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Sample records for homology-dependent interactions determine

  1. Homology-dependent gene silencing and host defense in plants.

    PubMed

    Matzke, Marjori A; Aufsatz, Werner; Kanno, Tatsuo; Mette, M Florian; Matzke, Antonius J M

    2002-01-01

    Analyses of transgene silencing phenomena in plants and other organisms have revealed the existence of epigenetic silencing mechanisms that are based on recognition of nucleic acid sequence homology at either the DNA or RNA level. Common triggers of homology-dependent gene silencing include inverted DNA repeats and double-stranded RNA, a versatile silencing molecule that can induce both degradation of homologous RNA in the cytoplasm and methylation of homologous DNA sequences in the nucleus. Inverted repeats might be frequently associated with silencing because they can potentially interact in cis and in trans to trigger DNA methylation via homologous DNA pairing, or they can be transcribed to produce double-stranded RNA. Homology-dependent gene silencing mechanisms are ideally suited for countering natural parasitic sequences such as transposable elements and viruses, which are usually present in multiple copies and/or produce double-stranded RNA during replication. These silencing mechanisms can thus be regarded as host defense strategies to foreign or invasive nucleic acids. The high content of transposable elements and, in some cases, endogenous viruses in many plant genomes suggests that host defenses do not always prevail over invasive sequences. During evolution, slightly faulty genome defense responses probably allowed transposable elements and viral sequences to accumulate gradually in host chromosomes and to invade host genes. Possible beneficial consequences of this "foreign" DNA buildup include the establishment of genome defense-derived epigenetic control mechanisms for regulating host gene expression and acquired hereditary immunity to some viruses.

  2. Non-Mendelian inheritance and homology-dependent effects in ciliates.

    PubMed

    Meyer, Eric; Garnier, Olivier

    2002-01-01

    Ciliates are single-celled eukaryotes that harbor two kinds of nuclei. The germline micronuclei function only to perpetuate the genome during sexual reproduction; the macronuclei are polyploid, somatic nuclei that differentiate from the micronuclear lineage at each sexual generation. Macronuclear development involves extensive and reproducible rearrangements of the genome, including chromosome fragmentation and precise excision of numerous internal sequence elements. In Paramecium and Tetrahymena, homology-dependent maternal effects have been evidenced by transformation of the vegetative macronucleus with germline sequences containing internal eliminated sequences (short single-copy elements), which can result in a specific inhibition of the excision of the homologous elements during development of a new macronucleus in the sexual progeny of transformed clones. Furthermore, transformation of the Paramecium maternal macronucleus with cloned macronuclear sequences can specifically induce new fragmentation patterns or internal deletions in the zygotic macronucleus. These experiments show that the processing of many germline sequences in the developing macronucleus is sensitive to the presence and copy number of homologous sequences in the maternal macronucleus. The generality and sequence specificity of this transnuclear, epigenetic regulation of rearrangements suggest that it is mediated by pairing interactions between zygotic sequences and sequences originating from the maternal macronucleus, presumably RNA molecules. Alternative macronuclear versions of the genome can be maternally inherited across sexual generations, suggesting a molecular model for some of the long-known cases of non-Mendelian inheritance, and in particular for the developmental determination and maternal inheritance of mating types in Paramecium tetraurelia.

  3. Homology-Dependent Silencing by an Exogenous Sequence in the Drosophila Germline

    PubMed Central

    Pöyhönen, Maria; de Vanssay, Augustin; Delmarre, Valérie; Hermant, Catherine; Todeschini, Anne Laure; Teysset, Laure; Ronsseray, Stéphane

    2012-01-01

    The study of P transposable element repression in Drosophila melanogaster led to the discovery of the trans-silencing effect (TSE), a homology-dependent repression mechanism by which a P-transgene inserted in subtelomeric heterochromatin (Telomeric Associated Sequences) represses in trans, in the female germline, a homologous P-lacZ transgene inserted in euchromatin. TSE shows variegation in ovaries and displays a maternal effect as well as epigenetic transmission through meiosis. In addition, TSE is highly sensitive to mutations affecting heterochromatin components (including HP1) and the Piwi-interacting RNA silencing pathway (piRNA), a homology-dependent silencing mechanism that functions in the germline. TSE appears thus to involve the piRNA-based silencing proposed to play a major role in P repression. Under this hypothesis, TSE may also be established when homology between the telomeric and target loci involves sequences other than P elements, including sequences exogenous to the D. melanogaster genome. We have tested whether TSE can be induced via lacZ sequence homology. We generated a piggyBac-otu-lacZ transgene in which lacZ is under the control of the germline ovarian tumor promoter, resulting in strong expression in nurse cells and the oocyte. We show that all piggyBac-otu-lacZ transgene insertions are strongly repressed by maternally inherited telomeric P-lacZ transgenes. This repression shows variegation between egg chambers when it is incomplete and presents a maternal effect, two of the signatures of TSE. Finally, this repression is sensitive to mutations affecting aubergine, a key player of the piRNA pathway. These data show that TSE can occur when silencer and target loci share solely a sequence exogenous to the D. melanogaster genome. This functionally supports the hypothesis that TSE represents a general repression mechanism which can be co-opted by new transposable elements to regulate their activity after a transfer to the D. melanogaster

  4. Genomic assay reveals tolerance of DNA damage by both translesion DNA synthesis and homology-dependent repair in mammalian cells.

    PubMed

    Izhar, Lior; Ziv, Omer; Cohen, Isadora S; Geacintov, Nicholas E; Livneh, Zvi

    2013-04-16

    DNA lesions can block replication forks and lead to the formation of single-stranded gaps. These replication complications are mitigated by DNA damage tolerance mechanisms, which prevent deleterious outcomes such as cell death, genomic instability, and carcinogenesis. The two main tolerance strategies are translesion DNA synthesis (TLS), in which low-fidelity DNA polymerases bypass the blocking lesion, and homology-dependent repair (HDR; postreplication repair), which is based on the homologous sister chromatid. Here we describe a unique high-resolution method for the simultaneous analysis of TLS and HDR across defined DNA lesions in mammalian genomes. The method is based on insertion of plasmids carrying defined site-specific DNA lesions into mammalian chromosomes, using phage integrase-mediated integration. Using this method we show that mammalian cells use HDR to tolerate DNA damage in their genome. Moreover, analysis of the tolerance of the UV light-induced 6-4 photoproduct, the tobacco smoke-induced benzo[a]pyrene-guanine adduct, and an artificial trimethylene insert shows that each of these three lesions is tolerated by both TLS and HDR. We also determined the specificity of nucleotide insertion opposite these lesions during TLS in human genomes. This unique method will be useful in elucidating the mechanism of DNA damage tolerance in mammalian chromosomes and their connection to pathological processes such as carcinogenesis.

  5. Solvent interactions determine carbohydrate conformation

    PubMed Central

    Kirschner, Karl N.; Woods, Robert J.

    2001-01-01

    The relationship between the three-dimensional structures of oligosaccharides and polysaccharides and their biological properties has been the focus of many recent studies. The overall conformation of an oligosaccharide depends primarily on the orientation of the torsion angles (φ, ψ, and ω) between glycosyl residues. Numerous experimental studies have shown that in glucopyranosides the ω-torsion angle (O6-C6-C5-O5) displays a preference for gauche orientations, in disagreement with predictions based on gas-phase quantum mechanics calculations. In contrast, the ω-angle in galactopyranosides displays a high proportion of the anti-orientation. For oligosaccharides containing glycosidic linkages at the 6-position (1→6 linked), variations in rotamer population have a direct effect on the oligosaccharides' structure and function, and yet the physical origin of these conformational preferences remains unclear. Although it is generally recognized that the gauche effect in carbohydrates is a solvent-dependent phenomenon, the mechanism through which solvent induces the gauche preference is not understood. In the present work, quantum mechanics and solvated molecular dynamics calculations were performed on two representative carbohydrates, methyl α-d-glucopyranoside and methyl α-d-galactopyranoside. We show that correct reproduction of the experimental rotamer distributions about the ω-angles is obtained only after explicit water is included in the molecular dynamics simulations. The primary role of the water appears to be to disrupt the hydrogen bonding within the carbohydrate, thereby allowing the rotamer populations to be determined by internal electronic and steric repulsions between the oxygen atoms. The results reported here provide a quantitative explanation of the conformational behavior of (1→6)-linked carbohydrates. PMID:11526221

  6. Identification of viruses and viroids by next-generation sequencing and homology-dependent and homology-independent algorithms.

    PubMed

    Wu, Qingfa; Ding, Shou-Wei; Zhang, Yongjiang; Zhu, Shuifang

    2015-01-01

    A fast, accurate, and full indexing of viruses and viroids in a sample for the inspection and quarantine services and disease management is desirable but was unrealistic until recently. This article reviews the rapid and exciting recent progress in the use of next-generation sequencing (NGS) technologies for the identification of viruses and viroids in plants. A total of four viroids/viroid-like RNAs and 49 new plant RNA and DNA viruses from 18 known or unassigned virus families have been identified from plants since 2009. A comparison of enrichment strategies reveals that full indexing of RNA and DNA viruses as well as viroids in a plant sample at single-nucleotide resolution is made possible by one NGS run of total small RNAs, followed by data mining with homology-dependent and homology-independent computational algorithms. Major challenges in the application of NGS technologies to pathogen discovery are discussed.

  7. Three-baryon interaction generated by determinant interaction of quarks

    NASA Astrophysics Data System (ADS)

    Ohnishi, Akira; Kashiwa, Kouji; Morita, Kenji

    2017-07-01

    We discuss the 3-baryon interaction generated by the determinant interaction of quarks, known as the Kobayashi-Maskawa-'t Hooft (KMT) interaction. The expectation value of the KMT interaction operator is calculated in fully antisymmetrized quark-cluster model wave functions for 1-, 2-, and 3-octet-baryon states. The 3-baryon potential from the KMT interaction is found to be repulsive for NNΛ and NΛΛ systems, while it is zero for the NNN system. The strength and range of the 3-baryon potential are found to be comparable to those for the NNN 3-body potential obtained in lattice QCD simulations. The contribution to the Λ single particle potential in nuclear matter is found to be 0.28{ MeV} and 0.73{ MeV} in neutron matter and symmetric nuclear matter at normal nuclear density, respectively. These repulsive forces are not enough to solve the hyperon puzzle, but may be measured in high-precision hyperisotope experiments.

  8. Glycan Determinants of Heparin-Tau Interaction.

    PubMed

    Zhao, Jing; Huvent, Isabelle; Lippens, Guy; Eliezer, David; Zhang, Anqiang; Li, Quanhong; Tessier, Peter; Linhardt, Robert J; Zhang, Fuming; Wang, Chunyu

    2017-03-14

    Tau aggregates into paired helical filaments within neurons, a pathological hallmark of Alzheimer's disease. Heparin promotes tau aggregation and recently has been shown to be involved in the cellular uptake of tau aggregates. Although the tau-heparin interaction has been extensively studied, little is known about the glycan determinants of this interaction. Here, we used surface plasmon resonance (SPR) and NMR spectroscopy to characterize the interaction between two tau fragments, K18 and K19, and several polysaccharides, including heparin, heparin oligosaccharides, chemically modified heparin, and related glycans. Using a heparin-immobilized chip, SPR revealed that tau K18 and K19 bind heparin with a KD of 0.2 and 70 μM, respectively. In SPR competition experiments, N-desulfation and 2-O-desulfation had no effect on heparin binding to K18, whereas 6-O-desulfation severely reduced binding, suggesting a critical role for 6-O-sulfation in the tau-heparin interaction. The tau-heparin interaction became stronger with longer-chain heparin oligosaccharides. As expected for an electrostatics-driven interaction, a moderate amount of salt (0.3 M NaCl) abolished binding. NMR showed the largest chemical-shift perturbation (CSP) in R2 in tau K18, which was absent in K19, revealing differential binding sites in K18 and K19 to heparin. Dermatan sulfate binding produced minimal CSP, whereas dermatan disulfate, with the additional 6-O-sulfo group, induced much larger CSP. 2-O-desulfated heparin induced much larger CSP in K18 than 6-O-desulfated heparin. Our data demonstrate a crucial role for the 6-O-sulfo group in the tau-heparin interaction, which to our knowledge has not been reported before.

  9. Homology-dependent repair is involved in 45S rDNA loss in plant CAF-1 mutants.

    PubMed

    Muchová, Veronika; Amiard, Simon; Mozgová, Iva; Dvořáčková, Martina; Gallego, Maria E; White, Charles; Fajkus, Jiří

    2015-01-01

    Arabidopsis thaliana mutants in FAS1 and FAS2 subunits of chromatin assembly factor 1 (CAF1) show progressive loss of 45S rDNA copies and telomeres. We hypothesized that homology-dependent DNA damage repair (HDR) may contribute to the loss of these repeats in fas mutants. To test this, we generated double mutants by crossing fas mutants with knock-out mutants in RAD51B, one of the Rad51 paralogs of A. thaliana. Our results show that the absence of RAD51B decreases the rate of rDNA loss, confirming the implication of RAD51B-dependent recombination in rDNA loss in the CAF1 mutants. Interestingly, this effect is not observed for telomeric repeat loss, which thus differs from that acting in rDNA loss. Involvement of DNA damage repair in rDNA dynamics in fas mutants is further supported by accumulation of double-stranded breaks (measured as γ-H2AX foci) in 45S rDNA. Occurrence of the foci is not specific for S-phase, and is ATM-independent. While the foci in fas mutants occur both in the transcribed (intranucleolar) and non-transcribed (nucleoplasmic) fraction of rDNA, double fas rad51b mutants show a specific increase in the number of the intranucleolar foci. These results suggest that the repair of double-stranded breaks present in the transcribed rDNA region is RAD51B dependent and that this contributes to rDNA repeat loss in fas mutants, presumably via the single-stranded annealing recombination pathway. Our results also highlight the importance of proper chromatin assembly in the maintenance of genome stability.

  10. The Arabidopsis HOMOLOGY-DEPENDENT GENE SILENCING1 Gene Codes for an S-Adenosyl-l-Homocysteine Hydrolase Required for DNA Methylation-Dependent Gene Silencing

    PubMed Central

    Rocha, Pedro S.C.F.; Sheikh, Mazhar; Melchiorre, Rosalba; Fagard, Mathilde; Boutet, Stéphanie; Loach, Rebecca; Moffatt, Barbara; Wagner, Conrad; Vaucheret, Hervé; Furner, Ian

    2005-01-01

    Genes introduced into higher plant genomes can become silent (gene silencing) and/or cause silencing of homologous genes at unlinked sites (homology-dependent gene silencing or HDG silencing). Mutations of the HOMOLOGY-DEPENDENT GENE SILENCING1 (HOG1) locus relieve transcriptional gene silencing and methylation-dependent HDG silencing and result in genome-wide demethylation. The hog1 mutant plants also grow slowly and have low fertility and reduced seed germination. Three independent mutants of HOG1 were each found to have point mutations at the 3′ end of a gene coding for S-adenosyl-l-homocysteine (SAH) hydrolase, and hog1-1 plants show reduced SAH hydrolase activity. A transposon (hog1-4) and a T-DNA tag (hog1-5) in the HOG1 gene each behaved as zygotic embryo lethal mutants and could not be made homozygous. The results suggest that the homozygous hog1 point mutants are leaky and result in genome demethylation and poor growth and that homozygous insertion mutations result in zygotic lethality. Complementation of the hog1-1 point mutation with a T-DNA containing the gene coding for SAH hydrolase restored gene silencing, HDG silencing, DNA methylation, fast growth, and normal seed viability. The same T-DNA also complemented the zygotic embryo lethal phenotype of the hog1-4 tagged mutant. A model relating the HOG1 gene, DNA methylation, and methylation-dependent HDG silencing is presented. PMID:15659630

  11. β-HPV 5 and 8 E6 Disrupt Homology Dependent Double Strand Break Repair by Attenuating BRCA1 and BRCA2 Expression and Foci Formation

    PubMed Central

    Wallace, Nicholas A.; Robinson, Kristin; Howie, Heather L.; Galloway, Denise A.

    2015-01-01

    Recent work has explored a putative role for the E6 protein from some β-human papillomavirus genus (β-HPVs) in the development of non-melanoma skin cancers, specifically β-HPV 5 and 8 E6. Because these viruses are not required for tumor maintenance, they are hypothesized to act as co-factors that enhance the mutagenic capacity of UV-exposure by disrupting the repair of the resulting DNA damage. Supporting this proposal, we have previously demonstrated that UV damage signaling is hindered by β-HPV 5 and 8 E6 resulting in an increase in both thymine dimers and UV-induced double strand breaks (DSBs). Here we show that β-HPV 5 and 8 E6 further disrupt the repair of these DSBs and provide a mechanism for this attenuation. By binding and destabilizing a histone acetyltransferase, p300, β-HPV 5 and 8 E6 reduce the enrichment of the transcription factor at the promoter of two genes critical to the homology dependent repair of DSBs (BRCA1 and BRCA2). The resulting diminished BRCA1/2 transcription not only leads to lower protein levels but also curtails the ability of these proteins to form repair foci at DSBs. Using a GFP-based reporter, we confirm that this reduced foci formation leads to significantly diminished homology dependent repair of DSBs. By deleting the p300 binding domain of β-HPV 8 E6, we demonstrate that the loss of robust repair is dependent on viral-mediated degradation of p300 and confirm this observation using a combination of p300 mutants that are β-HPV 8 E6 destabilization resistant and p300 knock-out cells. In conclusion, this work establishes an expanded ability of β-HPV 5 and 8 E6 to attenuate UV damage repair, thus adding further support to the hypothesis that β-HPV infections play a role in skin cancer development by increasing the oncogenic potential of UV exposure. PMID:25803638

  12. Biomaterial surface proteomic signature determines interaction with epithelial cells.

    PubMed

    Abdallah, Mohamed-Nur; Tran, Simon D; Abughanam, Ghada; Laurenti, Marco; Zuanazzi, David; Mezour, Mohamed A; Xiao, Yizhi; Cerruti, Marta; Siqueira, Walter L; Tamimi, Faleh

    2017-03-01

    Cells interact with biomaterials indirectly through extracellular matrix (ECM) proteins adsorbed onto their surface. Accordingly, it could be hypothesized that the surface proteomic signature of a biomaterial might determine its interaction with cells. Here, we present a surface proteomic approach to test this hypothesis in the specific case of biomaterial-epithelial cell interactions. In particular, we determined the surface proteomic signature of different biomaterials exposed to the ECM of epithelial cells (basal lamina). We revealed that the biomaterial surface chemistry determines the surface proteomic profile, and subsequently the interaction with epithelial cells. In addition, we found that biomaterials with surface chemistries closer to that of percutaneous tissues, such as aminated PMMA and aminated PDLLA, promoted higher selective adsorption of key basal lamina proteins (laminins, nidogen-1) and subsequently improved their interactions with epithelial cells. These findings suggest that mimicking the surface chemistry of natural percutaneous tissues can improve biomaterial-epithelial integration, and thus provide a rationale for the design of improved biomaterial surfaces for skin regeneration and percutaneous medical devices.

  13. Interspecies interactions are an integral determinant of microbial community dynamics

    PubMed Central

    Aziz, Fatma A. A.; Suzuki, Kenshi; Ohtaki, Akihiro; Sagegami, Keita; Hirai, Hidetaka; Seno, Jun; Mizuno, Naoko; Inuzuka, Yuma; Saito, Yasuhisa; Tashiro, Yosuke; Hiraishi, Akira; Futamata, Hiroyuki

    2015-01-01

    This study investigated the factors that determine the dynamics of bacterial communities in a complex system using multidisciplinary methods. Since natural and engineered microbial ecosystems are too complex to study, six types of synthetic microbial ecosystems (SMEs) were constructed under chemostat conditions with phenol as the sole carbon and energy source. Two to four phenol-degrading, phylogenetically and physiologically different bacterial strains were used in each SME. Phylogeny was based on the nucleotide sequence of 16S rRNA genes, while physiologic traits were based on kinetic and growth parameters on phenol. Two indices, J parameter and “interspecies interaction,” were compared to predict which strain would become dominant in an SME. The J parameter was calculated from kinetic and growth parameters. On the other hand, “interspecies interaction,” a new index proposed in this study, was evaluated by measuring the specific growth activity, which was determined on the basis of relative growth of a strain with or without the supernatant prepared from other bacterial cultures. Population densities of strains used in SMEs were enumerated by real-time quantitative PCR (qPCR) targeting the gene encoding the large subunit of phenol hydroxylase and were compared to predictions made from J parameter and interspecies interaction calculations. In 4 of 6 SEMs tested the final dominant strain shown by real-time qPCR analyses coincided with the strain predicted by both the J parameter and the interspecies interaction. However, in SMEII-2 and SMEII-3 the final dominant Variovorax strains coincided with prediction of the interspecies interaction but not the J parameter. These results demonstrate that the effects of interspecies interactions within microbial communities contribute to determining the dynamics of the microbial ecosystem. PMID:26539177

  14. Consumer species richness and nutrients interact in determining producer diversity

    PubMed Central

    Groendahl, Sophie; Fink, Patrick

    2017-01-01

    While it is crucial to understand the factors that determine the biodiversity of primary producer communities, the relative importance of bottom-up and top-down control factors is still poorly understood. Using freshwater benthic algal communities in the laboratory as a model system, we find an unimodal relationship between nutrient availability and producer diversity, and that increasing number of consumer species increases producer diversity, but overall grazing decreases algal biodiversity. Interestingly, these two factors interact strongly in determining producer diversity, as an increase in nutrient supply diminishes the positive effect of consumer species richness on producer biodiversity. This novel and thus-far overlooked interaction of bottom-up and top-down control mechanisms of biodiversity may have a pronounced impact on ecosystem functioning and thus have repercussions for the fields of biodiversity conservation and restoration. PMID:28303953

  15. Determination Quantification of Molecular Interactions in Protein Films: A Review

    PubMed Central

    Hammann, Felicia; Schmid, Markus

    2014-01-01

    Protein based films are nowadays also prepared with the aim of replacing expensive, crude oil-based polymers as environmentally friendly and renewable alternatives. The protein structure determines the ability of protein chains to form intra- and intermolecular bonds, whereas the degree of cross-linking depends on the amino acid composition and molecular weight of the protein, besides the conditions used in film preparation and processing. The functionality varies significantly depending on the type of protein and affects the resulting film quality and properties. This paper reviews the methods used in examination of molecular interactions in protein films and discusses how these intermolecular interactions can be quantified. The qualitative determination methods can be distinguished by structural analysis of solutions (electrophoretic analysis, size exclusion chromatography) and analysis of solid films (spectroscopy techniques, X-ray scattering methods). To quantify molecular interactions involved, two methods were found to be the most suitable: protein film swelling and solubility. The importance of non-covalent and covalent interactions in protein films can be investigated using different solvents. The research was focused on whey protein, whereas soy protein and wheat gluten were included as further examples of proteins. PMID:28788285

  16. Nuclear matter radii determined by interaction cross sections

    SciTech Connect

    Ozawa, A.

    2005-10-19

    Experimental studies on nuclear matter radii determined by the interaction cross sections ({sigma}I) are reviewed. In particular, the procedure to determine the root-mean square matter radii from the measured {sigma}I by Galuber model analysis is described. Future {sigma}I measurements at the RI beam factory (RIBF) in RIKEN are introduced. As new calculations, the sensitivity of the skin is discussed in the case with a proton target based on Glauber-model calculations. In the energy region of RIBF, {sigma}I is sensitive for the skin; however, measurements with high accuracies are needed.

  17. Neutrino-nucleus interactions and the determination of oscillation parameters

    NASA Astrophysics Data System (ADS)

    Benhar, Omar; Huber, Patrick; Mariani, Camillo; Meloni, Davide

    2017-07-01

    We review the status and prospects of theoretical studies of neutrino-nucleus interactions, and discuss the influence of the treatment of nuclear effects on the determination of oscillation parameters. The models developed to describe the variety of reaction mechanisms contributing to the nuclear cross sections are analyzed, with emphasis placed on their capability to explain the large body of available electron scattering data. The impact of the uncertainties associated with the description of nuclear structure and dynamics on the determination of oscillation parameters is illustrated through examples, and possible avenues towards a better understanding of the signals detected by accelerator-based experiments are outlined.

  18. Determination of protein-ligand interactions using differential scanning fluorimetry.

    PubMed

    Vivoli, Mirella; Novak, Halina R; Littlechild, Jennifer A; Harmer, Nicholas J

    2014-09-13

    A wide range of methods are currently available for determining the dissociation constant between a protein and interacting small molecules. However, most of these require access to specialist equipment, and often require a degree of expertise to effectively establish reliable experiments and analyze data. Differential scanning fluorimetry (DSF) is being increasingly used as a robust method for initial screening of proteins for interacting small molecules, either for identifying physiological partners or for hit discovery. This technique has the advantage that it requires only a PCR machine suitable for quantitative PCR, and so suitable instrumentation is available in most institutions; an excellent range of protocols are already available; and there are strong precedents in the literature for multiple uses of the method. Past work has proposed several means of calculating dissociation constants from DSF data, but these are mathematically demanding. Here, we demonstrate a method for estimating dissociation constants from a moderate amount of DSF experimental data. These data can typically be collected and analyzed within a single day. We demonstrate how different models can be used to fit data collected from simple binding events, and where cooperative binding or independent binding sites are present. Finally, we present an example of data analysis in a case where standard models do not apply. These methods are illustrated with data collected on commercially available control proteins, and two proteins from our research program. Overall, our method provides a straightforward way for researchers to rapidly gain further insight into protein-ligand interactions using DSF.

  19. Particle-Surface Interaction Model and Method of Determining Particle-Surface Interactions

    NASA Technical Reports Server (NTRS)

    Hughes, David W. (Inventor)

    2012-01-01

    A method and model of predicting particle-surface interactions with a surface, such as the surface of a spacecraft. The method includes the steps of: determining a trajectory path of a plurality of moving particles; predicting whether any of the moving particles will intersect a surface; predicting whether any of the particles will be captured by the surface and/or; predicting a reflected trajectory and velocity of particles reflected from the surface.

  20. Mood and personality interact to determine cognitive biases in pigs

    PubMed Central

    Asher, Lucy; Friel, Mary; Griffin, Kym

    2016-01-01

    Cognitive bias has become a popular way to access non-human animal mood, though inconsistent results have been found. In humans, mood and personality interact to determine cognitive bias, but to date, this has not been investigated in non-human animals. Here, we demonstrate for the first time, to the best of our knowledge, in a non-human animal, the domestic pig (Sus scrofa domesticus), that mood and personality interact, impacting on judgement. Pigs with a more proactive personality were more likely to respond optimistically to unrewarded ambiguous probes (spatially positioned between locations that were previously rewarded and unrewarded) independent of their housing (or enrichment) conditions. However, optimism/pessimism of reactive pigs in this task was affected by their housing conditions, which are likely to have influenced their mood state. Reactive pigs in the less enriched environment were more pessimistic and those in the more enriched environment, more optimistic. These results suggest that judgement in non-human animals is similar to humans, incorporating aspects of stable personality traits and more transient mood states. PMID:27852940

  1. Interactions among thermal parameters determine offspring sex under temperature-dependent sex determination

    PubMed Central

    Warner, Daniel A.; Shine, Richard

    2011-01-01

    In many animals, temperatures experienced by developing embryos determine offspring sex (e.g. temperature-dependent sex determination, TSD), but most studies focus strictly on the effects of mean temperature, with little emphasis on the importance of thermal fluctuations. In the jacky dragon (Amphibolurus muricatus), an Australian lizard with TSD, data from nests in the field demonstrate that offspring sex ratios are predictable from thermal fluctuations but not from mean nest temperatures. To clarify this paradox, we incubated eggs in a factorial experiment with two levels of mean temperature and three levels of diel fluctuation. We show that offspring sex is determined by an interaction between these critical thermal parameters. Intriguingly, because these two thermal descriptors shift in opposing directions throughout the incubation season, this interactive effect inhibits seasonal shifts in sex ratio. Hence, our results suggest that TSD can yield offspring sex ratios that resemble those produced under genotypic sex-determining systems. These findings raise important considerations for understanding the diversity of TSD reaction norms, for designing experiments that evaluate the evolutionary significance of TSD, and for predicting sex ratios under past and future climate change scenarios. PMID:20685704

  2. Thunderstorm-environment interactions determined with three-dimensional trajectories

    NASA Technical Reports Server (NTRS)

    Wilson, G. S.

    1980-01-01

    Diagnostically determined three dimensional trajectories were used to reveal some of the scale interaction processes that occur between convective storms and their environment. Data from NASA's fourth Atmospheric Variability Experiment are analyzed. Two intense squall lines and numerous reports of severe weather occurred during the period. Convective storm systems with good temporal and spatial continuity are shown to be related to the development and movement of short wave circulation systems aloft that propagate eastward within a zonal mid tropospheric wind pattern. These short wave systems are found to produce the potential instability and dynamic triggering needed for thunderstorm formation. The environmental flow patterns, relative to convective storm systems, are shown to produce large upward air parcel movements in excess of 50 mb/3h in the immediate vicinity of the storms. The air undergoing strong lifting originates as potentially unstable low level air traveling into the storm environment from southern and southwestern directions. The thermo and hydrodynamical processes that lead to changes in atmospheric structure before, during, and after convective storm formation are described using total time derivatives of pressure or net vertical displacement, potential temperature, and vector wind calculated by following air parcels.

  3. Apparatus and method for determining microscale interactions based on compressive sensors such as crystal structures

    DOEpatents

    McAdams, Harley; AlQuraishi, Mohammed

    2015-04-21

    Techniques for determining values for a metric of microscale interactions include determining a mesoscale metric for a plurality of mesoscale interaction types, wherein a value of the mesoscale metric for each mesoscale interaction type is based on a corresponding function of values of the microscale metric for the plurality of the microscale interaction types. A plurality of observations that indicate the values of the mesoscale metric are determined for the plurality of mesoscale interaction types. Values of the microscale metric are determined for the plurality of microscale interaction types based on the plurality of observations and the corresponding functions and compressed sensing.

  4. Ideology and Interaction: Debating Determinisms in Literacy Studies

    ERIC Educational Resources Information Center

    Collin, Ross; Street, Brian V.

    2014-01-01

    In this exchange, Street and Collin debate the merits of the interaction model of literacy that Collin outlined in a recent issue of Reading Research Quarterly. Built as a complement and a counter to Street's ideological model of literacy, Collin's interaction model defines literacies as technologies that coevolve with sociocultural…

  5. Determinants of Internet Use for Interactive Learning: An Exploratory Study

    ERIC Educational Resources Information Center

    Castaño, Jonatan; Duart, Josep M.; Sancho-Vinuesa, Teresa

    2015-01-01

    The use of the Internet in higher education teaching can facilitate the interactive learning process and thus improve educational outcomes. The aim of the study presented here is to explore which variables are linked to higher intensity of Internet-based interactive educational practices. The study is based on data obtained from an online survey…

  6. Interaction webs in arctic ecosystems: Determinants of arctic change?

    PubMed

    Schmidt, Niels M; Hardwick, Bess; Gilg, Olivier; Høye, Toke T; Krogh, Paul Henning; Meltofte, Hans; Michelsen, Anders; Mosbacher, Jesper B; Raundrup, Katrine; Reneerkens, Jeroen; Stewart, Lærke; Wirta, Helena; Roslin, Tomas

    2017-02-01

    How species interact modulate their dynamics, their response to environmental change, and ultimately the functioning and stability of entire communities. Work conducted at Zackenberg, Northeast Greenland, has changed our view on how networks of arctic biotic interactions are structured, how they vary in time, and how they are changing with current environmental change: firstly, the high arctic interaction webs are much more complex than previously envisaged, and with a structure mainly dictated by its arthropod component. Secondly, the dynamics of species within these webs reflect changes in environmental conditions. Thirdly, biotic interactions within a trophic level may affect other trophic levels, in some cases ultimately affecting land-atmosphere feedbacks. Finally, differential responses to environmental change may decouple interacting species. These insights form Zackenberg emphasize that the combination of long-term, ecosystem-based monitoring, and targeted research projects offers the most fruitful basis for understanding and predicting the future of arctic ecosystems.

  7. Chitosan-soyprotein interaction as determined by thermal unfolding experiments.

    PubMed

    Takeuchi, Tomoko; Morita, Kazuhisa; Saito, Tsutomu; Kugimiya, Wataru; Fukamizo, Tamo

    2006-07-01

    Chitosan interaction with soybean beta-conglycinin beta(3) was investigated by thermal unfolding experiments using CD spectroscopy. The negative ellipticity of the protein was enhanced with rising solution temperature. The transition temperature of thermal unfolding of the protein (T(m)) was 63.4 degrees C at pH 3.0 (0.15 M KCl). When chitosan was added to the protein solution, the T(m) value was elevated by 7.7 degrees C, whereas the T(m) elevation upon addition of chitosan hexamer (GlcN)(6) was 2.2 degrees C. These carbohydrates appear to interact with the protein stabilizing the protein structure, and the interaction ability could be evaluated from the T(m) elevation. Similar experiments were conducted at various pHs from 2.0 to 3.5, and the T(m) elevation was found to be enhanced in the higher pH region. We conclude that chitosan interacts with beta-conglycinin through electrostatic interactions between the positive charges of the chitosan polysaccharide and the negative charges of the protein surface.

  8. STUDENT-TEACHER INTERACTION AS A DETERMINER OF EFFECTIVE TEACHING.

    ERIC Educational Resources Information Center

    LEWIS, EDWIN C.

    THIS STUDY TESTED THE HYPOTHESIS THAT THE EFFECTIVENESS OF A GIVEN TEACHER VARIES FROM ONE STUDENT TO ANOTHER AND THAT THIS DIFFERENCE IN EFFECTIVENESS IS A RESULT OF THE INTERACTION OF THE PERSONALITY PATTERNS OF THE STUDENT AND TEACHER. STUDENTS MAJORING IN MECHANICAL ENGINEERING, ANIMAL HUSBANDRY, AND HOME ECONOMICS WERE THE SUBJECTS. PERSONS…

  9. Experimental determination of sound and high-speed flow interaction

    NASA Technical Reports Server (NTRS)

    Lumsdaine, E.; Silcox, R.

    1976-01-01

    A facility that was used to measure the interaction of flow with sound at high Mach numbers is described. Four inlets with different area variations (or axial gradients) were tested. Sound of selected frequencies and modes (0,0), (1,0), (2,0) was generated with eight circumferential acoustic drivers.

  10. Cracking the phosphatase code: docking interactions determine substrate specificity.

    PubMed

    Roy, Jagoree; Cyert, Martha S

    2009-12-08

    Phosphoserine- and phosphothreonine-directed phosphatases display remarkable substrate specificity, yet the sites that they dephosphorylate show little similarity in amino acid sequence. Studies reveal that docking interactions are key for the recognition of substrates and regulators by two conserved phosphatases, protein phosphatase 1 (PP1) and the Ca2+-calmodulin-dependent phosphatase calcineurin. In each case, a small degenerate sequence motif in the interacting protein directs low-affinity binding to a docking surface on the phosphatase that is distinct from the active site; several such interactions combine to confer overall binding specificity. Some docking surfaces are conserved, such as a hydrophobic groove on a face opposite the active site that serves as a major recognition surface for the "RVxF" motif of proteins that interact with PP1 and the "PxIxIT" motif of substrates of calcineurin. Secondary motifs combine with this primary targeting sequence to specify phosphatase binding. A comprehensive interactome for mammalian PP1 was described, analysis of which defines several PP1-binding motifs. Studies of "LxVP," a secondary calcineurin-binding sequence, establish that this motif is a conserved feature of calcineurin substrates and that the immunosuppressants FK506 and cyclosporin A inhibit the phosphatase by interfering with LxVP-mediated docking.

  11. Towards a First-Principles Determination of Effective Coulomb Interactions in Correlated Electron Materials: Role of Intershell Interactions

    NASA Astrophysics Data System (ADS)

    Seth, Priyanka; Hansmann, Philipp; van Roekeghem, Ambroise; Vaugier, Loig; Biermann, Silke

    2017-08-01

    The determination of the effective Coulomb interactions to be used in low-energy Hamiltonians for materials with strong electronic correlations remains one of the bottlenecks for parameter-free electronic structure calculations. We propose and benchmark a scheme for determining the effective local Coulomb interactions for charge-transfer oxides and related compounds. Intershell interactions between electrons in the correlated shell and ligand orbitals are taken into account in an effective manner, leading to a reduction of the effective local interactions on the correlated shell. Our scheme resolves inconsistencies in the determination of effective interactions as obtained by standard methods for a wide range of materials, and allows for a conceptual understanding of the relation of cluster model and dynamical mean field-based electronic structure calculations.

  12. An ancient protein-DNA interaction underlying metazoan sex determination.

    PubMed

    Murphy, Mark W; Lee, John K; Rojo, Sandra; Gearhart, Micah D; Kurahashi, Kayo; Banerjee, Surajit; Loeuille, Guy-André; Bashamboo, Anu; McElreavey, Kenneth; Zarkower, David; Aihara, Hideki; Bardwell, Vivian J

    2015-06-01

    DMRT transcription factors are deeply conserved regulators of metazoan sexual development. They share the DM DNA-binding domain, a unique intertwined double zinc-binding module followed by a C-terminal recognition helix, which binds a pseudopalindromic target DNA. Here we show that DMRT proteins use a unique binding interaction, inserting two adjacent antiparallel recognition helices into a widened DNA major groove to make base-specific contacts. Versatility in how specific base contacts are made allows human DMRT1 to use multiple DNA binding modes (tetramer, trimer and dimer). Chromatin immunoprecipitation with exonuclease treatment (ChIP-exo) indicates that multiple DNA binding modes also are used in vivo. We show that mutations affecting residues crucial for DNA recognition are associated with an intersex phenotype in flies and with male-to-female sex reversal in humans. Our results illuminate an ancient molecular interaction underlying much of metazoan sexual development.

  13. An ancient protein-DNA interaction underlying metazoan sex determination

    PubMed Central

    Murphy, Mark W.; Lee, John K.; Rojo, Sandra; Gearhart, Micah D.; Kurahashi, Kayo; Banerjee, Surajit; Loeuille, Guy-André; Bashamboo, Anu; McElreavey, Kenneth; Zarkower, David; Aihara, Hideki; Bardwell, Vivian J.

    2015-01-01

    DMRT transcription factors are deeply conserved regulators of metazoan sexual development. They share the DM DNA binding domain, a unique intertwined double zinc-binding module followed by a C-terminal recognition helix, which binds to a pseudopalindromic target DNA. Here we show that DMRT proteins employ a unique binding interaction, inserting two adjacent antiparallel recognition helices into a widened DNA major groove to make base-specific contacts. Versatility in how specific base contacts are made allows human DMRT1 to employ multiple DNA binding modes (tetramer, trimer, dimer). ChIP-Exo indicates that multiple DNA binding modes also are used in vivo. We show that mutations affecting residues crucial for DNA recognition are associated with an intersex phenotype in flies and in male-to-female sex reversal in humans. Our results illuminate an ancient molecular interaction that underlies much of metazoan sexual development. PMID:26005864

  14. An ancient protein-DNA interaction underlying metazoan sex determination

    SciTech Connect

    Murphy, Mark W.; Lee, John K.; Rojo, Sandra; Gearhart, Micah D.; Kurahashi, Kayo; Banerjee, Surajit; Loeuille, Guy-André; Bashamboo, Anu; McElreavey, Kenneth; Zarkower, David; Aihara, Hideki; Bardwell, Vivian J.

    2015-05-25

    DMRT transcription factors are deeply conserved regulators of metazoan sexual development. They share the DM DNA-binding domain, a unique intertwined double zinc-binding module followed by a C-terminal recognition helix, which binds a pseudopalindromic target DNA. In this paper, we show that DMRT proteins use a unique binding interaction, inserting two adjacent antiparallel recognition helices into a widened DNA major groove to make base-specific contacts. Versatility in how specific base contacts are made allows human DMRT1 to use multiple DNA binding modes (tetramer, trimer and dimer). Chromatin immunoprecipitation with exonuclease treatment (ChIP-exo) indicates that multiple DNA binding modes also are used in vivo. We show that mutations affecting residues crucial for DNA recognition are associated with an intersex phenotype in flies and with male-to-female sex reversal in humans. Finally, our results illuminate an ancient molecular interaction underlying much of metazoan sexual development.

  15. An ancient protein-DNA interaction underlying metazoan sex determination

    DOE PAGES

    Murphy, Mark W.; Lee, John K.; Rojo, Sandra; ...

    2015-05-25

    DMRT transcription factors are deeply conserved regulators of metazoan sexual development. They share the DM DNA-binding domain, a unique intertwined double zinc-binding module followed by a C-terminal recognition helix, which binds a pseudopalindromic target DNA. In this paper, we show that DMRT proteins use a unique binding interaction, inserting two adjacent antiparallel recognition helices into a widened DNA major groove to make base-specific contacts. Versatility in how specific base contacts are made allows human DMRT1 to use multiple DNA binding modes (tetramer, trimer and dimer). Chromatin immunoprecipitation with exonuclease treatment (ChIP-exo) indicates that multiple DNA binding modes also are usedmore » in vivo. We show that mutations affecting residues crucial for DNA recognition are associated with an intersex phenotype in flies and with male-to-female sex reversal in humans. Finally, our results illuminate an ancient molecular interaction underlying much of metazoan sexual development.« less

  16. Interactions of nanoparticles with proteins: determination of equilibrium constants.

    PubMed

    Treuel, Lennart; Malissek, Marcelina

    2013-01-01

    The behavior of nanoparticles towards proteins is an important aspect across wide areas of nanotoxicology and nanomedicine. In this chapter, we describe a procedure to study the adsorption of proteins onto nanoparticle surfaces. Circular dichroism (CD) spectroscopy is utilized to quantify the amount of free protein in a solution, and the experimental information is evaluated to derive equilibrium constants for the protein adsorption/desorption equilibrium. These equilibrium constants are comparable parameters in describing the interactions between proteins and nanoparticles.

  17. Determining Interactions in PSA models: Application to a Space PSA

    SciTech Connect

    C. Smith; E. Borgonovo

    2010-06-01

    This paper addresses use of an importance measure interaction study of a probabilistic risk analysis (PSA) performed for a hypothetical aerospace lunar mission. The PSA methods used in this study follow the general guidance provided in the NASA Probabilistic Risk Assessment Procedures Guide for NASA Managers and Practitioners. For the PSA portion, we used phased-based event tree and fault tree logic structures are used to model a lunar mission, including multiple phases (from launch to return to the Earth surface) and multiple critical systems. Details of the analysis results are not provided in this paper – instead specific basic events are denoted by number (e.g., the first event is 1, the second is 2, and so on). However, in the model, we used approximately 150 fault trees and over 800 basic events. Following analysis and truncation of cut sets, we were left with about 400 basic events to evaluate. We used this model to explore interactions between different basic events and systems. These sensitivity studies provide high-level insights into features of the PSA for the hypothetical lunar mission.

  18. Identifying Interactions that Determine Fragment Binding at Protein Hotspots.

    PubMed

    Radoux, Chris J; Olsson, Tjelvar S G; Pitt, Will R; Groom, Colin R; Blundell, Tom L

    2016-05-12

    Locating a ligand-binding site is an important first step in structure-guided drug discovery, but current methods do little to suggest which interactions within a pocket are the most important for binding. Here we illustrate a method that samples atomic hotspots with simple molecular probes to produce fragment hotspot maps. These maps specifically highlight fragment-binding sites and their corresponding pharmacophores. For ligand-bound structures, they provide an intuitive visual guide within the binding site, directing medicinal chemists where to grow the molecule and alerting them to suboptimal interactions within the original hit. The fragment hotspot map calculation is validated using experimental binding positions of 21 fragments and subsequent lead molecules. The ligands are found in high scoring areas of the fragment hotspot maps, with fragment atoms having a median percentage rank of 97%. Protein kinase B and pantothenate synthetase are examined in detail. In each case, the fragment hotspot maps are able to rationalize a Free-Wilson analysis of SAR data from a fragment-based drug design project.

  19. Determination of the CD148-Interacting Region in Thrombospondin-1

    PubMed Central

    Jiang, Rosie; Brantley-Sieders, Dana M.; Chen, Jin; Mernaugh, Raymond L.; Takahashi, Takamune

    2016-01-01

    CD148 is a transmembrane protein tyrosine phosphatase that is expressed in multiple cell types, including vascular endothelial cells and duct epithelial cells. Previous studies have shown a prominent role of CD148 to reduce growth factor signals and suppress cell proliferation and transformation. Further, we have recently shown that thrombospondin-1 (TSP1) serves as a functionally important ligand for CD148. TSP1 has multiple structural elements and interacts with various cell surface receptors that exhibit differing effects. In order to create the CD148-specific TSP1 fragment, here we investigated the CD148-interacting region in TSP1 using a series of TSP1 fragments and biochemical and biological assays. Our results demonstrate that: 1) CD148 binds to the 1st type 1 repeat in TSP1; 2) Trimeric TSP1 fragments that contain the 1st type repeat inhibit cell proliferation in A431D cells that stably express wild-type CD148 (A431D/CD148wt cells), while they show no effects in A431D cells that lack CD148 or express a catalytically inactive form of CD148. The anti-proliferative effect of the TSP1 fragment in A431D/CD148wt cells was largely abolished by CD148 knockdown and antagonized by the 1st, but not the 2nd and 3rd, type 1 repeat fragment. Furthermore, the trimeric TSP1 fragments containing the 1st type repeat increased the catalytic activity of CD148 and reduced phospho-tyrosine contents of EGFR and ERK1/2, defined CD148 substrates. These effects were not observed in the TSP1 fragments that lack the 1st type 1 repeat. Last, we demonstrate that the trimeric TSP1 fragment containing the 1st type 1 repeat inhibits endothelial cell proliferation in culture and angiogenesis in vivo. These effects were largely abolished by CD148 knockdown or deficiency. Collectively, these findings indicate that the 1st type 1 repeat interacts with CD148, reducing growth factor signals and inhibiting epithelial or endothelial cell proliferation and angiogenesis. PMID:27149518

  20. Determining protein function and interaction from genome analysis

    DOEpatents

    Eisenberg, David; Marcotte, Edward M.; Thompson, Michael J.; Pellegrini, Matteo; Yeates, Todd O.

    2004-08-03

    A computational method system, and computer program are provided for inferring functional links from genome sequences. One method is based on the observation that some pairs of proteins A' and B' have homologs in another organism fused into a single protein chain AB. A trans-genome comparison of sequences can reveal these AB sequences, which are Rosetta Stone sequences because they decipher an interaction between A' and B. Another method compares the genomic sequence of two or more organisms to create a phylogenetic profile for each protein indicating its presence or absence across all the genomes. The profile provides information regarding functional links between different families of proteins. In yet another method a combination of the above two methods is used to predict functional links.

  1. Charged group surface accessibility determines micelleplexes formation and cellular interaction

    NASA Astrophysics Data System (ADS)

    Zhang, Yu; Liu, Yang; Sen, Soumyo; Král, Petr; Gemeinhart, Richard A.

    2015-04-01

    Micelleplexes are a class of nucleic acid carriers that have gained acceptance due to their size, stability, and ability to synergistically carry small molecules. MicroRNAs (miRNAs) are small non-coding RNA gene regulator that is consists of 19-22 nucleotides. Altered expression of miRNAs plays an important role in many human diseases. Using a model 22-nucleotide miRNA sequence, we investigated the interaction between charged groups on the micelle surface and miRNA. The model micelle system was formed from methoxy-poly(ethylene glycol)-b-poly(lactide) (mPEG-PLA) mixed with methoxy-poly(ethylene glycol)-b-poly(lactide)-b-oligoarginine (mPEG-PLA-Rx, x = 8 or 15). Surface properties of the micelles were varied by controlling the oligoarginine block length and conjugation density. Micelles were observed to have a core-shell conformation in the aqueous environment where the PLA block constituted the hydrophobic core, mPEG and oligoarginine formed a hydrophilic corona. Significantly different thermodynamic behaviors were observed during the interaction of single stranded miRNA with micelles of different surface properties, and the resulting micelleplexes mediated substantial cellular association. Depending upon the oligoarginine length and density, micelles exhibited miRNA loading capacity directly related to the presentation of charged groups on the surface. The effect of charged group accessibility of cationic micelle on micelleplex properties provides guidance on future miRNA delivery system design.Micelleplexes are a class of nucleic acid carriers that have gained acceptance due to their size, stability, and ability to synergistically carry small molecules. MicroRNAs (miRNAs) are small non-coding RNA gene regulator that is consists of 19-22 nucleotides. Altered expression of miRNAs plays an important role in many human diseases. Using a model 22-nucleotide miRNA sequence, we investigated the interaction between charged groups on the micelle surface and miRNA. The

  2. Determining robot actions for tasks requiring sensor interaction

    NASA Technical Reports Server (NTRS)

    Budenske, John; Gini, Maria

    1989-01-01

    The performance of non-trivial tasks by a mobile robot has been a long term objective of robotic research. One of the major stumbling blocks to this goal is the conversion of the high-level planning goals and commands into the actuator and sensor processing controls. In order for a mobile robot to accomplish a non-trivial task, the task must be described in terms of primitive actions of the robot's actuators. Most non-trivial tasks require the robot to interact with its environment; thus necessitating coordination of sensor processing and actuator control to accomplish the task. The main contention is that the transformation from the high level description of the task to the primitive actions should be performed primarily at execution time, when knowledge about the environment can be obtained through sensors. It is proposed to produce the detailed plan of primitive actions by using a collection of low-level planning components that contain domain specific knowledge and knowledge about the available sensors, actuators, and sensor/actuator processing. This collection will perform signal and control processing as well as serve as a control interface between an actual mobile robot and a high-level planning system. Previous research has shown the usefulness of high-level planning systems to plan the coordination of activities such to achieve a goal, but none have been fully applied to actual mobile robots due to the complexity of interacting with sensors and actuators. This control interface is currently being implemented on a LABMATE mobile robot connected to a SUN workstation and will be developed such to enable the LABMATE to perform non-trivial, sensor-intensive tasks as specified by a planning system.

  3. Multivalent Rab interactions determine tether-mediated membrane fusion

    PubMed Central

    Lürick, Anna; Gao, Jieqiong; Kuhlee, Anne; Yavavli, Erdal; Langemeyer, Lars; Perz, Angela; Raunser, Stefan; Ungermann, Christian

    2017-01-01

    Membrane fusion at endomembranes requires cross-talk between Rab GTPases and tethers to drive SNARE-mediated lipid bilayer mixing. Several tethers have multiple Rab-binding sites with largely untested function. Here we dissected the lysosomal HOPS complex as a tethering complex with just two binding sites for the Rab7-like Ypt7 protein to determine their relevance for fusion. Using tethering and fusion assays combined with HOPS mutants, we show that HOPS-dependent fusion requires both Rab-binding sites, with Vps39 being the stronger Ypt7 interactor than Vps41. The intrinsic amphipathic lipid packaging sensor (ALPS) motif within HOPS Vps41, a target of the vacuolar kinase Yck3, is dispensable for tethering and fusion but can affect tethering if phosphorylated. In combination, our data demonstrate that a multivalent tethering complex uses its two Rab bindings to determine the place of SNARE assembly and thus fusion at endomembranes. PMID:27852901

  4. Interaction of growth-determining systems with gravity

    NASA Astrophysics Data System (ADS)

    Merkys, A.; Laurinavičius, R.; Bendoraityté, D.; Švegždiené, D.; Rupainiené, O.

    The experiments have been carried out with lettuce shoots on board the Salyut-7 orbital station, the Kosmos-1667 biological satellite and under ground conditions at 180° plant inversion. By means of the centrifuge Biogravistat-1M the threshold value of gravitational sensitivity of lettuce shoots has been determined on board the Salyut-7 station. It was found to be equal to 2.9 × 10-3g for hypocotyls and 1.5 × 10-4g for roots. The following results have been received in the experiment performed on board the Kosmos-1667 satellite: a) under microgravity the proliferation of the meristem cells and the growth of roots did not differ from the control; b) the growth of hypocotyls in length was significantly enhanced in microgravity; c) under microgravity transverse growth of hypocotyls (increase in cross sectional area) was significantly increased due to enhancement of cortical parenchyma cell growth. At 180° inversion in Earth's gravity root extension growth and rate of cell division in the root apical meristem were decreased. The determination of DNA-fuchsin value in the nuclei of the cell root apexes showed that inversion affected processess of the cell cycle preceeding cytokinesis.

  5. Reproductive interference determines persistence and exclusion in species interactions.

    PubMed

    Kishi, Shigeki; Nishida, Takayoshi; Tsubaki, Yoshitaka

    2009-09-01

    1. Reproductive interference is a negative interspecific sexual interaction that adversely affects the fitness of males and females during reproductive process. Theoretical studies suggest that because reproductive interference is characterized by positive frequency dependence it is far more likely to cause species exclusion than the density dependence of resource competition. However, the respective contributions of resource competition and reproductive interference to species exclusion, which have been frequently observed in many competition studies, remain unclear. 2. We show that reproductive interference is a far more critical cause of species exclusion than resource competition in the competition between Callosobruchus bean weevil species. In competition experiments over several generations, we manipulated the initial relative abundance of the adzuki bean beetle, Callosobruchus chinensis, and the southern cowpea beetle, Callosobruchus maculatus. When the initial adult ratio of C. chinensis : C. maculatus were 6 : 2 and 4 : 4, C. chinensis excluded C. maculatus. However, when C. maculatus was four times more abundant than C. chinensis at the start, we observed the opposite outcome. 3. A behavioural experiment using adults of the two species revealed asymmetric reproductive interference. The fecundity and longevity of C. maculatus females, but not those of C. chinensis females, decreased when the females were kept with heterospecific males. Fecundities of females of both species decreased as the number of heterospecific males increased. In contrast, resource competition at the larval stage resulted in higher survival of C. maculatus than of C. chinensis. 4. These results suggest that the positive frequency-dependent effect of reproductive interference resulted in species exclusion, depending on the initial population ratio of the two species, and the asymmetry of the interference resulted in C. chinensis being dominant in this study, as in previous studies

  6. Attractive interactions among intermediate filaments determine network mechanics in vitro.

    PubMed

    Pawelzyk, Paul; Mücke, Norbert; Herrmann, Harald; Willenbacher, Norbert

    2014-01-01

    Mechanical and structural properties of K8/K18 and vimentin intermediate filament (IF) networks have been investigated using bulk mechanical rheometry and optical microrheology including diffusing wave spectroscopy and multiple particle tracking. A high elastic modulus G0 at low protein concentration c, a weak concentration dependency of G0 (G0 ∼ c(0.5 ± 0.1)) and pronounced strain stiffening are found for these systems even without external crossbridgers. Strong attractive interactions among filaments are required to maintain these characteristic mechanical features, which have also been reported for various other IF networks. Filament assembly, the persistence length of the filaments and the network mesh size remain essentially unaffected when a nonionic surfactant is added, but strain stiffening is completely suppressed, G0 drops by orders of magnitude and exhibits a scaling G0 ∼ c(1.9 ± 0.2) in agreement with microrheological measurements and as expected for entangled networks of semi-flexible polymers. Tailless K8Δ/K18ΔT and various other tailless filament networks do not exhibit strain stiffening, but still show high G0 values. Therefore, two binding sites are proposed to exist in IF networks. A weaker one mediated by hydrophobic amino acid clusters in the central rod prevents stretched filaments between adjacent cross-links from thermal equilibration and thus provides the high G0 values. Another strong one facilitating strain stiffening is located in the tail domain with its high fraction of hydrophobic amino acid sequences. Strain stiffening is less pronounced for vimentin than for K8/K18 due to electrostatic repulsion forces partly compensating the strong attraction at filament contact points.

  7. Political dynamics determined by interactions between political leaders and voters.

    SciTech Connect

    Bernard, Michael Lewis; Bier, Asmeret; Backus, George A.; Hills, Richard Guy

    2010-03-01

    The political dynamics associated with an election are typically a function of the interplay between political leaders and voters, as well as endogenous and exogenous factors that impact the perceptions and goals of the electorate. This paper describes an effort by Sandia National Laboratories to model the attitudes and behaviors of various political groups along with that population's primary influencers, such as government leaders. To accomplish this, Sandia National Laboratories is creating a hybrid system dynamics-cognitive model to simulate systems- and individual-level political dynamics in a hypothetical society. The model is based on well-established psychological theory, applied to both individuals and groups within the modeled society. Confidence management processes are being incorporated into the model design process to increase the utility of the tool and assess its performance. This project will enhance understanding of how political dynamics are determined in democratic society.

  8. Insufficiently dehydrated hydrogen bonds as determinants of protein interactions

    PubMed Central

    Fernández, Ariel; Scheraga, Harold A.

    2003-01-01

    The prediction of binding sites and the understanding of interfaces associated with protein complexation remains an open problem in molecular biophysics. This work shows that a crucial factor in predicting and rationalizing protein–protein interfaces can be inferred by assessing the extent of intramolecular desolvation of backbone hydrogen bonds in monomeric structures. Our statistical analysis of native structures shows that, in the majority of soluble proteins, most backbone hydrogen bonds are thoroughly wrapped intramolecularly by nonpolar groups except for a few ones. These latter underwrapped hydrogen bonds may be dramatically stabilized by removal of water. This fact implies that packing defects are “sticky” in a way that decisively contributes to determining the binding sites for proteins, as an examination of numerous complexes demonstrates. PMID:12518060

  9. A toolkit for determining historical eco-hydrological interactions

    NASA Astrophysics Data System (ADS)

    Singer, M. B.; Sargeant, C. I.; Evans, C. M.; Vallet-Coulomb, C.

    2016-12-01

    Contemporary climate change is predicted to result in perturbations to hydroclimatic regimes across the globe, with some regions forecast to become warmer and drier. Given that water is a primary determinant of vegetative health and productivity, we can expect shifts in the availability of this critical resource to have significant impacts on forested ecosystems. The subject is particularly complex in environments where multiple sources of water are potentially available to vegetation and which may also exhibit spatial and temporal variability. To anticipate how subsurface hydrological partitioning may evolve in the future and impact overlying vegetation, we require well constrained, historical data and a modelling framework for assessing the dynamics of subsurface hydrology. We outline a toolkit to retrospectively investigate dynamic water use by trees. We describe a synergistic approach, which combines isotope dendrochronology of tree ring cellulose with a biomechanical model, detailed climatic and isotopic data in endmember waters to assess the mean isotopic composition of source water used in annual tree rings. We identify the data requirements and suggest three versions of the toolkit based on data availability. We present sensitivity analyses in order to identify the key variables required to constrain model predictions and then develop empirical relationships for constraining these parameters based on climate records. We demonstrate our methodology within a Mediterranean riparian forest site and show how it can be used along with subsurface hydrological modelling to validate source water determinations, which are fundamental to understanding climatic fluctuations and trends in subsurface hydrology. We suggest that the utility of our toolkit is applicable in riparian zones and in a range of forest environments where distinct isotopic endmembers are present.

  10. Homology-dependent Gene Silencing in Paramecium

    PubMed Central

    Ruiz, Françoise; Vayssié, Laurence; Klotz, Catherine; Sperling, Linda; Madeddu, Luisa

    1998-01-01

    Microinjection at high copy number of plasmids containing only the coding region of a gene into the Paramecium somatic macronucleus led to a marked reduction in the expression of the corresponding endogenous gene(s). The silencing effect, which is stably maintained throughout vegetative growth, has been observed for all Paramecium genes examined so far: a single-copy gene (ND7), as well as members of multigene families (centrin genes and trichocyst matrix protein genes) in which all closely related paralogous genes appeared to be affected. This phenomenon may be related to posttranscriptional gene silencing in transgenic plants and quelling in Neurospora and allows the efficient creation of specific mutant phenotypes thus providing a potentially powerful tool to study gene function in Paramecium. For the two multigene families that encode proteins that coassemble to build up complex subcellular structures the analysis presented herein provides the first experimental evidence that the members of these gene families are not functionally redundant. PMID:9529389

  11. Determinants of potential drug-drug interaction associated dispensing in community pharmacies in the Netherlands.

    PubMed

    Becker, Matthijs L; Caspers, Peter W J; Kallewaard, Marjon; Bruinink, Riekert J; Kylstra, Nico B; Heisterkamp, Siem; de Valk, Vincent; van der Veen, André A; Stricker, Bruno H Ch

    2007-04-01

    There are many drug-drug interactions (D-DI) of which some may cause severe adverse patient outcomes. Dispensing interacting drug combinations should be avoided when the risks are higher than the benefits. The objective of this study was to identify determinants of dispensing undesirable interacting drug combinations by community pharmacies in the Netherlands. A total of 256 Dutch community pharmacies were selected, based on the dispensing of 11 undesirable interacting drug combinations between January 1st, 2001 and October 31st, 2002. These pharmacies were sent a questionnaire by the Inspectorate for Health Care (IHC) concerning their process and structure characteristics. The number of times the 11 undesirable interacting drug combinations were dispensed. Two hundred and forty-six questionnaires (response rate 96.1%) were completed. Dispensing determinants were only found for the D-DI between macrolide antibiotics and digoxin but not for the other 10 D-DIs. Pharmacies using different medication surveillance systems differed in the dispensing of this interacting drug combination, and pharmacies, which were part of a health care centre dispensed this interacting drug combination more often. Medication surveillance in Dutch community pharmacies seems to be effective. Although for most D-DIs no determinants were found, process and structure characteristics may have consequences for the dispensing of undesirable interacting drug combinations.

  12. The importance of particle-support interaction on particle size determination by gas chemisorption.

    PubMed

    Torrente-Murciano, L

    The interaction of the metal-support and particle shape has a key role on the determination of the particle size by gas chemisorption. This paper demonstrates mathematically that, assuming metal particles with hemispherical shapes (a common assumption in this type of characterisation) can provide misleading results of up to one order of magnitude. Thus, the metal particle sizes are underestimated when the metal strongly interacts with the support and overestimated when there is a weak metal-support interaction. Additionally, we also demonstrate that although the assumption of spherical shapes always underestimates the size of particles, this error is considerably lower with regular geometries than that associated to the effect of the metal-support interaction due to their effect on the particle shape. Herein, it is demonstrated the importance of introducing the particle-support interaction factor in the chemisorption particle size determination.

  13. Steady-State and Kinetics-Based Affinity Determination in Effector-Effector Target Interactions.

    PubMed

    Reinhard, André; Nürnberger, Thorsten

    2017-01-01

    Dissecting the functional basis of pathogenicity and resistance in the context of plant innate immunity benefits greatly from detailed knowledge about biomolecular interactions, as both resistance and virulence depend on specific interactions between pathogen and host biomolecules. While in vivo systems provide biological context to host-pathogen interactions, these experiments typically cannot provide quantitative biochemical characterization of biomolecular interactions. However, in many cases, the biological function does not only depend on whether an interaction occurs at all, but rather on the "intensity" of the interaction, as quantified by affinity. Specifically, microbial effector proteins may bind more than one host target to exert virulence functions, and looking at these interactions more closely than would be possible in a purely black-and-white qualitative assay (as classically based on plant or yeast systems) can reveal new insights into the evolutionary arms race between host and pathogen. Recent advances in biomolecular interaction assays that can be performed in vitro allow quantification of binding events with ever greater fidelity and application range. Here, we describe assays based on microscale thermophoresis (MST) and surface plasmon resonance (SPR). Using these technologies allows affinity determination both in steady-state and in kinetic configurations, providing two conceptually independent pathways to arrive at quantitative affinity data describing the interactions of pathogen and host biomolecules.

  14. Experimental and bioinformatic approaches for interrogating protein-protein interactions to determine protein function.

    PubMed

    Droit, Arnaud; Poirier, Guy G; Hunter, Joanna M

    2005-04-01

    An ambitious goal of proteomics is to elucidate the structure, interactions and functions of all proteins within cells and organisms. One strategy to determine protein function is to identify the protein-protein interactions. The increasing use of high-throughput and large-scale bioinformatics-based studies has generated a massive amount of data stored in a number of different databases. A challenge for bioinformatics is to explore this disparate data and to uncover biologically relevant interactions and pathways. In parallel, there is clearly a need for the development of approaches that can predict novel protein-protein interaction networks in silico. Here, we present an overview of different experimental and bioinformatic methods to elucidate protein-protein interactions.

  15. Perceptual incongruity and social interaction as determinants of infants' reaction to novel persons.

    PubMed

    Greenberg, D J; Hillman, D; Grice, D

    1975-12-01

    To investigate the contrary position of perceptual incongruity and social interaction theories regarding birth order and reactions to novel persons within the first year of life, novel persons were presented to 96 first and later borns 8 and 12 months of age. Because firstborns, exposed to more positive social interaction within the family within the first year of life, were more positive towards strangers than were the later borns, the authors concluded that by the end of the first year of life the nature of the infant's social interaction within the family, rather than the number of perceptual encounters, is the major determinant of infants' reaction to novel persons in their enviornment.

  16. In search of the determinants of enhancer-promoter interaction specificity.

    PubMed

    van Arensbergen, Joris; van Steensel, Bas; Bussemaker, Harmen J

    2014-11-01

    Although it was originally believed that enhancers activate only the nearest promoter, recent global analyses enabled by high-throughput technology suggest that the network of enhancer-promoter interactions is far more complex. The mechanisms that determine the specificity of enhancer-promoter interactions are still poorly understood, but they are thought to include biochemical compatibility, constraints imposed by the three-dimensional architecture of chromosomes, insulator elements, and possibly the effects of local chromatin composition. In this review, we assess the current insights into these determinants, and highlight the functional genomic approaches that will lead the way towards better mechanistic understanding. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. LEADERSHIP STATUS AS A MODULATOR OF THE DETERMINATION OF SOCIAL INTERACTION BY PRIOR REINFORCEMENT.

    DTIC Science & Technology

    determine degree of shift in judgment. Interaction effects on analysis of variance were significant for leader vs. non-leaders, positive vs. negative ... reinforcement . Thus, leaders are found to respond to cues in the outside world, non-leaders to ’internal’ mediating systems. (Author)

  18. The influence of bonding agents in improving interactions in composite propellants determined using image analysis.

    PubMed

    Dostanić, J; Husović, T V; Usćumlić, G; Heinemann, R J; Mijin, D

    2008-12-01

    Binder-oxidizer interactions in rocket composite propellants can be improved using adequate bonding agents. In the present work, the effectiveness of different 1,3,5-trisubstituted isocyanurates was determined by stereo and metallographic microscopy and using the software package Image-Pro Plus. The chemical analysis of samples was performed by a scanning electron microscope equipped for energy dispersive spectrometry.

  19. Parental Interaction As A Determining Factor in Social Growth of the Individual in the Family.

    ERIC Educational Resources Information Center

    Markowitz, Max; Kadis, Asya L.

    Parental interaction is a prime determining factor in an individual's growth. Complementary relationships of the mother and father within the family: i.e., the bringing together of both the mothering attitude and the expectation of "growing up", contribute to the individual's maturation. Many analysts, realizing the importance of triadic…

  20. Historical contingency and ecological determinism interact to prime speciation in sticklebacks, Gasterosteus.

    PubMed

    Taylor, E B; McPhail, J D

    2000-12-07

    Historical contingency and determinism are often cast as opposing paradigms under which evolutionary diversification operates. It may be, however, that both factors act together to promote evolutionary divergence, although there are few examples of such interaction in nature. We tested phylogenetic predictions of an explicit historical model of divergence (double invasions of freshwater by marine ancestors) in sympatric species of three-spined sticklebacks (Gasterosteus aculeatus) where determinism has been implicated as an important factor driving evolutionary novelty. Microsatellite DNA variation at six loci revealed relatively low genetic variation in freshwater populations, supporting the hypothesis that they were derived by colonization of freshwater by more diverse marine ancestors. Phylogenetic and genetic distance analyses suggested that pairs of sympatric species have evolved multiple times, further implicating determinism as a factor in speciation. Our data also supported predictions based on the hypothesis that the evolution of sympatric species was contingent upon 'double invasions' of postglacial lakes by ancestral marine sticklebacks. Sympatric sticklebacks, therefore, provide an example of adaptive radiation by determinism contingent upon historical conditions promoting unique ecological interactions, and illustrate how contingency and determinism may interact to generate geographical variation in species diversity

  1. Quantifying Functional Group Interactions that Determine Urea Effects on Nucleic Acid Helix Formation

    PubMed Central

    Guinn, Emily J.; Schwinefus, Jeffrey J.; Cha, Hyo Keun; McDevitt, Joseph L.; Merker, Wolf E.; Ritzer, Ryan; Muth, Gregory W.; Engelsgjerd, Samuel W.; Mangold, Kathryn E.; Thompson, Perry J.; Kerins, Michael J.; Record, Thomas

    2013-01-01

    Urea destabilizes helical and folded conformations of nucleic acids and proteins, as well as protein-nucleic acid complexes. To understand these effects, extend previous characterizations of interactions of urea with protein functional groups, and thereby develop urea as a probe of conformational changes in protein and nucleic acid processes, we obtain chemical potential derivatives (μ23 = dμ2/dm3) quantifying interactions of urea (component 3) with nucleic acid bases, base analogs, nucleosides and nucleotide monophosphates (component 2) using osmometry and hexanol-water distribution assays. Dissection of these μ23 yields interaction potentials quantifying interactions of urea with unit surface areas of nucleic acid functional groups (heterocyclic aromatic ring, ring methyl, carbonyl and phosphate O, amino N, sugar (C,O)); urea interacts favorably with all these groups, relative to interactions with water. Interactions of urea with heterocyclic aromatic rings and attached methyl groups (as on thymine) are particularly favorable, as previously observed for urea-homocyclic aromatic ring interactions. Urea m-values determined for double helix formation by DNA dodecamers near 25°C are in the range 0.72 to 0.85 kcal mol−1 m−1 and exhibit little systematic dependence on nucleobase composition (17–42% GC). Interpretation of these results using the urea interaction potentials indicates that extensive (60–90%) stacking of nucleobases in the separated strands in the transition region is required to explain the m-value. Results for RNA and DNA dodecamers obtained at higher temperatures, and literature data, are consistent with this conclusion. This demonstrates the utility of urea as a quantitative probe of changes in surface area (ΔASA) in nucleic acid processes. PMID:23510511

  2. An ELISA Based Binding and Competition Method to Rapidly Determine Ligand-receptor Interactions.

    PubMed

    Syedbasha, Mohameedyaseen; Linnik, Janina; Santer, Deanna; O'Shea, Daire; Barakat, Khaled; Joyce, Michael; Khanna, Nina; Tyrrell, D Lorne; Houghton, Michael; Egli, Adrian

    2016-03-14

    A comprehensive understanding of signaling pathways requires detailed knowledge regarding ligand-receptor interaction. This article describes two fast and reliable point-by-point protocols of enzyme-linked immunosorbent assays (ELISAs) for the investigation of ligand-receptor interactions: the direct ligand-receptor interaction assay (LRA) and the competition LRA. As a case study, the ELISA based analysis of the interaction between different lambda interferons (IFNLs) and the alpha subunit of their receptor (IL28RA) is presented: the direct LRA is used for the determination of dissociation constants (KD values) between receptor and IFN ligands, and the competition LRA for the determination of the inhibitory capacity of an oligopeptide, which was designed to compete with the IFNLs at their receptor binding site. Analytical steps to estimate KD and half maximal inhibitory concentration (IC50) values are described. Finally, the discussion highlights advantages and disadvantages of the presented method and how the results enable a better molecular understanding of ligand-receptor interactions.

  3. Interactions between Ether Phospholipids and Cholesterol as Determined by Scattering and Molecular Dynamics Simulations

    PubMed Central

    Pan, Jianjun; Cheng, Xiaolin; Heberle, Frederick A.; Mostofian, Barmak; Kučerka, Norbert; Drazba, Paul; Katsaras, John

    2012-01-01

    Cholesterol and ether lipids are ubiquitous in mammalian cell membranes, and their interactions are crucial in ether lipid mediated cholesterol trafficking. We report on cholesterol’s molecular interactions with ether lipids as determined using a combination of small-angle neutron and X-ray scattering, and all-atom molecular dynamics (MD) simulations. A scattering density profile model for an ether lipid bilayer was developed using MD simulations, which was then used to simultaneously fit the different experimental scattering data. From the analysis of the data the various bilayer structural parameters were obtained. Surface area constrained MD simulations were also performed to reproduce the experimental data. This iterative analysis approach resulted in good agreement between the experimental and simulated form factors. The molecular interactions taking place between cholesterol and ether lipids were then determined from the validated MD simulations. We found that in ether membranes, cholesterol primarily hydrogen bonds with the lipid headgroup phosphate oxygen, while in their ester membrane counterparts, cholesterol hydrogen bonds with the backbone ester carbonyls. This different mode of interaction between ether lipids and cholesterol induces cholesterol to reside closer to the bilayer surface, dehydrating the headgroup’s phosphate moiety. Moreover, the three-dimensional lipid chain spatial density distribution around cholesterol indicates anisotropic chain packing, causing cholesterol to tilt. These insights lend a better understanding of ether lipid mediated cholesterol trafficking and the roles that the different lipid species have in determining the structural and dynamical properties of membrane associated biomolecules. PMID:23199292

  4. Interactions between Ether Phospholipids and Cholesterol as Determined by Scattering and Molecular Dynamics Simulations

    SciTech Connect

    Pan, Jianjun; Cheng, Xiaolin; Heberle, Frederick A; Mostofian, Barmak; Kucerka, Norbert; Drazba, Paul; Katsaras, John

    2012-01-01

    Cholesterol and ether lipids are ubiquitous in mammalian cell membranes, and their interactions are crucial in ether lipid mediated cholesterol trafficking. We report on cholesterol s molecular interactions with ether lipids as determined using a combination of small-angle neutron and Xray scattering, and all-atom molecular dynamics (MD) simulations. A scattering density profile model for an ether lipid bilayer was developed using MD simulations, which was then used to simultaneously fit the different experimental scattering data. From analysis of the data the various bilayer structural parameters were obtained. Surface area constrained MD simulations were also performed to reproduce the experimental data. This iterative analysis approach resulted in good agreement between the experimental and simulated form factors. The molecular interactions taking place between cholesterol and ether lipids were then determined from the validated MD simulations. We found that in ether membranes cholesterol primarily hydrogen bonds with the lipid headgroup phosphate oxygen, while in their ester membrane counterparts cholesterol hydrogen bonds with the backbone ester carbonyls. This different mode of interaction between ether lipids and cholesterol induces cholesterol to reside closer to the bilayer surface, dehydrating the headgroup s phosphate moiety. Moreover, the three-dimensional lipid chain spatial density distribution around cholesterol indicates anisotropic chain packing, causing cholesterol to tilt. These insights lend a better understanding of ether lipid-mediated cholesterol trafficking and the roles that the different lipid species have in determining the structural and dynamical properties of membrane associated biomolecules.

  5. Signal transduction meets systems biology: deciphering specificity determinants for protein-protein interactions

    PubMed Central

    Bourret, Robert B.

    2008-01-01

    Two recent papers [Gao et al. Mol. Microbiol. 69, 1358 (2008); Skerker et al. Cell 133, 1043 (2008)] describe investigations into the specificity of protein-protein interactions that occur during signal transduction by two-component regulatory systems. This MicroCommentary summarizes and provides context for the reported findings. The results offer insights into molecular determinants that provide specificity to maintain signal separation and thus prevent deleterious crosstalk between pathways, as well as the potential extent and nature of interactions that may combine signals to achieve beneficial cross regulation among pathways. The methods employed are suitable for application to other systems. PMID:18694439

  6. Determination of protein-ligand interactions using accelerator mass spectrometry: modified crosslinking assay.

    PubMed

    Hah, Sang Soo

    2009-05-01

    A highly sensitive detection method for the determination of protein-ligand interactions has been developed. Radiocarbon-labeled 17beta-estradiol was incubated with estrogen receptor-alpha; as a selective binding partner, and covalently attached using crosslinking agents, to form covalently linked protein-ligand complexes. After separation using a denaturing gel, the (14)C content in the sliced gels was identified by accelerator mass spectrometry. The obtained data demonstrated specific binding of the small molecule to its binding partner. In theory, this method can be applied to most protein-ligand interaction studies.

