmental chemistry, biology, physnlogy and computer science, BLM model can use readily available water quality data to predict the bioavailability and toxicity of quite a few metals for many biological species. Water quality data can be obtained in routine water quality monitoring. Theoretical background as well as current application for BIM model in surface waters in China and other countries was introduced, drawbacks of the model were also discussed.

  14. Multi-linear regression analysis, preliminary biotic ligand modeling, and cross species comparison of the effects of water chemistry on chronic lead toxicity in invertebrates.

    Science.gov (United States)

    Esbaugh, A J; Brix, K V; Mager, E M; De Schamphelaere, K; Grosell, M

    2012-03-01

    The current study examined the chronic toxicity of lead (Pb) to three invertebrate species: the cladoceran Ceriodaphnia dubia, the snail Lymnaea stagnalis and the rotifer Philodina rapida. The test media consisted of natural waters from across North America, varying in pertinent water chemistry parameters including dissolved organic carbon (DOC), calcium, pH and total CO(2). Chronic toxicity was assessed using reproductive endpoints for C. dubia and P. rapida while growth was assessed for L. stagnalis, with chronic toxicity varying markedly according to water chemistry. A multi-linear regression (MLR) approach was used to identify the relative importance of individual water chemistry components in predicting chronic Pb toxicity for each species. DOC was an integral component of MLR models for C. dubia and L. stagnalis, but surprisingly had no predictive impact on chronic Pb toxicity for P. rapida. Furthermore, sodium and total CO(2) were also identified as important factors affecting C. dubia toxicity; no other factors were predictive for L. stagnalis. The Pb toxicity of P. rapida was predicted by calcium and pH. The predictive power of the C. dubia and L. stagnalis MLR models was generally similar to that of the current C. dubia BLM, with R(2) values of 0.55 and 0.82 for the respective MLR models, compared to 0.45 and 0.79 for the respective BLMs. In contrast the BLM poorly predicted P. rapida toxicity (R(2)=0.19), as compared to the MLR (R(2)=0.92). The cross species variability in the effects of water chemistry, especially with respect to rotifers, suggests that cross species modeling of invertebrate chronic Pb toxicity using a C. dubia model may not always be appropriate.

  15. 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

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

    Science.gov (United States)

    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 (60mg CaCO3 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 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 (LogK values) were calculated based on free ion relationships as determined by geochemical equilibrium modeling software (WHAM ver. 7.02). The logK 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 guidelines and criteria for Dy and possibly REEs in general and offers insight into the complex bio-geochemical nature of this element.

  17. Toxicity of silver nanoparticles to green algae – towards a biotic ligand understanding

    DEFF Research Database (Denmark)

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

    growth inhibition tests and a newly developed 4-h photosynthesis inhibition algal test. The tested AgNPs were of the same primary size (30 nm) but with different capping agents (citrate, mercaptoundecanoic acid, …MARINA). Characterization included ICP-OES, DLS, NTA, and TEM before and after incubation....... Results show that the toxicity of AgNO3 and citrate-stabilized AgNP decreased significantly when the pH was lowered from 8.2 to 7.0. This is in contrast to PHREEQC predictions, but in agreement with the biotic ligand theory. The poster will focus a trends in changes in toxicity of AgNP as a result...

  18. 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.

  19. Ligand modeling and design

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-10-01

    The purpose of this work is to develop and implement a molecular design basis for selecting organic ligands that would be used tin applications for the cost-effective removal of specific radionuclides from nuclear waste streams.

  20. Biotic modifiers, environmental modulation and species distribution models

    NARCIS (Netherlands)

    Linder, H. Peter; Bykova, Olga; Dyke, James; Etienne, Rampal S.; Hickler, Thomas; Kuehn, Ingolf; Marion, Glenn; Ohlemueller, Ralf; Schymanski, Stanislaus J.; Singer, Alexander

    2012-01-01

    The ability of species to modulate environmental conditions and resources has long been of interest. In the past three decades the impacts of these biotic modifiers have been investigated as ecosystem engineers, niche constructors, facilitators and keystone species. This environmental modulation can

  1. Potential role of biotic transport models in low-level-waste management. [Shallow land burial

    Energy Technology Data Exchange (ETDEWEB)

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

    1982-06-15

    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.

  2. Biotic element analysis of reptiles of China: A test of vicariance model

    Institute of Scientific and Technical Information of China (English)

    Youhua CHEN

    2013-01-01

    In this contribution,I identify possible biotic elements of reptiles of China using biotic element analysis.I test whether the vicariance model could significantly shape reptilian current distribution patterns.My results show that dispersal is prevailing for reptiles in China.There are four major biotic elements in reptilian distribution,which are East Xizang,YunnanGuizhou Plateau,Taiwan and Hainan,respectively.The test of distributional areas is significantly more clustered than expected by chance,while in another test that closely related species are homogeneously distributed across biotic elements cannot be rejected.Therefore I argued that vicariance might be one of the key processes in patterning reptilian distribution in China.In addition,I develop an improved biotic element analysis in biogeographic studies,by performing biotic element analysis in an iterative manner in order to diagnose more geographically restricted elements until no noise components found.The importance of antecedent selection of distributional data for the subsequent analysis is also discussed.Besides,my study indicates that biodiversity hotspots are not fully overlapped with areas of endemism for reptilians in East Asia.

  3. Biotic origin for Mima mounds supported by numerical modeling

    Science.gov (United States)

    Gabet, Emmanuel J.; Perron, J. Taylor; Johnson, Donald L.

    2014-02-01

    Mima mounds are ~ 1-m-high hillocks found on every continent except Antarctica. Despite often numbering in the millions within a single field, their origin has been a mystery, with proposed explanations ranging from glacial processes to seismic shaking. One hypothesis proposes that mounds in North America are built by burrowing mammals to provide refuge from seasonally saturated soils. We test this hypothesis with a numerical model, parameterized with measurements of soil transport by gophers from a California mound field, that couples animal behavior with geomorphic processes. The model successfully simulates the development of the mounds as well as key details such as the creation of vernal pools, small intermound basins that provide habitat for endemic species. Furthermore, we demonstrate that the spatial structure of the modeled mound fields is similar to actual mound fields and provides an example of self-organized topographic features. We conclude that, scaled by body mass, Mima mounds are the largest structures built by nonhuman mammals and may provide a rare example of an evolutionary coupling between landforms and the organisms that create them.

  4. Biotic Origin for Mima Mounds Supported by Numerical Model

    Science.gov (United States)

    Gabet, E. J.; Perron, J.; Johnson, D. L.

    2013-12-01

    Mima mounds are ~1-m-high hillocks found on every continent except Antarctica. Despite often numbering in the millions within a single field, their origin has been a mystery, with proposed explanations ranging from glacial processes to seismic shaking. One hypothesis proposes that mounds in North America are built by burrowing mammals to provide refuge from seasonally saturated soils. We test this hypothesis with a numerical model, parameterized with measurements of soil transport by gophers from a California mound field, that couples animal behavior with geomorphic processes. The model successfully simulates the development of the mounds, as well as key details such as the creation of vernal pools, small intermound basins that provide habitat for endemic species. Furthermore, we demonstrate that the spatial structure of the modeled mound fields is similar to actual mound fields and provides an example of self-organized topographic features. We conclude that, scaled by body mass, Mima mounds are the largest structures built by non-human mammals, and may provide a rare example of an evolutionary coupling between landforms and the organisms that create them.

  5. Quantifying effects of abiotic and biotic drivers on community dynamics with multivariate autoregressive (MAR) models.

    Science.gov (United States)

    Hampton, Stephanie E; Holmes, Elizabeth E; Scheef, Lindsay P; Scheuerell, Mark D; Katz, Stephen L; Pendleton, Daniel E; Ward, Eric J

    2013-12-01

    Long-term ecological data sets present opportunities for identifying drivers of community dynamics and quantifying their effects through time series analysis. Multivariate autoregressive (MAR) models are well known in many other disciplines, such as econometrics, but widespread adoption of MAR methods in ecology and natural resource management has been much slower despite some widely cited ecological examples. Here we review previous ecological applications of MAR models and highlight their ability to identify abiotic and biotic drivers of population dynamics, as well as community-level stability metrics, from long-term empirical observations. Thus far, MAR models have been used mainly with data from freshwater plankton communities; we examine the obstacles that may be hindering adoption in other systems and suggest practical modifications that will improve MAR models for broader application. Many of these modifications are already well known in other fields in which MAR models are common, although they are frequently described under different names. In an effort to make MAR models more accessible to ecologists, we include a worked example using recently developed R packages (MAR1 and MARSS), freely available and open-access software.

  6. Biotic Interactions in Microbial Communities as Modulators of Biogeochemical Processes: Methanotrophy as a Model System.

    Science.gov (United States)

    Ho, Adrian; Angel, Roey; Veraart, Annelies J; Daebeler, Anne; Jia, Zhongjun; Kim, Sang Yoon; Kerckhof, Frederiek-Maarten; Boon, Nico; Bodelier, Paul L E

    2016-01-01

    Microbial interaction is an integral component of microbial ecology studies, yet the role, extent, and relevance of microbial interaction in community functioning remains unclear, particularly in the context of global biogeochemical cycles. While many studies have shed light on the physico-chemical cues affecting specific processes, (micro)biotic controls and interactions potentially steering microbial communities leading to altered functioning are less known. Yet, recent accumulating evidence suggests that the concerted actions of a community can be significantly different from the combined effects of individual microorganisms, giving rise to emergent properties. Here, we exemplify the importance of microbial interaction for ecosystem processes by analysis of a reasonably well-understood microbial guild, namely, aerobic methane-oxidizing bacteria (MOB). We reviewed the literature which provided compelling evidence for the relevance of microbial interaction in modulating methane oxidation. Support for microbial associations within methane-fed communities is sought by a re-analysis of literature data derived from stable isotope probing studies of various complex environmental settings. Putative positive interactions between active MOB and other microbes were assessed by a correlation network-based analysis with datasets covering diverse environments where closely interacting members of a consortium can potentially alter the methane oxidation activity. Although, methanotrophy is used as a model system, the fundamentals of our postulations may be applicable to other microbial guilds mediating other biogeochemical processes.

  7. Development of a mercury speciation, fate, and biotic uptake (BIOTRANSPEC) model: Application to Lahontan Reservoir (Nevada, USA)

    Science.gov (United States)

    Gandhi, N.; Bhavsar, S.P.; Diamond, M.L.; Kuwabara, J.S.; Marvin-DiPasquale, M.; Krabbenhoft, D.P.

    2007-01-01

    A mathematically linked mercury transport, speciation, kinetic, and simple biotic uptake (BIOTRANSPEC) model has been developed. An extension of the metal transport and speciation (TRANSPEC) model, BIOTRANSPEC estimates the fate and biotic uptake of inorganic (Hg(II)), elemental (Hg(0)) and organic (MeHg) forms of mercury and their species in the dissolved, colloidal (e.g., dissolved organic matter [DOM]), and particulate phases of surface aquatic systems. A pseudo-steady state version of the model was used to describe mercury dynamics in Lahontan Reservoir (near Carson City, NV, USA), where internal loading of the historically deposited mercury is remobilized, thereby maintaining elevated water concentrations. The Carson River is the main source of total mercury (THg), of which more than 90% is tightly bound in a gold-silver-mercury amalgam, to the system through loadings in the spring, with negligible input from the atmospheric deposition. The speciation results suggest that aqueous species are dominated by Hg-DOM, Hg(OH)2, and HgClOH. Sediment-to-water diffusion of MeHg and Hg-DOM accounts for approximately 10% of total loadings to the water column. The water column acts as a net sink for MeHg by reducing its levels through two competitive processes: Uptake by fish, and net MeHg demethylation. Although reservoir sediments produce significant amounts of MeHg (4 g/d), its transport from sediment to water is limited (1.6 g/d), possibly because of its adsorption on metal oxides of iron and manganese at the sediment-water interface. Fish accumulate approximately 45% of the total MeHg mass in the water column, and 9% of total MeHg uptake by fish leaves the system because of fishing. Results from this new model reiterate the previous conclusion that more than 90% of THg input is retained in sediment, which perpetuates elevated water concentrations. ?? 2007 SETAC.

  8. Increased biotic metabolism of the biosphere inferred from observed data and models

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A 35 year record of production and respiration in the Northern Hemisphere bas been derived from monthly records of atmospheric concentration, fossil fuel combustion, and oceanic absorption of carbon dioxide using a method developed by Hall et al. The original conclusion of Hall et al. that there was no significant change in biotic metabolism, is confirmed by measuring both production and respiration from 1958 to 1972. But the analysis of the subsequent record shows that both production and respiration have been enhanced since the early 1970s by some large scale global change, probably of human origin. Our results also show that high-latitude regions in the Northern Hemisphere are changing more than regions further south. Nevertheless, the ratio of production to respiration (P/R) remains unchanged during the time period examined. Thus, no argument can be made for net carbon storage of or release from the biosphere from this analysis, although the turnover rate of the biosphere appears to be enhanced.

  9. Increased biotic metabolism of the biosphere inferred from observed data and models

    Institute of Scientific and Technical Information of China (English)

    田汉勤[1; CharlesA.S.Hall[2; 叶琦[3

    2000-01-01

    A 35 year record ot production and respiration in tne Northern Hemisphere bas been derived from monthly records of atmospheric concentration, fossil fuel combustion, and oceanic absorption of carbon dioxide using a method developed by Hall et al. The original conclusion of Hall et al. that there was no significant change in biotic metabolism, is confirmed by measuring both production and respiration from 1958 to 1972. But the analysis of the subsequent record shows that both production and respiration have been enhanced since the early 1970s by some large scale global change, probably of human origin. Our results also show that high-latitude regions in the Northern Hemisphere are changing more than regions further south. Nevertheless, the ratio of production to respiration (P/R) remains unchanged during the time period examined. Thus, no argument can be made for net carbon storage of or release from the biosphere from this analysis, although the turnover rate of the biosphere appears to be enhanced.

  10. Development and application of a multimetal multibiotic ligand model for assessing aquatic toxicity of metal mixtures.

    Science.gov (United States)

    Santore, Robert C; Ryan, Adam C

    2015-04-01

    A multimetal, multiple binding site version of the biotic ligand model (mBLM) has been developed for predicting and explaining the bioavailability and toxicity of mixtures of metals to aquatic organisms. The mBLM was constructed by combining information from single-metal BLMs to preserve compatibility between the single-metal and multiple-metal approaches. The toxicities from individual metals were predicted by assuming additivity of the individual responses. Mixture toxicity was predicted based on both dissolved metal and mBLM-normalized bioavailable metal. Comparison of the 2 prediction methods indicates that metal mixtures frequently appear to have greater toxicity than an additive estimation of individual effects on a dissolved metal basis. However, on an mBLM-normalized basis, mixtures of metals appear to be additive or less than additive. This difference results from interactions between metals and ligands in solutions including natural organic matter, processes that are accounted for in the mBLM. As part of the mBLM approach, a technique for considering variability was developed to calculate confidence bounds (called response envelopes) around the central concentration-response relationship. Predictions using the mBLM and response envelope were compared with observed toxicity for a number of invertebrate and fish species. The results show that the mBLM is a useful tool for considering bioavailability when assessing the toxicity of metal mixtures.

  11. 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.

  12. BIOACCUMULATION DYNAMICS OF HEAVY METALS IN Oreochromis nilotycus: PREDICTED THROUGH A BIOACCUMULATION MODEL CONSTRUCTED BASED ON BIOTIC LIGAND MODEL (BLM)

    OpenAIRE

    Noegrohati, Sri

    2010-01-01

    In estuarine ecosystem, sediments are not only functioning as heavy metal scavenger, but also as one of potential sources for heavy metals to the ecosystem. Due the capability of aquatic organisms to accumulate heavy metals, there is possibility of heavy metals to exert their toxic effect towards the organisms and other organisms positioned in higher trophic level, such as fish, and further to human beings. To understand the different processes of heavy metal bioaccumulation in a dynamic mann...

  13. Biotic Population Dynamics: Creative Biotic Patterns

    Science.gov (United States)

    Sabelli, Hector; Kovacevic, Lazar

    We present empirical studies and computer models of population dynamics that demonstrate creative features and we speculate that these creative processes may underline evolution. Changes in population size of lynx, muskrat, beaver, salmon, and fox display diversification, episodic changes in pattern, novelty, and evidence for nonrandom causation. These features of creativity characterize bios, and rule out random, periodic, chaotic, and random walk patterns. Biotic patterns are also demonstrated in time series generated with multi-agent predator-prey simulations. These results indicate that evolutionary processes are continually operating. In contrast to standard evolutionary theory (random variation, competition for scarce resources, selection by survival of the fittest, and directionless, meaningless evolution), we propose that biological evolution is a creative development from simple to complex in which (1) causal actions generate biological variation; (2) bipolar feedback (synergy and antagonism, abundance and scarcity) generates information (diversification, novelty and complexity); (3) connections (of molecules, genes, species) construct systems in which simple processes have priority for survival but complex processes acquire supremacy.

  14. Inversion analysis of estimating interannual variability and its uncertainties in biotic and abiotic parameters of a parsimonious physiologically based model after wind disturbance

    Science.gov (United States)

    Toda, M.; Yokozawa, M.; Richardson, A. D.; Kohyama, T.

    2011-12-01

    The effects of wind disturbance on interannual variability in ecosystem CO2 exchange have been assessed in two forests in northern Japan, i.e., a young, even-aged, monocultured, deciduous forest and an uneven-aged mixed forest of evergreen and deciduous trees, including some over 200 years old using eddy covariance (EC) measurements during 2004-2008. The EC measurements have indicated that photosynthetic recovery of trees after a huge typhoon occurred during early September in 2004 activated annual carbon uptake of both forests due to changes in physiological response of tree leaves during their growth stages. However, little have been resolved about what biotic and abiotic factors regulated interannual variability in heat, water and carbon exchange between an atmosphere and forests. In recent years, an inverse modeling analysis has been utilized as a powerful tool to estimate biotic and abiotic parameters that might affect heat, water and CO2 exchange between the atmosphere and forest of a parsimonious physiologically based model. We conducted the Bayesian inverse model analysis for the model with the EC measurements. The preliminary result showed that the above model-derived NEE values were consistent with observed ones on the hourly basis with optimized parameters by Baysian inversion. In the presentation, we would examine interannual variability in biotic and abiotic parameters related to heat, water and carbon exchange between the atmosphere and forests after disturbance by typhoon.

  15. A palaeobiogeographic model for biotic diversification within Amazonia over the past three million years.

    Science.gov (United States)

    Ribas, Camila C; Aleixo, Alexandre; Nogueira, Afonso C R; Miyaki, Cristina Y; Cracraft, Joel

    2012-02-22

    Many hypotheses have been proposed to explain high species diversity in Amazonia, but few generalizations have emerged. In part, this has arisen from the scarcity of rigorous tests for mechanisms promoting speciation, and from major uncertainties about palaeogeographic events and their spatial and temporal associations with diversification. Here, we investigate the environmental history of Amazonia using a phylogenetic and biogeographic analysis of trumpeters (Aves: Psophia), which are represented by species in each of the vertebrate areas of endemism. Their relationships reveal an unforeseen 'complete' time-slice of Amazonian diversification over the past 3.0 Myr. We employ this temporally calibrated phylogeny to test competing palaeogeographic hypotheses. Our results are consistent with the establishment of the current Amazonian drainage system at approximately 3.0-2.0 Ma and predict the temporal pattern of major river formation over Plio-Pleistocene times. We propose a palaeobiogeographic model for the last 3.0 Myr of Amazonian history that has implications for understanding patterns of endemism, the temporal history of Amazonian diversification and mechanisms promoting speciation. The history of Psophia, in combination with new geological evidence, provides the strongest direct evidence supporting a role for river dynamics in Amazonian diversification, and the absence of such a role for glacial climate cycles and refugia.

  16. The biotic ligand model approach for addressing effects of exposure water chemistry on aquatic toxicity of metals: Genesis and challenges

    Science.gov (United States)

    A major uncertainty in many aquatic risk assessments for toxic chemicals is the aggregate effect of the physicochemical characteristics of exposure media on toxicity, and how this affects extrapolation of laboratory test results to natural systems. A notable example of this is h...

  17. Biotic interactions as a structuring force in soil communities: evidence from the micro-arthropods of an Antarctic moss model system.

    Science.gov (United States)

    Caruso, Tancredi; Trokhymets, Vladlen; Bargagli, Roberto; Convey, Peter

    2013-06-01

    Current meta-community theories postulate that the structure of local communities depends on dispersal, environmental filtering, and biotic interactions. However, disentangling the relative effects of these factors in the field and for diverse assemblages is a major challenge. A solution is to address natural but simple communities (i.e. with low numbers of species in few trophic levels), wherein one of these factors is predominant. Here, we analyse the micro-arthropod community of a moss-turf habitat typical of the Antarctic Peninsula region, and test the widely accepted hypothesis that this system is abiotically driven. In the austral summers 2006/7 and 2007/8, we sampled nearly 80 units of moss from four islands in the Argentine Islands. Using variance partitioning, we quantified the relative contribution of: (1) multiple scale spatio-temporal autocorrelation; (2) environmental effects; (3) the island effect. Little variance (1 %) was accounted for by sources 1 (1 %, significant) and 2 (structured environmental variation (7 %). Null models demonstrated that species co-occurred less frequently than expected by chance, suggesting the prevalence of negative interactions. Our data support the novel hypothesis that negative biotic interactions are the most important structuring force of this micro-arthropod community. The analysed system is a good proxy for more complex communities in terms of taxonomic composition and the functional groups present. Thus, biotic interaction might be a predominant factor in soil meta-community dynamics.

  18. Molecular modeling of sigma 1 receptor ligands: a model of binding conformational and electrostatic considerations.

    Science.gov (United States)

    Gund, Tamara M; Floyd, Jie; Jung, Dawoon

    2004-01-01

    We have performed molecular modeling studies on several sigma 1 specific ligands, including PD144418, spipethiane, haloperidol, pentazocine, and others to develop a pharmacophore for sigma 1 receptor-ligand binding, under the assumption that all the compounds interact at the same receptor binding site. The modeling studies have investigated the conformational and electrostatic properties of the ligands. Superposition of active molecules gave the coordinates of the hypothetical 5-point sigma 1 pharmacophore, as follows: R1 (0.85, 7.26, 0.30); R2 (5.47, 2.40, -1.51); R3 (-2.57, 4.82, -7.10); N (-0.71, 3.29, -6.40); carbon centroid (3.16, 4.83, -0.60), where R1, R2 were constructed onto the aromatic ring of each compound to represent hydrophobic interactions with the receptor; and R3 represents a hydrogen bond between the nitrogen atom and the receptor. Additional analyses were used to describe secondary binding sites to electronegative groups such as oxygen or sulfur atom. Those coordinates are (2.34, 5.08, -4.18). The model was verified by fitting other sigma 1 receptor ligands. This model may be used to search conformational databases for other possibly active ligands. In conjunction with rational drug design techniques the model may be useful in design and synthesis of novel sigma 1 ligands of high selectivity and potency. Calculations were performed using Sybyl 6.5.

  19. A Tunable Coarse-Grained Model for Ligand-Receptor Interaction

    Science.gov (United States)

    Guantes, Raúl; Miguez, David G.

    2013-01-01

    Cell-surface receptors are the most common target for therapeutic drugs. The design and optimization of next generation synthetic drugs require a detailed understanding of the interaction with their corresponding receptors. Mathematical approximations to study ligand-receptor systems based on reaction kinetics strongly simplify the spatial constraints of the interaction, while full atomistic ligand-receptor models do not allow for a statistical many-particle analysis, due to their high computational requirements. Here we present a generic coarse-grained model for ligand-receptor systems that accounts for the essential spatial characteristics of the interaction, while allowing statistical analysis. The model captures the main features of ligand-receptor kinetics, such as diffusion dependence of affinity and dissociation rates. Our model is used to characterize chimeric compounds, designed to take advantage of the receptor over-expression phenotype of certain diseases to selectively target unhealthy cells. Molecular dynamics simulations of chimeric ligands are used to study how selectivity can be optimized based on receptor abundance, ligand-receptor affinity and length of the linker between both ligand subunits. Overall, this coarse-grained model is a useful approximation in the study of systems with complex ligand-receptor interactions or spatial constraints. PMID:24244115

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

    Science.gov (United States)

    Kaushik, Ananth P; Clancy, Paulette

    2012-03-21

    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.

  1. 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.

  2. Development of a unique 3D interaction model of endogenous and synthetic peripheral benzodiazepine receptor ligands

    Science.gov (United States)

    Cinone, Nunzia; Höltje, Hans-Dieter; Carotti, Angelo

    2000-11-01

    Different classes of Peripheral-type Benzodiazepine Receptor (PBR) ligands were examined and common structural elements were detected and used to develop a rational binding model based on energetically allowed ligand conformations. Two lipophilic regions and one electrostatic interaction site are essential features for high affinity ligand binding, while a further lipophilic region plays an important modulator role. A comparative molecular field analysis, performed over 130 PBR ligands by means of the GRID/GOLPE methodology, led to a PLS model with both high fitting and predictive values (r2 = 0.898, Q2 = 0.761). The outcome from the 3D QSAR model and the GRID interaction fields computed on the putative endogenous PBR ligands DBI (Diazepam Binding Inhibitor) and TTN (Tetracontatetraneuropeptide) was used to identify the amino acids most probably involved in PBR binding. Three amino acids, bearing lipophilic side chains, were detected in DBI (Phe49, Leu47 and Met46) and in TTN (Phe33, Leu31 and Met30) as likely residues underlying receptor binding. Moreover, a qualitative comparison of the molecular electrostatic potentials of DBI, TTN and selected synthetic ligands indicated also similar electronic properties. Convergent results from the modeling studies of synthetic and endogenous ligands suggest a common binding mode to PBRs. This may help the rational design of new high affinity PBR ligands.

  3. Insights into Protein–Ligand Interactions: Mechanisms, Models, and Methods

    Directory of Open Access Journals (Sweden)

    Xing Du

    2016-01-01

    Full Text Available Molecular recognition, which is the process of biological macromolecules interacting with each other or various small molecules with a high specificity and affinity to form a specific complex, constitutes the basis of all processes in living organisms. Proteins, an important class of biological macromolecules, realize their functions through binding to themselves or other molecules. A detailed understanding of the protein–ligand interactions is therefore central to understanding biology at the molecular level. Moreover, knowledge of the mechanisms responsible for the protein-ligand recognition and binding will also facilitate the discovery, design, and development of drugs. In the present review, first, the physicochemical mechanisms underlying protein–ligand binding, including the binding kinetics, thermodynamic concepts and relationships, and binding driving forces, are introduced and rationalized. Next, three currently existing protein-ligand binding models—the “lock-and-key”, “induced fit”, and “conformational selection”—are described and their underlying thermodynamic mechanisms are discussed. Finally, the methods available for investigating protein–ligand binding affinity, including experimental and theoretical/computational approaches, are introduced, and their advantages, disadvantages, and challenges are discussed.

  4. Ligand efficiency-based support vector regression models for predicting bioactivities of ligands to drug target proteins.

    Science.gov (United States)

    Sugaya, Nobuyoshi

    2014-10-27

    The concept of ligand efficiency (LE) indices is widely accepted throughout the drug design community and is frequently used in a retrospective manner in the process of drug development. For example, LE indices are used to investigate LE optimization processes of already-approved drugs and to re-evaluate hit compounds obtained from structure-based virtual screening methods and/or high-throughput experimental assays. However, LE indices could also be applied in a prospective manner to explore drug candidates. Here, we describe the construction of machine learning-based regression models in which LE indices are adopted as an end point and show that LE-based regression models can outperform regression models based on pIC50 values. In addition to pIC50 values traditionally used in machine learning studies based on chemogenomics data, three representative LE indices (ligand lipophilicity efficiency (LLE), binding efficiency index (BEI), and surface efficiency index (SEI)) were adopted, then used to create four types of training data. We constructed regression models by applying a support vector regression (SVR) method to the training data. In cross-validation tests of the SVR models, the LE-based SVR models showed higher correlations between the observed and predicted values than the pIC50-based models. Application tests to new data displayed that, generally, the predictive performance of SVR models follows the order SEI > BEI > LLE > pIC50. Close examination of the distributions of the activity values (pIC50, LLE, BEI, and SEI) in the training and validation data implied that the performance order of the SVR models may be ascribed to the much higher diversity of the LE-based training and validation data. In the application tests, the LE-based SVR models can offer better predictive performance of compound-protein pairs with a wider range of ligand potencies than the pIC50-based models. This finding strongly suggests that LE-based SVR models are better than pIC50-based

  5. Using RosettaLigand for small molecule docking into comparative models.

    Directory of Open Access Journals (Sweden)

    Kristian W Kaufmann

    Full Text Available Computational small molecule docking into comparative models of proteins is widely used to query protein function and in the development of small molecule therapeutics. We benchmark RosettaLigand docking into comparative models for nine proteins built during CASP8 that contain ligands. We supplement the study with 21 additional protein/ligand complexes to cover a wider space of chemotypes. During a full docking run in 21 of the 30 cases, RosettaLigand successfully found a native-like binding mode among the top ten scoring binding modes. From the benchmark cases we find that careful template selection based on ligand occupancy provides the best chance of success while overall sequence identity between template and target do not appear to improve results. We also find that binding energy normalized by atom number is often less than -0.4 in native-like binding modes.

  6. Modeling RNA-ligand interactions: the Rev-binding element RNA-aminoglycoside complex.

    Science.gov (United States)

    Leclerc, F; Cedergren, R

    1998-01-15

    An approach to the modeling of ligand-RNA complexes has been developed by combining three-dimensional structure-activity relationship (3D-SAR) computations with a docking protocol. The ability of 3D-SAR to predict bound conformations of flexible ligands was first assessed by attempting to reconstruct the known, bound conformations of phenyloxazolines complexed with human rhinovirus 14 (HRV14) RNA. Subsequently, the same 3D-SAR analysis was applied to the identification of bound conformations of aminoglycosides which associate with the Rev-binding element (RBE) RNA. Bound conformations were identified by parsing ligand conformational data sets with pharmacophores determined by the 3D-SAR analysis. These "bioactive" structures were docked to the receptor RNA, and optimization of the complex was undertaken by extensive searching of ligand conformational space coupled with molecular dynamics computations. The similarity between the bound conformations of the ligand from the 3D-SAR analysis and those found in the docking protocol suggests that this methodology is valid for the prediction of bound ligand conformations and the modeling of the structure of the ligand-RNA complexes.

  7. 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.

  8. 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.

  9. 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. PMID:24019908

  10. Novel pyridine containing ligands as models for the copper centres in nitrite reductase

    CERN Document Server

    Arnold, P J

    2001-01-01

    This thesis is concerned with the synthesis of a series of novel pyridine containing ligands and their copper co-ordination chemistry. The aim was to design ligands which would produce copper complexes which model the active sites within certain copper-containing Nitrite Reductase enzymes. The first chapter reviews previous work in this area and details the promising nature of pyridine-containing ligands. The remainder of this thesis is concerned with the synthesis and characterisation of some novel pyridine-containing ligands and their copper chemistry. The synthetic routes developed during this work enabled tris(pyrid-2-yl)methylamine ligands to be produced and studied which were tripodal in form but which had a primary amine group at the cap which could be further elaborated. Additional substituents were also placed on the pyridine rings to investigate their impact on the chemistry of their copper complexes. These ligands showed a variety, counter ion dependent chemistry. The structures of number of the co...

  11. 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

    The rapidly increasing number of high-resolution X-ray structures of G-protein coupled receptors (GPCRs) creates a unique opportunity to employ comparative modeling and docking to provide valuable insight into the function and ligand binding determinants of novel receptors, to assist in virtual...... 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...

  12. Does natural variation in diversity affect biotic resistance?

    Science.gov (United States)

    Harrison, Susan; Cornell, Howard; Grace, James B.

    2015-01-01

    Theories linking diversity to ecosystem function have been challenged by the widespread observation of more exotic species in more diverse native communities. Few studies have addressed the key underlying process by dissecting how community diversity is shaped by the same environmental gradients that determine biotic and abiotic resistance to new invaders. In grasslands on highly heterogeneous soils, we used addition of a recent invader, competitor removal and structural equation modelling (SEM) to analyse soil influences on community diversity, biotic and abiotic resistance and invader success. Biotic resistance, measured by reduction in invader success in the presence of the resident community, was negatively correlated with species richness and functional diversity. However, in the multivariate SEM framework, biotic resistance was independent of all forms of diversity and was positively affected by soil fertility via community biomass. Abiotic resistance, measured by invader success in the absence of the resident community, peaked on infertile soils with low biomass and high community diversity. Net invader success was determined by biotic resistance, consistent with this invader's better performance on infertile soils in unmanipulated conditions. Seed predation added slightly to biotic resistance without qualitatively changing the results. Soil-related genotypic variation in the invader also did not affect the results. Synthesis. In natural systems, diversity may be correlated with invasibility and yet have no effect on either biotic or abiotic resistance to invasion. More generally, the environmental causes of variation in diversity should not be overlooked when considering the potential functional consequences of diversity.

  13. Plant biotic interactions

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    occurring after infestation by olive fly larvae. The last research article by Niu et al.(2016) describes a growth-promoting rhizobacterium that primes induced systemic resistance by suppressing a host R gene-targeting micro RNA pairs and activating host immune responses. This finding further supports the important roles of plant endogenous small RNAs in plant-pathogen interactions. Hailing Jin, Professor Special Issue Editor UC President’s Chair Director of Genetics, Genomics and Bioinformatics Graduate Program, Center for Plant Cell Biology, Institute for Integrative Genome Biology, University of California, Riverside, USA doi:10.1111/jipb.12476 ©2016 Institute of Botany, Chinese Academy of Sciences REFERENCES Alagna F, Kal enbach M, Pompa A, De Marchis F, Rao R, Baldwin IT, Bonaventure G, Baldoni L (2016) Olive fruits infested with olive fly larvae respond with an ethylene burst and the emission of specific volatiles. J Integr Plant Biol 58:413–425 Castiblanco LF, Sundin GW (2016) New insights on molecular regulation of biofilm formation in plant-associated bacteria. J Integr Plant Biol 58:362–372 da GraSca JV, Douhan GW, Halbert SE, Keremane ML, Lee RF, Vidalakis G, Zhao H (2016) Huanglongbing: An overview of a complex pathosystem ravaging the world’s citrus. J Integr Plant Biol 58:373–387 Giovino A, Martinel i F, Saia S (2016) Rhynchophorus ferrugineus attack affects a group of compounds rather than rearranging Phoenix canariensis metabolic pathways. J Integr Plant Biol 58:388–396 Huang J, Yang M, Zhang X (2016) The function of smal RNAs in plant biotic stress response. J Integr Plant Biol 58:312–327 Kaloshian I, Wal ing LL (2016) Hemipteran and dipteran pests: Effectors and plant host immune regulators. J Integr Plant Biol 58:350–361 Mermigka G, Verret F, Kalantidis K (2016) RNA silencing movement in plants. J Integr Plant Biol 58:328–342 Niu D, Xia J, Jiang C, Qi B, Ling X, Lin S, Zhang W, Guo J, Jin H, Zhao H (2016) Bacil us cereus AR156

  14. In Pursuit of Fully Flexible Protein-Ligand Docking: Modeling the Bilateral Mechanism of Binding.

    Science.gov (United States)

    Henzler, Angela M; Rarey, Matthias

    2010-03-15

    Modern structure-based drug design aims at accounting for the intrinsic flexibility of therapeutic relevant targets. Over the last few years a considerable amount of docking approaches that encounter this challenging problem has emerged. Here we provide the readership with an overview of established methods for fully flexible protein-ligand docking and current developments in the field. All methods are based on one of two fundamental models which describe the dynamic behavior of proteins upon ligand binding. Methods for ensemble docking (ED) model the protein conformational change before the ligand is placed, whereas induced-fit docking (IFD) optimizes the protein structure afterwards. A third category of docking approaches is formed by recent approaches that follow both concepts. This categorization allows to comprehensively discover strengths and weaknesses of the individual processes and to extract information for their applicability in real world docking scenarios.

  15. Modelling of trace metal uptake by roots taking into account complexation by exogenous organic ligands

    Science.gov (United States)

    Jean-Marc, Custos; Christian, Moyne; Sterckeman, Thibault

    2010-05-01

    The context of this study is phytoextraction of soil trace metals such as Cd, Pb or Zn. Trace metal transfer from soil to plant depends on physical and chemical processes such as minerals alteration, transport, adsorption/desorption, reactions in solution and biological processes including the action of plant roots and of associated micro-flora. Complexation of metal ions by organic ligands is considered to play a role on the availability of trace metals for roots in particular in the event that synthetic ligands (EDTA, NTA, etc.) are added to the soil to increase the solubility of the contaminants. As this role is not clearly understood, we wanted to simulate it in order to quantify the effect of organic ligands on root uptake of trace metals and produce a tool which could help in optimizing the conditions of phytoextraction.We studied the effect of an aminocarboxilate ligand on the absorption of the metal ion by roots, both in hydroponic solution and in soil solution, for which we had to formalize the buffer power for the metal. We assumed that the hydrated metal ion is the only form which can be absorbed by the plants. Transport and reaction processes were modelled for a system made up of the metal M, a ligand L and the metal complex ML. The Tinker-Nye-Barber model was adapted to describe the transport of solutes M, L and ML in the soil and absorption of M by the roots. This allowed to represent the interactions between transport, chelating reactions, absorption of the solutes at the root surface, root growth with time, in order to simulate metal uptake by a whole root system.Several assumptions were tested such as i) absorption of the metal by an infinite sink and according to a Michaelis-Menten kinetics, solutes transport by diffusion with and without ii) mass flow and iii) soil buffer power for the ligand L. In hydroponic solution (without soil buffer power), ligands decreased the trace metal flux towards roots, as they reduced the concentration of hydrated

  16. Directed Ligand Passage Over the Surface of Diffusion-Controlled Enzymes: A Cellular Automata Model

    CERN Document Server

    Ghaemi, M; Sarbolouki, M N; Ghaemi, Mehrdad; Rezaei-Ghaleh, Nasrollah; Sarbolouki, Mohammad-Nabi

    2004-01-01

    The rate-limiting step of some enzymatic reactions is a physical step, i.e. diffusion. The efficiency of such reactions can be improved through an increase in the arrival rate of the substrate molecules, e.g. by a directed passage of substrate (ligand) to active site after its random encounter with the enzyme surface. Herein, we introduce a cellular automata model simulating the ligand passage over the protein surface to its destined active site. The system is simulated using the lattice gas automata with probabilistic transition rules. Different distributions of amino acids over the protein surface are examined. For each distribution, the hydration pattern is achieved and the mean number of iteration steps needed for the ligand to arrive at the active site calculated. Comparison of results indicates that the rate at which ligand arrives at the active site is clearly affected by the distribution of amino acids outside the active side. Such a process can facilitate the ligand diffusion towards the active site ...

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

    Science.gov (United States)

    Baran, Ł.; Sokołowski, S.

    2017-02-01

    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.

  18. Computational quantum chemistry and adaptive ligand modeling in mechanistic QSAR.

    Science.gov (United States)

    De Benedetti, Pier G; Fanelli, Francesca

    2010-10-01

    Drugs are adaptive molecules. They realize this peculiarity by generating different ensembles of prototropic forms and conformers that depend on the environment. Among the impressive amount of available computational drug discovery technologies, quantitative structure-activity relationship approaches that rely on computational quantum chemistry descriptors are the most appropriate to model adaptive drugs. Indeed, computational quantum chemistry descriptors are able to account for the variation of the intramolecular interactions of the training compounds, which reflect their adaptive intermolecular interaction propensities. This enables the development of causative, interpretive and reasonably predictive quantitative structure-activity relationship models, and, hence, sound chemical information finalized to drug design and discovery.

  19. Proneurogenic Ligands Defined by Modeling Developing Cortex Growth Factor Communication Networks.

    Science.gov (United States)

    Yuzwa, Scott A; Yang, Guang; Borrett, Michael J; Clarke, Geoff; Cancino, Gonzalo I; Zahr, Siraj K; Zandstra, Peter W; Kaplan, David R; Miller, Freda D

    2016-09-01

    The neural stem cell decision to self-renew or differentiate is tightly regulated by its microenvironment. Here, we have asked about this microenvironment, focusing on growth factors in the embryonic cortex at a time when it is largely comprised of neural precursor cells (NPCs) and newborn neurons. We show that cortical NPCs secrete factors that promote their maintenance, while cortical neurons secrete factors that promote differentiation. To define factors important for these activities, we used transcriptome profiling to identify ligands produced by NPCs and neurons, cell-surface mass spectrometry to identify receptors on these cells, and computational modeling to integrate these data. The resultant model predicts a complex growth factor environment with multiple autocrine and paracrine interactions. We tested this communication model, focusing on neurogenesis, and identified IFNγ, Neurturin (Nrtn), and glial-derived neurotrophic factor (GDNF) as ligands with unexpected roles in promoting neurogenic differentiation of NPCs in vivo.

  20. Macromolecular Modelling and Docking Simulations for the Discovery of Selective GPER Ligands.

    Science.gov (United States)

    Rosano, Camillo; Ponassi, Marco; Santolla, Maria Francesca; Pisano, Assunta; Felli, Lamberto; Vivacqua, Adele; Maggiolini, Marcello; Lappano, Rosamaria

    2016-01-01

    Estrogens influence multiple physiological processes and are implicated in many diseases as well. Cellular responses to estrogens are mainly mediated by the estrogen receptors (ER)α and ERβ, which act as ligand-activated transcription factors. Recently, a member of the G protein-coupled receptor (GPCR) superfamily, namely GPER/GPR30, has been identified as a further mediator of estrogen signalling in different pathophysiological conditions, including cancer. Today, computational methods are commonly used in all areas of health science research. Among these methods, virtual ligand screening has become an established technique for hit discovery and optimization. The absence of an established three-dimensional structure of GPER promoted studies of structure-based drug design in order to build reliable molecular models of this receptor. Here, we discuss the results obtained through the structure-based virtual ligand screening for GPER, which allowed the identification and synthesis of different selective agonist and antagonist moieties. These compounds led significant advances in our understanding of the GPER function at the cellular, tissue, and organismal levels. In particular, selective GPER ligands were critical toward the evaluation of the role elicited by this receptor in several pathophysiological conditions, including cancer. Considering that structure-based approaches are fundamental in drug discovery, future research breakthroughs with the aid of computer-aided molecular design and chemo-bioinformatics could generate a new class of drugs that, acting through GPER, would be useful in a variety of diseases as well as in innovative anticancer strategies.

  1. Model for Adsorption of Ligands to Colloidal Quantum Dots with Concentration-Dependent Surface Structure

    Energy Technology Data Exchange (ETDEWEB)

    Morris-cohen, Adam J [Northwestern University, Evanston; Vasilenko, Vladislav [Northwestern University, Evanston; Amin, Victor A [Northwestern University, Evanston; Reuter, Matthew G [ORNL; Weiss, Emily A [Northwestern University, Evanston

    2012-01-01

    A study of the adsorption equilibrium of solution-phase CdS quantum dots (QDs) and acid-derivatized viologen ligands (N-[1-heptyl],N'-[3-carboxypropyl]-4,4'-bipyridinium dihexafluorophosphate, V{sup 2+}) reveals that the structure of the surfaces of the QDs depends on their concentration. This adsorption equilibrium is monitored through quenching of the photoluminescence of the QDs by V{sup 2+} upon photoinduced electron transfer. When modeled with a simple Langmuir isotherm, the equilibrium constant for QD-V{sup 2+} adsorption, K{sub a}, increases from 6.7 x 10{sup 5} to 8.6 x 10{sup 6} M{sup -1} upon decreasing the absolute concentration of the QDs from 1.4 x 10{sup 6} to 5.1 x 10{sup 8} M. The apparent increase in K{sub a} upon dilution results from an increase in the mean number of available adsorption sites per QD from 1.1 (for [QD] = 1.4 x 10{sup 6} M) to 37 (for [QD] = 5.1 x 10{sup 8} M) through desorption of native ligands from the surfaces of the QDs and through disaggregation of soluble QD clusters. A new model based on the Langmuir isotherm that treats both the number of adsorbed ligands per QD and the number of available binding sites per QD as binomially distributed quantities is described. This model yields a concentration-independent value for K{sub a} of 8.7 x 10{sup 5} M{sup -1} for the QD-V{sup 2+} system and provides a convenient means for quantitative analysis of QD-ligand adsorption in the presence of competing surface processes.

  2. Ligand-receptor affinities computed by an adapted linear interaction model for continuum electrostatics and by protein conformational averaging.

    Science.gov (United States)

    Nunes-Alves, Ariane; Arantes, Guilherme Menegon

    2014-08-25

    Accurate calculations of free energies involved in small-molecule binding to a receptor are challenging. Interactions between ligand, receptor, and solvent molecules have to be described precisely, and a large number of conformational microstates has to be sampled, particularly for ligand binding to a flexible protein. Linear interaction energy models are computationally efficient methods that have found considerable success in the prediction of binding free energies. Here, we parametrize a linear interaction model for implicit solvation with coefficients adapted by ligand and binding site relative polarities in order to predict ligand binding free energies. Results obtained for a diverse series of ligands suggest that the model has good predictive power and transferability. We also apply implicit ligand theory and propose approximations to average contributions of multiple ligand-receptor poses built from a protein conformational ensemble and find that exponential averages require proper energy discrimination between plausible binding poses and false-positives (i.e., decoys). The linear interaction model and the averaging procedures presented can be applied independently of each other and of the method used to obtain the receptor structural representation.

  3. Synthesis and Characterization of Porphyrin.Trisbenzimidazole Dinucleating Ligand and Its Heterodinuclear Complex as CcO Active Site Model

    Institute of Scientific and Technical Information of China (English)

    LuWei-bing; WangCun-xin; DengLi-zhi; ZhouXiao-hai; RenJian-guo

    2003-01-01

    A new dinucleating ligand having two metalbinding sites has been designed and synthesized as model ligand for Cytochrome c Oxidase. The corresponding heterodinuclear complex, as an active site model of Cytochrome c Oxidase, consisting of a porphyrinatocobalt compound covalently linked with a copper derivative of tris(2-benzimidazylmethyl)amine bearing three benzimidazole ligands for copper was synthesized and spectroscopically characterized. The spectra data suggest that there are interactions between the cobalt and copper coordination units. The cobalt is coordinated to four central nitrogens of the porphyrin and the copper has pentacoordinate geometry with the four tertiary amine nitrogens and a chloride.

  4. Uranium isotopes fingerprint biotic reduction

    Science.gov (United States)

    Stylo, Malgorzata; Neubert, Nadja; Wang, Yuheng; Monga, Nikhil; Romaniello, Stephen J.; Weyer, Stefan; Bernier-Latmani, Rizlan

    2015-01-01

    Knowledge of paleo-redox conditions in the Earth’s history provides a window into events that shaped the evolution of life on our planet. The role of microbial activity in paleo-redox processes remains unexplored due to the inability to discriminate biotic from abiotic redox transformations in the rock record. The ability to deconvolute these two processes would provide a means to identify environmental niches in which microbial activity was prevalent at a specific time in paleo-history and to correlate specific biogeochemical events with the corresponding microbial metabolism. Here, we demonstrate that the isotopic signature associated with microbial reduction of hexavalent uranium (U), i.e., the accumulation of the heavy isotope in the U(IV) phase, is readily distinguishable from that generated by abiotic uranium reduction in laboratory experiments. Thus, isotope signatures preserved in the geologic record through the reductive precipitation of uranium may provide the sought-after tool to probe for biotic processes. Because uranium is a common element in the Earth’s crust and a wide variety of metabolic groups of microorganisms catalyze the biological reduction of U(VI), this tool is applicable to a multiplicity of geological epochs and terrestrial environments. The findings of this study indicate that biological activity contributed to the formation of many authigenic U deposits, including sandstone U deposits of various ages, as well as modern, Cretaceous, and Archean black shales. Additionally, engineered bioremediation activities also exhibit a biotic signature, suggesting that, although multiple pathways may be involved in the reduction, direct enzymatic reduction contributes substantially to the immobilization of uranium. PMID:25902522

  5. 猪切口疝模型的建立及使用生物型补片修补的研究%Empirical study of establishing piglet model of incisional hernia and repairing the hernia with biotic patch

    Institute of Scientific and Technical Information of China (English)

    邓美海; 林楠; 胡昆鹏; 钟跃思; 胡啷; 徐国风; 黄慧妍

    2008-01-01

    Objective To establish a piglet model of incisional hernia and explore the feasibility of repairing the hernia with biotic patch. Methods The model of incisional hernia was established by the defect of abdominal muscle and fascia made on the epigastric zone of piglet. The incisional hernias were repaired with biotic patch tension-free in the one-stage operation and second-stage operation respectively. The complication of infection of incisional wound and recurrence of hernia, pathological change of the patch were investigated. Results The model of incisional hernia was established one week postoperatively and typically. There was not oceurrence of incisional hernia in the one-stage operation group and the incisional hernias were repaired successfully in 6 piglets of the second-stage operation group,but two piglets' repair operations failed because of infection of incisional wound and discharging of the patch. The collagen of the biotic patch deformed and was absorbed and replaced by connective tissue gradually, then the patch turned to be dense connective tissue and tendinous membrane by the assimilation of piglet. Conclusion The model of incisional hernia established in this study is successful and of good repeatability. It is feasible to repair the incisional hernia of piglet with biotic patch, and the biotic patch could be an ideal patch for repairing abdominal external hernia.%目的 建立小猪切口疝模型并探讨生物型疝补片在切口疝修补治疗中应用的可行性.方法 通过在小猪上腹部制作一个肌肉筋膜层缺损区的方法 建立切口疝模型,分别采用二期修补和一期修补的方式,使用生物型补片无张力修补切口疝.观察术后切口感染、疝复发等并发症及补片组织的病理学变化.结果 术后1周时可获得典型的切口疝模型;一期修补组未发生切口疝,二期修补组6只小猪成功,2只因切口感染、补片排出而失败.术后6个月内观察,生物补片的胶原变

  6. Evolution of off-lattice model proteins under ligand binding constraints

    Science.gov (United States)

    Nelson, Erik D.; Grishin, Nick V.

    2016-08-01

    We investigate protein evolution using an off-lattice polymer model evolved to imitate the behavior of small enzymes. Model proteins evolve through mutations to nucleotide sequences (including insertions and deletions) and are selected to fold and maintain a specific binding site compatible with a model ligand. We show that this requirement is, in itself, sufficient to maintain an ordered folding domain, and we compare it to the requirement of folding an ordered (but otherwise unrestricted) domain. We measure rates of amino acid change as a function of local environment properties such as solvent exposure, packing density, and distance from the active site, as well as overall rates of sequence and structure change, both along and among model lineages in star phylogenies. The model recapitulates essentially all of the behavior found in protein phylogenetic analyses, and predicts that amino acid substitution rates vary linearly with distance from the binding site.

  7. Successful virtual screening for a submicromolar antagonist of the neurokinin-1 receptor based on a ligand-supported homology model.

    Science.gov (United States)

    Evers, Andreas; Klebe, Gerhard

    2004-10-21

    The neurokinin-1 (NK1) receptor belongs to the family of G-protein-coupled receptors (GPCRs), which represents one of the most relevant target families in small-molecule drug design. In this paper, we describe a homology modeling of the NK1 receptor based on the high-resolution X-ray structure of rhodopsin and the successful virtual screening based on this protein model. The NK1 receptor model has been generated using our new MOBILE (modeling binding sites including ligand information explicitly) approach. Starting with preliminary homology models, it generates improved models of the protein binding pocket together with bound ligands. Ligand information is used as an integral part in the homology modeling process. For the construction of the NK1 receptor, antagonist CP-96345 was used to restrain the modeling. The quality of the obtained model was validated by probing its ability to accommodate additional known NK1 antagonists from structurally diverse classes. On the basis of the generated model and on the analysis of known NK1 antagonists, a pharmacophore model was deduced, which subsequently guided the 2D and 3D database search with UNITY. As a following step, the remaining hits were docked into the modeled binding pocket of the NK1 receptor. Finally, seven compounds were selected for biochemical testing, from which one showed affinity in the submicromolar range. Our results suggest that ligand-supported homology models of GPCRs may be used as effective platforms for structure-based drug design.

  8. Computational approaches to modeling receptor flexibility upon ligand binding: Application to interfacially activated enzymes

    DEFF Research Database (Denmark)

    Wade, R.C.; Sobolev, V.; Ortiz, A.R. .

    1998-01-01

    Receptors generally undergo conformational change upon ligand binding. We describe how fairly simple techniques may be used in docking and design studies to account for some of the changes in the conformations of proteins on ligand binding. Simulations of protein-ligand interactions that give...... a more complete description of the dynamics important for ligand binding are then discussed. These methods are illustrated for phospholipase A(2) and lipase, enzymes that both undergo interfacial activation....

  9. Iron(III) complexes of certain tetradentate phenolate ligands as functional models for catechol dioxygenases

    Indian Academy of Sciences (India)

    Mallayan Palaniandavar; Marappan Velusamy; Ramasamy Mayilmurugan

    2006-11-01

    Catechol 1,2-dioxygenase (CTD) and protocatechuate 3,4-dioxygenase (PCD) are bacterial non-heme iron enzymes, which catalyse the oxidative cleavage of catechols to cis, cis-muconic acids with the incorporation of molecular oxygen via a mechanism involving a high-spin ferric centre. The iron(III) complexes of tripodal phenolate ligands containing N3O and N2O2 donor sets represent the metal binding region of the iron proteins. In our laboratory iron(III) complexes of mono- and bisphenolate ligands have been studied successfully as structural and functional models for the intradiol-cleaving catechol dioxygenase enzymes. The single crystal X-ray crystal structures of four of the complexes have been determined. One of the bis-phenolato complexes contains a FeN2O2Cl chromophore with a novel trigonal bipyramidal coordination geometry. The Fe-O-C bond angle of 136.1° observed for one of the iron(III) complex of a monophenolate ligand is very similar to that in the enzymes. The importance of the nearby sterically demanding coordinated -NMe2 group has been established and implies similar stereochemical constraints from the other ligated amino acid moieties in the 3,4-PCD enzymes, the enzyme activity of which is traced to the difference in the equatorial and axial Fe-O(tyrosinate) bonds (Fe-O-C, 133, 148°). The nature of heterocyclic rings of the ligands and the methyl substituents on them regulate the electronic spectral features, FeIII/FeII redox potentials and catechol cleavage activity of the complexes. Upon interacting with catecholate anions, two catecholate to iron(III) charge transfer bands appear and the low energy band is similar to that of catechol dioxygenase-substrate complex. Four of the complexes catalyze the oxidative cleavage of H2DBC by molecular oxygen to yield intradiol cleavage products. Remarkably, the more basic N-methylimidazole ring in one of the complexes facilitates the rate-determining productreleasing phase of the catalytic reaction. The present

  10. Modeling multivalent ligand-receptor interactions with steric constraints on configurations of cell surface receptor aggregates

    Energy Technology Data Exchange (ETDEWEB)

    Monine, Michael [Los Alamos National Laboratory; Posner, Richard [TRANSLATION GENOMICS RESAEARCH INSTITUTE; Savage, Paul [BYU; Faeder, James [UNIV OF PITTSBURGH; Hlavacek, William S [UNM

    2008-01-01

    Signal transduction generally involves multivalent protein-protein interactions, which can produce various protein complexes and post-translational modifications. The reaction networks that characterize these interactions tend to be so large as to challenge conventional simulation procedures. To address this challenge, a kinetic Monte Carlo (KMC) method has been developed that can take advantage of a model specification in terms of reaction rules for molecular interactions. A set of rules implicitly defines the reactions that can occur as a result of the interactions represented by the rules. With the rule-based KMC method, explicit generation of the underlying chemical reaction network implied by rules is avoided. Here, we apply and extend this method to characterize the interactions of a trivalent ligand with a bivalent cell-surface receptor. This system is also studied experimentally. We consider the following kinetic models: an equivalent-site model, an extension of this model, which takes into account steric constraints on the configurations of receptor aggregates, and finally, a model that accounts for cyclic receptor aggregates. Simulation results for the equivalent-site model are consistent with an equilibrium continuum model. Using these models, we investigate the effects of steric constraints and the formation of cyclic aggregates on the kinetics and equilibria of small and large aggregate formation and the percolation phase transition that occurs in this system.