  7. Combined ESTs from plant-microbe interactions: using GC counting to determine the species of origin.

    PubMed

    Huitema, Edgar; Torto, Trudy A; Styer, Allison; Kamoun, Sophien

    2003-01-01

    A diversity of microorganisms establishes intimate associations with plants. Whether pathogenic or symbiotic, such interactions are the result of complex recognition events between plants and microbes, leading to signaling cascades and regulation of countless genes involved in the interaction. A key step in unraveling the mysteries of plant-microbe interactions lies in defining the transcriptional changes that occur in both the host and the microbe during their association. The sum of the transcripts, from both host and microbe, which are produced during their association, has been defined as the interaction transcriptome. One approach to analyze interaction transcriptomes is to perform large-scale sequencing of cDNAs (expressed sequence tags or ESTs) obtained from infected plant tissue and representing a mixture of host and microbe sequences. In some cases, the two organisms have markedly different GC content, allowing most ESTs to be easily distinguished on this basis. In this chapter, we describe a GC counting method to determine the species of origin of ESTs obtained from interactions between plants and oomycetes or other high GC content microbes.

  8. Environmental responses, not species interactions, determine synchrony of dominant species in semiarid grasslands.

    PubMed

    Tredennick, Andrew T; de Mazancourt, Claire; Loreau, Michel; Adler, Peter B

    2017-02-01

    Temporal asynchrony among species helps diversity to stabilize ecosystem functioning, but identifying the mechanisms that determine synchrony remains a challenge. Here, we refine and test theory showing that synchrony depends on three factors: species responses to environmental variation, interspecific interactions, and demographic stochasticity. We then conduct simulation experiments with empirical population models to quantify the relative influence of these factors on the synchrony of dominant species in five semiarid grasslands. We found that the average synchrony of per capita growth rates, which can range from 0 (perfect asynchrony) to 1 (perfect synchrony), was higher when environmental variation was present (0.62) rather than absent (0.43). Removing interspecific interactions and demographic stochasticity had small effects on synchrony. For the dominant species in these plant communities, where species interactions and demographic stochasticity have little influence, synchrony reflects the covariance in species responses to the environment. This article is protected by copyright. All rights reserved.

  9. Environmental responses, not species interactions, determine synchrony of dominant species in semiarid grasslands

    PubMed Central

    Tredennick, Andrew T.; de Mazancourt, Claire; Loreau, Michel; Adler, Peter B.

    2017-01-01

    Temporal asynchrony among species helps diversity to stabilize ecosystem functioning, but identifying the mechanisms that determine synchrony remains a challenge. Here, we refine and test theory showing that synchrony depends on three factors: species responses to environmental variation, interspecific interactions, and demographic stochasticity. We then conduct simulation experiments with empirical population models to quantify the relative influence of these factors on the synchrony of dominant species in five semiarid grasslands. We found that the average synchrony of per capita growth rates, which can range from 0 (perfect asynchrony) to 1 (perfect synchrony), was higher when environmental variation was present (0.62) rather than absent (0.43). Removing interspecific interactions and demographic stochasticity had small effects on synchrony. For the dominant species in these plant communities, where species interactions and demographic stochasticity have little influence, synchrony reflects the covariance in species’ responses to the environment. PMID:28144939

  10. Interaction Behavior Between Niclosamide and Pepsin Determined by Spectroscopic and Docking Methods.

    PubMed

    Guo, Liuqi; Ma, Xiaoli; Yan, Jin; Xu, Kailin; Wang, Qing; Li, Hui

    2015-11-01

    The interaction between niclosamide (NIC) and pepsin was investigated using multispectroscopic and molecular docking methods. Binding constant, number of binding sites, and thermodynamic parameters at different temperatures were measured. Results of fluorescence quenching and synchronous fluorescence spectroscopy in combination with three-dimensional fluorescence spectroscopy showed that changes occurred in the microenvironment of tryptophan residues and the molecular conformation of pepsin. Molecular interaction distance and energy-transfer efficiency between pepsin and NIC were determined based on Förster nonradiative energy-transfer mechanism. Furthermore, the binding of NIC inhibited pepsin activity in vitro. All these results indicated that NIC bound to pepsin mainly through hydrophobic interactions and hydrogen bonds at a single binding site. In conclusion, this study provided substantial molecular-level evidence that NIC could induce changes in pepsin structure and conformation.

  11. Gastropod grazers and nutrients, but not light, interact in determining periphytic algal diversity.

    PubMed

    Liess, Antonia; Kahlert, Maria

    2007-05-01

    The potential interactions of grazing, nutrients and light in influencing autotroph species diversity have not previously been considered. Earlier studies have shown that grazing and nutrients interact in determining autotroph species diversity, since grazing decreases species diversity when nutrients (i.e. N or P) limit autotroph growth, but increases it when nutrients are replete. We hypothesized that increased light intensities would intensify the interactions between grazing and nutrients on algal species diversity, resulting in even stronger reductions in algal species diversity through grazing under nutrient-poor conditions, and to even stronger increases of algal species diversity through grazing under nutrient-rich conditions. We studied the effects of grazing (absent, present), nutrients (ambient, N + P enriched) and light (low light, high light) on benthic algal diversity and periphyton C:nutrient ratios (which can indicate algal nutrient limitation) in a factorial laboratory experiment, using the gastropod grazer Viviparus viviparus. Grazing decreased algal biomass and algal diversity, but increased C:P and N:P ratios of periphyton. Grazing also affected periphyton species composition, by decreasing the proportion of Spirogyra sp. and increasing the proportion of species in the Chaetophorales. Grazing effects on diversity as well as on periphyton N:P ratios were weakened when nutrients were added (interaction between grazing and nutrients). Chlorophyll a (Chl a) per area increased with nutrient addition and decreased with high light intensities. Light did not increase the strength of the interaction between grazing and nutrients on periphytic algal diversity. This study shows that nutrient addition substantially reduced the negative effects of grazing on periphytic algal diversity, whereas light did not interact with grazing or nutrient enrichment in determining periphytic algal diversity.

  12. Life history determines genetic structure and evolutionary potential of host–parasite interactions

    PubMed Central

    Barrett, Luke G.; Thrall, Peter H.; Burdon, Jeremy J.; Linde, Celeste C.

    2009-01-01

    Measures of population genetic structure and diversity of disease-causing organisms are commonly used to draw inferences regarding their evolutionary history and potential to generate new variation in traits that determine interactions with their hosts. Parasite species exhibit a range of population structures and life-history strategies, including different transmission modes, life-cycle complexity, off-host survival mechanisms and dispersal ability. These are important determinants of the frequency and predictability of interactions with host species. Yet the complex causal relationships between spatial structure, life history and the evolutionary dynamics of parasite populations are not well understood. We demonstrate that a clear picture of the evolutionary potential of parasitic organisms and their demographic and evolutionary histories can only come from understanding the role of life history and spatial structure in influencing population dynamics and epidemiological patterns. PMID:18947899

  13. Parameter-free determination of actual temperature at chemical freeze-out in nuclear interactions

    NASA Astrophysics Data System (ADS)

    Panagiotou, A. D.; Mavromanolakis, G.; Tzoulis, J.

    1995-07-01

    We propose a method to determine the actual temperature at chemical freeze-out in relativistic nucleus-nucleus collisions, using the experimental μq/T and μs/T values, obtained from strange particle ratios. We employ the Hadron Gas formalism, assuming only local thermal equilibration, to relate the quarkchemical potential and temperature. This relation constrains the allowed values of μq/T, μs/T and T, enabling the determination of the actual temperature. Comparison of the inverse slope parameter of the mT-distributions with the actual temperature determines the transverse flow velocity of the fireball matter. Knowledge of these quantities is essential in determining the EoS of nuclear matter and in evaluating interactions with regard to a possible phase transition to QGP.

  14. Unusual role of epilayer–substrate interactions in determining orientational relations in van der Waals epitaxy

    PubMed Central

    Liu, Lei; Siegel, David A.; Chen, Wei; Liu, Peizhi; Guo, Junjie; Duscher, Gerd; Zhao, Chong; Wang, Hao; Wang, Wenlong; Bai, Xuedong; McCarty, Kevin F.; Zhang, Zhenyu; Gu, Gong

    2014-01-01

    Using selected-area low-energy electron diffraction analysis, we showed strict orientational alignment of monolayer hexagonal boron nitride (h-BN) crystallites with Cu(100) surface lattices of Cu foil substrates during atmospheric pressure chemical vapor deposition. In sharp contrast, the graphene–Cu(100) system is well-known to assume a wide range of rotations despite graphene’s crystallographic similarity to h-BN. Our density functional theory calculations uncovered the origin of this surprising difference: The crystallite orientation is determined during nucleation by interactions between the cluster’s edges and the substrate. Unlike the weaker B– and N–Cu interactions, strong C–Cu interactions rearrange surface Cu atoms, resulting in the aligned geometry not being a distinct minimum in total energy. The discovery made in this specific case runs counter to the conventional wisdom that strong epilayer–substrate interactions enhance orientational alignment in epitaxy and sheds light on the factors that determine orientational relation in van der Waals epitaxy of 2D materials. PMID:25385622

  15. Determination of 1-deoxynojirimycin in mulberry leaves using hydrophilic interaction chromatography with evaporative light scattering detection.

    PubMed

    Kimura, Toshiyuki; Nakagawa, Kiyotaka; Saito, Yuko; Yamagishi, Kenji; Suzuki, Masahiro; Yamaki, Kohji; Shinmoto, Hiroshi; Miyazawa, Teruo

    2004-03-24

    A simple and rapid method for determining 1-deoxynojirimycin (DNJ), a potent glucosidase inihibitor present in mulberry leaves (Morus alba and Morus bombysis), by high-performance liquid chromatography coupled to an evaporative light scattering detector (ELSD) has been developed. DNJ was separated from an extract of mulberry leaves on a TSKgel Amide-80 column, which is a representative column for hydrophilic interaction chromatography. During postcolumn detection, DNJ was detected by ELSD and concurrently identified by mass spectrometry. The detection limit was 100 ng. This method is sufficiently sensitive for determining DNJ in mulberry leaves and other related products.

  16. Heparin inhibits membrane interactions and lipid-induced fibrillation of a prion amyloidogenic determinant.

    PubMed

    Bazar, Ehud; Sheynis, Tania; Dorosz, Jerzy; Jelinek, Raz

    2011-03-21

    Glycosaminoglycans (GAGs), particularly heparin, are known to reduce the toxicities of various amyloidogenic proteins. The molecular factors underlying the antitoxic effects of GAGs, however, are still not fully understood. Because interactions of amyloidogenic proteins and their aggregates with membranes are believed to play major roles in affecting amyloid pathogenesis, our objective in this study was to elucidate the effect of heparin on membrane interactions of the 21-residue amyloidogenic determinant of the prion protein [PrP(106-126)]. Indeed, the experimental results indicate that heparin significantly interferes in membrane interactions of the prion peptide. Specifically, we show that there is direct competition for binding of PrP(106-126) between heparin on the one hand and negatively charged phospholipids on the other hand. The data reveal that heparin, even in very low molar concentrations, exhibited high affinity towards PrP(106-126) and consequently suppressed interactions of the peptide with lipid vesicles. Interestingly, whereas heparin significantly inhibited lipid-induced PrP(106-126) fibrillation, it still promoted fibril formation in aqueous solutions independently of the lipid vesicles present. Our results strongly suggest that the primary effects of GAGs in attenuating amyloid toxicities are due to blocking of membrane interactions of the amyloidogenic proteins rather than modulation of their fibrillation properties. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Molecular determinants of the interaction between Doa1 and Hse1 involved in endosomal sorting.

    PubMed

    Han, Seungsu; Shin, Donghyuk; Choi, Hoon; Lee, Sangho

    2014-03-28

    Yeast Doa1/Ufd3 is an adaptor protein for Cdc48 (p97 in mammal), an AAA type ATPase associated with endoplasmic reticulum-associated protein degradation pathway and endosomal sorting into multivesicular bodies. Doa1 functions in the endosomal sorting by its association with Hse1, a component of endosomal sorting complex required for transport (ESCRT) system. The association of Doa1 with Hse1 was previously reported to be mediated between PFU domain of Doa1 and SH3 of Hse1. However, it remains unclear which residues are specifically involved in the interaction. Here we report that Doa1/PFU interacts with Hse1/SH3 with a moderate affinity of 5 μM. Asn-438 of Doa1/PFU and Trp-254 of Hse1/SH3 are found to be critical in the interaction while Phe-434, implicated in ubiquitin binding via a hydrophobic interaction, is not. Small-angle X-ray scattering measurements combined with molecular docking and biochemical analysis yield the solution structure of the Doa1/PFU:Hse1/SH3 complex. Taken together, our results suggest that hydrogen bonding is a major determinant in the interaction of Doa1/PFU with Hse1/SH3.

  18. Specific neosaxitoxin interactions with the Na+ channel outer vestibule determined by mutant cycle analysis.

    PubMed Central

    Penzotti, J L; Lipkind, G; Fozzard, H A; Dudley, S C

    2001-01-01

    The voltage-gated Na+ channel alpha-subunit consists of four homologous domains arranged circumferentially to form the pore. Several neurotoxins, including saxitoxin (STX), block the pore by binding to the outer vestibule of this permeation pathway, which is composed of four pore-forming loops (P-loops), one from each domain. Neosaxitoxin (neoSTX) is a variant of STX that differs only by having an additional hydroxyl group at the N1 position of the 1,2,3 guanidinium (N1-OH). We used this structural variant in mutant cycle experiments to determine interactions of the N1-OH and its guanidinium with the outer vestibule. NeoSTX had a higher affinity for the adult rat skeletal muscle Na+ channel (muI or Scn4a) than for STX (DeltaG approximately = 1.3 kcal/mol). Mutant cycle analysis identified groups that potentially interacted with each other. The N1 toxin site interacted most strongly with muI Asp-400 and Tyr-401. The interaction between the N1-OH of neoSTX and Tyr-401 was attractive (DeltaDeltaG = -1.3 +/- 0.1 kcal/mol), probably with formation of a hydrogen bond. A second possible attractive interaction to Asp-1532 was identified. There was repulsion between Asp-400 and the N1-OH (DeltaDeltaG = 1.4 +/- 0.1 kcal/mol), and kinetic analysis further suggested that the N1-OH was interacting negatively with Asp-400 at the transition state. Changes in pH altered the affinity of neoSTX, as would be expected if the N1-OH site were partially deprotonated. These interactions offer an explanation for most of the difference in blocking efficacy between neoSTX and STX and for the sensitivity of neoSTX to pH. Kinetic analysis suggested significant differences in coupling energies between the transition and the equilibrium, bound states. This is the first report to identify points of interaction between a channel and a non-peptide toxin. This interaction pattern was consistent with previous proposals describing the interactions of STX with the outer vestibule (Lipkind, G. M., and H

  19. Columnar interactions determine horizontal propagation of recurrent network activity in neocortex

    PubMed Central

    Wester, Jason C.; Contreras, Diego

    2012-01-01

    The cortex is organized in vertical and horizontal circuits that determine the spatiotemporal properties of distributed cortical activity. Despite detailed knowledge of synaptic interactions among individual cells in the neocortex, little is known about the rules governing interactions among local populations. Here we used self-sustained recurrent activity generated in cortex, also known as up-states, in rat thalamocortical slices in vitro to understand interactions among laminar and horizontal circuits. By means of intracellular recordings and fast optical imaging with voltage sensitive dyes, we show that single thalamic inputs activate the cortical column in a preferential L4→L2/3→L5 sequence, followed by horizontal propagation with a leading front in supra and infragranular layers. To understand the laminar and columnar interactions, we used focal injections of TTX to block activity in small local populations, while preserving functional connectivity in the rest of the network. We show that L2/3 alone, without underlying L5, does not generate self-sustained activity and is inefficient propagating activity horizontally. In contrast, L5 sustains activity in the absence of L2/3 and is necessary and sufficient to propagate activity horizontally. However, loss of L2/3 delays horizontal propagation via L5. Finally, L5 amplifies activity in L2/3. Our results show for the first time that columnar interactions between supra and infragranular layers are required for the normal propagation of activity in the neocortex. Our data suggest that supra and infragranular circuits with their specific and complex set of inputs and outputs, work in tandem to determine the patterns of cortical activation observed in vivo. PMID:22514308

  20. Abundance and phenology patterns of two pond-breeding salamanders determine species interactions in natural populations.

    PubMed

    Anderson, Thomas L; Hocking, Daniel J; Conner, Christopher A; Earl, Julia E; Harper, Elizabeth B; Osbourn, Michael S; Peterman, William E; Rittenhouse, Tracy A G; Semlitsch, Raymond D

    2015-03-01

    Phenology often determines the outcome of interspecific interactions, where early-arriving species often dominate interactions over those arriving later. The effects of phenology on species interactions are especially pronounced in aquatic systems, but the evidence is largely derived from experimental studies. We examined whether differences in breeding phenology between two pond-breeding salamanders (Ambystoma annulatum and A. maculatum) affected metamorph recruitment and demographic traits within natural populations, with the expectation that the fall-breeding A. annulatum would negatively affect the spring-breeding A. maculatum. We monitored populations of each species at five ponds over 4 years using drift fences. Metamorph abundance and survival of A. annulatum were affected by intra- and interspecific processes, whereas metamorph size and date of emigration were primarily influenced by intraspecific effects. Metamorph abundance, snout-vent length, date of emigration and survival for A. maculatum were all predicted by combinations of intra- and interspecific effects, but often showed negative relationships with A. annulatum metamorph traits and abundance. Size and date of metamorphosis were strongly correlated within each species, but in opposite patterns (negative for A. annulatum and positive for A. maculatum), suggesting that the two species use alternative strategies to enhance terrestrial survival and that these factors may influence their interactions. Our results match predictions from experimental studies that suggest recruitment is influenced by intra- and interspecific processes which are determined by phenological differences between species. Incorporating spatiotemporal variability when modeling population dynamics is necessary to understand the importance of phenology in species interactions, especially as shifts in phenology occur under climate change.

  1. Structural determinants for the interaction of formyl peptide receptor 2 with peptide ligands.

    PubMed

    He, Hui-Qiong; Troksa, Erica L; Caltabiano, Gianluigi; Pardo, Leonardo; Ye, Richard D

    2014-01-24

    Unlike formyl peptide receptor 1 (FPR1), FPR2/ALX (FPR2) interacts with peptides of diverse sequences but has low affinity for the Escherichia coli-derived chemotactic peptide fMet-Leu-Phe (fMLF). Using computer modeling and site-directed mutagenesis, we investigated the structural requirements for FPR2 to interact with formyl peptides of different length and composition. In calcium flux assay, the N-formyl group of these peptides is necessary for activation of both FPR2 and FPR1, whereas the composition of the C-terminal amino acids appears more important for FPR2 than FPR1. FPR2 interacts better with pentapeptides (fMLFII, fMLFIK) than tetrapeptides (fMLFK, fMLFW) and tripeptide (fMLF) but only weakly with peptides carrying negative charges at the C terminus (e.g. fMLFE). In contrast, FPR1 is less sensitive to negative charges at the C terminus. A CXCR4-based homology model of FPR1 and FPR2 suggested that Asp-281(7.32) is crucial for the interaction of FPR2 with certain formyl peptides as its negative charge may be repulsive with the terminal COO- group of fMLF and negatively charged Glu in fMLFE. Asp-281(7.32) might also form a stable interaction with the positively charged Lys in fMLFK. Site-directed mutagenesis was performed to remove the negative charge at position 281 in FPR2. The D281(7.32)G mutant showed improved affinity for fMLFE and fMLF and reduced affinity for fMLFK compared with wild type FPR2. These results indicate that different structural determinants are used by FPR1 and FPR2 to interact with formyl peptides.

  2. Structural Determinants for the Interaction of Formyl Peptide Receptor 2 with Peptide Ligands*

    PubMed Central

    He, Hui-Qiong; Troksa, Erica L.; Caltabiano, Gianluigi; Pardo, Leonardo; Ye, Richard D.

    2014-01-01

    Unlike formyl peptide receptor 1 (FPR1), FPR2/ALX (FPR2) interacts with peptides of diverse sequences but has low affinity for the Escherichia coli-derived chemotactic peptide fMet-Leu-Phe (fMLF). Using computer modeling and site-directed mutagenesis, we investigated the structural requirements for FPR2 to interact with formyl peptides of different length and composition. In calcium flux assay, the N-formyl group of these peptides is necessary for activation of both FPR2 and FPR1, whereas the composition of the C-terminal amino acids appears more important for FPR2 than FPR1. FPR2 interacts better with pentapeptides (fMLFII, fMLFIK) than tetrapeptides (fMLFK, fMLFW) and tripeptide (fMLF) but only weakly with peptides carrying negative charges at the C terminus (e.g. fMLFE). In contrast, FPR1 is less sensitive to negative charges at the C terminus. A CXCR4-based homology model of FPR1 and FPR2 suggested that Asp-2817.32 is crucial for the interaction of FPR2 with certain formyl peptides as its negative charge may be repulsive with the terminal COO- group of fMLF and negatively charged Glu in fMLFE. Asp-2817.32 might also form a stable interaction with the positively charged Lys in fMLFK. Site-directed mutagenesis was performed to remove the negative charge at position 281 in FPR2. The D2817.32G mutant showed improved affinity for fMLFE and fMLF and reduced affinity for fMLFK compared with wild type FPR2. These results indicate that different structural determinants are used by FPR1 and FPR2 to interact with formyl peptides. PMID:24285541

  3. Interactions and Diffusion in Fine-Stranded β-lactoglobulin Gels Determined via FRAP and Binding

    PubMed Central

    Schuster, Erich; Hermansson, Anne-Marie; Öhgren, Camilla; Rudemo, Mats; Lorén, Niklas

    2014-01-01

    The effects of electrostatic interactions and obstruction by the microstructure on probe diffusion were determined in positively charged hydrogels. Probe diffusion in fine-stranded gels and solutions of β-lactoglobulin at pH 3.5 was determined using fluorescence recovery after photobleaching (FRAP) and binding, which is widely used in biophysics. The microstructures of the β-lactoglobulin gels were characterized using transmission electron microscopy. The effects of probe size and charge (negatively charged Na2-fluorescein (376Da) and weakly anionic 70kDa FITC-dextran), probe concentration (50 to 200 ppm), and β-lactoglobulin concentration (9% to 12% w/w) on the diffusion properties and the electrostatic interaction between the negatively charged probes and the positively charged gels or solutions were evaluated. The results show that the diffusion of negatively charged Na2-fluorescein is strongly influenced by electrostatic interactions in the positively charged β-lactoglobulin systems. A linear relationship between the pseudo-on binding rate constant and the β-lactoglobulin concentration for three different probe concentrations was found. This validates an important assumption of existing biophysical FRAP and binding models, namely that the pseudo-on binding rate constant equals the product of the molecular binding rate constant and the concentration of the free binding sites. Indicators were established to clarify whether FRAP data should be analyzed using a binding-diffusion model or an obstruction-diffusion model. PMID:24411257

  4. Interactions and diffusion in fine-stranded β-lactoglobulin gels determined via FRAP and binding.

    PubMed

    Schuster, Erich; Hermansson, Anne-Marie; Ohgren, Camilla; Rudemo, Mats; Lorén, Niklas

    2014-01-07

    The effects of electrostatic interactions and obstruction by the microstructure on probe diffusion were determined in positively charged hydrogels. Probe diffusion in fine-stranded gels and solutions of β-lactoglobulin at pH 3.5 was determined using fluorescence recovery after photobleaching (FRAP) and binding, which is widely used in biophysics. The microstructures of the β-lactoglobulin gels were characterized using transmission electron microscopy. The effects of probe size and charge (negatively charged Na2-fluorescein (376Da) and weakly anionic 70kDa FITC-dextran), probe concentration (50 to 200 ppm), and β-lactoglobulin concentration (9% to 12% w/w) on the diffusion properties and the electrostatic interaction between the negatively charged probes and the positively charged gels or solutions were evaluated. The results show that the diffusion of negatively charged Na2-fluorescein is strongly influenced by electrostatic interactions in the positively charged β-lactoglobulin systems. A linear relationship between the pseudo-on binding rate constant and the β-lactoglobulin concentration for three different probe concentrations was found. This validates an important assumption of existing biophysical FRAP and binding models, namely that the pseudo-on binding rate constant equals the product of the molecular binding rate constant and the concentration of the free binding sites. Indicators were established to clarify whether FRAP data should be analyzed using a binding-diffusion model or an obstruction-diffusion model.

  5. Protein-protein interaction site predictions with minimum covariance determinant and Mahalanobis distance.

    PubMed

    Qiu, Zhijun; Zhou, Bo; Yuan, Jiangfeng

    2017-09-01

    Protein-protein interaction site (PPIS) prediction must deal with the diversity of interaction sites that limits their prediction accuracy. Use of proteins with unknown or unidentified interactions can also lead to missing interfaces. Such data errors are often brought into the training dataset. In response to these two problems, we used the minimum covariance determinant (MCD) method to refine the training data to build a predictor with better performance, utilizing its ability of removing outliers. In order to predict test data in practice, a method based on Mahalanobis distance was devised to select proper test data as input for the predictor. With leave-one-validation and independent test, after the Mahalanobis distance screening, our method achieved higher performance according to Matthews correlation coefficient (MCC), although only a part of test data could be predicted. These results indicate that data refinement is an efficient approach to improve protein-protein interaction site prediction. By further optimizing our method, it is hopeful to develop predictors of better performance and wide range of application. Copyright © 2017. Published by Elsevier Ltd.

  6. Comparison of signaling interactions determining annual and perennial plant growth in response to low temperature

    PubMed Central

    Wingler, Astrid

    2015-01-01

    Low temperature inhibits plant growth despite the fact that considerable rates of photosynthetic activity can be maintained. Instead of lower rates of photosynthesis, active inhibition of cell division and expansion is primarily responsible for reduced growth. This results in sink limitation and enables plants to accumulate carbohydrates that act as compatible solutes or are stored throughout the winter to enable re-growth in spring. Regulation of growth in response to temperature therefore requires coordination with carbon metabolism, e.g., via the signaling metabolite trehalose-6-phosphate. The phytohormones gibberellin (GA) and jasmonate (JA) play an important role in regulating growth in response to temperature. Growth restriction at low temperature is mainly mediated by DELLA proteins, whose degradation is promoted by GA. For annual plants, it has been shown that the GA/DELLA pathway interacts with JA signaling and C-repeat binding factor dependent cold acclimation, but these interactions have not been explored in detail for perennials. Growth regulation in response to seasonal factors is, however, particularly important in perennials, especially at high latitudes. In autumn, growth cessation in trees is caused by shortening of the daylength in interaction with phytohormone signaling. In perennial grasses seasonal differences in the sensitivity to GA may enable enhanced growth in spring. This review provides an overview of the signaling interactions that determine plant growth at low temperature and highlights gaps in our knowledge, especially concerning the seasonality of signaling responses in perennial plants. PMID:25628637

  7. Determination of the fermion pair size in a resonantly interacting superfluid.

    PubMed

    Schunck, Christian H; Shin, Yong-Il; Schirotzek, André; Ketterle, Wolfgang

    2008-08-07

    Fermionic superfluidity requires the formation of particle pairs, the size of which varies from the femtometre scale in neutron stars and nuclei to the micrometre scale in conventional superconductors. Many properties of the superfluid depend on the pair size relative to the interparticle spacing. This is expressed in 'BCS-BEC crossover' theories, describing the crossover from a Bardeen-Cooper-Schrieffer (BCS)-type superfluid of loosely bound, large Cooper pairs to Bose-Einstein condensates (BECs) of tightly bound molecules. Such a crossover superfluid has been realized in ultracold atomic gases where high-temperature superfluidity has been observed. The microscopic properties of the fermion pairs can be probed using radio-frequency spectroscopy. However, previous work was difficult to interpret owing to strong final-state interactions that were not well understood. Here we realize a superfluid spin mixture in which such interactions have negligible influence and present fermion pair dissociation spectra that reveal the underlying pairing correlations. This allows us to determine that the spectroscopic pair size in the resonantly interacting gas is 20 per cent smaller than the interparticle spacing. These are the smallest pairs so far observed in fermionic superfluids, highlighting the importance of small fermion pairs for superfluidity at high critical temperatures. We have also identified transitions from fermion pairs to bound molecular states and to many-body bound states in the case of strong final-state interactions.

  8. Determination of heat transfer coefficient for an interaction of sub-cooled gas and metal

    NASA Astrophysics Data System (ADS)

    Zaidi Sidek, Mohd; Syahidan Kamarudin, Muhammad

    2016-02-01

    Heat transfer coefficient (HTC) for a hot metal surface and their surrounding is one of the need be defined parameter in hot forming process. This study has been conducted to determine the HTC for an interaction between sub-cooled gas sprayed on a hot metal surface. Both experiments and finite element have been adopted in this work. Initially, the designated experiment was conducted to obtain temperature history of spray cooling process. Then, an inverse method was adopted to calculate the HTC value before we validate in a finite element simulation model. The result shows that the heat transfer coefficient for interaction of subcooled gas and hot metal surface is 1000 W/m2K.

  9. Interactions between Intracellular Domains as Key Determinants of the Quaternary Structure and Function of Receptor Heteromers*

    PubMed Central

    Navarro, Gemma; Ferré, Sergi; Cordomi, Arnau; Moreno, Estefania; Mallol, Josefa; Casadó, Vicent; Cortés, Antoni; Hoffmann, Hanne; Ortiz, Jordi; Canela, Enric I.; Lluís, Carme; Pardo, Leonardo; Franco, Rafael; Woods, Amina S.

    2010-01-01

    G protein-coupled receptor (GPCR) heteromers are macromolecular complexes with unique functional properties different from those of its individual protomers. Little is known about what determines the quaternary structure of GPCR heteromers resulting in their unique functional properties. In this study, using resonance energy transfer techniques in experiments with mutated receptors, we provide for the first time clear evidence for a key role of intracellular domains in the determination of the quaternary structure of GPCR heteromers between adenosine A2A, cannabinoid CB1, and dopamine D2 receptors. In these interactions, arginine-rich epitopes form salt bridges with phosphorylated serine or threonine residues from CK1/2 consensus sites. Each receptor (A2A, CB1, and D2) was found to include two evolutionarily conserved intracellular domains to establish selective electrostatic interactions with intracellular domains of the other two receptors, indicating that these particular electrostatic interactions constitute a general mechanism for receptor heteromerization. Mutation experiments indicated that the interactions of the intracellular domains of the CB1 receptor with A2A and D2 receptors are fundamental for the correct formation of the quaternary structure needed for the function (MAPK signaling) of the A2A-CB1-D2 receptor heteromers. Analysis of MAPK signaling in striatal slices of CB1 receptor KO mice and wild-type littermates supported the existence of A1-CB1-D2 receptor heteromer in the brain. These findings allowed us to propose the first molecular model of the quaternary structure of a receptor heteromultimer. PMID:20562103

  10. Determination of histamine in seafood by hydrophilic interaction chromatography/tandem mass spectrometry.

    PubMed

    Yoshida, Tatsuo; Hamada, Hirotoshi; Murakawa, Hiroshi; Yoshimoto, Hidekazu; Tobino, Toshiaki; Toda, Kei

    2012-01-01

    A simple method was developed to determine histamine, an important compound in chemical food poisoning, by extraction followed by hydrophilic interaction chromatography-tandem mass spectrometry using a hydrophilic column with sulfobetaine-type zwitterion groups. The quantitation range in seafood products was from 0.4 to 200 mg kg(-1) for 5 g food samples. Quantitative recoveries were obtained with four types of seafood product. These results agreed well with those from the more complex, conventional HPLC method, which requires sample derivatization with dansyl chloride.

  11. [Studies on the interaction between RNA with neutral red and determination of RNA by spectrophotometry].

    PubMed

    Si, Wen-Hui

    2007-06-01

    An analytical method for the determination of ribonucleic acid by spectrophotometry was established. At the maximum absorption wavelength for neutral red in B-R buffer solution, and under the best conditions, the decrease in the absorbance was linear with the amount of ribonucleic acid. The linearity range was 0.0-9.0 microg x mL(-1), the detection limit was 0.52 microg x mL(-1), and the correlation coeffient was 0.999 8. This method was simple, rapid, and selective. So its application to the determination of ribonucleic acid was satisfactory. The reaction mechanism was that the electrostatic interaction leads to molecular association of RNA with neutral red, resulting in anti-ion permutation and bonding reaction.

  12. Precision nuclear orientation measurements for determining mixed magnetic dipole/electric quadrupole hyperfine interactions

    NASA Astrophysics Data System (ADS)

    Brewer, W. D.; Roman, P.; Marshak, H.

    1989-06-01

    We report the temperature dependence of the gamma-ray anisotropies from oriented160Tb nuclei produced by neutron activation of the central portion of a high-purity single crystal Tb slab. The magnetically saturated sample was studied over a wide temperature range from 18 mK to 150 mK. The temperatures were determined using precision resistance thermometry with in situ calibration by a magnetically shielded six-element superconducting fixed point device. Temperature stability during data acquisition was better than 0.1%, and least-squares fitting of the resulting temperature dependences of 0° and 90° anisotropies allowed both the magnetic dipole and the electric quadrupole hyperfine interaction frequencies to be determined with good accuracy. The weighted averages for 18 gamma rays are v M=1393.8 (8.1) MHz and v P=178.0 (2.1) MHz, in excellent agreement with NMR results on ion-implanted samples.

  13. Macromolecular depletion as a determinant of RBC adhesive interactions: why blood is thicker than water.

    PubMed

    Neu, Björn; Meiselman, Herbert J

    2014-01-01

    If a surface is in contact with a solution containing macromolecules or proteins, and the loss of configurational entropy of these molecules at the surface is not balanced by adsorption energy, a polymer-poor layer will develop near the surface. If two such layers overlap, an attractive force develops due to the osmotic pressure difference between these depletion zones and the bulk phase. Recent studies have shown that depletion interaction plays a major role in red blood cell (RBC) aggregation and hence it is a major determinate of blood flow stability; depletion interaction also markedly affects RBC adhesion to vascular endothelial cells. Understanding and quantitating factors that regulate depletion in vivo are thus of importance, yet made difficult since only very small changes of the cell surface (e.g., glycocalyx thickness) such as seen during RBC aging can lead to massive changes of depletion interaction and hence cell-cell adhesion. It is suggested that insight into the in vivo relevance of depletion mechanisms may lead to an improved understanding of how and why blood flow is altered in many diseases, and may also provide new biomarkers (e.g., surface properties) that will aid in the development of novel or improved diagnostic and therapeutic tools.

  14. Effects of strong interactions in a half-metallic magnet: A determinant quantum Monte Carlo study

    DOE PAGES

    Jiang, M.; Pickett, W. E.; Scalettar, R. T.

    2013-04-03

    Understanding the effects of electron-electron interactions in half-metallic magnets (HMs), which have band structures with one gapped spin channel and one metallic channel, poses fundamental theoretical issues as well as having importance for their potential applications. Here we use determinant quantum Monte Carlo to study the impacts of an on-site Hubbard interaction U, finite temperature, and an external (Zeeman) magnetic field on a bilayer tight-binding model which is a half-metal in the absence of interactions, by calculating the spectral density, conductivity, spin polarization of carriers, and local magnetic properties. We quantify the effect of U on the degree of thermalmore » depolarization, and follow relative band shifts and monitor when significant gap states appear, each of which can degrade the HM character. For this model, Zeeman coupling induces, at fixed particle number, two successive transitions: compensated half-metal with spin-down band gap → metallic ferromagnet → saturated ferromagnetic insulator. However, over much of the more relevant parameter regime, the half-metallic properties are rather robust to U.« less

  15. Effects of strong interactions in a half-metallic magnet: A determinant quantum Monte Carlo study

    SciTech Connect

    Jiang, M.; Pickett, W. E.; Scalettar, R. T.

    2013-04-03

    Understanding the effects of electron-electron interactions in half-metallic magnets (HMs), which have band structures with one gapped spin channel and one metallic channel, poses fundamental theoretical issues as well as having importance for their potential applications. Here we use determinant quantum Monte Carlo to study the impacts of an on-site Hubbard interaction U, finite temperature, and an external (Zeeman) magnetic field on a bilayer tight-binding model which is a half-metal in the absence of interactions, by calculating the spectral density, conductivity, spin polarization of carriers, and local magnetic properties. We quantify the effect of U on the degree of thermal depolarization, and follow relative band shifts and monitor when significant gap states appear, each of which can degrade the HM character. For this model, Zeeman coupling induces, at fixed particle number, two successive transitions: compensated half-metal with spin-down band gap → metallic ferromagnet → saturated ferromagnetic insulator. However, over much of the more relevant parameter regime, the half-metallic properties are rather robust to U.

  16. Direct determination of spin-orbit interaction coefficients and realization of the persistent spin helix symmetry

    NASA Astrophysics Data System (ADS)

    Sasaki, A.; Nonaka, S.; Kunihashi, Y.; Kohda, M.; Bauernfeind, T.; Dollinger, T.; Richter, K.; Nitta, J.

    2014-09-01

    The spin-orbit interaction plays a crucial role in diverse fields of condensed matter, including the investigation of Majorana fermions, topological insulators, quantum information and spintronics. In III-V zinc-blende semiconductor heterostructures, two types of spin-orbit interaction—Rashba and Dresselhaus—act on the electron spin as effective magnetic fields with different directions. They are characterized by coefficients α and β, respectively. When α is equal to β, the so-called persistent spin helix symmetry is realized. In this condition, invariance with respect to spin rotations is achieved even in the presence of the spin-orbit interaction, implying strongly enhanced spin lifetimes for spatially periodic spin modes. Existing methods to evaluate α/β require fitting analyses that often include ambiguity in the parameters used. Here, we experimentally demonstrate a simple and fitting parameter-free technique to determine α/β and to deduce the absolute values of α and β. The method is based on the detection of the effective magnetic field direction and the strength induced by the two spin-orbit interactions. Moreover, we observe the persistent spin helix symmetry by gate tuning.

  17. Age, growth and size interact with stress to determine life span and mortality

    PubMed Central

    Roach, Deborah Ann

    2012-01-01

    Individuals in a large experimental field population, of the short-lived perennial species Plantago lanceolata, were followed to determine the sources of variation that influence mortality and life span. The design included multiple age groups with initially similar genetic structure, which made it possible to separate age effects from period effects and to identify the genetic component to variation in life span. During a period of stress, individuals of all ages showed parallel increases in mortality but different cohorts experienced this period of high mortality at different ages. This then influenced the distribution of life spans across cohorts. Age and size-age interactions influenced mortality during the period of stress. Smaller individuals died but only if they were old. Additionally, growth and age interacted with stress such that older individuals had negative growth and high mortality whereas younger individuals had positive growth and relatively lower mortality during stress. The results of this study show that it is not simply the environment that can have a major impact on demography in natural populations, rather, age, size and growth can interact with the environment to influence mortality and life span when the environment is stressful. PMID:22664575

  18. Dietary ligands as determinants of iron-zinc interactions at the absorptive enterocyte.

    PubMed

    Iyengar, Vasuprada; Pullakhandam, Raghu; Nair, K Madhavan

    2010-10-01

    Iron and zinc interact at the enterocyte and influence the absorption of one another. We have previously reported that zinc noncompetitively inhibits iron uptake in Caco-2 cells, a widely accepted model of the absorptive enterocyte. However, the determinants of this interaction, such as the effect of dietary ligands, remain uncharacterized. Dietary ligands selectively chelate iron and zinc in definite stoichiometric proportions and thus alter the bioavailability from food matrices. Here, we have used common dietary ligands, such as ascorbic acid, phytic acid, tannic acid, tartaric acid, cysteine, histidine, and methionine to characterize iron, zinc uptake individually and in combination, using Caco-2 cells. Selective chelation of zinc, using cysteine, decreased the magnitude of inhibition of iron uptake but could not reverse the inhibition. On the other hand, selective increase in iron uptake in the presence of methionine resulted in increased zinc uptake, rather than inhibition. Taken together, these in vitro results suggest that dietary ligands can modulate iron-zinc interaction and that zinc cannot competitively inhibit iron uptake.

  19. Methods to determine the interactions of micro- and nanoparticles with mucus.

    PubMed

    Grießinger, Julia; Dünnhaupt, Sarah; Cattoz, Beatrice; Griffiths, Peter; Oh, Sejin; Borrós i Gómez, Salvador; Wilcox, Matthew; Pearson, Jeffrey; Gumbleton, Mark; Abdulkarim, Muthanna; Pereira de Sousa, Irene; Bernkop-Schnürch, Andreas

    2015-10-01

    The present review provides an overview of methods and techniques for studying interactions of micro- and nanoparticulate drug delivery system with mucus. Nanocarriers trapped by mucus are featuring a change in particle size and zeta potential that can be utilized to predict their mucus permeation behavior. Furthermore, interactions between nanoparticulate drug delivery systems and mucus layer modify the viscoelasticity of mucus which can be detected via rheological studies and quartz crystal microbalance with dissipation monitoring (QCM-D) analysis. Having a closer look at molecular interactions between drug carrier and mucus small-angle neutron scattering (SANS) is an appropriate analysis technique. Moreover, different methods to determine particle diffusion in mucus such as the newly established Transwell diffusion system, rotating silicone tube technique, multiple-particle tracking (MPT) and diffusion NMR are summarized within this review. The explanations and discussed pros and cons of collated methods and techniques should provide a good starting point for all those looking forward to move in this interesting field.

  20. Determination of the centroid of interaction of crystals in block detectors for pet

    NASA Astrophysics Data System (ADS)

    Picard, Y.; Thompson, C. J.

    1994-08-01

    Cut blocks of bismuth germanate (BGO) are the most common detectors used in current positron emission tomography (PET) imaging systems. The distribution of light received by four photo-multiplier (PMT) cathodes is used to assign each gamma ray to one crystal. Most 511-keV gamma rays undergo Compton scattering in the crystal before being photoelectrically absorbed. This, and the effects of dense metal septa between blocks change the response of the crystals depending on their position in the block and the angle of incidence of gamma rays on the block. For each projection, we used Monte Carlo simulation to determine the 'centroid of interaction' for each crystal in the block. We found the crystals appear to be packed slightly closer in each block than their geometrical distance. We found the location of the crystal's centroid relative to its center changes along each projection. We simulated the 4 x 4 crystal arrays of the Scanditronix PC2048-B, determined the centroid of interaction for each crystal, then modified the reconstruction program's interpolation parameters. The spatial resolution improved by up to 10%, and a distortion of 1.5 mm at the edge of the imaging field was eliminated.

  1. Abiotic and biotic interactions determine whether increased colonization is beneficial or detrimental to metapopulation management.

    PubMed

    Southwell, Darren M; Rhodes, Jonathan R; McDonald-Madden, Eve; Nicol, Sam; Helmstedt, Kate J; McCarthy, Michael A

    2016-06-01

    Increasing the colonization rate of metapopulations can improve persistence, but can also increase exposure to threats. To make good decisions, managers must understand whether increased colonization is beneficial or detrimental to metapopulation persistence. While a number of studies have examined interactions between metapopulations, colonization, and threats, they have assumed that threat dynamics respond linearly to changes in colonization. Here, we determined when to increase colonization while explicitly accounting for non-linear dependencies between a metapopulation and its threats. We developed patch occupancy metapopulation models for species susceptible to abiotic, generalist, and specialist threats and modeled the total derivative of the equilibrium proportion of patches occupied by each metapopulation with respect to the colonization rate. By using the total derivative, we developed a rule for determining when to increase metapopulation colonization. This rule was applied to a simulated metapopulation where the dynamics of each threat responded to increased colonization following a power function. Before modifying colonization, we show that managers must understand: (1) whether a metapopulation is susceptible to a threat; (2) the type of threat acting on a metapopulation; (3) which component of threat dynamics might depend on colonization, and; (4) the likely response of a threat-dependent variable to changes in colonization. The sensitivity of management decisions to these interactions increases uncertainty in conservation planning decisions. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  2. Protein-nanoparticle interactions evaluation by immunomethods: Surfactants can disturb quantitative determinations.

    PubMed

    Fornaguera, Cristina; Calderó, Gabriela; Solans, Conxita; Vauthier, Christine

    2015-08-01

    The adsorption of proteins on nanoparticle surface is one of the first events that occur when nanoparticles enter in the blood stream, which influences nanoparticles lifetime and further biodistribution. Albumin, which is the most abundant protein in serum and which has been deeply characterized, is an interesting model protein to investigate nanoparticle-protein interactions. Therefore, the interaction of nanoparticles with serum albumin has been widely studied. Immunomethods were suggested for the investigation of adsorption isotherms because of their ease to quantify the non-adsorbed bovine serum albumin without the need of applying separation methods that could modify the balance between the adsorbed and non-adsorbed proteins. The present work revealed that this method should be applied with caution. Artifacts in the determination of free protein can be generated by the presence of surfactants such as polysorbate 80, widely used in the pharmaceutical and biomedical field, that are needed to preserve the stability of nanoparticle dispersions. It was shown that the presence of traces of polysorbate 80 in the dispersion leads to an overestimation of the amount of bovine serum albumin remaining free in the dispersion medium when determined by both radial immunodiffusion and rocket immunoelectrophoresis. However, traces of poloxamer 188 did not result in clear perturbed migrations. These methods are not appropriate to perform adsorption isotherms of proteins on nanoparticle dispersions containing traces of remaining free surfactant. They should only be applied on dispersions that are free of surfactant that is not associated with nanoparticles.

  3. Micelle-enhanced and terbium-sensitized spectrofluorimetric determination of gatifloxacin and its interaction mechanism.

    PubMed

    Guo, Changchuan; Wang, Lei; Hou, Zhun; Jiang, Wei; Sang, Lihong

    2009-05-01

    A terbium-sensitized spectrofluorimetric method using an anionic surfactant, sodium dodecyl benzene sulfonate (SDBS), was developed for the determination of gatifloxacin (GFLX). A coordination complex system of GFLX-Tb(3+)-SDBS was studied. It was found that SDBS significantly enhanced the fluorescence intensity of the complex (about 11-fold). Optimal experimental conditions were determined as follows: excitation and emission wavelengths of 331 and 547nm, pH 7.0, 2.0x10(-4)moll(-1) terbium (III), and 2.0x10(-4)moll(-1) SDBS. The enhanced fluorescence intensity of the system (DeltaI(f)) showed a good linear relationship with the concentration of GFLX over the range of 5.0x10(-10) to 5.0x10(-8)moll(-1) with a correlation coefficient of 0.9996. The detection limit (3sigma) was determined as 6.0x10(-11)moll(-1). This method has been successfully applied to the determination of GFLX in pharmaceuticals and human urine/serum samples. Compared with most of other methods reported, the rapid and simple procedure proposed in the text offers higher sensitivity, wider linear range, and better stability. The interaction mechanism of the system is also studied by the research of ultraviolet absorption spectra, surface tension, solution polarity and fluorescence polarization.

  4. Orbit Determination and Navigation of the Time History of Events and Macroscale Interactions during Substorms (THEMIS)

    NASA Technical Reports Server (NTRS)

    Morinelli, Patrick; Cosgrove, jennifer; Blizzard, Mike; Nicholson, Ann; Robertson, Mika

    2007-01-01

    This paper provides an overview of the launch and early orbit activities performed by the NASA Goddard Space Flight Center's (GSFC) Flight Dynamics Facility (FDF) in support of five probes comprising the Time History of Events and Macroscale Interactions during Substorms (THEMIS) spacecraft. The FDF was tasked to support THEMIS in a limited capacity providing backup orbit determination support for validation purposes for all five THEMIS probes during launch plus 30 days in coordination with University of California Berkeley Flight Dynamics Center (UCB/FDC). The FDF's orbit determination responsibilities were originally planned to be as a backup to the UCB/FDC for validation purposes only. However, various challenges early on in the mission and a Spacecraft Emergency declared thirty hours after launch placed the FDF team in the role of providing the orbit solutions that enabled contact with each of the probes and the eventual termination of the Spacecraft Emergency. This paper details the challenges and various techniques used by the GSFC FDF team to successfully perform orbit determination for all five THEMIS probes during the early mission. In addition, actual THEMIS orbit determination results are presented spanning the launch and early orbit mission phase. Lastly, this paper enumerates lessons learned from the THEMIS mission, as well as demonstrates the broad range of resources and capabilities within the FDF for supporting critical launch and early orbit navigation activities, especially challenging for constellation missions.

  5. Orbit Determination and Navigation of the Time History of Events and Macroscale Interactions during Substorms (THEMIS)

    NASA Technical Reports Server (NTRS)

    Morinelli, Patrick; Cosgrove, Jennifer; Blizzard, Mike; Robertson, Mike

    2007-01-01

    This paper provides an overview of the launch and early orbit activities performed by the NASA Goddard Space Flight Center's (GSFC) Flight Dynamics Facility (FDF) in support of five probes comprising the Time History of Events and Macroscale Interactions during Substorms (THEMIS) spacecraft. The FDF was tasked to support THEMIS in a limited capacity providing backup orbit determination support for validation purposes for all five THEMIS probes during launch plus 30 days in coordination with University of California Berkeley Flight Dynamics Center (UCB/FDC)2. The FDF's orbit determination responsibilities were originally planned to be as a backup to the UCB/FDC for validation purposes only. However, various challenges early on in the mission and a Spacecraft Emergency declared thirty hours after launch placed the FDF team in the role of providing the orbit solutions that enabled contact with each of the probes and the eventual termination of the Spacecraft Emergency. This paper details the challenges and various techniques used by the GSFC FDF team to successfully perform orbit determination for all five THEMIS probes during the early mission. In addition, actual THEMIS orbit determination results are presented spanning the launch and early orbit mission phase. Lastly, this paper enumerates lessons learned from the THEMIS mission, as well as demonstrates the broad range of resources and capabilities within the FDF for supporting critical launch and early orbit navigation activities, especially challenging for constellation missions.

  6. Quantitative determination of pairing interactions for high-temperature superconductivity in cuprates

    PubMed Central

    Bok, Jin Mo; Bae, Jong Ju; Choi, Han-Yong; Varma, Chandra M.; Zhang, Wentao; He, Junfeng; Zhang, Yuxiao; Yu, Li; Zhou, X. J.

    2016-01-01

    A profound problem in modern condensed matter physics is discovering and understanding the nature of fluctuations and their coupling to fermions in cuprates, which lead to high-temperature superconductivity and the invariably associated strange metal state. We report the quantitative determination of normal and pairing self-energies, made possible by laser-based angle-resolved photoemission measurements of unprecedented accuracy and stability. Through a precise inversion procedure, both the effective interactions in the attractive d-wave symmetry and the repulsive part in the full symmetry are determined. The latter is nearly angle-independent. Near Tc, both interactions are nearly independent of frequency and have almost the same magnitude over the complete energy range of up to about 0.4 eV, except for a low-energy feature at around 50 meV that is present only in the repulsive part, which has less than 10% of the total spectral weight. Well below Tc, they both change similarly, with superconductivity-induced features at low energies. Besides finding the pairing self-energy and the attractive interactions for the first time, these results expose the central paradox of the problem of high Tc: how the same frequency-independent fluctuations can dominantly scatter at angles ±π/2 in the attractive channel to give d-wave pairing and lead to angle-independent repulsive scattering. The experimental results are compared with available theoretical calculations based on antiferromagnetic fluctuations, the Hubbard model, and quantum-critical fluctuations of the loop-current order. PMID:26973872

  7. Quantitative determination of pairing interactions for high-temperature superconductivity in cuprates.

    PubMed

    Bok, Jin Mo; Bae, Jong Ju; Choi, Han-Yong; Varma, Chandra M; Zhang, Wentao; He, Junfeng; Zhang, Yuxiao; Yu, Li; Zhou, X J

    2016-03-01

    A profound problem in modern condensed matter physics is discovering and understanding the nature of fluctuations and their coupling to fermions in cuprates, which lead to high-temperature superconductivity and the invariably associated strange metal state. We report the quantitative determination of normal and pairing self-energies, made possible by laser-based angle-resolved photoemission measurements of unprecedented accuracy and stability. Through a precise inversion procedure, both the effective interactions in the attractive d-wave symmetry and the repulsive part in the full symmetry are determined. The latter is nearly angle-independent. Near T c, both interactions are nearly independent of frequency and have almost the same magnitude over the complete energy range of up to about 0.4 eV, except for a low-energy feature at around 50 meV that is present only in the repulsive part, which has less than 10% of the total spectral weight. Well below T c, they both change similarly, with superconductivity-induced features at low energies. Besides finding the pairing self-energy and the attractive interactions for the first time, these results expose the central paradox of the problem of high T c: how the same frequency-independent fluctuations can dominantly scatter at angles ±π/2 in the attractive channel to give d-wave pairing and lead to angle-independent repulsive scattering. The experimental results are compared with available theoretical calculations based on antiferromagnetic fluctuations, the Hubbard model, and quantum-critical fluctuations of the loop-current order.

  8. Climate warming and agricultural stressors interact to determine stream periphyton community composition.

    PubMed

    Piggott, Jeremy J; Salis, Romana K; Lear, Gavin; Townsend, Colin R; Matthaei, Christoph D

    2015-01-01

    Lack of knowledge about how the various drivers of global climate change will interact with multiple stressors already affecting ecosystems is the basis for great uncertainty in projections of future biological change. Despite concerns about the impacts of changes in land use, eutrophication and climate warming in running waters, the interactive effects of these stressors on stream periphyton are largely unknown. We manipulated nutrients (simulating agricultural runoff), deposited fine sediment (simulating agricultural erosion) (two levels each) and water temperature (eight levels, 0-6 °C above ambient) simultaneously in 128 streamside mesocosms. Our aim was to determine the individual and combined effects of the three stressors on the algal and bacterial constituents of the periphyton. All three stressors had pervasive individual effects, but in combination frequently produced synergisms at the population level and antagonisms at the community level. Depending on sediment and nutrient conditions, the effect of raised temperature frequently produced contrasting response patterns, with stronger or opposing effects when one or both stressors were augmented. Thus, warming tended to interact negatively with nutrients or sediment by weakening or reversing positive temperature effects or strengthening negative ones. Five classes of algal growth morphology were all affected in complex ways by raised temperature, suggesting that these measures may prove unreliable in biomonitoring programs in a warming climate. The evenness and diversity of the most abundant bacterial taxa increased with temperature at ambient but not with enriched nutrient levels, indicating that warming coupled with nutrient limitation may lead to a more evenly distributed bacterial community as temperatures rise. Freshwater management decisions that seek to avoid or mitigate the negative effects of agricultural land use on stream periphyton should be informed by knowledge of the interactive effects of

  9. Interaction between water and polar groups of the helix backbone: An important determinant of helix propensities

    PubMed Central

    Luo, Peizhi; Baldwin, Robert L.

    1999-01-01

    We report an enthalpic factor involved in determining helix propensities of nonpolar amino acids. Thermal unfolding curves of the five 13-residue peptides, Ac-KA4XA4KGY-NH2 (X = Ala, Leu, Ile, Val, Gly), have been measured by using CD in water/trifluoroethanol (TFE) mixtures. The peptide helix contents show that the rank order of helix propensities changes with temperature: although Ala has the highest helix propensity at 0°C in all TFE concentrations, it is lower than Leu, Ile, and Val at 50°C in 20% TFE. This change is attributed to shielding by nonpolar side chains of the interaction between water and polar groups in the helix backbone for the following reasons. (i) Helix content is directly related to helix propensity for these designed peptides because side-chain–side-chain interactions are absent. (ii) The change in rank order with temperature is enthalpic in origin: in water, the apparent enthalpy of helix formation calculated from the thermal unfolding curves varies widely among the five peptides and has the same rank order as the helix propensities at 0°C. The rank order does not result from burial of nonpolar surface area because the calculated heat capacity change (ΔCp) on helix formation is opposite in sign from the expected ΔCp. (iii) A nonpolar side chain can exclude water from interacting with helix polar groups, according to calculations of water-accessible surface area, and the polar interaction between water and peptide polar groups is entirely enthalpic, as shown by amide transfer data. PMID:10220396

  10. The Interaction of Intrinsic Dynamics and Network Topology in Determining Network Burst Synchrony

    PubMed Central

    Gaiteri, Chris; Rubin, Jonathan E.

    2011-01-01

    The pre-Bötzinger complex (pre-BötC), within the mammalian respiratory brainstem, represents an ideal system for investigating the synchronization properties of complex neuronal circuits via the interaction of cell-type heterogeneity and network connectivity. In isolation, individual respiratory neurons from the pre-BötC may be tonically active, rhythmically bursting, or quiescent. Despite this intrinsic heterogeneity, coupled networks of pre-BötC neurons en bloc engage in synchronized bursting that can drive inspiratory motor neuron activation. The region's connection topology has been recently characterized and features dense clusters of cells with occasional connections between clusters. We investigate how the dynamics of individual neurons (quiescent/bursting/tonic) and the betweenness centrality of neurons’ positions within the network connectivity graph interact to govern network burst synchrony, by simulating heterogeneous networks of computational model pre-BötC neurons. Furthermore, we compare the prevalence and synchrony of bursting across networks constructed with a variety of connection topologies, analyzing the same collection of heterogeneous neurons in small-world, scale-free, random, and regularly structured networks. We find that several measures of network burst synchronization are determined by interactions of network topology with the intrinsic dynamics of neurons at central network positions and by the strengths of synaptic connections between neurons. Surprisingly, despite the functional role of synchronized bursting within the pre-BötC, we find that synchronized network bursting is generally weakest when we use its specific connection topology, which leads to synchrony within clusters but poor coordination across clusters. Overall, our results highlight the relevance of interactions between topology and intrinsic dynamics in shaping the activity of networks and the concerted effects of connectivity patterns and dynamic heterogeneities

  11. The interaction of intrinsic dynamics and network topology in determining network burst synchrony.

    PubMed

    Gaiteri, Chris; Rubin, Jonathan E

    2011-01-01

    The pre-Bötzinger complex (pre-BötC), within the mammalian respiratory brainstem, represents an ideal system for investigating the synchronization properties of complex neuronal circuits via the interaction of cell-type heterogeneity and network connectivity. In isolation, individual respiratory neurons from the pre-BötC may be tonically active, rhythmically bursting, or quiescent. Despite this intrinsic heterogeneity, coupled networks of pre-BötC neurons en bloc engage in synchronized bursting that can drive inspiratory motor neuron activation. The region's connection topology has been recently characterized and features dense clusters of cells with occasional connections between clusters. We investigate how the dynamics of individual neurons (quiescent/bursting/tonic) and the betweenness centrality of neurons' positions within the network connectivity graph interact to govern network burst synchrony, by simulating heterogeneous networks of computational model pre-BötC neurons. Furthermore, we compare the prevalence and synchrony of bursting across networks constructed with a variety of connection topologies, analyzing the same collection of heterogeneous neurons in small-world, scale-free, random, and regularly structured networks. We find that several measures of network burst synchronization are determined by interactions of network topology with the intrinsic dynamics of neurons at central network positions and by the strengths of synaptic connections between neurons. Surprisingly, despite the functional role of synchronized bursting within the pre-BötC, we find that synchronized network bursting is generally weakest when we use its specific connection topology, which leads to synchrony within clusters but poor coordination across clusters. Overall, our results highlight the relevance of interactions between topology and intrinsic dynamics in shaping the activity of networks and the concerted effects of connectivity patterns and dynamic heterogeneities.

  12. Depth of interaction determination in monolithic scintillator with double side SiPM readout.

    PubMed

    Morrocchi, Matteo; Ambrosi, Giovanni; Bisogni, Maria Giuseppina; Bosi, Filippo; Boretto, Marco; Cerello, Piergiorgio; Ionica, Maria; Liu, Ben; Pennazio, Francesco; Piliero, Maria Antonietta; Pirrone, Giovanni; Postolache, Vasile; Wheadon, Richard; Del Guerra, Alberto

    2017-12-01

    Monolithic scintillators read out by arrays of photodetectors represent a promising solution to obtain high spatial resolution and the depth of interaction (DOI) of the annihilation photon. We have recently investigated a detector geometry composed of a monolithic scintillator readout on two sides by silicon photomultiplier (SiPM) arrays, and we have proposed two parameters for the DOI determination: the difference in the number of triggered SiPMs on the two sides of the detector and the difference in the maximum collected signal on a single SiPM on each side. This work is focused on the DOI calibration and on the determination of the capability of our detector. For the DOI calibration, we studied a method which can be implemented also in detectors mounted in a full PET scanner. We used a PET detector module composed of a monolithic 20 × 20 × 10 mm(3) LYSO scintillator crystal coupled on two opposite faces to two arrays of SiPMs. On each side, the scintillator was coupled to 6 × 6 SiPMs. In this paper, the two parameters previously proposed for the DOI determination were calibrated with two different methods. The first used a lateral scan of the detector with a collimated 511 keV pencil beam at steps of 0.5 mm to study the detector DOI capability, while the second used the background radiation of the (176)Lu in the scintillator. The DOI determination capability was tested on different regions of the detector using each parameter and the combination of the two. With both parameters for the DOI determination, in the lateral scan, the bias between the mean reconstructed DOI and the real beam position was lower than 0.3 mm, and the DOI distribution had a standard deviation of about 1.5 mm. When using the calibration with the radioactivity of the LYSO, the mean bias increased of about 0.2 mm but with no degradation of the standard deviation of the DOI distribution. The two parameters allow to achieve a DOI resolution comparable with the state of the

  13. Determination of dominant frequency of resting-state brain interaction within one functional system.

    PubMed

    Zhang, Yu-Jin; Duan, Lian; Zhang, Han; Biswal, Bharat B; Lu, Chun-Ming; Zhu, Chao-Zhe

    2012-01-01

    Accumulating evidence has revealed that the resting-state functional connectivity (RSFC) is frequency specific and functional system dependent. Determination of dominant frequency of RSFC (RSFC(df)) within a functional system, therefore, is of importance for further understanding the brain interaction and accurately assessing the RSFC within the system. Given the unique advantages over other imaging techniques, functional near-infrared spectroscopy (fNIRS) holds distinct merits for RSFC(df) determination. However, an obstacle that hinders fNIRS from potential RSFC(df) investigation is the interference of various global noises in fNIRS data which could bring spurious connectivity at the frequencies unrelated to spontaneous neural activity. In this study, we first quantitatively evaluated the interferences of multiple systemic physiological noises and the motion artifact by using simulated data. We then proposed a functional system dependent and frequency specific analysis method to solve the problem by introducing anatomical priori information on the functional system of interest. Both the simulated and real resting-state fNIRS experiments showed that the proposed method outperforms the traditional one by effectively eliminating the negative effects of the global noises and significantly improving the accuracy of the RSFC(df) estimation. The present study thus provides an effective approach to RSFC(df) determination for its further potential applications in basic and clinical neurosciences.

  14. Chemical genomic interaction profiling reveals determinants of intrinsic antibiotic resistance in Mycobacterium tuberculosis.

    PubMed

    Xu, Weizhen; DeJesus, Michael A; Rücker, Nadine; Engelhart, Curtis A; Wright, Meredith G; Healy, Claire; Lin, Kan; Wang, Ruojun; Park, Sae Woong; Ioerger, Thomas R; Schnappinger, Dirk; Ehrt, Sabine

    2017-09-11

    Chemotherapy for tuberculosis (TB) is lengthy and could benefit from synergistic adjuvant therapeutics that enhance current and novel drug regimens. To identify genetic determinants of intrinsic antibiotic susceptibility in Mycobacterium tuberculosis (Mtb) we applied a chemical genetic interaction (CGI) profiling approach. We screened a saturated transposon mutant library and identified mutants that exhibit altered fitness in the presence of partially-inhibitory concentrations of rifampicin, ethambutol, isoniazid, vancomycin and meropenem, antibiotics of diverse mechanisms-of-action. This screen identified Mtb's cell envelope as a major determinant of antibiotic susceptibility but did not yield mutants whose increase in susceptibility was due to transposon insertions in genes encoding efflux pumps. Intrinsic antibiotic resistance determinants affecting multiple antibiotics included the peptidoglycan-arabinogalactan ligase Lcp1, the mycolic acid synthase MmaA4, the protein translocase SecA2, the mannosyltransferase PimE, the cell envelope-associated protease CaeA/Hip1, and FecB, a putative iron-dicitrate-binding protein. Characterization of a deletion mutant confirmed FecB to be involved in the intrinsic resistance to every antibiotic analyzed. In contrast to its predicted function, FecB was dispensable for growth in low iron medium, and instead functioned as a critical mediator of envelope integrity. Copyright © 2017 American Society for Microbiology.

  15. Plant genetics and interspecific competitive interactions determine ectomycorrhizal fungal community responses to climate change.

    PubMed

    Gehring, Catherine; Flores-Rentería, Dulce; Sthultz, Christopher M; Leonard, Tierra M; Flores-Rentería, Lluvia; Whipple, Amy V; Whitham, Thomas G

    2014-03-01

    Although the importance of plant-associated microbes is increasingly recognized, little is known about the biotic and abiotic factors that determine the composition of that microbiome. We examined the influence of plant genetic variation, and two stressors, one biotic and one abiotic, on the ectomycorrhizal (EM) fungal community of a dominant tree species, Pinus edulis. During three periods across 16 years that varied in drought severity, we sampled the EM fungal communities of a wild stand of P. edulis in which genetically based resistance and susceptibility to insect herbivory was linked with drought tolerance and the abundance of competing shrubs. We found that the EM fungal communities of insect-susceptible trees remained relatively constant as climate dried, while those of insect-resistant trees shifted significantly, providing evidence of a genotype by environment interaction. Shrub removal altered the EM fungal communities of insect-resistant trees, but not insect-susceptible trees, also a genotype by environment interaction. The change in the EM fungal community of insect-resistant trees following shrub removal was associated with greater shoot growth, evidence of competitive release. However, shrub removal had a 7-fold greater positive effect on the shoot growth of insect-susceptible trees than insect-resistant trees when shrub density was taken into account. Insect-susceptible trees had higher growth than insect-resistant trees, consistent with the hypothesis that the EM fungi associated with susceptible trees were superior mutualists. These complex, genetic-based interactions among species (tree-shrub-herbivore-fungus) argue that the ultimate impacts of climate change are both ecological and evolutionary.

  16. Tomato ethylene sensitivity determines interaction with plant growth-promoting bacteria.

    PubMed

    Ibort, Pablo; Molina, Sonia; Núñez, Rafael; Zamarreño, Ángel María; García-Mina, José María; Ruiz-Lozano, Juan Manuel; Orozco-Mosqueda, Maria Del Carmen; Glick, Bernard R; Aroca, Ricardo

    2017-07-01

    Plant growth-promoting bacteria (PGPB) are soil micro-organisms able to interact with plants and stimulate their growth, positively affecting plant physiology and development. Although ethylene plays a key role in plant growth, little is known about the involvement of ethylene sensitivity in bacterial inoculation effects on plant physiology. Thus, the present study was pursued to establish whether ethylene perception is critical for plant-bacteria interaction and growth induction by two different PGPB strains, and to assess the physiological effects of these strains in juvenile and mature tomato ( Solanum lycopersicum ) plants. An experiment was performed with the ethylene-insensitive tomato never ripe and its isogenic wild-type line in which these two strains were inoculated with either Bacillus megaterium or Enterobacter sp. C7. Plants were grown until juvenile and mature stages, when biomass, stomatal conductance, photosynthesis as well as nutritional, hormonal and metabolic statuses were analysed. Bacillus megaterium promoted growth only in mature wild type plants. However, Enterobacter C7 PGPB activity affected both wild-type and never ripe plants. Furthermore, PGPB inoculation affected physiological parameters and root metabolite levels in juvenile plants; meanwhile plant nutrition was highly dependent on ethylene sensitivity and was altered at the mature stage. Bacillus megaterium inoculation improved carbon assimilation in wild-type plants. However, insensitivity to ethylene compromised B. megaterium PGPB activity, affecting photosynthetic efficiency, plant nutrition and the root sugar content. Nevertheless, Enterobacter C7 inoculation modified the root amino acid content in addition to stomatal conductance and plant nutrition. Insensitivity to ethylene severely impaired B. megaterium interaction with tomato plants, resulting in physiological modifications and loss of PGPB activity. In contrast, Enterobacter C7 inoculation stimulated growth independently of

  17. Diversification of the Structural Determinants of Fibroblast Growth Factor-Heparin Interactions

    PubMed Central

    Xu, Ruoyan; Ori, Alessandro; Rudd, Timothy R.; Uniewicz, Katarzyna A.; Ahmed, Yassir A.; Guimond, Scott E.; Skidmore, Mark A.; Siligardi, Giuliano; Yates, Edwin A.; Fernig, David G.

    2012-01-01

    The functions of a large number (>435) of extracellular regulatory proteins are controlled by their interactions with heparan sulfate (HS). In the case of fibroblast growth factors (FGFs), HS binding determines their transport between cells and is required for the assembly of high affinity signaling complexes with their cognate FGF receptor. However, the specificity of the interaction of FGFs with HS is still debated. Here, we use a panel of FGFs (FGF-1, FGF-2, FGF-7, FGF-9, FGF-18, and FGF-21) spanning five FGF subfamilies to probe their specificities for HS at different levels as follows: binding parameters, identification of heparin-binding sites (HBSs) in the FGFs, changes in their secondary structure caused by heparin binding and structures in the sugar required for binding. For interaction with heparin, the FGFs exhibit KD values varying between 38 nm (FGF-18) and 620 nm (FGF-9) and association rate constants spanning over 20-fold (FGF-1, 2,900,000 m−1 s−1 and FGF-9, 130,000 m−1 s−1). The canonical HBS in FGF-1, FGF-2, FGF-7, FGF-9, and FGF-18 differs in its size, and these FGFs have a different complement of secondary HBS, ranging from none (FGF-9) to two (FGF-1). Differential scanning fluorimetry identified clear preferences in these FGFs for distinct structural features in the polysaccharide. These data suggest that the differences in heparin-binding sites in both the protein and the sugar are greatest between subfamilies and may be more restricted within a FGF subfamily in accord with the known conservation of function within FGF subfamilies. PMID:23019343

  18. Membrane targeting peptides toward antileishmanial activity: Design, structural determination and mechanism of interaction.

    PubMed

    Martins, Danubia Batista; Vieira, Maira Ramos; Fadel, Valmir; Santana, Viviane Aparecida Camargo; Guerra, Mirian Elisa Rodrigues; Lima, Marta Lopes; Tempone, Andre G; Dos Santos Cabrera, Marcia Perez

    2017-08-02

    Leishmaniasis threatens poor areas population worldwide, requiring new drugs less prone to resistance development. Antimicrobial peptides with antileishmanial activity are considered among fulfilling alternatives, but not much is known about the mode of action of membrane-targeting peptides, considering promastigote and infected macrophage membranes. In a previous work, structural features of very active known peptides were prospected using molecular dynamics simulations. Combining sequences of these peptides, analogs were designed. The structure of analog DecP-11 was validated by NMR. In vitro bioassays determined the peptide cytotoxicity toward mammalian cells, IC50 values on promastigotes and amastigotes, and membranolytic activity compared to Decoralin, one of the parent peptides. With biophysical methods, the mechanism of interaction with membrane mimetic systems was investigated. The designed peptide exhibits potent cytolytic and membrane permeabilizing activities, and decreased antileishmanial activity compared to the parent peptide. Interactions with lipid bilayers mimicking those of promastigotes, infected macrophage and mammalian cells showed that these peptides strongly bind to vesicles with intense lytic activity at low concentrations. Additionally, circular dichroism and light scattering experiments showed changes in the secondary structure of peptides and in vesicle size, depending on vesicles compositions. Altogether they suggest that DecP-11 antileishmanial activity is impaired by the aggregation and that aminophospholipids are probably involved. DecP-11 potent cytolytic and membranolytic activities with lack of selectivity toward promastigote model membranes warrant further structural studies to improve selectivity. Strong interactions of peptides with aminophospholipids, abundant in parasite membranes, potentially lead to aggregated forms impairing activity. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Genome-wide analysis captures the determinants of the antibiotic cross-resistance interaction network

    PubMed Central

    Lázár, Viktória; Nagy, István; Spohn, Réka; Csörgő, Bálint; Györkei, Ádám; Nyerges, Ákos; Horváth, Balázs; Vörös, Andrea; Busa-Fekete, Róbert; Hrtyan, Mónika; Bogos, Balázs; Méhi, Orsolya; Fekete, Gergely; Szappanos, Balázs; Kégl, Balázs; Papp, Balázs; Pál, Csaba

    2014-01-01

    Understanding how evolution of antimicrobial resistance increases resistance to other drugs is a challenge of profound importance. By combining experimental evolution and genome sequencing of 63 laboratory-evolved lines, we charted a map of cross-resistance interactions between antibiotics in Escherichia coli, and explored the driving evolutionary principles. Here, we show that (1) convergent molecular evolution is prevalent across antibiotic treatments, (2) resistance conferring mutations simultaneously enhance sensitivity to many other drugs and (3) 27% of the accumulated mutations generate proteins with compromised activities, suggesting that antibiotic adaptation can partly be achieved without gain of novel function. By using knowledge on antibiotic properties, we examined the determinants of cross-resistance and identified chemogenomic profile similarity between antibiotics as the strongest predictor. In contrast, cross-resistance between two antibiotics is independent of whether they show synergistic effects in combination. These results have important implications on the development of novel antimicrobial strategies. PMID:25000950

  20. General purpose computer program for interacting supersonic configurations. User's manual. [determining unsteady aerodynamic foreces

    NASA Technical Reports Server (NTRS)

    Crill, W.; Dale, B.

    1977-01-01

    The input data required to execute the computer program ISCON are described. The program generates a numerical procedure for the determination of unsteady aerodynamic forces on arbitrarily interacting wings and tails in supersonic flow. A velocity potential gradient method is used. Constant Mach number is assumed throughout the flow field. Lifting surfaces are represented by trapezoidal elements which can be generated automatically by the program. The wake field is represented by rectangular strip elements. The formulation is reviewed as well as input overview and input format. Instruction on how to use ISCON, a sample problem, and the restart feature are discussed. Program size limitations, computer program flow, and error messages are also included along with a description of the SS31 program used to compute the coefficients of surface spline.

  1. Rigorous surface charge method for determining electrostatic interaction energies in biomolecular systems

    NASA Astrophysics Data System (ADS)

    Doerr, T. P.; Obolensky, O. I.; Ogurtsov, A. Y.; Yu, Yi-Kuo

    2014-03-01

    Classical electrostatics plays a crucial role in bimolecular systems, dominating the interactions that determine the formation and dissolution of complexes responsible for the operation of cells. For systems that can be modeled as a set of piecewise-constant dielectric bodies, surface charge methods are usually preferable in both analytical and numerical contexts. We present a numerical implementation of a surface charge method previously used in analytical contexts. The method is applied to a realistic model of trypsin, an important protein involved in digesting other proteins, and one of its inhibitors, benzamidine. The classical calculations are complemented by density function theory calculations at short separations for which the classical model is inappropriate. We find that the surface charge method correctly distinguishes between correct and incorrect docking sites. This research was supported by the Intramural Research Program of the NIH, National Library of Medicine.

  2. Determination of the specific interaction between palmatine and bovine serum albumin.

    PubMed

    Ou-Yang, Yu; Li, Xiao-Ling; Wang, Hong; Fang, Min; Hu, Yan-Jun

    2012-05-01

    The binding of palmatine to bovine serum albumin (BSA) was studied under physiological conditions (pH = 7.40) by molecular spectroscopic approach. It was proved that the fluorescence quenching of BSA by palmatine is a result of the formation of palmatine-BSA complex. Binding parameters were determined using the modified Stern-Volmer equation and Scatchard equation, to measure the specific binding between palmatine and BSA. The thermodynamic parameters calculated, ∆G°, ∆H° and ∆S° indicate that the electrostatic interactions play a major role in the palmatine-BSA association. Site marker competitive displacement experiments demonstrated that palmatine binds with specific affinity to site II (subdomain IIIA) of BSA. Furthermore, the specific binding distance r (3.36 nm) was obtained according to fluorescence resonance energy transfer. The results of synchronous fluorescence spectra and UV-Visible absorption spectra show that the conformation of bovine serum albumin has been changed.