  11. Biotic and abiotic factors predicting the global distribution and population density of an invasive large mammal

    Science.gov (United States)

    Lewis, Jesse S.; Farnsworth, Matthew L.; Burdett, Chris L.; Theobald, David M.; Gray, Miranda; Miller, Ryan S.

    2017-01-01

    Biotic and abiotic factors are increasingly acknowledged to synergistically shape broad-scale species distributions. However, the relative importance of biotic and abiotic factors in predicting species distributions is unclear. In particular, biotic factors, such as predation and vegetation, including those resulting from anthropogenic land-use change, are underrepresented in species distribution modeling, but could improve model predictions. Using generalized linear models and model selection techniques, we used 129 estimates of population density of wild pigs (Sus scrofa) from 5 continents to evaluate the relative importance, magnitude, and direction of biotic and abiotic factors in predicting population density of an invasive large mammal with a global distribution. Incorporating diverse biotic factors, including agriculture, vegetation cover, and large carnivore richness, into species distribution modeling substantially improved model fit and predictions. Abiotic factors, including precipitation and potential evapotranspiration, were also important predictors. The predictive map of population density revealed wide-ranging potential for an invasive large mammal to expand its distribution globally. This information can be used to proactively create conservation/management plans to control future invasions. Our study demonstrates that the ongoing paradigm shift, which recognizes that both biotic and abiotic factors shape species distributions across broad scales, can be advanced by incorporating diverse biotic factors. PMID:28276519

  12. Molecular modeling, structural analysis and identification of ligand binding sites of trypanothione reductase from Leishmania mexicana

    Directory of Open Access Journals (Sweden)

    Ozal Mutlu

    2013-01-01

    Full Text Available Background & objectives: Trypanothione reductase (TR is a member of FAD-dependent NADPH oxidoreductase protein family and it is a key enzyme which connects the NADPH and the thiol-based redox system. Inhibition studies indicate that TR is an essential enzyme for parasite survival. Therefore, it is an attractive target enzyme for novel drug candidates. There is no structural model for TR of Leishmania mexicana (LmTR in the protein databases. In this work, 3D structure of TR from L. mexicana was identified by template-based in silico homology modeling method, resultant model was validated, structurally analyzed and possible ligand binding pockets were identified. Methods: For computational molecular modeling study, firstly, template was identified by BLAST search against PDB database. Multiple alignments were achieved by ClustalW2. Molecular modeling of LmTR was done and possible drug targeting sites were identified. Refinement of the model was done by performing local energy minimization for backbone, hydrogen and side chains. Model was validated by web-based servers. Results: A reliable 3D model for TR from L. mexicana was modeled by using L. infantum trypanothione reductase (LiTR as a template. RMSD results according to C-alpha, visible atoms and backbone were 0.809 Å, 0.732 Å and 0.728 Å respectively. Ramachandran plot indicates that model shows an acceptable stereochemistry. Conclusion: Modeled structure of LmTR shows high similarity with LiTR based on overall structural features like domains and folding patterns. Predicted structure will provide a source for the further docking studies of various peptide-based inhibitors.

  13. Proteochemometric modeling of the bioactivity spectra of HIV-1 protease inhibitors by introducing protein-ligand interaction fingerprint.

    Directory of Open Access Journals (Sweden)

    Qi Huang

    Full Text Available HIV-1 protease is one of the main therapeutic targets in HIV. However, a major problem in treatment of HIV is the rapid emergence of drug-resistant strains. It should be particularly helpful to clinical therapy of AIDS if one method can be used to predict antivirus capability of compounds for different variants. In our study, proteochemometric (PCM models were created to study the bioactivity spectra of 92 chemical compounds with 47 unique HIV-1 protease variants. In contrast to other PCM models, which used Multiplication of Ligands and Proteins Descriptors (MLPD as cross-term, one new cross-term, i.e. Protein-Ligand Interaction Fingerprint (PLIF was introduced in our modeling. With different combinations of ligand descriptors, protein descriptors and cross-terms, nine PCM models were obtained, and six of them achieved good predictive abilities (Q(2(test>0.7. These results showed that the performance of PCM models could be improved when ligand and protein descriptors were complemented by the newly introduced cross-term PLIF. Compared with the conventional cross-term MLPD, the newly introduced PLIF had a better predictive ability. Furthermore, our best model (GD & P & PLIF: Q(2(test = 0.8271 could select out those inhibitors which have a broad antiviral activity. As a conclusion, our study indicates that proteochemometric modeling with PLIF as cross-term is a potential useful way to solve the HIV-1 drug-resistant problem.

  14. Modeling the construction of polymeric adsorbent media: Effects of counter-ions on ligand immobilization and pore structure

    Science.gov (United States)

    Riccardi, Enrico; Wang, Jee-Ching; Liapis, Athanasios I.

    2014-02-01

    Molecular dynamics modeling and simulations are employed to study the effects of counter-ions on the dynamic spatial density distribution and total loading of immobilized ligands as well as on the pore structure of the resultant ion exchange chromatography adsorbent media. The results show that the porous adsorbent media formed by polymeric chain molecules involve transport mechanisms and steric resistances which cause the charged ligands and counter-ions not to follow stoichiometric distributions so that (i) a gradient in the local nonelectroneutrality occurs, (ii) non-uniform spatial density distributions of immobilized ligands and counter-ions are formed, and (iii) clouds of counter-ions outside the porous structure could be formed. The magnitude of these counter-ion effects depends on several characteristics associated with the size, structure, and valence of the counter-ions. Small spherical counter-ions with large valence encounter the least resistance to enter a porous structure and their effects result in the formation of small gradients in the local nonelectroneutrality, higher ligand loadings, and more uniform spatial density distributions of immobilized ligands, while the formation of exterior counter-ion clouds by these types of counter-ions is minimized. Counter-ions with lower valence charges, significantly larger sizes, and elongated shapes, encounter substantially greater steric resistances in entering a porous structure and lead to the formation of larger gradients in the local nonelectroneutrality, lower ligand loadings, and less uniform spatial density distributions of immobilized ligands, as well as substantial in size exterior counter-ion clouds. The effects of lower counter-ion valence on pore structure, local nonelectroneutrality, spatial ligand density distribution, and exterior counter-ion cloud formation are further enhanced by the increased size and structure of the counter-ion. Thus, the design, construction, and functionality of

  15. Ligand and structure-based classification models for Prediction of P-glycoprotein inhibitors

    DEFF Research Database (Denmark)

    Klepsch, Freya; Poongavanam, Vasanthanathan; Ecker, Gerhard Franz

    2014-01-01

    The ABC transporter P-glycoprotein (P-gp) actively transports a wide range of drugs and toxins out of cells, and is therefore related to multidrug resistance and the ADME profile of therapeutics. Thus, development of predictive in silico models for the identification of P-gp inhibitors is of great...... interest in the field of drug discovery and development. So far in-silico P-gp inhibitor prediction was dominated by ligand-based approaches, due to the lack of high-quality structural information about P-gp. The present study aims at comparing the P-gp inhibitor/non-inhibitor classification performance...... an algorithm based on Euclidean distance. Results show that random forest and SVM performed best for classification of P-gp inhibitors and non-inhibitors, correctly predicting 73/75 % of the external test set compounds. Classification based on the docking experiments using the scoring function Chem...

  16. Dynamic ligand-based pharmacophore modeling and virtual screening to identify mycobacterial cyclopropane synthase inhibitors

    Indian Academy of Sciences (India)

    CHINMAYEE CHOUDHURY; U DEVA PRIYAKUMAR; G NARAHARI SASTRY

    2016-05-01

    Multidrug resistance in Mycobacterium tuberculosis (M. Tb) and its coexistence with HIV arethe biggest therapeutic challenges in anti-M. Tb drug discovery. The current study reports a Virtual Screening(VS) strategy to identify potential inhibitors of Mycobacterial cyclopropane synthase (CmaA1), an importantM. Tb target considering the above challenges. Five ligand-based pharmacophore models were generatedfrom 40 different conformations of the cofactors of CmaA1 taken from molecular dynamics (MD) simulationstrajectories of CmaA1. The screening abilities of these models were validated by screening 23 inhibitors and1398 non-inhibitors of CmaA1. A VS protocol was designed with four levels of screening i.e., ligand-basedpharmacophore screening, structure-based pharmacophore screening, docking and absorption, distribution,metabolism, excretion and the toxicity (ADMET) filters. In an attempt towards repurposing the existing drugsto inhibit CmaA1, 6,429 drugs reported in DrugBank were considered for screening. To find compounds thatinhibit multiple targets of M. Tb as well as HIV, we also chose 701 and 11,109 compounds showing activitybelow 1 μM range on M. Tb and HIV cell lines, respectively, collected from ChEMBL database. Thus, a totalof 18,239 compounds were screened against CmaA1, and 12 compounds were identified as potential hits forCmaA1 at the end of the fourth step. Detailed analysis of the structures revealed these compounds to interactwith key active site residues of CmaA1.

  17. Design of protein-ligand binding based on the molecular-mechanics energy model.

    Science.gov (United States)

    Boas, F Edward; Harbury, Pehr B

    2008-07-04

    While the molecular-mechanics field has standardized on a few potential energy functions, computational protein design efforts are based on potentials that are unique to individual laboratories. Here we show that a standard molecular-mechanics potential energy function without any modifications can be used to engineer protein-ligand binding. A molecular-mechanics potential is used to reconstruct the coordinates of various binding sites with an average root-mean-square error of 0.61 A and to reproduce known ligand-induced side-chain conformational shifts. Within a series of 34 mutants, the calculation can always distinguish between weak (K(d)>1 mM) and tight (K(d)mechanics potential is used to redesign a ribose-binding site. Out of a search space of 2 x 10(12) sequences, the calculation selects a point mutant of the native protein as the top solution (experimental K(d)=17 microM) and the native protein as the second best solution (experimental K(d)=210 nM). The quality of the predictions depends on the accuracy of the generalized Born electrostatics model, treatment of protonation equilibria, high-resolution rotamer sampling, a final local energy minimization step, and explicit modeling of the bound, unbound, and unfolded states. The application of unmodified molecular-mechanics potentials to protein design links two fields in a mutually beneficial way. Design provides a new avenue for testing molecular-mechanics energy functions, and future improvements in these energy functions will presumably lead to more accurate design results.

  18. Synthesis and Characterization of Porphyrin- Trisbenzimidazole Dinucleating Ligand and Its Heterodinuclear Complex as CcO Active Site Model

    Institute of Scientific and Technical Information of China (English)

    Lu Wei-bing; Wang Cun-xin; Deng Li-zhi; Zhou Xiao-hai; Ren Jian-guo

    2003-01-01

    A new dinucleating ligand having two metal-binding sites has been designed and synthesized as model lig-and for Cytochrome c Oxidase. The corresponding heterodi-nuclear complex, as an active site model of Cytochrome c Oxi-dase, consisting of a porphyrinatocobalt compound covalently linked with a copper derivative of tris(2-benzimidazylmethyl)amine bearing three benzimidazole ligands for copper was syn-thesized and spectroscopically characterized. The spectra data suggest that there are interactions between the cobalt and copper coordination units. The cobalt is coordinated to four central nitrogens of the porphyrin and the copper has pentaeo-ordinate geometry with the four tertiary amine nitrogens and a chloride.

  19. Ligand and Charge Distribution (LCD) model for the description of fulvic acid adsorption to goethite.

    Science.gov (United States)

    Weng, Liping; Van Riemsdijk, Willem H; Koopal, Luuk K; Hiemstra, Tjisse

    2006-10-15

    The LCD model (Ligand and Charge Distribution) has recently been proposed to describe the adsorption of humic substances to oxides, in which the CD-MUSIC model and the NICA model for ion binding to respectively oxides and humic substances are integrated. In this paper, the LCD model is improved by applying the ADAPT model (ADsorption and AdaPTation) to calculate the equilibrium distribution of the humic substances based on the change of the average chemical state of the particles. The improved LCD model is applied to calculate the adsorption of fulvic acid (Strichen) to goethite, in which it is assumed that the carboxylic type of groups of fulvic acid can form innersphere complexes with the surface sites. The charge of the carboxylic groups in the innersphere complexes is distributed between the 0- and d-plane, whereas the charge of the other carboxylic and phenolic groups is located in the d-plane. The average distribution of the carboxylic and phenolic groups among their various chemical states (carboxylic groups: innersphere complex, protonated and deprotonated; phenolic groups: protonated and deprotonated) depends on pH, ionic strength and loading, and are the outcome of the model. The calculation shows that the LCD model can describe sufficiently the effects of pH, ionic strength and loading on the adsorption of fulvic acid, using one adjustable parameter (logK (S,1)). The model calculations indicate that the chemical complexation between fulvic acid and goethite is the main driving force of the adsorption, while the electrostatic repulsion between the particles and the surface is the major limiting factor for further adsorption.

  20. Comparative effects of α2δ-1 ligands in mouse models of colonic hypersensitivity

    Science.gov (United States)

    Meleine, Mathieu; Boudieu, Ludivine; Gelot, Agathe; Muller, Emilie; Lashermes, Amandine; Matricon, Julien; Silberberg, Celine; Theodorou, Vassilia; Eschalier, Alain; Ardid, Denis; Carvalho, Frederic A

    2016-01-01

    AIM To investigate anti-hypersensitive effects of α2δ-1 ligands in non-inflammatory and inflammation-associated colonic hypersensitivity (CHS) mouse models. METHODS To induce an inflammation-associated CHS, 1% dextran sulfate sodium (DSS) was administered to C57Bl/6J male mice, in drinking water, for 14 d. Regarding the non-inflammatory neonatal maternal separation (NMS) -induced CHS model, wild-type C57BI/6J pups were isolated from their mother from day 2 to day 14 (P2 to P14), three hours per day (from 9:00 a.m. to 12:00 p.m.). Colorectal distension was performed by inflating distension probe from 20 μL to 100 μL by 20 μL increment step every 10 s. After a first colorectal distension (CRD), drugs were administered subcutaneously, in a cumulative manner, (Gabapentin at 30 mg/kg and 100 mg/kg; Pregabalin at 10 mg/kg and 30 mg/kg; Carbamazepine at 10 mg/kg and 30 mg/kg) and a second CRD was performed one hour after each injection. RESULTS The visceromotor response (VMR) to CRD was increased by our NMS paradigm protocol in comparison to non-handled (NH) mice, considering the highest distension volumes (80 μL: 0.783 ± 0.056 mV/s vs 0.531 ± 0.034 mV/s, P NMS and NH mice, respectively). In the inflammation-associated CHS, DSS-treated mice showed a dramatic and significant increase in VMR at 60 and 80 μL distension volumes when compared to control mice (60 μL: 0.920 ± 0.079 mV/s vs 0.426 ± 0.100 mV/s P NMS-induced CHS model for the acute subcutaneous administration of the highest cumulative dose (30 mg/kg) and significantly reduced CHS in low-dose DSS-treated mice in a dose-dependent manner. Finally, the percent decrease of AUC induced by acute GBP or Pregabalin treatment were higher in the inflammatory DSS-induced CHS model in comparison to the non-inflammatory NMS-induced CHS model. CONCLUSION This preclinical study demonstrates α2δ-1 ligands efficacy on inflammation-associated CHS, highlighting their potential clinical interest in patients with chronic

  1. Evaluation of immobilized metal-ion affinity chromatography and electrospray ionization tandem mass spectrometry for recovery and identification of copper(II-binding ligands in seawater using the model ligand 8-hydroxyquinoline

    Directory of Open Access Journals (Sweden)

    Richard L Nixon

    2016-11-01

    Full Text Available Complexation by organic ligands dominates the speciation of iron (Fe, copper (Cu, and other bioactive trace metals in seawater, controlling their bioavailability and distribution in the marine environment. Several classes of high-affinity Fe-binding ligands (siderophores have been identified in seawater but the chemical structures of marine Cu-complexing ligands remain unknown. Immobilized metal-ion affinity chromatography (IMAC allows Cu ligands to be isolated from bulk dissolved organic matter (DOM in seawater and separated into fractions which can be characterized independently using electrochemical and spectroscopic techniques. Attempts have been made to combine IMAC with electrospray ionization mass spectrometry (ESI-MS to characterize marine Cu ligands, but results have proven inconclusive due to the lack of tandem mass spectrometry (MS/MS data to confirm ligand recovery. We used 8-hydroxyquinoline (8-HQ, a well-characterized model ligand that forms strong 1:2 metal:ligand complexes with Cu2+ at pH 8 (log β2 = 18.3, to evaluate Cu(II-IMAC and ESI-MS/MS for recovery and identification of copper(II-complexing ligands in seawater. One-litre samples of 0.45µm-filtered surface seawater were spiked with 8-HQ at low concentrations (up to 100 nM and fractionated by IMAC. Fractions eluted with acidified artificial seawater were desalted and re-suspended in methanol via solid-phase extraction (SPE to obtain extracts suitable for ESI-MS analysis. Recovery of 8-HQ by Cu(II-IMAC was confirmed unambiguously by MS/MS and found to average 81% based upon accurate quantitation via multiple reaction monitoring (MRM. Cu(II-IMAC fractionation of unspiked seawater using multiple UV detection wavelengths suggests an optimal fraction size of 2 mL for isolating and analyzing Cu ligands with similar properties.

  2. An Introductory Classroom Exercise on Protein Molecular Model Visualization and Detailed Analysis of Protein-Ligand Binding

    Science.gov (United States)

    Poeylaut-Palena, Andres, A.; de los Angeles Laborde, Maria

    2013-01-01

    A learning module for molecular level analysis of protein structure and ligand/drug interaction through the visualization of X-ray diffraction is presented. Using DeepView as molecular model visualization software, students learn about the general concepts of protein structure. This Biochemistry classroom exercise is designed to be carried out by…

  3. DFT modeling and spectroscopic study of metal ligand bonding in La(III) complex of coumarin-3-carboxylic acid

    Science.gov (United States)

    Mihaylov, Tz.; Trendafilova, N.; Kostova, I.; Georgieva, I.; Bauer, G.

    2006-09-01

    The binding mode of coumarin-3-carboxylic acid (HCCA) to La(III) is elucidated at experimental and theoretical level. The complexation ability of the deprotonated ligand (CCA -) to La(III) is studied using elemental analysis, DTA and TGA data as well as FTIR, 1H NMR and 13C NMR spectra. The experimental data suggest the complex formula La(CCA) 2(NO 3)(H 2O) 2. B3LYP, BHLYP, B3P86, B3PW91, PW91P86 and MPW1PW91 functionals are tested for geometry and frequency calculations of the neutral ligand and all of them show bond length deviations bellow 1%. B3LYP/6-31G(d) level combined with large quasi-relativistic effective core potential for lanthanum is selected to describe the molecular, electronic and vibrational structures as well as the conformational behavior of HCCA, CCA - and La-CCA complex. The metal-ligand binding mode is predicted through molecular modeling and energy estimation of different La-CCA structures. The calculated atomic charges and the bonding orbital polarizations point to strong ionic metal-ligand bonding in La-CCA complex and insignificant donor acceptor interaction. Detailed vibrational analysis of HCCA, CCA - and La(CCA) 2(NO 3)(H 2O) 2 systems based on both calculated and experimental frequencies confirms the suggested metal-ligand binding mode.

  4. The role of organic ligands in iron cycling and primary productivity in the Antarctic Peninsula: A modeling study

    Science.gov (United States)

    Jiang, Mingshun; Barbeau, Katherine A.; Selph, Karen E.; Measures, Christopher I.; Buck, Kristen N.; Azam, Farooq; Greg Mitchell, B.; Zhou, Meng

    2013-06-01

    Iron (Fe) is the limiting nutrient for primary productivity in the Southern Ocean, with much of the dissolved iron (dFe) bound to organic ligands or colloids. A Fe model for the Southern Ocean (SOFe) is developed to understand the role of bacteria and organic ligands in controlling Fe cycling and productivity. The model resolves the classical food web and microbial loop, including three types of nutrients (N, Si, Fe) and two types of Fe ligands. Simulations of the zero-dimensional (0-D) model are calibrated with detailed results of shipboard grow-out incubation experiments conducted with Antarctic Peninsula phytoplankton communities during winter 2006 to provide the best estimate of key biological parameters. Then a one-dimensional (1-D) model is developed by coupling the biological model with the Regional Oceanic Modeling System (ROMS) for a site on the Antarctic Peninsula shelf, and the model parameters are further calibrated with data collected from two surveys (summer 2004 and winter 2006) in the area. The results of the numerical simulations agree reasonably well with observations. An analysis of the 1-D model results suggests that bacteria and organic ligands may play an important role in Fe cycling, which can be categorized into a relatively fast mode within the euphotic zone dominated by photo-reactions (summer d Fe residence time about 600 days) and complexation and a slow mode below with most of the dFe biologically complexed (summer dFe residence time >10 years). The dFe removal from the euphotic zone is dominated by colloidal formation and further aggregations with additional contribution from biological uptake, and an increase of organic ligands would reduce Fe export. The decrease of Fe removal rate over depth is due to the continuous dissolution and remineralization of particulate Fe. A number of sensitivity experiments are carried out for both 0-D and 1-D models to understand the importance of photo-reactive processes in primary productivity

  5. Molecular modeling study of the differential ligand-receptor interaction at the μ, δ and κ opioid receptors

    Science.gov (United States)

    Filizola, Marta; Carteni-Farina, Maria; Perez, Juan J.

    1999-07-01

    3D models of the opioid receptors μ, δ and κ were constructed using BUNDLE, an in-house program to build de novo models of G-protein coupled receptors at the atomic level. Once the three opioid receptors were constructed and before any energy refinement, models were assessed for their compatibility with the results available from point-site mutations carried out on these receptors. In a subsequent step, three selective antagonists to each of three receptors (naltrindole, naltrexone and nor-binaltorphamine) were docked onto each of the three receptors and subsequently energy minimized. The nine resulting complexes were checked for their ability to explain known results of structure-activity studies. Once the models were validated, analysis of the distances between different residues of the receptors and the ligands were computed. This analysis permitted us to identify key residues tentatively involved in direct interaction with the ligand.

  6. Stronger biotic resistance in tropics relative to temperate zone: effects of predation on marine invasion dynamics.

    Science.gov (United States)

    Freestone, Amy L; Rutz, Gregory M; Torchin, Mark E

    2013-06-01

    Latitudinal patterns of nonnative species richness suggest fewer successful invasions in the tropics, relative to temperate regions. One main hypothesis for this pattern is that biotic resistance to invasion is stronger in the tropics than at higher latitudes. Biotic resistance can limit the distribution and abundance of nonnative species and, in extreme cases, can prevent establishment. We provide the first experimental test of this hypothesis, comparing the strength of biotic resistance in a tropical and a temperate marine ecosystem. Predation is one mechanism of biotic resistance, and since predation can be stronger at lower latitudes, we predicted that predation will serve to increase biotic resistance more in the tropics than at higher latitude. We conducted predator-exclusion experiments on marine epifaunal communities, a heavily invaded system, focusing on nonnative tunicates as a model fauna. The effect of predation on species richness of nonnative tunicates was more than three times greater at sites in tropical Panama than in temperate Connecticut, consistent with the prediction of stronger biotic resistance in the tropics. In Connecticut, predation reduced the abundance of one nonnative tunicate but did not affect the abundances of any other nonnative tunicate species, and no species were excluded from communities. In contrast, predation resulted in striking reductions in abundance and often exclusion of nonnative tunicates from experimental communities in Panama. If proved to be general, latitudinal differences in the biotic resistance of communities to nonnative species establishment may help explain emerging patterns of global invasions.

  7. Modeling of ligand binding to G protein coupled receptors: cannabinoid CB1, CB2 and adrenergic β 2 AR.

    Science.gov (United States)

    Latek, Dorota; Kolinski, Michal; Ghoshdastider, Umesh; Debinski, Aleksander; Bombolewski, Rafal; Plazinska, Anita; Jozwiak, Krzysztof; Filipek, Slawomir

    2011-09-01

    Cannabinoid and adrenergic receptors belong to the class A (similar to rhodopsin) G protein coupled receptors. Docking of agonists and antagonists to CB(1) and CB(2) cannabinoid receptors revealed the importance of a centrally located rotamer toggle switch and its possible participation in the mechanism of agonist/antagonist recognition. The switch is composed of two residues, F3.36 and W6.48, located on opposite transmembrane helices TM3 and TM6 in the central part of the membranous domain of cannabinoid receptors. The CB(1) and CB(2) receptor models were constructed based on the adenosine A(2A) receptor template. The two best scored conformations of each receptor were used for the docking procedure. In all poses (ligand-receptor conformations) characterized by the lowest ligand-receptor intermolecular energy and free energy of binding the ligand type matched the state of the rotamer toggle switch: antagonists maintained an inactive state of the switch, whereas agonists changed it. In case of agonists of β(2)AR, the (R,R) and (S,S) stereoisomers of fenoterol, the molecular dynamics simulations provided evidence of different binding modes while preserving the same average position of ligands in the binding site. The (S,S) isomer was much more labile in the binding site and only one stable hydrogen bond was created. Such dynamical binding modes may also be valid for ligands of cannabinoid receptors because of the hydrophobic nature of their ligand-receptor interactions. However, only very long molecular dynamics simulations could verify the validity of such binding modes and how they affect the process of activation.

  8. 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.

  9. 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.

  10. Ligand-Based Pharmacophore Modeling and Virtual Screening of RAD9 Inhibitors

    Directory of Open Access Journals (Sweden)

    Nirmal K. Prasad

    2013-01-01

    Full Text Available Human RAD9 is a key cell-cycle checkpoint protein that participates in DNA repair, activation of multiple cell cycle phase checkpoints, and apoptosis. Aberrant RAD9 expression has been linked to breast, lung, thyroid, skin, and prostate tumorigenesis. Overexpression of RAD9 interacts with BCL-2 proteins and blocks the binding sites of BCL-2 family proteins to interact with chemotherapeutic drugs and leads to drug resistance. Focusing on this interaction, the present study was designed to identify the interaction sites of RAD9 to bind BCL-2 protein and also to inhibit RAD9-BCL-2 interactions by designing novel small molecule inhibitors using pharmacophore modeling and to restore BCL-2 for interacting with anticancer drugs. The bioactive molecules of natural origin act as excellent leads for new drug development. Thus, in the present study, we used the compounds of natural origin like camptothecin, ascididemin, and Dolastatin and also compared them with synthetic molecule NSC15520. The results revealed that camptothecin can act as an effective inhibitor among all the ligands taken and can be used as an RAD9 inhibitor. The amino acids ARG45 and ALA134 of RAD9 protein are interacting commonly with the drugs and BCL-2 protein.

  11. Design and syntheses of electron-transfer photochromic metal-organic complexes using nonphotochromic ligands: a model compound and the roles of its ligands.

    Science.gov (United States)

    Zhang, Cui-Juan; Chen, Zi-Wei; Lin, Rong-Guang; Zhang, Ming-Jian; Li, Pei-Xin; Wang, Ming-Sheng; Guo, Guo-Cong

    2014-01-21

    The model compound [Zn(HCOO)2(4,4'-bipy)] (1; 4,4'-bipy = 4,4'-bipyridine) is selected in this work to demonstrate the effectiveness of our previously proposed design strategy for electron-transfer photochromic metal-organic complexes. The electron-transfer photochromic behavior of 1 has been discovered for the first time. Experimental and theoretical data illustrate that the photochromism of 1 can be attributed to the electron transfer from formato to 4,4'-bipy and the formation of a radical photoproduct. The electron transfer prefers to occur between formato and 4,4'-bipy, which are combined directly by the Zn(II) atoms. A high-contrast (up to 8.3 times) photoluminescence switch occurs during the photochromic process. The similarity of photochromic behaviors among 1 and its analogues as well as viologen compounds has also been found. Photochromic studies of this model compound indicate that new electron-transfer photochromic metal-organic complexes can be largely designed and synthesized by the rational assembly of nonphotochromic electron-donating and electron-accepting ligands.

  12. Modeling the adsorption of weak organic acids on goethite: the ligand and charge distribution model

    NARCIS (Netherlands)

    Filius, J.D.

    2001-01-01

    A detailed study is presented in which the CD-MUSIC modeling approach is used in a new modeling approach that can describe the binding of large organic molecules by metal (hydr)oxides taking the full speciation of the adsorbed molecule into account. Batch equilibration experiments were performed usi

  13. Normal mode gating motions of a ligand-gated ion channel persist in a fully hydrated lipid bilayer model.

    Science.gov (United States)

    Bertaccini, Edward J; Trudell, James R; Lindahl, Erik

    2010-08-18

    We have previously used molecular modeling and normal-mode analyses combined with experimental data to visualize a plausible model of a transmembrane ligand-gated ion channel. We also postulated how the gating motion of the channel may be affected by the presence of various ligands, especially anesthetics. As is typical for normal-mode analyses, those studies were performed in vacuo to reduce the computational complexity of the problem. While such calculations constitute an efficient way to model the large scale structural flexibility of transmembrane proteins, they can be criticized for neglecting the effects of an explicit phospholipid bilayer or hydrated environment. Here, we show the successful calculation of normal-mode motions for our model of a glycine α-1 receptor, now suspended in a fully hydrated lipid bilayer. Despite the almost uniform atomic density, the introduction of water and lipid does not grossly distort the overall gating motion. Normal-mode analysis revealed that even a fully immersed glycine α-1 receptor continues to demonstrate an iris-like channel gating motion as a low-frequency, high-amplitude natural harmonic vibration consistent with channel gating. Furthermore, the introduction of periodic boundary conditions allows the examination of simultaneous harmonic vibrations of lipid in synchrony with the protein gating motions that are compatible with reasonable lipid bilayer perturbations. While these perturbations tend to influence the overall protein motion, this work provides continued support for the iris-like motion model that characterizes gating within the family of ligand-gated ion channels.

  14. 3D models related to the publication: Neogene sloth assemblages (Mammalia, Pilosa) of the Cocinetas Basin (La Guajira, Colombia): implications for the Great American Biotic Interchange

    OpenAIRE

    Amson, Eli; Carrillo, Juan David; Jaramillo, Carlos

    2016-01-01

    INTRODUCTION : We here present the surface models of two specimens of sloths(Mammalia, Tardigrada) coming from the Late Pliocene WareFormation (Cocinetas Basin, La Guajira, Colombia, see Table 1). Along with three additional sloth taxa found in the same Formation, these specimens document the great diversity of this Neotropical locality. Furthermore, they represent a sloth assemblage from a locality just a few hundred thousand years older than the classically recognized first main pulse of th...

  15. Partitioning, diffusion, and ligand binding of raft lipid analogs in model and cellular plasma membranes.

    Science.gov (United States)

    Sezgin, Erdinc; Levental, Ilya; Grzybek, Michal; Schwarzmann, Günter; Mueller, Veronika; Honigmann, Alf; Belov, Vladimir N; Eggeling, Christian; Coskun, Unal; Simons, Kai; Schwille, Petra

    2012-07-01

    Several simplified membrane models featuring coexisting liquid disordered (Ld) and ordered (Lo) lipid phases have been developed to mimic the heterogeneous organization of cellular membranes, and thus, aid our understanding of the nature and functional role of ordered lipid-protein nanodomains, termed "rafts". In spite of their greatly reduced complexity, quantitative characterization of local lipid environments using model membranes is not trivial, and the parallels that can be drawn to cellular membranes are not always evident. Similarly, various fluorescently labeled lipid analogs have been used to study membrane organization and function in vitro, although the biological activity of these probes in relation to their native counterparts often remains uncharacterized. This is particularly true for raft-preferring lipids ("raft lipids", e.g. sphingolipids and sterols), whose domain preference is a strict function of their molecular architecture, and is thus susceptible to disruption by fluorescence labeling. Here, we analyze the phase partitioning of a multitude of fluorescent raft lipid analogs in synthetic Giant Unilamellar Vesicles (GUVs) and cell-derived Giant Plasma Membrane Vesicles (GPMVs). We observe complex partitioning behavior dependent on label size, polarity, charge and position, lipid headgroup, and membrane composition. Several of the raft lipid analogs partitioned into the ordered phase in GPMVs, in contrast to fully synthetic GUVs, in which most raft lipid analogs mis-partitioned to the disordered phase. This behavior correlates with the greatly enhanced order difference between coexisting phases in the synthetic system. In addition, not only partitioning, but also ligand binding of the lipids is perturbed upon labeling: while cholera toxin B binds unlabeled GM1 in the Lo phase, it binds fluorescently labeled GMI exclusively in the Ld phase. Fluorescence correlation spectroscopy (FCS) by stimulated emission depletion (STED) nanoscopy on intact

  16. DFT modeling and spectroscopic study of metal-ligand bonding in La(III) complex of coumarin-3-carboxylic acid

    Energy Technology Data Exchange (ETDEWEB)

    Mihaylov, Tz. [Institute of General and Inorganic Chemistry, Bulgarian Academy of Sciences, 1113 Sofia (Bulgaria); Trendafilova, N. [Institute of General and Inorganic Chemistry, Bulgarian Academy of Sciences, 1113 Sofia (Bulgaria)], E-mail: ntrend@svr.igic.bas.bg; Kostova, I. [Department of Chemistry, Faculty of Pharmacy, Medical University, Sofia 1000 (Bulgaria); Georgieva, I. [Institute of General and Inorganic Chemistry, Bulgarian Academy of Sciences, 1113 Sofia (Bulgaria); Bauer, G. [Institute of Chemical Technologies and Analytics, Technical University of Vienna, Vienna A-1060 (Austria)

    2006-09-11

    The binding mode of coumarin-3-carboxylic acid (HCCA) to La(III) is elucidated at experimental and theoretical level. The complexation ability of the deprotonated ligand (CCA{sup -}) to La(III) is studied using elemental analysis, DTA and TGA data as well as FTIR, {sup 1}H NMR and {sup 13}C NMR spectra. The experimental data suggest the complex formula La(CCA){sub 2}(NO{sub 3})(H{sub 2}O){sub 2}. B3LYP, BHLYP, B3P86, B3PW91, PW91P86 and MPW1PW91 functionals are tested for geometry and frequency calculations of the neutral ligand and all of them show bond length deviations bellow 1%. B3LYP/6-31G(d) level combined with large quasi-relativistic effective core potential for lanthanum is selected to describe the molecular, electronic and vibrational structures as well as the conformational behavior of HCCA, CCA{sup -} and La-CCA complex. The metal-ligand binding mode is predicted through molecular modeling and energy estimation of different La-CCA structures. The calculated atomic charges and the bonding orbital polarizations point to strong ionic metal-ligand bonding in La-CCA complex and insignificant donor acceptor interaction. Detailed vibrational analysis of HCCA, CCA{sup -} and La(CCA){sub 2}(NO{sub 3})(H{sub 2}O){sub 2} systems based on both calculated and experimental frequencies confirms the suggested metal-ligand binding mode.

  17. Synthesis, characterisation, spectral, thermal, XRD, molecular modelling and potential antibacterial study of metal complexes containing octadentate azodye ligands

    Science.gov (United States)

    Mahapatra, Bipin Bihari; Chaulia, Satyanarayan; Sarangi, Ashish Kumar; Dehury, Satyanarayan; Panda, Jnyanaranjan

    2015-05-01

    Twelve tetrametallic complexes of Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II) with two new octadentate azodye ligands, 4,4‧-bis(2‧,4‧-dihydroxy-5‧carboxyphenylazo) diphenylether (LH6) and 4,4‧-bis(2‧,4‧-dihydroxy-5‧-acylphenylazo) diphenylether (L‧H4) have been synthesised. The structural elucidation of the complexes was made basing upon analytical, conductance, magnetic susceptibility, IR, electronic spectra, ESR, NMR, ESI-MS, TG, DTG, DTA and X-ray diffraction (powder pattern) data. The cobalt (II) and nickel (II) complexes are found to be octahedral, copper (II) complexes are distorted octahedral and a tetrahedral stereochemistry has been suggested to zinc (II), cadmium (II) and mercury (II) complexes. The thermal analysis data provided the kinetic parameters as order of decomposition reaction, activation energy and frequency factor. The geometry of the ligands and their Co(II), Ni(II), Cu(II) and Zn(II) complexes were optimised and their physicochemical properties were calculated by using molecular modelling procedure. The ESI-MS determination supports the molecular formula and molecular weight of the ligands and the complexes. The Ni(II) complex is found to have a triclinic crystal system. The potential antibacterial study of the two ligands and eight metal complexes was made by cup-plate method against one gram positive and one gram negative bacteria. The results showed increase in the activity of some metal complexes as compare with azodye ligands.

  18. Inclusion complexes of poly-. beta. -cyclodextrin: a model for pressure effects upon ligand-protein complexes

    Energy Technology Data Exchange (ETDEWEB)

    Torgerson, P.M.; Drickamer, H.G.; Weber, G.

    1979-07-10

    Certain protein-ligand complexes are destabilized by application of pressures of the order of 5 to 10 kbar while others are stabilized. This divergent behavior is attributed to differences in compressibility of the protein binding sites. Pressure-stabilized binding is thought by us to be characteristic of soft binding sites, sites in which rotation about backbone bonds permits reduction of the site dimensions under pressure. In contradistinction, hard binding sites do not decrease their size when pressure is applied. As a model for this latter kind we have measured the changes in equilibrium with pressure of complexes of poly-..beta..-cyclodextrin with two fluorescent probes: 8-anilinonaphthalene-1-sulfonate and 6-propionyl-2-(dimethylamino)naphthalene. The standard volume change upon formation of the complexes at 1 atm is similar in both (+9.3 mL/mol), and as expected the incompressibility of the cyclodextrin rings results in a site from which the probes are dissociated by pressure. On the assmption of incompressibility of the binding site, the experimental data permit the calculation of the pressure vs volume curves (compressibility curves) for the probes molecularly dispersed in water. These curves are in broad agreement with those of liquid aliphatic and aromatic hydrocarbons in the low-pressure range (1 to 4 kbar) but indicate a reduced compressibility at the higher pressures. Considerations of relative compressibility offer a quantitative alternative to the usual qualitative discussion of the effects of high pressures upon proteins in terms of the participation of hydrophobic and other bonds.

  19. MOLS 2.0: software package for peptide modeling and protein-ligand docking.

    Science.gov (United States)

    Paul, D Sam; Gautham, N

    2016-10-01

    We previously developed an algorithm to perform conformational searches of proteins and peptides, and to perform the docking of ligands to protein receptors. In order to identify optimal conformations and docked poses, this algorithm uses mutually orthogonal Latin squares (MOLS) to rationally sample the vast conformational (or docking) space, and then analyzes this relatively small sample using a variant of mean field theory. The conformational search part of the algorithm was denoted MOLS 1.0. The docking portion of the algorithm, which allows only "flexible ligand/rigid receptor" docking, was denoted MOLSDOCK. Both are FORTRAN-based command-line-only molecular docking computer programs, though a GUI was developed later for MOLS 1.0. Both the conformational search and the rigid receptor docking parts of the algorithm have been extensively validated. We have now further enhanced the capabilities of the program by incorporating "induced fit" side-chain receptor flexibility for docking peptide ligands. Benchmarking and extensive testing is now being carried out for the flexible receptor portion of the docking. Additionally, to make both the peptide conformational search and docking algorithms (the latter including both flexible ligand/rigid receptor and flexible ligand/flexible receptor techniques) more accessible to the research community, we have developed MOLS 2.0, which incorporates a new Java-based graphical user interface (GUI). Here, we give a detailed description of MOLS 2.0. The source code and binary for MOLS 2.0 are distributed free (under a GNU Lesser General Public License) to the scientific community. They are freely available for download at https://sourceforge.net/projects/mols2-0/files/ .

  20. Ligand fitting with CCP4

    Science.gov (United States)

    2017-01-01

    Crystal structures of protein–ligand complexes are often used to infer biology and inform structure-based drug discovery. Hence, it is important to build accurate, reliable models of ligands that give confidence in the interpretation of the respective protein–ligand complex. This paper discusses key stages in the ligand-fitting process, including ligand binding-site identification, ligand description and conformer generation, ligand fitting, refinement and subsequent validation. The CCP4 suite contains a number of software tools that facilitate this task: AceDRG for the creation of ligand descriptions and conformers, Lidia and JLigand for two-dimensional and three-dimensional ligand editing and visual analysis, Coot for density interpretation, ligand fitting, analysis and validation, and REFMAC5 for macromolecular refinement. In addition to recent advancements in automatic carbohydrate building in Coot (LO/Carb) and ligand-validation tools (FLEV), the release of the CCP4i2 GUI provides an integrated solution that streamlines the ligand-fitting workflow, seamlessly passing results from one program to the next. The ligand-fitting process is illustrated using instructive practical examples, including problematic cases such as post-translational modifications, highlighting the need for careful analysis and rigorous validation. PMID:28177312

  1. Prediction of binding affinity and efficacy of thyroid hormone receptor ligands using QSAR and structure-based modeling methods

    Energy Technology Data Exchange (ETDEWEB)

    Politi, Regina [Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, University of North Carolina, Chapel Hill, NC 27599 (United States); Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States); Rusyn, Ivan, E-mail: iir@unc.edu [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States); Tropsha, Alexander, E-mail: alex_tropsha@unc.edu [Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, University of North Carolina, Chapel Hill, NC 27599 (United States)

    2014-10-01

    The thyroid hormone receptor (THR) is an important member of the nuclear receptor family that can be activated by endocrine disrupting chemicals (EDC). Quantitative Structure–Activity Relationship (QSAR) models have been developed to facilitate the prioritization of THR-mediated EDC for the experimental validation. The largest database of binding affinities available at the time of the study for ligand binding domain (LBD) of THRβ was assembled to generate both continuous and classification QSAR models with an external accuracy of R{sup 2} = 0.55 and CCR = 0.76, respectively. In addition, for the first time a QSAR model was developed to predict binding affinities of antagonists inhibiting the interaction of coactivators with the AF-2 domain of THRβ (R{sup 2} = 0.70). Furthermore, molecular docking studies were performed for a set of THRβ ligands (57 agonists and 15 antagonists of LBD, 210 antagonists of the AF-2 domain, supplemented by putative decoys/non-binders) using several THRβ structures retrieved from the Protein Data Bank. We found that two agonist-bound THRβ conformations could effectively discriminate their corresponding ligands from presumed non-binders. Moreover, one of the agonist conformations could discriminate agonists from antagonists. Finally, we have conducted virtual screening of a chemical library compiled by the EPA as part of the Tox21 program to identify potential THRβ-mediated EDCs using both QSAR models and docking. We concluded that the library is unlikely to have any EDC that would bind to the THRβ. Models developed in this study can be employed either to identify environmental chemicals interacting with the THR or, conversely, to eliminate the THR-mediated mechanism of action for chemicals of concern. - Highlights: • This is the largest curated dataset for ligand binding domain (LBD) of the THRβ. • We report the first QSAR model for antagonists of AF-2 domain of THRβ. • A combination of QSAR and docking enables

  2. 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

  3. 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...

  4. Limits of ligand selectivity from docking to models: in silico screening for A(1 adenosine receptor antagonists.

    Directory of Open Access Journals (Sweden)

    Peter Kolb

    Full Text Available G protein-coupled receptors (GPCRs are attractive targets for pharmaceutical research. With the recent determination of several GPCR X-ray structures, the applicability of structure-based computational methods for ligand identification, such as docking, has increased. Yet, as only about 1% of GPCRs have a known structure, receptor homology modeling remains necessary. In order to investigate the usability of homology models and the inherent selectivity of a particular model in relation to close homologs, we constructed multiple homology models for the A(1 adenosine receptor (A(1AR and docked ∼2.2 M lead-like compounds. High-ranking molecules were tested on the A(1AR as well as the close homologs A(2AAR and A(3AR. While the screen yielded numerous potent and novel ligands (hit rate 21% and highest affinity of 400 nM, it delivered few selective compounds. Moreover, most compounds appeared in the top ranks of only one model. These findings have implications for future screens.

  5. Insights to ligand binding to the monoamine transporters – from homology modeling to LeuBAT and dDAT

    Directory of Open Access Journals (Sweden)

    Heidi eKoldsø

    2015-09-01

    Full Text Available Understanding of drug binding to the human biogenic amine transporters is essential to explain the mechanism of action of these pharmaceuticals but more importantly to be able to develop new and improved compounds to be used in the treatment of depression or drug addiction. Until recently no high resolution structure was available of the biogenic amine transporters and homology modeling was a necessity. Various studies have revealed experimentally validated binding modes of numerous ligands to the biogenic amine transporters using homology modeling. Here we examine and discuss the similarities between the binding models of substrates, antidepressants, psychostimulants and anti-abuse drugs in homology models of the human biogenic amine transporters and the recently published crystal structures of the drosophila dopamine transporter and the engineered protein, LeuBAT. The comparison reveals that careful computational modeling combined with experimental data can be utilized to predict binding of molecules to proteins that agree very well with crystal structures.

  6. Linear Interaction Energy (LIE) Models for Ligand Binding in Implicit Solvent:  Theory and Application to the Binding of NNRTIs to HIV-1 Reverse Transcriptase.

    Science.gov (United States)

    Su, Yang; Gallicchio, Emilio; Das, Kalyan; Arnold, Eddy; Levy, Ronald M

    2007-01-01

    Expressions for Linear Interaction Energy (LIE) estimators for the binding of ligands to a protein receptor in implicit solvent are derived based on linear response theory and the cumulant expansion expression for the free energy. Using physical arguments, values of the LIE linear response proportionality coefficients are predicted for the explicit and implicit solvent electrostatic and van der Waals terms. Motivated by the fact that the receptor and solution media may respond differently to the introduction of the ligand, a novel form of the LIE regression equation is proposed to model independently the processes of insertion of the ligand in the receptor and in solution. We apply these models to the problem of estimating the binding free energy of two non-nucleoside classes of inhibitors of HIV-1 RT (HEPT and TIBO analogues). We develop novel regression models with greater predictive ability than more standard LIE formulations. The values of the regression coefficients generally conform to linear response predictions, and we use this fact to develop a LIE regression equation with only one adjustable parameter (excluding the intercept parameter) which is superior to the other models we tested and to previous results in terms of predictive accuracy for the HEPT and TIBO compounds individually. The new models indicate that, due to the different effects of induced steric strain of the receptor, an increase of ligand size alone opposes binding for ligands of the HEPT class, whereas it favors binding for ligands of the TIBO class.

  7. 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 ...... through ubiquitination. The wide range of biotic and abiotic stresses that affect crop plants limits agricultural production.......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...

  8. Properties of a general PK/PD model of antibody-ligand interactions for therapeutic antibodies that bind to soluble endogenous targets.

    Science.gov (United States)

    Davda, Jasmine P; Hansen, Ryan J

    2010-01-01

    Antibodies that target endogenous soluble ligands are an important class of biotherapeutic agents. While much focus has been placed on characterization of antibody pharmacokinetics, less emphasis has been given to characterization of antibody effects on their soluble targets. We describe here the properties of a generalized mechanism-based PK/PD model used to characterize the in vivo interaction of an antibody and an endogenous soluble ligand. The assumptions and properties of the model are explored, and situations are described when deviations from the basic assumptions may be necessary. This model is most useful for in vivo situations where both antibody and ligand levels are available following drug administration. For a given antibody exposure, the extent and duration of suppression of free ligand is impacted by the apparent affinity of the interaction, as well as by the rate of ligand turnover. The applicability of the general equilibrium model of in vivo antibody-ligand interaction is demonstrated with an anti-Aß antibody.

  9. 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.

  10. 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.

  11. Mixed ligand complexation of some transition metal ions in solution and solid state: Spectral characterization, antimicrobial, antioxidant, DNA cleavage activities and molecular modeling

    Science.gov (United States)

    Shobana, Sutha; Dharmaraja, Jeyaprakash; Selvaraj, Shanmugaperumal

    2013-04-01

    Equilibrium studies of Ni(II), Cu(II) and Zn(II) mixed ligand complexes involving a primary ligand 5-fluorouracil (5-FU; A) and imidazoles viz., imidazole (him), benzimidazole (bim), histamine (hist) and L-histidine (his) as co-ligands(B) were carried out pH-metrically in aqueous medium at 310 ± 0.1 K with I = 0.15 M (NaClO4). In solution state, the stoichiometry of MABH, MAB and MAB2 species have been detected. The primary ligand(A) binds the central M(II) ions in a monodentate manner whereas him, bim, hist and his co-ligands(B) bind in mono, mono, bi and tridentate modes respectively. The calculated Δ log K, log X and log X' values indicate higher stability of the mixed ligand complexes in comparison to binary species. Stability of the mixed ligand complex equilibria follows the Irving-Williams order of stability. In vitro biological evaluations of the free ligand(A) and their metal complexes by well diffusion technique show moderate activities against common bacterial and fungal strains. Oxidative cleavage interaction of ligand(A) and their copper complexes with CT DNA is also studied by gel electrophoresis method in the presence of oxidant. In vitro antioxidant evaluations of the primary ligand(A), CuA and CuAB complexes by DPPH free radical scavenging model were carried out. In solid, the MAB type of M(II)sbnd 5-FU(A)sbnd his(B) complexes were isolated and characterized by various physico-chemical and spectral techniques. Both the magnetic susceptibility and electronic spectral analysis suggest distorted octahedral geometry. Thermal studies on the synthesized mixed ligand complexes show loss of coordinated water molecule in the first step followed by decomposition of the organic residues subsequently. XRD and SEM analysis suggest that the microcrystalline nature and homogeneous morphology of MAB complexes. Further, the 3D molecular modeling and analysis for the mixed ligand MAB complexes have also been carried out.

  12. Dissecting electrostatic screening, specific ion binding, and ligand binding in an energetic model for glycine riboswitch folding

    Energy Technology Data Exchange (ETDEWEB)

    Lipfert, Jan; Sim, Adelene Y.L.; Herschlag, Daniel; Doniach, Sebastian (Stanford)

    2010-09-17

    Riboswitches are gene-regulating RNAs that are usually found in the 5{prime}-untranslated regions of messenger RNA. As the sugar-phosphate backbone of RNA is highly negatively charged, the folding and ligand-binding interactions of riboswitches are strongly dependent on the presence of cations. Using small angle X-ray scattering (SAXS) and hydroxyl radical footprinting, we examined the cation dependence of the different folding stages of the glycine-binding riboswitch from Vibrio cholerae. We found that the partial folding of the tandem aptamer of this riboswitch in the absence of glycine is supported by all tested mono- and divalent ions, suggesting that this transition is mediated by nonspecific electrostatic screening. Poisson-Boltzmann calculations using SAXS-derived low-resolution structural models allowed us to perform an energetic dissection of this process. The results showed that a model with a constant favorable contribution to folding that is opposed by an unfavorable electrostatic term that varies with ion concentration and valency provides a reasonable quantitative description of the observed folding behavior. Glycine binding, on the other hand, requires specific divalent ions binding based on the observation that Mg{sup 2+}, Ca{sup 2+}, and Mn{sup 2+} facilitated glycine binding, whereas other divalent cations did not. The results provide a case study of how ion-dependent electrostatic relaxation, specific ion binding, and ligand binding can be coupled to shape the energetic landscape of a riboswitch and can begin to be quantitatively dissected.

  13. Testing the Coulomb/Accessible Surface Area solvent model for protein stability, ligand binding, and protein design

    Directory of Open Access Journals (Sweden)

    Bathelt Christine

    2008-03-01

    Full Text Available Abstract Background Protein structure prediction and computational protein design require efficient yet sufficiently accurate descriptions of aqueous solvent. We continue to evaluate the performance of the Coulomb/Accessible Surface Area (CASA implicit solvent model, in combination with the Charmm19 molecular mechanics force field. We test a set of model parameters optimized earlier, and we also carry out a new optimization in this work, using as a target a set of experimental stability changes for single point mutations of various proteins and peptides. The optimization procedure is general, and could be used with other force fields. The computation of stability changes requires a model for the unfolded state of the protein. In our approach, this state is represented by tripeptide structures of the sequence Ala-X-Ala for each amino acid type X. We followed an iterative optimization scheme which, at each cycle, optimizes the solvation parameters and a set of tripeptide structures for the unfolded state. This protocol uses a set of 140 experimental stability mutations and a large set of tripeptide conformations to find the best tripeptide structures and solvation parameters. Results Using the optimized parameters, we obtain a mean unsigned error of 2.28 kcal/mol for the stability mutations. The performance of the CASA model is assessed by two further applications: (i calculation of protein-ligand binding affinities and (ii computational protein design. For these two applications, the previous parameters and the ones optimized here give a similar performance. For ligand binding, we obtain reasonable agreement with a set of 55 experimental mutation data, with a mean unsigned error of 1.76 kcal/mol with the new parameters and 1.47 kcal/mol with the earlier ones. We show that the optimized CASA model is not inferior to the Generalized Born/Surface Area (GB/SA model for the prediction of these binding affinities. Likewise, the new parameters perform

  14. New Trends in Inspecting GPCR-ligand Recognition Process: the Contribution of the Molecular Modeling Section (MMS) at the University of Padova.

    Science.gov (United States)

    Ciancetta, Antonella; Cuzzolin, Alberto; Deganutti, Giuseppe; Sturlese, Mattia; Salmaso, Veronica; Cristiani, Andrea; Sabbadin, Davide; Moro, Stefano

    2016-09-01

    In this review, we present a survey of the recent advances carried out by our research groups in the field of ligand-GPCRs recognition process simulations recently implemented at the Molecular Modeling Section (MMS) of the University of Padova. We briefly describe a platform of tools we have tuned to aid the identification of novel GPCRs binders and the better understanding of their binding mechanisms, based on two extensively used computational techniques such as molecular docking and MD simulations. The developed methodologies encompass: (i) the selection of suitable protocols for docking studies, (ii) the exploration of the dynamical evolution of ligand-protein interaction networks, (iii) the detailed investigation of the role of water molecules upon ligand binding, and (iv) a glance at the way the ligand might go through prior reaching the binding site.