  3. Determination of major phlorotannins in Eisenia bicyclis using hydrophilic interaction chromatography: seasonal variation and extraction characteristics.

    PubMed

    Kim, Sang Min; Kang, Suk Woo; Jeon, Je-Seung; Jung, Yu-Jin; Kim, Woo-Ri; Kim, Chul Young; Um, Byung-Hun

    2013-06-15

    In this study, a hydrophilic interaction chromatography (HILIC) condition was developed for the simultaneous determination of five major phlorotannins from an extract of Eisenia bicyclis (Kjellman) Setchell with good linearity (r(2)>0.999). Based on this method, the seasonal variations and extraction characteristics, in terms of total extraction yield and the content of the phlorotannins, were investigated under various extraction conditions. In results, the yields and phlorotannins were increased two-to-four times in summer (June-October) and then, were decreased to normal levels in winter (November-March). In the extraction of E. bicyclis, ethanol percentage in water, extraction time and washing time significantly affected the yield of the extract and the phlorotannins, whereas the temperature and the sample/solvent ratio impacted the extraction to a lesser degree. These results will be useful information in the application of this macroalga in the commercial areas related to nutraceuticals, pharmaceuticals, and cosmeceuticals.

  4. Local electron-electron interaction strength in ferromagnetic nickel determined by spin-polarized positron annihilation

    PubMed Central

    Ceeh, Hubert; Weber, Josef Andreass; Böni, Peter; Leitner, Michael; Benea, Diana; Chioncel, Liviu; Ebert, Hubert; Minár, Jan; Vollhardt, Dieter; Hugenschmidt, Christoph

    2016-01-01

    We employ a positron annihilation technique, the spin-polarized two-dimensional angular correlation of annihilation radiation (2D-ACAR), to measure the spin-difference spectra of ferromagnetic nickel. The experimental data are compared with the theoretical results obtained within a combination of the local spin density approximation (LSDA) and the many-body dynamical mean-field theory (DMFT). We find that the self-energy defining the electronic correlations in Ni leads to anisotropic contributions to the momentum distribution. By direct comparison of the theoretical and experimental results we determine the strength of the local electronic interaction U in ferromagnetic Ni as 2.0 ± 0.1 eV. PMID:26879249

  5. Stoichiometry determined exchange interactions in amorphous ternary transition metal oxides: Theory and experiment

    SciTech Connect

    Hu, Shu-jun; Yan, Shi-shen Zhang, Yun-peng; Zhao, Ming-wen; Kang, Shi-shou; Mei, Liang-mo

    2014-07-28

    Amorphous transition metal oxides exhibit exotic transport and magnetic properties, while the absence of periodic structure has long been a major obstacle for the understanding of their electronic structure and exchange interaction. In this paper, we have formulated a theoretical approach, which combines the melt-quench approach and the spin dynamic Monte-Carlo simulations, and based on it, we explored amorphous Co{sub 0.5}Zn{sub 0.5}O{sub 1−y} ternary transition metal oxides. Our theoretical results reveal that the microstructure, the magnetic properties, and the exchange interactions of Co{sub 0.5}Zn{sub 0.5}O{sub 1−y} are strongly determined by the oxygen stoichiometry. In the oxygen-deficient sample (y > 0), we have observed the long-range ferromagnetic spin ordering which is associated with the non-stoichiometric cobalt-rich region rather than metallic clusters. On the other hand, the microstructure of stoichiometric sample takes the form of continuous random networks, and no long-range ferromagnetism has been observed in it. Magnetization characterization of experimental synthesized Co{sub 0.61}Zn{sub 0.39}O{sub 1−y} films verifies the relation between the spin ordering and the oxygen stoichiometry. Furthermore, the temperature dependence of electrical transport shows a typical feature of semiconductors, in agreement with our theoretical results.

  6. Vortices determine the dynamics of biodiversity in cyclical interactions with protection spillovers

    NASA Astrophysics Data System (ADS)

    Szolnoki, Attila; Perc, Matjaž

    2015-11-01

    If rock beats scissors and scissors beat paper, one might assume that rock beats paper too. But this is not the case for intransitive relationships that make up the famous rock-paper-scissors game. However, the sole presence of paper might prevent rock from beating scissors, simply because paper beats rock. This is the blueprint for the rock-paper-scissors game with protection spillovers, which has recently been introduced as a new paradigm for biodiversity in well-mixed microbial populations. Here we study the game in structured populations, demonstrating that protection spillovers give rise to spatial patterns that are impossible to observe in the classical rock-paper-scissors game. We show that the spatiotemporal dynamics of the system is determined by the density of stable vortices, which may ultimately transform to frozen states, to propagating waves, or to target waves with reversed propagation direction, depending further on the degree and type of randomness in the interactions among the species. If vortices are rare, the fixation to waves and complex oscillatory solutions is likelier. Moreover, annealed randomness in interactions favors the emergence of target waves, while quenched randomness favors collective synchronization. Our results demonstrate that protection spillovers may fundamentally change the dynamics of cyclic dominance in structured populations, and they outline the possibility of programming pattern formation in microbial populations.

  7. Protein-protein interactions among components of the Drosophila primary sex determination signal.

    PubMed

    Liu, Y; Belote, J M

    1995-07-28

    Sex determination in Drosophila melanogaster is initiated in the early embryo by a signal provided by three types of genes: (1) X-linked numerator elements [e.g., sisterless-a (sis-a) and sisterless-b (sis-b)], (2) autosomally linked denominator elements [e.g., deadpan (dpn)], and (3) maternal factors [e.g., daughterless (da)]. This signal acts to stimulate transcription from an embryo-specific promoter of the master regulatory gene Sex-lethal (Sxl) in embryos that have two X chromosomes (females), while it fails to activate Sxl in those with only one X (males). It has been previously proposed that competitive dimerizations among the components of this signal might provide the molecular basis for this sex specificity. Here, we use the yeast two-hybrid system to demonstrate specific protein-protein interactions among the above-mentioned factors, and to delimit their interacting domains. These results support and extend the model of the molecular basis of the X/A ratio signal.

  8. Interactions between the direct and indirect effects of predators determine life history evolution in a killifish.

    PubMed

    Walsh, Matthew R; Reznick, David N

    2008-01-15

    The ecological impacts of the indirect effects of predators are well established, but the evolutionary consequences are unknown. Predators often decrease prey density, which indirectly increases the resources available to surviving prey. This ecological effect could provide a link to evolution because it is generally assumed that resource availability influences life history evolution. Yet, predictions from theory that consider food availability are inconsistent, and evidence for an important role of resources in shaping life history evolution is absent. We compared life history traits in a Trinidadian killifish, Rivulus hartii, from fish communities that differ in predation intensity; predators are associated with lower population density and faster growth rates. To determine whether the indirect effects of predators influence evolutionary change, we reared second-generation-born fish under two food levels that approximated natural differences in resources between communities. Rivulus from sites with predators are younger and smaller at maturity. They have increased reproductive investment and produce many small eggs and smaller hatchlings. Such divergence is predicted as a direct effect of predation. We also found significant interactions between predator community and food level for age and size at maturity, fecundity, and egg size. These interactions, whereby the differences between communities were more pronounced at high-food levels, argue that evolution in Rivulus has been influenced by the indirect effects of predators mediated through resource availability. Rivulus from sites with predators better exploit the higher resources in those habitats. Therefore, both direct and indirect effects of predators have evolutionary consequences.

  9. A practical method for depth of interaction determination in monolithic scintillator PET detectors.

    PubMed

    van Dam, Herman T; Seifert, Stefan; Vinke, Ruud; Dendooven, Peter; Löhner, Herbert; Beekman, Freek J; Schaart, Dennis R

    2011-07-07

    Several new methods for determining the depth of interaction (DOI) of annihilation photons in monolithic scintillator detectors with single-sided, multi-pixel readout are investigated. The aim is to develop a DOI decoding method that allows for practical implementation in a positron emission tomography system. Specifically, calibration data, obtained with perpendicularly incident gamma photons only, are being used. Furthermore, neither detector modifications nor a priori knowledge of the light transport and/or signal variances is required. For this purpose, a clustering approach is utilized in combination with different parameters correlated with the DOI, such as the degree of similarity to a set of reference light distributions, the measured intensity on the sensor pixel(s) closest to the interaction position and the peak intensity of the measured light distribution. The proposed methods were tested experimentally on a detector comprised of a 20 mm × 20 mm × 12 mm polished LYSO:Ce crystal coupled to a 4 × 4 multi-anode photomultiplier. The method based on the linearly interpolated measured intensities on the sensor pixels closest to the estimated (x, y)-coordinate outperformed the other methods, yielding DOI resolutions between ∼1 and ∼4.5 mm FWHM depending on the DOI, the (x, y) resolution and the amount of reference data used.

  10. A practical method for depth of interaction determination in monolithic scintillator PET detectors

    NASA Astrophysics Data System (ADS)

    van Dam, Herman T.; Seifert, Stefan; Vinke, Ruud; Dendooven, Peter; Löhner, Herbert; Beekman, Freek J.; Schaart, Dennis R.

    2011-07-01

    Several new methods for determining the depth of interaction (DOI) of annihilation photons in monolithic scintillator detectors with single-sided, multi-pixel readout are investigated. The aim is to develop a DOI decoding method that allows for practical implementation in a positron emission tomography system. Specifically, calibration data, obtained with perpendicularly incident gamma photons only, are being used. Furthermore, neither detector modifications nor a priori knowledge of the light transport and/or signal variances is required. For this purpose, a clustering approach is utilized in combination with different parameters correlated with the DOI, such as the degree of similarity to a set of reference light distributions, the measured intensity on the sensor pixel(s) closest to the interaction position and the peak intensity of the measured light distribution. The proposed methods were tested experimentally on a detector comprised of a 20 mm × 20 mm × 12 mm polished LYSO:Ce crystal coupled to a 4 × 4 multi-anode photomultiplier. The method based on the linearly interpolated measured intensities on the sensor pixels closest to the estimated (x, y)-coordinate outperformed the other methods, yielding DOI resolutions between ~1 and ~4.5 mm FWHM depending on the DOI, the (x, y) resolution and the amount of reference data used.

  11. Discovery of novel plant interaction determinants from the genomes of 163 root nodule bacteria

    SciTech Connect

    Seshadri, Rekha; Reeve, Wayne G.; Ardley, Julie K.; Tennessen, Kristin; Woyke, Tanja; Kyrpides, Nikos C.; Ivanova, Natalia N.

    2015-11-20

    Root nodule bacteria (RNB) or “rhizobia” are a type of plant growth promoting bacteria, typified by their ability to fix nitrogen for their plant host, fixing nearly 65% of the nitrogen currently utilized in sustainable agricultural production of legume crops and pastures. In this study, we sequenced the genomes of 110 RNB from diverse hosts and biogeographical regions, and undertook a global exploration of all available RNB genera with the aim of identifying novel genetic determinants of symbiotic association and plant growth promotion. Specifically, we performed a subtractive comparative analysis with non-RNB genomes, employed relevant transcriptomic data, and leveraged phylogenetic distribution patterns and sequence signatures based on known precepts of symbioticand host-microbe interactions. A total of 184 protein families were delineated, including known factors for nodulation and nitrogen fixation, and candidates with previously unexplored functions, for which a role in host-interaction, -regulation, biocontrol, and more, could be posited. Lastly, these analyses expand our knowledge of the RNB purview and provide novel targets for strain improvement in the ultimate quest to enhance plant productivity and agricultural sustainability.

  12. Discovery of Novel Plant Interaction Determinants from the Genomes of 163 Root Nodule Bacteria

    PubMed Central

    Seshadri, Rekha; Reeve, Wayne G.; Ardley, Julie K.; Tennessen, Kristin; Woyke, Tanja; Kyrpides, Nikos C.; Ivanova, Natalia N.

    2015-01-01

    Root nodule bacteria (RNB) or “rhizobia” are a type of plant growth promoting bacteria, typified by their ability to fix nitrogen for their plant host, fixing nearly 65% of the nitrogen currently utilized in sustainable agricultural production of legume crops and pastures. In this study, we sequenced the genomes of 110 RNB from diverse hosts and biogeographical regions, and undertook a global exploration of all available RNB genera with the aim of identifying novel genetic determinants of symbiotic association and plant growth promotion. Specifically, we performed a subtractive comparative analysis with non-RNB genomes, employed relevant transcriptomic data, and leveraged phylogenetic distribution patterns and sequence signatures based on known precepts of symbiotic- and host-microbe interactions. A total of 184 protein families were delineated, including known factors for nodulation and nitrogen fixation, and candidates with previously unexplored functions, for which a role in host-interaction, -regulation, biocontrol, and more, could be posited. These analyses expand our knowledge of the RNB purview and provide novel targets for strain improvement in the ultimate quest to enhance plant productivity and agricultural sustainability. PMID:26584898

  13. Carbon Mineralizability Determines Interactive Effects on Mineralization of Pyrogenic Organic Matter and Soil Organic Carbon

    SciTech Connect

    Whitman, Thea L.; Zhu, Zihua; Lehmann, Johannes C.

    2014-10-31

    Soil organic carbon (SOC) is a critical and active pool in the global C cycle, and the addition of pyrogenic organic matter (PyOM) has been shown to change SOC cycling, increasing or decreasing mineralization rates (often referred to as priming). We adjusted the amount of easily mineralizable C in the soil, through 1-day and 6-month pre-incubations, and in PyOM made from maple wood at 350°C, through extraction. We investigated the impact of these adjustments on C mineralization interactions, excluding pH and nutrient effects and minimizing physical effects. We found short-term increases (+20-30%) in SOC mineralization with PyOM additions in the soil pre-incubated for 6 months. Over the longer term, both the 6-month and 1-day pre-incubated soils experienced net ~10% decreases in SOC mineralization with PyOM additions. This was possibly due to stabilization of SOC on PyOM surfaces, suggested by nanoscale secondary ion mass spectrometry. Additionally, the duration of pre-incubation affected priming interactions, indicating that there may be no optimal pre-incubation time for SOC mineralization studies. We show conclusively that relative mineralizability of SOC in relation to PyOM-24 C is an important determinant of the effect of PyOM additions on SOC mineralization.

  14. A test of the role of electrostatic interactions in determining the CO stretch frequency in carbonmonoxymyoglobin.

    PubMed

    Decatur, S M; Boxer, S G

    1995-07-06

    The vibrational frequency of CO bound to myoglobin can be varied by up to 60 cm-1 by making site-specific mutations in the distal pocket. These changes may result from specific chemical interactions between distal amino acids and the CO or from changes in the electrostatic field of the distal pocket. In this paper, we separate the relative contributions of these two effects by comparing the IR spectra of the carbonmonoxy complexes of human myoglobin mutants V68N, V68D, and V68E. The effect of replacing valine with these polar amino acids on the electrostatic environment of the distal heme pocket has been independently determined earlier by measurements of the heme reduction potential and electronic absorption spectral band shifts. While all three mutations result in a negative dipole pointing towards the CO ligand, the CO stretch frequency shifts differently in each case. These differences are attributed to specific chemical interactions between the amino acids and the CO ligand.

  15. Discovery of novel plant interaction determinants from the genomes of 163 root nodule bacteria

    DOE PAGES

    Seshadri, Rekha; Reeve, Wayne G.; Ardley, Julie K.; ...

    2015-11-20

    Root nodule bacteria (RNB) or “rhizobia” are a type of plant growth promoting bacteria, typified by their ability to fix nitrogen for their plant host, fixing nearly 65% of the nitrogen currently utilized in sustainable agricultural production of legume crops and pastures. In this study, we sequenced the genomes of 110 RNB from diverse hosts and biogeographical regions, and undertook a global exploration of all available RNB genera with the aim of identifying novel genetic determinants of symbiotic association and plant growth promotion. Specifically, we performed a subtractive comparative analysis with non-RNB genomes, employed relevant transcriptomic data, and leveraged phylogeneticmore » distribution patterns and sequence signatures based on known precepts of symbioticand host-microbe interactions. A total of 184 protein families were delineated, including known factors for nodulation and nitrogen fixation, and candidates with previously unexplored functions, for which a role in host-interaction, -regulation, biocontrol, and more, could be posited. Lastly, these analyses expand our knowledge of the RNB purview and provide novel targets for strain improvement in the ultimate quest to enhance plant productivity and agricultural sustainability.« less

  16. Non-invasive determination of external forces in vortex-pair-cylinder interactions

    NASA Astrophysics Data System (ADS)

    Hartmann, D.; Schröder, W.; Shashikanth, B. N.

    2012-06-01

    Expressions for the conserved linear and angular momenta of a dynamically coupled fluid + solid system are derived. Based on the knowledge of the flow velocity field, these expressions allow the determination of the external forces exerted on a body moving in the fluid such as, e.g., swimming fish. The verification of the derived conserved quantities is done numerically. The interaction of a vortex pair with a circular cylinder in various configurations of motions representing a generic test case for a dynamically coupled fluid + solid system is investigated in a weakly compressible Navier-Stokes setting using a Cartesian cut-cell method, i.e., the moving circular cylinder is represented by cut cells on a moving mesh. The objectives of this study are twofold. The first objective is to show the robustness of the derived expressions for the conserved linear and angular momenta with respect to bounded and discrete data sets. The second objective is to study the coupled dynamics of the vortex pair and a neutrally buoyant cylinder free to move in response to the fluid stresses exerted on its surface. A comparison of the vortex-body interaction with the case of a fixed circular cylinder evidences significant differences in the vortex dynamics. When the cylinder is fixed strong secondary vorticity is generated resulting in a repeating process between the primary vortex pair and the cylinder. In the neutrally buoyant cylinder case, a stable structure consisting of the primary vortex pair and secondary vorticity shear layers stays attached to the moving cylinder. In addition to these fundamental cases, the vortex-pair-cylinder interaction is studied for locomotion at constant speed and locomotion at constant thrust. It is shown that a similar vortex structure like in the neutrally buoyant cylinder case is obtained when the cylinder moves away from the approaching vortex pair at a constant speed smaller than the vortex pair translational velocity. Finally, the idealized

  17. Differential MS2 Interaction with Food Contact Surfaces Determined by Atomic Force Microscopy and Virus Recovery.

    PubMed

    Shim, J; Stewart, D S; Nikolov, A D; Wasan, D T; Wang, R; Yan, R; Shieh, Y C

    2017-10-06

    ). Virus surrogate MS2 demonstrated less adhesion force via AFM to glass than to PVC, with the force contributing factors including intrinsic nature and topography of the contact surfaces. This adhesion is consistent with the virus recoveries, which were indirectly determined. Greater numbers of viruses were recovered from glass than PVC applied at the same level. The stronger MS2 adhesion onto PVC could be interrupted by incorporating a surfactant during the interaction between viruses and contact surfaces. This study facilitates our understanding of virus adhesion in microenvironment, and permits ways to mitigate virus adhesion onto contact surfaces. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

  18. Using SEM Analysis on Ion-Milled Shale Surface to Determine Shale-Fracturing Fluid Interaction

    NASA Astrophysics Data System (ADS)

    Lu, J.; Mickler, P. J.; Nicot, J. P.

    2014-12-01

    It is important to document and assess shale-fluid interaction during hydraulic fracturing (HF) in order to understand its impact on flowback water chemistry and rock property. A series of autoclave experiments were conducted to react shale samples from major oil and gas shales with synthetic HF containing various additives. To better determine mineral dissolution and precipitation at the rock-fluid interface, ion-milling technique was applied to create extremely flat rock surfaces that were examined before and after the autoclave experiments using a scanning electron microscope (SEM) coupled with energy dispersive spectroscopy (EDS) detectors. This method is able to reveal a level of detail not observable on broken surface or mechanically polished surface. It allows direct comparison of the same mineral and organic matter particles before and after the reaction experiments. Minerals undergone dissolution and newly precipitated materials are readily determined by comparing to the exact locations before reaction. The dissolution porosity and the thickness of precipitates can be quantified by tracing and measuring the geometry of the pores and precipitates. Changes in porosity and permeability were confirmed by mercury intrusion capillary tests.

  19. Sensitive determination of DNA based on the interaction between prulifloxacin-terbium(III) complex and DNA.

    PubMed

    Wu, Ting; Fang, Biyun; Chang, Lin; Liu, Min; Chen, Fang

    2013-01-01

    A simple spectrofluorimetric method is described for the determination of DNA, based on its enhancement of the fluorescence intensity of prulifloxacin (PUFX)-Tb(3+). The luminescence intensity of the PUFX-Tb(3+) complex increased up to 10-fold after adding DNA. The excitation and emission wavelengths were 345 and 545 nm, respectively. Under optimum conditions, variations in the fluorescence intensity showed a good linear relationship with the concentration of hsDNA in the range of 3.0 × 10(-9) to 1.0 × 10(-6) g/mL, with a correlation coefficient (R) of 0.997, and the detection limit was 2.1 × 10(-9) g/mL. The method was successfully applied to the determination of DNA in synthetic samples, and recoveries were in the range 97.3-102.0%. The mechanism of fluorescence enhancement of the PUFX-Tb(3+) complex by DNA is also discussed. The mechanism may involve formation of a ternary complex mainly by intercalation binding together with weak electrostatic interaction, which will increase the energy transition from ligand to Tb(3+), increasing the rigidity of the complex, and decreasing the radiationless energy loss through O-H vibration of the H2O molecule in the PUFX-Tb(3+) complex. Compared with the previous DNA probes, the proposed method is not only more robust and friendly to the environment, but also of relatively higher sensitivity.

  20. Relative electron density determination using a physics based parameterization of photon interactions in medical DECT.

    PubMed

    van Abbema, Joanne K; van Goethem, Marc-Jan; Greuter, Marcel J W; van der Schaaf, Arjen; Brandenburg, Sytze; van der Graaf, Emiel R

    2015-05-07

    Radiotherapy and particle therapy treatment planning require accurate knowledge of the electron density and elemental composition of the tissues in the beam path to predict the local dose deposition. We describe a method for the analysis of dual energy computed tomography (DECT) images that provides the electron densities and effective atomic numbers of tissues. The CT measurement process is modelled by system weighting functions, which apply an energy dependent weighting to the parameterization of the total cross section for photon interactions with matter. This detailed parameterization is based on the theoretical analysis of Jackson and Hawkes and deviates, at most, 0.3% from the tabulated NIST values for the elements H to Zn. To account for beam hardening in the object as present in the CT image we implemented an iterative process employing a local weighting function, derived from the method proposed by Heismann and Balda. With this method effective atomic numbers between 1 and 30 can be determined. The method has been experimentally validated on a commercially available tissue characterization phantom with 16 inserts made of tissue substitutes and aluminium that has been scanned on a dual source CT system with tube potentials of 100 kV and 140 kV using a clinical scan protocol. Relative electron densities of all tissue substitutes have been determined with accuracy better than 1%. The presented DECT analysis method thus provides high accuracy electron densities and effective atomic numbers for radiotherapy and especially particle therapy treatment planning.

  1. Determination of iminosugars in mulberry leaves and silkworms using hydrophilic interaction chromatography-tandem mass spectrometry.

    PubMed

    Nakagawa, Kiyotaka; Ogawa, Kenta; Higuchi, Ohki; Kimura, Toshiyuki; Miyazawa, Teruo; Hori, Masatoshi

    2010-09-15

    Mulberry 1-deoxynojirimycin (DNJ, a potent alpha-glycosidase inhibitor) has been investigated thoroughly for its analytical methods and therapeutic potential against diabetes, whereas little attention has been given to other iminosugars such as 2-O-alpha-D-galactopyranosyl-DNJ (GAL-DNJ) and fagomine. For instance, concentration and composition of these iminosugars in mulberry leaves as well as sericulture products have not been fully characterized due to lack of suitable analytical methods. Here we developed a simultaneous determination method for DNJ, GAL-DNJ, and fagomine using hydrophilic interaction chromatography (HILIC) with tandem mass spectrometry (MS/MS). When mulberry leaf extracts were subjected to HILIC-MS/MS with multiple reaction monitoring (MRM), individual iminosugars could be separated and detected. The developed method is sufficiently sensitive for determining iminosugars in mulberry leaves as well as silkworms, providing new information (e.g., different amounts of iminosugars in mulberry leaf varieties; high DNJ and low GAL-DNJ in the silkworm body, especially in the blood) that is useful for producing iminosugar-rich products for nutraceutical purposes. 2010 Elsevier Inc. All rights reserved.

  2. Determination of ankle external fixation stiffness by expedited interactive finite element analysis.

    PubMed

    Nielsen, Jonathan K; Saltzman, Charles L; Brown, Thomas D

    2005-11-01

    Interactive finite element analysis holds the potential to quickly and accurately determine the mechanical stiffness of alternative external fixator frame configurations. Using as an example Ilizarov distraction of the ankle, a finite element model and graphical user interface were developed that provided rapid, construct-specific information on fixation rigidity. After input of specific construct variables, the finite element software determined the resulting tibial displacement for a given configuration in typically 15s. The formulation was employed to investigate constructs used to treat end-stage arthritis, both in a parametric series and for five specific clinical distraction cases. Parametric testing of 15 individual variables revealed that tibial half-pins were much more effective than transfixion wires in limiting axial tibial displacement. Factors most strongly contributing to stiffening the construct included placing the tibia closer to the fixator rings, and mounting the pins to the rings at the nearest circumferential location to the bone. Benchtop mechanical validation results differed inappreciably from the finite element computations.

  3. Enhanced spectrophotometric determination of Losartan potassium based on its physicochemical interaction with cationic surfactant.

    PubMed

    Abdel-Fattah, Laila; Abdel-Aziz, Lobna; Gaied, Mariam

    2015-02-05

    In this study, a simple and sensitive spectrophotometric method was developed for determination of Losartan potassium (LST K), an angiotensin-II receptor (type AT1) antagonist, in presence of cationic surfactant cetyltrimethylammonium bromide (CTAB). The physicochemical interaction of LST K with CTAB was investigated. The effect of cationic micelles on the spectroscopic and acid-base properties of LST K was studied at pH 7.4. The binding constant (Kb) and the partition coefficient (Kx) of LST K-CTAB were 1.62×10(5) M(-1) and 1.38×10(5); respectively. The binding of LST K to CTAB micelles implied a shift in drug acidity constant (ΔpKa=0.422). The developed method is linear over the range 0.5-28 μg mL(-1). The accuracy was evaluated and was found to be 99.79±0.509% and the relative standard deviation for intraday and interday precision was 0.821 and 0.963; respectively. The method was successfully applied to determine LST K in pharmaceutical formulations.

  4. Enhanced spectrophotometric determination of Losartan potassium based on its physicochemical interaction with cationic surfactant

    NASA Astrophysics Data System (ADS)

    Abdel-Fattah, Laila; Abdel-Aziz, Lobna; Gaied, Mariam

    2015-02-01

    In this study, a simple and sensitive spectrophotometric method was developed for determination of Losartan potassium (LST K), an angiotensin-II receptor (type AT1) antagonist, in presence of cationic surfactant cetyltrimethylammonium bromide (CTAB). The physicochemical interaction of LST K with CTAB was investigated. The effect of cationic micelles on the spectroscopic and acid-base properties of LST K was studied at pH 7.4. The binding constant (Kb) and the partition coefficient (Kx) of LST K-CTAB were 1.62 × 105 M-1 and 1.38 × 105; respectively. The binding of LST K to CTAB micelles implied a shift in drug acidity constant (ΔpKa = 0.422). The developed method is linear over the range 0.5-28 μg mL-1. The accuracy was evaluated and was found to be 99.79 ± 0.509% and the relative standard deviation for intraday and interday precision was 0.821 and 0.963; respectively. The method was successfully applied to determine LST K in pharmaceutical formulations.

  5. Determinants of malnutrition in Senegal: individual, household, community variables, and their interaction.

    PubMed

    Linnemayr, Sebastian; Alderman, Harold; Ka, Abdoulaye

    2008-07-01

    The relationship between poverty and nutrition is a two-sided one: on the one hand, economic growth (which is generally associated with an eradication of poverty) leads to reduced malnutrition. On the other hand, nutrition is one of the key ingredients for human capital formation, which in turn represents one of the fundamental factors of growth. There are numerous studies that show the correlates of malnutrition using both household- and community-level variables. However, few of these studies allow for the potential endogeneity of community infrastructure or indicate their interplay with characteristics of the mother. The current study considers the socio-economic determinants of child malnutrition and investigates how programs compensate for the increased risks facing young mothers and their children or substitute for a low social status of the mother in the household. The empirical results show that children of mothers giving birth at a young age are disadvantaged in terms of their anthropometric status. Interaction effects of the presence of a non-governmental organization (NGO) or a health post in the village with characteristics of the mother stress the important role played by these institutions in helping disadvantaged mothers overcome their difficulties. These findings have implications for efficient program design and represent a further step towards gaining an improved understanding of the complex determinants of child (mal)nutrition.

  6. Relative electron density determination using a physics based parameterization of photon interactions in medical DECT

    NASA Astrophysics Data System (ADS)

    van Abbema, Joanne K.; van Goethem, Marc-Jan; Greuter, Marcel J. W.; van der Schaaf, Arjen; Brandenburg, Sytze; van der Graaf, Emiel R.

    2015-05-01

    Radiotherapy and particle therapy treatment planning require accurate knowledge of the electron density and elemental composition of the tissues in the beam path to predict the local dose deposition. We describe a method for the analysis of dual energy computed tomography (DECT) images that provides the electron densities and effective atomic numbers of tissues. The CT measurement process is modelled by system weighting functions, which apply an energy dependent weighting to the parameterization of the total cross section for photon interactions with matter. This detailed parameterization is based on the theoretical analysis of Jackson and Hawkes and deviates, at most, 0.3% from the tabulated NIST values for the elements H to Zn. To account for beam hardening in the object as present in the CT image we implemented an iterative process employing a local weighting function, derived from the method proposed by Heismann and Balda. With this method effective atomic numbers between 1 and 30 can be determined. The method has been experimentally validated on a commercially available tissue characterization phantom with 16 inserts made of tissue substitutes and aluminium that has been scanned on a dual source CT system with tube potentials of 100 kV and 140 kV using a clinical scan protocol. Relative electron densities of all tissue substitutes have been determined with accuracy better than 1%. The presented DECT analysis method thus provides high accuracy electron densities and effective atomic numbers for radiotherapy and especially particle therapy treatment planning.

  7. Learning with Interactive Whiteboards: Determining the Factors on Promoting Interactive Whiteboards to Students by Technology Acceptance Model

    ERIC Educational Resources Information Center

    Kilic, Eylem; Güler, Çetin; Çelik, H. Eray; Tatli, Cemal

    2015-01-01

    Purpose: The purpose of this study is to investigate the factors which might affect the intention to use interactive whiteboards (IWBs) by university students, using Technology Acceptance Model by the structural equation modeling approach. The following hypothesis guided the current study: H1. There is a positive relationship between IWB…

  8. Learning with Interactive Whiteboards: Determining the Factors on Promoting Interactive Whiteboards to Students by Technology Acceptance Model

    ERIC Educational Resources Information Center

    Kilic, Eylem; Güler, Çetin; Çelik, H. Eray; Tatli, Cemal

    2015-01-01

    Purpose: The purpose of this study is to investigate the factors which might affect the intention to use interactive whiteboards (IWBs) by university students, using Technology Acceptance Model by the structural equation modeling approach. The following hypothesis guided the current study: H1. There is a positive relationship between IWB…

  9. Solubility and thermodynamics of apremilast in different mono solvents: Determination, correlation and molecular interactions.

    PubMed

    Shakeel, Faiyaz; Haq, Nazrul; Alanazi, Fars K; Alsarra, Ibrahim A

    2017-05-15

    The solubility data of recently launched poorly soluble antipsoriatic drug apremilast (APM) in any mono solvent or cosolvent mixtures with respect to temperature are not available in literature. Hence, in this research work, the solubility of APM in twelve different mono solvents namely "water, methanol, ethanol, isopropanol (IPA), ethylene glycol (EG), propylene glycol (PG), 1-butanol, 2-butanol, ethyl acetate (EA), dimethyl sulfoxide (DMSO), polyethylene glycol-400 (PEG-400) and Transcutol(®)" was determined at temperatures "T=298.2K to 318.2K" and pressure "p=0.1 MPa". Eexperimental solubilities of APM in mole fraction were determined by a static equilibrium method using high performance liquid chromatography at 254nm. Experimental solubilities of APM in mole fraction were correlated well with "Van't Hoff and Apelblat models". The solubilities of APM in mole fraction were recorded highest in DMSO (9.91×10(-2)), followed by EA (2.54×10(-2)), Transcutol (2.51×10(-2)), PEG-400 (2.16×10(-2)),PG (4.01×10(-3)), EG (1.61×10(-3)), IPA (4.96×10(-4)), 1-butanol (4.18×10(-4)), 2-butanol (3.91×10(-4)), methanol (2.25×10(-4)), ethanol (2.20×10(-4)) and water (1.29×10(-6)) at "T=318.2K" and similar results were also obtained at each temperature evaluated. The molecular interactions between solute and solvent molecules were evaluated by the determination of activity coefficients. Based on activity coefficients, the higher solute-solvents molecular interactions were recorded in APM-DMSO, APM-EA, APM-Transcutol and APM-PEG-400 in comparison with other combination of solute and solvents. "Apparent standard thermodynamic parameters" of APM indicated an "endothermic and entropy-driven dissolution" of APM in all mono solvents evaluated. Based on these results, APM was proposed as freely soluble in DMSO, EA and Transcutol, sparingly soluble in PEG0-400, slightly soluble in methanol, ethanol, IPA, EG, PG, 1-butanol and 2-butanol and practically insoluble in water. Hence

  10. An Interactive network of long non-coding RNAs facilitates the Drosophila sex determination decision

    PubMed Central

    Mulvey, Brett B.; Olcese, Ursula; Cabrera, Janel R.; Horabin, Jamila I.

    2014-01-01

    Genome analysis in several eukaryotes shows a surprising number of transcripts which do not encode conventional messenger RNAs. Once considered noise, these non-coding RNAs (ncRNAs) appear capable of controlling gene expression by various means. We find Drosophila sex determination, specifically the master-switch gene Sex-lethal (Sxl), is regulated by long ncRNAs (>200 nt). The lncRNAs influence the dose sensitive establishment promoter of Sxl, SxlPe, which must be activated to specify female sex. They are primarily from two regions, R1 and R2, upstream of SxlPeand show a dynamic developmental profile. Of the four lncRNA strands only one, R2 antisense, has its peak coincident with SxlPe transcription, suggesting it may promote activation. Indeed, its expression is regulated by the X chromosome counting genes, whose dose determines whether SxlPe is transcribed. Transgenic lines which ectopically express each of the lncRNAs show they can act in trans, impacting the process of sex determination but also altering the levels of the other lncRNAs. Generally, expression of R1 is negative whereas R2 is positive to females. This ectopic expression also results in a change in the local chromatin marks, affecting the timing and strength of SxlPe transcription. The chromatin marks are those deposited by the Polycomb and Trithorax groups of chromatin modifying proteins, which we find bind to the lncRNAs. We suggest the increasing numbers of non-coding transcripts being identified are a harbinger of interacting networks similar to the one we describe. PMID:24954180

  11. An Evolving Genetic Architecture Interacts with Hill–Robertson Interference to Determine the Benefit of Sex

    PubMed Central

    Whitlock, Alexander O. B.; Peck, Kayla M.; Azevedo, Ricardo B. R.; Burch, Christina L.

    2016-01-01

    Sex is ubiquitous in the natural world, but the nature of its benefits remains controversial. Previous studies have suggested that a major advantage of sex is its ability to eliminate interference between selection on linked mutations, a phenomenon known as Hill–Robertson interference. However, those studies may have missed both important advantages and important disadvantages of sexual reproduction because they did not allow the distributions of mutational effects and interactions (i.e., the genetic architecture) to evolve. Here we investigate how Hill–Robertson interference interacts with an evolving genetic architecture to affect the evolutionary origin and maintenance of sex by simulating evolution in populations of artificial gene networks. We observed a long-term advantage of sex—equilibrium mean fitness of sexual populations exceeded that of asexual populations—that did not depend on population size. We also observed a short-term advantage of sex—sexual modifier mutations readily invaded asexual populations—that increased with population size, as was observed in previous studies. We show that the long- and short-term advantages of sex were both determined by differences between sexual and asexual populations in the evolutionary dynamics of two properties of the genetic architecture: the deleterious mutation rate (Ud) and recombination load (LR). These differences resulted from a combination of selection to minimize LR, which is experienced only by sexuals, and Hill–Robertson interference experienced primarily by asexuals. In contrast to the previous studies, in which Hill–Robertson interference had only a direct impact on the fitness advantages of sex, the impact of Hill–Robertson interference in our simulations was mediated additionally by an indirect impact on the efficiency with which selection acted to reduce Ud. PMID:27098911

  12. An Evolving Genetic Architecture Interacts with Hill-Robertson Interference to Determine the Benefit of Sex.

    PubMed

    Whitlock, Alexander O B; Peck, Kayla M; Azevedo, Ricardo B R; Burch, Christina L

    2016-06-01

    Sex is ubiquitous in the natural world, but the nature of its benefits remains controversial. Previous studies have suggested that a major advantage of sex is its ability to eliminate interference between selection on linked mutations, a phenomenon known as Hill-Robertson interference. However, those studies may have missed both important advantages and important disadvantages of sexual reproduction because they did not allow the distributions of mutational effects and interactions (i.e., the genetic architecture) to evolve. Here we investigate how Hill-Robertson interference interacts with an evolving genetic architecture to affect the evolutionary origin and maintenance of sex by simulating evolution in populations of artificial gene networks. We observed a long-term advantage of sex-equilibrium mean fitness of sexual populations exceeded that of asexual populations-that did not depend on population size. We also observed a short-term advantage of sex-sexual modifier mutations readily invaded asexual populations-that increased with population size, as was observed in previous studies. We show that the long- and short-term advantages of sex were both determined by differences between sexual and asexual populations in the evolutionary dynamics of two properties of the genetic architecture: the deleterious mutation rate ([Formula: see text]) and recombination load ([Formula: see text]). These differences resulted from a combination of selection to minimize [Formula: see text] which is experienced only by sexuals, and Hill-Robertson interference experienced primarily by asexuals. In contrast to the previous studies, in which Hill-Robertson interference had only a direct impact on the fitness advantages of sex, the impact of Hill-Robertson interference in our simulations was mediated additionally by an indirect impact on the efficiency with which selection acted to reduce [Formula: see text]. Copyright © 2016 by the Genetics Society of America.

  13. Oxygen and energy availability interact to determine flight performance in the Glanville fritillary butterfly.

    PubMed

    Fountain, Toby; Melvin, Richard G; Ikonen, Suvi; Ruokolainen, Annukka; Woestmann, Luisa; Hietakangas, Ville; Hanski, Ilkka

    2016-05-15

    Flying insects have the highest known mass-specific demand for oxygen, which makes it likely that reduced availability of oxygen might limit sustained flight, either instead of or in addition to the limitation due to metabolite resources. The Glanville fritillary butterfly (Melitaea cinxia) occurs as a large metapopulation in which adult butterflies frequently disperse between small local populations. Here, we examine how the interaction between oxygen availability and fuel use affects flight performance in the Glanville fritillary. Individuals were flown under either normoxic (21 kPa O2) or hypoxic (10 kPa O2) conditions and their flight metabolism was measured. To determine resource use, levels of circulating glucose, trehalose and whole-body triglyceride were recorded after flight. Flight performance was significantly reduced in hypoxic conditions. When flown under normoxic conditions, we observed a positive correlation among individuals between post-flight circulating trehalose levels and flight metabolic rate, suggesting that low levels of circulating trehalose constrains flight metabolism. To test this hypothesis experimentally, we measured the flight metabolic rate of individuals injected with a trehalase inhibitor. In support of the hypothesis, experimental butterflies showed significantly reduced flight metabolic rate, but not resting metabolic rate, in comparison to control individuals. By contrast, under hypoxia there was no relationship between trehalose and flight metabolic rate. Additionally, in this case, flight metabolic rate was reduced in spite of circulating trehalose levels that were high enough to support high flight metabolic rate under normoxic conditions. These results demonstrate a significant interaction between oxygen and energy availability for the control of flight performance. © 2016. Published by The Company of Biologists Ltd.

  14. Different interaction of codeine and morphine with DNA: a concept for simultaneous determination.

    PubMed

    Ensafi, Ali A; Heydari-Bafrooei, E; Rezaei, B

    2013-03-15

    In this study, the interaction between codeine and morphine with dsDNA was assessed at pH 7.0. Poly(diallyldimethylammonium chloride), PDDA, was used as a dispersant of MWCNTs. Using differential pulse voltammetry (DPV) at pencil graphite electrode (PGE) showed that both molecules were electrochemically oxidized due to the presence of phenolic and amino groups in their structures. When DNA was added to the solution, the electrochemical signal of codeine and morphine was decreased and shifted to more negative and positive potentials, respectively. The interaction modes were respectively electrostatic for codeine and intercalation for morphine with two anodic peaks of codeine being merged into them when DNA concentration was increased. At high DNA concentrations, a sharp anodic wave for codeine and a clear discrimination of codeine and morphine oxidation peaks were observed. Finally, a pencil graphite electrode was modified with carbon nanotubes and DNA was tested in order to determine codeine and morphine in solution. Electrochemical oxidation of codeine and morphine bonded on dsDNA/MWCNTs-PDDA/PGE was used to obtain an analytical signal. Allowing five min as an accumulation time, a linear dependence was observed between 0.05 and 40 μg mL(-1) for codeine and 0.05 and 42 μg mL(-1) for morphine. Detection limits of 0.041 and 0.043 μg mL(-1) were obtained for codeine and morphine, respectively. The biosensor was applied to validate its capability for the analysis of codeine and morphine in blood serum, urine samples and pharmaceutical formulations. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Climate warming and agricultural stressors interact to determine stream macroinvertebrate community dynamics.

    PubMed

    Piggott, Jeremy J; Townsend, Colin R; Matthaei, Christoph D

    2015-05-01

    Global climate change is likely to modify the ecological consequences of currently acting stressors, but potentially important interactions between climate warming and land-use related stressors remain largely unknown. Agriculture affects streams and rivers worldwide, including via nutrient enrichment and increased fine sediment input. We manipulated nutrients (simulating agricultural run-off) and deposited fine sediment (simulating agricultural erosion) (two levels each) and water temperature (eight levels, 0-6°C above ambient) simultaneously in 128 streamside mesocosms to determine the individual and combined effects of the three stressors on macroinvertebrate community dynamics (community composition and body size structure of benthic, drift and insect emergence assemblages). All three stressors had pervasive individual effects, but in combination often produced additive or antagonistic outcomes. Changes in benthic community composition showed a complex interplay among habitat quality (with or without sediment), resource availability (with or without nutrient enrichment) and the behavioural/physiological tendency to drift or emerge as temperature rose. The presence of sediment and raised temperature both resulted in a community of smaller organisms. Deposited fine sediment strongly increased the propensity to drift. Stressor effects were most prominent in the benthic assemblage, frequently reflected by opposite patterns in individuals quitting the benthos (in terms of their propensity to drift or emerge). Of particular importance is that community measures of stream health routinely used around the world (taxon richness, EPT richness and diversity) all showed complex three-way interactions, with either a consistently stronger temperature response or a reversal of its direction when one or both agricultural stressors were also in operation. The negative effects of added fine sediment, which were often stronger at raised temperatures, suggest that streams already

  16. Multiple interaction types determine the impact of ant predation of caterpillars in a forest community.

    PubMed

    Clark, Robert E; Farkas, Timothy E; Lichter-Marck, Isaac; Johnson, Emily R; Singer, Michael S

    2016-12-01

    Direct and indirect effects of predators are highly variable in complex communities, and understanding the sources of this variation is a research priority in community ecology. Recent evidence indicates that herbivore community structure is a primary determinant of predation strength and its cascading impacts on plants. In this study, we use variation in herbivore community structure among plant species to experimentally test two hypotheses in a temperate forest food web. First, variation in the strength of predator effects, such as ant predation of caterpillars, is predicted to be density dependent, exhibiting stronger effects when prey abundance is high (density-dependent predation hypothesis). Second, mutualistic interactions between ants and sap-feeding herbivores are expected to increase the abundance of predatory ants, strengthening predation effects on herbivores with cascading effects on host plants (keystone mutualism hypothesis). Using a large-scale predator exclusion experiment across eight dominant tree species, we tracked changes in insect density on 862 plants across two years, recording 2,322 ants, 1,062 sap-feeders, 5,322 caterpillars, and quantifying herbivory on 199, 338 leaves. In this experiment, density-dependent predation did not explain variation in the direct or indirect effects of ants on caterpillars and herbivory. In partial support of the keystone mutualism hypothesis, sap-feeders strengthened top-down effects of ants on caterpillars under some conditions. However, stronger ant predation of caterpillars did not lead to measurable trophic cascades on trees occupied by sap-feeders. Instead, the presence of sap-feeders was associated with increased per capita feeding damage by caterpillars, and this bottom-up effect attenuated the indirect effects of ants on host plants. These findings demonstrate that examining the multi-trophic impacts of mutualisms and predation in the context of the broader community can reveal patterns otherwise

  17. Determination of inorganic pharmaceutical counterions using hydrophilic interaction chromatography coupled with a Corona CAD detector.

    PubMed

    Huang, Z; Richards, M A; Zha, Y; Francis, R; Lozano, R; Ruan, J

    2009-12-05

    A simple generic approach was investigated for the determination of inorganic pharmaceutical counterions in drug substances using conventional high performance liquid chromatographic (HPLC) instruments. An intuitive approach combined Corona charged aerosol detection (CAD) with a polymer-based zwitterionic stationary phase in the hydrophilic interaction chromatography (HILIC) mode. Two generic methods based on this HILIC/CAD technique were developed to quantitate counterions such as Cl-, Br-, SO(4)(2-), K+, Ca2+ and Mg2+ in different pharmaceutical compounds. The development and capability of this HILIC/CAD technique analysis were examined. HILIC/CAD was compared to ion chromatography (IC), the most commonly used methodology for pharmaceutical counterion analysis. HILIC/CAD was found to have significant advantages in terms of: (1) being able to quantitate both anions and cations simultaneously without a need to change column/eluent or detection mode; (2) imposing much less restriction on the allowable organic percentage of the eluents than IC, and therefore being more appropriate for analysis of counterions of poorly water-soluble drugs; (3) requiring minimal training of the operating analysts. The precision and accuracy of counterion analysis using HILIC/CAD was not compromised. A typical precision of <2.0% was observed for all tested inorganic counterions; the determinations were within 2.0% relative to the theoretical counterion amount in the drug substance. Additionally, better accuracy was shown for Cl- in several drug substances as compared to IC. The main drawback of HILIC/CAD is its unsuitability for many of the current silica-based HILIC columns, because slight dissolution of silica leads to high baseline noise in the CAD detector. As a result of the universal detection characteristics of Corona CAD and the unique separation capabilities of a zwitterionic stationary phase, an intuitive and robust HPLC method was developed for the generic determination of

  18. The compact conformation of fibronectin is determined by intramolecular ionic interactions.

    PubMed

    Johnson, K J; Sage, H; Briscoe, G; Erickson, H P

    1999-05-28

    Fibronectin exists in a compact or extended conformation, depending upon environmental pH and salt concentration. Using recombinant fragments expressed in bacteria and baculovirus, we determined the domains responsible for producing fibronectin's compact conformation. Our velocity and equilibrium sedimentation data show that FN2-14 (a protein containing FN-III domains 2 through 14) forms dimers in low salt. Experiments with smaller fragments indicates that the compact conformation is produced by binding of FN12-14 of one subunit to FN2-3 of the other subunit in the dimer. The binding is weakened at higher salt concentrations, implying an electrostatic interaction. Furthermore, segment FN7-14+A, which contains the alternatively spliced A domain between FN11 and 12, forms dimers, whereas FN7-14 without A does not. Segment FN12-14+A also forms dimers, but the isolated A domain does not. These data imply an association of domain A with FN12-14, and the presence of A may favor an open conformation by competing with FN2-3 for binding to FN12-14.

  19. Determining an Effective Shear Modulus in Tubular Organs for Fluid-Structure Interaction

    NASA Astrophysics Data System (ADS)

    Chisena, Robert; Brasseur, James; Costanzo, Francesco; Gregersen, Hans; Zhao, Jingbo

    2014-11-01

    Fluid-structure interaction (FSI) is central to the mechanics of fluid-filled tubular organs such as the intestine and esophagus. The motions of fluid chyme are driven by a muscularis wall layer of circular and longitudinal muscle fibers. The coupled motions of the fluid and elastic solid phases result from a local balance between active and passive muscle stress components, fluid pressure, and fluid viscous stresses. Model predictions depend on the passive elastic response of the muscularis layer, which is typically parameterized with an average isotropic elastic modulus (EM), currently measured in vivo and in vitro with estimates for total hoop stress within a distension experiment. We have shown that this approach contains serious error due to the overwhelming influence of incompressibility on the hydrostatic component. We present a new approach in which an effective shear modulus, containing only deviatoric contributions, is measured to overcome this serious error. Using in vitro measurements from pig intestines, we compare our new approach to the current method, showing vastly different predictions. We will also report on our current analysis which aims to determine the influence of residual stress on the EM measurements and comment on it use in FSI simulations.

  20. Aerosol-cloud interaction determined by satellite data over the Baltic Sea countries

    NASA Astrophysics Data System (ADS)

    Saponaro, Giulia; Kolmonen, Pekka; Sogacheva, Larisa; de Leeuw, Gerrit

    2015-04-01

    The present study investigates the use of long-term satellite data to assess the influence of aerosols upon cloud parameters over the Baltic Sea region. This particular area offers the contrast of a very clean environment (Fennoscandia) against a more polluted one (Germany, Poland). The datasets consists of Collection 6 Level 3 daily observations from 2002 to 2014 collected by the NASA's Moderate-Resolution Imaging Spectrometer (MODIS) instrument on-board the Aqua platform. The MODIS aerosol optical depth (AOD) product is used as a proxy for the number concentration of aerosol particles while the cloud effective radius (CER) and cloud optical thickness (COT) describe cloud microphysical and optical properties respectively. Satellite data have certain limitations, such as the restriction to summer season due to solar zenith angle restrictions and the known problem of the ambiguity of the aerosol-cloud interface, for instance. Through the analysis of a 12-years dataset, distribution maps provide information on a regional scale about the first aerosol indirect effect (AIE) by determining the aerosol-cloud interaction (ACI). The ACI is defined as the change in cloud optical depth or effective radius as a function of aerosol load for a fixed liquid water path (LWP). The focusing point of the current study is the evaluation of regional trends of ACI over the observed area of the Baltic Sea.

  1. Self-interaction chromatography in pre-packed columns: a critical evaluation of self-interaction chromatography methodology to determine the second virial coefficient.

    PubMed

    Rakel, Natalie; Schleining, Kristina; Dismer, Florian; Hubbuch, Juergen

    2013-06-07

    The characterization of protein-protein interactions is commonly conducted via self-interaction chromatography to describe magnitude and direction of the interactions with the resulting osmotic second virial coefficient (B22). However, the method is invasive and protein immobilization on the adsorber surface can influence the results obtained. In order to replace batch immobilization procedures followed by a column packing, direct on-column preparation was optimized in terms of protein immobilization under a continuous flow. Surface load was measured applying a novel method based on partial least squares analysis of spectral scans to reduce analytical error when determining the amount of immobilized protein. Subsequently influencing parameters such as the effects of absolute surface load, injected protein concentration and distribution of protein orientation were analyzed and system performance evaluated. The results disprove the consistency of the SIC method regarding the non-random orientation of proteins on adsorber particles. Thus the determined B22-values differ quantitatively from those determined with static light scattering. Furthermore, variations in immobilization conditions influence the results obtained. These results make clear that SIC does not fulfill the theoretical framework of B22-analysis. It is rather a qualitative measure of protein-protein interactions in the respective system used for experimentation.

  2. Characterization of membrane and protein interaction determinants of the Agrobacterium tumefaciens VirB11 ATPase.

    PubMed Central

    Rashkova, S; Spudich, G M; Christie, P J

    1997-01-01

    The VirB11 ATPase is a putative component of the transport machinery responsible for directing the export of nucleoprotein particles (T complexes) across the Agrobacterium tumefaciens envelope to susceptible plant cells. Fractionation and membrane treatment studies showed that approximately 30% of VirB11 partitioned as soluble protein, whereas the remaining protein was only partially solubilized with urea from cytoplasmic membranes of wild-type strain A348 as well as a Ti-plasmidless strain expressing virB11 from an IncP replicon. Mutations in virB11 affecting protein function were mapped near the amino terminus (Q6L, P13L, and E25G), just upstream of a region encoding a Walker A nucleotide-binding site (F154H;L155M), and within the Walker A motif (P170L, K175Q, and delta GKT174-176). The K175Q and delta GKT174-176 mutant proteins partitioned almost exclusively with the cytoplasmic membrane, suggesting that an activity associated with nucleotide binding could modulate the affinity of VirB11 for the cytoplasmic membrane. The virB11F154H;L155M allele was transdominant over wild-type virB11 in a merodiploid assay, providing strong evidence that at least one form of VirB11 functions as a homo- or heteromultimer. An allele with a deletion of the first half of the gene, virB11 delta1-156, was transdominant in a merodiploid assay, indicating that the C-terminal half of VirB11 contains a protein interaction domain. Products of both virB11 delta1-156 and virB11 delta158-343, which synthesizes the N-terminal half of VirB11, associated tightly with the A. tumefaciens membrane, suggesting that both halves of VirB11 contain membrane interaction determinants. PMID:9006008

  3. Cell-free Determination of Binary Complexes That Comprise Extended Protein-Protein Interaction Networks of Yersinia pestis.

    PubMed

    Keasey, Sarah L; Natesan, Mohan; Pugh, Christine; Kamata, Teddy; Wuchty, Stefan; Ulrich, Robert G

    2016-10-01

    Binary protein interactions form the basic building blocks of molecular networks and dynamic assemblies that control all cellular functions of bacteria. Although these protein interactions are a potential source of targets for the development of new antibiotics, few high-confidence data sets are available for the large proteomes of most pathogenic bacteria. We used a library of recombinant proteins from the plague bacterium Yersinia pestis to probe planar microarrays of immobilized proteins that represented ∼85% (3552 proteins) of the bacterial proteome, resulting in >77,000 experimentally determined binary interactions. Moderate (KD ∼μm) to high-affinity (KD ∼nm) interactions were characterized for >1600 binary complexes by surface plasmon resonance imaging of microarrayed proteins. Core binary interactions that were in common with other gram-negative bacteria were identified from the results of both microarray methods. Clustering of proteins within the interaction network by function revealed statistically enriched complexes and pathways involved in replication, biosynthesis, virulence, metabolism, and other diverse biological processes. The interaction pathways included many proteins with no previously known function. Further, a large assembly of proteins linked to transcription and translation were contained within highly interconnected subregions of the network. The two-tiered microarray approach used here is an innovative method for detecting binary interactions, and the resulting data will serve as a critical resource for the analysis of protein interaction networks that function within an important human pathogen. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Using a local-interaction model to determine the resistance to penetration of projectiles into sandy soil

    NASA Astrophysics Data System (ADS)

    Kotov, V. L.; Balandin, V. V.; Bragov, A. M.; Linnik, E. Yu.; Balandin, V. V.

    2013-07-01

    A local-interaction model describing the penetration of axisymmetric projectiles into sandy soil at a constant velocity is studied experimentally and theoretically. Two approaches to the determination of the parameters of the quadratic local-interaction model are considered. The first approach is based on the use of the solution of the problem of spherical-cavity expansion taking into account the dynamic compressibility and shear resistance of soil. In the second approach, model parameters are determined based on the experimental dependence of the resistance to penetration of conical projectiles into a sandy soil on the impact velocity. Good agreement was obtained between the results of experiments, two-dimensional numerical calculations, and calculations for the local interaction model based on the solution of the spherical-cavity expansion problem and used to determine the maximum resistance to penetration of conical and spherical projectiles.

  5. Metal-Sulfur Valence Orbital Interaction Energies in Metal–Dithiolene Complexes: Determination of Charge and Overlap Interaction Energies by Comparison of Core and Valence Ionization Energy Shifts

    PubMed Central

    Wiebelhaus, Nicholas J.; Cranswick, Matthew A.; Klein, Eric L.; Lockett, L. Tori; Lichtenberger, Dennis L.; Enemark, John H.

    2011-01-01

    The electronic interactions between metals and dithiolenes are important in the biological processes of many metalloenzymes as well as in diverse chemical and material applications. Of special note is the ability of the dithiolene ligand to support metal centers in multiple coordination environments and oxidation states. To better understand the nature of metal-dithiolene electronic interactions, new capabilities in gas-phase core photoelectron spectroscopy for molecules with high sublimation temperatures have been developed and applied to a series of molecules of the type Cp2M(bdt) (Cp = η5-cyclopentadienyl, M = Ti, V, Mo, and bdt = benzenedithiolato). Comparison of the gas-phase core and valence ionization energy shifts provides a unique quantitative energy measure of valence orbital overlap interactions between the metal and sulfur orbitals that is separated from the effects of charge redistribution. The results explain the large amount of sulfur character in the redox-active orbitals and the ‘leveling’ of oxidation state energies in metal-dithiolene systems. The experimentally-determined orbital interaction energies reveal a previously unidentified overlap interaction of the predominantly sulfur HOMO of the bdt ligand with filled π orbitals of the Cp ligands, suggesting that direct dithiolene interactions with other ligands bound to the metal could be significant for other metal-dithiolene systems in chemistry and biology. PMID:21988484

  6. Double-Bottom Chaotic Map Particle Swarm Optimization Based on Chi-Square Test to Determine Gene-Gene Interactions

    PubMed Central

    Yang, Cheng-Hong; Chang, Hsueh-Wei

    2014-01-01

    Gene-gene interaction studies focus on the investigation of the association between the single nucleotide polymorphisms (SNPs) of genes for disease susceptibility. Statistical methods are widely used to search for a good model of gene-gene interaction for disease analysis, and the previously determined models have successfully explained the effects between SNPs and diseases. However, the huge numbers of potential combinations of SNP genotypes limit the use of statistical methods for analysing high-order interaction, and finding an available high-order model of gene-gene interaction remains a challenge. In this study, an improved particle swarm optimization with double-bottom chaotic maps (DBM-PSO) was applied to assist statistical methods in the analysis of associated variations to disease susceptibility. A big data set was simulated using the published genotype frequencies of 26 SNPs amongst eight genes for breast cancer. Results showed that the proposed DBM-PSO successfully determined two- to six-order models of gene-gene interaction for the risk association with breast cancer (odds ratio > 1.0; P value <0.05). Analysis results supported that the proposed DBM-PSO can identify good models and provide higher chi-square values than conventional PSO. This study indicates that DBM-PSO is a robust and precise algorithm for determination of gene-gene interaction models for breast cancer. PMID:24895547

  7. Double-bottom chaotic map particle swarm optimization based on chi-square test to determine gene-gene interactions.

    PubMed

    Yang, Cheng-Hong; Lin, Yu-Da; Chuang, Li-Yeh; Chang, Hsueh-Wei

    2014-01-01

    Gene-gene interaction studies focus on the investigation of the association between the single nucleotide polymorphisms (SNPs) of genes for disease susceptibility. Statistical methods are widely used to search for a good model of gene-gene interaction for disease analysis, and the previously determined models have successfully explained the effects between SNPs and diseases. However, the huge numbers of potential combinations of SNP genotypes limit the use of statistical methods for analysing high-order interaction, and finding an available high-order model of gene-gene interaction remains a challenge. In this study, an improved particle swarm optimization with double-bottom chaotic maps (DBM-PSO) was applied to assist statistical methods in the analysis of associated variations to disease susceptibility. A big data set was simulated using the published genotype frequencies of 26 SNPs amongst eight genes for breast cancer. Results showed that the proposed DBM-PSO successfully determined two- to six-order models of gene-gene interaction for the risk association with breast cancer (odds ratio > 1.0; P value <0.05). Analysis results supported that the proposed DBM-PSO can identify good models and provide higher chi-square values than conventional PSO. This study indicates that DBM-PSO is a robust and precise algorithm for determination of gene-gene interaction models for breast cancer.

  8. Determining confidence of predicted interactions between HIV-1 and human proteins using conformal method.

    PubMed

    Nouretdinov, Ilia; Gammerman, Alex; Qi, Yanjun; Klein-Seetharaman, Judith

    2012-01-01

    Identifying protein-protein interactions (PPI's) is critical for understanding virtually all cellular molecular mechanisms. Previously, predicting PPI's was treated as a binary classification task and has commonly been solved in a supervised setting which requires a positive labeled set of known PPI's and a negative labeled set of non-interacting protein pairs. In those methods, the learner provides the likelihood of the predicted interaction, but without a confidence level associated with each prediction. Here, we apply a conformal prediction framework to make predictions and estimate confidence of the predictions. The conformal predictor uses a function measuring relative 'strangeness' interacting pairs to check whether prediction of a new example added to the sequence of already known PPI's would conform to the 'exchangeability' assumption: distribution of interacting pairs is invariant with any permutations of the pairs. In fact, this is the only assumption we make about the data. Another advantage is that the user can control a number of errors by providing a desirable confidence level. This feature of CP is very useful for a ranking list of possible interactive pairs. In this paper, the conformal method has been developed to deal with just one class - class interactive proteins - while there is not clearly defined of 'non-interactive'pairs. The confidence level helps the biologist in the interpretation of the results, and better assists the choices of pairs for experimental validation. We apply the proposed conformal framework to improve the identification of interacting pairs between HIV-1 and human proteins.

  9. [Determination of melamine and ammeline in eggs and meat using hydrophilic interaction liquid chromatography].

    PubMed

    Li, Yanzhao; Hao, Weiqiang; Wang, Yubo; Chen, Qiang; Li, Jinchun; Sun, Xiaoli

    2012-07-01

    A hydrophilic interaction liquid chromatographic (HILIC) method for the determination of melamine and its degradation product ammeline in eggs and meat has been developed. The separation was carried out on a ZIC-HILIC column with 3 mmol/L NH4H2PO4 (pH 6.9)-acetonitrile (20: 80, v/v) as mobile phase at the flow rate of 0.8 mL/min, and detected at 220 nm. Compared with the reversed-phase liquid chromatography, this method can avoid the use of ion pair reagents and thus simplify the composition of mobile phase. Under the above chromatographic conditions, melamine and ammeline had good peak shapes and moderate retention times. Good separation between these compounds and the substances that were naturally contained in the samples can be achieved. For the sample preparation, the analytes were first extracted with 0.1% phosphoric acid due to the basicity of melamine and ammeline. Then, metaphosphoric acid and acetonitrile were used to remove proteins and saccharides by precipitation. After the filtration and removal of acetonitrile by rotary evaporation under vacuum, the filtrate was cleaned-up by solid-phase extraction (SPE) technique in which a cation exchange column was used. The SPE column was activated by using methanol and 0.1% phosphoric acid. A solution of 5% ammonia methanol was chosen as eluent. The residues obtained from the eluant by evaporating the solvent were resolved in the mobile phase. It was found that there was a good linear relationship between concentration and detector response within the range of 0.4-40 mg/L. The limits of detection were 2 mg/kg for both melamine and ammeline. The average recoveries were between 80% and 105% in the spiked range of 2-10 mg/kg. The relative standard deviations were not more than 10%. The solutions of melamine and ammeline were stable in a month. The established method can be used in practice to determine melamine and ammeline simultaneously in egg and meat samples.

  10. Determining minimum set of driver nodes in protein-protein interaction networks.

    PubMed

    Zhang, Xiao-Fei; Ou-Yang, Le; Zhu, Yuan; Wu, Meng-Yun; Dai, Dao-Qing

    2015-05-07

    Recently, several studies have drawn attention to the determination of a minimum set of driver proteins that are important for the control of the underlying protein-protein interaction (PPI) networks. In general, the minimum dominating set (MDS) model is widely adopted. However, because the MDS model does not generate a unique MDS configuration, multiple different MDSs would be generated when using different optimization algorithms. Therefore, among these MDSs, it is difficult to find out the one that represents the true driver set of proteins. To address this problem, we develop a centrality-corrected minimum dominating set (CC-MDS) model which includes heterogeneity in degree and betweenness centralities of proteins. Both the MDS model and the CC-MDS model are applied on three human PPI networks. Unlike the MDS model, the CC-MDS model generates almost the same sets of driver proteins when we implement it using different optimization algorithms. The CC-MDS model targets more high-degree and high-betweenness proteins than the uncorrected counterpart. The more central position allows CC-MDS proteins to be more important in maintaining the overall network connectivity than MDS proteins. To indicate the functional significance, we find that CC-MDS proteins are involved in, on average, more protein complexes and GO annotations than MDS proteins. We also find that more essential genes, aging genes, disease-associated genes and virus-targeted genes appear in CC-MDS proteins than in MDS proteins. As for the involvement in regulatory functions, the sets of CC-MDS proteins show much stronger enrichment of transcription factors and protein kinases. The results about topological and functional significance demonstrate that the CC-MDS model can capture more driver proteins than the MDS model. Based on the results obtained, the CC-MDS model presents to be a powerful tool for the determination of driver proteins that can control the underlying PPI networks. The software

  11. Structural determinants for NF-Y/DNA interaction at the CCAAT box.

    PubMed

    Nardone, Valentina; Chaves-Sanjuan, Antonio; Nardini, Marco

    2017-05-01

    The recently determined crystal structures of the sequence-specific transcription factor NF-Y have illuminated the structural mechanism underlying transcription at the CCAAT box. NF-Y is a trimeric protein complex composed by the NF-YA, NF-YB, and NF-YC subunits. NF-YB and NF-YC contain a histone-like domain and assemble on a head-to-tail fashion to form a dimer, which provides the structural scaffold for the DNA sugar-phosphate backbone binding (mimicking the nucleosome H2A/H2B-DNA assembly) and for the interaction with NF-YA. The NF-YA subunit hosts two structurally extended α-helices; one is involved in NF-YB/NF-YC binding and the other inserts deeply into the DNA minor groove, providing exquisite sequence-specificity for recognition and binding of the CCAAT box. The analysis of these structural data is expected to serve as a powerful guide for future experiments aimed at understanding the role of post-translational modification at NF-Y regulation sites and to unravel the three-dimensional architecture of higher order complexes formed between NF-Y and other transcription factors that act synergistically for transcription activation. Moreover, these structures represent an excellent starting point to challenge the formation of a stable hybrid nucleosome between NF-Y and core histone proteins, and to rationalize the fine molecular details associated with the wide combinatorial association of plant NF-Y subunits. This article is part of a Special Issue entitled: Nuclear Factor Y in Development and Disease, edited by Prof. Roberto Mantovani. Copyright © 2016. Published by Elsevier B.V.

  12. Amphiphilicity Is a Key Determinant in the Membrane Interactions of Synthetic 14-mer Cationic Peptide Analogues.

    PubMed

    Fillion, Matthieu; Goudreault, Maxime; Voyer, Normand; Bechinger, Burkhard; Auger, Michèle

    2016-12-13

    Cationic antimicrobial peptides are a component of the innate immune system of several organisms and represent an interesting alternative to fight multiresistant bacteria. In this context, we have elaborated a synthetic peptide scaffold allowing the study of the impact of different molecular determinants on the membrane interactions. The aim of the present study was to elucidate the mechanism of action of two cationic peptides that derive from a neutral 14-mer template peptide and where the hydrophilic portion is composed of a crown ether. The R5R10 peptide is active in the presence of both negatively charged and zwitterionic membranes (nonselective) and adopts an α-helical conformation, whereas the R4R11 peptide is more active in the presence of negatively charged membranes (selective) and forms intermolecular β-sheet structures. Both the membrane topology and the location of the peptides have been assessed using solid-state NMR and attenuated total reflectance Fourier transform infrared spectroscopy. In addition, fluorescence experiments have been performed on different membrane mixtures to evaluate the ability of the peptides to induce a positive curvature to the membrane. Overall, for both the R5R10 and R4R11 peptides, the results are consistent with a mechanism of action similar to the sinking-raft model in which the peptides are mainly lying flat on the membrane surface and impose a bending stress to the membrane, thus leading to the formation of pores. Furthermore, the difference of membrane selectivity between R5R10 and R4R11 peptides is due to their differing amphipathic properties which modulate the membrane activity on zwitterionic model membranes.

  13. Interactions between local climate and grazing determine the population dynamics of the small herb Viola biflora.

    PubMed

    Evju, Marianne; Halvorsen, Rune; Rydgren, Knut; Austrheim, Gunnar; Mysterud, Atle

    2010-08-01

    Plants of low stature may benefit from the presence of large herbivores through removal of tall competitive neighbours and increased light availability. Accordingly, removal of grazers has been predicted to disfavour small species. In addition to this indirect beneficial effect, the population dynamics of plants is strongly influenced by variation in external conditions such as temperature and precipitation. However, few studies have examined the interaction between large herbivores and inter-annual variation in climate for the population dynamics of small plant species not preferred by herbivores. We studied three populations of the perennial herb Viola biflora exposed to different sheep densities (high, low and zero) for 6 years in a field experiment. Plants were also impacted by invertebrate and small vertebrate herbivores (rodents). Rates of growth were marginally higher at high sheep densities, and during warm summers both survival and growth were higher when sheep were present. Thus, while the height of tall herbs was positively related to July temperature, it was less so in the treatments with sheep, suggesting that sheep reduce the negative effects of interspecific competition for this small herb. Life table response experiment analyses revealed that the population growth rate (lambda) was slightly lower in the absence of sheep, but between-year variation in lambda was larger than variation among sheep density treatments. lambda was negatively related to July temperature, with an additional negative effect of vertebrate grazing frequency (sheep or rodent grazing). The evidence from this 6-year study suggests that the population dynamics of Viola biflora is determined by a complex interplay between climate and grazing by both large and small herbivores.

  14. [Morphogenesis and differentiation of the female genital tract. Genetic determinism and epithelium-stromal interactions].

    PubMed

    Amălinei, Cornelia

    2007-01-01

    The epithelium-stromal interaction is important in the process of morphogenesis, differentiation, and hormone response, in female genital tract. This review is organized in four sections: i) female genital tract morphogenesis, based on genetic determinism; ii) hormonal control of endometrial proliferation; iii) TGF-beta key-role in epithelium-stromal communication; iv) endometrial apoptosis. Female genital tract derives from the Müllerian ducts, a number of genes being involved in its regulation, like Lim1, Lhx9, Emx, Pax-2, Hox-A9, Hox-A10, Hox-A11, Hox-A13, Wnt-4, Wnt-7, WT1, SF-1, and GATA-4. TGF-beta, whose expression is modulated by ovarian steroids, regulates cell growth, differentiation, apoptosis, inflammatory and immune responses, extracellular matrix deposition, adhesion molecules, proteases, and protease inhibitor expression. In the endometrium, TGF-beta regulates its own expression, and that of extracellular matrix, adhesion molecules and proteases implicated in trophoblast invasion, angiogenesis, and tumor metastasis during embryo implantation, endometriosis, irregular bleeding, and endometrial cancer. Cellular response elicited by TGF-beta, mediated through a serine/threonine kinase receptor, induces the recruitment of multiple intracellular signals, specifically Smads, whose activation and subsequent translocation into the nucleus results in gene expression. Ubiquitin is involved in the degradation of short lived, regulatory or misfolded proteins, by tagging them to be taken to the proteasome. In the endometrium, ubiquitin may allow cells of stromal origin to grow, survive and evade T-cell mediated disposal, showing a functional duality. A complete understanding of the complex regulatory endometrial epithelium-stromal mechanism, concertating genes, hormones, and cytokines, may provide new therapeutic targets in female reproductive tract pathology.

  15. Interaction of exposure concentration and duration in determining acute toxic effects of sarin vapor in rats.

    PubMed

    Mioduszewski, R; Manthei, J; Way, R; Burnett, D; Gaviola, B; Muse, W; Thomson, S; Sommerville, D; Crosier, R

    2002-04-01

    Sarin (GB) vapor exposure is associated with both systemic and local toxic effects occurring primarily via the inhalation and ocular routes. The objective of these studies was to develop models for predicting dose-response effects of GB vapor concentrations as a function of exposure duration. Thus, the probability of GB vapor-induced lethality was estimated in rats exposed to various combinations of exposure concentration and duration. Groups of male and female Sprague-Dawley rats were exposed to one of a series of GB vapor concentrations for a single duration (5-360 min) in a whole-body dynamic chamber. The onset of clinical signs and changes in blood cholinesterase activity were measured with each exposure. Separate effective concentrations for lethality in 50% of the exposed population (LC50) and corresponding dose-response slopes were determined for each exposure duration by the Bliss probit method. Contrary to that predicted by Haber's rule, the interaction of LC50 x time (LCT50) values increased with exposure duration (i.e., the CT for 50% lethality in the exposed population and corresponding dose-response slope was not constant over time). A plot of log (LCT50) versus log (exposure time) showed significant curvature. Predictive models derived from multifactor probit analysis of results describing the relationship between exposure conditions and probability of lethality in the rat are discussed. Overall, female rats were more sensitive to GB vapor toxicity than male rats over the range of exposure concentration and duration studied. Miosis was the initial clinical sign noted after the start of GB vapor exposure. Although blood cholinesterase activity was significantly inhibited by GB vapor exposure, poor correlation between cholinesterase inhibition and exposure conditions or cholinesterase inhibition and severity of clinical signs was noted.

  16. Attributions about, and Instructions on How To Treat, Their Neonates as Determinants of Mothers' Interaction Behavior.

    ERIC Educational Resources Information Center

    Hollenbeck, Albert R.; Gewirtz, Jacob L.

    Two experiments explored the influence of neonate characteristics on maternal behavior. Experiment 1 investigated the influence of maternal attribution to the neonate of certain behavioral characteristics on maternal behavior in interaction. After videotaped mother-neonate pair interaction, neonates were removed for a nominal examination. Mothers…

  17. Ab initio determination of coarse-grained interactions in double-stranded DNA

    NASA Astrophysics Data System (ADS)

    Hsu, Chia Wei; Fyta, Maria; Lakatos, Greg; Melchionna, Simone; Kaxiras, Efthimios

    2012-09-01

    We derive the coarse-grained interactions between DNA nucleotides from ab initio total-energy calculations based on density functional theory (DFT). The interactions take into account base and sequence specificity, and are decomposed into physically distinct contributions that include hydrogen bonding, stacking interactions, backbone, and backbone-base interactions. The interaction energies of each contribution are calculated from DFT for a wide range of configurations and are fitted by simple analytical expressions for use in the coarse-grained model, which reduces each nucleotide into two sites. This model is not derived from experimental data, yet it successfully reproduces the stable B-DNA structure and gives good predictions for the persistence length. It may be used to realistically probe dynamics of DNA strands in various environments at the μs time scale and the μm length scale.

  18. Moving forward: dispersal and species interactions determine biotic responses to climate change.

    PubMed

    Urban, Mark C; Zarnetske, Phoebe L; Skelly, David K

    2013-09-01

    We need accurate predictions about how climate change will alter species distributions and abundances around the world. Most predictions assume simplistic dispersal scenarios and ignore biotic interactions. We argue for incorporating the complexities of dispersal and species interactions. Range expansions depend not just on mean dispersal, but also on the shape of the dispersal kernel and the population's growth rate. We show how models using species-specific dispersal can produce more accurate predictions than models applying all-or-nothing dispersal scenarios. Models that additionally include species interactions can generate distinct outcomes. For example, species interactions can slow climate tracking and produce more extinctions than models assuming no interactions. We conclude that (1) just knowing mean dispersal is insufficient to predict biotic responses to climate change, and (2) considering interspecific dispersal variation and species interactions jointly will be necessary to anticipate future changes to biological diversity. We advocate for collecting key information on interspecific dispersal differences and strong biotic interactions so that we can build the more robust predictive models that will be necessary to inform conservation efforts as climates continue to change.