  15. Biotic and abiotic carbon to sulfur bond cleavage. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Frost, J.W.

    1994-05-01

    The microbial desulfurization of organosulfur compounds occurs by unprecedented and largely unexplored biochemical processes. A study of such biotic desulfurizations can be expected to give rise to new and useful chemistry and enzymology. The potential value of understanding and harnessing these processes is seen in relation to the need for methods for the removal of organically bound sulfur from coal and the degradation of organic sulfur-containing pollutants. This research effort has been directed towards an examination of desulfurization ability in well characterized microorganisms, the isolation of bacteria with desulfurization ability from natural sources, the characterization and mechanistic evaluation of the observed biocatalytic processes, the development of biomimetic synthetic organic chemistry based on biotic desulfurization mechanisms and the design and preparation of improved coal model compounds for use in microbial selection processes. A systematic approach to studying biodesulfurizations was undertaken in which organosulfur compounds have been broken down into classes based on the oxidation state of the sulfur atom and the structure of the rest of the organic material. Microbes have been evaluated in terms of ability to degrade organosulfur compounds with sulfur in its sulfonic acid oxidation state. These compounds are likely intermediates in coal desulfurization and are present in the environment as persistent pollutants in the form of detergents. It is known that oxygen bonded to sulfur lowers the carbon-sulfur bond energy, providing a thermodynamic basis for starting with this class of compounds.

  16. Femtomolar Zn(II) affinity in a peptide-based ligand designed to model thiolate-rich metalloprotein active sites.

    Science.gov (United States)

    Petros, Amy K; Reddi, Amit R; Kennedy, Michelle L; Hyslop, Alison G; Gibney, Brian R

    2006-12-11

    Metal-ligand interactions are critical components of metalloprotein assembly, folding, stability, electrochemistry, and catalytic function. Research over the past 3 decades on the interaction of metals with peptide and protein ligands has progressed from the characterization of amino acid-metal and polypeptide-metal complexes to the design of folded protein scaffolds containing multiple metal cofactors. De novo metalloprotein design has emerged as a valuable tool both for the modular synthesis of these complex metalloproteins and for revealing the fundamental tenets of metalloprotein structure-function relationships. Our research has focused on using the coordination chemistry of de novo designed metalloproteins to probe the interactions of metal cofactors with protein ligands relevant to biological phenomena. Herein, we present a detailed thermodynamic analysis of Fe(II), Co(II), Zn(II), and[4Fe-4S]2(+/+) binding to IGA, a 16 amino acid peptide ligand containing four cysteine residues, H2N-KLCEGG-CIGCGAC-GGW-CONH2. These studies were conducted to delineate the inherent metal-ion preferences of this unfolded tetrathiolate peptide ligand as well as to evaluate the role of the solution pH on metal-peptide complex speciation. The [4Fe-4S]2(+/+)-IGA complex is both an excellent peptide-based synthetic analogue for natural ferredoxins and is flexible enough to accommodate mononuclear metal-ion binding. Incorporation of a single ferrous ion provides the FeII-IGA complex, a spectroscopic model of a reduced rubredoxin active site that possesses limited stability in aqueous buffers. As expected based on the Irving-Williams series and hard-soft acid-base theory, the Co(II) and Zn(II) complexes of IGA are significantly more stable than the Fe(II) complex. Direct proton competition experiments, coupled with determinations of the conditional dissociation constants over a range of pH values, fully define the thermodynamic stabilities and speciation of each MII-IGA complex. The

  17. Biotic interactions mediate the expansion of black mangrove (Avicennia germinans) into salt marshes under climate change.

    Science.gov (United States)

    Guo, Hongyu; Zhang, Yihui; Lan, Zhenjiang; Pennings, Steven C

    2013-09-01

    Many species are expanding their distributions to higher latitudes due to global warming. Understanding the mechanisms underlying these distribution shifts is critical for better understanding the impacts of climate changes. The climate envelope approach is widely used to model and predict species distribution shifts with changing climates. Biotic interactions between species, however, may also influence species distributions, and a better understanding of biotic interactions could improve predictions based solely on climate envelope models. Along the northern Gulf of Mexico coast, USA, subtropical black mangrove (Avicennia germinans) at the northern limit of its distribution grows sympatrically with temperate salt marsh plants in Florida, Louisiana, and Texas. In recent decades, freeze-free winters have led to an expansion of black mangrove into salt marshes. We examined how biotic interactions between black mangrove and salt marsh vegetation along the Texas coast varied across (i) a latitudinal gradient (associated with a winter-temperature gradient); (ii) the elevational gradient within each marsh (which creates different marsh habitats); and (iii) different life history stages of black mangroves (seedlings vs. juvenile trees). Each of these variables affected the strength or nature of biotic interactions between black mangrove and salt marsh vegetation: (i) Salt marsh vegetation facilitated black mangrove seedlings at their high-latitude distribution limit, but inhibited black mangrove seedlings at lower latitudes; (ii) mangroves performed well at intermediate elevations, but grew and survived poorly in high- and low-marsh habitats; and (iii) the effect of salt marsh vegetation on black mangroves switched from negative to neutral as black mangroves grew from seedlings into juvenile trees. These results indicate that the expansion of black mangroves is mediated by complex biotic interactions. A better understanding of the impacts of climate change on ecological

  18. Synthesis, binding, and modeling studies of new cytisine derivatives, as ligands for neuronal nicotinic acetylcholine receptor subtypes.

    Science.gov (United States)

    Tasso, Bruno; Canu Boido, Caterina; Terranova, Emanuela; Gotti, Cecilia; Riganti, Loredana; Clementi, Francesco; Artali, Roberto; Bombieri, Gabriella; Meneghetti, Fiorella; Sparatore, Fabio

    2009-07-23

    The availability of drug affecting neuronal nicotinic acetylcholine receptors (nAChRs) may have important therapeutic potential for the treatment of several CNS pathologies. Pursuing our efforts on the systematic structural modification of cytisine and N-arylalkyl and N-aroylalkyl cytisines were synthesized and tested for the displacement of [(3)H]-epibatidine and [(125)I]-alpha-bungarotoxin from the most widespread brain nAChRs subtypes alpha(4)beta(2) and alpha(7), respectively. While the affinity for alpha(7) subtype was rather poor (K(i) from 0.4 to >50 microM), the affinity for alpha(4)beta(2) subtype was very interesting, with nanomolar K(i) values for the best compounds. The N-substituted cytisines were docked into the rat and human alpha(4)beta(2) nAChR models based on the extracellular domain of a molluscan acetylcholine binding protein. The docking results agreed with the binding data, allowing the detection of discrete amino acid residues of the alpha and beta subunits essential for the ligand binding on rat and human nAChRs, providing a novel structural framework for the development of new alpha(4)beta(2) selective ligands.

  19. Reactivity and molecular modeling of new solvatochromic mixed-ligand copper(II) chelates of 2-acetylbutyrolactone and dinitrogen bases.

    Science.gov (United States)

    Taha, A; Adly, Omima M I; Shebl, Magdy

    2015-04-01

    A new series of solvatochromic mononuclear mixed ligand chelates with the general formula: Cu(AcBL)(L)X; where AcBL=2-acetylbutyrolactonate, L=N,N,N',N'-tetramethylethylenediamine (Me4en), N,N,N',N'-tetramethylpropylene diamine (Me4pn), 1,10-phenanthroline (Phen) or 2,2'-bipyridyl (Bipy) and X=ClO4-, NO3- or Br- have been synthesized and characterized by the analytical and spectral methods, as well as magnetic and molar conductance measurements. The d-d absorption bands of Me4en-chelates as Nujol mulls or weak donor solvents solutions revealed square-planar, distorted octahedral and/or distorted trigonal bipyramid geometries for the perchlorate, nitrate and bromide chelates, respectively. However, an octahedral structure is identified for chelates in strong donor solvents. Perchlorate chelates show a remarkable color change from violet to green as the Lewis basicity of the donor solvent increases, whereas bromide chelates are mainly affected by the Lewis acidity of solvent. Specific and non-specific interactions of solvent molecules with the chelates were investigated on the basis of unified solvation model. Structural parameters of the free ligands and their Cu(II)-chelates have been calculated on the basis of semiempirical PM3 level and correlated with the experimental data.

  20. Force modulating dynamic disorder: A physical model of catch-slip bond transitions in receptor-ligand forced dissociation experiments

    Science.gov (United States)

    Liu, Fei; Ou-Yang, Zhong-Can

    2006-11-01

    Recent experiments found that some adhesive receptor-ligand complexes have counterintuitive catch-slip transition behaviors: the mean lifetimes of these complexes first increase (catch) with initial application of a small external force, and then decrease (slip) when the force is beyond some threshold. In this work we suggest that the forced dissociation of these complexes might be a typical rate process with dynamic disorder. The one-dimensional force modulating Agmon-Hopfield model is used to describe the transitions in the single-bond P-selectin glycoprotein ligand 1-P-selectin forced dissociation experiments, which were respectively performed in the constant force [Marshall , Nature (Landon) 423, 190 (2003)] and the ramping force [Evans , Proc. Natl. Acad. Sci. U.S.A 98, 11281 (2004)] modes. We find that, an external force can not only accelerate the bond dissociation, but also modulate the complex from the lower-energy barrier to the higher one; the catch-slip bond transition can arise from a particular energy barrier shape. The agreement between our calculation and the experimental data is satisfactory.

  1. Mathematical modelling and computational study of two-dimensional and three-dimensional dynamics of receptor-ligand interactions in signalling response mechanisms.

    Science.gov (United States)

    García-Peñarrubia, Pilar; Gálvez, Juan J; Gálvez, Jesús

    2014-09-01

    Cell signalling processes involve receptor trafficking through highly connected networks of interacting components. The binding of surface receptors to their specific ligands is a key factor for the control and triggering of signalling pathways. But the binding process still presents many enigmas and, by analogy with surface catalytic reactions, two different mechanisms can be conceived: the first mechanism is related to the Eley-Rideal (ER) mechanism, i.e. the bulk-dissolved ligand interacts directly by pure three-dimensional (3D) diffusion with the specific surface receptor; the second mechanism is similar to the Langmuir-Hinshelwood (LH) process, i.e. 3D diffusion of the ligand to the cell surface followed by reversible ligand adsorption and subsequent two-dimensional (2D) surface diffusion to the receptor. A situation where both mechanisms simultaneously contribute to the signalling process could also occur. The aim of this paper is to perform a computational study of the behavior of the signalling response when these different mechanisms for ligand-receptor interactions are integrated into a model for signal transduction and ligand transport. To this end, partial differential equations have been used to develop spatio-temporal models that show trafficking dynamics of ligands, cell surface components, and intracellular signalling molecules through the different domains of the system. The mathematical modeling developed for these mechanisms has been applied to the study of two situations frequently found in cell systems: (a) dependence of the signal response on cell density; and (b) enhancement of the signalling response in a synaptic environment.

  2. The cell recognition model in chlorolichens involving a fungal lectin binding to an algal ligand can be extended to cyanolichens.

    Science.gov (United States)

    Vivas, M; Sacristán, M; Legaz, M E; Vicente, C

    2010-07-01

    Leptogium corniculatum, a cyanolichen containing Nostoc as photobiont, produces and secretes arginase to culture medium containing arginine. This secreted arginase was pre-purified by affinity chromatography on beads of activated agarose to which a polygalactosylated urease, purified from Evernia prunastri, was attached. Arginase was eluted from the beads with 50 mm alpha-d-galactose. The eluted arginase binds preferentially to the cell surface of Nostoc isolated from this lichen thallus, although it is also able to bind, to some extent, to the cell surface of the chlorobiont isolated from E. prunastri. Previous studies in chlorolichens have shown that a fungal lectin that develops subsidiary arginase activity can be a factor in recognition of compatible algal cells through binding to a polygalactosylated urease, which acts as a lectin ligand in the algal cell wall. Our experiments demonstrate that this model can now be extended to cyanolichens.

  3. KiDoQ: using docking based energy scores to develop ligand based model for predicting antibacterials

    Directory of Open Access Journals (Sweden)

    Tewari Rupinder

    2010-03-01

    Full Text Available Abstract Background Identification of novel drug targets and their inhibitors is a major challenge in the field of drug designing and development. Diaminopimelic acid (DAP pathway is a unique lysine biosynthetic pathway present in bacteria, however absent in mammals. This pathway is vital for bacteria due to its critical role in cell wall biosynthesis. One of the essential enzymes of this pathway is dihydrodipicolinate synthase (DHDPS, considered to be crucial for the bacterial survival. In view of its importance, the development and prediction of potent inhibitors against DHDPS may be valuable to design effective drugs against bacteria, in general. Results This paper describes a methodology for predicting novel/potent inhibitors against DHDPS. Here, quantitative structure activity relationship (QSAR models were trained and tested on experimentally verified 23 enzyme's inhibitors having inhibitory value (Ki in the range of 0.005-22(mM. These inhibitors were docked at the active site of DHDPS (1YXD using AutoDock software, which resulted in 11 energy-based descriptors. For QSAR modeling, Multiple Linear Regression (MLR model was engendered using best four energy-based descriptors yielding correlation values R/q2 of 0.82/0.67 and MAE of 2.43. Additionally, Support Vector Machine (SVM based model was developed with three crucial descriptors selected using F-stepping remove-one approach, which enhanced the performance by attaining R/q2 values of 0.93/0.80 and MAE of 1.89. To validate the performance of QSAR models, external cross-validation procedure was adopted which accomplished high training/testing correlation values (q2/r2 in the range of 0.78-0.83/0.93-0.95. Conclusions Our results suggests that ligand-receptor binding interactions for DHDPS employing QSAR modeling seems to be a promising approach for prediction of antibacterial agents. To serve the experimentalist to develop novel/potent inhibitors, a webserver "KiDoQ" has been developed http

  4. Temporal dynamics of biotic and abiotic drivers of litter decomposition.

    Science.gov (United States)

    García-Palacios, Pablo; Shaw, E Ashley; Wall, Diana H; Hättenschwiler, Stephan

    2016-05-01

    Climate, litter quality and decomposers drive litter decomposition. However, little is known about whether their relative contribution changes at different decomposition stages. To fill this gap, we evaluated the relative importance of leaf litter polyphenols, decomposer communities and soil moisture for litter C and N loss at different stages throughout the decomposition process. Although both microbial and nematode communities regulated litter C and N loss in the early decomposition stages, soil moisture and legacy effects of initial differences in litter quality played a major role in the late stages of the process. Our results provide strong evidence for substantial shifts in how biotic and abiotic factors control litter C and N dynamics during decomposition. Taking into account such temporal dynamics will increase the predictive power of decomposition models that are currently limited by a single-pool approach applying control variables uniformly to the entire decay process.

  5. How reliable are pseudocontact shifts induced in proteins and ligands by mobile paramagnetic metal tags? A modelling study

    Energy Technology Data Exchange (ETDEWEB)

    Shishmarev, Dmitry; Otting, Gottfried, E-mail: gottfried.otting@anu.edu.au [Australian National University, Research School of Chemistry (Australia)

    2013-07-15

    The anisotropic component of the magnetic susceptibility tensor ({Delta}{chi} tensor) associated with various paramagnetic metal ions can induce pseudocontact shifts (PCSs) and residual dipolar couplings (RDCs) in proteins, yielding valuable restraints in structural studies. In particular, PCSs have successfully been used to study ligands that bind to proteins tagged with a paramagnetic metal ion, which is of great interest in fragment-based drug design. To create easy-to-interpret PCSs, the metal ion must be attached to the protein in a rigid manner. Most of the existing methods for site-specific attachment of a metal tag, however, result in tethers with residual flexibility. Here we present model calculations to quantify the extent, to which mobility of the metal-binding tag can compromise the quality of the {Delta}{chi} tensor that can be determined from the PCSs observed in the protein. Assuming that the protein can be approximated by a sphere and the tag is attached by a single tether, the results show that a single effective Increment {chi} tensor can describe the PCSs and RDCs of the protein spins very well even in the presence of substantial tag mobility, implying that PCSs of ligands in binding pockets of the protein can be predicted with similar accuracy. In contrast, the quality of the PCS prediction for nuclear spins positioned above the surface of the protein is significantly poorer, with implications for studies of protein-protein complexes. The simulations probed the sensitivity of the effective {Delta}{chi} tensor to different parameters, including length of the tether between protein and metal ion, protein size, type and amplitude of tag motion, tensor orientation relative to the protein and direction of tag motion. Tether length and amplitude of motion were identified as two key parameters. It is shown that the amplitude of tag motions cannot be quantified by simple comparisons of the effective {Delta}{chi} tensor with the alignment tensor

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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

  11. Guinea-pig ileum as ex vivo model useful to characterize ligands displaying Imidazoline I2 and Adrenergic alpha2 mixed activity: a preliminary study

    Directory of Open Access Journals (Sweden)

    Marialessandra Contino

    2013-01-01

    Full Text Available The lack of an effective analgesic treatment makes pain a clinical challenge and the need of a novel approach to identify new agents is urgent. In this scenario I2-ligands can be considered an alternative strategy in pain therapy. The development of an ex vivo model useful for the evaluation of functional activities at both a2 and I2-IBs (imidazoline binding sites is an important task in pharmacological sciences since several I2 ligands display activity also towards a receptors. The present study aims to develop an ex vivo model for estimating the activity of I2-IBs ligands in a biological sample where a1 and a2 adrenergic receptors are present. For this purpose the imidalzoline endogenous ligand, harmane, reference compounds, 2BFI and BU224, and imidazoline derivatives 1-3 have been selected taking into account their in vitro activity towards IBs and adrenergic receptors. All compounds have been tested ex vivo in guinea pig-ileum where a2A-ARs are prejunctionally and I2-IBS postjunctionally localized. Adrenergic component has been identified by the studying the interference of compounds on the electrically-evoked contraction while I2-IBs activity by testing the ability of compounds to inhibit the carbachol-evoked contractions in the presence of prazosin to mask the a1 adrenoceptors. Compounds 1 and 2 were found I2-IBs antago nists (pIC50=4.2 and 4.0, respectively whereas compound 3 was I2-IBs agonist (EC50=0.38 mM; All ligands were a2 adrenergic agonists. This paper suggests guinea-pig ileum as the first ex vivo approach for establishing both the intrinsic activity of I2-IBs ligands and the physiological correlation between IBs and adrenergic system.

  12. Ligand K-edge x-ray adsorption spectroscopic studies of the electronic structure of inorganic model complexes and metalloprotein active sites

    Science.gov (United States)

    Shadle, S. E.

    1994-08-01

    Ligand K-edge X-ray absorption spectroscopy (XAS) has been developed as a technique for the investigation of ligand-metal bonding and has been applied to the study of electronic structure in organic model complexes and metalloprotein active sites. Ligand K-edge XAS has been measured at the chloride K-edge for a series of complexes containing chloride ligands bound to open shell d(sup 9) copper ions. The intensity of the pre-edge feature in these spectra reflects the covalency in the half-occupied d(sub x)2(sub -y)2-derived molecular orbital (HOMO) of the complex. The energy of the pre-edge feature is related to both the charge on the ligand and the HOMO energy. An analysis of the intensity and energy of the pre-edge feature as well as the energy of the rising edge absorption provides quantitative information about the covalency of the ligand-metal interaction, the charge donated by the chloride, and the energy of the copper d-manifold. The results demonstrate that ligand K-edge XAS features can be used to obtain quantitative information about ligand-metal bonding. The results also identify the chemical basis for trends in the XAS data for the complexes: D(sub 4h)CuCl4(sup 2-), D(sub 2d)CuCl4(sup 2-), planar, trans-CuCl2(pdmp)(sub 2) (pdmp=N-phenyl-3,5-dimethylpyrazole), square pyramidal CuCl5(sup 3-), the planar dimer KCuCl3, the distorted tetrahedral dimer (Ph4P)CuCl3, and two dimers with mixed ligation, one containing a bridging chloride, and the other, terminally bound chloride. A geometric distortion from square planar to distorted tetrahedral results in a decrease in the chloride-copper HOMO covalency but an increase in the total charge donation by the chlorides. Thus, while the geometry can maximize the overlap for a highly covalent HOMO, this does not necessarily reflect the overall charge donation. The Cl-Cu(II) bonding interactions are dependent on the nature of the other coordinating ligands.

  13. End-Triassic nonmarine biotic events

    Institute of Scientific and Technical Information of China (English)

    Spencer G. Lucas; Lawrence H. Tanner

    2015-01-01

    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 af-fecting 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 dif-ferent 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 paleolfora largely driven by lithofacies changes resulting in changing taphonomic iflters. 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 cor-relation 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 non-marine 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 signiifcant environmental perturbations (cooling

  14. Mixed ligand Cu(II)N2O2 complexes: biomimetic synthesis, activities in vitro and biological models, theoretical calculations.

    Science.gov (United States)

    Li, Chen; Yin, Bing; Kang, Yifan; Liu, Ping; Chen, Liang; Wang, Yaoyu; Li, Jianli

    2014-12-15

    Three new mixed ligand Cu(II)N2O2 complexes, namely, [Cu(II)(2-A-6-MBT)2(m-NB)2] (1), [Cu(II)(2-ABT)2(m-NB)2] (2), and [Cu(II)(2-ABT)2(o-NB)2] (3), (2-A-6-MBT = 2-amino-6-methoxybenzothiazole, m-NB = m-nitrobenzoate, 2-ABT = 2-aminobenzothiazole, and o-NB = o-nitrobenzoate), have been prepared by the biomimetic synthesis strategy, and their structures were determined by X-ray crystallography studies and spectral methods. These complexes exhibited the effective superoxide dismutase (SOD) activity and catecholase activity. On the basis of the experimental data and computational studies, the structure-activity relationship for these complexes was investigated. The results reveal that electron-accepting abilities of these complexes and coordination geometries have significant effects on the SOD activity and catecholase activity. Then, we found that 1 and 2 exerted potent intracellular antioxidant capacity in the model of H2O2-induced oxidative stress based on HeLa cervical cancer cells, which were screened out by the cytotoxicity assays of different kinds of cells. Furthermore, 1-3 showed the favorable biocompatibility in two different biological models: Saccharomyces cerevisiae and human vascular endothelial cells. These biological experimental data are indicative of the promising application potential of these complexes in biology and pharmacology.

  15. 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.

  16. 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.

  17. Synthesis, pharmacological evaluation and molecular modeling studies of triazole containing dopamine D3 receptor ligands.

    Science.gov (United States)

    Peng, Xin; Wang, Qi; Mishra, Yogesh; Xu, Jinbin; Reichert, David E; Malik, Maninder; Taylor, Michelle; Luedtke, Robert R; Mach, Robert H

    2015-02-01

    A series of 2-methoxyphenyl piperazine analogues containing a triazole ring were synthesized and their in vitro binding affinities at human dopamine D2 and D3 receptors were evaluated. Compounds 5b, 5c, 5d, and 4g, demonstrate high affinity for dopamine D3 receptors and moderate selectivity for the dopamine D3 versus D2 receptor subtypes. To further examine their potential as therapeutic agents, their intrinsic efficacy at both D2 and D3 receptors was determined using a forskolin-dependent adenylyl cyclase inhibition assay. Affinity at dopamine D4 and serotonin 5-HT1A receptors was also determined. In addition, information from previous molecular modeling studies of the binding of a panel of 163 structurally-related benzamide analogues at dopamine D2 and D3 receptors was applied to this series of compounds. The results of the modeling studies were consistent with our previous experimental data. More importantly, the modeling study results explained why the replacement of the amide linkage with the hetero-aromatic ring leads to a reduction in the affinity of these compounds at D3 receptors.

  18. Ligand placement based on prior structures: the guided ligand-replacement method

    Energy Technology Data Exchange (ETDEWEB)

    Klei, Herbert E. [Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Bristol-Myers Squibb, Princeton, NJ 08543-4000 (United States); Moriarty, Nigel W., E-mail: nwmoriarty@lbl.gov; Echols, Nathaniel [Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Terwilliger, Thomas C. [Los Alamos National Laboratory, Los Alamos, NM 87545-0001 (United States); Baldwin, Eric T. [Bristol-Myers Squibb, Princeton, NJ 08543-4000 (United States); Natural Discovery LLC, Princeton, NJ 08542-0096 (United States); Pokross, Matt; Posy, Shana [Bristol-Myers Squibb, Princeton, NJ 08543-4000 (United States); Adams, Paul D. [Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); University of California at Berkeley, Berkeley, CA 94720-1762 (United States)

    2014-01-01

    A new module, Guided Ligand Replacement (GLR), has been developed in Phenix to increase the ease and success rate of ligand placement when prior protein-ligand complexes are available. The process of iterative structure-based drug design involves the X-ray crystal structure determination of upwards of 100 ligands with the same general scaffold (i.e. chemotype) complexed with very similar, if not identical, protein targets. In conjunction with insights from computational models and assays, this collection of crystal structures is analyzed to improve potency, to achieve better selectivity and to reduce liabilities such as absorption, distribution, metabolism, excretion and toxicology. Current methods for modeling ligands into electron-density maps typically do not utilize information on how similar ligands bound in related structures. Even if the electron density is of sufficient quality and resolution to allow de novo placement, the process can take considerable time as the size, complexity and torsional degrees of freedom of the ligands increase. A new module, Guided Ligand Replacement (GLR), was developed in Phenix to increase the ease and success rate of ligand placement when prior protein–ligand complexes are available. At the heart of GLR is an algorithm based on graph theory that associates atoms in the target ligand with analogous atoms in the reference ligand. Based on this correspondence, a set of coordinates is generated for the target ligand. GLR is especially useful in two situations: (i) modeling a series of large, flexible, complicated or macrocyclic ligands in successive structures and (ii) modeling ligands as part of a refinement pipeline that can automatically select a reference structure. Even in those cases for which no reference structure is available, if there are multiple copies of the bound ligand per asymmetric unit GLR offers an efficient way to complete the model after the first ligand has been placed. In all of these applications, GLR

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Relevance of biotic pathways to the long-term regulation of nuclear waste disposal. A report on Tasks 1 and 2 of Phase I. [Shallow land burial

    Energy Technology Data Exchange (ETDEWEB)

    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.

  4. Time after time: flowering phenology and biotic interactions

    NARCIS (Netherlands)

    Elzinga, J.A.; Atlan, A.; Biere, A.; Gigord, L.; Weis, A.E.; Bernasconi, G.

    2007-01-01

    The role of biotic interactions in shaping plant flowering phenology has long been controversial; plastic responses to the abiotic environment, limited precision of biological clocks and inconsistency of selection pressures have generally been emphasized to explain phenological variation. However, p

  5. Preliminary Biotic Survey of Cane Creek, Calhoun County, AL

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — A biotic survey of Cane Creek (Calhoun County, AL) was completed in the Fall (1992) and Winter (1993) at six sites within Cane Creek to determine the effects of...

  6. Modeling signal propagation mechanisms and ligand-based conformational dynamics of the Hsp90 molecular chaperone full-length dimer.

    Directory of Open Access Journals (Sweden)

    Giulia Morra

    2009-03-01

    Full Text Available Hsp90 is a molecular chaperone essential for protein folding and activation in normal homeostasis and stress response. ATP binding and hydrolysis facilitate Hsp90 conformational changes required for client activation. Hsp90 plays an important role in disease states, particularly in cancer, where chaperoning of the mutated and overexpressed oncoproteins is important for function. Recent studies have illuminated mechanisms related to the chaperone function. However, an atomic resolution view of Hsp90 conformational dynamics, determined by the presence of different binding partners, is critical to define communication pathways between remote residues in different domains intimately affecting the chaperone cycle. Here, we present a computational analysis of signal propagation and long-range communication pathways in Hsp90. We carried out molecular dynamics simulations of the full-length Hsp90 dimer, combined with essential dynamics, correlation analysis, and a signal propagation model. All-atom MD simulations with timescales of 70 ns have been performed for complexes with the natural substrates ATP and ADP and for the unliganded dimer. We elucidate the mechanisms of signal propagation and determine "hot spots" involved in interdomain communication pathways from the nucleotide-binding site to the C-terminal domain interface. A comprehensive computational analysis of the Hsp90 communication pathways and dynamics at atomic resolution has revealed the role of the nucleotide in effecting conformational changes, elucidating the mechanisms of signal propagation. Functionally important residues and secondary structure elements emerge as effective mediators of communication between the nucleotide-binding site and the C-terminal interface. Furthermore, we show that specific interdomain signal propagation pathways may be activated as a function of the ligand. Our results support a "conformational selection model" of the Hsp90 mechanism, whereby the protein may

  7. Lymphocytes with Aberrant Expression of Fas or Fas-ligand Attenuate Immune Bone Marrow Failure in a Mouse Model

    Science.gov (United States)

    Omokaro, Stephanie O.; Desierto, Marie J.; Eckhaus, Michael A.; Ellison, Felicia M.; Chen, Jichun; Young, Neal S.

    2012-01-01

    Bone marrow (BM) and lymphocyte samples from aplastic anemia patients show up-regulated Fas and Fas-ligand (FasL) expression respectively, supporting a relationship between immune-mediated BM destruction and the Fas apoptotic pathway. Mice with spontaneous lymphoproliferation (lpr) and generalized lymphoproliferative disease (gld) mutations exhibit abnormal expression of Fas and FasL; serving as potential models to elucidate underlying mechanisms of BM failure. We examined cellular and functional characteristics of lpr and gld mutants on the C57BL/6 (B6) background. Lymph node (LN) cells from lpr and gld mice produced less apoptosis when co-incubated with C.B10-H2b/LilMcd (C.B10) BM cells in vitro. This functional difference was confirmed by infusing lpr, gld, and B6 LN cells into sub-lethally irradiated CB10 mice; all donor LN cells showed significant T cell expansion and activation but only B6 LN cells caused severe BM destruction. Mice infused with gld LN cells developed mild to moderate BM failure, despite receiving FasL-deficient effectors, thus suggesting the existence of alternative pathways or incomplete penetrance of the mutation. Paradoxically, mice that received Fas-deficient lpr LN cells also had reduced BM failure, likely due to down-regulation of pro-apoptotic genes, an effect that can be overcome by higher doses of lpr LN cells. Our model demonstrates that abnormal Fas or FasL expression interferes with the development of pancytopenia and marrow hypoplasia, validating a major role for the Fas/FasL cytotoxic pathway in immune-mediated BM failure, although disruption of this pathway does not completely abolish marrow destruction. PMID:19265119

  8. Lymphocytes with aberrant expression of Fas or Fas ligand attenuate immune bone marrow failure in a mouse model.

    Science.gov (United States)

    Omokaro, Stephanie O; Desierto, Marie J; Eckhaus, Michael A; Ellison, Felicia M; Chen, Jichun; Young, Neal S

    2009-03-15

    Bone marrow (BM) and lymphocyte samples from aplastic anemia patients show up-regulated Fas and Fas-ligand (FasL) expression, respectively, supporting a relationship between immune-mediated BM destruction and the Fas apoptotic pathway. Mice with spontaneous lymphoproliferation (lpr) and generalized lymphoproliferative disease (gld) mutations exhibit abnormal expression of Fas and FasL, serving as potential models to elucidate underlying mechanisms of BM failure. We examined cellular and functional characteristics of lpr and gld mutants on the C57BL/6 (B6) background. Lymph node (LN) cells from lpr and gld mice produced less apoptosis when coincubated with C.B10-H2(b)/LilMcd (C.B10) BM cells in vitro. This functional difference was confirmed by infusing lpr, gld, and B6 LN cells into sublethally irradiated CB10 mice. All donor LN cells showed significant T cell expansion and activation, but only B6 LN cells caused severe BM destruction. Mice infused with gld LN cells developed mild to moderate BM failure despite receiving FasL-deficient effectors, thus suggesting the existence of alternative pathways or incomplete penetrance of the mutation. Paradoxically, mice that received Fas-deficient lpr LN cells also had reduced BM failure, likely due to down-regulation of proapoptotic genes, an effect that can be overcome by higher doses of lpr LN cells. Our model demonstrates that abnormal Fas or FasL expression interferes with the development of pancytopenia and marrow hypoplasia, validating a major role for the Fas/FasL cytotoxic pathway in immune-mediated BM failure, although disruption of this pathway does not completely abolish marrow destruction.

  9. Scaled biotic disruption during early Eocene global warming events

    OpenAIRE

    Gibbs, S. J.; Bown, P. R.; Murphy, B. H.; Sluijs, A.; Edgar, K. M.; Pälike, H.; C. T. Bolton; Zachos, J. C.

    2012-01-01

    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 o...

  10. Decrypting the sequence of structural events during the gating transition of pentameric ligand-gated ion channels based on an interpolated elastic network model.

    Directory of Open Access Journals (Sweden)

    Wenjun Zheng

    Full Text Available Despite many experimental and computational studies of the gating transition of pentameric ligand-gated ion channels (pLGICs, the structural basis of how ligand binding couples to channel gating remains unknown. By using a newly developed interpolated elastic network model (iENM, we have attempted to compute a likely transition pathway from the closed- to the open-channel conformation of pLGICs as captured by the crystal structures of two prokaryotic pLGICs. The iENM pathway predicts a sequence of structural events that begins at the ligand-binding loops and is followed by the displacements of two key loops (loop 2 and loop 7 at the interface between the extracellular and transmembrane domain, the tilting/bending of the pore-lining M2 helix, and subsequent movements of M4, M3 and M1 helices in the transmembrane domain. The predicted order of structural events is in broad agreement with the Φ-value analysis of α subunit of nicotinic acetylcholine receptor mutants, which supports a conserved core mechanism for ligand-gated channel opening in pLGICs. Further perturbation analysis has supported the critical role of certain intra-subunit and inter-subunit interactions in dictating the above sequence of events.

  11. Uranium Isotope Fractionation during Adsorption, (Co)precipitation, and Biotic Reduction.

    Science.gov (United States)

    Dang, Duc Huy; Novotnik, Breda; Wang, Wei; Georg, R Bastian; Evans, R Douglas

    2016-12-06

    Uranium contamination of surface environments is a problem associated with both U-ore extraction/processing and situations in which groundwater comes into contact with geological formations high in uranium. Apart from the environmental concerns about U contamination, its accumulation and isotope composition have been used in marine sediments as a paleoproxy of the Earth's oxygenation history. Understanding U isotope geochemistry is then essential either to develop sustainable remediation procedures as well as for use in paleotracer applications. We report on parameters controlling U immobilization and U isotope fractionation by adsorption onto Mn/Fe oxides, precipitation with phosphate, and biotic reduction. The light U isotope ((235)U) is preferentially adsorbed on Mn/Fe oxides in an oxic system. When adsorbed onto Mn/Fe oxides, dissolved organic carbon and carbonate are the most efficient ligands limiting U binding resulting in slight differences in U isotope composition (δ(238)U = 0.22 ± 0.06‰) compared to the DOC/DIC-free configuration (δ(238)U = 0.39 ± 0.04‰). Uranium precipitation with phosphate does not induce isotope fractionation. In contrast, during U biotic reduction, the heavy U isotope ((238)U) is accumulated in reduced species (δ(238)U up to -1‰). The different trends of U isotope fractionation in oxic and anoxic environments makes its isotope composition a useful tracer for both environmental and paleogeochemical applications.

  12. Copper(I) nitro complex with an anionic [HB(3,5-Me2Pz)3]− ligand: a synthetic model for the copper nitrite reductase active site.

    Science.gov (United States)

    Hsu, Sodio C N; Chang, Yu-Lun; Chuang, Wan-Jung; Chen, Hsing-Yin; Lin, I-Jung; Chiang, Michael Y; Kao, Chai-Lin; Chen, Hsuan-Ying

    2012-09-03

    The new copper(I) nitro complex [(Ph(3)P)(2)N][Cu(HB(3,5-Me(2)Pz)(3))(NO(2))] (2), containing the anionic hydrotris(3,5-dimethylpyrazolyl)borate ligand, was synthesized, and its structural features were probed using X-ray crystallography. Complex 2 was found to cocrystallize with a water molecule, and X-ray crystallographic analysis showed that the resulting molecule had the structure [(Ph(3)P)(2)N][Cu(HB(3,5-Me(2)Pz)(3))(NO(2))]·H(2)O (3), containing a water hydrogen bonded to an oxygen of the nitrite moiety. This complex represents the first example in the solid state of an analogue of the nitrous acid intermediate (CuNO(2)H). A comparison of the nitrite reduction reactivity of the electron-rich ligand containing the CuNO(2) complex 2 with that of the known neutral ligand containing the CuNO(2) complex [Cu(HC(3,5-Me(2)Pz)(3))(NO(2))] (1) shows that reactivity is significantly influenced by the electron density around the copper and nitrite centers. The detailed mechanisms of nitrite reduction reactions of 1 and 2 with acetic acid were explored by using density functional theory calculations. Overall, the results of this effort show that synthetic models, based on neutral HC(3,5-Me(2)Pz)(3) and anionic [HB(3,5-Me(2)Pz)(3)](-) ligands, mimic the electronic influence of (His)(3) ligands in the environment of the type II copper center of copper nitrite reductases (Cu-NIRs).

  13. Stoichiometry and geometry of the CXC chemokine receptor 4 complex with CXC ligand 12: Molecular modeling and experimental validation

    Science.gov (United States)

    Kufareva, Irina; Stephens, Bryan S.; Holden, Lauren G.; Qin, Ling; Zhao, Chunxia; Kawamura, Tetsuya; Abagyan, Ruben; Handel, Tracy M.

    2014-01-01

    Chemokines and their receptors regulate cell migration during development, immune system function, and in inflammatory diseases, making them important therapeutic targets. Nevertheless, the structural basis of receptor:chemokine interaction is poorly understood. Adding to the complexity of the problem is the persistently dimeric behavior of receptors observed in cell-based studies, which in combination with structural and mutagenesis data, suggest several possibilities for receptor:chemokine complex stoichiometry. In this study, a combination of computational, functional, and biophysical approaches was used to elucidate the stoichiometry and geometry of the interaction between the CXC-type chemokine receptor 4 (CXCR4) and its ligand CXCL12. First, relevance and feasibility of a 2:1 stoichiometry hypothesis was probed using functional complementation experiments with multiple pairs of complementary nonfunctional CXCR4 mutants. Next, the importance of dimers of WT CXCR4 was explored using the strategy of dimer dilution, where WT receptor dimerization is disrupted by increasing expression of nonfunctional CXCR4 mutants. The results of these experiments were supportive of a 1:1 stoichiometry, although the latter could not simultaneously reconcile existing structural and mutagenesis data. To resolve the contradiction, cysteine trapping experiments were used to derive residue proximity constraints that enabled construction of a validated 1:1 receptor:chemokine model, consistent with the paradigmatic two-site hypothesis of receptor activation. The observation of a 1:1 stoichiometry is in line with accumulating evidence supporting monomers as minimal functional units of G protein-coupled receptors, and suggests transmission of conformational changes across the dimer interface as the most probable mechanism of altered signaling by receptor heterodimers. PMID:25468967

  14. Type 1 cannabinoid receptor ligands display functional selectivity in a cell culture model of striatal medium spiny projection neurons.

    Science.gov (United States)

    Laprairie, Robert B; Bagher, Amina M; Kelly, Melanie E M; Dupré, Denis J; Denovan-Wright, Eileen M

    2014-09-05

    Modulation of type 1 cannabinoid receptor (CB1) activity has been touted as a potential means of treating addiction, anxiety, depression, and neurodegeneration. Different agonists of CB1 are known to evoke varied responses in vivo. Functional selectivity is the ligand-specific activation of certain signal transduction pathways at a receptor that can signal through multiple pathways. To understand cannabinoid-specific functional selectivity, different groups have examined the effect of individual cannabinoids on various signaling pathways in heterologous expression systems. In the current study, we compared the functional selectivity of six cannabinoids, including two endocannabinoids (2-arachidonyl glycerol (2-AG) and anandamide (AEA)), two synthetic cannabinoids (WIN55,212-2 and CP55,940), and two phytocannabinoids (cannabidiol (CBD) and Δ(9)-tetrahydrocannabinol (THC)) on arrestin2-, Gα(i/o)-, Gβγ-, Gα(s)-, and Gα(q)-mediated intracellular signaling in the mouse STHdh(Q7/Q7) cell culture model of striatal medium spiny projection neurons that endogenously express CB1. In this system, 2-AG, THC, and CP55,940 were more potent mediators of arrestin2 recruitment than other cannabinoids tested. 2-AG, AEA, and WIN55,212-2, enhanced Gα(i/o) and Gβγ signaling, with 2-AG and AEA treatment leading to increased total CB1 levels. 2-AG, AEA, THC, and WIN55,212-2 also activated Gα(q)-dependent pathways. CP55,940 and CBD both signaled through Gα(s). CP55,940, but not CBD, activated downstream Gα(s) pathways via CB1 targets. THC and CP55,940 promoted CB1 internalization and decreased CB1 protein levels over an 18-h period. These data demonstrate that individual cannabinoids display functional selectivity at CB1 leading to activation of distinct signaling pathways. To effectively match cannabinoids with therapeutic goals, these compounds must be screened for their signaling bias.

  15. Stoichiometry and geometry of the CXC chemokine receptor 4 complex with CXC ligand 12: molecular modeling and experimental validation.

    Science.gov (United States)

    Kufareva, Irina; Stephens, Bryan S; Holden, Lauren G; Qin, Ling; Zhao, Chunxia; Kawamura, Tetsuya; Abagyan, Ruben; Handel, Tracy M

    2014-12-16

    Chemokines and their receptors regulate cell migration during development, immune system function, and in inflammatory diseases, making them important therapeutic targets. Nevertheless, the structural basis of receptor:chemokine interaction is poorly understood. Adding to the complexity of the problem is the persistently dimeric behavior of receptors observed in cell-based studies, which in combination with structural and mutagenesis data, suggest several possibilities for receptor:chemokine complex stoichiometry. In this study, a combination of computational, functional, and biophysical approaches was used to elucidate the stoichiometry and geometry of the interaction between the CXC-type chemokine receptor 4 (CXCR4) and its ligand CXCL12. First, relevance and feasibility of a 2:1 stoichiometry hypothesis was probed using functional complementation experiments with multiple pairs of complementary nonfunctional CXCR4 mutants. Next, the importance of dimers of WT CXCR4 was explored using the strategy of dimer dilution, where WT receptor dimerization is disrupted by increasing expression of nonfunctional CXCR4 mutants. The results of these experiments were supportive of a 1:1 stoichiometry, although the latter could not simultaneously reconcile existing structural and mutagenesis data. To resolve the contradiction, cysteine trapping experiments were used to derive residue proximity constraints that enabled construction of a validated 1:1 receptor:chemokine model, consistent with the paradigmatic two-site hypothesis of receptor activation. The observation of a 1:1 stoichiometry is in line with accumulating evidence supporting monomers as minimal functional units of G protein-coupled receptors, and suggests transmission of conformational changes across the dimer interface as the most probable mechanism of altered signaling by receptor heterodimers.

  16. 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

  17. 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.

  18. Ligand-Receptor Interactions

    CERN Document Server

    Bongrand, Pierre

    2008-01-01

    The formation and dissociation of specific noncovalent interactions between a variety of macromolecules play a crucial role in the function of biological systems. During the last few years, three main lines of research led to a dramatic improvement of our understanding of these important phenomena. First, combination of genetic engineering and X ray cristallography made available a simultaneous knowledg of the precise structure and affinity of series or related ligand-receptor systems differing by a few well-defined atoms. Second, improvement of computer power and simulation techniques allowed extended exploration of the interaction of realistic macromolecules. Third, simultaneous development of a variety of techniques based on atomic force microscopy, hydrodynamic flow, biomembrane probes, optical tweezers, magnetic fields or flexible transducers yielded direct experimental information of the behavior of single ligand receptor bonds. At the same time, investigation of well defined cellular models raised the ...

  19. Structure and reactivity of As(III)- and As(V)-rich schwertmannites and amorphous ferric arsenate sulfate from the Carnoulès acid mine drainage, France: Comparison with biotic and abiotic model compounds and implications for As remediation

    Science.gov (United States)

    Maillot, Fabien; Morin, Guillaume; Juillot, Farid; Bruneel, Odile; Casiot, Corinne; Ona-Nguema, Georges; Wang, Yuheng; Lebrun, Sophie; Aubry, Emmanuel; Vlaic, Gilberto; Brown, Gordon E.

    2013-03-01

    Poorly ordered nanocrystalline hydroxysulfate minerals of microbial origin, such as schwertmannite, Fe8O8(OH)6SO4, are important arsenic scavengers in sulfate-rich acid mine drainage (AMD) environments. However, despite the fact that As(III) and As(V) have been shown to sorb on schwertmannite, little is known about the actual mechanism of arsenic scavenging processes after microbial Fe(II) oxidation in AMD environments. The major focus of the present study is to determine the molecular-level structure of poorly ordered As(III) and As(V) bearing Fe oxyhydroxysulfate minerals from the Carnoulès AMD, France, which exhibits exceptional As(III) concentrations. Powder X-ray diffraction (XRD) and extended X-ray absorption fine structure (EXAFS) spectroscopy were used to compare field samples with a large set of synthetic analogs prepared via biotic or abiotic pathways, with As/Fe ratios typical of minerals and mineraloids ranging from nanocrystalline schwertmannite to amorphous hydroxysulfate compounds. Our results yield further evidence for the poisoning effect of As(V) in limiting the nucleation of schwertmannite. For initial dissolved As(V)/Fe(III) molar ratios ⩾0.2, amorphous Fe(III)-As(V) hydroxysulfate forms, with a local structure consistent with that of amorphous ferric arsenate. EXAFS data for this amorphous material are consistent with corner-sharing FeO6 octahedra to which AsO4 tetrahedra attach via double-corner 2C linkages. For As(V)/Fe(III) molar ratios lower than 0.2, As(V) binds to schwertmannite via 2C surface complexes. In contrast with the As(V)-containing samples, As(III) has a lower affinity for schwertmannite following its nucleation, as this mineral phase persists up to an initial As(III)/Fe(III) molar ratio of 0.6. EXAFS data indicate that during the precipitation process, As(III) forms dominantly 2C surface complexes on schwertmannite surfaces, likely on the sides of double-chains of Fe(III)(O,OH)6 octahedra, with a smaller proportion of edge

  20. Mechanisms of biotic resistance across complex life cycles.

    Science.gov (United States)

    Rius, Marc; Potter, Elaine E; Aguirre, J David; Stachowicz, John J

    2014-01-01

    Biotic resistance is the ability of communities to inhibit the establishment, spread or impact of novel species. However, the interactions that underlie biotic resistance depend heavily on the contexts in which species interact. Consequently, studies of biotic resistance that consider single processes, patches, species or life-history stages may provide an incomplete picture of the capacity for communities to resist invasion. Many organisms have multiphasic life cycles, where individuals can occupy distinct niches at different stages of the life history. Generally, studies of biotic resistance focus on interactions within a single life-history stage, and interactions at other life-history stages are overlooked. Here, we demonstrate that different mechanisms of biotic resistance occur across the life history and together limit the invasion success of an introduced marine invertebrate (Ciona intestinalis) in Northern California. We tested the role of interactions (competition and predation) with the resident community in limiting the abundance of Ciona through experiments conducted on fertilization, larval survival, settlement, early postsettlement survival, and the survival of juveniles and adults. Under some circumstances, Ciona became abundant in mid-successional stages and showed more rapid growth rates than a morphologically similar native species, Ascidia ceratodes. However, predators reduced Ciona abundance much more than that of Ascidia at several life stages. Furthermore, Ciona appeared to be a weaker competitor at the adult stage. Early life-history interactions with other sessile species at the fertilization, larval and recruit stages had modest to no effects on Ciona abundance. The presence of biotic resistance mechanisms acting at multiple life stages, and potentially under different conditions, suggests that different components of biotic resistance interact to enhance the resident community's resistance to invasion.

  1. Combining molecular dynamics simulation and ligand-receptor contacts analysis as a new approach for pharmacophore modeling: beta-secretase 1 and check point kinase 1 as case studies.

    Science.gov (United States)

    Hatmal, Ma'mon M; Jaber, Shadi; Taha, Mutasem O

    2016-12-01

    Ligand-based pharmacophore modeling require relatively long lists of active compounds, while a pharmacophore based on a single ligand-receptor crystallographic structure is often promiscuous. These problems prompted us to combine molecular dynamics (MD) simulation with ligand-receptor contacts analysis as means to develop valid pharmacophore model(s). The particular ligand-receptor complex is allowed to perturb over a few nano-seconds using MD simulation. Subsequently, ligand-receptor contact points (≤2.5 Å) are identified. Ligand-receptor contacts maintained above certain threshold during molecular dynamics simulation are considered critical and used to guide pharmacophore development. We termed this method as Molecular-Dynamics Based Ligand-Receptor Contact Analysis. We implemented this new methodology to develop valid pharmacophore models for check point kinase 1 (Chk1) and beta-secretase 1 (BACE1) inhibitors as case studies. The resulting pharmacophore models were validated by receiver operating characteristic curved analysis against inhibitors obtained from CHEMBL database.

  2. Combining molecular dynamics simulation and ligand-receptor contacts analysis as a new approach for pharmacophore modeling: beta-secretase 1 and check point kinase 1 as case studies

    Science.gov (United States)

    Hatmal, Ma'mon M.; Jaber, Shadi; Taha, Mutasem O.

    2016-12-01

    Ligand-based pharmacophore modeling require relatively long lists of active compounds, while a pharmacophore based on a single ligand-receptor crystallographic structure is often promiscuous. These problems prompted us to combine molecular dynamics (MD) simulation with ligand-receptor contacts analysis as means to develop valid pharmacophore model(s). The particular ligand-receptor complex is allowed to perturb over a few nano-seconds using MD simulation. Subsequently, ligand-receptor contact points (≤2.5 Å) are identified. Ligand-receptor contacts maintained above certain threshold during molecular dynamics simulation are considered critical and used to guide pharmacophore development. We termed this method as Molecular-Dynamics Based Ligand-Receptor Contact Analysis. We implemented this new methodology to develop valid pharmacophore models for check point kinase 1 (Chk1) and beta-secretase 1 (BACE1) inhibitors as case studies. The resulting pharmacophore models were validated by receiver operating characteristic curved analysis against inhibitors obtained from CHEMBL database.

  3. Synthesis, spectral characterization, molecular modeling, thermal study and biological evaluation of transition metal complexes of a bidentate Schiff base ligand.

    Science.gov (United States)

    Chandra, Sulekh; Bargujar, Savita; Nirwal, Rita; Qanungo, Kushal; Sharma, Saroj K

    2013-09-01

    Complexes of copper(II) and nickel(II) of general composition M(L)2X2, have been synthesized [where L=3-Bromoacetophenone thiosemicarbazone and X=CH3COO(-), Cl(-) and NO3(-)]. All the complexes were characterized by elemental analysis, magnetic moments, IR, electronic and EPR spectral studies. The ligand behaved as bidentate and coordinated through sulfur of -C=S group and nitrogen atoms of -C=N group. The copper(II) and nickel(II) complexes were found to have magnetic moments 1.94-2.02 BM, 2.96-3.02 BM respectively which was corresponding to one and two unpaired electrons respectively. The molar conductance of the complexes in solution of DMSO lies in the range of 10-20 Ω(-1) cm(2) mol(-1) indicating their non-electrolytic behavior. On the basis of EPR, electronic and infrared spectral studies, tetragonal geometry has been assigned for copper(II) complexes and an octahedral geometry for nickel(II) complexes. The values of Nephelauxetic parameter β lie in the range 0.19-0.37 which indicated the covalent character in metal ligand 'σ' bond. Synthesized ligand and its copper(II) and nickel(II) complexes have also been screened against different bacterial and fungal species which suggested that complexes are more active than the ligands in antimicrobial activities.

  4. 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 u

  5. Expert knowledge-based assessment of farming practices for different biotic indicators using fuzzy logic.

    Science.gov (United States)

    Sattler, Claudia; Stachow, Ulrich; Berger, Gert

    2012-03-01

    The study presented here describes a modeling approach for the ex-ante assessment of farming practices with respect to their risk for several single-species biodiversity indicators. The approach is based on fuzzy-logic techniques and, thus, is tolerant to the inclusion of sources of uncertain knowledge, such as expert judgment into the assessment. The result of the assessment is a so-called Index of Suitability (IS) for the five selected biotic indicators calculated per farming practice. Results of IS values are presented for the comparison of crops and for the comparison of several production alternatives per crop (e.g., organic vs. integrated farming, mineral vs. organic fertilization, and reduced vs. plow tillage). Altogether, the modeled results show that the different farming practices can greatly differ in terms of their suitability for the different biotic indicators and that the farmer has a certain scope of flexibility in opting for a farming practice that is more in favor of biodiversity conservation. Thus, the approach is apt to identify farming practices that contribute to biodiversity conservation and, moreover, enables the identification of farming practices that are suitable with respect to more than one biotic indicator.

  6. A new bioactive Schiff base ligands derived from propylazo-N-pyrimidin-2-yl-benzenesulfonamides Mn(II) and Cu(II) complexes: synthesis, thermal and spectroscopic characterization biological studies and 3D modeling structures.

    Science.gov (United States)

    Tawfik, Abdelrazak M; El-Ghamry, Mosad A; Abu-El-Wafa, Samy M; Ahmed, Naglaa M

    2012-11-01

    New series of Schiff base ligand H(2)L and their Cu(II) and Mn(II) complexes derived from azosulfapyrimidine were synthesized and characterized by elemental and thermal studies conductance measurements IR, electronic and EPR spectra. 3D modeling of the ligand indicate that azo group does not participate in complex formation and surface potential on one of the ligand under study indicate that electron density around azomethine groups are much higher than the azo group therefore coordination takes place around azomethine groups. The variety in the geometrical structures depends on the nature of both the metal ions and the Schiff base ligands. The thermo kinetic parameters are calculated and discussed. The biological activities of the ligands and complexes have been screened in vitro against some bacteria and fungi to study their capacity to inhibit their growth and to study the toxicity of the compounds.

  7. Glutamate receptor ligands attenuate allodynia and hyperalgesia and potentiate morphine effects in a mouse model of neuropathic pain.

    Science.gov (United States)

    Osikowicz, Maria; Mika, Joanna; Makuch, Wioletta; Przewlocka, Barbara

    2008-09-30

    Recent studies have indicated that metabotropic glutamate receptors mGluR5, mGluR2/3 and mGluR7 are present in the regions of central nervous system important for nociceptive transmission, but their involvement in neuropathic pain has not been well established. We demonstrated that acute and chronic administration of MPEP (mGluR5 antagonist), LY379268 (mGluR2/3 agonist), and AMN082 (mGluR7 agonist) attenuated allodynia (von Frey test) and hyperalgesia (cold plate test) as measured in Swiss albino mice on day seven after chronic constriction injury (CCI) to the sciatic nerve. Moreover, single administration of MPEP (30 mg/kg; i.p.) or LY379268 (10mg/kg; i.p.) injected 30 min before morphine potentiated morphine's effects (20mg/kg; i.p.) in the mouse CCI model, as measured by both the tests mentioned above. However, a single administration of AMN082 (3mg/kg; i.p.) potentiated the effects of a single morphine injection (20mg/kg; i.p.) in the von Frey test only. Chronic administration (7 days) of low doses of MPEP, LY379268 or AMN082 (all drugs at 3mg/kg; i.p.) potentiated the effects of single doses of morphine (3, 10, and 20mg/kg; i.p.) administered on day seven; however, AMN082 only potentiated the effect in the cold plate test. Additionally, the same doses of MPEP and LY379268 (but not AMN082) chronically co-administered with morphine (40 mg/kg; i.p.) attenuated the development of morphine tolerance in CCI-exposed mice. Our data suggest that mGluR5, mGluR2/3, and mGluR7 are involved in injury-induced plastic changes in nociceptive pathways and that the mGluR5 and mGluR2/3 ligands enhanced morphine's effectiveness in neuropathy, which could have therapeutic implications.