  19. The masculinity paradox: facial masculinity and beardedness interact to determine women's ratings of men's facial attractiveness.

    PubMed

    Dixson, B J W; Sulikowski, D; Gouda-Vossos, A; Rantala, M J; Brooks, R C

    2016-11-01

    In many species, male secondary sexual traits have evolved via female choice as they confer indirect (i.e. genetic) benefits or direct benefits such as enhanced fertility or survival. In humans, the role of men's characteristically masculine androgen-dependent facial traits in determining men's attractiveness has presented an enduring paradox in studies of human mate preferences. Male-typical facial features such as a pronounced brow ridge and a more robust jawline may signal underlying health, whereas beards may signal men's age and masculine social dominance. However, masculine faces are judged as more attractive for short-term relationships over less masculine faces, whereas beards are judged as more attractive than clean-shaven faces for long-term relationships. Why such divergent effects occur between preferences for two sexually dimorphic traits remains unresolved. In this study, we used computer graphic manipulation to morph male faces varying in facial hair from clean-shaven, light stubble, heavy stubble and full beards to appear more (+25% and +50%) or less (-25% and -50%) masculine. Women (N = 8520) were assigned to treatments wherein they rated these stimuli for physical attractiveness in general, for a short-term liaison or a long-term relationship. Results showed a significant interaction between beardedness and masculinity on attractiveness ratings. Masculinized and, to an even greater extent, feminized faces were less attractive than unmanipulated faces when all were clean-shaven, and stubble and beards dampened the polarizing effects of extreme masculinity and femininity. Relationship context also had effects on ratings, with facial hair enhancing long-term, and not short-term, attractiveness. Effects of facial masculinization appear to have been due to small differences in the relative attractiveness of each masculinity level under the three treatment conditions and not to any change in the order of their attractiveness. Our findings suggest that

  20. Dietary fat and gut microbiota interactions determine diet-induced obesity in mice.

    PubMed

    Kübeck, Raphaela; Bonet-Ripoll, Catalina; Hoffmann, Christina; Walker, Alesia; Müller, Veronika Maria; Schüppel, Valentina Luise; Lagkouvardos, Ilias; Scholz, Birgit; Engel, Karl-Heinz; Daniel, Hannelore; Schmitt-Kopplin, Philippe; Haller, Dirk; Clavel, Thomas; Klingenspor, Martin

    2016-12-01

    Gut microbiota may promote positive energy balance; however, germfree mice can be either resistant or susceptible to diet-induced obesity (DIO) depending on the type of dietary intervention. We here sought to identify the dietary constituents that determine the susceptibility to body fat accretion in germfree (GF) mice. GF and specific pathogen free (SPF) male C57BL/6N mice were fed high-fat diets either based on lard or palm oil for 4 wks. Mice were metabolically characterized at the end of the feeding trial. FT-ICR-MS and UPLC-TOF-MS were used for cecal as well as hepatic metabolite profiling and cecal bile acids quantification, respectively. Hepatic gene expression was examined by qRT-PCR and cecal gut microbiota of SPF mice was analyzed by high-throughput 16S rRNA gene sequencing. GF mice, but not SPF mice, were completely DIO resistant when fed a cholesterol-rich lard-based high-fat diet, whereas on a cholesterol-free palm oil-based high-fat diet, DIO was independent of gut microbiota. In GF lard-fed mice, DIO resistance was conveyed by increased energy expenditure, preferential carbohydrate oxidation, and increased fecal fat and energy excretion. Cecal metabolite profiling revealed a shift in bile acid and steroid metabolites in these lean mice, with a significant rise in 17β-estradiol, which is known to stimulate energy expenditure and interfere with bile acid metabolism. Decreased cecal bile acid levels were associated with decreased hepatic expression of genes involved in bile acid synthesis. These metabolic adaptations were largely attenuated in GF mice fed the palm-oil based high-fat diet. We propose that an interaction of gut microbiota and cholesterol metabolism is essential for fat accretion in normal SPF mice fed cholesterol-rich lard as the main dietary fat source. This is supported by a positive correlation between bile acid levels and specific bacteria of the order Clostridiales (phylum Firmicutes) as a characteristic feature of normal SPF mice

  1. Using Lamm-Equation Modeling of Sedimentation Velocity Data to Determine the Kinetic and Thermodynamic Properties of Macromolecular Interactions

    PubMed Central

    Brautigam, Chad A.

    2011-01-01

    The interaction of macromolecules with themselves and with other macromolecules is fundamental to the functioning of living systems. Recent advances in the analysis of sedimentation velocity (SV) data obtained by analytical ultracentrifugation allow the experimenter to determine important features of such interactions, including the equilibrium association constant and information about the kinetic off-rate of the interaction. The determination of these parameters is made possible by the ability of modern software to fit numerical solutions of the Lamm Equation with kinetic considerations directly to SV data. Herein, the SV analytical advances implemented in the software package SEDPHAT are summarized. Detailed analyses of SV data using these strategies are presented. Finally, a few highlights of recent literature reports that feature this type of SV data analysis are surveyed. PMID:21187153

  2. Development and validation of a hydrophilic interaction liquid chromatographic method for determination of aromatic amines in environmental water

    USDA-ARS?s Scientific Manuscript database

    A simple, precise, and accurate hydrophilic interaction liquid chromatographic (HILIC) method has been developed for the determination of 5 aromatic amines in environmental water samples. Chromatography was carried out on a bare silica column, using a mixture of acetonitrile: phosphate buffer (10 mM...

  3. Field Dependence and Prior Reinforcement as Determinants of Social Interaction in Judgment

    ERIC Educational Resources Information Center

    Mausner, Bernard; Graham, Judith

    1970-01-01

    Explores the relationship of anxiety and field dependency in individuals to their tendency to conform to the judgments of others. A significant interaction occurred between field dependency and the prior reinforcement of a subject's judgment. Tables and bibliography. (RW)

  4. DETERMINING CONFIDENCE OF PREDICTED INTERACTIONS BETWEEN HIV-1 AND HUMAN PROTEINS USING CONFORMAL METHOD

    PubMed Central

    Nouretdinov, Ilia; Gammerman, Alex; Qi, Yanjun; Klein-Seetharaman, Judith

    2011-01-01

    Identifying protein-protein interactions (PPI’s) is critical for understanding virtually all cellular molecular mechanisms. Previously, predicting PPI’s was treated as a binary classification task and has commonly been solved in a supervised setting which requires a positive labeled set of known PPI’s and a negative labeled set of non-interacting protein pairs. In those methods, the learner provides the likelihood of the predicted interaction, but without a confidence level associated with each prediction. Here, we apply a conformal prediction framework to make predictions and estimate confidence of the predictions. The conformal predictor uses a function measuring relative ’strangeness’ interacting pairs to check whether prediction of a new example added to the sequence of already known PPI’s would conform to the ’exchangeability’ assumption: distribution of interacting pairs is invariant with any permutations of the pairs. In fact, this is the only assumption we make about the data. Another advantage is that the user can control a number of errors by providing a desirable confidence level. This feature of CP is very useful for a ranking list of possible interactive pairs. In this paper, the conformal method has been developed to deal with just one class - class interactive proteins - while there is not clearly defined of ’non-interactive’ pairs. The confidence level helps the biologist in the interpretation of the results, and better assists the choices of pairs for experimental validation. We apply the proposed conformal framework to improve the identification of interacting pairs between HIV-1 and human proteins. PMID:22174286

  5. Determination of the interaction impedance of coupled cavity slow wave structures

    NASA Technical Reports Server (NTRS)

    Connolly, D. J.

    1976-01-01

    The interaction impedance of coupled cavity slow wave structures can be measured by perturbing the resonances of a shorted length of the structure using a dielectric rod. An analysis of this procedure is presented. The analysis retains radial as well as axial electric fields and all significant space harmonics. The results obtained are easily programmed formulas for calculating total interaction impedance or Pierce impedance using the experimental data.

  6. Virus-plus-susceptibility gene interaction determines Crohn's disease gene Atg16L1 phenotypes in intestine.

    PubMed

    Cadwell, Ken; Patel, Khushbu K; Maloney, Nicole S; Liu, Ta-Chiang; Ng, Aylwin C Y; Storer, Chad E; Head, Richard D; Xavier, Ramnik; Stappenbeck, Thaddeus S; Virgin, Herbert W

    2010-06-25

    It is unclear why disease occurs in only a small proportion of persons carrying common risk alleles of disease susceptibility genes. Here we demonstrate that an interaction between a specific virus infection and a mutation in the Crohn's disease susceptibility gene Atg16L1 induces intestinal pathologies in mice. This virus-plus-susceptibility gene interaction generated abnormalities in granule packaging and unique patterns of gene expression in Paneth cells. Further, the response to injury induced by the toxic substance dextran sodium sulfate was fundamentally altered to include pathologies resembling aspects of Crohn's disease. These pathologies triggered by virus-plus-susceptibility gene interaction were dependent on TNFalpha and IFNgamma and were prevented by treatment with broad spectrum antibiotics. Thus, we provide a specific example of how a virus-plus-susceptibility gene interaction can, in combination with additional environmental factors and commensal bacteria, determine the phenotype of hosts carrying common risk alleles for inflammatory disease.

  7. Species distribution models contribute to determine the effect of climate and interspecific interactions in moving hybrid zones.

    PubMed

    Engler, J O; Rödder, D; Elle, O; Hochkirch, A; Secondi, J

    2013-11-01

    Climate is a major factor delimiting species' distributions. However, biotic interactions may also be prominent in shaping geographical ranges, especially for parapatric species forming hybrid zones. Determining the relative effect of each factor and their interaction of the contact zone location has been difficult due to the lack of broad scale environmental data. Recent developments in species distribution modelling (SDM) now allow disentangling the relative contributions of climate and species' interactions in hybrid zones and their responses to future climate change. We investigated the moving hybrid zone between the breeding ranges of two parapatric passerines in Europe. We conducted SDMs representing the climatic conditions during the breeding season. Our results show a large mismatch between the realized and potential distributions of the two species, suggesting that interspecific interactions, not climate, account for the present location of the contact zone. The SDM scenarios show that the southerly distributed species, Hippolais polyglotta, might lose large parts of its southern distribution under climate change, but a similar gain of novel habitat along the hybrid zone seems unlikely, because interactions with the other species (H. icterina) constrain its range expansion. Thus, whenever biotic interactions limit range expansion, species may become 'trapped' if range loss due to climate change is faster than the movement of the contact zone. An increasing number of moving hybrid zones are being reported, but the proximate causes of movement often remain unclear. In a global context of climate change, we call for more interest in their interactions with climate change.

  8. The Interaction of Genotype and Environment Determines Variation in the Maize Kernel Ionome

    PubMed Central

    Asaro, Alexandra; Ziegler, Gregory; Ziyomo, Cathrine; Hoekenga, Owen A.; Dilkes, Brian P.; Baxter, Ivan

    2016-01-01

    Plants obtain soil-resident elements that support growth and metabolism from the water-flow facilitated by transpiration and active transport processes. The availability of elements in the environment interacts with the genetic capacity of organisms to modulate element uptake through plastic adaptive responses, such as homeostasis. These interactions should cause the elemental contents of plants to vary such that the effects of genetic polymorphisms will be dramatically dependent on the environment in which the plant is grown. To investigate genotype by environment interactions underlying elemental accumulation, we analyzed levels of elements in maize kernels of the Intermated B73 × Mo17 (IBM) recombinant inbred population grown in 10 different environments, spanning a total of six locations and five different years. In analyses conducted separately for each environment, we identified a total of 79 quantitative trait loci (QTL) controlling seed elemental accumulation. While a set of these QTL was found in multiple environments, the majority were specific to a single environment, suggesting the presence of genetic by environment interactions. To specifically identify and quantify QTL by environment interactions (QEIs), we implemented two methods: linear modeling with environmental covariates, and QTL analysis on trait differences between growouts. With these approaches, we found several instances of QEI, indicating that elemental profiles are highly heritable, interrelated, and responsive to the environment. PMID:27770027

  9. Aggrecan nanoscale solid-fluid interactions are a primary determinant of cartilage dynamic mechanical properties.

    PubMed

    Nia, Hadi Tavakoli; Han, Lin; Bozchalooi, Iman Soltani; Roughley, Peter; Youcef-Toumi, Kamal; Grodzinsky, Alan J; Ortiz, Christine

    2015-03-24

    Poroelastic interactions between interstitial fluid and the extracellular matrix of connective tissues are critical to biological and pathophysiological functions involving solute transport, energy dissipation, self-stiffening and lubrication. However, the molecular origins of poroelasticity at the nanoscale are largely unknown. Here, the broad-spectrum dynamic nanomechanical behavior of cartilage aggrecan monolayer is revealed for the first time, including the equilibrium and instantaneous moduli and the peak in the phase angle of the complex modulus. By performing a length scale study and comparing the experimental results to theoretical predictions, we confirm that the mechanism underlying the observed dynamic nanomechanics is due to solid-fluid interactions (poroelasticity) at the molecular scale. Utilizing finite element modeling, the molecular-scale hydraulic permeability of the aggrecan assembly was quantified (kaggrecan = (4.8 ± 2.8) × 10(-15) m(4)/N·s) and found to be similar to the nanoscale hydraulic permeability of intact normal cartilage tissue but much lower than that of early diseased tissue. The mechanisms underlying aggrecan poroelasticity were further investigated by altering electrostatic interactions between the molecule's constituent glycosaminoglycan chains: electrostatic interactions dominated steric interactions in governing molecular behavior. While the hydraulic permeability of aggrecan layers does not change across species and age, aggrecan from adult human cartilage is stiffer than the aggrecan from newborn human tissue.

  10. Chromosomal Replication Dynamics and Interaction with the β Sliding Clamp Determine Orientation of Bacterial Transposable Elements

    PubMed Central

    Gómez, Manuel J.; Díaz-Maldonado, Héctor; González-Tortuero, Enrique; López de Saro, Francisco J.

    2014-01-01

    Insertion sequences (ISs) are small transposable elements widespread in bacterial genomes, where they play an essential role in chromosome evolution by stimulating recombination and genetic flow. Despite their ubiquity, it is unclear how ISs interact with the host. Here, we report a survey of the orientation patterns of ISs in bacterial chromosomes with the objective of gaining insight into the interplay between ISs and host chromosomal functions. We find that a significant fraction of IS families present a consistent and family-specific orientation bias with respect to chromosomal DNA replication, especially in Firmicutes. Additionally, we find that the transposases of up to nine different IS families with different transposition pathways interact with the β sliding clamp, an essential replication factor, suggesting that this is a widespread mechanism of interaction with the host. Although we find evidence that the interaction with the β sliding clamp is common to all bacterial phyla, it also could explain the observed strong orientation bias found in Firmicutes, because in this group β is asymmetrically distributed during synthesis of the leading or lagging strands. Besides the interaction with the β sliding clamp, other asymmetries also play a role in the biased orientation of some IS families. The utilization of the highly conserved replication sliding clamps suggests a mechanism for host regulation of IS proliferation and also a universal platform for IS dispersal and transmission within bacterial populations and among phylogenetically distant species. PMID:24614824

  11. Reconsidering risk: adapting public policies to intergenerational determinants and biosocial interactions in health-related needs.

    PubMed

    Strully, Kate W; Conley, Dalton

    2004-12-01

    According to recent research, interactions between infant health and environment can play crucial roles in clustering health and economic disadvantage among certain families. Researchers have provided a clear example of such intergenerational biosocial cycles when they document that interactions between parental low birth weight status and prenatal environment are associated with the risk of a low birth weight, and that interactions between a child's birth weight status and early childhood environment are associated with adult socioeconomic outcomes. In this article, we consider how existing policies may be revised to more effectively address such interactions between social and biological risk categories. We are particularly concerned in this discussion with revising risk categories so they can encompass biological risk, social risk, and developmental frameworks. A framework of biosocial risk is quite flexible and may be applied to a variety of issues and programs; however, in this article we focus on the single case of low birth weight to illustrate our argument. In considering specific applications, we further explore how attention to biosocial interactions may reshape Medicaid, special education, the Earned Income Tax Credit, and Temporary Assistance for Needy Families.

  12. Application of the Stoner-Wohlfarth model with interaction for the determination of the saturation magnetisation, anisotropy field, and mean field interaction in bulk amorphous ferromagnets

    NASA Astrophysics Data System (ADS)

    Collocott, S. J.

    2011-08-01

    Magnetic hysteresis curves of bulk amorphous ferromagnet alloys of composition Nd 60Fe 30Al 10, Nd 60Fe 20Co 10Al 10 and Pr 58Fe 24Al 18 have been measured in applied magnetic fields up to 9 T at temperatures in the range 10-350 K. The behaviour of the demagnetisation curve in the first quadrant is interpreted using a mean field interaction model as proposed by Callen et al. [Phys. Rev. B 16 (1977) 263], which extends the Stoner-Wohlfarth model [Philos. Trans. Roy. Soc. A 240 (1948) 599] for a random distribution of non-interacting uniaxial grains. Application of the mean field interaction model enables the determination of the saturation magnetisation Ms, anisotropy field Ha, and interaction parameter d, and from these other magnetic parameters, such as the anisotropy constant, K, are deduced. For the three alloys, the temperature dependent behaviour of Ms, Ha, d and K over the range 20-350 K are found to be qualitatively similar, though there are quantitative differences. In all cases Ms increases with decreasing temperature, both Ha and K increase with decreasing temperature, reaching a peak in the range 75-120 K, and then decreasing, and d decreases approximately linearly as the temperature decreases. The physical mechanisms responsible for coercivity in these materials are discussed in the context of random anisotropy and a strong pinning model of domain walls.

  13. Interfacial and intermolecular interactions determining the rotational orientation of C60 adsorbed on Au(111)

    NASA Astrophysics Data System (ADS)

    Paßens, Michael; Karthäuser, Silvia

    2015-12-01

    Close-packed monolayers of fullerenes on metallic substrates are very rich systems with respect to their rotational degrees of freedom and possible interactions with different adsorption sites or next neighbours. In this connection, we report in detail on the (2√3 × 2√3)R30°-superstructure of C60 with respect to the Au(111)-surface. We use molecular orbital imaging in systematic UHV-STM studies to reveal the delicate balance of interfacial and intermolecular interactions in this system. Thus, bright C60-molecules in 5:6-top and 6:6-top geometries are observed depending on the respective next neighbours. Moreover, tiny changes in the appearance of the unoccupied molecular orbitals of dim C60-molecules in hex-vac positions are identified which are caused by the respective interaction with the facets surrounding the Au-vacancy.

  14. Ab initio determination of coarse-grained interactions in double stranded DNA

    NASA Astrophysics Data System (ADS)

    Hsu, Chia Wei; Fyta, Maria; Lakatos, Greg; Melchionna, Simone; Kaxiras, Efthimios

    2012-02-01

    We derive the coarse-grained interactions between DNA nucleotides from ab initio calculations using density functional theory (DFT). The interactions take into account the base and sequence specificity, and are decomposed into physically distinct contributions. The interactions energies calculated from DFT for a wide range of configurations are fitted to simple analytical expressions for use in the coarse-grained model, which reduces each nucleotide into two sites. This non-empirical model accurately yields structural properties of B-DNA even in extreme conditions, and predicts persistence length in excellent agreement with experiments. The model enables quantitative an efficient investigations of the dynamics of long DNA strands in various environments, making it possible to reach microsecond time scales and beyond.

  15. Mass-Sensitive Biosensor Systems to Determine the Membrane Interaction of Analytes.

    PubMed

    Hoß, Sebastian G; Bendas, Gerd

    2017-01-01

    Biosensors are devices that transform a biological interaction into a readout signal, which is evaluable for analytical purposes. The general strength of biosensor approaches is the avoidance of time-consuming and cost-intensive labeling procedures of the analytes. In this chapter, we give insight into a mass-sensitive surface-acoustic wave (SAW) biosensor, which represents an elegant and highly sensitive method to investigate binding events at a molecular level. The principle of SAW technology is based on the piezoelectric properties of the sensors, so as to binding events and their accompanied mass increase at the sensor surface are detectable by a change in the oscillation of the surface acoustic wave. In combination with model membranes, transferred to the sensor surface, the analytical value of SAW biosensors has strongly been increased and extended to different topics of biomedical investigations, including antibiotic research. The interaction with the bacterial membrane or certain target structures therein is the essential mode of action for various antibacterial compounds. Beside targeted interaction, an unspecific membrane binding or membrane insertion of drugs can contribute to the antibacterial activity by changing the lateral order of membrane constituents or by interfering with the membrane barrier function. Those pleiotropic effects are hardly to illustrate in the bacterial systems and need a detailed view at the in vitro level. Here, we illustrate the usefulness of a SAW biosensor in combination with model membranes to investigate the mode of membrane interaction of antibiotic active peptides. Using two different peptides we exemplary describe the interaction analysis in a two-step gain of information: (1) a binding intensity or affinity by analyzing the phase changes of oscillation, and (2) mode of membrane interaction, i.e., surface binding or internalization of the peptide by following the amplitude of oscillation.

  16. An Interactive Classroom Activity Demonstrating Reaction Mechanisms and Rate-Determining Steps

    ERIC Educational Resources Information Center

    Jennings, Laura D.; Keller, Steven W.

    2005-01-01

    An interactive classroom activity that includes two-step reaction of unwrapping and eating chocolate candies is described which brings not only the reaction intermediate, but also the reactants and products into macroscopic view. The qualitative activation barriers of both steps can be adjusted independently.

  17. Use of Factorial Analysis to Determine the Interaction Between Parameters of a Land Surface Model

    NASA Astrophysics Data System (ADS)

    Varejão, C. G.; Varejão, E. V.; Costa, M. H.

    2007-05-01

    Land surface models use several parameters to represent biophysical processes. These parameters frequently are unknown, reproducing with uncertainty the characteristics of the ecosystem in study. Model calibration techniques find values for each parameter that reduce uncertainty. However, the calibration process is computationally expensive, since is necessary a lot of model runs to have their parameters adjusted. The more parameters are considered, more difficult the process is, particularly when there are interactions among them, and a modification in a parameter value implies in the change of the optimum value of the other parameters. The use of a factorial experiment allows the identification of possible inert parameters, whose values do not influence the final result of the experiment and, therefore, could be excluded from the calibration process. In this work we used factorial analysis to verify the existence of interaction among 5 parameters of the land surface IBIS model - Beta2 (distribution of fine roots), Vmax (maximum Rubisco enzyme capacity), m (coefficient related to the stomatal conductance), CHS (heat capacity of stems) and CHU (heat capacity of leaves) - evaluated against the output fluxes Rn (net radiation), H (sensible heat flux), LE (latent heat flux) and NEE (net ecosystem CO2 exchange). Data was collected at the Amazon tropical rainforest site known as K83, near Santarem, Brazil. The knowledge of the existing interactions between the parameters can considerably reduce the computational cost of further optimization processes, since each parameter that does not interact with others should be optimized independently.

  18. π–π Interaction Energies as Determinants of the Photodimerization of Mono-, Di-, and Triazastilbenes

    PubMed Central

    2015-01-01

    We describe the quantitative [2 + 2] photocycloaddition of crystalline trans-2,4-dichloro-6-styrylpyrimidine to produce the corresponding htt r-ctt cyclobutane dimer, and we present 1H NMR analysis of the photolysis of this and six other mono-, di-, and triazastilbenes in solid and solution states. Density functional (M06-2X) and correlated ab initio (MP2) calculations were used to obtain interaction energies between two monomers of each azastilbene. These energies mirror the relative polarization of the stilbene moieties and can be quantitatively correlated with the rate of reaction and selective formation of the htt r-ctt dimers. In the solid state, poor correlation is observed between interaction energy and reactivity/selectivity. This lack of correlation is explained through X-ray analysis of the azastilbene monomers and is shown to be in accordance with the principles of Schmidt’s topochemical postulate. Conversely, in solution there is a strong positive correlation (R2 = 0.96) between interaction energies and formation of the htt r-ctt dimer. These results are the first to show this correlation and to demonstrate the utility of calculated interaction energies as a tool for the prediction of stereo- and regioselectivity in solution-state stilbene-type photocycloadditions. PMID:24837276

  19. Second virial coefficient determination of a therapeutic peptide by self-interaction chromatography.

    PubMed

    Payne, Robert W; Nayar, Rajiv; Tarantino, Ralph; Del Terzo, Sam; Moschera, John; Di, Jie; Heilman, David; Bray, Brian; Manning, Mark Cornell; Henry, Charles S

    2006-01-01

    Self-interaction of macromolecules has been shown to play an important role in a number of physical processes, including crystallization, solubility, viscosity, and aggregation. Peptide self-interaction is not as well studied as for larger proteins, but should play an equally important role. The osmotic second virial coefficient, B, can be used to quantify peptide and protein self-interaction. B values are typically measured using static light scattering (SLS). Peptides, however, do not scatter enough light to allow such measurements. This study describes the first use of self-interaction chromatography (SIC) for the measurement of peptide B values because SIC does not have the molecular size limitations of SLS. In the present work, SIC was used to measure B for enfuvirtide, a 36-amino acid therapeutic peptide, as a function of salt concentration, salt type, and pH. B was found to correlate strongly with solubility and apparent molecular weight. In general, the solubility of enfuvirtide increases with pH from 6 to 10 and decreases as the salt concentration increases from 0 to 0.5M for three different salts. The effect of peptide concentration on B was also investigated and shown to have a significant effect, but only at high concentrations (>80 mg/mL).

  20. Species interactions determine the spatial mortality patterns emerging in plant communities after extreme events.

    PubMed

    Liao, Jinbao; Bogaert, Jan; Nijs, Ivan

    2015-06-08

    Gap disturbance is assumed to maintain species diversity by creating environmental heterogeneity. However, little is known about how interactions with neighbours, such as competition and facilitation, alter the emerging gap patterns after extreme events. Using a spatially explicit community model we demonstrate that negative interactions, especially intraspecific competition, greatly promote both average gap size and gap-size diversity relative to positive interspecific interaction. This suggests that competition would promote diversity maintenance but also increase community invasibility, as large gaps with a wide size variety provide more diverse niches for both local and exotic species. Under interspecific competition, both gap metrics interestingly increased with species richness, while they were reduced under intraspecific competition. Having a wider range of species interaction strengths led to a smaller average gap size only under intraspecific competition. Increasing conspecific clumping induced larger gaps with more variable sizes under intraspecific competition, in contrast to interspecific competition. Given the range of intraspecific clumping in real communities, models or experiments based on randomly synthesized communities may yield biased estimates of the opportunities for potential colonizers to fill gaps. Overall, our "static" model on gap formation offers perspectives to better predict recolonization opportunity and thus community secondary succession under extreme event regimes.

  1. Determinants of Mobile Wireless Technology for Promoting Interactivity in Lecture Sessions: An Empirical Analysis

    ERIC Educational Resources Information Center

    Gan, Chin Lay; Balakrishnan, Vimala

    2014-01-01

    The aim of this paper is to identify adoption factors of mobile wireless technology to increase interactivity between lecturers and students during lectures. A theoretical framework to ascertain lecturers' intentions to use mobile wireless technology during lectures (dependent variable) is proposed with seven independent variables. The…

  2. Determining virus-host interactions and glycerol metabolism profiles in geographically diverse solar salterns with metagenomics

    PubMed Central

    Moller, Abraham G.

    2017-01-01

    Solar salterns are excellent model ecosystems for studying virus-microbial interactions because of their low microbial diversity, environmental stability, and high viral density. By using the power of CRISPR spacers to link viruses to their prokaryotic hosts, we explored virus-host interactions in geographically diverse salterns. Using taxonomic profiling, we identified hosts such as archaeal Haloquadratum, Halorubrum, and Haloarcula and bacterial Salinibacter, and we found that community composition related to not only salinity but also local environmental dynamics. Characterizing glycerol metabolism genes in these metagenomes suggested Halorubrum and Haloquadratum possess most dihydroxyacetone kinase genes while Salinibacter possesses most glycerol-3-phosphate dehydrogenase genes. Using two different methods, we detected fewer CRISPR spacers in Haloquadratum-dominated compared with Halobacteriaceae-dominated saltern metagenomes. After CRISPR detection, spacers were aligned against haloviral genomes to map virus to host. While most alignments for each saltern metagenome linked viruses to Haloquadratum walsbyi, there were also alignments indicating interactions with the low abundance taxa Haloarcula and Haloferax. Further examination of the dinucleotide and trinucleotide usage differences between paired viruses and their hosts confirmed viruses and hosts had similar nucleotide usage signatures. Detection of cas genes in the salterns supported the possibility of CRISPR activity. Taken together, our studies suggest similar virus-host interactions exist in different solar salterns and that the glycerol metabolism gene dihydroxyacetone kinase is associated with Haloquadratum and Halorubrum. PMID:28097058

  3. Species interactions determine the spatial mortality patterns emerging in plant communities after extreme events

    PubMed Central

    Liao, Jinbao; Bogaert, Jan; Nijs, Ivan

    2015-01-01

    Gap disturbance is assumed to maintain species diversity by creating environmental heterogeneity. However, little is known about how interactions with neighbours, such as competition and facilitation, alter the emerging gap patterns after extreme events. Using a spatially explicit community model we demonstrate that negative interactions, especially intraspecific competition, greatly promote both average gap size and gap-size diversity relative to positive interspecific interaction. This suggests that competition would promote diversity maintenance but also increase community invasibility, as large gaps with a wide size variety provide more diverse niches for both local and exotic species. Under interspecific competition, both gap metrics interestingly increased with species richness, while they were reduced under intraspecific competition. Having a wider range of species interaction strengths led to a smaller average gap size only under intraspecific competition. Increasing conspecific clumping induced larger gaps with more variable sizes under intraspecific competition, in contrast to interspecific competition. Given the range of intraspecific clumping in real communities, models or experiments based on randomly synthesized communities may yield biased estimates of the opportunities for potential colonizers to fill gaps. Overall, our “static” model on gap formation offers perspectives to better predict recolonization opportunity and thus community secondary succession under extreme event regimes. PMID:26054061

  4. The interaction of genotype and environment determines variation in the maize kernal ionome

    USDA-ARS?s Scientific Manuscript database

    Plants obtain soil-resident elements that support growth and metabolism via water-mediated flow due to transpiration and active transport processes. The availability of elements in the environment can interact with the genetic capacity of the organism to modulate element uptake through plastic adapt...

  5. An Interactive Classroom Activity Demonstrating Reaction Mechanisms and Rate-Determining Steps

    ERIC Educational Resources Information Center

    Jennings, Laura D.; Keller, Steven W.

    2005-01-01

    An interactive classroom activity that includes two-step reaction of unwrapping and eating chocolate candies is described which brings not only the reaction intermediate, but also the reactants and products into macroscopic view. The qualitative activation barriers of both steps can be adjusted independently.

  6. Determinants of Mobile Wireless Technology for Promoting Interactivity in Lecture Sessions: An Empirical Analysis

    ERIC Educational Resources Information Center

    Gan, Chin Lay; Balakrishnan, Vimala

    2014-01-01

    The aim of this paper is to identify adoption factors of mobile wireless technology to increase interactivity between lecturers and students during lectures. A theoretical framework to ascertain lecturers' intentions to use mobile wireless technology during lectures (dependent variable) is proposed with seven independent variables. The…

  7. Determining virus-host interactions and glycerol metabolism profiles in geographically diverse solar salterns with metagenomics.

    PubMed

    Moller, Abraham G; Liang, Chun

    2017-01-01

    Solar salterns are excellent model ecosystems for studying virus-microbial interactions because of their low microbial diversity, environmental stability, and high viral density. By using the power of CRISPR spacers to link viruses to their prokaryotic hosts, we explored virus-host interactions in geographically diverse salterns. Using taxonomic profiling, we identified hosts such as archaeal Haloquadratum, Halorubrum, and Haloarcula and bacterial Salinibacter, and we found that community composition related to not only salinity but also local environmental dynamics. Characterizing glycerol metabolism genes in these metagenomes suggested Halorubrum and Haloquadratum possess most dihydroxyacetone kinase genes while Salinibacter possesses most glycerol-3-phosphate dehydrogenase genes. Using two different methods, we detected fewer CRISPR spacers in Haloquadratum-dominated compared with Halobacteriaceae-dominated saltern metagenomes. After CRISPR detection, spacers were aligned against haloviral genomes to map virus to host. While most alignments for each saltern metagenome linked viruses to Haloquadratum walsbyi, there were also alignments indicating interactions with the low abundance taxa Haloarcula and Haloferax. Further examination of the dinucleotide and trinucleotide usage differences between paired viruses and their hosts confirmed viruses and hosts had similar nucleotide usage signatures. Detection of cas genes in the salterns supported the possibility of CRISPR activity. Taken together, our studies suggest similar virus-host interactions exist in different solar salterns and that the glycerol metabolism gene dihydroxyacetone kinase is associated with Haloquadratum and Halorubrum.

  8. Weak antibody-cyclodextrin interactions determined by quartz crystal microbalance and dynamic/static light scattering.

    PubMed

    Härtl, Elisabeth; Dixit, Nitin; Besheer, Ahmed; Kalonia, Devendra; Winter, Gerhard

    2013-11-01

    In a quest to elucidate the mechanism by which hydroxypropyl β-cyclodextrin (HPβCD) stabilizes antibodies against shaking stress, two heavily debated hypotheses exist, namely that stabilization is due to HPβCD's surface activity, or due to specific interactions with proteins. In a previous study by Serno et al. (Pharm. Res. 30 (2013) 117), we could refute the first hypothesis by proving that, although HPβCD is slightly surface active, it does not displace the antibody at the air-water interface, and accordingly, its surface activity is not the underlying stabilizing mechanism. In the present study, we investigated the possibility of interactions between HPβCD and monoclonal antibodies as the potential stabilization mechanism using quartz crystal microbalance (QCM) and static as well as dynamic light scattering. In the presence of HPβCD, the adsorption of IgG antibodies in the native state (IgG A) and the unfolded state (IgG A and IgG B) on gold-coated quartz crystals was studied by QCM. Results show that HPβCD causes a reduction in protein adsorption in both the folded and the unfolded states, probably due to an interaction between the protein and the cyclodextrin, leading to a reduced hydrophobicity of the protein and consequently a lower extent of adsorption. These results were supported by investigation of the interaction between the native protein and HPβCD using static and dynamic light scattering experiments, which provide the protein-protein interaction parameters, B22 and kD, respectively. Both B22 and kD showed an increase in magnitude with increasing HPβCD-concentrations, indicating a rise in net repulsive forces between the protein molecules. This is further evidence for the presence of interactions between HPβCD and the studied antibodies, since an association of HPβCD on the protein surface leads to a change in the intermolecular forces between the protein molecules. In conclusion, this study provides evidence that the previously observed

  9. Interaction Mechanism of Oil-in-Water Emulsions with Asphaltenes Determined Using Droplet Probe AFM.

    PubMed

    Shi, Chen; Zhang, Ling; Xie, Lei; Lu, Xi; Liu, Qingxia; Mantilla, Cesar A; van den Berg, Frans G A; Zeng, Hongbo

    2016-03-15

    Emulsions with interface-active components at the oil/water interface have long been of fundamental and practical interest in many fields. In this work, the interaction forces between two oil droplets in water in the absence/presence of asphaltenes were directly measured using droplet probe atomic force microscopy (AFM) and analyzed using a theoretical model based on Reynolds lubrication theory and the augmented Young-Laplace equation by including the effects of disjoining pressure. It was revealed that the interaction forces measured between two pristine oil droplets (i.e., toluene) could be well described by the classical Derjaguin-Landau-Verwey-Overbeek (DLVO) theory, while an additional steric interaction should be included in the presence of asphaltenes in the oil. The surface interaction and the stability of oil droplets in aqueous solution were demonstrated to be significantly influenced by the asphaltenes concentration in oil, salt concentration, pH, and presence of divalent ions (Ca(2+)) in water. Adsorbed asphaltenes at the oil/water interface led to more negative surface potential of the oil/water interface and also induced steric repulsion between oil droplets, inhibiting the drop coalescence and stabilizing the oil-in-water emulsion. Lower pH of aqueous solution could lead to less negative surface potential and weaken the repulsion between oil droplets. Addition of divalent ions (Ca(2+)) was found to disrupt the protecting effects of adsorbed asphaltenes at oil/water interface and induce coalescence of oil droplets. Our results provide a useful methodology for quantifying the interaction forces and investigating the properties of asphaltenes at the oil/water interfaces and provide insights into the stabilization mechanism of oil-in-water emulsions due to asphaltenes in oil production and water treatment.

  10. Experimental Determination of the Electrostatic Nature of Carbonyl Hydrogen-Bonding Interactions Using IR-NMR Correlations.

    PubMed

    Kashid, Somnath M; Bagchi, Sayan

    2014-09-18

    Hydrogen-bonding plays a fundamental role in the structure, function, and dynamics of various chemical and biological systems. Understanding the physical nature of interactions and the role of electrostatics in hydrogen-bonding has been the focus of several theoretical and computational research. We present an experimental approach involving IR-(13)C NMR correlations to determine the electrostatic nature of carbonyl hydrogen-bonding interactions. This report provides a direct experimental evidence of the classical nature of hydrogen-bonding interaction in carbonyls, independent of any theoretical approximation. These results have important implications in chemistry and biology and can be applied to probe the reaction mechanisms involving carbonyl activation/stabilization by hydrogen bonds using spectroscopic techniques.

  11. Intrinsic histone-DNA interactions are not the major determinant of nucleosome positions in vivo.

    PubMed

    Zhang, Yong; Moqtaderi, Zarmik; Rattner, Barbara P; Euskirchen, Ghia; Snyder, Michael; Kadonaga, James T; Liu, X Shirley; Struhl, Kevin

    2009-08-01

    We assess the role of intrinsic histone-DNA interactions by mapping nucleosomes assembled in vitro on genomic DNA. Nucleosomes strongly prefer yeast DNA over Escherichia coli DNA, indicating that the yeast genome evolved to favor nucleosome formation. Many yeast promoter and terminator regions intrinsically disfavor nucleosome formation, and nucleosomes assembled in vitro show strong rotational positioning. Nucleosome arrays generated by the ACF assembly factor have fewer nucleosome-free regions, reduced rotational positioning and less translational positioning than obtained by intrinsic histone-DNA interactions. Notably, nucleosomes assembled in vitro have only a limited preference for specific translational positions and do not show the pattern observed in vivo. Our results argue against a genomic code for nucleosome positioning, and they suggest that the nucleosomal pattern in coding regions arises primarily from statistical positioning from a barrier near the promoter that involves some aspect of transcriptional initiation by RNA polymerase II.

  12. Determining the elastic properties of aptamer-ricin single molecule multiple pathway interactions

    NASA Astrophysics Data System (ADS)

    Wang, Bin; Park, Bosoon; Kwon, Yongkuk; Xu, Bingqian

    2014-05-01

    We report on the elastic properties of ricin and anti-ricin aptamer interactions, which showed three stable binding conformations, each of which has its special elastic properties. These different unbinding pathways were investigated by the dynamic force spectroscopy. A series-spring model combining the worm-like-chain model and Hook's law was used to estimate the apparent spring constants of the aptamer and linker molecule polyethylene glycol. The aptamer in its three different unbinding pathways showed different apparent spring constants. The two reaction barriers in the unbinding pathways also influence the apparent spring constant of the aptamer. This special elastic behavior of aptamer was used to distinguish its three unbinding pathways under different loading rates. This method also offered a way to distinguish and discard the non-specific interactions in single molecule experiments.

  13. Direct Determination of Multiple Ligand Interactions with the Extracellular Domain of the Calcium-sensing Receptor*

    PubMed Central

    Zhang, Chen; Zhuo, You; Moniz, Heather A.; Wang, Shuo; Moremen, Kelley W.; Prestegard, James H.; Brown, Edward M.; Yang, Jenny J.

    2014-01-01

    Numerous in vivo functional studies have indicated that the dimeric extracellular domain (ECD) of the CaSR plays a crucial role in regulating Ca2+ homeostasis by sensing Ca2+ and l-Phe. However, direct interaction of Ca2+ and Phe with the ECD of the receptor and the resultant impact on its structure and associated conformational changes have been hampered by the large size of the ECD, its high degree of glycosylation, and the lack of biophysical methods to monitor weak interactions in solution. In the present study, we purified the glycosylated extracellular domain of calcium-sensing receptor (CaSR) (ECD) (residues 20–612), containing either complex or high mannose N-glycan structures depending on the host cell line employed for recombinant expression. Both glycosylated forms of the CaSR ECD were purified as dimers and exhibit similar secondary structures with ∼50% α-helix, ∼20% β-sheet content, and a well buried Trp environment. Using various spectroscopic methods, we have shown that both protein variants bind Ca2+ with a Kd of 3.0–5.0 mm. The local conformational changes of the proteins induced by their interactions with Ca2+ were visualized by NMR with specific 15N Phe-labeled forms of the ECD. Saturation transfer difference NMR approaches demonstrated for the first time a direct interaction between the CaSR ECD and l-Phe. We further demonstrated that l-Phe increases the binding affinity of the CaSR ECD for Ca2+. Our findings provide new insights into the mechanisms by which Ca2+ and amino acids regulate the CaSR and may pave the way for exploration of the structural properties of CaSR and other members of family C of the GPCR superfamily. PMID:25305020

  14. A selective determination of azide by ion-interaction reversed-phase HPLC

    SciTech Connect

    Gennaro, M.C.; Abrigo, C.; Marengo, E.; Liberatori, A.

    1993-01-01

    A method is presented for the analysis of sodium azide, based on the use of ion-interaction reversed-phase HPLC chromatography. A C-18 reversed-phase is the stationary phase and octylammonium ortho-phosphate at different pH values is the interaction reagent. Spectrophotometric detection at 230 nm is employed. The analysis is free from interference by acetate, carbonate, chloride, fluoride, sulfite, hydrazine, hydroxylamine, nitrate, bromide, iodide, sulfide, thiocyanate and nitrite. A good correlation (r[sup 2] = 0.9782) is obtained between peak area and concentration in the range between 1 and 250 ppb. Samples of tap water spiked with sodium azide (in the range within 25 and 250 ppb) gave per cent average recovery of 98%. The method sensitivity, expressed as signal-to-noise ratio equal to 3, is 50 ppb when the pH of the interaction reagent is equal to 3.0, 30 ppb for pH 6.4 and 10 ppb at pH 8.0.

  15. Molecular determinants of α–synuclein mutants’ oligomerization and membrane interactions

    PubMed Central

    Tsigelny, Igor F.; Sharikov, Yuriy; Kouznetsova, Valentina L.; Greenberg, Jerry P.; Wrasidlo, Wolf; Overk, Cassia; Gonzalez, Tania; Trejo, Margarita; Spencer, Brian; Kosberg, Kori; Masliah, Eliezer

    2016-01-01

    Parkinson’s disease (PD) is associated with the formation of toxic α-synuclein oligomers and their penetration the cell membrane. Familial forms of PD are caused by the point mutations A53T, A30P, E46K, and H50Q. Artificial point mutations E35K and E57K also increase oligomerization and pore formation. We generated structural conformations of α-synuclein and the abovementioned mutants using molecular dynamics. We elucidated four main regions in these conformers contacting the membrane and found that the region including residues 37–45 (Zone2) may have maximum membrane penetration. E57K mutant had the highest rate of interaction with the membrane by Zone2, followed by A53T, E46K, E35K mutants, and wt α-synuclein. The mutant A30P had the smallest percentage of conformers that contact the membrane than all other mutants and wt α-synuclein. These results were confirmed by experiments. We identified the key amino acids that can interact with the membrane (Y38, E62, and N65 (1st hydrophilic layer); E104, E105, and D115 (2nd hydrophilic layer), and V15 and V26 (central hydrophobic layer)) and the residues that are involved in the interprotein contacts (L38, V48, V49, Q62, and T64). Understanding the molecular interactions of α-synuclein mutants is important for the design of compounds blocking the formation of toxic oligomers. PMID:25561023

  16. Antigen availability determines CD8+ T cell-dendritic cell interaction kinetics and memory fate decisions

    PubMed Central

    Henrickson, Sarah E.; Stutte, Susanne; Quigley, Michael; Alexe, Gabriela; Iannacone, Matteo; Flynn, Michael P.; Omid, Shaida; Jesneck, Jonathan L.; Imam, Sabrina; Mempel, Thorsten R.; Mazo, Irina B.; Haining, William N.; von Andrian, Ulrich H.

    2014-01-01

    Summary T cells are activated by antigen (Ag) bearing dendritic cells (DCs) in lymph nodes in 3 phases. The duration of the initial phase of transient, serial DC-T cell interactions is inversely correlated with Ag dose. The second phase, characterized by stable DC-T cell contacts, is believed to be necessary for full-fledged T cell activation. Here we have shown that this is not the case. CD8+ T cells interacting with DCs presenting low-dose, short-lived Ag did not transition to phase 2, while higher Ag dose yielded phase 2 transition. Both antigenic constellations promoted T cell proliferation and effector differentiation, but yielded different transcriptome signatures at 12h and 24h. T cells that experienced phase 2 developed long-lived memory, whereas conditions without stable contacts yielded immunological amnesia. Thus, T cells make fate decisions within hours after Ag exposure resulting in long-term memory or abortive effector responses, correlating with T cell-DCs interaction kinetics. PMID:24054328

  17. Determination of the interaction parameter and topological scaling features of symmetric star polymers in dilute solution.

    PubMed

    Rai, Durgesh K; Beaucage, Gregory; Ratkanthwar, Kedar; Beaucage, Peter; Ramachandran, Ramnath; Hadjichristidis, Nikos

    2015-07-01

    Star polymers provide model architectures to understand the dynamic and rheological effects of chain confinement for a range of complex topological structures like branched polymers, colloids, and micelles. It is important to describe the structure of such macromolecular topologies using small-angle neutron and x-ray scattering to facilitate understanding of their structure-property relationships. Modeling of scattering from linear, Gaussian polymers, such as in the melt, has applied the random phase approximation using the Debye polymer scattering function. The Flory-Huggins interaction parameter can be obtained using neutron scattering by this method. Gaussian scaling no longer applies for more complicated chain topologies or when chains are in good solvents. For symmetric star polymers, chain scaling can differ from ν=0.5(d(f)=2) due to excluded volume, steric interaction between arms, and enhanced density due to branching. Further, correlation between arms in a symmetric star leads to an interference term in the scattering function first described by Benoit for Gaussian chains. In this work, a scattering function is derived which accounts for interarm correlations in symmetric star polymers as well as the polymer-solvent interaction parameter for chains of arbitrary scaling dimension using a hybrid Unified scattering function. The approach is demonstrated for linear, four-arm and eight-arm polyisoprene stars in deuterated p-xylene.

  18. Determination of Lipid-Protein Interactions in Lung Surfactants Using Computer Simulations and Structural Bioinformatics.

    NASA Astrophysics Data System (ADS)

    Kaznessis, Yiannis

    2001-06-01

    Proteins are the primary components of the networks that conduct the flows of mass, energy and information in living organisms. The discovery of the principles of protein structure and function allows the development of design rules for biological activities. The microscopic nature of the operating mechanisms of protein activity, and the vast complexity of the networks of interaction call for the employment of powerful computational methodologies that can decipher the physicochemical and evolutionary principles underlying protein structure and function. An example will be presented that reflects the strength of computational approaches. Atomistic molecular dynamics simulations and structural bioinformatics tools are employed to investigate the interactions between the first 25 N-terminal residues of surfactant protein B (SP-B 1-25) and the lipid components of the lung surfactant (LS). An understanding of the molecular level interactions between the LS components is essential for the establishment of design rules for the development of synthetic LS and the treatment of the neonatal respiratory distress syndrome, which results from deficiency or inactivation of LS.

  19. Interactions and trade-offs among physiological determinants of performance and reproductive success.

    PubMed

    Moore, Ignacio T; Hopkins, William A

    2009-10-01

    How an animal performs in its natural environment ultimately plays a key role in its reproductive success. While a number of studies have investigated how selection acts on performance-related traits, far fewer studies have examined the mechanisms responsible for variation in performance. Among mechanisms, variable morphology has received the most attention. Although physiological traits have received less attention, they are intrinsically related to performance and ultimately to reproductive success. We present a framework whereby investigators can link some basic physiological functions with organismal performance and ultimately with reproductive success. We propose that performance and ultimately reproductive success are strongly influenced by hormones, immune functions, and energetics. We further argue that no physiological function can be considered in isolation and thus our model emphasizes interactions and trade-offs both within each physiological function as well as among them. Some of the most commonly studied trade-offs are between reproduction and immune functions, with energetics as one of the key common currencies for these trade-offs. From an evolutionary perspective, the largest gaps in our knowledge lie in how these interactions and trade-offs influence reproductive success. We believe that a full understanding of how hormones, immune functions, and energetics influence performance traits related to reproduction and, ultimately, lifetime reproductive success requires recognition of the complex relationships, interactions, and trade-offs among these processes.

  20. Molecular interactions of dimethyl methylphosphonate (DMMP) with metalloporphyrins: determination of the binding mechanism by spectroscopic methods.

    PubMed

    Zhang, Suyi; Yang, Limin; Huo, Danqun; Liu, Xiaojuan; Li, Juan; Fa, Huanbao; Zhang, Liang; Hou, Changjun

    2012-03-01

    The molecular interactions of 5,10,15,20-tetraphenylporphine zinc (ZnTPP) and 5,10,15,20-tetraphenyl-21H,23H-porphine cobalt(II) (CoTPP) with dimethyl methylphosphonate (DMMP) have been investigated by absorption/absorption difference spectroscopy. The interactions between the metalloporphyrins and DMMP change the absorbance characteristics of the porphyrins resulted from the formation of the metalloporphyrin-DMMP complexes. According to the Benesi-Hildebrand (B-H) equation, the equilibrium constants and stoichiometries of the binding systems at four different temperatures (288, 293, 298 and 303 K) were obtained. Experimental results showed that both ZnTPP and CoTPP bind to DMMP via axial coordination, resulting in the formation of 1:1 metalloporphyrin-DMMP complexes. However, it was found that ZnTPP showed stronger binding capacity with the equilibrium constant (K) of 83.864 M(-1) at room temperature, while CoTPP exhibited weaker binding with K of 24.904 M(-1). The thermodynamic parameters, enthalpy change (Δ(r)H(m)(θ)), entropy change (Δ(r)S(m)(θ)) and free energy changes (Δ(r)G(m)(θ)) were also studied for the interactions, indicating that the formation of the metalloporphyrins-DMMP complex was an exothermic reaction. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. The Cα—H⋅⋅⋅O hydrogen bond: A determinant of stability and specificity in transmembrane helix interactions

    PubMed Central

    Senes, Alessandro; Ubarretxena-Belandia, Iban; Engelman, Donald M.

    2001-01-01

    The Cα—H⋅⋅⋅O hydrogen bond has been given little attention as a determinant of transmembrane helix association. Stimulated by recent calculations suggesting that such bonds can be much stronger than has been supposed, we have analyzed 11 known membrane protein structures and found that apparent carbon α hydrogen bonds cluster frequently at glycine-, serine-, and threonine-rich packing interfaces between transmembrane helices. Parallel right-handed helix–helix interactions appear to favor Cα—H⋅⋅⋅O bond formation. In particular, Cα—H⋅⋅⋅O interactions are frequent between helices having the structural motif of the glycophorin A dimer and the GxxxG pair. We suggest that Cα—H⋅⋅⋅O hydrogen bonds are important determinants of stability and, depending on packing, specificity in membrane protein folding. PMID:11481472

  2. Phase equilibrium calculations of ternary liquid mixtures with binary interaction parameters and molecular size parameters determined from molecular dynamics.

    PubMed

    Oh, Suk Yung; Bae, Young Chan

    2010-07-15

    The method presented in this paper was developed to predict liquid-liquid equilibria in ternary liquid mixtures by using a combination of a thermodynamic model and molecular dynamics simulations. In general, common classical thermodynamic models have many parameters which are determined by fitting a model with experimental data. This proposed method, however, provides a simple procedure for calculating liquid-liquid equilibria utilizing binary interaction parameters and molecular size parameters determined from molecular dynamics simulations. This method was applied to mixtures containing water, hydrocarbons, alcohols, chlorides, ketones, acids, and other organic liquids over various temperature ranges. The predicted results agree well with the experimental data without the use of adjustable parameters.

  3. Label-Free Determination of the Dissociation Constant of Small Molecule-Aptamer Interaction by Isothermal Titration Calorimetry.

    PubMed

    Vogel, Marc; Suess, Beatrix

    2016-01-01

    Isothermal titration calorimetry (ITC) is a powerful label-free technique to determine the binding constant as well as thermodynamic parameters of a binding reaction and is therefore well suited for the analysis of small molecule-RNA aptamer interaction. We will introduce you to the method and present a protocol for sample preparation and the calorimetric measurement. A detailed note section will point out useful tips and pitfalls.

  4. A methodology for determining interactions in probabilistic safety assessment models by varying one parameter at a time.

    PubMed

    Borgonovo, Emanuele

    2010-03-01

    In risk analysis problems, the decision-making process is supported by the utilization of quantitative models. Assessing the relevance of interactions is an essential information in the interpretation of model results. By such knowledge, analysts and decisionmakers are able to understand whether risk is apportioned by individual factor contributions or by their joint action. However, models are oftentimes large, requiring a high number of input parameters, and complex, with individual model runs being time consuming. Computational complexity leads analysts to utilize one-parameter-at-a-time sensitivity methods, which prevent one from assessing interactions. In this work, we illustrate a methodology to quantify interactions in probabilistic safety assessment (PSA) models by varying one parameter at a time. The method is based on a property of the functional ANOVA decomposition of a finite change that allows to exactly determine the relevance of factors when considered individually or together with their interactions with all other factors. A set of test cases illustrates the technique. We apply the methodology to the analysis of the core damage frequency of the large loss of coolant accident of a nuclear reactor. Numerical results reveal the nonadditive model structure, allow to quantify the relevance of interactions, and to identify the direction of change (increase or decrease in risk) implied by individual factor variations and by their cooperation.

  5. Trophic interactions determine the effects of drought on an aquatic ecosystem.

    PubMed

    Amundrud, Sarah L; Srivastava, Diane S

    2016-06-01

    Species interactions can be important mediators of community and ecosystem responses to environmental stressors. However, we still lack a mechanistic understanding of the indirect ecological effects of stress that arise via altered species interactions. To understand how species interactions will be altered by environmental stressors, we need to know if the species that are vulnerable to such stressors also have large impacts on the ecosystem. As predators often exhibit certain traits that are linked to a high vulnerability to stress (e.g., large body size, long generation time), as well as having large effects on communities (e.g., top-down trophic effects), predators may be particularly likely to mediate ecological effects of environmental stress. Other functional groups, like facilitators, are known to have large impacts on communities, but their vulnerability to perturbations remains undocumented. Here, we use aquatic insect communities in bromeliads to examine the indirect effects of an important stressor (drought) on community and ecosystem responses. In a microcosm experiment, we manipulated predatory and facilitative taxa under a range of experimental droughts, and quantified effects on community structure and ecosystem function. Drought, by adversely affecting the top predator, had indirect cascading effects on the entire food web, altering community composition and decomposition. We identified the likely pathway of how drought cascaded through the food web from the top-down as drought -->predator --> shredder --> decomposition. This stress-induced cascade depended on predators exhibiting both a strong vulnerability to drought and large impacts on prey (especially shredders), as well as shredders exhibiting high functional importance as decomposers.

  6. Uncontrollable and unpredictable stress interacts with subclinical depression and anxiety scores in determining anxiety response.

    PubMed

    Havranek, Michael M; Bolliger, Bianca; Roos, Sophie; Pryce, Christopher R; Quednow, Boris B; Seifritz, Erich

    2016-01-01

    According to learned helplessness theory, uncontrollable stress is assumed to be a critical etiological factor in the pathogenesis of depression. In contrast, unpredictability of stressors is assumed to facilitate the development of sustained anxiety. Despite the frequent co-morbidity of depression and anxiety disorders, these two factors have rarely been studied simultaneously in humans. Therefore, we investigated whether there are interaction effects of uncontrollability and unpredictability on anxiety response in healthy participants. Seventy-nine healthy participants performed a visual dot probe task with emotional faces, while receiving mild electrical shocks in four different conditions (2 × 2 factorial design). In (un)controllable conditions, participants were (not) able to attenuate shock intensity. In (un)predictable conditions, participants were (not) able to anticipate shock occurrence. Before the experiment, participants' subclinical depression and anxiety scores were measured using the Beck Depression and Anxiety Inventories (BDI/BAI). During the experiment, continuous skin conductance and self-reported state anxiety were assessed and attentional biases towards angry faces were calculated. As expected, participants showed greater anxiety in uncontrollable compared to controllable and in unpredictable compared to predictable conditions. Additionally, anxiety decreased within the test sessions in participants with low BDI/BAI scores but not in participants with higher BDI/BAI scores. Most importantly, controllability and predictability interacted with each other and with BDI/BAI scores with regard to anxiety. Our results provide evidence that uncontrollability and unpredictability of stressors not only have separate but also interaction effects on several anxiety measures in susceptible individuals and may provide insights into the psychological mechanisms underlying a depressive/anxiety co-morbidity.

  7. Small-scale indirect effects determine the outcome of a tripartite plant-disperser-granivore interaction.

    PubMed

    Boulay, Raphaël; Carro, Francisco; Soriguer, Ramón C; Cerdá, Xim

    2009-09-01

    The microhabitat in which plants grow affects the outcome of their interactions with animals, particularly non-specialist consumers. Nevertheless, as most research on this topic has dealt with either mutualists or antagonists, little is known about the indirect effects of plant microhabitats on the outcome of tripartite interactions involving plants and both mutualists (e.g. seed dispersers) and antagonists (e.g. granivores). During three consecutive years, we analysed small-scale variations in the interaction of a perennial myrmecochore, Helleborus foetidus, with its seed dispersers and consumers as a function of the intensity of plant cover. Most seeds were released during the day and were rapidly removed by ants. Nevertheless, the proportion of ant-removed seeds was higher for plants located in open microhabitats than for plants surrounded by dense vegetation and rocky cover. Ant sampling revealed that seed removers were equally abundant, irrespective of the level of cover. By contrast, a few tiny ant species that feed on the reward without transporting the seeds were more abundant in highly covered microhabitats, irrespective of hellebore diaspore availability. These "cheaters" decrease the chance of removal by removers and increase the probability of seeds remaining on the ground until night, when granivore mice Apodemus sylvaticus become active. Mice also preferred foraging in covered microhabitats, where they consumed a larger proportion of seeds. Therefore, the density of cover indirectly increased seed predation risk by attracting more seed predators and cheater ants that contribute to increase seed availability for seed predators. Our results emphasize the importance of considering the indirect effects of plant microhabitat on their dispersal success. They highlight the indirect effect of cheaters that are likely to interfere in mutualisms and may lead to their collapse unless external factors such as spatio-temporal heterogeneity in seed availability

  8. Potentiometric Determination of Phytic Acid and Investigations of Phytate Interactions with Some Metal Ions.

    PubMed

    Marolt, Gregor; Pihlar, Boris

    2015-01-01

    Determination of correct amount (concentration) of phytic acid is of vital importance when dealing with protonation and/or metal complexation equilibria. A novel approach for precise and reliable assay of phytic acid, based on the difference between end points by potentiometric titration, has been presented. Twelve phytic acid protons are classified into three groups of acidity, which enables detection of 2 to 3 distinct equivalent points (EPs) depending on experimental conditions, e.g. counter-ion concentration. Using the differences between individual EPs enables correct phytate determination as well as identification of potential contamination and/or determination of initial protonation degree. Impact of uncertainty of phytate amount on the calculation of protonation constants has been evaluated using computer simulation program (Hyperquad2013). With the analysis of titration curves different binding sites on phytate ligand have been proposed for complexation of Ca2+ and Fe3+ ions.

  9. Using Isothermal Titration Calorimetry to Determine Thermodynamic Parameters of Protein–Glycosaminoglycan Interactions

    PubMed Central

    Dutta, Amit K.; Rösgen, Jörg; Rajarathnam, Krishna

    2015-01-01

    It has now become increasingly clear that a complete atomic description of how biomacromolecules recognize each other requires knowledge not only of the structures of the complexes but also of how kinetics and thermodynamics drive the binding process. In particular, such knowledge is lacking for protein–glycosaminoglycan (GAG) complexes. Isothermal titration calorimetry (ITC) is the only technique that can provide various thermodynamic parameters—enthalpy, entropy, free energy (binding constant), and stoichiometry—from a single experiment. Here we describe different factors that must be taken into consideration in carrying out ITC titrations to obtain meaningful thermodynamic data of protein–GAG interactions. PMID:25325962

  10. Heparin stability by determining unsubstituted amino groups using hydrophilic interaction chromatography mass spectrometry.

    PubMed

    Fu, Li; Li, Lingyun; Cai, Chao; Li, Guoyun; Zhang, Fuming; Linhardt, Robert J

    2014-09-15

    The thermal instability of the anticoagulant heparin is associated, in part, with the solvolytic loss of N-sulfo groups. This study describes a new method to assess the increased content of unsubstituted amino groups present in thermally stressed and autoclave-sterilized heparin formulations. N-Acetylation of heparin samples with acetic anhydride-d6 is followed by exhaustive heparinase treatment and disaccharide analysis by hydrophilic interaction chromatography mass spectrometry (HILIC-MS). The introduction of a stable isotopic label provides a sensitive probe for the detection and localization of the lost N-sulfo groups, potentially providing valuable insights into the degradation mechanism and the reasons for anticoagulant potency loss.

  11. Using isothermal titration calorimetry to determine thermodynamic parameters of protein-glycosaminoglycan interactions.

    PubMed

    Dutta, Amit K; Rösgen, Jörg; Rajarathnam, Krishna

    2015-01-01

    It has now become increasingly clear that a complete atomic description of how biomacromolecules recognize each other requires knowledge not only of the structures of the complexes but also of how kinetics and thermodynamics drive the binding process. In particular, such knowledge is lacking for protein-glycosaminoglycan (GAG) complexes. Isothermal titration calorimetry (ITC) is the only technique that can provide various thermodynamic parameters-enthalpy, entropy, free energy (binding constant), and stoichiometry-from a single experiment. Here we describe different factors that must be taken into consideration in carrying out ITC titrations to obtain meaningful thermodynamic data of protein-GAG interactions.

  12. Determination of Intermolecular Interactions Using Polarization Compensated Heteronuclear Overhauser Effect of Hyperpolarized Spins.

    PubMed

    Kim, Jihyun; Liu, Mengxiao; Chen, Hsueh-Ying; Hilty, Christian

    2015-11-03

    The nuclear Overhauser effect (NOE) has long been used as a selective indicator for intermolecular interactions. Due to relatively small changes of signal intensity, often on the order of several percent, quantitative NOE measurements can be challenging. Hyperpolarization of nuclear spins can dramatically increase the NOE intensity by increasing population differences, but poses its own challenge in quantifying the original polarization level. Here, we demonstrate a method for the accurate measurement of intermolecular heteronuclear cross-relaxation rates by simultaneous acquisition of signals from both nuclei. Using this method, we measure cross-relaxation rates between water protons and (19)F of trifluoroacetic acid at concentrations ranging from 23 to 72 mM. A concentration-independent value of 2.46 × 10(-4) ± 1.02 × 10(-5) s(-1) M(-1) is obtained at a temperature of 301 K and validated using a nonhyperpolarized measurement. In a broader context, accurate measurement of heteronuclear cross-relaxation rates may enable the study of intermolecular interactions including those involving macromolecules where (19)F atoms can be introduced as site-selective labels.

  13. Determination of the exchange interaction energy from the polarization expansion of the wave function

    NASA Astrophysics Data System (ADS)

    Gniewek, Piotr; Jeziorski, Bogumił

    2016-10-01

    The exchange contribution to the energy of the hydrogen atom interacting with a proton is calculated from the polarization expansion of the wave function using the conventional surface-integral formula and two formulas involving volume integrals: the formula of the symmetry-adapted perturbation theory (SAPT) and the variational formula recommended by us. At large internuclear distances R , all three formulas yield the correct expression -(2 /e ) R e-R , but they approximate it with very different convergence rates. In the case of the SAPT formula, the convergence is geometric with the error falling as 3-K, where K is the order of the applied polarization expansion. The error of the surface-integral formula decreases exponentially as aK/(K +1 ) , where a =ln2 - 1/2. The variational formula performs best, its error decays as K1 /2[aK/(K+1 ) ] 2 . These convergence rates are much faster than those resulting from approximating the wave function through the multipole expansion. This shows the efficiency of the partial resummation of the multipole series effected by the polarization expansion. Our results demonstrate also the benefits of incorporating the variational principle into the perturbation theory of molecular interactions.

  14. Interaction between hypothalamic dorsomedial nucleus and the suprachiasmatic nucleus determines intensity of food anticipatory behavior

    PubMed Central

    Acosta-Galvan, Guadalupe; Yi, Chun-Xia; van der Vliet, Jan; Jhamandas, Jack H.; Panula, Pertti; Angeles-Castellanos, Manuel; del Carmen Basualdo, María; Escobar, Carolina; Buijs, Ruud M.

    2011-01-01

    Food anticipatory behavior (FAA) is induced by limiting access to food for a few hours daily. Animals anticipate this scheduled meal event even without the suprachiasmatic nucleus (SCN), the biological clock. Consequently, a food-entrained oscillator has been proposed to be responsible for meal time estimation. Recent studies suggested the dorsomedial hypothalamus (DMH) as the site for this food-entrained oscillator, which has led to considerable controversy in the literature. Herein we demonstrate by means of c-Fos immunohistochemistry that the neuronal activity of the suprachiasmatic nucleus (SCN), which signals the rest phase in nocturnal animals, is reduced when animals anticipate the scheduled food and, simultaneously, neuronal activity within the DMH increases. Using retrograde tracing and confocal analysis, we show that inhibition of SCN neuronal activity is the consequence of activation of GABA-containing neurons in the DMH that project to the SCN. Next, we show that DMH lesions result in a loss or diminution of FAA, simultaneous with increased activity in the SCN. A subsequent lesion of the SCN restored FAA. We conclude that in intact animals, FAA may only occur when the DMH inhibits the activity of the SCN, thus permitting locomotor activity. As a result, FAA originates from a neuronal network comprising an interaction between the DMH and SCN. Moreover, this study shows that the DMH–SCN interaction may serve as an intrahypothalamic system to gate activity instead of rest overriding circadian predetermined temporal patterns. PMID:21402951

  15. How van der Waals interactions determine the unique properties of water.

    PubMed

    Morawietz, Tobias; Singraber, Andreas; Dellago, Christoph; Behler, Jörg

    2016-07-26

    Whereas the interactions between water molecules are dominated by strongly directional hydrogen bonds (HBs), it was recently proposed that relatively weak, isotropic van der Waals (vdW) forces are essential for understanding the properties of liquid water and ice. This insight was derived from ab initio computer simulations, which provide an unbiased description of water at the atomic level and yield information on the underlying molecular forces. However, the high computational cost of such simulations prevents the systematic investigation of the influence of vdW forces on the thermodynamic anomalies of water. Here, we develop efficient ab initio-quality neural network potentials and use them to demonstrate that vdW interactions are crucial for the formation of water's density maximum and its negative volume of melting. Both phenomena can be explained by the flexibility of the HB network, which is the result of a delicate balance of weak vdW forces, causing, e.g., a pronounced expansion of the second solvation shell upon cooling that induces the density maximum.

  16. Interaction between hypothalamic dorsomedial nucleus and the suprachiasmatic nucleus determines intensity of food anticipatory behavior.

    PubMed

    Acosta-Galvan, Guadalupe; Yi, Chun-Xia; van der Vliet, Jan; Jhamandas, Jack H; Panula, Pertti; Angeles-Castellanos, Manuel; Del Carmen Basualdo, María; Escobar, Carolina; Buijs, Ruud M

    2011-04-05

    Food anticipatory behavior (FAA) is induced by limiting access to food for a few hours daily. Animals anticipate this scheduled meal event even without the suprachiasmatic nucleus (SCN), the biological clock. Consequently, a food-entrained oscillator has been proposed to be responsible for meal time estimation. Recent studies suggested the dorsomedial hypothalamus (DMH) as the site for this food-entrained oscillator, which has led to considerable controversy in the literature. Herein we demonstrate by means of c-Fos immunohistochemistry that the neuronal activity of the suprachiasmatic nucleus (SCN), which signals the rest phase in nocturnal animals, is reduced when animals anticipate the scheduled food and, simultaneously, neuronal activity within the DMH increases. Using retrograde tracing and confocal analysis, we show that inhibition of SCN neuronal activity is the consequence of activation of GABA-containing neurons in the DMH that project to the SCN. Next, we show that DMH lesions result in a loss or diminution of FAA, simultaneous with increased activity in the SCN. A subsequent lesion of the SCN restored FAA. We conclude that in intact animals, FAA may only occur when the DMH inhibits the activity of the SCN, thus permitting locomotor activity. As a result, FAA originates from a neuronal network comprising an interaction between the DMH and SCN. Moreover, this study shows that the DMH-SCN interaction may serve as an intrahypothalamic system to gate activity instead of rest overriding circadian predetermined temporal patterns.

  17. Host Fate is Rapidly Determined by Innate Effector-Microbial Interactions During Acinetobacter baumannii Bacteremia

    PubMed Central

    Bruhn, Kevin W.; Pantapalangkoor, Paul; Nielsen, Travis; Tan, Brandon; Junus, Justin; Hujer, Kristine M.; Wright, Meredith S.; Bonomo, Robert A.; Adams, Mark D.; Chen, Wangxue; Spellberg, Brad

    2015-01-01

    Background. Acinetobacter baumannii is one of the most antibiotic-resistant pathogens. Defining mechanisms driving pathogenesis is critical to enable new therapeutic approaches. Methods. We studied virulence differences across a diverse panel of A. baumannii clinical isolates during murine bacteremia to elucidate host-microbe interactions that drive outcome. Results. We identified hypervirulent strains that were lethal at low intravenous inocula and achieved very high early, and persistent, blood bacterial densities. Virulent strains were nonlethal at low inocula but lethal at 2.5-fold higher inocula. Finally, relatively avirulent (hypovirulent) strains were nonlethal at 20-fold higher inocula and were efficiently cleared by early time points. In vivo virulence correlated with in vitro resistance to complement and macrophage uptake. Depletion of complement, macrophages, and neutrophils each independently increased bacterial density of the hypovirulent strain but insufficiently to change lethality. However, disruption of all 3 effector mechanisms enabled early bacterial densities similar to hypervirulent strains, rendering infection 100% fatal. Conclusions. The lethality of A. baumannii strains depends on distinct stages. Strains resistant to early innate effectors are able to establish very high early bacterial blood density, and subsequent sustained bacteremia leads to Toll-like receptor 4–mediated hyperinflammation and lethality. These results have important implications for translational efforts to develop therapies that modulate host-microbe interactions. PMID:25378635

  18. Physiological responses in a Concealed Information Test are determined interactively by encoding procedure and questioning format.

    PubMed

    Ambach, Wolfgang; Dummel, Sebastian; Lüer, Theresa; Vaitl, Dieter

    2011-09-01

    Physiological responses in the Concealed Information Test (CIT) are known to depend on the depth of encoding critical items; CIT questions commonly refer to knowledge about critical items. It is unclear to what extent (1) different modes of item handling in a mock-crime, and (2) alternative questioning formats, e.g. asking about participants' particular actions with the critical items, influence the physiological responses. In the presented mock-crime study with fifty-three participants, two questioning formats, i.e. "Did you see …?" (viewing questioning) and "Did you steal …?" (stealing questioning), were compared between subjects. The mode of encoding, stealing vs. merely viewing the critical objects, was varied within subject. Skin conductance, electrocardiogram, respiration, and finger pulse were recorded. For both questioning formats and each physiological measure, physiological responses to stolen as well as merely viewed objects differed from those to irrelevant objects. Considering viewing questioning, responses to stolen and merely viewed objects did not differ, with the exception of greater phasic decreases of heart rate for stolen objects. Considering stealing questioning, responses to stolen objects exceeded those to merely viewed objects with each physiological measure. The statistically proven interaction between mode of encoding a particular object and questioning format sheds light on the factors influencing the physiological responses in a CIT. The level of subjective significance of a particular item might emerge interactively from the mode of item handling and the questioning format.

  19. How van der Waals interactions determine the unique properties of water

    PubMed Central

    Morawietz, Tobias; Singraber, Andreas; Dellago, Christoph; Behler, Jörg

    2016-01-01

    Whereas the interactions between water molecules are dominated by strongly directional hydrogen bonds (HBs), it was recently proposed that relatively weak, isotropic van der Waals (vdW) forces are essential for understanding the properties of liquid water and ice. This insight was derived from ab initio computer simulations, which provide an unbiased description of water at the atomic level and yield information on the underlying molecular forces. However, the high computational cost of such simulations prevents the systematic investigation of the influence of vdW forces on the thermodynamic anomalies of water. Here, we develop efficient ab initio-quality neural network potentials and use them to demonstrate that vdW interactions are crucial for the formation of water’s density maximum and its negative volume of melting. Both phenomena can be explained by the flexibility of the HB network, which is the result of a delicate balance of weak vdW forces, causing, e.g., a pronounced expansion of the second solvation shell upon cooling that induces the density maximum. PMID:27402761

  20. Interaction of personality traits with social deprivation in determining mental wellbeing and health behaviours.

    PubMed

    Packard, Chris J; Cavanagh, Jonathan; McLean, Jennifer S; McConnachie, Alex; Messow, Claudia-Martina; Batty, G David; Burns, Harry; Deans, Kevin A; Sattar, Naveed; Shiels, Paul G; Velupillai, Yoga N; Tannahill, Carol; Millar, Keith

    2012-12-01

    Associations between personality traits, mental wellbeing and good health behaviours were examined to understand further the social and psychological context of the health divide. In a cross-sectional study, 666 subjects recruited from areas of high and low socioeconomic deprivation had personality traits and mental wellbeing assessed, and lifestyle behaviours quantified. Regression models (using deprivation as a moderating variable) assessed the extent to which personality traits and mental wellbeing predicted health behaviour. Deprived (vs. affluent) subjects exhibited similar levels of extraversion but higher levels of neuroticism and psychoticism, more hopelessness, less sense of coherence, lower self-esteem and lower self-efficacy (all P< 0.001). They ate less fruit and vegetables, smoked more and took less aerobic exercise (all P< 0.001). In the deprived group, personality traits were significantly more important predictors of mental wellbeing than in the least deprived group (P< 0.01 for interaction), and mental wellbeing and extraversion appeared more strongly related to good health behaviours. Persistence of a social divide in health may be related to interactions between personality, mental wellbeing and the adoption of good health behaviours in deprived areas. Effectiveness of health messages may be enhanced by accommodating the variation in the levels of extraversion, neuroticism, hopelessness and sense of coherence.

  1. The Determinants of Negative Maternal Parenting Behaviours: Maternal, Child, and Paternal Characteristics and Their Interaction

    ERIC Educational Resources Information Center

    Kopala-Sibley, Daniel C.; Zuroff, David C.; Koestner, Richard

    2012-01-01

    This study tested Belsky's determinants of parenting, namely maternal characteristics, child characteristics, and contextual issues, namely the mother's perception of the husband as a father, husband, and person. Three hundred and seventy-nine mothers first investigated by Sears, Maccoby, and Levin completed a standardised interview to assess…

  2. Which shape characteristics of the intermolecular interaction of liquid water determine its compressibility ?

    NASA Astrophysics Data System (ADS)

    Yasutomi, Makoto

    2016-05-01

    We consider a fluid of spherical particles with a pair potential given by a hard core repulsion and a tail, and show that the isothermal compressibility of liquid water is determined by the degree of steepness of the soft repulsion near the hard-core contact. This helps us understand the thermodynamic mechanism that causes the compressibility anomaly of liquid water.

  3. The Determinants of Negative Maternal Parenting Behaviours: Maternal, Child, and Paternal Characteristics and Their Interaction

    ERIC Educational Resources Information Center

    Kopala-Sibley, Daniel C.; Zuroff, David C.; Koestner, Richard

    2012-01-01

    This study tested Belsky's determinants of parenting, namely maternal characteristics, child characteristics, and contextual issues, namely the mother's perception of the husband as a father, husband, and person. Three hundred and seventy-nine mothers first investigated by Sears, Maccoby, and Levin completed a standardised interview to assess…

  4. Determinants of geographic patterns of diseases: interaction of lactose/lactase status and sunshine exposure.

    PubMed

    Szilagyi, Andrew

    2010-11-01

    Geographic patterns of diseases depend on multilayered causes. However, the division of the world's population into two phenotypes regarding lactose digestion and sunshine exposure to fixed areas of the globe are two relatively slow changing variables. It is hypothesized that it is a vectorial interaction between these two variables that provide a backbone to risk modification of many diseases. Lactase non persistence status tends to follow sunshine exposure particularly in Europe but Lactase persistence status is also been shown to be related to pastoral life styles in spotty regions of Africa, Middle East and China. Current emphasis of research favours the modifying role of vitamin D and sunshine. Nevertheless it was demonstrated that national digester/nondigester status has mathematical relationships to geographic distribution of some diseases. These relationships are also similar to that described for the effects of latitude through sunshine and vitamin D. This observation raises a question as to how each one affects disease outcome. In this paper lactose/lactase interactions are first reviewed for eight exemplary diseases. Based on population findings and corroborative meta-analyses gleaned from the literature 6 types of interactions may be classified. Then in a preliminary fashion lactose digester and maldigester status are related to relative annual sunshine exposure. Further the relative national annual sunshine exposure is evaluated to outcomes of the same exemplary diseases. The patterns related to sunshine reflect that obtained with national lactase status proportions and also corroborate a literature review. However, correlations are weak to moderate and only ovarian cancer reached conventional statistical significance. Because these comparisons are based on modest number of national data firm conclusions cannot be made. However, it is argued that evolutionary pressures exerted by regional sunshine exposure may have had influence on a number of relevant

  5. Weak and Transient Protein Interactions Determined by Solid-State NMR.

    PubMed

    Dannatt, Hugh R W; Felletti, Michele; Jehle, Stefan; Wang, Yao; Emsley, Lyndon; Dixon, Nicholas E; Lesage, Anne; Pintacuda, Guido

    2016-06-01

    Despite their roles in controlling many cellular processes, weak and transient interactions between large structured macromolecules and disordered protein segments cannot currently be characterized at atomic resolution by X-ray crystallography or solution NMR. Solid-state NMR does not suffer from the molecular size limitations affecting solution NMR, and it can be applied to molecules in different aggregation states, including non-crystalline precipitates and sediments. A solid-state NMR approach based on high magnetic fields, fast magic-angle sample spinning, and deuteration provides chemical-shift and relaxation mapping that enabled the characterization of the structure and dynamics of the transient association between two regions in an 80 kDa protein assembly. This led to direct verification of a mechanism of regulation of E. coli DNA metabolism. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Flow environment and matrix structure interact to determine spatial competition in Pseudomonas aeruginosa biofilms.

    PubMed

    Nadell, Carey D; Ricaurte, Deirdre; Yan, Jing; Drescher, Knut; Bassler, Bonnie L

    2017-01-13

    Bacteria often live in biofilms, which are microbial communities surrounded by a secreted extracellular matrix. Here, we demonstrate that hydrodynamic flow and matrix organization interact to shape competitive dynamics in Pseudomonas aeruginosa biofilms. Irrespective of initial frequency, in competition with matrix mutants, wild-type cells always increase in relative abundance in planar microfluidic devices under simple flow regimes. By contrast, in microenvironments with complex, irregular flow profiles - which are common in natural environments - wild-type matrix-producing and isogenic non-producing strains can coexist. This result stems from local obstruction of flow by wild-type matrix producers, which generates regions of near-zero shear that allow matrix mutants to locally accumulate. Our findings connect the evolutionary stability of matrix production with the hydrodynamics and spatial structure of the surrounding environment, providing a potential explanation for the variation in biofilm matrix secretion observed among bacteria in natural environments.

  7. Interactions between social structure, demography, and transmission determine disease persistence in primates.

    PubMed

    Ryan, Sadie J; Jones, James H; Dobson, Andrew P

    2013-01-01

    Catastrophic declines in African great ape populations due to disease outbreaks have been reported in recent years, yet we rarely hear of similar disease impacts for the more solitary Asian great apes, or for smaller primates. We used an age-structured model of different primate social systems to illustrate that interactions between social structure and demography create 'dynamic constraints' on the pathogens that can establish and persist in primate host species with different social systems. We showed that this varies by disease transmission mode. Sexually transmitted infections (STIs) require high rates of transmissibility to persist within a primate population. In particular, for a unimale social system, STIs require extremely high rates of transmissibility for persistence, and remain at extremely low prevalence in small primates, but this is less constrained in longer-lived, larger-bodied primates. In contrast, aerosol transmitted infections (ATIs) spread and persist at high prevalence in medium and large primates with moderate transmissibility;, establishment and persistence in small-bodied primates require higher relative rates of transmissibility. Intragroup contact structure - the social network - creates different constraints for different transmission modes, and our model underscores the importance of intragroup contacts on infection prior to intergroup movement in a structured population. When alpha males dominate sexual encounters, the resulting disease transmission dynamics differ from when social interactions are dominated by mother-infant grooming events, for example. This has important repercussions for pathogen spread across populations. Our framework reveals essential social and demographic characteristics of primates that predispose them to different disease risks that will be important for disease management and conservation planning for protected primate populations.

  8. [Infobarris: an interactive tool to monitor and disseminate information on health and its determinants in the neighbourhoods of Barcelona (Spain)].

    PubMed

    Llimona, Pere; Pérez, Glòria; Rodríguez-Sanz, Maica; Novoa, Ana M; Espelt, Albert; García de Olalla, Patricia; Borrell, Carme

    In order to know about the health of the population, it is necessary to perform a systematic and continuous analysis of their health status and social and economic health determinants. The objective of this paper is to describe the development and implementation of the Infobarris tool, which allows to visualize a wide battery of indicators and social determinants of health by neighbourhoods in the city of Barcelona (Spain). For the development of the Infobarris tool, we used an agile methodology that allows the development of a project in iterative and incremental stages, which are the following: selection of indicators, design of the prototype, development of the tool, data loading, and tool review and improvements. Infobarris displays 64 indicators of health and its determinants through graphics, maps and tables, in a friendly, interactive and attractive way, which facilitates health surveillance in the neighbourhoods of Barcelona. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Using circular dichroism collected as a function of temperature to determine the thermodynamics of protein unfolding and binding interactions

    PubMed Central

    Greenfield, Norma J.

    2009-01-01

    Circular dichroism (CD) is an excellent spectroscopic technique for following the unfolding and folding of proteins as a function of temperature. One of its principal applications is to determine the effects of mutations and ligands on protein and polypeptide stability If the change in CD as a function of temperature is reversible, analysis of the data may be used to determined the van't Hoff enthalpy (ΔH) and entropy (ΔS) of unfolding, the midpoint of the unfolding transition (TM) and the free energy (ΔG) of unfolding. Binding constants of protein-protein and protein-ligand interactions may also be estimated from the unfolding curves. Analysis of CD spectra obtained as a function of temperature is also useful to determine whether a protein has unfolding intermediates. Measurement of the spectra of five folded proteins and their unfolding curves at a single wavelength takes approximately eight hours. PMID:17406506

  10. Identification of novel interaction sites that determine specificity between fibroblast growth factor homologous factors and voltage-gated sodium channels.

    PubMed

    Wang, Chaojian; Wang, Chuan; Hoch, Ethan G; Pitt, Geoffrey S

    2011-07-08

    Fibroblast growth factor homologous factors (FHFs, FGF11-14) bind to the C termini (CTs) of specific voltage-gated sodium channels (VGSC) and thereby regulate their function. The effect of an individual FHF on a specific VGSC varies greatly depending upon the individual FHF isoform. How individual FHFs impart distinctive effects on specific VGSCs is not known and the specificity of these pairwise interactions is not understood. Using several biochemical approaches combined with functional analysis, we mapped the interaction site for FGF12B on the Na(V)1.5 C terminus and discovered previously unknown determinants necessary for FGF12 interaction. Also, we demonstrated that FGF12B binds to some, but not all Na(V)1 CTs, suggesting specificity of interaction. Exploiting a human single nucleotide polymorphism in the core domain of FGF12 (P149Q), we identified a surface proline that contributes a part of this pairwise specificity. This proline is conserved among all FHFs, and mutation of the homologous residue in FGF13 also leads to loss of interaction with a specific VGSC CT (Na(V)1.1) and loss of modulation of the resultant Na(+) channel function. We hypothesized that some of the specificity mediated by this proline may result from differences in the affinity of the binding partners. Consistent with this hypothesis, surface plasmon resonance data showed that the P149Q mutation decreased the binding affinity between FHFs and VGSC CTs. Moreover, immunocytochemistry revealed that the mutation prevented proper subcellular targeting of FGF12 to the axon initial segment in neurons. Together, these results give new insights into details of the interactions between FHFs and Na(V)1.x CTs, and the consequent regulation of Na(+) channels.

  11. Interaction of Exposure Concentration and Duration in Determining Acute Toxic Effects of Sarin Vapor in Rats

    DTIC Science & Technology

    2002-01-01

    effects occur in the rat and 2) develop models for predicting dose - response effects of low CW agent concentrations as a function of exposure duration. Sarin...effective concentrations for lethality (LC50) and miosis (EC50) in 50% of the exposed population and corresponding dose - response slopes were determined for...exposure duration (i.e., the CT for 50% lethality exposed population and corresponding dose - response slope was not constant over time). A plot of Log (LCt50

  12. Interaction of a potential vacuolar targeting receptor with amino- and carboxyl-terminal targeting determinants.

    PubMed

    Kirsch, T; Saalbach, G; Raikhel, N V; Beevers, L

    1996-06-01

    A protein of 80 kD from developing pea (Pisum sativum) cotyledons has previously been shown to exhibit characteristics of a vacuolar targeting receptor by means of its affinity for the amino-terminal vacuolar targeting sequence of proaleurain from barley (Hordeum vulgare). In this report we show that the same protein also binds to the amino-terminal targeting peptide of prosporamin from sweet potato (Ipomoea batatas) and to the carboxyl-terminal targeting determinant of pro-2S albumin from Brazil nut (Bertholletia excelsa). The receptor protein does not bind to the carboxyl-terminal propeptide (representing the targeting sequence) of barley lectin. The binding of the 80-kD protein to the sporamin determinant involves a motif (NPIR) that has been shown to be crucial for vacuolar targeting in vivo. The binding to the carboxyl-terminal targeting determinant of pro-2S albumin appears to involve the carboxyl-terminal propeptide and the adjacent five amino acids of the mature protein. The 80-kD protein does not bind to peptide sequences that have been shown to be incompetent in directing vacuolar targeting.

  13. Comparison of zonal elution and nonlinear chromatography in determination of the interaction between seven drugs and immobilised β(2)-adrenoceptor.

    PubMed

    Li, Qian; Wang, Jing; Zheng, Yuqing Yuan; Yang, Lingjian; Zhang, Yajun; Bian, Liujiao; Zheng, Jianbin; Li, Zijian; Zhao, Xinfeng; Zhang, Youyi

    2015-07-03

    Zonal elution and nonlinear chromatography are two mainstream models for the determination of drug-protein interaction in affinity chromatography. This work intended to compare the results by zonal elution with that by nonlinear chromatography when it comes to the analysis of the interaction between seven drugs and immobilised β2-adrenoceptor (β2-AR). The results of the zonal elution showed that clorprenaline, clenbuterol, methoxyphenamine, salbutamol, terbutaline, tulobuterol and bambuterol have only one type of binding site on immobilised β2-AR, while nonlinear chromatography confirmed the existence of at least two types of binding sites between β2-AR and clorprenaline, clenbuterol and bambuterol. On these sites, both zonal elution and nonlinear chromatography presented the same rank order for the association constants of the seven drugs. Compared with the data from zonal elution, the association constants calculated using nonlinear chromatography gave a good linear response to the corresponding values by radio-ligand binding assay. The sampling efficiencies of nonlinear chromatography were clearly higher than zonal elution. Nonlinear chromatography will probably become a powerful alternative for the high throughput determination of drug-protein interaction.

  14. Virus-Plus-Susceptibility Gene Interaction Determines Crohn’s Disease Gene Atg16L1 Phenotypes in Intestine

    PubMed Central

    Cadwell, Ken; Patel, Khushbu K.; Maloney, Nicole S.; Liu, Ta-Chiang; Ng, Aylwin C.Y.; Storer, Chad E.; Head, Richard D.; Xavier, Ramnik; Stappenbeck, Thaddeus S.; Virgin, Herbert W.

    2010-01-01

    SUMMARY It is unclear why disease occurs in only a small proportion of persons carrying common risk alleles of disease susceptibility genes. Here we demonstrate that an interaction between a specific virus infection and a mutation in the Crohn’s disease susceptibility gene Atg16L1 induces intestinal pathologies in mice. This virus-plus-susceptibility gene interaction generated abnormalities in granule packaging and unique patterns of gene expression in Paneth cells. Further, the response to injury induced by the toxic substance dextran sodium sulfate was fundamentally altered to include pathologies resembling aspects of Crohn’s disease. These pathologies triggered by virus-plus-susceptibility gene interaction were dependent on TNFα and IFNγ and were prevented by treatment with broad spectrum antibiotics. Thus, we provide a specific example of how a virus-plus-susceptibility gene interaction can, in combination with additional environmental factors and commensal bacteria, determine the phenotype of hosts carrying common risk alleles for inflammatory disease. PMID:20602997

  15. Determinants of male health: the interaction of biological and social factors

    PubMed Central

    de Kretser, David M.

    2010-01-01

    This review discusses the social and biological factors that may influence male development from conception to adulthood and also underlie the development of health disorders. It will provide assistance to those who may be considering the formulation of a male health policy. It aims to emphasize that social determinants function on a biological background that is profoundly influenced by a male's genome, inherited from his parents. The importance of the male-specific reproductive disorders is emphasized, but these also affect somatic structures through the secretion of androgens secreted from the testes. In turn, the function of the cardiovascular and nervous systems can significantly influence reproductive processes such as erectile dysfunction. PMID:20364153

  16. Determination of the Polymer-Solvent Interaction Parameter for PEG Hydrogels in Water: Application of a Self Learning Algorithm

    PubMed Central

    Akalp, Umut; Chu, Stanley; Skaalure, Stacey C.; Bryant, Stephanie J.; Doostan, Alireza; Vernerey, Franck J.

    2015-01-01

    Concentrating on the case of poly(ethylene glycol) hydrogels, this paper introduces a methodology that enables a natural integration between the development of a so-called mechanistic model and experimental data relating material’s processing to response. In a nutshell, we develop a data-driven modeling component that is able to learn and indirectly infer its own parameters and structure by observing experimental data. Using this method, we investigate the relationship between processing conditions, microstructure and chemistry (cross-link density and polymer-solvent interactions) and response (swelling and elasticity) of non-degradable and degradable PEG hydrogels. We show that the method not only enables the determination of the polymer-solvent interaction parameter, but also it predicts that this parameter, among others, varies with processing conditions and degradation. The proposed methodology therefore offers a new approach that accounts for subtle changes in the hydrogel processing. PMID:25999615

  17. F-Chart/SLR: an interactive program for determining the performance of active and passive solar buildings

    SciTech Connect

    Sullivan, P.; Wright, W.

    1980-01-01

    Methods for determining the performance of active and passive buildings have been developed by the University of Wisconsin-Madison, Solar Energy Laboratory and the Los Alamos Scientific Laboratory, respectively. The University of Wisconsin work, FCHART, is documented in Solar Heating Design by the F-chart Method, and in an interactive computer program available from the University. Los Alamos' work, the Solar Load Ratio (SLR) method, is documented in a number of individual papers as well as in the Passive Design Handbook. The SLR method is at present primarily a hand calculational procedure although the main features of the program have previously been incorporated in a hand-held programmable calculator program, PASCALC. An overview of a Northeast Solar Energy Center/Total Environmental Action, Inc. computer program which combines the detailed calculational procedures of the SLR method with the interactive features of the FCHART program is presented.

  18. Determination of Base Binding Strength and Base Stacking Interaction of DNA Duplex Using Atomic Force Microscope

    PubMed Central

    Zhang, Tian-biao; Zhang, Chang-lin; Dong, Zai-li; Guan, Yi-fu

    2015-01-01

    As one of the most crucial properties of DNA, the structural stability and the mechanical strength are attracting a great attention. Here, we take advantage of high force resolution and high special resolution of Atom Force Microscope and investigate the mechanical force of DNA duplexes. To evaluate the base pair hydrogen bond strength and base stacking force in DNA strands, we designed two modes (unzipping and stretching) for the measurement rupture forces. Employing k-means clustering algorithm, the ruptured force are clustered and the mean values are estimated. We assessed the influence of experimental parameters and performed the force evaluation for DNA duplexes of pure dG/dC and dA/dT base pairs. The base binding strength of single dG/dC and single dA/dT were estimated to be 20.0 ± 0.2 pN and 14.0 ± 0.3 pN, respectively, and the base stacking interaction was estimated to be 2.0 ± 0.1 pN. Our results provide valuable information about the quantitative evaluation of the mechanical properties of the DNA duplexes. PMID:25772017

  19. Determinants of aggressive behavior: Interactive effects of emotional regulation and inhibitory control.

    PubMed

    Hsieh, I-Ju; Chen, Yung Y

    2017-01-01

    Aggressive behavior can be defined as any behavior intended to hurt another person, and it is associated with many individual and social factors. This study examined the relationship between emotional regulation and inhibitory control in predicting aggressive behavior. Seventy-eight participants (40 males) completed self-report measures (Negative Mood Regulation Scale and Buss-Perry Aggression Questionnaire), a stop signal task, and engaged in a modified version of Taylor Aggression Paradigm (TAP) exercise, in which the outcome was used as a measure of direct physical aggression. We used a hierarchical, mixed-model multiple regression analysis test to examine the effects of emotion regulation and inhibitory control on physical reactive aggression. Results indicated an interaction between emotion regulation and inhibitory control on aggression. For participants with low inhibitory control only, there was a significant difference between high and low emotion regulation on aggression, such that low emotion regulation participants registered higher aggression than high emotion regulation participants. This difference was not found among participants with high inhibitory control. These results have implications for refining and targeting training and rehabilitation programs aimed at reducing aggressive behavior.

  20. Electron-ion interaction cross sections determined by x-ray spectroscopy on EBIT

    SciTech Connect

    Beiersdorfer, P.; Cauble, R.; Chantrenne, S.; Chen, M.; Knapp, D.; Marrs, R.; Phillips, T.; Reed, K.; Schneider, M.; Scofield, J.; Wong, K.; Vogel, D.; Zasadzinski, R. ); Wargelin, B. . Space Sciences Lab.); Bitter, M.; von Goeler, S. . Plasma Physics Lab.)

    1991-06-26

    The Livermore electron beam ion trap (EBIT) is used to measure electron-ion interactions with high-resolution x-ray spectroscopy. Measurements are presented of the K{alpha} x-ray emission of heliumlike Fe{sup 24+} that demonstrate the effect of various processes on the spectrum of highly charged heliumlike ions. In particular, we have studied how dielectronic recombination into high-n Rydberg levels and resonance excitation processes contribute to the x-ray emission near threshold for direct electron-impact excitation. From these and other measurements we infer the cross sections for impact excitation of heliumlike titanium, chromium, manganese, and iron. Comparing the results with theoretical cross sections from distorted-wave calculations we find excellent agreement for all transitions but the heliumlike resonance transition from 1s2p {sup 1}P{sub 1} to ground, whose excitation cross section is measured to be 10%--20% smaller than calculated. 36 refs., 6 figs., 1 tab.

  1. Determination of base binding strength and base stacking interaction of DNA duplex using atomic force microscope.

    PubMed

    Zhang, Tian-biao; Zhang, Chang-lin; Dong, Zai-li; Guan, Yi-fu

    2015-03-16

    As one of the most crucial properties of DNA, the structural stability and the mechanical strength are attracting a great attention. Here, we take advantage of high force resolution and high special resolution of Atom Force Microscope and investigate the mechanical force of DNA duplexes. To evaluate the base pair hydrogen bond strength and base stacking force in DNA strands, we designed two modes (unzipping and stretching) for the measurement rupture forces. Employing k-means clustering algorithm, the ruptured force are clustered and the mean values are estimated. We assessed the influence of experimental parameters and performed the force evaluation for DNA duplexes of pure dG/dC and dA/dT base pairs. The base binding strength of single dG/dC and single dA/dT were estimated to be 20.0 ± 0.2 pN and 14.0 ± 0.3 pN, respectively, and the base stacking interaction was estimated to be 2.0 ± 0.1 pN. Our results provide valuable information about the quantitative evaluation of the mechanical properties of the DNA duplexes.

  2. Class I TCP-DELLA interactions in inflorescence shoot apex determine plant height.

    PubMed

    Davière, Jean-Michel; Wild, Michael; Regnault, Thomas; Baumberger, Nicolas; Eisler, Herfried; Genschik, Pascal; Achard, Patrick

    2014-08-18

    Regulation of plant height, one of the most important agronomic traits, is the focus of intensive research for improving crop performance. Stem elongation takes place as a result of repeated cell divisions and subsequent elongation of cells produced by apical and intercalary meristems. The gibberellin (GA) phytohormones have long been known to control stem and internodal elongation by stimulating the degradation of nuclear growth-repressing DELLA proteins; however, the mechanism allowing GA-responsive growth is only slowly emerging. Here, we show that DELLAs directly regulate the activity of the plant-specific class I TCP transcription factor family, key regulators of cell proliferation. Our results demonstrate that class I TCP factors directly bind the promoters of core cell-cycle genes in Arabidopsis inflorescence shoot apices while DELLAs block TCP function by binding to their DNA-recognition domain. GAs antagonize such repression by promoting DELLA destruction and therefore cause a concomitant accumulation of TCP factors on promoters of cell-cycle genes. Consistent with this model, the quadruple mutant tcp8 tcp14 tcp15 tcp22 exhibits severe dwarfism and reduced responsiveness to GA action. Altogether, we conclude that GA-regulated DELLA-TCP interactions in inflorescence shoot apex provide a novel mechanism to control plant height. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Biotic interactions as determinants of ecosystem structure in prairie wetlands: An example using fish

    USGS Publications Warehouse

    Hanson, M.A.; Zimmer, K.D.; Butler, Malcolm G.; Tangen, B.A.; Herwig, B.R.; Euliss, N.H.

    2005-01-01

    Wetlands are abundant throughout the prairie pothole region (PPR), an area comprising over 700,000 km2 in central North America. Prairie wetland communities are strongly influenced by regional physiography and climate, resulting in extreme spatial and temporal variability relative to other aquatic ecosystems. Given the strong influence of abiotic factors, PPR wetland communities have been viewed traditionally in the context of their responses to chemical and physical features of landscape and climate. Although useful, this physical-chemical paradigm may fail to account for ecosystem variability due to biotic influences, particularly those associated with presence of fish. Spatial and temporal variability in fish populations, in turn, may reflect anthropogenic activities, landscape characteristics, and climate-mediated effects on water levels, surface connectivity, and hydroperiods. We reviewed studies assessing influences of fish on prairie wetlands and examined precipitation patterns and biological data from PPR wetlands in east-central North Dakota and western Minnesota, USA. Our review and analysis indicated that native fish influence many characteristics of permanently flooded prairie wetlands, including water clarity and abundance of phytoplankton, submerged macrophytes, and aquatic invertebrates. We suggest that ecologists and managers will benefit from conceptual paradigms that better meld biotic interactions associated with fish, and perhaps other organisms, with chemical and physical influences on prairie wetland communities. ?? 2005, The Society of Wetland Scientists.

  4. DETERMINATION OF THE CREEP–FATIGUE INTERACTION DIAGRAM FOR ALLOY 617

    SciTech Connect

    Wright, J. K.; Carroll, L. J.; Sham, T. -L.; Lybeck, N. J.; Wright, R. N.

    2016-08-01

    Alloy 617 is the leading candidate material for an intermediate heat exchanger for the very high temperature reactor. To evaluate the behavior of this material in the expected service conditions, creep-fatigue testing was performed. Testing has been performed primarily on a single heat of material at 850 and 950°C for total strain ranges of 0.3 to 1% and tensile hold times as long as 240 minutes. At 850°C, increases in the tensile hold duration degraded the creep fatigue resistance, at least to the investigated strain-controlled hold time of up to 60 minutes at the 0.3% strain range and 240 minutes at the 1.0% strain range. At 950°C, the creep-fatigue cycles to failure becomes constant with increasing hold times, indicating saturation occurs at relatively short hold times. The creep and fatigue damage fractions have been calculated and plotted on a creep-fatigue interaction D-diagram. Results from earlier creep-fatigue tests at 800 and 1000°C on an additional heat of Alloy 617 are also plotted on the D-diagram. The methodology for calculating the damage fractions will be presented, and the effects of strain rate, strain range, temperature, hold time, and strain profile (i.e. holds in tension, compression or both) on the creep-fatigue damage will be explored.

  5. Flow environment and matrix structure interact to determine spatial competition in Pseudomonas aeruginosa biofilms

    PubMed Central

    Nadell, Carey D; Ricaurte, Deirdre; Yan, Jing; Drescher, Knut; Bassler, Bonnie L

    2017-01-01

    Bacteria often live in biofilms, which are microbial communities surrounded by a secreted extracellular matrix. Here, we demonstrate that hydrodynamic flow and matrix organization interact to shape competitive dynamics in Pseudomonas aeruginosa biofilms. Irrespective of initial frequency, in competition with matrix mutants, wild-type cells always increase in relative abundance in planar microfluidic devices under simple flow regimes. By contrast, in microenvironments with complex, irregular flow profiles – which are common in natural environments – wild-type matrix-producing and isogenic non-producing strains can coexist. This result stems from local obstruction of flow by wild-type matrix producers, which generates regions of near-zero shear that allow matrix mutants to locally accumulate. Our findings connect the evolutionary stability of matrix production with the hydrodynamics and spatial structure of the surrounding environment, providing a potential explanation for the variation in biofilm matrix secretion observed among bacteria in natural environments. DOI: http://dx.doi.org/10.7554/eLife.21855.001 PMID:28084994

  6. Determination of ethyl glucuronide in human hair by hydrophilic interaction liquid chromatography-tandem mass spectrometry.

    PubMed

    Yaldiz, Fadile; Daglioglu, Nebile; Hilal, Ahmet; Keten, Alper; Gülmen, Mete Korkut

    2013-10-01

    Ethyl glucuronide (EtG) is a direct metabolite of ethanol and has been utilized as a marker for alcohol intake. This study presents development, validation and application of a new hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) method for the analysis of EtG in human hair samples. The linearity was assessed in the range of 5-2000 pg/mg hair, with a correlation coefficient of >0.99. The method was selective and sensitive, with a limit of detection (LOD) and limit of quantitation (LOQ) of 0.05 pg/mg and 0.18 pg/mg in hair, respectively. Differently from the extraction procedures in the literature, a fast and simple liquid-liquid method was used and highest recoveries and cleanest extracts were obtained. The method was successfully applied to 30 human hair samples which were taken from those who state they consume alcohol. EtG concentrations in the hair samples of alcohol users participated in this study, ranged between 1.34 and 82.73 pg/mg. From the concentration of EtG in hair strands 20 of the 30 subjects can be considered regular moderate drinkers. Copyright © 2013 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  7. Determination of Oxidized Phosphatidylcholines by Hydrophilic Interaction Liquid Chromatography Coupled to Fourier Transform Mass Spectrometry

    PubMed Central

    Sala, Pia; Pötz, Sandra; Brunner, Martina; Trötzmüller, Martin; Fauland, Alexander; Triebl, Alexander; Hartler, Jürgen; Lankmayr, Ernst; Köfeler, Harald C.

    2015-01-01

    A novel liquid chromatography-mass spectrometry (LC-MS) approach for analysis of oxidized phosphatidylcholines by an Orbitrap Fourier Transform mass spectrometer in positive electrospray ionization (ESI) coupled to hydrophilic interaction liquid chromatography (HILIC) was developed. This method depends on three selectivity criteria for separation and identification: retention time, exact mass at a resolution of 100,000 and collision induced dissociation (CID) fragment spectra in a linear ion trap. The process of chromatography development showed the best separation properties with a silica-based Kinetex column. This type of chromatography was able to separate all major lipid classes expected in mammalian samples, yielding increased sensitivity of oxidized phosphatidylcholines over reversed phase chromatography. Identification of molecular species was achieved by exact mass on intact molecular ions and CID tandem mass spectra containing characteristic fragments. Due to a lack of commercially available standards, method development was performed with copper induced oxidation products of palmitoyl-arachidonoyl-phosphatidylcholine, which resulted in a plethora of lipid species oxidized at the arachidonoyl moiety. Validation of the method was done with copper oxidized human low-density lipoprotein (LDL) prepared by ultracentrifugation. In these LDL samples we could identify 46 oxidized molecular phosphatidylcholine species out of 99 possible candidates. PMID:25874761

  8. Promiscuous interactions and protein disaggregases determine the material state of stress-inducible RNP granules.

    PubMed

    Kroschwald, Sonja; Maharana, Shovamayee; Mateju, Daniel; Malinovska, Liliana; Nüske, Elisabeth; Poser, Ina; Richter, Doris; Alberti, Simon

    2015-08-04

    RNA-protein (RNP) granules have been proposed to assemble by forming solid RNA/protein aggregates or through phase separation into a liquid RNA/protein phase. Which model describes RNP granules in living cells is still unclear. In this study, we analyze P bodies in budding yeast and find that they have liquid-like properties. Surprisingly, yeast stress granules adopt a different material state, which is reminiscent of solid protein aggregates and controlled by protein disaggregases. By using an assay to ectopically nucleate RNP granules, we further establish that RNP granule formation does not depend on amyloid-like aggregation but rather involves many promiscuous interactions. Finally, we show that stress granules have different properties in mammalian cells, where they show liquid-like behavior. Thus, we propose that the material state of RNP granules is flexible and that the solid state of yeast stress granules is an adaptation to extreme environments, made possible by the presence of a powerful disaggregation machine.

  9. Promiscuous interactions and protein disaggregases determine the material state of stress-inducible RNP granules

    PubMed Central

    Kroschwald, Sonja; Maharana, Shovamayee; Mateju, Daniel; Malinovska, Liliana; Nüske, Elisabeth; Poser, Ina; Richter, Doris; Alberti, Simon

    2015-01-01

    RNA-protein (RNP) granules have been proposed to assemble by forming solid RNA/protein aggregates or through phase separation into a liquid RNA/protein phase. Which model describes RNP granules in living cells is still unclear. In this study, we analyze P bodies in budding yeast and find that they have liquid-like properties. Surprisingly, yeast stress granules adopt a different material state, which is reminiscent of solid protein aggregates and controlled by protein disaggregases. By using an assay to ectopically nucleate RNP granules, we further establish that RNP granule formation does not depend on amyloid-like aggregation but rather involves many promiscuous interactions. Finally, we show that stress granules have different properties in mammalian cells, where they show liquid-like behavior. Thus, we propose that the material state of RNP granules is flexible and that the solid state of yeast stress granules is an adaptation to extreme environments, made possible by the presence of a powerful disaggregation machine. DOI: http://dx.doi.org/10.7554/eLife.06807.001 PMID:26238190

  10. Mycobacterium leprae–host-cell interactions and genetic determinants in leprosy: an overview

    PubMed Central

    Pinheiro, Roberta Olmo; de Souza Salles, Jorgenilce; Sarno, Euzenir Nunes; Sampaio, Elizabeth Pereira

    2011-01-01

    Leprosy, also known as Hansen’s disease, is a chronic infectious disease caused by Mycobacterium leprae in which susceptibility to the mycobacteria and its clinical manifestations are attributed to the host immune response. Even though leprosy prevalence has decreased dramatically, the high number of new cases indicates active transmission. Owing to its singular features, M. leprae infection is an attractive model for investigating the regulation of human immune responses to pathogen-induced disease. Leprosy is one of the most common causes of nontraumatic peripheral neuropathy worldwide. The proportion of patients with disabilities is affected by the type of leprosy and delay in diagnosis. This article briefly reviews the clinical features as well as the immunopathological mechanisms related to the establishment of the different polar forms of leprosy, the mechanisms related to M. leprae–host cell interactions and prophylaxis and diagnosis of this complex disease. Host genetic factors are summarized and the impact of the development of interventions that prevent, reverse or limit leprosy-related nerve impairments are discussed. PMID:21366421

  11. Sexually-trimorphic interactions with colour polymorphism determine nectar quality in a herbaceous perennial

    PubMed Central

    Varga, Sandra; Soulsbury, Carl D.

    2017-01-01

    Amongst gynodioecious plant breeding systems, there can exist intermediate morphs with a reduction in their male function (i.e. reduced number of functional anthers). Along with this sexual trimorphism, plants can also show floral colour polymorphism. Such intricate mixtures of phenotypes within a species may have complex effects on floral rewards. Floral rewards are known to vary between sexually dimorphic species and to a lesser extent between colour morphs. However, the interactive effect of sexual trimorphism and colour polymorphism is unexplored. We measured nectar’s sugar content in the sexually trimorphic Geranium sylvaticum, a gynodioecious plant with a light/dark floral polymorphism. We found that nectar reward differed across genders and colour morphs. Results were not however consistent within the three genders; dark female and hermaphrodite flowers had higher sugar content than light morphs, whereas intermediate flowers did not. As expected, females and hermaphrodites had different nectar reward, with intermediate morphs being midway between the other genders. In intermediates, the sugar content was not related to the number of functional stamens. We show for the first time the existence of sex-specific differences between flower gender and colour morphs in nectar rewards. Our results demonstrate the importance of considering multiple and conflicting selection pressures to explain rewards. PMID:28374829

  12. Precise, fast, and flexible determination of protein interactions by affinity capillary electrophoresis: part 3: anions.

    PubMed

    Xu, Yuanhong; Redweik, Sabine; El-Hady, Deia Abd; Albishri, Hassan M; Preu, Lutz; Wätzig, Hermann

    2014-08-01

    The binding of physiologically anionic species or negatively charged drug molecules to proteins is of great importance in biochemistry and medicine. Since affinity capillary electrophoresis (ACE) has already proven to be a suitable analytical tool to study the influence of ions on proteins, this technique was applied here for comprehensively studying the influence of various anions on proteins of BSA, β-lactoglobulin, ovalbumin, myoglobin, and lysozyme. The analysis was performed using different selected anions of succinate, glutamate, phosphate, acetate, nitrate, iodide, thiocyanate, and pharmaceuticals (salicylic acid, aspirin, and ibuprofen) that exist in the anionic form at physiological pH 7.4. Due to the excellent repeatability and precision of the ACE measurements, not necessarily strong but significant influences of the anions on the proteins were found in many cases. Different influences in the observed bindings indicated change of charge, mass, or conformational changes of the proteins due to the binding with the studied anions. Combining the mobility-shift and pre-equilibrium ACE modes, rapidity and reversibility of the protein-anion bindings were discussed. Further, circular dichroism has been used as an orthogonal approach to characterize the interactions between the studied proteins and anions to confirm the ACE results. Since phosphate and various anions from amino acids and small organic acids such as succinate or acetate are present in very high concentrations in the cellular environment, even weak influences are certainly relevant as well.

  13. Performance of zwitterionic hydrophilic interaction LC for the determination of iodinated X-ray contrast agents.

    PubMed

    Echeverría, Silvia; Herrero, Pol; Borrull, Francesc; Fontanals, Núria; Pocurull, Eva

    2013-12-01

    This study compares the separation performance of a group of iodinated X-ray contrast media on four different columns. The first three were two stationary phases (SPs) modified with C18 and a polar-embedded SP (polar amide group bonded to an alkyl chain), all of which worked under RP-LC mode. The fourth was a zwitterionic sulphoalkylbetaine SP, working under the hydrophilic interaction LC (HILIC) mode. After the optimisation of the different parameters, the zwitterionic column displayed the best separation, which also overcomes the problems encountered when these analytes were separated under RP-LC. Moreover, when HILIC is coupled to MS/MS, sensitivity is enhanced. However, when sewage samples were analysed by SPE followed by the optimal HILIC-MS/MS, the sensitivity of the method was affected due to the high matrix effect, which had to be solved by dilution of the extract. Finally, the method was preliminarily validated with sewage and the figures of merit were comparable to those of the SPE-RP-LC-MS/MS.

  14. Lifetime Number of Mates Interacts with Female Age to Determine Reproductive Success in Female Guppies

    PubMed Central

    Evans, Jonathan P.

    2012-01-01

    In many species, mating with multiple males confers benefits to females, but these benefits may be offset by the direct and indirect costs associated with elevated mating frequency. Although mating frequency (number of mating events) is often positively associated with the degree of multiple mating (actual number of males mated), most studies have experimentally separated these effects when exploring their implications for female fitness. In this paper I describe an alternative approach using the guppy Poecilia reticulata, a livebearing freshwater fish in which females benefit directly and indirectly from mating with multiple males via consensual matings but incur direct and indirect costs of mating as a consequence of male sexual harassment. In the present study, females were experimentally assigned different numbers of mates throughout their lives in order to explore how elevated mating frequency and multiple mating combine to influence lifetime reproductive success (LRS) and survival (i.e. direct components of female fitness). Under this mating design, survival and LRS were not significantly affected by mating treatment, but there was a significant interaction between brood size and reproductive cycle (a correlate of female age) because females assigned to the high mating treatment produced significantly fewer offspring later in life compared to their low-mating counterparts. This negative effect of mating treatment later in life may be important in these relatively long-lived fishes, and this effect may be further exacerbated by the known cross-generational fitness costs of sexual harassment in guppies. PMID:23071816

  15. Determination of interaction forces between parallel dislocations by the evaluation of J integrals of plane elasticity

    NASA Astrophysics Data System (ADS)

    Lubarda, Vlado A.

    2016-03-01

    The Peach-Koehler expressions for the glide and climb components of the force exerted on a straight dislocation in an infinite isotropic medium by another straight dislocation are derived by evaluating the plane and antiplane strain versions of J integrals around the center of the dislocation. After expressing the elastic fields as the sums of elastic fields of each dislocation, the energy momentum tensor is decomposed into three parts. It is shown that only one part, involving mixed products from the two dislocation fields, makes a nonvanishing contribution to J integrals and the corresponding dislocation forces. Three examples are considered, with dislocations on parallel or intersecting slip planes. For two edge dislocations on orthogonal slip planes, there are two equilibrium configurations in which the glide and climb components of the dislocation force simultaneously vanish. The interactions between two different types of screw dislocations and a nearby circular void, as well as between parallel line forces in an infinite or semi-infinite medium, are then evaluated.

  16. A new method for depth of interaction determination in PET detectors

    NASA Astrophysics Data System (ADS)

    Pizzichemi, M.; Stringhini, G.; Niknejad, T.; Liu, Z.; Lecoq, P.; Tavernier, S.; Varela, J.; Paganoni, M.; Auffray, E.

    2016-06-01

    A new method for obtaining depth of interaction (DOI) information in PET detectors is presented in this study, based on sharing and redirection of scintillation light among multiple detectors, together with attenuation of light over the length of the crystals. The aim is to obtain continuous DOI encoding with single side readout, and at the same time without the need for one-to-one coupling between scintillators and detectors, allowing the development of a PET scanner with good spatial, energy and timing resolutions while keeping the complexity of the system low. A prototype module has been produced and characterized to test the proposed method, coupling a LYSO scintillator matrix to a commercial SiPMs array. Excellent crystal separation is obtained for all the scintillators in the array, light loss due to depolishing is found to be negligible, energy resolution is shown to be on average 12.7% FWHM. The mean DOI resolution achieved is 4.1 mm FWHM on a 15 mm long crystal and preliminary coincidence time resolution was estimated in 353 ps FWHM.

  17. Interaction between the TP63 and SHH pathways is an important determinant of epidermal homeostasis

    PubMed Central

    Chari, N S; Romano, R A; Koster, M I; Jaks, V; Roop, D; Flores, E R; Teglund, S; Sinha, S; Gruber, W; Aberger, F; Medeiros, L J; Toftgard, R; McDonnell, T J

    2013-01-01

    Deregulation of the hedgehog (HH) pathway results in overexpression of the GLI target BCL2 and is an initiating event in specific tumor types including basal cell carcinoma of the skin. Regulation of the HH pathway during keratinocyte differentiation is not well understood. We measured HH pathway activity in response to differentiation stimuli in keratinocytes. An upregulation of suppressor of fused (SUFU), a negative regulator of the HH pathway, lowered HH pathway activity and was accompanied by loss of BCL2 expression associated with keratinocyte differentiation. We used in vitro and in vivo models to demonstrate that ΔNp63α, a crucial regulator of epidermal development, activates SUFU transcription in keratinocytes. Increasing SUFU protein levels inhibited GLI-mediated gene activation in suprabasal keratinocytes and promoted differentiation. Loss of SUFU expression caused deregulation of keratinocyte differentiation and BCL2 overexpression. Using in vivo murine models, we also provide evidence of GLI-mediated regulation of the TP63 pathway. p63 expression appears essential to establish an optimally functioning HH pathway. These observations present a regulatory mechanism by which SUFU acts as an interacting node between the HH and TP63 pathways to mediate differentiation and maintain epidermal homeostasis. Disruption of this regulatory node can be an important contributor to multistep carcinogenesis. PMID:23686138

  18. Determination of interfacial Dzyaloshinskii-Moriya exchange interaction from static domain size imaging

    NASA Astrophysics Data System (ADS)

    Agrawal, Parnika; Lemesh, Ivan; Schlotter, Sarah; Beach, Geoffrey

    Dzyaloshinskii-Moriya interaction (DMI) has been identified [1-2] as a necessary ingredient for the formation of chiral spin structures such as skyrmions and Néel domain walls in perpendicularly magnetized thin films. Various simulation and experimental studies have tried to quantify DMI from domain wall and skyrmion [3-4] motion with applied currents and magnetic fields. Here, a means to quantify DMI in multilayer films using only static magnetic characterizations is proposed. Static domain structure is observed using magnetic force microscopy (MFM) in multilayer stacks of [Pt(2.5-7.5nm)/CoFeB(0.8nm)/MgO(1.5nm)]15 where the thickness tpt of the Pt layer is systematically varied from 2.5 nm to 7.5 nm. A variation of domain size from ~300 nm to ~70 nm is seen in the labyrinthine demagnetized state as tpt is decreased. It is shown that the domain size as a function of tpt can be well-fitted analytically by a model in which the domain wall energy is the sole free parameter. Additional measurements of magnetic anisotropy of the film reveal the significant contribution of interfacial DMI (~1.4 mJ/m2) to the domain wall energy.

  19. Lifetime number of mates interacts with female age to determine reproductive success in female guppies.

    PubMed

    Evans, Jonathan P

    2012-01-01

    In many species, mating with multiple males confers benefits to females, but these benefits may be offset by the direct and indirect costs associated with elevated mating frequency. Although mating frequency (number of mating events) is often positively associated with the degree of multiple mating (actual number of males mated), most studies have experimentally separated these effects when exploring their implications for female fitness. In this paper I describe an alternative approach using the guppy Poecilia reticulata, a livebearing freshwater fish in which females benefit directly and indirectly from mating with multiple males via consensual matings but incur direct and indirect costs of mating as a consequence of male sexual harassment. In the present study, females were experimentally assigned different numbers of mates throughout their lives in order to explore how elevated mating frequency and multiple mating combine to influence lifetime reproductive success (LRS) and survival (i.e. direct components of female fitness). Under this mating design, survival and LRS were not significantly affected by mating treatment, but there was a significant interaction between brood size and reproductive cycle (a correlate of female age) because females assigned to the high mating treatment produced significantly fewer offspring later in life compared to their low-mating counterparts. This negative effect of mating treatment later in life may be important in these relatively long-lived fishes, and this effect may be further exacerbated by the known cross-generational fitness costs of sexual harassment in guppies.

  20. The expected drug and its expected effect interact to determine placebo responses to alcohol and caffeine.

    PubMed

    Fillmore, M T; Mulvihill, L E; Vogel-Sprott, M

    1994-07-01

    This study tested placebo responses in psychomotor performance when caffeine or alcohol was expected. Fifty male university students were assigned to one of four placebo groups or to a no-treatment control group. Two groups received placebo caffeine and two received placebo alcohol. Subjects performed 12 trials on a pursuit rotor task and performance was measured by the percent time on target. Then they received information about the expected drug effect on the task. One caffeine placebo group (C+) and one alcohol placebo group (A+) were led to expect enhanced performance on the task. The other caffeine placebo group (C-) and alcohol placebo group (A-) were led to expect impaired performance. Subjects subsequently performed 12 trials on the task. An interaction was obtained between the expected type of effect and the expected type of drug. The C+ group displayed superior performance compared to the C- group, and the reverse relationship was observed between the A+ and A- group. In addition, subjects led to expect alcohol-induced impairment (A-) performed better than subjects led to expect caffeine-induced impairment (C-). Subjects also reported greater motivation to resist impairment when they expected alcohol rather than caffeine. The research indicates that understanding and predicting placebo responses may require consideration of the drug that is expected as well as its expected effect.

  1. Parameterization of solvent-protein interaction and its use on NMR protein structure determination

    NASA Astrophysics Data System (ADS)

    Wang, Yu; Schwieters, Charles D.; Tjandra, Nico

    2012-08-01

    NMR structure determination is frequently hindered by an insufficient amount of distance information for determining the correct fold of the protein in its early stages. In response we introduce a simple and general structure-based metric that can be used to incorporate NMR-based restraints on protein surface accessibility. This metric is inversely proportional to the sum of the inverse square distances to neighboring heavy atoms. We demonstrate the use of this restraint using a dataset from the water to protein magnetization transfer experiment on the protein Bax and the solvent paramagnetic relaxation enhancement experiment on the protein ubiquitin and Qua1 homodimer. The calculated solvent accessibility values using the new empirical function are well correlated with the experimental data. By incorporating an associated energy term into Xplor-NIH, we show that structure calculation with a limited number of additional experimental restraints, improves both the precision and accuracy of the resulting structures. This new empirical energy term will have general applicability to other types of solvent accessibility data.

  2. Two hydrophobic residues can determine the specificity of mitogen-activated protein kinase docking interactions.

    PubMed

    Bardwell, A Jane; Bardwell, Lee

    2015-10-30

    MAPKs bind to many of their upstream regulators and downstream substrates via a short docking motif (the D-site) on their binding partner. MAPKs that are in different families (e.g. ERK, JNK, and p38) can bind selectively to D-sites in their authentic substrates and regulators while discriminating against D-sites in other pathways. Here we demonstrate that the short hydrophobic region at the distal end of the D-site plays a critical role in determining the high selectivity of JNK MAPKs for docking sites in their cognate MAPK kinases. Changing just 1 or 2 key hydrophobic residues in this submotif is sufficient to turn a weak JNK-binding D-site into a strong one, or vice versa. These specificity-determining differences are also found in the D-sites of the ETS family transcription factors Elk-1 and Net. Moreover, swapping two hydrophobic residues between these D-sites switches the relative efficiency of Elk-1 and Net as substrates for ERK versus JNK, as predicted. These results provide new insights into docking specificity and suggest that this specificity can evolve rapidly by changes to just 1 or 2 amino acids. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Two Hydrophobic Residues Can Determine the Specificity of Mitogen-activated Protein Kinase Docking Interactions*

    PubMed Central

    Bardwell, A. Jane; Bardwell, Lee

    2015-01-01

    MAPKs bind to many of their upstream regulators and downstream substrates via a short docking motif (the D-site) on their binding partner. MAPKs that are in different families (e.g. ERK, JNK, and p38) can bind selectively to D-sites in their authentic substrates and regulators while discriminating against D-sites in other pathways. Here we demonstrate that the short hydrophobic region at the distal end of the D-site plays a critical role in determining the high selectivity of JNK MAPKs for docking sites in their cognate MAPK kinases. Changing just 1 or 2 key hydrophobic residues in this submotif is sufficient to turn a weak JNK-binding D-site into a strong one, or vice versa. These specificity-determining differences are also found in the D-sites of the ETS family transcription factors Elk-1 and Net. Moreover, swapping two hydrophobic residues between these D-sites switches the relative efficiency of Elk-1 and Net as substrates for ERK versus JNK, as predicted. These results provide new insights into docking specificity and suggest that this specificity can evolve rapidly by changes to just 1 or 2 amino acids. PMID:26370088

  4. Individual and social determinants of obesity in strategic health messages: Interaction with political ideology.

    PubMed

    Young, Rachel; Hinnant, Amanda; Leshner, Glenn

    2016-07-01

    Antiobesity health communication campaigns often target individual behavior, but these ads might inflate the role of individual responsibility at the expense of other health determinants. In a 2 × 2 full-factorial, randomized, online experiment, 162 American adults viewed antiobesity advertisements that varied in emphasizing social or individual causation for obesity through text and images. Locus for attribution of responsibility for obesity causes and solutions was measured, as was how these responses were moderated by political ideology. Participants who viewed text emphasizing individual responsibility were less likely to agree that genetic factors caused obesity. Conservative participants who viewed images of overweight individuals were less likely than liberal participants to agree that social factors were responsible for causing obesity. In addition, among conservative participants who viewed images of fast food versus images of overweight individuals, agreement that the food industry bore some responsibility mediated support for policy solutions to obesity. These findings, among others, demonstrate that awareness of multilevel determinants of health outcomes can be a precursor of support for policy solutions to obesity among those not politically inclined to support antiobesity policy. In addition, stigmatizing images of overweight individuals in antiobesity campaigns might overemphasize the role of individual behavior in obesity at the expense of other factors.

  5. Sigma and Pi Interactions of the Pyrrolic Ligand Sandwich-Like Lanthanide Phthalocyanines Determined from Magnetic Susceptibility and Ligand-Field Theory

    DTIC Science & Technology

    1990-06-25

    ACCESSION NO. 11, TITLE (include Security Classification) UNCLASSIFIED: Sigma and Pi Interactions of the Pyrro- lic Ligand Sandwich-Like Lanthanide ...4135007---05 TECHNICAL REPORT NO. 36 Sigma and Pi Interactions of the Pyrrolic Ligand Sandwich-Like Lanthanide Phthalocyanines Determined From Magnetic...Hill Chapel Hill, North Carolina 27599-3290 Sigma and Pi Interactions of the Pyrrolic Ligand Sandwich-Like Lanthanide Phthalocyanines Determined From

  6. Intramitochondrial positions of ubiquinone and iron-sulphur centres determined by dipolar interactions with paramagnetic ions.

    PubMed Central

    Case, G D; Ohnishi, T; Leigh, J S

    1976-01-01

    E.p.r. (electron-paramagnetic-resonance) spectra of ubisemiquinone (QH) organic radicals and all of the known iron-sulphur centres were studied in normal and 'nickle-plated' pigeon heart mitochondria, submitochondrial particles and submitochondrial particles from which succinate dehydrogenase had been removed. Incubation of pigeon heart mitochondria, submitochondrial particles or succinate dehydrogenase-depleted submitochondrial particles with substrate in the presence of pure O2 results in the accumulation of Q-H. In mitochondria, the e.p.r. spectrum of Q-H is characterized by in-homogeneous line broadening. A heterogeneous population of semiquinones appears to be partly responsible for these effects in mitochondria. Additon of Ni(II) to mitochondria renders saturation of the Q-H resonance more difficult. On the other hand, the resonance in either submitochondrial particles or succinate dehydrogenase-depleted particles is narrower than the same spectrum in mitochondria, and saturates like a homogeneous line. The presence of Ni(II) in either of these preparations, further, has no effect on either the A-H spectrum or the saturation curve. Therefore QH appears to be situated on the exterior surface of the mitochondrion. Likewise, the e.p.r. spectra and saturation curves of iron-sulphur centre N-2 exhibit characteristics of inhomogeneous line broadening, not only in intact mitochondria but also in both submitochondrial particles and succinate dehydrogenase-depleted particles. Because of the small pool size of centre N-2, this effect is likely to arise from a spin interaction with some other component in the membrane. Ni(II) has no effect on the saturation in centre N-2 in mitochondria or submitochondrial particles, and only a marginal effect in the succinate dehydrogenase-depleted preparation. These results are indeterminate with respect to the position of centre N-2 in the membrane; but suggest that its distance from the succinate dehydrogenase binding site is on the

  7. The role of surface interactions and morphology in determining thermal dynamic properties of polymer nanocomposites

    NASA Astrophysics Data System (ADS)

    Pack, Seongchan

    Since interfacial properties rely on interactions between polymers and nanoparticles at interfaces, obtaining a minimization of the interfacial energy can be complicated when nanoparticles are added in a polymer blend, even more complicated when the blend is mixed with conventional flame retardant (FR) agents. We here show that the addition of nanoparticles, such as layered silicates and carbon nanotubes (CNTs), could not only enhance the compatibilization of immiscible polymer blends but also improve the degree of the dispersion of FR agents, since the nanoparticles were seen at either the blend interfaces or the FR agents. In addition, we have demonstrated that the addition of the clays can stabilize the blends against further phase segregation, thereby suppressing the formation of either ribbon-like or tubular-like structures along the interfaces during heating. These structures can significantly improve flame retardant properties, such as heat release rate (HRR) and mass loss rate (MLR), which can be evidenced by enhanced thermal conduction within the structures. In spite of these improvements, most polymer blends with the nanoparticles cannot be rendered self-extinguishing unless the conventional FR agents are added. Furthermore, too much added FR agents deteriorate material properties because the FR agents can be classified as an additive. Therefore, we have showed that the FR agents can be directly absorbed on the clay surface, which not only improves the dispersion of FR agents but also results in the exfoliation and/or intercalation in several homopolymers. The strong absorption of FR agents on the nanoparticles can effectively achieve the result of self-extinguishment. This is obtained from the interfaces between the FR agents and the nanoparticles, where a synergy may be attributed to the interfacial activity and the improved thermal conductivity. Finally, we here explain a mechanism of the self-extinguishment of nanocomposites containing both the FR

  8. Evolutionary History and Novel Biotic Interactions Determine Plant Responses to Elevated CO2 and Nitrogen Fertilization

    PubMed Central

    Wooliver, Rachel; Senior, John K.; Schweitzer, Jennifer A.; O'Reilly-Wapstra, Julianne M.; Langley, J. Adam; Chapman, Samantha K.; Bailey, Joseph K.

    2014-01-01

    A major frontier in global change research is predicting how multiple agents of global change will alter plant productivity, a critical component of the carbon cycle. Recent research has shown that plant responses to climate change are phylogenetically conserved such that species within some lineages are more productive than those within other lineages in changing environments. However, it remains unclear how phylogenetic patterns in plant responses to changing abiotic conditions may be altered by another agent of global change, the introduction of non-native species. Using a system of 28 native Tasmanian Eucalyptus species belonging to two subgenera, Symphyomyrtus and Eucalyptus, we hypothesized that productivity responses to abiotic agents of global change (elevated CO2 and increased soil N) are unique to lineages, but that novel interactions with a non-native species mediate these responses. We tested this hypothesis by examining productivity of 1) native species monocultures and 2) mixtures of native species with an introduced hardwood plantation species, Eucalyptus nitens, to experimentally manipulated soil N and atmospheric CO2. Consistent with past research, we found that N limits productivity overall, especially in elevated CO2 conditions. However, monocultures of species within the Symphyomyrtus subgenus showed the strongest response to N (gained 127% more total biomass) in elevated CO2 conditions, whereas those within the Eucalyptus subgenus did not respond to N. Root:shoot ratio (an indicator of resource use) was on average greater in species pairs containing Symphyomyrtus species, suggesting that functional traits important for resource uptake are phylogenetically conserved and explaining the phylogenetic pattern in plant response to changing environmental conditions. Yet, native species mixtures with E. nitens exhibited responses to CO2 and N that differed from those of monocultures, supporting our hypothesis and highlighting that both plant

  9. Determination of the Dzyaloshinskii Moriya interaction for various hetero-structure (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    You, Chun-Yeol

    2016-10-01

    We investigated non-reciprocal spin wave (SW) dispersion relations by using Brillouin Light Scattering (BLS) in inversion symmetry breaking heterostructures. The non-reciprocal SW dispersion relation is a fingerprint of the existence of asymmetric exchange coupling, Dzyaloshinskii-Moriya Interaction (DMI). The quantification of DMI is important, because it is an essential ingredient of the domain wall motion and skyrmion based logic devices. We obtained DMI energy densities of various NM1/ferromagnetic(Co, CoFeB)/NM2 structures, where NM1,2 are non-magnetic heavy metals (Pt, Ir, Ta) or insulators (MgO, AlOx). We revealed that DMI is proportional to the inverse of ferromagnetic layer thickness, which strong evidence of interface nature of DMI in the heterostructure. In order to exclude the possible source of non-reciprocal SW dispersions, we carefully examined DMI with three independent measurement methods, field strength dependence, SW wave vector magnitude dependence, and SW propagating angle dependences, and found all three measurements gave the same results. It implies our measurement results are more reliable compared with other methods. We also found that sign and strength are sensitive function of materials, interface qualities, layer orders, and annealing conditions. Since the strong spin-orbit coupling (SOC) between ferromagnetic and the heavy metal layers is a source DMI, we also investigated SOC related quantities such as perpendicular magnetic anisotropy, magneto-optical Kerr effect, and spin pumpings. And we found that the relation between SOC and DMI is not the same with other SOC-related physical quantities.

  10. Interactive effects of herbivory and competition intensity determine invasive plant performance.

    PubMed

    Huang, Wei; Carrillo, Juli; Ding, Jianqing; Siemann, Evan

    2012-10-01

    Herbivory can reduce plant fitness, and its effects can be increased by competition. Though numerous studies have examined the joint effects of herbivores and competitors on plant performance, these interactive effects are seldom considered in the context of plant invasions. Here, we examined variation in plant performance within a competitive environment in response to both specialist and generalist herbivores using Chinese tallow as a model species. We combined tallow plants from native and invasive populations to form all possible pairwise combinations, and designated invasive populations as stronger neighbours and native populations as weaker neighbours. We found that when no herbivory was imposed, invasive populations always had higher total biomass than natives, regardless of their neighbours, which is consistent with our assumption of increased competitive ability. Defoliation by either generalist or specialist herbivores suppressed plant growth but the effects of specialists were generally stronger for invasive populations. Invasive populations had their lowest biomass when fed upon by specialists while simultaneously competing with stronger neighbours. The root/shoot ratios of invasive populations were lower than those of native populations under almost all conditions, and invasive plants were taller than native plants overall, especially when herbivores were present, suggesting that invasive populations may adopt an "aboveground first" strategy to cope with herbivory and competition. These results suggest that release from herbivores, especially specialists, improves an invader's performance and helps to increase its competitive ability. Therefore, increasing interspecific competition intensity by planting a stronger neighbour while simultaneously releasing a specialist herbivore may be an especially effective method of managing invasive plants.

  11. HIV-1 Capsid-Cyclophilin Interactions Determine Nuclear Import Pathway, Integration Targeting and Replication Efficiency

    PubMed Central

    Schaller, Torsten; Ocwieja, Karen E.; Rasaiyaah, Jane; Price, Amanda J.; Brady, Troy L.; Roth, Shoshannah L.; Hué, Stéphane; Fletcher, Adam J.; Lee, KyeongEun; KewalRamani, Vineet N.; Noursadeghi, Mahdad; Jenner, Richard G.; James, Leo C.; Bushman, Frederic D.; Towers, Greg J.

    2011-01-01

    Lentiviruses such as HIV-1 traverse nuclear pore complexes (NPC) and infect terminally differentiated non-dividing cells, but how they do this is unclear. The cytoplasmic NPC protein Nup358/RanBP2 was identified as an HIV-1 co-factor in previous studies. Here we report that HIV-1 capsid (CA) binds directly to the cyclophilin domain of Nup358/RanBP2. Fusion of the Nup358/RanBP2 cyclophilin (Cyp) domain to the tripartite motif of TRIM5 created a novel inhibitor of HIV-1 replication, consistent with an interaction in vivo. In contrast to CypA binding to HIV-1 CA, Nup358 binding is insensitive to inhibition with cyclosporine, allowing contributions from CypA and Nup358 to be distinguished. Inhibition of CypA reduced dependence on Nup358 and the nuclear basket protein Nup153, suggesting that CypA regulates the choice of the nuclear import machinery that is engaged by the virus. HIV-1 cyclophilin-binding mutants CA G89V and P90A favored integration in genomic regions with a higher density of transcription units and associated features than wild type virus. Integration preference of wild type virus in the presence of cyclosporine was similarly altered to regions of higher transcription density. In contrast, HIV-1 CA alterations in another patch on the capsid surface that render the virus less sensitive to Nup358 or TRN-SR2 depletion (CA N74D, N57A) resulted in integration in genomic regions sparse in transcription units. Both groups of CA mutants are impaired in replication in HeLa cells and human monocyte derived macrophages. Our findings link HIV-1 engagement of cyclophilins with both integration targeting and replication efficiency and provide insight into the conservation of viral cyclophilin recruitment. PMID:22174692

  12. Geometry of simple molecules: nonbonded interactions, not bonding orbitals, and primarily determine observed geometries.

    PubMed

    See, R F; Dutoi, A D; McConnell, K W; Naylor, R M

    2001-03-28

    The forces responsible for the observed geometries of the YX(3) (Y = N or P; X = H, F, or Cl) molecules were studied through ab initio computations at the HF-SCF/6-31G level. The calculated molecular orbitals were grouped as contributing primarily to (a) the covalent bonds, (b) the terminal atom nonbonding electrons (for X = F or Cl), and (c) the central atom nonbonding electrons. This grouping was accomplished through 3-D plotting and an atomic population analysis of the molecular orbitals. The molecules were then moved through a X-Y-X angular range from 90 degrees to 119 degrees, in four or five degree increments. Single-point calculations were done at each increment, so as to quantify the energy changes in the molecular orbital groups as a function of geometry. These calculations show that the nonbonding electrons are much more sensitive to geometry change than are the bonding orbitals, particularly in the trihalide compounds. The molecular orbitals representing the nonbonding electrons on the terminal atoms (both valence and core electrons) contribute to the spreading forces, as they favor a wider X-Y-X angle. The contracting forces, which favor a smaller X-Y-X angle, consist of the orbitals comprising the nonbonding electrons on the central atom (again, both valence and core electrons). The observed geometry is seen as the balance point between these two sets of forces. A simple interaction-distance model of spreading and contracting forces supports this hypothesis. Highly linear trends are obtained for both the nitrogen trihalides (R(2) = 0.981) and phosphorus trihalides (R(2) = 0.992) when the opposing forces are plotted against each other. These results suggest that a revision of the popular conceptual models (hybridization and VSEPR) of molecular geometry might be appropriate.

  13. Tree species identity and interactions with neighbors determine nutrient leaching in model tropical forests.

    PubMed

    Ewel, John J; Bigelow, Seth W

    2011-12-01

    An ecosystem containing a mixture of species that differ in phenology, morphology, and physiology might be expected to resist leaching of soil nutrients to a greater extent than one composed of a single species. We tested the effects of species identity and plant-life-form richness on nutrient leaching at a lowland tropical site where deep infiltration averages >2 m year(-1). Three indigenous tree species with contrasting leafing phenologies (evergreen, dry-season deciduous, and wet-season deciduous) were grown in monoculture and together with two other life-forms with which they commonly occur in tropical forests: a palm and a giant, perennial herb. To calculate nutrient leaching over an 11-year period, concentrations of nutrients in soil water were multiplied by drainage rates estimated from a water balance. The effect of plant-life-form richness on retention differed according to tree species identity and nutrient. Nitrate retention was greater in polycultures of the dry-season deciduous tree species (mean of 7.4 kg ha(-1) year(-1) of NO(3)-N lost compared to 12.7 in monoculture), and calcium and magnesium retention were greater in polycultures of the evergreen and wet-season deciduous tree species. Complementary use of light led to intensification of soil exploitation by roots, the main agent responsible for enhanced nutrient retention in some polycultures. Other mechanisms included differences in nutrient demand among species, and avoidance of catastrophic failure due to episodic weather events or pest outbreaks. Even unrealistically simple multi-life-form mimics of tropical forest can safeguard a site's nutrient capital if careful attention is paid to species' characteristics and temporal changes in interspecific interactions.

  14. A new predictive model for determining solar wind-terrestrial planet interactions

    NASA Technical Reports Server (NTRS)

    Spreiter, J. R.; Stahara, S. S.

    1980-01-01

    A computational model has been developed for the determination of the gasdynamic and magnetic field properties of the solar wind flow around a magnetic planet, such as the earth, or a nonmagnetic planet, such as Venus. The procedures are based on an established single-fluid, steady, dissipationless, magnetogasdynamic model and are appropriate for the calculation of axisymmetric, supersonic, super-Alfvenic solar wind flow past a planetary magneto/ionosphere. Sample results are reported for a variety of solar wind and planetary conditions. Some of these are new applications; others are included to show that the new procedures produce the same results as previous procedures when applied to the same conditions. The new methods are completely automated and much more efficient and versatile than those employed heretofore.

  15. A new predictive model for determining solar wind-terrestrial planet interactions

    NASA Technical Reports Server (NTRS)

    Spreiter, J. R.; Stahara, S. S.

    1980-01-01

    A computational model has been developed for the determination of the gasdynamic and magnetic field properties of the solar wind flow around a magnetic planet, such as the earth, or a nonmagnetic planet, such as Venus. The procedures are based on an established single-fluid, steady, dissipationless, magnetogasdynamic model and are appropriate for the calculation of axisymmetric, supersonic, super-Alfvenic solar wind flow past a planetary magneto/ionosphere. Sample results are reported for a variety of solar wind and planetary conditions. Some of these are new applications; others are included to show that the new procedures produce the same results as previous procedures when applied to the same conditions. The new methods are completely automated and much more efficient and versatile than those employed heretofore.

  16. Vibrational spectroscopic determination of local solvent electric field, solute-solvent electrostatic interaction energy, and their fluctuation amplitudes.

    PubMed

    Lee, Hochan; Lee, Gayeon; Jeon, Jonggu; Cho, Minhaeng

    2012-01-12

    IR probes have been extensively used to monitor local electrostatic and solvation dynamics. Particularly, their vibrational frequencies are highly sensitive to local solvent electric field around an IR probe. Here, we show that the experimentally measured vibrational frequency shifts can be inversely used to determine local electric potential distribution and solute-solvent electrostatic interaction energy. In addition, the upper limits of their fluctuation amplitudes are estimated by using the vibrational bandwidths. Applying this method to fully deuterated N-methylacetamide (NMA) in D(2)O and examining the solvatochromic effects on the amide I' and II' mode frequencies, we found that the solvent electric potential difference between O(═C) and D(-N) atoms of the peptide bond is about 5.4 V, and thus, the approximate solvent electric field produced by surrounding water molecules on the NMA is 172 MV/cm on average if the molecular geometry is taken into account. The solute-solvent electrostatic interaction energy is estimated to be -137 kJ/mol, by considering electric dipole-electric field interaction. Furthermore, their root-mean-square fluctuation amplitudes are as large as 1.6 V, 52 MV/cm, and 41 kJ/mol, respectively. We found that the water electric potential on a peptide bond is spatially nonhomogeneous and that the fluctuation in the electrostatic peptide-water interaction energy is about 10 times larger than the thermal energy at room temperature. This indicates that the peptide-solvent interactions are indeed important for the activation of chemical reactions in aqueous solution.

  17. Comparison Between Interactive Closest Point and Procrustes Analysis for Determining the Median Sagittal Plane of Three-Dimensional Facial Data.

    PubMed

    Xiong, Yuxue; Zhao, Yijiao; Yang, Huifang; Sun, Yucun; Wang, Yong

    2016-03-01

    To compare 2 digital methods to determine median sagittal plane of three-dimensional facial data-the interactive closest point algorithm and Procrustes analysis. The three-dimensional facial data of the 30 volunteers were got by the Face Scan 3D optical sensor (3D-Shape GmbH, Erlangen, Germany), and then were input to the reverse engineering software Imageware 13.0 (Siemens, Plano, TX) and Geomagic 2012 (Cary, NC). Their mirrored data were acquired and superimposed with the original data by the methods of interactive closest points and Procrustes analysis. The median sagittal planes of the 2 methods were extracted from the original and mirrored facial data respectively, 3 asymmetry indices were measured for comparison. Differences between the facial asymmetry indices of the 2 methods were evaluated using the paired sample t-test. In terms of the 3 asymmetry indices, there were no significant differences between interactive closest points and Procrustes analysis for extracting median sagittal plane from three-dimensional facial data.(t = 0.0.060, P = 0.953 for asymmetry index (AI) 1, t = -0.926, P = 0.362 for AI 2, t = 1.1172, P = 0.0.251 for AI 3). In this evaluation of 30 subjects, the Procrustes analysis and the interactive closest point median-sagittal planes were similar in terms of the 3 asymmetry indices. Thus, Procrustes analysis and interactive closest point can both be used to abstract median sagittal plane from three-dimensional facial data.

  18. [Effect of ligand concentration on the precision of determining the parameters of ligand-receptor interaction by serial dilution methods].

    PubMed

    Bobrovnik, S A

    2004-01-01

    Earlier we suggested the method of serial dilution, which allows one to determine the parameters of ligand-receptor interaction even if the reactants are in a mixture and their concentrations are unknown. The method is especially useful if the liability of studied receptor does not allow its separation from corresponding ligand. The important prerequisite of the method's precision is that the concentration of the ligand should be sufficiently high comparing to the concentration of the receptor. In the present paper it was demonstrated that the method allows one to obtain sufficiently good precision even in the case when the concentration of the ligand is only one tenth of the receptor concentration.

  19. Determining Phosphorus-sediment Interactions in a Groundwater-fed River through In Situ Measurement

    NASA Astrophysics Data System (ADS)

    Mullinger, N. J.; Heathwaite, L.; Zhang, H.; Keenan, P. O.

    2011-12-01

    In stream processing is potentially important in the regulation and availability of nutrients to riverine flora and also in attenuating point and non-point source inputs to rivers, such as wastewater outflows and agricultural runoff. Phosphorus is an important macronutrient and often cited as a limiting factor to plant and algal growth in freshwater systems. The particle-reactive nature of the orthophosphate anion means that river sediments can play an important role in phosphorus attenuation and availability in rivers. However, it is also known that plant root exudates can also affect the mobilisation of sediment adsorbed phosphorus. Results are presented from high resolution (centimetre) measurements of vertical riverbed pore water profiles at a field site in the River Leith, Cumbria, UK. The River Leith is a sub-catchment of the River Eden and is characterised by significant groundwater-surface water interactions at the monitoring site. In situ measurements of soluble reactive phosphorus (SRP) in riverbed pore waters were made using passive sampling diffusive gradient and diffusive equilibration in thin film (DGT and DET) probes. These probes allow in situ measurements of riverbed pore waters to be made to a depth of 30 cm below the riverbed at centimetre resolution. The resulting profiles provide information on the variability in phosphorus pore waters for vegetated and non-vegetated regions of the riverbed. The impact of vegetated root zones in riverbed sediments is poorly characterised for hyporheic exchanges. Comparison of the vertical profiles obtained by DGT and DET probes identifies the potential of sediments to act sources or sinks of in stream phosphorus. Simultaneous analysis for redox sensitive elements provides additional information on the redox status of riverbed sediments. Initial results show spatial and temporal variability of phosphorus in different sedimentary environments and also between vegetated and non-vegetated areas of the riverbed

  20. The behavior of multiple independent managers and ecological traits interact to determine prevalence of weeds.

    PubMed

    Coutts, Shaun R; Yokomizo, Hiroyuki; Buckley, Yvonne M

    2013-04-01

    Management of damaging invasive plants is often undertaken by multiple decision makers, each managing only a small part of the invader's population. As weeds can move between properties and re-infest eradicated sites from unmanaged sources, the dynamics of multiple decision makers plays a significant role in weed prevalence and invasion risk at the landscape scale. We used a spatially explicit agent-based simulation to determine how individual agent behavior, in concert with weed population ecology, determined weed prevalence. We compared two invasive grass species that differ in ecology, control methods, and costs: Nassella trichotoma (serrated tussock) and Eragrostis curvula (African love grass). The way decision makers reacted to the benefit of management had a large effect on the extent of a weed. If benefits of weed control outweighed the costs, and either net benefit was very large or all agents were very sensitive to net benefits, then agents tended to act synchronously, reducing the pool of infested agents available to spread the weed. As N. trichotoma was more damaging than E. curvula and had more effective control methods, agents chose to manage it more often, which resulted in lower prevalence of N. trichotoma. A relatively low number of agents who were intrinsically less motivated to control weeds led to increased prevalence of both species. This was particularly apparent when long-distance dispersal meant each infested agent increased the invasion risk for a large portion of the landscape. In this case, a small proportion of land mangers reluctant to control, regardless of costs and benefits, could lead to the whole landscape being infested, even when local control stopped new infestations. Social pressure was important, but only if it was independent of weed prevalence, suggesting that early access to information, and incentives to act on that information, may be crucial in stopping a weed from infesting large areas. The response of our model to both

  1. Genetic determinants of cardiometabolic risk: a proposed model for phenotype association and interaction.

    PubMed

    Blackett, Piers R; Sanghera, Dharambir K

    2013-01-01

    This review provides a translational and unifying summary of metabolic syndrome genetics and highlights evidence that genetic studies are starting to unravel and untangle origins of the complex and challenging cluster of disease phenotypes. The associated genes effectively express in the brain, liver, kidney, arterial endothelium, adipocytes, myocytes, and β cells. Progression of syndrome traits has been associated with ectopic lipid accumulation in the arterial wall, visceral adipocytes, myocytes, and liver. Thus, it follows that the genetics of dyslipidemia, obesity, and nonalcoholic fatty liver disease are central in triggering progression of the syndrome to overt expression of disease traits and have become a key focus of interest for early detection and for designing prevention and treatments. To support the "birds' eye view" approach, we provide a road-map depicting commonality and interrelationships between the traits and their genetic and environmental determinants based on known risk factors, metabolic pathways, pharmacologic targets, treatment responses, gene networks, pleiotropy, and association with circadian rhythm. Although only a small portion of the known heritability is accounted for and there is insufficient support for clinical application of gene-based prediction models, there is direction and encouraging progress in a rapidly moving field that is beginning to show clinical relevance.

  2. Epithelial-macrophage interactions determine pulmonary fibrosis susceptibility in Hermansky-Pudlak syndrome

    PubMed Central

    Young, Lisa R.; Gulleman, Peter M.; Short, Chelsi W.; Tanjore, Harikrishna; Sherrill, Taylor; Qi, Aidong; McBride, Andrew P.; Zaynagetdinov, Rinat; Benjamin, John T.; Lawson, William E.; Novitskiy, Sergey V.; Blackwell, Timothy S.