  8. Estimation of the pKa values of water ligands in transition metal complexes using density functional theory with polarized continuum model solvent corrections.

    Science.gov (United States)

    Gilson, Ronan; Durrant, Marcus C

    2009-12-14

    The deprotonation energies of the water ligands in a set of 40 d-block metal complexes have been calculated using density functional theory with polarized continuum model solvent corrections. The complexes include 13 aqua ions [M(OH(2))(n)](2+/3+) and a variety of aqua complexes with organic co-ligands, whose experimental pK(a) values have been reported in the literature. For comparison, the deprotonation energies of a set of 60 organic and inorganic molecules with experimental pK(a) values ranging from -25 (HSbF(6)) to +52 (C(2)H(6)) have also been calculated. Three different classes of acids are identified as giving different slopes in plots of pK(a) versus deprotonation energies; namely non-hydroxy acids, hydroxy acids, and the metal complexes. The correlation coefficients for the straight lines obtained for these three classes are 0.96, 0.97 and 0.92 respectively. Better correlations are found for sub-sets of the complexes, such as the 31 first row complexes (correlation coefficient 0.95).For several of the complexes, comparison of the calculated and observed pK(a) values, together with changes in the geometry upon optimization, offer new insights into the possible solution structures. It is concluded that DFT calculations incorporating solvent corrections can be used to give reasonable estimates of pK(a) values for the aqua ligands in a range of complex types.

  9. Repeated administration of AC-5216, a ligand for the 18 kDa translocator protein, improves behavioral deficits in a mouse model of post-traumatic stress disorder.

    Science.gov (United States)

    Qiu, Zhi-Kun; Zhang, Li-Ming; Zhao, Nan; Chen, Hong-Xia; Zhang, You-Zhi; Liu, Yan-Qin; Mi, Tian-Yue; Zhou, Wen-Wen; Li, Yang; Yang, Ri-Fang; Xu, Jiang-Ping; Li, Yun-Feng

    2013-08-01

    Post-traumatic stress disorder (PTSD) is a severely disabling anxiety disorder that may occur following exposure to a serious traumatic event. It is a psychiatric condition that can afflict anyone who has experienced a life-threatening or violent event. Previous studies have shown that changes in 18 kDa translocator protein (TSPO) expression (or function), a promising target for treating neurological disorders without benzodiazepine-like side effects, may correlate with PTSD. However, few studies have investigated the anti-PTSD effects of TSPO ligands. AC-5216, a ligand for TSPO, induces anxiolytic- and anti-depressant-like effects in animal models. The present study aimed to determine whether AC-5216 ameliorates PTSD behavior in mice. Following the training session consisting of exposure to inescapable electric foot shocks, animals were administered AC-5216 daily during the behavioral assessments, i.e., situational reminders (SRs), the open field (OF) test, the elevated plus-maze (EPM) test, and the staircase test (ST). The results indicated that exposure to foot shocks induced long-term behavioral deficiencies in the mice, including freezing and anxiety-like behavior, which were significantly ameliorated by repeated treatment with AC-5216 but without any effect on spontaneous locomotor activity or body weight. In summary, this study demonstrated the anti-PTSD effects of AC-5216 treatment, suggesting that TSPO may represent a therapeutic target for anti-PTSD drug discovery and that TSPO ligands may be a promising new class of drugs for the future treatment of PTSD.

  10. Model of the initiation of signal transduction by ligands in a cell culture: Simulation of molecules near a plane membrane comprising receptors

    Science.gov (United States)

    Plante, Ianik; Cucinotta, Francis A.

    2011-11-01

    Cell communication is a key mechanism in tissue responses to radiation. Several molecules are implicated in radiation-induced signaling between cells, but their contributions to radiation risk are poorly understood. Meanwhile, Green's functions for diffusion-influenced reactions have appeared in the literature, which are applied to describe the diffusion of molecules near a plane membrane comprising bound receptors with the possibility of reversible binding of a ligand and activation of signal transduction proteins by the ligand-receptor complex. We have developed Brownian dynamics algorithms to simulate particle histories in this system which can accurately reproduce the theoretical distribution of distances of a ligand from the membrane, the number of reversibly bound particles, and the number of receptor complexes activating signaling proteins as a function of time, regardless of the number of time steps used for the simulation. These simulations will be of great importance to model interactions at low doses where stochastic effects induced by a small number of molecules or interactions come into play.

  11. TOPOLOGY DESIGN OPTIMIZATION BASED ON BIOTIC BRANCH NET

    Institute of Scientific and Technical Information of China (English)

    Ding Xiaohong; Li Guojie; Yamazaki Koestu

    2005-01-01

    The biotic branch nets are extreme high-tech product. In order to achieve a certain functional objective, they can adjust their growth direction and growth velocity by according to the varying growth environment. An innovative and effective methodology of topology design optimization based on the growth mechanism of biotic branch nets is suggested, and it is applied to a layout design problem of a conductive cooling channel in a heat transfer system. The effectiveness of the method is validated by the FEM analysis.

  12. Long-term studies on anticonvulsant tolerance and withdrawal characteristics of benzodiazepine receptor ligands in different seizure models in mice. I. Comparison of diazepam, clonazepam, clobazam and abecarnil.

    Science.gov (United States)

    Löscher, W; Rundfeldt, C; Hönack, D; Ebert, U

    1996-11-01

    We have reported recently that the seizure model and experimental protocol may markedly influence anticonvulsant tolerance and withdrawal characteristics of benzodiazepine (BDZ) receptor ligands so that predictions on tolerance and dependence liability of novel drugs should be based on a battery of chronic experiments. In the present study, we compared BDZ receptor ligands with different intrinsic efficacy and/or gamma-aminobutyric acidA/BDZ receptor subtype selectivity in two seizure models, by using different experimental approaches to assess the tolerance and dependence liability. In one approach, mice were chronically treated with either diazepam, clonazepam, clobazam or the novel anxiolytic and anticonvulsant beta-carboline derivative abecarnil for 4 weeks, at doses which were about equipotent to increase the threshold for myoclonic seizures induced by pentylenetetrazole. Anticonvulsant activity was determined several times during the period of chronic treatment as well as up to 2 weeks after termination of treatment in the same group of animals per drug. The threshold for electroshock-induced tonic seizures was used as a second seizure model in separate groups of mice. In another approach, drug treatment protocols were the same but the seizures were induced only twice during the 4-week period of treatment to reduce the number of trials which could lead to "learned" tolerance. In additional groups of mice, the seizure thresholds were only determined before and after the period of treatment to assess whether repeated seizure induction during the chronic treatment affects the development of dependence. All four drugs lost anticonvulsant activity during the chronic treatment in the different models and experimental approaches, without indication for a significant involvement of learned tolerance. However, marked protocol-related differences were seen with respect to withdrawal symptoms, i.e., measures of physical dependence-inducing properties of the different

  13. Further evidence for differences between non-selective and BZ-1 (omega 1) selective, benzodiazepine receptor ligands in murine models of "state" and "trait" anxiety.

    Science.gov (United States)

    Griebel, G; Sanger, D J; Perrault, G

    1996-01-01

    The behavioural effects of several BZ (omega) receptor ligands were compared in mice using the light/dark choice task, an animal model of "state" anxiety, and the free-exploration test, which has been proposed as an experimental model of "trait" anxiety. The drugs used included non-selective full (alprazolam, clorazepate, chlordiazepoxide and diazepam), partial agonists (bretazenil, imidazenil and Ro 19-8022) and BZ-1 (omega 1) selective receptor ligands (abecarnil, CL 218,872 and zolpidem). In the light/dark choice task, non-selective full agonists elicited clear anxiolytic-like effects increasing time spent in the lit box and simultaneously reducing attempts at entry into the illuminated cage followed by withdrawal responses, a measure of risk assessment. With the exception of abecarnil, both non-selective partial agonists and BZ-1 (omega 1) selective receptor ligands displayed reduced efficacy compared to the full agonists as they decreased risk assessment responses without altering time in the lit box. In addition, the weak anxiolytic-like actions displayed by selective BZ-1 (omega 1) agents were evident only at doses which reduced locomotor activity, indicating that this effect may be non-specific. In the free-exploration test, non-selective BZ (omega) receptor agonists markedly increased the percentage of time spent in the novel compartment and reduced the number of attempts to enter whereas selective BZ-1 (omega 1) receptor ligands displayed a weaker neophobia-reducing effect as they reduced risk assessment responses only. As was the case in the light/dark choice task, this latter effect was observed at locomotor depressant doses. These findings indicate that while both full and partial BZ (omega) receptor agonists are equally effective against "trait" anxiety, full agonists may be superior in reducing "state" anxiety. In addition, the lack of specific effects of selective BZ-1 (omega 1) receptor ligands in reducing both types of anxiety suggests that the BZ

  14. Coordination mode of pentadentate ligand derivative of 5-amino-1,3,4-thiadiazole-2-thiol with nickel(II) and copper(II) metal ions: synthesis, spectroscopic characterization, molecular modeling and fungicidal study.

    Science.gov (United States)

    Chandra, Sulekh; Gautam, Seema; Kumar, Amit; Madan, Molly

    2015-02-01

    Complexes of nickel(II), and copper(II) were synthesized with pantadentate ligand i.e. 3,3'-thiodipropionicacid-bis(5-amino-1,3,4-thiadiazole-2-thiol) (L). The ligand was synthesized by the condensation of thiodipropionic acid and 5-amino-1,3,4-thiadiazole-2-thiol in 1:2 ratio, respectively. Synthesized ligand was characterized by elemental analysis, mass, (1)H NMR, IR, and molecular modeling. All the complexes were characterized by elemental analysis, molar conductance, magnetic moment, IR, electronic spectra, ESR, and molecular modeling. The newly synthesized complexes possessed general composition [M(L)X2] where M = Ni(II), Cu(II), L = pantadentate ligand and X = Cl(-), CH3COO(-). The IR spectral data indicated that the ligand behaved as a pantadentate ligand and coordinated to the metal ion through N2S3 donor atoms. The molar conductance value of Ni(II), and Cu(II) complexes in DMSO corresponded to their electrolytic behavior. On the basis of spectral study, octahedral and tetragonal geometry was assigned for Ni(II) and Cu(II) complexes, respectively. In vitro fungicidal study of ligand and its complexes was investigated against fungi Candida albicans, Candida parapsilosis, Candidia krusei, and Candida tropicalis by means of well diffusion method.

  15. Models for the active site in galactose oxidase: Structure, spectra and redox of copper(II) complexes of certain phenolate ligands

    Indian Academy of Sciences (India)

    Mathrubootham Vaidyanathan; Mallayan Palaniandavar

    2000-06-01

    Galactose oxidase (GOase) is a fungal enzyme which is unusual among metalloenzymes in appearing to catalyse the two electron oxidation of primary alcohols to aldehydes and H2O2. The crystal structure of the enzyme reveals that the coordination geometry of mononuclear copper(II) ion is square pyramidal, with two histidine imidazoles, a tyrosinate, and either H2O (H 7.0) or acetate (from buffer, H 4.5) in the equatorial sites and a tyrosinate ligand weakly bound in the axial position. This paper summarizes the results of our studies on the structure, spectral and redox properties of certain novel models for the active site of the inactive form of GOase. The monophenolato Cu(II) complexes of the type [Cu(L1)X][H(L1) = 2-(bis(pyrid-2-ylmethyl)aminomethyl)-4-nitrophenol and X-= Cl-1, NCS-2, CH3COO-3, ClO$_{4}^{-}$ 4] reveal a distorted square pyramidal geometry around Cu(II) with an unusual axial coordination of phenolate moiety. The coordination geometry of 3 is reminiscent of the active site of GOase with an axial phenolate and equatorial CH3COO- ligands. All the present complexes exhibit several electronic and EPR spectral features which are also similar to the enzyme. Further, to establish the structural and spectroscopic consequences of the coordination of two tyrosinates in GOase enzyme, we studied the monomeric copper(II) complexes containing two phenolates and imidazole/pyridine donors as closer structural models for GOase. N,Ndimethylethylenediamine and N,N -dimethylethylenediamine have been used as starting materials to obtain a variety of 2,4-disubstituted phenolate ligands. The X-ray crystal structures of the complexes [Cu(L5)(py)], (8) [H2 (L5) = N,N-dimethyl-N ,N -bis(2-hydroxy-4-nitrobenzyl) ethylenediamine, py = pyridine] and [Cu(L8)(H2O)] (11), [H2(L8) = N,N -dimethyl-N,N -bis(2-hydroxy-4-nitrobenzyl)ethylenediamine] reveal distorted square pyramidal geometries around Cu(II) with the axial tertiary amine nitrogen and water coordination respectively

  16. Elucidating biotic factors that influence assembly of fungal endophyte communities

    Science.gov (United States)

    Most plants harbor a diverse assemblage of non-mycorrhizal fungal endophytes. These fungi can directly influence the host plant, and can instigate trophic cascades that affect surrounding communities of herbivores, plants, and animals. Despite this, biotic mechanisms that influence assembly of funga...

  17. 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 effec

  18. 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.

  19. 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 ch

  20. 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)

  1. Ecogenomics of plant resistance to biotic and abiotic stresses

    NARCIS (Netherlands)

    Davila Olivas, N.H.

    2016-01-01

    Summary

    In natural and agricultural ecosystems, plants are exposed to a wide diversity of abiotic and biotic stresses such as drought, salinity, pathogens and insect herbivores. Under natural conditions, these stresses do not occur in isolation but commonly occur simultaneo

  2. Scaled biotic disruption during early Eocene global warming events

    Directory of Open Access Journals (Sweden)

    S. J. Gibbs

    2012-01-01

    Full Text Available Late Paleocene and early Eocene hyperthermals are transient global warming events associated with massive carbon injection or carbon redistribution in the ocean-atmosphere system, 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, including 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.

  3. 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.

  4. A multi-resolution model to capture both global fluctuations of an enzyme and molecular recognition in the ligand-binding site

    CERN Document Server

    Fogarty, Aoife C; Kremer, Kurt

    2016-01-01

    In multi-resolution simulations, different system components are simultaneously modelled at different levels of resolution, these being smoothly coupled together. In the case of enzyme systems, computationally expensive atomistic detail is needed in the active site to capture the chemistry of substrate binding. Global properties of the rest of the protein also play an essential role, determining the structure and fluctuations of the binding site; however, these can be modelled on a coarser level. Similarly, in the most computationally efficient scheme only the solvent hydrating the active site requires atomistic detail. We present a methodology to couple atomistic and coarse-grained protein models, while solvating the atomistic part of the protein in atomistic water. This allows a free choice of which protein and solvent degrees of freedom to include atomistically, without loss of accuracy in the atomistic description. This multi-resolution methodology can successfully model stable ligand binding, and we furt...

  5. Studies on some metal complexes of quinoxaline based unsymmetric ligand: Synthesis, spectral characterization, in vitro biological and molecular modeling studies.

    Science.gov (United States)

    Dhanaraj, Chellaian Justin; Johnson, Jijo

    2016-08-01

    Mononuclear Co(II), Ni(II), Cu(II) and Zn(II) complexes of an unsymmetric Schiff base ligand, 3-(-(3-(-3,5-dichloro-2-hydroxybenzylideneamino)propylimino)methyl)quinoxalin-2(1H) -one (L) were synthesized and characterized by various analytical and spectral techniques. The molar conductance values of metal complexes indicate non-electrolytic behavior of the metal complexes. The Schiff base act as tetra dentate ONNO donor ligand in Co(II), Ni(II), Zn(II) complexes and tridentate NNO donor in Cu(II) complex. Thermal stabilities of the newly synthesized compounds were determined by thermal analysis. Crystallinity, average grain size and unit cell parameters were determined from powder X-ray diffraction study. Electrochemical behaviors of the compounds were examined by cyclic voltammetry technique. The Schiff base and its complexes have been screened for their in vitro antimicrobial activities against some bacterial and fungal strains by disc diffusion method. The interaction of the compounds with calf thymus DNA (CT DNA) has been investigated by electronic absorption spectral titration and viscosity measurement (hydrodynamic) methods. Furthermore, the pUC18 DNA cleavage activities of the complexes have been explored. The compounds were also subjected to in vitro antioxidant, anticancer activity screening, druglikeness and bioactivity predictions using Molinspiration software. Molecular docking studies of the present compounds were carried out against B-DNA dodecamer d(CGCGAATTCGCG)2 and vascular endothelial growth factor receptor (VEGFR-2) kinase. Quantum chemical calculations were done with DFT method to determine the optimum geometry of the ligand and its metal complexes. From the quantum chemical parameters, the reactivity parameters of the compounds were established.

  6. Molecular modeling of the human P2Y14 receptor: A template for structure-based design of selective agonist ligands.

    Science.gov (United States)

    Trujillo, Kevin; Paoletta, Silvia; Kiselev, Evgeny; Jacobson, Kenneth A

    2015-07-15

    The P2Y14 receptor (P2Y14R) is a Gi protein-coupled receptor that is activated by uracil nucleotides UDP and UDP-glucose. The P2Y14R structure has yet to be solved through X-ray crystallography, but the recent agonist-bound crystal structure of the P2Y12R provides a potentially suitable template for its homology modeling for rational structure-based design of selective and high-affinity ligands. In this study, we applied ligand docking and molecular dynamics refinement to a P2Y14R homology model to qualitatively explain structure-activity relationships of previously published synthetic nucleotide analogues and to probe the quality of P2Y14R homology modeling as a template for structure-based design. The P2Y14R model supports the hypothesis of a conserved binding mode of nucleotides in the three P2Y12-like receptors involving functionally conserved residues. We predict phosphate group interactions with R253(6.55), K277(7.35), Y256(6.58) and Q260(6.62), nucleobase (anti-conformation) π-π stacking with Y102(3.33) and the role of F191(5.42) as a means for selectivity among P2Y12-like receptors. The glucose moiety of UDP-glucose docked in a secondary subpocket at the P2Y14R homology model. Thus, P2Y14R homology modeling may allow detailed prediction of interactions to facilitate the design of high affinity, selective agonists as pharmacological tools to study the P2Y14R.

  7. A small molecule TrkB ligand reduces motor impairment and neuropathology in R6/2 and BACHD mouse models of Huntington's disease.

    Science.gov (United States)

    Simmons, Danielle A; Belichenko, Nadia P; Yang, Tao; Condon, Christina; Monbureau, Marie; Shamloo, Mehrdad; Jing, Deqiang; Massa, Stephen M; Longo, Frank M

    2013-11-27

    Loss of neurotrophic support in the striatum caused by reduced brain-derived neurotrophic factor (BDNF) levels plays a critical role in Huntington's disease (HD) pathogenesis. BDNF acts via TrkB and p75 neurotrophin receptors (NTR), and restoring its signaling is a prime target for HD therapeutics. Here we sought to determine whether a small molecule ligand, LM22A-4, specific for TrkB and without effects on p75(NTR), could alleviate HD-related pathology in R6/2 and BACHD mouse models of HD. LM22A-4 was administered to R6/2 mice once daily (5-6 d/week) from 4 to 11 weeks of age via intraperitoneal and intranasal routes simultaneously to maximize brain levels. The ligand reached levels in the R6/2 forebrain greater than the maximal neuroprotective dose in vitro and corrected deficits in activation of striatal TrkB and its key signaling intermediates AKT, PLCγ, and CREB. Ligand-induced TrkB activation was associated with a reduction in HD pathologies in the striatum including decreased DARPP-32 levels, neurite degeneration of parvalbumin-containing interneurons, inflammation, and intranuclear huntingtin aggregates. Aggregates were also reduced in the cortex. Notably, LM22A-4 prevented deficits in dendritic spine density of medium spiny neurons. Moreover, R6/2 mice given LM22A-4 demonstrated improved downward climbing and grip strength compared with those given vehicle, though these groups had comparable rotarod performances and survival times. In BACHD mice, long-term LM22A-4 treatment (6 months) produced similar ameliorative effects. These results support the hypothesis that targeted activation of TrkB inhibits HD-related degenerative mechanisms, including spine loss, and may provide a disease mechanism-directed therapy for HD and other neurodegenerative conditions.

  8. Biotic Interaction in Space and Time

    DEFF Research Database (Denmark)

    Schmidt, Andreas Kelager

    it is highly sensitive to the ongoing environmental change caused by humans. The main drivers for its decline are changed land-use and associated habitat loss or fragmentation, and (in more recent times) drainage, increased eutrophication and lack of appropriate management, but future climate change may...... 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...... anthropogenic change and that conservation should focus on preserving or establishing functional network of habitats to support viable metapopulations. In chapter IV, we found that the suitability of M. alcon in Europe is likely to be geographically stable because of its tight dependence on the climatically...

  9. Synthesis, spectral and thermal studies of some transition metal mixed ligand complexes: modeling of equilibrium composition and biological activity.

    Science.gov (United States)

    Neelakantan, M A; Sundaram, M; Nair, M Sivasankaran

    2011-09-01

    Several mixed ligand Ni(II), Cu(II) and Zn(II) complexes of 2-amino-3-hydroxypyridine (AHP) and imidazoles viz., imidazole (him), benzimidazole (bim), histamine (hist) and L-histidine (his) have been synthesized and characterized by elemental and spectral (vibrational, electronic, 1H NMR and EPR) data as well as by magnetic moment values. On the basis of elemental analysis and molar conductance values, all the complexes can be formulated as [MAB]Cl except histidine complexes as MAB. Thermogravimetric studies reveal the presence of coordinated water molecules in most of the complexes. From the magnetic measurements and electronic spectral data, octahedral structure was proposed for Ni(II) and Cu(II)-AHP-his, tetrahedral for Cu(II)-AHP-him/bim/hist, but square planar for the Cu(II)-AHP complex. The g∥/A∥ calculated supports tetrahedral environment around the Cu(II) in Cu(II)-AHP-him/bim/hist and distorted octahedral for Cu(II)-AHP-his complexes. The morphology of the reported metal complexes was investigated by scanning electron micrographs (SEM). The potentiometric study has been performed in aqueous solution at 37 °C and I=0.15 mol dm(-3) NaClO4. MABH, MAB and MAB2 species has been identified in the present systems. Proton dissociation constants of AHP and stability constants of metal complexes were determined using MINIQUAD-75. The most probable structure of the mixed ligand species is discussed based upon their stability constants. The in vitro biological activity of the complexes was tested against the Gram positive and Gram negative bacteria, fungus and yeast. The oxidative DNA cleavage studies of the complexes were performed using gel electrophoresis method. Cu(II) complexes have been found to promote DNA cleavage in presence of biological reductant such as ascorbate and oxidant like hydrogen peroxide.

  10. Synthesis, spectral and thermal studies of some transition metal mixed ligand complexes: Modeling of equilibrium composition and biological activity

    Science.gov (United States)

    Neelakantan, M. A.; Sundaram, M.; Nair, M. Sivasankaran

    2011-09-01

    Several mixed ligand Ni(II), Cu(II) and Zn(II) complexes of 2-amino-3-hydroxypyridine (AHP) and imidazoles viz., imidazole (him), benzimidazole (bim), histamine (hist) and L-histidine (his) have been synthesized and characterized by elemental and spectral (vibrational, electronic, 1H NMR and EPR) data as well as by magnetic moment values. On the basis of elemental analysis and molar conductance values, all the complexes can be formulated as [MAB]Cl except histidine complexes as MAB. Thermogravimetric studies reveal the presence of coordinated water molecules in most of the complexes. From the magnetic measurements and electronic spectral data, octahedral structure was proposed for Ni(II) and Cu(II)-AHP-his, tetrahedral for Cu(II)-AHP-him/bim/hist, but square planar for the Cu(II)-AHP complex. The g∥/ A∥ calculated supports tetrahedral environment around the Cu(II) in Cu(II)-AHP-him/bim/hist and distorted octahedral for Cu(II)-AHP-his complexes. The morphology of the reported metal complexes was investigated by scanning electron micrographs (SEM). The potentiometric study has been performed in aqueous solution at 37 °C and I = 0.15 mol dm -3 NaClO 4. MABH, MAB and MAB 2 species has been identified in the present systems. Proton dissociation constants of AHP and stability constants of metal complexes were determined using MINIQUAD-75. The most probable structure of the mixed ligand species is discussed based upon their stability constants. The in vitro biological activity of the complexes was tested against the Gram positive and Gram negative bacteria, fungus and yeast. The oxidative DNA cleavage studies of the complexes were performed using gel electrophoresis method. Cu(II) complexes have been found to promote DNA cleavage in presence of biological reductant such as ascorbate and oxidant like hydrogen peroxide.

  11. 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

    but is more deeply anchored to the peptide-MHC (pep/MHC) ligand than TCRs, notably through numerous interactions of its heavy chain. The present model accounts well for the experimentally determined binding affinity of a set of 144 single amino acid substituted Ha analogues and the observed shared specificity......-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...

  12. Scouting new sigma receptor ligands: Synthesis, pharmacological evaluation and molecular modeling of 1,3-dioxolane-based structures and derivatives.

    Science.gov (United States)

    Franchini, Silvia; Battisti, Umberto Maria; Prandi, Adolfo; Tait, Annalisa; Borsari, Chiara; Cichero, Elena; Fossa, Paola; Cilia, Antonio; Prezzavento, Orazio; Ronsisvalle, Simone; Aricò, Giuseppina; Parenti, Carmela; Brasili, Livio

    2016-04-13

    Herein we report the synthesis and biological activity of new sigma receptor (σR) ligands obtained by combining different substituted five-membered heterocyclic rings with appropriate σR pharmacophoric amines. Radioligand binding assay, performed on guinea pig brain membranes, identified 25b (1-(1,4-dioxaspiro[4.5]decan-2-ylmethyl)-4-benzylpiperazine) as the most interesting compound of the series, displaying high affinity and selectivity for σ1R (pKiσ1 = 9.13; σ1/σ2 = 47). The ability of 25b to modulate the analgesic effect of the κ agonist (-)-U-50,488H and μ agonist morphine was evaluated in vivo by radiant heat tail-flick test. It exhibited anti-opioid effects on both κ and μ receptor-mediated analgesia, suggesting an agonistic behavior at σ1R. Docking studies were performed on the theoretical σ1R homology model. The present work represents a new starting point for the design of more potent and selective σ1R ligands.

  13. Ecogenomics of plant resistance to biotic and abiotic stresses

    OpenAIRE

    Davila Olivas, N.H.

    2016-01-01

    Summary In natural and agricultural ecosystems, plants are exposed to a wide diversity of abiotic and biotic stresses such as drought, salinity, pathogens and insect herbivores. Under natural conditions, these stresses do not occur in isolation but commonly occur simultaneously. However, plants have developed sophisticated mechanisms to survive and reproduce under suboptimal conditions. Genetic screenings and molecular genetic assays have shed light on the molecular players that provide resis...

  14. 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.

  15. The abiotic and biotic drivers of rapid diversification in Andean bellflowers (Campanulaceae).

    Science.gov (United States)

    Lagomarsino, Laura P; Condamine, Fabien L; Antonelli, Alexandre; Mulch, Andreas; Davis, Charles C

    2016-06-01

    The tropical Andes of South America, the world's richest biodiversity hotspot, are home to many rapid radiations. While geological, climatic, and ecological processes collectively explain such radiations, their relative contributions are seldom examined within a single clade. We explore the contribution of these factors by applying a series of diversification models that incorporate mountain building, climate change, and trait evolution to the first dated phylogeny of Andean bellflowers (Campanulaceae: Lobelioideae). Our framework is novel for its direct incorporation of geological data on Andean uplift into a macroevolutionary model. We show that speciation and extinction are differentially influenced by abiotic factors: speciation rates rose concurrently with Andean elevation, while extinction rates decreased during global cooling. Pollination syndrome and fruit type, both biotic traits known to facilitate mutualisms, played an additional role in driving diversification. These abiotic and biotic factors resulted in one of the fastest radiations reported to date: the centropogonids, whose 550 species arose in the last 5 million yr. Our study represents a significant advance in our understanding of plant evolution in Andean cloud forests. It further highlights the power of combining phylogenetic and Earth science models to explore the interplay of geology, climate, and ecology in generating the world's biodiversity.

  16. 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

    variables, but few SDM studies include biotic predictors to help explain species distributions. Therefore, most predictions of species distributions under future climates assume implicitly that biotic interactions remain constant or exert only minor influence on large-scale spatial distributions, which...... different sets of predictor variables: biotic, abiotic, and the combination of both sets. We used variance partitioning to estimate the proportion of the variance explained by biotic and abiotic predictors, jointly and independently. Inclusion of biotic predictors improved the SDMs substantially. The joint...... and are dominant across the landscape. The influence of biotic variables on SDM performance indicates that community composition and other local biotic factors or abiotic processes not included in the abiotic predictors strongly influence prediction of species distributions. Improved prediction of species...

  17. A new chiral, poly-imidazole N8-ligand and the related di- and tri-copper(II) complexes: synthesis, theoretical modelling, spectroscopic properties, and biomimetic stereoselective oxidations.

    Science.gov (United States)

    Mutti, Francesco G; Gullotti, Michele; Casella, Luigi; Santagostini, Laura; Pagliarin, Roberto; Andersson, K Kristoffer; Iozzi, Maria Francesca; Zoppellaro, Giorgio

    2011-05-28

    The new poly-imidazole N(8) ligand (S)-2-piperazinemethanamine-1,4-bis[2-((N-(1-acetoxy-3-(1-methyl-1H-imidazol-4-yl))-2-(S)-propyl)-(N-(1-methyl-1H-imidazol-2-ylmethyl)))ethyl]-N-(phenylmethyl)-N-(acetoxy), also named (S)-Pz-(C2-(HisIm))(2) (L), containing three chiral (S) centers, was obtained by a multi-step synthesis and used to prepare dinuclear [Cu(2)(L)](4+) and trinuclear [Cu(3)(L)](6+) copper(II) complexes. Low-temperature EPR experiments performed on [Cu(2)(L)](4+) demonstrated that the two S = ½ centers behaved as independent paramagnetic units, while the EPR spectra used to study the trinuclear copper complex, [Cu(3)(L)](6+), were consistent with a weakly coupled three-spin ½ system. Theoretical models for the two complexes were obtained by DFT/RI-BP86/TZVP geometry optimization, where the structural and electronic characteristics nicely supported the EPR experimental findings. In addition, the theoretical analysis unveiled that the conformational flexibility encoded in both [Cu(2)(L)](4+) and [Cu(3)(L)](6+) arises not only from the presence of several σ-bonds and the bulky residues attached to the (S)-Pz-(C2-(HisIm))(2) ligand scaffold, but also from the poor coordination ability of the tertiary amino groups located in the ligand side-chains containing the imidazole units towards the copper(II) ions. Both the dinuclear and trinuclear complexes are efficient catalysts in the stereoselective oxidation of several catechols and flavonoid compounds, yielding the corresponding quinones. The structural features of the substrate-catalyst adduct intermediates were assessed by searching the conformational space of the molecule through MMFF94/Monte Carlo (MMFF94/MC) methods. The conformational flexibility of the bound ligand in the complexes proves to be beneficial for substrate binding and recognition. For the dinuclear complex, chiral recognition of the optically active substrates derives from weak electrostatic interactions between bound substrates and

  18. Ligand-based pharmacophore modeling; atom-based 3D-QSAR analysis and molecular docking studies of phosphoinositide-dependent kinase-1 inhibitors

    Directory of Open Access Journals (Sweden)

    P Kirubakaran

    2012-01-01

    Full Text Available Phosphoinositide-dependent kinase-1 plays a vital role in the PI3-kinase signaling pathway that regulates gene expression, cell cycle growth and proliferation. The common human cancers include lung, breast, blood and prostate possess over stimulation of the phosphoinositide-dependent kinase-1 signaling and making phosphoinositide-dependent kinase-1 an interesting therapeutic target in oncology. A ligand-based pharmacophore and atom-based 3D-QSAR studies were carried out on a set of 82 inhibitors of PDK1. A six point pharmacophore with two hydrogen bond acceptors (A, three hydrogen bond donors (D and one hydrophobic group (H was obtained. The pharmacophore hypothesis yielded a 3D-QSAR model with good partial least square statistics results. The training set correlation is characterized by partial least square factors (R2 = 0.9557, SD = 0.2334, F = 215.5, P = 1.407e-32. The test set correlation is characterized by partial least square factors (Q2 ext = 0.7510, RMSE = 0.5225, Pearson-R =0.8676. The external validation indicated that our QSAR model possess high predictive power with good value of 0.99 and value of 0.88. The docking results show the binding orientations of these inhibitors at active site amino acid residues (Ala162, Thr222, Glu209 and Glu166 of phosphoinositide-dependent kinase-1 protein. The binding free energy interactions of protein-ligand complex have been calculated, which plays an important role in molecular recognition and drug design approach.

  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. Fully Flexible Docking of Medium Sized Ligand Libraries with RosettaLigand.

    Directory of Open Access Journals (Sweden)

    Samuel DeLuca

    Full Text Available RosettaLigand has been successfully used to predict binding poses in protein-small molecule complexes. However, the RosettaLigand docking protocol is comparatively slow in identifying an initial starting pose for the small molecule (ligand making it unfeasible for use in virtual High Throughput Screening (vHTS. To overcome this limitation, we developed a new sampling approach for placing the ligand in the protein binding site during the initial 'low-resolution' docking step. It combines the translational and rotational adjustments to the ligand pose in a single transformation step. The new algorithm is both more accurate and more time-efficient. The docking success rate is improved by 10-15% in a benchmark set of 43 protein/ligand complexes, reducing the number of models that typically need to be generated from 1000 to 150. The average time to generate a model is reduced from 50 seconds to 10 seconds. As a result we observe an effective 30-fold speed increase, making RosettaLigand appropriate for docking medium sized ligand libraries. We demonstrate that this improved initial placement of the ligand is critical for successful prediction of an accurate binding position in the 'high-resolution' full atom refinement step.

  1. Abiotic Versus Biotic Weathering Of Olivine As Possible Biosignatures

    Science.gov (United States)

    Longazo, Teresa G.; Wentworth, Susan J.; Clemett, Simon J.; Southam, Gordon; McKay, David S.

    2001-01-01

    We are investigating the weathering of silicate minerals by both purely inorganic, and biologically mediated processes using field-emission scanning electron microscopy (FESEM) and energy dispersive x-ray spectroscopy (EDS). By resolving surface textures and chemical compositions of weathered surfaces at the sub-micron scale we hope to be able to distinguish abiotic from biotic weathering processes and so establish a new biosignature applicable to the study of astromaterials including but not limited to the Martian meteorites. Sterilized olivine grains (San Carlos, Arizona) no more than 1-2 mm in their longest dimension were optically assayed to be uniform in color and free of inclusions were selected as weathering subjects. Prior to all experiments surface morphologies and Fe/Mg ratios were determined for each grain using FE-SEM and EDS. Experiments were divided into two categories abiotic and biotic and were compared with "naturally" weathered samples. For the preliminary experiments, two trials (open and closed to the ambient laboratory environment) were performed under abiotic conditions, and three trials under biotic conditions (control, day 1 and day 2). The open system abiotic trials used sterile grains heated at 98 C and 200 C for both 24 and 48 hours in 1L double distilled de-ionized water. The closed system abiotic trials were conducted under the same conditions but in a sealed two layer steel/Teflon "bomb" apparatus. The biotic trials used sterile grains mounted in a flow-through device attached to a wellhead on the Columbia River aquifer. Several discolored, altered, grains were selected to document "natural" weathering surface textures for comparison with the experimental samples. Preliminary results indicate there are qualitative differences in weathered surface textures among all the designed experiments. The olivine grains in abiotic trials displayed etching, pitting, denticulate margins, dissolution and clay formation. The scale of the features

  2. Identifying biotic integrity and water chemistry relations in nonwadeable rivers of Wisconsin: Toward the development of nutrient criteria

    Science.gov (United States)

    Weigel, B.M.; Robertson, D.M.

    2007-01-01

    We sampled 41 sites on 34 nonwadeable rivers that represent the types of rivers in Wisconsin, and the kinds and intensities of nutrient and other anthropogenic stressors upon each river type. Sites covered much of United States Environmental Protection Agency national nutrient ecoregions VII-Mostly Glaciated Dairy Region, and VIII-Nutrient Poor, Largely Glaciated upper Midwest. Fish, macroinvertebrates, and three categories of environmental variables including nutrients, other water chemistry, and watershed features were collected using standard protocols. We summarized fish assemblages by index of biotic integrity (IBI) and its 10 component measures, and macroinvertebrates by 2 organic pollution tolerance and 12 proportional richness measures. All biotic and environmental variables represented a wide range of conditions, with biotic measures ranging from poor to excellent status, despite nutrient concentrations being consistently higher than reference concentrations reported for the regions. Regression tree analyses of nutrients on a suite of biotic measures identified breakpoints in total phosphorus (~0.06 mg/l) and total nitrogen (~0.64 mg/l) concentrations at which biotic assemblages were consistently impaired. Redundancy analyses (RDA) were used to identify the most important variables within each of the three environmental variable categories, which were then used to determine the relative influence of each variable category on the biota. Nutrient measures, suspended chlorophyll a, water clarity, and watershed land cover type (forest or row-crop agriculture) were the most important variables and they explained significant amounts of variation within the macroinvertebrate (R 2 = 60.6%) and fish (R 2 = 43.6%) assemblages. The environmental variables selected in the macroinvertebrate model were correlated to such an extent that partial RDA analyses could not attribute variation explained to individual environmental categories, assigning 89% of the explained

  3. Treatment of waste effluent water in Studsvik. Thermodynamic modelling on the distribution of organic ligands between the liquid and solid phases

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Y.; Puigdomenech, I. [Royal Inst. of Technology, Stockholm (Sweden)

    2000-10-01

    This preliminary study based on theoretical chemical equilibrium calculations has been carried out in order to analyse the effects of complexing reagents such as EDTA, NTA and oxalate on the treatment of waste effluent water in Studsvik. The necessary stability constants have been selected and added into the database in MEDUSA software for thermodynamic modelling. The modelling has been performed for a synthetic system of various components: Al{sup 3+} -Am{sup 3+} -Ca{sup 2+} -Co{sup 2+} -Cu{sup 2+} -Fe{sup 3+} -K{sup +} -Mg{sup 2+} -Na{sup +} -UO{sub 2}{sup 2+} -Zn{sup 2+} -SO{sub 4}{sup 2-} -Cl{sup -} , in the absence an presence of one of the complexing ligands, EDTA, NTA and C{sub 2}O{sub 4}{sup 2-} (oxalate). The concentration conditions for the modelling are based on the data supplied in the previous reports on the waste effluent water in Studsvik. The calculated results are represented in graphic diagrams, compared and discussed. It is generally concluded: No solid phase of the complexing reagents concerned, except for calcium oxalate, may form according to the present modelling. It means that the distribution of EDTA and NTA between the slurry and the clean solution is mainly dependent upon the volume ratio of the liquid phase. Oxalate, however, may mostly precipitate as calcium oxalate in the slurry. The major eventual problem with the presence of the complexing reagents in the slurry is the probable re-dissolution of the radioactive components such as Am(OH){sub 3} and CaUO{sub 4}. Therefore, it is necessary to study the solid formation of those radioactive compounds in the slurry, their stability in the presence of the complexing reagents and the respective conditions to avoid their re-dissolution. Sorption of organic ligands into the Fe(III)-hydroxides has not been included in the model, but available literature data suggest that sorption is improbable under the conditions used (at pH {>=} 8)

  4. 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

  5. An autologous in situ tumor vaccination approach for hepatocellular carcinoma. 2. Tumor-specific immunity and cure after radio-inducible suicide gene therapy and systemic CD40-ligand and Flt3-ligand gene therapy in an orthotopic tumor model.

    Science.gov (United States)

    Kawashita, Yujo; Deb, Niloy J; Garg, Madhur K; Kabarriti, Rafi; Fan, Zuoheng; Alfieri, Alan A; Roy-Chowdhury, Jayanta; Guha, Chandan

    2014-08-01

    Diffuse hepatocellular carcinoma (HCC) is a lethal disease that radiation therapy (RT) currently has a limited role in treating because of the potential for developing fatal radiation-induced liver disease. However, recently diffuse HCC, "radio-inducible suicide gene therapy" has been shown to enhance local tumor control and residual microscopic disease within the liver for diffuse HCC, by using a combination of chemoactivation and molecular radiosensitization. We have demonstrated that the addition of recombinant adenovirus-expressing human Flt3 ligand (Adeno-Flt3L) after radio-inducible suicide gene therapy induced a Th1-biased, immune response and enhanced tumor control in an ectopic model of HCC. We hypothesized that sequential administration of recombinant adenovirus-expressing CD40L (Adeno-CD40L) could further potentiate the efficacy of our trimodal therapy with RT + HSV-TK + Adeno-Flt3L. We examined our hypothesis in an orthotopic model of diffuse HCC using BNL1ME A.7R.1 (BNL) cells in Balb/c mice. BNL murine hepatoma cells (5 × 10(4)) transfected with an expression vector of HSV-TK under the control of a radiation-inducible promoter were injected intraportally into BALB/cJ mice. Fourteen days after the HCC injection, mice were treated with a 25 Gy dose of radiation to the whole liver, followed by ganciclovir (GCV) treatment and systemic adenoviral cytokine gene therapy (Flt3L or CD40L or both). Untreated mice died in 27 ± 4 days. Radiation therapy alone had a marginal effect on survival (median = 35 ± 7 days) and the addition of HSV-TK/GCV gene therapy improved the median survival to 47 ± 6 days. However, the addition of Adeno-Flt3L to radiation therapy and HSV-TK/GCV therapy significantly (P = 0.0005) increased survival to a median of 63 ± 20 days with 44% (7/16) of the animals still alive 116 days after tumor implantation. The curative effect of Flt3L was completely abolished when using immunodeficient nude mice or mice depleted for CD4, CD8 and

  6. Managing biotic interactions for ecological intensification of agroecosystem

    Directory of Open Access Journals (Sweden)

    Sabrina eGaba

    2014-06-01

    Full Text Available Agriculture faces the challenge of increasing food production while simultaneously reducing the use of inputs and delivering other ecosystem services. Ecological intensification of agriculture is a paradigm shift, which has recently been proposed to meet such challenges through the manipulation of biotic interactions. While this approach opens up new possibilities, there are many constraints related to the complexity of agroecosystems that make it difficult to implement. Future advances, which are essential to guide agricultural policy, require an eco-evolutionary framework to ensure that ecological intensification is beneficial in the long term.

  7. Abiotic and Biotic Mechanisms Controlling In Situ Remediation of NDMA

    Science.gov (United States)

    2009-05-01

    of microbiota in removing potentially oxidizing species such as nitrate or oxygen. Alternatively, the biotic pathway may be more significant 0 20...than previously shown at pH 10.5 (Figures 4.6 and 4.10; half-life as fast as 8 hours) due to a smaller sediment/water ratio used in the...primarily abiotic, as described in previous experi- ments (Figure 4.36). NDMA mineraliza- tion was surprisingly fast , with an average half-life of 410

  8. Biotic homogenization can decrease landscape-scale forest multifunctionality

    DEFF Research Database (Denmark)

    van der Plas, Fons; Manning, Pete; Soliveres, Santiago;

    2016-01-01

    -diversity and landscape-scale multifunctionality were always positive, because a high spatial turnover in species composition was closely related to a high spatial turnover in functions that were supported at high levels. Our findings have major implications for forest management and indicate that biotic homogenization...... a comprehensive pan-European dataset, including 16 ecosystem functions measured in 209 forest plots across six European countries, and performed simulations to investigate how local plot-scale richness of tree species (α-diversity) and their turnover between plots (β-diversity) are related to landscape...

  9. 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.

  10. Patterns in salt-marsh ecosystems: the role of biotic and abiotic forcings

    Science.gov (United States)

    D'Alpaos, A.; Marani, M.

    2010-12-01

    The dynamics of salt-marsh ecosystems are governed by interacting physical and biological processes, whose intertwined feedbacks critically affect the evolution. Salt marshes are characterised by complex patterns, both in their geomorphic and biological features, arising through the elaboration of a network structure driven by the tidal forcing and through the interaction between hydrodynamical, geophysical, and biological components. The complexity observed in tidal geomorphological patterns is deemed to arise from the mutual influence of biotic and abiotic components. The results from a 2D numerical model, accounting for biotic and geomorphic processes, show that the average marsh elevation within the tidal frame decreases with increasing rates of sea-level rise, decreasing sediment availability, and decreasing vegetation productivity. The spatial variability in platform elevations and biomass distribution, increases with increasing rates of sea-level rise, increasing sediment availability, and decreasing vegetation productivity. Supply-limited settings tend to develop uniform marsh surface elevations and biomass distribution, whereas supply-rich settings tend to develop sedimentation patterns characterized by large heterogeneities. Our analyses also suggest that the fate of tidal landforms and their possible geomorphological restoration should be addressed through approaches which explicitly incorporate bio-morphodynamic processes.

  11. 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.

  12. 'Trophic whales' as biotic buffers: weak interactions stabilize ecosystems against nutrient enrichment.

    Science.gov (United States)

    Schwarzmüller, Florian; Eisenhauer, Nico; Brose, Ulrich

    2015-05-01

    Human activities may compromise biodiversity if external stressors such as nutrient enrichment endanger overall network stability by inducing unstable dynamics. However, some ecosystems maintain relatively high diversity levels despite experiencing continuing disturbances. This indicates that some intrinsic properties prevent unstable dynamics and resulting extinctions. Identifying these 'ecosystem buffers' is crucial for our understanding of the stability of ecosystems and an important tool for environmental and conservation biologists. In this vein, weak interactions have been suggested as stabilizing elements of complex systems, but their relevance has rarely been tested experimentally. Here, using network and allometric theory, we present a novel concept for a priori identification of species that buffer against externally induced instability of increased population oscillations via weak interactions. We tested our model in a microcosm experiment using a soil food-web motif. Our results show that large-bodied species feeding at the food web's base, so called 'trophic whales', can buffer ecosystems against unstable dynamics induced by nutrient enrichment. Similar to the functionality of chemical or mechanical buffers, they serve as 'biotic buffers' that take up stressor effects and thus protect fragile systems from instability. We discuss trophic whales as common functional building blocks across ecosystems. Considering increasing stressor effects under anthropogenic global change, conservation of these network-intrinsic biotic buffers may help maintain the stability and diversity of natural ecosystems.

  13. Insights into the interaction of negative allosteric modulators with the metabotropic glutamate receptor 5: discovery and computational modeling of a new series of ligands with nanomolar affinity.

    Science.gov (United States)

    Anighoro, Andrew; Graziani, Davide; Bettinelli, Ilaria; Cilia, Antonio; De Toma, Carlo; Longhi, Matteo; Mangiarotti, Fabio; Menegon, Sergio; Pirona, Lorenza; Poggesi, Elena; Riva, Carlo; Rastelli, Giulio

    2015-07-01

    Metabotropic glutamate receptor 5 (mGlu5) is a biological target implicated in major neurological and psychiatric disorders. In the present study, we have investigated structural determinants of the interaction of negative allosteric modulators (NAMs) with the seven-transmembrane (7TM) domain of mGlu5. A homology model of the 7TM receptor domain built on the crystal structure of the mGlu1 template was obtained, and the binding modes of known NAMs, namely MPEP and fenobam, were investigated by docking and molecular dynamics simulations. The results were validated by comparison with mutagenesis data available in the literature for these two ligands, and subsequently corroborated by the recently described mGlu5 crystal structure. Moreover, a new series of NAMs was synthesized and tested, providing compounds with nanomolar affinity. Several structural modifications were sequentially introduced with the aim of identifying structural features important for receptor binding. The synthesized NAMs were docked in the validated homology model and binding modes were used to interpret and discuss structure-activity relationships within this new series of compounds. Finally, the models of the interaction of NAMs with mGlu5 were extended to include important non-aryl alkyne mGlu5 NAMs taken from the literature. Overall, the results provide useful insights into the molecular interaction of negative allosteric modulators with mGlu5 and may facilitate the design of new modulators for this class of receptors.

  14. Science Letters: A synthetic Toll-like receptor 2 ligand decreases allergic immune responses in a mouse rhinitis model sensitized to mite allergen

    Institute of Scientific and Technical Information of China (English)

    Cheng ZHOU; Xiao-dong KANG; Zhi CHEN

    2008-01-01

    It has been proposed that activation of Toll-like receptors (TLRs) plays crucial roles in the polarization of adaptive immune responses. A synthetic Toll-like receptor 2 (TLR2) ligand, Pam3CSK4, has been reported to modulate the balance of Thl/Tn2 responses. We evaluated the modulation effect of Pam3CSK4 on allergic immune response in a mouse rhinitis model sensitized to house dust mite allergen (HDM). Mice were sensitized and challenged with Dermatophagoides farinae allergen (Der f), and then the allergic mice were treated by Pam3CSK4. Nasal allergic symptoms and eosinophils were scored. Der f-specific cytokine responses were examined in the splenocytes and bronchoalveolar lavage fluid (BALF). Serum level of total IgE was also detected. After establishing a mouse allergic rhinitis model with HDM, we have showed that Pam3CSK4 treatment not only ameliorated the nasal allergic symptoms remarkably but also decreased the eosinophils and total inflammation cells in BALF significantly. Analysis of cytokine profile found that' IFN-γ released from either BALF or stimulated splenocytes increased markedly in Pam3CSK4-treated mice, while IL-13 decreased significantly. Moreover, serum level of total IgE was significantly lower in Pam3CSK4-treated mice than in the untreated. Thus, in an allergic rhinitis mouse model developed with HDM, Pam3CSK4 was shown to exhibit an antiallergic effect, indicating its potential application in allergic diseases.

  15. Model predictions of copper speciation in coastal water compared to measurements by analytical voltammetry.

    Science.gov (United States)

    Ndungu, Kuria

    2012-07-17

    Trace metal toxicity to aquatic biota is highly dependent on the metaĺs chemical speciation. Accordingly, metal speciation is being incorporated in to water quality criteria and toxicity regulations using the Biotic Ligand Model (BLM) but there are currently no BLM for biota in marine and estuarine waters. In this study, I compare copper speciation measurements in a typical coastal water made using Competitive ligand exchange-adsorptive cathodic stripping voltammetry (CLE-ACSV) to model calculations using Visual MINTEQ. Both Visual MINTEQ and BLM use similar programs to model copper interactions with dissolved organic matter-DOM (i.e., the Stockholm Humic Model and WHAM-Windermere Humic Aqueous Model, respectively). The total dissolved (14). The modeled [Cu2+] could be fitted to the experimental values better after the conditional stability constant for copper binding to fulvic acid (FA) complexes in DOM in the SHM was adjusted to account for higher concentration of strong Cu-binding sites in FA.

  16. The function of small RNAs in plant biotic stress response

    Institute of Scientific and Technical Information of China (English)

    Juan Huang; Meiling Yang; Xiaoming Zhang

    2016-01-01

    Small RNAs (sRNAs) play essential roles in plants upon biotic stress. Plants utilize RNA silencing machinery to facilitate pathogen-associated molecular pattern-triggered immunity and effector-triggered immunity to defend against pathogen attack or to facilitate defense against insect herbivores. Pathogens, on the other hand, are also able to generate effectors and sRNAs to counter the host immune response. The arms race between plants and pathogens/insect herbivores has triggered the evolution of sRNAs, RNA silencing machinery and pathogen effectors. A great number of studies have been performed to investigate the roles of sRNAs in plant defense, bringing in the opportunity to utilize sRNAs in plant protection. Transgenic plants with pathogen-derived resistance ability or trans-generational defense have been generated, which show promising potential as solutions for pathogen/insect herbi-vore problems in the field. Here we summarize the recent progress on the function of sRNAs in response to biotic stress, mainly in plant-pathogen/insect herbivore interaction, and the application of sRNAs in disease and insect herbivore control.

  17. 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.

  18. Biotic Interactions Shape the Ecological Distributions of Staphylococcus Species

    Directory of Open Access Journals (Sweden)

    Erik K. Kastman

    2016-10-01

    Full Text Available 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.

  19. Biotic immigration events, speciation, and the accumulation of biodiversity in the fossil record

    Science.gov (United States)

    Stigall, Alycia L.; Bauer, Jennifer E.; Lam, Adriane R.; Wright, David F.

    2017-01-01

    Biotic Immigration Events (BIMEs) record the large-scale dispersal of taxa from one biogeographic area to another and have significantly impacted biodiversity throughout geologic time. BIMEs associated with biodiversity increases have been linked to ecologic and evolutionary processes including niche partitioning, species packing, and higher speciation rates. Yet substantial biodiversity decline has also been documented following BIMEs due to elevated extinction and/or reduced speciation rates. In this review, we develop a conceptual model for biodiversity accumulation that links BIMEs and geographic isolation with local (α) diversity, regional (β) diversity, and global (γ) diversity metrics. Within the model, BIME intervals are characterized by colonization of existing species within new geographic regions and a lack of successful speciation events. Thus, there is no change in γ-diversity, and α-diversity increases at the cost of β-diversity. An interval of regional isolation follows in which lineage splitting results in successful speciation events and diversity increases across all three metrics. Alternation of these two regimes can result in substantial biodiversity accumulation. We tested this conceptual model using a series of case studies from the paleontological record. We primarily focus on two intervals during the Middle through Late Ordovician Period (470-458 Ma): the globally pervasive BIMEs during the Great Ordovician Biodiversification Event (GOBE) and a regional BIME, the Richmondian Invasion. We further test the conceptual model by examining the Great Devonian Interchange, Neogene mollusk migrations and diversification, and the Great American Biotic Interchange. Paleontological data accord well with model predictions. Constraining the mechanisms of biodiversity accumulation provides context for conservation biology. Because α-, β-, and γ-diversity are semi-independent, different techniques should be considered for sustaining various

  20. Biotic Acceptance in Introduced Amphibians and Reptiles in Europe and North America

    OpenAIRE

    Poessel, S. A.; Beard, Karen H.; Callahan, C. M.; Ferreira, R.B.; Cologgi, E. T.

    2013-01-01

    Aim: The biotic resistance hypothesis argues that complex plant and animal communities are more resistant to invasion than simpler communities. Conversely, the biotic acceptance hypothesis states that non-native and native species richness are positively related. Most tests of these hypotheses at continental scales, typically conducted on plants, have found support for biotic acceptance. We tested these hypotheses on both amphibians and reptiles across Europe and North America. Location: Cont...

  1. Structural model of a putrescine-cadaverine permease from Trypanosoma cruzi predicts residues vital for transport and ligand binding.

    Science.gov (United States)

    Soysa, Radika; Venselaar, Hanka; Poston, Jacqueline; Ullman, Buddy; Hasne, Marie-Pierre

    2013-06-15

    The TcPOT1.1 gene from Trypanosoma cruzi encodes a high affinity putrescine-cadaverine transporter belonging to the APC (amino acid/polyamine/organocation) transporter superfamily. No experimental three-dimensional structure exists for any eukaryotic member of the APC family, and thus the structural determinants critical for function of these permeases are unknown. To elucidate the key residues involved in putrescine translocation and recognition by this APC family member, a homology model of TcPOT1.1 was constructed on the basis of the atomic co-ordinates of the Escherichia coli AdiC arginine/agmatine antiporter crystal structure. The TcPOT1.1 homology model consisted of 12 transmembrane helices with the first ten helices organized in two V-shaped antiparallel domains with discontinuities in the helical structures of transmembrane spans 1 and 6. The model suggests that Trp241 and a Glu247-Arg403 salt bridge participate in a gating system and that Asn245, Tyr148 and Tyr400 contribute to the putrescine-binding pocket. To test the validity of the model, 26 site-directed mutants were created and tested for their ability to transport putrescine and to localize to the parasite cell surface. These results support the robustness of the TcPOT1.1 homology model and reveal the importance of specific aromatic residues in the TcPOT1.1 putrescine-binding pocket.

  2. 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.

  3. Novel computational methodologies for structural modeling of spacious ligand binding sites of G-protein-coupled receptors: development and application to human leukotriene B4 receptor.

    Science.gov (United States)

    Ishino, Yoko; Harada, Takanori

    2012-01-01

    This paper describes a novel method to predict the activated structures of G-protein-coupled receptors (GPCRs) with high accuracy, while aiming for the use of the predicted 3D structures in in silico virtual screening in the future. We propose a new method for modeling GPCR thermal fluctuations, where conformation changes of the proteins are modeled by combining fluctuations on multiple time scales. The core idea of the method is that a molecular dynamics simulation is used to calculate average 3D coordinates of all atoms of a GPCR protein against heat fluctuation on the picosecond or nanosecond time scale, and then evolutionary computation including receptor-ligand docking simulations functions to determine the rotation angle of each helix of a GPCR protein as a movement on a longer time scale. The method was validated using human leukotriene B4 receptor BLT1 as a sample GPCR. Our study demonstrated that the proposed method was able to derive the appropriate 3D structure of the active-state GPCR which docks with its agonists.

  4. Ligand Efficiency Outperforms pIC50 on Both 2D MLR and 3D CoMFA Models: A Case Study on AR Antagonists.

    Science.gov (United States)

    Li, Jiazhong; Bai, Fang; Liu, Huanxiang; Gramatica, Paola

    2015-12-01

    The concept of ligand efficiency is defined as biological activity in each molecular size and is widely accepted throughout the drug design community. Among different LE indices, surface efficiency index (SEI) was reported to be the best one in support vector machine modeling, much better than the generally and traditionally used end-point pIC50. In this study, 2D multiple linear regression and 3D comparative molecular field analysis methods are employed to investigate the structure-activity relationships of a series of androgen receptor antagonists, using pIC50 and SEI as dependent variables to verify the influence of using different kinds of end-points. The obtained results suggest that SEI outperforms pIC50 on both MLR and CoMFA models with higher stability and predictive ability. After analyzing the characteristics of the two dependent variables SEI and pIC50, we deduce that the superiority of SEI maybe lie in that SEI could reflect the relationship between molecular structures and corresponding bioactivities, in nature, better than pIC50. This study indicates that SEI could be a more rational parameter to be optimized in the drug discovery process than pIC50.

  5. Ubiquitous transgenic overexpression of C-C chemokine ligand 2: a model to assess the combined effect of high energy intake and continuous low-grade inflammation.

    Science.gov (United States)

    Rodríguez-Gallego, Esther; Riera-Borrull, Marta; Hernández-Aguilera, Anna; Mariné-Casadó, Roger; Rull, Anna; Beltrán-Debón, Raúl; Luciano-Mateo, Fedra; Menendez, Javier A; Vazquez-Martin, Alejandro; Sirvent, Juan J; Martín-Paredero, Vicente; Corbí, Angel L; Sierra-Filardi, Elena; Aragonès, Gerard; García-Heredia, Anabel; Camps, Jordi; Alonso-Villaverde, Carlos; Joven, Jorge

    2013-01-01

    Excessive energy management leads to low-grade, chronic inflammation, which is a significant factor predicting noncommunicable diseases. In turn, inflammation, oxidation, and metabolism are associated with the course of these diseases; mitochondrial dysfunction seems to be at the crossroads of mutual relationships. The migration of immune cells during inflammation is governed by the interaction between chemokines and chemokine receptors. Chemokines, especially C-C-chemokine ligand 2 (CCL2), have a variety of additional functions that are involved in the maintenance of normal metabolism. It is our hypothesis that a ubiquitous and continuous secretion of CCL2 may represent an animal model of low-grade chronic inflammation that, in the presence of an energy surplus, could help to ascertain the afore-mentioned relationships and/or to search for specific therapeutic approaches. Here, we present preliminary data on a mouse model created by using targeted gene knock-in technology to integrate an additional copy of the CCl2 gene in the Gt(ROSA)26Sor locus of the mouse genome via homologous recombination in embryonic stem cells. Short-term dietary manipulations were assessed and the findings include metabolic disturbances, premature death, and the manipulation of macrophage plasticity and autophagy. These results raise a number of mechanistic questions for future study.

  6. Ubiquitous Transgenic Overexpression of C-C Chemokine Ligand 2: A Model to Assess the Combined Effect of High Energy Intake and Continuous Low-Grade Inflammation

    Directory of Open Access Journals (Sweden)

    Esther Rodríguez-Gallego

    2013-01-01

    Full Text Available Excessive energy management leads to low-grade, chronic inflammation, which is a significant factor predicting noncommunicable diseases. In turn, inflammation, oxidation, and metabolism are associated with the course of these diseases; mitochondrial dysfunction seems to be at the crossroads of mutual relationships. The migration of immune cells during inflammation is governed by the interaction between chemokines and chemokine receptors. Chemokines, especially C-C-chemokine ligand 2 (CCL2, have a variety of additional functions that are involved in the maintenance of normal metabolism. It is our hypothesis that a ubiquitous and continuous secretion of CCL2 may represent an animal model of low-grade chronic inflammation that, in the presence of an energy surplus, could help to ascertain the afore-mentioned relationships and/or to search for specific therapeutic approaches. Here, we present preliminary data on a mouse model created by using targeted gene knock-in technology to integrate an additional copy of the CCl2 gene in the Gt(ROSA26Sor locus of the mouse genome via homologous recombination in embryonic stem cells. Short-term dietary manipulations were assessed and the findings include metabolic disturbances, premature death, and the manipulation of macrophage plasticity and autophagy. These results raise a number of mechanistic questions for future study.

  7. 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/.

  8. 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.

  9. Molecular modeling of the human serotonin(1A) receptor : role of membrane cholesterol in ligand binding of the receptor

    NARCIS (Netherlands)

    Paila, Yamuna Devi; Tiwari, Shrish; Sengupta, Durba; Chattopadhyay, Amitabha

    2011-01-01

    Serotonin(1A) receptors are important neurotransmitter receptors and belong to the superfamily of G-protein coupled receptors (GPCRs). Although it is an important drug target, the crystal structure of the serotonin(1A) receptor has not been solved yet. Earlier homology models of the serotonin(1A) re

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

    CERN Document Server

    Majumdar, Liton; 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 of the rate coefficients of various reactions which take place in the ISM & molecular clouds. In order to obtain accurate final compositions in the ISM, we find out 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 find out the chemical evolution and the final abundances of the 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 collapsing phase of a proto-star. We study extensively the formation of these molecules via successive neutral-neutral(NN) and radical-radical(RR)/radical-molecular(RM) 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....

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

    Institute of Scientific and Technical Information of China (English)

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

    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/radicalmolecular 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.If all the

  12. Coenzyme B12 model studies: Equilibrium constants for the H-dependent axial ligation of benzyl(aquo)cobaloxime by various N- and S-donor ligands

    Indian Academy of Sciences (India)

    D Sudarshan Reddy; N Ravi Kumar Reddy; V Sridhar; S Satyanarayana

    2002-02-01

    Equilibria of the axial ligation of benzyl(aquo)cobaloximes by imidazole, 1-methyl imidazole, histidine, histamine, glycine, ethyl glycine ester, thiourea and urea have been spectrophotometrically measured in aqueous solutions of ionic strength 1.0 M (KCl) at 25°C as a function of H. The equilibrium constants are in the order CN- > 1-methyl imidazole > imidazole > histidine > histamine > glycine > ethyl glycine ester > thiourea > urea. The order of stability of benzyl(ligand)cobaloxime is explained based on the basicity of the ligand, Co(III) → - back bonding and soft-soft and soft-hard interaction. Imidazole, substituted imidazoles, histidine and histamine form more stable complexes than glycine, ethyl glycine ester in contrast to the basicity of the ligands. Benzyl(ligand)cobaloximes were isolated and characterized by elemental analysis, IR and 1H NMR spectra.

  13. An Economic Valuation of Biotic Pollination Services in Georgia.

    Science.gov (United States)

    Barfield, Ashley S; Bergstrom, John C; Ferreira, Susana; Covich, Alan P; Delaplane, Keith S

    2015-04-01

    As agriculture faces documented decline in bees and other insect pollinators, empirical assessments of potential economic losses are critical for contextualizing the impacts of this decline and for prioritizing research needs. For the state of Georgia, we show that the annual economic value of biotic pollinators is substantial--US$367 million, equivalent to 13 percent of the total production value of crops studied and 3 percent of the total production value of Georgia's agricultural sector. Our unique Geographic Information Systems analysis reveals an irregular pattern of vulnerability. While the Georgia counties displaying the highest economic values of pollination are clustered in southern Georgia, those with the highest dependency on pollinators in terms of their contribution to crop production value are more dispersed throughout the state.

  14. 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.

  15. Multiple ligand simultaneous docking: orchestrated dancing of ligands in binding sites of protein.

    Science.gov (United States)

    Li, Huameng; Li, Chenglong

    2010-07-30

    Present docking methodologies simulate only one single ligand at a time during docking process. In reality, the molecular recognition process always involves multiple molecular species. Typical protein-ligand interactions are, for example, substrate and cofactor in catalytic cycle; metal ion coordination together with ligand(s); and ligand binding with water molecules. To simulate the real molecular binding processes, we propose a novel multiple ligand simultaneous docking (MLSD) strategy, which can deal with all the above processes, vastly improving docking sampling and binding free energy scoring. The work also compares two search strategies: Lamarckian genetic algorithm and particle swarm optimization, which have respective advantages depending on the specific systems. The methodology proves robust through systematic testing against several diverse model systems: E. coli purine nucleoside phosphorylase (PNP) complex with two substrates, SHP2NSH2 complex with two peptides and Bcl-xL complex with ABT-737 fragments. In all cases, the final correct docking poses and relative binding free energies were obtained. In PNP case, the simulations also capture the binding intermediates and reveal the binding dynamics during the recognition processes, which are consistent with the proposed enzymatic mechanism. In the other two cases, conventional single-ligand docking fails due to energetic and dynamic coupling among ligands, whereas MLSD results in the correct binding modes. These three cases also represent potential applications in the areas of exploring enzymatic mechanism, interpreting noisy X-ray crystallographic maps, and aiding fragment-based drug design, respectively.

  16. Biotic Habitat Complexity Controls Species Diversity and Nutrient Effects on Net Biomass Production

    NARCIS (Netherlands)

    Eriksson, Britas Klemens; Rubach, Anja; Hillebrand, Helmut

    2006-01-01

    Canopy-forming plants and algae commonly contribute to spatial variation in habitat complexity for associated organisms and thereby create a biotic patchiness of communities. In this study, we tested for interaction effects between biotic habitat complexity and resource availability on net biomass p

  17. The Recognition of Identical Ligands by Unrelated Proteins.

    Science.gov (United States)

    Barelier, Sarah; Sterling, Teague; O'Meara, Matthew J; Shoichet, Brian K

    2015-12-18

    The binding of drugs and reagents to off-targets is well-known. Whereas many off-targets are related to the primary target by sequence and fold, many ligands bind to unrelated pairs of proteins, and these are harder to anticipate. If the binding site in the off-target can be related to that of the primary target, this challenge resolves into aligning the two pockets. However, other cases are possible: the ligand might interact with entirely different residues and environments in the off-target, or wholly different ligand atoms may be implicated in the two complexes. To investigate these scenarios at atomic resolution, the structures of 59 ligands in 116 complexes (62 pairs in total), where the protein pairs were unrelated by fold but bound an identical ligand, were examined. In almost half of the pairs, the ligand interacted with unrelated residues in the two proteins (29 pairs), and in 14 of the pairs wholly different ligand moieties were implicated in each complex. Even in those 19 pairs of complexes that presented similar environments to the ligand, ligand superposition rarely resulted in the overlap of related residues. There appears to be no single pattern-matching "code" for identifying binding sites in unrelated proteins that bind identical ligands, though modeling suggests that there might be a limited number of different patterns that suffice to recognize different ligand functional groups.

  18. 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

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

    Science.gov (United States)

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

    2013-12-01

    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 and P

  20. Cloning and characterization of a biotic-stress-inducible glutathione transferase from Phaseolus vulgaris.

    Science.gov (United States)

    Chronopoulou, Evangelia; Madesis, Panagiotis; Tsaftaris, Athanasios; Labrou, Nikolaos E

    2014-01-01

    Glutathione transferases (GSTs, EC 2.5.1.18) are ubiquitous proteins in plants that play important roles in stress tolerance and in the detoxification of toxic chemicals and metabolites. In this study, we systematically examined the catalytic diversification of a GST isoenzyme from Phaseolus vulgaris (PvGST) which is induced under biotic stress treatment (Uromyces appendiculatus infection). The full-length cDNA of this GST isoenzyme (termed PvGSTU3-3) with complete open reading frame, was isolated using RACE-RT and showed that the deduced amino acid sequence shares high homology with the tau class plant GSTs. PvGSTU3-3 catalyzes several different reactions and exhibits wide substrate specificity. Of particular importance is the finding that the enzyme shows high antioxidant catalytic function and acts as hydroperoxidase, thioltransferase, and dehydroascorbate reductase. In addition, its K m for GSH is about five to ten times lower compared to other plant GSTs, suggesting that PvGSTU3-3 is able to perform efficient catalysis under conditions where the concentration of reduced glutathione is low (e.g., oxidative stress). Its ability to conjugate GSH with isothiocyanates may provide an additional role for this enzyme to act as a regulator of the released isothiocyanates from glucosinolates as a response of biotic stress. Molecular modeling showed that PvGSTU3-3 shares the same overall fold and structural organization with other plant cytosolic GSTs, with major differences at their hydrophobic binding sites (H-sites) and some differences at the level of C-terminal domain and the linker between the C- and N-terminal domains. PvGSTU3-3, in general, exhibits restricted ability to bind xenobiotics in a nonsubstrate manner, suggesting that the biological role of PvGSTU3-3, is restricted mainly to the catalytic function. Our findings highlight the functional and catalytic diversity of plant GSTs and demonstrate their pivotal role for addressing biotic stresses in Phaseolus

  1. Model peptides provide new insights into the role of histidine residues as potential ligands in human cellular copper acquisition via Ctr1.

    Science.gov (United States)

    Haas, Kathryn L; Putterman, Allison B; White, Daniel R; Thiele, Dennis J; Franz, Katherine J

    2011-03-30

    Cellular acquisition of copper in eukaryotes is primarily accomplished through the Ctr family of copper transport proteins. In both humans and yeast, methionine-rich "Mets" motifs in the amino-terminal extracellular domain of Ctr1 are thought to be responsible for recruitment of copper at the cell surface. Unlike yeast, mammalian Ctr1 also contains extracellular histidine-rich motifs, although a role for these regions in copper uptake has not been explored in detail. Herein, synthetic model peptides containing the first 14 residues of the extracellular domain of human Ctr1 (MDHSHHMGMSYMDS) have been prepared and evaluated for their apparent binding affinity to both Cu(I) and Cu(II). These studies reveal a high affinity Cu(II) binding site (log K = 11.0 ± 0.3 at pH 7.4) at the amino-terminus of the peptide as well as a high affinity Cu(I) site (log K = 10.2 ± 0.2 at pH 7.4) that utilizes adjacent HH residues along with an additional His or Met ligand. These model studies suggest that the histidine domains may play a direct role in copper acquisition from serum copper-binding proteins and in facilitating the reduction of Cu(II) to the active Ctr1 substrate, Cu(I). We tested this hypothesis by expressing a Ctr1 mutant lacking only extracellular histidine residues in Ctr1-knockout mouse embryonic fibroblasts. Results from live cell studies support the hypothesis that extracellular amino-terminal His residues directly participate in the copper transport function of Ctr1.

  2. Potential of PEGylated Toll-Like Receptor 7 Ligands for Controlling Inflammation and Functional Changes in Mouse Models of Asthma and Silicosis.

    Science.gov (United States)

    Ferreira, Tatiana Paula Teixeira; Mariano, Lívia Lacerda; Ghilosso-Bortolini, Roberta; de Arantes, Ana Carolina Santos; Fernandes, Andrey Junior; Berni, Michelle; Cecchinato, Valentina; Uguccioni, Mariagrazia; Maj, Roberto; Barberis, Alcide; Silva, Patricia Machado Rodrigues E; Martins, Marco Aurélio

    2016-01-01

    Prior investigations show that signaling activation through pattern recognition receptors can directly impact a number of inflammatory lung diseases. While toll-like receptor (TLR) 7 agonists have raised interest for their ability to inhibit allergen-induced pathological changes in experimental asthma conditions, the putative benefit of this treatment is limited by adverse effects. Our aim was to evaluate the therapeutic potential of two PEGylated purine-like compounds, TMX-302 and TMX-306, characterized by TLR7 partial agonistic activity; therefore, the compounds are expected to induce lower local and systemic adverse reactions. In vitro approaches and translation to murine models of obstructive and restrictive lung diseases were explored. In vitro studies with human PBMCs showed that both TMX-302 and TMX-306 marginally affects cytokine production as compared with equivalent concentrations of the TLR7 full agonist, TMX-202. The PEGylated compounds did not induce monocyte-derived DC maturation or B cell proliferation, differently from what observed after stimulation with TMX-202. Impact of PEGylated ligands on lung function and inflammatory changes was studied in animal models of acute lung injury, asthma, and silicosis following Lipopolysaccharide (LPS), allergen (ovalbumin), and silica inhalation, respectively. Subcutaneous injection of TMX-302 prevented LPS- and allergen-induced airway hyper-reactivity (AHR), leukocyte infiltration, and production of pro-inflammatory cytokines in the lung. However, intranasal instillation of TMX-302 led to neutrophil infiltration and failed to prevent allergen-induced AHR, despite inhibiting leukocyte counts in the BAL. Aerosolized TMX-306 given prophylactically, but not therapeutically, inhibited pivotal asthma features. Interventional treatment with intranasal instillation of TMX-306 significantly reduced the pulmonary fibrogranulomatous response and the number of silica particles in lung interstitial space in silicotic mice

  3. Partial least square and hierarchical clustering in ADMET modeling: prediction of blood-brain barrier permeation of α-adrenergic and imidazoline receptor ligands.

    Science.gov (United States)

    Nikolic, Katarina; Filipic, Slavica; Smoliński, Adam; Kaliszan, Roman; Agbaba, Danica

    2013-01-01

    PURPOSE. Rate of brain penetration (logPS), brain/plasma equilibration rate (logPS-brain), and extent of blood-brain barrier permeation (logBB) of 29 α-adrenergic and imidazoline-receptors ligands were examined in Quantitative-Structure-Property Relationship (QSPR) study. METHODS. Experimentally determined chromatographic retention data (logKw at pH 4.4, slope (S) at pH 4.4, logKw at pH 7.4, slope (S) at pH 7.4, logKw at pH 9.1, and slope (S) at pH 9.1) and capillary electrophoresis migration parameters (μeff at pH 4.4, μeff at pH 7.4, and μeff at pH 9.1), together with calculated molecular descriptors, were used as independent variables in the QSPR study by use of partial least square (PLS) methodology. RESULTS. Predictive potential of the formed QSPR models, QSPR(logPS), QSPR(logPS-brain), QSPR(logBB), was confirmed by cross- and external validation. Hydrophilicity (Hy) and H-indices (H7m) were selected as significant parameters negatively correlated with both logPS and logPS-brain, while topological polar surface area (TPSA(NO)) was chosen as molecular descriptor negatively correlated with both logPS and logBB. The principal component analysis (PCA) and hierarchical clustering analysis (HCA) were applied to cluster examined drugs based on their chromatographic, electrophoretic and molecular properties. Significant positive correlations were obtained between the slope (S) at pH 7.4 and logBB in A/B cluster and between the logKw at pH 9.1 and logPS in C/D cluster. CONCLUSIONS. Results of the QSPR, clustering and correlation studies could be used as novel tool for evaluation of blood-brain barrier permeation of related α-adrenergic/imidazoline receptor ligands.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.PURPOSE. Rate of brain penetration (logPS), brain/plasma equilibration rate (logPS-brain), and extent of blood-brain barrier permeation (logBB) of 29

  4. Mononuclear non-heme iron(III) complexes of linear and tripodal tridentate ligands as functional models for catechol dioxygenases: Effect of -alkyl substitution on regioselectivity and reaction rate

    Indian Academy of Sciences (India)

    Mallayan Palaniandavar; Kusalendiran Visvaganesan

    2011-03-01

    Catechol dioxygenases are responsible for the last step in the biodegradation of aromatic molecules in the environment. The iron(II) active site in the extradiol-cleaving enzymes cleaves the C-C bond adjacent to the hydroxyl group, while the iron(III) active site in the intradiol-cleaving enzymes cleaves the C-C bond in between two hydroxyl groups. A series of mononuclear iron(III) complexes of the type [Fe(L)Cl3], where L is the linear -alkyl substituted bis(pyrid-2-ylmethyl)amine, -alkyl substituted -(pyrid-2-ylmethyl)ethylenediamine, linear tridentate 3N ligands containing imidazolyl moieties and tripodal ligands containing pyrazolyl moieties have been isolated and studied as structural and functional models for catechol dioxygenase enzymes. All the complexes catalyse the cleavage of catechols using molecular oxygen to afford both intra- and extradiol cleavage products. The rate of oxygenation depends on the solvent and the Lewis acidity of iron(III) center as modified by the sterically demanding -alkyl groups. Also, our studies reveal that stereo-electronic factors like the Lewis acidity of the iron(III) center and the steric demand of ligands, as regulated by the -alkyl substituents, determine the regioselectivity and the rate of dioxygenation. In sharp contrast to all these complexes, the pyrazole-containing tripodal ligand complexes yield mainly the oxidized product benzoquinone.

  5. Impacts of biotic resource enrichment on a predator-prey population.

    Science.gov (United States)

    Safuan, H M; Sidhu, H S; Jovanoski, Z; Towers, I N

    2013-10-01

    The environmental carrying capacity is usually assumed to be fixed quantity in the classical predator-prey population growth models. However, this assumption is not realistic as the environment generally varies with time. In a bid for greater realism, functional forms of carrying capacities have been widely applied to describe varying environments. Modelling carrying capacity as a state variable serves as another approach to capture the dynamical behavior between population and its environment. The proposed modified predator-prey model is based on the ratio-dependent models that have been utilized in the study of food chains. Using a simple non-linear system, the proposed model can be linked to an intra-guild predation model in which predator and prey share the same resource. Distinct from other models, we formulate the carrying capacity proportional to a biotic resource and both predator and prey species can directly alter the amount of resource available by interacting with it. Bifurcation and numerical analyses are presented to illustrate the system's dynamical behavior. Taking the enrichment parameter of the resource as the bifurcation parameter, a Hopf bifurcation is found for some parameter ranges, which generate solutions that posses limit cycle behavior.

  6. 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.

  7. Seed treatment with Trichoderma harzianum alleviates biotic, abiotic, and physiological stresses in germinating seeds and seedlings.

    Science.gov (United States)

    Mastouri, Fatemeh; Björkman, Thomas; Harman, Gary E

    2010-11-01

    Trichoderma spp. are endophytic plant symbionts that are widely used as seed treatments to control diseases and to enhance plant growth and yield. Although some recent work has been published on their abilities to alleviate abiotic stresses, specific knowledge of mechanisms, abilities to control multiple plant stress factors, their effects on seed and seedlings is lacking. We examined the effects of seed treatment with T. harzianum strain T22 on germination of seed exposed to biotic stress (seed and seedling disease caused by Pythium ultimum) and abiotic stresses (osmotic, salinity, chilling, or heat stress). We also evaluated the ability of the beneficial fungus to overcome physiological stress (poor seed quality induced by seed aging). If seed were not under any of the stresses noted above, T22 generally had little effect upon seedling performance. However, under stress, treated seed germinated consistently faster and more uniformly than untreated seeds whether the stress was osmotic, salt, or suboptimal temperatures. The consistent response to varying stresses suggests a common mechanism through which the plant-fungus association enhances tolerance to a wide range of abiotic stresses as well as biotic stress. A common factor that negatively affects plants under these stress conditions is accumulation of toxic reactive oxygen species (ROS), and we tested the hypothesis that T22 reduced damages resulting from accumulation of ROS in stressed plants. Treatment of seeds reduced accumulation of lipid peroxides in seedlings under osmotic stress or in aged seeds. In addition, we showed that the effect of exogenous application of an antioxidant, glutathione, or application of T22, resulted in a similar positive effect on seed germination under osmotic stress or in aged seed. This evidence supports the model that T. harzianum strain T22 increases seedling vigor and ameliorates stress by inducing physiological protection in plants against oxidative damage.

  8. 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

  9. Increased accuracy of ligand sensing by receptor internalization

    CERN Document Server

    Aquino, Gerardo

    2010-01-01

    Many types of cells can sense external ligand concentrations with cell-surface receptors at extremely high accuracy. Interestingly, ligand-bound receptors are often internalized, a process also known as receptor-mediated endocytosis. While internalization is involved in a vast number of important functions for the life of a cell, it was recently also suggested to increase the accuracy of sensing ligand as the overcounting of the same ligand molecules is reduced. Here we show, by extending simple ligand-receptor models to out-of-equilibrium thermodynamics, that internalization increases the accuracy with which cells can measure ligand concentrations in the external environment. Comparison with experimental rates of real receptors demonstrates that our model has indeed biological significance.

  10. Invasion biology in non-free-living species: interactions between abiotic (climatic) and biotic (host availability) factors in geographical space in crayfish commensals (Ostracoda, Entocytheridae).

    Science.gov (United States)

    Mestre, Alexandre; Aguilar-Alberola, Josep A; Baldry, David; Balkis, Husamettin; Ellis, Adam; Gil-Delgado, Jose A; Grabow, Karsten; Klobučar, Göran; Kouba, Antonín; Maguire, Ivana; Martens, Andreas; Mülayim, Ayşegül; Rueda, Juan; Scharf, Burkhard; Soes, Menno; S Monrós, Juan; Mesquita-Joanes, Francesc

    2013-12-01

    In invasion processes, both abiotic and biotic factors are considered essential, but the latter are usually disregarded when modeling the potential spread of exotic species. In the framework of set theory, interactions between biotic (B), abiotic (A), and movement-related (M) factors in the geographical space can be hypothesized with BAM diagrams and tested using ecological niche models (ENMs) to estimate A and B areas. The main aim of our survey was to evaluate the interactions between abiotic (climatic) and biotic (host availability) factors in geographical space for exotic symbionts (i.e., non-free-living species), using ENM techniques combined with a BAM framework and using exotic Entocytheridae (Ostracoda) found in Europe as model organisms. We carried out an extensive survey to evaluate the distribution of entocytherids hosted by crayfish in Europe by checking 94 European localities and 12 crayfish species. Both exotic entocytherid species found, Ankylocythere sinuosa and Uncinocythere occidentalis, were widely distributed in W Europe living on the exotic crayfish species Procambarus clarkii and Pacifastacus leniusculus, respectively. No entocytherids were observed in the remaining crayfish species. The suitable area for A. sinuosa was mainly restricted by its own limitations to minimum temperatures in W and N Europe and precipitation seasonality in circum-Mediterranean areas. Uncinocythere occidentalis was mostly restricted by host availability in circum-Mediterranean regions due to limitations of P. leniusculus to higher precipitation seasonality and maximum temperatures. The combination of ENMs with set theory allows studying the invasive biology of symbionts and provides clues about biogeographic barriers due to abiotic or biotic factors limiting the expansion of the symbiont in different regions of the invasive range. The relative importance of abiotic and biotic factors on geographical space can then be assessed and applied in conservation plans. This

  11. Fusion of ligand-coated nanoparticles with lipid bilayers: effect of ligand flexibility.

    Science.gov (United States)

    Van Lehn, Reid C; Alexander-Katz, Alfredo

    2014-08-07

    Amphiphilic, monolayer-protected gold nanoparticles (AuNPs) have recently been shown to insert into and fuse with lipid bilayers, driven by the hydrophobic effect. The inserted transmembrane state is stabilized by the "snorkeling" of charged ligand end groups out of the bilayer interior. This snorkeling process is facilitated by the backbone flexibility of the alkanethiol ligands that comprise the monolayer. In this work, we show that fusion is favorable even in the absence of backbone flexibility by modeling the ligands as rigid rods. For rigid ligands, snorkeling is still accommodated by rotations of the ligand with respect to the grafting point, but the process incurs a more significant free energy penalty than if the backbone were fully flexible. We show that the rigid rod model predicts similar trends in the free energy change for insertion as the previous flexible model when the size of the AuNPs is varied. However, the rigidity of the ligand backbone reduces the overall magnitude of the free energy change compared to that of the flexible model. These results thus generalize previous findings to systems with hindered backbone flexibility due to either structural constraints or low temperature.

  12. 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

    2016-09-02

    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 [Formula: see text] 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 [Formula: see text] and the binding constant [Formula: see text] of soluble variants of the receptors and ligands that lack the membrane anchors and are free to diffuse in 3 dimensions (3D).

  13. 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.

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

    Science.gov (United States)

    Klanderud, Kari; Vandvik, Vigdis; Goldberg, Deborah

    2015-01-01

    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.

  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. Paleosol formation during the Early Triassic Biotic Crisis in Norway

    Science.gov (United States)

    Knies, Jochen; Müller, Axel; Zwingmann, Horst; Fredin, Ola; Brönner, Marco; Viola, Giulio

    2016-04-01

    Fractured and kaolinite weathered basement rocks have been discovered in various wells off the Norwegian coast and inferences on timing, source to sink relationships, and environmental implications have been widely discussed. The reason for the kaolitinization has often been related to intensive chemical weathering during late Triassic to early Jurassic times. Chronological control has primarily been inferred from the overlying late Jurassic/early Cretaceous marine transgression and poorly constrained K-Ar datings from weathered basement onshore as well as climate conditions favourable for kaolinite formation. In this study, we present evidence that the deeply weathered basement off the mid-Norwegian coast represent a complete paleosol profile. Quartz geochemical fingerprinting indicate that transgressional marine inorganic sediments of late Jurassic age are derived from the paleosols. Whole-rock XRD analysis suggests characteristic mineral alteration zones topped with a kaolinite-Fe-oxyhyroxide zones composed of >80% kaolinite. Potassium feldspar is practically absent in the uppermost kaolinitic zones. Mass-balance changes show significant depletion-enrichment trends. Applying potassium/argon (K/Ar) geochronology on authigenic illite clay that grew in-situ at the time of paleosol formation reveals a early Triassic age (~250 Ma). The age corroborates with the Early Triassic biotic crisis and suggest a causal relationship between intense chemical weathering, high atmospheric CO2 concentration, extreme ocean warming, increased riverine flux of nutrients and widespread anoxia/euxinia on adjacent epicontinental seas.

  17. Epigenetic Signals on Plant Adaptation: A Biotic Stress Perspective.

    Science.gov (United States)

    Neto, José Ribamar Costa Ferreira; da Silva, Manassés Daniel; Pandolfi, Valesca; Crovella, Sérgio; Benko-Iseppon, Ana Maria; Kido, Ederson Akio

    2016-07-24

    For sessile organisms such as plants, regulatory mechanisms of gene expression are vital, since they remain exposed to climatic and biological threats. Thus, they have to face hazards with instantaneous reorganization of their internal environment. For this purpose, besides the use of transcription factors, the participation of chromatin as an active factor in the regulation of transcription is crucial. Chemical changes in chromatin structure affect the accessibility of the transcriptional machinery and acting in signaling, engaging/inhibiting factors that participate in the transcription processes. Mechanisms in which gene expression undergoes changes without the occurrence of DNA gene mutations in the monomers that make up DNA, are understood as epigenetic phenomena. These include (1) post-translational modifications of histones, which results in stimulation or repression of gene activity and (2) cytosine methylation in the promoter region of individual genes, both preventing access of transcriptional activators as well as signaling the recruitment of repressors. There is evidence that such modifications can pass on to subsequent generations of daughter cells and even generations of individuals. However, reports indicate that they persist only in the presence of a stressor factor (or an inductor of the above-mentioned modifications). In its absence, these modifications weaken or lose heritability, being eliminated in the next few generations. In this review, it is argued how epigenetic signals influence gene regulation, the mechanisms involved and their participation in processes of resistance to biotic stresses, controlling processes of the plant immune system.

  18. Biotic homogenization can decrease landscape-scale forest multifunctionality.

    Science.gov (United States)

    van der Plas, Fons; Manning, Pete; Soliveres, Santiago; Allan, Eric; Scherer-Lorenzen, Michael; Verheyen, Kris; Wirth, Christian; Zavala, Miguel A; Ampoorter, Evy; Baeten, Lander; Barbaro, Luc; Bauhus, Jürgen; Benavides, Raquel; Benneter, Adam; Bonal, Damien; Bouriaud, Olivier; Bruelheide, Helge; Bussotti, Filippo; Carnol, Monique; Castagneyrol, Bastien; Charbonnier, Yohan; Coomes, David Anthony; Coppi, Andrea; Bastias, Cristina C; Dawud, Seid Muhie; De Wandeler, Hans; Domisch, Timo; Finér, Leena; Gessler, Arthur; Granier, André; Grossiord, Charlotte; Guyot, Virginie; Hättenschwiler, Stephan; Jactel, Hervé; Jaroszewicz, Bogdan; Joly, François-Xavier; Jucker, Tommaso; Koricheva, Julia; Milligan, Harriet; Mueller, Sandra; Muys, Bart; Nguyen, Diem; Pollastrini, Martina; Ratcliffe, Sophia; Raulund-Rasmussen, Karsten; Selvi, Federico; Stenlid, Jan; Valladares, Fernando; Vesterdal, Lars; Zielínski, Dawid; Fischer, Markus

    2016-03-29

    Many experiments have shown that local biodiversity loss impairs the ability of ecosystems to maintain multiple ecosystem functions at high levels (multifunctionality). In contrast, the role of biodiversity in driving ecosystem multifunctionality at landscape scales remains unresolved. We used a comprehensive pan-European dataset, including 16 ecosystem functions measured in 209 forest plots across six European countries, and performed simulations to investigate how local plot-scale richness of tree species (α-diversity) and their turnover between plots (β-diversity) are related to landscape-scale multifunctionality. After accounting for variation in environmental conditions, we found that relationships between α-diversity and landscape-scale multifunctionality varied from positive to negative depending on the multifunctionality metric used. In contrast, when significant, relationships between β-diversity and landscape-scale multifunctionality were always positive, because a high spatial turnover in species composition was closely related to a high spatial turnover in functions that were supported at high levels. Our findings have major implications for forest management and indicate that biotic homogenization can have previously unrecognized and negative consequences for large-scale ecosystem multifunctionality.

  19. Reductive transformation of carbamazepine by abiotic and biotic processes.

    Science.gov (United States)

    König, Anne; Weidauer, Cindy; Seiwert, Bettina; Reemtsma, Thorsten; Unger, Tina; Jekel, Martin

    2016-09-15

    The antiepileptic drug carbamazepine (CBZ) is ubiquitously present in the anthropogenic water cycle and is therefore of concern regarding the potable water supply. Despite of its persistent behavior in the aquatic environment, a redox dependent removal at bank filtration sites with anaerobic aquifer passage was reported repeatedly but not elucidated in detail yet. The reductive transformation of CBZ was studied, using abiotic systems (catalytic hydrogenation, electrochemistry) as well as biologically active systems (column systems, batch degradation tests). In catalytic hydrogenation CBZ is gradually hydrogenated and nine transformation products (TPs) were detected by liquid chromatography high-resolution mass spectrometry. 10,11-Dihydro-CBZ ((2H)-CBZ) was the major stable product in these abiotic, surface catalyzed reduction processes and turned out to be not a precursor of the more hydrogenated TPs. In the biotic reduction processes the formation of (2H)-CBZ alone could not explain the observed CBZ decline. There, also traces of (6H)-CBZ and (8H)-CBZ were formed by microbes under anaerobic conditions and four phase-II metabolites of reduced CBZ could be detected and tentatively identified. Thus, the spectrum of reduction products of CBZ is more diverse than previously thought. In environmental samples CBZ removal along an anaerobic soil passage was confirmed and (2H)-CBZ was determined at one of the sites.

  20. 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.

  1. Toll-like receptor 22 in Labeo rohita: molecular cloning, characterization, 3D modeling, and expression analysis following ligands stimulation and bacterial infection.

    Science.gov (United States)

    Samanta, Mrinal; Swain, Banikalyan; Basu, Madhubanti; Mahapatra, Girishbala; Sahoo, Bikash R; Paichha, Mahismita; Lenka, Saswati S; Jayasankar, Pallipuram

    2014-09-01

    Toll-like receptors (TLRs) are a class of innate immune receptors that sense pathogens or their molecular signatures and activate signaling cascades to induce a quick and non-specific immune response in the host. Among various types of TLRs, TLR22 is exclusively present in teleosts and amphibians and is expected to play the distinctive role in innate immunity. This report describes molecular cloning, three-dimensional (3D) modeling, and expression analysis of TLR22 in rohu (Labeo rohita), the most commercially important freshwater fish species in the Indian subcontinent. The open reading frame (ORF) of rohu TLR22 (LrTLR22) comprised of 2,838 nucleotides (nt), encoding 946 amino acid (aa) residues with the molecular mass of ∼ 107.6 kDa. The secondary structure of deduced LrTLR22 exhibited the presence of signal peptide (1-22 aa), 18 leucine-rich repeat (LRR) regions (79-736 aa), and TIR domain (792-935 aa). The 3D model of LrTLR22-LRR regions together elucidated the horse-shoe-shaped structure having parallel β-strands at the concave surface and few α-helices at the convex surface. The TIR domain structure revealed alternate presence of five α-helices and β-sheets. Phylogenetically, LrTLR22 was closely related to common carp and exhibited significant similarity (92.2 %) and identity (86.1 %) in their amino acids. In rohu, TLR22 was constitutively expressed in all embryonic developmental stages, and tissue-specific analysis illustrated its expression in all examined tissues, highest was in liver and lowest in brain. In vivo modulation of TLR22 gene expression was analyzed by quantitative real-time PCR (qRT-PCR) assay following stimulation with lipopolysaccharide (LPS), synthetic double stranded RNA (polyinosinic-polycytidylic acid), and bacterial (Aeromonas hydrophila) RNA. Among these ligands, bacterial RNA most significantly (p < 0.05) induced TLR22 gene expression in most of the tested tissues. In A. hydrophila infection, induction of TLR22 gene expression

  2. Ligands of Therapeutic Utility for the Liver X Receptors

    Directory of Open Access Journals (Sweden)

    Rajesh Komati

    2017-01-01

    Full Text Available Liver X receptors (LXRs have been increasingly recognized as a potential therapeutic target to treat pathological conditions ranging from vascular and metabolic diseases, neurological degeneration, to cancers that are driven by lipid metabolism. Amidst intensifying efforts to discover ligands that act through LXRs to achieve the sought-after pharmacological outcomes, several lead compounds are already being tested in clinical trials for a variety of disease interventions. While more potent and selective LXR ligands continue to emerge from screening of small molecule libraries, rational design, and empirical medicinal chemistry approaches, challenges remain in minimizing undesirable effects of LXR activation on lipid metabolism. This review provides a summary of known endogenous, naturally occurring, and synthetic ligands. The review also offers considerations from a molecular modeling perspective with which to design more specific LXRβ ligands based on the interaction energies of ligands and the important amino acid residues in the LXRβ ligand binding domain.

  3. LigandRNA: computational predictor of RNA-ligand interactions.

    Science.gov (United States)

    Philips, Anna; Milanowska, Kaja; Lach, Grzegorz; Bujnicki, Janusz M

    2013-12-01

    RNA molecules have recently become attractive as potential drug targets due to the increased awareness of their importance in key biological processes. The increase of the number of experimentally determined RNA 3D structures enabled structure-based searches for small molecules that can specifically bind to defined sites in RNA molecules, thereby blocking or otherwise modulating their function. However, as of yet, computational methods for structure-based docking of small molecule ligands to RNA molecules are not as well established as analogous methods for protein-ligand docking. This motivated us to create LigandRNA, a scoring function for the prediction of RNA-small molecule interactions. Our method employs a grid-based algorithm and a knowledge-based potential derived from ligand-binding sites in the experimentally solved RNA-ligand complexes. As an input, LigandRNA takes an RNA receptor file and a file with ligand poses. As an output, it returns a ranking of the poses according to their score. The predictive power of LigandRNA favorably compares to five other publicly available methods. We found that the combination of LigandRNA and Dock6 into a "meta-predictor" leads to further improvement in the identification of near-native ligand poses. The LigandRNA program is available free of charge as a web server at http://ligandrna.genesilico.pl.

  4. Physical, biotic, and sampling influences on diel habitat use by stream-dwelling bull trout

    Science.gov (United States)

    Banish, N.P.; Peterson, J.T.; Thurow, R.F.

    2008-01-01

    We used daytime and nighttime underwater observation to assess microhabitat use by bull trout Salvelinus confluentus (N = 213) in streams of the intermountain western USA during the summers of 2001 and 2002. We recorded fish focal points and measured a set of habitat characteristics as well as habitat availability via line transects. Bull trout were benthic and solitary; most (88%) were observed at night. We developed a conditional logistic regression model to account for the effect of fish movement in response to snorkeling, and we fitted 18 candidate models to evaluate the relative influences of biotic and abiotic factors on habitat use. The candidate models were also fitted with a naive logistic regression (i.e., no movement) to evaluate the effects of movement on inferences of microhabitat use. The most plausible model describing bull trout habitat use was the same for the conditional and nai??ve regressions and included depth, velocity, percent rubble substratum, and the day X depth, body size X depth, and body size X day X depth interactions. The presence of brook trout S. fontinalis and the abundance of conspecifics did not strongly influence microhabitat use by bull trout. The relative rankings of the remaining models differed substantially between the conditional and nai??ve models. Relative to the conditional models, the naive models overestimated the importance of diurnal differences in habitat use and overestimated the use of deepwater habitats, particularly during the day. Both model types suggested that all sizes of bull trout were generally found in deeper, low-velocity habitat at night, whereas small bull trout (70-90 mm total length) were found in shallower habitats during the day. We recommend lhat biologists account for fish movement in response to sampling to avoid biasing modeled habitat use patterns by bull trout. ?? Copyright by the American Fisheries Society 2008.

  5. Predicting protein-ligand affinity with a random matrix framework.

    Science.gov (United States)

    Lee, Alpha A; Brenner, Michael P; Colwell, Lucy J

    2016-11-29

    Rapid determination of whether a candidate compound will bind to a particular target receptor remains a stumbling block in drug discovery. We use an approach inspired by random matrix theory to decompose the known ligand set of a target in terms of orthogonal "signals" of salient chemical features, and distinguish these from the much larger set of ligand chemical features that are not relevant for binding to that particular target receptor. After removing the noise caused by finite sampling, we show that the similarity of an unknown ligand to the remaining, cleaned chemical features is a robust predictor of ligand-target affinity, performing as well or better than any algorithm in the published literature. We interpret our algorithm as deriving a model for the binding energy between a target receptor and the set of known ligands, where the underlying binding energy model is related to the classic Ising model in statistical physics.

  6. Biotic Nitrogen Enrichment Regulates Calcium Sources to Forests

    Science.gov (United States)

    Pett-Ridge, J. C.; Perakis, S. S.; Hynicka, J. D.

    2015-12-01

    Calcium is an essential nutrient in forest ecosystems that is susceptible to leaching loss and depletion. Calcium depletion can affect plant and animal productivity, soil acid buffering capacity, and fluxes of carbon and water. Excess nitrogen supply and associated soil acidification are often implicated in short-term calcium loss from soils, but the long-term role of nitrogen enrichment on calcium sources and resupply is unknown. Here we use strontium isotopes (87Sr/86Sr) as a proxy for calcium to investigate how soil nitrogen enrichment from biological nitrogen fixation interacts with bedrock calcium to regulate both short-term available supplies and the long-term sources of calcium in montane conifer forests. Our study examines 22 sites in western Oregon, spanning a 20-fold range of bedrock calcium on sedimentary and basaltic lithologies. In contrast to previous studies emphasizing abiotic control of weathering as a determinant of long-term ecosystem calcium dynamics and sources (via bedrock fertility, climate, or topographic/tectonic controls) we find instead that that biotic nitrogen enrichment of soil can strongly regulate calcium sources and supplies in forest ecosystems. For forests on calcium-rich basaltic bedrock, increasing nitrogen enrichment causes calcium sources to shift from rock-weathering to atmospheric dominance, with minimal influence from other major soil forming factors, despite regionally high rates of tectonic uplift and erosion that can rejuvenate weathering supply of soil minerals. For forests on calcium-poor sedimentary bedrock, we find that atmospheric inputs dominate regardless of degree of nitrogen enrichment. Short-term measures of soil and ecosystem calcium fertility are decoupled from calcium source sustainability, with fundamental implications for understanding nitrogen impacts, both in natural ecosystems and in the context of global change. Our finding that long-term nitrogen enrichment increases forest reliance on atmospheric

  7. Tricyclic pyrazoles. Part 8. Synthesis, biological evaluation and modelling of tricyclic pyrazole carboxamides as potential CB2 receptor ligands with antagonist/inverse agonist properties.

    Science.gov (United States)

    Deiana, Valeria; Gómez-Cañas, María; Pazos, M Ruth; Fernández-Ruiz, Javier; Asproni, Battistina; Cichero, Elena; Fossa, Paola; Muñoz, Eduardo; Deligia, Francesco; Murineddu, Gabriele; García-Arencibia, Moisés; Pinna, Gerard A

    2016-04-13

    Previous studies have investigated the relevance and structure-activity relationships (SARs) of pyrazole derivatives in relation with cannabinoid receptors, and the series of tricyclic 1,4-dihydroindeno[1,2-c]pyrazoles emerged as potent CB2 receptor ligands. In the present study, novel 1,4-dihydroindeno[1,2-c]pyrazole and 1H-benzo[g]indazole carboxamides containing a cyclopropyl or a cyclohexyl substituent were designed and synthesized to evaluate the influence of these structural modifications towards CB1 and CB2 receptor affinities. Among these derivatives, compound 15 (6-cyclopropyl-1-(2,4-dichlorophenyl)-N-(adamantan-1-yl)-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamide) showed the highest CB2 receptor affinity (Ki = 4 nM) and remarkable selectivity (KiCB1/KiCB2 = 2232), whereas a similar affinity, within the nM range, was seen for the fenchyl derivative (compound 10: Ki = 6 nM), for the bornyl analogue (compound 14: Ki = 38 nM) and, to a lesser extent, for the aminopiperidine derivative (compound 6: Ki = 69 nM). Compounds 10 and 14 were also highly selective for the CB2 receptor (KiCB1/KiCB2 > 1000), whereas compound 6 was relatively selective (KiCB1/KiCB2 = 27). The four compounds were also subjected to GTPγS binding analysis showing antagonist/inverse agonist properties (IC50 for compound 14 = 27 nM, for 15 = 51 nM, for 10 = 80 nM and for 6 = 294 nM), and this activity was confirmed for the three more active compounds in a CB2 receptor-specific in vitro bioassay consisting in the quantification of prostaglandin E2 release by LPS-stimulated BV2 cells, in the presence and absence of WIN55,212-2 and/or the investigated compounds. Modelling studies were also conducted with the four compounds, which conformed with the structural requirements stated for the binding of antagonist compounds to the human CB2 receptor.

  8. 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.

  9. Meteoritic Versus Biotic Amino Acids: An Update on Aib and Iva

    Science.gov (United States)

    Brückner, H.; Degenkolb, T.; Fox, S.

    2016-08-01

    Biotically synthesized Aib and Iva hav been found in >1,350 structurally characterized microbial peptides. However, the structural diversity of the non-proteinogenic amino acids in CM-type meteorites is not displayed in individual fungal peptides.

  10. Biotic wetland connectivity-supporting a new approach for wetland policy

    NARCIS (Netherlands)

    Amezaga, J.M.; Santamaria, L.; Green, A.J.

    2002-01-01

    Wetlands are key habitats connected physically and socially with processes occurring over a much wider territory. The biotic connection through dispersal mechanisms among wetlands is of primary importance to wetland management and policies. However, traditional wetland conservation approaches are ba

  11. Coarse-grained molecular dynamics simulations of protein-ligand binding.

    Science.gov (United States)

    Negami, Tatsuki; Shimizu, Kentaro; Terada, Tohru

    2014-09-30

    Coarse-grained molecular dynamics (CGMD) simulations with the MARTINI force field were performed to reproduce the protein-ligand binding processes. We chose two protein-ligand systems, the levansucrase-sugar (glucose or sucrose), and LinB-1,2-dichloroethane systems, as target systems that differ in terms of the size and shape of the ligand-binding pocket and the physicochemical properties of the pocket and the ligand. Spatial distributions of the Coarse-grained (CG) ligand molecules revealed potential ligand-binding sites on the protein surfaces other than the real ligand-binding sites. The ligands bound most strongly to the real ligand-binding sites. The binding and unbinding rate constants obtained from the CGMD simulation of the levansucrase-sucrose system were approximately 10 times greater than the experimental values; this is mainly due to faster diffusion of the CG ligand in the CG water model. We could obtain dissociation constants close to the experimental values for both systems. Analysis of the ligand fluxes demonstrated that the CG ligand molecules entered the ligand-binding pockets through specific pathways. The ligands tended to move through grooves on the protein surface. Thus, the CGMD simulations produced reasonable results for the two different systems overall and are useful for studying the protein-ligand binding processes.

  12. Effect of Mining Activities in Biotic Communities of Villa de la Paz, San Luis Potosi, Mexico

    OpenAIRE

    2014-01-01

    Mining is one of the most important industrial activities worldwide. During its different stages numerous impacts are generated to the environment. The activities in the region have generated a great amount of mining residues, which have caused severe pollution and health effects in both human population and biotic components. The aim of this paper was to assess the impact of mining activities on biotic communities within the district of Villa de la Paz. The results showed that the concentrat...

  13. The Great American Biotic Interchange: Dispersals, Tectonics, Climate, Sea Level and Holding Pens

    OpenAIRE

    Woodburne, Michael O.

    2010-01-01

    The biotic and geologic dynamics of the Great American Biotic Interchange are reviewed and revised. Information on the Marine Isotope Stage chronology, sea level changes as well as Pliocene and Pleistocene vegetation changes in Central and northern South America add to a discussion of the role of climate in facilitating trans-isthmian exchanges. Trans-isthmian land mammal exchanges during the Pleistocene glacial intervals appear to have been promoted by the development of diverse non-tropical...

  14. Anti-biotic Effect of Slightly Acidic Electrolyzed Water on Plant Bacterial / Fungal Pathogen

    OpenAIRE

    津野, 和宣; 中村, 悌一

    2012-01-01

    The anti-biotic effect of slightly acidic electrolyzed water on plant pathogen was determined. The spores of 4 kinds of fungal pathogen and 17 kinds of plant pathogenic bacteria were applied at different concentration.###Slightly acidic electrolyzed water showed strong growth inhibition in germination of fungi spores tested. In addition, by the treatment with slightly acidic electrolyzed water for 30 sec., all kinds of bacteria tested were inhibited to grow on the medium.###The anti-biotic ef...

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

    OpenAIRE

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

    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 ecosys...

  16. 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

  17. Superior serum half life of albumin tagged TNF ligands

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, Nicole [Division of Molecular Internal Medicine, Department of Internal Medicine II, University Hospital Wuerzburg, Roentgenring 11, 97070 Wuerzburg (Germany); Schneider, Britta; Pfizenmaier, Klaus [Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart (Germany); Wajant, Harald, E-mail: harald.wajant@mail.uni-wuerzburg.de [Division of Molecular Internal Medicine, Department of Internal Medicine II, University Hospital Wuerzburg, Roentgenring 11, 97070 Wuerzburg (Germany)

    2010-06-11

    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.

  18. Pre-biotic organic molecules in hydrothermal quartz veins from the Archaean Yilgarn province, Australia

    Science.gov (United States)

    Mayer, Christian; Schreiber, Ulrich; Dyker, Gerald; Kirnbauer, Thomas; Mulder, Ines; Sattler, Tobias; Schöler, Heinfried; Tubbesing, Christoph

    2013-04-01

    According to a model recently published by Schreiber et al. (OLEB 2012), pre-biotic organic molecules as earliest markers for a chemical evolution have been formed in tectonic faults of the first Archaean cratons. These faults are often documented by quartz- and other hydrothermal vein mineralization. During the growth of these quartzes, small portions of hydrothermal fluids are enclosed which conserve the chemical composition of the given fluid medium. According to our model, the preconditions for the geochemical formation of organic molecules are a suitable carbon source (e.g. carbon dioxide), varying P/T conditions, and catalysts. This given, rising hydrothermal fluids such as mineral-rich water and supercritical carbon dioxide in deep faults with contacts to the upper earth mantle offer conditions which allow for reactions similar to the Fischer-Tropsch synthesis. So far, the inclusions which possibly have conserved the products of these reactions have not been analyzed for possible organic constituents. First analytical results of a Mesozoic hydrothermal quartz vein from central Germany (Taunus) reveal that several organic compounds are found in fluid inclusions. However, the true origin of these compounds is unclear due to possible contamination by adjacent Corg-rich metasediments. Therefore, we have extended the study to hydrothermal quartz veins from the Archaean Yilgarn craton, to impact-generated quartz veins of the Shoemaker-Crater as well as to hydrothermal quartz boulders from a 2.7 to 3 billion years old conglomerate near Murchison (Western Australia). In one of the samples from the conglomerate, a wide spectrum of organic compounds such as bromomethane, butane, isoprene, benzene, and toluene have been detected. The time interval between the quartz formation, its erosion and its sedimentation is unknown. Possibly, the analyzed quartz sample was formed in a hydrothermal vein long before any living cells have existed on earth. In this case, the given

  19. 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.