    2016-01-01

    Alveolar epithelial cell (AEC) dysfunction underlies the pathogenesis of pulmonary fibrosis in Hermansky-Pudlak syndrome (HPS) and other genetic syndromes associated with interstitial lung disease; however, mechanisms linking AEC dysfunction and fibrotic remodeling are incompletely understood. Since increased macrophage recruitment precedes pulmonary fibrosis in HPS, we investigated whether crosstalk between AECs and macrophages determines fibrotic susceptibility. We found that AECs from HPS mice produce excessive MCP-1, which was associated with increased macrophages in the lungs of unchallenged HPS mice. Blocking MCP-1/CCR2 signaling in HPS mice with genetic deficiency of CCR2 or targeted deletion of MCP-1 in AECs normalized macrophage recruitment, decreased AEC apoptosis, and reduced lung fibrosis in these mice following treatment with low-dose bleomycin. We observed increased TGF-β production by HPS macrophages, which was eliminated by CCR2 deletion. Selective deletion of TGF-β in myeloid cells or of TGF-β signaling in AECs through deletion of TGFBR2 protected HPS mice from AEC apoptosis and bleomycin-induced fibrosis. Together, these data reveal a feedback loop in which increased MCP-1 production by dysfunctional AECs results in recruitment and activation of lung macrophages that produce TGF-β, thus amplifying the fibrotic cascade through AEC apoptosis and stimulation of fibrotic remodeling. PMID:27777976

  3. Selective determination of thiram residues in fruit and vegetables by hydrophilic interaction LC-MS.

    PubMed

    Ringli, Daniela; Schwack, Wolfgang

    2013-01-01

    Thiram belongs to the most important class of dithiocarbamate (DTC) fungicides including dimethyldithiocarbamates (DMDs), ethylenebis(dithiocarbamtes) (EBDs) and propylenebis(dithiocarbamates) (PBDs). During the surface extraction of fruit and vegetables for the LC-MS determination of residues of DMDs, EBDs and PBDs, thiram is reduced by the penicillamine buffer to the DMD anion, thus resulting in false-positive findings of DMD fungicides like ziram. Therefore, an alkaline sulfite buffer was applied for surface extraction, quantitatively transforming thiram into the DMD anion and a stable DMD-sulfite adduct that was used as a selective marker for thiram. Separation was performed isocratically on a ZIC-pHILIC column with acetonitrile-10 mM ammonium hydroxide solution (85/15). Mass selective detection was carried out on a single-quadrupole mass spectrometer coupled to an electrospray ionisation interface operating in negative mode. Using d12-thiram as the internal standard, recoveries of 80-108% were obtained from apples, tomatoes, grapes and sweet peppers, spiked in the range of 0.02-1 mg kg(-1). Limits of detection and quantification were 0.6 and 2 µg kg(-1), respectively.

  4. Human and Helicobacter pylori Interactions Determine the Outcome of Gastric Diseases

    PubMed Central

    Gobert, Alain P.; Wilson, Keith T.

    2017-01-01

    The innate immune response is a critical hallmark of Helicobacter pylori infection. Epithelial and myeloid cells produce effectors, including the chemokine CXCL8, reactive oxygen species (ROS), and nitric oxide (NO), in response to bacterial components. Mechanistic and epidemiologic studies have emphasized that dysregulated and persistent release of these products leads to the development of chronic inflammation and to the molecular and cellular events related to carcinogenesis. Moreover, investigations in H. pylori-infected patients about polymorphisms of the genes encoding CXCL8 and inducible NO synthase, and epigenetic control of the ROS-producing enzyme spermine oxidase, have further proven that overproduction of these molecules impacts the severity of gastric diseases. Lastly, the critical effect of the crosstalk between the human host and the infecting bacterium in determining the severity of H. pylori-related diseases has been supported by phylogenetic analysis of the human population and their H. pylori isolates in geographic areas with varying clinical and pathologic outcomes of the infection. PMID:28124148

  5. Plasmid ColE1 incompatibility determined by interaction of RNA I with primer transcript.

    PubMed Central

    Tomizawa, J; Itoh, T

    1981-01-01

    Mutants of plasmid pNT7 that can coexist with plasmid pMB9 in growing bacteria have been isolated. These mutants show altered incompatibility properties and increased copy numbers. Each mutant has a single base change at or near the center of one of the three palindromes in the region that specifies two RNA species: a larger one (primer transcripts) that provides a primer for DNA replication and a smaller one (RNA I) that is the incompatibility-specific inhibitor of primer formation. In vitro transcription studies show that the single base changes affect both the ability of RNA I to inhibit primer formation and the sensitivity of primer formation to inhibition by RNA I. RNA I hybridizes to the primer transcript, and the rate of hybridization is reduced by the single base changes. Based on analyses of inhibition of in vitro primer formation by RNA I and of in vivo properties of the mutant plasmids, we conclude that incompatibility between two plasmids can be attributed to inhibition of primer formation on one of the plasmids by the RNA I of the other. Inhibition of primer formation by RNA I appears to be the mechanism that determines the copy number of pNT7 and its derivatives. Images PMID:6171811

  6. Spectroscopic studies on the interaction between norfloxacin and p-amino benzoic acid: Analytical application on determination of norfloxacin

    NASA Astrophysics Data System (ADS)

    More, V. R.; Mote, U. S.; Patil, S. R.; Kolekar, G. B.

    2009-10-01

    Fluorescence (Förster) Resonance Energy Transfer (FRET) between norfloxacin (NF) and p-amino benzoic acid (PABA) has been investigated by fluorescence and UV-vis absorption spectroscopy. It was found that the quenching of fluorescence of PABA is followed by simultaneous sensitization of NF fluorescence. The hydrophobic and electrostatic interaction plays an important role to stabilize the complex. The binding constant ( K), binding site number ( n) and corresponding thermodynamic parameters like free energy change (Δ G), enthalpy change (Δ H) and entropy change (Δ S) were determined according to van't Hoff equation. Using FRET, the distance ( r) between donor (PABA) and acceptor (NF) was obtained. This method is simple, selective and relatively free of interference from co-existing substances. The method was successfully applied to the determination of norfloxacin from pharmaceutical tablets.

  7. Pharmacogenetic determination of the effects of codeine and prediction of drug interactions.

    PubMed

    Caraco, Y; Sheller, J; Wood, A J

    1996-09-01

    To define the differences in codeine pharmacodynamics in extensive (EMs) and poor (PMs) metabolizers of debrisoquin and to determine whether the inhibition of codeine's metabolism by quinidine produces phenotypically dependent pharmacodynamic changes, we studied 16 healthy nonsmoking males, 10 EMs and 6 PMs of debrisoquin. The subjects received in random double-blind fashion 120 mg of codeine plus placebo, 120 mg of codeine plus 100 mg of quinidine and 100 mg of quinidine plus placebo. Blood was obtained over 24 hr and urine was collected for 48 hr. Respiratory, psychomotor and pupillary effects of codeine were greater in the EMs than in the PMs (P < .01). Morphine and morphine metabolites were detectable only in plasma from EMs. Codeine metabolic clearance by O-demethylation was almost 200-fold greater in the EMs than in the PMs. After coadministration of quinidine, morphine and morphine metabolites were not detectable in the plasma of either phenotype and mean (+/- S.E.M.) O-demethylation clearance was reduced in the EMs from 162.7 +/- 36.6 to 17.0 +/- 5.0 ml/min (P < .003), but not in the PMs. The diminished production of morphine in the EMs was associated with significantly reduced respiratory, psychomotor and pupillary effects (P < .01). Thus, CYP2D6 mediated O-demethylation of codeine to morphine is central to its pharmacodynamic effects. Patients who lack CYP2D6 or whose CYP2D6 is inhibited would not be expected to benefit from codeine. Thus, phenotyping for CYP2D6 and the avoidance of CYP2D6 inhibitors is justified in patients with chronic path before initiating long-term therapy with analgesics whose in vivo activation is dependent on CYP2D6 activity (i.e., codeine, hydrocodone and oxycodone.

  8. Questioning the answer: questioning style, choice and self-determination in interactions with young people with intellectual disabilities.

    PubMed

    Pilnick, Alison; Clegg, Jennifer; Murphy, Elizabeth; Almack, Kathryn

    2010-03-01

    For young people with intellectual disabilities (ID), the transition from children's to adult services has long been recognised as a challenging move. One of the aims of the White Paper Valuing People (2001) was to address some of the problems associated with this transition. This paper reports on data from a project which examines the impact of these service changes, and the ways in which transition is negotiated by carers, professionals and users. It presents a conversation analysis of eight tape-recorded formal review meetings at which transition to adult services is discussed. It takes as its starting point the existing interactional work on ID and the way in which this demonstrates the effects of the local and contextual specifics of particular kinds of interaction on the eventual outcomes (e.g. Rapley 2004, Antaki 2001, Maynard and Marlaire 1992). We show that an attempt to allow self-determination in the context of transitions can paradoxically result in undermining user choice and control. We also argue that, while a rule-based approach to practice may offer moral clarity for professionals, it can result in interactional and practical difficulties which cannot be easily reconciled.

  9. Questioning the answer: questioning style, choice and self-determination in interactions with young people with intellectual disabilities*

    PubMed Central

    Pilnick, Alison; Clegg, Jennifer; Murphy, Elizabeth; Almack, Kathryn

    2010-01-01

    For young people with intellectual disabilities (ID), the transition from children's to adult services has long been recognised as a challenging move. One of the aims of the White Paper Valuing People (2001) was to address some of the problems associated with this transition. This paper reports on data from a project which examines the impact of these service changes, and the ways in which transition is negotiated by carers, professionals and users. It presents a conversation analysis of eight tape-recorded formal review meetings at which transition to adult services is discussed. It takes as its starting point the existing interactional work on ID and the way in which this demonstrates the effects of the local and contextual specifics of particular kinds of interaction on the eventual outcomes (e.g. Rapley 2004, Antaki 2001, Maynard and Marlaire 1992). We show that an attempt to allow self-determination in the context of transitions can paradoxically result in undermining user choice and control. We also argue that, while a rule-based approach to practice may offer moral clarity for professionals, it can result in interactional and practical difficulties which cannot be easily reconciled. PMID:20415789

  10. Discovery of potent Keap1-Nrf2 protein-protein interaction inhibitor based on molecular binding determinants analysis.

    PubMed

    Jiang, Zheng-Yu; Lu, Meng-Chen; Xu, Li Li; Yang, Ting-Ting; Xi, Mei-Yang; Xu, Xiao-Li; Guo, Xiao-Ke; Zhang, Xiao-Jin; You, Qi-Dong; Sun, Hao-Peng

    2014-03-27

    Keap1 is known to mediate the ubiquitination of Nrf2, a master regulator of the antioxidant response. Directly interrupting the Keap1-Nrf2 interaction has been emerged as a promising strategy to develop novel class of antioxidant, antiinflammatory, and anticancer agents. On the basis of the molecular binding determinants analysis of Keap1, we successfully designed and characterized the most potent protein-protein interaction (PPI) inhibitor of Keap1-Nrf2, compound 2, with K(D) value of 3.59 nM binding to Keap1 for the first time to single-digit nanomolar. Compound 2 can effectively disrupt the Nrf2-Keap1 interaction with an EC50 of 28.6 nM in the fluorescence polarization assay. It can also activate the Nrf2 transcription activity in the cell-based ARE-luciferase reporter assay in a dose-dependent manner. The qRT-PCR results of Nrf2 transcription targets gave the consistent results. These results confirm direct and highly efficient interruption of the Keap1-Nrf2 PPI can be fully achieved by small molecules.

  11. Reliable Determinations of Protein-Ligand Interactions by Direct ESI-MS Measurements. Are We There Yet?

    NASA Astrophysics Data System (ADS)

    Kitova, Elena N.; El-Hawiet, Amr; Schnier, Paul D.; Klassen, John S.

    2012-03-01

    The association-dissociation of noncovalent interactions between protein and ligands, such as other proteins, carbohydrates, lipids, DNA, or small molecules, are critical events in many biological processes. The discovery and characterization of these interactions is essential to a complete understanding of biochemical reactions and pathways and to the design of novel therapeutic agents that may be used to treat a variety of diseases and infections. Over the last 20 y, electrospray ionization mass spectrometry (ESI-MS) has emerged as a versatile tool for the identification and quantification of protein-ligand interactions in vitro. Here, we describe the implementation of the direct ESI-MS assay for the determination of protein-ligand binding stoichiometry and affinity. Additionally, we outline common sources of error encountered with these measurements and various strategies to overcome them. Finally, we comment on some of the outstanding challenges associated with the implementation of the assay and highlight new areas where direct ESI-MS measurements are expected to make significant contributions in the future.

  12. Determining Effects of Non-synonymous SNPs on Protein-Protein Interactions using Supervised and Semi-supervised Learning

    PubMed Central

    Zhao, Nan; Han, Jing Ginger; Shyu, Chi-Ren; Korkin, Dmitry

    2014-01-01

    Single nucleotide polymorphisms (SNPs) are among the most common types of genetic variation in complex genetic disorders. A growing number of studies link the functional role of SNPs with the networks and pathways mediated by the disease-associated genes. For example, many non-synonymous missense SNPs (nsSNPs) have been found near or inside the protein-protein interaction (PPI) interfaces. Determining whether such nsSNP will disrupt or preserve a PPI is a challenging task to address, both experimentally and computationally. Here, we present this task as three related classification problems, and develop a new computational method, called the SNP-IN tool (non-synonymous SNP INteraction effect predictor). Our method predicts the effects of nsSNPs on PPIs, given the interaction's structure. It leverages supervised and semi-supervised feature-based classifiers, including our new Random Forest self-learning protocol. The classifiers are trained based on a dataset of comprehensive mutagenesis studies for 151 PPI complexes, with experimentally determined binding affinities of the mutant and wild-type interactions. Three classification problems were considered: (1) a 2-class problem (strengthening/weakening PPI mutations), (2) another 2-class problem (mutations that disrupt/preserve a PPI), and (3) a 3-class classification (detrimental/neutral/beneficial mutation effects). In total, 11 different supervised and semi-supervised classifiers were trained and assessed resulting in a promising performance, with the weighted f-measure ranging from 0.87 for Problem 1 to 0.70 for the most challenging Problem 3. By integrating prediction results of the 2-class classifiers into the 3-class classifier, we further improved its performance for Problem 3. To demonstrate the utility of SNP-IN tool, it was applied to study the nsSNP-induced rewiring of two disease-centered networks. The accurate and balanced performance of SNP-IN tool makes it readily available to study the rewiring of

  13. Development and validation of a hydrophilic interaction liquid chromatographic method for determination of aromatic amines in environmental water.

    PubMed

    Li, Ruiping; Zhang, Yi; Lee, Charles C; Lu, Rongrong; Huang, Yingping

    2010-03-12

    A simple, precise, and accurate hydrophilic interaction liquid chromatographic (HILIC) method has been developed for the determination of five aromatic amines in environmental water samples. Chromatography was carried out on a bare silica column, using a mixture of acetonitrile and a buffer of NaH(2)PO(4)-H(3)PO(4) (pH 1.5, containing 10mM NaH(2)PO(4)) (85:15, v/v) as a mobile phase at a flow rate of 1 mL min(-1). Aromatic amines were detected by UV absorbance at 254 nm. The linear range of amines was good (r(2)>0.998) and limit of detection (LOD) within 0.02-0.2 mg L(-1) (S/N=3). The retention mechanism for the analytes under the optimum conditions was determined to be a combination of adsorption, partition and ionic interactions. The proposed method was applied to the environmental water samples. Aromatic amines were isolated from aqueous samples using solid-phase extraction (SPE) with Oasis HLB cartridges. Recoveries of greater than 75% with precision (RSD) less than 12% were obtained at amine concentrations of 5-50 microg L(-1) from 100mL river water and influents from a wastewater treatment plant (WWTP). The present HILIC technique proved to be a viable method for the analysis of aromatic amines in the environmental water samples.

  14. Determination of Rate Constants and Equilibrium Constants for Solution-Phase Drug–Protein Interactions by Ultrafast Affinity Extraction

    PubMed Central

    2015-01-01

    A method was created on the basis of ultrafast affinity extraction to determine both the dissociation rate constants and equilibrium constants for drug–protein interactions in solution. Human serum albumin (HSA), an important binding agent for many drugs in blood, was used as both a model soluble protein and as an immobilized binding agent in affinity microcolumns for the analysis of free drug fractions. Several drugs were examined that are known to bind to HSA. Various conditions to optimize in the use of ultrafast affinity extraction for equilibrium and kinetic studies were considered, and several approaches for these measurements were examined. The dissociation rate constants obtained for soluble HSA with each drug gave good agreement with previous rate constants reported for the same drugs or other solutes with comparable affinities for HSA. The equilibrium constants that were determined also showed good agreement with the literature. The results demonstrated that ultrafast affinity extraction could be used as a rapid approach to provide information on both the kinetics and thermodynamics of a drug–protein interaction in solution. This approach could be extended to other systems and should be valuable for high-throughput drug screening or biointeraction studies. PMID:24911267

  15. Determination of dopamine hydrochloride by host-guest interaction based on water-soluble pillar[5]arene

    NASA Astrophysics Data System (ADS)

    Xiao, Xue-Dong; Shi, Lin; Guo, Li-Hui; Wang, Jun-Wen; Zhang, Xiang

    2017-02-01

    The supramolecular interaction between the water-soluble pillar[5]arene (WP[5]) as host and dopamine hydrochloride (DH) as guest was studied by spectrofluorometry. The fluorescence intensity of DH gradually decreased with increasing WP[5] concentration, and the possible interaction mechanism between WP[5] and DH was confirmed by 1H NMR, 2D NOESY, and molecular modelling. Based on significant DH fluorescence, a highly sensitive and selective method for DH determination was developed for the first time. The fluorescence intensity was measured at 312 nm, with excitation at 285 nm. The effects of pH, temperature, and reaction time on the fluorescence spectra of the WP[5]-DH complex were investigated. A linear relationship between fluorescence intensity and DH concentration in the range of 0.07-6.2 μg mL- 1 was obtained. The corresponding linear regression equation is ΔF = 25.76 C + 13.56 (where C denotes the concentration in μg mL- 1), with the limit of detection equal to 0.03 μg mL- 1 and the correlation coefficient equal to 0.9996. This method can be used for the determination of dopamine in injection and urine samples. In addition, the WP[5]-DH complex has potential applications in fluorescent sensing and pharmacokinetics studies of DH.

  16. Determination of rate constants and equilibrium constants for solution-phase drug-protein interactions by ultrafast affinity extraction.

    PubMed

    Zheng, Xiwei; Li, Zhao; Podariu, Maria I; Hage, David S

    2014-07-01

    A method was created on the basis of ultrafast affinity extraction to determine both the dissociation rate constants and equilibrium constants for drug-protein interactions in solution. Human serum albumin (HSA), an important binding agent for many drugs in blood, was used as both a model soluble protein and as an immobilized binding agent in affinity microcolumns for the analysis of free drug fractions. Several drugs were examined that are known to bind to HSA. Various conditions to optimize in the use of ultrafast affinity extraction for equilibrium and kinetic studies were considered, and several approaches for these measurements were examined. The dissociation rate constants obtained for soluble HSA with each drug gave good agreement with previous rate constants reported for the same drugs or other solutes with comparable affinities for HSA. The equilibrium constants that were determined also showed good agreement with the literature. The results demonstrated that ultrafast affinity extraction could be used as a rapid approach to provide information on both the kinetics and thermodynamics of a drug-protein interaction in solution. This approach could be extended to other systems and should be valuable for high-throughput drug screening or biointeraction studies.

  17. Progenitor/Stem Cell Fate Determination: Interactive Dynamics of Cell Cycle and Microvesicles

    PubMed Central

    Lee, David; Puente, Napoleon; Faradyan, Sam; Sears, Edmund H.; Amaral, Ashley; Goldberg, Laura; Dooner, Mark S.; Pereira, Mandy; Quesenberry, Peter J.

    2012-01-01

    We have shown that hematopoietic stem/progenitor cell phenotype and differentiative potential change throughout cell cycle. Lung-derived microvesicles (LDMVs) also change marrow cell phenotype by inducing them to express pulmonary epithelial cell-specific mRNA and protein. These changes are accentuated when microvesicles isolated from injured lung. We wish to determine if microvesicle-treated stem/progenitor cell phenotype is linked to cell cycle and to the injury status of the lung providing microvesicles. Lineage depleted, Sca-1+ (Lin-/Sca-1+) marrow isolated from mice were cultured with interleukin 3 (IL-3), IL-6, IL-11, and stem cell factor (cytokine-cultured cells), removed at hours zero (cell cycle phase G0/G1), 24 (late G1/early S), and 48 (late S/early G2/M), and cocultured with lung tissue, lung conditioned media (LCM), or LDMV from irradiated or nonirradiated mice. Alternatively, Lin-/Sca-1+ cells not exposed to exogenous cytokines were separated into G0/G1 and S/G2/M cell cycle phase populations by fluorescence-activated cell sorting (FACS) and used in coculture. Separately, LDMV from irradiated and nonirradiated mice were analyzed for the presence of adhesion proteins. Peak pulmonary epithelial cell-specific mRNA expression was seen in G0/G1 cytokine-cultured cells cocultured with irradiated lung and in late G1/early S cells cocultured with nonirradiated lung. The same pattern was seen in cytokine-cultured Lin-/Sca-1 cells cocultured with LCM and LDMV and when FACS-separated Lin-/Sca-1 cells unexposed to exogenous cytokines were used in coculture. Cells and LDMV expressed adhesion proteins whose levels differed based on cycle status (cells) or radiation injury (LDMV), suggesting a mechanism for microvesicle entry. These data demonstrate that microvesicle modification of progenitor/stem cells is influenced by cell cycle and the treatment of the originator lung tissue. PMID:22214238

  18. Interaction of lipocalin 2, transferrin, and siderophores determines the replicative niche of Klebsiella pneumoniae during pneumonia.

    PubMed

    Bachman, Michael A; Lenio, Steven; Schmidt, Lindsay; Oyler, Jennifer E; Weiser, Jeffrey N

    2012-11-20

    severe disease. Accordingly, the host defense protein lipocalin 2 exploits this common target by binding enterobactin and disrupting its function. However, pathogenic bacteria often make additional siderophores that lipocalin 2 cannot bind, such as yersiniabactin, which could make this host defense ineffective. This work compares the pattern and severity of pneumonia caused by K. pneumoniae based on which siderophores it produces. The results indicate that enterobactin promotes growth around blood vessels that are rich in the iron-binding protein transferrin, but yersiniabactin does not. Together, transferrin and lipocalin 2 protect this space against all types of K. pneumoniae tested. Therefore, the ability to acquire iron determines where bacteria can grow in the lung.

  19. Characterizing the Coding Region Determinant-Binding Protein (CRD-BP)-Microphthalmia-associated Transcription Factor (MITF) mRNA interaction.

    PubMed

    Rensburg, Gerrit van; Mackedenski, Sebastian; Lee, Chow H

    2017-01-01

    Coding region determinant-binding protein (CRD-BP) binds to the 3'-UTR of microphthalmia-associated transcription factor (MITF) mRNA to prevent its targeted degradation by miR-340. Here, we aim to further understand the molecular interaction between CRD-BP and MITF RNA. Using point mutation in the GXXG motif of each KH domains, we showed that all four KH domains of CRD-BP are important for their physical association with MITF RNA. We mapped the CRD-BP-binding site in the 3'-UTR of MITF RNA from nts 1330-1740 and showed that the 49-nt fragment 1621-1669 is the minimal size MITF RNA for binding. Upon deletion of nts 1621-1669 within the nts1550-1740 of MITF RNA, there was a 3-fold increase in dissociation constant Kd, which further confirms the critical role sequences within nts 1621-1669 in binding to CRD-BP. Amongst the eight antisense oligonucleotides designed against MITF RNA 1550-1740, we found MHO-1 and MHO-7 as potent inhibitors of the CRD-BP-MITF RNA interaction. Using RNase protection and fluorescence polarization assays, we showed that both MHO-1 and MHO-7 have affinity for the MITF RNA, suggesting that both antisense oligonucleotides inhibited CRD-BP-MITF RNA interaction by directly binding to MITF RNA. The new molecular insights provided in this study have important implications for understanding the oncogenic function of CRD-BP and development of specific inhibitors against CRD-BP-MITF RNA interaction.

  20. A truly human interface: interacting face-to-face with someone whose words are determined by a computer program.

    PubMed

    Corti, Kevin; Gillespie, Alex

    2015-01-01

    We use speech shadowing to create situations wherein people converse in person with a human whose words are determined by a conversational agent computer program. Speech shadowing involves a person (the shadower) repeating vocal stimuli originating from a separate communication source in real-time. Humans shadowing for conversational agent sources (e.g., chat bots) become hybrid agents ("echoborgs") capable of face-to-face interlocution. We report three studies that investigated people's experiences interacting with echoborgs and the extent to which echoborgs pass as autonomous humans. First, participants in a Turing Test spoke with a chat bot via either a text interface or an echoborg. Human shadowing did not improve the chat bot's chance of passing but did increase interrogators' ratings of how human-like the chat bot seemed. In our second study, participants had to decide whether their interlocutor produced words generated by a chat bot or simply pretended to be one. Compared to those who engaged a text interface, participants who engaged an echoborg were more likely to perceive their interlocutor as pretending to be a chat bot. In our third study, participants were naïve to the fact that their interlocutor produced words generated by a chat bot. Unlike those who engaged a text interface, the vast majority of participants who engaged an echoborg did not sense a robotic interaction. These findings have implications for android science, the Turing Test paradigm, and human-computer interaction. The human body, as the delivery mechanism of communication, fundamentally alters the social psychological dynamics of interactions with machine intelligence.

  1. USING MULTIPLE-VIEWPOINT OBSERVATIONS TO DETERMINE THE INTERACTION OF THREE CORONAL MASS EJECTIONS OBSERVED ON 2012 MARCH 5

    SciTech Connect

    Colaninno, Robin C.; Vourlidas, Angelos E-mail: angelos.vourlidas@jhuapl.edu

    2015-12-10

    We examine the interaction of three coronal mass ejections (CMEs) that took place on 2012 March 5 at heights less than 20 R{sub ⊙} in the corona. We used a forward fitting model to reconstruct the three-dimensional trajectories and kinematics of the CMEs and determine their interaction in the observations from three viewpoints: Solar and Heliospheric Observatory (SOHO), STEREO-A, and STEREO-B. The first CME (CME-1), a slow-rising eruption near disk center, is already in progress at 02:45 UT when the second CME (CME-2) erupts from AR 11429 on the east limb. These two CMEs are present in the corona not interacting when a third CME (CME-3) erupts from AR 11429 at 03:34 UT. CME-3 has a constant velocity of 1456[±31] km s{sup −1} and drives a shock that is observed as a halo from all viewpoints. We find that the shock driven by CME-3 passed through CME-1 with no observable change in the geometry, trajectory, or velocity of CME-1. However, the elevated temperatures detected in situ when CME-1 reached Earth indicate that the plasma inside CME-1 may have been heated by the passage of the shock. CME-2 is accelerated by CME-3 to more than twice its initial velocity and remains a separate structure ahead of the CME-3 front. CME-2 is deflected 24° northward by CME-3 for a total deflection of 40° from its source region. These results suggest that the collision of CME-2 and CME-3 is superelastic. This work demonstrates the capability and utility of fitting forward models to complex and interacting CMEs observed in the corona from multiple viewpoints.

  2. Interaction of nalidixic acid and ciprofloxacin with wild type and mutated quinolone-resistance-determining region of DNA gyrase A.

    PubMed

    Vashist, Jitendra; Vishvanath; Kapoor, Renuka; Kapil, Arti; Yennamalli, Ragothaman; Subbarao, N; Rajeswari, Moganty R

    2009-04-01

    The quinolones exert their anti-bacterial activity by binding to DNA gyrase A (GyrA), an essential enzyme in maintenance of DNA topology within bacterial cell. The mutations conferring resistance to quinolones arise within the quinolone-resistance-determining region (QRDR) of GyrA. Therefore, quinolones interaction with wild and mutated GyrA can provide the molecular explanation for resistance. Resistant strains of Salmonella enterica of our hospital have shown mutations in the QRDR of GyrA of serine 83 (to phenylalanine or tyrosine) or aspartic acid 87 (to glycine or tyrosine). In order to understand the association between observed resistance and structural alterations of GyrA with respect to quinolone binding, we have studied the interaction of mutated QRDR of GyrA with nalidixic acid and ciprofloxacin by molecular modeling using GLIDE v4. Analysis of interaction parameters like G-score has revealed reduced interaction between nalidixic acid/ciprofloxacin with QRDR of GyrA in all four mutated cases of resistant strains. The mutation of Ser83 to Phe or Tyr shows least binding for nalidixic acid, while Asp87 to Gly or Tyr exhibits minimal binding for ciprofloxacin. The study also highlights the important role of arginines at 21, 91 and His at 45, which form strong hydrogen bonds (at < 3 A) with quinolones. The hydrophilic OH group of Serine 83, which is in close proximity to the quinolone binding site is replaced by aromatic moieties of Tyr or Phe in mutated GyrA. This replacement leads to steric hindrance for quinolone binding. Therefore, quinolone resistance developed by Salmonella appears to be due to the decreased selectivity and affinity of nalidixic acid/ciprofloxacin to QRDR of GyrA.

  3. A truly human interface: interacting face-to-face with someone whose words are determined by a computer program

    PubMed Central

    Corti, Kevin; Gillespie, Alex

    2015-01-01

    We use speech shadowing to create situations wherein people converse in person with a human whose words are determined by a conversational agent computer program. Speech shadowing involves a person (the shadower) repeating vocal stimuli originating from a separate communication source in real-time. Humans shadowing for conversational agent sources (e.g., chat bots) become hybrid agents (“echoborgs”) capable of face-to-face interlocution. We report three studies that investigated people’s experiences interacting with echoborgs and the extent to which echoborgs pass as autonomous humans. First, participants in a Turing Test spoke with a chat bot via either a text interface or an echoborg. Human shadowing did not improve the chat bot’s chance of passing but did increase interrogators’ ratings of how human-like the chat bot seemed. In our second study, participants had to decide whether their interlocutor produced words generated by a chat bot or simply pretended to be one. Compared to those who engaged a text interface, participants who engaged an echoborg were more likely to perceive their interlocutor as pretending to be a chat bot. In our third study, participants were naïve to the fact that their interlocutor produced words generated by a chat bot. Unlike those who engaged a text interface, the vast majority of participants who engaged an echoborg did not sense a robotic interaction. These findings have implications for android science, the Turing Test paradigm, and human–computer interaction. The human body, as the delivery mechanism of communication, fundamentally alters the social psychological dynamics of interactions with machine intelligence. PMID:26042066

  4. Characterizing the Coding Region Determinant-Binding Protein (CRD-BP)-Microphthalmia-associated Transcription Factor (MITF) mRNA interaction

    PubMed Central

    2017-01-01

    Coding region determinant-binding protein (CRD-BP) binds to the 3’-UTR of microphthalmia-associated transcription factor (MITF) mRNA to prevent its targeted degradation by miR-340. Here, we aim to further understand the molecular interaction between CRD-BP and MITF RNA. Using point mutation in the GXXG motif of each KH domains, we showed that all four KH domains of CRD-BP are important for their physical association with MITF RNA. We mapped the CRD-BP-binding site in the 3’-UTR of MITF RNA from nts 1330–1740 and showed that the 49-nt fragment 1621–1669 is the minimal size MITF RNA for binding. Upon deletion of nts 1621–1669 within the nts1550-1740 of MITF RNA, there was a 3-fold increase in dissociation constant Kd, which further confirms the critical role sequences within nts 1621–1669 in binding to CRD-BP. Amongst the eight antisense oligonucleotides designed against MITF RNA 1550–1740, we found MHO-1 and MHO-7 as potent inhibitors of the CRD-BP-MITF RNA interaction. Using RNase protection and fluorescence polarization assays, we showed that both MHO-1 and MHO-7 have affinity for the MITF RNA, suggesting that both antisense oligonucleotides inhibited CRD-BP-MITF RNA interaction by directly binding to MITF RNA. The new molecular insights provided in this study have important implications for understanding the oncogenic function of CRD-BP and development of specific inhibitors against CRD-BP-MITF RNA interaction. PMID:28182633

  5. Social determinants of health--a question of social or economic capital? Interaction effects of socioeconomic factors on health outcomes.

    PubMed

    Ahnquist, Johanna; Wamala, Sarah P; Lindstrom, Martin

    2012-03-01

    Social structures and socioeconomic patterns are the major determinants of population health. However, very few previous studies have simultaneously analysed the "social" and the "economic" indicators when addressing social determinants of health. We focus on the relevance of economic and social capital as health determinants by analysing various indicators. The aim of this paper was to analyse independent associations, and interactions, of lack of economic capital (economic hardships) and social capital (social participation, interpersonal and political/institutional trust) on various health outcomes. Data was derived from the 2009 Swedish National Survey of Public Health, based on a randomly selected representative sample of 23,153 men and 28,261 women aged 16-84 year, with a participation rate of 53.8%. Economic hardships were measured by a combined economic hardships measure including low household income, inability to meet expenses and lacking cash reserves. Social capital was measured by social participation, interpersonal (horizontal) trust and political (vertical/institutional trust) trust in parliament. Health outcomes included; (i) self-rated health, (i) psychological distress (GHQ-12) and (iii) musculoskeletal disorders. Results from multivariate logistic regression show that both measures of economic capital and low social capital were significantly associated with poor health status, with only a few exceptions. Significant interactive effects measured as synergy index were observed between economic hardships and all various types of social capital. The synergy indices ranged from 1.4 to 2.3. The present study adds to the evidence that both economic hardships and social capital contribute to a range of different health outcomes. Furthermore, when combined they potentiate the risk of poor health.

  6. A fast, simple, and reliable hydrophilic interaction liquid chromatography method for the determination of ascorbic and isoascorbic acids.

    PubMed

    Barros, Ana I R N A; Silva, Ana P; Gonçalves, Berta; Nunes, Fernando M

    2010-03-01

    A reliable method for the determination of total vitamin C must be able to resolve ascorbic acid (AA) and the epimeric isoascorbic acid (IAA) and determine the sum of AA and its oxidized form dehydroascorbic acid. AA and IAA are polar molecules with a low retention time in conventional reversed phase systems, and hence of difficult resolution. Hydrophilic interaction chromatography using a TSKgel Amide-80 stationary phase with isocratic elution was successful in resolving the two epimers. The column was compatible with injections of high concentrations of metaphosphoric acid, tris(2-carboxyethyl)-phosphine, and EDTA without drift of baseline and retention time. Total AA and IAA were extracted, stabilized, and reduced in one step at 40 °C, using 5% m-phosphoric acid, 2 mM of EDTA, and 2 mM of tris(2-carboxyethyl)-phosphine as reducing agent. This simple, fast, and robust hydrophilic interaction chromatography-DAD method was applied for the analysis of food products namely fruit juices, chestnut, and ham and also in pharmaceutical and multivitamin tablets. Method validation was performed on the food products, including parameters of precision, accuracy, linearity, limit of detection, and quantification (LOQ). The absence of matrix interferences was assessed by the standard addition method and Youden calibration. The method was fast, accurate, and precise with a LOQ(AA) of 1.5 mg/L and LOQ(IAA) of 3.7 mg/L. The simple experimental procedure, completed in 1 h, the possibility of using IAA as an internal standard, and low probability of artifacts are the major advantages of the proposed method for the routine determination of these compounds in a large number of samples.

  7. Gα12 Structural Determinants of Hsp90 Interaction Are Necessary for Serum Response Element–Mediated Transcriptional Activation

    PubMed Central

    Montgomery, Ellyn R.; Temple, Brenda R. S.; Peters, Kimberly A.; Tolbert, Caitlin E.; Booker, Brandon K.; Martin, Joseph W.; Hamilton, Tyler P.; Tagliatela, Alicia C.; Smolski, William C.; Rogers, Stephen L.; Jones, Alan M.

    2014-01-01

    The G12/13 class of heterotrimeric G proteins, comprising the α-subunits Gα12 and Gα13, regulates multiple aspects of cellular behavior, including proliferation and cytoskeletal rearrangements. Although guanine nucleotide exchange factors for the monomeric G protein Rho (RhoGEFs) are well characterized as effectors of this G protein class, a variety of other downstream targets has been reported. To identify Gα12 determinants that mediate specific protein interactions, we used a structural and evolutionary comparison between the G12/13, Gs, Gi, and Gq classes to identify “class-distinctive” residues in Gα12 and Gα13. Mutation of these residues in Gα12 to their deduced ancestral forms revealed a subset necessary for activation of serum response element (SRE)–mediated transcription, a G12/13-stimulated pathway implicated in cell proliferative signaling. Unexpectedly, this subset of Gα12 mutants showed impaired binding to heat-shock protein 90 (Hsp90) while retaining binding to RhoGEFs. Corresponding mutants of Gα13 exhibited robust SRE activation, suggesting a Gα12-specific mechanism, and inhibition of Hsp90 by geldanamycin or small interfering RNA–mediated lowering of Hsp90 levels resulted in greater downregulation of Gα12 than Gα13 signaling in SRE activation experiments. Furthermore, the Drosophila G12/13 homolog Concertina was unable to signal to SRE in mammalian cells, and Gα12:Concertina chimeras revealed Gα12-specific determinants of SRE activation within the switch regions and a C-terminal region. These findings identify Gα12 determinants of SRE activation, implicate Gα12:Hsp90 interaction in this signaling mechanism, and illuminate structural features that arose during evolution of Gα12 and Gα13 to allow bifurcated mechanisms of signaling to a common cell proliferative pathway. PMID:24435554

  8. Study of photorespiration in marine microalgae through the determination of glycolic acid using hydrophilic interaction liquid chromatography.

    PubMed

    Rigobello-Masini, Marilda; Penteado, José C P; Tiba, Maurício; Masini, Jorge C

    2012-01-01

    Determination of organic acids in intracellular extracts and in the cultivation media of marine microalgae aid investigations about metabolic routes related to assimilation of atmospheric carbon by these organisms, which are known by their role in the carbon dioxide sink. The separation of these acids was investigated by hydrophilic interaction liquid chromatography (HILIC) using isocratic elution with a mobile phase composed of 70:30 v/v acetonitrile/20 mmol/L ammonium acetate buffer (pH 6.8) and detection at 220 nm. HILIC allowed the determinations of glycolic acid, the most important metabolite for the evaluation of the photorespiration process in algae, to be made with better selectivity than that achieved by reversed phase liquid chromatography, but with less detectability. The concentration of glycolic acid was determined in the cultivation media and in intracellular extracts of the algae Tetraselmis gracilis and Phaeodactylum tricornutum submitted to different conditions of aeration: (i) without forced aeration, (ii) aeration with atmospheric air, and (iii) bubbling with N(2). The concentration of glycolic acid had a higher increase as the cultures were aerated with nitrogen, showing higher photorespiratory flux than that occurring in the cultures aerated with atmospheric air.

  9. Relative importance of phenotypic trait matching and species' abundances in determining plant-avian seed dispersal interactions in a small insular community.

    PubMed

    González-Castro, Aarón; Yang, Suann; Nogales, Manuel; Carlo, Tomás A

    2015-03-05

    Network theory has provided a general way to understand mutualistic plant-animal interactions at the community level. However, the mechanisms responsible for interaction patterns remain controversial. In this study we use a combination of statistical models and probability matrices to evaluate the relative importance of species morphological and nutritional (phenotypic) traits and species abundance in determining interactions between fleshy-fruited plants and birds that disperse their seeds. The models included variables associated with species abundance, a suite of variables associated with phenotypic traits (fruit diameter, bird bill width, fruit nutrient compounds), and the species identity of the avian disperser. Results show that both phenotypic traits and species abundance are important determinants of pairwise interactions. However, when considered separately, fruit diameter and bill width were more important in determining seed dispersal interactions. The effect of fruit compounds was less substantial and only important when considered together with abundance-related variables and/or the factor 'animal species'.

  10. Relative importance of phenotypic trait matching and species' abundances in determining plant–avian seed dispersal interactions in a small insular community

    PubMed Central

    González-Castro, Aarón; Yang, Suann; Nogales, Manuel; Carlo, Tomás A.

    2015-01-01

    Network theory has provided a general way to understand mutualistic plant–animal interactions at the community level. However, the mechanisms responsible for interaction patterns remain controversial. In this study we use a combination of statistical models and probability matrices to evaluate the relative importance of species morphological and nutritional (phenotypic) traits and species abundance in determining interactions between fleshy-fruited plants and birds that disperse their seeds. The models included variables associated with species abundance, a suite of variables associated with phenotypic traits (fruit diameter, bird bill width, fruit nutrient compounds), and the species identity of the avian disperser. Results show that both phenotypic traits and species abundance are important determinants of pairwise interactions. However, when considered separately, fruit diameter and bill width were more important in determining seed dispersal interactions. The effect of fruit compounds was less substantial and only important when considered together with abundance-related variables and/or the factor ‘animal species’. PMID:25750409

  11. Food Web Architecture and Basal Resources Interact to Determine Biomass and Stoichiometric Cascades along a Benthic Food Web

    PubMed Central

    Guariento, Rafael D.; Carneiro, Luciana S.; Caliman, Adriano; Leal, João J. F.; Bozelli, Reinaldo L.; Esteves, Francisco A.

    2011-01-01

    Understanding the effects of predators and resources on primary producers has been a major focus of interest in ecology. Within this context, the trophic cascade concept especially concerning the pelagic zone of lakes has been the focus of the majority of these studies. However, littoral food webs could be especially interesting because base trophic levels may be strongly regulated by consumers and prone to be light limited. In this study, the availability of nutrients and light and the presence of an omnivorous fish (Hyphessobrycon bifasciatus) were manipulated in enclosures placed in a humic coastal lagoon (Cabiúnas Lagoon, Macaé – RJ) to evaluate the individual and interactive effects of resource availability (nutrients and light) and food web configuration on the biomass and stoichiometry of periphyton and benthic grazers. Our findings suggest that light and nutrients interact to determine periphyton biomass and stoichiometry, which propagates to the consumer level. We observed a positive effect of the availability of nutrients on periphytic biomass and grazers' biomass, as well as a reduction of periphytic C∶N∶P ratios and an increase of grazers' N and P content. Low light availability constrained the propagation of nutrient effects on periphyton biomass and induced higher periphytic C∶N∶P ratios. The effects of fish presence strongly interacted with resource availability. In general, a positive effect of fish presence was observed for the total biomass of periphyton and grazer's biomass, especially with high resource availability, but the opposite was found for periphytic autotrophic biomass. Fish also had a significant effect on periphyton stoichiometry, but no effect was observed on grazers' stoichiometric ratios. In summary, we observed that the indirect effect of fish predation on periphyton biomass might be dependent on multiple resources and periphyton nutrient stoichiometric variation can affect consumers' stoichiometry. PMID:21789234

  12. Interactions between lower urinary tract symptoms and cardiovascular risk factors determine distinct patterns of erectile dysfunction: a latent class analysis.

    PubMed

    Barbosa, João A B A; Muracca, Eduardo; Nakano, Élcio; Assalin, Adriana R; Cordeiro, Paulo; Paranhos, Mario; Cury, José; Srougi, Miguel; Antunes, Alberto A

    2013-12-01

    An epidemiological association between lower urinary tract symptoms and erectile dysfunction is well established. However, interactions among multiple risk factors and the role of each in pathological mechanisms are not fully elucidated We enrolled 898 men undergoing prostate cancer screening for evaluation with the International Prostate Symptom Score (I-PSS) and simplified International Index of Erectile Function-5 (IIEF-5) questionnaires. Age, race, hypertension, diabetes, dyslipidemia, metabolic syndrome, cardiovascular disease, serum hormones and anthropometric parameters were also evaluated. Risk factors for erectile dysfunction were identified by logistic regression. The 333 men with at least mild to moderate erectile dysfunction (IIEF 16 or less) were included in a latent class model to identify relationships across erectile dysfunction risk factors. Age, hypertension, diabetes, lower urinary tract symptoms and cardiovascular event were independent predictors of erectile dysfunction (p<0.05). We identified 3 latent classes of patients with erectile dysfunction (R2 entropy=0.82). Latent class 1 had younger men at low cardiovascular risk and a moderate/high prevalence of lower urinary tract symptoms. Latent class 2 had the oldest patients at moderate cardiovascular risk with an increased prevalence of lower urinary tract symptoms. Latent class 3 had men of intermediate age with the highest prevalence of cardiovascular risk factors and lower urinary tract symptoms. Erectile dysfunction severity and lower urinary tract symptoms increased from latent class 1 to 3. Risk factor interactions determined different severities of lower urinary tract symptoms and erectile dysfunction. The effect of lower urinary tract symptoms and cardiovascular risk outweighed that of age. While in the youngest patients lower urinary tract symptoms acted as a single risk factor for erectile dysfunction, the contribution of vascular disease resulted in significantly more severe

  13. Aerosol-Cloud Interaction Determined by Both in Situ and Satellite Data Over a Northern High-Latitude Site

    NASA Technical Reports Server (NTRS)

    Lihavainen, H.; Kerminen, V.-M.; Remer, L. A.

    2009-01-01

    The first aerosol indirect effect over a clean, northern high-latitude site was investigated by determining the aerosol cloud interaction (ACI) using three different approaches; ground-based in situ measurements, combined ground-based in situ measurements 5 and satellite retrievals and using only satellite retrievals. The obtained values of ACI were highest for in situ ground-based data, clearly lower for combined ground-based and satellite data, and lowest for data relying solely on satellite retrievals. One of the key findings of this study was the high sensitivity of ACI to the definition of the aerosol burden. We showed that at least a part of the variability in ACI can be explained by 10 how different investigators have related dierent cloud properties to "aerosol burden".

  14. The Determination of the Spectrum Energy on the model of DNA-protein interactions using WKB approximation method

    NASA Astrophysics Data System (ADS)

    Syahroni, Edy; Suparmi, A.; Cari, C.

    2017-01-01

    The spectrum energy’s equation for Killingback potential on the model of DNA and protein interactions was obtained using WKB approximation method. The Killingbeck potential was substituted into the general equation of WKB approximation method to determine the energy. The general equation required the value of critical turning point to complete the form equation. In this research, the general form of Killingbeck potential was causing the equation of critical turning point turn into cube equation. In this case we take the value of critical turning point only with the real value. In mathematical condition, it was satisfied with requirement Discriminant was less than or equal to 0. If D=0, it would give two values of critical turning point and if D<0, it would give three values of critical turning point. In this research we present both of those requirements to complete the general Equation of Energy.

  15. Analysis of Performance of Jet Engine from Characteristics of Components II : Interaction of Components as Determined from Engine Operation

    NASA Technical Reports Server (NTRS)

    Goldstein, Arthur W; Alpert, Sumner; Beede, William; Kovach, Karl

    1949-01-01

    In order to understand the operation and the interaction of jet-engine components during engine operation and to determine how component characteristics may be used to compute engine performance, a method to analyze and to estimate performance of such engines was devised and applied to the study of the characteristics of a research turbojet engine built for this investigation. An attempt was made to correlate turbine performance obtained from engine experiments with that obtained by the simpler procedure of separately calibrating the turbine with cold air as a driving fluid in order to investigate the applicability of component calibration. The system of analysis was also applied to prediction of the engine and component performance with assumed modifications of the burner and bearing characteristics, to prediction of component and engine operation during engine acceleration, and to estimates of the performance of the engine and the components when the exhaust gas was used to drive a power turbine.

  16. Rapid hydrophilic interaction chromatography determination of lysine in pharmaceutical preparations with fluorescence detection after postcolumn derivatization with o-phtaldialdehyde.

    PubMed

    Douša, Michal; Břicháč, Jiří; Gibala, Petr; Lehnert, Petr

    2011-04-05

    A rapid procedure for the determination of lysine based on hydrophilic interaction chromatography (HILIC) separation of arginine and lysine with fluorescence detection has been developed. The separation conditions and parameters of lysine postcolumn derivatization with o-phtaldialdehyde (OPA)/2-mercaptoethanol were studied. The various HILIC columns were employed using isocratic elution. Fluorescence detection was performed at excitation and emission wavelength of 345 nm and 450 nm, respectively. An advantage of the reported method is a simple sample pre-treatment and a quick and very sensitive HPLC method. The developed method was successfully applied for analysis of commercial samples of Ibalgin Fast tablets (Zentiva, Czech Republic). Copyright © 2010 Elsevier B.V. All rights reserved.

  17. Ligand-transporter interaction in the AcrB multidrug efflux pump determined by fluorescence polarization assay

    PubMed Central

    Su, Chih-Chia; Nikaido, Hiroshi; Yu, Edward W.

    2007-01-01

    The AcrB of Escherichia coli pumps out a wide range of compounds, including most of the currently available antibiotics, and contributes significantly to the serious problem of multi-drug resistance of pathogenic bacteria. Quantitative analysis of drug efflux by this pump requires the measurement of the affinity of ligands. Yet there has been no success in determining these values. We introduce here an approach of steady-state fluorescence polarization to study the interactions between four different ligands and the purified AcrB transporter in a detergent environment. Our assays indicate that the transporter binds these drugs with KD values ranging from 5.5 to 74.1 μM. PMID:17910961

  18. Thermodynamic study of rhodamine 123-calf thymus DNA interaction: determination of calorimetric enthalpy by optical melting study.

    PubMed

    Masum, Abdulla Al; Chakraborty, Maharudra; Pandya, Prateek; Halder, Umesh Chandra; Islam, Md Maidul; Mukhopadhyay, Subrata

    2014-11-20

    In this paper, the interaction of rhodamine123 (R123) with calf thymus DNA has been studied using molecular modeling and other biophysical methods like UV-vis spectroscopy, fluoremetry, optical melting, isothermal titration calorimetry, and circular dichroic studies. Results showed that the binding energy is about -6 to -8 kcal/mol, and the binding process is favored by both negative enthalpy change and positive entropy change. A new method to determine different thermodynamic properties like calorimetric enthalpy and heat capacity change has been introduced in this paper. The obtained data has been crossed-checked by other methods. After dissecting the free-energy contribution, it was observed that the binding was favored by both negative hydrophobic free energy and negative molecular free energy which compensated for the positive free energies due to the conformational change loss of rotational and transitional freedom of the DNA helix.

  19. Determination of TNT explosive based on its selectively interaction with creatinine-capped CdSe/ZnS quantum dots.

    PubMed

    Carrillo-Carrión, Carolina; Simonet, Bartolomé M; Valcárcel, Miguel

    2013-08-20

    Here, a creatinine-modified CdSe/ZnS quantum dots fluorescent probe has been prepared and used for sensing 2,4,6,-trinitrotoluene explosive (TNT). The proposed method is based on the selective interaction between creatinine and nitroaromatic compounds according to the well-known Jaffé reaction. The procedure for the synthesis of creatinine-CdSe/ZnS reagent is very simple and reproducible and its fluorescent characteristics are reported. We found that the presence of TNT quenches the original fluorescence of creatinine-QD according to the Stern-Volmer model. Under the working conditions, the calibration plot of Io/I versus concentration of TNT was linear in the range 10-300μg L(-1) (R(2)=0.996). The mechanism interaction is discussed. The selectivity of fluorescence quenching of creatinine-QD for TNT has been evaluated. Finally, the potential application of the proposed methodology for the determination of TNT in spiked soils is demonstrated. For the analysis of soil samples a solid-liquid extraction is carried out and a four-point standard addition protocol is used to correct the matrix effect. The method, which is simple and rapid, allows the detection of 0.057μg g(-1) of TNT in soil samples. This sensor could be a useful tool for environmental studies, a crucial topic for nanotechnology nowadays.

  20. Two SERK Receptor-Like Kinases Interact with EMS1 to Control Anther Cell Fate Determination1[OPEN

    PubMed Central

    Wang, Yao; Ahsan, Nagib; Biener, Gabriel; Paprocki, Joel

    2017-01-01

    Cell signaling pathways mediated by leucine-rich repeat receptor-like kinases (LRR-RLKs) are essential for plant growth, development, and defense. The EMS1 (EXCESS MICROSPOROCYTES1) LRR-RLK and its small protein ligand TPD1 (TAPETUM DETERMINANT1) play a fundamental role in somatic and reproductive cell differentiation during early anther development in Arabidopsis (Arabidopsis thaliana). However, it is unclear whether other cell surface molecules serve as coregulators of EMS1. Here, we show that SERK1 (SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE1) and SERK2 LRR-RLKs act redundantly as coregulatory and physical partners of EMS1. The SERK1/2 genes function in the same genetic pathway as EMS1 in anther development. Bimolecular fluorescence complementation, Förster resonance energy transfer, and coimmunoprecipitation approaches revealed that SERK1 interacted biochemically with EMS1. Transphosphorylation of EMS1 by SERK1 enhances EMS1 kinase activity. Among 12 in vitro autophosphorylation and transphosphorylation sites identified by tandem mass spectrometry, seven of them were found to be critical for EMS1 autophosphorylation activity. Furthermore, complementation test results suggest that phosphorylation of EMS1 is required for its function in anther development. Collectively, these data provide genetic and biochemical evidence of the interaction and phosphorylation between SERK1/2 and EMS1 in anther development. PMID:27920157

  1. A model-based approach to determine the long-term effects of multiple interacting stressors on coral reefs.

    PubMed

    Blackwood, Julie C; Hastings, Alan; Mumby, Peter J

    2011-10-01

    The interaction between multiple stressors on Caribbean coral reefs, namely, fishing effort and hurricane impacts, is a key element in the future sustainability of reefs. We develop an analytic model of coral-algal interactions and explicitly consider grazing by herbivorous reef fish. Further, we consider changes in structural complexity, or rugosity, in addition to the direct impacts of hurricanes, which are implemented as stochastic jump processes. The model simulations consider various levels of fishing effort corresponding to' several hurricane frequencies and impact levels dependent on geographic location. We focus on relatively short time scales so we do not explicitly include changes in ocean temperature, chemistry, or sea level rise. The general features of our approach would, however, apply to these other stressors and to the management of other systems in the face of multiple stressors. It is determined that the appropriate management policy, either local reef restoration or fisheries management, greatly depends on hurricane frequency and impact level. For sufficiently low hurricane impact and macroalgal growth rate, our results indicate that regions with lower-frequency hurricanes require stricter fishing regulations, whereas management in regions with higher-frequency hurricanes might be less concerned with enhancing grazing and instead consider whether local-scale restorative activities to increase vertical structure are cost-effective.

  2. A turn-on fluorescence-sensing technique for glucose determination based on graphene oxide-DNA interaction.

    PubMed

    Zhang, Hao; Huang, Hui; Lin, Zihan; Su, Xingguang

    2014-11-01

    Graphene is a two-dimensional carbon nanomaterial one atom thick. Interactions between graphene oxide (GO) and ssDNA containing different numbers of bases have been proved to be remarkably different. In this paper we propose a novel approach for turn-on fluorescence sensing determination of glucose. Hydrogen peroxide (H2O2) is produced by glucose oxidase-catalysed oxidation of glucose. In the presence of ferrous iron (Fe(2+)) the hydroxyl radical (•OH) is generated from H2O2 by the Fenton reaction. This attacks FAM-labelled long ssDNA causing irreversible cleavage, as a result of the oxidative effect of •OH, producing an FAM-linked DNA fragment. Because of the weak interaction between GO and short FAM-linked DNA fragments, restoration of DNA fluorescence can be achieved by addition of glucose. Due to the excellent fluorescence quenching efficiency of GO and the specific catalysis of glucose oxidase, the sensitivity and selectivity of this method for GO-DNA sensing are extremely high. The linear range is from 0.5 to 10 μmol L(-1) and the detection limit for glucose is 0.1 μmol L(-1). The method has been successfully used for analysis of glucose in human serum.

  3. Membrane skeleton-bilayer interaction is not the major determinant of membrane phospholipid asymmetry in human erythrocytes.

    PubMed

    Gudi, S R; Kumar, A; Bhakuni, V; Gokhale, S M; Gupta, C M

    1990-03-30

    Transbilayer phospholipid distribution, membrane skeleton dissociation/association, and spectrin structure have been analysed in human erythrocytes after subjecting them to heating at 50 degrees C for 15 min. The membrane skeleton dissociation/association was determined by measuring the Tris-induced dissociation of Triton-insoluble membrane skeletons (Triton shells), the spectrin-actin extractability under low ionic conditions, and the binding of spectrin-actin with normal erythrocyte membrane inside-out vesicles (IOVs). The spectrin structure was ascertained by measuring the spectrin dimer-to-tetramer ratio as well as the spectrin tryptophan fluorescence. Both the Tris-induced Triton shell dissociation and the spectrin-actin extractability under low ionic conditions were considerably reduced by the heat treatment. Also, the binding of heated erythrocyte spectrin-actin to IOVs was significantly smaller than that observed with the normal cell spectrin-actin. Further, the quantity of spectrin dimers was appreciably increased in heat-treated erythrocytes as compared to the normal cells. This change in the spectrin dimer-to-tetramer ratio was accompanied by marked changes in the spectrin tryptophan fluorescence. In spite of these heat-induced alterations in structure and bilayer interactions of the membrane skeleton, the inside-outside glycerophospholipid distribution remained virtually unaffected in the heat-treated cells, as judged by employing bee venom and pancreatic phospholipase A2, fluorescamine and Merocyanine 540 as the external membrane probes. These results strongly indicate that membrane bilayer-skeleton interaction is not the major factor in determining the transbilayer phospholipid asymmetry in human erythrocyte membrane.

  4. Contingent interactions among biofilm-forming bacteria determine preservation or decay in the first steps toward fossilization of marine embryos.

    PubMed

    Raff, Elizabeth C; Andrews, Mary E; Turner, F Rudolf; Toh, Evelyn; Nelson, David E; Raff, Rudolf A

    2013-01-01

    Fossils of soft tissues provide important records of early animals and embryos, and there is substantial evidence for a role for microbes in soft tissue fossilization. We are investigating the initial events in interactions of bacteria with freshly dead tissue, using marine embryos as a model system. We previously found that microbial invasion can stabilize embryo tissue that would otherwise disintegrate in hours or days by generating a bacterial pseudomorph, a three dimensional biofilm that both replaces the tissue and replicates its morphology. In this study, we sampled seawater at different times and places near Sydney, Australia, and determined the range and frequency of different taphonomic outcomes. Although destruction was most common, bacteria in 35% of seawater samples yielded morphology‐preserving biofilms. We could replicate the taphonomic pathways seen with seawater bacterial communities using single cultured strains of marine gammaproteobacteria. Each given species reproducibly generated a consistent taphonomic outcome and we identified species that yielded each of the distinct pathways produced by seawater bacterial communities. Once formed,bacterial pseudomorphs are stable for over a year and resist attack by other bacteria and destruction by proteases and other lytic enzymes. Competition studies showed that the initial action of a pseudomorphing strain can be blocked by a strain that destroys tissues. Thus embryo preservation in nature may depend on contingent interactions among bacterial species that determine if pseudomorphing occurs.We used Artemia nauplius larvae to show that bacterial biofilm replacement of tissue is not restricted to embryos, but is relevant for preservation of small multicellular organisms. We present a model for bacterial self‐assembly of large‐scale three‐dimensional tissue pseudomorphs, based on smallscaleinteractions among individual bacterial cells to form local biofilms at structural boundaries within the tissue

  5. Delay-specific stimuli and genotype interact to determine temporal discounting in a rapid-acquisition procedure.

    PubMed

    Pope, Derek A; Newland, M Christopher; Hutsell, Blake A

    2015-05-01

    The importance of delay discounting to many socially important behavior problems has stimulated investigations of biological and environmental mechanisms responsible for variations in the form of the discount function. The extant experimental research, however, has yielded disparate results, raising important questions regarding Gene X Environment interactions. The present study determined the influence of stimuli that uniquely signal delays to reinforcement on delay discounting in two inbred mouse strains using a rapid-acquisition procedure. BALB/c and C57BL/6 mice responded under a six-component, concurrent-chained schedule in which the terminal-link delays preceding the larger-reinforcer were presented randomly across components of an individual session. Across conditions, components were presented either with or without delay-specific auditory stimuli, i.e., as multiple or mixed schedules. A generalized matching-based model was used to incorporate the impact of current and previous component reinforcer-delay ratios on current component response allocation. Sensitivity to reinforcer magnitude and delay were higher for BALB/c mice, but within-component preference reached final levels faster for C57Bl/6 mice. For BALB/c mice, acquisition of preference across blocks of a component was faster under the multiple than the mixed schedule, but final levels of sensitivity to reinforcement were unaffected by schedule. The speed of acquisition of preference was not different across schedules for C57Bl/6 mice, but sensitivity to reinforcement was higher under the multiple than the mixed schedule. Overall, differences in the acquisition and final form of the discount function were determined by a Gene X Environment interaction, but the presence of delay-specific stimuli attenuated genotype-dependent differences in magnitude and delay sensitivity.

  6. When sad groups expect to meet again: interactive affective sharing and future interaction expectation as determinants of work groups' analytical and creative task performance.

    PubMed

    Klep, Annefloor H M; Wisse, Barbara; van der Flier, Henk

    2013-12-01

    The present study examines the moderating role of future interaction expectation in the relationship between affective sharing and work groups' task performance. We argue that group affect, a group defining characteristic, becomes more salient to its members when it is interactively shared, and that the anticipation of future interaction may strengthen the effects of group defining characteristics on subsequent group member behaviour. As a consequence, interactive sharing (vs. non-interactive sharing) of negative affect is more likely to influence work group outcomes when group members expect to meet again. Results from a laboratory experiment with 66 three-person work groups indeed show that interactively shared (vs. non-interactively shared) negative affect facilitated work groups' analytical task performance, whereas it inhibited performance on a creative fluency task when groups have expectations of future interaction and not when they do not have such expectations. The discussion focuses on how these results add to theory on group affect and contribute to insights in the effects of future interaction expectation.

  7. Hydrophilic interaction liquid chromatography-solid phase extraction directly combined with protein precipitation for the determination of triptorelin in plasma.

    PubMed

    Wang, Jixia; Kong, Song; Yan, Jingyu; Jin, Gaowa; Guo, Zhimou; Shen, Aijin; Xu, Junyan; Zhang, Xiuli; Zou, Lijuan; Liang, Xinmiao

    2014-06-01

    Peptide drugs play a critical role in therapeutic treatment. However, as the complexity of plasma, determination of peptide drugs using liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a daunting task. To solve this problem, hydrophilic interaction liquid chromatography-solid phase extraction (HILIC-SPE) directly combined with protein precipitation (PPT) was developed for the selective extraction of triptorelin from plasma. The extracts were analyzed by reversed-phase liquid chromatography (RPLC). Proteins, phospholipids and highly polar interferences could be removed from plasma by the efficient combination of PPT, HILIC-SPE and RPLC-MS/MS. This method was evaluated by matrix effect, recovery and process efficiency at different concentration levels (50, 500 and 5,000 ng/mL) of triptorelin. Furthermore, the performance of HILIC-SPE was compared with that of reversed-phase C18 SPE and hydrophilic lipophilic balance (Oasis HLB) SPE. Among them, HILIC-SPE provided the minimum matrix effect (ranging from 96.02% to 103.41%), the maximum recovery (ranging from 80.68% to 90.54%) and the satisfactory process efficiency (ranging from 82.83% to 92.95%). The validated method was successfully applied to determine triptorelin in rat plasma. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Determination of nicotine and its metabolites accumulated in fish tissue using hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry.

    PubMed

    Chang, Yun-Wei; Nguyen, Hien P; Chang, Mike; Burket, S Rebekah; Brooks, Bryan W; Schug, Kevin A

    2015-07-01

    The determination of nicotine and its major metabolites (cotinine and anabasine) in fish tissue was performed using liquid chromatography and tandem mass spectrometry. Marine and freshwater fish were purchased from local grocery stores and were prepared based on a quick, easy, cheap, effective, rugged, and safe sample preparation protocol. To determine the highly polar compounds, hydrophilic interaction liquid chromatography was also used. There were modest suppressions on measured nicotine signals (10%) due to the matrix effects from marine fish but no obvious effects on freshwater fish signals. Method validation was incorporated with internal standards and carried out with matrix-matched calibration. The detection limits for nicotine, cotinine, and anabasine were 9.4, 3.0, and 1.5 ng/g in fish, respectively. Precision was quite acceptable returning less than 8% RSD at low, medium, and high concentrations. Acceptable and reproducible extraction recoveries (70-120%) of all three compounds were achieved, except for anabasine at low concentration (61%). The method was then applied to define nicotine bioaccumulation in a fathead minnow model, which resulted in rapid uptake with steady state internal tissue levels, reached within 12 h. This developed method offers a fast, easy, and sensitive way to evaluate nicotine and its metabolite residues in fish tissues.

  9. Supramolecular interaction of 18-crown-6 ether with mesalazine and spectrofluorimetric determination of mesalazine in pharmaceutical formulations.

    PubMed

    Elbashir, Abdalla A; Abdalla, Fatima Altayib Alasha; Aboul-Enein, Hassan Y

    2015-12-01

    The supramolecular interaction of protonated mesalazine (MSZ) and 18-crown-6 ether (18C6) has been examined by Ultraviolet-visible, FT-IR and fluorescence spectroscopy. The formation of the inclusion complex has been confirmed based on the changes of the spectral properties. The MSZ-18C6 host-guest complex formed in (1:1) stoichiometry and the inclusion constant (K = 1.411 × 10(2) L mol(-1)) was ascertained by the typical double reciprocal plots. Furthermore, the thermodynamic parameters (ΔG°, ΔH° and ΔS°) of (MSZ-18C6) were obtained. Based on the remarkable enhancement of the fluorescence intensity of MSZ produced through complex formation, a simple, accurate, rapid and highly sensitive spectrofluorometric method for the determination of MSZ in aqueous solution in the presence of 18C6 was developed. The measurement of relative fluorescence intensity was carried with excitation at 298 nm, emission 410 nm. All variables affecting the reactions were studied and optimized. Beer's law was obeyed in the concentration range of 0.1-0.9 µg/mL. The absorbance was found to increase linearly with increasing concentration of MSZ. The molar absorptivity, Sandell sensitivity, limit of detection (LOD) and limit of quantification (LOQ) were calculated. The validity of the described method was assessed, and the method was successfully applied to the determination of MSZ in its pharmaceutical formulation. In addition, a solid inclusion complex was synthesized by the coprecipitation method.

  10. Determination of aromatic amines in aqueous extracts of polyurethane foam using hydrophilic interaction liquid chromatography and mass spectrometry.

    PubMed

    Johnson, Jakob Riddar; Karlsson, Daniel; Dalene, Marianne; Skarping, Gunnar

    2010-09-23

    A method is presented for the determination of aromatic amines in aqueous extracts of polyurethane (PUR) foam. The method is based on the extraction of PUR foam using aqueous acetic acid (0.1%, w/v) followed by determination of extracted aromatic amines using hydrophilic interaction liquid chromatography (HILIC) and tandem mass spectrometry (MS/MS) with positive electrospray ionisation. The injections of volumes up to 5 μL of aqueous solutions were made possible by on-column focusing with partially filled loop injections. The fragmentation patterns for 2,4- and 2,6-toluene diamine (TDA) and 4,4'-methylene dianiline (MDA) were clarified by performing a hydrogen-deuterium exchange study. TDA and MDA were determined using trideuterated 2,4- and 2,6-TDA and dideuterated 4,4'-MDA as internal standards. Linear calibration graphs were obtained over the range 0.025-0.5 μg mL(-1) with correlation coefficients >0.996 and the instrumental detection limit for each compound was <50 fmol. The stability of the amines was influenced by the matrix, so their concentrations decreased over time. Agreement was observed between the results of analyses of PUR foam extracts by HILIC-MS/MS and results obtained by ethyl chloroformate derivatisation and reversed phase (RP) liquid chromatography-mass spectrometry (LC-MS/MS). TDA was observed to be unstable in extracts of foam but not in pure solutions. Copyright © 2010 Elsevier B.V. All rights reserved.

  11. Surface Energy Determined by Inverse Gas Chromatography as a Tool to Investigate Particulate Interactions in Dry Powder Inhalers.

    PubMed

    Das, Shyamal C; Tucker, Ian G; Stewart, Peter J

    2015-01-01

    Dry powder inhalers (DPIs) usually contain drug particles <6 µm which agglomerate and/ or adhere on the surfaces of large carriers particles. The detachment of drug particles from carriers and de-agglomeration of drug particles into primary particles is essential for drug deposition in the deep lung. These processes are influenced by the surface energy of particles. Inverse gas chromatography (IGC) has been used to determine the surface energy of powder particles used in DPI to characterize materials and to understand aerosolization behaviour. Early studies used an infinite dilution technique to determine nonpolar surface energy and free energy of adsorption for polar interactions separately. Although some correlations were observed with the change in nonpolar surface energy before and after micronization, milling and storage, a lack of consistency in the change of free energy of adsorption was common. Moreover, a consistent relationship between complex de-agglomeration behaviour and surface energy has not been established and there are even some examples of negative correlation. In fact, nonpolar surface energy at infinite dilution is an incomplete representation of powder surface characteristics. The techniques for measuring polar surface energy, total surface energy and surface energy distribution have provided more revealing information about surface energetics of powders. Surface energy distributions determined by IGC or surface energy analyser have been successfully used to understand energetic heterogeneity of surfaces, characterize different polymorphs and understand changes due to micronization, structural relaxation, dry coating and storage. Efforts have been made to utilize surface energy distribution data to calculate powder strength distribution and to explain complex de-agglomeration behaviour of DPI formulations.

  12. Interactions between traditional regional determinants and socio-economic status on dietary patterns in a sample of French men.

    PubMed

    Perrin, Anne-Elisabeth; Dallongeville, Jean; Ducimetière, Pierre; Ruidavets, Jean-Bernard; Schlienger, Jean-Louis; Arveiler, Dominique; Simon, Chantal

    2005-01-01

    The aim of the present study was to assess the respective contributions of regional and socio-economic factors to dietary pattern. We used the data from the final MONICA (MONItoring of trends and determinants in Cardiovascular disease) population survey conducted in the three French centres in 1995-7 among a representative sample of 976 men aged 45-64 years. Dietary intake was assessed using a 3-d record method. Dietary patterns were identified by a factor analysis, based on fifteen food items. An analysis of variance was then used to study their relationship with regional and socio-economic determinants. Two major dietary patterns were identified: a 'Western diet', characterized by high intakes of sugar and sweets, grains, butter, added fats, eggs, potatoes and cheese; a 'prudent diet', mainly distinguished by high intakes of fruit, vegetables, olive oil and fish and low intakes of alcohol, high-fat meat and potatoes. Strong associations were mostly observed with the 'prudent diet' pattern, with a significant relationship with region, educational and income-tax levels, leisure-time physical activity and smoking status. There was also a statistically significant interaction between region and educational level (P=0.05), and between region and income-tax level (P=0.03), indicating that the influence of socio-economic factors is different among regions. In conclusion, these results indicate large regional and socio-economic differences in the dietary patterns of this French male population. When considering the 'prudent diet' pattern, they also suggest that traditional regional influences may now be overcome by socio-economic determinants.

  13. Determination of gemifloxacin on dried blood spots by hydrophilic interaction liquid chromatography with fluorescence detector: application to pharmacokinetics in rats.

    PubMed

    Nageswara Rao, R; Naidu, Ch Gangu; Guru Prasad, K; Padiya, Raju; Agwane, Sachin B

    2012-12-01

    A highly selective, sensitive and rapid hydrophilic liquid interaction chromatographic method was developed and validated for determination of gemifloxacin on dried blood spots. The chromatographic separation was achieved on a reversed-phase zwitterionic hydrophilic interaction liquid chromatographic ZIC®HILIC-C₁₈ (4.6 × 100 mm; 5 µm) column using acetonitrile-10 mM ammonium acetate (pH 3.5; 80:20, v/v) as a mobile phase in an isocratic elution mode at a flow rate 0.6 mL/min at 27 °C. An on-line fluorescence detector set at excitation and emission wavelengths of 269 and 393 nm, respectively was used for monitoring column eluents. Ciprofloxacin was used as an internal standard. The method was validated for accuracy, precision, linearity and selectivity by design of experiments following ICH guidelines. The assay exhibited a linear range of 25-5000 ng/mL for gemifloxacin on dried blood spots. The lower limit of detection was found to be 10 ng/mL. The intra- and inter-assay coefficients of variation did not exceed 7.4% deviation of the nominal concentration. The recovery of GFX from dried blood spots was >95.0% and its stability was excellent with no evidence of degradation during sample processing for at least 3 months storage in a freezer at -20 °C. Copyright © 2012 John Wiley & Sons, Ltd.

  14. An Experimental and Modeling Synthesis to Determine Seasonality of Hydraulic Redistribution in Semi-arid Region with Multispecies Vegetation Interaction

    NASA Astrophysics Data System (ADS)

    Lee, E.; Kumar, P.; Barron-Gafford, G.; Scott, R. L.

    2016-12-01

    A key challenge in critical zone science is to understand and predict the interaction between aboveground and belowground eco-hydrologic processes. Roots play an important role in linking aboveground plant ecophysiological processes, such as carbon, water and energy exchange with the atmosphere, and the belowground processes associated with soil moisture and carbon, and microbial and nutrient dynamics. This study analyzes aboveground and belowground interaction through hydraulic redistribution (HR), a phenomenon that roots serve as preferential pathways for water movement from wet to dry soil layers. HR process is simulated by multi-layer canopy model and compared with relative measurements from the field to study effect of HR on different plant species where Posopis velutina Woot. (velvet mesquite) and understory co-exist and share resources. The study site is one of Ameriflux sites: Santa Rita Mesquite savanna, Arizona, with a distinct dry season that facilitates occurrence of HR. We analyzed how two vegetation species share and utilize the limited amount of water by HR in both dry and wet seasons. During dry season, water moves from deep layer to shallow layer through roots and hydraulic lift (HL) occurs. During wet season, water moves from shallow layer to deep layer through roots and hydraulic descent (HD) occurs. About 40% of precipitation is transferred to deep soil layer with HD and 15% of that is transported back to shallow soil layer with HL in dry season. Assuming water supplied through HL supports evapotranspiration of plants, HL supports 10% of evapotranspiration. The ratio of mesquite and understory root conductivities is an important factor that determines how two plant species interact and share resources in water-limited environment. The sensitivity analysis of root conductivities suggests that high understory root conductivity facilitates water transported by HR and increases mesquite transpiration and photosynthesis. Understory transpiration and

  15. Attention-Deficit/Hyperactivity Disorder (ADHD): Interaction between socioeconomic status and parental history of ADHD determines prevalence.

    PubMed

    Rowland, Andrew S; Skipper, Betty J; Rabiner, David L; Qeadan, Fares; Campbell, Richard A; Naftel, A Jack; Umbach, David M

    2017-08-12

    Many studies have reported a higher prevalence of Attention-Deficit/Hyperactivity Disorder (ADHD) among disadvantaged populations, but few have considered how parental history of ADHD might modify that relationship. We evaluated whether the prevalence of ADHD varies by socioeconomic status (SES) and parental history of ADHD in a population-sample of elementary school children age 6-14 years. We screened all children in grades 1-5 in 17 schools in one North Carolina (U.S.) county for ADHD using teacher rating scales and 1,160 parent interviews, including an ADHD structured interview (DISC). We combined parent and teacher ratings to determine DSM-IV ADHD status. Data analysis was restricted to 967 children with information about parental history of ADHD. SES was measured by family income and respondent education. We found an interaction between family income and parental history of ADHD diagnosis (p = .016). The SES gradient was stronger in families without a parental history and weaker among children with a parental history. Among children without a parental history of ADHD diagnosis, low income children had 6.2 times the odds of ADHD (95% CI 3.4-11.3) as high income children after adjusting for covariates. Among children with a parental history, all had over 10 times the odds of ADHD as high income children without a parental history but the SES gradient between high and low income children was less pronounced [odds ratio (OR) = 1.4, 95% CI 0.6-3.5]. Socioeconomic status and parental history of ADHD are each strong risk factors for ADHD that interact to determine prevalence. More research is needed to dissect the components of SES that contribute to risk of ADHD. Future ADHD research should evaluate whether the strength of other environmental risk factors vary by parental history. Early identification and interventions for children with low SES or parental histories of ADHD should be explored. © 2017 Association for Child and Adolescent Mental Health.

  16. Determinants and outcomes of decision-making, group coordination and social interactions during a foraging experiment in a wild primate.

    PubMed

    Pyritz, Lennart W; Fichtel, Claudia; Huchard, Elise; Kappeler, Peter M

    2013-01-01

    Social animals have to coordinate joint movements to maintain group cohesion, but the latter is often compromised by diverging individual interests. A widespread behavioral mechanism to achieve coordination relies on shared or unshared consensus decision-making. If consensus costs are high, group fission represents an alternative tactic. Exploring determinants and outcomes of spontaneous group decisions and coordination of free-ranging animals is methodologically challenging. We therefore conducted a foraging experiment with a group of wild redfronted lemurs (Eulemur rufifrons) to study decision outcomes, coordination of movements, individual foraging benefits and social interactions in response to the presentation of drinking platforms with varying baiting patterns. Behavioral observations were complemented with data from recordings of motion detector cameras installed at the platforms. The animal's behavior in the experimental conditions was compared to natural group movements. We could not determine the type of consensus decision-making because the group visited platforms randomly. The group fissioned during 23.3% of platform visits, and fissioning resulted in more individuals drinking simultaneously. As under natural conditions, adult females initiated most group movements, but overtaking by individuals of different age and sex classes occurred in 67% of movements to platforms, compared to only 18% during other movements. As a result, individual resource intake at the platforms did not depend on departure position, age or sex, but on arrival order. Aggression at the platforms did not affect resource intake, presumably due to low supplanting rates. Our findings highlight the diversity of coordination processes and related consequences for individual foraging benefits in a primate group living under natural conditions.