  20. 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

  1. Dockomatic - automated ligand creation and docking

    OpenAIRE

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

    2010-01-01

    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 frie...

  2. A comparative study between the two biotic ligand models (BLMs) on predicting the acute Zn toxicity to Daphnia magna%两种生物配体模型(BLM)预测Zn对大型蚤急性毒性的比较

    Institute of Scientific and Technical Information of China (English)

    陈中智; 朱琳; 姚琨; 李燕; 刘硕

    2008-01-01

    通过天津地区一系列景观水体和配制的模拟溶液,评价应用于大型蚤(Daphnia magna)毒性预测的两种急性Zn-生物配体(BLM)模型(模型A和模型B)的预测能力.采用Visual MINTEQ 2.5.2进行BLM的相关计算和金属形态分析.对一定水化学参数的测定表明,根据Zn对大型蚤的急性毒性数据建立的模型B能够在Zn的生态风险评价中考虑其生物有效性,预测结果准确;以鱼类为对象开发并下调LA50后应用于水蚤毒性预测的模型A的预测值普遍高于实测值.可见,通过调整LA50拓展模型适用性的方法过于简单,还有待进一步研究.

  3. Impact of biotic and abiotic stresses on the competitive ability of multiple herbicide resistant wild oat (Avena fatua.

    Directory of Open Access Journals (Sweden)

    Erik A Lehnhoff

    Full Text Available Ecological theory predicts that fitness costs of herbicide resistance should lead to the reduced relative abundance of resistant populations upon the cessation of herbicide use. This greenhouse research investigated the potential fitness costs of two multiple herbicide resistant (MHR wild oat (Avena fatua populations, an economically important weed that affects cereal and pulse crop production in the Northern Great Plains of North America. We compared the competitive ability of two MHR and two herbicide susceptible (HS A. fatua populations along a gradient of biotic and abiotic stresses The biotic stress was imposed by three levels of wheat (Triticum aestivum competition (0, 4, and 8 individuals pot(-1 and an abiotic stress by three nitrogen (N fertilization rates (0, 50 and 100 kg N ha(-1. Data were analyzed with linear mixed-effects models and results showed that the biomass of all A. fatua populations decreased with increasing T. aestivum competition at all N rates. Similarly, A. fatua relative growth rate (RGR decreased with increasing T. aestivum competition at the medium and high N rates but there was no response with 0 N. There were no differences between the levels of biomass or RGR of HS and MHR populations in response to T. aestivum competition. Overall, the results indicate that MHR does not confer growth-related fitness costs in these A. fatua populations, and that their relative abundance will not be diminished with respect to HS populations in the absence of herbicide treatment.

  4. The mutual influence of biotic and abiotic components on the long-term ecomorphodynamic evolution of salt-marsh ecosystems

    Science.gov (United States)

    D'Alpaos, Andrea

    2011-03-01

    Salt marshes are coastal ecosystems characterized by high biodiversity and rates of primary productivity, providing fundamental ecosystem services. Salt-marsh ecosystems are important indicators of environmental change as the dynamics are governed by interacting physical and biological processes, whose intertwined feedbacks critically affect the evolution. Settling deposition of inorganic sediment allows the platform to reach a threshold elevation for vegetation encroachment; the presence of vegetation then intensifies rates of accretion, thus, enhancing the resilience of marshes to increasing rates of sea level rise (SLR). The results from a two-dimensional numerical model, accounting for biotic and geomorphic processes, show that different morphological evolutionary regimes are followed depending on marsh biological processes. The average marsh elevation within the tidal frame decreases with increasing rates of SLR, decreasing availability of sediment, and decreasing productivity of vegetation. The spatial variability in platform elevations increases with increasing rates of SLR, increasing availability of sediment, and decreasing productivity of vegetation. Supply-limited settings tend to develop uniform marsh surface elevations, whereas supply-rich settings tend to develop patterns of sedimentation where large heterogeneities in marsh surface elevations occur. The complexity observed in tidal geomorphological patterns is deemed to arise from the mutual influence of biotic and abiotic components. The fate of tidal landforms and their possible geomorphological restoration should, thus, be addressed through approaches which explicitly incorporate bio-morphodynamic processes.

  5. Impact of biotic and abiotic stresses on the competitive ability of multiple herbicide resistant wild oat (Avena fatua).

    Science.gov (United States)

    Lehnhoff, Erik A; Keith, Barbara K; Dyer, William E; Menalled, Fabian D

    2013-01-01

    Ecological theory predicts that fitness costs of herbicide resistance should lead to the reduced relative abundance of resistant populations upon the cessation of herbicide use. This greenhouse research investigated the potential fitness costs of two multiple herbicide resistant (MHR) wild oat (Avena fatua) populations, an economically important weed that affects cereal and pulse crop production in the Northern Great Plains of North America. We compared the competitive ability of two MHR and two herbicide susceptible (HS) A. fatua populations along a gradient of biotic and abiotic stresses The biotic stress was imposed by three levels of wheat (Triticum aestivum) competition (0, 4, and 8 individuals pot(-1)) and an abiotic stress by three nitrogen (N) fertilization rates (0, 50 and 100 kg N ha(-1)). Data were analyzed with linear mixed-effects models and results showed that the biomass of all A. fatua populations decreased with increasing T. aestivum competition at all N rates. Similarly, A. fatua relative growth rate (RGR) decreased with increasing T. aestivum competition at the medium and high N rates but there was no response with 0 N. There were no differences between the levels of biomass or RGR of HS and MHR populations in response to T. aestivum competition. Overall, the results indicate that MHR does not confer growth-related fitness costs in these A. fatua populations, and that their relative abundance will not be diminished with respect to HS populations in the absence of herbicide treatment.

  6. Predicting Partitioning and Diffusion Properties of Nonpolar Chemicals in Biotic Media and Passive Sampler Phases by GC × GC.

    Science.gov (United States)

    Nabi, Deedar; Arey, J Samuel

    2017-02-14

    The chemical parameters needed to explain and predict bioavailability, biodynamics, and baseline toxicity are not readily available for most nonpolar chemicals detected in the environment. Here, we demonstrate that comprehensive two-dimensional gas chromatography (GC × GC) retention times can be used to predict 26 relevant properties for nonpolar chemicals, specifically: partition coefficients for diverse biotic media and passive sampler phases; aquatic baseline toxicity; and relevant diffusion coefficients. The considered biotic and passive sampler phases include membrane and storage lipids, serum and muscle proteins, carbohydrates, algae, mussels, polydimethylsiloxane, polyethylene, polyoxymethylene, polyacrylate, polyurethane, and semipermeable membrane devices. GC × GC-based chemical property predictions are validated with a compilation of 1038 experimental property data collected from the literature. As an example application, we overlay a map of baseline toxicity to fathead minnows onto the separated analyte signal of a polychlorinated alkanes (chlorinated paraffins) technical mixture that contains 7820 congeners. In a second application, GC × GC-estimated properties are used to parametrize multiphase partitioning models for mammalian tissues and organs. In a third example, we estimate chemical depuration kinetics for mussels. Finally, we illustrate an approach to screen the GC × GC chromatogram for nonpolar chemicals of potentially high concern, defined based on their GC × GC-estimated biopartitioning properties, diffusion properties, and baseline toxicity.

  7. Temperature-controlled synthesis and luminescent properties of two novel coordination polymers modeled by hexa-carboxylate ligand derived from cyclotriphosphazene.

    Science.gov (United States)

    Li, Bao; Dai, Xiaomei; Meng, Xianggao; Zhang, Tianle; Liu, Chengmei; Yu, Kaichao

    2013-02-21

    Solvothermal reactions of hexakis(4-formylphenoxy)cyclotriphosphazene (H(6)L1) with Cd(NO(3))(2)·4H(2)O in H(2)O/DMF under different synthesis temperatures produced two new compounds, namely, {[Cd(3)(C(42)H(24)O(18)P(3)N(3)) (H(2)O)(7)]·xGuest}(n) (1), and {[Cd(2)(C(42)H(24)O(18)P(3)N(3)) (H(2)O)(2)]·xGuest}(n) (2). Compound 1 exhibits a novel 3D framework adopting 2,4,6-connected 3-nodal topology with the point (Schläfli) symbol {4(4)·6(2)}{4(5)·6(2)·8(8)}{4} constructed from the joint of neutral Cd(2) SBUs, mono-Cd ions and L1 ligands. Compound 2 reveals a 2D crystal structure exhibiting a 3,6-connected 2-nodal kgd topology with the point (Schläfli) symbol {4(3)}(2){4(6)·6(6)·8(3)} constructed from the connection of Cd centers and L1 ligands. In these two compounds, the ligands L1 are fully deprotonated, whose six extended carboxyl arms connect six different/same metallic nodes to form high dimensional frameworks. The variable reaction temperature must be responsible for the higher coordination number and versatile coordination modes of carboxylates in 1 compared to the ones in 2, resulting in the formation of a distinct crystal structure. In the solid state, both complexes are photoluminescent (LMCT) at room temperature.

  8. 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.

  9. Analysis of competition between transformation pathways in the functioning of biotic abstract dual automata.

    Science.gov (United States)

    Popa, Radu; Cimpoiasu, Vily M

    2013-05-01

    Properties of avenues of transformation and their mutualism with forms of organization in dynamic systems are essential for understanding the evolution of prebiotic order. We have analyzed competition between two avenues of transformation in an A↔B system, using the simulation approach called BiADA (Biotic Abstract Dual Automata). We discuss means of avoiding common pitfalls of abstract system modeling and benefits of BiADA-based simulations. We describe the effect of the availability of free energy, energy sink magnitude, and autocatalysis on the evolution of energy flux and order in the system. Results indicate that prebiotic competition between avenues of transformation was more stringent in energy-limited environments. We predict that in such conditions the efficiency of autocatalysis during competition between alternative system states will increase for systems with forms of organization having short half-lives and thus information that is time-sensitive to energy starvation. Our results also offer a potential solution to Manfred Eigen's error catastrophe dilemma. In the conditions discussed above, the exponential growth of quasi species is curbed through the removal of less competitive "genetic" variants via energy starvation. We propose that one of the most important achievements (and selective edges) of a dynamic network during competition in energy-limited or energy-variable environments was the capacity to correlate the internal energy flux and the need for free energy with the availability of free energy in the environment.

  10. Biotic degradation at night, abiotic degradation at day: positive feedbacks on litter decomposition in drylands.

    Science.gov (United States)

    Gliksman, Daniel; Rey, Ana; Seligmann, Ron; Dumbur, Rita; Sperling, Or; Navon, Yael; Haenel, Sabine; De Angelis, Paolo; Arnone, John A; Grünzweig, José M

    2017-04-01

    The arid and semi-arid drylands of the world are increasingly recognized for their role in the terrestrial net carbon dioxide (CO2 ) uptake, which depends largely on plant litter decomposition and the subsequent release of CO2 back to the atmosphere. Observed decomposition rates in drylands are higher than predictions by biogeochemical models, which are traditionally based on microbial (biotic) degradation enabled by precipitation as the main mechanism of litter decomposition. Consequently, recent research in drylands has focused on abiotic mechanisms, mainly photochemical and thermal degradation, but they only partly explain litter decomposition under dry conditions, suggesting the operation of an additional mechanism. Here we show that in the absence of precipitation, absorption of dew and water vapor by litter in the field enables microbial degradation at night. By experimentally manipulating solar irradiance and nighttime air humidity, we estimated that most of the litter CO2 efflux and decay occurring in the dry season was due to nighttime microbial degradation, with considerable additional contributions from photochemical and thermal degradation during the daytime. In a complementary study, at three sites across the Mediterranean Basin, litter CO2 efflux was largely explained by litter moisture driving microbial degradation and ultraviolet radiation driving photodegradation. We further observed mutual enhancement of microbial activity and photodegradation at a daily scale. Identifying the interplay of decay mechanisms enhances our understanding of carbon turnover in drylands, which should improve the predictions of the long-term trend of global carbon sequestration.

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

    Science.gov (United States)

    Boyero, Luz; 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

    2016-04-27

    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.

  12. Influence of biotic variables on invertebrate size structure and diversity in coastal wetlands of Southeastern Spain

    Science.gov (United States)

    Antón-Pardo, María; Armengol, Xavier

    2016-10-01

    Biomass and size-based estimations provide relevant information regarding ecosystem functioning and biotic interactions. Our aims were to study the effect of fish and macrophytes on the size structure of invertebrate assemblages (from rotifers to insects) in a set of coastal water bodies, estimating the biomass (total and main invertebrate groups), the biomass-size spectra (model of Pareto) and size diversity. In fishless ponds, cladoceran and ostracod biomass were higher, and they presented greater size diversity. In fish ponds, rotifer biomass presented greater proportion; while in fishless ponds, cladocerans were usually the most abundant taxa and the largest organisms. The biomass size spectra showed more irregularities in fishless ponds, due to the low densities of small taxa (rotifers and copepod juveniles) and big taxa (malacostraceans or insects). Differences is size structure and diversity were also observed between spring and summer, suggesting a higher recruitment of juveniles in spring, and thus, a higher predation pressure upon zooplankton at that moment. Macrophyte cover did not apparently influence those parameters, except for the biomass of ostracods, copepods, and insects. Therefore, predation by fish strongly affected invertebrate biomass, reflecting their selective feeding, and allowing high densities of small taxa. Predation pressure decreased size diversity, by limiting the abundance of vulnerable taxa of specific size. Seasonal changes were likely related to the spring recruitment of fish juveniles. The presence of small fish and invertebrate predator taxa among the macrophytes, restrict their role as refuges for prey invertebrates.

  13. 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.

  14. 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.

  15. Enhanced nitrobenzene removal and column longevity by coupled abiotic and biotic processes in zero-valent iron column

    DEFF Research Database (Denmark)

    Yin, Weizhao; Wu, Jinhua; Huang, Weilin;

    2015-01-01

    /or co-precipitation and the reduction of NB to aniline (AN) via abiotic reaction in the abiotic column and via both abiotic and biotic reactions in the biotic column. Due to the interactive effect of ZVI and microorganisms, more effective iron consumption and more reactive minerals such as green rust......In this study, abiotic zero-valent iron (ZVI) column and biotic ZVI column were employed to investigate abiotic and biotic effects between iron and microorganisms on NB removal and column longevity. Physical removal and kinetics analysis revealed that NB was largely removed through adsorption and...... and iron sulfide were found in the biotic column. This led to approximately 50% higher total NB removal and 6 times higher AN production in the biotic column as compared to the abiotic column during the entire operation. According to the NB breakthrough curves, longer stability and longer life...

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

    Science.gov (United States)

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

    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.

  17. 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.

  18. 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.

  19. Toward models for the full oxygen-evolving complex of photosystem II by ligand coordination to lower the symmetry of the Mn3CaO4 cubane: demonstration that electronic effects facilitate binding of a fifth metal.

    Science.gov (United States)

    Kanady, Jacob S; Lin, Po-Heng; Carsch, Kurtis M; Nielsen, Robert J; Takase, Michael K; Goddard, William A; Agapie, Theodor

    2014-10-15

    Synthetic model compounds have been targeted to benchmark and better understand the electronic structure, geometry, spectroscopy, and reactivity of the oxygen-evolving complex (OEC) of photosystem II, a low-symmetry Mn4CaOn cluster. Herein, low-symmetry Mn(IV)3GdO4 and Mn(IV)3CaO4 cubanes are synthesized in a rational, stepwise fashion through desymmetrization by ligand substitution, causing significant cubane distortions. As a result of increased electron richness and desymmetrization, a specific μ3-oxo moiety of the Mn3CaO4 unit becomes more basic allowing for selective protonation. Coordination of a fifth metal ion, Ag(+), to the same site gives a Mn3CaAgO4 cluster that models the topology of the OEC by displaying both a cubane motif and a "dangler" transition metal. The present synthetic strategy provides a rational roadmap for accessing more accurate models of the biological catalyst.

  20. Macrocyclic G-quadruplex ligands

    DEFF Research Database (Denmark)

    Nielsen, M C; Ulven, Trond

    2010-01-01

    G-quadruplex stabilizing compounds have recently received increased interest due to their potential application as anticancer therapeutics. A significant number of structurally diverse G-quadruplex ligands have been developed. Some of the most potent and selective ligands currently known are macr...

  1. 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.

  2. Abiotic and biotic controls of cryptobenthic fish assemblages across a Caribbean seascape

    Science.gov (United States)

    Harborne, A. R.; Jelks, H. L.; Smith-Vaniz, W. F.; Rocha, L. A.

    2012-12-01

    The majority of fish studies on coral reefs consider only non-cryptic species and, despite their functional importance, data on cryptic species are scarce. This study investigates inter-habitat variation in Caribbean cryptobenthic fishes by re-analysing a comprehensive data set from 58 rotenone stations around Buck Island, U.S. Virgin Islands. Boosted regression trees were used to associate the density and diversity of non-piscivorous cryptobenthic fishes, both in the entire data set and on reef habitats alone, with 14 abiotic and biotic variables. The study also models the habitat requirements of the three commonest species. Dead coral cover was the first or second most important variable in six of the eight models constructed. For example, within the entire data set, the number of species and total fish density increased approximately linearly with increasing dead coral cover. Dead coral was also important in multivariate analyses that discriminated 10 assemblages within the entire data set. On reef habitats, the number of species and total fish density increased dramatically when dead coral exceeded ~55 %. Live coral cover was typically less important for explaining variance in fish assemblages than dead coral, but live corals were important for maintaining high fish diversity. Coral species favoured by cryptobenthic species may be particularly susceptible to mortality, but dead coral may also provide abundant food and shelter for many fishes. Piscivore density was a key variable in the final models, but typically increased with increasing cryptobenthic fish diversity and abundance, suggesting both groups of fishes are responding to the same habitat variables. The density of territorial damselfishes reduced the number of cryptobenthic fish species on reef habitats. Finally, habitats delineated by standard remote sensing techniques supported distinct cryptobenthic fish assemblages, suggesting that such maps can be used as surrogates of general patterns of cryptic

  3. 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.

  4. 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

    dechlorination. In all biotic microcosms 1,1,1-TCA was degraded with no apparent increase in the biotic degradation product 1,1-DCA. 1,1,1-TCA degradation was documented by a clear enrichment in 13C in all biotic microcosms, but not in the abiotic control, which suggests biotic or biotically mediated degradation...... 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......,1,1-TCA mediated by biotic FeS formation constitute an explanation for the observed 1,1,1-TCA degradation. This is supported by a high 1,1,1-TCA 13C enrichment factor consistent with abiotic degradation in biotic microcosms. 1,1-DCA carbon isotope field data suggest that this abiotic degradation of 1...

  5. Evolution of Neogene Mammals in Eurasia: Environmental Forcing and Biotic Interactions

    Science.gov (United States)

    Fortelius, Mikael; Eronen, Jussi T.; Kaya, Ferhat; Tang, Hui; Raia, Pasquale; Puolamäki, Kai

    2014-05-01

    The relative weights of physical forcing and biotic interaction as drivers of evolutionary change have been debated in evolutionary theory. The recent finding that species, genera, clades, and chronofaunas all appear to exhibit a symmetrical pattern of waxing and waning lends support to the view that biotic interactions shape the history of life. Yet, there is similarly abundant evidence that these primary units of biological evolution arise and wane in coincidence with major climatic change. We review these patterns and the process-level explanations offered for them. We also propose a tentative synthesis, characterized by interdependence between physical forcing and biotic interactions. We suggest that species with evolutionary novelties arise predominantly in "species factories" that develop under harsh environmental conditions, under dominant physical forcing, whereas exceptionally mild environments give rise to "oases in the desert," characterized by strong competition and survival of relics.

  6. Aerobic bacterial catabolism of persistent organic pollutants - potential impact of biotic and abiotic interaction.

    Science.gov (United States)

    Jeon, Jong-Rok; Murugesan, Kumarasamy; Baldrian, Petr; Schmidt, Stefan; Chang, Yoon-Seok

    2016-04-01

    Several aerobic bacteria possess unique catabolic pathways enabling them to degrade persistent organic pollutants (POPs), including polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), polybrominated diphenylethers (PBDEs), and polychlorinated biphenyls (PCBs). The catabolic activity of aerobic bacteria employed for removal of POPs in the environment may be modulated by several biotic (i.e. fungi, plants, algae, earthworms, and other bacteria) and abiotic (i.e. zero-valent iron, advanced oxidation, and electricity) agents. This review describes the basic biochemistry of the aerobic bacterial catabolism of selected POPs and discusses how biotic and abiotic agents enhance or inhibit the process. Solutions allowing biotic and abiotic agents to exert physical and chemical assistance to aerobic bacterial catabolism of POPs are also discussed.

  7. Iron(III) complexes of tripodal tetradentate 4N ligands as functional models for catechol dioxygenases: the electronic vs. steric effect on extradiol cleavage.

    Science.gov (United States)

    Balamurugan, Mani; Vadivelu, Prabha; Palaniandavar, Mallayan

    2014-10-21

    A few mononuclear iron(iii) complexes of the type [Fe(L)Cl2]Cl , where L is a tetradentate tripodal 4N ligand such as N,N-dimethyl-N',N'-bis(pyrid-2-ylmethyl)ethane-1,2-diamine (), N,N-diethyl-N',N'-bis(pyrid-2-ylmethyl)ethane-1,2-diamine (), N,N-dimethyl-N',N'-bis-(6-methylpyrid-2-ylmethyl)ethane-1,2-diamine (), N,N-dimethyl-N'-(pyrid-2-ylmethyl)-N'-(1-methyl-1H-imidazol-2-ylmethyl)ethane-1,2-diamine (), N,N-dimethyl-N',N'-bis(1-methyl-1H-imidazol-2-ylmethyl)ethane-1,2-diamine () and N,N-dimethyl-N',N'-bis(quinolin-2-ylmethyl)ethane-1,2-diamine (), have been isolated and characterized by CHN analysis, UV-Visible spectroscopy and electrochemical methods. The complex cation [Fe(H)Cl3](+) possesses a distorted octahedral geometry in which iron is coordinated by the monoprotonated 4N ligand in a tridentate fashion and the remaining three sites of the octahedron are occupied by chloride ions. The DFT optimized octahedral geometries of , and contain iron(iii) with a high-spin (S = 5/2) ground state. The catecholate adducts [Fe(L)(DBC)](+), where H2DBC is 3,5-di-tert-butylcatechol, of all the complexes have been generated in situ in acetonitrile solution and their spectral and redox properties and dioxygenase activities have been studied. The DFT optimized geometries of the catecholate adducts [Fe()(DBC)](+), [Fe()(DBC)](+) and [Fe()(DBC)](+) have also been generated to illustrate the ability of the complexes to cleave H2DBC in the presence of molecular oxygen to afford varying amounts of intra- (I) and extradiol (E) cleavage products. The extradiol to intradiol product selectivity (E/I, 0.1-2.0) depends upon the asymmetry in bidentate coordination of catecholate, as determined by the stereoelectronic properties of the ligand donor functionalities. While the higher E/I value obtained for [Fe()(DBC)](+) is on account of the steric hindrance of the quinolyl moiety to coordination the lower value observed for [Fe()(DBC)](+) and [Fe()(DBC)](+) is on account of the electron

  8. Synthesis, Characterization, and Crystal Structure of a Novel Copper(II) Complex with an Asymmetric Coordinated 2,2'-Bipyridine Derivative: A Model for the Associative Complex in the Ligand-Substitution Reactions of [Cu(tren)L](2+)?

    Science.gov (United States)

    Lu Zl, Zhong-lin; Duan Cy, Chun-ying; Tian Yp, Yu-peng; You Xz, Xiao-zeng; Huang Xy, Xiao-ying

    1996-04-10

    The titled compound, (tris(2-aminoethyl)amine)(4,5-diazafluoren-9-one) copper(II) perchlorate, [Cu(C(6)H(18)N(4))(C(11)H(6)N(2)O)(ClO(4))(2)], 1, has been designed, synthesized, and characterized. The electronic and ESR spectra are very different from those of [Cu(tren)L](2+) complexes where L is monodentate ligand. The X-ray analysis revealed that the complex crystallizes in the monoclinic space group P2(1)/c, with a = 10.726(6) Å, b = 14.921(7) Å, c = 14.649(4) Å, beta = 95.13(3) degrees, and Z = 4. The copper(II) ion is coordinated by four nitrogen atoms from tris(2-aminoethyl)amine (tren) and two nitrogen atoms from 4,5-diazafluoren-9-one (dzf) to form an unusual six-coordinate (4 + 1 + 1') geometry. The structure is very rare, and to our knowledge, it is the first example of an asymmetric bidentate phenanthroline derivative metal complex. The structure could be used as a model of the associative complex in the ligand-exchange and ligand-substitution reactions of [Cu(tren)L](2+) and the catalytic mechanisms of enzymes involving copper sites. From the electronic and variable-temperature ESR spectra in solution, the possible mechanism of these reactions has also been proposed. As a comparison, the complex [Cu(tren)(ImH)(ClO(4))(2)], 2, was also synthesized and characterized, where ImH is imidazole.

  9. 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

  10. The relative contribution of climatic, edaphic, and biotic drivers to risk of tree mortality from drought

    Science.gov (United States)

    March, R. G.; Moore, G. W.; Edgar, C. B.; Lawing, A. M.; Washington-Allen, R. A.

    2015-12-01

    In recorded history, the 2011 Texas Drought was comparable in severity only to a drought that occurred 300 years ago. By mid-September, 88% of the state experienced 'exceptional' conditions, with the rest experiencing 'extreme' or 'severe' drought. By recent estimates, the 2011 Texas Drought killed 6.2% of all the state's trees, at a rate nearly 9 times greater than average. The vast spatial scale and relatively uniform intensity of this drought has provided an opportunity to examine the comparative interactions among forest types, terrain, and edaphic factors across major climate gradients which in 2011 were subjected to extreme drought conditions that ultimately caused massive tree mortality. We used maximum entropy modeling (Maxent) to rank environmental landscape factors with the potential to drive drought-related tree mortality and test the assumption that the relative importance of these factors are scale-dependent. Occurrence data of dead trees were collected during the summer of 2012 from 599 field plots distributed across Texas with 30% used for model evaluation. Bioclimatic variables, ecoregions, soils characteristics, and topographic variables were modeled with drought-killed tree occurrence. Their relative contribution to the model was seen as their relative importance in driving mortality. To test determinants at a more local scale, we examined Landsat 7 scenes in East and West Texas with moderate-resolution data for the same variables above with the exception of climate. All models were significantly better than random in binomial tests of omission and receiver operating characteristic analyses. The modeled spatial distribution of probability of occurrence showed high probability of mortality in the east-central oak woodlands and the mixed pine-hardwood forest region in northeast Texas. Both regional and local models were dominated by biotic factors (ecoregion and forest type, respectively). Forest density and precipitation of driest month also

  11. The abundance of biotic exoplanets and life on planets of Red Dwarf stars

    Science.gov (United States)

    Wandel, Amri; Gale, Joseph

    2016-07-01

    The Kepler mission has shown that Earthlike planets orbiting within the Habitable Zones of their host stars are common. We derive an expression for the abundance of life bearing (biotic) extra-solar-system planets (exoplanets) in terms of the (yet unknown) probability for the evolution of biotic life. This "biotic probability" may be estimated by future missions and observations, e.g. spectral analyses of the atmospheres of exoplanets, looking for biomarkers. We show that a biotic probability in the range 0.001-1 implies that a biotic planet may be expected within ~10-100 light years from Earth. Of particular interest in the search for exolife are planets orbiting Red Dwarf (RD) stars, the most frequent stellar type. Previous researches suggested that conditions on planets near RDs would be inimical to life, e.g. the Habitable Zone of RDs is small, so their habitable planets would be close enough to be tidally locked. Recent calculations show that this and other properties of RDs, presumed hostile for the evolution of life, are less severe than originally estimated. We conclude that RD planets could be hospitable for the evolution of life as we know it, not less so than planets of solar-type stars. This result, together with the large number of RDs and their Kepler planet-statistics, makes finding life on RD planets ~10-1000 times more likely than on planets of solar-type stars. Our nearest biotic RD-planet is likely to be 2-10 times closer than the nearest solar-type one.

  12. Functional model of oxomolybdoenzymes: Synthesis and characterization of a molybdenum complex with sulphur and pterin ligands exhibiting saturation kinetics with pyridine N-oxide

    Indian Academy of Sciences (India)

    M D Afsar Ali; Parag S Roy

    2001-04-01

    Redox reaction between 6-acetonylisoxanthopterin (H2pte) and [MoVIO2(ssp)] [ssp = anion of 2-(salicylideneamino) benzenethiol] in CH3OH-C2H5OH medium produces a new mixed ligand compound [MoIV (ssp) (Hpte) (OCH3)] (1). It has been characterized by elemental analysis, ESMS data, UV-Vis, IR, 1H NMR (1D and 2D) spectroscopy and cyclic voltammetry. Kinetics of formation of this compound as well as that of its reaction with pyridine N-oxide have been followed spectrophotometrically. Both the reactions follow substrate saturation kinetics and involve metal-centred oxygen atom transfer process. Large negative values of entropy of activation indicate the operation of associative mechanism.

  13. Using thermodynamics to assess biotic and abiotic impediments to root water uptake

    Science.gov (United States)

    Bechmann, Marcel; Hildebrandt, Anke; Kleidon, Axel

    2016-04-01

    Root water uptake has been the subject of extensive research, dealing with understanding the processes limiting transpiration and understanding strategies of plants to avoid water stress. Many of those studies use models of water flow from the soil through the plant into the atmosphere to learn about biotic and abiotic factors affecting plant water relations. One important question in this context is to identify those processes that are most limiting to water transport, and specifically whether these processes lie within the plant or the soil? Here, we propose to use a thermodynamic formulation of root water uptake to answer this question. The method allows us to separate the energy exported at the root collar into a sum of energy fluxes related to all processes along the flow path, notably including the effect of increasing water retention in drier soils. Evaluation of the several contributions allows us to identify and rank the processes by how much these impede water flow from the soil to the atmosphere. The application of this approach to a complex 3-dimensional root water uptake model reveals insights on the role of root versus soil resistances to limit water flow. We investigate the efficiency of root water uptake in an ensemble of root systems with varying root hydraulic properties. While root morphology is kept the same, root radial and axial resistances are artificially varied. Starting with entirely young systems (uptake roots, high radial, low axial conductance) we increasingly add older roots (transport roots, high axial, low radial conductance) to improve transport within root systems. This yields a range of root hydraulic architectures, where the extremes are limited either by radial uptake capacity or low capacity to transport water along the root system. We model root water uptake in this range of root systems with a 3-dimensional root water uptake model in two different soils, applying constant flux boundary conditions in a dry down experiment and

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

    DEFF Research Database (Denmark)

    Arturi, Katarzyna Ratajczyk; Koch, Christian Bender; Søgaard, Erik Gydesen

    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...

  15. The Great American Biotic Interchange: Dispersals, Tectonics, Climate, Sea Level and Holding Pens.

    Science.gov (United States)

    Woodburne, Michael O

    2010-12-01

    The biotic and geologic dynamics of the Great American Biotic Interchange are reviewed and revised. Information on the Marine Isotope Stage chronology, sea level changes as well as Pliocene and Pleistocene vegetation changes in Central and northern South America add to a discussion of the role of climate in facilitating trans-isthmian exchanges. Trans-isthmian land mammal exchanges during the Pleistocene glacial intervals appear to have been promoted by the development of diverse non-tropical ecologies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10914-010-9144-8) contains supplementary material, which is available to authorized users.

  16. 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.

  17. Recommended Reference Genes for Quantitative PCR Analysis in Soybean Have Variable Stabilities during Diverse Biotic Stresses

    OpenAIRE

    Raman Bansal; Priyanka Mittapelly; CASSONE, BRYAN J.; Praveen Mamidala; Redinbaugh, Margaret G.; Andy Michel

    2015-01-01

    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 str...

  18. The ligands of CXCR4 in vascularization

    OpenAIRE

    Tuchscheerer, Nancy

    2012-01-01

    The formation of a functional and integrated vascular network is a basic process in the growth and maintenance of tissues and can be established by two forms of blood vessel growth in adults: angiogenesis and arteriogenesis. In this study, the ligands of the chemokine receptor CXCR4 and its role in angiogenesis (represented by the experimental myocardial infarction) and arteriogenesis (represented by the murine hind limb ischemia model) was investigated. The first approach identified the CXCL...

  19. Habitability for Complex Life and the Development and Self-Limitations of the Biotic Enhancement of Weathering

    Science.gov (United States)

    Schwartzman, D. W.; Volk, T.

    2014-12-01

    We submit that the tightly coupled coevolution of biota and climate is a critical driver of the self-organization of the biosphere over geologic time. The long-term carbon biogeochemical cycle includes a major influence of biology relevant to climatic, namely the biotic enhancement of weathering (BEW). According to a meta-analysis of field and experimental evidence, the likely magnitude of the present BEW is roughly two orders of magnitude, the culmination of its progressive increase over geologic time. Within the context of modeling this long-term cycle, this value can be used to estimate the likely abiotic temperature history of the Earth's surface, assuming plausible initial temperatures, and histories of volcanic outgassing and continental crust growth. The result of this modeling is that the Earth would have been habitable for thermophilic life (growing above 50 deg C) for the past 4.4 billion years, but not for low-temperature life, including plants and animals. Hence biospheric cooling due to biotic actions allowed the emergence of complex life. Much larger increases in BEW are self-limiting, since the atmospheric CO2 level would plunge below the lower limit potentially for photosynthesis, thereby driving a decline in the biological productivity and global BEW, related to reduced plant and soil activities, with the system being kept at this threshold or going back to higher CO2 levels, with scenarios dependent on volcanic outgassing and solar inputs. We will present astrobiological implications of this modeling. References: Schwartzman D (1999, 2002) Life, Temperature, and the Earth: The Self Organizing Biosphere. Columbia Univ. Press; Schwartzman, D. (2013) Keynote: The Geobiology of Weathering: The 13th Hypothesis. Goldschmidt Conference. (Schwartzman D. and Brantley S. (2013) Mineral. Mag. 77(5): 2170); Volk T (1998) Gaia's Body: Toward a Physiology of Earth. Copernicus.

  20. 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......-ray crystallographic analyses, chemical correlation, and CD spectral analyses. The effects of the individual stereoisomers at ionotropic and metabotropic (S)-Glu receptors (iGluRs and mGluRs) were characterized. Compounds with S-configuration at the alpha-carbon generally showed mGluR2 agonist activity of similar...... limited effect on pharmacology. Structure-activity relationships at iGluRs in the rat cortical wedge preparation showed a complex pattern, some compounds being NMDA receptor agonists [e.g., EC(50) =110 microM for (2S,5RS)-5-methyl-AA (6a,b)] and some compounds showing NMDA receptor antagonist effects [e...

  1. 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

  2. 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...

  3. Fine-scale niche structure of Neotropical forests reflects a legacy of the Great American Biotic Interchange.

    Science.gov (United States)

    Sedio, Brian E; Paul, John R; Taylor, Charlotte M; Dick, Christopher W

    2013-01-01

    The tendency of species to retain their ancestral niches may link processes that determine community assembly with biogeographic histories that span geological time scales. Biogeographic history is likely to have had a particularly strong impact on Neotropical forests because of the influence of the Great American Biotic Interchange, which followed emergence of a land connection between North and South America ~3 Ma. Here we examine the community structure, ancestral niches and ancestral distributions of the related, hyperdiverse woody plant genera Psychotria and Palicourea (Rubiaceae) in Panama. We find that 49% of the variation in hydraulic traits, a strong determinant of community structure, is explained by species' origins in climatically distinct biogeographic regions. Niche evolution models for a regional sample of 152 species indicate that ancestral climatic niches are associated with species' habitat distributions, and hence local community structure and composition, even millions of years after dispersal into new geographic regions.

  4. 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

  5. Kinetics of selenate sorption in soil as influenced by biotic and abiotic conditions: a stirred flow-through reactor study.

    Science.gov (United States)

    Garcia-Sanchez, L; Loffredo, N; Mounier, S; Martin-Garin, A; Coppin, F

    2014-12-01

    This study (i) quantified the kinetics of selenate sorption and (ii) measured the influence of biotic processes in soil selenate stabilisation. Stirred flow-through reactor experiments were conducted on samples of a silty clay soil (pH = 8, Eh = 240-300 mV) from Bure (France) in both non-sterile and sterile conditions. Parameters of the proposed two-site sorption model (EK), adapted from van Genuchten and Wagenet (1989), were estimated by nonlinear regression. Fast selenate sorption on type-1 sites was moderate, with an equilibrium constant of 25.5 and 39.1 L/kg for non-sterile and sterile conditions. Rate-limited sorption on type-2 sites increased with time, and was predominant for longer periods of time in non-sterile conditions. At equilibrium, it would represent over 96% of the sorbed inventory, with mean sorption times of 17 h and 191 h for non-sterile and sterile conditions. Our results showed for Bure soil that (i) selenate sorption in flowing and mildly-oxidising conditions was strongly kinetically controlled, especially in non-sterile conditions, (ii) selenate desorption was much slower than sorption, which suggests its pseudo-irreversible stabilisation, and (iii) microbial activity increased the contribution of rate-limited sorption on type-2 sites, for which it increased sorption rate by a factor 7 but also facilitated its reversibility. This work stresses the limits of the Kd approach to represent selenate sorption in flowing conditions and supports an alternative formulation like the EK model, but also points out that biotic conditions are significant sources of variability for sorption parameters.

  6. Biotic and abiotic oxidation and reduction of iron at circumneutral pH are inseparable processes under natural conditions

    NARCIS (Netherlands)

    Ionescu, Danny; Heim, Christine; Polerecky, L.; Thiel, Volker; de Beer, Dirk

    2015-01-01

    Oxidation and reduction of iron can occur through abiotic (chemical) and biotic (microbial) processes. Abiotic iron oxidation is a function of pH and O2 concentration. Biotic iron oxidation is carried out by a diverse group of bacteria, using O2 or NO3 as terminal electron acceptors. At circumneutra

  7. Biotic and Sedimentologic Signals Associated with Tempestite Deposition from Baffin Bay, Texas

    Science.gov (United States)

    Van Nieuwenhuise, D. S.

    2014-12-01

    In efforts to determine hurricane frequency prior to historical records, the often used model of counting presumed washover fans as coarse-grained hurricane deposits that interfinger with fine-grained, quiet, lagoon sediments may be oversimplified. The complexities of hurricane depositional events versus the usual dynamic sedimentological processes of barrier island complexes often makes it difficult to distinguish between expected and typical migrating coarse-grained facies from true hurricane deposits. To avoid some of this potential confusion and to better recognize the frequency of strong hurricane events, it is suggested that studies be focused further inland than the washover fans and that in addition to sedimentological indicators, they include biotic and chemical discriminators as well. These results are part of a broader study examining hurricane deposition along the Texas coast. The focus of this study is on slowly accumulating algal mats near Baffin Bay, Texas, that are punctuated by known hurricane deposits. This marginal lagoonal setting is more than 16 miles away from the Padre Island shorefront. Two cores were taken in 1974 that captured sediments from Hurricane Carla (1970) and Hurricane Beulah (1967). Algal mat depositional rates are on the order of 1.25 cm per year whereas the hurricane sediments are on the order of 45 cm per event. Sediments display flood and ebb surge stages for each event. Additional cores in other parts of the coast have similar sediment accumulation rates. In general, periods of relatively quiet deposition are dominated by Cyprideis ovata and Ammonia becarrii which can tolerate the conditions of these euryhaline and algal-floored ponds. In contrast, hurricane deposits show clear evidence of additional bay and shallow marine assemblages along with coarse-grained sediments, shell and shell fragments, and significant amounts of mud settling after the retreat of the storm surge.

  8. 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 str

  9. Comprehensive Analysis Suggests Overlapping Expression of Rice ONAC Transcription Factors in Abiotic and Biotic Stress Responses

    Directory of Open Access Journals (Sweden)

    Lijun Sun

    2015-02-01

    Full Text Available NAC (NAM/ATAF/CUC transcription factors comprise a large plant-specific gene family that contains more than 149 members in rice. Extensive studies have revealed that NAC transcription factors not only play important roles in plant growth and development, but also have functions in regulation of responses to biotic and abiotic stresses. However, biological functions for most of the members in the NAC family remain unknown. In this study, microarray data analyses revealed that a total of 63 ONAC genes exhibited overlapping expression patterns in rice under various abiotic (salt, drought, and cold and biotic (infection by fungal, bacterial, viral pathogens, and parasitic plants stresses. Thirty-eight ONAC genes exhibited overlapping expression in response to any two abiotic stresses, among which 16 of 30 selected ONAC genes were upregulated in response to exogenous ABA. Sixty-five ONAC genes showed overlapping expression patterns in response to any two biotic stresses. Results from the present study suggested that members of the ONAC genes with overlapping expression pattern may have pleiotropic biological functions in regulation of defense response against different abiotic and biotic stresses, which provide clues for further functional analysis of the ONAC genes in stress tolerance and pathogen resistance.

  10. Ecosystem services in grassland associated with biotic and abiotic soil parameters

    NARCIS (Netherlands)

    Eekeren, van N.J.M.; Boer, H.; 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 th

  11. 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 ...

  12. Subsequent biotic crises delayed marine recovery following the late Permian mass extinction event in northern Italy.

    Science.gov (United States)

    Foster, William J; Danise, Silvia; Price, Gregory D; Twitchett, Richard J

    2017-01-01

    The late Permian mass extinction event was the largest biotic crisis of the Phanerozoic and has the longest recovery interval of any extinction event. It has been hypothesised that subsequent carbon isotope perturbations during the Early Triassic are associated with biotic crises that impeded benthic recovery. We test this hypothesis by undertaking the highest-resolution study yet made of the rock and fossil records of the entire Werfen Formation, Italy. Here, we show that elevated extinction rates were recorded not only in the Dienerian, as previously recognised, but also around the Smithian/Spathian boundary. Functional richness increases across the Smithian/Spathian boundary associated with elevated origination rates in the lower Spathian. The taxonomic and functional composition of benthic faunas only recorded two significant changes: (1) reduced heterogeneity in the Dienerian, and (2) and a faunal turnover across the Smithian/Spathian boundary. The elevated extinctions and compositional shifts in the Dienerian and across the Smithian/Spathian boundary are associated with a negative and positive isotope excursion, respectively, which supports the hypothesis that subsequent biotic crises are associated with carbon isotope shifts. The Spathian fauna represents a more advanced ecological state, not recognised in the previous members of the Werfen Formation, with increased habitat differentiation, a shift in the dominant modes of life, appearance of stenohaline taxa and the occupation of the erect and infaunal tiers. In addition to subsequent biotic crises delaying the recovery, therefore, persistent environmental stress limited the ecological complexity of benthic recovery prior to the Spathian.

  13. Development of a wireless computer vision instrument to detect biotic stress in wheat

    Science.gov (United States)

    Knowledge of soil water deficits, crop water stress, and biotic stress from disease or insect pressure is important for optimal irrigation scheduling and water management. While spectral reflectance and thermometry provide a means to quantify crop stress remotely, measurements can be cumbersome, exp...

  14. Influence of environmental factors on biotic responses to nutrient enrichment in agricultural streams

    Science.gov (United States)

    Maret, Terry R.; Konrad, Christopher P.; Tranmer, Andrew W.

    2010-01-01

    The influence of environmental factors on biotic responses to nutrients was examined in three diverse agricultural regions of the United States. Seventy wadeable sites were selected along an agricultural land use gradient while minimizing natural variation within each region. Nutrients, habitat, algae, macroinvertebrates, and macrophyte cover were sampled during a single summer low-flow period in 2006 or 2007. Continuous stream stage and water temperature were collected at each site for 30 days prior to sampling. Wide ranges of concentrations were found for total nitrogen (TN) (0.07-9.61 mg/l) and total phosphorus (TP) (R2) for nutrients and biotic measures across all sites ranged from 0.08 to 0.32 and generally were not higher within each region. The biotic measures (RCHL, SCHL, and AQM) were combined in an index to evaluate eutrophic status across sites that could have different biotic responses to nutrient enrichment. Stepwise multiple regression identified TN, percent canopy, median riffle depth, and daily percent change in stage as significant factors for the eutrophic index (R2 = 0.50, p plant growth indicators should be used when evaluating eutrophication, especially when streams contain an abundance of macrophytes.

  15. 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.

  16. Characterization of the summer pack ice biotic community of Canada Basin

    Institute of Scientific and Technical Information of China (English)

    HE Ji anfeng; CAI Minghong; JIANG Xiaodong; CHEN Bo; YU Yong

    2005-01-01

    Summer pack ice biotic community of the Canada Basin was characterized during the Second Chinese National Arctic Research Expedition (CHINARE-2003, 20 August-5 September 2003). Bacteria, ice algae (diatoms and autotrophic flagellates) and protozoa (mainly heterotrophic flagellates) were observed throughout the whole ice column. The vertical distribufon of biotic taxa varied among sites.The integrated biomass ranged from 48.4 and 58.1 mg/m2, with an average of 55.2 mg/m2. Bacteria were the dominant of the assem-blage in pack ice, accounted for 84.1% of the integrated, and ice algae, which usually dominate the ice biotic community, constituted only 3.5% of the total. Considering the quick environmental changes of the Arctic Ocean in recent years, we suggested that quick melting of pack ice in summer was suggested, which caused such change of pack ice biotic community. The low salinity throughout the whole ice column and the continuous melting of the pack ice cumbered the formation of ice algae bloom in summer, finally resulting in the dominance of microbial food web with bacteria and heterotrophic flagellates as the most obvious characteristics. Considering the high ratio of pack ice primary production to the total found in previous studies, the quick change of pack ice community structure in summer would deeply influence the marine ecosystem of the high Arctic Ocean.

  17. Glycomimetic ligands for the human asialoglycoprotein receptor.

    Science.gov (United States)

    Mamidyala, Sreeman K; Dutta, Sanjay; Chrunyk, Boris A; Préville, Cathy; Wang, Hong; Withka, Jane M; McColl, Alexander; Subashi, Timothy A; Hawrylik, Steven J; Griffor, Matthew C; Kim, Sung; Pfefferkorn, Jeffrey A; Price, David A; Menhaji-Klotz, Elnaz; Mascitti, Vincent; Finn, M G

    2012-02-01

    The asialoglycoprotein receptor (ASGPR) is a high-capacity galactose-binding receptor expressed on hepatocytes that binds its native substrates with low affinity. More potent ligands are of interest for hepatic delivery of therapeutic agents. We report several classes of galactosyl analogues with varied substitution at the anomeric, C2-, C5-, and C6-positions. Significant increases in binding affinity were noted for several trifluoromethylacetamide derivatives without covalent attachment to the protein. A variety of new ligands were obtained with affinity for ASGPR as good as or better than that of the parent N-acetylgalactosamine, showing that modification on either side of the key C3,C4-diol moiety is well tolerated, consistent with previous models of a shallow binding pocket. The galactosyl pyranose motif therefore offers many opportunities for the attachment of other functional units or payloads while retaining low-micromolar or better affinity for the ASGPR.

  18. Design, synthesis and biological evaluation of bivalent ligands against A1-D1 receptor heteromers

    Institute of Scientific and Technical Information of China (English)

    Jian SHEN; Lei ZHANG; Wan-ling SONG; Tao MENG; Xin WANG; Lin CHEN; Lin-yin FENG

    2013-01-01

    Aim:To design and synthesize bivalent ligands for adenosine A1-dopamine D1 receptor heteromers (A1-D1R),and evaluate their pharmacological activities.Methods:Bivalent ligands and their corresponding A1R monovalent ligands were designed and synthesized.The affinities of the bivalent ligands for A1R and D1R in rat brain membrane preparation were examined using radiolabeled binding assays.To demonstrate the formation of A1-D1R,fluorescence resonance energy transfer (FRET) was conducted in HEK293 cells transfected with D1-CFP and A1-YFP.Molecular modeling was used to analyze the possible mode of protein-protein and protein-ligand interactions.Results:Two bivalent ligands for A1R and D1R (20a,20b),as well as the corresponding A1R monovalent ligands (21a,21b) were synthesized.In radiolabeled binding assays,the bivalent ligands showed affinities for A1R 10-100 times higher than those of the corresponding monovalent ligands.In FRET experiments,the bivalent ligands significantly increased the heterodimerization of A1R and D1R compared with the corresponding monovalent ligands.A heterodimer model with the interface of helixes 3,4,5 of A1R and helixes 1,6,7 from D1R was established with molecular modeling.The distance between the two ligand binding sites in the heterodimer model was approximately 48.4 (A),which was shorter than the length of the bivalent ligands.Conclusion:This study demonstrates the existence of A1-D1R in situ and a simultaneous interaction of bivalent ligands with both the receptors.

  19. Screening of candidate G-quadruplex ligands for the human c-KIT promotorial region and their effects in multiple in-vitro models

    Science.gov (United States)

    Zorzan, Eleonora; Ros, Silvia Da; Musetti, Caterina; Shahidian, Lara Zorro; Ramos Coelho, Nuno Filipe; Bonsembiante, Federico; Létard, Sébastien; Gelain, Maria Elena; Palumbo, Manlio; Dubreuil, Patrice; Giantin, Mery; Sissi, Claudia; Dacasto, Mauro

    2016-01-01

    Stabilization of G-quadruplex (G4) structures in promoters is a novel promising strategy to regulate gene expression at transcriptional and translational levels. c-KIT proto-oncogene encodes for a tyrosine kinase receptor. It is involved in several physiological processes, but it is also dysregulated in many diseases, including cancer. Two G-rich sequences able to fold into G4, have been identified in c-KIT proximal promoter, thus representing suitable targets for anticancer intervention. Herein, we screened an “in house” library of compounds for the recognition of these G4 elements and we identified three promising ligands. Their G4-binding properties were analyzed and related to their antiproliferative, transcriptional and post-transcriptional effects in MCF7 and HGC27 cell lines. Besides c-KIT, the transcriptional analysis covered a panel of oncogenes known to possess G4 in their promoters. From these studies, an anthraquinone derivative (AQ1) was found to efficiently downregulate c-KIT mRNA and protein in both cell lines. The targeted activity of AQ1 was confirmed using c-KIT–dependent cell lines that present either c-KIT mutations or promoter engineered (i.e., α155, HMC1.2 and ROSA cells). Present results indicate AQ1 as a promising compound for the target therapy of c-KIT-dependent tumors, worth of further and in depth molecular investigations. PMID:26942875

  20. Nutrient Concentrations and Their Relations to the Biotic Integrity of Nonwadeable Rivers in Wisconsin

    Science.gov (United States)

    Robertson, Dale M.; Weigel, Brian M.; Graczyk, David J.

    2008-01-01

    Excessive nutrient [phosphorus (P) and nitrogen (N)] input from point and nonpoint sources is frequently associated with degraded water quality in streams and rivers. Point-source discharges of nutrients are fairly constant and are controlled by the U.S. Environmental Protection Agency's (USEPA) National Pollutant Discharge Elimination System. To reduce inputs from nonpoint sources, agricultural performance standards and regulations for croplands and livestock operations are being proposed by various States. In addition, the USEPA is establishing regionally based nutrient criteria that can be refined by each State to determine whether actions are needed to improve water quality. More confidence in the environmental benefits of the proposed performance standards and nutrient criteria would be possible with improved understanding of the biotic responses to a range of nutrient concentrations in different environmental settings. To achieve this general goal, the U.S. Geological Survey and the Wisconsin Department of Natural Resources collected data from 282 streams and rivers throughout Wisconsin during 2001 through 2003 to: (1) describe how nutrient concentrations and biotic-community structure differ throughout the State, (2) determine which environmental characteristics are most strongly related to the distribution of nutrient concentrations and biotic-community structure, (3) determine reference conditions for water quality and biotic indices for streams and rivers in the State, (4) determine how the biotic communities in streams and rivers in different areas of the State respond to differences in nutrient concentrations, (5) determine the best regionalization scheme to describe the patterns in reference conditions and the corresponding responses in water quality and the biotic communities (primarily for smaller streams), and (6) develop algorithms to estimate nutrient concentrations in streams and rivers from a combination of biotic indices. The ultimate goal of

  1. Coordinate unsaturation with fluorinated ligands

    Energy Technology Data Exchange (ETDEWEB)

    Rack, J.L.; Hurlburt, P.K.; Anderson, O.P.; Strauss, S.H. [Colorado State Univ., Ft. Collins, CO (United States)

    1993-12-31

    The preparation and characterization of Zn(OTeF{sub 5}){sub 2} has resulted in a model compound with which to explore the concept of coordinative unsaturation. The coordination of solvents of varying donicity and dielectric constant to the Zn(II) ions in Zn(OTeF{sub 5}){sub 2} was studied by vapor phase monometry, NMR and IR spectroscopy, conductimetry, and X-Ray crystallography. The structures of [Zn(C{sub 6}H{sub 5}NO{sub 2}){sub 2}(OTeF{sub 5})2]2 and Zn(C{sub 6}H{sub 5}NO{sub 2}){sub 3}(OTEF{sub 5}){sub 2} demonstrate the electronic flexibility of some weakly coordinating solvents in that nitrobenzene can function as either an {eta}{sup 1}O or {eta}{sup 2}O,O`-ligand. The dependence of the number of bound solvent molecules and the degree of OTeF{sub 5}{minus} dissociation on solvent donor number and dielectric constant will be presented.

  2. The importance of biotic entrainment for base flow fluvial sediment transport

    Science.gov (United States)

    Rice, Stephen P.; Johnson, Matthew F.; Mathers, Kate; Reeds, Jake; Extence, Chris

    2016-05-01

    Sediment transport is regarded as an abiotic process driven by geophysical energy, but zoogeomorphological activity indicates that biological energy can also fuel sediment movements. It is therefore prudent to measure the contribution that biota make to sediment transport, but comparisons of abiotic and biotic sediment fluxes are rare. For a stream in the UK, the contribution of crayfish bioturbation to suspended sediment flux was compared with the amount of sediment moved by hydraulic forcing. During base flow periods, biotic fluxes can be isolated because nocturnal crayfish activity drives diel turbidity cycles, such that nighttime increases above daytime lows are attributable to sediment suspension by crayfish. On average, crayfish bioturbation contributed at least 32% (474 kg) to monthly base flow suspended sediment loads; this biotic surcharge added between 5.1 and 16.1 t (0.21 to 0.66 t km-2 yr-1) to the annual sediment yield. As anticipated, most sediment was moved by hydraulic forcing during floods and the biotic contribution from baseflow periods represented between 0.46 and 1.46% of the annual load. Crayfish activity is nonetheless an important impact during baseflow periods and the measured annual contribution may be a conservative estimate because of unusually prolonged flooding during the measurement period. In addition to direct sediment entrainment by bioturbation, crayfish burrowing supplies sediment to the channel for mobilization during floods so that the total biotic effect of crayfish is potentially greater than documented in this study. These results suggest that in rivers, during base flow periods, bioturbation can entrain significant quantities of fine sediment into suspension with implications for the aquatic ecosystem and base flow sediment fluxes. Energy from life rather than from elevation can make significant contributions to sediment fluxes.