  17. Interaction Behavior between Thrust Faulting and the National Highway No. 3 - Tianliao III bridge as Determined using Numerical Simulation

    NASA Astrophysics Data System (ADS)

    Li, C. H.; Wu, L. C.; Chan, P. C.; Lin, M. L.

    2016-12-01

    The National Highway No. 3 - Tianliao III Bridge is located in the southwestern Taiwan mudstone area and crosses the Chekualin fault. Since the bridge was opened to traffic, it has been repaired 11 times. To understand the interaction behavior between thrust faulting and the bridge, a discrete element method-based software program, PFC, was applied to conduct a numerical analysis. A 3D model for simulating the thrust faulting and bridge was established, as shown in Fig. 1. In this conceptual model, the length and width were 50 and 10 m, respectively. Part of the box bottom was moveable, simulating the displacement of the thrust fault. The overburden stratum had a height of 5 m with fault dip angles of 20° (Fig. 2). The bottom-up strata were mudstone, clay, and sand, separately. The uplift was 1 m, which was 20% of the stratum thickness. In accordance with the investigation, the position of the fault tip was set, depending on the fault zone, and the bridge deformation was observed (Fig. 3). By setting "Monitoring Balls" in the numerical model to analyzes bridge displacement, we determined that the bridge deck deflection increased as the uplift distance increased. Furthermore, the force caused by the loading of the bridge deck and fault dislocation was determined to cause a down deflection of the P1 and P2 bridge piers. Finally, the fault deflection trajectory of the P4 pier displayed the maximum displacement (Fig. 4). Similar behavior has been observed through numerical simulation as well as field monitoring data. Usage of the discrete element model (PFC3D) to simulate the deformation behavior between thrust faulting and the bridge provided feedback for the design and improved planning of the bridge.

  18. Characterization of CD4 glycoprotein determinant-HIV envelope protein interactions: perspectives for analog and vaccine development.

    PubMed

    Farrar, W L; Harel-Bellan, A; Ferris, D K

    1988-01-01

    The CD4 surface determinant, previously associated as a phenotypic marker for helper/inducer subsets of T lymphocytes, has now been critically identified as the binding/entry protein for human immunodeficiency viruses (HIV). The human CD4 molecule is readily detectable on monocytes, T lymphocytes, and brain tissues. Soluble HIV (HTLV IIIB) envelope protein (gp120) binds native or recombinant CD4 with equal affinity estimated to be 4 to 8 nM kDa. All human tissue sources of CD4 bind radiolabeled gp120 to the same relative degree; however, the murine homologous protein, L3T4, does not bind the HIV envelope protein. Lack of sufficient recognition by the recombinant L3T4 molecule suggests divergence in the gp120-binding epitope. The binding of gp120 to CD4 is dependent upon intact sulfhydryl bonds within cysteine residues and glycosylation. Deglycosylated native gp120 is unable to bind CD4 under physiological conditions. Recombinant deglycosylated fragments cannot bind to the CD4 receptor, although they serve as immunogen for neutralizing antibody development. A number of synthetic peptides to putative critical domains of gp120 have been studied for their antagonism of native gp120 binding. Peptide T analogs or synthetic cogeners of Neuroleukin proposed to bind the CD4 determinant involved in gp120 binding had no competitive displacement of native gp120 binding as assessed by two independent methods that measure gp120 interaction with CD4. Recombinant C-terminal fragments, also containing other putative domains, did not displace native gp120 from CD4. Glycosylation appears to be critical in the maintenance of the structure of the binding domain of gp120. Native gp120 binding to CD4 is sufficient for the activation of cellular metabolism that alters target cell gene expression and differentiation, suggesting that the virus binding contributes to the activation of the host cell.

  19. Determinants and Outcomes of Decision-Making, Group Coordination and Social Interactions during a Foraging Experiment in a Wild Primate

    PubMed Central

    Pyritz, Lennart W.; Fichtel, Claudia; Huchard, Elise; Kappeler, Peter M.

    2013-01-01

    Social animals have to coordinate joint movements to maintain group cohesion, but the latter is often compromised by diverging individual interests. A widespread behavioral mechanism to achieve coordination relies on shared or unshared consensus decision-making. If consensus costs are high, group fission represents an alternative tactic. Exploring determinants and outcomes of spontaneous group decisions and coordination of free-ranging animals is methodologically challenging. We therefore conducted a foraging experiment with a group of wild redfronted lemurs (Eulemur rufifrons) to study decision outcomes, coordination of movements, individual foraging benefits and social interactions in response to the presentation of drinking platforms with varying baiting patterns. Behavioral observations were complemented with data from recordings of motion detector cameras installed at the platforms. The animal's behavior in the experimental conditions was compared to natural group movements. We could not determine the type of consensus decision-making because the group visited platforms randomly. The group fissioned during 23.3% of platform visits, and fissioning resulted in more individuals drinking simultaneously. As under natural conditions, adult females initiated most group movements, but overtaking by individuals of different age and sex classes occurred in 67% of movements to platforms, compared to only 18% during other movements. As a result, individual resource intake at the platforms did not depend on departure position, age or sex, but on arrival order. Aggression at the platforms did not affect resource intake, presumably due to low supplanting rates. Our findings highlight the diversity of coordination processes and related consequences for individual foraging benefits in a primate group living under natural conditions. PMID:23326392

  20. Non-linear interactions determine the impact of sea-level rise on estuarine benthic biodiversity and ecosystem processes.

    PubMed

    Yamanaka, Tsuyuko; Raffaelli, David; White, Piran C L

    2013-01-01

    Sea-level rise induced by climate change may have significant impacts on the ecosystem functions and ecosystem services provided by intertidal sediment ecosystems. Accelerated sea-level rise is expected to lead to steeper beach slopes, coarser particle sizes and increased wave exposure, with consequent impacts on intertidal ecosystems. We examined the relationships between abundance, biomass, and community metabolism of benthic fauna with beach slope, particle size and exposure, using samples across a range of conditions from three different locations in the UK, to determine the significance of sediment particle size beach slope and wave exposure in affecting benthic fauna and ecosystem function in different ecological contexts. Our results show that abundance, biomass and oxygen consumption of intertidal macrofauna and meiofauna are affected significantly by interactions among sediment particle size, beach slope and wave exposure. For macrofauna on less sloping beaches, the effect of these physical constraints is mediated by the local context, although for meiofauna and for macrofauna on intermediate and steeper beaches, the effects of physical constraints dominate. Steeper beach slopes, coarser particle sizes and increased wave exposure generally result in decreases in abundance, biomass and oxygen consumption, but these relationships are complex and non-linear. Sea-level rise is likely to lead to changes in ecosystem structure with generally negative impacts on ecosystem functions and ecosystem services. However, the impacts of sea-level rise will also be affected by local ecological context, especially for less sloping beaches.

  1. Bottom-up determination of soil collembola diversity and population dynamics in response to interactive climatic factors.

    PubMed

    A'Bear, A Donald; Boddy, Lynne; Jones, T Hefin

    2013-11-01

    Soil invertebrate contributions to decomposition are climate dependent. Understanding the influence of abiotic factors on soil invertebrate population dynamics will strengthen predictions regarding ecosystem functioning under climate change. As well as being important secondary decomposers, mycophagous collembola exert a strong influence on the growth and activity of primary decomposers, particularly fungi. Species-specific grazing preferences for different fungi enable fungal community composition to influence the direct impacts of climate change on collembola populations. We investigate the interactive roles of altered abiotic conditions (warming, wetting and drying) and the identity of the dominant decomposer fungus in determining collembola community dynamics in woodland soil mesocosms. The bottom-up influence of the dominant component of the fungal resource base was an important mediator of the direct climatic impacts on collembola populations. The positive influences of warming and wetting, and the negative influence of drying, on collembola abundance and diversity were much less pronounced in fungal-inoculation treatments, in which populations were reduced compared with uninoculated mesocosms. We conclude that the thick, sclerotised cords of the competitively dominant decomposer fungi reduced the biomass of smaller, more palatable soil fungi, limiting the size of collembola populations and their ability to respond to altered abiotic conditions.

  2. Determination of aminoglycoside residues in kidney and honey samples by hydrophilic interaction chromatography-tandem mass spectrometry.

    PubMed

    Kumar, Praveen; Rúbies, Antoni; Companyó, Ramon; Centrich, Francesc

    2012-10-01

    Two methods based on liquid chromatography-tandem mass spectrometry were developed for the determination of ten aminoglycosides (streptomycin, dihydrostreptomycin, spectinomycin, apramycin, paromomycin, kanamycin A, gentamycin C1, gentamycin C2/C2a, gentamycin C1a, and neomycin B) in kidney samples from food-producing animals and in honey samples. The methods involved extraction with an aqueous solution (for the kidney samples) or sample dissolution in water (for the honey samples), solid-phase extraction with a weak cation exchange cartridge and injection of the eluate into a liquid chromatography-tandem mass spectrometry system. A zwitterionic hydrophilic interaction chromatography column was used for separation of aminoglycosides and a triple quadrupole mass analyzer was used for detection. The methods were validated according to Decision 2002/657/EC. The limits of quantitation ranged from 2 to 125 μg/kg in honey and 25 to 264 μg/kg in the kidney samples. Interday precision (RSD%) ranged from 6 to 26% in honey and 2 to 21% in kidney. Trueness, expressed as the percentage of error, ranged from 7 to 20% in honey and 1 to 11% in kidney.

  3. Non-Linear Interactions Determine the Impact of Sea-Level Rise on Estuarine Benthic Biodiversity and Ecosystem Processes

    PubMed Central

    Yamanaka, Tsuyuko; Raffaelli, David; White, Piran C. L.

    2013-01-01

    Sea-level rise induced by climate change may have significant impacts on the ecosystem functions and ecosystem services provided by intertidal sediment ecosystems. Accelerated sea-level rise is expected to lead to steeper beach slopes, coarser particle sizes and increased wave exposure, with consequent impacts on intertidal ecosystems. We examined the relationships between abundance, biomass, and community metabolism of benthic fauna with beach slope, particle size and exposure, using samples across a range of conditions from three different locations in the UK, to determine the significance of sediment particle size beach slope and wave exposure in affecting benthic fauna and ecosystem function in different ecological contexts. Our results show that abundance, biomass and oxygen consumption of intertidal macrofauna and meiofauna are affected significantly by interactions among sediment particle size, beach slope and wave exposure. For macrofauna on less sloping beaches, the effect of these physical constraints is mediated by the local context, although for meiofauna and for macrofauna on intermediate and steeper beaches, the effects of physical constraints dominate. Steeper beach slopes, coarser particle sizes and increased wave exposure generally result in decreases in abundance, biomass and oxygen consumption, but these relationships are complex and non-linear. Sea-level rise is likely to lead to changes in ecosystem structure with generally negative impacts on ecosystem functions and ecosystem services. However, the impacts of sea-level rise will also be affected by local ecological context, especially for less sloping beaches. PMID:23861863

  4. Interaction of gonadal status with systemic inflammation and opioid use in determining nutritional status and prognosis in advanced pancreatic cancer.

    PubMed

    Skipworth, Richard J E; Moses, Alastair G W; Sangster, Kathryn; Sturgeon, Catharine M; Voss, Anne C; Fallon, Marie T; Anderson, Richard A; Ross, James A; Fearon, Kenneth C H

    2011-03-01

    Hypogonadism has been linked with systemic inflammation and opioid use in males with advanced cancer. We aimed to investigate the interaction of gonadal status with systemic inflammation and opioids in determining nutritional status and prognosis in advanced pancreatic cancer. One hundred and seventy-five patients (92 males, 83 postmenopausal females) with unresectable pancreatic cancer were studied. Serum sex steroids (total testosterone [TT], calculated free testosterone [cFT], oestradiol, sex hormone binding globulin), gonadotropins (follicle-stimulating hormone and luteinising hormone) and pro-inflammatory mediators (C-reactive protein [CRP], interleukin-6 [IL-6], soluble tumour necrosis factor receptor 75 [sTNFR75]) were measured, and nutritional assessment and opioid use recorded. Seventy-three percent of males were hypogonadal (by cFT definition). cFT correlated positively with BMI (r (2) =0.349; p< 0.001) and grip strength (r (2) = 0.229; p = 0.034) and inversely with weight loss (r (2) = -0.287; p = 0.007), CRP (r (2) = -0.426; p < 0.001) and IL-6 (r (2) = -0.303; p = 0.004). CRP (p= 0.007), opioid dosage (p = 0.009) and BMI (p = 0.005) were independent determinants of cFT on ANOVA. Hypogonadal males demonstrated worsened survival compared with eugonadal patients (TT: OR of death = 2.87; p < 0.001; cFT: OR = 2.26; p = 0.011). Furthermore, male opioid use was associated with decreased TT (p < 0.001) and cFT (p < 0.001) and worsened survival (OR = 1.96; p = 0.012). In contrast, 18% of postmenopausal females exhibited premenopausal ("hyperoestrogenic") oestradiol levels. Oestradiol correlated positively with sTNFR75 (r (2) = 0.299; p = 0.008). CRP (p < 0.001) was an independent determinant of oestradiol. Hyperoestrogenic females demonstrated worsened survival compared with eugonadal patients (OR = 2.43; p = 0.013). In males with pancreatic cancer, systemic

  5. Path integral Monte Carlo determination of the fourth-order virial coefficient for unitary two-component Fermi gas with zero-range interactions

    NASA Astrophysics Data System (ADS)

    Yan, Yangqian; Blume, D.

    2016-05-01

    The unitary equal-mass Fermi gas with zero-range interactions constitutes a paradigmatic model system that is relevant to atomic, condensed matter, nuclear, particle, and astro physics. This work determines the fourth-order virial coefficient b4 of such a strongly-interacting Fermi gas using a customized ab inito path integral Monte Carlo (PIMC) algorithm. In contrast to earlier theoretical results, which disagreed on the sign and magnitude of b4, our b4 agrees with the experimentally determined value, thereby resolving an ongoing literature debate. Utilizing a trap regulator, our PIMC approach determines the fourth-order virial coefficient by directly sampling the partition function. An on-the-fly anti-symmetrization avoids the Thomas collapse and, combined with the use of the exact two-body zero-range propagator, establishes an efficient general means to treat small Fermi systems with zero-range interactions. We gratefully acknowledge support by the NSF.

  6. Path-Integral Monte Carlo Determination of the Fourth-Order Virial Coefficient for a Unitary Two-Component Fermi Gas with Zero-Range Interactions

    NASA Astrophysics Data System (ADS)

    Yan, Yangqian; Blume, D.

    2016-06-01

    The unitary equal-mass Fermi gas with zero-range interactions constitutes a paradigmatic model system that is relevant to atomic, condensed matter, nuclear, particle, and astrophysics. This work determines the fourth-order virial coefficient b4 of such a strongly interacting Fermi gas using a customized ab initio path-integral Monte Carlo (PIMC) algorithm. In contrast to earlier theoretical results, which disagreed on the sign and magnitude of b4 , our b4 agrees within error bars with the experimentally determined value, thereby resolving an ongoing literature debate. Utilizing a trap regulator, our PIMC approach determines the fourth-order virial coefficient by directly sampling the partition function. An on-the-fly antisymmetrization avoids the Thomas collapse and, combined with the use of the exact two-body zero-range propagator, establishes an efficient general means to treat small Fermi systems with zero-range interactions.

  7. NEXT-GENERATION ANALYSIS OF CATARACTS: DETERMINING KNOWLEDGE DRIVEN GENE-GENE INTERACTIONS USING BIOFILTER, AND GENE-ENVIRONMENT INTERACTIONS USING THE PHENX TOOLKIT*

    PubMed Central

    Pendergrass, Sarah A.; Verma, Shefali S.; Holzinger, Emily R.; Moore, Carrie B.; Wallace, John; Dudek, Scott M.; Huggins, Wayne; Kitchner, Terrie; Waudby, Carol; Berg, Richard; McCarty, Catherine A.; Ritchie, Marylyn D.

    2013-01-01

    Investigating the association between biobank derived genomic data and the information of linked electronic health records (EHRs) is an emerging area of research for dissecting the architecture of complex human traits, where cases and controls for study are defined through the use of electronic phenotyping algorithms deployed in large EHR systems. For our study, 2580 cataract cases and 1367 controls were identified within the Marshfield Personalized Medicine Research Project (PMRP) Biobank and linked EHR, which is a member of the NHGRI-funded electronic Medical Records and Genomics (eMERGE) Network. Our goal was to explore potential gene-gene and gene-environment interactions within these data for 529,431 single nucleotide polymorphisms (SNPs) with minor allele frequency > 1%, in order to explore higher level associations with cataract risk beyond investigations of single SNP-phenotype associations. To build our SNP-SNP interaction models we utilized a prior-knowledge driven filtering method called Biofilter to minimize the multiple testing burden of exploring the vast array of interaction models possible from our extensive number of SNPs. Using the Biofilter, we developed 57,376 prior-knowledge directed SNP-SNP models to test for association with cataract status. We selected models that required 6 sources of external domain knowledge. We identified 5 statistically significant models with an interaction term with p-value < 0.05, as well as an overall model with p-value < 0.05 associated with cataract status. We also conducted gene-environment interaction analyses for all GWAS SNPs and a set of environmental factors from the PhenX Toolkit: smoking, UV exposure, and alcohol use; these environmental factors have been previously associated with the formation of cataracts. We found a total of 288 models that exhibit an interaction term with a p-value ≤ 1×10−4 associated with cataract status. Our results show these approaches enable advanced searches for epistasis

  8. Land-use history, historical connectivity, and land management interact to determine longleaf pine woodland understory richness and composition.

    SciTech Connect

    Brudvig, Lars A.; Damschen, Ellen L.

    2010-08-13

    Restoration and management activities targeted at recovering biodiversity can lead to unexpected results. In part, this is due to a lack of understanding of how site-level characteristics, landscape factors, and land-use history interact with restoration and management practices to determine patterns of diversity. For plants, such factors may be particularly important since plant populations often exhibit lagged responses to habitat loss and degradation. Here, we assess the importance of site-level, landscape, and historical effects for understory plant species richness and composition across a set of 40 longleaf pine Pinus palustris woodlands undergoing restoration for the federally endangered red-cockaded woodpecker in the southeastern United States. Land-use history had an overarching effect on richness and composition. Relative to historically forested sites, sites with agricultural histories (i.e. former pastures or cultivated fields) supported lower species richness and an altered species composition due to fewer upland longleaf pine woodland community members. Landscape effects did not influence the total number of species in either historically forested or post-agricultural sites; however, understory species composition was affected by historical connectivity, but only for post-agricultural sites. The influences of management and restoration activities were only apparent once land-use history was accounted for. Prescribed burning and mechanical overstory thinning were key drivers of understory composition and promoted understory richness in post-agricultural sites. In historically forested sites these activities had no impact on richness and only prescribed fire influenced composition. Our findings reveal complex interplays between site-level, landscape, and historical effects, suggest fundamentally different controls over plant communities in longleaf pine woodlands with varying land-use history, and underscore the importance of considering land

  9. Multiscale fluid-structure interaction modelling to determine the mechanical stimulation of bone cells in a tissue engineered scaffold.

    PubMed

    Zhao, Feihu; Vaughan, Ted J; Mcnamara, Laoise M

    2015-04-01

    Recent studies have shown that mechanical stimulation, by means of flow perfusion and mechanical compression (or stretching), enhances osteogenic differentiation of mesenchymal stem cells and bone cells within biomaterial scaffolds in vitro. However, the precise mechanisms by which such stimulation enhances bone regeneration is not yet fully understood. Previous computational studies have sought to characterise the mechanical stimulation on cells within biomaterial scaffolds using either computational fluid dynamics or finite element (FE) approaches. However, the physical environment within a scaffold under perfusion is extremely complex and requires a multiscale and multiphysics approach to study the mechanical stimulation of cells. In this study, we seek to determine the mechanical stimulation of osteoblasts seeded in a biomaterial scaffold under flow perfusion and mechanical compression using multiscale modelling by two-way fluid-structure interaction and FE approaches. The mechanical stimulation, in terms of wall shear stress (WSS) and strain in osteoblasts, is quantified at different locations within the scaffold for cells of different attachment morphologies (attached, bridged). The results show that 75.4 % of scaffold surface has a WSS of 0.1-10 mPa, which indicates the likelihood of bone cell differentiation at these locations. For attached and bridged osteoblasts, the maximum strains are 397 and 177,200 με, respectively. Additionally, the results from mechanical compression show that attached cells are more stimulated (maximum strain = 22,600 με) than bridged cells (maximum strain = 10.000 με)Such information is important for understanding the biological response of osteoblasts under in vitro stimulation. Finally, a combination of perfusion and compression of a tissue engineering scaffold is suggested for osteogenic differentiation.

  10. LHX2 Interacts with the NuRD Complex and Regulates Cortical Neuron Subtype Determinants Fezf2 and Sox11

    PubMed Central

    Muralidharan, Bhavana; Khatri, Zeba; Maheshwari, Upasana; Gupta, Ritika; Roy, Basabdatta; Pradhan, Saurabh J.; Karmodiya, Krishanpal; Padmanabhan, Hari; Shetty, Ashwin S.; Balaji, Chinthapalli; Kolthur-Seetharam, Ullas; Macklis, Jeffrey D.; Galande, Sanjeev

    2017-01-01

    In the developing cerebral cortex, sequential transcriptional programs take neuroepithelial cells from proliferating progenitors to differentiated neurons with unique molecular identities. The regulatory changes that occur in the chromatin of the progenitors are not well understood. During deep layer neurogenesis, we show that transcription factor LHX2 binds to distal regulatory elements of Fezf2 and Sox11, critical determinants of neuron subtype identity in the mouse neocortex. We demonstrate that LHX2 binds to the nucleosome remodeling and histone deacetylase histone remodeling complex subunits LSD1, HDAC2, and RBBP4, which are proximal regulators of the epigenetic state of chromatin. When LHX2 is absent, active histone marks at the Fezf2 and Sox11 loci are increased. Loss of LHX2 produces an increase, and overexpression of LHX2 causes a decrease, in layer 5 Fezf2 and CTIP2-expressing neurons. Our results provide mechanistic insight into how LHX2 acts as a necessary and sufficient regulator of genes that control cortical neuronal subtype identity. SIGNIFICANCE STATEMENT The functional complexity of the cerebral cortex arises from an array of distinct neuronal subtypes with unique connectivity patterns that are produced from common progenitors. This study reveals that transcription factor LHX2 regulates the numbers of specific cortical output neuron subtypes by controlling the genes that are required to produce them. Loss or increase in LHX2 during neurogenesis is sufficient to increase or decrease, respectively, a particular subcerebrally projecting population. Mechanistically, LHX2 interacts with chromatin modifying protein complexes to edit the chromatin landscape of its targets Fezf2 and Sox11, which regulates their expression and consequently the identities of the neurons produced. Thus, LHX2 is a key component of the control network for producing neurons that will participate in cortical circuitry. PMID:28053041

  11. Interaction of cosmic ray muons with spent nuclear fuel dry casks and determination of lower detection limit

    NASA Astrophysics Data System (ADS)

    Chatzidakis, S.; Choi, C. K.; Tsoukalas, L. H.

    2016-08-01

    The potential non-proliferation monitoring of spent nuclear fuel sealed in dry casks interacting continuously with the naturally generated cosmic ray muons is investigated. Treatments on the muon RMS scattering angle by Moliere, Rossi-Greisen, Highland and, Lynch-Dahl were analyzed and compared with simplified Monte Carlo simulations. The Lynch-Dahl expression has the lowest error and appears to be appropriate when performing conceptual calculations for high-Z, thick targets such as dry casks. The GEANT4 Monte Carlo code was used to simulate dry casks with various fuel loadings and scattering variance estimates for each case were obtained. The scattering variance estimation was shown to be unbiased and using Chebyshev's inequality, it was found that 106 muons will provide estimates of the scattering variances that are within 1% of the true value at a 99% confidence level. These estimates were used as reference values to calculate scattering distributions and evaluate the asymptotic behavior for small variations on fuel loading. It is shown that the scattering distributions between a fully loaded dry cask and one with a fuel assembly missing initially overlap significantly but their distance eventually increases with increasing number of muons. One missing fuel assembly can be distinguished from a fully loaded cask with a small overlapping between the distributions which is the case of 100,000 muons. This indicates that the removal of a standard fuel assembly can be identified using muons providing that enough muons are collected. A Bayesian algorithm was developed to classify dry casks and provide a decision rule that minimizes the risk of making an incorrect decision. The algorithm performance was evaluated and the lower detection limit was determined.

  12. Determination of glibenclamide and puerarin in rat plasma by UPLC-MS/MS: application to their pharmacokinetic interaction study.

    PubMed

    Li, Ning; Deng, Ying; Wang, Dan; Qiao, Ying; Li, Famei

    2013-01-30

    In the treatment of diabetes mellitus, glibenclamide and puerarin may be co-administered unwittingly or wittingly. An ultra performance liquid chromatography-tandem mass spectrometry method was developed to determine the concentrations of glibenclamide and puerarin in rat plasma for the study of pharmacokinetic interaction between them. Analytes were extracted using liquid-liquid extraction. The separation was achieved on a Waters BEH C18 column using 5 mmol/L ammonium acetate solution (containing 0.1% formic acid) and methanol as mobile phase with a linear gradient program. Electrospray ionization source was applied and operated in the multiple reaction monitoring positive mode. The proposed method was proved simple, specific and reliable. Glibenclamide, Pueraria lobata extract and glibenclamide in combination with P. lobata extract were orally administered to rats, respectively. Pharmacokinetic parameters were estimated by Microsoft Excel software and analyzed by SPSS 12.0 software. Compared with glibenclamide group, pharmacokinetic parameters of glibenclamide in the co-administration group such as area under the curve and mean residence time were increased while clearance was decreased. Pharmacokinetic parameters of puerarin in the co-administration group such as peak concentration and area under the curve were enlarged while clearance and apparent volume of distribution were reduced compared with P. lobata extract group. These changes could enhance drug efficacy, but could also make drug accumulation to increase adverse effects, so it was suggested that the dosage should be adjusted or the drug concentration in plasma should be monitored if glibenclamide and puerarin were co-administered. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. [Determination of melamine residue in raw milk and dairy products using hydrophilic interaction chromatography-electrospray ionization tandem mass spectrometry].

    PubMed

    Yan, Lijuan; Wu, Min; Zhang, Zhigang; Zhou, Yu; Lin, Liyi; Fang, Enhua; Xu, Dunming; Chen, Luping

    2008-11-01

    A method for the determination of melamine residue in raw milk and dairy products was developed using hydrophilic interaction chromatography-electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS). The melamine residue in the test sample was extracted with 1% trichloroacetic acid-acetonitrile (1 : 1, v/v) solution. The homogenate was centrifuged and the supernatant was collected. The extract was cleaned up using a mixed-mode cation exchange (MCX) solid-phase extraction cartridge and then concentrated, and analyzed by HILIC-ESI-MS/MS. The gradient chromatographic separation was performed using a hydrophilic silica column (250 mm x 4.6 mm, 5 microm) with 10 mmol/L ammonium acetate buffer (pH 3.0) and acetonitrile as the mobile phases. Due to its hydrophilic property, melamine was well retained on the column and seperated from other compounds. It effectively reduced matrix effect. A triple quadruple mass spectrometer equipped with an electrospray ionization source was employed for the qualitative and quantitative measurement of melamine. The melamine was quantified using the fragments produced from the protonated melamine ion through multiple reaction monitoring (MRM) in positive ion mode. Two MRM transitions from the protonated melamine ion (m/z 127 --> 85 and m/z 127 --> 68) were monitored. The average recoveries were between 76.3% and 98.7% in the spiked range of 0.5 to 10 mg/kg in raw milk and dairy products, and the relative standard deviations were less than 6.8%. The linear range was from 0.05 to 10.0 mg/L. The limit of quantification (S/N > 10) was 0.05 mg/kg. The method is highly selective and sensitive for the measurements of melamine and adequate for the analysis of melamine in raw milk and dairy products.

  14. Hydrophilic interaction liquid chromatography coupled to high-resolution mass spectrometry to determine artificial sweeteners in environmental waters.

    PubMed

    Salas, Daniela; Borrull, Francesc; Fontanals, Núria; Marcé, Rosa Maria

    2015-06-01

    Artificial sweeteners are food additives employed as sugar substitutes which are now considered to be emerging organic contaminants. In the present study, a method is developed for the determination of a group of artificial sweeteners in environmental waters. Considering the polar and hydrophilic character of these compounds, hydrophilic interaction liquid chromatography is proposed for their separation as an alternative to traditional reversed-phase liquid chromatography. Two stationary phases with different chemistry were compared for this purpose. For the detection of the analytes, high-resolution mass spectrometry (Orbitrap) was employed to take advantage of its benefits in terms of reliable quantification and confirmation for the measurement of accurate masses. Solid-phase extraction was chosen as the sample treatment, in which the extract in a mixture of NH4OH:MeOH:ACN (1:4:15) was directly injected into the chromatographic system, simplifying the analytical procedure. The optimized method was validated on river and waste water samples. For example, in the case of effluent water samples, limits of detection ranged from 0.002 to 0.7 μg/L and limits of quantification ranged from 0.004 to 1.5 μg/L. Apparent (whole method) recoveries ranged from 57 to 74% with intra-day precision (%RSD, n = 5) ranging from 6 to 25%. The method was successfully applied to water samples from different rivers in Catalonia and different waste water treatment plants in Tarragona. Acesulfame, cyclamate, saccharine and sucralose were found in several samples.

  15. Foraging modality and plasticity in foraging traits determine the strength of competitive interactions among carnivorous plants, spiders and toads.

    PubMed

    Jennings, David E; Krupa, James J; Rohr, Jason R

    2016-07-01

    Foraging modalities (e.g. passive, sit-and-wait, active) and traits are plastic in some species, but the extent to which this plasticity affects interspecific competition remains unclear. Using a long-term laboratory mesocosm experiment, we quantified competition strength and the plasticity of foraging traits in a guild of generalist predators of arthropods with a range of foraging modalities. Each mesocosm contained eight passively foraging pink sundews, and we employed an experimental design where treatments were the presence or absence of a sit-and-wait foraging spider and actively foraging toad crossed with five levels of prey abundance. We hypothesized that actively foraging toads would outcompete the other species at low prey abundance, but that spiders and sundews would exhibit plasticity in foraging traits to compensate for strong competition when prey were limited. Results generally supported our hypotheses. Toads had a greater effect on sundews at low prey abundances, and toad presence caused spiders to locate webs higher above the ground. Additionally, the closer large spider webs were to the ground, the greater the trichome densities produced by sundews. Also, spider webs were larger with than without toads and as sundew numbers increased, and these effects were more prominent as resources became limited. Finally, spiders negatively affected toad growth only at low prey abundance. These findings highlight the long-term importance of foraging modality and plasticity of foraging traits in determining the strength of competition within and across taxonomic kingdoms. Future research should assess whether plasticity in foraging traits helps to maintain coexistence within this guild and whether foraging modality can be used as a trait to reliably predict the strength of competitive interactions.

  16. Determination of partial unfolding enthalpy for lysozyme upon interaction with dodecyltrimethylammonium bromide using an extended solvation model.

    PubMed

    Behbehani, G Rezaei; Saboury, A A; Taleshi, E

    2008-01-01

    The interactions of dodecyltrimethylammonium bromides (DTABs) with hen egg lysozyme have been investigated at pH = 7.0 and 27 degrees C in phosphate buffer by isothermal titration calorimetry. DTAB interacts endothermically and activate lysozyme. The endothermicity of the lysozyme-DTAB interaction is in marked contrast to the exothermic interactions between sodium dodecyl sulphate (SDS) and lysozyme which have been attributed to specific binding between the anionic sulphate head groups and cationic amino acid residues. The enthalpies of interaction between the cationic surfactant (DTAB) and lysozyme are dominated by the endothermic unfolding of the native structure followed by an exothermic solvation of the lysozyme-DTAB complex by the addition of extra DTAB. A new direct calorimetric method to follow protein denaturation, and the effect of surfactants on the stability of proteins was introduced. The extended solvation model was used to reproduce the enthalpies of lysozyme-DTAB interaction over the whole range of DTAB concentrations. The solvation parameters recovered from the new equation, attributed to the structural change of lysozyme and its biological activity. At low concentrations of DTAB, the binding is mainly electrostatic, with some simultaneous interaction of the hydrophobic tail with nearby hydrophobic patches on the lysozyme. These initial interactions presumably cause some protein unfolding and expose additional hydrophobic sites. The DTAB-induced denaturation enthalpy of lysozyme is 86.46 +/- 0.02 kJ mol(-1).

  17. Multivalent interactions of the SUMO-interaction motifs in RING finger protein 4 determine the specificity for chains of the SUMO.

    PubMed

    Keusekotten, Kirstin; Bade, Veronika N; Meyer-Teschendorf, Katrin; Sriramachandran, Annie Miriam; Fischer-Schrader, Katrin; Krause, Anke; Horst, Christiane; Schwarz, Günter; Hofmann, Kay; Dohmen, R Jürgen; Praefcke, Gerrit J K

    2014-01-01

    RNF4 (RING finger protein 4) is a STUbL [SUMO (small ubiquitin-related modifier)-targeted ubiquitin ligase] controlling PML (promyelocytic leukaemia) nuclear bodies, DNA double strand break repair and other nuclear functions. In the present paper, we describe that the sequence and spacing of the SIMs (SUMO-interaction motifs) in RNF4 regulate the avidity-driven recognition of substrate proteins carrying SUMO chains of variable length.

  18. Prevalence, Specificity and Determinants of Lipid-Interacting PDZ Domains from an In-Cell Screen and In Vitro Binding Experiments

    PubMed Central

    Kashyap, Rudra; Polanowska, Jolanta; Betzi, Stéphane; Lembo, Frédérique; Vermeiren, Elke; Chiheb, Driss; Lenfant, Nicolas; Morelli, Xavier; Borg, Jean-Paul; Reboul, Jérôme; Zimmermann, Pascale

    2013-01-01

    Background PDZ domains are highly abundant protein-protein interaction modules involved in the wiring of protein networks. Emerging evidence indicates that some PDZ domains also interact with phosphoinositides (PtdInsPs), important regulators of cell polarization and signaling. Yet our knowledge on the prevalence, specificity, affinity, and molecular determinants of PDZ-PtdInsPs interactions and on their impact on PDZ-protein interactions is very limited. Methodology/Principal Findings We screened the human proteome for PtdInsPs interacting PDZ domains by a combination of in vivo cell-localization studies and in vitro dot blot and Surface Plasmon Resonance (SPR) experiments using synthetic lipids and recombinant proteins. We found that PtdInsPs interactions contribute to the cellular distribution of some PDZ domains, intriguingly also in nuclear organelles, and that a significant subgroup of PDZ domains interacts with PtdInsPs with affinities in the low-to-mid micromolar range. In vitro specificity for the head group is low, but with a trend of higher affinities for more phosphorylated PtdInsPs species. Other membrane lipids can assist PtdInsPs-interactions. PtdInsPs-interacting PDZ domains have generally high pI values and contain characteristic clusters of basic residues, hallmarks that may be used to predict additional PtdInsPs interacting PDZ domains. In tripartite binding experiments we established that peptide binding can either compete or cooperate with PtdInsPs binding depending on the combination of ligands. Conclusions/Significance Our screen substantially expands the set of PtdInsPs interacting PDZ domains, and shows that a full understanding of the biology of PDZ proteins will require a comprehensive insight into the intricate relationships between PDZ domains and their peptide and lipid ligands. PMID:23390500

  19. Pharmacokinetic drug–drug interactions between 1,4-dihydropyridine calcium channel blockers and statins: factors determining interaction strength and relevant clinical risk management

    PubMed Central

    Zhou, Yi-Ting; Yu, Lu-Shan; Zeng, Su; Huang, Yu-Wen; Xu, Hui-Min; Zhou, Quan

    2014-01-01

    Background Coadministration of 1,4-dihydropyridine calcium channel blockers (DHP-CCBs) with statins (or 3-hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] reductase inhibitors) is common for patients with hypercholesterolemia and hypertension. To reduce the risk of myopathy, in 2011, the US Food and Drug Administration (FDA) Drug Safety Communication set a new dose limitation for simvastatin, for patients taking simvastatin concomitantly with amlodipine. However, there is no such dose limitation for atorvastatin for patients receiving amlodipine. The combination pill formulation of amlodipine/atorvastatin is available on the market. There been no systematic review of the pharmacokinetic drug–drug interaction (DDI) profile of DHP-CCBs with statins, the underlying mechanisms for DDIs of different degree, or the corresponding management of clinical risk. Methods The relevant literature was identified by performing a PubMed search, covering the period from January 1987 to September 2013. Studies in the field of drug metabolism and pharmacokinetics that described DDIs between DHP-CCB and statin or that directly compared the degree of DDIs associated with cytochrome P450 (CYP)3A4-metabolized statins or DHP-CCBs were included. The full text of each article was critically reviewed, and data interpretation was performed. Results There were three circumstances related to pharmacokinetic DDIs in the combined use of DHP-CCB and statin: 1) statin is comedicated as the precipitant drug (pravastatin–nimodipine and lovastatin–nicardipine); 2) statin is comedicated as the object drug (isradipine–lovastatin, lacidipine–simvastatin, amlodipine–simvastatin, benidipine-simvastatin, azelnidipine– simvastatin, lercanidipine–simvastatin, and amlodipine–atorvastatin); and 3) mutual interactions (lercanidipine–fluvastatin). Simvastatin has an extensive first-pass effect in the intestinal wall, whereas atorvastatin has a smaller intestinal first-pass effect. The interaction

  20. Simultaneous determination of erlotinib and tamoxifen in rat plasma using UPLC-MS/MS: Application to pharmacokinetic interaction studies.

    PubMed

    Maher, Hadir M; Alzoman, Nourah Z; Shehata, Shereen M

    2016-08-15

    Tamoxifen (TAM) is a non-steroidal estrogen receptor antagonist that enhances erlotinib (ERL)-induced cytotoxicity in the treatment of NSCLC. ERL and TAM are metabolized by CYP3A4 enzymes. In addition, both drugs have the potential of altering the enzymatic activity through either inhibition (ERL) or induction (TAM). Thus it was expected that pharmacokinetics (PK) drug-drug interactions (DDIs) could be encountered following their co-administration. In this respect, a bioanalytical UPLC-MS/MS method has been developed and validated for the simultaneous determination of ERL and TAM in rat plasma samples, using ondansetron (OND) as an internal standard (IS). Plasma samples were prepared using mixed mode cationic solid phase extraction (SPE) STRATA™ -X-C 33μm cartridges with good extraction recovery of both drugs from rat plasma (Er% from -13.92 to -3.32). The drugs were separated on a Waters BEH™ C18 column with an isocratic elution using a mobile phase composed of a mixture of acetonitrile and water, each with 0.15% formic acid, in the ratio of 80: 20, v/v. Quantitation was carried out using the positive ionization mode with multiple reaction monitoring (MRM) at m/z 394.20>278.04 (ERL), m/z 372.25>72.01 (TAM), and m/z 294.18>170.16 (OND). The method was fully validated as per the FDA guidelines over the concentration range of 0.2-50ng/mL with very low lower limit of quantification (LLOQ) of 0.2ng/mL for both ERL and TAM. The intra- and inter-day assay precision (in terms of relative standard deviation, RSD) and accuracy (in terms of percentage relative error, % Er) were evaluated for both drugs and the calculated values evaluated at four different concentration levels were within the acceptable limits (<15%) for concentrations other than LLOQ and 20% for LLOQ. The method was successfully applied to the study of possible PK-DDI following the oral administration of ERL and TAM in a combination, compared to their single administration.

  1. Simultaneous determination of four local anesthetics by CE with ECL and study on interaction between procainamide and human serum albumin.

    PubMed

    Duan, Hong-Bing; Cao, Jun-Tao; Yang, Jiu-Jun; Wang, Hui; Liu, Yan-Ming

    2016-07-01

    A new method of capillary electrophoresis (CE) coupled with tris(2, 2'-bipyridyl) ruthenium(II) electrochemiluminescence (ECL) detection has been developed to detect four local anesthetics procainamide (PAH), tetracaine (TCH), proparacaine (PCH) and cinchocaine (CIN) simultaneously. An europium (III)-doped prussian blue analogue film (Eu-PB) modified platinum electrode was prepared and applied to improve the detection sensitivity. The parameters including additives, concentration and pH of the running buffer, separation voltage and detection potential that affect CE separation and ECL detection were optimized in detail. The four local anesthetics were baseline separated and detected within 10min under the optimized conditions. The detection limits (LOD) of PAH, TCH, PCH and CIN are 5.5×10(-8), 9.6×10(-8), 2.5×10(-8) and 3.5×10(-8)molL(-1) (S/N=3), respectively. RSDs of the migration time for four analytes range from 1.2% to 2.5% within intraday and from 2.4% to 4.9% in interday, RSDs of the peak area for four analytes are from 1.7% to 3.3% within intraday and from 2.2% to 5.6% in interday, respectively. The limits of quantitation (LOQ) (S/N=10) for PAH, TCH, PCH and CIN in human urine sample are 5.9×10(-7), 9.2×10(-7), 8.3×10(-7) and 5.0×10(-7)molL(-1), separately. The recoveries (n=3) of four analytes in human urine are from 87.6% to 107.7% with less than 5.9% in RSDs. The developed method was used to determine four local anesthetics in human urine samples and investigate the interaction between PAH and human serum albumin (HSA). The number of binding sites and the binding constant of PAH with HSA were calculated to be 1.03 and 2.4×10(4)Lmol(-1), respectively.

  2. The Interaction between the Fiber Knob Domain and the Cellular Attachment Receptor Determines the Intracellular Trafficking Route of Adenoviruses

    PubMed Central

    Shayakhmetov, Dmitry M.; Li, Zong-Yi; Ternovoi, Vladimir; Gaggar, Anuj; Gharwan, Helen; Lieber, André

    2003-01-01

    Most of the presently used adenovirus (Ad) vectors are based on serotype 5. However, the application of these vectors is limited by the native tropism of Ad5. To address this problem, a series of fiber chimeric vectors were produced to take advantage of the different cellular receptors used by Ad of different subgroups. In this study we utilize an Ad5-based chimeric vector containing sequences encoding the Ad35 fiber knob domain instead of the Ad5 knob (Ad5/35L) to analyze factors responsible for selection of intracellular trafficking routes by Ads. By competition analysis with recombinant Ad5 and Ad35 knobs we showed that the Ad5/35L vector infected cells through a receptor different from the Ad5 receptor. Intracellular trafficking of Ad5 and Ad5/35L viruses was analyzed in HeLa cells by tracking fluorophore-conjugated Ad particles, by immunostaining for capsid hexon protein, by electron microscopy, and by Southern blotting for viral DNA. These studies showed that the interaction with the Ad35 receptor(s) predestines Ad5/35L vector to intracellular trafficking pathways different from those of Ad5. Ad5 efficiently escaped from the endosomes early after infection. In contrast, Ad5/35L remained longer in late endosomal/lysosomal compartments and used them to achieve localization to the nucleus. However, a significant portion of Ad5/35L particles appeared to be recycled back to the cell surface. This phenomenon resulted in significantly less efficient Ad5/35L-mediated gene transfer compared to that of Ad5. We also demonstrated that the selection of intracellular trafficking routes was determined by the fiber knob domain and did not depend on the length of the fiber shaft. This study contributes to a better understanding of the mechanisms that govern the infection of retargeted, capsid-modified vectors which have potential application for hematopoietic stem cell and tumor gene therapy. PMID:12610146

  3. Interactive Whiteboard Technologies in High School: A Comparison of Their Impact on the Levels of Measure That Determine a Return on Investment

    ERIC Educational Resources Information Center

    Schipper, Joseph M.; Yocum, Russell G.

    2016-01-01

    This quantitative, quasi-experimental, nonequivalent group study examined the impact on levels of measure that determine a return on investment of differing forms of interactive whiteboard (IWB) technology used at a high school in a suburban school district in southeastern Virginia. Three forms of IWB were compared: a full-screen IWB, a mobile…

  4. INTERACTION OF LASER RADIATION WITH MATTER: Absorption of a femtosecond laser pulse by metals and the possibility of determining effective electron—electron collision frequencies

    NASA Astrophysics Data System (ADS)

    Isakov, Vladimir A.; Kanavin, Andrey P.; Uryupin, Sergey A.

    2006-10-01

    A method is proposed for describing absorption of an electron-heating femtosecond laser pulse that interacts with a metal under conditions of high-frequency skin effect. It is shown that the effective frequencies of electron—electron collisions accompanied by umklapp processes can be determined by measuring the absorption or reflection coefficients of a femtosecond pulse.

  5. Interactive Whiteboard Technologies in High School: A Comparison of Their Impact on the Levels of Measure That Determine a Return on Investment

    ERIC Educational Resources Information Center

    Schipper, Joseph M.; Yocum, Russell G.

    2016-01-01

    This quantitative, quasi-experimental, nonequivalent group study examined the impact on levels of measure that determine a return on investment of differing forms of interactive whiteboard (IWB) technology used at a high school in a suburban school district in southeastern Virginia. Three forms of IWB were compared: a full-screen IWB, a mobile…

  6. Real-time non-invasive eyetracking and gaze-point determination for human-computer interaction and biomedicine

    NASA Technical Reports Server (NTRS)

    Talukder, Ashit; Morookian, John-Michael; Monacos, S.; Lam, R.; Lebaw, C.; Bond, A.

    2004-01-01

    Eyetracking is one of the latest technologies that has shown potential in several areas including human-computer interaction for people with and without disabilities, and for noninvasive monitoring, detection, and even diagnosis of physiological and neurological problems in individuals.

  7. Role of Dispersive Interactions in Determining Structural Properties of Organic-Inorganic Halide Perovskites: Insights from First-Principles Calculations.

    PubMed

    Egger, David A; Kronik, Leeor

    2014-08-07

    A microscopic picture of structure and bonding in organic-inorganic perovskites is imperative to understanding their remarkable semiconducting and photovoltaic properties. On the basis of a density functional theory treatment that includes both spin-orbit coupling and dispersive interactions, we provide detailed insight into the crystal binding of lead-halide perovskites and quantify the effect of different types of interactions on the structural properties. Our analysis reveals that cohesion in these materials is characterized by a variety of interactions that includes important contributions from both van der Waals interactions among the halide atoms and hydrogen bonding. We also assess the role of spin-orbit coupling and show that it causes slight changes in lead-halide bonding that do not significantly affect the lattice parameters. Our results establish that consideration of dispersive effects is essential for understanding the structure and bonding in organic-inorganic perovskites in general and for providing reliable theoretical predictions of structural parameters in particular.

  8. Real-time non-invasive eyetracking and gaze-point determination for human-computer interaction and biomedicine

    NASA Technical Reports Server (NTRS)

    Talukder, Ashit; Morookian, John-Michael; Monacos, S.; Lam, R.; Lebaw, C.; Bond, A.

    2004-01-01

    Eyetracking is one of the latest technologies that has shown potential in several areas including human-computer interaction for people with and without disabilities, and for noninvasive monitoring, detection, and even diagnosis of physiological and neurological problems in individuals.

  9. Simultaneous determination of gastrodin and puerarin in rat plasma by HPLC and the application to their interaction on pharmacokinetics.

    PubMed

    Jiang, Li; Dai, Jundong; Huang, Zhenlin; Du, Qinghua; Lin, Jiahao; Wang, Yurong

    2013-02-01

    Gastrodin (Gas) and puerarin (Pur) are bioactive substances derived from traditional Chinese medicine Gastrodia elata and Radix Puerariae, respectively, which were often used together in Chinese clinical prescriptions. Their injections were used in combined way for treatment of some cardiocerebrovascular diseases in clinic, especially for vertigo due to vertebrobasilar ischemia. In this paper, interaction of gastrodin and puerarin in rat plasma pharmacokinetics via intragastic (i.g.)/intravenous (i.v.) administration was investigated. A reliable HPLC method was developed for simultaneous determination of Gas and Pur in rat plasma with a linear range of 0.101-101 μg/mL for Gas and 0.0500-5.98 μg/mL for Pur (r(2)>0.993). The LLOQ, LOD of Gas and Pur were determined to be 0.101, 0.0486 μg/mL, and 0.05, 0.0245 μg/mL, respectively. The intra-day and inter-day precision were all less than 12.0%, whilst the accuracy were all within 96.4±6.00%. The proposed method has been successfully applied to the pharmacokinetic study of the analytes in rats after i.g./i.v. administration of Gas and Pur alone or combined with each other (i.g.: 40 mg/kg Gas, 400 mg/kg Pur; i.v.: 20 mg/kg Gas, 20 mg/kg Pur). Blood samples were collected from retinal vein plexus of rats at predetermined time points and plasma containing the internal standard tyrosol (IS) were precipitated by methanol and chromatography was carried out on a C(18) column with a gradient mobile phase of ACN-H(2)O with 0.05% phosphoric acid as a modifier. The pharmacokinetic profiles of combined administration were found to be distinct from those of given alone. The C(max), T(max), T(1/2), MRT of Gas administrated alone or combined with Pur via i.g. were 21.7 μg/mL, 0.250 h, 2.81 h, 0.830 h and 18.4 μg/mL, 0.550 h, 0.970 h, 1.37 h, respectively, of Pur administrated alone or combined with Gas via i.g. were 0.490 μg/mL, 1.95 h, 1.33 h, 2.10 h and 2.01 μg/mL, 0.570 h, 4.00 h, 5.10 h, respectively. The relative oral

  10. Determination of tetrodotoxin and its analogs in the puffer fish Takifugu oblongus from Bangladesh by hydrophilic interaction chromatography and mass-spectrometric detection.

    PubMed

    Diener, Marc; Christian, Bernd; Ahmed, M Sagir; Luckas, Bernd

    2007-11-01

    Tetrodotoxin (TTX) and its analogs (TTXs), widely distributed among marine as well as terrestrial animals, induce dangerous intoxications. These highly potential toxins are also known as the causative agent of puffer fish poisoning. A newly developed highly sensitive method for determination of TTXs based on hydrophilic interaction chromatography and mass-spectrometric detection is presented. TTX, anhydrotetrodotoxin, 11-deoxytetrodotoxin and trideoxytetrodotoxin were determined in separated tissues of Bangladeshi marine puffers, Takifugu oblongus. TTX was predominant in skin, muscle and liver, whereas trideoxytetrodotoxin preponderated in the ovary. The toxicity of the various tissues was determined by a mouse bioassay.

  11. Novel protein interactions with an actin homolog (MreB) of Helicobacter pylori determined by bacterial two-hybrid system.

    PubMed

    Zepeda Gurrola, Reyna Cristina; Fu, Yajuan; Rodríguez Luna, Isabel Cristina; Benítez Cardoza, Claudia Guadalupe; López López, María de Jesús; López Vidal, Yolanda; Gutíerrez, Germán Rubén Aguilar; Rodríguez Pérez, Mario A; Guo, Xianwu

    2017-08-01

    The bacterium Helicobacter pylori infects more than 50% of the world population and causes several gastroduodenal diseases, including gastric cancer. Nevertheless, we still need to explore some protein interactions that may be involved in pathogenesis. MreB, an actin homolog, showed some special characteristics in previous studies, indicating that it could have different functions. Protein functions could be realized via protein-protein interactions. In the present study, the MreB protein from H. pylori 26695 fused with two tags 10×His and GST in tandem was overexpressed and purified from Escherchia coli. The purified recombinant protein was used to perform a pull-down assay with H. pylori 26695 cell lysate. The pulled-down proteins were identified by mass spectrometry (MALDI-TOF), in which the known important proteins related to morphogenesis were absent but several proteins related to pathogenesis process were observed. The bacterial two-hybrid system was further used to evaluate the protein interactions and showed that new interactions of MreB respectively with VacA, UreB, HydB, HylB and AddA were confirmed but the interaction MreB-MreC was not validated. These results indicated that the protein MreB in H. pylori has a distinct interactome, does not participate in cell morphogenesis via MreB-MreC but could be related to pathogenesis. Copyright © 2017 Elsevier GmbH. All rights reserved.

  12. Lipid packing determines protein-membrane interactions: challenges for apolipoprotein A–I and High Density Lipoproteins

    PubMed Central

    Sánchez, Susana A.; Tricerri, M. Alejandra; Ossato, Giulia; Gratton, Enrico

    2010-01-01

    Summary Protein and protein-lipid interactions, with and within specific areas in the cell membrane, are critical in order to modulate the cell signaling events required to maintain cell functions and viability. Biological bilayers are complex, dynamic platforms, and thus in vivo observations usually need to be preceded by studies on model systems that simplify and discriminate the different factors involved in lipid-protein interactions. Fluorescence microscopy studies using giant unilamellar vesicles (GUVs) as membrane model systems provide a unique methodology to quantify protein binding, interaction and lipid solubilization in artificial bilayers. The large size of lipid domains obtainable on GUVs, together with fluorescence microscopy techniques, provides the possibility to localize and quantify molecular interactions. FCS (Fluorescence Correlation Spectroscopy) can be performed using the GUV model to extract information on mobility and concentration. Two-photon Laurdan GP (Generalized Polarization) reports on local changes in membrane water content (related to membrane fluidity) due to protein binding or lipid removal from a given lipid domain. In this review, we summarize the experimental microscopy methods used to study the interaction of human apolipoprotein A–I (apoA-I) in lipid-free and lipid-bound conformations with bilayers and natural membranes. Results described here help us to understand cholesterol homeostasis, and offer a methodological design suited to different biological systems. PMID:20347719

  13. Separating the role of biotic interactions and climate in determining adaptive response of plants to climate change.

    PubMed

    Tomiolo, Sara; Van der Putten, Wim H; Tielbörger, Katja

    2015-05-01

    Altered rainfall regimes will greatly affect the response of plant species to climate change. However, little is known about how direct effects of changing precipitation on plant performance may depend on other abiotic factors and biotic interactions. We used reciprocal transplants between climatically very different sites with simultaneous manipulation of soil, plant population origin, and neighbor conditions to evaluate local adaptation and possible adaptive response of four Eastern Mediterranean annual plant species to climate change. The effect of site on plant performance was negligible, but soil origin had a strong effect on fecundity, most likely due to differential water retaining ability. Competition by neighbors strongly reduced fitness. We separated the effects of the abiotic and biotic soil properties on plant performance by repeating the field experiment in a greenhouse under homogenous environmental conditions and including a soil biota manipulation treatment. As in the field, plant performance differed among soil origins and neighbor treatments. Moreover, we found plant species-specific responses to soil biota that may be best explained by the differential sensitivity to negative and positive soil biota effects. Overall, under the conditions of our experiment with two contrasting sites, biotic interactions had a strong effect on plant fitness that interacted with and eventually overrode climate. Because climate and biotic interactions covary, reciprocal transplants and climate gradient studies should consider soil biotic interactions and abiotic conditions when evaluating climate change effects on plant performance.

  14. MEK1act/tubulin interaction is an important determinant of mitotic stability in cultured HT1080 human fibrosarcoma cells

    PubMed Central

    Cao, Jia-ning; Shafee, Norazizah; Vickery, Larry; Kaluz, Stefan; Ru, Ning; Stanbridge, Eric J.

    2010-01-01

    Activation of the MAPK pathway plays a major role in neoplastic cell transformation. Using a proteomics approach we identified α tubulin and β tubulin as proteins that interact with activated MEK1, a central MAPK regulatory kinase. Confocal analysis revealed spatio-temporal control of MEK1-tubulin co-localization that was most prominent in the mitotic spindle apparatus in variant HT1080 human fibrosarcoma cells. Peptide arrays identified the critical role of positively charged amino acids R108, R113, R160 and K157 on the surface of MEK1 for tubulin interaction. Overexpression of activated MEK1 caused defects in spindle arrangement, chromosome segregation and ploidy. In contrast, chromosome polyploidy was reduced in the presence of an activated MEK1 mutant (R108A, R113A) that disrupted interactions with tubulin. Our findings indicate the importance of signaling by activated MEK1-tubulin in spindle organization and chromosomal instability. PMID:20570892

  15. Interactions among lactose, β-lactoglobulin and starch in co-lyophilized mixtures as determined by Fourier Transform Infrared Spectroscopy.

    PubMed

    Hajihashemi, Zohreh; Nasirpour, Ali; Scher, Joël; Desobry, Stéphane

    2014-11-01

    Processing and storage change food powders containing a large quantity of lactose due to lactose crystallization and interactions among components. Model food systems were prepared by co-lyophilization of lactose, β-lactoglobulin (BLG), and gelatinized starch. A mixture design was used to define the percentage of each mixture component to simulate a wide range of food powders. Interactions among lactose, BLG and starch were studied using Fourier Transform Infrared (FT-IR) at different relative humidities (RH), before and after 3 months storage. Results showed the presence of hydrogen bonds among these components. Moreover, interactions or formation of hydrogen bonds among lactose, starch and BLG preserved BLG against freezing and freeze-drying shocks. Lactose crystallization could be identified by comparing infrared spectra of amorphous and crystallized lactose at O - H and C - H stretching vibration bands.

  16. [Determining the parameters for receptor-ligand interaction by serial dilution method for the case when the ligand and receptor are in a pre-existing mixture].

    PubMed

    Bobrovnik, S A

    2005-01-01

    New methods of determining the binding parameters for ligand-receptor interaction are considered. The considered approaches are based on the earlier suggested method of serial dilution and application of so-called coordinates of dilution. It was shown that the suggested methods allow to evaluate affinity constant and ligand concentration even for the case, when the receptor and corresponding ligand of unknown concentration are in a mixture and their separation from each other is impossible. In this connection the suggested methods are especially useful for studying the ligand-receptor interaction if the receptor is very liable and its purification from the ligand would cause drastic changes of its binding properties.

  17. Identification of distinct nisin leader peptide regions that determine interactions with the modification enzymes NisB and NisC.

    PubMed

    Khusainov, Rustem; Moll, Gert N; Kuipers, Oscar P

    2013-01-01

    Nisin is the most prominent and applied bacteriocin that serves as a model for class I lantibiotics. The nisin leader peptide importantly determines interactions between precursor nisin and its modification enzymes NisB and NisC that mature nisin posttranslationally. NisB dehydrates serines and threonines, while NisC catalyzes the subsequent coupling of the formed dehydroamino acids to form lanthionines. Currently, little is known about how the nisin leader interacts with NisB and even less is known about its interactions with NisC. To investigate the nisin leader peptide requirements for functional interaction with the modification enzymes NisB and NisC, we systematically replaced six regions, of 2-4 amino acids each, with all-alanine regions. By performing NisB and NisC co-purification studies with these mutant leader peptides, we demonstrate that the nisin leader regions STKD(-22-19), FNLD(-18-15) and PR(-2-1) importantly contribute to the interactions of precursor nisin with both NisB and NisC, whereas the nisin leader region LVSV(-14-11) additionally contributes to the interaction of precursor nisin with NisC.

  18. A binding site outside the canonical PDZ domain determines the specific interaction between Shank and SAPAP and their function

    PubMed Central

    Zeng, Menglong; Shang, Yuan; Guo, Tingfeng; He, Qinghai; Yung, Wing-Ho; Liu, Kai; Zhang, Mingjie

    2016-01-01

    Shank and SAPAP (synapse-associated protein 90/postsynaptic density-95–associated protein) are two highly abundant scaffold proteins that directly interact with each other to regulate excitatory synapse development and plasticity. Mutations of SAPAP, but not other reported Shank PDZ domain binders, share a significant overlap on behavioral abnormalities with the mutations of Shank both in patients and in animal models. The molecular mechanism governing the exquisite specificity of the Shank/SAPAP interaction is not clear, however. Here we report that a sequence preceding the canonical PDZ domain of Shank, together with the elongated PDZ BC loop, form another binding site for a sequence upstream of the SAPAP PDZ-binding motif, leading to a several hundred-fold increase in the affinity of the Shank/SAPAP interaction. We provide evidence that the specific interaction afforded by this newly identified site is required for Shank synaptic targeting and the Shank-induced synaptic activity increase. Our study provides a molecular explanation of how Shank and SAPAP dosage changes due to their gene copy number variations can contribute to different psychiatric disorders. PMID:27185935

  19. Supply determines demand: influence of partner quality and quantity on the interactions between bats and pitcher plants.

    PubMed

    Schöner, Caroline R; Schöner, Michael G; Kerth, Gerald; Grafe, T Ulmar

    2013-09-01

    Interspecific relationships such as mutualism and parasitism are major drivers of biodiversity. Because such interactions often comprise more than two species, ecological studies increasingly focus on complex multispecies systems. However, the spatial heterogeneity of multi-species interactions is often poorly understood. Here, we investigate the unusual interaction of a bat (Kerivoula hardwickii hardwickii) and two pitcher plant species (Nepenthes hemsleyana and N. bicalcarata) whose pitchers serve as roost for bats. Nepenthes hemsleyana offers roosts of higher quality, indicated by a more stable microclimate compared to N. bicalcarata but occurs at lower abundance and is less common than the latter. Whereas N. hemsleyana benefits from the roosting bats by gaining nitrogen from their feces, the bats' interaction with N. bicalcarata seems to be commensal or even parasitic. Bats stayed longer in roosts of higher quality provided by N. hemsleyana and preferred them to pitchers of N. bicalcarata in a disturbance experiment. Moreover, bats roosting only in pitchers of N. hemsleyana had a higher body condition and were less infested with parasites compared to bats roosting in pitchers of N. bicalcarata. Our study shows how the local supply of roosts with different qualities affects the behavior and status of their inhabitants and-as a consequence-how the demand of the inhabitants can influence evolutionary adaptations of the roost providing species.

  20. The interaction of 2-mercaptobenzimidazole with human serum albumin as determined by spectroscopy, atomic force microscopy and molecular modeling.

    PubMed

    Li, Yuqin; Jia, Baoxiu; Wang, Hao; Li, Nana; Chen, Gaopan; Lin, Yuejuan; Gao, Wenhua

    2013-04-01

    The interaction of 2-mercaptobenzimidazole (MBI) with human serum albumin (HSA) was studied in vitro by equilibrium dialysis under normal physiological conditions. This study used fluorescence, ultraviolet-visible spectroscopy (UV-vis), Fourier transform infrared (FT-IR), circular dichroism (CD) and Raman spectroscopy, atomic force microscopy (AFM) and molecular modeling techniques. Association constants, the number of binding sites and basic thermodynamic parameters were used to investigate the quenching mechanism. Based on the fluorescence resonance energy transfer, the distance between the HSA and MBI was 2.495 nm. The ΔG(0), ΔH(0), and ΔS(0) values across temperature indicated that the hydrophobic interaction was the predominant binding Force. The UV, FT-IR, CD and Raman spectra confirmed that the HSA secondary structure was altered in the presence of MBI. In addition, the molecular modeling showed that the MBI-HSA complex was stabilized by hydrophobic forces, which resulted from amino acid residues. The AFM results revealed that the individual HSA molecule dimensions were larger after interaction with MBI. Overall, this study suggested a method for characterizing the weak intermolecular interaction. In addition, this method is potentially useful for elucidating the toxigenicity of MBI when it is combined with the biomolecular function effect, transmembrane transport, toxicological testing and other experiments.

  1. On their best behavior: how animal behavior can help determine the combined effects of species interactions and climate change.

    PubMed

    Harmon, Jason P; Barton, Brandon T

    2013-09-01

    The increasingly appreciated link between climate change and species interactions has the potential to help us understand and predict how organisms respond to a changing environment. As this connection grows, it becomes even more important to appreciate the mechanisms that create and control the combined effect of these factors. However, we believe one such important set of mechanisms comes from species' behavior and the subsequent trait-mediated interactions, as opposed to the more often studied density-mediated effects. Behavioral mechanisms are already well appreciated for mitigating the separate effects of the environment and species interactions. Thus, they could be at the forefront for understanding the combined effects. In this review, we (1) show some of the known behaviors that influence the individual and combined effects of climate change and species interactions; (2) conceptualize general ways behavior may mediate these combined effects; and (3) illustrate the potential importance of including behavior in our current tools for predicting climate change effects. In doing so, we hope to promote more research on behavior and other mechanistic factors that may increase our ability to accurately predict climate change effects. © 2013 New York Academy of Sciences.

  2. The calculation of electrostatic interactions and their role in determining the energies and geometries of explosive molecular crystals

    SciTech Connect

    Ritchie, J.P.; Kober, E.M.; Copenhaver, A.S.

    1993-01-01

    Three different procedures were used to calculate electrostatic interactions in explosive molecular crystals. The use of Potential Derived Charges (PDC's) and atom-centered multipole expansions (ACME's) provides reasonable fits of the molecular electrostatic potential. The ability of these approaches to reproduce observed crystal structures was also evaluated.

  3. Role of directed van der Waals bonded interactions in the determination of the structures of molecular arsenate solids.

    PubMed

    Gibbs, G V; Wallace, A F; Cox, D F; Dove, P M; Downs, R T; Ross, N L; Rosso, K M

    2009-01-29

    Bond paths, local energy density properties, and Laplacian, L(r) = -wedge(2)rho(r), composite isosurfaces of the electron density distributions were calculated for the intramolecular and intermolecular bonded interactions for molecular solids of As(2)O(3) and AsO(2) composition, an As(2)O(5) crystal, a number of arsenate molecules, and the arsenic metalloid, arsenolamprite. The directed intermolecular van der Waals As-O, O-O, and As-As bonded interactions are believed to serve as mainstays between the individual molecules in each of the molecular solids. As-O bond paths between the bonded atoms connect Lewis base charge concentrations and Lewis acid charge depletion domains, whereas the O-O and As-As paths connect Lewis base pair and Lewis acid pair domains, respectively, giving rise to sets of intermolecular directed bond paths. The alignment of the directed bond paths results in the periodic structures adopted by the arsenates. The arrangements of the As atoms in the claudetite polymorphs of As(2)O(3) and the As atoms in arsenolamprite are similar. Like the As(2)O(3) polymorphs, arsenolamprite is a molecular solid connected by relatively weak As-As intermolecular directed van der Waals bond paths between the layers of stronger As-As intramolecular bonded interactions. The bond critical point and local energy density properties of the intermolecular As-As bonded interactions in arsenolamprite are comparable with the As-As interactions in claudetite I. As such, the structure of claudetite I can be viewed as a stuffed derivative of the arsenolamprite structure with O atoms between pairs of As atoms comprising the layers of the structure. The cubic structure adopted by the arsenolite polymorph can be understood in terms of sets of directed acid-base As-O and base-base O-O pair domains and bond paths that radiate from the tetrahedral faces of its constituent molecules, serving as face-to-face key-lock mainstays in forming a periodic tetrahedral array of molecules

  4. Exercisers' perceptions of their fitness instructor's interacting style, perceived competence, and autonomy as a function of self-determined regulation to exercise, enjoyment, affect, and exercise frequency.

    PubMed

    Puente, Rogelio; Anshel, Mark H

    2010-02-01

    The primary purpose of the present investigation was to test the hypothesis, derived from Self-Determination Theory (SDT), that an individual's perceived competence and autonomy mediate the relationship between the exercisers' perception of their instructor's interaction style and the exercisers' motivation to exercise. A secondary purpose was to identify the affective and behavioral outcomes derived from self-determined regulation. It was hypothesized that SDT would significantly explain and predict exercise behavior. Participants consisted of 238 college students, 103 males and 135 females (M age = 20.4 years, SD = 2.16), who volunteered to participate in the study. They were asked to complete a battery of questionnaires measuring instructor's interacting style, self-regulation to exercise, perceived autonomy and competence, enjoyment, positive and negative affect, and exercise frequency. Using structural equation modeling with observed variables, the results showed that perceived competence and autonomy mediated the relationship between perceived instructor's interacting style and self-determined regulation. It was also found that self-determined regulation was significantly related to exercise enjoyment, positive affect, and exercise frequency. It was concluded that understanding the motivational factors and emotional and behavioral consequences of physical activity will partially explain an individual's motives to engage regularly in exercise.

  5. Determination of the enthalpy of solute-solvent interaction from the enthalpy of solution: aqueous solutions of erythritol and L-threitol.

    PubMed

    Lopes Jesus, A J; Tomé, Luciana I N; Eusébio, M Ermelinda S; Redinha, J S

    2006-05-11

    In this work the enthalpy of the solute-solvent interaction of erythritol and L-threitol in aqueous solution was determined from the values obtained for the enthalpy of solvation. The values for this property were calculated from those determined for the enthalpies of solution and sublimation. To determine the values of the enthalpy of solute-solvent interaction, the solvation process is considered as taking place in three steps: opening a cavity in the solvent to hold the solute molecule, changing the solute conformation when it passes from the gas phase into solution, and interaction between the solute and the solvent molecules. The cavity enthalpy was calculated by the scaled particle theory and the conformational enthalpy change was estimated from the value of this function in the gas phase and in solution. Both terms were determined by DFT calculations. The solvent effect on the solute conformation in solution was estimated using the CPCM solvation model. The importance of the cavity and conformational terms in the interpretation of the enthalpy of solvation is noted. While the cavity term has been used by some authors, the conformational term is considered for the first time. The structural features in aqueous solution of erythritol and L-threitol are discussed.

  6. Do intraspecific or interspecific interactions determine responses to predators feeding on a shared size-structured prey community?

    PubMed

    ten Brink, Hanna; Mazumdar, Abul Kalam Azad; Huddart, Joseph; Persson, Lennart; Cameron, Tom C

    2015-03-01

    Coexistence of predators that share the same prey is common. This is still the case in size-structured predator communities where predators consume prey species of different sizes (interspecific prey responses) or consume different size classes of the same species of prey (intraspecific prey responses). A mechanism has recently been proposed to explain coexistence between predators that differ in size but share the same prey species, emergent facilitation, which is dependent on strong intraspecific responses from one or more prey species. Under emergent facilitation, predators can depend on each other for invasion, persistence or success in a size-structured prey community. Experimental evidence for intraspecific size-structured responses in prey populations remains rare, and further questions remain about direct interactions between predators that could prevent or limit any positive effects between predators [e.g. intraguild predation (IGP)]. Here, we provide a community-wide experiment on emergent facilitation including natural predators. We investigate both the direct interactions between two predators that differ in body size (fish vs. invertebrate predator), and the indirect interaction between them via their shared prey community (zooplankton). Our evidence supports the most likely expectation of interactions between differently sized predators that IGP rates are high, and interspecific interactions in the shared prey community dominate the response to predation (i.e. predator-mediated competition). The question of whether emergent facilitation occurs frequently in nature requires more empirical and theoretical attention, specifically to address the likelihood that its pre-conditions may co-occur with high rates of IGP.

  7. Use of Molecular Modeling to Determine the Interaction and Competition of Gases within Coal for Carbon Dioxide Sequestration

    SciTech Connect

    Jeffrey D. Evanseck; Jeffry D. Madura

    2003-02-23

    A 3-dimensional coal structural model for the Argonne Premium Coal Pocahontas No. 3 has been generated. The model was constructed based on the wealth of structural information available in the literature with the enhancement that the structural diversity within the structure was represented implicitly (for the first time) based on image analysis of HRTEM in combination with LDMS data. The complex and large structural model (>10,000 carbon atoms) will serve as a basis for examining the interaction of gases within this low volatile bituminous coal. Simulations are of interest to permit reasonable simulations of the host-guest interactions with regard to carbon dioxide sequestration within coal and methane displacement from coal. The molecular structure will also prove useful in examining other coal related behavior such as solvent swelling, liquefaction and other properties. Molecular models of CO{sub 2} have been evaluated with water to analyze which classical molecular force-field parameters are the most reasonable to predict the interactions of CO{sub 2} with water. The comparison of the molecular force field models was for a single CO{sub 2}-H{sub 2}O complex and was compared against first principles quantum mechanical calculations. The interaction energies and the electrostatic interaction distances were used as criteria in the comparison. The ab initio calculations included Hartree-Fock, B3LYP, and Moeller-Plesset 2nd, 3rd, and 4th order perturbation theories with basis sets up to the aug-cc-pvtz basis set. The Steele model was the best literature model, when compared to the ab initio data, however, our new CO{sub 2} model reproduces the QM data significantly better than the Steele force-field model.

  8. Study on interactions of aminoglycoside antibiotics with calf thymus DNA and determination of calf thymus DNA via the resonance Rayleigh scattering technique.

    PubMed

    Qiao, Man; Li, Chunyan; Shi, Ying; Liu, Shaopu; Liu, Zhongfang; Hu, Xiaoli

    2015-11-01

    A simple and sensitive resonance Rayleigh scattering (RRS) spectra method was developed for the determination of calf thymus DNA (ctDNA). The enhanced RRS signals were based on the interactions between ctDNA and aminoglycoside antibiotics (AGs) including kanamycin (KANA), tobramycin (TOB), gentamicin (GEN) and neomycin (NEO) in a weakly acidic medium (pH 3.3-5.7). Parameters influencing the method were investigated. Under optimum conditions, increments in the scattering intensity (∆I) were directly proportional to the concentration of ctDNA over certain ranges. The detection limit ranged from 12.2 to 16.9 ng/mL. Spectroscopic methods, including RRS spectra, absorption spectra and circular dichroism (CD) spectroscopy, coupled with thermo-denaturation experiments were used to study the interactions, indicating that the interaction between AGs with ctDNA was electrostatic binding mode.

  9. Groucho is required for Drosophila neurogenesis, segmentation, and sex determination and interacts directly with hairy-related bHLH proteins.

    PubMed

    Paroush, Z; Finley, R L; Kidd, T; Wainwright, S M; Ingham, P W; Brent, R; Ish-Horowicz, D

    1994-12-02

    We have used the interaction trap, a yeast two-hybrid system, to identify proteins interacting with hairy, a basic-helix-loop-helix (bHLH) protein that represses transcription during Drosophila embryonic segmentation. We find that the groucho (gro) protein binds specifically to hairy and also to hairy-related bHLH proteins encoded by deadpan and the Enhancer of split complex. The C-terminal WRPW motif present in all these bHLH proteins is essential for this interaction. We demonstrate that these associations reflect in vivo maternal requirements for gro during neurogenesis, segmentation, and sex determination, three processes regulated by the above bHLH proteins, and we propose that gro is a transcriptional corepressor recruited to specific target promoters by hairy-related bHLH proteins.

  10. The use of UV-visible spectroscopy for the determination of hydrophobic interactions between neuropeptides and membrane model systems.

    PubMed

    Young, J K; Graham, W H; Beard, D J; Hicks, R P

    1992-08-01

    Ultraviolet-visible spectroscopy has been used as a rapid method to evaluate the hydrophobic interactions between a series of cationic and zwitterionic neuropeptides and dipeptides with the hydrophobic core of two membrane model systems; sodium dodecyl sulfate and lysophosphatidylcholine micelles. If a hydrophobic interaction occurs, a 1-nm bathochromic shift is observed in the uv-visible spectrum of the aromatic side chains when going from aqueous solution to a micellar solution. The aromatic residues of substance P, bradykinin, and Des-Arg9 bradykinin all exhibited the 1-nm bathochromic shift in the presence of sodium dodecyl sulfate while those of Met-enkephalin did not. The opposite effects were observed in the presence of lysophosphatidylcholine micelles.

  11. Determinants of child morbidity in Latin America: a pooled analysis of interactions between parental education and economic status.