  3. 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

  4. Biotic interaction strength and the intensity of selection.

    Science.gov (United States)

    Benkman, Craig W

    2013-08-01

    Although the ecological and evolutionary impacts of species interactions have been the foci of much research, the relationship between the strength of species interactions and the intensity of selection has been investigated only rarely. I develop a simple model demonstrating how the opportunity for selection varies with interaction strength, and then use the relationship between the maximum value of the selection differential and the opportunity for selection (Arnold & Wade 1984) to evaluate how selection differentials vary in relation to species interaction strength. This model predicts an initial deceleration and then an accelerating increase in the intensity of selection with increasing strength of antagonistic interactions and with decreasing strength of mutualistic interactions. Empirical data from several studies provide support for this model. These results further support an evolutionary mechanism for some striking patterns of evolutionary diversification including the latitudinal species gradient, and should be relevant to studies of eco-evolutionary dynamics.

  5. Climatic - biotic continuum - a few examples from the Pennsylvanian - Early Permian

    Science.gov (United States)

    Kossovaya, O.

    2012-04-01

    The subdivision of the Pennsylvanian Epoch based on the great difference in the biota composition and evolution. Extensive grows of the continental ice sheets near the Mississippian-Pennsylvanian (mid-Carboniferous) boundary expanded a large area comparative with Pleistocene (106 km2) (Crowley and Baum, 1991). One of the possible models is the restructuring of the oceanic circulation patterns (Saltzman, 2003). The Mid-Carboniferous boundary in the Urals demonstrates regional inconformity trigged by strong fall of the basin depth. Possibly following circulation was the reason of the positive carbon and isotope shift documented in the one of the Askyn key section of the South Urals. Renovated biota appeared far above the unconformity (Brand, Bruckschen, 2002, Kossovaya, 2009, 2010). The next level of biota replacement was found near by Mid-Pennsylvanian boundary. The isotope and microfacies fluctuations are traced in the Late Myachkovian -Kasimovian transitional in the "Kasimov quarry. The top of the Domodedovo Fm. is marked by double paleosoil profile emphasized by Microcodium crust (Leontiev, Kossovaya, 2011) and is characterized by δ 13C negative shift from +2,2 ‰ (sample Ks-23) up to - 4,4‰ (sample Ks -24) and possibly is reinforce by the presence of Microcodium. The extinction of the most of colonial rugosa (Petalaxidae) at this level in the Moscow Basin together with strong restriction of diversity of the other warm -water organisms is considered as biotic event which abiotic affinities are still not clear. The basin level fall is documented by a few erosion surfaces both in the Domodedovo and Peski Fms (Uppermost Myachkovian). Diachronic extinction embraced Perski interval. Data on stable isotope allows to propose the El-Nino scenario fro the first phase of the fauna replacement. Following diminishing of the carbon is indirectly relevant by change of carbonate to clay sedimentation at the beginning of the Voskresensk Fm. It is confirmed by low value of

  6. Role of ligand-dependent GR phosphorylation and half-life in determination of ligand-specific transcriptional activity.

    Science.gov (United States)

    Avenant, Chanel; Ronacher, Katharina; Stubsrud, Elisabeth; Louw, Ann; Hapgood, Janet P

    2010-10-07

    A central question in glucocorticoid mechanism of action via the glucocorticoid receptor (GR) is what determines ligand-selective transcriptional responses. Using a panel of 12 GR ligands, we show that the extent of GR phosphorylation at S226 and S211, GR half-life and transcriptional response, occur in a ligand-selective manner. While GR phosphorylation at S226 was shown to inhibit maximal transcription efficacy, phosphorylation at S211 is required for maximal transactivation, but not for transrepression efficacy. Both ligand-selective GR phosphorylation and half-life correlated with efficacy for transactivation and transrepression. For both expressed and endogenous GR, in two different cell lines, agonists resulted in the greatest extent of phosphorylation and the greatest extent of GR downregulation, suggesting a link between these functions. However, using phosphorylation-deficient GR mutants we established that phosphorylation of the GR at S226 or S211 does not determine the rank order of ligand-selective GR transactivation. These results are consistent with a model whereby ligand-selective GR phosphorylation and half-life are a consequence of upstream events, such as ligand-specific GR conformations, which are maintained in the phosphorylation mutants.

  7. 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.

  8. 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.

  9. How severe is the modern biotic crisis?——A comparison of global change and biotic crisis between Permian-Triassic transition and modern times

    Institute of Scientific and Technical Information of China (English)

    Hongfu YIN; Weihong HE; Shucheng XIE

    2011-01-01

    A comparison of the modern condition with the Permian-Triassic Boundary (PTB) times was made to estimate how severe the modern biotic crisis is. About the global changes, the two periods are correlative in carbon dioxide concentration and carbon isotope negative excursion, UV strengthening, temperature increase, ocean acidification, and weathering enhancement. The following tendencies of biotic crises are also correlative: acceleration of extinction rates accompanied by parabolic curve of extinction with a turning interval representing the critical crisis; decline of the three main ecosystems: reefs, tropical rain forests and marine phytoplankton. It is also interesting to note that certain leading organism in both periods undergo accelerated evolution during the crisis. The comparison shows that the modem crisis is about at the tuming point from decline to decimation. The extinction curve is now parabolic, and the extinction rate has been accelerated, but the decimation is not yet in real. This is also justified by the modem situation of the three main ecosystems. Modem biotic decline may worsen into decimation and mass extinction but may also get better and recover to ordinary evolution. Since human activities are the main cause of the deterioration of environments and organisms, mankind should be responsible and able to strive for the recovery of the crisis. For the future of mankind, Homo sapiens may become extinct, I.e.,disappear without leaving descendants, or evolve into a new and more advanced species, I.e., disappear but leave descendants. For a better future, mankind should be conscious of the facing danger and act as a whole to save biodiversity and harmonize with the environments.

  10. Associations between ectomycorrhizal fungi and bacterial needle endophytes in Pinus radiata: implications for biotic selection of microbial communities

    Directory of Open Access Journals (Sweden)

    Megan Arlene Rúa

    2016-03-01

    Full Text Available Studies of the ecological and evolutionary relationships between plants and their associated microbes have long been focused on single microbes, or single microbial guilds, but in reality, plants associate with a diverse array of microbes from a varied set of guilds. As such, multitrophic interactions among plant-associated microbes from multiple guilds represent an area of developing research, and can reveal how complex microbial communities are structured around plants. Interactions between coniferous plants and their associated microbes provide a good model system for such studies, as conifers host a suite of microorganisms including mutualistic ectomycorrhizal (ECM fungi and foliar bacterial endophytes. To investigate the potential role ECM fungi play in structuring foliar bacterial endophyte communities, we sampled three isolated, native populations of Monterey pine (Pinus radiata, and used constrained analysis of principal coordinates to relate the community matrices of the ECM fungi and bacterial endophytes. Our results suggest that ECM fungi may be important factors for explaining variation in bacterial endophyte communities but this effect is influenced by population and environmental characteristics, emphasizing the potential importance of other factors — biotic or abiotic — in determining the composition of bacterial communities. We also classified ECM fungi into categories based on known fungal traits associated with substrate exploration and nutrient mobilization strategies since variation in these traits allows the fungi to acquire nutrients across a wide range of abiotic conditions and may influence the outcome of multi-species interactions. Across populations and environmental factors, none of the traits associated with fungal foraging strategy types significantly structured bacterial assemblages, suggesting these ECM fungal traits are not important for understanding endophyte-ECM interactions. Overall, our results suggest

  11. Serum FLT-3 ligand in a busulphan-induced model of chronic bone marrow hypoplasia in the female CD-1 mouse.

    Science.gov (United States)

    Molyneux, Gemma; Gibson, Frances M; Whayman, Matthew; Turton, John A

    2008-04-01

    The concentration of the cytokine fms-like tyrosine kinase-3 ligand (FL) is elevated in the plasma of patients treated with chemotherapy or radiotherapy for malignant conditions. In addition, plasma FL is increased in patients with bone marrow failure resulting from stem-cell defects (e.g. aplastic anaemia). Our goal in the present study was to measure the concentration of serum FL in mice treated with the chemotherapeutic agent busulphan (BU) to induce bone marrow depression and relate changes in FL to effects on haemopoiesis. Female CD-1 mice were treated with BU (9.0 mg/kg) or vehicle by intraperitoneal injection on 10 occasions over 21 days. Animals were autopsied on days 1, 23, 72, 119 and 177 postdosing. A full blood count was performed, and serum prepared for FL analysis. Femoral marrow cell suspensions were prepared to assess the total femoral nucleated cell count (FNCC) and the number of committed haemopoietic progenitor cells (CFU-C). On days 1 and 23 postdosing, significant decreases were evident in many peripheral blood parameters; the FNCC and CFU-C were also reduced in BU-treated mice, in conjunction with increases in serum FL levels. On days 72, 119 and 177 postdosing, several peripheral blood and bone marrow parameters remained reduced and the concentration of serum FL continued to be significantly increased. Linear regression analysis demonstrated significant correlations between the concentration of serum FL in BU-treated mice and peripheral blood and bone marrow parameters; this suggests the possible use of serum FL as a potential biomarker for drug-induced bone marrow injury.

  12. Fluorescent ligand for human progesterone receptor imaging in live cells.

    Science.gov (United States)

    Weinstain, Roy; Kanter, Joan; Friedman, Beth; Ellies, Lesley G; Baker, Michael E; Tsien, Roger Y

    2013-05-15

    We employed molecular modeling to design and then synthesize fluorescent ligands for the human progesterone receptor. Boron dipyrromethene (BODIPY) or tetramethylrhodamine were conjugated to the progesterone receptor antagonist RU486 (Mifepristone) through an extended hydrophilic linker. The fluorescent ligands demonstrated comparable bioactivity to the parent antagonist in live cells and triggered nuclear translocation of the receptor in a specific manner. The BODIPY labeled ligand was applied to investigate the dependency of progesterone receptor nuclear translocation on partner proteins and to show that functional heat shock protein 90 but not immunophilin FKBP52 activity is essential. A tissue distribution study indicated that the fluorescent ligand preferentially accumulates in tissues that express high levels of the receptor in vivo. The design and properties of the BODIPY-labeled RU486 make it a potential candidate for in vivo imaging of PR by positron emission tomography through incorporation of (18)F into the BODIPY core.

  13. Nutrient concentrations and their relations to the biotic integrity of wadeable streams in Wisconsin

    Science.gov (United States)

    Robertson, Dale M.; Graczyk, David J.; Garrison, Paul J.; Wang, Lizhu; LaLiberte, Gina; Bannerman, Roger

    2006-01-01

    Excessive nutrient (phosphorus and nitrogen) loss from watersheds is frequently associated with degraded water quality in streams. To reduce this loss, agricultural performance standards and regulations for croplands and livestock operations are being proposed by various States. In addition, the U.S. Environmental Protection Agency is establishing regionally based nutrient criteria that can be refined by each State to determine whether actions are needed to improve a stream's water quality. More confidence in the environmental benefits of the proposed performance standards and nutrient criteria will be possible with a better understanding of the biotic responses to a range of nutrient concentrations in different environmental settings. The U.S. Geological Survey and the Wisconsin Department of Natural Resources collected data from 240 wadeable streams throughout Wisconsin to: 1) describe how nutrient concentrations and biotic-community structure vary throughout the State; 2) determine which environmental characteristics are most strongly related to the distribution of nutrient concentrations; 3) determine reference water-quality and biotic conditions for different areas of the State; 4) determine how the biotic community of streams in different areas of the State respond to changes in nutrient concentrations; 5) determine the best regionalization scheme to describe the patterns in reference conditions and the responses in water quality and the biotic community; and 6) develop new indices to estimate nutrient concentrations in streams from a combination of biotic indices. The ultimate goal of this study is to provide the information needed to guide the development of regionally based nutrient criteria for Wisconsin streams. For total nitrogen (N) and suspended chlorophyll (SCHL) concentrations and water clarity, regional variability in reference conditions and in the responses in water quality to changes in land use are best described by subdividing wadeable streams

  14. Ligand binding by the tandem glycine riboswitch depends on aptamer dimerization but not double ligand occupancy.

    Science.gov (United States)

    Ruff, Karen M; Strobel, Scott A

    2014-11-01

    The glycine riboswitch predominantly exists as a tandem structure, with two adjacent, homologous ligand-binding domains (aptamers), followed by a single expression platform. The recent identification of a leader helix, the inclusion of which eliminates cooperativity between the aptamers, has reopened the debate over the purpose of the tandem structure of the glycine riboswitch. An equilibrium dialysis-based assay was combined with binding-site mutations to monitor glycine binding in each ligand-binding site independently to understand the role of each aptamer in glycine binding and riboswitch tertiary interactions. A series of mutations disrupting the dimer interface was used to probe how dimerization impacts ligand binding by the tandem glycine riboswitch. While the wild-type tandem riboswitch binds two glycine equivalents, one for each aptamer, both individual aptamers are capable of binding glycine when the other aptamer is unoccupied. Intriguingly, glycine binding by aptamer-1 is more sensitive to dimerization than glycine binding by aptamer-2 in the context of the tandem riboswitch. However, monomeric aptamer-2 shows dramatically weakened glycine-binding affinity. In addition, dimerization of the two aptamers in trans is dependent on glycine binding in at least one aptamer. We propose a revised model for tandem riboswitch function that is consistent with these results, wherein ligand binding in aptamer-1 is linked to aptamer dimerization and stabilizes the P1 stem of aptamer-2, which controls the expression platform.

  15. SuperLigands – a database of ligand structures derived from the Protein Data Bank

    Directory of Open Access Journals (Sweden)

    Preissner Robert

    2005-05-01

    Full Text Available Abstract Background Currently, the PDB contains approximately 29,000 protein structures comprising over 70,000 experimentally determined three-dimensional structures of over 5,000 different low molecular weight compounds. Information about these PDB ligands can be very helpful in the field of molecular modelling and prediction, particularly for the prediction of protein binding sites and function. Description Here we present an Internet accessible database delivering PDB ligands in the MDL Mol file format which, in contrast to the PDB format, includes information about bond types. Structural similarity of the compounds can be detected by calculation of Tanimoto coefficients and by three-dimensional superposition. Topological similarity of PDB ligands to known drugs can be assessed via Tanimoto coefficients. Conclusion SuperLigands supplements the set of existing resources of information about small molecules bound to PDB structures. Allowing for three-dimensional comparison of the compounds as a novel feature, this database represents a valuable means of analysis and prediction in the field of biological and medical research.

  16. SuperLigands – a database of ligand structures derived from the Protein Data Bank

    Science.gov (United States)

    Michalsky, Elke; Dunkel, Mathias; Goede, Andrean; Preissner, Robert

    2005-01-01

    Background Currently, the PDB contains approximately 29,000 protein structures comprising over 70,000 experimentally determined three-dimensional structures of over 5,000 different low molecular weight compounds. Information about these PDB ligands can be very helpful in the field of molecular modelling and prediction, particularly for the prediction of protein binding sites and function. Description Here we present an Internet accessible database delivering PDB ligands in the MDL Mol file format which, in contrast to the PDB format, includes information about bond types. Structural similarity of the compounds can be detected by calculation of Tanimoto coefficients and by three-dimensional superposition. Topological similarity of PDB ligands to known drugs can be assessed via Tanimoto coefficients. Conclusion SuperLigands supplements the set of existing resources of information about small molecules bound to PDB structures. Allowing for three-dimensional comparison of the compounds as a novel feature, this database represents a valuable means of analysis and prediction in the field of biological and medical research. PMID:15943884

  17. 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....

  18. 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.

  19. Visualization of Metal-to-Ligand and Ligand-to-Ligand Charge Transfer in Metal-Ligand Complexes

    Institute of Scientific and Technical Information of China (English)

    Yong Ding; Jian-xiu Guo; Xiang-si Wang; Sha-sha Liu; Feng-cai Ma

    2009-01-01

    Three methods including the atomic resolved density of state, charge difference density, and the transition density matrix are used to visualize metal to ligand charge transfer (MLCT) in ruthenium(Ⅱ) ammine complex. The atomic resolved density of state shows that there is density of Ru on the HOMOs. All the density is localized on the ammine, which reveals that the excited electrons in the Ru complex are delocalized over the ammine ligand. The charge difference density shows that all the holes are localized on the Ru and the electrons on the ammine. The localization explains the MLCT on excitation. The transition density matrix shows that there is electron-hole coherence between Ru and ammine. These methods are also used to examine the MLCT in Os(bpy)(p0p)Cl ("Osp0p"; bpy=2,2'-bipyridyl; p0p=4,4'-bipyridyl) and the ligand-to-ligand charge transfer (LLCT) in Alq3. The calculated results show that these methods are powerful to examine MLCT and LLCT in the metal-ligand system.

  20. 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

  1. 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

  2. Biotic and abiotic studies on the biological fate, transport and ecotoxicity of toxic and hazardous waste in the Mississippi River basin

    Energy Technology Data Exchange (ETDEWEB)

    Abdelghani, A.; Pramar, Y.; Mandal, T.

    1996-05-02

    This project assesses the levels of xenobiotics in Devils Swamp and studies their biological fate, transport, ecotoxicity, and potential toxicity to man. This article reports on the following studies: assessment of the acute toxicity of individual xenobiotics and toxicity of organic compounds hexachlorobutadience (HCB) and hexachlorobenzene (HCBD) on juvenile crayfish; determination of the biotic influence of temperature, salinity, pH, oxidation-reduction potential, and sediment composition on the migration of xenobiotics; development of a pharmacokinetics model for xenobiotic absorption and storage, distribution and excretion by fish and crayfish.

  3. Development of a new toxic-unit model for the bioassessment of metals in streams

    Science.gov (United States)

    Schmidt, T.S.; Clements, W.H.; Mitchell, K.A.; Church, S.E.; Wanty, R.B.; Fey, D.L.; Verplanck, P.L.; San, Juan C.A.

    2010-01-01

    Two toxic-unit models that estimate the toxicity of trace-metal mixtures to benthic communities were compared. The chronic criterion accumulation ratio (CCAR), a modification of biotic ligand model (BLM) outputs for use as a toxic-unit model, accounts for the modifying and competitive influences of major cations (Ca2+, Mg2+, Na+, K+, H+), anions (HCO3−, CO32−,SO42−, Cl−, S2−) and dissolved organic carbon (DOC) in determining the free metal ion available for accumulation on the biotic ligand. The cumulative criterion unit (CCU) model, an empirical statistical model of trace-metal toxicity, considers only the ameliorative properties of Ca2+ and Mg2+ (hardness) in determining the toxicity of total dissolved trace metals. Differences in the contribution of a metal (e.g., Cu, Cd, Zn) to toxic units as determined by CCAR or CCU were observed and attributed to how each model incorporates the influences of DOC, pH, and alkalinity. Akaike information criteria demonstrate that CCAR is an improved predictor of benthic macroinvertebrate community metrics as compared with CCU. Piecewise models depict great declines (thresholds) in benthic macroinvertebrate communities at CCAR of 1 or more, while negative changes in benthic communities were detected at a CCAR of less than 1. We observed a 7% reduction in total taxa richness and a 43% decrease in Heptageniid abundance between background (CCAR = 0.1) and the threshold of chronic toxicity on the basis of continuous chronic criteria (CCAR = 1). In this first application of the BLM as a toxic-unit model, we found it superior to CCU.

  4. Why mercury prefers soft ligands

    Energy Technology Data Exchange (ETDEWEB)

    Riccardi, Demian M [ORNL; Guo, Hao-Bo [ORNL; Gu, Baohua [ORNL; Parks, Jerry M [ORNL; Summers, Anne [University of Georgia, Athens, GA; Miller, S [University of California, San Francisco; Liang, Liyuan [ORNL; Smith, Jeremy C [ORNL

    2013-01-01

    Mercury (Hg) is a major global pollutant arising from both natural and anthropogenic sources. Defining the factors that determine the relative affinities of different ligands for the mercuric ion, Hg2+, is critical to understanding its speciation, transformation, and bioaccumulation in the environment. Here, we use quantum chemistry to dissect the relative binding free energies for a series of inorganic anion complexes of Hg2+. Comparison of Hg2+ ligand interactions in the gaseous and aqueous phases shows that differences in interactions with a few, local water molecules led to a clear periodic trend within the chalcogenide and halide groups and resulted in the well-known experimentally observed preference of Hg2+ for soft ligands such as thiols. Our approach establishes a basis for understanding Hg speciation in the biosphere.

  5. Molecular Recognition and Ligand Association

    Science.gov (United States)

    Baron, Riccardo; McCammon, J. Andrew

    2013-04-01

    We review recent developments in our understanding of molecular recognition and ligand association, focusing on two major viewpoints: (a) studies that highlight new physical insight into the molecular recognition process and the driving forces determining thermodynamic signatures of binding and (b) recent methodological advances in applications to protein-ligand binding. In particular, we highlight the challenges posed by compensating enthalpic and entropic terms, competing solute and solvent contributions, and the relevance of complex configurational ensembles comprising multiple protein, ligand, and solvent intermediate states. As more complete physics is taken into account, computational approaches increase their ability to complement experimental measurements, by providing a microscopic, dynamic view of ensemble-averaged experimental observables. Physics-based approaches are increasingly expanding their power in pharmacology applications.

  6. Synthesis, biological evaluation, and three-dimensional in silico pharmacophore model for sigma(1) receptor ligands based on a series of substituted benzo[d]oxazol-2(3H)-one derivatives.

    Science.gov (United States)

    Zampieri, Daniele; Mamolo, Maria Grazia; Laurini, Erik; Florio, Chiara; Zanette, Caterina; Fermeglia, Maurizio; Posocco, Paola; Paneni, Maria Silvia; Pricl, Sabrina; Vio, Luciano

    2009-09-10

    Novel benzo[d]oxazol-2(3H)-one derivatives were designed and synthesized, and their affinities against sigma receptors were evaluated. On the basis of 31 compounds, a three-dimensional pharmacophore model for the sigma(1) receptor binding site was developed using the Catalyst 4.9 software package. The best 3D pharmacophore hypothesis, consisting of one positive ionizable, one hydrogen bond acceptor, two hydrophobic aromatic, and one hydrophobic features provided a 3D-QSAR model with a correlation coefficient of 0.89. The best hypothesis was also validated by three independent methods, i.e., the Fisher randomization test included in the CatScramble functionality of Catalyst, the leave-one-out test, and activity prediction of an additional test set. The achieved results will allow researchers to use this 3D pharmacophore model for the design and synthesis of a second generation of high affinity sigma(1) ligands, as well as to discover other lead compounds for this class of receptors.

  7. Application of INEPT 109Ag and 15N NMR spectroscopy for the study of metal-ligand interaction of silver analogues of Copper(I) model compounds

    NARCIS (Netherlands)

    Koten, G. van; Stein, G.C. van; Brevard, C.

    1983-01-01

    Because of the presence of copper (in its reduced state) at active sites in protein it has become very important to study copper(I) model complexes by spectroscopic techniques.We now report that if copper(I) in model complexes can be substituted by silver(I) with retention of the structural features

  8. Daily variation of zooplankton abundance and evenness in the Rosana reservoir, Brazil: biotic and abiotic inferences

    Directory of Open Access Journals (Sweden)

    Érica M. Takahashi

    2014-03-01

    Full Text Available The zooplankton community presents stochastic temporal fluctuation and heterogeneous spatial variation determined by the relationships among the organisms and environmental conditions. We predicted that the temporal and spatial zooplankton distribution is heterogeneous and discrete, respectively, and that the daily variation of most abundant species is related to environmental conditions, specifically the availability of resources. Zooplankton samples were collected daily at three sampling stations in a lateral arm of the Rosana Reservoir (SP/PR. The zooplankton did not present significant differences in abundance and evenness among sampling stations, but the temporal variation of these attributes was significant. Abiotic variables and algal resource availability have significantly explained the daily variation of the most abundant species (p<0.001, however, the species distribution makes inferences on biotic relationships between them. Thus, not only the food resource availability is influential on the abundance of principal zooplankton species, but rather a set of factors (abiotic variables and biotic relationships.

  9. Mercury anomalies and the timing of biotic recovery following the end-Triassic mass extinction.

    Science.gov (United States)

    Thibodeau, Alyson M; Ritterbush, Kathleen; Yager, Joyce A; West, A Joshua; Ibarra, Yadira; Bottjer, David J; Berelson, William M; Bergquist, Bridget A; Corsetti, Frank A

    2016-04-06

    The end-Triassic mass extinction overlapped with the eruption of the Central Atlantic Magmatic Province (CAMP), and release of CO2 and other volcanic volatiles has been implicated in the extinction. However, the timing of marine biotic recovery versus CAMP eruptions remains uncertain. Here we use Hg concentrations and isotopes as indicators of CAMP volcanism in continental shelf sediments, the primary archive of faunal data. In Triassic-Jurassic strata, Muller Canyon, Nevada, Hg levels rise in the extinction interval, peak before the appearance of the first Jurassic ammonite, remain above background in association with a depauperate fauna, and fall to pre-extinction levels during significant pelagic and benthic faunal recovery. Hg isotopes display no significant mass independent fractionation within the extinction and depauperate intervals, consistent with a volcanic origin for the Hg. The Hg and palaeontological evidence from the same archive indicate that significant biotic recovery did not begin until CAMP eruptions ceased.

  10. A biotic Fe0-H2O system for nitrobenzene removal from groundwater

    DEFF Research Database (Denmark)

    Wu, Jinhua; Yin, Weizhao; Gu, Jingjing;

    2013-01-01

    Batch experiment was conducted to evaluate the capability of a biotic Fe0-H2O for nitrobenzene (NB) removal from groundwater. In this study, iron dosage was 0.25gL-1 throughout the whole experiment and the Fe0-H2O system was amended with 180mgL-1 VSS of mixed culture. The biotic system was tested...... at low concentrations (50mgL-1 as COD) of organic substrates (e.g., ethanol, glucose and sodium acetate) and different concentrations of sulfate, nitrate and dissolved oxygen. The bio-iron system exhibited higher NB removal rate and more AN production. The increasing order of efficiency of tested......), and nitrate showed more significant suppression on NB removal as compared to sulfate. AN elimination occurred during both sulfate-reducing and nitrate-reducing processes and microorganisms got extra reduction capacity from the degradation of AN to reduce nitrate and sulfate, causing the mineralization of NB...

  11. 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.

  12. 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.

  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. 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.

  15. Silicon, the silver bullet for mitigating biotic and abiotic stress, and improving grain quality, in rice?

    OpenAIRE

    Meharg,Caroline; Andrew A Meharg

    2015-01-01

    Adequate silicon fertilization greatly boosts rice yield and mitigates biotic and abiotic stress, and improves grain quality through lowering the content of cadmium and inorganic arsenic. This review on silicon dynamics in rice considers recent advances in our understanding of the role of silicon in rice, and the challenges of maintaining adequate silicon fertility within rice paddy systems. Silicon is increasingly considered as an element required for optimal plant performance, particularly ...

  16. A BIOTIC CONTROL PERSPECTIVE ON NITRATE CONTAMINATION OF GROUNDWATER FROM AGRICULTURAL PRODUCTION

    OpenAIRE

    Erickson, Jon D.; Schlapfer, Felix

    2001-01-01

    Agronomists consider the continuity and nutrient capturing properties of cover crops as important determinants of nutrient cycling in agricultural systems. Managing for these biotic control functions can help limit nutrient loss and groundwater contamination between main crop harvests. This simulation study highlights the potential role of cover crop management in a welfare economics framework. The objective is to find the optimal combination of nutrient input to the main crop, the extent of ...

  17. Biotic wetland connectivity—supporting a new approach for wetland policy

    OpenAIRE

    Amezaga, J.M.; Santamaría, Luis; Green, Andy J.

    2002-01-01

    Wetlands are key habitats connected physically and socially with processes occurring over a much wider territory. The biotic connection through dispersal mechanisms among wetlands is of primary importance to wetland management and policies. However, traditional wetland conservation approaches are based on the preservation of isolated sites considered to be of special importance (typically owing to their importance for concentrations of migratory waterbirds). Research linking local species ric...

  18. Improvement of the characterization factor for biotic-resource depletion of fisheries

    OpenAIRE

    2014-01-01

    Langlois et al. (2012; 2014a) proposed characterization factors (CF) for fish biotic resource extraction impact assessment at the species level. This paper is an improvement of this approach. In the present work, the CF depends on the Maximum Sustainability Yield (MSY), weighted by the ratio of the current total fishing effort to the fishing effort at the MSY value. Because this ratio often cannot be computed from current databases, it is here obtained from the ratio of total catches to MSY a...

  19. Hydrogen sulfide regulates abiotic stress tolerance and biotic stress resistance in Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    Haitao Shi; Tiantian Ye; Ning Han; Hongwu Bian; Xiaodong Liu; Zhulong Chan

    2015-01-01

    Hydrogen sulfide (H2S) is an important gaseous molecule in various plant developmental processes and plant stress responses. In this study, the transgenic Arabidopsis thaliana plants with modulated expressions of two cysteine desulfhydrases, and exogenous H2S donor (sodium hydrosulfide, NaHS) and H2S scavenger (hypotaurine, HT) pre-treated plants were used to dissect the involvement of H2S in plant stress responses. The cysteine desulfhydrases overexpressing plants and NaHS pre-treated plants exhibited higher endogenous H2S level and improved abiotic stress tolerance and biotic stress resistance, while cysteine desulfhydrases knockdown plants and HT pre-treated plants displayed lower endogenous H2S level and decreased stress resistance. Moreover, H2S upregulated the transcripts of multiple abiotic and biotic stress-related genes, and inhibited reactive oxygen species (ROS) accumulation. Interest-ingly, MIR393-mediated auxin signaling including MIR393a/b and their target genes (TIR1, AFB1, AFB2, and AFB3) was transcrip-tional y regulated by H2S, and was related with H2S-induced antibacterial resistance. Moreover, H2S regulated 50 carbon metabolites including amino acids, organic acids, sugars, sugar alcohols, and aromatic amines. Taken together, these results indicated that cysteine desulfhydrase and H2S conferred abiotic stress tolerance and biotic stress resistance, via affecting the stress-related gene expressions, ROS metabolism, metabolic homeostasis, and MIR393-targeted auxin receptors.

  20. Effect of Mining Activities in Biotic Communities of Villa de la Paz, San Luis Potosi, Mexico

    Science.gov (United States)

    Espinosa-Reyes, Guillermo; González-Mille, Donaji J.; Ilizaliturri-Hernández, César A.; Mejía-Saavedra, Jesús; Cilia-López, V. Gabriela; Costilla-Salazar, Rogelio; Díaz-Barriga, Fernando

    2014-01-01

    Mining is one of the most important industrial activities worldwide. During its different stages numerous impacts are generated to the environment. The activities in the region have generated a great amount of mining residues, which have caused severe pollution and health effects in both human population and biotic components. The aim of this paper was to assess the impact of mining activities on biotic communities within the district of Villa de la Paz. The results showed that the concentrations of As and Pb in soil were higher than the national regulations for urban or agricultural areas. The bioavailability of these metals was certified by the presence of them in the roots of species of plants and in kidneys and livers of wild rodents. In regard to the community analysis, the sites that were located close to the mining district of Villa de la Paz registered a lower biological diversity, in both plants and wild rodents, aside from showing a change in the species composition of plant communities. The results of this study are evidence of the impact of mining on biotic communities, and the need to take into account the wildlife in the assessment of contaminated sites. PMID:24592381

  1. Effect of mining activities in biotic communities of Villa de la Paz, San Luis Potosi, Mexico.

    Science.gov (United States)

    Espinosa-Reyes, Guillermo; González-Mille, Donaji J; Ilizaliturri-Hernández, César A; Mejía-Saavedra, Jesús; Cilia-López, V Gabriela; Costilla-Salazar, Rogelio; Díaz-Barriga, Fernando

    2014-01-01

    Mining is one of the most important industrial activities worldwide. During its different stages numerous impacts are generated to the environment. The activities in the region have generated a great amount of mining residues, which have caused severe pollution and health effects in both human population and biotic components. The aim of this paper was to assess the impact of mining activities on biotic communities within the district of Villa de la Paz. The results showed that the concentrations of As and Pb in soil were higher than the national regulations for urban or agricultural areas. The bioavailability of these metals was certified by the presence of them in the roots of species of plants and in kidneys and livers of wild rodents. In regard to the community analysis, the sites that were located close to the mining district of Villa de la Paz registered a lower biological diversity, in both plants and wild rodents, aside from showing a change in the species composition of plant communities. The results of this study are evidence of the impact of mining on biotic communities, and the need to take into account the wildlife in the assessment of contaminated sites.

  2. 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.

  3. Biotic Homogenization Caused by the Invasion of Solidago canadensis in China

    Institute of Scientific and Technical Information of China (English)

    CHEN Guo-qi; ZHANG Chao-bin; MA Ling; QIANG Sheng; John A Silander; Li Li Qi

    2013-01-01

    Although studies argue that invasive species can cause biotic differentiation, some cases show that biological invasions actually decrease biodiversity through biotic homogenization. The concept of biotic homogenization through the invasion of a certain serious invasive plant species merit more studies. Hence, we used field surveys to quantitatively compare invasive populations of Solidago canadensis (SC) in China with the control sites (adjacent sites to SC present sites yet without the species) and SC native populations in the USA. We found that plant communities in SC invaded habitats shared similarities with those in SC native ranges. Bray-Curtis similarity clearly showed that the composition of plant communities in SC invaded habitats were similar to those in SC native ranges. Both in the native and introduced range, plant communities with SC present were characterized by SC being dominant, significantly lower species richness,α-diversity andβ-diversity, as well as a decrease in the correlation coefficient between geographic distance and floristic similarities. SC favors fertile and moist loam habitat, while it dominated in various habitats in China, where more than 20 different dominants should have occurred. In conclusion, serious invasive species can quickly remodel and homogenize diverse communities by dominating them.

  4. Comparative study of the corrosion product films formed in biotic and abiotic media

    Energy Technology Data Exchange (ETDEWEB)

    Videla, H.A.; Mele, M.F.L. de [Univ. of La Plata (Argentina). Dept. of Chemistry; Swords, C. [Univ. of Leeds (United Kingdom). School of Materials; Edyvean, R.G.J. [Univ. of Sheffield (United Kingdom). Dept. of Chemical and Processing Engineering; Beech, I.B. [Univ. of Portsmouth (United Kingdom). Dept. of Chemistry

    1999-11-01

    The growth of sulfate-reducing bacteria (SRB) affects several important parameters at the metal/solution interface of carbon steel in liquid media such as pH and redox potential values, as well as modifications of the composition and structure of corrosion product layers. Electrochemical techniques for corrosion assessment and surface analyses by energy dispersion X-ray analysis (EDAX), X-ray photoelectron spectra (XPS), X-ray distraction (XRD) and electron microprobe analysis (EPMA) complemented with scanning electron microscopy (SEM) and atomic force microscopy (MM) observations, were used to study the structure and composition of protective films on carbon steel in abiotic and biotic media containing different sulfur anions. The results revealed that in biotic and abiotic sulfide films the outer layers were formed by both FeS and FeS{sub 2}, although the relative content of these compounds varied in each case. Usually, the corrosion product films biotically formed were more adherent to the metal surface than those developed abiotically. The latter were flaky and loosely adherent, thus differing in their function during the corrosion process.

  5. Hydrogen sulfide regulates abiotic stress tolerance and biotic stress resistance in Arabidopsis.

    Science.gov (United States)

    Shi, Haitao; Ye, Tiantian; Han, Ning; Bian, Hongwu; Liu, Xiaodong; Chan, Zhulong

    2015-07-01

    Hydrogen sulfide (H2S) is an important gaseous molecule in various plant developmental processes and plant stress responses. In this study, the transgenic Arabidopsis thaliana plants with modulated expressions of two cysteine desulfhydrases, and exogenous H2S donor (sodium hydrosulfide, NaHS) and H2S scavenger (hypotaurine, HT) pre-treated plants were used to dissect the involvement of H2S in plant stress responses. The cysteine desulfhydrases overexpressing plants and NaHS pre-treated plants exhibited higher endogenous H2S level and improved abiotic stress tolerance and biotic stress resistance, while cysteine desulfhydrases knockdown plants and HT pre-treated plants displayed lower endogenous H2S level and decreased stress resistance. Moreover, H2S upregulated the transcripts of multiple abiotic and biotic stress-related genes, and inhibited reactive oxygen species (ROS) accumulation. Interestingly, MIR393-mediated auxin signaling including MIR393a/b and their target genes (TIR1, AFB1, AFB2, and AFB3) was transcriptionally regulated by H2S, and was related with H2S-induced antibacterial resistance. Moreover, H2S regulated 50 carbon metabolites including amino acids, organic acids, sugars, sugar alcohols, and aromatic amines. Taken together, these results indicated that cysteine desulfhydrase and H2S conferred abiotic stress tolerance and biotic stress resistance, via affecting the stress-related gene expressions, ROS metabolism, metabolic homeostasis, and MIR393-targeted auxin receptors.

  6. Effect of Mining Activities in Biotic Communities of Villa de la Paz, San Luis Potosi, Mexico

    Directory of Open Access Journals (Sweden)

    Guillermo Espinosa-Reyes

    2014-01-01

    Full Text Available Mining is one of the most important industrial activities worldwide. During its different stages numerous impacts are generated to the environment. The activities in the region have generated a great amount of mining residues, which have caused severe pollution and health effects in both human population and biotic components. The aim of this paper was to assess the impact of mining activities on biotic communities within the district of Villa de la Paz. The results showed that the concentrations of As and Pb in soil were higher than the national regulations for urban or agricultural areas. The bioavailability of these metals was certified by the presence of them in the roots of species of plants and in kidneys and livers of wild rodents. In regard to the community analysis, the sites that were located close to the mining district of Villa de la Paz registered a lower biological diversity, in both plants and wild rodents, aside from showing a change in the species composition of plant communities. The results of this study are evidence of the impact of mining on biotic communities, and the need to take into account the wildlife in the assessment of contaminated sites.

  7. 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.

  8. A response calculus for immobilized T cell receptor ligands

    DEFF Research Database (Denmark)

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

    2001-01-01

    To address the molecular mechanism of T cell receptor (TCR) signaling, we have formulated a model for T cell activation, termed the 2D-affinity model, in which the density of TCR on the T cell surface, the density of ligand on the presenting surface, and their corresponding two-dimensional affini...

  9. A race for RAGE ligands.

    Science.gov (United States)

    Schleicher, Erwin D

    2010-08-01

    In experimental animals a causal involvement of the multiligand receptor for advanced glycation end products (RAGE) in the development of diabetic vascular complications has been demonstrated. However, the nature of RAGE ligands present in patients with diabetic nephropathy has not yet been defined; this leaves open the relevance of the RAGE system to the human disease.

  10. Cationic Gold Clusters Ligated with Differently Substituted Phosphines: Effect of Substitution on Ligand Reactivity and Binding

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Grant E.; Olivares, Astrid M.; Hill, David E.; Laskin, Julia

    2015-01-01

    We present a systematic study of the effect of the number of methyl (Me) and cyclohexyl (Cy) functional groups in monodentate phosphine ligands on the solution-phase synthesis of ligated sub-nanometer gold clusters and their gas-phase fragmentation pathways. Small mixed ligand cationic gold clusters were synthesized using ligand exchange reactions between pre-formed triphenylphosphine ligated (PPh3) gold clusters and monodentate Me- and Cy-substituted ligands in solution and characterized using electrospray ionization mass spectrometry (ESI-MS) and collision-induced dissociation (CID) experiments. Under the same experimental conditions, larger gold-PPh3 clusters undergo efficient exchange of unsubstituted PPh3 ligands for singly Me- and Cy-substituted PPh2Me and PPh2Cy ligands. The efficiency of ligand exchange decreases with an increasing number of Me or Cy groups in the substituted phosphine ligands. CID experiments performed for a series of ligand-exchanged gold clusters indicate that loss of a neutral Me-substituted ligand is preferred over loss of a neutral PPh¬3 ligand while the opposite trend is observed for Cy-substituted ligands. The branching ratio of the competing ligand loss channels is strongly correlated with the electron donating ability of the phosphorous lone pair as determined by the relative proton affinity of the ligand. The results indicate that the relative ligand binding energies increase in the order PMe3 < PPhMe2 < PPh2Me < PPh3< PPh2Cy < PPhCy2< PCy3. Furthermore, the difference in relative ligand binding energies increases with the number of substituted PPh3-mMem or PPh3-mCym ligands (L) exchanged onto each cluster. This study provides the first experimental determination of the relative binding energies of ligated gold clusters containing differently substituted monophosphine ligands, which are important to controlling their synthesis and reactivity in solution. The results also indicate that ligand substitution is an important

  11. Taxonomic scale-dependence of habitat niche partitioning and biotic neighbourhood on survival of tropical tree seedlings.

    Science.gov (United States)

    Queenborough, Simon A; Burslem, David F R P; Garwood, Nancy C; Valencia, Renato

    2009-12-07

    In order to differentiate between mechanisms of species coexistence, we examined the relative importance of local biotic neighbourhood, abiotic habitat factors and species differences as factors influencing the survival of 2330 spatially mapped tropical tree seedlings of 15 species of Myristicaceae in two separate analyses in which individuals were identified first to species and then to genus. Using likelihood methods, we selected the most parsimonious candidate models as predictors of 3 year seedling survival in both sets of analyses. We found evidence for differential effects of abiotic niche and neighbourhood processes on individual survival between analyses at the genus and species levels. Niche partitioning (defined as an interaction of taxonomic identity and abiotic neighbourhood) was significant in analyses at the genus level, but did not differentiate among species in models of individual seedling survival. By contrast, conspecific and congeneric seedling and adult density were retained in the minimum adequate models of seedling survival at species and genus levels, respectively. We conclude that abiotic niche effects express differences in seedling survival among genera but not among species, and that, within genera, community and/or local variation in adult and seedling abundance drives variation in seedling survival. These data suggest that different mechanisms of coexistence among tropical tree taxa may function at different taxonomic or phylogenetic scales. This perspective helps to reconcile perceived differences of importance in the various non-mutually exclusive mechanisms of species coexistence in hyper-diverse tropical forests.

  12. Monsoonal variability in abiotic parameters in coastal waters off Trivandrum evokes press and pulse response in biotic variables

    Digital Repository Service at National Institute of Oceanography (India)

    Subina, N.S.; Bhosle, S.; Nair, S.; Lokabharathi, P.A.

    Trivandrum Coast experiences coastal upwelling during south west monsoon, which is accompanied by abiotic changes in physio-chemical parameters. The resultant biotic responses could range from an instantaneous pulse to a sustained press reaction...

  13. Recommended Reference Genes for Quantitative PCR Analysis in Soybean Have Variable Stabilities during Diverse Biotic Stresses.

    Science.gov (United States)

    Bansal, Raman; Mittapelly, Priyanka; Cassone, Bryan J; Mamidala, Praveen; Redinbaugh, Margaret G; Michel, Andy

    2015-01-01

    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.

  14. 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

  15. 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.

  16. The abiotic and biotic factors limiting establishment of predatory fishes at their expanding northern range boundaries in Ontario, Canada.

    Science.gov (United States)

    Alofs, Karen M; Jackson, Donald A

    2015-06-01

    There is a poor understanding of the importance of biotic interactions in determining species distributions with climate change. Theory from invasion biology suggests that the success of species introductions outside of their historical ranges may be either positively (biotic acceptance) or negatively (biotic resistance) related to native biodiversity. Using data on fish community composition from two survey periods separated by approximately 28 years during which climate was warming, we examined the factors influencing the establishment of three predatory centrarchids: Smallmouth Bass (Micropterus dolomieu), Largemouth Bass (M. salmoides), and Rock Bass (Ambloplites rupestris) in lakes at their expanding northern range boundaries in Ontario. Variance partitioning demonstrated that, at a regional scale, abiotic factors play a stronger role in determining the establishment of these species than biotic factors. Pairing lakes within watersheds where each species had established with lakes sharing similar abiotic conditions where the species had not established revealed both positive and negative relationships between the establishment of centrarchids and the historical presence of other predatory species. The establishment of these species near their northern range boundaries is primarily determined by abiotic factors at a regional scale; however, biotic factors become important at the lake-to-lake scale. Studies of exotic species invasions have previously highlighted how spatial scale mediates the importance of abiotic vs. biotic factors on species establishment. Our study demonstrates how concepts from invasion biology can inform our understanding of the factors controlling species distributions with changing climate.

  17. Protecting Ligands Enhance Selective Targeting of Multivalent Nanoparticles

    CERN Document Server

    Angioletti-Uberti, Stefano

    2016-01-01

    Nanoparticles functionalized with multiple ligands can be programmed to bind biological targets, e.g. cells, depending on the receptors they express, providing a general platform for the development of different technologies, from selective drug-delivery to biosensing. In order to be highly selective ligands should exclusively bind to specific targeted receptors, since formation of bonds with other, untargeted ones would lead to non-specific binding and potentially harmful behaviour. This poses a particular problem for multivalent nanoparticles, because even very weak bonds can collectively lead to strong binding. A statistical mechanical model is presented here to describe the extent to which bond strength and nanoparticle valency can induce non-selective adsorption. The same model is used to describe a possible solution: functionalization of the nanoparticles with "protective" receptors. The latter compete with cell receptors for the targeting ligands, and can be optimized to strongly reduce the effect of u...

  18. 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.

  19. Copper binding ligands: production by marine plankton and characterization by ESI-MS

    Science.gov (United States)

    Orians, K.; Ross, A.; Lawrence, M.; Ikonomou, M.

    2003-04-01

    Organic complexation affects the bioavailability and distribution of copper in the surface ocean. The cyanobacterium Synechococcus sp. PCC 7002 was cultured in the lab and subjected to near-toxic Cu concentrations. Strong Cu-binding ligands were produced under these conditions, as found for other species of Synechococcus. The copper-binding ligand produced had a log K'cond. (log conditional stability constant) of 12.2, similar to the natural ligands found in the surface ocean. The amount of ligand produced was proportional to the amount of copper present. Isolation and concentration of these compounds for characterization by electrospray mass spectrometry (ESI-MS) provides information about the structure of the organic ligands and their metal-ion complexes. Using model ligands, we'll show that ligands can be characterized by ESI-MS and that the location of the copper binding site can be determined in complex molecules. We'll also present results of copper-complexing ligands extracted from the coastal waters of British Columbia. Ligand concentrations are higher at low salinity and in surface waters, indicating that these ligands are produced in surface waters and/or delivered to the region via the Fraser River. Analysis of the extracts with highest UV absorbance identified two Cu2+ ligands of molecular weight 259 and 264. The mass and isotopic distributions are consistent with dipeptides and tripeptides containing two metal-binding amino groups. This result is consistent with the findings of other studies attempting to characterize Cu2+ ligands in seawater. The structure of the identified ligand is similar to that of rhodotorulic acid (a microbial siderophore), glutathione, and phytochelatins, indicating that small peptides and related compounds can act as strong, specific metal chelators in natural waters

  20. Rational design of cyclopropane-based chiral PHOX ligands for intermolecular asymmetric Heck reaction

    Directory of Open Access Journals (Sweden)

    Marina Rubina

    2014-07-01

    Full Text Available A novel class of chiral phosphanyl-oxazoline (PHOX ligands with a conformationally rigid cyclopropyl backbone was synthesized and tested in the intermolecular asymmetric Heck reaction. Mechanistic modelling and crystallographic studies were used to predict the optimal ligand structure and helped to design a very efficient and highly selective catalytic system. Employment of the optimized ligands in the asymmetric arylation of cyclic olefins allowed for achieving high enantioselectivities and significantly suppressing product isomerization. Factors affecting the selectivity and the rate of the isomerization were identified. It was shown that the nature of this isomerization is different from that demonstrated previously using chiral diphosphine ligands.

  1. New insight into the central benzodiazepine receptor-ligand interactions: design, synthesis, biological evaluation, and molecular modeling of 3-substituted 6-phenyl-4H-imidazo[1,5-a][1,4]benzodiazepines and related compounds.

    Science.gov (United States)

    Anzini, Maurizio; Valenti, Salvatore; Braile, Carlo; Cappelli, Andrea; Vomero, Salvatore; Alcaro, Stefano; Ortuso, Francesco; Marinelli, Luciana; Limongelli, Vittorio; Novellino, Ettore; Betti, Laura; Giannaccini, Gino; Lucacchini, Antonio; Daniele, Simona; Martini, Claudia; Ghelardini, Carla; Di Cesare Mannelli, Lorenzo; Giorgi, Gianluca; Mascia, Maria Paola; Biggio, Giovanni

    2011-08-25

    3-Substituted 6-phenyl-4H-imidazo[1,5-a][1,4]benzodiazepines and related compounds were synthesized as central benzodiazepine receptor (CBR) ligands. Most of the compounds showed high affinity for bovine and human CBR, their K(i) values spanning from the low nanomolar to the submicromolar range. In particular, imidazoester 5f was able to promote a massive flow of (36)Cl(-) in rat cerebrocortical synaptoneurosomes overlapping its efficacy profile with that of a typical full agonist. Compound 5f was then examined in mice for its pharmacological effects where it proved to be a safe anxiolytic agent devoid of the unpleasant myorelaxant and amnesic effects of the classical 1,4-benzodiazepines. Moreover, the selectivity of some selected compounds has been assessed in recombinant α(1)β(2)γ(2)L, α(2)β(1)γ(2)L, and α(5)β(2)γ(2)L human GABA(A) receptors. Finally, some compounds were submitted to molecular docking calculations along with molecular dynamics simulations in the Cromer's GABA(A) homology model.

  2. Vaccination with Altered Peptide Ligands of a Plasmodium berghei Circumsporozoite Protein CD8 T-Cell Epitope: A Model to Generate T Cells Resistant to Immune Interference by Polymorphic Epitopes

    Science.gov (United States)

    Minigo, Gabriela; Flanagan, Katie L.; Slattery, Robyn M.; Plebanski, Magdalena

    2017-01-01

    Many pathogens, including the malaria parasite Plasmodium falciparum, display high levels of polymorphism within T-cell epitope regions of proteins associated with protective immunity. The T-cell epitope variants are often non-cross-reactive. Herein, we show in a murine model, which modifies a protective CD8 T-cell epitope from the circumsporozoite protein (CS) of Plasmodium berghei (SYIPSAEKI), that simultaneous or sequential co-stimulation with two of its putative similarly non-cross-reactive altered peptide ligand (APL) epitopes (SYIPSAEDI or SYIPSAEAI) has radically different effects on immunity. Hence, co-immunization or sequential stimulation in vivo of SYIPSAEKI with its APL antagonist SYIPSAEDI decreases immunity to both epitopes. By contrast, co-immunization with SYIPSAEAI has no apparent initial effect, but it renders the immune response to SYIPSAEKI resistant to being turned off by subsequent immunization with SYIPSAEDI. These results suggest a novel strategy for vaccines that target polymorphic epitopes potentially capable of mutual immune interference in the field, by initiating an immune response by co-immunization with the desired index epitope, together with a carefully selected “potentiator” APL peptide.

  3. Inhibition of keratinocyte proliferation by phospholipid-conjugates of a TLR7 ligand in a Myc-induced hyperplastic actinic keratosis model in the absence of systemic side effects

    Science.gov (United States)

    CRAIN, Brian; YAO, Shiyin; KEOPHILAONE, Vina; PROMESSI, Victor; KANG, McNancy; BARBERIS, Alcide; MAJ, Roberto; MURA, Emanuela; PASSINI, Nadia; HOLLDACK, Johanna; OCHOA, Ricardo; COTTAM, Howard B.; CARSON, Dennis A.; HAYASHI, Tomoko

    2014-01-01

    Background The Toll-like receptor 7 (TLR7) activator imiquimod (IMQ) is safe and effective in treating actinic keratosis; however, an intermittent treatment regimen is necessary because of excessive local reactions. Objectives To evaluate in vitro potency, pharmacodynamics/pharmacokinetics, toxicity and efficacy in vivo of the newly developed TLR7 ligand-phospholipid conjugate, TMX-202, in a gel formulation. Material and Methods The effects of TMX-202 were assessed both in vitro on a murine macrophage cell line and in primary bone marrow-derived dendritic cells and in vivo on mice (C57BL/6-wild type, Myd88−/− and Tlr7−/−). Results TMX-202 was more potent than IMQ in vitro using murine and human cells. In contrast, in vivo it showed less systemic pro-inflammatory activity and better safety than IMQ. Moreover, the TMX-202 gel formulation exhibited at least comparable efficacy to Aldara in a mouse model for skin proliferative diseases. Conclusion TMX-202 is safe and efficacious without causing excessive adverse effects, suggesting that it may be an alternative to Aldara for the treatment of proliferative skin conditions. PMID:24225049

  4. THE EFFECT OF SEROTONIN 5-HT1A, 5-HT2 RECEPTOR LIGANDS, KETOPROFEN AND THEIR COMBINATION IN MODELS OF INDUCED PAIN IN MICE.

    Science.gov (United States)

    Zygmunt, Małgorzata; Chłoń-Rzepa, Grażyna; Sapa, Jacek

    2015-01-01

    The present study was carried out to investigate the effects of the 7-(3-chlorophenyl)piperazinylalkyl derivatives of 8-alkoxypurine-2,6-dione (compounds 1-4) in two animal models of induced pain and to compare their effects with ketoprofen and with their combination. All experiments were performed on albino mice. Mice were evaluated for their responsiveness to noxious stimuli using: the hot-plate test and the phenylbenzo-quinone-induced writhing test. All compounds showed analgesic activity only in the writhing test. The analgesic activities of compounds 3 and 4 were similar to ketoprofen. The compounds slightly increased the analgesic effect of ketoprofen when used in combination in the visceral type of pain. The possible mechanisms of the antinociceptive effect of these compounds are thought to involve the activation of analgesic effect mediated by the serotonergic pathways or combination of this mechanism with other important mediators playing a role in pain modulation.

  5. Metalloprotein-inhibitor binding: human carbonic anhydrase II as a model for probing metal-ligand interactions in a metalloprotein active site.

    Science.gov (United States)

    Martin, David P; Hann, Zachary S; Cohen, Seth M

    2013-11-01

    An ever-increasing number of metalloproteins are being discovered that play essential roles in physiological processes. Inhibitors of these proteins have significant potential for the treatment of human disease, but clinical success of these compounds has been limited. Herein, zinc(II)-dependent metalloprotein inhibitors in clinical use are reviewed, and the potential for using novel metal-binding groups (MBGs) in the design of these inhibitors is discussed. By using human carbonic anhydrase II as a model system, the nuances of MBG-metal interactions in the context of a protein environment can be probed. Understanding how metal coordination influences inhibitor binding may help in the design of new therapeutics targeting metalloproteins.

  6. 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.

  7. Antihyperalgesic effect of the GABA(A) ligand clobazam in a neuropathic pain model in mice: a pharmacokinetic-pharmacodynamic study.

    Science.gov (United States)

    Besson, Marie; Daali, Youssef; Di Lio, Alessandra; Dayer, Pierre; Zeilhofer, Hanns Ulrich; Desmeules, Jules

    2013-03-01

    Facilitation of spinal GABAergic inhibition with benzodiazepines (BZDs) reverses pain sensitization in animals; however, the use of BZDs in man is limited by their sedative effect. The antihyperalgesic effects of GABA(A) agonists are mediated by GABA(A) receptors containing α2 subunits, whereas sedation is linked to α1 subunit-containing receptors. α2 and α3 selective GABA(A) receptor modulators have been tested in animals but are not yet available for use in human beings. Clobazam is a 1,5-BZD, which exhibits less cognitive side effects than other benzodiazepines. Here, we studied its antihyperalgesic effects in a mouse model of neuropathic pain. Clobazam showed a dose-dependent antihyperalgesic effect in the chronic constriction injury (CCI) model of neuropathic pain, peaking at 1 hr after administration and lasting for 4 hr with no relevant sedation at a dose of 3 mg/kg. At higher doses, the antihyperalgesic effect was stronger, but sedation became significant. The blood and brain kinetics of clobazam were linear over the range of doses tested with a short half-life of the parent compound and a ready penetration of the blood-brain barrier. Clobazam blood concentrations decreased rapidly, falling below the limit of detection at 120 min. after drug application. Its main metabolite, N-desmethyl-clobazam, showed more delayed and prolonged pharmacokinetics, partly explaining why antihyperalgesia persisted when clobazam was no longer detectable in the blood. Considering its therapeutic margin and its pharmacokinetic properties, clobazam would be a valuable compound to assess the role of the GABAergic pathway in pain transmission in human beings.

  8. Controlled-deactivation cannabinergic ligands.

    Science.gov (United States)

    Sharma, Rishi; Nikas, Spyros P; Paronis, Carol A; Wood, Jodianne T; Halikhedkar, Aneetha; Guo, Jason Jianxin; Thakur, Ganesh A; Kulkarni, Shashank; Benchama, Othman; Raghav, Jimit Girish; Gifford, Roger S; Järbe, Torbjörn U C; Bergman, Jack; Makriyannis, Alexandros

    2013-12-27

    We report an approach for obtaining novel cannabinoid analogues with controllable deactivation and improved druggability. Our design involves the incorporation of a metabolically labile ester group at the 2'-position on a series of (-)-Δ(8)-THC analogues. We have sought to introduce benzylic substituents α to the ester group which affect the half-lives of deactivation through enzymatic activity while enhancing the affinities and efficacies of individual ligands for the CB1 and CB2 receptors. The 1'-(S)-methyl, 1'-gem-dimethyl, and 1'-cyclobutyl analogues exhibit remarkably high affinities for both CB receptors. The novel ligands are susceptible to enzymatic hydrolysis by plasma esterases in a controllable manner, while their metabolites are inactive at the CB receptors. In further in vitro and in vivo experiments key analogues were shown to be potent CB1 receptor agonists and to exhibit CB1-mediated hypothermic and analgesic effects.

  9. Privileged chiral ligands and catalysts

    CERN Document Server

    Zhou, Qi-Lin

    2011-01-01

    This ultimate ""must have"" and long awaited reference for every chemist working in the field of asymmetric catalysis starts with the core structure of the catalysts, explaining why a certain ligand or catalyst is so successful. It describes in detail the history, the basic structural characteristics, and the applications of these ""privileged catalysts"". A novel concept that gives readers a much deeper insight into the topic.

  10. Tumor targeting via integrin ligands

    Directory of Open Access Journals (Sweden)

    Udaya Kiran eMarelli

    2013-08-01

    Full Text Available Selective and targeted delivery of drugs to tumors is a major challenge for an effective cancer therapy and also to overcome the side effects associated with current treatments. Overexpression of various receptors on tumor cells is a characteristic structural and biochemical aspect of tumors and distinguishes them from physiologically normal cells. This abnormal feature is therefore suitable for selectively directing anticancer molecules to tumors by using ligands that can preferentially recognize such receptors. Several subtypes of integrin receptors that are crucial for cell adhesion, cell signaling, cell viability and motility have been shown to have an upregulated expression on cancer cells. Thus, ligands that recognize specific integrin subtypes represent excellent candidates to be conjugated to drugs or drug carrier systems and be targeted to tumors. In this regard, integrins recognizing the RGD cell adhesive sequence have been extensively targeted for tumor specific drug delivery. Here we review key recent examples on the presentation of RGD-based integrin ligands by means of distinct drug delivery systems, and discuss the prospects of such therapies to specifically target tumor cells.

  11. Biodiversity inventories in high gear: DNA barcoding facilitates a rapid biotic survey of a temperate nature reserve

    Science.gov (United States)

    Young, Monica R; Quinn, Jenna; Perez, Kate; Sobel, Crystal N; Sones, Jayme E; Levesque-Beaudin, Valerie; Derbyshire, Rachael; Fernandez-Triana, Jose; Rougerie, Rodolphe; Thevanayagam, Abinah; Boskovic, Adrian; Borisenko, Alex V; Cadel, Alex; Brown, Allison; Pages, Anais; Castillo, Anibal H; Nicolai, Annegret; Glenn Mockford, Barb Mockford; Bukowski, Belén; Wilson, Bill; Trojahn, Brock; Lacroix, Carole Ann; Brimblecombe, Chris; Hay, Christoper; Ho, Christmas; Steinke, Claudia; Warne, Connor P; Garrido Cortes, Cristina; Engelking, Daniel; Wright, Danielle; Lijtmaer, Dario A; Gascoigne, David; Hernandez Martich, David; Morningstar, Derek; Neumann, Dirk; Steinke, Dirk; Marco DeBruin, Donna DeBruin; Dobias, Dylan; Sears, Elizabeth; Richard, Ellen; Damstra, Emily; Zakharov, Evgeny V; Laberge, Frederic; Collins, Gemma E; Blagoev, Gergin A; Grainge, Gerrie; Ansell, Graham; Meredith, Greg; Hogg, Ian; McKeown, Jaclyn; Topan, Janet; Bracey, Jason; Guenther, Jerry; Sills-Gilligan, Jesse; Addesi, Joseph; Persi, Joshua; Layton, Kara K S; D'Souza, Kareina; Dorji, Kencho; Grundy, Kevin; Nghidinwa, Kirsti; Ronnenberg, Kylee; Lee, Kyung Min; Xie, Linxi; Lu, Liuqiong; Penev, Lyubomir; Gonzalez, Mailyn; Rosati, Margaret E; Kekkonen, Mari; Kuzmina, Maria; Iskandar, Marianne; Mutanen, Marko; Fatahi, Maryam; Pentinsaari, Mikko; Bauman, Miriam; Nikolova, Nadya; Ivanova, Natalia V; Jones, Nathaniel; Weerasuriya, Nimalka; Monkhouse, Norman; Lavinia, Pablo D; Jannetta, Paul; Hanisch, Priscila E; McMullin, R. Troy; Ojeda Flores, Rafael; Mouttet, Raphaëlle; Vender, Reid; Labbee, Renee N; Forsyth, Robert; Lauder, Rob; Dickson, Ross; Kroft, Ruth; Miller, Scott E; MacDonald, Shannon; Panthi, Sishir; Pedersen, Stephanie; Sobek-Swant, Stephanie; Naik, Suresh; Lipinskaya, Tatsiana; Eagalle, Thanushi; Decaëns, Thibaud; Kosuth, Thibault; Braukmann, Thomas; Woodcock, Tom; Roslin, Tomas; Zammit, Tony; Campbell, Victoria; Dinca, Vlad; Peneva, Vlada; Hebert, Paul D N

    2015-01-01

    specialist time. The final product is more than a comprehensive biotic inventory – it is also a rich dataset of fine-scale occurrence and sequence data, all archived and cross-linked in the major biodiversity data repositories. This model of rapid generation and dissemination of essential biodiversity data could be followed to conduct regional assessments of biodiversity status and change, and potentially be employed for evaluating progress towards the Aichi Targets of the Strategic Plan for Biodiversity 2011–2020. PMID:26379469

  12. 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

  13. Meta-analysis: abundance, behavior, and hydraulic energy shape biotic effects on sediment transport in streams.

    Science.gov (United States)

    Albertson, L K; Allen, D C

    2015-05-01

    An increasing number of studies have emphasized the need to bridge the disciplines of ecology and geomorphology. A large number of case studies show that organisms can affect erosion, but a comprehensive understanding of biological impacts on sediment transport conditions is still lacking. We use meta-analysis to synthesize published data to quantify the effects of the abundance, body size, and behavior of organisms on erosion in streams. We also explore the influence of current velocity, discharge, and sediment grain size on the strength of biotic effects on erosion. We found that species that both increase erosion (destabilizers) and decrease erosion (stabilizers) can alter incipient sediment motion, sediment suspension, and sediment deposition above control conditions in which the organisms were not present. When abundance was directly manipulated, these biotic effects were consistently stronger in the higher abundance treatment, increasing effect sizes by 66%. Per capita effect size and per capita biomass were also consistently positively correlated. Fish and crustaceans were the most studied organisms, but aquatic insects increased the effect size by 550 x compared to other types of organisms after accounting for biomass. In streams with lower discharge and smaller grain sizes, we consistently found stronger biotic effects. Taken collectively, these findings provide synthetic evidence that biology can affect physical processes in streams, and these effects can be mediated by hydraulic energy. We suggest that future studies focus on understudied organisms, such as biofilms, conducting experiments under realistic field conditions, and developing hypotheses for the effect of biology on erosion and velocity currents in the context of restoration to better understand the forces that mediate physical disturbances in stream ecosystems.

  14. Biotic interactions at hydrothermal vents: Recruitment inhibition by the mussel Bathymodiolus thermophilus

    Science.gov (United States)

    Lenihan, H. S.; Mills, S. W.; Mullineaux, L. S.; Peterson, C. H.; Fisher, C. R.; Micheli, F.

    2008-12-01

    The structure and dynamics of marine communities are regulated in part by variation in recruitment. As in other ecosystems, recruitment at deep-sea hydrothermal vents is controlled by the interplay of propagule supply and behavior, gradients in physical-chemical conditions, and biotic interactions during pre- and post-settlement periods. Recent research along the East Pacific Rise indicates that inhibition of recently settled larvae by mobile predators (mainly limpets) influences patterns of recruitment and subsequent community succession. We conducted a manipulative experiment at the same sites (˜2510 m water depth) to test whether high-density assemblages of the mussel Bathymodiolus thermophilus also inhibit recruitment. In a preliminary study, recruitment of vent invertebrates within the faunal zone dominated by B. thermophilus was strikingly different at two sites, East Wall and Worm Hole. East Wall had high densities of mussels but very low total recruitment. In contrast, Worm Hole had few mussels but high recruitment. Using the submersible Alvin, we transplanted a large number of mussels from East Wall to Worm Hole and quantified recruitment on basalt blocks placed in three treatments: (1) naturally high densities of mussels at East Wall; (2) naturally low densities of mussels at Worm Hole; and (3) high densities of transplanted mussels at Worm Hole. After 11 months, a total of 24 taxa had recruited to the basalt blocks. Recruitment was 44-60% lower in the transplanted high-density mussel patch at Worm Hole and the natural high-density patch at East Wall than within the natural low-density patch at Worm Hole. Biotic processes that may have caused the pattern of recruitment observed included predation of larvae via water filtration by mussels, larval avoidance of superior competitors, interference competition, and enhanced predation by species within the mussel-bed community. Our results indicate that biotic interactions affecting recruitment must be

  15. Mechanical stress induces biotic and abiotic stress responses via a novel cis-element.

    Directory of Open Access Journals (Sweden)

    Justin W Walley

    2007-10-01

    Full Text Available Plants are continuously exposed to a myriad of abiotic and biotic stresses. However, the molecular mechanisms by which these stress signals are perceived and transduced are poorly understood. To begin to identify primary stress signal transduction components, we have focused on genes that respond rapidly (within 5 min to stress signals. Because it has been hypothesized that detection of physical stress is a mechanism common to mounting a response against a broad range of environmental stresses, we have utilized mechanical wounding as the stress stimulus and performed whole genome microarray analysis of Arabidopsis thaliana leaf tissue. This led to the identification of a number of rapid wound responsive (RWR genes. Comparison of RWR genes with published abiotic and biotic stress microarray datasets demonstrates a large overlap across a wide range of environmental stresses. Interestingly, RWR genes also exhibit a striking level and pattern of circadian regulation, with induced and repressed genes displaying antiphasic rhythms. Using bioinformatic analysis, we identified a novel motif overrepresented in the promoters of RWR genes, herein designated as the Rapid Stress Response Element (RSRE. We demonstrate in transgenic plants that multimerized RSREs are sufficient to confer a rapid response to both biotic and abiotic stresses in vivo, thereby establishing the functional involvement of this motif in primary transcriptional stress responses. Collectively, our data provide evidence for a novel cis-element that is distributed across the promoters of an array of diverse stress-responsive genes, poised to respond immediately and coordinately to stress signals. This structure suggests that plants may have a transcriptional network resembling the general stress signaling pathway in yeast and that the RSRE element may provide the key to this coordinate regulation.

  16. Biotic variation in coastal water bodies in Sussex, England: Implications for saline lagoons

    Science.gov (United States)

    Joyce, Chris B.; Vina-Herbon, Cristina; Metcalfe, Daniel J.

    2005-12-01

    Coastal water bodies are a heterogeneous resource typified by high spatial and temporal variability and threatened by anthropogenic impacts. This includes saline lagoons, which support a specialist biota and are a priority habitat for nature conservation. This paper describes the biotic variation in coastal water bodies in Sussex, England, in order to characterise the distinctiveness of the saline lagoon community and elucidate environmental factors that determine its distribution. Twenty-eight coastal water bodies were surveyed for their aquatic flora and invertebrate fauna and a suite of exploratory environmental variables compiled. Ordination and cluster analyses were used to examine patterns in community composition and relate these to environmental parameters. Biotic variation in the coastal water body resource was high. Salinity was the main environmental parameter explaining the regional distribution of taxa; freshwater and saline assemblages were evident and related to sea water ingress. Freshwater sites were indicated by the plant Myriophyllum spicatum and gastropod mollusc Lymnaea peregra, while more saline communities supported marine and brackish water taxa, notably a range of chlorophytic algae and the bivalve mollusc Cerastoderma glaucum. Site community differences were also related to bank slope and parameters describing habitat heterogeneity. A saline lagoon community was discerned within the matrix of biotic variation consisting of specialist lagoonal species with associated typically euryhaline taxa. For fauna, the latter were the molluscs Abra tenuis and Hydrobia ulvae, and the crustaceans Corophium volutator and Palaemonetes varians, and for flora they were the algae Ulva lactuca, Chaetomorpha mediterranea, Cladophora spp. and Enteromorpha intestinalis. One non-native polychaete species, Ficopomatus enigmaticus, also strongly influenced community structure within the lagoonal resource. The community was not well defined as specialist and

  17. Background- versus event-level biotic variability: Hyperthermals of the late Paleocene and early Eocene

    Science.gov (United States)

    Gibbs, S.; Murphy, B. H.; Pälike, H.

    2009-12-01

    The Paleocene-Eocene Thermal Maximum (PETM) was an abrupt global warming event 55 million years ago (Ma) which has received much attention in recent years as an analogue for anthropogenic carbon emissions. We now know that the PETM was not unique, but was perhaps the most extreme of a number of abrupt carbon cycle perturbations throughout the late Paleocene and early Eocene. These inferred transient warming events, or ‘hyperthermals’, all have characteristic negative carbon isotope excursions (CIE). Unlike the PETM, it is currently unclear whether there was a significant biotic response to these additional CIEs, and if so, whether the amplitude of response varied systematically with excursion magnitude. Here, we present high-resolution nannofossil records from a two million year interval spanning the Paleocene-Eocene boundary at Ocean Drilling Program (ODP) Site 1209 in the paleo-subequatorial Pacific. This interval, from ~55 to 53 Ma, includes the PETM, a second hyperthermal named the Eocene Thermal Maximum 2 (ETM2 or ‘Elmo’), and a further number of smaller excursions. These data allow us to look for common biotic signatures and to document the level of assemblage variability relative to the inferred levels of environmental change associated with each CIE. We use this dataset as a case-study for investigating different statistical means of quantifying and comparing biotic responses to background and event-level perturbation. Preliminary analyses suggest that, as expected, the PETM exhibited the greatest level of assemblage variability, well above background levels, followed in order of CIE magnitude by the ETM2. Several of the smaller excursions have no significant assemblage variability above background levels, pointing to a critical threshold level of environmental perturbation.

  18. Solvent fluctuations induce non-Markovian kinetics in hydrophobic pocket-ligand binding

    CERN Document Server

    Weiß, R Gregor; Dzubiella, Joachim

    2016-01-01

    We investigate the impact of water fluctuations on the key-lock association kinetics of a hydrophobic ligand (key) binding to a hydrophobic pocket (lock) by means of a minimalistic stochastic model system. It describes the collective hydration behavior of the pocket by bimodal fluctuations of a water-pocket interface that dynamically couples to the diffusive motion of the approaching ligand via the hydrophobic interaction. This leads to a set of overdamped Langevin equations in 2D-coordinate-space, that is Markovian in each dimension. Numerical simulations demonstrate locally increased friction of the ligand, decelerated binding kinetics, and local non-Markovian (memory) effects in the ligand's reaction coordinate as found previously in explicit-water molecular dynamics studies of model hydrophobic pocket-ligand binding [1,2]. Our minimalistic model elucidates the origin of effectively enhanced friction in the process that can be traced back to long-time decays in the force-autocorrelation function induced by...

  19. 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.

  20. Unhindered copper uptake by glutaraldehyde-polyethyleneimine coatings in an artificial seawater model system with adsorbed swollen polysaccharides and competing ligand EDTA.

    Science.gov (United States)

    Kaur, Simarpreet; Kempson, Ivan M; Lindén, Johan B; Larsson, Mikael; Nydén, Magnus

    2017-02-01

    Shortly after a surface is submerged in the sea, a conditioning film is generally formed by adsorption of organic molecules, such as polysaccharides. This could affect transport of molecules and ions between the seawater and the surface. An artificial seawater model system was developed to understand how adsorbed polysaccharides impact copper binding by glutaraldehyde-crosslinked polyethyleneimine coatings. Coating performance was also determined when competed against copper-chelating EDTA. Polysaccharide adsorption and copper binding and distribution were investigated using advanced analytical techniques, including depth-resolved time-of-flight secondary ion mass spectroscopy, grazing incidence X-ray absorption near-edge spectroscopy, quartz crystal microbalance with dissipation monitoring and X-ray photoelectron spectroscopy. In artificial seawater, the polysaccharides adsorbed in a swollen state that copper readily penetrated and the glutaraldehyde-polyethyleneimine coatings outcompeted EDTA for copper binding. Furthermore, the depth distribution of copper species was determined with nanometre precision. The results are highly relevant for copper-binding and copper-releasing materials in seawater.

  1. Computational Exploration of a Protein Receptor Binding Space with Student Proposed Peptide Ligands

    Science.gov (United States)

    King, Matthew D.; Phillips, Paul; Turner, Matthew W.; Katz, Michael; Lew, Sarah; Bradburn, Sarah; Andersen, Tim; McDougal, Owen M.

    2016-01-01

    Computational molecular docking is a fast and effective "in silico" method for the analysis of binding between a protein receptor model and a ligand. The visualization and manipulation of protein to ligand binding in three-dimensional space represents a powerful tool in the biochemistry curriculum to enhance student learning. The…

  2. Looking for a synergic effect between NHCs and chiral P-ligands.

    Science.gov (United States)

    Toselli, Nicolas; Martin, David; Buono, Gérard

    2008-04-03

    The issue of the added value of NHCs in asymmetric catalysis with respect to trusted chiral P-ligands was addressed: considering a prototypical asymmetric allylic alkylation reaction as a model, the association of a priori inhibiting and achiral NHCs with modular P-ligand resulted in enhancement of er up to 508% and increased rates.

  3. [Callose accumulation during treatment of tomato (Lycopersicon esculentum L.) cells with biotic elicitors].

    Science.gov (United States)

    Emel'ianov, V I; Kravchuk, Zh N; Poliakovskiĭ, S A; Dmitriev, A P

    2008-01-01

    Time-course of induced accumulation of callose in tomato cells has been studied. Localization of callose in L. esculenthum cells was investigated by fluorescent microscopy technique, and the optimal time for its determination was found. Callose accumulation in tomato cells treated with different biotic elicitors was determined. Nonlinear dependence between callose accumulation and concentration of chitin oligomers (with 3-5 N-acetylglucosamine fragments) was established. Increasing of callose accumulation in tomato cells was proportional to the increase of concentration ofchitin dimer and chitosan in the culture medium.

  4. 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 C4 grasses and forbs (Hempstead Plains, HP) and one characterized by a mixture of C3 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

  5. Autotrophic denitrification performance and bacterial community at biocathodes of bioelectrochemical systems with either abiotic or biotic anodes.

    Science.gov (United States)

    Nguyen, Van Khanh; Hong, Sungsug; Park, Younghyun; Jo, Kyungmin; Lee, Taeho

    2015-02-01

    Two-chamber bioelectrochemical systems (BESs) have recently been developed for nitrate removal from nitrate-contaminated water. In this study, we compared the nitrate removal performance of biocathodes of BESs when using abiotic and biotic anodes. Acetate was used as electron donor in BESs with biotic anode, whereas a direct current power supply was used as energy source in BESs with abiotic anode. The nitrogen removal efficiency increased from 18.1% to 43.0% when the voltage supplied to the BES with abiotic anode increased from 0.7 V to 0.9 V, whereas no higher removal efficiency was obtained at a higher supplied voltage (1.1 V). The highest efficiency (78.0%) of autotrophic nitrogen removal was achieved when electron transfer from the biotic anode chamber of BESs was used. Unexpectedly, control of the cathode potential did not enhance nitrate removal in BESs with biotic anode. Special attention was paid to elucidate the differences of bacterial communities catalysing autotrophic denitrification in the biocathodes of BESs with abiotic and biotic anodes. Data from denaturing gradient gel electrophoresis and phylogenetic analysis suggested that denitrification in BESs with abiotic anode could be attributed to Nitratireductor sp., Shinella sp., and Dyella sp., whereas the dominant bacterial denitrifiers in BESs with biotic anode were found to be Pseudomonas sp., Curtobacterium sp., and Aeromonas sp. These results implied that biocathodes of BESs with biotic anode are more efficient than those of BESs with abiotic anode for nitrate removal from nitrate-contaminated water in practical applications.

  6. 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.

  7. Mapping of ligand-binding cavities in proteins.

    Science.gov (United States)

    Andersson, C David; Chen, Brian Y; Linusson, Anna

    2010-05-01

    The complex interactions between proteins and small organic molecules (ligands) are intensively studied because they play key roles in biological processes and drug activities. Here, we present a novel approach to characterize and map the ligand-binding cavities of proteins without direct geometric comparison of structures, based on Principal Component Analysis of cavity properties (related mainly to size, polarity, and charge). This approach can provide valuable information on the similarities and dissimilarities, of binding cavities due to mutations, between-species differences and flexibility upon ligand-binding. The presented results show that information on ligand-binding cavity variations can complement information on protein similarity obtained from sequence comparisons. The predictive aspect of the method is exemplified by successful predictions of serine proteases that were not included in the model construction. The presented strategy to compare ligand-binding cavities of related and unrelated proteins has many potential applications within protein and medicinal chemistry, for example in the characterization and mapping of "orphan structures", selection of protein structures for docking studies in structure-based design, and identification of proteins for selectivity screens in drug design programs.

  8. 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.

  9. Effect of ligands on thermal dissipation from gold nanorods.

    Science.gov (United States)

    Alper, Joshua; Hamad-Schifferli, Kimberly

    2010-03-16

    Thermal interface conductance was measured for soluble gold nanorods (NRs) coated with mercaptocarboxylic acids (HS-(CH(2))(n)COOH, n = 5, 10, 15), thiolated polyethylene glycols (MW = 356, 1000, 5000), and HS-(CH(2))(15)-COOH-coated NRs further coated with alternating layers of poly(diallyldimethylammonium chloride) and poly(sodium styrenesulfonate). Ferguson analysis determined ligand thickness. The thermal-diffusion-dominated regime of transient absorption spectra was fit to a continuum heat diffusion finite element model to obtain the thermal interface conductance, G, which varied with ligand chemistry but not molecule length. The results suggest that the ability to exclude water from the NR surface governs ligand G values.

  10. Memetic algorithms for ligand expulsion from protein cavities

    CERN Document Server

    Rydzewski, Jakub

    2015-01-01

    Ligand diffusion through a protein interior is a fundamental process governing biological signaling and enzymatic catalysis. A complex topology of channels in proteins leads often to difficulties in modeling ligand escape pathways by classical molecular dynamics simulations. In this paper two novel memetic methods for searching the exit paths and cavity space exploration are proposed: Memory Enhanced Random Acceleration (MERA) Molecular Dynamics and Immune Algorithm (IA). In MERA, a pheromone concept is introduced to optimize an expulsion force. In IA, hybrid learning protocols are exploited to predict ligand exit paths. They are tested on three protein channels with increasing complexity: M2 muscarinic GPCR receptor, enzyme nitrile hydratase and heme-protein cytochrome P450cam. In these cases, the memetic methods outperform Simulated Annealing and Random Acceleration Molecular Dynamics. The proposed algorithms are general and appropriate in all problems where an accelerated transport of an object through a n...

  11. 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.

  12. Smithian-Spathian boundary event: Evidence for global climatic change in the wake of the end-Permian biotic crisis

    Science.gov (United States)

    Galfetti, Thomas; Hochuli, Peter A.; Brayard, Arnaud; Bucher, Hugo; Weissert, Helmut; Vigran, Jorunn Os

    2007-04-01

    One of the most important carbon cycle perturbations following the end-Permian mass extinction event straddles the Smithian-Spathian boundary (SSB) (Olenekian, Early Triassic). This anomaly is characterized by a prominent positive carbon isotope excursion known from Tethyan marine rocks. Its global significance is established here by a new high paleolatitude record (Spitsbergen). Paleontological evidence, such as Boreal palynological data (Barents Sea, Norway) and global patterns of ammonoid distribution, indicates a synchronous major change in terrestrial and marine ecosystems near the SSB. The reestablishment of highly diverse plant ecosystems, including the rise of woody gymnosperms and decline of the formerly dominating lycopods, is interpreted as an effect of a major climate change. This hypothesis is supported by modeling of ammonoid paleobiogeography, the distribution patterns of which are interpreted as a proxy for sea surface temperatures (SST). The latest Smithian thus appears to have been a time of a warm and equable climate as expressed by an almost flat pole to equator SST gradient. In contrast, the steep Spathian SST gradient suggests latitudinally differentiated climatic conditions. We propose that this drastic climate change and the global carbon cycle perturbation were triggered by a massive end-Smithian CO2 injection. The SSB event could therefore represent one of the causes for stepwise and delayed recovery of marine and terrestrial biotas in the wake of the end-Permian biotic crisis.

  13. Comparison of biotic and abiotic treatment approaches for co-mingled perchlorate, nitrate, and nitramine explosives in groundwater

    Science.gov (United States)

    Schaefer, C. E.; Fuller, M. E.; Condee, C. W.; Lowey, J. M.; Hatzinger, P. B.

    2007-01-01

    Biological and abiotic approaches for treating co-mingled perchlorate, nitrate, and nitramine explosives in groundwater were compared in microcosm and column studies. In microcosms, microscale zero-valent iron (mZVI), nanoscale zero-valent iron (nZVI), and nickel catalyzed the reduction of RDX and HMX from initial concentrations of 9 and 1 mg/L, respectively, to below detection (0.02 mg/L), within 2 h. The mZVI and nZVI also degraded nitrate (3 mg/L) to below 0.4 mg/L, but none of the metal catalysts were observed to appreciably reduce perchlorate (˜ 5 mg/L) in microcosms. Perchlorate losses were observed after approximately 2 months in columns of aquifer solids treated with mZVI, but this decline appears to be the result of biodegradation rather than abiotic reduction. An emulsified vegetable oil substrate was observed to effectively promote the biological reduction of nitrate, RDX and perchlorate in microcosms, and all four target contaminants in the flow-through columns. Nitrate and perchlorate were biodegraded most rapidly, followed by RDX and then HMX, although the rates of biological reduction for the nitramine explosives were appreciably slower than observed for mZVI or nickel. A model was developed to compare contaminant degradation mechanisms and rates between the biotic and abiotic treatments.

  14. Climatic Versus Biotic Constraints on Carbon and Water Fluxes in Seasonally Drought-affected Ponderosa Pine Ecosystems. Chapter 2

    Science.gov (United States)

    Schwarz, P. A.; Law, B. E.; Williams, M.; Irvine, J.; Kurpius, M.; Moore, D.

    2005-01-01

    We investigated the relative importance of climatic versus biotic controls on gross primary production (GPP) and water vapor fluxes in seasonally drought-affected ponderosa pine forests. The study was conducted in young (YS), mature (MS), and old stands (OS) over 4 years at the AmeriFlux Metolius sites. Model simulations showed that interannual variation of GPP did not follow the same trends as precipitation, and effects of climatic variation were smallest at the OS (50%), and intermediate at the YS (<20%). In the young, developing stand, interannual variation in leaf area has larger effects on fluxes than climate, although leaf area is a function of climate in that climate can interact with age-related shifts in carbon allocation and affect whole-tree hydraulic conductance. Older forests, with well-established root systems, appear to be better buffered from effects of seasonal drought and interannual climatic variation. Interannual variation of net ecosystem exchange (NEE) was also lowest at the OS, where NEE is controlled more by interannual variation of ecosystem respiration, 70% of which is from soil, than by the variation of GPP, whereas variation in GPP is the primary reason for interannual changes in NEE at the YS and MS. Across spatially heterogeneous landscapes with high frequency of younger stands resulting from natural and anthropogenic disturbances, interannual climatic variation and change in leaf area are likely to result in large interannual variation in GPP and NEE.

  15. 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 M; 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 C; Warren, Gregory L; Westbrook, John D; Williams, Pamela; Yang, Huanwang; Young, Jasmine

    2016-04-01

    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 (PDB) archive, ∼75% include at least one non-polymeric ligand. Ligand geometrical and stereochemical quality, the suitability of ligand models for in silico drug discovery and 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 PDB/Cambridge Crystallographic Data Center/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 PDB? 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.

  16. Ground-based hyperspectral remote sensing to discriminate biotic stress in cotton crop

    Science.gov (United States)

    Nigam, Rahul; Kot, Rajsi; Sandhu, Sandeep S.; Bhattacharya, Bimal K.; Chandi, Ravinder S.; Singh, Manjeet; Singh, Jagdish; Manjunath, K. R.

    2016-05-01

    A large gap exists between the potential yield and the yield realized at the agricultural field. Among the factors contributing towards this yield gap are the biotic stresses that affect the crops growth and development. Severity of infestation of the pests and diseases differs between agroclimatic region, individual crops and seasons within a region. Information about the timing of start of infestation of these diseases and pests with their gradual progress in advance could enable plan necessary pesticide schedule for the season, region on the particular crop against the specific menace expected. This could be enabled by development of region, crop and pest-specific prediction models to forewarn these menaces. In India most (70%) of the land-holding size of farmers average 0.39 ha (some even 20 m x 20 m) and only 1% crop growers holdmarketing and trade (Prabhakar et al., 2011). India ranks first in global acreage, occupying about 33% of world cotton area. With regard to production it is ranked second next to China. In recent years, farmers are facing many challenges because of rising incidents of white flies, jassid, leafhoppers, aphids, mealybugs and stainers. Whiteflies are tiny, sap- sucking insects that may become abundant in vegetable and ornamental plantings, especially during warm weather. They excrete sticky honeydew and cause yellowing or death of leaves. Outbreaks often occur when the natural biological control is disrupted. Management is difficult once populations are high. White flies develop rapidly in warm weather, and populations can build up quickly in situations where natural enemies are ineffective and when weather and host plants favor outbreaks. Large colonies often develop on the undersides of leaves. The most common pest species such as greenhouse white fly (Trialeurodes vaporariorum) and sweet potato white fly (Bemisia tabaci) have a wide host range that includes many weeds and crops. White flies normally lay their tiny oblong eggs on the

  17. Optical Tweezers Studies on Notch: Single-molecule Interaction Strength is Independent of Ligand Endocytosis

    Science.gov (United States)

    Shergill, Bhupinder; Meloty-Kapella, Laurence; Musse, Abdiwahab A.; Weinmaster, Gerry; Botvinick, Elliot

    2012-01-01

    SUMMARY Notch signaling controls diverse cellular processes critical to development and disease. Cell surface ligands bind Notch on neighboring cells yet require endocytosis to activate signaling. The role ligand endocytosis plays in Notch activation has not been established. Here we integrate optical tweezers with cell biological and biochemical methods to test the prevailing model that ligand endocytosis facilitates recycling to enhance ligand interactions with Notch necessary to trigger signaling. Specifically, single-molecule measurements indicate that interference of ligand endocytosis and/or recycling does not alter the force required to rupture bonds formed between cells expressing the Notch ligand Delta-like1 (Dll1) and laser-trapped Notch1-beads. Together, our analyses eliminate roles for ligand endocytosis and recycling in Dll1-Notch1 interactions, and indicate that recycling indirectly affects signaling by regulating the accumulation of cell-surface ligand. Importantly, our study demonstrates the utility of optical tweezers to test a role for ligand endocytosis in generating cell-mediated mechanical force. PMID:22658935

  18. Integrated Record of Terrestrial Biotic Change from the Upper Triassic Chinle Formation of northern New Mexico

    Science.gov (United States)

    Irmis, R. B.; Lindström, S.; Dunlavey, M.; Whiteside, J. H.

    2010-12-01

    The Triassic Period was an interval of major biotic and environmental changes sandwiched between two major mass extinctions. During the Late Triassic (235-201.3 Ma), dinosaurs originated and diversified across Pangaea, and several major extant vertebrate groups also appeared for the first time. Unfortunately, few detailed stratigraphically-precise local-regional paleontological records exist for continental Triassic strata, which hinders any attempt to understand the tempo and mode of biotic change through the Late Triassic. We present a new stratigraphically well-constrained fossil vertebrate and palynomorph record (10-15 Ma in duration) from the upper Chinle Formation of the Chama Basin, northern New Mexico, an area that is famous for preserving one of the best records of early dinosaurs in North America. Our data indicate that vertebrate faunas were generally stable, experiencing only one identifiable species turnover event. Dinosaurs, although relatively diverse, were never abundant components of the fauna. Contemporaneous palynological records indicate that floral composition fluctuated considerably. The drought-tolerant conifer pollen Enzonalasporites and other gymnosperms such as Alisporites and Protodiploxypinus dominate most palynofloral assemblages, but there is a distinct increase in fern spore abundance near the top of the section. In combination with evidence of variability from organic carbon stable isotopes, these data indicate that the vertebrate fauna, including early dinosaurs, remained stable over millions of years despite living within a dynamic ecosystem associated with rapidly changing environmental conditions.

  19. Pre-biotic stage of life origin under non-photosynthetic conditions

    Science.gov (United States)

    Bartsev, S. I.; Mezhevikin, V. V.

    2005-01-01

    Spontaneous assembling of a simplest bacterial cell even if all necessary molecules are present in a solution seems to be extremely rare event and from the scientific standpoint has to be considered as impossible. Therefore, a predecessor of a living cell has to be very simple for providing its self-assembling and at the same time it should be able of progressive increase in complexity. Now phase-separated particles, first of all micelles, are put forward as possible predecessors of living cell. According to the offered working concept only phase-separated particles possessing autocatalytic properties can be considered as predecessors of living cells. The first stage of evolution of these phase-separated autocatalytic systems is the appearance of pre-biotic metabolism providing synthesis of amphiphiles for formation of capsules of these systems. This synthesis is maintained by the energy of a base reaction being a component of a planet-chemical cycle. Catalytic system providing functioning of pre-biotic metabolism is based on multivariate oligomeric autocatalyst, which reproduces itself from monomers, penetrating the particles from the outside. Since the autocatalyst realizes random polymerization then a collection of other oligomers possessing different catalytic functions is produced. In the paper the functioning of multivariate oligomeric autocatalyst in flow reactor is analyzed. c2005 Published by Elsevier Ltd on behalf of COSPAR.

  20. Development of a wireless computer vision instrument to detect biotic stress in wheat.

    Science.gov (United States)

    Casanova, Joaquin J; O'Shaughnessy, Susan A; Evett, Steven R; Rush, Charles M

    2014-09-23

    Knowledge of crop abiotic and biotic stress is important for optimal irrigation management. While spectral reflectance and infrared thermometry provide a means to quantify crop stress remotely, these measurements can be cumbersome. Computer vision offers an inexpensive way to remotely detect crop stress independent of vegetation cover. This paper presents a technique using computer vision to detect disease stress in wheat. Digital images of differentially stressed wheat were segmented into soil and vegetation pixels using expectation maximization (EM). In the first season, the algorithm to segment vegetation from soil and distinguish between healthy and stressed wheat was developed and tested using digital images taken in the field and later processed on a desktop computer. In the second season, a wireless camera with near real-time computer vision capabilities was tested in conjunction with the conventional camera and desktop computer. For wheat irrigated at different levels and inoculated with wheat streak mosaic virus (WSMV), vegetation hue determined by the EM algorithm showed significant effects from irrigation level and infection. Unstressed wheat had a higher hue (118.32) than stressed wheat (111.34). In the second season, the hue and cover measured by the wireless computer vision sensor showed significant effects from infection (p = 0.0014), as did the conventional camera (p computer vision system in this study is a viable option for determining biotic crop stress in irrigation scheduling. Such a low-cost system could be suitable for use in the field in automated irrigation scheduling applications.

  1. 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.

  2. 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.

  3. 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.

  4. An ecological role of fungal endophytes to ameliorate plants under biotic stress.

    Science.gov (United States)

    Chadha, Neha; Mishra, Manjita; Rajpal, Kartikeya; Bajaj, Ruchika; Choudhary, Devendra Kumar; Varma, Ajit

    2015-09-01

    It is our consensus that plants survive and flourish in stressed ecosystems because of endosymbiotic organisms that have co-evolved and were essential for their adaptation to changing environments. Some of these microbial components are noncultivable and vertically transmitted from generation to generation. They represent a vast reservoir of heritable DNA that can enhance plant performance in changing environments and add genetic flexibility to adaptation of long-lived plants. If such endophytes can be identified that not only persist in progeny of novel hosts, but can confer benefits in mechanized, agricultural systems, they would be increasingly important in agricultural production and lead to a rapid and economical method of providing novel germplasms of native and crop plants. In the present review, authors advocate the deployment of fungal diversity and its role to overcome the biotic stress in plants. Endophytic fungal association with plants helps it to protect from various pathogen and pests and adapt to survive in harsh biotic and abiotic stress condition.

  5. 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.

  6. Fragrance Allergens, Overview with a Focus on Recent Developments and Understanding of Abiotic and Biotic Activation

    Directory of Open Access Journals (Sweden)

    Johanna Bråred Christensson

    2016-06-01

    Full Text Available Fragrances and fragranced formulated products are ubiquitous in society. Contact allergies to fragrance chemicals are among the most common findings when patch-testing patients with suspected allergic contact dermatitis, as well as in studies of contact allergy in the general population. The routine test materials for diagnosing fragrance allergy consist mainly of established mixes of fragrance compounds and natural extracts. The situation is more complex as several fragrance compounds have been shown to be transformed by activation inside or outside the skin via abiotic and/or biotic activation, thus increasing the risk of sensitization. For these fragrance chemicals, the parent compound is often non-allergenic or a very weak allergen, but potent sensitizers will be formed which can cause contact allergy. This review shows a series of fragrance chemicals with well-documented abiotic and/or biotic activation that are indicative and illustrative examples of the general problem. Other important aspects include new technologies such as ethosomes which may enhance both sensitization and elicitation, the effect on sensitization by the mixtures of fragrances found in commercial products and the effect of antioxidants. A contact allergy to fragrances may severely affect quality of life and many patients have multiple allergies which further impact their situation. Further experimental and clinical research is needed to increase the safety for the consumer.

  7. Distribution of vascular epiphytes along a tropical elevational gradient: disentangling abiotic and biotic determinants.

    Science.gov (United States)

    Ding, Yi; Liu, Guangfu; Zang, Runguo; Zhang, Jian; Lu, Xinghui; Huang, Jihong

    2016-01-22

    Epiphytic vascular plants are common species in humid tropical forests. Epiphytes are influenced by abiotic and biotic variables, but little is known about the relative importance of direct and indirect effects on epiphyte distribution. We surveyed 70 transects (10 m × 50 m) along an elevation gradient (180 m-1521 m) and sampled all vascular epiphytes and trees in a typical tropical forest on Hainan Island, south China. The direct and indirect effects of abiotic factors (climatic and edaphic) and tree community characteristics on epiphytes species diversity were examined. The abundance and richness of vascular epiphytes generally showed a unimodal curve with elevation and reached maximum value at ca. 1300 m. The species composition in transects from high elevation (above 1200 m) showed a more similar assemblage. Climate explained the most variation in epiphytes species diversity followed by tree community characteristics and soil features. Overall, climate (relative humidity) and tree community characteristics (tree size represented by basal area) had the strongest direct effects on epiphyte diversity while soil variables (soil water content and available phosphorus) mainly had indirect effects. Our study suggests that air humidity is the most important abiotic while stand basal area is the most important biotic determinants of epiphyte diversity along the tropical elevational gradient.

  8. Understanding the Molecular Determinant of Reversible Human Monoamine Oxidase B Inhibitors Containing 2H-chromen-2-One Core: Structure-Based and Ligand-Based Derived 3-D QSAR Predictive Models.

    Science.gov (United States)

    Mladenovic, Milan; Patsilinakos, Alexandros; Pirolli, Adele; Sabatino, Manuela; Ragno, Rino

    2017-03-14

    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: (1) definition of optimized and validated structure-based (SB) 3-D QSAR models derived from available co-crystallized inhibitor-MAO B complexes; (2) elaboration of structure-activity relationships (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 rules 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 QSARs 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 result of rational SB/LB 3-D QSAR design

  9. 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.

  10. Predicting Electrophoretic Mobility of Protein-Ligand Complexes for Ligands from DNA-Encoded Libraries of Small Molecules.

    Science.gov (United States)

    Bao, Jiayin; Krylova, Svetlana M; Cherney, Leonid T; Hale, Robert L; Belyanskaya, Svetlana L; Chiu, Cynthia H; Shaginian, Alex; Arico-Muendel, Christopher C; Krylov, Sergey N

    2016-05-17

    Selection of target-binding ligands from DNA-encoded libraries of small molecules (DELSMs) is a rapidly developing approach in drug-lead discovery. Methods of kinetic capillary electrophoresis (KCE) may facilitate highly efficient homogeneous selection of ligands from DELSMs. However, KCE methods require accurate prediction of electrophoretic mobilities of protein-ligand complexes. Such prediction, in turn, requires a theory that would be applicable to DNA tags of different structures used in different DELSMs. Here we present such a theory. It utilizes a model of a globular protein connected, through a single point (small molecule), to a linear DNA tag containing a combination of alternating double-stranded and single-stranded DNA (dsDNA and ssDNA) regions of varying lengths. The theory links the unknown electrophoretic mobility of protein-DNA complex with experimentally determined electrophoretic mobilities of the protein and DNA. Mobility prediction was initially tested by using a protein interacting with 18 ligands of various combinations of dsDNA and ssDNA regions, which mimicked different DELSMs. For all studied ligands, deviation of the predicted mobility from the experimentally determined value was within 11%. Finally, the prediction was tested for two proteins and two ligands with a DNA tag identical to those of DELSM manufactured by GlaxoSmithKline. Deviation between the predicted and experimentally determined mobilities did not exceed 5%. These results confirm the accuracy and robustness of our model, which makes KCE methods one step closer to their practical use in selection of drug leads, and diagnostic probes from DELSMs.

  11. 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.

  12. Evaluation of nanoparticle-ligand distributions to determine nanoparticle concentration.

    Science.gov (United States)

    Uddayasankar, Uvaraj; Shergill, Ravi T; Krull, Ulrich J

    2015-01-20

    The concentration of nanoparticles in solution is an important, yet challenging, parameter to quantify. In this work, a facile strategy for the determination of nanoparticle concentration is presented. The method relies on the quantitative analysis of the inherent distribution of nanoparticle-ligand conjugates that are generated when nanoparticles are functionalized with ligands. Validation of the method was accomplished by applying it to gold nanoparticles and semiconductor nanoparticles (CdSe/ZnS; core/shell). Poly(ethylene glycol) based ligands, with functional groups that quantitatively react with the nanoparticles, were incubated with the nanoparticles at varying equivalences. Agarose gel electrophoresis was subsequently used to separate and quantify the nanoparticle-ligand conjugates of varying valences. The distribution in the nanoparticle-ligand conjugates agreed well with that predicted by the Poisson model. A protocol was then developed, where a series of only eight different ligand amounts could provide an estimate of the nanoparticle concentration that spans 3 orders of magnitude (1 μM to 1 mM). For the gold nanoparticles and semiconductor nanoparticles, the measured concentrations were found to deviate by only 7% and 2%, respectively, from those determined by UV-vis spectroscopy. The precision of the assay was evaluated, resulting in a coefficient of variation of 5-7%. Finally, the protocol was used to determine the extinction coefficient of alloyed semiconductor nanoparticles (CdSxSe1-x/ZnS), for which a reliable estimate is currently unavailable, of three different emission wavelengths (525, 575, and 630 nm). The extinction coefficient of the nanoparticles of all emission wavelengths was similar and was found to be 2.1 × 10(5) M(-1)cm(-1).

  13. CB receptor ligands from plants.

    Science.gov (United States)

    Woelkart, Karin; Salo-Ahen, Outi M H; Bauer, Rudolf

    2008-01-01

    Advances in understanding the physiology and pharmacology of the endogenous cannabinoid system have potentiated the interest of cannabinoid receptors as potential therapeutic targets. Cannabinoids have been shown to modulate a variety of immune cell functions and have therapeutic implications on central nervous system (CNS) inflammation, chronic inflammatory conditions such as arthritis, and may be therapeutically useful in treating autoimmune conditions such as multiple sclerosis. Many of these drug effects occur through cannabinoid receptor signalling mechanisms and the modulation of cytokines and other gene products. Further, endocannabinoids have been found to have many physiological and patho-physiological functions, including mood alteration and analgesia, control of energy balance, gut motility, motor and co-ordination activities, as well as alleviation of neurological, psychiatric and eating disorders. Plants offer a wide range of chemical diversity and have been a growing domain in the search for effective cannabinoid ligands. Cannabis sativa L. with the known plant cannabinoid, Delta(9-)tetrahydrocannabinol (THC) and Echinacea species with the cannabinoid (CB) receptor-binding lipophilic alkamides are the best known herbal cannabimimetics. This review focuses on the state of the art in CB ligands from plants, as well their possible therapeutic and immunomodulatory effects.

  14. 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.

  15. Central nicotinic receptors: structure, function, ligands, and therapeutic potential.

    Science.gov (United States)

    Romanelli, M Novella; Gratteri, Paola; Guandalini, Luca; Martini, Elisabetta; Bonaccini, Claudia; Gualtieri, Fulvio

    2007-06-01

    The growing interest in nicotinic receptors, because of their wide expression in neuronal and non-neuronal tissues and their involvement in several important CNS pathologies, has stimulated the synthesis of a high number of ligands able to modulate their function. These membrane proteins appear to be highly heterogeneous, and still only incomplete information is available on their structure, subunit composition, and stoichiometry. This is due to the lack of selective ligands to study the role of nAChR under physiological or pathological conditions; so far, only compounds showing selectivity between alpha4beta2 and alpha7 receptors have been obtained. The nicotinic receptor ligands have been designed starting from lead compounds from natural sources such as nicotine, cytisine, or epibatidine, and, more recently, through the high-throughput screening of chemical libraries. This review focuses on the structure of the new agonists, antagonists, and allosteric ligands of nicotinic receptors, it highlights the current knowledge on the binding site models as a molecular modeling approach to design new compounds, and it discusses the nAChR modulators which have entered clinical trials.

  16. Measurement of protein-ligand complex formation.

    Science.gov (United States)

    Lowe, Peter N; Vaughan, Cara K; Daviter, Tina

    2013-01-01

    Experimental approaches to detect, measure, and quantify protein-ligand binding, along with their theoretical bases, are described. A range of methods for detection of protein-ligand interactions is summarized. Specific protocols are provided for a nonequilibrium procedure pull-down assay, for an equilibrium direct binding method and its modification into a competition-based measurement and for steady-state measurements based on the effects of ligands on enzyme catalysis.

  17. Environmental Selenium Transformations: Distinguishing Abiotic and Biotic Factors Influencing Se Redox Transformations

    Science.gov (United States)

    Rosenfeld, C.; Kenyon, J.; James, B. R.; Santelli, C. M.

    2014-12-01

    Worldwide, selenium (Se) is proving to be a significant environmental concern, with many anthropogenic activities (e.g. coal mining and combustion, phosphate mining and agricultural irrigation) releasing potentially hazardous concentrations into surface and subsurface ecosystems. The US EPA is currently considering aquatic Se regulations, however no guidelines exist for excess soil Se, despite its ability to act as a persistent Se source. Various abiotic and biological processes mediate Se oxidation/reduction (redox) transformations in soils, thus influencing its solubility and bioavailability. In this research we assess (1) the ability of metal-transforming fungal species to aerobically reduce Se (Se (IV and/or VI) to Se(0)), and (2) the relative contribution of biotic and abiotic pathways for aerobic Se transformation. The primary objective of this research is to determine what abiotic and biotic factors enhance or restrict Se bioavailability. Results indicate that fungal-mediated Se reduction may be quite widespread, with at least 7 out of 10 species of known Mn(II)-oxidizing fungi isolated from metal impacted environments also identified as capable of aerobically reducing Se(IV) and/or Se(VI) to Se(0). Increasing concentrations of selenite (SeO32-; Se(IV)) and selenate (SeO42-; Se(VI)) generally reduced fungal growth rates, although selenate was more likely to inhibit fungal growth than selenite. To study oxidation, Se(0) was combined with Mn(III/IV) (hydr)oxides (henceforth referred to as Mn oxides), Se-transforming fungi (Alternaria alternata), and oxalic acid to mimic Se biogeochemistry at the plant-soil interface. Increased pH in the presence of fungi (7.2 with fungi, 6.8 without fungi after 24 days) was observed. Additionally, a slight decrease in redox potential was measured for incubations without Mn oxides (236 mV with Mn oxides, 205 mV without Mn oxides after 24 days), indicating that Mn oxides may enhance Se oxidation. Elemental Se oxidation rates to

  18. Regional consequences of a biotic interchange: insights from the Lessepsian invasion

    Science.gov (United States)

    Nawrot, Rafal; Albano, Paolo G.; Chattopadhyay, Devapriya; Zuschin, Martin

    2016-04-01

    The fossil record provides ample evidence of large-scale biotic interchanges and their pervasive effects on regional biotas, but mechanisms controlling such events are difficult to decipher in deep time. Massive invasion of Indo-Pacific species into the Mediterranean Sea triggered by the opening of the Suez Canal offers a unique opportunity to examine the ecological consequences of breaking down biogeographic barriers. We developed an extensive database of taxonomic composition, body size and ecological characteristics of the Red Sea and Mediterranean bivalve fauna in order to link biotic selectivity of the invasion process with its effects on the recipient biota. Shallow-water occurrence and presence outside the tropical zone in other regions are the strongest predictors of the successful transition through the Suez Canal. Subsequent establishment of alien species in the Mediterranean Sea correlates with early arrival and preference for hard substrates. Finally, large-bodied species and hard-bottom dwellers are over-represented among the invasive aliens that have reached the spread stage and impose a strong impact on native communities. Although body size is important only at the last invasion stage, alien species are significantly larger compared to native Mediterranean bivalves. This reflects biogeographic difference in the body-size distributions of the source and recipient species pools related to the recent geological history of the Mediterranean Sea. Contrary to the general expectations on the effects of temperature on average body size, continued warming of the Mediterranean Sea accelerates the entry of tropical aliens and thus indirectly leads to increase in the proportion of large-bodied species in local communities and the regional biota. Invasion-driven shifts in species composition are stronger in hard-substrate communities, which host a smaller pool of incumbent species and are more susceptible to the establishment of newcomers. Analogous differences

  19. A Big Bang or small bangs? Effects of biotic environment on hatching

    Directory of Open Access Journals (Sweden)

    Marina MANCA

    2008-08-01

    Full Text Available The beginning and end of diapause are two important transition points in cladoceran life history. The influence of environmental variables on the dynamics of these processes still deserves attention, especially as concerns the role of biotic factors. In this paper we focus on emergence from diapause, testing (1 whether ephippia of Daphnia obtusa Kurz can assess the presence in the water of typical planktivorous fish or ostracods, and (2 whether such an assessment results in changes in hatching strategy. Total number of hatchlings from D. obtusa ephippial eggs did not differ between the control and the treatments in which the presence of fish or ostracods could be detected (ANOVA, P = 0.884. However, hatching dynamics were different: most of the eggs hatched synchronously at day 4 (83.3% of the total hatchlings number in the control, while only a low proportion of eggs hatched on day 4 in the fish (38.3%, and ostracod treatments (24.0% of the total. Mean hatching time was longer, and variability larger, in the treatments than in the control; differences resulted statistically significant (ANOVA, P = 0.005. With respect to the control, representing a simple microcosm controlled by abiotic variables only, the treatments may be regarded as relatively complex environments, in which Daphnia is also exposed to biotic cues. Under these more complex conditions, the same number of hatchlings is obtained through different hatching dynamics. In the treatments, the first hatchlings appeared later and the hatching rate was more variable than in the control. These observations confirm previously observed patterns from laboratory experiments which tested the effect of competition and fluctuating environmental conditions (light:dark, temperature regimes on D. obtusa reproductive and demographic parameters. They are also in agreement with recently obtained evidence concerning the importance of biotic cues for hatching of ephippial eggs. Overall, the evidence

  20. Semiempirical modeling of abiotic and biotic factors controlling ecosystem respiration across eddy covariance sites

    NARCIS (Netherlands)

    Migliavacca, M.; Reichstein, M.; Richardson, A.D.; Colombo, R.; Sutton, M.A.; Lasslop, G.; Tomelleri, E.; Wohlfahrt, G.; Carvalhais, N.; Molen, van der M.K.

    2011-01-01

    In this study we examined ecosystem respiration (RECO) data from 104 sites belonging to FLUXNET, the global network of eddy covariance flux measurements. The goal was to identify the main factors involved in the variability of RECO: temporally and between sites as affected by climate, vegetation str

  1. Ligand-based identification of environmental estrogens

    Energy Technology Data Exchange (ETDEWEB)

    Waller, C.L. [Environmental Protection Agency, Research Triangle Park, NC (United States); Oprea, T.I. [Los Alamos National Lab., NM (United States); Chae, K. [National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States)] [and others

    1996-12-01

    Comparative molecular field analysis (CoMFA), a three-dimensional quantitative structure-activity relationship (3D-QSAR) paradigm, was used to e