    PubMed

    Hatt, Laurel E; Waters, Hugh R

    2006-01-01

    Diarrhea and respiratory infections account for more than two-fifths of all deaths among children under five. Parental education and economic status are well-known risk factors for child morbidity, but little is known about whether education and economic status operate synergistically or independently to influence children's health. Confirming the presence and direction of such interactions is important to better target education and development policies. Our objective is to test for interactions between parental education and economic status in predicting the risk of diarrhea and respiratory illness among children under five, before and after adjusting for key proximate risk factors. We pool 12 Demographic and Health Surveys (DHS) and nine Living Standards Measurement Surveys (LSMS) from Latin America, creating two large databases. Quintiles of economic status are constructed from principal components asset indices. We use logistic regression to analyze episodes of diarrhea and respiratory illness, and interactions between economic quintile and maternal and paternal education are evaluated via likelihood ratio tests. We find that mother's education and quintile interact synergistically in the DHS data, while results are inconclusive in the LSMS data. The effect of increasing maternal education appears to be more protective for children in wealthy families than for children in poor families. Conversely, improvements in economic status reduce health risks more for children whose mothers are better educated. Father's education is protective and operates independently of economic status. Our findings imply that poverty alleviation efforts occurring in concert with programs to educate women and girls will be more effective for improving children's health than either approach alone.

  12. Randomized controlled trial to determine the effectiveness of an interactive multimedia food safety education program for clients of the special supplemental nutrition program for women, infants, and children.

    PubMed

    Trepka, Mary Jo; Newman, Frederick L; Davila, Evelyn P; Matthew, Karen J; Dixon, Zisca; Huffman, Fatma G

    2008-06-01

    Pregnant women and the very young are among those most susceptible to foodborne infections and at high risk of a severe outcome from foodborne infections. To determine if interactive multimedia is a more effective method than pamphlets for delivering food safety education to Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) clients. A randomized controlled trial of WIC clients was conducted. Self-reported food safety practices were compared between pre- and postintervention questionnaires completed >or=2 months after the intervention. Pregnant WIC clients or female caregivers (usually mothers) of WIC clients who were 18 years of age or older and able to speak and read English were recruited from an inner-city WIC clinic. Participants were randomized to receive food safety pamphlets or complete an interactive multimedia food safety education program on a computer kiosk. Change from pre- to postintervention food safety scores. A mean food safety score was determined for each participant for the pre- and postintervention questionnaires. The scores were used in a two-group repeated measures analysis of variance. Of the 394 participants, 255 (64.7%) completed the postintervention questionnaire. Satisfaction with the program was high especially among those with no education beyond high school. When considering a repeated measures analysis of variance model with the two fixed between-subject effects of group and age, a larger improvement in score in the interactive multimedia group than in the pamphlet group (P=0.005) was found, but the size of the group effect was small (partial eta(2)=0.033). Women aged 35 years or older in the interactive multimedia group had the largest increase in score. The interactive multimedia was well-accepted and resulted in improved self-reported food safety practices, suggesting that interactive multimedia is an effective option for food safety education in WIC clinics.

  13. SiO2 nanoparticles modified CPE as a biosensor for determination of i-motif DNA/Tamoxifen interaction.

    PubMed

    Heydari, Elham; Raoof, Jahan Bakhsh; Ojani, Reza; Bagheryan, Zahra

    2016-08-01

    Cytosine-rich DNA sequences can form a highly ordered structure known as i-motif in slightly acidic solutions. The stability of the folded i-motif structure is a good strategy to inhibit the telomerase reaction in cancer cells. The electrochemical biosensor was prepared by modifying carbon paste electrode with SiO2 nanoparticles to investigate drugs which can stabilize this structure. Tamoxifen (Tam), an antiestrogen hormonal agent for treatment of breast cancer, was chosen as the model ligand and its interaction with i-motif structure was examined. The interaction between i-motif DNA and Tam was studied in PBS buffer and [Fe(CN)6](3-) through the cyclic voltammetry and square wave voltammetry methods. The oxidation peak of Tam, due to the i-motif DNA/Tam interaction, was observed after i-motif immobilized on the surface of the electrode. The i-motif formation was investigated by circular dichroism spectroscopy and the results showed that this structure can certainly be made with pH around 4.5, but its stability reduced by going to the more alkaline pH. The selectivity which was studied in the presence of complementary strand demonstrated that i-motif structure could be stabilized in acidic pH even in the presence of its complementary strand. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Antigen availability determines CD8⁺ T cell-dendritic cell interaction kinetics and memory fate decisions.

    PubMed

    Henrickson, Sarah E; Perro, Mario; Loughhead, Scott M; Senman, Balimkiz; Stutte, Susanne; Quigley, Michael; Alexe, Gabriela; Iannacone, Matteo; Flynn, Michael P; Omid, Shaida; Jesneck, Jonathan L; Imam, Sabrina; Mempel, Thorsten R; Mazo, Irina B; Haining, W Nicholas; von Andrian, Ulrich H

    2013-09-19

    T cells are activated by antigen (Ag)-bearing dendritic cells (DCs) in lymph nodes in three phases. The duration of the initial phase of transient, serial DC-T cell interactions is inversely correlated with Ag dose. The second phase, characterized by stable DC-T cell contacts, is believed to be necessary for full-fledged T cell activation. Here we have shown that this is not the case. CD8⁺ T cells interacting with DCs presenting low-dose, short-lived Ag did not transition to phase 2, whereas higher Ag dose yielded phase 2 transition. Both antigenic constellations promoted T cell proliferation and effector differentiation but yielded different transcriptome signatures at 12 hr and 24 hr. T cells that experienced phase 2 developed long-lived memory, whereas conditions without stable contacts yielded immunological amnesia. Thus, T cells make fate decisions within hours after Ag exposure, resulting in long-term memory or abortive effector responses, correlating with T cell-DCs interaction kinetics.

  15. Voltammetric method for determining the trace moisture content of organic solvents based on hydrogen-bonding interactions with quinones.

    PubMed

    Hui, Yanlan; Chng, Elaine Lay Khim; Chua, Louisa Pei-Lyn; Liu, Wan Zhen; Webster, Richard D

    2010-03-01

    Voltammetry experiments were performed on the natural quinone, vitamin K(1) (VK(1)), in a range of organic solvents of varying dielectric constant that are commonly used for electrochemical measurements [dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), acetonitrile (MeCN), propionitrile (EtCN), butyronitrile (PrCN), 1,2-dichloroethane (DCE), dichloromethane (DCM), and 1,1,2,2-tetrachloroethane (TCE)]. The water content of the solvents was accurately measured using Karl Fischer (KF) coulometric titrations, and the voltammetric data were used to estimate the degree of hydrogen-bonding interactions between the reduced forms of VK(1) and variable levels of water, thereby allowing a ranking of water-substrate interactions in the different solvents. The voltammetric data were analyzed based on interactions that occur between reduced forms of VK(1) and the water, the solvent, and the supporting electrolyte. Calibration data were obtained that are independent of the nature of the reference electrode and allow the water content of the solvents to be calculated by performing a single voltammetric scan in the presence of VK(1) and 0.2 M supporting electrolyte (Bu(4)NPF(6)).

  16. Environment and host genotype determine the outcome of a plant-virus interaction: from antagonism to mutualism.

    PubMed

    Hily, Jean-Michel; Poulicard, Nils; Mora, Miguel-Ángel; Pagán, Israel; García-Arenal, Fernando

    2016-01-01

    It has been hypothesized that plant-virus interactions vary between antagonism and conditional mutualism according to environmental conditions. This hypothesis is based on scant experimental evidence, and to test it we examined the effect of abiotic factors on the Arabidopsis thaliana-Cucumber mosaic virus (CMV) interaction. Four Arabidopsis genotypes clustering into two allometric groups were grown under six environments defined by three temperature and two light-intensity conditions. Plants were either CMV-infected or mock-inoculated, and the effects of environment and infection on temporal and resource allocation life-history traits were quantified. Life-history traits significantly differed between allometric groups over all environments, with group 1 plants tolerating abiotic stress better than those of group 2. The effect of CMV infection on host fitness (virulence) differed between genotypes, being lower in group 1 genotypes. Tolerance to abiotic stress and to infection was similarly achieved through life-history trait responses, which resulted in resource reallocation from growth to reproduction. Effects of infection varied according to plant genotype and environment from detrimental to beneficial for host fitness. These results are highly relevant and demonstrate that plant viruses can be pleiotropic parasites along the antagonism-mutualism continuum, which should be considered in analyses of the evolution of plant-virus interactions.

  17. Rubrene: The Interplay between Intramolecular and Intermolecular Interactions Determines the Planarization of Its Tetracene Core in the Solid State.

    PubMed

    Sutton, Christopher; Marshall, Michael S; Sherrill, C David; Risko, Chad; Brédas, Jean-Luc

    2015-07-15

    Rubrene is one of the most studied molecular semiconductors; its chemical structure consists of a tetracene backbone with four phenyl rings appended to the two central fused rings. Derivatization of these phenyl rings can lead to two very different solid-state molecular conformations and packings: One in which the tetracene core is planar and there exists substantive overlap among neighboring π-conjugated backbones; and another where the tetracene core is twisted and the overlap of neighboring π-conjugated backbones is completely disrupted. State-of-the-art electronic structure calculations show for all isolated rubrene derivatives that the twisted conformation is more favorable (by -1.7 to -4.1 kcal mol(-1)), which is a consequence of energetically unfavorable exchange-repulsion interactions among the phenyl side groups. Calculations based on available crystallographic structures reveal that planar conformations of the tetracene core in the solid state result from intermolecular interactions that can be tuned through well-chosen functionalization of the phenyl side groups and lead to improved intermolecular electronic couplings. Understanding the interplay of these intramolecular and intermolecular interactions provides insight into how to chemically modify rubrene and similar molecular semiconductors to improve the intrinsic materials electronic properties.

  18. Identification of Regions Interacting with Ovo(d) Mutations: Potential New Genes Involved in Germline Sex Determination or Differentiation in Drosophila Melanogaster

    PubMed Central

    Pauli, D.; Oliver, B.; Mahowald, A. P.

    1995-01-01

    Only a few Drosophila melanogaster germline sex determination genes are known, and there have been no systematic screens to identify new genes involved in this important biological process. The ovarian phenotypes produced by females mutant for dominant alleles of the ovo gene are modified in flies with altered doses of other loci involved in germline sex determination in Drosophila (Sex-lethal(+), sans fille(+) and ovarian tumor(+)). This observation constitutes the basis for a screen to identify additional genes required for proper establishment of germline sexual identity. We tested 300 deletions, which together cover ~58% of the euchromatic portion of the genome, for genetic interactions with ovo(D). Hemizygosity for more than a dozen small regions show interactions that either partially suppress or enhance the ovarian phenotypes of females mutant for one or more of the three dominant ovo mutations. These regions probably contain genes whose products act in developmental hierarchies that include ovo(+) protein. PMID:7713427

  19. ModuleRole: a tool for modulization, role determination and visualization in protein-protein interaction networks.

    PubMed

    Li, Guipeng; Li, Ming; Zhang, Yiwei; Wang, Dong; Li, Rong; Guimerà, Roger; Gao, Juntao Tony; Zhang, Michael Q

    2014-01-01

    Rapidly increasing amounts of (physical and genetic) protein-protein interaction (PPI) data are produced by various high-throughput techniques, and interpretation of these data remains a major challenge. In order to gain insight into the organization and structure of the resultant large complex networks formed by interacting molecules, using simulated annealing, a method based on the node connectivity, we developed ModuleRole, a user-friendly web server tool which finds modules in PPI network and defines the roles for every node, and produces files for visualization in Cytoscape and Pajek. For given proteins, it analyzes the PPI network from BioGRID database, finds and visualizes the modules these proteins form, and then defines the role every node plays in this network, based on two topological parameters Participation Coefficient and Z-score. This is the first program which provides interactive and very friendly interface for biologists to find and visualize modules and roles of proteins in PPI network. It can be tested online at the website http://www.bioinfo.org/modulerole/index.php, which is free and open to all users and there is no login requirement, with demo data provided by "User Guide" in the menu Help. Non-server application of this program is considered for high-throughput data with more than 200 nodes or user's own interaction datasets. Users are able to bookmark the web link to the result page and access at a later time. As an interactive and highly customizable application, ModuleRole requires no expert knowledge in graph theory on the user side and can be used in both Linux and Windows system, thus a very useful tool for biologist to analyze and visualize PPI networks from databases such as BioGRID. ModuleRole is implemented in Java and C, and is freely available at http://www.bioinfo.org/modulerole/index.php. Supplementary information (user guide, demo data) is also available at this website. API for ModuleRole used for this program can be

  20. Visualization of CD2 interaction with LFA-3 and determination of the two-dimensional dissociation constant for adhesion receptors in a contact area

    PubMed Central

    1996-01-01

    Many adhesion receptors have high three-dimensional dissociation constants (Kd) for counter-receptors compared to the KdS of receptors for soluble extracellular ligands such as cytokines and hormones. Interaction of the T lymphocyte adhesion receptor CD2 with its counter- receptor, LFA-3, has a high solution-phase Kd (16 microM at 37 degrees C), yet the CD2/LFA-3 interaction serves as an effective adhesion mechanism. We have studied the interaction of CD2 with LFA-3 in the contact area between Jurkat T lymphoblasts and planar phospholipid bilayers containing purified, fluorescently labeled LFA-3. Redistribution and lateral mobility of LFA-3 were measured in contact areas as functions of the initial LFA-3 surface density and of time after contact of the cells with the bilayers. LFA-3 accumulated at sites of contact with a half-time of approximately 15 min, consistent with the previously determined kinetics of adhesion strengthening. The two-dimensional Kd for the CD2/LFA-3 interaction was 21 molecules/microns 2, which is lower than the surface densities of CD2 on T cells and LFA-3 on most target or stimulator cells. Thus, formation of CD2/LFA-3 complexes should be highly favored in physiological interactions. Comparison of the two-dimensional (membrane- bound) and three-dimensional (solution-phase) KdS suggest that cell- cell contact favors CD2/LFA-3 interaction to a greater extent than that predicted by the three-dimensional Kd and the intermembrane distance at the site of contact. LFA-3 molecules in the contact site were capable of lateral diffusion in the plane of the phospholipid bilayer and did not appear to be irreversibly trapped in the contact area, consistent with a rapid off-rate. These data provide insights into the function of low affinity interactions in adhesion. PMID:8636222

  1. Interaction mechanisms between organic UV filters and bovine serum albumin as determined by comprehensive spectroscopy exploration and molecular docking.

    PubMed

    Ao, Junjie; Gao, Li; Yuan, Tao; Jiang, Gaofeng

    2015-01-01

    Organic UV filters are a group of emerging PPCP (pharmaceuticals and personal care products) contaminants. Current information is insufficient to understand the in vivo processes and health risks of organic UV filters in humans. The interaction mechanism of UV filters with serum albumin provides critical information for the health risk assessment of these active ingredients in sunscreen products. This study investigates the interaction mechanisms of five commonly used UV filters (2-hydroxy-4-methoxybenzophenone, BP-3; 2-ethylhexyl 4-methoxycinnamate, EHMC; 4-methylbenzylidene camphor, 4-MBC; methoxydibenzoylmethane, BDM; homosalate, HMS) with bovine serum albumin (BSA) by spectroscopic measurements of fluorescence, circular dichroism (CD), competitive binding experiments and molecular docking. Our results indicated that the fluorescence of BSA was quenched by these UV filters through a static quenching mechanism. The values of the binding constant (Ka) ranged from (0.78±0.02)×10(3) to (1.29±0.01)×10(5) L mol(-1). Further exploration by synchronous fluorescence and CD showed that the conformation of BSA was demonstrably changed in the presence of these organic UV filters. It was confirmed that the UV filters can disrupt the α-helical stability of BSA. Moreover, the results of molecular docking revealed that the UV filter molecule is located in site II (sub-domain IIIA) of BSA, which was further confirmed by the results of competitive binding experiments. In addition, binding occurred mainly through hydrogen bonding and hydrophobic interaction. This study raises critical concerns regarding the transportation, distribution and toxicity effects of organic UV filters in human body. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Protein folding rates and thermodynamic stability are key determinants for interaction with the Hsp70 chaperone system

    PubMed Central

    Sekhar, Ashok; Lam, Hon Nam; Cavagnero, Silvia

    2012-01-01

    The Hsp70 family of molecular chaperones participates in vital cellular processes including the heat shock response and protein homeostasis. E. coli's Hsp70, known as DnaK, works in concert with the DnaJ and GrpE co-chaperones (K/J/E chaperone system), and mediates cotranslational and post-translational protein folding in the cytoplasm. While the role of the K/J/E chaperones is well understood in the presence of large substrates unable to fold independently, it is not known if and how K/J/E modulates the folding of smaller proteins able to fold even in the absence of chaperones. Here, we combine experiments and computation to evaluate the significance of kinetic partitioning as a model to describe the interplay between protein folding and binding to the K/J/E chaperone system. First, we target three nonobligatory substrates, that is, proteins that do not require chaperones to fold. The experimentally observed chaperone association of these client proteins during folding is entirely consistent with predictions from kinetic partitioning. Next, we develop and validate a computational model (CHAMP70) that assumes kinetic partitioning of substrates between folding and interaction with K/J/E. CHAMP70 quantitatively predicts the experimentally measured interaction of RNase HD as it refolds in the presence of various chaperones. CHAMP70 shows that substrates are posed to interact with K/J/E only if they are slow-folding proteins with a folding rate constant kf <50 s−1, and/or thermodynamically unstable proteins with a folding free energy ΔG0UN ≥−2 kcal mol−1. Hence, the K/J/E system is tuned to use specific protein folding rates and thermodynamic stabilities as substrate selection criteria. PMID:22886941

  3. FIT: Computer Program that Interactively Determines Polynomial Equations for Data which are a Function of Two Independent Variables

    NASA Technical Reports Server (NTRS)

    Arbuckle, P. D.; Sliwa, S. M.; Roy, M. L.; Tiffany, S. H.

    1985-01-01

    A computer program for interactively developing least-squares polynomial equations to fit user-supplied data is described. The program is characterized by the ability to compute the polynomial equations of a surface fit through data that are a function of two independent variables. The program utilizes the Langley Research Center graphics packages to display polynomial equation curves and data points, facilitating a qualitative evaluation of the effectiveness of the fit. An explanation of the fundamental principles and features of the program, as well as sample input and corresponding output, are included.

  4. Determining the mode of interaction of calf thymus DNA with the drug sumatriptan using voltammetric and spectroscopic techniques

    NASA Astrophysics Data System (ADS)

    Shahabadi, Nahid; Moghadam, Neda Hosseinpour

    2012-12-01

    The interaction of native calf thymus DNA with sumatriptan(1-[3-(2-dimethylaminoethyl)-1H-indol-5-yl]-N-methyl-methanesulfonamide) at physiological pH was studied by spectrophotometry, circular dichroism, voltammetry and viscosimetric techniques. Sumatriptan molecule intercalated between base pairs of DNA, showed by a sharp increase in specific viscosity of DNA. In cyclic voltammetry, decrease of the peak current and positive shift indicated that this drug is able to intercalate between the DNA base pairs. In addition, the drug induced changes in the CD spectrum of CT-DNA, as well as hypochromism changes in its UV-vis spectrum.

  5. Chemical interactions in complex matrices: Determination of polar impurities in biofuels and fuel contaminants in building materials

    NASA Astrophysics Data System (ADS)

    Baglayeva, Ganna

    The solutions to several real-life analytical and physical chemistry problems, which involve chemical interactions in complex matrices are presented. The possible interferences due to the analyte-analyte and analyte-matrix chemical interactions were minimized on each step of the performed chemical analysis. Concrete and wood, as major construction materials, typically become contaminated with fuel oil hydrocarbons during their spillage. In the catastrophic scenarios (e.g., during floods), fuel oil mixes with water and then becomes entrained within the porous structure of wood or concrete. A strategy was proposed for the efficient extraction of fuel oil hydrocarbons from concrete to enable their monitoring. The impacts of sample aging and inundation with water on the extraction efficiency were investigated to elucidate the nature of analytematrix interactions. Two extraction methods, 4-days cold solvent extraction with shaking and 24-hours Soxhlet extraction with ethylacetate, methanol or acetonitrile yielded 95-100 % recovery of fuel oil hydrocarbons from concrete. A method of concrete remediation after contamination with fuel oil hydrocarbons using activated carbon as an adsorbent was developed. The 14 days remediation was able to achieve ca. 90 % of the contaminant removal even from aged water-submerged concrete samples. The degree of contamination can be qualitatively assessed using transport rates of the contaminants. Two models were developed, Fickian and empirical, to predict long-term transport behavior of fuel oil hydrocarbons under flood representative scenarios into wood. Various sorption parameters, including sorption rate, penetration degree and diffusion coefficients were obtained. The explanations to the observed three sorption phases are provided in terms of analyte-matrix interactions. The detailed simultaneous analysis of intermediate products of the cracking of triacylglycerol oils, namely monocarboxylic acids, triacyl-, diacyl- and

  6. Functional traits determine formation of mutualism and predation interactions in seed-rodent dispersal system of a subtropical forest

    NASA Astrophysics Data System (ADS)

    Chang, Gang; Zhang, Zhibin

    2014-02-01

    Network structure in plant-animal systems has been widely investigated but the roles of functional traits of plants and animals in formation of mutualism and predation interactions and community structure are still not fully understood. In this study, we quantitatively assessed interaction strength of mutualism and predation between 5 tree species and 7 rodent species by using semi-natural enclosures in a subtropical forest in southwest China. Seeds with high handling-time and nutrition traits (for both rat and mouse species) or high tannin trait (for mouse species) show high mutualism but low predation with rodents; while seeds with low handling-time and low nutrition traits show high predation but low mutualism with rodents. Large-sized rat species are more linked to seeds with high handling-time and high nutrition traits, while small-sized mouse species are more connected with seeds with low handling-time, low nutrition value and high tannin traits. Anti-predation seed traits tend to increase chance of mutualism instead of reducing predation by rodents, suggesting formation of mutualism may be connected with that of predation. Our study demonstrates that seed and animal traits play significant roles in the formation of mutualism and predation and network structure of the seed-rodent dispersal system.

  7. Structure of the bacterial cell division determinant GpsB and its interaction with penicillin-binding proteins.

    PubMed

    Rismondo, Jeanine; Cleverley, Robert M; Lane, Harriet V; Großhennig, Stephanie; Steglich, Anne; Möller, Lars; Mannala, Gopala Krishna; Hain, Torsten; Lewis, Richard J; Halbedel, Sven

    2016-03-01

    Each bacterium has to co-ordinate its growth with division to ensure genetic stability of the population. Consequently, cell division and growth are tightly regulated phenomena, albeit different bacteria utilise one of several alternative regulatory mechanisms to maintain control. Here we consider GpsB, which is linked to cell growth and division in Gram-positive bacteria. ΔgpsB mutants of the human pathogen Listeria monocytogenes show severe lysis, division and growth defects due to distortions of cell wall biosynthesis. Consistent with this premise, GpsB interacts both in vitro and in vivo with the major bi-functional penicillin-binding protein. We solved the crystal structure of GpsB and the interaction interfaces in both proteins are identified and validated. The inactivation of gpsB results in strongly attenuated virulence in animal experiments, comparable in degree to classical listerial virulence factor mutants. Therefore, GpsB is essential for in vitro and in vivo growth of a highly virulent food-borne pathogen, suggesting that GpsB could be a target for the future design of novel antibacterials.

  8. Gene-environment interactions in determining differences in genetic susceptibility to cancer in subsites of the head and neck.

    PubMed

    Maurya, Shailendra S; Katiyar, Tridiv; Dhawan, Ankur; Singh, Sudhir; Jain, Swatantra K; Pant, Mohan C; Parmar, Devendra

    2015-04-01

    Genetic differences in susceptibility to cancer in subsites of the head and neck were investigated in a case-control study involving 750 cases of cancers of the oral cavity, larynx, or pharynx, and an equal number of healthy controls. The prevalence of variant genotypes of cytochrome P450 (CYP) 1A1, 1B1, 2E1, or glutathione-S-transferase M1 (null) in cases suggests that polymorphisms in drug metabolizing enzymes (DMEs) modify cancer risk within subsites of the head and neck. Tobacco or alcohol use was found to increase the risk in cases of laryngeal, pharyngeal, or oral cavity cancers. Interaction between genetic variation in DMEs and tobacco smoke (or smoking) exposures conferred significant risk for laryngeal cancer. Likewise, strong associations of the polymorphic genotypes of DMEs with cases of pharyngeal and oral cavity cancer who were tobacco chewers or alcohol users demonstrate that gene-environment interactions may explain differences in genetic susceptibility for cancers of the oral cavity, larynx, and pharynx. © 2014 Wiley Periodicals, Inc.

  9. The evaluation of a semiautomated computer method to determine the effects of DMSO on Giardia lamblia-intestinal cell interaction.

    PubMed

    Gadelha, A P R; Travassos, R; Monteiro-Leal, L H

    2007-10-01

    In this work, we describe a semiautomated computer method to evaluate the activity of a common drug solvent, dimethyl sulfoxide (DMSO), on in vitro Giardia lamblia-host cell interaction. To compare the number of intestinal cells (IEC-6) and the adhered trophozoites over a specific area in control and treated coculture, a computer routine was created. Using video-light microscopy and digital image-processing tools, the operator was able to count the number of epithelial cells or parasites when they were still lying on the slide surface and without the need to detach them from the substrate for counting with a hemocytometer or other counting devices. Using this strategy, we calculated the total cell number per area and verified the effects of different concentrations of DMSO on G. lamblia-intestinal cell interaction and on the IEC-6 culture. At concentrations of 0.2% and 1%, this solvent produced a fragmentation on the monolayer of epithelial cells. However, DMSO did not affect the attachment of G. lamblia. In the course of these experiments, we compared the semiautomated method to the manual counting method and found that the first one generated smaller standard deviations (SD) than the second.

  10. Determining Wheel-Soil Interaction Loads Using a Meshfree Finite Element Approach Assisting Future Missions with Rover Wheel Design

    NASA Technical Reports Server (NTRS)

    Contreras, Michael T.; Peng, Chia-Yen; Wang, Dongdong; Chen, Jiun-Shyan

    2012-01-01

    A wheel experiencing sinkage and slippage events poses a high risk to rover missions as evidenced by recent mobility challenges on the Mars Exploration Rover (MER) project. Because several factors contribute to wheel sinkage and slippage conditions such as soil composition, large deformation soil behavior, wheel geometry, nonlinear contact forces, terrain irregularity, etc., there are significant benefits to modeling these events to a sufficient degree of complexity. For the purposes of modeling wheel sinkage and slippage at an engineering scale, meshfree finite element approaches enable simulations that capture sufficient detail of wheel-soil interaction while remaining computationally feasible. This study demonstrates some of the large deformation modeling capability of meshfree methods and the realistic solutions obtained by accounting for the soil material properties. A benchmark wheel-soil interaction problem is developed and analyzed using a specific class of meshfree methods called Reproducing Kernel Particle Method (RKPM). The benchmark problem is also analyzed using a commercially available finite element approach with Lagrangian meshing for comparison. RKPM results are comparable to classical pressure-sinkage terramechanics relationships proposed by Bekker-Wong. Pending experimental calibration by future work, the meshfree modeling technique will be a viable simulation tool for trade studies assisting rover wheel design.

  11. Dynamic model for coherent production of particles in nuclei. Determination of the cross section for resonance-particle interaction

    SciTech Connect

    Ponomarev, L.A.; Tarasov, V.E.

    1983-07-01

    The Drell-Hiida-Deck model modified to include rescattering effects has been used to obtain a formula for the coherent production of particles in nuclei. In contrast to the well known Kolbig-Margolis formula, our formula takes into account the dynamics of the process. The coherent diffraction processes NA..-->..(N..pi..)A and ..pi..A..-->..(3..pi..)A are analyzed. From analysis of the reaction NA..-->..(N..pi..)A it follows that the cross section for interaction of the beam of (N..pi..) with a nucleon has a ''normal'' value sigma/sup t//sub N/..pi..,Napprox. =sigma/sup t//sub N/N+sigma/sup t//sub piN/. Analysis of the reaction ..pi..N..-->..(3..pi..)A shows that the cross sections for interaction of a rho meson with a nucleon and with a nucleus are anomalously small: sigma/sup t//sub rhoA/approx. =0.6sigma/sup t//sub piA/ and sigma/sup t//sub rhoN/approx. =10--15 mb. The observed smallness of the cross sections is due to the smallness of the effective Pomeron vertex function for the rho meson.

  12. A hierarchical network of interreceptor interactions determines signal transduction by Neu differentiation factor/neuregulin and epidermal growth factor.

    PubMed Central

    Tzahar, E; Waterman, H; Chen, X; Levkowitz, G; Karunagaran, D; Lavi, S; Ratzkin, B J; Yarden, Y

    1996-01-01

    The ErbB family includes four homologous transmembrane tyrosine kinases. Whereas ErbB-1 binds to the epidermal growth factor (EGF), both ErbB-3 and ErbB-4 bind to the Neu differentiation factors (NDFs, or neuregulins), and ErbB-2, the most oncogenic family member, is an orphan receptor whose function is still unknown. Because previous lines of evidence indicated the existence of interreceptor interactions, we used ectopic expression of individual ErbB proteins and their combinations to analyze the details of receptor cross talks. We show that 8 of 10 possible homo-and heterodimeric complexes of ErbB proteins can be hierarchically induced by ligand binding. Although ErbB-2 binds neither ligand, even in a heterodimeric receptor complex, it is the preferred heterodimer partner of the three other members, and it favors interaction with ErbB-3. Selective receptor overexpression in human tumor cells appears to bias the hierarchical relationships. The ordered network is reflected in receptor transphosphorylation, ErbB-2-mediated enhancement of ligand affinities, and remarkable potentiation of mitogenesis by a coexpressed ErbB-2. The observed superior ability of ErbB-2 to form heterodimers, in conjunction with its uniquely high basal tyrosine kinase activity, may explain why ErbB-2 overexpression is associated with poor prognosis. PMID:8816440

  13. Interaction between the Linker, Pre-S1, and TRP Domains Determines Folding, Assembly, and Trafficking of TRPV Channels.

    PubMed

    Garcia-Elias, Anna; Berna-Erro, Alejandro; Rubio-Moscardo, Fanny; Pardo-Pastor, Carlos; Mrkonjić, Sanela; Sepúlveda, Romina V; Vicente, Rubén; González-Nilo, Fernando; Valverde, Miguel A

    2015-08-04

    Functional transient receptor potential (TRP) channels result from the assembly of four subunits. Here, we show an interaction between the pre-S1, TRP, and the ankyrin repeat domain (ARD)-S1 linker domains of TRPV1 and TRPV4 that is essential for proper channel assembly. Neutralization of TRPV4 pre-S1 K462 resulted in protein retention in the ER, defective glycosylation and trafficking, and unresponsiveness to TRPV4-activating stimuli. Similar results were obtained with the equivalent mutation in TRPV1 pre-S1. Molecular dynamics simulations revealed that TRPV4-K462 generated an alternating hydrogen network with E745 (TRP box) and D425 (pre-S1 linker), and that K462Q mutation affected subunit folding. Consistently, single TRPV4-E745A or TRPV4-D425A mutations moderately affected TRPV4 biogenesis while double TRPV4-D425A/E745A mutation resumed the TRPV4-K462Q phenotype. Thus, the interaction between pre-S1, TRP, and linker domains is mandatory to generate a structural conformation that allows the contacts between adjacent subunits to promote correct assembly and trafficking to the plasma membrane. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Determining Wheel-Soil Interaction Loads Using a Meshfree Finite Element Approach Assisting Future Missions with Rover Wheel Design

    NASA Technical Reports Server (NTRS)

    Contreras, Michael T.; Peng, Chia-Yen; Wang, Dongdong; Chen, Jiun-Shyan

    2012-01-01

    A wheel experiencing sinkage and slippage events poses a high risk to rover missions as evidenced by recent mobility challenges on the Mars Exploration Rover (MER) project. Because several factors contribute to wheel sinkage and slippage conditions such as soil composition, large deformation soil behavior, wheel geometry, nonlinear contact forces, terrain irregularity, etc., there are significant benefits to modeling these events to a sufficient degree of complexity. For the purposes of modeling wheel sinkage and slippage at an engineering scale, meshfree finite element approaches enable simulations that capture sufficient detail of wheel-soil interaction while remaining computationally feasible. This study demonstrates some of the large deformation modeling capability of meshfree methods and the realistic solutions obtained by accounting for the soil material properties. A benchmark wheel-soil interaction problem is developed and analyzed using a specific class of meshfree methods called Reproducing Kernel Particle Method (RKPM). The benchmark problem is also analyzed using a commercially available finite element approach with Lagrangian meshing for comparison. RKPM results are comparable to classical pressure-sinkage terramechanics relationships proposed by Bekker-Wong. Pending experimental calibration by future work, the meshfree modeling technique will be a viable simulation tool for trade studies assisting rover wheel design.

  15. Who's the Friend in the Background? Interactional Strategies in Determining Authenticity in Calls to a National Children's Helpline

    ERIC Educational Resources Information Center

    Emmison, Michael; Danby, Susan

    2007-01-01

    A significant number of calls made to Kids Help Line are seen by the organisation as not requiring counselling support, but are rather young people testing or "checking out" the service. Although the status of many of these "testing calls" is self-evident, determining the authenticity of others presents the helpline counsellors…

  16. Genomic and p16-specific DNA methylation of the mouse colon: elder age and dietary folate as interactive determinants

    USDA-ARS?s Scientific Manuscript database

    Elder age and inadequate folate intake are strongly implicated as important risk factors for colon cancer and each is associated with altered DNA methylation. This study was designed to determine the effect of aging and dietary folate on select features of DNA methylation in the colon that are relev...

  17. Structure determination of the functional domain interaction of a chimeric nonribosomal peptide synthetase from a challenging crystal with noncrystallographic translational symmetry

    SciTech Connect

    Sundlov, Jesse A.; Gulick, Andrew M.

    2013-08-01

    The structure of the functional interaction of NRPS adenylation and carrier protein domains, trapped with a mechanism-based inhibitor, is described. Crystals exhibit translational non-crystallographic symmetry, which challenged structure determination and refinement. The nonribosomal peptide synthetases (NRPSs) are a family of modular proteins that contain multiple catalytic domains joined in a single protein. Together, these domains work to produce chemically diverse peptides, including compounds with antibiotic activity or that play a role in iron acquisition. Understanding the structural mechanisms that govern the domain interactions has been a long-standing goal. During NRPS synthesis, amino-acid substrates are loaded onto integrated carrier protein domains through the activity of NRPS adenylation domains. The structures of two adenylation domain–carrier protein domain complexes have recently been determined in an effort that required the use of a mechanism-based inhibitor to trap the domain interaction. Here, the continued analysis of these proteins is presented, including a higher resolution structure of an engineered di-domain protein containing the EntE adenylation domain fused with the carrier protein domain of its partner EntB. The protein crystallized in a novel space group in which molecular replacement and refinement were challenged by noncrystallographic pseudo-translational symmetry. The structure determination and how the molecular packing impacted the diffraction intensities are reported. Importantly, the structure illustrates that in this new crystal form the functional interface between the adenylation domain and the carrier protein domain remains the same as that observed previously. At a resolution that allows inclusion of water molecules, additional interactions are observed between the two protein domains and between the protein and its ligands. In particular, a highly solvated region that surrounds the carrier protein cofactor is described.

  18. Yeast TATA Binding Protein Interaction with DNA: Fluorescence Determination of Oligomeric State, Equilibrium Binding, On-Rate, and Dissociation Kinetics†

    PubMed Central

    Perez-Howard, Gina M.; Weil, P. Anthony

    2010-01-01

    A combination of steady-state, stopped-flow, and time-resolved fluorescence of intrinsic tryptophan and extrinsically labeled fluorescent DNA is utilized to examine the interaction of yeast TATA binding protein (TBP) with DNA. TBP is composed of two structural domains, the carboxy domain (residues 61–240), which is responsible for DNA binding and initiation of basal level transcription, and an amino terminal domain (residues 1–60), whose function is currently unknown. The steady-state fluorescence emission spectrum of the single tryptophan in the amino terminal domain of TBP undergoes a huge (30–40 nm) red-shift upon interaction with stoichiometric amounts of TATA box containing DNA. From time-resolved tryptophan fluorescence anisotropy studies, we demonstrate that, in the absence of DNA, the protein exists as a multimer in solution and it contains (at least) two primary conformations, one with the amino terminus associated tightly with the protein(s) in a hydrophobic environment and one with the amino terminus decoupled away from the rest of the protein and solvent-exposed. Upon binding DNA, the protein dissociates into a monomeric complex, upon which only the solvent-exposed amino terminus conformation remains. Kinetic and equilibrium binding studies were performed on TATA box containing DNA which was extrinsically labeled with a fluorescent probe Rhodamine-X at the 5′-end. This “fluorescent” DNA allowed for the collection of quantitative spectroscopic binding, kinetic on-rate, and kinetic off-rate data at physiological concentrations. Global analysis of equilibrium binding studies performed from 500 pM to 50 nM DNA reveals a single dissociation constant (Kd) of approximately 5 nM. Global analysis of stopped-flow anisotropy on-rate experiments, with millisecond timing resolution and TBP concentrations ranging from 20 to 600 nM (20 nM DNA), can be perfectly described by a single second-order rate constant of 1.66 × 105 M−1 s−1. These measurements

  19. Age, sex, social class, and quality of family interaction as determinants of adolescents' future orientation: a developmental task interpretation.

    PubMed

    Nurmi, J E

    1987-01-01

    This study is concerned with the effect of age, sex, social class, and quality of family interaction on the future orientation of adolescents aged 10-11, 14-15, and 17-19 years. Seventy-three girls and 75 boys were interviewed about their future hopes and fears. The content and extension of each aim and fear as well as the amount of planning, knowledge, and perceived locus of control involved was estimated from answers. The contents of aims and fears were closely related to the developmental tasks. Nearly half the subjects were afraid of war. The extension of subjects' future orientation decreased, whereas their knowledge about the future increased with age. The subjects from the higher social classes were oriented farther into the future than those from the lower classes. An interpretation emphasizing the importance of the principal developmental tasks on young people's future orientation is discussed.

  20. Interactions between the dietary polyunsaturated fatty acid ratio and genetic factors determine susceptibility to pediatric Crohn's disease.

    PubMed

    Costea, Irina; Mack, David R; Lemaitre, Rozenn N; Israel, David; Marcil, Valerie; Ahmad, Ali; Amre, Devendra K

    2014-04-01

    Increased dietary ratios of ω6/ω3 polyunsaturated fatty acids have been implicated in the pathogenesis of Crohn's disease (CD), but epidemiologic data are limited. We investigated whether variants of genes that control polyunsaturated fatty acid metabolism (CYP4F3, FADS1, and FADS2), along with the dietary ratio of ω6/ω3, confers susceptibility to CD. Based on data from 182 children newly diagnosed with CD and 250 controls, we found that children who consumed a higher dietary ratio of ω6/ω3 were susceptible for CD if they were also carriers of specific variants of CYP4F3 and FADS2 genes. Our findings implicate diet-gene interactions in the pathogenesis of CD.

  1. How do self-interest and other-need interact in the brain to determine altruistic behavior?

    PubMed

    Hu, Jie; Li, Yue; Yin, Yunlu; Blue, Philip R; Yu, Hongbo; Zhou, Xiaolin

    2017-08-15

    Altruistic behavior, i.e., promoting the welfare of others at a cost to oneself, is subserved by the integration of various social, affective, and economic factors represented in extensive brain regions. However, it is unclear how different regions interact to process/integrate information regarding the helper's interest and recipient's need when deciding whether to behave altruistically. Here we combined an interactive game with functional Magnetic Resonance Imaging (fMRI) and transcranial direct current stimulation (tDCS) to characterize the neural network underlying the processing/integration of self-interest and other-need. At the behavioral level, high self-risk decreased helping behavior and high other-need increased helping behavior. At the neural level, activity in medial prefrontal cortex (MPFC) and right dorsolateral prefrontal cortex (rDLPFC) were positively associated with self-risk levels, and activity in right inferior parietal lobe (rIPL) and rDLPFC were negatively associated with other-need levels. Dynamic causal modeling further suggested that both MPFC and rIPL were extrinsically connected to rDLPFC; high self-risk enhanced the effective connectivity from MPFC to rDLPFC, and the modulatory effect of other-need on the connectivity from rIPL to rDLPFC positively correlated with the modulatory effect of other-need on individuals' helping rate. Two tDCS experiments provided causal evidence that rDLPFC affects both self-interest and other-need concerns, and rIPL selectively affects the other-need concerns. These findings suggest a crucial role of the MPFC-IPL-DLPFC network during altruistic decision-making, with rDLPFC as a central node for integrating and modulating motives regarding self-interest and other-need. Copyright © 2017. Published by Elsevier Inc.

  2. Past agricultural land use and present-day fire regimes can interact to determine the nature of seed predation.

    PubMed

    Stuhler, John D; Orrock, John L

    2016-06-01

    Historical agriculture and present-day fire regimes can have significant effects on contemporary ecosystems. Although past agricultural land use can lead to long-term changes in plant communities, it remains unclear whether these persistent land-use legacies alter plant-consumer interactions, such as seed predation, and whether contemporary disturbance (e.g., fire) alters the effects of historical agriculture on these interactions. We conducted a study at 27 sites distributed across 80,300 ha in post-agricultural and non-agricultural longleaf pine woodlands with different degrees of fire frequency to test the hypothesis that past and present-day disturbances that alter plant communities can subsequently alter seed predation. We quantified seed removal by arthropods and rodents for Tephrosia virginiana and Vernonia angustifolia, species of conservation interest. We found that the effects of land-use history and fire frequency on seed removal were contingent on granivore guild and microhabitat characteristics. Tephrosia virginiana removal was greater in low fire frequency sites, due to greater seed removal by rodents. Although overall removal of V. angustifolia did not differ among habitats, rodents removed more seeds than arthropods at post-agricultural sites and non-agricultural sites with low fire frequencies, but not at non-agricultural sites with high fire frequencies. Land-use history and fire frequency also affected the relationship between microhabitat characteristics and removal of V. angustifolia. Our results suggest that historical agriculture and present-day fire regimes may alter seed predation by shifting the impact of rodent and arthropod seed predators among habitats, with potential consequences for the establishment of rare plant species consumed by one or both predators.

  3. CO2 and vitamin B12 interactions determine bioactive trace metal requirements of a subarctic Pacific diatom

    PubMed Central

    King, Andrew L; Sañudo-Wilhelmy, Sergio A; Leblanc, Karine; Hutchins, David A; Fu, Feixue

    2011-01-01

    Phytoplankton growth can be limited by numerous inorganic nutrients and organic growth factors. Using the subarctic diatom Attheya sp. in culture studies, we examined how the availability of vitamin B12 and carbon dioxide partial pressure (pCO2) influences growth rate, primary productivity, cellular iron (Fe), cobalt (Co), zinc (Zn) and cadmium (Cd) quotas, and the net use efficiencies (NUEs) of these bioactive trace metals (mol C fixed per mol cellular trace metal per day). Under B12-replete conditions, cells grown at high pCO2 had lower Fe, Zn and Cd quotas, and used those trace metals more efficiently in comparison with cells grown at low pCO2. At high pCO2, B12-limited cells had ∼50% lower specific growth and carbon fixation rates, and used Fe ∼15-fold less efficiently, and Zn and Cd ∼3-fold less efficiently, in comparison with B12-replete cells. The observed higher Fe, Zn and Cd NUE under high pCO2/B12-replete conditions are consistent with predicted downregulation of carbon-concentrating mechanisms. Co quotas of B12-replete cells were ∼5- to 14-fold higher in comparison with B12-limited cells, suggesting that >80% of cellular Co of B12-limited cells was likely from B12. Our results demonstrate that CO2 and vitamin B12 interactively influence growth, carbon fixation, trace metal requirements and trace metal NUE of this diatom. This suggests the need to consider complex feedback interactions between multiple environmental factors for this biogeochemically critical group of phytoplankton in the last glacial maximum as well as the current and future changing ocean. PMID:21248860

  4. Concomitant Action of Structural Elements and Receptor Phosphorylation Determines Arrestin-3 Interaction with the Free Fatty Acid Receptor FFA4*

    PubMed Central

    Butcher, Adrian J.; Hudson, Brian D.; Shimpukade, Bharat; Alvarez-Curto, Elisa; Prihandoko, Rudi; Ulven, Trond; Milligan, Graeme; Tobin, Andrew B.

    2014-01-01

    In addition to being nutrients, free fatty acids act as signaling molecules by activating a family of G protein-coupled receptors. Among these is FFA4, previously called GPR120, which responds to medium and long chain fatty acids, including health-promoting ω-3 fatty acids, which have been implicated in the regulation of metabolic and inflammatory responses. Here we show, using mass spectrometry, mutagenesis, and phosphospecific antibodies, that agonist-regulated phosphorylation of the human FFA4 receptor occurred primarily at five residues (Thr347, Thr349, Ser350, Ser357, and Ser360) in the C-terminal tail. Mutation of these residues reduced both the efficacy and potency of ligand-mediated arrestin-3 recruitment as well as affecting recruitment kinetics. Combined mutagenesis of all five of these residues was insufficient to fully abrogate interaction with arrestin-3, but further mutagenesis of negatively charged residues revealed additional structural components for the interaction with arrestin-3 within the C-terminal tail of the receptor. These elements consist of the acidic residues Glu341, Asp348, and Asp355 located close to the phosphorylation sites. Receptor phosphorylation thus operates in concert with structural elements within the C-terminal tail of FFA4 to allow for the recruitment of arrestin-3. Importantly, these mechanisms of arrestin-3 recruitment operate independently from Gq/11 coupling, thereby offering the possibility that ligands showing stimulus bias could be developed that exploit these differential coupling mechanisms. Furthermore, this provides a strategy for the design of biased receptors to probe physiologically relevant signaling. PMID:24817122

  5. Bifidobacterial inulin-type fructan degradation capacity determines cross-feeding interactions between bifidobacteria and Faecalibacterium prausnitzii.

    PubMed

    Moens, Frédéric; Weckx, Stefan; De Vuyst, Luc

    2016-08-16

    Prebiotic inulin-type fructans (ITF) display a bifidogenic and butyrogenic effect. Four bifidobacterial strains (Bifidobacterium breve Yakult, Bifidobacterium adolescentis LMG 10734, Bifidobacterium angulatum LMG 11039(T), and Bifidobacterium longum subsp. longum LMG 11047), displaying different ITF degradation capacities, were each grown in cocultivation with Faecalibacterium prausnitzii DSM 17677(T), an ITF-degrading butyrate-producing colon bacterium, as to unravel their cross-feeding interactions. These coculture fermentations were performed in a medium for colon bacteria, whether or not including acetate (necessary for the growth of F. prausnitzii DSM 17677(T) and whether or not provided through cross-feeding), supplemented with oligofructose or inulin as the sole energy source. Bifidobacterium breve Yakult did not degrade oligofructose, resulting in the production of high concentrations of butyrate by F. prausnitzii DSM 17677(T) through oligofructose degradation. The degradation of oligofructose by B. adolescentis LMG 10734 and of oligofructose and inulin by B. angulatum LMG 11039(T) and B. longum LMG 11047 resulted in the production of acetate, which was cross-fed to F. prausnitzii DSM 17677(T), enabling the latter strain to degrade oligofructose and inulin. Slow preferential degradation of the short chain length fractions of oligofructose (intracellularly) by B. adolescentis LMG 10734 enabled substantial oligofructose degradation by F. prausnitzii DSM 17677(T). However, fast non-preferential degradation of all chain length fractions of oligofructose (extracellularly) and efficient degradation of the short chain length fractions of inulin by B. angulatum LMG 11039(T) and B. longum LMG 11047 made it impossible for F. prausnitzii DSM 17677(T) to compete for the available substrate. These results indicate that cross-feeding interactions between bifidobacteria and acetate-depending, butyrate-producing colon bacteria can be either a pure commensal or beneficial

  6. NMR Determines Transient Structure and Dynamics in the Disordered C-Terminal Domain of WASp Interacting Protein

    PubMed Central

    Haba, Noam Y.; Gross, Renana; Novacek, Jiri; Shaked, Hadassa; Zidek, Lukas; Barda-Saad, Mira; Chill, Jordan H.

    2013-01-01

    WASp-interacting protein (WIP) is a 503-residue proline-rich polypeptide expressed in human T cells. The WIP C-terminal domain binds to Wiskott-Aldrich syndrome protein (WASp) and regulates its activation and degradation, and the WIP-WASp interaction has been shown to be critical for actin polymerization and implicated in the onset of WAS and X-linked thrombocytopenia. WIP is predicted to be an intrinsically disordered protein, a class of polypeptides that are of great interest because they violate the traditional structure-function paradigm. In this first (to our knowledge) study of WIP in its unbound state, we used NMR to investigate the biophysical behavior of WIPC, a C-terminal domain fragment of WIP that includes residues 407–503 and contains the WASp-binding site. In light of the poor spectral dispersion exhibited by WIPC and the high occurrence (25%) of proline residues, we employed 5D-NMR13C-detected NMR experiments with nonuniform sampling to accomplish full resonance assignment. Secondary chemical-shift analysis, 15N relaxation rates, and protection from solvent exchange all concurred in detecting transient structure located in motifs that span the WASp-binding site. Residues 446–456 exhibited a propensity for helical conformation, and an extended conformation followed by a short, capped helix was observed for residues 468–478. The 13C-detected approach allows chemical-shift assignment in the WIPC polyproline stretches and thus sheds light on their conformation and dynamics. The effects of temperature on chemical shifts referenced to a denatured sample of the polypeptide demonstrate that heating reduces the structural character of WIPC. Thus, we conclude that the disordered WIPC fragment is comprised of regions with latent structure connected by flexible loops, an architecture with implications for binding affinity and function. PMID:23870269

  7. Molecular Determinants Underlying Binding Specificities of the ABL Kinase Inhibitors: Combining Alanine Scanning of Binding Hot Spots with Network Analysis of Residue Interactions and Coevolution

    PubMed Central

    Tse, Amanda; Verkhivker, Gennady M.

    2015-01-01

    Quantifying binding specificity and drug resistance of protein kinase inhibitors is of fundamental importance and remains highly challenging due to complex interplay of structural and thermodynamic factors. In this work, molecular simulations and computational alanine scanning are combined with the network-based approaches to characterize molecular determinants underlying binding specificities of the ABL kinase inhibitors. The proposed theoretical framework unveiled a relationship between ligand binding and inhibitor-mediated changes in the residue interaction networks. By using topological parameters, we have described the organization of the residue interaction networks and networks of coevolving residues in the ABL kinase structures. This analysis has shown that functionally critical regulatory residues can simultaneously embody strong coevolutionary signal and high network centrality with a propensity to be energetic hot spots for drug binding. We have found that selective (Nilotinib) and promiscuous (Bosutinib, Dasatinib) kinase inhibitors can use their energetic hot spots to differentially modulate stability of the residue interaction networks, thus inhibiting or promoting conformational equilibrium between inactive and active states. According to our results, Nilotinib binding may induce a significant network-bridging effect and enhance centrality of the hot spot residues that stabilize structural environment favored by the specific kinase form. In contrast, Bosutinib and Dasatinib can incur modest changes in the residue interaction network in which ligand binding is primarily coupled only with the identity of the gate-keeper residue. These factors may promote structural adaptability of the active kinase states in binding with these promiscuous inhibitors. Our results have related ligand-induced changes in the residue interaction networks with drug resistance effects, showing that network robustness may be compromised by targeted mutations of key mediating

  8. Absolute atomic charges in YBa2Cu3O7 lattice determined by analysis of the nuclear quadrupole interaction parameters

    NASA Astrophysics Data System (ADS)

    Bordovskii, G. A.; Terukov, E. I.; Marchenko, A. V.; Seregin, P. P.; Shaldenkova, A. V.

    2017-04-01

    The absolute charges of atoms in all sites of the YBa2Cu3O7 lattice were determined using Mössbauer data for 67Cu(67Zn) and 67Ga(67Zn) isotopes, NMR/NQR data for 17O and 137Ba isotopes, and calculations of the lattice electric-field gradient. The obtained charge distributions correspond to a hole occurring predominantly in the sublattice of chain oxygen.

  9. Interaction between sulfonephthalein dyes and chitosan in aqueous solution and its application to the determination of surfactants.

    PubMed

    Yamamoto, Koichi; Adachi, Kana

    2003-08-01

    A spectrophotometric method for the determination of ionic surfactants with Bromophenol Blue (BPB) based on incorporation into a precipitated chitosan was studied. Cationic surfactants (CS+), such as a quaternary ammonium ion containing a long-chain alkyl group, associate with BPB2- buffered at about pH 9 to form the ion associate (CS+)2 x BPB2-. CS+ associates with anionic surfactants (AS-). In the presence of a definite amount of CS+, an increase in the amount of AS- leads to a decrease in the amount of excess CS+, and therefore to a decrease in the amount of the ion associate of CS+ with BPB2-. The addition of a chitosan dissolved in acetic acid to a solution containing these ion associates leads immediately to precipitation of the chitosan and the incorporation of the ion associates (CS+)2 x BPB2- or CS+ x AS- into the precipitated chitosan. After centrifuging, ionic surfactants can be determined by the following two methods: (1) the absorbance of the supernatant solution is measured at 590 nm. (2) After the supernatant solution is separated, the precipitate is dissolved in an acetic acid solution and the absorbance is measured at 625 nm. Because the color of the precipitate is judged by the naked eye, this can be applied to the visual method. This is a simple and rapid method for the determination of a 10(-6) M order of ionic surfactants.

  10. A major determinant for gliding motility in Mycoplasma genitalium: the interaction between the terminal organelle proteins MG200 and MG491.

    PubMed

    Martinelli, Luca; Lalli, Daniela; García-Morales, Luis; Ratera, Mercè; Querol, Enrique; Piñol, Jaume; Fita, Ignacio; Calisto, Bárbara M

    2015-01-16

    Several mycoplasmas, such as the emergent human pathogen Mycoplasma genitalium, developed a complex polar structure, known as the terminal organelle (TO), responsible for a new type of cellular motility, which is involved in a variety of cell functions: cell division, adherence to host cells, and virulence. The TO cytoskeleton is organized as a multisubunit dynamic motor, including three main ultrastructures: the terminal button, the electrodense core, and the wheel complex. Here, we describe the interaction between MG200 and MG491, two of the main components of the TO wheel complex that connects the TO with the cell body and the cell membrane. The interaction between MG200 and MG491 has a KD in the 80 nm range, as determined by surface plasmon resonance. The interface between the two partners was confined to the "enriched in aromatic and glycine residues" (EAGR) box of MG200, previously described as a protein-protein interaction domain, and to a 25-residue-long peptide from the C-terminal region of MG491 by surface plasmon resonance and NMR spectroscopy studies. An atomic description of the MG200 EAGR box binding surface was also provided by solution NMR. An M. genitalium mutant lacking the MG491 segment corresponding to the peptide reveals specific alterations in cell motility and cell morphology indicating that the MG200-MG491 interaction plays a key role in the stability and functioning of the TO.

  11. Dual isotopic approach for determining groundwater origin and water-rock interactions in over exploited watershed in India

    NASA Astrophysics Data System (ADS)

    Negrel, Philippe; Pauwels, Hélène; Millot, Romain; Roy, Stéphane; Guerrot, Catherine

    2010-05-01

    Groundwater flow and storage in hard rock areas is becoming a matter of great interest and importance to researchers and water managers either with regards to the quantity, quality of water as well as delimitation of resources and aquifers. Degradation of groundwater resources by abstraction, contamination, ... has been increasing in many areas and is of growing concern for few decades. In terms of hydrogeology, hard rocks represent a quite heterogeneous and anisotropic media with irregular distribution of pathways of groundwater flow, typically consisting of three vertical zones, upper weathered, middle fractured and lower massive bedrock. Aim of this work is dual and the Maheshwaram watershed (53 km2, Andhra Pradesh, India) representative of watersheds in southern India in terms of geology, overpumping of its hard-rock aquifer (more than 700 classical open end wells in use), its cropping pattern (rice dominating), and its rural socio-economy mainly based on traditional agriculture is investigated through stable isotopes of the water molecule and lead isotopes in groundwater. The overall objective is to incorporate isotopic- and chemical-tracing data and constraints into methods for evaluating groundwater circulation. It divides into fingerprinting the groundwater recharge processes (e.g. the input by the monsoon) and the water use in such agricultural watershed, which is of primary importance in such semi-arid context and investigating the processes of water-rock interactions (e.g. granite-water interaction). In the frame of delimitation of resources and aquifers and long-term sustainability, we monitored the input from monsoon-precipitation over 2 years, and measured spatial and temporal variations in δ18O and δ2H in the groundwater and in precipitation. Individual recharge from the two monsoon periods was identified. This led to identification of periods during which evaporation affects groundwater quality through a higher concentration of salts and stable

  12. Three Principles for Determining the Relevancy of Store-and-Forward and Live Interactive Telemedicine: Reinterpreting Two Telemedicine Research Reviews and Other Research

    PubMed Central

    Ackerman, Michael

    2013-01-01

    Abstract The Agency for Healthcare Research and Quality sponsored two telemedicine research reviews. The latest review concluded that telemedicine is most relevant to specialties, such as psychiatry and neurology, where high levels of patient interaction are crucial to assessment. Telemedicine research studies cited in the reviews having positive findings in the specialties of ophthalmology, otolaryngology, obstetrics and gynecology, gastroenterology, and cardiology and more recent research in these areas are reviewed to identify criteria other than degree of interaction for determining the appropriateness of telemedicine interventions. These criteria include congruity or the extent that procedures used in telemedicine are similar to those of in-person examination, fidelity or the degree to which the information used for assessment in remote examinations is of similar quality to that used in-person, and reliability or the consistency with which information can be gathered and transmitted. PMID:23186085

  13. Determinants of the direction illusion: motion speed and dichoptic presentation interact to reveal systematic individual differences in sign.

    PubMed

    Chen, Tony T; Maloney, Ryan T; Clifford, Colin W G

    2014-07-17

    When two fields of dots with different directions of movement are presented in tandem, the perceived direction of one is biased by the presence of the other. Although this ‘‘direction illusion’’ typically involves repulsion, with an exaggeration of the perceived angular difference in direction between the dot fields, attraction effects, where the perceived difference is reduced, have also been found under certain presentation conditions. Earlier literature has been inconsistent, and there is debate surrounding the nature of the interactions that facilitate the direction illusion, as well as whether they occur at a local or global stage of the motion processing hierarchy. Here we measured the operating characteristics of the direction illusion by parametrically varying inducer contrast and coherence while examining the effects of stimulus speed and dichoptic presentation. It was found that the magnitude and sign of the direction illusion differed substantially from earlier research. Furthermore, there appeared to be significant interindividual variability, with dichoptic presentation producing an attractive rather than repulsive direction illusion in some participants.

  14. Evolution determines how global warming and pesticide exposure will shape predator-prey interactions with vector mosquitoes.

    PubMed

    Tran, Tam T; Janssens, Lizanne; Dinh, Khuong V; Op de Beeck, Lin; Stoks, Robby

    2016-07-01

    How evolution may mitigate the effects of global warming and pesticide exposure on predator-prey interactions is directly relevant for vector control. Using a space-for-time substitution approach, we addressed how 4°C warming and exposure to the pesticide endosulfan shape the predation on Culex pipiens mosquitoes by damselfly predators from replicated low- and high-latitude populations. Although warming was only lethal for the mosquitoes, it reduced predation rates on these prey. Possibly, under warming escape speeds of the mosquitoes increased more than the attack efficiency of the predators. Endosulfan imposed mortality and induced behavioral changes (including increased filtering and thrashing and a positional shift away from the bottom) in mosquito larvae. Although the pesticide was only lethal for the mosquitoes, it reduced predation rates by the low-latitude predators. This can be explained by the combination of the evolution of a faster life history and associated higher vulnerabilities to the pesticide (in terms of growth rate and lowered foraging activity) in the low-latitude predators and pesticide-induced survival selection in the mosquitoes. Our results suggest that predation rates on mosquitoes at the high latitude will be reduced under warming unless predators evolve toward the current low-latitude phenotype or low-latitude predators move poleward.

  15. Molecular dissection of Wnt3a-Frizzled8 interaction reveals essential and modulatory determinants of Wnt signaling activity

    PubMed Central

    2014-01-01

    Background Wnt proteins are a family of secreted signaling molecules that regulate key developmental processes in metazoans. The molecular basis of Wnt binding to Frizzled and LRP5/6 co-receptors has long been unknown due to the lack of structural data on Wnt ligands. Only recently, the crystal structure of the Wnt8-Frizzled8-cysteine-rich-domain (CRD) complex was solved, but the significance of interaction sites that influence Wnt signaling has not been assessed. Results Here, we present an extensive structure-function analysis of mouse Wnt3a in vitro and in vivo. We provide evidence for the essential role of serine 209, glycine 210 (site 1) and tryptophan 333 (site 2) in Fz binding. Importantly, we discovered that valine 337 in the site 2 binding loop is critical for signaling without contributing to binding. Mutations in the presumptive second CRD binding site (site 3) partly abolished Wnt binding. Intriguingly, most site 3 mutations increased Wnt signaling, probably by inhibiting Wnt-CRD oligomerization. In accordance, increasing amounts of soluble Frizzled8-CRD protein modulated Wnt3a signaling in a biphasic manner. Conclusions We propose a concentration-dependent switch in Wnt-CRD complex formation from an inactive aggregation state to an activated high mobility state as a possible modulatory mechanism in Wnt signaling gradients. PMID:24885675

  16. Determination of the interaction second virial coefficients for the carbon dioxide-ethane system from refractive index measurements

    SciTech Connect

    Jaeschke, M.

    1987-01-01

    The compressibility behavior of the CO/sub 2/-C/sub 2/H/sub 6/ system was investigated experimentally. In this work, the refractive indexes of the pure gases and the mixtures were measured using an optical apparatus. On the basis of these data, density and compressibility factors were computed using the Lorentz-Lorenz law. For the pure components, carbon dioxide and ethane, the data from the optical system were slightly adjusted by a fit to Burnett apparatus data measured separately. The experiments produced very accurate virial coefficients and refraction virial coefficients. This paper reports on the effect of temperature on the second and third virial coefficients. For the first refraction virial coefficient, no influence of temperature was found with the equipment used. The interaction second virial coefficient B /sub 12/ (as a function of temperature) was computed from experimental data for the CO/sub 2/-C/sub 2/H/sub 6/ binary system. The data, for which an accuracy of +/- 1.5 cm/sup 3/ mol/sup -1/ was estimated, are in agreement with the data published by Holste et al.

  17. Determination of dicyandiamide in infant formula by stable isotope dilution hydrophilic interaction liquid chromatography with tandem mass spectrometry.

    PubMed

    Inoue, Koichi; Sakamoto, Tasuku; Min, Jun Zhe; Todoroki, Kenichiro; Toyo'oka, Toshimasa

    2014-08-01

    Dicyandiamide is a compound for reducing the negative effects of greenhouse gas emissions and nitrate leaching into waterways. In this study, the trace contamination of dicyandiamide in infant formula was analysed by stable isotope dilution hydrophilic interaction liquid chromatography with tandem mass spectrometry (HILIC-MS/MS). Dicyandiamide and a stable isotope internal standard were monitored by multiple reaction-monitoring with mass transitions: m/z 85→68/43 and m/z 89→71/45 in the electrospray positive ion mode. For sample preparation of the infant formula, a diluted/filtered procedure was developed for this assay. The calculated LOD and LOQ values were 0.01 or 0.05ng/mL for the standard solution, respectively. The averaged recovery and precision were 110.8% and 7.4%, respectively. This assay was applied to monitor 23 infant formulas, and the dicyandiamide contamination in one sample was detected and quantified at 79.1±1.2ng/g (ppb) powder. We suggest that it is necessary to cautiously monitor the DCD in common products from international countries.

  18. Purification of bacterial membrane sensor kinases and biophysical methods for determination of their ligand and inhibitor interactions

    PubMed Central

    Hussain, Rohanah; Harding, Stephen E.; Hughes, Charlotte S.; Ma, Pikyee; Patching, Simon G.; Edara, Shalini; Siligardi, Giuliano; Henderson, Peter J.F.; Phillips-Jones, Mary K.

    2016-01-01

    This article reviews current methods for the reliable heterologous overexpression in Escherichia coli and purification of milligram quantities of bacterial membrane sensor kinase (MSK) proteins belonging to the two-component signal transduction family of integral membrane proteins. Many of these methods were developed at Leeds alongside Professor Steve Baldwin to whom this review is dedicated. It also reviews two biophysical methods that we have adapted successfully for studies of purified MSKs and other membrane proteins–synchrotron radiation circular dichroism (SRCD) spectroscopy and analytical ultracentrifugation (AUC), both of which are non-immobilization and matrix-free methods that require no labelling strategies. Other techniques such as isothermal titration calorimetry (ITC) also share these features but generally require high concentrations of material. In common with many other biophysical techniques, both of these biophysical methods provide information regarding membrane protein conformation, oligomerization state and ligand binding, but they possess the additional advantage of providing direct assessments of whether ligand binding interactions are accompanied by conformational changes. Therefore, both methods provide a powerful means by which to identify and characterize inhibitor binding and any associated protein conformational changes, thereby contributing valuable information for future drug intervention strategies directed towards bacterial MSKs. PMID:27284046

  19. Application of Analytical Quality by Design concept for bilastine and its degradation impurities determination by hydrophilic interaction liquid chromatographic method.

    PubMed

    Terzić, Jelena; Popović, Igor; Stajić, Ana; Tumpa, Anja; Jančić-Stojanović, Biljana

    2016-06-05

    This paper deals with the development of hydrophilic interaction liquid chromatographic (HILIC) method for the analysis of bilastine and its degradation impurities following Analytical Quality by Design approach. It is the first time that the method for bilastine and its impurities is proposed. The main objective was to identify the conditions where an adequate separation in minimal analysis duration could be achieved within a robust region. Critical process parameters which have the most influence on method performance were defined as acetonitrile content in the mobile phase, pH of the aqueous phase and ammonium acetate concentration in the aqueous phase. Box-Behnken design was applied for establishing a relationship between critical process parameters and critical quality attributes. The defined mathematical models and Monte Carlo simulations were used to identify the design space. Fractional factorial design was applied for experimental robustness testing and the method is validated to verify the adequacy of selected optimal conditions: the analytical column Luna(®) HILIC (100mm×4.6mm, 5μm particle size); mobile phase consisted of acetonitrile-aqueous phase (50mM ammonium acetate, pH adjusted to 5.3 with glacial acetic acid) (90.5:9.5, v/v); column temperature 30°C, mobile phase flow rate 1mLmin(-1), wavelength of detection 275nm. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Neighbourhood density and genetic relatedness interact to determine fruit set and abortion rates in a continuous tropical tree population.

    PubMed

    Jones, F A; Comita, L S

    2008-12-07

    Tropical trees may show positive density dependence in fruit set and maturation due to pollen limitation in low-density populations. However, pollen from closely related individuals in the local neighbourhood might reduce fruit set or increase fruit abortion in self-incompatible tree species. We investigated the role of neighbourhood density and genetic relatedness on individual fruit set and abortion in the neotropical tree Jacaranda copaia in a large forest plot in central Panama. Using nested neighbourhood models, we found a strong positive effect of increased conspecific density on fruit set and maturation. However, high neighbourhood genetic relatedness interacted with density to reduce total fruit set and increase the proportion of aborted fruit. Our results imply a fitness advantage for individuals growing in high densities as measured by fruit set, but realized fruit set is lowered by increased neighbourhood relatedness. We hypothesize that the mechanism involved is increased visitation by density-dependent invertebrate pollinators in high-density populations, which increases pollen quantity and carry-over and increases fruit set and maturation, coupled with self-incompatibility at early and late stages due to biparental inbreeding that lowers fruit set and increases fruit abortion. Implications for the reproductive ecology and conservation of tropical tree communities in continuous and fragmented habitats are discussed.

  1. The interactions between TiO2 and graphene with surface inhomogeneity determined using density functional theory.

    PubMed

    Bukowski, Brandon; Deskins, N Aaron

    2015-11-28

    TiO2/graphene composites have shown promise as photocatalysts, leading to improved electronic properties. We have modeled using density functional theory TiO2/graphene interfaces formed between graphene with various defects/functional groups (C vacancy, epoxide, and hydroxyl) and TiO2 clusters of various sizes. We considered clusters from 3 to 45 atoms, the latter a nanoparticle of ∼1 nm in size. Our results show that binding to pristine graphene is dominated by van der Waals forces, and that C vacancies or epoxide groups lead to much stronger binding between the graphene and TiO2. Such sites may serve to anchor TiO2 to graphene. Graphene surfaces with hydroxyls however lead to OH transfer to TiO2 and weak interactions between the graphene and the hydroxylated TiO2 cluster. Charge transfer may occur between TiO2 and graphene in various directions (graphene to TiO2 or TiO2 to graphene), depending on the state of the graphene surface, based on overlap of the density of states. Our work indicates that graphene surface defects or functional groups may have a significant effect on the stability, structure, and photoactivity of these materials.

  2. Selective incorporation of vRNP into influenza A virions determined by its specific interaction with M1 protein.

    PubMed

    Chaimayo, Chutikarn; Hayashi, Tsuyoshi; Underwood, Andrew; Hodges, Erin; Takimoto, Toru

    2017-05-01

    Influenza A viruses contain eight single-stranded, negative-sense RNA segments as viral genomes in the form of viral ribonucleoproteins (vRNPs). During genome replication in the nucleus, positive-sense complementary RNPs (cRNPs) are produced as replicative intermediates, which are not incorporated into progeny virions. To analyze the mechanism of selective vRNP incorporation into progeny virions, we quantified vRNPs and cRNPs in the nuclear and cytosolic fractions of infected cells, using a strand-specific qRT-PCR. Unexpectedly, we found that cRNPs were also exported to the cytoplasm. This export was chromosome region maintenance 1 (CRM1)-independent unlike that of vRNPs. Although both vRNPs and cRNPs were present in the cytosol, viral matrix (M1) protein, a key regulator for viral assembly, preferentially bound vRNPs over cRNPs. These results indicate that influenza A viruses selectively uptake cytosolic vRNPs through a specific interaction with M1 during viral assembly. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. The determination of organophosphonate nerve agent metabolites in human urine by hydrophilic interaction liquid chromatography tandem mass spectrometry.

    PubMed

    Mawhinney, Douglas B; Hamelin, Elizabeth I; Fraser, Rheaclare; Silva, Sathya S; Pavlopoulos, Antonis J; Kobelski, Robert J

    2007-06-01

    A sensitive, robust isotope dilution LC/MS/MS method is presented for the quantitative analysis of human urine for the alkyl methylphosphonic acid metabolites of five organophosphorus nerve agents (VX, rVX or VR, GB or Sarin, GD or Soman, and GF or Cyclosarin). The selective sample preparation method employs non-bonded silica solid-phase extraction and is partially automated. While working with a mobile phase composition that enhances the electrospray ionization process, the hydrophilic interaction chromatography method results in a 5-min injection-to-injection cycle time, excellent peak shapes and adequate retention (k'=3.1). These factors lead to limits of detection for these metabolites as low as 30 pg/mL in a 1-mL sample of human urine. The quality control data (15 and 75 ng/mL) demonstrate accurate (-0.5 to +3.4%) and precise (coefficients of variation of 2.1-3.6%) quantitative results over the clinically relevant urine concentration range of 1-200 ng/mL for a validation set of 20 standard and quality control sets prepared by five analysts over 54 days. The selectivity of the method is demonstrated for a 100-individual reference range study, as well as the analysis of relevant biological samples. The combined sample preparation and analysis portions of this method have a throughput of 288 samples per day.

  4. USE OF MOLECULAR MODELING TO DETERMINE THE INTERACTION AND COMPETITION OF GASES WITHIN COAL FOR CARBON DIOXIDE SEQUESTRATION

    SciTech Connect

    Jeffrey D. Evanseck; Jeffry D. Madura; Jonathan P. Mathews

    2005-05-27

    We have made progress in carrying out large scale molecular dynamics simulations using the CHARMM force field in order to refine our coal/guest interactions. There have been two issues facing us over the last year. First, we have had to create a completely new topology and parameter definition for coal. Since we are using a classical force field, we have adopted the strategy of treating coal composed of individual common fragments based upon a distribution of mass, composition, and bonding. Our procedure is similar to treating a protein as being composed of the discrete set of amino acids. Second, we have had to incorporate the quality CO{sub 2} parameters that we have developed over the last two years. There are the geometric and arithmetic procedures, which we have successfully implemented. We have utilized computational molecular modeling to generate a state-of-the-art large scale structural representation of a bituminous coal of low volatile bituminous rank. This structure(s) has been used to investigate the molecular forces between the bituminous coal structure (or idealized pores) and the molecular species CH{sub 4} and CO{sub 2}. We are close to carrying out molecular dynamics simulations, which will allow us to explore and test the newly created model of coal.

  5. Determination of creatinine, uric and ascorbic acid in bovine milk and orange juice by hydrophilic interaction HPLC.

    PubMed

    Zuo, Ruiting; Zhou, Si; Zuo, Yuegang; Deng, Yiwei

    2015-09-01

    Creatinine (Cr), uric (UA) and ascorbic acid (AA) are common constituents in human fluids. Their abnormal concentrations in human fluids are associated with various diseases. Thus, apart from the endogenous formation in human body, it is also important to examine their sources from food products. In this study, a rapid and accurate HILIC method was developed for simultaneous determination of Cr, UA and AA in bovine milk and orange juice. Milk samples were pretreated by protein precipitation, centrifugation and filtration, followed by HPLC separation and quantification using a Waters Spherisorb S5NH2 column. The developed method has been successfully applied to determine the concentration of UA, AA and Cr in milk and fruit juice samples. The milk samples tested were found to contain UA and creatinine in the concentration range of 24.1-86.0 and 5.07-11.2 μg mL(-1), respectively. The orange juices contain AA over 212 μg mL(-1). Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Cell surface-mediated cellular interactions: effects of B104 neuroblastoma surface determinants on C6 glioma cellular properties.

    PubMed

    Ciment, G; de Vellis, J

    1982-01-01

    To study the influence of cell surface-associated molecules on intercellular communication, C6 glioma cells were cultured both on plastic and on substrata of paraformaldehyde-fixed B104 neuroblastoma cells. By then comparing the phenotypic expression of these "cocultured" C6 cells with cells cultured on tissue culture plastic, the influence of the cellular substratum was determined. The beta-adrenergic-responsive cyclic AMP-generating system of C6 cells was compared on these various substrata. We found that fixed beds of dibutyryl cyclic AMP (dbcAMP)-treated B104 cells uncoupled beta-receptors from adenylate cyclase, whereas fixed beds of similarly treated C6 cells did not. However, other cellular properties were not affected by growth atop fixed dbcAMP-treated B104 cell beds including the rate of C6 cellular proliferation and their rate of protein synthesis. The cell surface-associated determinant on B104 cells capable of uncoupling the beta-responsive cyclase system of C6 cells is probably a protein, as judged by its susceptibility to protease treatment. Other properties of C6 cells were also affected by the various substrata including basal and hydrocortisone-induced levels of glycerol phosphate dehydrogenase (GPDH; an oligodendroglial marker) and the rate of RNA synthesis in these cells.

  7. Analysis of the interaction of a laser pulse with a silicon wafer - Determination of bulk lifetime and surface recombination velocity

    NASA Technical Reports Server (NTRS)

    Luke, Keung L.; Cheng, Li-Jen

    1987-01-01

    The decay of excess minority carriers produced in a silicon wafer of thickness d by a laser pulse is analyzed. A comprehensive theory based on this analysis is presented for the determination of bulk lifetime Tau(b) and surface recombination velocity S. It is shown that, starting with an exponential spatial profile, the carrier profile assumes a spatially symmetrical form after approximately one time constant of the fundamental mode of decay. Expressions for the spatial average of the carrier density as a function of time are derived for three temporal laser pulse shapes: impulse, square, and Gaussian. Particular attention is paid to the time constants of the fundamental and higher